calca-protein--human and Sepsis

Procalcitonin (PCT) is an acute-phase reactant that has been used to diagnose and potentially track the treatment of sepsis. Procalcitonin values rise initially as the infection sets in and eventually fall with resolution. Its level has been reported to be significantly higher in potential nonsurvivors of a septic episode than among survivors. However, there is also a significant amount of evidence against this. We thus conducted a meta-analysis to pool data from all the available studies regarding PCT levels in survivors and nonsurvivors of sepsis. An extensive literature search was conducted using the key words "procalcitonin," "sepsis," and "prognosis." The references of the relevant studies were also scanned. The data from the eligible studies were extracted and analyzed for any significant pooled mean difference between survivors and nonsurvivors both on days 1 and 3. The mean difference in the day 1 PCT values between survivors and nonsurvivors was found to be statistically significant (P = 0.02). The mean difference on day 3 was also statistically significant (P = 0.002). However, in a subgroup consisting of studies on patients with severe sepsis and septic shock, day 1 difference was not found to be significant (P = 0.62). We found heterogeneity of 90% in our study population, which decreased to 62% after exclusion of studies conducted in emergency department patients. Procalcitonin levels in early stages of sepsis are significantly lower among survivors as compared with nonsurvivors of sepsis.

Topics: Acute-Phase Proteins; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Survival Analysis; Survivors; Time Factors

The objective of this study is to evaluate the benefits of adjuvant treatment with crude rhubarb in patients with systemic inflammation reaction syndrome/sepsis by conducting a meta-analysis.. We conducted a systematic literature search of medical electronic databases (up to October 2013). Only randomized controlled trials (RCTs) assessing adjuvant treatment with crude rhubarb in septic patients were included.. A total of 15 RCTs with 869 patients were identified. Pooled analysis showed that interleukin 6 (standardized mean differences [SMDs], -1.30; 95% confidence intervals [CIs], -1.94 to -0.66), tumor necrosis factor α (SMD, -0.95; 95% CI, -1.55 to -0.36), procalcitonin (SMD, -1.50; 95% CI, -2.20 to -0.80), von Willebrand factor (mean differences [MDs], -144.11; 95% CI, -253.87 to -34.35), prothrombin time (MD, -2.38; 95% CI, -2.67 to -2.10), acute physiology and chronic health evaluation II scores (MD, -4.51; 95% CI, -5.30 to -3.73), and gastrointestinal dysfunction (risk ratio, 0.28; 95% CI, 0.16-0.49) were significantly reduced after treatment with crude rhubarb. Platelet number (MD, 58.16; 95% CI, 51.16-65.15) was significantly increased. However, crude rhubarb therapy did not significantly reduce 28-day mortality (risk ratio, 0.60; 95% CI, 0.36-1.00) compared with the usual treatment.. Adjuvant treatment with crude rhubarb appears to have additional benefits in septic patients. Antiinflammation and anticoagulant/antiaggregant properties may be its potential mechanism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Phytotherapy; Protein Precursors; Randomized Controlled Trials as Topic; Rheum; Sepsis; Systemic Inflammatory Response Syndrome; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Effective antimicrobial stewardship is an increasingly important concern for healthcare providers globally. Antibiotics are frequently prescribed for patients who develop sepsis in the intensive care unit and traditionally courses are prolonged, with uncertain benefit and probable harm. There is little evidence to support many guidelines recommending between 10 and 14 days, and a number of studies suggest substantially shorter courses of less than 7 days may suffice. Safely reducing course length is likely to depend on a number of preconditions, including thorough eradication of any septic foci; optimization of serum antibiotic concentrations, particularly when there is physiological derangement; and use of novel biomarkers such as procalcitonin. The critical care environment is well suited to this aim as patients are closely monitored. With these measures in place, it is reasonable to believe short antibiotic courses can safely be used for the majority of intensive care infections.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Drug Administration Schedule; Enterobacteriaceae; Haemophilus influenzae; Humans; Intensive Care Units; Microbial Sensitivity Tests; Protein Precursors; Pseudomonas; Sepsis; Staphylococcus aureus; Streptococcus pneumoniae; Time Factors

Sepsis is one of the main causes of mortality in severe burns. However, it is difficult to diagnose early. Procalcitonin (PCT) has been reported as a biomarker for sepsis with controversial results. The aim of the study is to assess the diagnostic value of serum PCT for sepsis in burn patients through a meta-analysis of published studies.. A comprehensive literature search of PubMed, Embase, Web of Science and the Cochrane Library databases for studies published up to 1st March 2014 that evaluated PCT as a marker for diagnosing sepsis in burn patients was conducted. The summary receiver operating characteristic curves served to evaulate overall test performance. Meta-Disc 1.4 software and Stata 12.1 were used to analyze the data.. A total of 566 patients (samples) from nine trials were identified and analyzed. The pooled sensitivity and specificity were 0.74 and 0.88, respectively. No threshold effect was found among studies. The area under the SROC curve (AUC) was 0.92.. The results suggest that serum PCT is a useful biomarker (AUC=0.92) for early diagnosis of sepsis in burn patients. However, the results should be used with caution, because of obvious heterogeneity among those studies. Further large-scale research should regard more attention to the uniform cut-off value, and laboratories test methods.

Topics: Area Under Curve; Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis

Surgery associated with trauma and soft tissue injuries after surgery significantly activates the systemic immune response. If an infection after surgery occurs, the response is even stronger. Due to spontaneous activation of immune response and elevated biomarkers for sepsis and cytokines, posttraumatic complications such as new-coming postoperative infections are difficult to diagnose. Sepsis as systemic inflammatory response syndrome (SIRS) rapidly progresses through severe sepsis to septic shock and organ failure, and with no applied antibiotic treatment, the disease often ends at death of the patients. In the treatment of non-surgery patients, the biomarkers like white cell blood count, C-reactive protein (CRP) or procalcitonin (PCT) proved to be useful in sepsis recognition. However, diagnostics after surgeries are more complicated and these biomarkers are not ideal. The solution is a sepsis biomarker, which would have high sensitivity and specificity, that can improve diagnostic accuracy of sepsis, should also be measured easily by the patients, and should not be too expensive. We think more sensitive and specific biomarkers such as presepsin (sCD14-ST) or CD64 index on neutrophils could be useful. A diagnosis of sepsis should be based on clinical signs, and clinicians should use biomarker that is not only most sensitive and specific but also is cost effective. Furthermore, confirmation of the bacterial or fungal infection with blood cultures or with the use of broad range polymerase chain reaction (PCR), when culturing is impossible, should be performed.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Lipopolysaccharide Receptors; Peptide Fragments; Postoperative Complications; Protein Precursors; Receptors, IgG; Sepsis; Severity of Illness Index; Surgical Procedures, Operative; Systemic Inflammatory Response Syndrome

Sepsis is an important cause of worldwide morbidity and mortality. Early recognition and diagnosis are keys to achieving improved outcomes. Procalcitonin has been widely investigated as a potential biomarker for sepsis. Furthermore, management of sepsis and other infectious disease is becoming increasingly complicated by the emergence of antibiotic resistant strains of pathogens. Good antibiotic governance is important in reducing the risk of the development of further antibiotic resistance. We reviewed the current literature on the use of procalcitonin in sepsis to determine whether it should be recommended for use in either of these roles. Procalcitonin should not be used as a stand-alone diagnostic test to rule-in or rule-out sepsis or bacterial infection, or for prognostication, in the absence of clinical judgment. Used as part of a clinical algorithm, however, it has been shown to reduce antibiotic prescribing in critical care environments and for respiratory tract infections.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Prognosis; Protein Precursors; Sepsis

Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I2 index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05-3.30) using a random-effects model (I(2) = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73-0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67-0.82) and 0.64 (95% CI, 0.52-0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35-3.95) using a fixed-effects model (I(2) = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75-0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58-0.82) and 0.77 (95% CI, 0.55-0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Humans; Intensive Care Units; Mortality; Odds Ratio; Protein Precursors; Sepsis

Critically ill patients are frequently at risk of sepsis or inflammatory conditions. Procalcitonin (PCT) is a biomarker for critically ill patients to differentiate sepsis from non-infectious triggers of the systemic inflammatory response syndrome. It has been recently shown that PCT is a valuable tool to guide antibiotic treatment in patients with bacteria infections. However, PCT is also less than a universal and perfect biomarker, and its physiologic role remains unknown. An increase in PCT is associated not only with localized bacterial infection, but also with non-infectious disease or other microbial infections. Numerous studies have suggested that use of PCT would reduce patients' exposure to antibiotics; however, the use of PCT-guided management of antibiotics strategy needs further study to validate their safety in daily practice in ICU settings. Data supporting this concept from randomized trials are still required. Future studies should focus on PCT kinetics. On the other hand, the need for biologic role of PCT shall be highlighted. Immunoneutralization of PCT will likely be a therapeutic approach for human sepsis only if its physiologic effects are elaborated. The aim of this review is to summarize and discuss the current evidence for PCT in a series of clinical settings.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Protein Precursors; Sepsis

Procalcitonin is a protein synthesized during sepsis and inflammation. In these states, its production is stimulated by inflammatory mediators and bacterial toxins. Routine determination of PCT concentration is useful in the rapid detection and monitoring of bacterial and fungal infections. The article presents the latest meta-analysis and clinical reports on the use of the PCT and comparison of its diagnostic sensitivity and specificity with other indicators of inflammation and infection in both neonates and in the adult population. Synthesis, properties and metabolism of PCT and the available methods and conditions of the determination are discussed. Presented data indicate a high sensitivity and specificity of PCT determinations, especially in bacterial infection and, what is very important, short duration of the assay and the use of a small sample volume. Assess the dynamics of changes in the concentrations of PCT can provide information not only about the course of infection but also facilitates the decision to introduce and then to discontinue antibiotic therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Inflammation; Male; Middle Aged; Mycoses; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

Neutropenic fever is the most common infective complication in patients receiving cytotoxic chemotherapy, and may result in severe sepsis, septic shock and mortality. Advancements in approaches to empiric antimicrobial therapy and prophylaxis have resulted in improved outcomes. Mortality may, however, still be as high as 50% in high-risk cancer populations. The objective of this review is to summarize factors associated with reduced mortality in patients with neutropenic fever, highlighting components of clinical care with potential for inclusion in quality improvement programs.. Risks for mortality are multifactorial, and include patient, disease and treatment-related factors. Historically, guidelines for management of neutropenic fever have focused upon antimicrobial therapy. There is, however, a recognized need for early identification of sepsis to enable timely administration of antibiotic therapy and for this to be integrated with a whole of systems approach within healthcare facilities. Use of Systemic Inflammatory Response Syndrome criteria is beneficial, but validation is required in neutropenic fever populations.. In the context of emerging and increasing infections because of antimicrobial-resistant bacteria in patients with neutropenic fever, quality improvement initiatives to reduce mortality must encompass antimicrobial stewardship, early detection of sepsis, and use of valid tools for clinical assessment. C-reactive protein and procalcitonin hold potential for inclusion into clinical pathways for management of neutropenic fever.

Topics: Anti-Bacterial Agents; Antibiotic Prophylaxis; Antifungal Agents; Antineoplastic Agents; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chemotherapy-Induced Febrile Neutropenia; Humans; Neoplasms; Practice Guidelines as Topic; Protein Precursors; Quality Improvement; Risk Assessment; Sepsis; Treatment Outcome

Determination of the presence or absence of bacterial infection is important to guide appropriate therapy and reduce antibiotic exposure. Procalcitonin (PCT) is an inflammatory marker that has been suggested as a marker for bacterial infection.. To assess the clinical effectiveness and cost-effectiveness of adding PCT testing to the information used to guide antibiotic therapy in adults and children (1) with confirmed or highly suspected sepsis in intensive care and (2) presenting to the emergency department (ED) with suspected bacterial infection.. Twelve databases were searched to June 2014. Randomised controlled trials were assessed for quality using the Cochrane Risk of Bias tool. Summary relative risks (RRs) and weighted mean differences (WMDs) were estimated using random-effects models. Heterogeneity was assessed visually using forest plots and statistically using the I (2) and Q statistics and investigated through subgroup analysis. The cost-effectiveness of PCT testing in addition to current clinical practice was compared with current clinical practice using a decision tree with a 6 months' time horizon.. Eighteen studies (36 reports) were included in the systematic review. PCT algorithms were associated with reduced antibiotic duration [WMD -3.19 days, 95% confidence interval (CI) -5.44 to -0.95 days, I (2) = 95.2%; four studies], hospital stay (WMD -3.85 days, 95% CI -6.78 to -0.92 days, I (2) = 75.2%; four studies) and a trend towards reduced intensive care unit (ICU) stay (WMD -2.03 days, 95% CI -4.19 to 0.13 days, I (2) = 81.0%; four studies). There were no differences for adverse clinical outcomes. PCT algorithms were associated with a reduction in the proportion of adults (RR 0.77, 95% CI 0.68 to 0.87; seven studies) and children (RR 0.86, 95% CI 0.80 to 0.93) receiving antibiotics, reduced antibiotic duration (two studies). There were no differences for adverse clinical outcomes. All but one of the studies in the ED were conducted in people presenting with respiratory symptoms. Cost-effectiveness: the base-case analyses indicated that PCT testing was cost-saving for (1) adults with confirmed or highly suspected sepsis in an ICU setting; (2) adults with suspected bacterial infection presenting to the ED; and (3) children with suspected bacterial infection presenting to the ED. Cost-savings ranged from £368 to £3268. Moreover, PCT-guided treatment resulted in a small quality-adjusted life-year (QALY) gain (ranging between < 0.001 and 0.005). Cost-effectiveness acceptability curves showed that PCT-guided treatment has a probability of ≥ 84% of being cost-effective for all settings and populations considered (at willingness-to-pay thresholds of £20,000 and £30,000 per QALY).. The limited available data suggest that PCT testing may be effective and cost-effective when used to guide discontinuation of antibiotics in adults being treated for suspected or confirmed sepsis in ICU settings and initiation of antibiotics in adults presenting to the ED with respiratory symptoms and suspected bacterial infection. However, it is not clear that observed costs and effects are directly attributable to PCT testing, are generalisable outside people presenting with respiratory symptoms (for the ED setting) and would be reproducible in the UK NHS. Further studies are needed to assess the effectiveness of adding PCT algorithms to the information used to guide antibiotic treatment in children with suspected or confirmed sepsis in ICU settings. Additional research is needed to examine whether the outcomes presented in this report are fully generalisable to the UK.. This study is registered as PROSPERO CRD42014010822.. The National Institute for Health Research Health Technology Assessment programme.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Cost-Benefit Analysis; Emergency Service, Hospital; Humans; Intensive Care Units; Length of Stay; Models, Economic; Protein Precursors; Sepsis; Technology Assessment, Biomedical; Treatment Outcome

The serum procalcitonin (PCT) concentration reflects both the systemic response to bacterial infection and its severity. However, its accuracy in distinguishing intensive care unit (ICU) patients with and without infection remains low owing to a lack of specificity and the time lapse between infection onset and the PCT rise. Hence, PCT cannot be used as a marker to start or withhold antibiotic therapy for ICU patients. However, the kinetics of the PCT concentration decrease under antibiotic therapy can adequately monitor infection evolution with therapy and can help to customise antibiotic duration. PCT-guided algorithms to guide antibiotic discontinuation were able to shorten antibiotic duration without impacting patient outcomes in several multicentre randomised studies. Notably, antibiotics can be stopped very early when PCT is low and remains low as this indicates that bacterial infection is unlikely. When PCT falls to <0.5 ng/mL or >80% from its peak value, antibiotics for non-localised infections can safely be stopped.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Drug Monitoring; Humans; Intensive Care Units; Protein Precursors; Sepsis; Treatment Outcome

After decades of extensive experimental and clinical research, septic shock and the related multiple organ dysfunction still remain the leading cause of mortality in intensive care units (ICUs) worldwide. Defining sepsis is a difficult task, but what is even more challenging is differentiating infection-induced from non-infection-induced systemic inflammatory response-related multiple organ dysfunction. As conventional signs of infection are often unreliable in intensive care, biomarkers are used, of which one of the most frequently investigated is procalcitonin. Early stabilisation of vital functions via adequate supportive therapy and antibiotic treatment has resulted in substantial improvements in outcome over the last decades. However, there are certain patients who may need extra help, hence modulation of the immune system and the host's response may also be an important therapeutic approach in these situations. Polyclonal intravenous immunoglobulins have been used in critical care for decades. A relatively new potential approach could be attenuation of the overwhelming cytokine storm by specific cytokine adsorbents. Both interventions have been applied in daily practice on a large scale, with firm pathophysiological rationale but weak evidence supported by clinical trials. The purpose of this review is to give an overview on the pathophysiology of sepsis as well as the role and interpretation of biomarkers and their potential use in assisting adjunctive therapies in sepsis in the future.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Monitoring; Drug Therapy; Humans; Protein Precursors; Sepsis

Antibiotic overconsumption and subsequent bacterial multidrug resistance are associated with increased mortality, length of hospitalisation and healthcare costs. Discontinuation of antibiotic treatment in severe infections, such as bloodstream infections (BSIs), is a demanding clinical decision. In this review, we aim to investigate the usefulness of procalcitonin (PCT) monitoring in guiding appropriate treatment duration in BSIs and its impact on clinical outcomes. Data from clinical studies conducted after 2005 that included patients with BSIs indicate that change of PCT is an early indicator for prognosis in terms of survival and, overall, support the usefulness of a PCT-guided clinical algorithm in reducing the duration of antibiotic treatment without compromising survival. Furthermore, the presented data indicate that PCT assessment is helpful in the diagnosis of infective endocarditis. In conclusion, monitoring of PCT together with evaluation of the clinical situation is a valuable tool in reducing the length of antimicrobial treatment in BSIs.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Monitoring; Drug Therapy; Humans; Protein Precursors; Sepsis; Time

To assess the clinical value of procalcitonin (PCT ) in the diagnosis of sepsis in adults.. An extensive search for related literature from the Wanfang data, CNKI, VIP, Medline/PubMed, Embase/OvidSP and the Cochrane Library up to December 2014 was performed. The articles, including prospective observational studies or randomized controlled trials, regarding PCT for the diagnosing of sepsis were enrolled. Only patients older than 18 years were included. Patients with sepsis, severe sepsis, or septic shock served as the experimental group, and those with a systemic inflammatory response syndrome (SIRS) of non-infectious origin as control group. The language of literature included was English or Chinese. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Heterogeneity, pooled diagnostic odds ratio (DOR), pooled sensitivity, pooled specificity, pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the summary receiver operating characteristic curve (SROC) and subgroup analysis were analyzed with the software of Metadisc 1.4.. A total of 6 385 published reports were collected, and among them 24 met the inclusion criteria, including a total. of 3 107 patients. The studies showed substantial heterogeneity (I2 = 69.4%), and random effect model was used for Meta analysis, showing that the pooled DOR was 10.37 [95% confidence interval (95%CI) = 7.10-15.17]. No evidence of a threshold effect was found (Spearman correlation coefficient = 0.27, calculated by logarithm of sensitivity and logarithm of 1-specificity, P = 0.20). The DOR values of pooled and each study were not distributed along the same line in forest plots, and Cochran-Q = 78.33, P = 0.000 0, showing that there was heterogeneity in result from non threshold effect. Except for partial heterogeneity caused by non threshold effect, the result of Meta regression analysis including PCT detection method, categories of disease, research location and so on showed P values were all higher than 0.05. Thus, the heterogeneity could not be explained by Meta regression analysis. The pooled sensitivity was 74% (95% CI = 72%-76%), the pooled specificity was 70% (95% CI = 67%-72%), the pooled positive likelihood ratio was 2.79 (95% CI = 2.31-3.38), the pooled negative likelihood ratio was 0.34 (95% CI = 0.28-0.41), and the pooled AUC was 0.83 (95% CI = 0.79-0.87). AUC in medical patients was 0.80 (95% CI = 0.75-0.85), which was higher than that in surgical patients [0.71 (95% CI = 0.65-0.81)].. Our results indicate a moderate degree of value of PCT for diagnosis of sepsis in adult patients. The diagnostic accuracy in medical patients is higher than that in surgical patients. PCT is a good auxiliary biomarker for diagnosis of sepsis.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Observational Studies as Topic; Prospective Studies; Protein Precursors; Randomized Controlled Trials as Topic; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Fast and appropriate therapy is the cornerstone in the therapy of sepsis. However, the discrimination of sepsis from non-infectious causes of inflammation may be difficult. Biomarkers have been suggested to aid physicians in this decision. There is currently no biochemical technique available which alone allows a rapid and reliable discrimination between sepsis and non-infectious inflammation. Procalcitonin (PCT) is currently the most investigated biomarker for this purpose. C-reactive protein and interleukin 6 perform inferior to PCT in most studies and their value in diagnosing sepsis is not defined. All biomarkers including PCT are also released after various non-infectious inflammatory impacts. This shortcoming needs to be taken into account when biomarkers are used to aid the physician in the diagnosis of sepsis. Polymerase chain reaction (PCR) based pathogen detection may improve time to adequate therapy but cannot rule out the presence of infection when negative.

Topics: Acute-Phase Proteins; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Humans; Interleukin-6; Membrane Glycoproteins; Polymerase Chain Reaction; Protein Precursors; Receptors, Immunologic; Receptors, Urokinase Plasminogen Activator; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

To perform a quantitative review of the evidence on the diagnostic value of inflammatory markers in maternal serum or umbilical cord blood for the diagnosis of early-onset neonatal sepsis (EONS).. We searched multiple databases for studies published through March 2013 that evaluated the diagnostic performance of procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and leukocyte count (white blood cell, WBC) in either umbilical cord blood or maternal serum for diagnosis of EONS. We summarized test performance characteristics with the use of forest plots, hierarchical summary receiver operating characteristic curves and bivariate random effects models.. Our search identified 3874 citations, of which 15 studies evaluating 2178 episodes of suspected neonatal infection were included for analysis. IL-6 in cord blood with a pooled-positive likelihood ratio (LR+) of 9.47 (95% confidence interval: 3.86 to 23.3), PCT in cord blood with a LR+ of 5.72 (1.56 to 21.0) and IL-6 in maternal serum with a LR+ of 5.47 (2.10 to 14.2) can be qualified as a valid rule-in test. IL-6 in cord blood with a LR- of 0.10 (0.05 to 0.21) and PCT in cord blood with a LR- of 0.20 (0.12-0.37) can be qualified as a useful rule-out test. Either CRP or WBC was inadequate for diagnosis of EONS.. For cord blood sample, IL-6 or PCT can be used as reliable rule-in and rule-out tool. For maternal serum, only IL-6 appeared to be sufficient for rule-in diagnosis. An interventional study may be needed to answer whether the addition of these tests will improve the outcome of patients with EONS.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Fetal Blood; Humans; Infant, Newborn; Inflammation Mediators; Interleukin-6; Protein Precursors; Sepsis

Sepsis is a serious infection and still a common cause of morbidity and mortality in resource-limited settings such as India. Even when microbiologic diagnostics are available, bacteremia is only identified in a proportion of patients who present with sepsis and bloodstream infections. Biomarkers have been used in a variety of disease processes and can help aid in diagnosing bacterial infections. There have been numerous biomarkers investigated to aid with diagnosis and prognostication in sepsis with the majority suffering from lack of sensitivity or specificity. Procalcitonin has been heralded as the biomarker that holds the most promise for bloodstream infections. Data are emerging in India, and in this review, we focus on the current data of biomarkers in sepsis with particular attention to how biomarkers could be used to augment diagnosis and treatment in India.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; India; Membrane Glycoproteins; Protein Precursors; Receptors, Immunologic; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

Bloodstream infections are a major concern because of high levels of antibiotic consumption and of the increasing prevalence of antimicrobial resistance. Bacteraemia is identified in a small percentage of patients with signs and symptoms of sepsis. Biomarkers are widely used in clinical practice and they are useful for monitoring the infectious process. Procalcitonin (PCT) and C-reactive protein (CRP) have been most widely used, but even these have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. PCT has been used to guide empirical antibacterial therapy in patients with respiratory infections and help to determine if antibacterial therapy can be stopped. New biomarkers such as those in this review will discuss the major types of biomarkers of bloodstream infections/sepsis, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble urokinase-type plasminogen receptor (suPAR), proadrenomedullin (ProADM), and presepsin.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis

Procalcitonin (PCT) is used as a biomarker for the diagnosis of sepsis, severe sepsis and septic shock. At the same time, PCT has also been used to guide antibiotic therapy. This review outlines the main indications for PCT measurement and points out possible pitfalls. The classic indications for PCT measurement are: (i) confirmation or exclusion of diagnosis of sepsis, severe sepsis, or septic shock, (ii) severity assessment and follow up of systemic inflammation mainly induced by microbial infection, and (iii) individual, patient adapted guide of antibiotic therapy and focus treatment. Using serially monitored PCT levels, the duration and need of antibiotic therapy can be better adapted to the individual requirements of the patient. This individualized approach has been evaluated in various studies, and it is recommended to be a part of an antibiotic stewardship program.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Severity of Illness Index; Shock, Septic

Sepsis, the body`s overwhelming response to systemic infections, is responsible for significant morbidity, mortality, and financial burden. Pathogens and their antigens stimulate pro- and anti-inflammatory mediators and immune markers which characterize the host defense and orchestrate leukocyte recruitment to the acute site of infection. Different immune and metabolic biomarkers have been studied in relation to sepsis for their diagnostic and/or prognostic aid. Recent studies have provided abundant evidence that specific immune and metabolic biomarkers improve a physician`s ability to guide early sepsis recognition, severity assessment and therapeutic decisions in individual patients. This may allow for a transition from bundled sepsis care (protocols combining several medical practices) to more individualized management. First, lactate has now been widely used for risk stratification and guidance of fluid resuscitation. Second, procalcitonin correlates with risks of bacterial infections and helps guide therapeutic decisions about initiation and withdrawal of anti-microbial therapy. Third, prognostic markers such as pro-adrenomedullin improve early mortality prediction and thereby site-of-care decisions in respiratory infections. For these markers interventional trials have documented their value when integrated in clinical protocols.

Topics: Adrenomedullin; Algorithms; Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Humans; Lactic Acid; Precision Medicine; Prognosis; Protein Precursors; Resuscitation; Sepsis

This study was intended to assess the clinical usefulness of blood procalcitonin (PCT) concentrations for the diagnosis and therapeutic monitoring of nosocomial neonatal sepsis.. The enrolment criterion was sepsis clinically manifesting after three days of life. PCT concentrations were measured in venous blood from 52 infected and 88 uninfected neonates. The results were interpreted against C-reactive protein (CRP) concentrations and white blood cell counts (WBC).. Differences between the two groups in PCT and CRP concentrations were highly significant. No significant differences between the groups were noted for WBC. The threshold value on the receiver operator characteristic curve was 2.06 ng/mL for PCT (SE 75%; SP 80.68%; PPV 62.22%; NPV 88.75%; AUC 0.805), 5.0 mg/L for CRP (SE 67.44%; SP 73.68%; PPV 42.02%; NPV 88.89%; AUC 0.801), and 11.9 x109/L for WBC (SE 51.16%; SP 50.68%; PPV 23.16%; NPV 78.13%; AUC 0.484). Procalcitonin concentrations decreased 24 hours after initiation of antibiotic therapy and reverted to the control level after 5-7 days. C-reactive protein concentrations began to decline after two days of antibiotic therapy but were still higher than in the control group after 5-7 days of treatment. No significant changes in WBC during the treatment were observed.. Procalcitonin concentrations in blood appear to be of use for the diagnosis and therapeutic monitoring of nosocomial infections in neonates as this parameter demonstrates greater sensitivity and specificity than C-reactive protein. White blood cell counts appear to be of little diagnostic value in the early phase of infection or for therapeutic monitoring.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Humans; Infant, Newborn; Leukocyte Count; Monitoring, Physiologic; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis

Over the past two decades, the body of literature on the clinical usefulness of procalcitonin (PCT) in adults has grown rapidly. Although this approach has led to increased insight, it has also prompted debate regarding its potential use in diagnosis and management of severe infection. Clinicians, however, are less familiar with the use of PCT in pediatric populations. In this review, we examine PCT as a marker of severe clinical pediatric conditions including its role in systemic inflammation, infection, and sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Infections; Intensive Care Units, Neonatal; Meningitis; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

For the past thirty years, since IL-1β and TNFα were first cloned, there have been efforts to measure plasma cytokine concentrations in patients with severe sepsis and trauma, and to use these measurements to predict clinical outcome and response to therapies. The numbers of cytokines and chemokines that have been measured in the plasma have literally exploded with the development of multiplex immune approaches. Dozens of relatively small cohort studies have shown plasma cytokine concentrations correlating with outcome in sepsis and trauma. Despite what appears to be a consensus that plasma cytokine concentrations should be useful in the clinical setting, only two cytokines, IL-6 and procalcitonin, have approached routine clinical use. IL-6 has been used as a research tool for entry into sepsis-intervention trials, while procalcitonin is being used clinically at a large number of institutions to distinguish sepsis from other inflammatory processes. For most cytokines, the relative lack of sensitivity and specificity of individual or multiplex cytokine measurements has hindered their utility to predict clinical trajectory in individual patients. The problem rests with a general misunderstanding of cytokine biology, failing to appreciate the general paracrine nature of these mediators, the presence of binding proteins, chaperones and inhibitors in the plasma, and the rapid clearance of these proteins by binding to cell receptors and clearance predominantly by the kidney. The future of using plasma cytokine measurements as an indicator of sepsis/trauma severity or predicting outcome is generally behind us, although there is optimism that procalcitonin measurements may ultimately prove to have utility in the diagnosis of severe sepsis.

Topics: APACHE; Artifacts; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Humans; Interleukin-6; Prognosis; Protein Precursors; Sensitivity and Specificity; Sepsis; Trauma Severity Indices; Wounds and Injuries

Traditional biomarkers, including C-reactive protein, leukocytes, erythrocyte sedimentation rate, and clinical signs and symptoms, are not sufficiently sensitive or specific enough to guide treatment decisions in infectious febrile diseases. Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. A growing body of evidence supports the use of PCT as a marker to improve the diagnosis of bacterial infections and to guide antibiotic therapy. Clinically, PCT levels may help guide the need for empirical antibiotic therapy, source control for infections, and duration of antibiotic therapy. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and to discuss the reliability of this marker in order to provide physicians with an overview of the potential for PCT to guide antibiotic therapy.

Topics: Algorithms; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis

Sepsis, severe sepsis, and septic shock cause significant morbidity and mortality worldwide. Rapid diagnosis and therapeutic interventions are desirable to improve the overall mortality in patients with sepsis. However, gold standard laboratory diagnostic methods for sepsis, pose a significant challenge to rapid diagnosis of sepsis by physicians and laboratories. This article discusses the usefulness and potential of biomarkers and molecular test methods for a more rapid clinical and laboratory diagnosis of sepsis. Because new technologies are quickly emerging, physicians and laboratories must appreciate the key factors and characteristics that affect the clinical usefulness and diagnostic accuracy of these test methodologies.

Topics: Acute-Phase Proteins; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Clinical Laboratory Techniques; Humans; Interleukin-6; Interleukin-8; Laboratories; Membrane Glycoproteins; Nucleic Acid Amplification Techniques; Protein Precursors; Sepsis; Serum Amyloid P-Component; Vasopressins

The utility of procalcitonin to manage patients with infections is unclear. A systematic review of comparative studies using procalcitonin-guided antibiotic therapy in patients with infections was performed.. Randomized, controlled trials comparing procalcitonin-guided initiation, intensification, or discontinuation of antibiotic therapy to clinically guided therapy were included. Outcomes were antibiotic usage, morbidity, and mortality. MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990 to December 16, 2011.. Eighteen randomized, controlled trials were included. Data were pooled into clinically similar patient populations. In adult intensive care unit (ICU) patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without increasing morbidity or mortality. In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increased antibiotic usage and morbidity. In adult patients with respiratory tract infections, procalcitonin guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total antibiotic exposure without affecting morbidity or mortality. A single, good quality study of neonates with suspected sepsis demonstrated reduced antibiotic duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on antibiotics for ≥ 72 hours by 27% (P = 0.002) with procalcitonin guidance.. Procalcitonin guidance can safely reduce antibiotic usage when used to discontinue antibiotic therapy in adult ICU patients and when used to initiate or discontinue antibiotics in adult patients with respiratory tract infections.

Topics: Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sepsis; Treatment Outcome

Major trauma still represents one of the leading causes of death in the first four decades of life. Septic complications represent the predominant causes of late death (45% of overall mortality) in polytrauma patients. The ability of clinicians to early differentiate between systemic inflammatory response syndrome (SIRS) and sepsis is demonstrated to improve clinical outcome and mortality. The identification of an "ideal" biomarker able to early recognize incoming septic complications in trauma patients is still a challenge for researchers.. To evaluate the existing evidence regarding the role of biomarkers to predict or facilitate early diagnosis of sepsis in trauma patients, trying to compile some recommendations for the clinical setting.. An Internet-based search of the MEDLINE, EMBASE and Cochrane Library databases was performed using the search terms: "Biomarkers", "Sepsis" and "Trauma" in various combinations. The methodological quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies Checklist (QUADAS). After data extraction, the level of evidence available for each bio-marker was rated and presented using the "best-evidence synthesis" method, in line with the US Agency for Healthcare Research and Quality.. Thirty studies were eligible for the final analysis: 13 case-control studies and 17 cohort studies. The "strong evidence" available demonstrated the potential use of procalcitonin as an early indicator of post-traumatic septic complications and reported the inability of c-reactive protein (CRP) to specifically identify infective complications. Moderate, conflicting and limited evidence are available for the other 31 biomarkers.. Several biomarkers have been evaluated for predicting or making early diagnosis of sepsis in trauma patients. Current evidence does not support the use of a single biomarker in diagnosing sepsis. However, procalcitonin trend was found to be useful in early identification of post-traumatic septic course and its use is suggested (Recommendation Grade: B) in clinical practice.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Humans; Inflammation; Male; Middle Aged; Multiple Trauma; Protein Precursors; Sepsis; United States; Young Adult

Sepsis is defined as systemic inflammatory response syndrome (SIRS) in the context of an underlying infectious process, and is associated with high rates of morbidity and mortality, particularly when initial therapy is delayed. Numerous biomarkers, including but not limited to cytokines (interleukins-2 and -6 [IL-2, IL-6] and tumor necrosis factor-α [TNF-α]), leukotrienes, acute-phase proteins (C-reactive protein [CRP]), and adhesion molecules, have been evaluated and rejected as unsuitable for the diagnosis of sepsis, predicting its severity, and guiding its treatment. Most recently, procalcitonin (PCT) has been suggested as a novel biomarker that may be useful in guiding therapeutic decision making in the management of sepsis. This article assesses critically the published literature on the clinical utility of PCT concentrations for guiding the treatment of sepsis in adult patients.. A comprehensive search of all published studies of the use of serum concentrations of PCT to guide the treatment of sepsis in adult patients (1996 to 2011) was conducted with PubMed and Google Scholar. The search focused on the value of PCT concentrations to guide the diagnosis, prognosis, monitoring, and escalation and de-escalation of antbiotic therapy in these patients. Keywords searched included "procalcitonin," "sepsis," "sepsis biomarker," "sepsis diagnosis," "sepsis prognosis," "sepsis mortality," "antibiotic escalation," "antibiotic de-escalation," "antibiotic duration," and "antimicrobial stewardship.". Forty-six trials evaluating the efficacy of PCT concentrations in diagnosing sepsis have been published, with 39 of these trials yielding positive results and 7 yielding negative results. Wanner et al. published the largest study (n=405) demonstrating that peak PCT concentrations occur early after injury in both patients with sepsis and those with multiple organ dysfunction syndrome (MODS). Among 17 trials assessing the prognostic value of PCT concentrations with regard to clinical outcome and morbidity, 12 trials yielded positive results and five showed negative or equivocal results. Reith et al. published the largest study of the prognostic use of PCT concentrations (n=246), demonstrating that median PCT values on post-operative days (POD) one, four, and 10 were predictive of mortality in patients with abdominal sepsis (p<0.01). Among 14 trials of the utility of PCT concentrations for establishing an infectious cause of sepsis, 13 yielded positive results and only one yielded negative results. The largest study of this use of PCT concentrations, conducted by Baykut et al. (n=400), evaluated these concentrations in post-operative patients with infection, and demonstrated that concentrations of PCT remained elevated until POD 4, with a second increase observed between POD 4 and POD 6. In uninfected patients, PCT concentrations began to decrease on POD 2. Only a single study has assessed the utility of PCT concentrations in guiding the escalation of antibiotic therapy, and its results were negative. Specifically, Jensen et al. (n=1,200) compared a PCT-guided antibiotic escalation strategy with the standard of care for sepsis and found no difference in outcomes. They also found that the PCT group had a longer average stay in the intensive care unit (ICU), greater rates of mechanical ventilation, and a decreased estimated glomerular filtration rate (eGFR). Among four trials focusing on PCT concentrations and antibiotic de-escalation, all showed positive results with the measurement of PCT concentrations. The largest such study, by Bouadma et al. (n=621), demonstrated a four-day decrease in antibiotic duration when PCT concentrations were used to guide therapy relative to the study arm given the standard of care, with no increase in mortality (p=0.003).. The diagnostic value of serum PCT concentrations for discriminating among SIRS, sepsis, severe sepsis, and septic shock remains to be established. Although higher PCT concentrations suggest a systemic bacterial infection as opposed to a viral, fungal, or inflammatory etiology of sepsis, serum PCT concentrations do not correlate with the severity of sepsis or with mortality. At present, PCT concentrations are solely investigational with regard to determining the timing and appropriateness of escalation of antimicrobial therapy in sepsis. Nevertheless, serum PCT concentrations have established utility in monitoring the clinical response to medical and surgical therapy for sepsis, and in surveillance for the development of sepsis in burn and ICU patients, and may have a role in guiding the de-escalation of antibiotic therapy.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnostic Tests, Routine; Drug Monitoring; Humans; Protein Precursors; Sepsis

Procalcitonin (PCT) is a biomarker that is increasingly being used to help in decision making when managing febrile patients. This is a non exhaustive review of the literature regarding the use of PCT in deciding to begin or discontinue antibiotic treatment. PCT appears to be useful in patients with respiratory infections or sepsis. In both these situations and using evaluated algorithms, a low PCT (< 0.25 microg), enables withholding or discontinuing antibiotic treatment, without negatively affecting clinical outcomes. For other indications there is however insufficient evidence to support the systematic measurement of PCT in all febrile patients. In particular, in patients with autoimmune disease or in the postoperative setting, PCT is insufficiently sensitive or specific to rule out or confirm a bacterial infection requiring antibiotic treatment.

Topics: Algorithms; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Decision Making; Fever; Humans; Protein Precursors; Respiratory Tract Infections; Sensitivity and Specificity; Sepsis

Procalcitonin (PCT) algorithms for antibiotic treatment decisions have been studied in adult patients from primary care, emergency department, and intensive care unit (ICU) settings, suggesting that procalcitonin-guided therapy may reduce antibiotic exposure without increasing the mortality rate. However, information on the efficacy and safety of this approach in the most vulnerable population of critically ill patients with severe sepsis and septic shock is missing.. Two reviewers independently performed a systematic search in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect, Cochrane Central Register of Controlled Trials, http://www.ClinicalTrials.gov and http://www.ISRCTN.org. Eligible studies had to be randomized controlled clinical trials or cohort studies which compare procalcitonin-guided therapy with standard care in severe sepsis patients and report at least one of the following outcomes: hospital mortality, 28-day mortality, duration of antimicrobial therapy, length of stay in the intensive care unit or length of hospital stay. Disagreements about inclusion of studies and judgment of bias were solved by consensus.. Finally seven studies comprising a total of 1,075 patients with severe sepsis or septic shock were included in the meta-analysis. Both hospital mortality (RR [relative risk]: 0.91, 95%CI [confidence interval]: 0.61; 1.36) and 28-day mortality (RR: 1.02, 95%CI: 0.85; 1.23) were not different between procalcitonin-guided therapy and standard treatment groups. Duration of antimicrobial therapy was significantly reduced in favor of procalcitonin-guided therapy (HR [hazard ratio]: 1.27, 95%CI: 1.01; 1.53). Combined estimates of the length of stay in the ICU and in hospital did not differ between groups.. Procalcitonin-guided therapy is a helpful approach to guide antibiotic therapy and surgical interventions without a beneficial effect on mortality. The major benefit of PCT-guided therapy consists of a shorter duration of antibiotic treatment compared to standard care. Trials are needed to investigate the effect of PCT-guided therapy on mortality, length of ICU and in-hospital stay in severe sepsis patients.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Administration Schedule; Glycoproteins; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Protein Precursors; Sepsis; Shock, Septic

Sepsis is one of the leading causes of death in the critically ill. Early diagnosis is important to avoid delay in instituting appropriate treatment. However, diagnosis can be delayed because of difficulty in interpreting clinical features. Sepsis biomarkers can aid early diagnosis. This article reviews the application of readily available biomarkers for diagnosis of sepsis, for predicting prognosis, and for antibiotic stewardship. 178 biomarkers are described in the literature--ranging from specimen cultures, which lack sensitivity and specificity for early diagnosis of sepsis, to biomarkers such as C-reactive protein, procalcitonin, and genetic biomarkers, which have their own limitations. Future research will mainly focus on use of more than one biomarker, but the main problem in sepsis biomarker research seems to be a lack of a recommended biomarker.

Topics: Antigens, Bacterial; Biomarkers; Blood Cell Count; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Genome; Humans; Predictive Value of Tests; Prognosis; Protein Precursors; Proteomics; Receptors, Immunologic; Sepsis; Treatment Outcome

Procalcitonin is a promising marker for identification of bacterial infections. We assessed the accuracy and clinical value of procalcitonin for diagnosis of sepsis in critically ill patients.. We searched Medline, Embase, ISI Web of Knowledge, the Cochrane Library, Scopus, BioMed Central, and Science Direct, from inception to Feb 21, 2012, and reference lists of identified primary studies. We included articles written in English, German, or French that investigated procalcitonin for differentiation of septic patients--those with sepsis, severe sepsis, or septic shock--from those with a systemic inflammatory response syndrome of non-infectious origin. Studies of healthy people, patients without probable infection, and children younger than 28 days were excluded. Two independent investigators extracted patient and study characteristics; discrepancies were resolved by consensus. We calculated individual and pooled sensitivities and specificities. We used I(2) to test heterogeneity and investigated the source of heterogeneity by metaregression.. Our search returned 3487 reports, of which 30 fulfilled the inclusion criteria, accounting for 3244 patients. Bivariate analysis yielded a mean sensitivity of 0 · 77 (95% CI 0 · 72-0 · 81) and specificity of 0 · 79 (95% CI 0 · 74-0 · 84). The area under the receiver operating characteristic curve was 0 · 85 (95% CI 0 · 81-0 · 88). The studies had substantial heterogeneity (I(2)=96%, 95% CI 94-99). None of the subgroups investigated--population, admission category, assay used, severity of disease, and description and masking of the reference standard--could account for the heterogeneity.. Procalcitonin is a helpful biomarker for early diagnosis of sepsis in critically ill patients. Nevertheless, the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment.. Ministry of Education and Research, the Deutsche Forschungsgemeinschaft, Thuringian Ministry for Education, Science and Culture, the Thuringian Foundation for Technology, Innovation and Research, and the German Sepsis Society.

Topics: Age Factors; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Databases, Factual; Humans; Prevalence; Protein Precursors; Regression Analysis; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

The paper analyzes the most important clinical studies dealing with the measurement of procalcitonin concentrations in patients with lower respiratory tract infections or sepsis. Procalcitonin is a marker of bacterial infection, which is successfully used for diagnosis and antimicrobial therapy monitoring in patients with pneumonia or in septic states. The review presents the latest algorithms for interpreting the concentrations of procalcitonin in clinical practice.

Topics: Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Monitoring; Early Diagnosis; Humans; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sepsis

As a continuation of "Postmortem Chemistry Update Part I," Part II deals with molecules linked to liver and cardiac functions, alcohol intake and alcohol misuse, myocardial ischemia, inflammation, sepsis, anaphylaxis, and hormonal disturbances. A very important array of new material concerning these situations had appeared in the forensic literature over the last two decades. Some molecules, such as procalcitonin and C-reactive protein, are currently researched in cases of suspected sepsis and inflammation, whereas many other analytes are not integrated into routine casework. As in part I, a literature review concerning a large panel of molecules of forensic interest is presented, as well as the results of our own observations, where possible.

Topics: Alcohol Drinking; Alcoholism; Anaphylaxis; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Forensic Pathology; Glucuronates; Heart Diseases; Heart Function Tests; Hormones; Humans; Inflammation; Liver; Liver Function Tests; Postmortem Changes; Protein Precursors; Sepsis; Sulfuric Acid Esters; Transferrin

Sepsis is the clinical syndrome derived from the host response to an infection and severe sepsis is the leading cause of death in critically ill patients. Several biomarkers have been tested for use in diagnosis and prognostication in patients with sepsis. Soluble urokinase-type plasminogen activator receptor (suPAR) levels are increased in various infectious diseases, in the blood and also in other tissues. However, the diagnostic value of suPAR in sepsis has not been well defined, especially compared to other more established biomarkers, such as C-reactive protein (CRP) and procalcitonin (PCT). On the other hand, suPAR levels have been shown to predict outcome in various kinds of bacteremia and recent data suggest they may have predictive value, similar to that of severity scores, in critically ill patients. This narrative review provides a descriptive overview of the clinical value of this biomarker in the diagnosis, prognosis and therapeutic guidance of sepsis.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Disease Progression; Early Diagnosis; Humans; Predictive Value of Tests; Prognosis; Protein Precursors; Receptors, Urokinase Plasminogen Activator; Sepsis

Topics: Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Respiratory Tract Infections; Sepsis

The biomarker procalcitonin (PCT) has been used to diagnose and monitor a number of clinically significant infections. Serum levels of PCT are often increased in the presence of bacterial and fungal infections but not viral infections or noninfectious inflammation. Intra-abdominal infections (IAIs) are serious conditions that pose difficult challenges to physicians and the healthcare system. Researchers have evaluated PCT in the management of IAIs, both for diagnosis and for guiding antibiotic therapy. The studies have produced mixed results, leading to controversy on the utility of PCT in IAIs. PCT appears to be most useful in diagnosing postoperative infections and necrotizing pancreatitis. This review aims to summarize these data, explore the pathophysiology of PCT in sepsis from IAIs, discuss the strengths and weaknesses of PCT monitoring in IAIs, and provide guidance for the interpretation of PCT levels.

Topics: Biological Assay; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Databases, Bibliographic; Enterobacteriaceae; Humans; Inflammation; Intraabdominal Infections; Pancreas; Pancreatitis, Acute Necrotizing; Postoperative Complications; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

Procalcitonin (PCT) has emerged as the most specific biomarker for bacterial infection. As clinicians become more familiar with its use, a multitude of observational studies have reported on its diagnostic potential in distinct types of infections and various clinical situations, such as in neutropenia or in the postoperative period. In the Intensive Care Unit setting, however, the prognostic value of a single PCT measurement at the time of admission on a patient with sepsis is suboptimal. Especially in cases of community-acquired pneumonia, cardiovascular biomarkers, such as mid-regional proadrenomedullin, seem to carry stronger prognostic potential than PCT. Nevertheless, the study of PCT kinetics may still be of use as a risk assessment tool for the general population of critically ill patients with sepsis syndrome. The most recent significant development in the field of PCT monitoring, is the publication of several randomized controlled trials that investigated its use as a decision making tool for the initiation and/or the duration of antibiotic treatment. Currently, the available evidence suggests that the incorporation of PCT measurements to assist with the duration of antibiotic stewardship programs may decrease antibiotic use without compromising clinical outcomes. Nevertheless, this strategy still needs further validation in large prospective studies.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Humans; Prognosis; Protein Precursors; Sepsis; Treatment Outcome

Since the 1990s, finding the most efficient markers or combinations as predictors of early-onset neonatal sepsis has been the hot topic of studies. But there is no review of such biomarkers detected in umbilical blood at birth. By comparing clinical values of common inflammatory markers detected in cord blood shortly after birth, in this study we tried to find the most performing one or the most efficient combination that might be potentially used in birth room, as the earliest predictor of early-onset neonatal sepsis.. We searched PubMed and Elsevier's Web of Science for studies evaluating cord blood inflammatory markers in relation to early-onset neonatal sepsis.. Among C-reactive protein (CRP), procalcitonin (PCT), IL-6, IL-8, TNF-α and IL-1β, none of them could be used individually to establish or exclude the diagnosis of early-onset neonatal sepsis, but PCT, IL-6 and IL-8 have great superiority to CRP, TNF-α and IL-1β. When combined with other hematological markers and clinical observation, the clinical reliability of PCT, IL-6 and IL-8 could be improved. Prolonging the sample collection time window seems to have a positive effect on the clinical utility of IL-6 and IL-8.. More researches focusing on the combination of different umbilical cord biomarkers in different clinical settings are needed to achieve clearer conclusions. Multi-center, large-sized analysis, especially examining groups of cytokines, is also expected.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Fetal Blood; Humans; Infant, Newborn; Predictive Value of Tests; Protein Precursors; Sepsis

The aim of this study was to determine the accuracy of the procalcitonin (PCT) test for diagnosis of bacterial sepsis in pediatric cancer patients with febrile neutropenia.. Three major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies that evaluated the diagnostic value of PCT alone or compared with other laboratory markers such as C-reactive protein (CRP) to identify bacterial sepsis in children with fever and neutropenia. A bivariate model was used to derive summary sensitivity and specificity of the diagnostic tests.. A total of 10 studies looking into PCT tests and 8 studies looking into CRP tests were included in the final analysis. The prevalence of bacterial sepsis was 304 of 1031 (29.5%) in PCT studies and 741 of 1316 (56.3%) in CRP studies. In terms of area under the receiver operating characteristic curve, PCT had comparable discrimination to CRP (area under the curve: 0.75 versus 0.74). PCT was not as sensitive as the CRP test. The pooled sensitivity of PCT was 0.59 (95% confidence interval [CI]: 0.42-0.74) as compared with 0.75 (95% CI: 0.61-0.85) for CRP. PCT was more specific than sensitive whereas CRP was more sensitive than specific in this population. The pooled specificity was 0.76 (95% CI: 0.64-0.85) for PCT and 0.62 (95% CI: 0.49-0.73) for CRP. PCT had greater likelihood ratio positive (2.50; 95% CI: 1.64-3.81), making it the better rule-in test.. Of three markers potentially useful for diagnosing bacterial sepsis in children with fever and neutropenia, PCT had comparable diagnostic accuracy to CRP.

Topics: Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Fever of Unknown Origin; Humans; Neutropenia; Protein Precursors; Sepsis; Statistics as Topic

There is convincing evidence linking early start of fluid resuscitation and initiation of appropriate antimicrobial therapy to improved outcomes in patients with sepsis in the emergency department. Blood biomarkers measured on admission and during follow-up have the ability to guide early sepsis recognition, severity assessment and therapeutic decisions in individual patients and may allow transition from bundled sepsis care to more individualized management in single patients.. Although a large number of promising diagnostic and prognostic biomarkers have been put forward in observational studies, only few have been evaluated in prospective randomized-controlled intervention trials. Markers such as lactate for risk stratification and guidance of fluid resuscitation, procalcitonin for assessing risk of bacterial infections and guiding therapeutic decisions about initiation and duration of antimicrobial therapy, and recently proadrenomedullin for early mortality prediction and site-of-care decisions in respiratory infections, have shown to improve patient management.. For few biomarkers, recent study results demonstrate that well defined clinical protocols have the potential to guide decisions about the individual risk stratification and treatment of patients with suspicion of sepsis ultimately leading to improved patient care and outcomes. For other biomarkers, promising observation data have been put forward, but their potential needs to be evaluated in large-scale, well designed prospective intervention studies before clinical use can be recommended.

Topics: Adrenomedullin; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Humans; Intensive Care Units; Patient Care; Practice Guidelines as Topic; Prognosis; Protein Precursors; Risk Assessment; Sepsis

The purpose of this systematic review was to assess the evidence for use of routine procalcitonin testing to diagnose the presence of sepsis in the burn patient. The electronic databases MEDLINE, Cochrane, CINAHL, ProQuest, and SCOPUS were searched for relevant studies using the MeSH terms burn, infection, procalcitonin, and meta-analysis. The focus of the review was the adult burn population, but other relevant studies of critically ill patients were included as data specific to the patient with burns are limited. Studies were compiled in tabular form and critically appraised for quality and level of evidence. Four meta-analyses, one review of the literature, one randomized controlled trial, nine prospective observational, and three retrospective studies were retrieved. Six of these studies were specific to the burn population, with one specific to burned children. Only one meta-analysis, one adult burn and one pediatric burn study reported no benefit of procalcitonin testing to improve diagnosis of sepsis or differentiate sepsis from non-infectious systemic inflammatory response. The collective findings of the included studies demonstrated benefit of incorporating procalcitonin assay into clinical sepsis determination. Evaluation of the burn specific studies is limited by the use of guidelines to define sepsis and inconsistent results from the burn studies. Utility of the procalcitonin assay is limited due to the lack of availability of rapid, inexpensive tests. However, it appears procalcitonin assay is a safe and beneficial addition to the clinical diagnosis of sepsis in the burn intensive care unit.

Topics: Adult; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Protein Precursors; Sepsis

Procalcitonin (PCT) levels are below the detection level in healthy subjects, while pre-procalcitonin mRNA is over expressed in human medullar thyroid carcinoma, in small cell lung tumor, and occasionally in other rare neuroendocrine tumors such as phaeochromocytoma. PCT is known as a sensitive and specific biomarker for bacterial sepsis, being produced by extra-thyroidal parenchymal tissues, mainly hepatocytes. The increase in plasma level correlates with the severity of infection and the magnitude and the time course of its increase can be strictly related to the patient's outcome, and to the bacterial load. So far, data on serum PCT levels in patients with cardiogenic shock and in those with acute coronary syndromes (ACS) are scarce and controversial. While some studies report that PCT levels are increased in ACS patients on admission, other investigations document that plasma PCT concentrations are in the normal range. We recently reported that the degree of myocardial ischemia (clinically indicated by the whole spectrum of ACS, from unstable angina to cardiogenic shock following ST-elevation myocardial infarction) and the related inflammatory-induced response are better reflected by C-reactive protein (which was positive in most acute cardiac care patients of all our subgroups) than by PCT, which seems more sensitive to a higher degree of inflammatory activation, being positive only in patients with cardiogenic shock. Few studies investigated the dynamics of PCT in cardiac acute patients, and, despite the paucity of data and differences in patients' selection criteria, an increase in PCT values seems to be associated with the development of complications. In acute cardiac patients, the clinical values of procalcitonin rely not on its absolute value, but only on its kinetics over time.

Topics: Acute Coronary Syndrome; Acute Disease; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Shock, Cardiogenic

Sepsis is a clinical syndrome defined by physiologic changes indicative of systemic inflammation, which are likely attributable to documented or suspected infection. Septic shock is the progression of those physiologic changes to the extent that delivery of oxygen and metabolic substrate to tissues is compromised. Biomarkers have the potential to diagnose, monitor, stratify and predict outcome in these syndromes. C-reactive protein is elevated in inflammatory and infectious conditions and has long been used as a biomarker indicating infection. Procalcitonin has more recently been shown to better distinguish infection from inflammation. Newer candidate biomarkers for infection include IL-18 and CD64. Lactate facilitates the diagnosis of septic shock and the monitoring of its progression. Multiple stratification biomarkers based on genome-wide expression profiling are under active investigation and present exciting future possibilities.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Infections; Inflammation; Interleukin-18; Lactates; Protein Precursors; Receptors, IgG; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Recent news in the field of bloodstream infection and sepsis relevant for the practitioner include the recommendation in the newly revised German sepsis guideline to introduce selective intestinal decontamination with non-absorbable antimicrobial substances for the prevention of secondary infections in ventilated patients. This intervention, however, remains controversial because there are indications of unfavourable effects (increased development of resistance), and because the effect size has been rather low. Other news indicate not only that procalcitonin can be reasonably used as an aid to determine the duration of antibiotic treatment in community-acquired respiratory infection and pneumonia. A procalcitonin-based algorithm can also be used in critical care patients to shorten the duration of antibiotic administration without worsening outcomes. Recent data indicate that E. coli and S. aureus continue to be the most frequent pathogens isolated in bloodstream infection. The proportion of E. coli strains producing extended-spectrum beta lactamase (ESBL) is increasing. New epidemiologic evidence shows that infections with this pathogen, resistant to many standard antibiotics, are associated with an increased mortality rate, similar to infections due to methicillin-resistant Staphylococcus aureus (MSRA). The incidence of MRSA bacteraemia in Germany can now be estimated better as it has become a notifiable infection.

Topics: Algorithms; Anti-Bacterial Agents; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Care; Cross Infection; Cross-Sectional Studies; Drug Resistance, Multiple, Bacterial; Escherichia coli Infections; Germany; Humans; Methicillin-Resistant Staphylococcus aureus; Opportunistic Infections; Practice Guidelines as Topic; Protein Precursors; Sepsis; Splenectomy; Staphylococcal Infections

To assess the value of serum procalcitonin (PCT) for the differentiation between patients with and without neonatal sepsis.. We systematically searched PubMed, Scopus, and the Cochrane Library for studies evaluating PCT in neonatal sepsis. PCT had to be measured in neonatal blood samples, at the initial presentation of patients with suspected sepsis, before the administration of antibiotics. We performed a bivariate meta-analysis of sensitivity and specificity, and constructed a hierarchical summary receiver-operating characteristic (HSROC) curve.. Overall, 29 studies eligible for inclusion were identified. We analyzed the 16 studies (involving 1,959 neonates) that evaluated PCT in neonates with culture-proven or clinically diagnosed sepsis in comparison with ill neonates with other conditions. The pooled (95% confidence interval) sensitivity and specificity were 81% (74-87%) and 79% (69-87%), respectively. The area under the HSROC curve (AUC) was 0.87. The diagnostic accuracy of PCT seemed higher for neonates with late-onset sepsis (>72 h of life) than for those with early onset sepsis; the AUC for these analyses was 0.95 and 0.78, respectively. However, fewer data were available for late-onset sepsis. High statistical heterogeneity was observed for all analyses.. Our findings suggest that serum PCT at presentation has very good diagnostic accuracy (AUC = 0.87) for the diagnosis of neonatal sepsis. However, in view of the marked observed statistical heterogeneity, along with the lack of a uniform definition for neonatal sepsis, the interpretation of these findings should be done with appropriate caution.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Intensive Care, Neonatal; Predictive Value of Tests; Protein Precursors; Sepsis

Sepsis is a leading cause of mortality in critically ill patients. Delay in diagnosis and initiation of antibiotics have been shown to increase mortality in this cohort. However, differentiating sepsis from non-infectious triggers of the systemic inflammatory response syndrome (SIRS) is difficult, especially in critically ill patients who may have SIRS for other reasons. It is this conundrum that predominantly drives broad-spectrum antimicrobial use and the associated evolution of antibiotic resistance in critical care environments. It is perhaps unsurprising, therefore, that the search for a highly accurate biomarker of sepsis has become one of the holy grails of medicine. Procalcitonin (PCT) has emerged as the most studied and promising sepsis biomarker. For diagnostic and prognostic purposes in critical care, PCT is an advance on C-reactive protein and other traditional markers of sepsis, but is not accurate enough for clinicians to dispense with clinical judgement. There is stronger evidence, however, that measurement of PCT has a role in reducing the antibiotic exposure of critical care patients. For units intending to incorporate PCT assays into routine clinical practice, the cost-effectiveness of this is likely to depend on the pre-implementation length of an average antibiotic course and the subsequent impact of implementation on emerging antibiotic resistance. In most of the trials to date, the average baseline duration of the antibiotic course was longer than is currently standard practice in many UK critical care units. Many other biomarkers are currently being investigated. To be highly useful in clinical practice, it may be necessary to combine these with other novel biomarkers and/or traditional markers of sepsis.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Drug Resistance, Bacterial; Drug Utilization; Humans; Prognosis; Protein Precursors; Sepsis; United Kingdom

Infection and/or sepsis biomarkers should help to make the diagnosis and thus initiate therapy earlier, help to differentiate between infectious and sterile inflammation, allow the use of more-specific antimicrobials, shorten the time of antimicrobial use, and ideally identify distinct phenotypes that may benefit from specific adjunctive sepsis therapies. Procalcitonin (PCT) was proposed as a sepsis and infection marker more than 15 years ago. Meanwhile, PCT has been evaluated in various clinical settings. In this review the present use of PCT on the ICU and in critically ill patients is summarized, included it's role for diagnosis of severe sepsis and septic shock and antibiotic stewardship with PCT.

Topics: Anti-Infective Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Prognosis; Protein Precursors; Sepsis

Sepsis is one of the most cost-intensive conditions of critically ill patients in intensive care medicine. Furthermore, sepsis is known to be the leading cause of morbidity and of mortality in intensive care patients. Early initiation of antibiotic therapy can significantly reduce mortality. The development of resistance of bacterial species against antibiotics is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently no laboratory marker has been available to distinguish bacterial infections from viral or non-infectious inflammatory responses. However, procalcitonin (PCT) appears to be the first among a large array of inflammatory markers that offers this possibility. Regular procalcitonin measurements can significantly shorten the length of antibiotic therapy, show positive influence on antibiotic costs and have no adverse affects on patient outcome.

Topics: Adult; Algorithms; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Critical Care; Critical Illness; Humans; Protein Precursors; Sepsis; Virus Diseases

Sepsis remains a common cause of death in the intensive care units worldwide. However, in the last decade a significant development could be noticed in sepsis research regarding diagnostic markers that can help the physicians to recognize the disease in the early phase, which is the clue of the successful treatment of sepsis. This development provided the identification of new molecules and structures (i.e. cytokines, cell surface markers, receptors) that are potential biomarkers of sepsis in the clinical settings. Besides, the advance in the understanding of the pathophysiologic, immunologic and biochemical pathway of sepsis has made the way for assignment of new drug targets in the therapy of sepsis. This review aims to provide a summary about these novelties regarding our knowledge about sepsis published in the medical literature recently. We will describe the presumed pathophysiological role and diagnostic value of sepsis markers that are used even more widely in the clinical practice (i.e. procalcitonin, IL-6), summarize the data regarding the sepsis marker candidates that are investigated in some initial study (i.e. matrix metalloproteinases, microRNA fingerprints), and we will discuss substances that may be specific markers for certain organ failures related to sepsis (i.e. neutrophil gelatinase-derived lipocalin in acute renal failure). Furthermore, we will review the mediators of the immuno-inflammatory cascade in sepsis concerning their potential applicability as therapeutic targets in the treatment of this often lethal disease. In addition, we present some insights into the identification of genetic markers of sepsis.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Genetic Markers; Humans; Inflammation; Interleukin-6; Lipocalins; Matrix Metalloproteinases; MicroRNAs; Protein Precursors; Sepsis

Sepsis, an innate immunological response of systemic inflammation to infection, is a growing problem worldwide with a relatively high mortality rate. Immediate treatment is required, necessitating quick, early and accurate diagnosis. Rapid molecular-based tests have been developed to address this need, but still suffer some disadvantages. The most commonly studied biomarkers of sepsis are reviewed for their current uses and diagnostic accuracies, including C-reactive protein, procalcitonin, serum amyloid A, mannan and IFN-γ-inducible protein 10, as well as other potentially useful biomarkers. A singular ideal biomarker has not yet been identified; an alternative approach is to shift research focus to determine the diagnostic relevancy of multiple biomarkers when used in concert. Challenges facing biomarker research, including lack of methodology standardization and assays with better detection limits, are discussed. The ongoing efforts in the development of a multiplex point-of-care testing kit, enabling quick and reliable detection of serum biomarkers, may have great potential for early diagnosis of sepsis.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chemokine CXCL10; Early Diagnosis; Humans; Mannans; Mycoses; Protein Precursors; Sensitivity and Specificity; Sepsis; Serum Amyloid A Protein; Virus Diseases

There are a number of limitations to using conventional diagnostic markers for patients with clinical suspicion of infection. As a consequence, unnecessary and prolonged exposure to antimicrobial agents adversely affect patient outcomes, while inappropriate antibiotic therapy increases antibiotic resistance. A growing body of evidence supports the use of procalcitonin (PCT) to improve diagnosis of bacterial infections and to guide antibiotic therapy. For patients with upper and lower respiratory tract infection, post-operative infections and for severe sepsis patients in the intensive care unit, randomized-controlled trials have shown a benefit of using PCT algorithms to guide decisions about initiation and/or discontinuation of antibiotic therapy. For some other types of infections, observational studies have shown promising first results, but further intervention studies are needed before use of PCT in clinical routine can be recommended. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and discuss the reliability of this marker when used with validated diagnostic algorithms.

Topics: Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Laboratory Techniques; Drug Monitoring; Humans; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sepsis; Surgical Wound Infection; Treatment Outcome

The management of bloodstream infections especially sepsis is a difficult task. An optimal antibiotic therapy (ABX) is paramount for success. Procalcitonin (PCT) is a well investigated biomarker that allows close monitoring of the infection and management of ABX. It has proven to be a cost-efficient diagnostic tool. In Diagnoses Related Groups (DRG) based reimbursement systems, hospitals get only a fixed amount of money for certain treatments. Thus it's very important to obtain an optimal balance of clinical treatment and resource consumption namely the length of stay in hospital and especially in the Intensive Care Unit (ICU). We investigated which economic effects an optimized PCT-based algorithm for antibiotic management could have.. We collected inpatient episode data from 16 hospitals. These data contain administrative and clinical information such as length of stay, days in the ICU or diagnoses and procedures. From various RCTs and reviews there are different algorithms for the use of PCT to manage ABX published. Moreover RCTs and meta-analyses have proven possible savings in days of ABX (ABD) and length of stay in ICU (ICUD). As the meta-analyses use studies on different patient populations (pneumonia, sepsis, other bacterial infections), we undertook a short meta-analyses of 6 relevant studies investigating in sepsis or ventilator associated pneumonia (VAP). From this analyses we obtained savings in ABD and ICUD by calculating the weighted mean differences. Then we designed a new PCT-based algorithm using results from two very recent reviews. The algorithm contains evidence from several studies. From the patient data we calculated cost estimates using German National standard costing information for the German G-DRG system. We developed a simulation model where the possible savings and the extra costs for (in average) 8 PCT tests due to our algorithm were brought into equation.. We calculated ABD savings of 4 days and ICUD reductions of -1.8 days. Our algorithm contains recommendations for ABX onset (PCT ≥ 0.5 ng/ml), validation whether ABX is appropriate or not (Delta from day 2 to day 3 ≥ 30% indicates inappropriate ABX) and recommendations for discontinuing ABX (PCT ≤ 0.25 ng/ml). We received 278,264 episode datasets where we identified by computer-based selection 3,263 cases with sepsis. After excluding cases with length of stay (LOS) too short to achieve the intended savings, we ended with 1,312 cases with ICUD and 268 cases without ICUD. Average length of stay of ICU-patients was 27.7 ± 25.7 days and for Non-ICU patients 17.5 ± 14.6 days respectively. ICU patients had an average of 8.8 ± 8.7 ICUD. - After applying the simulation model on this population we calculated possible savings of Euro -1,163,000 for ICU-patients and Euro -36,512 for Non-ICU patients.. Our findings concerning the savings from the reduction of ABD are consistent with other publications. Savings ICUD had never been economically evaluated so far. Our algorithm is able to possibly set a new standard in PCT-based ABX. However the findings are based on data modelling. The algorithm will be implemented in 5-10 hospitals in 2012 and effects in clinical reality measured 6 months after implementation.. Managing sepsis with daily monitoring of PCT using our refined algorithm is suitable to save substantial costs in hospitals. Implementation in clinical routine settings will show how much of the calculated effect will be achieved in reality.

Topics: Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Computer Simulation; Critical Care; Diagnosis-Related Groups; Germany; Humans; Intensive Care Units; Length of Stay; Pneumonia, Ventilator-Associated; Protein Precursors; Sepsis

To establish the relationship between plasma levels of thioredoxin (Trx) and macrophage migration inhibitory factor (MIF) in systemic inflammatory stress syndrome (SIRS)/sepsis.. Enzyme-linked immunosorbent assay measurements of Trx, MIF, IL-6, -8, and -10 and enzyme-linked fluorescent assay determination of procalcitonin (PCT) in plasma from patients with SIRS/sepsis, neutropenic sepsis, healthy volunteers and pre-oesophagectomy patients.. Thioredoxin was significantly higher in SIRS/sepsis patients [101.3 ng ml(-1), interquartile range (IQR) 68.7-155.6, n = 32] compared with that in healthy controls (49.5 ng ml(-1), IQR 31.4-71.1, P < 0.001, n = 17) or pre-oesophagectomy patients (40.5 ng ml(-1), IQR 36.9-63.2, P < 0.01, n = 7), but was not raised in neutropenics (n = 5). MIF levels were also significantly higher in SIRS/sepsis patients (12.1 ng ml(-1), IQR 9.5-15.5, n = 35), but not in the neutropenic group, when compared with healthy controls (9.3 ng ml(-1), IQR 7.3-10.7, P < 0.01, n = 20). Trx levels correlated, positively, with MIF levels and APACHE II scores. Plasma levels of IL-6, -8 and -10 and PCT increased significantly in patients with SIRS/sepsis (P < 0.001) and with neutropenic sepsis, but did not correlate with Trx or MIF levels.. Plasma levels of Trx, MIF, IL-6, -8, -10 and PCT were raised in patients with SIRS/sepsis. Comparisons between mediators suggest a unique correlation of Trx with MIF. Moreover, Trx and MIF differed from cytokines and PCT in that levels were significantly lower in patients with neutropenia compared with the main SIRS/sepsis group. By contrast, IL-8 and PCT levels were significantly greater in the neutropenic patient group. The link between MIF and Trx highlighted in this study has implications for future investigations into the pathogenesis of SIRS/sepsis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Macrophage Migration-Inhibitory Factors; Neutropenia; Protein Precursors; Sepsis; Thioredoxins

The worldwide yearly mortality from sepsis is substantial, greater than that of cancer of the lung and breast combined. Moreover, its incidence is increasing, and its response to therapy has not appreciably improved. In this condition, the secretion of procalcitonin (ProCT), the prohormone of calcitonin, is augmented greatly, attaining levels up to thousands of fold of normal. This hypersecretion emanates from multiple tissues throughout the body that are not traditionally viewed as being endocrine. The serum values of ProCT correlate with the severity of sepsis; they recede with its improvement and worsen with exacerbation. Accordingly, as highlighted in this review, serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions. It is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement. Moreover, it has been demonstrated that the administration of ProCT to septic animals greatly increases mortality, and several toxic effects of ProCT have been elucidated by in vitro experimental studies. Antibodies have been developed that neutralize the harmful effects of ProCT, and their use markedly decreases the symptomatology and mortality of animals that harbour a highly virulent sepsis analogous to that occurring in humans. This therapy is facilitated by the long duration of serum ProCT elevation, which allows for a broad window of therapeutic opportunity. An experimental groundwork has been established that suggests a potential applicability of such therapy in septic humans.

Topics: Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Inflammation; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Procalcitonin is a surrogate biomarker for estimating the likelihood of a bacterial infection. Procalcitonin-guided initiation and termination of antibiotic therapy is a novel approach utilized to reduce antibiotic overuse. This is essential to decrease the risk of side effects and emerging bacterial multiresistance. Interpretation of procalcitonin levels must always comprise the clinical setting and knowledge about assay characteristics. Only highly sensitive procalcitonin assays should be used in clinical practice and cut-off ranges must be adapted to the disease and setting. Highly sensitive procalcitonin measurements, embedded in diagnosis-specific clinical algorithms, have been shown to markedly reduce the overuse of antibiotic therapy without increasing risk to patients in 11 randomized controlled trials including over 3500 patients from different European countries. In primary care and emergency department patients with mild and mostly viral respiratory infections (acute bronchitis), the initial prescription of antibiotics was reduced by 30-80%. In hospitalized and more severely ill patients with community-acquired pneumonia and sepsis, the main effect was a reduction of the duration of antibiotic courses by 25-65%. This review aims to provide physicians with an overview of the strengths and limitations of procalcitonin guidance for antibiotic therapy when used in different clinical settings and in patients with different underlying infections.

Topics: Algorithms; Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cricetinae; Humans; Protein Precursors; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Sepsis

There is increasing interest for strategies that could curtail antibiotic resistance in the critical care setting. We sought to determine the effectiveness and safety of procalcitonin-guided algorithms in the management of septic patients in the intensive care unit.. MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (through April 2010), reference lists of retrieved publications, and queries of corresponding authors. No language restrictions were applied.. We included only randomized controlled studies reporting on antibiotic use and clinical outcomes of intensive care unit patients managed with a procalcitonin-guided algorithm or according to routine practice.. Data on study characteristics, interventions, and outcomes were retrieved by two independent reviewers. Pooled odds ratios, weighted mean differences, and 95% confidence intervals were calculated by implementing both the Mantel-Haenszel fixed effect model and the DerSimonian-Laird random effects model.. Seven randomized controlled studies involving 1131 intensive care unit patients (adults = 1010; neonates = 121) were included. In comparison with routine practice, the implementation of procalcitonin-guided algorithms decreased the duration of antibiotic therapy for the first episode of infection by approximately 2 days (weighted mean difference = -2.36 days; 95% confidence interval, -3.11 to -1.61) and the total duration of antibiotic treatment by 4 days (fixed effect model: weighted mean difference: -4.19 days; 95% confidence interval, -4.98 to -3.39). The comparison between the procalcitonin and the routine practice group was not associated with any apparent adverse clinical outcome: 28-day mortality (fixed effect model: odds ratio = 0.93; 95% confidence interval, 0.69 to 1.26), intensive care unit length of stay (fixed effect model: pooled weighted mean difference = -0.49 days, 95% confidence interval, -1.55 to 0.57), and relapsed/persistent infection rate (fixed effect model: odds ratio = 0.97; 95% confidence interval, 0.56 to 1.69).. The implementation of a procalcitonin-based algorithm may reduce antibiotic exposure in critically ill, septic patients without compromising clinical outcomes, but further research is necessary before the wide adoption of this strategy.

Topics: Adult; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Infant, Newborn; Intensive Care Units; Intensive Care Units, Neonatal; Protein Precursors; Recurrence; Sepsis

A meta-analysis was performed to assess the accuracy of the procalcitonin (PCT) test for diagnosing neonatal sepsis. The major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies published between January 1996 and May 2009 that evaluated PCT as a diagnostic marker for neonatal sepsis and provided sufficient data to calculate sensitivity and specificity. Twenty-two studies were included in the analysis. Trials that evaluated the PCT test for the diagnosis of early-onset neonatal sepsis at different time points (birth, 0-12 h, 12-24 h, and 24-48 h) and late-onset neonatal sepsis (LONS) all showed moderate accuracy (Q* = 0.79, 0.86, 0.81, 0.82, and 0.77, respectively). The PCT test was more accurate than the C-reactive protein (CRP) test for the diagnosis of LONS. A sensitivity analysis found that differences in PCT assay producer, gestational age and severity of sepsis in the study population may partially explain the between-studies heterogeneity. The PCT test showed moderate accuracy in diagnosing neonatal sepsis, regardless of differences in diagnostic criteria and time points for testing. For the diagnosis of LONS, the PCT test showed better accuracy than the CRP test. PCT is a valuable additional tool for the diagnosis of neonatal sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Trials as Topic; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Despite several consensus conferences, the criteria for the definition of sepsis are still considered too sensitive and insufficiently specific. The traditional clinical signs of infection and routine laboratory tests used to diagnose bacterial infection and sepsis lack diagnostic accuracy and can be misleading, particularly in patients with immunodeficiencies. The problems with sepsis definitions and diagnoses are indications of the need to focus on biochemical mediators capable not only of distinguishing the inflammatory response to infection from other types of inflammation, but also of indicating the severity and prognosis of the disease. Thus, physicians need an early and rapid marker for detecting bacterial infection and distinguishing it from viral infection. Several studies revealed that elevated procalcitonin (PCT) levels in human blood could be detected in cases of sepsis and bacterial infection. PCT is a protein that can act as a hormone and a cytokine. It can be produced by several cell types and many organs in response to proinflammatory stimuli, particularly bacterial infection. It provides a rapid diagnostic test, available at the patient's bedside, and its half-life is suitable for daily monitoring of the disease progress.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Monitoring, Physiologic; Prognosis; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis

For decades, many investigators have attempted to identify clinical or laboratory markers that can accurately differentiate severe bacterial from self-limiting viral infections in young children with fever without source. Unfortunately, no perfect marker has been discovered so far. Many guidelines recommend white blood cell count as a screening marker in fever without source, whereas compelling evidence in the literature emphasizes the superior characteristics of C-reactive protein and procalcitonin. One way to improve predictive value is the combination of prediction rules of different tests for clinical and laboratory markers. Several clinical decision rules, reviewed in this article, have been suggested but seem to be difficult to implement in practice due to their complexity. Recently, procalcitonin, C-reactive protein and urinary dipstick were combined in a simple risk index score that displayed promising predictive value in severe bacterial infections in children. Ultimately, impact analyses still have to be performed to show improved quality of care in this setting.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Clinical Trials as Topic; Diagnosis, Differential; Fever of Unknown Origin; Humans; Infant; Infant, Newborn; Leukocyte Count; Protein Precursors; Sensitivity and Specificity; Sepsis; Virus Diseases

The use of biomarkers might help to avoid antibiotic misuse and overuse and to curb the rising incidence of microbial resistance. Amongst >100 biomarkers proposed for use as infection/sepsis markers, procalcitonin is the most frequently evaluated. It has been tested in 11 randomised controlled trials with more than 3500 patients and resulted in a considerable 35-70% reduction in antibiotic use without an apparent negative impact on patient outcome. Testing was carried out in hospital, Intensive Care Unit, emergency and primary care settings; most of the patients had lower respiratory tract infections and only smaller studies exist in surgical patients with infectious complications, immunocompromised patients and patients with sepsis. There are, however, concerns - trials designed to show non-inferiority of procalcitonin to standard management allowed rather large differences for mortality rates, in the range of 7.5-10%, thus clinically relevant excess mortality by procalcitonin-guided antibiotic therapy cannot be completely ruled out. Marker panels derived from transcriptomic or proteomic profiling hold promise in overcoming the limitations of procalcitonin for differentiating non-infectious from infection-associated inflammation. However, the utility of these novel diagnostic tools in the clinical setting remains to be proven.

Topics: Anti-Infective Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Trials as Topic; Drug Utilization; Humans; Protein Precursors; Sepsis; Treatment Outcome

The duration of antibiotic treatment in patients with an infectious process is based on empirical considerations and those with intraabdominal infections are no exception. Therefore, the recommended duration of antibiotic therapy in intraabdominal infection is controversial and no consensus has been reached due to the lack of controlled studies that would provide sufficient scientific evidence. Excessive duration of antibiotic therapy can increase the risk of developing bacterial resistance as well as treatment-associated costs. These considerations have led to the exploration of "short-term treatment" strategies, lasting 3-5 days, with encouraging results. However, the development of biomarkers such as procalcitonin opens the door to individualized treatment that might allow the duration of antibiotic treatment in intraabdominal and other infections to be individually tailed to patient response.

Topics: Abdomen; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Cross Infection; Double-Blind Method; Drug Administration Schedule; Drug Resistance, Microbial; Humans; Practice Guidelines as Topic; Protein Precursors; Randomized Controlled Trials as Topic; Sepsis; Soft Tissue Infections

In inflammatory states, particularly in response to infectious stimuli, local procalcitonin (PCT) production rises, and because these tissues cannot further process PCT into calcitonin, serum levels increase. In the critical care setting, PCT should be considered a useful tool to help physicians in some specific, although frequent, situations. Serial measurements of PCT levels may indicate the effectiveness of medical decisions such as the appropriateness of antibiotic therapy, the detection of new infections, and the exclusion of a diagnosis of sepsis. PCT-guided algorithms may also help to decrease the duration of antimicrobial therapy. However, the role of PCT as a prognostic marker in critically ill patients is controversial. In a study by Karlsson and colleagues, PCT concentrations did not differ between hospital survivors and nonsurvivors, but the outcome was better in patients whose PCT concentrations decreased more than 50%. The study of PCT kinetics thus could offer an individual risk assessment in patients with severe sepsis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Protein Precursors; Sepsis

Infections are highly prevalent in the neonatal period. Unfortunately the symptoms of infection are non-specific and are seen in other neonatal diseases as: respiratory distress syndrome, metabolic diseases, intracranial hemorrhages. Diagnosis is based on the clinics, microbiologic tests and laboratory markers of infection. Considering the high mortality and serious morbidity associated with neonatal sepsis, a diagnostic marker with a very high sensitivity and negative predictive value approaching 100% is desirable. Unfortunately there is no laboratory marker that has all of the characteristics of ideal infection marker. Procalcitonin, interleukins 6 and 8, CD 11b are early, sensitive markers of infection. C- reactive protein is a late specific marker of infection. CD 64 is the most sensitive marker of late, nosocomial infection. Serial measurement of infection markers will certainly improve the diagnostic sensitivity of these tests, because in most circumstances it is not certain at which stage of the infection the specimen should be taken for analysis. In addition, the use of multiple markers, in particular, combining an early sensitive marker with a late specific test will further enhance the diagnostic accuracy of these mediators in identifying infected cases.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Communicable Diseases; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Interleukins; Protein Precursors; Sepsis

The prompt recognition and management of septic patients remains a challenge within the busy Emergency Department (ED). Prognostic screening aids have traditionally required time-delayed laboratory measurements not validated upon the emergency medicine population. Recently, a brief prognostic tool has been derived and subsequently validated in heterogeneous ED populations.. Can a risk-stratification tool predict 1-month mortality in ED patients with suspected infection?. Six studies evaluating the Mortality in the Emergency Department Sepsis (MEDS) score were identified and evaluated.. Higher MEDS scores are associated with increasing mortality. MEDS score's short- and long-term prognostic accuracy is superior to other sepsis scales as well as isolated biomarkers C-reactive protein and procalcitonin. MEDS' prognostic accuracy in severe sepsis is inferior to undifferentiated systemic inflammatory response syndrome (SIRS) patients.. The MEDS score is an accurate and reliable prognostic tool for 28-day mortality in ED SIRS patients, but may not be optimal for those with severe sepsis.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Evidence-Based Emergency Medicine; Female; Hospital Mortality; Humans; Lactic Acid; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Assessment; ROC Curve; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

This review aims to provide physicians with an overview of the potential of procalcitonin to guide antibiotic therapy in respiratory tract infections and in sepsis. Knowledge of the strengths and weaknesses of procalcitonin are prerequisites for a rational and safe use in clinical routine. In most infections a true gold standard for diagnosis does not exist, therefore physicians must remain sceptical towards observational studies evaluating procalcitonin. Interpretation of procalcitonin levels must always include the clinical setting and knowledge of assay characteristics, particularly the setting of specific cut-off ranges and functional assay sensitivities. Highly sensitive procalcitonin measurements, embedded in a clearly defined setting and prospectively validated with clinical algorithms were repeatedly effective in markedly reducing the (over)-utilisation of antimicrobial therapy. Today, this concept has been proven for lower respiratory tract infections and in pilot studies for meningitis and critically ill patients with sepsis. The higher the absolute risk for adverse outcome of a patient, the more cautious physicians must remain and empirical antibiotic therapies must be considered despite initial low procalcitonin levels at the initial presentation. In these patients a procalcitonin-guided shortening of antibiotic courses seems appropriate. The prognostic utility of initial procalcitonin measurement in respiratory tract infections is suboptimal. Other biomarkers including cortisol, human growth hormone and prohormones from adrenomedullin and vasopressin ("copeptin") have a superior predictive potential to estimate the risk for short and long term mortality and other adverse outcomes in different diseases. An accurate prognostic assessment has the potential to optimise the management of patients and the allocation of our limited health care resources by lowering unnecessary hospitalisations and associated cost. Future intervention studies must prove if these biomarkers indeed improve clinical decision making and thus the overall medical management of patients.

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Catheter-Related Infections; Disease Progression; Drug Administration Schedule; Humans; Pneumonia; Protein Precursors; Sepsis

Prompt diagnosis, intervention, and risk assessment are critical in caring for septic patient but remain difficult with currently available methods. Biomarkers may become useful adjuncts to clinicians and ultimately serve as targets for future therapeutic trials in sepsis. The most relevant markers are reviewed in this article, including interleukin-6, C-reactive protein, procalcitonin, triggering receptor expressed on myeloid cells-1, and biomarker panels.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Interleukin-6; Macrophages; Membrane Glycoproteins; Monocytes; Neutrophils; Predictive Value of Tests; Prognosis; Protein Precursors; Receptors, Immunologic; Risk Assessment; Sepsis; Shock, Septic; Triggering Receptor Expressed on Myeloid Cells-1

For the treatment of septic patients, it is important to perform a rapid and accurate identification of the causative microorganisms of the syndrome, and to use appropriate medicine. Blood culture has been an established method for the identification of causative bacteria in patients with sepsis, and the measurement of CRP has been used to estimate the severity of disorders. However, the blood culture method has a low sensitivity for detecting surviving bacteria in patients with sepsis because of the possible administration of antibiotics in advance of the test. Although the identification of causative bacteria must be performed quickly, the method requires several days to detect and identify the bacteria and to test for susceptibility to antibiotics. In addition, CRP measurement is not able to distinguish systemic bacterial infection from nonbacterial infection or non-infectious inflammation. To overcome the disadvantages of these tests for the diagnosis of sepsis, new methods have been developed. In this issue, we introduce two new methods for the diagnosis of sepsis. One involves the detection of the bacterial gene ingested by neutrophils by the in-situ hybridization method, and the other is the measurement of procalcitonin in blood samples. Since these tests have several advantages in comparison with the conventional blood culture method or the measurement of CRP to verify the presence of bacterial infection and identify the causal bacteria in a shorter period, we need to combine these tests with the conventional methods to facilitate an accurate diagnosis and administer appropriate antibiotics to septic patients.

Topics: Bacteriological Techniques; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Genes, Bacterial; Humans; In Situ Hybridization; Neutrophils; Protein Precursors; Sepsis

The use of procalcitonin (ProCT) as a marker of several clinical conditions, in particular, systemic inflammation, infection, and sepsis, will be clarified, and its current limitations will be delineated. In particular, the need for a more sensitive assay will be emphasized. For these purposes, the medical literature comprising clinical studies pertaining to the measurement of serum ProCT in various clinical settings was examined.. A PubMed search (1965 through November 2007) was conducted, including manual cross-referencing. Pertinent complete publications were obtained using the MeSH terms procalcitonin, C-reactive protein, sepsis, and biological markers. Textbook chapters were also read and extracted.. Available clinical and other patient data from these sources were reviewed, including any data relating to precipitating factors, clinical findings, associated illnesses, and patient outcome. Published data concerning sensitivity, specificity, and reproducibility of ProCT assays were reviewed.. Based on available data, the measurement of serum ProCT has definite utility as a marker of severe systemic inflammation, infection, and sepsis. However, publications concerning its diagnostic and prognostic utility are contradictory. In addition, patient characteristics and clinical settings vary markedly, and the data have been difficult to interpret and often extrapolated inappropriately to clinical usage. Furthermore, attempts at meta-analyses are greatly compromised by the divergent circumstances of reported studies and by the sparsity and different timing of the ProCT assays. Although a high ProCT commonly occurs in infection, it is also elevated in some noninfectious conditions. Thus, the test is not a specific indicator of either infection or sepsis. Moreover, in any individual patient, the precipitating cause of an illness, the clinical milieu, and complicating conditions may render tenuous any reliable estimations of severity or prognosis. It also is apparent that even a febrile septic patient with documented bacteremia may not necessarily have a serum ProCT that is elevated above the limit of functional sensitivity of the assay. In this regard, the most commonly applied assay (i.e., LUMItest) is insufficiently sensitive to detect potentially important mild elevations or trends. Clinical studies with a more sensitive ProCT assay that is capable of rapid and practicable day-to-day monitoring are needed and shortly may be available. In addition, investigations showing that ProCT and its related peptides may have mediator relevance point to the need for evaluating therapeutic countermeasures and studying the pathophysiologic effect of hyperprocalcitonemia in serious infection and sepsis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Inflammation; Protein Precursors; Sensitivity and Specificity; Sepsis

The biphasic waveform (BPW) is an abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time on a specific photometric haemostasis autoanalyzer. This abnormality is related to calcium-dependent formation of complexes between C reactive protein and very low density lipoprotein. Biphasic waveform had a high sensitivity and negative predictive value for the identification of patients with severe sepsis and septic shock. On day 3, the time course of the biphasic waveform is a marker for the prognosis of sepsis-related mortality. The BPW is not a surrogate marker for C-reactive protein or procalcitonin and provides additional information. Further trials should be necessary using BPW for diagnostic and management procedures. Compared with other laboratory markers such as C reactive protein or procalcitonin, activated partial thromboplastin time waveform analysis is a tool that is rapid, inexpensive, effective and available 24 hours a day. When the analyzer is locally available, waveform analysis of this routine coagulation test provides information for the diagnosis of severe sepsis and the prognosis of septic patients.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Partial Thromboplastin Time; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis

Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Diagnosis, Differential; Emergency Medical Services; Humans; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Neonatal sepsis occurs from 1 to 21 newborns out of 1 000 live births with mortality rates as high as 30% up to 69%. The most important risk factors are prematurity, low birth weight, invasive medical procedure and prolonged hospitalization in neonatal intensive care units. An aimed and restrictive antibiotic therapy has an outstanding importance to reduce both morbidity-mortality rates and multiple drug-resistance. Generally, preterm newborns present nonspecific clinical signs of infection. The use of high sensitivity infection markers and a negative predictive value (near 100%) are important to distinguish infected and noninfected patients before the culture results and to verify adequacy and duration of antibiotic therapy. This article reviews the immunologic function and practical use of C reactive protein (CRP) and other markers in the diagnosis of neonatal sepsis. While CRP is a specific late infection marker, cytokines, cell surface markers and procalcitonin (PCT) are early infection markers. The use of multiple markers as CRP, PCT, IL-6, IL-8, CD64, CD11b is useful both to early (24-48 h) diagnose of neonatal sepsis, and to monitorate the antibiotic treatment while waiting for the results of cultural examinations.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Predictive Value of Tests; Protein Precursors; Risk Factors; Sensitivity and Specificity; Sepsis

Procalcitonin measurement has been claimed as a helpful marker in bacterial infection and sepsis. It has obtained FDA approval and is now widely marketed in the United States and Europe. This review summarises the current assays available, the evidence for its use and possible future applications of the assay.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term "hormokine" encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.

Topics: Adrenomedullin; Animals; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Critical Pathways; Diagnosis, Differential; Glycopeptides; Humans; Natriuretic Peptides; Pneumonia, Bacterial; Predictive Value of Tests; Prognosis; Protein Precursors; Respiratory Tract Infections; Sepsis

Procalcitonin (PCT) is the precursor of calcitonin, normally synthesized in the C-cells of the thyroid gland. Systemic inflammation and sepsis induce PCT production by various cell types, including hepatocytes, nephrons, monocytes. PCT begins to rise four hours after exposure to bacterial endotoxins, peaking at six to eight hours, and remaining raised for at least 24 hours with a half-life of 25-30 hours. Serum PCT levels significantly increase in systemic bacterial infection, necrotizing enterocolitis, and during both early and late onset neonatal sepsis. By using a cut-off limit of 0,5 microg/L, the PCT positive likelihoud ratio was found of 12.5. PCT has a theoretical advantage as a marker of systemic induction in sepsis and its half-life suitable for daily monitoring of disease progress. PCT may be useful in assessing the severity of infection, following the progress of treatment, and predicting outcomes.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Protein Precursors; Sepsis

Sepsis and its complications are the most common cause of the death in the intensive care unit. In spite of the treatment mortality remains up to 28-50%, and 60-90% of the patients are lost because of the complications of sepsis. So it is very important to diagnose this pathology and start the treatment early. The diagnosis of sepsis is complicated for clinical signs and symptoms are not specific and manifest in the patients who have non-infective diseases, when systemic inflammatory response is involved. Parameters of systemic inflammatory response, such as body temperature, heart rate, respiratory rate, leukocyte count, and C-reactive protein concentration, used in clinical practice are neither specific, non sensitive. These parameters often provide information that is inadequate for the discrimination of bacterial and nonbacterial infections and for diagnosis. So it is impossible to differentiate systemic inflammatory response and sepsis. Procalcitonin is a new parameter for diagnosis of bacterial, fungal and parasitical infections. In healthy humans almost all procalcitonin, which is produced in thyroid gland, is resolved and does not reach the blood stream. Its half-life in plasma is only few minutes, so in healthy humans the level of procalcitonin is very low (<0.1 ng/ml) and is not detectable by standard methods. In the case of infection the level of procalcitonin rapidly increases during 2-6 hours and reaches the maximum level after 6-12 hours. The measurement of procalcitonin levels can be used for instant diagnosis as well as for evaluation of the treatment effectiveness. In our article we review the new literature data on the importance of procalcitonin level for sepsis diagnosis in comparison with other parameters of systemic inflammatory reaction, and discuss the indications for procalcitonin analysis.

Topics: Adult; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Diagnosis, Differential; Humans; Infant, Newborn; Intensive Care Units; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome; Time Factors

To quantify the accuracy of serum procalcitonin as a diagnostic test for sepsis, severe sepsis, or septic shock in adults in intensive care units or after surgery or trauma, alone and compared with C-reactive protein. To draw and compare the summary receiver operating characteristics curves for procalcitonin and C-reactive protein from the literature.. MEDLINE (keywords: procalcitonin, intensive care, sepsis, postoperative sepsis, trauma); screening of the literature.. Meta-analysis of all 49 published studies in medical, surgical, or polyvalent intensive care units or postoperative wards. Children, medical patients, and immunocompromised patients were excluded.. Thirty-three studies fulfilled inclusion criteria (3,943 patients, 1,828 males, 922 females; mean age: 56.1 yrs; 1,825 patients with sepsis, severe sepsis, or septic shock; 1,545 with only systemic inflammatory response syndrome); eight studies could not be analyzed statistically. Global mortality rate was 29.3%.. Global odds ratios for diagnosis of infection complicated by systemic inflammation were 15.7 for the 25 studies (2,966 patients) using procalcitonin (95% confidence interval, 9.1-27.1) and 5.4 for the 15 studies (1,322 patients) using C-reactive protein (95% confidence interval, 3.2-9.2). The summary receiver operating characteristics curve for procalcitonin was better than for C-reactive protein. In the 15 studies using both markers, the Q* value (intersection of summary receiver operating characteristics curve with the diagonal line where sensitivity equals specificity) was significantly higher for procalcitonin than for C-reactive protein (0.78 vs. 0.71, p = .02), the former test showing better accuracy.. Procalcitonin represents a good biological diagnostic marker for sepsis, severe sepsis, or septic shock, difficult diagnoses in critically ill patients. Procalcitonin is superior to C-reactive protein. Procalcitonin should be included in diagnostic guidelines for sepsis and in clinical practice in intensive care units.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Male; Middle Aged; Postoperative Complications; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Wounds and Injuries

Procalcitonin, a propeptide of calcitonin, is normally produced in the C-cells of the thyroid gland, but it's plasma level markedly increases, mostly due to extra-thyroidal production in cases of severe infections (bacterial, parasitic and fungal) with systemic manifestations, especially in the presence of septic shock. Since noninfectious inflammatory reaction, viral infection and localized bacterial infections manifest only small to modest increases of procalcitonin in plasma, procalcitonin levels may be useful in differentiating between these diseases and sepsis. In addition, it has been suggested that procalcitonin is an early and good marker of elevated cytokines in patients with sepsis, and that it's plasma level is correlated with Sepsis-related Organ Failure Assessment (SOFA) score. Since plasma procalcitonin is measured easily, quickly and accurately by immunoluminometric assay, it is useful for early diagnosis of sepsis in patients with severe systemic inflammatory response syndrome and as an indicator of severity of sepsis in such patients.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Protein Precursors; Sepsis; Virus Diseases

In febrile children and adults, it is frequently difficult, based on the sole clinical examination, to differentiate a bacterial illness from systemic inflammatory syndromes or severe viral infections. However, the positive and rapid diagnosis of a severe bacterial infection or a sepsis is essential to initiate lifesaving therapies. Among the numerous infectious biomarkers that have recently been investigated, procalcitonin has the best diagnostic yield. Plasma levels below 0.5 microg/l usually rule out a severe bacterial disease, whereas values above 2 microg/l are strongly indicative of a bacterial sepsis. The usefulness and the limitations of the measurement of procalcitonin as a diagnostic and a prognostic tool during severe bacterial infections are discussed in this paper.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Diagnosis, Differential; Fever; Glycoproteins; Humans; Inflammation; Protein Precursors; Sepsis; Syndrome; Virus Diseases

Evaluation of procalcitonin levels is a sensitive investigation which is significant for differentiation between microbial and non-microbial infection, a determination of its dynamics and a prediction of therapy results. It is, however, necessary to evaluate its levels in relation to other investigations and their dynamics (other inflammatory markers, organ function dynamics), which specify diagnosis with the clinical condition of a patient. Even today, 10 years after the discovery of procalcitonin as an inflammatory marker and likely mediator of a cytokine cascade, there are many unanswered questions regarding its production in relation to physiological significance during the defensive response of an organism (12). Boucher formulated a simple conclusion in 2000: Procalcitonin should not be seen as the marker of sepsis but as one of many potentially useful markers.

Topics: Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Inflammation; Inflammation Mediators; Protein Precursors; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Humans; Hypercalcemia; Hypocalcemia; Immunoradiometric Assay; Inflammation; Kidney Failure, Chronic; Luminescent Measurements; Osteoporosis; Protein Precursors; Radioimmunoassay; Reference Values; Sepsis; Thyroid Neoplasms

The purpose of this review is to indicate recent developments in biomarkers of sepsis and to evaluate their impact on clinical use. According to the 'surviving sepsis campaign,' diagnosis of sepsis and infection is urgent; early and specific treatment is most effective to reduce complications and to decrease mortality.. A variety of biomarkers of sepsis is presently available. The diagnostic spectrum of the various markers, however, is different. Some primarily indicate severity of inflammation (e.g. interleukin-6), others respond to infection, but do not indicate the host response well (endotoxin, lipoprotein binding protein, triggering receptor on myeloid cells). There are new markers with limited clinical experience, for example triggering receptor on myeloid cells or mid-pro atrial natriuretic peptide (Seristra, Brahms AG, Hennigsdorf, Germany). Procalcitonin is a well-established biomarker of sepsis that fulfills several criteria of clinical needs: it responds both to infection and severity of inflammation and thus has an impact on therapy. Recent studies indicate that antibiotic treatment can also be guided by procalcitonin. Further indications, including diagnosis of invasive bacterial infections and diagnosis of sepsis in neonates and children have been reported recently.. Recent data and cumulative analyses indicate that biomarkers of sepsis improve diagnosis of sepsis. However, only a few markers have impact on therapy and fulfill the clinical requirements. Procalcitonin is a well-established marker, indicating infection, sepsis, and progression to the more severe stages of the disease. Today, this biomarker should be in the diagnostic portfolio of an intensive care unit or emergency ward.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Interleukin-6; Protein Precursors; Sepsis

An ideal marker for bacterial infections should allow an early diagnosis, inform about the course and prognosis of the disease and facilitate therapeutic decisions. Procalcitonin (ProCT) covers these features better as compared to other, more commonly used biomarkers, and thus, the current hype on ProCT has a solid scientific basis. A superior diagnostic accuracy of ProCT has been shown for a variety of infections, eg respiratory tract infections, meningitis, acute infectious endocarditis and pancreatitis. Importantly, a ProCT-based therapeutic strategy can safely and markedly reduce antibiotic usage in lower respiratory tract infections, the major cause of sepsis. Being a hormokine mediator, immunoneutralisation of ProCT might offer new hope for more effective treatment options in sepsis. It is now evidence-based that ProCT provides more information and, thereby, questions the currently used "gold standards" for the diagnosis of clinically relevant bacterial infections. Yet, ProCT is less than a perfect marker. ProCT can be increased in non-infectious conditions, and may remain low in infections. The diagnosis of bacterial infections will continue to require a critical clinical awareness, careful patient history, dedicated physical examination, and appropriate cultures. This review aims to help the clinician to understand the physiopathological basis, to appreciate strengths and weaknesses of this biomarker, and thereby to promote a rational implementation of ProCT in a routine setting.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Switzerland

Infections and sepsis are among the most devastating complications in abdominal surgery and significantly contribute to morbidity and mortality. Early and reliable diagnosis of septic complications is notoriously difficult, and the search for novel approaches to overcome this problem is still a compelling issue for clinicians. Among a large array of inflammatory parameters, procalcitonin (PCT), the 116-amino-acid pro-peptide of calcitonin, has gained considerable importance in identifying patients at risk of developing infection and sepsis in clinical practice.. Along with the latest insights into pathophysiological aspects of this pro-hormone, the literature as well as our own experience on the usefulness of PCT determinations in patients with severe inflammatory abdominal disorders was reviewed.. Although the term "sepsis" does not embrace the integral properties of PCT, a remarkable number of clinical studies have demonstrated the pivotal role of this parameter in the host response to microbial and fungal infections. In acute pancreatitis PCT allows early severity stratification and closely correlates with the development of subsequent pancreatic infections. In patients with peritonitis PCT reflects overall disease severity and is an early and reliable indicator of overall prognosis. Postoperative monitoring of PCT is a helpful tool to identify patients with evolving or persisting septic complications after elective and emergency abdominal surgery.. Compared with established biochemical routine variables, PCT significantly contributes to earlier and better stratification of patients at risk of developing septic complications and provides excellent prognostic assessment in severe abdominal inflammation. The currently available test systems render PCT an applicable and readily available parameter under clinical routine and emergency conditions.

Topics: Abdomen; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Peritonitis; Protein Precursors; Sepsis; Surgical Procedures, Operative

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Multigene Family; Protein Precursors; RNA, Messenger; Sepsis

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Humans; Infant; Infant, Newborn; Meningitis, Bacterial; Meningitis, Viral; Pneumonia, Bacterial; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Urinary Tract Infections

Elevation in the serum concentration of procalcitonin (PCT) is associated with systemic infection. This association has led to the proposed use of PCT as a novel biomarker of bacterial sepsis. The advantages and limitations of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) definitions of sepsis are an important consideration that affects the impact of any diagnostic test for sepsis and these issues are discussed. Our main objective is to perform a systematic health technology assessment of PCT as a diagnostic test for sepsis. In an adult intensive care unit (ICU) population, we identify a specific and important question-can PCT accurately distinguish sepsis in patients with systemic inflammatory response syndrome (SIRS) who have a suspected infection? Likelihood ratios are calculated from published data to attempt to find the best answer. The published evidence does not support a general claim that PCT is a useful decision support tool for diagnosing sepsis in patients who have SIRS. Procalcitonin has a slightly better ability to exclude the diagnosis of sepsis. The role for using PCT testing in the ICU will continue to evolve along with our understanding and definition of sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Predictive Value of Tests; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Technology Assessment, Biomedical

Prompt diagnosis and treatment with appropriate antimicrobial chemotherapy is of paramount importance to reduce morbidity and mortality associated with sepsis. Inflammatory markers currently in use, such as C-reactive protein (CRP) do not reliably differentiate between the systemic inflammatory response and sepsis. Procalcitonin (PCT), a precursor of calcitonin, is a 116 amino acid protein that has been proposed as a marker of disease severity in conditions such as septicaemia, meningitis, pneumonia, urinary tract infection (UTI) and fungal and parasitic infection. In particular, serial measurements are useful in order to monitor response to therapy. Together with good clinical judgement and judicious use of antimicrobial agents, PCT should serve as a valuable adjunct in the diagnosis and management of sepsis.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Intensive Care Units; Protein Precursors; Sepsis

Induction of the protein procalcitonin during infection and inflammation was first described approximately 10 years ago. A large number of publications, primarily clinical studies, demonstrate the increasing use of procalcitonin in modern clinical practice. However, data on the biological function and origin of procalcitonin is scarce. Findings regarding the possible role and source of procalcitonin in sepsis and infection were recently published, and the pathophysiology of the protein has meanwhile been investigated in various experimental models. Procalcitonin obviously has certain biological functions, and it is also known to be specifically induced. Given the hormonal origin of the mature protein and the inflammation-related functions of its propeptides, some investigators suggest that procalcitonin should be referred to as a "hormokine," although its biological functions should be studied in more detail. This review will survey the data now available in recent publications on the induction, production sources, possible biological functions and clinical uses of procalcitonin.

Topics: Amino Acid Sequence; Animals; Calcitonin; Calcitonin Gene-Related Peptide; Gene Expression Regulation; Humans; Inflammation; Molecular Sequence Data; Protein Precursors; Protein Processing, Post-Translational; Sepsis; Sequence Homology, Amino Acid

Procalcitonin is a polypeptide present in the plasma of healthy subjects in minimal levels (< 0.5 ng/ml). Serum procalcitonin is markedly increased a few hours after the administration of endotoxin to human volunteers and in invasive bacterial infection (sepsis, septic shock, meningitis). Procalcitonin is moderately increased in local bacterial infection (pneumonia pyelonephritis) and is unchanged in viral infections or bacterial colonization. Procalcitonin is increased in serious bacterial infections in neonates, children and adults and is currently the best diagnostic marker of severe bacterial infection, being better than leukocyte, interleukin or C-reactive protein counts. C-reactive protein levels can be normal in severe sepsis and some viral infections. We studied 54 children with sepsis in whom plasma procalcitonin levels showed a positive correlation with the vasoactive drugs necessary to maintain cardiovascular activity. The semiquantitative procalcitonin test is simple and easy to use at the bedside at any time and in any hospital as no instruments are required. Within 30 minutes, the test identifies the type of infection and whether antibiotics are indicated.

Topics: Adult; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Humans; Meningitis, Bacterial; Protein Precursors; Sepsis; Shock, Septic

Topics: Animals; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis

In diagnosing sepsis the rapid identification of bacteremia at an early stage of the disease is critical for a favorable outcome. Furthermore, it is important that exact information on the stage of the disease be obtained rapidly in order to choose and initiate the appropriate therapy. In recent years many new techniques have been added to the diagnostic tools. In this review we will focus on three new methods for the early diagnosis of sepsis. These are: polymerase chain reaction, which offers the possibility to attain detailed information about the involved bacterial (or viral) species, and the laboratory markers procalcitonin and hypophosphatemia, which are indicators of the presence of infection with gram-negative bacteria. The approaches reviewed here were developed to expedite the diagnosis of especially early sepsis and might be a further step towards the improvement of therapy for sepsis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Hypophosphatemia; Polymerase Chain Reaction; Protein Precursors; Sepsis

Calcitonin was discovered in the early 1960s [1], at which time it was assumed to be a single hormone with a yet-to-be-determined role in human physiology. Since then it has been found to be only one entity among a large array of related circulating peptides, at least one of which has a pivotal role in the host response to microbial infections [2, 3]. The aim of this review is to describe this metamorphosis of an endocrine hormone to a new class of hormokine mediators in infectious diseases.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Practice Guidelines as Topic; Protein Precursors; Sensitivity and Specificity; Sepsis

Topics: Acute-Phase Proteins; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Inflammation; Protein Precursors; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Protein Precursors; Sepsis

Any delay in the management of infection is deleterious, especially in patients whose illness is severe. It is of paramount importance to shorten this delay. This article emphasizes the different ways to reach this goal, including the use of new biologic markers, such as cytokines or procalcitonin.

Topics: Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Humans; Inflammation; Intensive Care Units; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Prognosis; Protein Precursors; Respiratory Distress Syndrome; Sepsis

Procalcitonin (PCT), a glycoprotein consisting of 116 amino acids, has been proposed as a new marker of severe infection. The site of production under this condition remains unknown. The serum PCT concentration is determined by an immunoluminometric assay of 40 microliters serum or plasma requiring approximately two hours. Elevations of PCT are for instance associated with levels of lipopolysaccharide and the cytokines TNF-alpha and IL-6. Bacterial, parasitic or fungal infections developing septic complications in contrast to local infections, often show values exceeding 2 ng/ml. The specificity of the parameter in this context increases with its concentrations. Therapeutic actions that confine the infection locally are reflected by a decrease of the PCT value. PCT may be elevated within the first days after extended surgery or polytrauma, in some malignancies, heat-stroke and during treatment of some hematologic diseases without an existing sepsis or severe infection. Previous studies indicate certain benefits of PCT compared to traditional markers of inflammation or sepsis, where the ability to indicate a generalized infection is the primary advantage.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Protein Precursors; Sepsis

To explore the effect of Compound Tongtu Granule (CTG) on intestinal permeability in elderly sepsis patients.. Eighty elderly sepsis patients were randomly assigned to the experimental group and the control group by randomized double blinded method, 40 in each group. On the basis of conventional antiseptic treatment program, patients in the experimental group took CTG, while those in the control group took placebos. The dosage for CTG or placebos was 14.3 g each package, one package each time, twice daily for 14 successive days. Patients' abdominal symptoms and signs, levels of serum inflammatory factors (high-sensitivity C-reactive protein and procalcitonin), levels of plasma endotoxin, and the intestinal permeability (IP, represented by urinary lactulose/mannitol excretion rate) were compared between the two groups before and after treatment.. After 14-day treatment, patients in the experimental group had improved abdominal symptoms, increased frequency of defecation, significantly decreased levels of plasma endotoxin and IP, when compared with the control group (P < 0.05).. CTG could improve the intestinal barrier function in elderly sepsis patients.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Defecation; Drugs, Chinese Herbal; Endotoxins; Humans; Intestinal Mucosa; Permeability; Protein Precursors; Sepsis

A continued need exists for effective diagnostic biomarkers in bacterial sepsis among critically ill patients, despite increasing use of available biomarkers such as procalcitonin (PCT). Interleukin-27 (IL-27) has shown early promise in a recent preliminary study, exhibiting high specificity and positive predictive values for bacterial infection in critically ill children. This validation study was performed to assess the value of IL-27 in predicting bacterial infection among patients admitted to the pediatric intensive care unit and to compare its performance with that of PCT.. A single-center (n = 702) prospective study was performed comparing both IL-27 and PCT levels between bacterially infected and uninfected cohorts in the pediatric intensive care unit. Infected status was determined by a chart review by an intensivist blinded to biomarker results. Formal performance comparisons included calculations of receiver operating characteristic (ROC) curves for IL-27 and PCT individually in addition to a combination strategy using a decision tree generated by classification and regression tree (CART) methodology. Secondary analysis focusing on subjects with documented bloodstream infections was performed.. The overall infection rate was 27 %. ROC curves for the primary analysis yielded areas under the curve (AUCs) of 0.64 (0.59 to 0.68) for IL-27 and 0.61 (0.56 to 0.65) for PCT. Secondary analysis defining infected status exclusively through positive blood cultures yielded AUCs of 0.75 (0.68 to 0.81) for IL-27 and 0.64 (0.57 to 0.71) for PCT, with a specificity of 95 % (92 % to 97 %) for the prior established IL-27 cut-point value of at least 5.0 ng/ml. Similar AUCs were found for the subset of immunocompromised patients. In a CART-derived analysis taking immunocompromised status into consideration, a combination of IL-27 and PCT yielded an AUC of 0.81 (0.75 to 0.86), statistically improved from either IL-27 or PCT alone.. Despite having a modest predictive value for infection independent of source, IL-27 may serve as a useful biomarker in estimating risk of bacterial infection among critically ill pediatric patients with bloodstream infections. In particular, among immunocompromised subjects, this diagnostic biomarker may be helpful either alone or using a combination strategy with other available biomarkers.

Topics: Adolescent; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Interleukins; Male; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Organ Dysfunction Scores; Patient Admission; Prospective Studies; Protein Precursors; Sepsis; Single-Blind Method; Systemic Inflammatory Response Syndrome

Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT).. This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment.. Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 μg/L (median 3.4 to 45.2) and 10.8 μg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65).. In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Italy; Lipopolysaccharide Receptors; Male; Middle Aged; Mortality; Peptide Fragments; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis; Serum Albumin; Treatment Outcome

Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.. Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.. Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.. Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.. ClinicalTrials.gov identifier NCT01434121.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Demography; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Multiple Organ Failure; Placebos; Protein Precursors; Sepsis; Thrombomodulin

The aim of this study was to evaluate the diagnostic and prognostic value of presepsin in patients with severe sepsis and septic shock during the first week of ICU treatment.. In total, 116 patients with suspected severe sepsis or septic shock were included during the first 24 hours of ICU treatment. Blood samples for biomarker measurements of presepsin, procalcitonin (PCT), interleukin 6 (IL-6), C reactive protein (CRP) and white blood cells (WBC) were drawn at days 1, 3 and 8. All patients were followed up for six months. Biomarkers were tested for diagnosis of sepsis, severe sepsis, septic shock and for prognosis of 30-days and 6-months all-cause mortality at days 1, 3 and 8. Diagnostic and prognostic utilities were tested by determining diagnostic cutoff levels, goodness criteria, C-statistics and multivariable Cox regression models.. Presepsin increased significantly from the lowest to most severe sepsis groups at days 1, 3 and 8 (test for linear trend P <0.03). Presepsin levels revealed valuable diagnostic capacity to diagnose severe sepsis and septic shock at days 1, 3 and 8 (range of diagnostic area under the curves (AUC) 0.72 to 0.84, P = 0.0001) compared to IL-6, PCT, CRP and WBC. Goodness criteria for diagnosis of sepsis severity were analyzed (≥sepsis, cutoff = 530 pg/ml; ≥severe sepsis, cutoff = 600 pg/ml; ≥septic shock, cutoff = 700 pg/ml; P <0.03). Presepsin levels revealed significant prognostic value for 30 days and 6 months all-cause mortality (presepsin: range of AUC 0.64 to 0.71, P <0.02). Patients with presepsin levels of the 4th quartile were 5 to 7 times more likely to die after six months than patients with lower levels. The prognostic value for all-cause mortality of presepsin was comparable to that of IL-6 and better than that of PCT, CRP or WBC.. In patients with suspected severe sepsis and septic shock, presepsin reveals valuable diagnostic capacity to differentiate sepsis severity compared to PCT, IL-6, CRP, WBC. Additionally, presepsin and IL-6 reveal prognostic value with respect to 30 days and 6 months all-cause mortality throughout the first week of ICU treatment.. ClinicalTrials.gov http://NCT01535534. Registered 14 February 2012.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Intensive Care Units; Interleukin-6; Leukocyte Count; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Time Factors

The role of procalcitonin (PCT), a widely used sepsis biomarker, in critically ill patients with sepsis is undetermined.. To investigate the effect of a low PCT cut-off on antibiotic prescription and to describe the relationships between PCT plasma concentration and sepsis severity and mortality.. This was a multicenter (11 Australian intensive care units [ICUs]), prospective, single-blind, randomized controlled trial involving 400 patients with suspected bacterial infection/sepsis and expected to receive antibiotics and stay in ICU longer than 24 hours. The primary outcome was the cumulative number of antibiotics treatment days at Day 28.. PCT was measured daily while in the ICU. A PCT algorithm, including 0.1 ng/ml cut-off, determined antibiotic cessation. Published guidelines and antimicrobial stewardship were used in all patients. Primary analysis included 196 (PCT) versus 198 standard care patients. Ninety-three patients in each group had septic shock. The overall median (interquartile range) number of antibiotic treatment days were 9 (6-21) versus 11 (6-22), P = 0.58; in patients with positive pulmonary culture, 11 (7-27) versus 15 (8-27), P = 0.33; and in patients with septic shock, 9 (6-22) versus 11 (6-24), P = 0.64; with an overall 90-day all-cause mortality of 35 (18%) versus 31 (16%), P = 0.54 in the PCT versus standard care, respectively. Using logistic regression, adjusted for age, ventilation status, and positive culture, the decline rate in log(PCT) over the first 72 hours independently predicted hospital and 90-day mortality (odds ratio [95% confidence interval], 2.76 [1.10-6.96], P = 0.03; 3.20 [1.30-7.89], P = 0.01, respectively).. In critically ill adults with undifferentiated infections, a PCT algorithm including 0.1 ng/ml cut-off did not achieve 25% reduction in duration of antibiotic treatment. Clinical trial registered with http://www.anzctr.org.au (ACTRN12610000809033).

Topics: Adult; Aged; Algorithms; Anti-Bacterial Agents; Australia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Single-Blind Method

The aims of the present study were to evaluate the prognostic value of adrenomedullin (AM) in septic patients in the emergency department (ED) and to compare it with procalcitonin (PCT) and Mortality in Emergency Department Sepsis (MEDS) score.. We enrolled 837 consecutive patients who fulfilled the systemic inflammatory response syndrome criteria and were admitted to the ED of Beijing Chaoyang Hospital and 100 age-matched healthy controls. Serum AM and PCT were determined, and MEDS score was calculated at enrollment. The prognostic value of AM was compared with PCT and MEDS score. Primary outcome was in-hospital mortality.. On admission, mean levels of AM were 28.66 ± 6.05 ng/L in 100 healthy controls, 31.65 ± 6.47 ng/L in 153 systemic inflammatory response syndrome patients, 33.24 ± 8.59 ng/L in 376 sepsis patients, 34.81 ± 8.33 ng/L in 210 severe sepsis patients, and 45.15 ± 9.87 ng/L in 98 septic shock patients. The differences between the 2 groups were significant. Adrenomedullin level was higher in nonsurvivors than in survivors in every group. The area under receiver operating characteristic curve of AM for predicting in-hospital mortality in septic patients was 0.773, which was better than PCT (0.701) and MEDS score (0.721). Combination of AM and MEDS score improved the accuracy of AM and MEDS score in predicting the risk of in-hospital mortality (area under receiver operating characteristic curve, 0.817). In logistic regression analysis, AM and MEDS score were independent predictors of in-hospital mortality.. Adrenomedullin is valuable for prognosis in septic patients in the ED.

Topics: Adrenomedullin; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

To determine an effective method for predicting severity of sepsis and 28-day mortality of emergency department (ED) patients, we compared the Mortality in Emergency Department Sepsis (MEDS) score with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) and evaluated the MEDS score combined with relevant biomarkers.. A total of 501 adult ED patients with sepsis were selected for this prospective clinical study. The optimal combination was assessed by logistic regression. All cases were divided into the sepsis group (319 cases) and the severe sepsis and septic shock group (182 cases) according to the severity of sepsis, as well as the survivor group (367 cases) and nonsurvivor group (134 cases) according to the 28-day outcomes.. The area under the curve of the MEDS score, PCT, IL-6, and CRP was 0.793, 0.712, 0.695, and 0.681 for severity of sepsis and 0.776, 0.681, 0.692, and 0.661 for 28-day mortality, respectively. Only PCT was an independent predictor when combined with the MEDS score. The new combination of the MEDS score with PCT improved the area under the curve for severity (0.852) and mortality (0.813). This new combination for evaluation of severity had better sensitivity (63.2%), specificity (92.2%), and positive predictive (82.1%) and negative predictive (81.4%) values.. The predictive ability of the MEDS score for severity and 28-day mortality of septic ED patients is better than PCT, IL-6, and CRP levels. The MEDS score combined with PCT enhances the ability of risk stratification and prognostic evaluation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Decision Support Techniques; Emergency Service, Hospital; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Young Adult

To investigate the significance of dynamic monitoring of procalcitonin (PCT) in guiding the use of antibiotics for treating patients with sepsis in intensive care unit (ICU).. Eighty-two patients with sepsis from January 2012 to June 2013 hospitalized in ICU of First Hospital of Jilin University were enrolled, and they were randomly divided into regular antibiotic therapy group (RAT group, n=40) and PCT monitoring in guiding the use of antibiotics group (PCT group, n=42). Patients in RAT group were treated according to principle of antibiotics usage, while in PCT group patients' PCT value was observed everyday. When no active symptoms of infection were shown, and acute physiology and chronic health evaluation II (APACHEII) scores declined, PCT value decreased over 90% or PCT value lower than 0.25 μg/L time point were selected as drug withdrawal indication. The general status of the patient, antimicrobial drug use time, and prognosis were compared between the two groups, and Kaplan-Meier method was used for survival curve analysis. Variance analysis was used for repeating measurement to observe dynamic serum PCT level of the two groups of patients for survival and death during 7 days.. Mann-Whitney U test or χ(2) test showed that there were no statistical significance in age, gender, APACHEII score, blood culture positive rate, sputum culture positive rate, cardiac insufficiency, renal failure, respiratory failure, and ventilator and hemofiltration usage (all P>0.05). Log Rank test results showed that the time of antimicrobial drug usage was significantly reduced in PCT group than that in RAT group [days: 8.1±0.3, 95% confidence interval (95%CI 8.3-9.7) vs. 9.3±0.3 (95%CI 8.7-10.1), P=0.013]. Kaplan-Meier univariate survival curves showed that the speed of curve declination in PCT group was faster significantly than that in RAT group, suggesting that the time of using antimicrobial drug was shortened. There was no significant difference in length of hospital stay, ICU stay time, number of death in 28 days, number of cases of recurrence in 28 days and clinical cure rate between two groups (all P>0.05). PCT level in non-survivors in both groups was significantly higher than that in the survivors, exceeding more than 10 μg/L in the early and late stages of treatment.. Dynamic monitoring of PCT can effectively reduce antimicrobial drug use in ICU patients with sepsis, but there is no significant difference in patients' prognosis.

Topics: Adult; Aged; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis

Infectious complications frequently occur after major trauma, leading to increased morbidity and mortality. Thrombin-activatable fibrinolysis inhibitor (TAFI), a procarboxypeptidase in plasma, plays a dual role in regulating both coagulation and inflammation. Activated TAFI (TAFIa) has broad anti-inflammatory properties due to its inactivation of active inflammatory mediators (anaphylatoxins C3a and C5a, bradykinin, osteopontin).. The purpose of this study was to determine if TAFI plays a role in the development of inflammatory complications after major trauma.. Upon arrival at the emergency department (ED), plasma levels of TAFI and TAFIa were measured in 26 multiple traumatized patients for 10 consecutive days. Systemic levels of inflammatory mediators, including interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) and leukocytes were determined.. Fifteen patients developed pneumonia and/or sepsis (compl) and 11 had no complications (wo compl). Overall injury severity and age were comparable in both groups. Complications occurred approximately 5 days after trauma. IL-6 increased on day 5, whereas CRP, PCT and leukocytes started to increase on day 6 in the compl-group. Upon arrival at the ED and on days 1 and 4, TAFI levels were significantly lower in the compl-group compared to the wo compl-group (p=0.0215). Similarly, TAFIa was significantly lower on day 4 in the compl-group than in the wo compl-group (p=0.049).. This pilot study shows that TAFI levels are inversely correlated with inflammation-associated development of complications after major trauma.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carboxypeptidase B2; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Leukocyte Count; Male; Middle Aged; Multiple Trauma; Pilot Projects; Pneumonia; Protein Precursors; Sepsis; Time Factors

Early-onset sepsis (EOS) is one of the main causes for the admission of newborns to the neonatal intensive care unit. However, traditional infection markers are poor diagnostic markers of EOS. Pancreatic stone protein (PSP) is a promising sepsis marker in adults. The aim of this study was to investigate whether determining PSP improves the diagnosis of EOS in comparison with other infection markers.. This was a prospective multicentre study involving 137 infants with a gestational age of >34 weeks who were admitted with suspected EOS. PSP, procalcitonin (PCT), soluble human triggering receptor expressed on myeloid cells-1 (sTREM-1), macrophage migration inhibitory factor (MIF) and C-reactive protein (CRP) were measured at admission. Receiver-operating characteristic (ROC) curve analysis was performed.. The level of PSP in infected infants was significantly higher than that in uninfected ones (median 11.3 vs. 7.5 ng/ml, respectively; p = 0.001). The ROC area under the curve was 0.69 [95 % confidence interval (CI) 0.59-0.80; p < 0.001] for PSP, 0.77 (95 % CI 0.66-0.87; p < 0.001) for PCT, 0.66 (95 % CI 0.55-0.77; p = 0.006) for CRP, 0.62 (0.51-0.73; p = 0.055) for sTREM-1 and 0.54 (0.41-0.67; p = 0.54) for MIF. PSP independently of PCT predicted EOS (p < 0.001), and the use of both markers concomitantly significantly increased the ability to diagnose EOS. A bioscore combining PSP (>9 ng/ml) and PCT (>2 ng/ml) was the best predictor of EOS (0.83; 95 % CI 0.74-0.93; p < 0.001) and resulted in a negative predictive value of 100 % and a positive predictive value of 71 %.. In this prospective study, the diagnostic performance of PSP and PCT was superior to that of traditional markers and a combination bioscore improved the diagnosis of sepsis. Our findings suggest that PSP is a valuable biomarker in combination with PCT in EOS.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Lithostathine; Macrophage Migration-Inhibitory Factors; Male; Membrane Glycoproteins; Prospective Studies; Protein Precursors; Receptors, Immunologic; ROC Curve; Sepsis; Switzerland; Triggering Receptor Expressed on Myeloid Cells-1

REsearching severe Sepsis and Organ dysfunction in children: A gLobal perspective (RESOLVE), a phase III trial of drotrecogin alfa (activated) in pediatric severe sepsis, examined biomarker changes in inflammation and coagulation. This report describes biomarker profiles in early severe sepsis and the pharmacodynamic assessment of drotrecogin alfa (activated) in RESOLVE.. Serial measurements of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tissue necrosis factor-α, procalcitonin, D-dimer, and thrombin-antithrombin complex were performed at baseline and daily over the first five study days. Protein C levels were performed at baseline and at the end of the 96-hr study drug infusion. Analysis of variance-based log-transformed data compared the treatment groups for each measured variable.. : One hundred four pediatric intensive care units in 18 countries.. Four hundred seventy-seven children between 38 wks corrected gestational age and 17 yrs with sepsis-induced cardiovascular and respiratory dysfunction.. Drotrecogin alfa (activated).. Pharmacodynamic activity of drotrecogin alfa (activated) compared with placebo was observed with reduction of D-dimer on day 1 (p < .01) and thrombin-antithrombin complex on days 1-4 (p < .05). There were no significant changes by treatment in multiple cytokines or procalcitonin. In the overall population, a median protein C difference was not observed (p > .05) with drotrecogin alfa (activated) administration compared with placebo, although a difference (median percentage change from baseline) in favor of drotrecogin alfa (activated) was observed in patients >1 yr old (p = .0449).. While children in the RESOLVE trial were similar to adults in that they showed a relationship between severity of coagulation and inflammation abnormalities and mortality, their pharmacodynamic response to drotrecogin alfa (activated) differed with respect to changes in protein C activity and systemic inflammation.

Topics: Adolescent; Anti-Infective Agents; Antithrombin III; Biomarkers; Blood Proteins; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cytokines; Disseminated Intravascular Coagulation; Double-Blind Method; Female; Fibrin Fibrinogen Degradation Products; Humans; Infant; Infant, Newborn; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Peptide Hydrolases; Protein C; Protein Precursors; Recombinant Proteins; Respiratory Insufficiency; Sepsis; Survival Analysis; Time Factors; Tumor Necrosis Factor-alpha

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 μg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

Topics: Aged; Anti-Bacterial Agents; Bacteria; Calcitonin; Calcitonin Gene-Related Peptide; Drug Therapy; Female; Fever of Unknown Origin; Humans; Leukocytosis; Male; Protein Precursors; Recurrence; Sepsis; Treatment Outcome

Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality.. This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group (n = 75) received Se for 14 days (1,000 μg on day 1,500 μg/day on days 2-14). Patients in both the control (Se-) group (n = 75) and the Se+ group received a standard Se dose (<75 μg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28.. Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP (P = 0.035), PCT (P = 0.022) and SOFA (P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences.. High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups.

Topics: Adult; Aged; Antioxidants; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Multiple Organ Failure; Prealbumin; Prospective Studies; Protein Precursors; Selenium; Sepsis

For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.. Randomized controlled open-label trial.. Nine multidisciplinary intensive care units across Denmark.. A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥ 24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive).. : Patients were randomized either to the "standard-of-care-only arm," receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the "procalcitonin arm," in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements.. The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] -4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0-6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15-1.27).. Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.

Topics: Aged; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Protein Precursors; Respiration, Artificial; Sepsis; Time Factors

The aim of this study was to compare the efficacy of serum amyloid A (SAA) with that of C-reactive protein (CRP), and procalcitonin (PCT) in diagnosis and follow-up of necrotizing enterocolitis (NEC) in preterm infants.. A total of 152 infants were enrolled into this observational study. The infants were classified into 3 groups: group 1 (58 infants with NEC and sepsis), group 2 (54 infants with only sepsis), and group 3 (40 infants with neither sepsis nor NEC, or control group). The data including whole blood count, CRP, PCT, SAA, and cultures that were obtained at diagnosis (0 hour), at 24 and 48 hours, and at 7 and 10 days were evaluated.. A total of 58 infants had a diagnosis of NEC. Mean CRP (7.4 ± 5.2 mg/dL) and SAA (46.2 ± 41.3 mg/dL) values of infants in group 1 at 0 hour were significantly higher than those in groups 2 and 3. Although the area under the curve of CRP was higher at 0 hour in infants with NEC, there were no significant differences between groups with respect to the areas under the curve of SAA, CRP, and PCT at all measurement times. Levels of SAA decreased earlier than CRP and PCT in the follow-up of NEC (mean SAA levels were 45.8 ± 45.2, 21.9 ± 16.6, 10.1 ± 8.3, and 7.9 ± 5.1 mg/dL at evaluation times, respectively). Levels of CRP and SAA of infants with NEC stages II and III were significantly higher than those with only sepsis and/or NEC stage I.. Serum amyloid A, CRP, and PCT all are accurate and reliable markers in diagnosis of NEC, in addition to clinical and radiographic findings. Higher CRP and SAA levels might indicate advanced stage of NEC. Serial measurements of SAA, CRP, and PCT, either alone or in combination, can be used safely in the diagnosis and follow-up of NEC.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Enterocolitis, Necrotizing; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Protein Precursors; Sepsis; Serum Amyloid A Protein

Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success.. To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis.. This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children's Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age >or=34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48-72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values.. 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics >or=72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12-0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events.. Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Decision Making; Drug Monitoring; Early Diagnosis; Female; Gestational Age; Humans; Infant, Newborn; Male; Prospective Studies; Protein Precursors; Sepsis; Treatment Outcome

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Granulocyte-Macrophage Colony-Stimulating Factor; HLA-DR Antigens; Humans; Immunologic Factors; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenic Acid; Kynurenine; Male; Middle Aged; Placebos; Protein Precursors; Quinolinic Acid; Sepsis; Serotonin; Shock, Septic; Treatment Outcome; Tryptophan

Diagnosis/grading of infection and the systemic response to infection may be difficult on admission to the intensive care unit, but it is even more complicated for severely ill patients with long intensive care stays. The ACCP-SCCM criteria are difficult to apply for such patients, and objective, validated biomarkers would be of great use in this setting.. Long-term (>6 days) critically ill patients in the general ICU of University Hospital were prospectively enrolled in the study. All patients were assessed daily by the attending physician using the ACCP-SCCM classification. C-reactive protein (CRP, mg/dL), procalcitonin (PCT, ng/mL), and interleukin-6 (IL-6, pg/mL) of daily stored sera were measured after each patient's discharge. After discharge, an independent, overall clinical evaluation and an a posteriori ACCP-SCCM classification were chosen as the reference standard for all comparisons. The assessor was aware of the patient's clinical course but was blinded to levels of biomarkers.. We studied clinical variables and biomarkers of 26 patients over a total of 592 patient days. The day-by-day ACCP-SCCM classification of the attending physician overestimated the severity of the inflammatory response to infection. The diagnostic discriminative ability of severe-sepsis/septic-shock for PCT was high (ROC area 0.952 [0.931-0.973]) and had a best threshold value of 1.58 (83.7% sensitivity, 94.6 % specificity). IL-6 had better discriminative ability than CRP, but both were worse than PCT.. PCT > 0.43 ng/mL could add to the clinical propensity for sepsis vs. SIRS not related to infection. Values higher than 1.58 ng/mL may support the bedside clinical diagnosis of severe-sepsis. PCT between 0.5 and 1.0 suggest tight daily monitoring of clinical conditions and re-evaluation of PCT.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Decision Making; Diagnosis, Differential; Female; Hospitals, University; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Single-Blind Method; Systemic Inflammatory Response Syndrome

Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications. Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation. Therefore, many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven. With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis.. The study is designed as randomized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment. Term and near-term infants (gestational age ≥ 34 0/7 weeks) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included. The duration of antibiotic therapy in the standard group is based on the attending physician's assessment of the likelihood of infection (infection unlikely, possible, probable or proven). In the Procalcitonin group, if infection is considered to be unlikely or possible, antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range. Co-primary outcome measures are the duration of antibiotic therapy (superiority aspect of the trial) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and/or death in the first month of life (safety of study intervention, non-inferiority aspect of the trial). The number of infants to be included equals 800 per arm. With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety, i.e. excluding a disadvantage difference larger than 2% for the experimental arm, will both be greater than 80%.. Benefit of the study is a possible limitation of unnecessary use of antibiotics. The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early, resulting in the development of a neonatal infection with its morbidity and mortality.. This trial is registered in the U.S. National Institutes of Health's register, located at http://www.clinicaltrials.gov. (NCT00854932).

Topics: Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Administration Schedule; Early Diagnosis; Female; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; International Cooperation; Male; Protein Precursors; Secondary Prevention; Sepsis; Treatment Outcome

Adequate indication and duration of administration are central issues of modern antibiotic treatment in intensive care medicine. The biochemical variable procalcitonin (PCT) is known to indicate systemically relevant bacterial infections with high accuracy. In the present study, we aimed to investigate the clinical usefulness of PCT for guiding antibiotic treatment in surgical intensive care patients with severe sepsis.. Patients were randomly assigned to a PCT-guided or a control group requiring antibiotic treatment. All patients received a calculated antibiotic regimen according to the presumed microbiological spectrum. In the PCT-guided group, antibiotic treatment was discontinued if clinical signs of infection improved and the PCT value was either <1 ng/ml or decreased to <35% of the initial concentration within three consecutive days. In the control group, antibiotic treatment was directed by empirical rules.. The PCT-guided group (n = 14 patients) and the control group (n = 13 patients) did not differ in terms of biological variables, underlying diseases, and overall disease severity. PCT guidance led to a significant reduction of antibiotic treatment from 6.6 +/- 1.1 days (mean +/- SD) compared with 8.3 +/- 0.7 days in control patients (p < 0.001) along with a reduction of antibiotic treatment costs of 17.8% (p < 0.01) without any adverse effects on outcome.. Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients with severe sepsis. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistances and costs in intensive care medicine.

Topics: Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Drug Administration Schedule; Female; Hospital Mortality; Humans; Length of Stay; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis

The efficacy of direct hemoperfusion with polymyxin B-immobilized fiber columns (PMX) has already been demonstrated in clinical studies for the treatment of septic shock. However, serum procalcitonin levels following PMX remain unknown.. This prospective, multicenter, nonrandomized clinical study was performed at 12 institutions. Forty-five patients with severe sepsis or septic shock due to colorectal perforation underwent PMX. Patients' outcome as well as circulating levels of endotoxin, procalcitonin and IL-6 were monitored.. Before surgery, procalcitonin level, but not endotoxin and IL-6 levels, was elevated according to patients' septic conditions. Procalcitonin was significantly and positively correlated with sequential organ failure assessment score. Circulating levels of procalcitonin peaked 24 h after PMX treatment. Change in serum procalcitonin level was significantly higher in nonsurvivors than survivors. Nine mortalities were observed within 28 days. The best predictor for 28-day mortality was procalcitonin >85.7 ng/ml at 24 h after PMX (area under the receiver operating characteristic curve: 0.808 +/- 0.105).. Procalcitonin may be a good indicator of severity of sepsis secondary to colorectal perforation. Furthermore, procalcitonin level at 24 h after PMX appears to predict outcome after PMX. Therefore, procalcitonin may be a useful diagnostic marker to evaluate patients' condition in candidates for PMX treatment.

Topics: Aged; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Colonic Diseases; Endotoxins; Female; Hemoperfusion; Humans; Interleukin-6; Intestinal Perforation; Male; Peritoneal Diseases; Polymyxin B; Prospective Studies; Protein Precursors; Rectal Diseases; Sepsis; Severity of Illness Index; Treatment Outcome

The development of resistance by bacterial species is a compelling issue to reconsider indications and administration of antibiotic treatment. Adequate indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care setting. Until recently, no laboratory marker has been available to differentiate bacterial infection from viral or non-infectious inflammatory reaction; however, over the past years, procalcitonin (PCT) is the first among a large array of inflammatory variables that offers this possibility. The present study aimed to investigate the clinical usefulness of PCT for guiding antibiotic therapy in surgical intensive care patients.. All patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections and at least two concomitant systemic inflammatory response syndrome criteria were eligible. Patients were randomly assigned to either a PCT-guided (study group) or a standard (control group) antibiotic regimen. Antibiotic therapy in the PCT-guided group was discontinued, if clinical signs and symptoms of infection improved and PCT decreased to <1 ng/ml or the PCT value was >1 ng/ml, but had dropped to 25 to 35% of the initial value over three days. In the control group antibiotic treatment was applied as standard regimen over eight days.. A total of 110 surgical intensive care patients receiving antibiotic therapy after confirmed or high-grade suspected infections were enrolled in this study. In 57 patients antibiotic therapy was guided by daily PCT and clinical assessment and adjusted accordingly. The control group comprised 53 patients with a standardized duration of antibiotic therapy over eight days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter than compared to controls (5.9 +/- 1.7 versus 7.9 +/- 0.5 days, P < 0.001) without negative effects on clinical outcome.. Monitoring of PCT is a helpful tool for guiding antibiotic treatment in surgical intensive care patients. This may contribute to an optimized antibiotic regimen with beneficial effects on microbial resistance and costs in intensive care medicine. ANNOTATION: Results were previously published in German in Anaesthesist 2008; 57: 571-577 (PMID: 18463831).. ISRCTN10288268.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Drug Monitoring; Female; Humans; Male; Postoperative Complications; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Sepsis and complications to sepsis are major causes of mortality in critically ill patients. Rapid treatment of sepsis is of crucial importance for survival of patients. The infectious status of the critically ill patient is often difficult to assess because symptoms cannot be expressed and signs may present atypically. The established biological markers of inflammation (leucocytes, C-reactive protein) may often be influenced by other parameters than infection, and may be unacceptably slowly released after progression of an infection. At the same time, lack of a relevant antimicrobial therapy in an early course of infection may be fatal for the patient. Specific and rapid markers of bacterial infection have been sought for use in these patients.. Multi-centre randomized controlled interventional trial. Powered for superiority and non-inferiority on all measured end points. Complies with, "Good Clinical Practice" (ICH-GCP Guideline (CPMP/ICH/135/95, Directive 2001/20/EC)). Inclusion: 1) Age > or = 18 years of age, 2) Admitted to the participating intensive care units, 3) Signed written informed consent.Exclusion: 1) Known hyper-bilirubinaemia. or hypertriglyceridaemia, 2) Likely that safety is compromised by blood sampling, 3) Pregnant or breast feeding. Computerized Randomisation: Two arms (1:1), n = 500 per arm: Arm 1: standard of care. Arm 2: standard of care and Procalcitonin guided diagnostics and treatment of infection. Primary Trial Objective: To address whether daily Procalcitonin measurements and immediate diagnostic and therapeutic response on day-to-day changes in procalcitonin can reduce the mortality of critically ill patients.. For the first time ever, a mortality-endpoint, large scale randomized controlled trial with a biomarker-guided strategy compared to the best standard of care, is conducted in an Intensive care setting. Results will, with a high statistical power answer the question: Can the survival of critically ill patients be improved by actively using biomarker procalcitonin in the treatment of infections? 700 critically ill patients are currently included of 1000 planned (June 2008). Two interim analyses have been passed without any safety or futility issues, and the third interim analysis is soon to take place. Trial registration number at clinicaltrials.gov: Id. nr.: NCT00271752).

Topics: Adolescent; Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Male; Protein Precursors; Sepsis

The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.. To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock.. In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased 90% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 microg/L) or Day 5 (if baseline PCT levels were >/=1 microg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.. Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (intention-to-treat, n = 79, P = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per protocol, n = 68, P = 0.003) and a smaller overall antibiotic exposure (P = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).. Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm.

Topics: Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Protocols; Critical Illness; Female; Glycoproteins; Humans; Kaplan-Meier Estimate; Length of Stay; Male; Middle Aged; Protein Precursors; Recurrence; Sepsis; Shock, Septic

The development of resistance by infective bacterial species is an incentive to reconsider the indications and administration of available antibiotics. Correct recognition of the indications and duration of therapy are particularly important for the use of highly potent substances in the intensive care situation. There has as yet been no clinical chemical parameter which is capable of specifically distinguishing a bacterial infection from a viral or non-infectious inflammatory reaction, but it now appears that procalcitonin (PCT) offers this possibility. The present study was intended to clarify whether PCT can be used to guide antibiotic therapy in surgical intensive care patients. A total of 110 patients in a surgical intensive care ward receiving antibiotic therapy after confirmed infection or a high grade suspicion of infection were enrolled in this study. In 57 of these patients a new decision was reached each day as to whether the antibiotic therapy should be continued after daily PCT determination and clinical assessment. The control group consisted of 53 patients with a standardized duration of antibiotic therapy over 8 days. Demographic and clinical data were comparable in both groups. However, in the PCT group the duration of antibiotic therapy was significantly shorter compared to controls (5.9+/-1.7 vs. 7.9+/-0.5 days, p<0.001) without unfavorable effects on clinical outcome.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Drug Resistance, Bacterial; Female; Humans; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Treatment Outcome

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever; Humans; Lymphadenitis; Male; Protein Precursors; Sepsis; Stomatitis, Aphthous; Syndrome

In surgical sepsis, the rapid identification of source of infection at an early stage after surgery or serious trauma is crucial for favorable outcome. The discrimination between local and generalized infection is critical for correct treatment.. In a randomized, controlled, single-centre study we investigated 72 patients with severe sepsis after major abdominal surgery or surgery for multiple trauma. Patients were divided in 2 groups: in the first group (PCT, n=38), more important role in the treatment decision was given to PCT level (severe sepsis with PCT >2 ng/mL signalled bacteremia and pushed us to change antibiotics and intravascular devices, severe sepsis with PCT < or =2 ng/mL prompted use of ultrasonography and/or CT, followed by repeated surgery in patients with localized infection). The control group (CON, n=34) was treated by standard evaluation of all parameters by consultant surgeon. We investigated 28-day all-cause mortality, sepsis-related complications, the duration of stay in the intensive care unit, and ventilated days.. The hospital mortality was in PCT group 26% and 38% in control group (p = 0.28). Average SOFA score was 7.9 +/- 2.8 in PCT group vs. 9.3 +/- 3.3 (p = 0.06). The decline of ICU days (16.1 +/- 6.9 vs. 19.4 +/- 8.9; p = 0.09) and ventilated days (10.3 +/- 7.8 vs. 13.9 +/- 9.4; p = 0.08) in PCT group was observed, but the difference was not significant.. We observed a clear tendency to decrease extent of multiple organ dysfunction syndrome in patients, in which therapeutic decision was made earlier using procalcitonin as an additional marker separating local infection from generalized one.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Decision Support Techniques; Female; Humans; Injury Severity Score; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Postoperative Complications; Predictive Value of Tests; Protein Precursors; Reoperation; Respiration, Artificial; Sepsis

The therapeutic effect of crude rhubarb on intestinal permeability was investigated in septic patients. Forty septic patients were enrolled in this study and randomly divided into two groups: the crude rhubarb treatment group (n = 18) and the control group (n = 22). The same treatments were given to both groups except that the crude rhubarb treatment group was administrated with crude rhubarb powders (3 g, tid, p.o). The levels of procalcitonin, D-lactate in plasma and lactulose/mannitol (L/M) ratio in the urine were determined on the first day and the sixth day after treatment with or without crude rhubarb. There were no significant differences in procalcitonin, L/M ratio and D-lactate on the first day between the crude rhubarb treatment group and the control group (p > 0.05). However, the ratio of L/M on the sixth day for the control group was 0.167 +/- 0.036, while that of the crude rhubarb treatment group was 0.062 +/- 0.013 (p < 0.05). Moreover, the levels of procalcitonin and D-lactate in the crude rhubarb treatment group were obviously lower than those in the control group on the sixth day (procalcitonin: 4.11 +/- 1.40 microg/L vs. 2.21 +/- 0.61 mug/L; D-lactate: 0.24 +/- 0.06 ng/L vs. 0.09 +/- 0.03 ng/L, p < 0.05, both). These data confirmed that crude rhubarb's effects on septic patients of ameliorating intestinal permeability.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intestinal Absorption; Lactates; Lactulose; Male; Mannitol; Middle Aged; Phytotherapy; Plant Preparations; Protein Precursors; Rheum; Sepsis

To investigate the effects of raw rhubarb (RR) on levels of plasma D-lactate and procalcitonin in patients with sepsis.. Forty patients with sepsis enrolled were randomly divided into two groups, the RR group (n=18, treated with RR 9 g/d) and the control group (n=22, treated with conventional treatment). Plasma procalcitonin and D-lactate were determined before and after treatment.. Before treatment, there was no significant difference in the levels of plasma procalcitonin and D-lactate between the two groups (procalcitonin: 6.50 +/- 2.37 microg/L vs 6.98 +/- 2.89 microg/L; D-lactate: 0.18 +/- 0.05 mmol/L vs 0.19 +/- 0.06 mmol/L, P > 0.05). However, after treatment, two indexes in the RR group were significantly lower than those in the control group (procalcitonin: 4.11 +/- 1.40 microg/L vs 2.21 +/- 0.61 microg/L; D-lactate: 0.24 +/- 0.06 ng/L vs 0.09 +/- 0.03 ng/L, both P < 0.05).. RR could ameliorate the intestinal permeability and reduce the shifting of intestinal bacteria, so as to ease the condition of disease in patients with sepsis.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Drugs, Chinese Herbal; Female; Humans; Lactic Acid; Male; Middle Aged; Phytotherapy; Protein Precursors; Rheum; Sepsis

Evaluation the value of procalcitonin as a diagnostic and prognostic marker in septic patients and patients with systemic inflammatory response syndrome (SIRS).. 126 patients were included into the study. The patients were divided into four groups: 1--septic patients with positive blood cultures, 2--septic patients with negative blood cultures, 3--patients with SIRS, 4--patients without sepsis and SIRS. PCT level was measured by imunoluminometric assay (LUMItest) and immunochromatographic assay (PCT-Q).. PCT level is higher in patients with sepsis than in patients with SIRS. PCT level is only slightly elevated in patients without sepsis and SIRS. The highest PCT level is found in patients with septic shock. In patients with the clinical improvement the frequency of PCT level increase is approximately twice lower than in patients who died.. Measurement of PCT level on the first, second and third day of hospitalization has no prognostic value. There is no significant difference in PCT level in sepsis caused by Gram positive and Gram negative bacteria. PCT is a useful marker in diagnosis of sepsis but its role in monitoring the severity of sepsis requires more clinical studies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Chromatography; Female; Humans; Immunoassay; Male; Middle Aged; Protein Precursors; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

The aim of this study was to investigate the effect of low-dose hydrocortisone on glomerular permeability measured by the microalbuminuria to creatinine ratio (MACR) and on other markers of sepsis in severe septic patients.. Randomized prospective study.. University intensive care unit.. The study involved 40 patients with severe sepsis randomized into the hydrocortisone group (n = 20) and the standard therapy group (n = 20).. The hydrocortisone group received standard therapy plus a continuous infusion of hydrocortisone for 6 days, whereas the standard therapy group received only standard therapy.. MACR, serum C-reactive protein, and procalcitonin concentrations were recorded every day from the day before the steroid therapy (T(0)) until the 6 days after (T(1), T(2), T(3), T(4), T(5), and T(6)). Concentrations in the hydrocortisone group and the standard therapy group were compared using Mann-Whitney test at each time. We also compared with Wilcoxon signed rank test the values determined in each group at T(0) with those at each subsequent time. Median MACR decreased from T(0) to T(6) in both patient groups; however, values were significantly lower in the hydrocortisone group from T(3) through to T(6). Median serum C-reactive protein also decreased from T(0) in both patient groups, with significantly lower values in the hydrocortisone group from T(3) through to T(6). There were no significant differences in procalcitonin between groups compared with baseline values or at any individual time point.. Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis. Further studies are needed to confirm these results and to understand the underlying molecular mechanisms.

Topics: Aged; Albuminuria; Anti-Inflammatory Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Humans; Hydrocortisone; Intensive Care Units; Middle Aged; Prospective Studies; Protein Precursors; Sepsis

To describe the course of plasma sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin (PCT), and C-reactive protein (CRP) concentrations during sepsis and their clinical informative value in predicting outcome.. Prospective, noninterventional study.. Medical adult intensive care unit at a university hospital in France.. Sixty-three critically ill patients with sepsis, severe sepsis, or septic shock.. None.. Soluble TREM-1 concentrations were significantly lower at admission in nonsurvivors (n = 21) than in survivors (n = 42) (94 [30-258] vs. 154 [52-435] pg/mL, p = .02), whereas PCT levels were higher among nonsurvivors (19.2 [0.3-179] vs. 2.4 (0-254) pg/mL, p = .001). CRP levels did not differ between the two groups of patients. Plasma PCT and CRP decreased during the 14-day period of study in both survivors and nonsurvivors. Conversely, sTREM-1 plasma concentrations remained stable or even increased in nonsurviving patients and decreased in survivors. An elevated baseline sTREM-1 level was found to be an independent protective factor with an odds of dying of 0.1 (95% confidence interval, 0.1-0.8).. A progressive decline of plasma sTREM-1 concentration indicates a favorable clinical evolution during the recovery phase of sepsis. In addition, baseline sTREM-1 level may prove useful in predicting outcome of septic patients.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sepsis; Survival Analysis; Time Factors; Triggering Receptor Expressed on Myeloid Cells-1

Despite recent advances in the prospective identification of the patient with sepsis who may benefit from anti-inflammatory or antithrombotic therapies, successful treatment regimens have been fairly modest. We have explored whether determination of several proinflammatory cytokine or mediator concentrations can complement physiologic scoring systems to identify patients with severe sepsis who will survive or expire within 28 days. The design of the study included an exploratory analysis performed in conjunction with a prospective, randomized, double-blind, placebo-controlled, multicenter, clinical trial and involved 33 academic institutions in the United States. One hundred twenty-four patients with severe sepsis with or without septic shock were included in this analysis. Blood samples were obtained at baseline and on days 1 through 4, and were evaluated for proinflammatory and anti-inflammatory cytokine concentrations, as well as for procalcitonin and total protein C levels. Baseline concentrations and changes in the concentrations of these mediators were evaluated in relationship to the Acute Physiology and Chronic Health Evaluation (APACHE) II and multiple organ dysfunction (MOD) scores, and 28-day all-cause mortality. Using univariate logistic regression analyses, APACHE II and MOD scores, age (but not gender), and baseline plasma interleukin (IL)-6 and soluble tumor necrosis factor receptor (sTNFR) 1 (log transformed) concentrations were all predictive of increased 28-day all-cause mortality (P < 0.01). Baseline total protein C, IL-8, IL-10, TNF-alpha, and procalcitonin concentrations, and the change in plasma cytokine concentrations from baseline over the initial 4 days were not useful in predicting outcome. Selected baseline proinflammatory cytokine concentrations and APACHE II score were correlated (P < 0.01). IL-6 concentration is a strong candidate for predicting clinical outcome in patients with severe sepsis alone, or when combined with the APACHE II or MOD scores. The potential usefulness of the combination of cytokine measurements and prognostic scores to identify patients who may benefit from treatment with anti-inflammatory or antithrombotic therapies should be further evaluated.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Placebos; Prognosis; Protein C; Protein Precursors; Receptors, Tumor Necrosis Factor; Regression Analysis; Respiratory Distress Syndrome; Risk; Sepsis; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

The clinical relevancy of an attractive new multiparametric method, cytometric beads assay (CBA), was evaluated for the monitoring of cytokines in sepsis.. A total of 52 samples (26 patients) were simultaneously tested by CBA and chemiluminescence (IL-6, IL-8, IL-1beta, and TNFalpha) or ELISA (IL-10, IL-12 p40, IL-12 p70, and soluble TNFalpha-RI).. CBA standard curves were linear from 20-5,000 ng/L except for IL-1beta (40-5,000 ng/L). IL-6 and IL-8 were detected in 41 and 48 samples (44-5,000 ng/L and 22-5,000 ng/L), respectively, and out of range in six samples. IL-10 and IL-1beta were detected in 14 and 15 samples (21-1,548 ng/L and 29-582 ng/L), respectively. TNFalpha was rarely detected, and IL-12 p70 was never detected. Accuracy and repeatability were good (CV for IL-6 was 2.1-8.7%; for IL-8 3.7-5.3%; for IL-10 2.5-9.1%; for IL-12 5.2-6.5%; for IL-1 beta 4-12%; and for TNFalpha 3-19.3%). Reproducibility of four standard curves and 20 samples (-1.1 to +1.03%) was excellent between tests done at two- to six-week intervals. CBA values were correlated (r2 > 0.89; P < 0.001) with our reference methods, but were lower on CBA (TNFalpha 45% +/- 8; IL-6 49% +/- 7), probably due to interactions with patients' serum, as confirmed by spiking diluted standards in one patient's serum with end stage renal failure and high levels of TNF soluble receptor (i.e., TNFalpha levels 34 and 21%).. Finally, these results suggest that IL-6, IL-8, IL-1beta, and Il-10 are clinically promising for sepsis evaluation. However, sensitivity of TNFalpha has to be improved and IL-12 p70 should be replaced with more relevant parameters such as TNF-R, procalcitonin, or neopterin.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Flow Cytometry; Humans; Intensive Care Units; Luminescent Measurements; Male; Microspheres; Middle Aged; Protein Precursors; Sepsis

The diagnosis of sepsis in critically ill patients is challenging because traditional markers of infection are often misleading. The present study was conducted to determine the procalcitonin level at early diagnosis (and differentiation) in patients with systemic inflammatory response syndrome (SIRS) and sepsis, in comparison with C-reactive protein, IL-2, IL-6, IL-8 and tumour necrosis factor-alpha.. Thirty-three intensive care unit patients were diagnosed with SIRS, sepsis or septic shock, in accordance with the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. Blood samples were taken at the first and second day of hospitalization, and on the day of discharge or on the day of death. For multiple group comparisons one-way analysis of variance was applied, with post hoc comparison. Sensitivity, specificity and predictive values of PCT and each cytokine studied were calculated.. PCT, IL-2 and IL-8 levels increased in parallel with the severity of the clinical condition of the patient. PCT exhibited a greatest sensitivity (85%) and specificity (91%) in differentiating patients with SIRS from those with sepsis. With respect to positive and negative predictive values, PCT markedly exceeded other variables.. In the present study PCT was found to be a more accurate diagnostic parameter for differentiating SIRS and sepsis, and therefore daily determinations of PCT may be helpful in the follow up of critically ill patients.

Topics: Adult; Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Interleukin-2; Interleukin-6; Interleukin-8; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

A number of European studies have documented the ability of procalcitonin (PCT), a novel inflammatory marker, to discriminate patients with sepsis from those with other causes of systemic inflammatory response syndrome (SIRS). The aim of this study was to assess procalcitonin's performance in an Australian intensive care unit (ICU) setting to examine whether it could discriminate between these two conditions. One hundred and twenty-three consecutive adult ICU patients fulfilling criteria for SIRS were enlisted in the study. Over a period of five days, daily serum PCT and C-reactive protein (CRP) levels were measured. At least two sets of cultures were taken of blood, sputum/broncho-alveolar lavage (BAL) and urine. Other cultures were taken as clinically indicated. Questionnaires to ascertain clinical suspicion of sepsis were prospectively answered by the ICU senior registrars. PCT values were ten times higher in patients with positive blood cultures; CRP values were also significantly higher in the bacteraemic patients. Both PCT and CRP had a good ability to discriminate bacteraemia from non-infectious SIRS, with the area under receiver operating characteristics (ROC) curves for PCT being 0.8 and for CRP being 0.82. However neither PCT or CRP was able to discriminate patients with localized sepsis from those without. Utilizing both tests resulted in a more sensitive screen than either one alone, while PCT was a more accurate diagnostic test for bacteraemia than CRP. The PCT value also differed between those who died in hospital and those who survived. Measurement of PCT alone or in combination with CRP can aid discrimination of septicaemia/bacteriemia with associated SIRS from non-infectious SIRS in an Australian ICU setting.

Topics: Australia; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Type and frequency of postoperative abnormalities were registered after cardiovascular surgery to evaluate the aetiology and diagnostic value of increased concentrations of procalcitonin (PCT) and C-reactive protein (CRP) during the early postoperative period.. Prospective, observational study.. Two hundred and eight patients undergoing coronary artery bypass grafting or valve replacement requiring cardiopulmonary bypass were monitored for 7 days postoperatively for various types of infectious or non-infectious complications. Plasma PCT and CRP levels were measured on day 1 and day 2 after surgery and, when increased, until day 7.. More patients with PCT above 2 ng/ml on day 1 or 2 (n=55) had postoperative abnormalities (95%) than patients with lower PCT (59%). Specifically, the incidence of three or more criteria of the "systemic inflammatory response syndrome" was 45% versus 4% (area under the curve of the receiver operating characteristic 0.866); positive inotropic support was needed in 65% versus 9% (0.870); respiratory insufficiency (PaO(2)/FIO(2)<200) 38% versus 12% (0.704); proven and suspected bacterial infection 9% versus 1% (0.900) and 24% versus 1% (0.897), respectively. For CRP, the respective areas under the curve were all below 0.63, while all patients had elevated CRP levels, whether they had a complication or not.. Elevated PCT, but not CRP, correlates with evidence of systemic inflammation and other complications early postoperatively after cardiac surgery. Although the PCT levels do not rise as quickly as the criteria of the systemic inflammatory response syndrome appear, they do reflect systemic inflammation. Early identification and quantification of a systemic inflammatory response may help reduce postoperative complications.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Humans; Male; Postoperative Complications; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis.. Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores.. Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either.. Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.

Topics: Adolescent; Adult; Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Glasgow Coma Scale; Humans; Immunoglobulin A; Immunoglobulin M; Length of Stay; Male; Middle Aged; Protein Precursors; Sepsis; Treatment Outcome

: In critically ill patients, severe infection and systemic inflammation due to non-infectious causes produce very similar clinical presentations, and traditional infection markers do not always differentiate these two conditions. Both procalcitonin and neopterin have been suggested to aid in the early diagnosis of bacterial infections and in differentiating bacterial infections from systemic inflammatory, non-infectious diseases or from viral infections.. : Procalcitonin (PCT) and neopterin were analyzed in 208 ICU patients who developed acute fever or septic shock. Blood samples were taken every 8th h within 48 h of the onset of fever or septic shock.. : A total 162/208 of patients had infection, the most common location being the respiratory tract. Mortality was higher in infected patients (31.4% vs. 10.9%; P < 0.01). The optimum cut-off levels in identifying patients with infection of daily peak PCT were 0.8 microg/L on day 1 and 0.9 microg/L on day 2, and both sensitivity (67.7% and 60.9%, respectively) and specificity (47.8% and 63%) were poor. Accordingly, the optimum cut-off values of peak neopterin were 18 and 16 pg/L. The sensitivity was 62.7% on day 1 and 69.3% on day 2, while specificity was correspondingly 78.3% and 67.9%. There were no significant differences between the markers in discriminating between patients with infection or inflammation. Both PCT and neopterin increased with the severity of infection. They were higher in non-survivors.. : PCT and neopterin were equally effective, although not very accurate in differentiating between infection and inflammation in critically ill patients. Neopterin was more specific than PCT, suggesting that neopterin is related to the activity of inflammatory response.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever; Hospital Mortality; Humans; Infections; Male; Middle Aged; Neopterin; Protein Precursors; Sepsis; Shock; Survivors

Does procalcitonin (PCT) allow differentiation between infection and rejection following liver transplantation in the case of fever of unknown origin (FUO)?. Open prospective trial.. transplant intensive care unit at a university hospital.. Forty patients after liver transplantation.. Liver biopsy for diagnosis of rejection, transcutaneous aspiration cytology for monitoring of lymphocyte activation.. Procalcitonin from EDTA plasma, APACHE II, Sepsis, score (Elbute and Stoner).. Eleven patients suffered an infectious complication resulting in an increase in PCT levels (2.2-41.7 ng/ml). Eleven patients developed a rejection episode; none of these patients showed a rise in PCT levels. The statistical difference between PCT levels in rejection and infection was significant (p<0.05) on the day of diagnosis.. PCT allows differentiation between rejection and infection in the case of FUO. Elevation of PCT plasma levels develops early postoperatively due to operation trauma, and, in the case of FUO with no rise in PCT, a rejection may be suspected.

Topics: Analysis of Variance; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Fever of Unknown Origin; Graft Rejection; Humans; Liver Transplantation; Male; Postoperative Complications; Prospective Studies; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis

To understand the presence or absence of bacterial infection in patients with systemic inflammatory response syndrome (SIRS), the level of procalcitonin (PCT), a precursor of calcitonin, was determined. Subjects consisted of 14 SIRS patients without complication by bacterial infection, 14 SIRS patients complicated by sepsis, and 14 SIRS patients complicated by severe sepsis and septic shock. PCT levels in SIRS patients with sepsis (2.9 +/- 2.3 ng/ml) were significantly higher than those in SIRS patients without complication by infection (0.7 +/- 1.1 ng/ml). However, there were no significant differences in the levels of C-reactive protein (CRP), interleukin 6 (I-6) or tumor necrosis factor-alpha (TNF-alpha) between the two groups. PCT levels in SIRS patients with severe sepsis and septic shock (172.2 +/- 276.3 ng/ml) were significantly higher than those in SIRS patients with sepsis. Levels of CRP, IL-6 and TNF-alpha were also significantly higher in the patients with sepsis compared to those in patients with local infection. Significant correlations were observed between the levels of PCT and those of CRP, IL-6 and TNF-alpha in SIRS patients. It was suggested that to measure the levels of procalcitonin in patients with SIRS is useful to diagnose the infection and severity of illness.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Infections; Middle Aged; Protein Precursors; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Patients (n=242) admitted to intensive care unit for longer than 48 hours were categorised for sepsis according to American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) Consensus Conference criteria. Body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT) as well as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, IL-10 and HLA-DR expression on monocytes were determined. Data of one randomly chosen day per patient entered analysis. Immunologic mediators contributing significantly to outcome were determined by logistic regression analysis. Area under the curves (AUC) of receiver operating characteristic curves of clinical markers of inflammation predicting prognosis were compared with AUC of relevant immunologic mediators. TNF-alpha, IL-6 and HLA-DR expression on monocytes were significantly associated with outcome; the AUC's were 0.835, 0.844 and 0.761 respectively. AUC's for clinical markers were 0.878, 0.811, 0.620 and 0.614 for PCT, CRP, leukocyte count and body temperature respectively. PCT had the highest AUC compared to other clinical markers. These data indicate that PCT might be a better marker than the classic criteria of inflammation, CRP, leukocyte count, and body temperature to identify patients endangered by severe infection or sepsis.

Topics: Adult; Aged; Biomarkers; Body Temperature; Calcitonin; Calcitonin Gene-Related Peptide; Female; HLA-DR Antigens; Humans; Inflammation; Interleukin-6; Leukocyte Count; Male; Middle Aged; Outcome Assessment, Health Care; Prognosis; Protein Precursors; Regression Analysis; Sepsis; Tumor Necrosis Factor-alpha

Topics: Adult; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

To evaluate the association of Procalcitonin (PCT) with severity in Coronavirus disease 2019 (COVID-19), hospitalised patients and to test the hypothesis that it is an independent predictor of mortality.. This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine and Department of Medicine, Aga Khan University (AKU), Karachi Pakistan. Electronic medical records of all in-patients including both genders and all age groups with documented COVID-19 from March to August 2020 were reviewed and recorded on a pre-structured performa. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. Between-group differences were tested using the Chi-square and Mann-Whitney's U-test. The receiver operating characteristic curve was plotted for serum PCT with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analysed using SPSS.. 336 patients were reviewed as declared COVID-19 positive during the study duration, and 136 were included in the final analysis including 101 males and 35 females. A statistically significant difference in PCT was found between severe and non-severe COVID-19 (p value=0.01); and survivors and nonsurvivors (p value<0.0001). PCT, older age and increased duration of hospital stay were revealed as variables independently associated with mortality. On ROC analysis, an AUC of 0.76 for mortality prediction was generated for PCT.. Baseline serum PCT concentration is a promising predictor of mortality and severity in COVID-19 cases when considered in combination with clinical details and other laboratory tests.

Topics: Aged; Biomarkers; Calcitonin Gene-Related Peptide; COVID-19; Female; Hospitalization; Humans; Inpatients; Male; Pakistan; Procalcitonin; Prognosis; Retrospective Studies; SARS-CoV-2; Sepsis; Severity of Illness Index

Our objective is to analyze whether the combination of C-reactive protein (CRP), procalcitonin (PCT), presepsin or SCD14-ST and mid-regional pro-adrenomedullin (MR-proADM) measured in the first 24 h from ICU admission allowing a better management of septic patients (diagnostic and prognostic) both in severe sepsis (SS) and septic shock (SSh).. Cohort study of 388 patients admitted in the ICU during 12 months of whom 142 were controls. Biomarkers were measured through immunoluminometric assays in samples of serum or plasma within the first 24 h after admission. Data were evaluated with non-parametric statistics bivariant, ROC curve analysis for diagnostic evaluation and multivariate analyses for survival analysis.. In the analyzed cohort, 61.8% of patients were males, mean age: 63 years range (18-90) and 67.8% in controls mean age: 63 years, range (39-91). PCT showed the highest area under the curve (AUC) (0.989) as compared with the rest of biomarkers (p<0.01). PCT also enabled the difference between Gram-positive or Gram-negative bacteria to be determined. The AUCs for CRP (0.922) and presepsin (0.948) showed a similar diagnostic value. In cases of SSh, the AUC of presepsin experienced a noticeable increase (p<0.0001). MR-proADM showed a better prognostic value (p=0.00022) particularly in cases of SSh (p=0.00001) increasing along with the APACHE-II score.. PCT, MR-proADM and presepsin are complementary markers that could be of great help in the management of septic patients when they are measured in the first 24 h after ICU admission.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Immunologic Techniques; Lipopolysaccharide Receptors; Luminescent Measurements; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Survival Analysis; Young Adult

Rapid and accurate prediction for sepsis remains a challenge in surgical intensive care units. Detection of individual biomarkers is often of marginal usefulness, and several biomarkers are difficult to measure in the clinical setting. The aim of this study was to evaluate the diagnostic and prognostic performance of three routine biomarkers, procalcitonin (PCT), B-type natriuretic peptide (BNP), and lymphocyte percentage, as individual or in combination for sepsis in surgical critically ill patients.. Circulating PCT, BNP, and lymphocyte percentage were measured in surgical patients on admission to the intensive care unit. A bioscore system combining these biomarkers was constructed. All studied variables were analyzed according to the diagnosis and clinical outcomes of sepsis.. A total of 320 consecutive patients were included in the analysis. One hundred fifty-six patients presented with sepsis. In the patients with sepsis, levels of PCT and BNP increased and lymphocyte percentage decreased. For individual biomarkers, PCT achieved the best area under the curve for the diagnosis of sepsis, whereas the diagnostic performance of the bioscore was better than that of each individual biomarker (area under the curve, 0.914 [95% confidence interval, 0.862-0.951]). Levels of BNP and bioscore increased in nonsurvivors in the entire cohort, but the accuracy of these two variables for mortality prediction was lower than that shown by Acute Physiology and Chronic Health Evaluation II score. Furthermore, bioscore failed to predict outcomes in septic patients.. A simple bioscore combining PCT together with BNP and lymphocyte percentage improves the diagnostic accuracy for sepsis in surgical critically ill patients but fails to predict outcomes in surgical patients with sepsis.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Support Techniques; Female; Humans; Lymphocyte Count; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Prognosis; Prospective Studies; Protein Precursors; Sepsis

Presepsin is a useful marker for differentiating sepsis from non-infection-related systemic inflammatory response syndrome. There are data describing elevated presepsin concentrations in patients with kidney dysfunction even in the absence of sepsis, but corresponding data for patients with end-stage kidney disease (ESKD) undergoing living kidney transplantation (LKT) are lacking. We investigated the changes in presepsin concentrations in this patient group in order to elucidate any relationship with renal function. Written informed consent was obtained from patients with ESKD requiring hemodialysis who underwent LKT from June 2014 through March 2015 at Hirosaki University Hospital. Patients with obvious signs of infection were excluded. Perioperative presepsin and procalcitonin concentrations were measured before induction of anesthesia, on admission to the intensive care unit after surgery, and on postoperative day (POD) 1 and POD 2. Preoperative presepsin concentration was markedly higher than the upper limit of normal in patients with ESKD (1252 ± 451 pg/mL). Presepsin concentrations consistently decreased after LKT. Moreover, presepsin concentration was strongly correlated with serum creatinine (r (2) = 0.72, n = 24, p < 0.001). These data suggest that the kidney clearly plays an important role in the metabolism and excretion of presepsin.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Kidney Failure, Chronic; Kidney Function Tests; Kidney Transplantation; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Pilot Projects; Protein Precursors; Sepsis

Numerous investigations on procalcitonin (PCT) have been carried out, although few with large sample size. To deal with the complexity of sepsis, an understanding of PCT in heterogeneous clinical conditions is required.. Hospitalized patients aged 10-79 years were included in this retrospective and cross-sectional study. PCT tests were assayed within 2 days of blood culture.. A total of 2952 cases (from 2538 patients) were enrolled in this study, including 440 cases in the 'positive BC' group, 123 cases in the 'positive body fluid culture' group, and 2389 cases in the 'negative all culture' group. Median PCT values were 4.53 ng/ml, 2.95 ng/ml, and 0.49 ng/ml, respectively. Median PCT values in the gram-negative BC group and gram-positive BC group, respectively, were 6.99 ng/ml and 2.96 ng/ml. Median PCT values in the 'positive hydrothorax culture' group, 'positive ascites culture' group, 'positive bile culture' group, and 'positive cerebrospinal fluid culture' group, respectively, were 1.39 ng/ml, 8.32 ng/ml, 5.98 ng/ml, and 0.46 ng/ml. In all, 357 cases were classified into the 'sepsis' group, 150 of them were classified into the 'severe sepsis' group. Median PCT values were 5.63 ng/ml and 11.06 ng/ml, respectively.. PCT could be used in clinical algorithms to diagnose positive infections and sepsis. Different PCT levels could be related to different kinds of microbemia, different infection sites, and differing severity of sepsis.

Topics: Adolescent; Adult; Aged; Algorithms; Bacteremia; Biomarkers; Body Fluids; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; China; Cross-Sectional Studies; Female; Hospitalization; Humans; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis; Severity of Illness Index; Young Adult

The aim of this study was to determine whether neutrophil CD64 (nCD64) combined with procalcitonin (PCT), C-reactive protein (CRP) and white blood cell count (WBC) can increase the sensitivity and accuracy of neonatal sepsis diagnosis.. The serum levels of nCD64, CRP, PCT and WBC were detected in 60 patients with neonatal sepsis and 60 patients with non-sepsis. Sensitivity, specificity, positive and negative predictive values, receiver operating characteristic (ROC) area under the curve (AUC), and logistic regression analysis were performed to evaluate the diagnostic value of these markers on neonatal sepsis.. Serum levels of nCD64, PCT, CRP and WBC were higher in the sepsis group than non-sepsis group (p<0.001). The sensitivities of nCD64, PCT, CRP and WBC at the recommended cut-off level for all infants were 79.5%, 68.2%, 38.6% and 52.3%, respectively. The best combination was nCD64 and PCT, which obtained sensitivity of 90.9%, largest AUC of 0.922, and a negative predictive value of 89.2%. However by using an optimal cut-off value, the sensitivities of all four biomarkers for the diagnosis of neonatal sepsis were increased to 95.5%. Except for WBC, the birth weight and gestational age had no effects on the diagnostic value of these serum biomarkers.. nCD64 and PCT are better diagnostic biomarkers for early diagnosis of neonatal sepsis as compared to CRP. With the help of optimal cut-off value based on ROC curve and logistic regression analysis, the combination of these biomarkers could improve the sensitivity for the diagnosis of suspected late-onset neonatal sepsis based on common serum biomarkers.

Topics: Area Under Curve; Biomarkers; Birth Weight; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Early Diagnosis; Female; Gestational Age; Humans; Infant; Infant, Newborn; Leukocyte Count; Logistic Models; Male; Neutrophils; Odds Ratio; Protein Precursors; Receptors, IgG; Retrospective Studies; ROC Curve; Sepsis

This study aims to assess the diagnostic and prognostic value of endocan in patients with severe sepsis or septic shock on a medical intensive care unit (ICU).. 150 patients suspected for at least severe sepsis were enrolled on a medical ICU. On days 1, 3, and 8, plasma levels of endocan, procalcitonin (PCT), and interleukin (IL)-6 were measured. Follow-up on all-cause mortality was performed after 30 days and 6 months.. Endocan correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II) (P < .006). Endocan was higher in patients with at least severe sepsis compared with systemic inflammatory response syndrome (SIRS) or sepsis patients (P = .0006) on days 1, 3, and 8. With a minimum sensitivity of 70%, uniform cutoff levels were set for ≥ sepsis at 1.8 ng/mL, for ≥ severe sepsis at 2.6 ng/mL, for ≥ septic shock at 2.9 ng/mL. On day 1, endocan levels of the fourth quartile were significantly associated with 30-days and 6-months mortality compared to lower levels. After adjustment in Cox regressions, endocan still revealed prognostic value.. Endocan showed diagnostic capacity to diagnose patients with severe sepsis and septic shock and revealed prognostic information for 30-days and 6-months all-cause mortality.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Neoplasm Proteins; Predictive Value of Tests; Prognosis; Protein Precursors; Proteoglycans; Regression Analysis; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Cytoreductive-surgery for peritoneal-malignancy (PM) involves extensive intra-abdominal surgery and a massive post-operative systemic-inflammatory-response (SIRS). It is often challenging to differentiate SIRS that are solely surgery-associated from those of post-operative infections. White-Cell-Counts (WCC) and C-Reactive-Protein (CRP) are routinely used as markers for infection, but are non-specific and their elevation is often delayed in PM cases. Other markers need to be evaluated to assist early identification/prediction of post-operative infections.. Prospective evaluation of serum procalcitonin (PCT), CRP and WCC in 50 patients pre-operatively (Day0), and on post-operative days (POD) 1, 3 & 6, following cytoreductive-surgery with or without splenectomy.. Day0 PCT, CRP and WCC values were within normal limits, but increasing physiologically in post-operative period without infection, with noticeable higher PCT in splenectomized patients. In our cohort post-operative infections were diagnosed in 14 patients, often within 48 h. There was a trend for faster rise in serum PCT on POD1 compared to CRP and WCC, and faster PCT decline following appropriate therapy on POD3 and POD6 when infected cases were clinically resolving while WCC and CRP continued to rise, particularly in non-spelenectomised patients. The AUC on POD1 was significantly higher for PCT (0.689) vs. WCC (0.476) and CRP (0.477) (p = 0.04). Sensitivity, specificity, positive-predictive-value and negative-predictive-values for PCT ranged between (57%-100%), (22%-74%), (33%-47%) & (81%-100%), for CRP (28%-78%), (5.5%-86%), (18%-44.4%) & (40%-75.5%) and for WCC (14%-26.5%), (65.5-80.5%), (22%-25%), (67%-70%) respectively.. PCT, like WCC and CRP, needs to be interpreted with extreme cautions in the context of infections post-cytoreductive-surgery and should only be used in association with other clinical and investigational findings.

Topics: Adult; Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytoreduction Surgical Procedures; Diagnosis, Differential; Female; Humans; Infections; Intraabdominal Infections; Leukocyte Count; Male; Middle Aged; Peritoneal Neoplasms; Pneumonia, Bacterial; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Splenectomy; Surgical Wound Infection; Systemic Inflammatory Response Syndrome; Time Factors

The objective of this study was to assess the diagnostic accuracy of C-reactive protein (CRP), procalcitonin (PCT), and cellular immune markers levels in sepsis. This was a prospective observational study in adult intensive care unit (ICU) patients, between 2012 and 2014. The 8-color flow cytometric biomarker panel included CD64, CD163, and HLA-DR. Index test results were compared with sepsis, using receiver operating characteristic curve analyses. Multivariate logistic regression assessed the relationship of sets of markers with the probability of sepsis. Of 219 enrolled patients, 120 had sepsis. C-statistic was the highest for CRP (0.86) followed by neutrophil CD64 expression (0.83), procalcitonin (0.82), and Acute Physiology and Chronic Health Evaluation (APACHE) IV (0.72). After adjustment for APACHE IV, the combination of CRP, PCT, and neutrophil CD64 measure remained a significant predictor of sepsis with an excellent AUC (0.90). In a targeted ICU population at increased risk of sepsis, CRP, PCT, and neutrophil CD64 combined improve the diagnostic accuracy of sepsis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Chemical Analysis; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Double-Blind Method; Female; Flow Cytometry; Humans; Leukocytes; Male; Membrane Proteins; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Cell-free circulating DNA (cf-DNA) can be detected by various of laboratory techniques. We described a branched DNA-based Alu assay for measuring cf-DNA in septic patients. Compared to healthy controls and systemic inflammatory response syndrome (SIRS) patients, serum cf-DNA levels were significantly higher in septic patients (1426.54 ± 863.79 vs 692.02 ± 703.06 and 69.66 ± 24.66 ng/mL). The areas under the receiver operating characteristic curve of cf-DNA for normal vs sepsis and SIRS vs sepsis were 0.955 (0.884-1.025), and 0.856 (0.749-0.929), respectively. There was a positive correlation between cf-DNA and interleukin 6 or procalcitonin or Acute Physiology and Chronic Health Evaluation II. The cf-DNA concentration was higher in intensive care unit nonsurviving patients compared to surviving patients (2183.33 ± 615.26 vs 972.46 ± 648.36 ng/mL; P < .05). Branched DNA-based Alu assays are feasible and useful to quantify serum cf-DNA levels. Increased cf-DNA levels in septic patients might complement C-reactive protein and procalcitonin in a multiple marker format. Cell-free circulating DNA might be a new marker in discrimination of sepsis and SIRS.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cell-Free System; DNA; Female; Humans; Interleukin-6; Male; Mass Screening; Middle Aged; Predictive Value of Tests; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

The level of soluble urokinase-type plasminogen activator receptor (suPAR) is significantly increased in sepsis. We investigated whether suPAR could be a valuable biomarker in sepsis.. We measured suPAR and procalcitonin (PCT) levels, recorded the Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores of engaged subjects, and drew Receiver Operating Characteristics curves.. The plasma suPAR and serum PCT levels of the sepsis group were higher than those of the systemic inflammatory response syndrome and control groups. Using suPAR to distinguish systemic inflammatory response syndrome from sepsis on day 1, the area under the curve (AUC) curve was 0.817, and when suPAR and PCT were used in combination to diagnose sepsis, the AUC was 0.927. At a cutoff point of 9.52 ng/mL, the sensitivity and specificity for diagnosis of sepsis using suPAR were 71.93% and 95.46%, respectively. At a cutoff point of 12.01 ng/mL, the sensitivity and specificity for distinguishing survival and mortality by suPAR were 87.1% and 72.5%, respectively. When suPAR and the APACHE II score were combined to distinguish survival from mortality, the AUC was 0.857. The plasma suPAR level was positively correlated with the serum PCT level (r = 0.326, P < .001), APACHE II score (r = 0.492, P < .001), and Sequential Organ Failure Assessment score (r = 0.386, P < .001).. Use of both plasma suPAR and PCT levels enhanced the efficiency of sepsis diagnosis, and the combination of plasma suPAR and APACHE II score improved mortality prediction.

Topics: APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; China; Diagnosis, Differential; Female; Hospital Mortality; Humans; Male; Middle Aged; Organ Dysfunction Scores; Predictive Value of Tests; Prognosis; Protein Precursors; Receptors, Urokinase Plasminogen Activator; Sepsis

Sepsis is a major cause of morbidity and mortality in the emergency department. This study aimed to evaluate the assessment of severity of sepsis by and prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL) compared with other widely used biological markers of inflammation in patients with sepsis.. NGAL, procalcitonin, and C-reactive protein values were measured in 470 patients with suspected sepsis, and the Mortality in Emergency Department Sepsis (MEDS) score was obtained for all enrolled subjects, who were followed for up to 28days.. The median plasma NGAL value was increased with sepsis severity according to the MEDS score. The plasma NGAL value was higher in nonsurvivors than in survivors. The area under the receiver operating characteristic curve of NGAL (0.797) was greater than that of procalcitonin (0.599) and MEDS score (0.774) in predicting 28-day hospital mortality. Multivariable logistic regression found that the plasma NGAL value was an independent predictor for hospital mortality in patients with sepsis. The plasma NGAL values were positively correlated with C-reactive protein and procalcitonin levels, and MEDS scores.. Plasma NGAL is a valuable biological marker in the assessment of severity and prediction of prognosis of patients with sepsis in the emergency department.

Topics: Acute-Phase Proteins; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Lipocalin-2; Lipocalins; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Protein Precursors; Proto-Oncogene Proteins; Sepsis; Severity of Illness Index; Survival Rate

Urosepsis, a severe form of sepsis requires immediate medical attention for prognosis. It is clinically diagnosed by estimating serum procalcitonin (PCT) levels along with time taking urine and blood cultures. We explored NMR based profiling, deriving metabolites that could potentially aid diagnosis.. The proton NMR of serum and urine samples of healthy control subjects (n=32) and urosepsis cases (n=35) based on PCT levels, were analyzed. Four clinically identified non-urosepsis cases with high PCT levels were also differentiated through principal component analysis (PCA) of the serum samples.. Quantification of serum and urine through Discriminant Function Analysis (DFA) afforded 93.7% and 91.7% correct classification respectively, along with identification of malonate and urea as potential biomarkers for the disease in both urine and serum samples. The partial least square discriminant analysis (PLS-DA) showed an R(2) value of 0.97 in both biofluids with Q(2)=0.87 and 0.85 for serum and urine respectively. The training set of serum samples provided precise prediction of the test set in a small cohort through random re-sampling method, while in urine samples, the predictions were inconclusive.. Our pilot study reveals that (1)H NMR of serum metabolic profiling in combination with PCT levels may provide a rapid method for differentiation of urosepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Diagnosis, Differential; Humans; Magnetic Resonance Spectroscopy; Pilot Projects; Protein Precursors; Sepsis; Time Factors; Urinary Tract Infections

To investigate the changes in plasma gelsolin (pGSN) levels in severe burn patients with sepsis, and to evaluate the prognosis of patients when combined with other related clinical indexes.. Sixty-five severe burn patients with sepsis hospitalized from June 2013 to June 2015 conforming to the study criteria were divided into death group (n=24) and survival group (n=41) according to the clinical outcome on post sepsis diagnosis day (PSD) 28. The pGSN levels of patients were determined on PSD 1, 3, 7, and 14 with double antibody sandwich enzyme-linked immunosorbent assay. The serum level of C-reactive protein (CRP), serum level of procalcitonin, lactate level of arterial blood, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and Sequential Organ Failure Assessment (SOFA) score were determined or recorded on PSD 1. Data were processed with repeated measurement analysis of variance, t test, and chi-square test. On PSD 1, the pGSN level, serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of 65 patients were collected to screen the independent risk factors related to death with single factor and multi-factor Logistic regression analysis. Receiver operating characteristic (ROC) curves of the independent risk factors related to death were plotted to evaluate the predictive power for death in 65 patients.. (1) The pGSN levels of patients in death group on PSD 1, 3, 7, and 14 were respectively (146±44), (85±24), (28±7), and (19±4) mg/L, obviously lower than those in survival group [(287±82), (179±51), (196±56), and (249±67) mg/L, with t values from 1.735 to 4.304, P<0.05 or P<0.01]. (2) The serum level of CRP, serum level of procalcitonin, lactate level of arterial blood, APACHE II score, and SOFA score of patients in death group on PSD 1 were respectively (56±7) mg/L, (12.54±0.82) μg/L, (2.74±0.27) mmol/L, (24.3±2.4) points, and (11.43±0.57) points, significantly higher than those in survival group [(35±4) mg/L, (2.38±0.16) μg/L, (1.83±0.12) mmol/L, (15.0±1.5) points, and (7.22±0.23) points, with t values from 1.902 to 3.883, P<0.05 or P<0.01]. (3) Multi-factor Logistic regression analysis showed that the pGSN level (odds ratio: 6.83, 95% confidence interval: 4.33-10.25, P<0.01) and APACHE II score (odds ratio: 5.27, 95% confidence interval: 2.28-9.16, P<0.01) were the independent risk factors related to death in 65 patients on PSD 1. (4) The total areas under the ROC curves of pGSN level and APACHE II score for predicting death of 65 patients on PSD 1 were respectively 0.89 and 0.86, and 142 mg/L and 21 points were respectively chosen as the optimal threshold values, with sensitivity of 87% and 83% and specificity of 86% and 89%.. For severe burn patients with sepsis, lowering of pGSN level and elevation of APACHE II score are obviously correlated with increase in case fatality rates. Monitoring the dynamic changes in pGSN level and APACHE II score during the early stage may be useful to predict the prognosis of severe burn patients with sepsis.

Topics: Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Gelsolin; Hospitalization; Humans; Organ Dysfunction Scores; Prognosis; Protein Precursors; Regression Analysis; Risk Factors; ROC Curve; Sepsis; Severity of Illness Index

To compare the results of thrombelastography (TEG) and the conventional coagulability test in patients with sepsis, and to discuss the value of TEG in monitoring blood coagulation dysfunction in patients with sepsis.. The clinical data of 92 adult patients with sepsis admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. The patients were divided into sequential organ failure assessment (SOFA) score ≥ 12 group (n = 47) and SOFA < 12 group (n = 45). Thirty-five non-sepsis adult patients with normal coagulation function served as control group. The venous blood was collected for conventional blood coagulation test and routine examination of blood, D-dimer, procalcitonin (PCT), and TEG, and the differences were compared among three groups. Correlations between SOFA and various indexes of patients with sepsis were analyzed by Spearman rank correlation method.. As shown in the results of the conventional blood coagulation test, D-dimer was gradually increased with the aggravation of the disease, the values in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.523 (0.273, 0.928), 0.863 (0.673, 4.221), and 4.118 (2.420, 5.653) mg/L respectively (Z = 25.163, P = 0.000). Platelet count (PLT) in SOFA ≥ 12 group was significantly lower than that of the SOFA < 12 group and non-sepsis group [×10(9)/L: 28.6 (12.8, 48.9) vs. 257.3 (152.6, 339.8), 182.0 (118.0, 229.0), both P < 0.01]. There was no significant difference in prothrombin time (PT) and international normalized ratio (INR) among three groups, and it indicated that the conventional blood coagulation test might not respond quickly to the change in coagulation status of sepsis patients. As shown in the results of TEG, the values of reaction time (R value) and kinetics time (K value) in SOFA < 12 group were lower than those of the non-sepsis group [R value (minutes): 4.4 (3.6, 6.1) vs. 6.3 (6.0, 6.7), P < 0.01; K value (minutes): 1.1 (1.0, 1.5) vs. 1.5 (1.3, 1.8), P < 0.05], while they were higher in SOFA ≥ 12 group than those of the non-sepsis group [R value (minutes): 7.0 (5.7, 8.7) vs. 6.3 (6.0, 6.7), P > 0.05; K value (minutes): 4.2 (3.4, 7.1) vs. 1.5 (1.3, 1.8), P < 0.01]. The α angle, maximum amplitude (MA) and coagulation index (CI) in SOFA < 12 group were higher than those of the non-sepsis group [α angle (degree angle): 73.3 (68.5, 74.7) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 71.7 (61.9, 73.3) vs. 60.3 (58.2, 63.8), P < 0.01; CI: 3.1 (-0.1, 3.9) vs. 0.9 (-0.4, 1.3), P < 0.05], while they were lower in SOFA ≥ 12 group than those of the non-sepsis group [α angle (degree angle): 48.1 (36.6, 53.0) vs. 66.8 (62.2, 69.0), P < 0.01; MA (mm): 37.8 (30.0, 45.7) vs. 60.3 (58.2, 63.8), P < 0.01; CI: -5.6 (-8.4, -3.6) vs. 0.9 (-0.4, 1.3), P < 0.01]. The above results indicated that TEG could distinguish quickly the hypercoagulability and hypocoagulability status in septic patients. PCT in non-sepsis, SOFA < 12, and SOFA ≥ 12 groups were 0.27 (0.05, 1.80), 0.68 (0.10, 10.00), 41.10 (4.24, 100.00) μg/L respectively (Z = 195.475, P = 0.000), which indicate the severity of infectious disease. Correlation analysis results showed that SOFA score was negatively correlated with PLT, α angle, MA, and CI (r value was -0.853, -0.833, -0.881, and -0.859, respectively, all P = 0.000), and it was positively correlated with activated partial thromboplastin time (APTT), D-dimer, R. TEG can effectively monitor the change in coagulation in patients with sepsis, and distinguish the hypercoagulable and hypocoagulable state. TEG may be a valuable tool to evaluate degree and risk of sepsis objectively.

Topics: Adult; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; China; Fibrin Fibrinogen Degradation Products; Humans; Platelet Count; Protein Precursors; Retrospective Studies; Sepsis; Thrombelastography

To analyze the changes in serum procalcitonin (PCT) in patients with extremely severe burn and sepsis, and to evaluate its clinical significance in the prognosis of patients.. Thirteen patients with extremely severe burn and sepsis injured in the aluminum dust explosion accident, which occurred in Kunshan of Jiangsu province, were admitted to our unit on August 2nd, 2014. They were involved in this retrospective study and divided into death group (n=5) and survival group (n=8) according to the outcome. Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score and Sequential Organ Failure Assessment (SOFA) score at post admission hour (PAH) 24 were compared among the patients between two groups. Serum level of PCT, serum level of C-reactive protein (CRP), white cell count, neutrophils, platelet count, level of aspartate transaminase (AST), level of prealbumin (PA), level of creatinine, level of urea nitrogen, and level of blood sodium were compared among the patients between two groups in post admission week (PAW) 1, 2, 3, and 4. Data were processed with Fisher's exact test, analysis of variance for repeated measurement, t test, and Mann-Whitney test. Receiver operating characteristic (ROC) curves of serum PCT values were plotted to evaluate the predictive value for death of 13 patients in PAW 3 and 4.. The differences in APACHE Ⅱ score and SOFA score at PAH 24 and serum level of CRP, white cell count, level of AST, level of creatinine, level of urea nitrogen, and level of blood sodium from PAW 1 to 4 of the patients between two groups were not statistically significant (with t values from -1.164 to 0.587, Z values from -1.872 to -0.442, P values above 0.05). The serum levels of PCT in patients of death group in PAW 3 and 4 were respectively (15.8±14.9) and (13.6±5.6) ng/mL, which were significantly higher than those of survival group [(2.4±1.8) and (4.9±6.1) ng/mL, with Z values respectively -2.635 and -2.208, P<0.05 or P<0.01]. The serum levels of PCT of patients in death group and survival group in PAW 1 and 2 were close (with Z values respectively -0.732 and -1.025, P values above 0.05). Compared with those of survival group, neutrophils in PAW 4 was significantly increased (t=-3.690, P<0.01), the platelet count in PAW 4 was significantly decreased (t=4.858, P<0.01), and the level of PA in PAW 2 was significantly increased in patients of death group (t=-2.320, P<0.05). There were no statistically significant differences in neutrophils, platelet count, and the level of PA at the other time points of patients between death group and survival group (with t values from -1.562 to 1.904, P values above 0.05). The total areas under ROC curves of serum level of PCT for predicting death of 13 patients with extremely severe burn and sepsis in PAW 3 and 4 were respectively 0.938 and 0.906, and 7.45 ng/mL and 8.77 ng/mL were respectively chosen as the optimal threshold values, with sensitivity of 75.0% and 100.0% and specificity of 100.0% and 87.5%.. Serum level of PCT in PAW 3 and 4 can be used as the vital prognostic indicators for patients with extremely severe burn and sepsis, and it can be considered as a guide for rational treatment in clinic.

Topics: Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis

Severe sepsis, septic shock and bacteremia are critical illnesses, and patients with these conditions require close monitoring and immediate medical treatment. Any delay in diagnosis may lead to an increase in mortality in such critically ill patients. Serum procalcitonin (PCT) has emerged as a highly accurate biomarker for differentiating sepsis from other non-infectious triggers.. In this study, we investigated the effectiveness of PCT in obtaining early diagnosis and efficient prognosis for such patients at the Emergency Department of Rajavithi Hospital.. A prospective study was performed of 110 adult patients who attended the emergency service department between August 1 2013 and October 31 2013. The effectiveness of PCT as a specific blood test analysis tool for detecting and classifying the severity of patients with sepsis was investigated, and sensitivity, specificity, negative predictive values (NPV), positive predictive values (PPV) and positive likelihood ratio (LR+) were used to differentiate infected patients.. One hundred and ten patients were enrolled and classified into 3 categories as follows: severe sepsis (n = 34, 30.9%), septic shock (n = 13, 11.8%), and bacteremia (n = 23, 20.9%). At a PCT level of ≥ 2 ng/dL, it was feasible to categorize patients as having severe sepsis (p < 0.001; RR 3.58; 95% CI 2.18-5.89), septic shock (p = 0.001; 5.73; 2.06- 15.93) or bacteremia (p < 0.001; 3.91; 1.98-7.73). Moreover, the PCT value yielded the following diagnostic performances for patients with: severe sepsis (PPV 70.8%; NPV 80.2%; LR+ 5.0; sensitivity 50.0%; specificity 90.8%); septic shock (33.3%; 94.2%; 3.6; 61.5%; 83.5%); and bacteremia (50.0%; 87.2%; 3.7; 52.2%; 86.2%).. PCT can be usefully employed as a promising chemical biomarker to differentiate the severity of infections in critically ill patients. Used together with clinical data, the PCT value of ≥ 2 ng/dL is efficient in categorizing such patients as having severe sepsis, septic shock or bacteremia.

Topics: Adult; Aged; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

In recent years, serum levels of the prohormone procalcitonin have been investigated in a number of studies in relation to postmortem sepsis diagnostics, as macroscopic and histomorphological findings are, as a rule, nonspecific. However, due to advanced haemolysis, it is often not possible to determine serum procalcitonin (PCT) levels in cases of sepsis-related death. Moreover, the impact of postmortem interval on PCT levels is largely unclarified. In view of this, the present pilot study investigated PCT levels in the serum, aqueous humour, and cerebrospinal fluid in a study population of 25 persons who died of sepsis and a control population of 25 deaths unrelated to sepsis. Using the Mann-Whitney U test, statistically significant differences in PCT levels were determined for all the analysed samples from the study and control populations. Logistic regression analysis was used to calculate cut-off values for sepsis diagnosis for all the sample types. Furthermore, the serum elimination rates published by Tsokos et al. (Int J Legal Med 114:237-243, 2001) were used to calculate the PCT levels at the time of death for the cases with a known postmortem interval. The results of our study demonstrate that, taking account of the postmortem elimination process, it is possible to infer the value at the time of death from the procalcitonin levels measured in all three sample types and to interpret this with the aid of a defined cut-off value. The findings need to be verified based on a larger study population.

Topics: Aged; Aqueous Humor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Logistic Models; Male; Middle Aged; Pilot Projects; Postmortem Changes; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

To evaluate the value of procalcitonin (PCT) as an early marker for diagnosis and differentiation of without urosepsis, urosepsis, severe urosepsis, and uroseptic shock following PCNL and the ability of PCT to assess the effectiveness of antibiotic therapy in patients with urosepsis. From June 2012 to August 2013, 267 patients undergoing PCNL for renal calculi, and who fulfilled selection criteria, were recruited into our study. The patients' medical records were reviewed retrospectively. One of selection criteria was the scores of PCT and WBC were collected at operative day, postoperative day one, day two, day three, day five and day seven. The area under the ROC curve for the prediction of urosepsis was 0.960 for PCT and 0.634 for WBC. PCT concentrations were higher in patients with uroseptic shock versus severe urosepsis versus urosepsis versus without urosepsis following PCNL. WBC values showed no significant difference between patients with urosepsis, severe urosepsis and uroseptic shock following PCNL. With time, in patients with successfully treated urosepsis following PCNL, the PCT concentrations significantly declined and kept decreasing from postoperative day two to postoperative day seven and the WBC scores showed no significant change over the first postoperative 2 days and were decreased only after postoperative day three. PCT appears to be a useful early marker to diagnosis and discriminate urosepsis, severe urosepsis and uroseptic shock following PCNL. Daily PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in urosepsis following PCNL.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Leukocyte Count; Nephrostomy, Percutaneous; Protein Precursors; Sepsis; Urinary Tract Infections

Pancreatic stone protein/regenerating protein has recently emerged as an interesting diagnostic and prognostic marker of inflammation and sepsis in the clinical field. Increased blood concentrations have been described in patients with sepsis. Moreover, a high accuracy in predicting fatal outcomes in septic patients admitted to intensive care units has been reported. In this study, we investigated pancreatic stone protein/regenerating protein in postmortem serum in a series of sepsis-related fatalities, local infections and non-infectious cases that underwent medico-legal investigations. Procalcitonin, C-reactive protein, interleukin 6, soluble triggering receptor expressed on myeloid cells-1 and pancreatic stone protein/regenerating protein were measured in the postmortem serum collected during autopsy in a group of sepsis-related deaths, local infections and non-septic intensive care unit patients. Statistically significant differences in pancreatic stone protein/regenerating protein concentrations were observed between sepsis and control patients. A significant positive correlation was found between procalcitonin and pancreatic stone protein/regenerating protein values in septic cases. Pancreatic stone protein/regenerating protein is measurable in postmortem serum from femoral blood collected during autopsy. Additionally, as in the clinical field, pancreatic stone protein/regenerating protein can be used as a postmortem biochemical marker for the diagnosis of sepsis.

Topics: Adult; Aged; Autopsy; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Lithostathine; Male; Membrane Glycoproteins; Middle Aged; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

The purpose of the study is to compare the clearance of procalcitonin (PCT-c) in the first 24 and 48 hours of treatment of severe sepsis and septic shock with another early prognostic marker represented by the 48-hour Δ Sequential Organ Failure Assessment (SOFA).. Prospective, observational cohort study conducted in a general intensive care unit including patients with severe sepsis and septic shock. The PCT-c was determined at the diagnosis of sepsis and after 24 and 48 hours. The SOFA score was determined at the time of intensive care unit admission and after 48 hours.. One hundred thirty adult patients with severe sepsis and septic shock were studied over an 18-month period. The 24- and 48-hour PTC-c scores were significantly higher in survivors (P < .0001). In nonsurvivors, the initial SOFA was significantly higher, and the 48-hour Δ SOFA was significantly smaller (P = .01). The area under the receiver operating characteristic curve was 0.68 for Δ SOFA and 0.76 for 24- and 48-hour PCT-c.. The 48-hour Δ SOFA score and the clearance of 24- and 48-hour PCT are useful markers of prognosis in patients with severe sepsis and septic shock. A decrease in PCT-c in the first 24 hours of treatment should prompt the reassessment of the appropriateness and adequacy of treatment.

Topics: Adult; Aged; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Organ Dysfunction Scores; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Survivors; Time Factors

Differentiation between culture-negative sepsis and noninfectious systemic inflammatory response syndrome (SIRS) remains a diagnostic challenge for clinicians, both conditions having similar clinical presentations. Therefore, a swift accurate diagnostic tool, which helps differentiate these 2 conditions would immensely aid appropriate therapeutic continuum. This prospective study was conducted to evaluate the potential diagnostic role of biomarkers, procalcitonin (PCT) and interleukin 6 (IL-6), in culture-negative sepsis patients.. Enrolled patients (208) included 46 noninfectious SIRS, 90 culture-negative sepsis, and 72 culture-positive sepsis. Culture, PCT, and IL-6 estimations were performed on day 1 of intensive care unit admission.. Procalcitonin and IL-6 levels were significantly higher (P < .001) in both culture-negative and culture-positive groups as compared with SIRS group. Procalcitonin was a better predictor of sepsis in both culture-negative (area under curves 0.892 vs 0.636) and culture-positive (area under curves 0.959 vs 0.784) groups as compared with IL-6. In culture-negative group, the best cutoff point for PCT was at 1.43 ng/mL (92% sensitivity; 83% negative predictive value), best cutoff point for IL-6 was at 219.85 pg/mL (47% sensitivity and 42% negative predictive value).. Procalcitonin can accurately differentiate culture-negative sepsis from noninfectious SIRS and thereby contribute to early diagnosis and effective management of these conditions.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Area Under Curve; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Early Diagnosis; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

Procalcitonin is the prohormone of calcitonin and present in minute quantities in health. However, during infection, its levels rise considerably and are correlated with the severity of the infection. Several assays have been developed for measurement of procalcitonin levels; in this article, we will briefly present the PCT-sensitive Kryptor(®) test (Brahms, Hennigsdorf, Germany), one of the most widely used assays for procalcitonin in recent studies. Many studies have demonstrated the value of procalcitonin levels for diagnosing sepsis and assessing disease severity. Procalcitonin levels have also been successfully used to guide antibiotic administration. However, procalcitonin is not specific for sepsis, and values need to be interpreted in the context of a full clinical examination and the presence of other signs and symptoms of sepsis.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Monitoring; Energy Transfer; Humans; Immunoassay; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Spectrometry, Fluorescence

The purpose of this study was to determine whether vitamin D levels correlate with procalcitonin (PCT) levels and mortality in septic patients.. The following data were collected from 236 patients upon admission to intensive care units (ICUs): demographics; Acute Physiology and Chronic Health Evaluation (APACHE) II score; Sequential Organ Failure Assessment (SOFA) score; 25-hydroxyvitamin D (25OHD), PCT, intact PTH, albumin, creatinine, and ionized calcium (iCa) levels; 25OHD sampling seasonality; fluid load (colloid and crystalloid before 25OHD sampling); mechanical ventilation duration; and length of stay (LOS) in the ICU. The primary endpoint was all-cause mortality 28 days after ICU admission.. Patients with 25OHD deficiency had significantly higher APACHE II and SOFA scores, positive blood culture rates, PCT levels, intact PTH levels, and 28-day mortality rates. These patients also had lower iCa levels, longer LOS in the ICU, and longer ventilator durations than patients with 25OHD insufficiency or sufficiency. Age, sex, 25OHD sampling seasonality, serum albumin and creatinine levels, and fluid load did not vary among the 3 groups. Serum 25OHD levels at admission were significantly negatively correlated with PCT levels. PTH responders had significantly higher 28-day mortality rates than did PTH nonresponders. Cox regression showed that a 25OHD level of <20 ng/mL was an independent risk factor for 28-day mortality.. Lower serum 25OHD levels at ICU admission were associated with 28-day mortality in septic patients. Serum 25OHD levels were inversely correlated with PCT levels. Hypovitaminosis D was associated with higher mortality rates in PTH responders than in nonresponders.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Vitamin D; Vitamin D Deficiency

We recently derived and validated a multi-biomarker-based model (ASSIST) to stratify patients with sepsis based on initial mortality risk.. The objective of this study was to compare the performance of ASSIST to interleukin-6 (IL6) and procalcitonin (PCT).. The area-under-the-receiver operating characteristic curve for predicting 28-d mortality using ASSIST was compared with that of IL6 (n = 452) and PCT (n = 235).. The area under the curve for ASSIST was greater than that of IL6 and PCT.. ASSIST estimated the probability of mortality more reliably than IL6 and PCT in this cohort of patients with sepsis.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; Reproducibility of Results; Risk Assessment; Risk Factors; ROC Curve; Sepsis; Severity of Illness Index; Shock, Septic; Survival Analysis; Survival Rate

To investigate the correlation between procalcitonin (PCT), C-reactive protein (CRP) and acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score, and to investigate the value in assessment of PCT and CRP in prognosis in patients with sepsis.. Clinical data of patients admitted to intensive care unit (ICU) of Changzheng Hospital Affiliated to the Second Military Medical University from January 2011 to June 2014 were retrospectively analyzed. 201 sepsis patients who received PCT and CRP tests, and evaluation of APACHE II score and SOFA score were enrolled. The values of PCT, CRP, APACHE II score and SOFA score between survivals (n = 136) and non-survivals (n = 65) were compared. The values of PCT and CRP among groups with different APACHE II scores and SOFA scores were compared. The relationships between PCT, CRP and APACHE II score and SOFA score were analyzed by Spearman correlation analysis. Receiver operating characteristic (ROC) curve was plotted to assess the prognostic value of PCT and CRP for prognosis of patients with sepsis.. Compared with survival group, the values of PCT [μg/L: 11.03 (19.17) vs. 1.39 (2.61), Z = -4.572, P < 0.001], APACHE II score (19.16±5.32 vs. 10.01±3.88, t = -13.807, P < 0.001) and SOFA score (9.66±4.28 vs. 4.27±3.19, t = -9.993, P < 0.001) in non-survival group were significantly increased, but the value of CRP was not significantly different between non-survival group and survival group [mg/L: 75.22 (110.94) vs. 56.93 (100.75), Z = -0.731, P = 0.665]. The values of PCT were significantly correlated with APACHE II score and SOFA score (r1 = 0.373, r2 = 0.392, both P < 0.001), but the values of CRP were not significantly correlated with APACHE II score and SOFA score (r1 = -0.073, P1 = 0.411; r2 = -0.106, P2 = 0.282). The values of PCT rose significantly as the APACHE II score and SOFA score became higher, but the value of CRP was not significantly increased. When APACHE II score was 0-10, 11-20, and > 20, the value of PCT was 1.45 (2.62), 1.96 (9.04), and 7.41 (28.9) μg/L, respectively, and the value of CRP was 57.50 (83.40), 59.00 (119.70), and 77.60 (120.00) mg/L, respectively. When SOFA score was 0-5, 6-10, and > 10, the value of PCT was respectively 1.43 (3.09), 3.41 (9.75), and 5.43 (29.60) μg/L, and the value of CRP was 49.30 (86.20), 76.00 (108.70), and 75.60 (118.10) mg/L, respectively. There was significant difference in PCT between any two groups with different APACHE II and SOFA scores (P < 0.05 or P < 0.01), but no significant differences in CRP were found. The area under the ROC curve (AUC) of PCT for prognosis was significantly greater than that of CRP [0.872 (95% confidence interval 0.811-0.943) vs. 0.512 (95% confidence interval 0.427-0.612), P < 0.001]. When the cut-off value of PCT was 3.36 μg/L, the sensitivity was 66.8%, and the specificity was 45.4%. When the cut-off value of CRP was 44.50 mg/L, the sensitivity was 82.2%, and the specificity was 80.3%.. Compared with CRP, PCT was more significantly correlated with APACHE II score and SOFA score. PCT can be a better indicator for evaluation of degree of severity, and also prognosis in sepsis patients.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; China; Humans; Intensive Care Units; Organ Dysfunction Scores; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis

To observe the changes in plasma interleukin-33 (IL-33) in patients with sepsis and its regularity, the association between IL-33 and the infection, and the significance of IL-33 in predicting the prognosis of sepsis.. A prospective single-center single-blind clinical study was conducted. Forty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medical University from May 2012 to January 2013 were enrolled. The patients were divided into general sepsis, severe sepsis and septic shock groups according to the severity of systemic infection and presence of organ dysfunction. The sepsis patients were again divided into 28-day death group and survival group. Ten healthy volunteers and 11 patients with systemic inflammatory response syndrome (SIRS) were enrolled as healthy control and SIRS groups. The levels of procalcitonin (PCT), IL-33, IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-33 receptor sST2 were determined with enzyme linked immunosorbent assay (ELISA) within 3 hours, and 24 hours and 5 days after enrollment to ICU. The acute physiology and chronic health evaluation II (APACHE II) score was calculated. The clinical outcome, length of stay in ICU, and duration of mechanical ventilation were recorded. The relationship between IL-33 and each parameter was analyzed by Spearman analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate IL-33 in predicting the outcome of sepsis.. Plasma IL-33 in sepsis patients within 3 hours after admission was significantly increased compared with that of the healthy controls and SIRS group (ng/L: 15.43±7.22 vs. 0.67±0.24, 1.25±1.09, both P < 0.01). Compared with SIRS group, PCT in sepsis group was significantly increased [μg/L: 52.23 (19.69, 73.37) vs. 1.22 (0.69, 3.73), Z = -2.447, P < 0.001]. With exacerbation of illness, APACHE II score, the values of PCT and IL-33 were gradually increased in general sepsis, severe sepsis and septic shock groups, while the length of stay in ICU and the duration of mechanical ventilation were gradually prolonged (P < 0.05 or P < 0.01). The concentration of IL-33 (ng/L) of sepsis patients admitted to ICU within 3 hours, and 24 hours and 5 days of the illness was 15.43±7.22, 11.82±6.16, 5.55±2.25, respectively (F = 4.823, P = 0.004). There was a positive correction between IL-33 within 3 hours after ICU admission and APACHE II score (r = 0.351, P = 0.031), PCT (r = 0.412, P = 0.005), IL-6 (r = 0.535, P = 0.030), IL-1β (r = 0.674, P = 0.030), TNF-α (r = 0.250, P = 0.030), sST2 (r = 0.620, P < 0.001), and length of stay in ICU (r = 0.296, P = 0.013), duration of mechanical ventilation (r = 0.385, P = 0.011). Decreased plasma IL-33 level could be found in the survivors (n = 37, F = 7.798, P < 0.01), and its level in non-survivors (n = 3) was increased (F = 37.283, P > 0.05). The area under the ROC curve (AUC) of IL-33 and PCT in ROC curve were 0.821, 0.829. When the cut-off value of IL-33 was 13.79 ng/L, the sensitivity was 74.2%, the specificity was 79.6%; when the cut-off value of PCT was 4.70 μg/L, the sensitivity was 87.5%, and the specificity was 81.4%.. The concentration of IL-33 3 hours after ICU admission was obviously increased in sepsis patients, and it was positively correlated with PCT, therefore it is valuable in the diagnosis of the infection. In addition plasma IL-33 is related to the severity of sepsis. Its trend of change is valuable in predicting the outcome and in distinguishing sepsis from SIRS.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; China; Humans; Intensive Care Units; Interleukin-1beta; Interleukin-33; Interleukin-6; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Single-Blind Method; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha

There are few investigations regarding the relationships between procalcitonin (PCT) and the acute kidney injury (AKI) in the diagnosis of sepsis. The purpose of this study was to clarify the diagnostic accuracy of the use of PCT levels in patients with or without AKI.. This study was conducted as a single-center retrospective study. We enrolled 393 patients in whom PCT were measured on admission. We grouped the patients into non-AKI and AKI, and those with AKI were classified according to the RIFLE criteria (Risk, Injury, Failure). The patients in each group were further classified into the sepsis and the non-sepsis group. We subsequently investigated the diagnostic accuracy of the PCT for detecting sepsis in these groups.. The levels of PCT were significantly higher in the sepsis group than in the non-sepsis group among the non-AKI and each AKI patients (p < 0.0001). The diagnostic accuracy of the PCT for detecting sepsis was determined according to a ROC analysis; AUC value was 0.958 in the non-AKI group, in the Risk, Injury and Failure groups were 0.888 and 0.917, 0.857, respectively. AUC value for non-AKI group was significantly different from that of Failure group (p < 0.05).. In Failure AKI patients, the diagnostic accuracy of the PCT level is significantly lower than non-AKI patients. It is therefore suggested that we should be careful in using PCT value to diagnose sepsis in patients with Failure under RIFLE criteria.

Topics: Acute Kidney Injury; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis

To evaluate the correlation between Acute Physiology and Chronic Health Evaluation II (APACHE II) score and plasma concentrations of copeptin, C-reactive protein (CRP) and procalcitonin in patients with sepsis.. Patients with sepsis were prospectively enrolled. APACHE II scores were determined during the first 24 h after admission to the intensive care unit. Plasma copeptin, CRP and procalcitonin were quantified at admission, 24 h, 48 h, and 72 h. Survival at 28 days after admission was recorded.. APACHE II score was significantly positively correlated with plasma copeptin, CRP and procalcitonin concentrations. Survivors (n = 15) had significantly lower APACHE II scores and copeptin, CRP and procalcitonin concentrations than nonsurvivors (n = 26). APACHE II score, copeptin at 72 h, CRP at 48 h and procalcitonin at 24 h were independent risk factors for death.. Plasma copeptin, CRP and procalcitonin concentrations were positively correlated with APACHE II score in patients with sepsis, and reflected disease severity.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycopeptides; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Survival Analysis

Procalcitonin has emerged as a promising biomarker of bacterial infection. Published literature demonstrates that use of procalcitonin testing and an associated treatment pathway reduces duration of antibiotic therapy without impacting mortality. The objective of this study was to determine the financial impact of utilizing a procalcitonin-guided treatment algorithm in hospitalized patients with sepsis.. Cost-minimization and cost-utility analysis.. Hypothetical cohort of adult ICU patients with suspected bacterial infection and sepsis.. Utilizing published clinical and economic data, a decision analytic model was developed from the U.S. hospital perspective. Effectiveness and utility measures were defined using cost-per-clinical episode and cost per quality-adjusted life years (QALYs). Upper and lower sensitivity ranges were determined for all inputs. Univariate and probabilistic sensitivity analyses assessed the robustness of our model and variables. Incremental cost-effectiveness ratios (ICERs) were calculated and compared to predetermined willingness-to-pay thresholds.. Base-case results predicted the use of a procalcitonin-guided treatment algorithm dominated standard care with improved quality (0.0002 QALYs) and decreased overall treatment costs ($65). The model was sensitive to a number of key variables that had the potential to impact results, including algorithm adherence (<42.3%), number and cost of procalcitonin tests ordered (≥9 and >$46), days of antimicrobial reduction (<1.6 d), incidence of nephrotoxicity and rate of nephrotoxicity reduction.. The combination of procalcitonin testing with an evidence-based treatment algorithm may improve patients' quality of life while decreasing costs in ICU patients with suspected bacterial infection and sepsis; however, results were highly dependent on a number of variables and assumptions.

Topics: Adult; Algorithms; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Decision-Making; Cost-Benefit Analysis; Hospital Costs; Hospitalization; Humans; Models, Economic; Protein Precursors; Quality-Adjusted Life Years; Sepsis; United States

Inflammation and coagulation are closely interrelated processes in the pathogenesis of sepsis. This study aimed to determine whether intravenous immunoglobulin (IVIg) could improve the hyperinflammatory state and coagulation/fibrinolysis abnormalities in patients with sepsis.. Forty-one patients with sepsis were included. Nineteen patients were treated with IVIg (IVIg group; 5.0 g daily for 3 days within 2 days after hospitalization), and 22 patients were not (non-IVIg group). Inflammatory and coagulation/fibrinolysis molecular markers, Japanese Association for Acute Medicine disseminated intravascular coagulation score, and the Sequential Organ Failure Assessment score were evaluated in each group.. On admission, patients in the IVIg group had a significantly more severe condition. In the IVIg group, after treatment, C-reactive protein, procalcitonin, and interleukin-6 levels significantly decreased relative to values on admission. Also, compared with admission, the various coagulation/fibrinolysis molecular markers decreased after treatment. Moreover, the Japanese Association for Acute Medicine disseminated intravascular coagulation score and the Sequential Organ Failure Assessment score also significantly decreased after treatment. In contrast, in the non-IVIg group, only interleukin-6 level and thrombin-antithrombin complex levels significantly decreased. The 28-day mortality rate of the IVIg group was approximately one third of the value of the non-IVIg group (IVIg: 5.3% vs non-IVIg: 18.2%).. Intravenous immunoglobulin treatment significantly improved hemostatic abnormalities along with the hyperinflammatory state in patients with sepsis. Accordingly, IVIg treatment should be classified as an adjunctive therapy for patients complicated with sepsis-induced coagulopathy.

Topics: Aged, 80 and over; Antithrombin III; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hemostasis; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Interleukin-6; Male; Middle Aged; Organ Dysfunction Scores; Peptide Hydrolases; Protein Precursors; Retrospective Studies; Sepsis

Sepsis is a serious problem in intensive care units all over the world. Biomarkers could be useful to identify patients at risk. We focused especially on the performance of presepsin (sCD14-ST), compared to C-reactive protein (CRP), procalcitonin (PCT) and CD64, to determine its diagnostic and prognostic indications.. The study was conducted on 47 hospitalized patients after procedures, who were divided into three groups; systemic inflammatory response (SIRS), sepsis and septic shock. Expression of CD64 on neutrophils presented as CD64 index, sCD14-ST, CRP and PCT were measured in whole blood or plasma samples. All patients had standard samples like urine, respiratory tract samples etc. taken for culturing. Blood cultures were drawn to confirm bloodstream infection.. Forty (85 %) patients had SIRS with bacterial infection and seven (15 %) patients had SIRS with no infection. All infections were confirmed with blood cultures. Biomarkers were evaluated in all patients. In patients with confirmed infection the values were high. The patients with bacterial infection showed statistical significance with CD64 index (p = 0.003), CRP (p = 0.049) and sCD14-ST (p = 0.026), but not with PCT (p = 1.000). The severity of diagnosed SIRS was significant only with PCT (p < 0.001).. CD64 index, CRP and sCD14-ST served as good parameters to determine possible infection in patients that needed intensive care after major procedures. Values of PCT were the only ones to predict SIRS severity and could distinguish between sepsis and severe sepsis or septic shock.

Topics: Austria; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospitalization; Humans; Intensive Care Units; Lipopolysaccharide Receptors; Male; Peptide Fragments; Prevalence; Prognosis; Protein Precursors; Receptors, IgG; Reproducibility of Results; Risk Assessment; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

The aim of this study was to describe the role of intestinal fatty acid-binding protein (iFABP) and allergy-related diamine oxidase (DAO) in patients with heat stroke (HS).. A total of 10 patients with HS in intensive care unit and 10 healthy volunteers were enrolled in this study. The plasma intestinal permeability markers iFABP and DAO were measured since the time of admission. The whole blood endotoxin was also assessed. The associations between iFABP, DAO, and endotoxin level were analyzed. Then, white blood cell count, procalcitonin, and C-reactive protein were examined. In addition, we also determined the levels of proinflammatory cytokines such as IL-1α, IL-6, and TNF-α.. Comparing with the healthy control, the plasma iFABP and DAO level in patients with HS increased significantly (P < .05). The kinetic curve showed that plasma iFABP and DAO level reached peak value at day 3 and day 4 after admission, respectively. The endotoxin level was positively correlated with iFABP and DAO level. We also observed a significantly increased level of procalcitonin and C-reactive protein but not white blood count in patients with HS. After treatment, the iFABP and DAO level decreased significantly (P < .05). A significant increase in level of IL-1α and IL-6 was also found in patients with HS.. The plasma concentrations of DAO and iFABP could reflect a better function of the intestinal mucosa barrier in patients with HS. Plasma iFABP and DAO level decreased significantly after the treatment and, thus, might be a predictor for the severity of HS.

Topics: Adult; Amine Oxidase (Copper-Containing); C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cytokines; Disease Progression; Endotoxins; Fatty Acid-Binding Proteins; Female; Heat Stroke; Humans; Interleukin-1alpha; Interleukin-6; Intestinal Mucosa; Male; Middle Aged; Permeability; Protein Precursors; Sepsis; Severity of Illness Index; Shock; Tumor Necrosis Factor-alpha; Young Adult

To explore the value of α-1-acid glycoprotein (AGP) for the early diagnostic and prognostic assessment of patients with sepsis.. Eighty-five patients with systemic inflammatory response syndrome (SIRS) and 192 patients with sepsis were enrolled. White blood cell counts and serum levels of AGP, C-reactive protein, and procalcitonin were tested on the day of admission to intensive care unit (ICU; day 1) and the following days 3, 5, 7, and 10.. The sepsis group exhibited significantly higher levels of AGP than did the SIRS group on day 1 (P < .05); the area under the curve (AUC) of AGP was 0.869 with a specificity of 0.902 on diagnosis of sepsis. The differences were statistically significant among sepsis subgroups. On prognostic assessment, the areas under the curve of AGP, Sequential Organ Failure Assessment (SOFA) scores, and SOFA + AGP on ICU admission were 0.793, 0.813, and 0.878, respectively. The results of logistic regression showed that the odds ratios of AGP, SOFA, Acute Physiology and Chronic Health Evaluation II, and the length of ICU stay were 1.450, 1.212, 1.673, and 1.130.. α-1-Acid glycoprotein could distinguish sepsis from SIRS and also be used to effectively assess the severity of sepsis. In addition, combined AGP and SOFA scores had a great predicting value in prognosis of sepsis.

Topics: Adult; Aged; APACHE; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; China; Early Diagnosis; Female; Humans; Intensive Care Units; Length of Stay; Leukocyte Count; Logistic Models; Male; Middle Aged; Organ Dysfunction Scores; Orosomucoid; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Neutropaenic patients are at a high risk of contracting severe infections. In particular, in these patients, parameters with a high negative predictive value are desirable for excluding infection or bacteraemia. This study evaluated sepsis biomarkers in neutropaenic patients suffering from systemic inflammatory response syndrome (SIRS). Further, the predictive capacities of evaluated biomarkers in neutropaenic SIRS patients were compared to non-neutropaenic SIRS patients.. In this prospective observational cohort study, patients with clinically suspected sepsis were screened. The predictive capacities of procalcitonin (PCT), C-reactive protein and lipopolysaccharide-binding protein (LBP) in neutropaenic SIRS patients were evaluated in terms of their potential to identify infection or bacteraemia and were compared to results for non-neutropaenic SIRS patients. To select an appropriate control cohort, propensity score matching was applied, balancing confounding factors between neutropaenic and non-neutropaenic SIRS patients.. Of 3370 prospectively screened patients with suspected infection, 51 patients suffered from neutropaenic SIRS. For the identification of infection, none of the assessed biomarkers presented a clinically relevant discriminatory potency. Lipopolysaccharide-binding protein and PCT demonstrated discriminatory capacity to discriminate between nonbacteraemic and bacteraemic SIRS in patients with neutropaenia [receiver-operating characteristics-area under the curves (ROC-AUCs): 0.860, 0.818]. In neutropaenic SIRS patients, LBP had a significantly better ROC-AUC than in a comparable non-neutropaenic patient cohort for identifying bacteraemia (P = 0.01).. In neutropaenic SIRS patients, none of the evaluated biomarkers was able to adequately identify infection. LBP and PCT presented a good performance in identifying bacteraemia. Therefore, these markers could be used for screening purposes to increase the pretest probability of blood culture analysis.

Topics: Acute-Phase Proteins; Adult; Aged; Area Under Curve; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Case-Control Studies; Cohort Studies; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Neutropenia; Predictive Value of Tests; Propensity Score; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

To discuss the differences of inflammatory parameters such as procalcitonin (PCT), C-reactive protein (CRP), endotoxin, white blood cell (WBC), neutrophil ratio (Neut%) in blood of septic patients caused by bacterial bloodstream infection, and their correlation with the severity of disease.. 292 septic patients with positive blood culture were enrolled in Beijing Shijitan Hospital Affiliated to Capital Medical University from February 2012 to March 2015, and their gender, age, acute physiology and chronic health evaluation II (APACHEII) score, bacterial species and other general information were retrospectively collected. The differences in inflammatory parameters (PCT, CRP, endotoxin, WBC, Neut%) in septic patients caused by bacterial bloodstream infection were compared, their correlations with APACHEII scores within 24 hours were analyzed, and their diagnostic efficacies were also analyzed.. (1) It was shown by Pearson correlation coefficients that positively statistical correlation was found between PCT (r=0.638), CRP (r=0.620), endotoxin (r=0.284), WBC (r=0.209) and APACHE II score (all P=0.000) in bacterial bloodstream infective patients (n=292), and positively statistical correlation was found between PCT (r=0.626), CRP (r=0.616), Neut% (r=0.297) and APACHE II score (all P<0.01 ) in Gram positive bacterial (G+) group (n=86), and positively statistical correlation was shown between PCT (r=0.631), CRP (r=0.616), endotoxin (r=0.301), WBC (r=0.226 ) and APACHE II score (all P<0.01) in Gram negative bacterial (G-) group (n=206). (2) It was shown that PCT and CRP of both G+/G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup, respectively [G+ group: PCT (μg/L):0.92 (0.38, 4.75) vs. 0.43 (0.22, 1.00), CRP (mg/L): 118.45±62.60 vs. 57.97±32.41; G- group: PCT (μg/L):6.92 (1.94, 25.90) vs. 1.28 (0.27, 4.12), CRP (mg/L): 130.99±60.18 vs. 49.18±26.87, all P<0.01], and the endotoxin and WBC in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those of sepsis subgroup [endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 10.00 (5.00, 18.52), WBC (×10(9)/L): 12.13±6.72 vs. 9.61±5.01, both P<0.01]. The PCT and endotoxin in G- bacterial severe sepsis and septic shock subgroup were significantly higher than those in G+ severe sepsis and septic shock subgroup [PCT (μg/L): 6.92 (1.94, 25.90) vs. 0.92 (0.38, 4.75), endotoxin (ng/L): 19.40 (9.62, 33.87) vs. 2.56 (1.11, 4.01), both P<0.01]. (3) The diagnostic efficacy of inflammatory parameters for severe sepsis and septic shock subgroup were: PCT area under receiver operating characteristic (ROC) curve (AUC)=0.683, the cut-off point=0.55 μg/L, sensitivity 63.2%, specificity 69.0%; CRP AUC=0.802, the cut-off point=92.25 mg/L, sensitivity 73.7%, specificity 86.2%; WBC AUC=0.614, the cut-off point=7.35×10(9)/L, sensitivity 75.4%, specificity 48.3%; Neut% AUC=0.622, the cut-off point=0.882, sensitivity 43.9%, specificity 79.3% in G+ group. At the same time, it was shown that PCT AUC=0.780, the cut-off point=6.80 μg/L, sensitivity 51.0%, specificity 93.9%; CRP AUC=0.907, the cut-off point=90.10 mg/L, sensitivity 73.2%, specificity 95.9%; endotoxin AUC=0.694, the cut-off point=17.54 ng/L, sensitivity 57.3%, specificity 75.5%; WBC AUC=0.611, the cut-off point=10.54×10(9)/L, sensitivity 54.1%, specificity 69.4%; Neut% AUC=0.621, the cut-off. The plasma PCT and CRP have the best correlation between inflammatory parameters and severity of disease in bloodstream infective sepsis patients. CRP has the best diagnostic effect in severe sepsis/septic shock patients with bloodstream infection.

Topics: APACHE; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Humans; Leukocyte Count; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Shock, Septic

To evaluate interleukin-27 (IL-27) as a sepsis diagnostic biomarker in critically ill adults with sepsis.. A retrospetive study was conducted. A total of 176 systemic inflammatory response syndrome (SIRS) patients in Department of Critical Care Medicine of Xinxiang Medical College First Affiliated Hospital from March to November in 2014 were enrolled. The patients were divided into no sepsis group (n=66), pulmonary originated sepsis group (n=65), and non-pulmonary originated sepsis group (n=45). Plasma IL-27 and procalcitonin (PCT) were determined with enzyme linked immunosorbent assay (ELISA). Receiver operating characteristic curve (ROC) and classification and regression tree methodology was used to evaluate diagnostic biomarker performance.. The proportion of patients in pulmonary original sepsis group whose body temperature in line with SIRS criteria was significantly higher than no sepsis group (66.2% vs. 44.5%, P<0.05), and they were easy to suffer from tumor (44.6% vs. 22.7%, P<0.05). The proportion of patients in non-pulmonary originated sepsis group whose white blood cell count in line with SIRS criteria was significantly higher than no sepsis group (68.9% vs. 42.7%, P<0.05). It indicated that patients in pulmonary originated sepsis group and non-pulmonary originated sepsis group were more in line with SIRS criteria compared with no sepsis group. It was shown by ROC curve that IL-27 and PCT was not effective in discriminating sepsis among unselected patients showing symptoms and signs of SIRS. The area under the curve (AUC) was 0.59 [95% confidence interval (95%CI)=0.49-0.65] and 0.61 (95%CI=0.55-0.71). According to the further analysis from different infection sources, the highest AUC was 0.71 (95%CI=0.59-0.79) for IL-27 in patients with a non-pulmonary originated sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.78 (95%CI=0.71-0.87) in patients with a non-pulmonary originated sepsis, which was higher than IL-27 [0.71(95%CI=0.59-0.79)] or PCT [0.65 (95%CI=0.57-0.78)]. Compared to that of pediatric cohort with sepsis, lower expression of IL-27 was found in adult patients.. IL-27 performed overall poorly as a sepsis diagnostic biomarker in adults. IL-27 may be a more reliable diagnostic biomarker for sepsis in children than in adults. The combination of IL-27 and PCT can reasonably estimate the risk of sepsis in subjects with a non-pulmonary originated sepsis.

Topics: Adult; Area Under Curve; Biomarkers; Blood Pressure; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Humans; Interleukins; Leukocyte Count; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

To evaluate the diagnostic and prognostic value of the serum procalcitonin (PCT) level in the non-acquired immune deficiency syndrome (AIDS) immunocompromised critically ill patients suspected to have infection.. A retrospective study was conducted in the non-AIDS immunocompromised patients who were admitted to Department of Critical Care Medicine of Xiangya Hospital, Central South University during January 2011 to December 2014. Demographic characteristics, underlying disease, acute physiology and chronic health evaluation II (APACHEII) score at admission, and clinical records including baseline and peak levels of temperature, white blood count (WBC), PCT, and survival rate within 28 days, infection focus, infectious agents (bacterial, fungi or mixed infection), and the severity of infection (sepsis, severe sepsis, or septic shock) were recorded. Receiver operating characteristic (ROC) curve was plotted, and the diagnostic and protective value of above parameters was evaluated.. A total of 98 patients (43 male and 55 female) were enrolled in the study with a median age of 44 (28, 52) years old and a median APACHEII score of 17 (11, 20); 47 with malignant hematological tumor, 45 with autoimmune diseases, and 6 post solid organ transplantation. Among them 53 patients (54.1%) died within 28 days. Twenty-seven patients were diagnosed as systemic inflammatory response syndrome (SIRS) without infection. Among 71 patients with infection, 45 were diagnosed as bacterial infection, 10 with fungal infection, and 16 with mixed infection. Sepsis was diagnosed in 7 patients, severe sepsis in 32 patients, and septic shock in 32 patients. (1) There was no statistical significance in the baseline and peak levels of PCT and WBC, or baseline level of temperature between the groups of SIRS patients without infection and infected patients. The peak level of temperature was significantly higher in the patients with infection as compared with that of the SIRS without infection patients [centigrade: 39.4 (38.9, 40.0) vs. 38.8 (37.8, 39.2), Z=-3.268, P=0.001]. It was showed by subgroup analysis that in patients with hematological malignant disease or autoimmune diseases, higher level of body temperature was found in infection group compared with non-infection SIRS group [centigrade: 39.5 (39.0, 40.0) vs. 39.0 (38.4, 39.4), Z=-2.349, P=0.019; 39.0 (38.4, 39.5) vs. 38.2 (37.0, 38.9), Z=-2.221, P=0.026]. (2) The baseline level of PCT (μg/L) were 0.54 (0.20, 4.19), 2.78 (0.50, 9.54), 1.00 (0.45, 6.89), and 0.22 (0.07, 1.86) in non-infection SIRS patients or the patients with bacterial, fungal, and mixed infection, respectively. The peak level of PCT (μg/L) were 4.19 (1.95, 13.42), 12.37 (3.82, 45.89), 1.82 (0.49, 17.86), and 5.14 (2.66, 12.62), respectively, in each subgroup. When the comparison was conducted among the patients with different infectious agent, the baseline level of PCT in patients with bacterial infection was significantly higher than that in SIRS patients without infection (P=0.026) and mixed infection patients (P=0.001), and the peak level of PCT was significantly higher than that in the SIRS patients without infection (P=0.009) and the patients with fungal infection (P=0.016). ROC curve showed that the higher value was found in the baseline and peak levels of PCT for diagnosis of septic shock in all patients [ area under ROC curve (AUC) of baseline level=0.681±0.054, P=0.001; AUC of peak level=0.690±0.054, P=0.002], and the same value was. The serum level of PCT is found to be a reliable marker for the diagnosis of bacterial infection in immunocompromised critical patients, especially in those with hematologic malignancy. Additionally, PCT provides a useful tool for evaluating the severity of infection and the prognosis of critically ill patients.

Topics: Adult; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Survival Rate; Systemic Inflammatory Response Syndrome

Rapid diagnosis of bacterial infections is crucial for adequate antibiotic treatment. Serum molecules such as Procalcitonin (PCT) have been used as biomarkers of infection. Recently, the mid-regional pro-Adrenomedullin (MR-proADM) has been evaluated in combination with PCT for sepsis diagnosis. The diagnostic role of PCT and MR-proADM both in sepsis and in localized infections together with their contribution to effective antibiotic therapy has been evaluated. One hundred and eighty-two patients with bacterial infection has been enrolled: PCT and MR-proADM were measured at admission (T = 0), at 12-24 h (T = 1) and in the third or fifth day of antibiotic therapy (T = 3-5). ROC curve (receiver operating characteristic) and post-test probability were calculated. MR-proADM increased with the severity of the infection. PCT resulted significantly higher in sepsis than localized infection. After antibiotic therapy, PCT significantly decreased in localized respiratory infections and in sepsis, while MR-proADM decreased significantly after antibiotic therapy only in patients with severe sepsis/septic shock. The threshold values of PCT and MR-proADM were >0.1 ng/mL and >0.8 nmol/L, respectively. The combined use of PCT and MR-proADM increased the post-test probability of the diagnosis of bacterial infections compared to PCT alone. In conclusion, PCT and MR-proADM combination improves the diagnosis of bacterial infection and contribute to prognosis and antibiotic therapy effectiveness.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Sepsis; Young Adult

The purpose of this study was to confirm the prognostic value of pancreatic stone protein (PSP) in patients with severe infections requiring ICU management and to develop and validate a model to enhance mortality prediction by combining severity scores with biomarkers.. We enrolled prospectively patients with severe sepsis or septic shock in mixed tertiary ICUs in Switzerland (derivation cohort) and Brazil (validation cohort). Severity scores (APACHE [Acute Physiology and Chronic Health Evaluation] II or Simplified Acute Physiology Score [SAPS] II) were combined with biomarkers obtained at the time of diagnosis of sepsis, including C-reactive-protein, procalcitonin (PCT), and PSP. Logistic regression models with the lowest prediction errors were selected to predict in-hospital mortality.. Mortality rates of patients with septic shock enrolled in the derivation cohort (103 out of 158) and the validation cohort (53 out of 91) were 37% and 57%, respectively. APACHE II and PSP were significantly higher in dying patients. In the derivation cohort, the models combining either APACHE II, PCT, and PSP (area under the receiver operating characteristic curve [AUC], 0.721; 95% CI, 0.632-0.812) or SAPS II, PCT, and PSP (AUC, 0.710; 95% CI, 0.617-0.802) performed better than each individual biomarker (AUC PCT, 0.534; 95% CI, 0.433-0.636; AUC PSP, 0.665; 95% CI, 0.572-0.758) or severity score (AUC APACHE II, 0.638; 95% CI, 0.543-0.733; AUC SAPS II, 0.598; 95% CI, 0.499-0.698). These models were externally confirmed in the independent validation cohort.. We confirmed the prognostic value of PSP in patients with severe sepsis and septic shock requiring ICU management. A model combining severity scores with PCT and PSP improves mortality prediction in these patients.

Topics: Biomarkers; Brazil; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Hospital Mortality; Humans; Lithostathine; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Switzerland

Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice.. A decision tree was developed to estimate the health economic consequences of the PCT algorithm for antibiotic discontinuation from a Dutch hospital perspective. Input data were obtained from a systematic literature review. When necessary, additional information was gathered from open interviews with clinical chemists and intensivists. The primary effectiveness measure is defined as the number of antibiotic days, and cost-effectiveness is expressed as incremental costs per antibiotic day avoided.. The PCT algorithm for antibiotic discontinuation is expected to reduce hospital spending by circa € 3503 per patient, indicating savings of 9.2%. Savings are mainly due to reductions in length of hospital stay, number of blood cultures performed, and, importantly, days on antibiotic therapy. Probabilistic and one-way sensitivity analyses showed the model outcome to be robust against changes in model inputs.. Proven safe, a PCT algorithm for antibiotic discontinuation is a cost-effective means of reducing antibiotic exposure in adult ICU patients with sepsis, compared to current practice. Additional resources required for PCT are more than offset by downstream cost savings. This finding is highly important given the aim of preventing widespread antibiotic resistance.

Topics: Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cost-Benefit Analysis; Decision Trees; Dialysis; Humans; Intensive Care Units; Length of Stay; Netherlands; Protein Precursors; Respiration, Artificial; Sepsis

Topics: Adult; Antipsychotic Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Female; Humans; Male; Protein Precursors; Psychiatric Status Rating Scales; Schizophrenia; Sepsis

To perform a systematic review assessing accuracy and completeness of diagnostic studies of procalcitonin (PCT) for early-onset neonatal sepsis (EONS) using the Standards for Reporting of Diagnostic Accuracy (STARD) initiative.EONS, diagnosed during the first 3 days of life, remains a common and serious problem. Increased PCT is a potentially useful diagnostic marker of EONS, but reports in the literature are contradictory. There are several possible explanations for the divergent results including the quality of studies reporting the clinical usefulness of PCT in ruling in or ruling out EONS.We systematically reviewed PubMed, Scopus, and the Cochrane Library databases up to October 1, 2014. Studies were eligible for inclusion in our review if they provided measures of PCT accuracy for diagnosing EONS. A data extraction form based on the STARD checklist and adapted for neonates with EONS was used to appraise the quality of the reporting of included studies.We found 18 articles (1998-2014) fulfilling our eligibility criteria which were included in the final analysis. Overall, the results of our analysis showed that the quality of studies reporting diagnostic accuracy of PCT for EONS was suboptimal leaving ample room for improvement. Information on key elements of design, analysis, and interpretation of test accuracy were frequently missing.Authors should be aware of the STARD criteria before starting a study in this field. We welcome stricter adherence to this guideline. Well-reported studies with appropriate designs will provide more reliable information to guide decisions on the use and interpretations of PCT test results in the management of neonates with EONS.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Humans; Infant, Newborn; Male; Protein Precursors; Reproducibility of Results; Sepsis

To assess the clinical value ofprocalcitonin in cirrhotic patients with severe infection by comparing the serum procalcitonin levels in those patients with and without liver cirrhosis when suffering from sepsis.. A total of 225 septic patients were included in the study,including 91 patients without hepatopathy, 80 patients with cirrhosis, and 54 patients with chronic liver disease. The serum procalcitonin level was measured in all patients and statistically assessed for correlation with relevant clinical biochemistry indicators. The t-test, ANOVA test, Mann-Whitney U test, chi-square test and Spearman's correlation analysis were used for statistical analyses.. The patients with cirrhosis showed significantly lower serum procalcitonin levels (0.84 (0.32-3.44) ng/ml) than the patients with no hepatopathy (2.17 (0.70-9.18) ng/ml) or the patients with chronic liver disease (2.12 (0.33-13.61) ng/ml) (both P less than 0.05); the patients in the no hepatopathy group and the chronic liver disease group showed statistically similar levels of serum procalcitonin (P=0.616). The patients with cirrhosis of Child-Pugh grade C showed significantly higher level of serum procalcitonin (1.25 (0.54-4.61) ng/ml) than those patients with Child-Pugh grade B (0.33 (0.14-1.31) ng/ml; P=0.026), suggesting that patients with Child-Pugh C stage cirrhosis may be more susceptible to gram-negative bacterial infection. In the cirrhosis group,serum procalcitonin level was positively correlated with white blood cell (WBC) count (r=0.312) and percentage of neutrophils (N%) (r=0.228) (both P less than 0.05). Correlation analysis of the no hepatopathy group and the chronic liver disease group showed no correlation between serum procalcitonin level and either WBC or N%.. Under the sepsis condition, cirrhotic patients have lower serum procalcitonin level than patients without cirrhosis, and the serum procalcitonin level is positively correlated with WBC count and N%.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Liver Cirrhosis; Protein Precursors; Sepsis

Sepsis remains a diagnostic challenge in the intensive care unit (ICU), and the use of biomarkers may help in differentiating bacterial sepsis from other causes of systemic inflammatory syndrome (SIRS). The goal of this study was to assess test characteristics of a number of biomarkers for identifying ICU patients with a very low likelihood of bacterial sepsis. A prospective cohort study was conducted in a medical ICU of a university hospital. Immunocompetent patients with presumed bacterial sepsis were consecutively enrolled from January 2012 to May 2013. Concentrations of nine biomarkers (α-2 macroglobulin, C-reactive protein [CRP], ferritin, fibrinogen, haptoglobin, procalcitonin [PCT], serum amyloid A, serum amyloid P, and tissue plasminogen activator) were determined at baseline and at 24 h, 48 h, and 72 h after enrollment. Performance characteristics were calculated for various combinations of biomarkers for discrimination of bacterial sepsis from other causes of SIRS. Seventy patients were included during the study period; 31 (44%) had bacterial sepsis, and 39 (56%) had other causes of SIRS. PCT and CRP values were significantly higher at all measured time points in patients with bacterial sepsis. A number of combinations of PCT and CRP, using various cutoff values and measurement time points, demonstrated high negative predictive values (81.1% to 85.7%) and specificities (63.2% to 79.5%) for diagnosing bacterial sepsis. Combinations of PCT and CRP demonstrated a high ability to discriminate bacterial sepsis from other causes of SIRS in medical ICU patients. Future studies should focus on the use of these algorithms to improve antibiotic use in the ICU setting.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Immunocompetence; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Necrotizing fasciitis (NF) is a potentially fatal subcutaneous tissue and fascia infection. We studied the role of serum procalcitonin in the identification and assessment of severity of sepsis in patients with NF.. A retrospective analysis was conducted from January 2000 to December 2013 for all patients who admitted to surgical intensive care with provisional diagnosis of NF. Patients were categorized into four groups based on the initial procalcitonin concentrations (Group I: <0.5 low risk, Group II: ≥0.5-<2 moderate risk, Group III: ≥2-<10 high risk, and Group IV: ≥10 ng/mL high likelihood of severe sepsis).. During the study period, 331 cases were identified to have NF with a mean age of 51 ± 14 years. Serum procalcitonin was tested in 62 cases (only between 2011 and December 2013) and all were positive (Group I: 22%, Group II: 18%, Group III: 21%, and Group IV: 39%). The most common affected regions were thigh and chest in Group II (46% and 9%, respectively), lower limbs in Group III (46%), and perineum and abdomen in Group IV (25% and 21%, respectively). In the four groups, 21 patients developed septic shock (Group I: 0%, Group II: 14%, Group III: 24%, and Group IV: 62%). The cut off procalcitonin value for septic shock was 5.6 ng/mL. Using receiver-operating characteristic curve, this cut off with the Area under the Curve (AUC) of 0.77 was found to have sensitivity 81% and specificity 67%. Sequential Organ Failure Assessment (SOFA) score was substantially greater in Group III and Group IV in comparison to Group I and Group II, p = 0.006. Procalcitonin levels were correlated well with SOFA score (r = 0.34, p = 0.007). There were 17 deaths in the four groups (Group I: 6%, Group II: 23%, Group III: 12%, and Group IV: 59%).. Initial procalcitonin concentration in NF carries an important prognostic value and it correlates well with SOFA score and can predict the development of septic shock early in patients with NF.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Fasciitis, Necrotizing; Female; Humans; Male; Middle Aged; Prognosis; Protein Precursors; Retrospective Studies; Risk Assessment; Sepsis

This study aimed to evaluate the superiority of procalcitonin (PCT), C-reactive protein (CRP) levels, white blood cell (WBC) counts, and erythrocyte sedimentation rate (ESR) in discriminating among infection, systemic inflammatory response syndrome (SIRS), and sepsis, and their differences according to age groups.. The patients were divided into an adult group and a geriatric group (over 65 years) and classified according to the presence of infection, SIRS, and sepsis. The patients' laboratory values (PCT, CRP, WBC, ESR), demographic characteristics, and vital signs were taken into consideration.. When the laboratory parameters were evaluated, there were no significant differences in the PCT, WBC, and ESR values between the age groups (P > 0.05). CRP was significantly higher in the adult patient group compared to the geriatric group (P < 0.001). When the two groups were compared in terms of infection, there were no significant differences in the PCT levels and the WBC count (P > 0.05) in SIRS and sepsis. In addition, the CRP levels and the ESR were significantly higher in the adult sepsis patients when compared with the geriatric patients (P < 0.001).. PCT levels do not distinguish among infection, SIRS, and sepsis in adult and geriatric age groups.

Topics: Adolescent; Adult; Age Factors; Aged; Bacterial Infections; Biomarkers; Blood Sedimentation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Emergency Service, Hospital; Female; Geriatric Assessment; Hospitalization; Humans; Leukocyte Count; Male; Middle Aged; Protein Precursors; Reproducibility of Results; Retrospective Studies; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

Sepsis is still a major cause of morbidity and mortality despite the improvements in diagnosis and treatment. The aim of this study was to investigate the values of procalcitonin and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the differential diagnosis of patients with sepsis and noninfectious systemic inflammatory response syndrome (NI-SIRS) and measure their importance in the prognosis of patients with sepsis.. This prospective study included 41 NI-SIRS and 33 sepsis patients hospitalized in Celal Bayar University Hospital, Manisa, Turkey. Blood samples were taken from NI-SIRS patients on days 0 and 3 and from sepsis patients on days 0, 3, 4, 7, and 14. Clinical status of the patients was determined with the SOFA scoring system.. The SOFA scoring system and procalcitonin and sTREM-1 measurements were significant in the differential diagnosis of sepsis and NI-SIRS patients. The SOFA scoring system was considered the most important indicator in determining the prognosis of sepsis patients. Procalcitonin and sTREM-1 levels increased progressively in nonsurvivors and decreased in survivors, but changes were statistically insignificant.. In the differentiation of sepsis and NI-SIRS, and evaluation of the prognosis of sepsis, combined measurements of procalcitonin and sTREM-1 levels are important.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sepsis; Systemic Inflammatory Response Syndrome; Triggering Receptor Expressed on Myeloid Cells-1

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Decision Making; Emergency Service, Hospital; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Humans; Prognosis; Protein Precursors; Sepsis

Sepsis is a lethal and complex clinical syndrome caused by infection or suspected infection. Cold-inducible RNA-binding protein (CIRP) is a widely distributed cold-shock protein that plays a proinflammatory role in sepsis and that may induce organ damage. However, clinical studies regarding the use of CIRP for the prognostic evaluation of sepsis are lacking. The purpose of this research was to investigate the prognostic significance of peripheral blood concentrations of CIRP in sepsis. Sepsis was assessed using several common measures, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score; the Sepsis-related Organ Failure Assessment (SOFA) score; the lactate, serum creatinine, and procalcitonin (PCT) levels; the white blood cell (WBC) count; and the neutrophil ratio (N%).. Sixty-nine adult patients with sepsis were enrolled in this study. According to the mortality data from the hospital, 38 patients were survivors, and 31 were nonsurvivors. The plasma levels of the biomarkers were measured and the APACHE II and SOFA scores were calculated within 24 hours of patient enrollment into our study. The CIRP level was measured via ELISA.. The plasma level of CIRP was significantly higher in the nonsurvivors than in the survivors (median (IQR) 4.99 (2.37-30.17) ng/mL and 1.68 (1.41-13.90) ng/mL, respectively; p = 0.013). The correlations of the CIRP level with the APACHE II score (r = 0.248, p = 0.040, n = 69), the SOFA score (r = 0.323, p = 0.007, n = 69), the serum creatinine level (r = 0.316, p = 0.008, n = 69), and the PCT level (r = 0.282, p = 0.019, n = 69) were significant. Receiver operator characteristic (ROC) curve analysis showed that the area under the ROC curve (AUC) for the CIRP level was 0.674 (p = 0.013). According to Cox proportional hazards models, the CIRP level independently predicts sepsis mortality. When the CIRP level in the peripheral blood increased by 10 ng/mL, the mortality risk increased by 1.05-fold (p = 0.012). Thus, the CIRP level reflects the degree of renal injury but does not predict the severity of sepsis or organ damage.. An elevated plasma concentration of CIRP was significantly associated with poor prognosis among patients with sepsis. Therefore, CIRP is a potential predictor of sepsis prognosis.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Female; Humans; Lactic Acid; Male; Middle Aged; Prognosis; Protein Precursors; RNA-Binding Proteins; Sepsis

Procalcitonin is a reliable biomarker of infection and sepsis. We aimed to determine whether tracheotomy influences the procalcitonin concentrations in patients without sepsis and assess whether operative duration and procedure affect the peak procalcitonin level.. A total of 38 non-septic patients who required a tracheotomy underwent either a percutaneous dilatational tracheotomy (n=19) or a surgical tracheotomy (n=19). Procalcitonin levels were measured at the beginning of the tracheotomy and at 2 h, 4 h, 8 h, 24 h, 48 h and 72 h after the procedure.. The baseline procalcitonin concentration before the tracheotomy was 0.24 ± 0.13 ng/mL. The postoperative levels increased rapidly, with a 4-fold elevation after 2 h, reaching a peak 4 h later with a 5-fold increase over baseline. Thereafter, the levels gradually returned to 2-fold greater than the baseline level within 72 h. The peak levels of procalcitonin showed a significant positive correlation with operative durations (r=0.710, p<0.001) and procedures (rho=0.670, p<0.001).. In patients without sepsis, tracheotomy induces a rapid release of serum procalcitonin, and the operative duration and procedure have significant impacts on the peak procalcitonin levels. Thus, the nonspecific increase in procalcitonin levels following tracheotomy needs to be considered when this measure is used to evaluate infection.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Electrochemical Techniques; Female; Humans; Luminescent Measurements; Male; Middle Aged; Operative Time; Prospective Studies; Protein Precursors; Sepsis; Time Factors; Tracheotomy

Because acute liver failure (ALF) patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT) has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.. Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD) subjects served as controls.. Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169). PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001)). Subjects with acetaminophen (APAP) toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.. While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Inflammation; Liver Failure, Acute; Male; Middle Aged; Prospective Studies; Protein Precursors; Retrospective Studies; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

Soluble CD22 (sCD22) is a fragment of CD22, a B cell-specific membrane protein that negatively regulates B-cell receptor signaling. To date, sCD22 has only been regarded as a tumor marker of B-cell malignancies. Its expression in infectious diseases has not yet been assessed.. Serum concentrations of sCD22, procalcitonin (PCT) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assays in patients with intra-abdominal Gram-negative bacterial infection. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers in this type of infection. The correlations between biomarkers and the Acute Physiology and Chronic Health Evaluation (APACHE) II scores were also analyzed.. Concentrations of sCD22 were significantly elevated in patients with sepsis and the elevation is correlated with the severity of sepsis. sCD22 was also slightly elevated in patients with non-infected systemic inflammatory response syndrome or local infection. The diagnostic accuracy of sCD22 for sepsis was equivalent to that of PCT or IL-6. In addition, the correlation of sCD22 with APACHE II scores was stronger than that of PCT or IL-6.. Serum sCD22 is a novel inflammatory mediator released during infection. This soluble biomarker plays a potential role in the diagnosis of Gram-negative bacterial sepsis, with a diagnostic accuracy as efficient as that of PCT or IL-6. Furthermore, sCD22 is more valuable to predict the outcomes in patients with sepsis than PCT or IL-6. The present study suggested that sCD22 might be potentially useful in supplementing current criteria for sepsis.

Topics: Adult; Aged; APACHE; Biliary Tract Diseases; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gram-Negative Bacterial Infections; Humans; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Sialic Acid Binding Ig-like Lectin 2

Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting.. A prospective international multicenter cohort study.. Seven different emergency departments in Sweden, Canada, and the United States.. Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count).. None.. Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort.. In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Area Under Curve; Biomarkers; Blood Proteins; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Canada; Carrier Proteins; Cause of Death; Cohort Studies; Critical Illness; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Internationality; Male; Middle Aged; Multiple Organ Failure; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Assessment; Sepsis; Survival Analysis; Sweden; Systemic Inflammatory Response Syndrome; Treatment Outcome; United States

To evaluate the value of pancreatic stone protein/regenerating protein (PSP/reg) in severity evaluation and prognosis prediction for children with sepsis.. In this prospective case-control study, 159 children with sepsis (106 cases in the sepsis group; 53 cases in the severe sepsis group, including 12 cases of septic shock) and 20 children without sepsis (control group) were enrolled. ELISA was applied to measure plasma PSP/reg levels on days 1, 3, and 7 of admission to the PICU. The Spearman rank correlation test was applied to assess the correlations between plasma PSP/reg level and serum procalcitonin (PCT), CRP, WBC count, and pediatric critical illness score (PCIS). The area under the receiver operating characteristic curve (AUC) was used to assess the value of each index in determining severity and predicting prognosis for children with sepsis.. On day 1 of admission to the PICU, plasma PSP/reg levels in the sepsis and severe sepsis groups were significantly higher than in the control group (P<0.05), and the severe sepsis group had a significantly higher plasma PSP/reg level than the sepsis group (P<0.05). On day 1 of admission to the PICU, the survival group (n=132) had a significantly lower plasma PSP/reg level than the non-survival group (n=27) (P<0.05). On day 1 of admission to the PICU, plasma PSP/reg level in children with sepsis was positively correlated with WBC count and serum PCT level (rs=0.212 and 0.548, respectively; both P<0.05), and negatively correlated with PCIS score (rs=-0.373; P<0.05). The AUCs of plasma PSP/reg level and serum PCT for determination of severe sepsis, septic shock, and death were higher than 0.7 (P<0.05).. PSP/reg is closely related to infection, and has a certain clinical value in risk stratification of sepsis and prognosis evaluation.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lithostathine; Male; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

Elevated cytokines levels correlate with sepsis severity and mortality but their role in the diagnosis is controversial, whereas Procalcitonin (PCT) has been largely used. Recently, the mid-regional proadrenomedullin (MR-proADM) has been combined with PCT for diagnosis optimization. In this study the combined measurement of PCT, MR-proADM, and cytokines in patients with sepsis was evaluated.. One hundred and four septic patients and 101 controls were enrolled. Receiver operating characteristic (ROC) analysis and multiple logistic regression were used to evaluate applicant markers for sepsis diagnosis. Markers with best Odds Ratio (OR) were combined, and the posttest probability and a composite score were computed.. Based upon ROC curves analysis, PCT, MR-proADM, IL-6, IL-10, TNF-α, and MCP-1 were considered applicant for sepsis diagnosis. Among these PCT, MR-proADM , IL-6, and TNF-α showed the best OR. A better posttest probability was found with the combination of PCT with MR-proADM and PCT with IL-6 or TNF-α compared to the single marker. A composite score of PCT, MR-proADM, and TNF-α showed the best ROC curve in the early diagnosis of sepsis.. The combination of PCT with other markers should expedite diagnosis and treatment of sepsis optimizing clinical management.

Topics: Adrenomedullin; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Chemokine CCL2; Female; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Tumor Necrosis Factor-alpha

To investigate the effects of application of intermittent hemofiltration combined with hemoperfusion (HP) in the early stage of severe burn in the prevention and treatment of sepsis.. Forty severely burned patients, admitted to our burn ward from June 2011 to March 2013, conforming to the study criteria, were divided into conventional treatment group (CT, n=20) and blood purification group (BP, n=20) according to the random number table. Patients in group CT received CT according to the accepted principles of treatment for a severe burn. Patients in group BP received CT and intermittent hemofiltration combined with HP once respectively on post injury day (PID) 3, 5, and 7, spanning 6 to 8 hours for each treatment. On PID 3, 5, 7, 10, and 14, body temperature, heart rate, and respiratory rate were recorded; white blood cell count (WBC), neutrophil granulocytes, blood urea nitrogen (BUN), and creatinine were determined; levels of IL-1, IL-6, TNF-α, and high-mobility group box 1 (HMGB1) in serum were determined by ELISA; level of LPS in serum was determined with the chromogenic substrate limulus amebocyte lysate method; level of procalcitonin (PCT) in serum was determined by double antibody sandwich immune chemiluminescence method. The symptoms and signs of sepsis were observed during the treatment. Data were processed with Fisher's exact test, chi-square test, analysis of variance for repeated measurement, and LSD-t test.. (1) Except for that on PID 5, the mean body temperature of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.87 to 2.97, P values below 0.05). The heart rate was significantly slower in patients of group BP than in group CT from PID 3 to 14 (with t values from 1.78 to 3.59, P values below 0.05). Except for that on PID 3, the respiratory rate of patients in group BP was significantly slower than that of group CT at each of the rest time points (with t values from 1.93 to 2.85, P values below 0.05). (2) The levels of WBC, neutrophil granulocytes, BUN, and creatinine of patients in group BP were significantly lower than those of group CT (with t values from 1.78 to 4.23, P values below 0.05). (3) Except for that on PID 3, the level of IL-1 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 1.97 to 4.16, P values below 0.05). Except for that on PID 7, the level of IL-6 of patients in group BP was significantly lower than that of group CT at each of the rest time points (with t values from 2.11 to 6.34, P values below 0.05). The levels of TNF-α and HMGB1 of patients in group BP were significantly lower than those of group CT from PID 3 to 14 (with t values from 1.98 to 5.29, P values below 0.05). (4) On PID 3, 5, 7, 10, and 14, the levels of LPS and PCT of patients in group BP were respectively (0.23 ± 0.07), (0.27 ± 0.09), (0.22 ± 0.06), (0.20 ± 0.08), (0.15 ± 0.07) EU/mL, and (0.44 ± 0.12), (0.67 ± 0.13), (0.74 ± 0.13), (0.64 ± 0.12), (0.71 ± 0.10) ng/mL, and they were lower than those of group CT [(0.37 ± 0.08), (0.45 ± 0.09), (0.56 ± 0.09), (0.48 ± 0.08), (0.40 ± 0.08) EU/mL, and (0.74 ± 0.11), (1.16 ± 0.12), (1.40 ± 0.13), (1.55 ± 0.15), (1.49 ± 0.14) ng/mL, with t values from 1.88 to 3.43, P values below 0.05]. (5) The incidence of sepsis of patients in group BP was obviously lower than that of group CT (χ² = 6.94, P<0.01).. Intermittent hemofiltration combined with HP can effectively improve blood biochemical indexes and vital signs and reduce the occurrence of burn sepsis by decreasing the levels of proinflammatory cytokines, LPS, and PCT.

Topics: Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Hemofiltration; Hemoperfusion; HMGB1 Protein; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Protein Precursors; Sepsis; Serum; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor-alpha

Presepsin (soluble CD14 subtype) has been shown to be beneficial as a sepsis marker in adults. Nevertheless, very few data are available in neonates. The aim of the present study was to determine reference ranges of presepsin in term and preterm neonates.. Healthy term neonates and preterm neonates without clinical signs of infection admitted to the Neonatal Unit were consecutively enrolled. Presepsin concentrations in whole blood were measured using a point-of-care assay system located in the Unit. Demographic data, antenatal and perinatal variables commonly affecting C-reactive protein and procalcitonin values were considered.. Of the 684 neonates enrolled in the study, 484 (70.8%) were born at term and 200 (29.2%) were preterm (24-36 weeks' gestation). In term infants, presepsin median value was 603.5 pg/mL (interquartile range: 466.5-791 pg/mL; 5th and 95th centiles: 315 and 1178 pg/mL respectively). In preterm infants, presepsin median value was slightly higher, equal to 620 pg/mL (interquartile range: 503-864 pg/mL; 5th and 95th centiles: 352 and 1370 pg/mL respectively). The reference ranges of presepsin we determined were much higher than those seen in healthy adults. No correlation between presepsin levels and postnatal age was observed, as well as no significant difference was demonstrated in preterm neonates at different gestational ages. None of the variables analyzed affected presepsin levels at a clinical significant extent.. For the first time, this study provides reference ranges of presepsin in term and preterm neonates. Having reliable reference values is crucial for obtaining an adequate diagnostic accuracy. Based on our results, most variables commonly affecting C-reactive protein and procalcitonin values do not affect presepsin levels, which suggests that presepsin could be an effective sepsis marker. Further investigations in large groups of neonates with sepsis are needed to determine the diagnostic and prognostic value of this biomarker.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lipopolysaccharide Receptors; Peptide Fragments; Point-of-Care Systems; Pregnancy; Prognosis; Protein Precursors; Reference Values; Sepsis; Term Birth

To explore the early diagnostic value of pro-adrenomedullin (pro-ADM) in sepsis.. A prospective study was conducted. Eighty-two patients with acute infection admitted to Department of Emergency of Shanxi Medical University Second Hospital from April 2013 to March 2014 were enrolled. According to the diagnostic criteria of sepsis, the patients with acute infection were divided into ordinary infection group [infection without systemic inflammatory response syndrome (SIRS), n = 25] and sepsis group (infection combined with SIRS, n = 57). According to degree of severity of sepsis, the latter group was subdivided into three subgroups: sepsis group (n = 22), severe sepsis group (n = 27) and septic shock group (n = 8). Twenty-four healthy persons were included to serve as healthy control group. The venous blood from all the research objects in hospital was collected within 24 hours. The levels of pro-ADM and procalcitonin ( PCT ) were determined by enzyme linked immunosorbent assay (ELISA), and acute physiology and chronic health evaluation II (APACHE II ) score was recorded. The relationship between pro-ADM and PCT and also APACHE II score was analyzed with Pearson correlation analysis. The receiver-operating characteristic curve (ROC) of pro-ADM and PCT were used to evaluate the diagnostic acuity of sepsis.. The plasma levels of pro-ADM, PCT and APACHE II score in sepsis group were significantly higher than those in ordinary infection group and healthy control group [pro-ADM (ng/L): 66.69 ± 1.73 vs. 53.43 ± 2.70, 45.87 ± 1.43; PCT (ng/L): 1 336.49 ± 40.26 vs. 1 083.09 ± 47.99, 959.04 ± 37.53; APACHE II score: 14.60 ± 0.81 vs. 8.10 ± 1.14, 3.00 ± 1.15, all P < 0.01]. With the aggravation of sepsis, the levels of pro-ADM, PCT and APACHE II score were gradually increased, and there were significant differences among sepsis, severe sepsis, and septic shock groups [pro-ADM (ng/L): 64.91 ± 2.50, 73.56 ± 2.80, 84.67 ± 4.52; PCT (ng/L): 1 152.65 ± 48.62, 1 233.93 ± 63.06, 1 475.71 ± 109.93; APACHE II score: 12.91 ± 1.15, 14.55 ± 1.14, 19.37 ± 2.40, P < 0.05 or P < 0.01]. Pearson correlation analysis results showed that the level of pro-ADM was positively related with PCT (r = 0.473, P = 0.006), and it was also positively correlated with APACHE II score (r = 0.707, P = 0.008). ROC curve analysis showed that area under the ROC curve (AUC) of pro-ADM for diagnosis of sepsis was 0.823 (P = 0.003). When the cutoff value was 59.40 ng/L, the sensitivity was 80.7%, the specificity was 68.0%, the positive predictive value was 85.2%, and the negative predictive value was 60.7%. AUC of the PCT for diagnosis of sepsis was 0.653 (P = 0.043). When the cutoff value was 1 194.67 ng/L, the sensitivity was 68.4%, the specificity was 64.0%, the positive predictive value was 81.8%, and the negative predictive value was 44.7%. It was proved that the pro-ADM had a higher diagnostic value for sepsis than PCT.. The plasma levels of pro-ADM can be used as an early indicator in diagnosis and severity evaluation and prognosis in patients with sepsis.

Topics: Adrenomedullin; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Humans; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

In the critical care setting, increasing levels of midregional proadrenomedullin (MRproADM), midregional proatrial natriuretic peptide (MRproANP), procalcitonin (PCT), copeptin, and proendothelin-1 (proET-1) have been shown to be correlated with increasing severity of sepsis. The objective of this study was to investigate the utility of sepsis biomarkers in an Emergency Department (ED) population.. Through a prospective, observational pilot study, we investigated the utility of MRproADM, MRproANP, PCT, copeptin, and proET-1 in predicting a diagnosis of early sepsis in patients presenting to the ED for suspected infection. Data were analyzed using nonparametric Mann-Whitney U-tests, χ²-tests, and receiver operating characteristic curves.. Of the 66 patients enrolled in this study, 37 (56.1%) were men, with a median age of 58 years [interquartile range (IQR) 39-69 years], and 19 (28.8%) had a final diagnosis of early sepsis. A higher percentage of sepsis patients compared with no-sepsis patients met systemic inflammatory response syndrome (SIRS) criteria at initial presentation (85.7 vs. 41.3%; P<0.0001) and were admitted to the hospital (84.2 vs. 55.6%; P=0.02). PCT was higher in sepsis patients [median 0.32 ng/ml (IQR 0.19-1.17) vs. 0.18 ng/ml (IQR 0.07-0.54); P=0.04]. There were no differences between groups for MRproADM, MRproANP, copeptin, or proET-1 (P≥0.53). The C-statistic was maximized with the combination of SIRS criteria and PCT levels (0.92±0.05), which was better than PCT alone (0.67±0.08; P=0.005) or SIRS alone (0.75±0.07; P=0.04).. In this pilot study, we found that the combination of SIRS criteria and PCT levels is useful for the early detection of sepsis in ED patients with suspected infection. Larger studies investigating use of PCT are necessary.

Topics: Adrenomedullin; Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Endothelin-1; Female; Glycopeptides; Humans; Male; Middle Aged; Pilot Projects; Prospective Studies; Protein Precursors; Sepsis

Sepsis is an important cause of neonatal death and perinatal brain damage, particularly in preterm infants. It is thought that activation of the inflammatory cascade triggered by cytokine might play a role in the pathogenesis of sepsis. Recent evidence supports a role for resistin in inflammation. There are no data in the literature on resistin levels of premature newborns with sepsis, which can also cause inflammatory response. The objective of this study was to evaluate whether resistin can be used as an indicator in neonatal sepsis of preterm babies.. Forty-three premature newborns considered to have sepsis were included in the study. Forty-three gestational and postnatal age- and sex-matched premature newborns without premature prolonged rupture of membrane or sepsis served as controls.. The median resistin and interleukin-6 (IL-6) levels of the premature babies with sepsis were 85.9 ng/mL and 342.7 pg/mL, respectively, and were higher than those of the control group (29.9 ng/mL and 17.7 pg/mL, respectively). The sensitivity, specificity, positive, and negative predictive values for resistin were 73.7%, 45.8%, 68.3%, and 52.4%, respectively.. Resistin levels were higher in premature newborns with sepsis and correlated with IL-6 levels, which is an indicator of neonatal sepsis. This suggests that resistin may also be used in the diagnosis of neonatal sepsis. However, it has limited value when compared with the other inflammatory markers including C-reactive protein, procalcitonin, and IL-6.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Interleukin-6; Male; Protein Precursors; Resistin; Sepsis

Diagnosing sepsis is difficult in burn patients because of the inflammatory mediators that alter postburn metabolic profile. Here, we compare a new marker presepsin with procalcitonin (PCT), c-reactive protein (CRP) and white blood cell (WBC) in diagnosis and follow up of sepsis in burn patients.. Patients admitted to burn center of our institute were prospectively investigated. Presepsin, PCT, CRP and WBC levels were measured at admission and every 6h for first day and daily thereafter. At all timing samples, patients were classified as sepsis or non-sepsis according to the current American Burn Association Consensus Criteria (ABA) 2007.. 37 adult patients were evaluated. A total data of 611 time points were supplied. Sepsis time points differ significantly from non-sepsis in presepsin (p < 0.0001), PCT (p = 0.0012) and CRP (p < 0.0001) levels. Non-surviving patient results differ significantly from survivors in presepsin (p < 0.0001), PCT (p = 0.0210) and CRP (p = 0.0008). AUC-ROC % values for diagnosing sepsis were 83.4% for presepsin, 84.7% for PCT, 81.9% for CRP and 50.8% for WBC. Sepsis patients had significantly different presepsin, CRP and WBC but not PCT levels on their first day of sepsis compared to previous days.. Plasma presepsin levels have comparable performance in burn sepsis.

Topics: Adult; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Leukocyte Count; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Young Adult

Delta neutrophil index (DNI) has been reported to be useful in the diagnosis of sepsis. We evaluated the role of DNI for differentiating true bacteremia from blood contamination and compared the DNI value with previously validated markers such as procalcitonin (PCT) and C-reactive protein (CRP).. The blood culture positive group was subdivided into true bacteremia (n=199) and contamination (n=158). The blood cultures were incubated in the BacT/Alert 3D (bioMérieux, Marcyl'Etoile, France) and BACTEC FX (Becton Dickinson, Sparks, MD, USA) systems for 5days. Data of complete blood cell count were collected from an automatic cell analyzer (ADVIA2120 Hematology System, Siemens Healthcare Diagnostics) to calculate DNI.. Concentrations for DNI, PCT, and CRP were significantly higher in the true bacteremia group. When the gram-positive and gram-negative infections were compared among true bacteremia, only PCT was increased significantly in GNB bacteremia. DNI levels were well correlated with PCT (r=0.564, P<0.0001) and CRP (r=0.344, P<0.001) using the Spearman test among the culture positive bacteremia. The area under the ROC curve was 0.75 for PCT, 0.69 for CRP, and 0.69 for DNI.. We demonstrated the usefulness of DNI in differentiating true bacteremia from contamination in patients with a positive blood culture.

Topics: Aged; Artifacts; Bacteremia; Bacteriological Techniques; Blood Specimen Collection; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cell Count; Equipment Contamination; Female; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Protein Precursors; ROC Curve; Sepsis

The vascular endothelium has been shown to play a pivotal role in the pathophysiology of sepsis through the expression of surface proteins and secretion of soluble mediators. Endocan (endothelial cell-specific molecule-1), a 50-kDa dermatan sulfate proteoglycan, is expressed by endothelial cells in lung and kidney and can be detected at low levels in the serum of healthy subjects. Increased concentrations were described in patients with sepsis, severe sepsis and septic shock compared to healthy individuals, with serum concentrations related to the severity of illness. In the present study, we investigated endocan, procalcitonin and C-reactive protein in postmortem serum from femoral blood in a series of sepsis-related fatalities and control individuals who underwent medicolegal investigations. Endocan was also measured in pericardial fluid. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases with documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various noninfectious causes of death. Postmortem serum endocan concentrations were significantly higher in the sepsis group, with values ranging from 0.519 ng/ml to 6.756 ng/ml. In the control group, endocan levels were undetectable in eleven out of sixteen cases. The results of the data analysis revealed similar endocan concentrations in the pericardial fluid of both studied groups. Endocan can be considered a suitable biological parameter for the detection of sepsis-related deaths in forensic pathology routine.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis; Humans; Neoplasm Proteins; Pericardial Effusion; Prospective Studies; Protein Precursors; Proteoglycans; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Procalcitonin (PCT) is a relatively new, promising indirect parameter for infection. In the intensive care unit (ICU) it can be used as a marker for sepsis. However, in the ICU there is a need for reliable markers for clinical deterioration in the critically ill patients. This study determines the clinical value of PCT concentrations in recognizing surgical complications in a heterogeneous group of general surgical patients in the ICU.. We prospectively collected PCT concentration data from April 2010 to June 2012 for all general surgical patients admitted to the ICU. Both the relationships between PCT levels and events (diagnostic and therapeutic interventions) as well as between PCT levels and surgical complications (abscesses, bleeding, perforation, ischemia, and ileus) were studied.. PCT concentrations were lower in patients who developed complications than those who did not develop complications on the same day, although not significant (P = 0.27). A 10% increase in PCT levels resulted in a 2% higher complication odds, but again this was not significant (odds ratio [OR], 1.020; 95% confidence interval [CI], 0.961-1.083; P = 0.51). Even a 20% or 30% increase in PCT concentrations did not result in higher complication probability (OR, 1.039; 95% CI, 0.927-1.165 and OR, 1.057; 95% CI, 0.897-1.246). Furthermore, an increase in PCT levels did not show an increase or a reduction in the number of diagnostic and therapeutic interventions.. An increase in PCT levels does not help to predict surgical complications in critically ill surgical patients.

Topics: Abscess; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Hospital Mortality; Humans; Ileus; Intensive Care Units; Ischemia; Male; Middle Aged; Postoperative Hemorrhage; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Surgical Wound Infection

Because clinical symptoms and biological markers are neither sensitive nor specific, newborns are frequently suspected of having an infection. In France, 30-50% of newborns are suspected of having early-onset sepsis (EOS) and many of them undergo laboratory tests and empirical antibiotic treatments while awaiting results. The aim of this study was to evaluate the diagnostic value of various suspicion criteria for EOS as recommended by the Anaes since 2002, and the value of umbilical cord blood procalcitonin (PCT), currently assayed in our maternity ward.. This 4-year retrospective study in the CHU of Nantes included hospitalized newborns with suspected early neonatal infection. Infection status was established according to the Anaes definitions and clinical evolution.. The study included 2151 newborns. Among anamnestic criteria, only prematurity significantly increased the risk of EOS (relative risk of 3.1; 95% CI 1.4-7.0). The relative risk of infection for a symptomatic newborn was 12.2 (95% CI 4.9-30.2; P<0.0001). Laboratory test results were the most predictive criteria. The relative risk to be infected was 291.6 (95% CI 70.7-1,214.0; P<0.0001) with a blood cord PCT value>0.6 ng/L. The positive post-test probability was 28% (95% CI: 23-33) and the negative post-test probability was close to 0 (95% CI: 0-0).. Clinical criteria of postnatal life adaptation are more predictive of early-onset neonatal infection than anamnestic criteria are. The blood cord PCT value could be a helpful marker in the identification of infected newborns. PCT measured in umbilical cord blood could be included in a general algorithm in order to identify as soon as possible newborns with a high risk of EOS.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross-Sectional Studies; Diagnosis, Differential; Empiricism; Female; Fetal Blood; France; Hospitals, University; Humans; Infant, Newborn; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Male; Predictive Value of Tests; Pregnancy; Probability; Protein Precursors; Retrospective Studies; Risk; Sepsis

Systemic inflammatory response syndrome and sepsis frequently occur after cardiac surgery with cardiopulmonary bypass. The aim of the present study was to investigate whether preoperative cholesterol levels can predict sepsis onset and postoperative complications in patients undergoing cardiac surgery with cardiopulmonary bypass.. Prospective observational study.. Surgical ICU of a French university hospital.. Two hundred and seventeen consecutive patients older than 18 years admitted for planned cardiac surgery with cardiopulmonary bypass.. Measurements of plasma blood lipids and inflammation markers before anesthesia induction (baseline), at cardiopulmonary bypass start, at cardiopulmonary bypass end, and 3 and 24 hours after cardiac surgery. Outcomes were compared in systemic inflammatory response syndrome patients with sepsis (n = 15), systemic inflammatory response syndrome patients without sepsis (n = 95), and non-systemic inflammatory response syndrome patients (n = 107).. A gradual decrease in plasma cholesterol concentration occurred during surgery with cardiopulmonary bypass but was no longer present after correction for hemodilution. Corrected cholesterol levels were significantly lower at baseline in sepsis patients than in other subgroups, and it remained lower in the sepsis group during and after cardiopulmonary bypass. With regard to sepsis, the discriminatory power of baseline cholesterol was fairly good as indicated by receiver operating characteristic curve analysis (area under the curve, 0.78; 95% CI, 0.72-0.84). The frequency of sepsis progressively decreased with increasing baseline cholesterol level quintiles (18.6% and 0% in the bottom and top quintiles, respectively, p = 0.005). In multivariate analysis, baseline cholesterol levels and cardiopulmonary bypass duration were significant and independent determinants of the 3-hour postcardiopulmonary bypass increase in concentrations of procalcitonin and interleukin-8, but not of interleukin-6.. Low cholesterol levels before elective cardiac surgery with cardiopulmonary bypass may be a simple biomarker for the early identification of patients with a high risk of sepsis.

Topics: Aged; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cholesterol; Critical Care; Cytokines; Elective Surgical Procedures; Female; Humans; Lipoproteins; Logistic Models; Male; Middle Aged; Postoperative Complications; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Systemic Inflammatory Response Syndrome; Treatment Outcome

To determine the usefulness of procalcitonin (PCT) in decision-making when faced with suspected infection in patients with extensive burns.. Retrospective, observational follow-up study.. Burn Unit of the Complexo Hospitalario Universitario A Coruña (CHUAC), Spain.. We included all patients admitted to the Unit from June 2011 to March 2012 with ≥20% total body surface area burned or ≥10% full-thickness body surface area burned with suspected infection (17 patients with 34 events of suspected infection).. The infections were confirmed in 16/34 episodes (47.1%), and documented in 44.1% (n=15). There were no statistically significant differences in the PCT figures at the time the infection was suspected between the cases with confirmed and unconfirmed infection (p=0.682). The PCT values showed no discriminative value for differentiating patients with SIRS from those with sepsis, severe sepsis and septic shock (area under ROC curve (AUC)=0.546; 95% CI: 0.326-0.766). No significant correlation was found between SOFA and PCT, although there were differences in the PCT values in the patients who had tissue hypoperfusion.. Results show that PCT is not a precise indicator of sepsis at the time of diagnosis. A correlation between PCT levels and hypoperfusion was observed.

Topics: Adult; Aged; Area Under Curve; Biomarkers; Burn Units; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Shock, Septic; Smoke Inhalation Injury; Systemic Inflammatory Response Syndrome; Young Adult

After endovascular aortic repair (EVAR) for treatment of aortoiliac aneurysms, patients commonly develop an inflammatory reaction: Postimplantation syndrome (PIS). Clinically, it may be hard to separate PIS from an infectious complication. Procalcitonin (PCT) is a diagnostic marker for severe bacterial infections and sepsis. We hypothesize that low-PCT levels facilitate the PIS diagnosis after EVAR.. Sixty-nine elective EVAR patients were included. Tympanic temperature, C-reactive protein (CRP), white blood cell count (WBC), and PCT were measured on days -1 and +1, +3 and +5. Complications, in-hospital stay, and infections were recorded. PIS was defined by a body temperature of ≥38°C and WBC ≥12,000/μL combined with no other detected complication or surgical event explaining the inflammatory response. Three cohort subgroups were compared: the noncomplication group, those with PIS, and the patients with complications or additional open surgical events.. All patients developed various extents of postoperative inflammatory responses including a rise in WBC, CRP, and/or temperature. PIS was diagnosed in 12 patients. Forty patients had no complication and seventeen suffered complications or had an additional open surgical event. All PIS patients showed low-PCT levels. On day +3, in the PIS group, median PCT was 0.22 ng/mL (95% confidence interval [CI]: 0.15-0.28), WBC 13.2 × 10(9)/L (11.4-15.6), and CRP 196 mg/L (149-243). High PCT was observed in 6 patients, out of which 4 had complications or additional open surgical procedures.. In patients with PIS after EVAR, there was a strong inflammatory reaction. In the PIS condition, PCT remains low. This pilot study shows that PCT may be useful for the PIS diagnosis.

Topics: Aged; Aged, 80 and over; Aortic Aneurysm; Bacterial Infections; Biomarkers; Blood Vessel Prosthesis Implantation; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Endovascular Procedures; Female; Humans; Iliac Aneurysm; Inflammation; Length of Stay; Leukocyte Count; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Protein Precursors; Sepsis; Time Factors; Treatment Outcome

It would be helpful if we could predict positive or negative blood culture results. This study considered the usefulness of measuring procalcitonin (PCT) level and standard clinical biomarkers such as white blood cell (WBC) count, C-reactive protein (CRP) level, and platelet (PLT) count to predict blood culture results.. We retrospectively analyzed the data from 422 specimens collected at our emergency center within the preceding 36 consecutive months. Primary component analysis (PCA) was used for detecting the degree of the relational contribution of each of the 4 biomarkers to the blood culture results.. Procalcitonin alone (cut-off value, 0.5 ng/mL) yielded a positive blood culture rate of 34.0%. Procalcitonin plus 3 biomarkers (WBC, CRP, and PLT) analyzed by PCA yielded 45.9% or 35.3% when a case was in the first or fourth quadrant, which was significantly higher than cases in the second or third quadrant. Primary component analysis also revealed that positive blood culture results were mainly affected by primary component 1, to which PCT and PLT (not WBC or CRP) predominantly contribute.. Although it is difficult to predict blood culture results, even using 4 biomarkers analyzed by PCA, our new finding that blood culture results are affected not by WBC and CRP, but mainly by PCT and PLT, might help explain the mechanism of sepsis.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Leukocyte Count; Luminescence; Male; Platelet Count; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis

Sepsis still represents an obstacle in modern medicine. The aim of this study was to evaluate the effectiveness and safety of the combined use of lipopolysaccharide adsorption and haemodialysis (HD) with high cut-off haemofilters as part of the complex intensive care of patients with severe sepsis after cardiac surgery.. The study group included 26 patients, 57 (48-62) years of age, with severe sepsis. The inclusion criteria were clinical signs of severe sepsis (systemic inflammatory response syndrome + infection site + failure of two or more organs) together with endotoxin activity assay (EAA) ≥0.6 and procalcitonin (PCT) levels ≥2 ng/ml. Antimicrobial therapy was initiated in the first hour after the diagnosis of severe sepsis and extracorporeal therapy was initiated within 24 h. All of the patients in the study group received standard therapy. Additionally, they received treatment consisting of two LPS adsorption procedures and HD procedures with high cut-off haemofilters in a single circuit. For the control group, 30 comparable patients, 57 (51-61) years of age, were selected and received only standard therapy.. After the last HD procedure within the extracorporeal therapy, we noted an increase in the mean arterial pressure from 76 to 90 mm Hg, p < 0.01, and oxygenation index (from 226 to 291, p < 0.02), in addition to decreases in the LPS concentration according to EAA (from 0.73 to 0.59, p < 0.01) and the Limulus amebocyte lysate test (from 1.44 to 0.36 IU/ml, p < 0.01); PCT falls from 8.19 to 2.44 ng/ml, p < 0.01, and sepsis-related organ failure assessment scores decreases from 13 to 10, p = 0.007. When we compared the data between the study group the day after the procedures and the control group 3 days after the start of intensive care, we discovered that there were statistically significant differences in mean arterial pressure (90 vs. 81 mm Hg, p = 0.0004), oxygenation index (291 vs. 229, p = 0.01), and EAA levels (0.59 vs. 0.67, p = 0.05). Differences in the PCT were not significant (2.44 vs. 3.41, p = 0.15). The 28-day survival rate in the study group was higher than that in the control group (65.4 vs. 33.3%, p = 0.03).. The combined use of LPS adsorption and HD with high cut-off haemofilters in conjunction with standard therapy is a safe, effective method for treating patients who have severe sepsis.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Equipment Design; Female; Humans; Limulus Test; Lipopolysaccharides; Male; Middle Aged; Postoperative Complications; Prospective Studies; Protein Precursors; Renal Dialysis; Sepsis; Severity of Illness Index; Sorption Detoxification

We explored the value of procalcitonin (PCT) to differentiate sepsis from systemic inflammatory response syndrome (SIRS), and determine sepsis severity in the neurological intensive care unit (NICU). Blood samples were measured for C-reactive protein (CRP) and PCT levels upon NICU admission, on the day of diagnosis of SIRS or sepsis, and at 3 and 7 days after diagnosis. We found that there were significant differences in serum levels of CRP and PCT as well as Glasgow Coma Scale (GCS) score upon admission between the SIRS and sepsis groups (p<0.05). CRP and white blood cell levels were not significantly different when attempting to differentiate sepsis severity (p>0.05). Multiple comparisons showed that significant differences in serum PCT levels were observed between sepsis and severe sepsis groups, as well as sepsis and septic shock groups (p<0.05). We obtained the highest sensitivity and specificity for SIRS and sepsis with cut-off values of 2 ng/mL for PCT, 44 mg/dL for CRP, and 4 for the GCS. There were no differences in CRP and PCT levels between cerebrovascular disease and non-cerebrovascular disease groups (p>0.05). No differences were found between viral and bacterial meningitis groups (p>0.05). PCT levels are valuable in discriminating sepsis from SIRS and determining sepsis severity in critically ill patients with neurological disease.

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

Procalcitonin and interleukin 6 (IL-6) are well-known predictors of blood culture positivity in patients with sepsis. However, the association of procalcitonin and IL-6 with blood culture positivity was assessed separately in previous studies. This study aims to examine and compare the performance of procalcitonin and IL-6, measured concomitantly, in predicting blood culture positivity in patients with sepsis.. Forty adult patients with sepsis were enrolled in the study. Blood cultures were drawn before the institution of antibiotic therapy. The area under the curve (AUC) of the receiver operating characteristic curve was estimated to assess the performance of procalcitonin and IL-6 in predicting blood culture positivity.. Positive blood cultures were detected in 10 patients (25%). The AUC of procalcitonin and IL-6 was 0.85 and 0.61, respectively. The combined performance of procalcitonin and IL-6 was similar to that of procalcitonin alone, AUC of 0.85. On univariate analysis, only procalcitonin and IL-6 were associated with blood culture positivity. Multivariate logistic regression analysis showed that only procalcitonin was associated with blood culture positivity (odds ratio, 12.15 [1.29-114.0] for levels above the median compared with levels below the median). Using procalcitonin cut points of 1.35 and 2.14 (nanogram per milliliter) enabled 100% and 90% identification of positive blood cultures and reduced the need of blood cultures by 47.5% and 57.5%, respectively.. Compared with IL-6, procalcitonin better predicts blood culture positivity in patients with sepsis. Using a predefined procalcitonin cut points will predict most positive blood cultures and reduce the need of blood cultures in almost half of patients with sepsis.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Israel; Male; Predictive Value of Tests; Protein Precursors; Risk Factors; Sepsis

Utilizing procalcitonin (PCT) levels to limit antimicrobial overuse would be beneficial from a humanistic and economic perspective.. To assess whether introducing PCT at a teaching hospital reduced antimicrobial exposure in critically ill patients.. Patients wereadmitted to the intensive care unit (ICU) for >72 hours with sepsis and/or pneumonia. PCT levels were drawn on admission to the ICU or with new suspected infection, with at least 1 PCT level being drawn at least 48 hours later. Patients were matched in a 1:1 fashion to historical patients on age, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, gender, and primary diagnosis. The primary outcome was duration of initial antimicrobial exposure defined as days from initiation of antimicrobial therapy to the intentional discontinuation of therapy by the physician. Secondary end points included length of stay, readmission to the hospital, and relapse of infection.. There were 50 patients in the PCT group and 50 patients in the historical group. The initial duration of antimicrobials was 10 (±4.9) days compared with 13.3 (±7.2), which was statistically significant (P = .0238). The duration of stay in the hospital (13.5 compared with 17.8 days; P = .0299), readmission to the hospital (9 compared with 17; P = .055), and relapse of infection (3 compared with 11; P = .02) were seen less in the PCT group compared with controls.. Introducing PCT levels resulted in a shorter duration of initial antimicrobial therapy and was not associated with adverse treatment outcomes.

Topics: Aged; Anti-Infective Agents; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Illness; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Patient Readmission; Pneumonia; Protein Precursors; Recurrence; Sepsis

Systemic inflammatory response syndrome (SIRS) occurs frequently after aneurysmal subarachnoid hemorrhage (aSAH). It is a clinical challenge to distinguish between SIRS and incipient infection. Procalcitonin (PCT) has been studied among general critical care patients as a biomarker for infection. We hypothesized that PCT could be useful to distinguish SIRS from sepsis in aSAH patients.. Prospective, observational study conducted in the multidisciplinary intensive care unit at Mayo Clinic, Jacksonville, FL between August 2009 and September 2010. Main predictor was serum PCT obtained on admission and with subsequent episodes of SIRS. A level of 0.2 ng/mL or higher was considered as elevated PCT. Main outcome was clinical infection, which was subsequently subcategorized into major (systemic) and minor (localized) infections in the sensitivity analysis.. Forty consecutive patients were enrolled. Majority (88 %) developed SIRS during the hospitalization. Infection developed in 16 (40 %) patients, with 6 patients meeting criteria for major infection. Overall, PCT was found to be highly specific for all infections and the subcategory of major infections (97 and 93 %, respectively) with related high negative predictive values. Odds ratio for elevated PCT with clinical infections ranged from 25.2 (95 % CI 2.7-233) to 33.3 (95 % CI 4.3-261) for all and major infections, respectively. Related receiver operating characteristic curves for elevated PCT were 0.74 and 0.96 for all and major infections, respectively.. Procalcitonin of 0.2 ng/mL or greater was demonstrated to be very specific for sepsis among patients with aSAH. Further studies should validate this result and establish its clinical applicability.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Fever; Humans; Infections; Length of Stay; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Subarachnoid Hemorrhage; Systemic Inflammatory Response Syndrome

The aim of our study is to test procalcitonin (PCT) as surrogate marker of identification of Candida spp. by blood culture (BC) and real-time-polymerase chain reaction (PCR), whether alone or in association with bacteria, in septic patients.. We performed a single-centre retrospective study. We reviewed the clinical charts of patients with a diagnosis of severe sepsis or septic shock treated at our general intensive care unit from March 2009 to March 2013. We analysed all diagnostic episodes consisting of BC, real-time PCR assay and dosage of PCT. We registered age, sex, white blood count, sequential organ failure assessment score and type of admission between medical or surgical. When inclusion criteria were met more than once, we registered the new diagnostic episode as subsequent diagnostic episode. The diagnostic performance of PCT to predict Candida spp. identification alone or in mixed infections by either BC or PCR was tested using the receiver-operative characteristic curve. Logistic regression was constructed using presence of Candida spp. as the dependent variable.. A total of 260 diagnostic episodes met the inclusion criteria. According to BC results classification, a significantly lower value of PCT was observed in Candida spp. BSI (0.99 ng/ml, 0.86 - 1.34) than in BSI caused by bacteria (16.7 ng/ml, 7.65 - 50.2) or in mixed infections (4.76 ng/ml, 2.98 - 6.08). Similar findings were observed considering PCR results. A cut-off of ≤ 6.08 ng/ml for PCT yielded a sensitivity of 86.8%, a specificity of 87.4%, a positive predictive value of 63.9%, a negative predictive value (NPV) of 96.3% and an area under the curve of 0.93 for Candida spp. identification by BC. A similar high NPV for a cut-off ≤ 6.78 ng/ml was observed considering the classification of diagnostic episodes according to PCR results, with an AUC of 0.85. A subsequent diagnostic episode was independently associated with Candida spp. detection either by BC or PCR.. PCT could represent a useful diagnostic tool to exclude the detection of Candida spp. by BC and PCR in septic patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Candida; Female; Humans; Male; Middle Aged; Protein Precursors; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sepsis; Shock, Septic

To investigate the correlation between serum procalcitonin (PCT) level and pediatric critical illness score (PCIS) and their prognostic values in children with sepsis.. Sixty-one children with sepsis in the pediatric intensive care unit were enrolled. According to PCIS, these patients were divided into non-critical (n=18), critical (n=20), and extremely critical groups (n=23). Within 24 hours after admission, serum levels of PCT, C-reactive protein (CRP), and lactic acid (LA) and routine blood counts were measured. These parameters were compared between the three groups. The Pearson correlation analysis was performed to determine the correlation of PCT with PCIS and other serological parameters. Based on clinical outcomes, these patients were divided into survival (n=39) and death groups (n=22). The PCT, PCIS, and other serological parameters were compared between the two groups.. The serum levels of PCT and CRP in the non-critical group were significantly lower than those in critical group and extremely critical groups (P<0.05), and the two parameters were significantly lower in the critical group than in the extremely critical groups (P<0.05). The extremely critical group had a significantly higher mortality than the critical group non-critical groups (61% vs 35% and 6%, P<0.05). Serum PCT level had a significantly negative correlation with PCIS (r=-0.63, P<0.001) but a significantly positive correlation with serum CRP level (r=0.73, P=0.003). Compared with the death group, the survival group had significantly higher serum levels of PCT and LA (P<0.05) but a significantly lower PCIS (P<0.05).. There is a good correlation between serum PCT level and PCIS. For children with sepsis, the lower the PCIS, the higher the serum PCT level, resulting in a poorer prognosis. A combination of serum PCT and PCIS can be used as an early prognostic indicator in children with sepsis.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Male; Prognosis; Protein Precursors; Sepsis

To determine a combination of biomarkers that assure the diagnosis of sepsis and severe sepsis in patients in emergency department (ED).. A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.A total of 652 patients with systemic inflammatory response syndrome (SIRS) were enrolled for this prospective study in the ED of Beijing Chaoyang Hospital of the Capital Medical University between March 2010 and March 2013. Eight biomarkers were determined, including levels of procalcitonin (PCT), interleukin-6 (IL-6), D-dimer, C-reactive protein (CRP), brain natriuretic peptide (BNP), white blood cell count (WBC), percentage of immature neutrophil, and platelet count (PLT). Patients were divided into the sepsis group (452 cases) and non-sepsis group (200 cases) according to the diagnostic criteria of sepsis. Then all these patients were stratified into severe sepsis group (190 cases, including septic shock) and non-severe sepsis group (462 cases) according to the diagnosis of severe sepsis. Logistic regression was performed to identify the independent factors for the diagnosis of sepsis and severe sepsis, and the optimal combination of biomarkers was established. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic ability of the combination and the biomarkers.. PCT, IL-6 and D-dimer were independent factors for diagnosis of sepsis and severe sepsis. The area under the ROC curve (AUC) of the combination of three biomarkers was 0.866 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803), IL-6 (0.770) and D-dimer (0.737) alone, and this new combination showed better sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values than that when the three biomarkers was used individually (the results of combination were 81.2%, 81.0%, 90.6%, 56.5%; that of PCT were 75.2%, 80.0%, 89.5%, 58.8%; that of IL-6 were 81.0%, 61.0%, 82.4%, 58.7%; and that of D-dimer were 79.9%, 59.0%, 81.5%, 56.5%, respectively). The AUC of the combination was 0.815 for the diagnosis of severe sepsis and was better than the three biomarkers used alone, which was 0.758 for PCT, 0.740 for IL-6, and 0.704 for D-dimer respectively. Moreover, the sensitivity, specificity, PPV and NPV of the combination were higher than that of the three biomarkers used singularly (the results of combination were 81.6%, 73.6%, 56.0%, 90.6%; that of PCT were 79.5%, 65.0%, 48.2%, 88.5%; that of IL-6 were 65.8%, 70.6%, 47.9%, 83.4%; and that of D-dimer were 60.5%, 73.2%, 48.1%, 81.8%, respectively).. The combination of PCT, IL-6 and D-dimer enhances the diagnostic ability for sepsis and severe sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

To investigate the expression of different inflammatory variables, such as procalcitonin (PCT), C-reactive protein (CRP), and endotoxin in septic patients with bacterial bloodstream infection, in order to assess the value of these variables in early diagnosis.. The clinical data of 132 bacterial bloodstream infection patients with clinical diagnosis of sepsis in intensive care unit (ICU) of Beijing Shijitan Hospital of Capital Medical University from February 2012 to May 2013 were analyzed retrospectively. Patients were divided into Gram-negative (G(-)) bacterial bloodstream infection group (n=98) and Gram-positive (G(+)) bacterial bloodstream infection group (n=34) according to the result of blood culture. The inflammatory variables including white blood cell (WBC) count, percentage of neutrophils (N), CRP, PCT and level of endotoxin in blood of both groups within 6 hours of bloodstream infection were compared, and their correlation was analyzed. The receiver operating characteristic (ROC) curve of inflammatory variables for the diagnosis of bloodstream infection was plotted, and their diagnostic value for bloodstream infection was evaluated according to area under ROC curve (AUC), and finally the sensitivity and specificity of inflammatory variables for bloodstream infection were assessed based on the best diagnostic cut-off points.. (1) The levels of the variables, including PCT, CRP, and endotoxin content in the G(-) bacterial bloodstream infection group were significantly higher than that of G(+) bacterial bloodstream infection group [PCT: 5.11 (0.99, 18.00) μg/L vs. 1.00 (0.36, 2.73) μg/L, Z=49.647, P=0.000; CRP: 111.5±57.4 mg/L vs. 75.9±56.6 mg/L, t=9.947, P=0.000; endotoxin: 18.00 (8.75, 28.00) ng/L vs. 5.00 (5.00, 6.25) ng/L, Z=52.333, P=0.000]. There was no significant difference in WBC and N between two groups. (2) The results of the correlation coefficient of the inflammatory variables showed: in G(-) bacterial bloodstream infection group positive correlation was found between PCT and CRP (r=0.671, P=0.000), PCT and endotoxin (r=0.916, P=0.000), CRP and endotoxin (r=0.687, P=0.004). On the other hand, in G(+) bacterial bloodstream infection group, correlation was shown between PCT and CRP (r=0.620, P=0.000), PCT and endotoxin (r=0.487, P=0.010), PCT and WBC (r=0.537, P=0.001), PCT and N (r=0.432, P=0.011), CRP and endotoxin (r=0.674, P=0.000), endotoxin and WBC (r=0.197, P=0.024). In all of bloodstream infection patients positive correlation was found between PCT and CRP (r=0.538, P=0.000), PCT and endotoxin (r=0.740, P=0.000), PCT and WBC (r=0.259, P=0.003), CRP and endotoxin (r=0.579, P=0.000), endotoxin and WBC (r=0.197, P=0.024). (3) The ROC curve in patients with the diagnosis of sepsis due to bloodstream infection showed that: in the G(-) bacterial bloodstream infection group, AUC for PCT was 0.825, sensitivity of 71.4% and specificity of 96.2% with the best cut-off value >2.455 μg/L; AUC for CRP was 0.761, sensitivity of 64.3% and specificity of 80.8% with the best cut-off value >79.45 mg/L; AUC for endotoxin was 0.797, sensitivity of 61.2% and specificity of 94.2% with the best cut-off value >15.5 ng/L. In the G(+) bacterial bloodstream infection group, AUC for PCT was 0.619, sensitivity of 41.2% and specificity of 82.7% with the best cut-off value >1.585 μg/L; AUC for CRP was 0.533, sensitivity of 32.4% and specificity of 82.7% with the best cut-off value >95.25 mg/L.. The concentrations of PCT, CRP, and endotoxin in patients with G(-) bacterial bloodstream infection were significantly higher than those of G(+) bacterial bloodstream infection group. They are valuable for the early diagnosis of bloodstream infection, and judgment of its severity, and it is more valuable with the combination of PCT, CRP, and endotoxin concentration determinations.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Endotoxins; Female; Humans; Leukocyte Count; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis

To investigate the prognostic significance of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), N-terminal probrain natriuretic peptide (NT-pro-BNP), C-reactive protein (CRP), cytokines, and clinical severity scores in patients with sepsis.. A total of 102 patients with sepsis were divided into survival group (n = 60) and nonsurvival group (n = 42) based on 28-day mortality. Serum levels of biomarkers and cytokines were measured on days 1, 3, and 5 after admission to an ICU, meanwhile the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were calculated.. Serum sTREM-1, PCT, and IL-6 levels of patients in the nonsurvival group were significantly higher than those in the survival group on day 1 (P < 0.01). The area under a ROC curve for the prediction of 28 day mortality was 0.792 for PCT, 0.856 for sTREM-1, 0.953 for SOFA score, and 0.923 for APACHE II score. Multivariate logistic analysis showed that serum baseline sTREM-1 PCT levels and SOFA score were the independent predictors of 28-day mortality. Serum PCT, sTREM-1, and IL-6 levels showed a decrease trend over time in the survival group (P < 0.05). Serum NT-pro-BNP levels showed the predictive utility from days 3 and 5 (P < 0.05).. In summary, elevated serum sTREM-1 and PCT levels provide superior prognostic accuracy to other biomarkers. Combination of serum sTREM-1 and PCT levels and SOFA score can offer the best powerful prognostic utility for sepsis mortality.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Interleukin-6; Male; Membrane Glycoproteins; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Receptors, Immunologic; ROC Curve; Sepsis; Time Factors; Treatment Outcome; Triggering Receptor Expressed on Myeloid Cells-1

Serum cholesterol procalcitonin (PCT) and C-reactive protein (CRP) levels were measured consecutively in 76 critically ill patients at admission to the intensive care unit. The presence of infection was defined according to the CDC (Centers for Disease Control and Prevention) criteria; in-house mortality, underlying diseases, and severity of sepsis were monitored. Nonsurvivors had significantly lower cholesterol levels compared with survivors (69 mg/dL [range, 37-88 mg/dL] vs. 96 mg/dL [range, 71-132 mg/dL], P = 0.006) whereas no significant differences were noted for serum PCT and CRP levels. In a cohort of patients with cholesterol levels of 50 mg/dL or less, 82% did not survive as compared with patients with cholesterol levels of 100 mg/dL or greater (mortality, 21%). In a control group without infection, no difference of cholesterol, PCT, or CRP was found between survivors and nonsurvivors. Our data show that low cholesterol levels in patients with infectious disease have a prognostic value and may be useful markers to identify high-risk patients already at admission.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cholesterol; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Young Adult

A new, highly sensitive fluorescence immunoassay for a TIRF (total internal reflection)-based point-of-care testing (POCT) device was developed for the detection of procalcitonin (PCT), a specific and early marker for sepsis and microbial infections. The immunoassay was performed on a bench-top system that fulfilled all the necessary characteristics of a POCT application, including a short measurement time (<9 min), no sample pre-treatment requirements and application directly near patients. New rat monoclonal antibodies targeting PCT were screened and characterized. The best combinations of antibodies were then integrated into single-use cartridges, and the reduction of nonspecific binding was achieved by supplying suitable additives. Moreover, human recombinant PCT (hrPCT) for use as a standard was developed in the native form of hPCT in plasma (PCT1-116, PCT3-116). The assay achieves the required sensitivity range in human plasma to allow reliable differentiation between healthy persons and varying stages of infection severity (LOD=0.04 ng/mL; LOQ=0.12 ng/mL). Furthermore, the developed PCT assay can be applied in whole human blood with an adequate sensitivity (LOD=0.02 ng/mL; LOQ=0.09 ng/mL). To the best of our knowledge, this is the first diagnostic test for sepsis to use whole blood, which is a crucial requirement for POCT. We were able to detect native PCT in patient samples and showed a good correlation (R(2)=0.988) with the results of the Kryptor(®) device from BRAHMS, a state of the art device for the detection of PCT.

Topics: Animals; Antibodies, Monoclonal; Biomarkers; Biosensing Techniques; Calcitonin; Calcitonin Gene-Related Peptide; Equipment Design; Humans; Immunoassay; Point-of-Care Systems; Protein Precursors; Rats; Sensitivity and Specificity; Sepsis

We studied the predictive value of cord blood procalcitonin (PCT) and interleukin-6 (IL-6) in the diagnosis of early-onset sepsis (EOS) in the preterm infant. Retrospectively, PCT and IL-6 were correlated with clinical and/or blood culture positive EOS and negative infectious status between February 2008 and March 2011. Receiver operating curves (ROC) were generated and the area under the curve (AUC) was calculated by use of Youden's Index to detect the best cut-off values for sensitivity and specificity. Thirty of 218 preterm infants (13.8%) were diagnosed as having EOS. The optimal cut-off value for PCT was 0.235 μg/L (sensitivity 78.6%, specificity 86.3%), and for IL-6 15.85 ng/L (sensitivity 73.7%, specificity 84.2%), the combination of PCT and IL-6 revealed sensitivity 77.1% and specificity 91.7%. The combined determination of PCT and IL-6 from cord blood was highly sensitive and specific in the prediction of EOS.

Topics: Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Interleukin-6; Male; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis

We investigated the diagnostic and prognostic utilities of procalcitonin (PCT), B-type natriuretic peptide (BNP), and neutrophil gelatinase-associated lipocalin (NGAL) in critically ill patients with suspected sepsis, for whom sepsis was diagnosed clinically or based on PCT concentrations.. PCT, BNP, and NGAL concentrations were measured in 340 patients and were followed up in 109 patients. All studied biomarkers were analyzed according to the diagnosis, severity, and clinical outcomes of sepsis.. Clinical sepsis and PCT-based sepsis showed poor agreement (kappa = 0.2475). BNP and NGAL showed significant differences between the two groups of PCT-based sepsis (P = 0.0001 and P < 0.0001), although there was no difference between the two groups of clinical sepsis. BNP and NGAL were significantly different according to the PCT staging and sepsis-related organ failure assessment subscores (P < 0.0001, all). BNP and PCT concentrations were significantly higher in the non-survivors than in the survivors (P = 0.0002) and showed an equal ability to predict in-hospital mortality (P = 0.0001). In the survivors, the follow-up NGAL and PCT concentrations were significantly lower than the initial values (148.7 ng/mL vs. 214.5 ng/mL, P < 0.0001; 0.61 ng/mL vs. 5.56 ng/mL, P = 0.0012).. PCT-based sepsis diagnosis seems to be more reliable and discriminating than clinical sepsis diagnosis. Multimarker approach using PCT, BNP, and NGAL would be useful for the diagnosis, staging, and prognosis prediction in the critically ill patients with suspected sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Lipocalins; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined.. 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test.. Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure.. Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Neoplasm Proteins; Organ Dysfunction Scores; Partial Thromboplastin Time; Predictive Value of Tests; Prognosis; Protein Precursors; Proteoglycans; Prothrombin Time; Retrospective Studies; ROC Curve; Sepsis; Severity of Illness Index; Up-Regulation

To understand how coupled plasma filtration and adsorption (CPFA) could influence the time course of the advanced stages of sepsis, mean arterial pressure (MAP) and norepinephrine dosage.. Patients with severe sepsis and septic shock with ≥2 organ failures not responding to volume resuscitation and vasopressor infusion were treated with CPFA within 8 h of admission to the intensive care unit.. Thirty-nine patients were treated (median age: 63 years, median SAPS II score: 45) and 28 survived advanced sepsis. In the latter, the median MAP increased and the norepinephrine dosage decreased significantly after CPFA, whereas in the nonsurvivors these values did not change significantly. The volume of treated plasma was significantly higher in survivors than nonsurvivors.. These results suggest a possible existence of a dose-response effect for CPFA. Future studies are therefore recommended to evaluate the efficacy of this treatment and to determine its best timing and intensity.

Topics: Aged; Arterial Pressure; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hemodynamics; Hemofiltration; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Treatment Outcome

Autophagy is a highly conserved mechanism of eukaryotic cells implicated in cell homeostasis and elimination of intracellular pathogens. Functional polymorphisms in genes encoding for autophagy have been associated with susceptibility to inflammatory and infectious diseases, but data on severe infections are missing. The aim of the present study was to assess whether polymorphisms in genes encoding proteins involved in autophagy influence susceptibility to ventilator-associated pneumonia (VAP). Mechanically ventilated patients with VAP were studied. Genotyping for autophagy-related 16-like 1 (ATG16L1, rs2241880) functional polymorphism was performed using the TaqMan single-nucleotide assay. Monocytes were isolated from patients and stimulated with lipopolysaccharide (LPS). Tumor necrosis factor-α (TNF-α) was measured in the supernatants of monocytes using an enzyme-linked immunosorbent assay. Procalcitonin (PCT) was also measured in the serum of patients by an immuno-time-resolved amplified cryptate technology assay. A total of 155 patients with VAP were enrolled in the study. Carriage of the minor A allele of ATG16L1 was associated with septic shock with at least one organ failure (odds ratio (OR): 2.40, p: 0.036). TNF-α production was significantly greater among the carriers of the polymorphism presenting with at least one organ failure (p: 0.040). PCT was increased upon worsening to septic shock and organ failure only among carriers of the minor frequency A alleles. In a homogeneous cohort of septic patients with VAP, the carriage of autophagy polymorphisms predisposes to VAP severity and septic shock development. This may be related with predisposition to immunoparalysis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autophagy-Related Proteins; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Female; Genetic Predisposition to Disease; Genotype; Genotyping Techniques; Humans; Male; Middle Aged; Pneumonia, Ventilator-Associated; Polymorphism, Genetic; Protein Precursors; Sepsis; Tumor Necrosis Factor-alpha; Young Adult

Procalcitonin (PCT) is currently the most studied infection biomarker and its blood levels seem to mirror the severity of illness and outcome. PCT is widely used together with other biomarkers, such as white blood cells (WBC) count and C reactive protein (CRP), in order to guide antibiotic therapy. This study aimed to verify the diagnostic and prognostic power of WBC, CRP and PCT in patients with suspected infection in emergency department (ED).. A total of 513 patients presenting to the ED with signs/symptoms of local infections or sepsis were enrolled. APACHEII score and in-hospital death were recorded. Patients were subdivided into quartiles by age, and the biomarkers were measured at baseline. Receiver operating characteristics (ROC) curves for evaluating diagnostic and prognostic role of PCT, CRP and WBC were calculated for each variable alone and combined.. When compared each other for PCT, CRP, and WBC there was no significant difference between the four subgroups. A direct correlation between PCT and WBC was found in the II, III, and IV quartiles (the highest correlation, r=0.34, p<0.0003). PCT alone or when combined with WBC showed the best diagnostic and prognostic power at ROC analysis.. Our data demonstrate that WBC, but more CRP and PCT are reliable diagnostic and prognostic biomarkers, when considered in combination and with severity clinical score. PCT confirms its stronger usefulness as a diagnostic marker of sepsis. A multi-diagnostic tools approach is fundamental to perform a correct and rapid diagnosis of infection and sepsis in ED.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Leukocyte Count; Male; Prognosis; Protein Precursors; Reproducibility of Results; Sepsis

We recently identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in children. Here we assess IL-27 as a sepsis diagnostic biomarker in critically ill adults with systemic inflammatory response syndrome and sepsis.. IL-27 and procalcitonin (PCT) were measured from plasma samples in three groups: no sepsis (n = 78), pulmonary source of sepsis (n = 66), and non-pulmonary source of sepsis (n = 43). Receiver operating characteristic curves and classification and regression tree methodology were used to evaluate biomarker performance.. IL-27 did not discriminate effectively between sepsis and sterile systemic inflammatory response syndrome in unselected patients. The highest area under the curve (AUC) was 0.70 (95% C.I. 0.60 - 0.80) for IL-27 in subjects with a non-pulmonary source of sepsis. A decision tree incorporating IL-27, PCT, and age had an AUC of 0.79 (0.71-0.87) in subjects with a non-pulmonary source of sepsis. Compared to children with sepsis, adults with sepsis express less IL-27.. IL-27 performed overall poorly in this cohort as a sepsis diagnostic biomarker. Combining IL-27, PCT, and age reasonably estimated the risk of sepsis in subjects with a non-pulmonary source of sepsis. IL-27 may be a more reliable sepsis diagnostic biomarker in children than in adults.

Topics: Age Factors; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Trees; Diagnosis, Differential; Female; Humans; Interleukin-27; Male; Middle Aged; Protein Precursors; Respiratory Tract Infections; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

Accurate diagnosis of sepsis is difficult in patients post burn due to the large inflammatory response produced by the major insult. We aimed to estimate the values of serum N-terminal pro-B-type natriuretic peptide and procalcitonin and the changes in hemodynamic variables as markers of sepsis in critically ill burn patients.. Prospective, observational study.. A quaternary-level university-affiliated ICU.. Fifty-four patients with burns to total body surface area of greater than or equal to 15%, intubated with no previous cardiovascular comorbidities, were enrolled.. At admission, a FloTrac/Vigileo system was attached and daily blood samples taken from the arterial catheter. Infection surveillance was carried out daily with patients classified as septic/nonseptic according to American Burns Consensus criteria.. N-terminal pro-B-type natriuretic peptide, procalcitonin, and waveform analysis of changes in stroke volume index and systemic vascular resistance index were measured within the first 24 hours after burn and daily thereafter for the length of the ICU stay or until their first episode of sepsis. Prevalences of stroke volume variation less than 12% (normovolemia) with hypotension (systolic blood pressure < 90 mm Hg) were recorded. Patients with sepsis differed significantly from "no sepsis" for N-terminal pro-B-type natriuretic peptide, systemic vascular resistance index, and stroke volume index on days 3-7. Procalcitonin did not differ between sepsis and "no sepsis" except for day 3. Area under the receiver operating characteristic curves showed excellent discriminative power for B-type natriuretic peptide (p = 0.001; 95% CI, 0.99-1.00), systemic vascular resistance index (p < 0.001; 95% CI, 0.97-0.99), and stroke volume index (p < 0.01; 95% CI, 0.96-0.99) in predicting sepsis but not for procalcitonin (not significant; 95% CI, 0.29-0.46). A chi-square crosstab found that there was no relationship between hypotension with normovolemia (stroke volume variation < 12%) and sepsis.. Serum N-terminal pro-B-type natriuretic peptide levels and certain hemodynamic changes can be used as an early indicator of sepsis in patients with burn injury. Procalcitonin did not assist in the early diagnosis of sepsis.

Topics: Adolescent; Adult; Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Hemodynamics; Hospital Mortality; Hospitals, University; Humans; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Young Adult

A relevant amount of patients with clinical suspect of sepsis is admitted and treated in medical wards (MW). These patients have a better prognosis but are older and with more comorbidities compared to those admitted to intensive care units (ICU). Procalcitonin (PCT) is extensively used in emergency departments for the diagnosis of sepsis, but its accuracy in the setting of a MW has not been thoroughly investigated. Predicted low PCT levels also call for the comparison of immunomagnetic-chemiluminescent (L-PCT) and time-resolved amplified cryptate emission (TRACE, K-PCT) technologies, in PCT determination.. In 80 patients with systemic inflammatory response syndrome (SIRS) diagnostic criteria and suspect of sepsis newly admitted to a MW, PCT was determined with L- and K-PCT method.. Sixty patients were diagnosed as sepsis (20 microbiologically and 40 clinically proven) and 20 with non-infective SIRS. The sepsis group had significantly higher levels of both PCTs, with no differences between the clinically and microbiologically proven subgroups. The areas under ROC curves for L- and K-PCT were 0.72 and 0.78 (p<0.001 for each), respectively. Based on MW customized cut-off values of 0.150 (L-PCT) and 0.143 ng/mL (K-PCT), overall accuracies were 66.8 (95% CI 58.7-78.9) and 78.2% (69.8-87.2), respectively, compared to the 55% (44.2-66) of 0.5 ng/mL canonical cut-off. Neither PCT-L nor -K held prognostic value on survival.. In MW patients, customized PCT cut-off levels provide better accuracy than customary levels adopted from ICU, and TRACE technology seems to offer a wider analysis range.

Topics: Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Patient Admission; Prognosis; Protein Precursors; Sepsis; Time Factors

The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients.. We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene.. One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers.. Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; DNA; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

In human medicine, procalcitonin (PCT) is a very common and well-established biomarker for sepsis. Even though sepsis is also a leading cause of death in foals and adult horses, up to now, no data about the role of equine PCT in septic horses has been available. Based on monoclonal antibodies targeted against human PCT, we report here the development of a sandwich ELISA for the quantification of equine PCT in equine plasma samples. The ELISA was characterized for intra- and interassay variance and a working range from 25 to 1,000 ng mL(-1) was defined as within this range; both intra- and interassay variances were below 15 %. The target recovery ranged between 73 and 106 %. The ELISA was used to determine the equine PCT concentration in 24 healthy and 5 septic horses to show the potential for clinical evaluation of equine PCT. Significantly different (P = 0.0006) mean equine PCT concentrations were found for the healthy control group and the sepsis group (47 and 8,450 ng mL(-1)).

Topics: Animals; Antibodies, Monoclonal; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; Horses; Humans; Inflammation; Male; Protein Precursors; Recombinant Proteins; Reproducibility of Results; ROC Curve; Sepsis

The purpose of this study is to investigate the effect of serial lysophosphatidylcholine (LPC) measurement on 28-day mortality prediction in patients with severe sepsis or septic shock admitted to the medical intensive care unit (ICU).. This is a prospective observational study of 74 ICU patients in a tertiary hospital. Serum LPC, white blood cell, C-reactive protein, and procalcitonin (PCT) levels were measured at baseline (day 1 of enrollment) and day 7. The LPC concentrations were compared with inflammatory markers using their absolute levels and relative changes.. The LPC concentration on day 7 was significantly lower in nonsurvivors than in survivors (68.45 ± 42.36 μmol/L and 99.76 ± 73.65 μmol/L; P = .04). A decreased LPC concentration on day 7 to its baseline as well as a sustained high concentration of PCT on day 7 at more than 50% of its baseline value was useful for predicting the 28-day mortality. Prognostic utility was substantially improved when combined LPC and PCT criteria were applied to 28-day mortality outcome predictions. Furthermore, LPC concentrations increased over time in patients with appropriate antibiotics but not in those with inappropriate antibiotics.. Serial measurements of LPC help in the prediction of 28-day mortality in ICU patients with severe sepsis or septic shock.

Topics: Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospitalization; Humans; Intensive Care Units; Lymphocyte Count; Lysophosphatidylcholines; Male; Middle Aged; Organ Dysfunction Scores; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Time Factors

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Leukocytes; Middle Aged; Protein Precursors; Sepsis

Sepsis is one of the leading causes of mortality in critically ill patients, and providing a timely diagnosis and early intervention is necessary for successful treatment. Procalcitonin (PCT) may be a better marker of sepsis than conventional inflammatory markers. The aim of this study was to evaluate the clinical utility of the PCT level as a marker of sepsis.. Forty-five patients with sepsis, 24 patients with pneumonia who did not meet the SIRS criteria (PN) and 56 controls were enrolled in this study. The levels of PCT and other serum markers were measured, and their utility as markers of sepsis was assessed.. The serum PCT levels exhibited statistically significant differences between the three groups (p<0.0001). The PCT levels in the sepsis group (29.3 ± 85.3 ng/mL) were significantly higher (p<0.001) than those observed in the PN group (0.34 ± 8.6 ng/mL) and the control group (0.74 ± 2.1 ng/mL), according to a post hoc analysis. There were no differences in the white blood cell (WBC) counts or C-reactive protein (CRP) levels between the three groups. Fourteen of the 45 patients with sepsis had positive microbiological blood cultures (Gram-positive cocci [GPC] in seven patients, Gram-negative rods [GNR] in six patients, other types of bacteria in one patient). The 13 patients with GNR or GPC were categorized into the GNR group or GPC group according to the identified pathogens. The serum PCT levels were significantly higher in the GNR group (149.8 ± 199.7 ng/mL) than in the GPC group (19.1 ± 41.8 ng/mL) (p<0.05), although there were no differences in the WBC counts or CRP levels between these groups. When the cut-off value for the PCT level was set at 16.9 ng/mL, the sensitivity and specificity for the detection of GNR infection were 85.7% and 83.3%, respectively.. The PCT level is a potentially useful marker of the type of causative pathogen in patients with sepsis whose measurement may facilitate the selection of appropriate empiric antibiotic treatment.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Follow-Up Studies; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Gram-Positive Cocci; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Reproducibility of Results; ROC Curve; Sepsis

Procalcitonin is useful for the diagnosis of sepsis but its prognostic value regarding mortality is unclear. This prospective observational study was designed to study the prognostic value of procalcitonin in prediction of 28 day mortality in patients of sepsis. Fifty-four consecutive patients of sepsis, severe sepsis and septic shock defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria from medical Intensive Care Unit (ICU) of a tertiary care center in New Delhi, India were enrolled from July 2011 to June 2013. Procalcitonin (PCT), C-reactive protein (CRP) measurements were recorded on day 1, day 7 and day 28 of follow up.. Procalcitonin value was a better predictor of all-cause short-term mortality than C-reactive protein. Those patients with Procalcitonin levels <7 ng/ml showed higher cumulative survival than those with level [greater than or equal to]7 ng/ml (69.1% vs. 39.5%, p = 0.02). No such effect was observed in relation to C-reactive protein. Procalcitonin levels [greater than or equal to]7 ng/ml predicted mortality with a hazard ratio of 2.6(1.1-6.3).. A Procalcitonin value [greater than or equal to]7 ng/ml obtained at the time of admission to the ICU is a predictor of short-term mortality and thus may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Topics: Adult; Aged; Bacteria; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; Humans; India; Intensive Care Units; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Tertiary Care Centers; Time Factors

Presepsin has recently emerged as a new useful sepsis marker, and our study is focused on the usefulness of presepsin as earlier detection and monitoring biomarker for sepsis comparing with other conventional biomarkers.. We compared the mean values of presepsin, procalcitonin, interleukin 6, and high-sensitivity C-reactive protein levels between infection group and noninfection group of study subjects and assessed whether the values decreased during treatment. Furthemore, we evaluated the diagnostic accuracy of presepsin in sepsis and compared the mean level of presepsin to the Acute Physiology and Chronic Health Evaluation III score and mortality rate on the 30th day.. Mean presepsin levels were significantly different between infection group and noninfection group (1403.47 pg/mL vs 239.00 pg/mL). During treatment, mean levels of presepsin decreased significantly, and in the receiver operating characteristic curve analysis, the area under curve value of presepsin was significantly higher than that of other biomarkers. The presepsin levels did not correlate significantly with Acute Physiology and Chronic Health Evaluation III scores and mortality rates on the 30th day.. Presepsin showed significantly higher values in infection group than in noninfection group. The diagnostic accuracy of presepsin was higher than other conventional biomarkers. For early diagnosis and treatment of bacterial sepsis, presepsin could be a more useful marker than the other markers.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Area Under Curve; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Interleukin-6; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Protein Precursors; ROC Curve; Sepsis

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Humans; Intensive Care Units; Natriuretic Peptide, C-Type; Prognosis; Protein Precursors; Sepsis

Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein.. Single-center prospective cohort study.. Tertiary care, academic, university hospital.. One hundred fourteen critically ill patients with cancer with fever.. None.. Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59-0.82) and procalcitonin (0.71; 95% CI, 0.60-0.83) compared with C-reactive protein (0.53; 95% CI, 0.39-0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients' mortality within 2 months after their fever onset. Regarding patients' response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71-0.92) and procalcitonin (0.73; 95% CI, 0.60-0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45-0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001).. In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.

Topics: Academic Medical Centers; Adrenomedullin; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Sepsis

Differentiating sepsis from other noninfectious causes of systemic inflammation is often difficult in the elderly. The aim of this study was to evaluate the ability of C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), procalcitonin (PCT), and Interleukin-6 (IL-6) to identify elderly patients with sepsis. In this single center prospective observational study, we included all consecutive elderly patients admitted with suspected sepsis and systemic inflammatory response syndrome (SIRS) in an emergency department. Blood samples for measuring CRP, PCT, IL-6, ESR and white blood cells (WBC) count were taken at first day of admission. Sensitivity, specificity, positive and negative predictive values were calculated for each inflammatory markers being studied. A total of 150 elderly patients aged 65 and older, 50 with sepsis and 50 with SIRS, and fifty individuals in a normal health status were included. CRP exhibited the greatest sensitivity (98%) and negative predictive value (98.6%) and performed best in differentiating patients with sepsis from those with SIRS. In a receiver operating characteristic curve analysis, IL-6 performed best in distinguishing between SIRS and the control group (AUC 0.75, 95% CI). On the other hand, both CRP and ESR appeared to be a more accurate diagnostic parameter for differentiating sepsis from SIRS among elderly patients.

Topics: Aged; Biomarkers; Blood Sedimentation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Inflammation; Interleukin-6; Leukocyte Count; Male; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

Sepsis is one of the most serious and life-threatening clinical conditions of childhood. This study has been designed to evaluate how useful multiplex real-time polymerase chain reaction (PCR) is in the early diagnosis of responsible microorganisms of sepsis and to specify how serial procalcitonin level measurement is helpful to support diagnosis of sepsis.. A total of 79 blood samples from 69 consecutive patients were collected for this prospective study between 01 Sept 2009 - 29 Feb 2012.. In the evaluation of patients who are diagnosed with sepsis out of 69 patients with 79 clinical sepsis, 24 (30.37%) had positive blood culture and 19 (24%) samples were positive for PCR. When blood culture and multiplex real-time PCR results were compared, multiplex real-time PCR had a sensitivity of 75% and specificity of 100%. When the 2 microorganisms that multiplex real-time PCR cannot detect are excluded sensitivity increased to 81.8% and specificity did not differ. Procalcitonin levels on the day sepsis is suspected had a mean level of 13.91 ng/mL (+/- 49.26), on the 1st day (after 24 hours) the mean level of procalcitonin was 15.05 ng/mL (+/- 43.95), on the 2nd day (after 48 hours) it was 14.89 ng/mL (+/- 41.57). Mean procalcitonin levels of 50 children admitted with complaints other than infection and systemic inflammation was 0.06 ng/mL (+/- 0.04).. In conclusion, multiplex real-time PCR test would be useful in the early diagnosis of sepsis. Studying procalcitonin levels is helpful in the early diagnosis of sepsis but does not have any correlation with the isolation of microorganisms in blood culture and survival.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Multiplex Polymerase Chain Reaction; Prospective Studies; Protein Precursors; Real-Time Polymerase Chain Reaction; Sepsis

To evaluate the clinical implication of serum procalcitonin (PCT) in patients with burn sepsis by analyzing its change.. Twenty-eight extensively burned patients with sepsis hospitalized from January 2012 to December 2013 were recruited in this retrospective study. These patients were divided into death group (n = 12) and survival group (n = 16) according to the outcome. The baseline characteristics of patients in the two groups were similar. Some conventional indexes of sepsis, including white blood cell count, percentage of neutrophils, platelet count, organ function parameters [ALT, AST, total bile acid (TBA), creatinine, blood sodium], and acute physiology and chronic health evaluation (APACHE) II score were compared between the two groups when sepsis was diagnosed. Serum levels of PCT of patients in the two groups were determined immediately after diagnosis of sepsis, from post sepsis day (PSD) 1 to 4, and from PSD 5 to 8. Data were processed with t test, chi-square test, and nonparametric rank sum test (Keuskal-Wallis). Receiver operating characteristic (ROC) curve of serum PCT value was used to predict death for 28 burn patients when sepsis was diagnosed.. There were no statistically significant differences in white blood cell count, percentage of neutrophils, platelet count, APACHE II score, and organ function parameters between death group and survival group when sepsis was diagnosed (with t values from -0.601 to 1.726, P values above 0.05). The serum levels of PCT in death group immediately after diagnosis of sepsis, from PSD 1 to 4, and from PSD 5 to 8 were respectively (38.5 ± 41.3), (26.8 ± 38.5), (19.3 ± 16.3) ng/mL, which were significantly higher than those in survival group [(6.1 ± 2.3), (5.4 ± 2.9), (4.9 ± 3.6) ng/mL, with Z values from -4.364 to -2.955, P values below 0.01]. The total area under ROC curve of serum PCT value for predicting death for 28 patients with burn sepsis was 0.990, and 10.9 ng/mL was chosen as the optimal threshold value, with sensitivity of 91.7% and specificity of 100.0%.. Serum PCT value can be served as a vital prognostic indicator for patients with burn sepsis, which can be considered as a guide for rational use of antibiotics, also provide as a reference for treatment, in order to reduce mortality.

Topics: Aged; Anti-Bacterial Agents; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Serum; Statistics, Nonparametric

Procalcitonin is used as a marker for sepsis but there is little known about the correlation of the procalcitonin elevation with the causative organism in sepsis. All patients aged 18 to 80 years who were admitted to the surgery service from June 2010 to May 2012 and who had a procalcitonin drawn were evaluated. Culture data were reviewed to determine the causative organism. Infections analyzed included pneumonia, urinary tract infection (UTI), bloodstream infection, and Clostridium difficile. Other parameters assessed included reason for admission, body mass index, pressor use, antibiotic duration, and disposition. Two hundred thirty-two patient records were reviewed. Patients without a known infection/source of sepsis had a mean procalcitonin of 3.95. Those with pneumonia had a procalcitonin of 20.59 (P = 0.03). Those with a UTI had a mean procalcitonin of 66.84 (P = 0.0005). Patients with a bloodstream infection had a mean procalcitonin of 33.30 (P = 0.003). Those with C. difficile had a procalcitonin of 47.20 (P = 0.004). When broken down by causative organisms, those with Gram-positive sepsis had a procalcitonin of 23.10 (P = 0.02) compared with those with Gram-negative sepsis at 32.75 (P = 0.02). Those with fungal infections had a procalcitonin of 42.90 (P = 0.001). These data suggest that procalcitonin elevation can help guide treatment by indicating likely causative organism and infection type. These data may provide a good marker for initiation of antifungal therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Pneumonia; Protein Precursors; Sepsis; Young Adult

Procalcitonin (PCT) has been shown to be a useful surrogate marker in identifying patients with various bacterial infections. PCT has been studied as a diagnostic marker in differentiating bacterial pneumonia from other respiratory conditions such as chronic obstructive pulmonary disease exacerbations or viral pneumonia. Differentiating bacterial from nonbacterial pneumonia using PCT has shown to reduce antibiotic usage, length of stay, and antibiotic-related adverse effects. PCT has also been studied in patients with sepsis in an effort to reduce unnecessary antibiotic usage and decrease the length of antibiotic therapy. This article focuses on the use of PCT in patients with various degrees of chronic kidney disease in addition to various forms of dialysis, as chronic kidney disease may alter baseline levels of PCT and thus result in inappropriate use of PCT in this population.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Dialysis; Humans; Protein Precursors; Renal Insufficiency, Chronic; Renal Replacement Therapy; Sepsis

To explore the diagnostic and prognostic values of serum procalcitonin (PCT) and C-reactive protein (CRP) in patients of bacterial sepsis.. From July 2012 to May 2013, a total of 120 critically ill patients at our intensive care unit (ICU) were recruited. They included septic (sepsis group, n = 63) local infection (local infection group, n = 57) and healthy people (control group, n = 30). The serum levels of PCT and CRP were measured. Septic patients were divided into survival and death groups according to the prognosis. They were also divided into gram-positive and gram-negative bacteria groups according to the results of bacterial cultivation.. The serum levels of PCT and CRP, as well as acute physiology and chronic health evaluation II (APACHEII) scores and sepsis related organ failure assessment (SOFA) scores in the sepsis group were significantly higher than those in the local infection and control groups (P < 0.05). And those in the local infection group were higher than those in the control group (P < 0.05). The sensitivity, specificity, positive predictive value and negative predictive value for serum PCT in diagnosing bacterial sepsis were significantly larger than those for serum CRP (P < 0.05). The serum levels of PCT and CRP in survival group were less than those in death group at Day 1, 5, 10 and 15 (P < 0.05). Moreover, there were significant time effects on the serum levels of PCT and CRP in the survival group (P < 0.05), but not in the death group (P > 0.05). When PCT was ≥ 10.0 µg/L, the patients of gram-negative bacteria were more than those of gram-positive bacteria (P < 0.05).. The serum levels of PCT and CRP are reliable in the diagnostic and prognostic evaluations of bacterial sepsis. Both also have certain reference value for local infection. Moreover the sensitivity and specificity of serum PCT were better those of serum CRP.

Topics: Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Prognosis; Prospective Studies; Protein Precursors; Reference Values; Sensitivity and Specificity; Sepsis

This study was aimed to investigate the correlation of coagulation indicators [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB), antithrombinIII (ATIII), D-dimer (D-D) levels] with inflammatory markers [procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)] for sepsis in hematologic malignancy patients. A total of 326 febrile in patients with hematologic diseases from 2062 patients in West China Hospital, Sichuan University from March 2011 to April 2013 were retrospectively analyzed. The patients were divided into sepsis group(n = 72), non-sepsis group(n = 176) and non-sepsis with low Alb group (n = 78) according to blood culture. The results showed that the values of PT, APTT, D-dimer, Plt in sepsis group were higher than those in non-sepsis group, and the difference between them was statistically significant. While the ATIII level in the sepsis group was lower than that in non-sepsis group, and the difference between them was statistically significant (P < 0.05). And the four inflammatory biomarkers in the sepsis patients were higher than those in non-sepsis patients (P < 0.05). TT and FIB level were not significantly different (P > 0.05). There was not a significant difference in these indicators between non-sepsis group and non-sepsis with low Alb group. The correlation analysis suggested that the level of PCT positively correlated with APTT, D-dimer level (P < 0.05); and negatively correlated with the ATIII (P < 0.05). It is concluded that sepsis results in the concurrent activation of inflammatory and procoagulant pathways. The hematologic malignancy patients with sepsis have an obviously higher systemic inflammatory response, and accompanied with coagulation dysfunction.

Topics: Biomarkers; Blood Coagulation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Fibrin Fibrinogen Degradation Products; Hematologic Neoplasms; Humans; Interleukin-6; Partial Thromboplastin Time; Protein Precursors; Retrospective Studies; Sepsis; Serum Amyloid A Protein; Thrombin Time

Although the clinical application of procalcitonin (PCT) as an infection marker in patients with impaired renal function (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m(2)) has been increasing recently, it is unclear whether PCT is more accurate than C-reactive protein (CRP). We investigated the clinical value of CRP and PCT based on renal function.. From November 2008 to July 2011, a total of 493 patients who simultaneously underwent CRP and PCT tests were enrolled. The area under the receiver operating characteristic (ROC) curve and characteristics of both markers were analyzed according to infection severity and renal function.. In patients with impaired renal function, the area under the ROC curve was 0.876 for CRP and 0.876 for PCT. In patients with infection, CRP levels differed depending on whether the infection was localized, septic, or severely septic, whereas PCT levels were higher in patients with severe sepsis or septic shock. In patients without infection, CRP did not correlate with eGFR, while PCT was negatively correlated with eGFR.. This study demonstrates that CRP is accurate for predicting infection in patients with impaired renal function. The study suggests that in spite of its higher cost, PCT is not superior to CRP as an infection marker in terms of diagnostic value.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Protein Precursors; Renal Insufficiency; Sepsis

The purpose of this study was to evaluate the postmortem distributions of procalcitonin (PCT), C-reactive protein (CRP), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and soluble interleukin-2 receptor (sIL-2R) levels in postmortem serum from femoral blood, pericardial fluid and pleural fluid in a series of sepsis-related fatalities (12 subjects) and control cases (20 subjects) that underwent medico-legal investigations. Our aim was to assess the diagnostic potential of the results obtained from pericardial and pleural fluid analysis in identifying sepsis-related deaths. All sepsis-related cases had a documented, clinical diagnosis that was established in vivo during hospitalization. Pneumonia was the main infectious focus identified during autopsy and histology. Pseudomonas aeruginosa, Klebsiella pnemoniae and Escherichia coli were the most commonly identified bacteria in blood and lung tissue cultures. The preliminary results corroborate the usefulness of PCT, CRP, sTREM-1 and sIL-2R determination in postmortem serum for the identification of sepsis-related deaths. Moreover, the data suggest that, as far as PCT, CRP, sTREM-1 and sIL-2R measurements are concerned, pericardial and pleural fluids can be considered suitable alternatives to postmortem serum should femoral blood prove unavailable at autopsy.

Topics: Aged; Autopsy; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Pericardium; Pleura; Prospective Studies; Protein Precursors; Receptors, Immunologic; Receptors, Interleukin-2; Sensitivity and Specificity; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

In the early phase after pediatric liver transplantation (pLT) several concomitant factors may reduce the performance of established sepsis markers. To date, their clinical interpretation is hindered by a lack of information on their postoperative kinetics. To gather more information on the postoperative course and their changes in bacterial sepsis, we prospectively studied C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) on 9 perioperative days in 25 consecutive pLTs. After an initial postoperative peak, IL-6 and CRP levels significantly re-increased in patients with bacterial sepsis (P < .001). In contrast, PCT had very high postoperative levels; therefore severe infection was a comparatively inferior trigger for PCT elevation compared with the initial operation. The area under the receiver operating characteristic curve to diagnose postoperative sepsis for PCT was only 0.52, compared with 0.95 for IL-6 and 0.89 for CRP. None of the studied biomarkers were depressed by poor graft function. In conclusion, PCT performs poorly as a biomarker for sepsis in the early phase after pLT. With a rapid decline of initially elevated levels, IL-6 provides the best kinetics for detection of postoperative bacterial sepsis.

Topics: Adolescent; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Interleukin-6; Liver Transplantation; Male; Postoperative Complications; Prospective Studies; Protein Precursors; ROC Curve; Sepsis

Infections and sepsis remain the leading cause of morbidity and mortality in secondary peritonitis. Clinicians are still challenged with the task of finding an early and reliable diagnosis of septic complications. The role of inflammatory markers (Procalcitonin (PCT), C-reactive Protein (CRP) and thyroid hormones in determining the severity of secondary peritonitis was evaluated in this study.. On the preoperative and first, third, fifth, seventh, and fourteenth postoperative days, PCT, CRP, and thyroid hormone concentrations were measured in serum taken from eighty-four consecutive patients who were operated on for secondary peritonitis between January 2008 and January 2010. All data was entered and analyzed using the Statistical Package for Social Sciences, version 15.0 and clinical parameters were compared using the student's t-test.. For the groups diagnosed with perforated viscus, PCT concentrations were significantly low in contrast to high thyroid hormone levels in patients who developed postoperative complications or died when compared to patients whose postoperative course was uneventful or discharged. The PCT concentration significantly correlated with the CRP concentration and WBC count.. In the absence of postoperative complications, PCT is a better predictor of outcome than CRP in secondary peritonitis. Our study showed that a low thyroid hormone level can serve as an important prognostic parameter of disease severity in secondary peritonitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Leukocyte Count; Male; Middle Aged; Peritonitis; Postoperative Complications; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Thyroid Hormones; Young Adult

The purpose of this study was to compare the diagnostic performance of the delta neutrophil index (DNI) with procalcitonin and C-reactive protein (CRP) for the prediction of sepsis and its outcome.. A total of 128 consecutive patients who were tested by blood culture were enrolled. The DNI, procalcitonin, and CRP were measured, the blood was cultured, and other clinical data were obtained by retrospective chart review.. The DNI, procalcitonin and CRP increased with increasing disease severity (p < 0.05). The DNI (area under the curve (AUC) 0.932 for sepsis, 0.800 for survival) and procalcitonin (AUC 0.918 for sepsis, 0.831 for survival) had high diagnostic performance for the prediction of sepsis and survival. CRP also has good diagnostic power in predicting sepsis and survival (AUC 0.819 for sepsis, 0.723 for survival). The combination of the DNI and procalcitonin had higher AUC (0.964) than each of the biomakers for the prediction of sepsis. The cutoffs for the DNI, procalcitonin, CRP, and 'procalcitonin + DNI' for the diagnosis of sepsis were 12.3%, > 1.44 ng/mL, > 6.84 mg/L, and > 19.24, respectively. At least one of the DNI or procalcitonin values was high (> cutoff levels) in all sepsis or septic shock patients.. The DNI can be obtained easily from automated hematological analysis and is cost effective. Furthermore, the DNI has a high diagnostic power for predicting sepsis and survival, similar to procalcitonin and better than CRP. The combination of DNI and procalcitonin may improve the ability to predict the severity of sepsis and survival.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Automation, Laboratory; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Predictive Value of Tests; Prognosis; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Severity of Illness Index; Survival Analysis

Procalcitonin (PCT) is a frequently used marker for bacterial sepsis. The present study was aimed to assess the usefulness of PCT measurement in patient with sepsis. We studied the relationship between serum PCT level and blood culture in clinical 209 cases admitted from January 2010 through June 2010. We compared PCT level with blood culture results and other clinical data, and diagnosis such as sepsis and systemic inflammatory response syndrome (SIRS) were obtained from the medical records. In the case of patients with positive blood cultures and PCT < 0.5 ng/mL, the false- positive blood culture was suspected. The possibility of bacteremia was high when PCT level was more than 0.5 ng/mL. Patients with PCT ≥ 2 ng/mL had significant correlation with the presence of sepsis. The PCT measurement could be performed and reported rapidly and provided valuable information before availability of culture results. In this study, we found that the PCT would be a useful biomarker for confirming and ruling out sepsis.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Young Adult

Obesity is a growing problem in industrial nations. Our aim was to examine how overweight patients coped with systemic inflammatory response syndrome (SIRS) after polytrauma.. A total of 651 patients were included in this retrospective study, with an ISS ≥ 16 and age ≥ 16 years. The sample was subdivided into three groups: body mass index (BMI; all in kg/m(2))<25, BMI 25-30 and BMI>30, or low, intermediate and high BMI. The SIRS score was measured over 31 days after admission together with measurements of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT). Data are given as the mean ± SEM if not otherwise indicated. Kruskal-Wallis and χ(2) tests were used for statistical analysis and the significance level was set at p<.05.. The maximum SIRS score was reached in the low BMI-group at 3.4 ± 0.4, vs. 2.3 ± 0.1 and 2.5 ± 0.2 in the intermediate BMI-group and high BMI-group, respectively (p<.0001). However, the maximum SIRS score was reached earlier in the BMI 25-30 group at 1.8 ± 0.2 days, vs. 3.4 ± 0.4 and 2.5 ± 0.2 days in the BMI<25 and BMI>30 groups, respectively (p<.0001). The incidence of sepsis was significantly higher in the low BMI group at 46.1%, vs. 0.2% and 0% in the BMI 25-30 and BMI>30 groups, respectively (p<.0001). No significant differences in the CRP, IL-6 or PCT levels were found between groups.. A higher BMI seemed to be protective for these patients with polytrauma-associated inflammatory problems.

Topics: Adult; Aged; Body Mass Index; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Multiple Trauma; Obesity; Protein Precursors; Retrospective Studies; Sepsis; Systemic Inflammatory Response Syndrome

Absolute eosinophil count (AEC) and procalcitonin (PCT) level may have a prognostic value in critically ill patients. However, their role in cirrhotic patients has never been studied. We evaluated the role of AEC and PCT, obtained at admission, in predicting in-hospital mortality in cirrhotic patients with systemic inflammatory response syndrome (SIRS).. In consecutive cirrhotic patients with SIRS (with or without sepsis), the levels of AEC and PCT were estimated at admission. Their outcome was correlated with these baseline parameters.. One hundred patients were enrolled [median age 52 (range 17-78) years, 84% men]. The etiology of cirrhosis was alcohol (47%), cryptogenic (35%), viral (13%), and others (5%). Their median model for end-stage liver disease (MELD) and Child-Turcotte-Pugh scores were 24 (range 6-40) and 11 (range 5-15), respectively. Infection was present in 59 patients and the rest of the 41 patients had SIRS without infection. There was a significant difference between the median levels of AEC and PCT between patients who had infection and those who did not have infection (P<0.01). Sixty-three patients recovered from SIRS and were discharged, 33 patients died, and four patients received orthotopic liver transplantation during the same admission. Baseline AEC and PCT levels were significantly different between patients who recovered and died. On multivariate analysis, baseline AEC values could independently predict in-hospital mortality, in addition to MELD and serum sodium. The area under receiver operating characteristic curve of AEC for predicting mortality was 0.785, and the best cutoff of AEC, obtained by Youden's index, was 104 cells/cumm, indicating that patients with baseline AEC values less than 104 cells/cumm had higher in-hospital mortality (sensitivity 78%, specificity 70%, positive predictive value 60%, negative predictive value 85%, and accuracy 73%).. In critically ill cirrhotic patients with SIRS, a baseline AEC value of less than 104 cells/cumm accurately predicts in-hospital mortality. The prediction of mortality by AEC is independent of the MELD score and serum sodium.

Topics: Adolescent; Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Eosinophils; Epidemiologic Methods; Female; Humans; Leukocyte Count; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Prognosis; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q(®)-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q(®)-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Forensic Pathology; Granulocytes; Humans; Kidney; Leukocytes; Liver; Lung; Male; Middle Aged; Myocardium; Prospective Studies; Protein Precursors; Sepsis; Spleen; Young Adult

To evaluate the diagnostic and prognostic usefulness of procalcitonin (PCT) in patients admitted to the Emergency Department (ED) with signs of infections and to assess the prognostic value of repeated measurements in predicting hospital mortality.. A prospective, observational study was conducted in our 400-bed General Teaching Hospital. 261 patients arriving in ED with signs/symptoms of infection were enrolled. PCT was performed upon arrival in the ED (T0), and 5 days after antibiotic therapy (T5). Blood cultures were performed in all patients upon arrival in the ED.. Mean T0 PCT value was 7.1±17.9 ng/ml, and at T5 3±9.1 ng/ml (p < 0.0001). Mean PCT in septic non-survivors was increased at T5 compared to T0 but not significantly. The PCT increase at T5 was an independent factor of mortality (OR = 1.29, p < 0.02) in septic patients. Compared to baseline mean delta % PCT decrease at T5 was 28%. Patients with a decrease delta % PCT > 28% showed a lower number of deaths, with a statistical significant difference if compared to those patients with a < 28% decrease (p < 0.004). ROC curve of delta % PCT for prediction of death has an AUC = 0.82 (p < 0.03).. PCT is a useful marker for diagnosis of systemic and local infections, and for prognostic stratification in patients with acute infectious diseases at their arrival in ED. PCT variations after antibiotic therapy are highly predictive for in-hospital mortality. PCT normalization during antibiotic therapy suggests a good response to infection possibly leading to less infection-related deaths.

Topics: Acute Disease; Aged; Aged, 80 and over; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Communicable Diseases; Emergency Service, Hospital; Female; Hospital Mortality; Hospitals, General; Hospitals, Teaching; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Admission; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Factors; ROC Curve; Rome; Sepsis; Time Factors; Treatment Outcome

To evaluate the diagnostic value of measuring serum C-reactive protein (CRP) and procalcitonin (PCT) levels, within 6 hours after admission to the pediatric intensive care unit (PICU) in children with bloodstream infection (BSI)-associated sepsis and septic infection at other sites.. A retrospective analysis was performed on 30 children with a confirmed diagnosis of systemic inflammatory response syndrome who were admitted to the Shengjing Hospital of China Medical University between January 2010 and January 2012. Clinical data on serum CRP, PCT and D-dimer levels were collected within 6 hours after admission. The diagnostic values of the indices were determined by comparative analysis.. Serum CRP and PCT levels in children with BSI-associated sepsis were significantly higher than in children with septic infection at other sites (P<0.05), but there was no significant difference in serum D-dimer levels between the two groups (P>0.05). Serum PCT level was superior to serum CRP level in distinguishing children with BSI-associated sepsis from those with septic infection at other sites. Serum PCT level could not realistically be used for diagnosing BSI-associated sepsis when it was less than 2 ng/mL (negative predictive value: 100%), but could be reliably used when it was more than 10 ng/mL (positive predictive value: 77%).. Serum PCT level is superior to serum CRP level in distinguishing children with BSI-associated sepsis from those with septic infection at other sites within 6 hours after admission to the PICU. Serum PCT level has a better diagnostic value for BSI-associated sepsis when it is more than 10 ng/mL.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Fibrin Fibrinogen Degradation Products; Humans; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis

Procalcitonin (PCT) is an early, sensitive, and accurate marker for diagnosing infection and sepsis. As sepsis and septic shock are dominant causes of acute kidney injury (AKI), we investigated whether PCT is an early predictor of AKI in patients with symptoms of infection.. Between January 2011 and October 2011, 1361 inpatients in West China Hospital who displayed infection symptoms were enrolled in our study. Levels of PCT, serum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and white blood cell count (WBC) were determined and participants' renal function was monitored for 3 consecutive days.. The rate of AKI occurrence 3 days after enrollment was 14.6%. Higher PCT levels were correlated with higher AKI occurrence rates and higher levels of serum urea, creatinine, and cystatin C (p<0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for PCT was 0.823, making it more predictive (p<0.0001) than SAA, CRP, IL-6, or WBC. The cut-off value of 1.575 ng/mL for PCT had the highest validity for predicting AKI in patients with infection symptoms. The sensitivity, specificity, negative-predictive value (NPV), positive-predictive value (PPV), negative-likelihood ratio (LR-), and positive-likelihood ratio (LR+) for this cut-off value were 61.7%, 84.6%, 93.6%, 37.5%, 0.415, and 4.98, respectively.. PCT can be used as a predictive marker for sepsis-induced acute kidney injury in patients with symptoms of infection.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Young Adult

Prediction of bacteremia/sepsis in childhood oncology patients with febrile neutropenia still remains a challenge for the medical community due to the lack of reliable biomarkers, especially at the beginning of infectious process. The objective of this study was to evaluate diagnostic value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, HLA-G) and procalcitonin (PCT) in the identification of infectious process at the beginning of a febrile episode in pediatric oncology patients.. A total of 62 episodes of febrile neutropenia in 37 childhood oncology patients were enrolled in this study. Serum samples were collected at presentation after confirmation of febrile neutropenia and analyzed according to recommendations of manufacturers. Patients were classified into bacteremia/sepsis and fever of unknown origin groups.. Median of PCT and sIL-2R were considerably higher in bacteremia/sepsis group compared to fever of unknown origin group, whereas median of sHLA-G and presepsin levels between investigated groups did not differ sufficiently.. PCT and sIL-2R determination might be used as an additional diagnostic tool for the detection of bacteremia/sepsis in childhood oncology patients with febrile neutropenia.

Topics: Adolescent; Bacteremia; Biomarkers, Tumor; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Demography; Drug-Related Side Effects and Adverse Reactions; Female; Fever; HLA-G Antigens; Humans; Infant; Lipopolysaccharide Receptors; Male; Neoplasms; Neutropenia; Predictive Value of Tests; Protein Precursors; Receptors, Interleukin-2; Sepsis; Solubility

Procalcitonin (PCT) is expressed in nonthryoidal tissues of humans during severe infections. Serum PCT levels are measured to diagnose and guide therapy, and there is some evidence that PCT may also contribute to the pathogenesis of sepsis. We tested whether disruption of the gene encoding PCT in mice affected the course of sepsis. Mice with exons 2-5 of the gene encoding calcitonin/calcitonin gene-related polypeptide α (Calca) knocked out and congenic C57BL/6J control mice were challenged with aerosolized Streptococcus pneumoniae or Pseudomonas aeruginosa, or injected intraperitoneally with S. pneumoniae. There were no significant differences in the survival of knockout and control mice in the two pneumonia models, and no significant differences in weight loss, splenic bacterial counts, or blood leukocyte levels in the peritoneal sepsis model. To verify disruption of the Calca gene in knockout mice, the absence of calcitonin in the serum of knockout mice and its presence and inducibility in control mice were confirmed. To evaluate PCT expression in nonthyroidal tissues of control mice, transcripts were measured in multiple organs. PCT transcripts were not significantly expressed in liver or spleen of control mice challenged with aerosolized P. aeruginosa or intraperitoneal endotoxin, and were expressed in lung only at low levels, even though serum IL-6 rose 3,548-fold. We conclude that mice are not an ideal loss-of-function model to test the role of PCT in the pathogenesis of sepsis because of low nonendocrine PCT expression during infection and inflammation. Nonetheless, our studies demonstrate that nonendocrine PCT expression is not necessary for adverse outcomes from sepsis.

Topics: Animals; Bacterial Load; Calcitonin; Calcitonin Gene-Related Peptide; Exons; Gene Deletion; Interleukin-6; Lung; Mice; Mice, Inbred C57BL; Mice, Knockout; Peritonitis; Pneumococcal Infections; Protein Precursors; Pseudomonas aeruginosa; Pseudomonas Infections; Sepsis; Severity of Illness Index; Spleen; Streptococcus pneumoniae

Procalcitonin (PCT)-protocols to guide antibiotic treatment in severe infections are known to be effective. But less is known about the long-term effects of such protocols on antibiotic consumption under real life conditions. This retrospective study analyses the effects on antibiotic use in patients with severe sepsis and septic shock after implementation of a PCT-protocol.. We conducted a retrospective ICU-database search for adult patients between 2005 and 2009 with sepsis and organ dysfunction who where treated accordingly to a PCT-guided algorithm as follows: Daily measurements of PCT (BRAHMS PCT LIA(®); BRAHMS Aktiengesellschaft, Hennigsdorf, Germany). Antibiotic therapy was discontinued if 1) clinical signs and symptoms of infection improved and PCT decreased to ≤1 ng/ml, or 2) if the PCT value was >1 ng/ml, but had dropped to 25-35% of the initial value within three days. The primary outcome parameters were: antibiotic days on ICU, ICU re-infection rate, 28-day mortality rate, length of stay (LOS) in ICU, mean antibiotic costs (per patient) and ventilation hours. Data from 141 patients were included in our study. Primary outcome parameters were analysed using covariance analyses (ANCOVA) to control for effects by gender, age, SAPS II, APACHE II and effective cost weight.. From baseline data of 2005, duration of antibiotic therapy was reduced by an average of 1.0 day per year from 14.3 ±1.2 to 9.0 ±1.7 days in 2009 (p=0.02). ICU re-infection rate was decreased by yearly 35.1% (95% CI -53 to -8.5; p=0.014) just as ventilation hours by 42 hours per year (95% CI -72.6 to -11.4; p=0.008). ICU-LOS was reduced by 2.7 days per year (p<0.001). Trends towards an average yearly reduction of 28-day mortality by -22.4% (95% CI -44.3 to 8.1; p=0.133) and mean cost for antibiotic therapy/ patient by -14.3 Euro (95% CI -55.7 to 27.1) did not reach statistical significance.. In a real-life clinical setting, implementation of a PCT-protocol was associated with a reduced duration of antibiotic therapy in septic ICU patients without compromising clinical or economical outcomes. GERMAN CLINICAL TRIALS REGISTER: DRKS00003490.

Topics: Adult; Aged; Aged, 80 and over; Algorithms; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Monitoring; Drug Utilization; Female; Germany; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis; Treatment Outcome

Neutrophil elastase plays a crucial role in the development of acute lung injury (ALI) in patients with systemic inflammatory response syndrome (SIRS). The clinical efficacy of the neutrophil elastase inhibitor, sivelestat, for patients with ALI associated with SIRS has not been convincingly demonstrated. The aim of this study was to determine if there are clinical features of patients with this condition that affect the efficacy of sivelestat.. This was a retrospective study of 110 ALI patients with SIRS. Clinical information, including the etiology of ALI, the number of organs failing, scoring systems for assessing the severity of illness, and laboratory data, was collected at the time of diagnosis. Information on the number of ventilator-free days (VFDs) and changes in PaO(2)/F(I)O(2) (ΔP/F) before and 7 days after the time of ALI diagnosis was also collected. The effect of sivelestat on ALI patients was also examined based on whether they had sepsis and whether their initial serum procalcitonin level was ≥0.5 ng/mL.. There were 70 patients who were treated with sivelestat and 40 control patients. VFDs and ΔP/F were significantly higher in the treated patients than in the control patients. However, there was no significant difference in the patient survival rate between the two groups. Sivelestat was more effective in ALI patients with a PaO(2)/F(I)O(2) ratio ≥ 140 mmHg or sepsis. Sivelestat significantly prolonged survival and led to higher VFDs and increased ΔP/F in septic patients and patients with initial serum procalcitonin levels ≥ 0.5 ng/mL.. The results may facilitate a future randomized controlled trial to determine whether sivelestat is beneficial for ALI patients with sepsis.

Topics: Acute Lung Injury; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycine; Humans; Male; Middle Aged; Oxygen; Protein Precursors; Proteinase Inhibitory Proteins, Secretory; Retrospective Studies; Sepsis; Serine Proteinase Inhibitors; Sulfonamides; Survival Rate

Topics: Adult; Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Lung Injury; Male; Middle Aged; Neopterin; Prospective Studies; Protein Precursors; Respiratory Distress Syndrome; Sepsis; Young Adult

Analysis of the examination and treatment results was conducted in 92 patients, suffering the obturation jaundice syndrome. There was elaborated a diagnostic program, in which the existing diagnostic standard for obturation jaundice and its complicated forms, an acute cholangitis and biliary sepsis, was added by determination of the blood procalcitonin level, microbiological investigation of the blood and bile, the bile microscopy, the analysis of the system inflammatory response syndrome signs and the organs dysfunction (according to SOFA scale). The program introduction have permitted to perform differential diagnosis of uncomplicated--in 30 (32.6%) patients, and complicated--in 42 (45.7%) obturation jaundice in an acute cholangitis and in 20 (21.7%)--in biliary sepsis. The treatment program is characterized by differentiated approach, depending on the disease kind, and includes the conduction of urgent decompression and sanation of biliary ducts. The method and volume of complex conservative therapy have differed essentially in patients, suffering obturation jaundice, an acute cholangitis and biliary sepsis.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Bile; Bile Ducts; Calcitonin; Calcitonin Gene-Related Peptide; Cholangitis; Decompression, Surgical; Diagnosis, Differential; Disease Management; Female; Humans; Jaundice, Obstructive; Male; Microscopy; Middle Aged; Minimally Invasive Surgical Procedures; Protein Precursors; Sepsis

In recent years, procalcitonin has emerged as a promising marker for bacterial infection, with the high sensitivity and specificity.. This report presents a 76-year-old woman with fever, vomiting and diarrhea. The clinical and laboratory examination revealed that the patient had a suspected serious intestinal infection and sepsis. The extremely high level of procalcitonin and positive blood culture result confirmed our diagnosis.. Early identification of severe sepsis sometimes is very difficult. Procalcitonin is a useful tool in the early diagnosis of sepsis, differentiating from other inflammatory syndrome. The high PCT level (10 ng/ml) in this case could suggest serious bacterial infection and sepsis, and also predicts mortality and worse outcome.

Topics: Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intestinal Diseases; Prognosis; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

The aim of the study was to identify the diagnostic significance of presepsin in acute abdominal conditions and also to examine the correlation between presepsin, procalcitonin (PCT) and other parameters.. To detect presepsin we used a new rapid method based on a chemiluminescent enzyme immunoassay. The clinical usefulness of presepsin to differentiate bacterial and non-bacterial infection [including systemic inflammation response syndrome (SIRS)] was studied and compared with PCT, C-reactive protein (CRP) and white blood cells (WBC).. The presepsin values in different conditions were (mean±standard deviation): healthy group (n=70) 258.7±92.53 pg/mL; SIRS (n=30) 430.0±141.33 pg/mL; sepsis (n=30) 1508.3±866.6 pg/mL. The presepsin values were significantly higher in patients with sepsis than the SIRS group (p<0.0001, Mann-Whitney U-test). The area under the receiver operating characteristics (ROC) curve (AUC) for discriminating of the SIRS from the sepsis patients was 0.996 for presepsin and it was greater than the AUC of PCT (0.912), CRP (0.857) or WBC (0.777).. The ROC curve of the SIRS patient without infection and the sepsis patient showed that the presepsin concentration was a significantly sensitive indicator of sepsis and useful marker for the rapid diagnosis of sepsis.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Immunoenzyme Techniques; Lipopolysaccharide Receptors; Luminescent Measurements; Male; Middle Aged; Protein Isoforms; Protein Precursors; ROC Curve; Sepsis; Solubility; Systemic Inflammatory Response Syndrome

The aim of this study was to investigate the diagnostic utility of plasma neutrophil gelatinase-associated lipocalin (NGAL) as an early objective biomarker to predict acute kidney injury (AKI) in critically ill patients with suspected sepsis, for whom procalcitonin (PCT) was used for the diagnosis and staging of sepsis.. Plasma NGAL was measured using the Triage NGAL Test (Alere, Inc., San Diego, CA, USA) in 231 samples obtained from patients with suspected sepsis. The results of NGAL were compared with those of Elecsys BRAHMS PCT (Roche Diagnostics, Basel, Switzerland). Renal failure was assessed using the renal subscore of Sepsis-related Organ Failure Assessment (SOFA) score. AKI was defined according to the Acute Kidney Injury Network criteria.. The concentrations of plasma NGAL were significantly different according to the five groups of PCT concentration (P<0.0001) and the renal subscore of SOFA score (P<0.0001). Plasma NGAL was significantly increased in the patients with AKI compared with those without AKI (416.5 ng/mL vs. 181.0 ng/mL, P=0.0223).. Plasma NGAL seems to be a highly sensitive and objective predictor of AKI in patients with sepsis. Plasma NGAL can be added for the diagnosis and staging of renal failure in sepsis.

Topics: Acute Kidney Injury; Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Lipocalin-2; Lipocalins; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Proto-Oncogene Proteins; Reagent Kits, Diagnostic; Sepsis; Severity of Illness Index

Although absolute values for C-reactive protein (CRP) and procalcitonin (PCT) are well known to predict sepsis in the critically ill, it remains unclear how changes in CRP and PCT compare in predicting evolution of: infectious disease, invasiveness and severity (e.g. development of septic shock, organ failure and non-survival) in response to treatment. The current study attempts to clarify these aspects.. In 72 critically ill patients with new onset fever, CRP and PCT were measured on Day 0, 1, 2 and 7 after inclusion, and clinical courses were documented over a week with follow up to Day 28. Infection was microbiologically defined, while septic shock was defined as infection plus shock. The sequential organ failure assessment (SOFA) score was assessed.. From peak at Day 0-2 to Day 7, CRP decreased when (bloodstream) infection and septic shock (Day 0-2) resolved and increased when complications such as a new (bloodstream) infection or septic shock (Day 3-7) supervened. PCT decreased when septic shock resolved and increased when a new bloodstream infection or septic shock supervened. Increased or unchanged SOFA scores were best predicted by PCT increases and Day 7 PCT, in turn, was predictive for 28-day outcome.. The data, obtained during ICU-acquired fever and infections, suggest that CRP may be favoured over PCT courses in judging response to antibiotic treatment. PCT, however, may better indicate the risk of complications, such as bloodstream infection, septic shock, organ failure and mortality, and therefore might help deciding on safe discontinuation of antibiotics. The analysis may thus help interpreting current literature and design future studies on guiding antibiotic therapy in the ICU.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease Progression; Female; Fever; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Survival Analysis

Close monitoring and repeated risk assessment of sepsis patients in the intensive care unit (ICU) is important for decisions regarding care intensification or early discharge to the ward. We studied whether considering plasma kinetics of procalcitonin, a biomarker of systemic bacterial infection, over the first 72 critical care hours improved mortality prognostication of septic patients from two US settings.. This retrospective analysis included consecutively treated eligible adults with a diagnosis of sepsis from critical care units in two independent institutions in Clearwater, FL and Chicago, IL. Cohorts were used for derivation or validation to study the association between procalcitonin change over the first 72 critical care hours and mortality.. ICU/in-hospital mortality rates were 29.2%/31.8% in the derivation cohort (n=154) and 17.6%/29.4% in the validation cohort (n=102). In logistic regression analysis of both cohorts, procalcitonin change was strongly associated with ICU and in-hospital mortality independent of clinical risk scores (Acute Physiology, Age and Chronic Health Evaluation IV or Simplified Acute Physiology Score II), with area under the curve (AUC) from 0.67 to 0.71. When procalcitonin decreased by at least 80%, the negative predictive value for ICU/in-hospital mortality was 90%/90% in the derivation cohort, and 91%/79% in the validation cohort. When procalcitonin showed no decrease or increased, the respective positive predictive values were 48%/48% and 36%/52%.. In septic patients, procalcitonin kinetics over the first 72 critical care hours provide prognostic information beyond that available from clinical risk scores. If these observations are confirmed, procalcitonin monitoring may assist physician decision-making regarding care intensification or early transfer from the ICU to the floor.

Topics: Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Care; Female; Hospital Mortality; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis

Topics: Acute Kidney Injury; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Hemofiltration; Humans; Membranes, Artificial; Protein Precursors; Sepsis; Veins

Previous studies have shown that cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) is a novel lipopolysaccharide (LPS)-binding protein, and the upregulation of CRISPLD2 expression protects mice against LPS-induced lethality. The aim of this study was to examine the expression of CRISPLD2 in patients with sepsis and characterize the association of this protein with procalcitonin.. The expression of CRISPLD2 was determined in 100 healthy volunteers and 119 septic patients. According to the definition of sepsis, patients were divided into three groups sepsis, severe sepsis, and septic shock. The relationship between CRISPLD2 levels and procalcitonin was also examined and statistically analyzed.. The CRISPLD2 levels in healthy individuals were 219.3±69.1 µg/ml. Patients with sepsis exhibited higher CRISPLD2 levels than observed in healthy individuals (p = 0.001), but CRISPLD2 expression was not upregulated in patients with septic shock. No significant differences were observed between the levels of CRISPLD2 in surviving and non-surviving spesis patients. CRISPLD2 levels were negatively correlated with procalcitonin levels (r = -0.334, p<0.001).. The present study is the first to demonstrate the decreased expression of CRISPLD2 in septic shock and its association with PCT in sepsis. Further studies are needed to clarify the potential association between CRISPLD2 expression and clinical outcomes to determine if it could be used as a novel sepsis biomarker.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cell Adhesion Molecules; Female; Gene Expression; Humans; Interferon Regulatory Factors; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Treatment Outcome

The utility of procalcitonin (PCT) and C-reactive protein (CRP) as infectious biomarkers following infant cardiothoracic surgery is not well defined.. We designed a prospective cohort study to evaluate PCT and CRP after infant cardiothoracic surgery. PCT and CRP were drawn preoperatively and 24/72 h postoperation or daily in delayed sternal closure patients. Presence of infection within 10 d of surgery, vasoactive-inotropic scores at 24 and 72 h, and length of intubation, intensive care unit stay, and hospital stay were documented.. PCT and CRP were elevated at 24 h. PCT then decreased while CRP increased in patients undergoing delayed sternal closure or cardiopulmonary bypass. In the delayed sternal closure group, PCT was significantly higher on postoperative days 2-5 in patients who ultimately developed infection. Higher PCT was independently associated with increased vasoactive-inotropic score at 72 h. CRP did not correlate with infection or postoperative support.. PCT rises after cardiothoracic surgery in infants but decreases by 72 h while CRP remains elevated. Sternal closure may affect CRP but not PCT. PCT is independently associated with circulatory support requirements at 72 h postoperation and with development of infection. PCT may have greater utility as a biomarker in this population.

Topics: Analysis of Variance; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiovascular Surgical Procedures; Cohort Studies; Humans; Infant; Infant, Newborn; Kinetics; Linear Models; Liver Function Tests; Postoperative Complications; Prospective Studies; Protein Precursors; Sepsis; Statistics, Nonparametric; Time Factors

We previously identified interleukin 27 (IL-27) as a sepsis diagnostic biomarker in critically ill children. The current study tested the performance of IL-27 alone and in combination with procalcitonin (PCT) for diagnosing sepsis in critically ill adults.. Serum samples were made available from a prior prospective study of sepsis biomarkers in critically ill adults. The primary analysis used receiver operating characteristic curves to evaluate the performance of IL-27 and PCT. Secondary analysis explored IL-27 performance in subgroups of patients with sepsis secondary to lung and nonlung sources of infection. The net reclassification improvement was used to estimate the incremental predictive ability of IL-27 compared with PCT alone. Classification and regression tree analysis was used to generate an IL-27- and PCT-based decision tree.. There were 145 patients with sepsis and 125 without sepsis. The receiver operating characteristic curve for IL-27 was inferior (area under the curve [AUC], 0.68; 95% confidence interval [CI], 0.62-0.75) to that of PCT (AUC, 0.84; 95% CI, 0.79-0.89). Similar findings were observed when comparing patients with a lung source of infection and those without sepsis. For sepsis patients with a nonlung source of infection, adding IL-27 to PCT improved discrimination (net reclassification improvement = 0.685; P < 0.001). The AUC for the classification and regression tree-derived decision tree was 0.92 (95% CI, 0.88-0.96) and was significantly greater than that of PCT alone.. When used in combination with PCT, IL-27 may improve classification of critically ill adults with sepsis secondary to a nonlung source of infection.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Decision Trees; Humans; Interleukin-27; Lung Diseases; Predictive Value of Tests; Protein Precursors; Respiratory Tract Infections; Retrospective Studies; Sensitivity and Specificity; Sepsis

Our objective is to develop an assay based on magnetic particles (MPs) to determine the concentration of procalcitonin (PCT) using a chemiluminescence immunoassay (CLIA). Fluorescein isothiocyanate (FITC) and N-(aminobutyl)-N-(ethylisoluminol) (ABEI) were used to label two different anti-procalcitonin (PCT) monoclonal antibodies. The labeled antibodies, the PCT antigen, and the anti-FITC antibody-coated MPs formed a double-sandwiched immunocomplex. The measured relative light units (RLUs) of ABEI in the substrate solution were directly proportional to the amount of PCT present in the samples. The proposed method was linear to 600 ng/mL with a detection limit of 0.03 ng/mL. The coefficient of variation (CV) was <5% and <6% for the intra- and inter-assay precision, respectively. The average recoveries were between 95 and 107%. The linearity-dilution effect gave a linear correlation coefficient of 0.9912. This proposed assay provided an alternative method to quantitatively measure PCT in serum for the diagnosis of sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Magnetics; Protein Precursors; Sepsis

To describe the dynamics changes of sCD163, soluble serum triggering receptor expressed on myeloid cells-1 (sTREM-1), procalcitonin (PCT), and C-reactive protein (CRP) during the course of sepsis, as well as their outcome prediction.. An SIRS group (30 cases) and a sepsis group (100 cases) were involved in this study. Based on a 28-day survival, the sepsis was further divided into the survivors' and nonsurvivors' groups. Serum sTREM-1, sCD163, PCT, CRP, and WBC counts were tested on days 1, 3, 5, 7, 10, and 14.. On the ICU admission, the sepsis group displayed higher levels of sTREM-1, sCD163, PCT, and CRP than the SIRS group (P < 0.05). Although PCT and sTREM-1 are good markers to identify severity, sTREM-1 is more reliable, which proved to be a risk factor related to sepsis. During a 14-day observation, sCD163, sTREM-1, PCT, and SOFA scores continued to climb among nonsurvivors, while their WBC and CRP went down. Both sCD163 and SOFA scores are risk factors impacting the survival time.. With regard to sepsis diagnosis and severity, sTREM-1 is more ideal and constitutes a risk factor. sCD163 is of a positive value in dynamic prognostic assessment and may be taken as a survival-impacting risk factor.

Topics: Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Disease Progression; Female; Humans; Leukocyte Count; Male; Membrane Glycoproteins; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Protein Precursors; Receptors, Cell Surface; Receptors, Immunologic; Reproducibility of Results; Risk Factors; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

The soluble form of the urokinase-type plasminogen activator receptor (suPAR) and proadrenomedullin (proADM) are two new and promising sepsis biomarkers. We assessed the prognostic value of a single determination of proADM and suPAR, comparing them with C-reactive protein (CRP) and procalcitonin (PCT), and evaluating whether their addition to severity scores (APACHE II and SOFA) could improve their prognostic accuracy.. A single-centre prospective observational study conducted in an adult intensive care department at Marques de Valdecilla University Hospital in Spain. APACHE II and SOFA scores, CRP, PCT, suPAR and proADM levels on the day of ICU admission were collected.. A total of 137 consecutive septic patients were studied. The best area under the curve (AUC) for the prediction of in-hospital mortality was for APACHE II (0.82) and SOFA (0.75) scores. The ROC curve for suPAR yielded an AUC of 0.67, higher than proADM (0.62), CRP (0.50) and PCT (0.44). Significant dose-response trends were found between hospital mortality and suPAR (OR Q4 = 4.83, 95% CI 1.60-14.62) and pro-ADM (OR Q4 = 3.00, 95% CI 1.06-8.46) quartiles. Non-significant associations were found for PCT and CRP. The combination of severity scores and each biomarker did not provide superior AUCs.. SuPAR and, to a lesser extent, proADM levels on ICU admission were better tools in prognosticating in-hospital mortality than CRP or PCT. However, neither of the two new biomarkers has been demonstrated to be excessively useful in the current setting. The prognostic accuracy was better for severity scores than for any of the biomarkers.

Topics: Adrenomedullin; Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Receptors, Urokinase Plasminogen Activator; Sepsis; Spain

Procalcitonin has been proposed as a specific biomarker of bacterial infections and has been related to the severity of sepsis. The prognostic ability of the initial concentrations of procalcitonin in sepsis is controversial. Some studies find higher initial concentrations in non-survivors but others find no differences. Prognostic assessment based on follow-up of procalcitonin levels may be better than evaluation of the initial levels of procalcitonin. The persistence of elevated procalcitonin levels is indicative of poor prognosis and is associated with mortality. Procalcitonin kinetics could be a tool for assessing the evolution of severe sepsis and sepsis shock. Procalcitonin should find its place as a biomarker for predicting treatment failure of severe sepsis and septic shock.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Male; Protein Precursors; Sepsis

Triggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be up-regulated in various inflammatory diseases as well as in bacterial sepsis. Increased cell-surface TREM-1 expression was also shown to result in marked plasma elevation of the soluble form of this molecule (sTREM-1) in patients with bacterial infections. In this study, we investigated sTREM-1, procalcitonin and C-reactive protein in postmortem serum in a series of sepsis-related fatalities and control individuals who underwent medico-legal investigations. sTREM-1 was also measured in pericardial fluid and urine.. Two study groups were prospectively formed, a sepsis-related fatalities group and a control group. The sepsis-related fatalities group consisted of sixteen forensic autopsy cases. Eight of these had a documented clinical diagnosis of sepsis in vivo. The control group consisted of sixteen forensic autopsy cases with various causes of death.. Postmortem serum sTREM-1 concentrations were higher in the sepsis group with a mean value of 173.6 pg/ml in septic cases and 79.2 pg/ml in control individuals. The cutoff value of 90 pg/ml provided the best sensitivity and specificity. Pericardial fluid sTREM-1 values were higher in the septic group, with a mean value of 296.7 pg/ml in septic cases and 100.9 pg/ml in control individuals. The cutoff value of 135 pg/ml provided the best sensitivity and specificity. Mean urine sTREM-1 concentration was 102.9 pg/ml in septic cases and 89.3 pg/ml in control individuals.. Postmortem serum sTREM-1, individually considered, did not provide better sensitivity and specificity than procalcitonin in detecting sepsis. However, simultaneous assessment of procalcitonin and sTREM-1 in postmortem serum can be of help in clarifying contradictory postmortem findings. sTREM-1 determination in pericardial fluid can be an alternative to postmortem serum in those situations in which biochemical analyses are required and blood collected during autopsy proves insufficient.

Topics: Autopsy; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Membrane Glycoproteins; Pericardium; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Sepsis; Statistics, Nonparametric; Triggering Receptor Expressed on Myeloid Cells-1

Sepsis refers to severe systemic inflammation in response to invading pathogens. To understand the molecular events that initiate the systemic inflammatory response, various inflammatory mediators were analyzed in neonatal sepsis samples and compared with normal samples.. We initially measured the levels of the various classical inflammatory mediators such as acute phase proteins [C-reactive protein (CRP) and procalcitonin (PCT)], granule-associated mediators (NE, MPO and NO), proinflammatory cytokines [tumour necrosis factor-α (TNFα), IL-1β and IL-6), antiinflammatory cytokines (IL-10 and IL-13) and chemokines [IL-8 and monocyte chemotactic protein (MCP-1)] and novel cytokines (IL-12/IL-23p40, IL-21 and IL-23) using ELISA. We also used the human inflammation antibody array membrane to profile the inflammatory proteins that are involved in neonatal sepsis.. There were significantly higher levels of CRP (5.4 ± 0.70 mg/L), PCT (1.500 ± 0.2400 μg/L); NE (499.2 ± 22.01 μg/L), NO (54.22 ± 3.131 μM/L); TNFα (396.6 ± 37.40 pg/mL), IL-1β (445.3 ± 34.25 pg/mL), IL-6 (320.9 ± 43.38 pg/mL); IL-8 (429.5 ± 64.08 pg/mL) MCP-1 (626.25 ± 88.91 pg/mL), IL-10 (81.80 ± 9.45 pg/mL), IL-12/IL-23p40 (30.25 ± 0.6 pg/mL), IL-21 (8,263.3 ± 526.8 pg/mL) and IL-23 (6,083 ± 781.3 pg/mL) in neonates with sepsis compared to normal. The levels of MPO (21.20 ± 3.099 ng/mL) were downregulated, whereas there was no change in IL-13 (188.7 ± 10.63 pg/mL) levels in septic neonates when compared with normal. Using the human inflammation antibody array membrane, we detected the presence of 17 inflammatory proteins such as IL-3, IL6R, IL12p40, IL-16, TNFα, TNFβ, TNF R1, chemokines I-309, IP-10 (IFN-γ inducible protein 10), MCP-1, MCP-2, MIP 1β (macrophage inflammatory protein), MIP-1δ, eotaxin-2, growth factors TGFβ1 (transforming growth factor beta), PDGF (platelet derived growth factor), and cell adhesion molecule ICAM-1 (intracellular adhesion molecule) that were upregulated whereas RANTES which was downregulated in neonatal sepsis.. The simultaneous secretion and release of multiple mediators such as proinflammatory cytokines and chemokines, cell adhesion molecules, and growth factors were found to be involved in the initiation of systemic inflammation in neonatal sepsis. Therefore, measuring the concentration of multiple mediators may help in the early detection of neonatal sepsis and help to avoid unnecessary antibiotic treatment.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chemokine CCL5; Female; Humans; Infant, Newborn; Inflammation Mediators; Intercellular Adhesion Molecule-1; Leukocyte Elastase; Male; Nitric Oxide; Peroxidase; Protein Precursors; Sepsis

Soluble thrombomodulin (sTM) is a sensitive marker of endothelial damage. In this study we investigated the role of sTM in the evaluation of the severity and prognosis of septic patients in the emergency department (ED).. A prospective, observational cohort study was performed in the ED of an urban, university hospital. Patients who had suspected infection with two or more criteria of systemic inflammatory response syndrome were consecutively enrolled. sTM, D-Dimer and procalcitonin levels were measured on enrollment, and the Mortality in Emergency Department Sepsis (MEDS) score was calculated. A 30-day follow-up was performed for all patients.. A total of 372 patients with sepsis, 210 patients with severe sepsis and 98 patients with septic shock were enrolled in this study. According to the disease severity, patients were divided into sepsis subgroup and severe sepsis subgroup (including septic shock). In addition, patients were divided into survivors subgroup and non-survivors subgroup according to the 30-day mortality. Plasma sTM levels in patients with severe sepsis were higher than those with sepsis (P<0.001). Compared with survivors, non-survivors has higher plasma sTM levels (P<0.001). Multivariate logistic regression analysis showed that sTM was an independent predictor of severe sepsis (odds ratio 1.11) and 30-day mortality (odds ratio 1.059). Receiver operating characteristic curve analysis showed that sTM was a useful parameter in prediction of severe sepsis (0.859) and 30-day mortality (0.78). Compared with the MEDS score alone, combination of sTM and the MEDS score can improve the accuracy in prediction of severe sepsis and 30-day mortality.. sTM is a valuable biomarker in the risk stratification and prognosis evaluation of ED sepsis. Furthermore, sTM can enhance the ability of the MEDS score in prediction of severe sepsis and 30-day mortality.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Emergency Service, Hospital; Female; Fibrin Fibrinogen Degradation Products; Humans; Immunohistochemistry; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock, Septic; Thrombomodulin; Triage

To assess retrospectively the diagnostic value of procalcitonin (PCT) in excluding suspected bloodstream infection, establish cut-off values for PCT levels, and compare PCT with other clinical markers.. The predictive accuracy of different continuous parameters was estimated by univariate analysis of the area under the receiver operating characteristic curve. Optimized cut-off points for the parameters were selected according to the maximum Youden index values, which in turn were used to define positive and negative predictive values of different parameters in diagnosing bloodstream infection.. The PCT level yielded a statistically significant area under the receiver operating characteristic curve of 0.765, with a best cut-off value of 0.80 ng/ml (83% sensitivity; 65% specificity, Youden index, J = 0.48). Positive and negative predictive values at this cut-off value were 38% and 94%, respectively. Mann-Whitney U-test revealed significantly higher values for PCT, C-reactive protein and percentage of neutrophils, but not for white blood cell count, in patients with bloodstream infection.. The serum PCT level can potentially be used as surrogate marker to exclude bacteraemia and to inform critical management decisions regarding antibiotic usage, in patients admitted with suspected bloodstream infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Diagnosis, Differential; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Statistics, Nonparametric

Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL) assay that uses a laser light-scattering particle-counting method. In the present study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay for the evaluation of sepsis after emergency gastrointestinal surgery. A total of 174 samples were collected from 40 adult patients undergoing emergency gastrointestinal surgery and 10 patients with colorectal cancer undergoing elective surgery as nonseptic controls. Plasma endotoxin levels were measured with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin levels increased corresponding to the degree of sepsis. Endotoxin scattering photometry significantly discriminated between patients with or without septic shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%; negative predictive value, 93.8%; and accuracy, 77.6%. The area under the receiver operating characteristic curve for septic shock with the ESP assay (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 ± 0.0301 (95% confidence interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to that of turbidimetric assay (difference, 0.1965 ± 0.0588; 95% confidence interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in predictive power between ESP and procalcitonin assay. Endotoxin scattering photometry also discriminated between patients with and without sepsis. Area under the receiver operating characteristic curve analysis showed that ESP had the best predictive power for diagnosing sepsis. In conclusion, compared with turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and significantly discriminated between sepsis and septic shock in patients undergoing gastrointestinal emergency surgery.

Topics: Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergencies; Endotoxins; Female; Gastrointestinal Tract; Humans; Lasers; Limulus Test; Male; Middle Aged; Nephelometry and Turbidimetry; Photometry; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Protein Precursors; Scattering, Radiation; Sepsis; Shock, Septic

To evaluate the value of percentage of highly fluorescent lymphocytic cells (HFLC%) for rapidly assessing septicemia in tumor patients.. Blood samples were collected from 130 patients with tumors (60 septicemia patients and 70 non-septicemia patients) and 80 healthy controls. HFLC% was analyzed with Sysmex XE-5000, the level of C-reactive protein (CRP) measured with a commercially available turbidimetric immunoassay kit and the level of procalcitonin (PCT) determined with a semiquantitative chromatographic immunoassay kit. The diagnostic values of HFLC% and CRP in septicemia were evaluated with ROC analysis.. The values of HFLC% and CRP were significantly higher in the septicemia group than those in the non-septicemia and healthy groups (0.30% (0.10%-0.70%) vs 0.10% (0-0.20%), 0.10% (0-0.20%) ; 80.3 (28.5-129.5) vs 3.3 (1.4-41.4) , 1.4 (0.6-2.5) mg/L, all P < 0.01) . The ROC-AUCs for HFLC% and CRP for a diagnosis of septicemia were 0.72 (sensitivity 71.7%, specificity 58.7%) and 0.92 (sensitivity 96.7%, specificity 82.0%). Both of them could judge septicemia better. Additionally, HFLC% was correlated with the levels of PCT and CRP (r = 0.637, 0.241, both P < 0.01).. HFLC% may be used as a rapid and simple auxiliary indicator in the diagnosis of septicemia in patients with tumors. And it is conducive to make an early diagnosis of septicemia and avoid unnecessary use of antibiotics.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child; Child, Preschool; Cytophotometry; Early Diagnosis; Female; Humans; Infant; Lymphocytes; Male; Middle Aged; Neoplasms; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

Diagnosis of bacterial sepsis in preterm neonates can be difficult when using serum markers that rely on physiological changes because these changes may not necessarily be the result of bacterial infections alone. This retrospective investigation explores the potential use of the DNA methylation pattern of CpG sites in the promoter region of the calcitonin-related polypeptide α (CALCA) gene as an epigenetic biomarker for bacterial sepsis in preterm newborns. Four novel changes in the DNA methylation of eight CpG sites were detected in this gene and are present only in neonates with bacterial sepsis: (1) partial methylation at -769 CpG in gram-negative or gram-positive early onset sepsis (EOS) and late onset sepsis (LOS) episodes; (2) demethylation of 8 CpGs in gram-negative EOS followed by LOS (ELS) and in gram-negative EOS; (3) demethylation of 7 CpGs in gram-positive ELS and gram-positive EOS; (4) -771 C:G>T:A; 5' de novo -778 CpG mutation on both alleles in EOS. These changes were not detected in birth weight and gestational age matched controls or in newborns with isolated infections. Our results indicate that the DNA methylation pattern of the promoter region of the CALCA gene varies in different types of bacterial preterm sepsis, thus suggesting a potential use as an epigenetic biomarker. A prospective confirmation of these results is essential.

Topics: Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; CpG Islands; DNA Methylation; Epigenesis, Genetic; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Promoter Regions, Genetic; Protein Precursors; Retrospective Studies; Sepsis

Presepsin levels are known to be increased in sepsis. The aim of this study was to evaluate the early diagnostic and prognostic value of Presepsin compared with procalcitonin (PCT), Mortality in Emergency Department Sepsis (MEDS) score and Acute Physiology and Chronic Health Evaluation II (APACHE II) score in septic patients in an emergency department (ED) and to investigate Presepsin as a new biomarker of sepsis.. This study enrolled 859 consecutive patients with at least two diagnostic criteria for systemic inflammatory response syndrome (SIRS) who were admitted to Beijing Chao-yang Hospital ED from December 2011 to October 2012, and 100 age-matched healthy controls. Patients were stratified into four groups: SIRS, sepsis, severe sepsis, and septic shock. Plasma Presepsin and serum PCT were measured, and MEDS score and APACHE II score were calculated at enrollment. Comparisons were analyzed using the Kruskal-Wallis and Mann-Whitney U tests.. On admission, the median levels of plasma Presepsin increased with sepsis severity. The areas under the receiver operating characteristic (AUC) curves of Presepsin were greater than those of PCT in diagnosing sepsis, and predicting severe sepsis and septic shock. The AUC of Presepsin for predicting 28-day mortality in septic patients was slightly lower than that of PCT, MEDS score and APACHE II score. The AUC of a combination of Presepsin and MEDS score or APACHE II score was significantly higher than that of MEDS score or APACHE II score alone in predicting severe sepsis, and was markedly higher than that of Presepsin alone in predicting septic shock and 28-day mortality in septic patients, respectively. Plasma Presepsin levels in septic patients were significantly higher in non-survivors than in survivors at 28 days' follow-up. Presepsin, MEDS score and APACHE II score were found to be independent predictors of severe sepsis, septic shock and 28-day mortality in septic patients. The levels of plasma Presepsin were positively correlated with PCT, MEDS score and APACHE II score in every septic group.. Presepsin is a valuable biomarker for early diagnosis of sepsis, risk stratification, and evaluation of prognosis in septic patients in the ED.

Topics: Aged; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; China; Female; Humans; Lipopolysaccharide Receptors; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

To evaluate the clinical application of measuring procalcitonin (PCT) level for diagnosis of bacterial sepsis in patients with and without systemic inflammatory response syndrome(SIRS), we studied the relationship between blood culture (BC) and serum PCT level in clinical 207 cases. In addition, we evaluated the time courses of PCT and other inflammatory markers: tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), E-selectin, WBC count and C-reactive protein (CRP) in 5 bacterial septic patients with SIRS. Serum PCT showed sensitivity of 41% and specificity of 61%, while BC showed specificity of 88%. In 27 BC-positive cases, serum PCT was significantly elevated in gram-negative bacterial sepsis. We observed 11 cases with BC(+) and serum PCT below 0.5 ng/ml. Major causes of these discrepancies were probably due to gram-positive bacterial infection, local bacterial infection or pretreatment with broad-spectrum antibiotics. In contrast, 10 cases with BC(-) and serum PCT over 10 ng/ml were presumably due to some cytokine elevation caused by virus infection or collagen diseases. In 5 cases studied for inflammatory markers, TNF-alpha level elevated earlier than the others and followed by PCT, IL-6, WBC, CRP, and E-selectin. It was suggested that the measurement of serum procalcitonin in septic patients is clinically useful marker to diagnose gram-negative bacterial septic patients with SIRS.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Procalcitonin /PCT/ is a reliable marker for the diagnosis of early onset neonatal sepsis but its sensitivity and specificity in literature vary widely mostly due to existing unclarity on its normal values and kinetics in the postnatal period. Aim of our research is to study the normal values of PCT and its dynamics during the first 24 hours of life for the Bulgarian population.. 70 healthy neonates were prospectively enrolled and separated in the following 3 groups (Group 1- immediately afterbirth; Group 2- 0-12 h afterbirth; Group 3- 12-24 h afterbirth) regarding the age at the time of PCT testing. The selected method of PCT testing is direct chemiluminescence. Results were analyzed with Statistical Package for Social Science (SPSS).. For group 1 and group 2 the mean PCT level was 0.06 and 0.59 ng/ml respectively. In group 3 PCT concentrations reached peak mean values of 3.35ng/ml. In the last group also the greatest variations were observed PCTmin - 0.31 ng/ml, PCTmax - 23.81 ng/ml. No correlation between PCT concentrations, sex, mode of delivery and parity was found.. During the first 24 hours of life PCT values in healthy term neonates show broad variations, most marked in the interval 12-24 h. The dynamics of PCT concentrations is characterized by a gradual increase from birth reaching peak levels approximately 24 hours later.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Luminescent Measurements; Male; Pregnancy; Prospective Studies; Protein Precursors; Sepsis

Procalcitonin (PCT) levels can distinguish between infectious and non-infectious systemic inflammatory response. However, there are some differences between Gram-negative (G-), Gram-positive (G+), and fungal bloodstream infections, particularly in different cytokine profiles, severity and mortality. The aim of current study was to examine whether PCT levels can serve as a distinguishing mark between G+, G-, and fungal sepsis as well. One hundred and sixty-six septic patients with positive blood cultures were examined on C-reactive protein (CRP) and PCT on the same date of blood culture evaluation. The median (interquartile range, IQR) of CRP and PCT in G+, G-, and fungal cohorts and comparison of measured values between groups were made using the Kruskal-Wallis test with subsequent Bonferroni's corrections, with p < 0.05. In 83/166 (50 %) of blood cultures, G+ microbes, 78/166 (47 %) G- rods, and 5/166 (3 %) fungi were detected. PCT concentrations (ng/ml) were significantly higher in G- compared to other cohorts: 8.90 (1.88; 32.60) in G-, 0.73 (0.22; 3.40) in G+, and 0.58 (0.35; 0.73) in fungi (p < 0.00001). CRP concentrations did not differ significantly in groups. Significantly higher PCT levels could differentiate G- sepsis from G+ and fungemia. In contrast to CRP, PCT is a good discriminative biomarker in different bloodstream infections.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Middle Aged; Mycoses; Protein Precursors; Retrospective Studies; Sepsis

To assess the usefulness of procalcitonin (PCT) upon admission to the Intensive Care Unit (ICU) in the diagnosis and prognosis of sepsis. A 12-month prospective observational cohort study was carried out. An 11-bed polyvalent ICU Belonging to a University hospital. Fifty patients with systemic inflammatory response syndrome (SIRS) were included. The mean age of the patients was 51.66 years, and 68% of them were males. Upon admission, the concentration of PCT and C-reactive protein (CRP) was assessed. At discharge, the final diagnosis and outcome were reviewed. Thirty-six patients had sepsis. Mean PCT ± SD was higher in sepsis than in non-infectious SIRS (19.3 ± 4.9 vs. 0.65 ± 0.2) ng/ml) (P=.001). PCT had greater discriminating power than CRP (AUC 0.932 vs. 0.827). The cut-off value of PCT for the diagnosis of sepsis was 0.92 ng/dl, with a sensitivity of 80.56%, specificity 85.71%, positive predictive value 93.55% and negative predictive value 63.16%, LR+ 5.64 and LR- 0.23. Mortality was higher in patients with sepsis (52.78% vs. 21.43%) (P=.039). Mean PCT ± SD upon admission among survivors and deceased patients with sepsis was 18.7 ± 6.7 and 19.5 ± 7.5 ng/ml, respectively (P=.934).. PCT upon admission to the ICU is useful for the diagnosis of sepsis, and is more effective than PCR in this respect. However, it is of no help in estimating the short-term prognosis.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Plasma concentration of procalcitonin (PCT) and its value in the diagnosis of infection in paediatric patients treated with extracorporeal membrane oxygenation (ECMO) are undefined. This study aimed to define the levels of PCT and C-reactive protein (CRP) in paediatric cardiac ECMO patients and to determine their role in predicting infection, severity of organ dysfunction and clinical outcome.. PCT and CRP plasma concentrations were measured daily in 20 consecutive infants and young children treated with veno-arterial ECMO. Each patient was examined daily for signs of infection and multiple organ dysfunction syndrome (MODS). A total of 139 patient days were classified for infection and MODS.. The median PCT and CRP plasma concentrations were not increased during infection: 2.4 vs 8.8 ng/ml and 223.8 vs 240.6 mg/l, in patients with vs without infection, respectively. PCT, but not CRP, was significantly elevated during MODS (10.9 vs 1.85 ng/ml) (P = 0.001). The area under the receiver operating characteristic (ROC) curve was 0.984 for PCT (95% confidence interval [CI], 0.962-1.000) compared with 0.347 for CRP (95% CI, 0.211-0.484) (P = 0.001). Only PCT differed significantly in patients weaned from ECMO who survived (2.6 ng/ml) vs patients not weaned from ECMO (10.5 ng/ml) (P = 0.001). The area under the ROC curve was 0.871 (95% CI, 0.786-0.956) compared with 0.261 for CRP (95% CI, 0.145-0.377) (P = 0.001).. Neither PCT nor CRP are reliable markers of infection in paediatric cardiac ECMO patients. However, high levels of PCT are associated with MODS. PCT may be used as a prognostic indicator of clinical outcome in this high-risk population.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Extracorporeal Membrane Oxygenation; Female; Humans; Infant; Infant, Newborn; Infections; Linear Models; Male; Multiple Organ Failure; Protein Precursors; ROC Curve; Sepsis; Statistics, Nonparametric; Treatment Outcome

Topics: Acute-Phase Proteins; Birth Weight; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Lipocalin-2; Lipocalins; Male; Protein Precursors; Proto-Oncogene Proteins; ROC Curve; Sensitivity and Specificity; Sepsis

The aims of this study were twofold. The first was to investigate the diagnostic performance of two biochemical markers, procalcitonin (PCT) and lipopolysaccharide-binding protein (LBP), considering each individually and then combined, for the postmortem diagnosis of sepsis. We also tested the usefulness of pericardial fluid for postmortem LBP determination. Two study groups were formed, a sepsis-related fatalities group of 12 cases and a control group of 30 cases. Postmortem native CT scans, autopsy, histology, neuropathology, and toxicology as well as other postmortem biochemical investigations were performed in all cases. Microbiological investigations were also carried out in the septic group. Postmortem serum PCT and LBP levels differed between the two groups. Both biomarkers, individually considered, allowed septic states to be diagnosed, whereas increases in both postmortem serum PCT and LBP levels were only observed in cases of sepsis. Similarly, normal PCT and LBP values in postmortem serum were identified only in non-septic cases. Pericardial fluid LBP levels do not correlate with the presence of underlying septic states. No relationship was observed between postmortem serum and pericardial fluid LBP levels in either septic or non-septic groups, or between pericardial fluid PCT and LBP levels.

Topics: Acute-Phase Proteins; Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Case-Control Studies; Female; Forensic Pathology; Humans; Male; Membrane Glycoproteins; Middle Aged; Pericardium; Postmortem Changes; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

The early diagnosis of sepsis plays a central role in patient management. Many mediators to be the cause of sepsis have been proposed. In the present study the combined measurement of procalcitonin (PCT) and mid-regional pro-adrenomedullin (MR-proADM) and their appropriate cut-off values in sepsis patients were evaluated.. PCT and MR-proADM were measured with commercially available immunoluminometric assays (Brahms, Hennigsdorf, Germany) in 200 septic patients, 90 patients with SIRS and 30 healthy individuals. Data were analyzed with ROC curve analysis and likelihood ratios with the MedCalc 11.6.1.0 package.. Healthy controls and non-infectious SIRS were clearly distinguished from sepsis patients using the follow ing cut-off values: 0.30 ng/mL for PCT and 1 nmol/L for ADM. In the 200 septic patients the areas under the curve (AUCs) for PCT and MR-proADM were 0.921 and 0.977, respectively, with a statistically significant difference between the two areas of 0.0563 (p = 0.0002). Gram-positive, Gram-negative, yeast and polymicrobial sepsis patients showed different geometric means of the two biomarkers: this difference was relevant in Gram-positive sepsis and in yeast sepsis, 0.0819 (p = 0.0076) and 0.188 (p = 0.0062), respectively. The combined use of PCT and MR-proADM gave a post-test probability of 0.998 in the cohort of all septic patients. By test combination the post-test probability changed from 0.803 to 0.957 in Gram-positive sepsis and from 0.928 to 0.995 in yeast sepsis.. In conclusion, data from this study demonstrates that the combined use of PCT and MR-proADM, may substantially improve the early diagnosis of sepsis.

Topics: Adrenomedullin; Biomarkers; Blood Chemical Analysis; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis

To establish whether in critically ill patients without sepsis at intensive care unit (ICU) admission the percentage immature platelet fraction (IPF%) is a cellular marker predicting sepsis to verify a possible correlation between IPF% changes and manifest sepsis and describe the IPF% time course after ICU admission.. Prospective, observational 7-day study of 64 adult patients admitted to a general ICU at a University Hospital with no sepsis criteria. We measured daily IPF%, procalcitonin (PCT), C-reactive protein, platelets, white blood cell count and coagulation variables. Thirty-one patients with sepsis at ICU admission were studied as controls.. The only variable we tested at ICU admission that predicted sepsis was plasma IPF% (p < 0.001; >4.7 %: sensitivity 56.2 % IC 37.7-73.6; specificity 90.0 % IC 73.4-97.8). IPF% and PCT values were higher for the patients who had sepsis at admission and during the study than in patients in whom sepsis never developed (IPF%: p = 0.017; PCT: p = 0.030). Among the outcome variables, logistic regression was identified as the only variable related to the development of sepsis, IPF% (r = 0.51; p = 0.004). In patients who developed sepsis IPF% was inversely correlated with platelet count (r = -0.60; p < 0.001) and had high values before sepsis became manifest, decreasing significantly on the 2nd day thereafter.. In patients without sepsis at ICU admission IPF% increases before sepsis becomes manifest. Measuring IPF% through an easily available technology can therefore provide an early cellular marker predicting the development of sepsis.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Early Diagnosis; Female; Humans; Intensive Care Units; Leukocyte Count; Logistic Models; Male; Middle Aged; Platelet Count; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Thrombocytopenia

The first aim of this study was to assess the diagnostic performance of presepsin (sCD14-ST) in postmortem serum from femoral blood compared to procalcitonin (PCT) to detect sepsis-related fatalities. The second aim was to compare sCD14-ST levels found in postmortem serum to the values in pericardial fluid to investigate the usefulness of the latter as an alternative biological fluid. Two study groups were formed, a sepsis-related fatalities group and a control group. Radiology (unenhanced CT scans and postmortem angiographies), autopsies, histology, neuropathology, and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Microbiological investigations on right cardiac blood were carried out exclusively in septic cases. The results of this study indicated that postmortem serum PCT and sCD14-ST levels, individually considered, allowed septic cases to be identified. Even though increases in both PCT and sCD14-ST concentrations were observed in the control cases, coherent PCT and sCD14-ST results in cases with suspected sepsis allowed the diagnosis to be confirmed. Conversely, no relevant correlation was identified between postmortem serum and pericardial fluid sCD14-ST levels in either the septic or control groups.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Forensic Pathology; Humans; Infant; Lipopolysaccharide Receptors; Luminescent Measurements; Male; Middle Aged; Pericardium; Postmortem Changes; Protein Precursors; Sensitivity and Specificity; Sepsis

The aim was to evaluate the clinical usefulness of a single plasma and bronchoalveolar lavage fluid (BALF) PCT and IL-6 measurement in discriminating septic from non-septic causes of acute respiratory distress syndrome (ARDS) and forecasting clinical outcomes.. One hundred patients were enrolled within 48 h of ALI/ARDS recognition. Demographic, clinical data, severity indices were recorded and PCT and IL-6 concentrations were measured in plasma and BALF.. Plasma PCT and IL-6 values were significantly higher in septic compared to non-septic individuals (p=0.001 and 0.0005, respectively), while there were no differences in their respective BALF values. As far as identification of septic vs. non-septic ARDS is concerned, the comparison of the areas under the curves favored PCT vs. IL-6 [0.88, (95% CI 0.81-0.95) vs. 0.71, (95% CI 0.60-0.81); χ(2)=9.04, p=0.003]. A plasma PCT level of 0.815 ng/mL was associated with 74.1% sensitivity and 97.6% specificity in identifying septic ARDS cases; this corresponded to a diagnostic odds ratio value of 116. Linear regression multivariable analysis disclosed a significant relation of plasma PCT with SOFA score in septic ARDS patients (p<0.001), while neither BALF PCT nor IL-6 levels were associated with clinical outcome.. Early plasma - but not BALF - PCT concentrations can discriminate between septic and non-septic ARDS causes and are associated with the severity of multiple organ dysfunction syndrome in septic ARDS patients. However, neither plasma or BALF IL-6 levels nor BALF PCT levels carry any prognostic potential. A single plasma PCT value higher than 0.815 ng/mL makes a non-septic cause of ARDS highly unlikely.

Topics: Adult; Aged; Bronchoalveolar Lavage Fluid; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Humans; Interleukin-6; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies; Protein Precursors; Respiratory Distress Syndrome; Sensitivity and Specificity; Sepsis

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Diagnostic Errors; Disseminated Intravascular Coagulation; Humans; Male; Muscle Relaxants, Central; Protein Precursors; Quinine; Sepsis

Intensive care mortality of HIV-positive patients has progressively decreased. However, critically ill HIV-positive patients with sepsis present a worse prognosis. To better understand this condition, we propose a study comparing clinical, etiological and inflammatory data, and the hospital course of HIV-positive and HIV-negative patients with severe sepsis or septic shock.. A prospective observational study enrolling patients with severe sepsis or septic shock associated or not with HIV infection, and admitted to intensive care unit (ICU). Clinical, microbiological and inflammatory parameters were assessed, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6, interleukin-10 and TNF-α. Outcome measures were in-hospital and six-month mortality.. The study included 58 patients with severe sepsis/septic shock admitted to ICU, 36 HIV-positive and 22 HIV-negative. All HIV-positive patients met the criteria for AIDS (CDC/2008). The main foci of infection in HIV-positive patients were pulmonary and abdominal (p=0.001). Fungi and mycobacteria were identified in 44.4% and 16.7% of HIV-positive patients, respectively. In contrast, the main etiologies for sepsis in HIV-negative patients were Gram-negative bacilli (36.4%) and Gram-positive cocci (36.4%) (p=0.001). CRP and PCT admission concentrations were lower in HIV-positive patients (130 vs. 168 mg/dL p=0.005, and 1.19 vs. 4.06 ng/mL p=0.04, respectively), with a progressive decrease in surviving patients. Initial IL-10 concentrations were higher in HIV-positive patients (4.4 pg/mL vs. 1.0 pg/mL, p=0.005), with moderate accuracy for predicting death (area under receiver-operating characteristic curve =0.74). In-hospital and six-month mortality were higher in HIV-positive patients (55.6 vs. 27.3% p=0.03, and 58.3 vs. 27.3% p=0.02, respectively).. The course of sepsis was more severe in HIV-positive patients, with distinct clinical, etiological and inflammatory characteristics.

Topics: Acquired Immunodeficiency Syndrome; Adult; Bacteremia; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Fungemia; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Treatment Outcome

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

The diagnosis and prognosis of sepsis after antimicrobial therapy among systemic inflammatory response syndrome (SIRS) patients were evaluated with the biomarkers procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell counts. Among 177 consecutive SIRS patients, 78 exhibited sepsis, with Escherichia coli (23.1%) being the most common pathogen. PCT showed the best diagnostic performance, with 74.4% and 93.7% sensitivity and 86.7% and 75.2% specificity among sepsis and severe sepsis/septic shock patients, respectively. PCT, IL-6, and CRP levels were significantly increased in nonsurvivors compared to survivors. Serial measurements at 0, 12, 24, 48, 72, and 96 h showed that IL-6 showed better kinetics in the survivor group and was decreased in more than 86% of survivors by the second day. PCT can support the diagnosis of bacterial infection, especially in septic shock and severe sepsis patients. IL6 exhibited the better kinetics for monitoring the effectiveness of antibiotic treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Blood Sedimentation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Interleukin-6; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

Sepsis is a leading healthcare problem, accounting for the vast majority of fatal events in critically ill patients. Beyond early diagnosis and appropriate treatment, this condition requires a multifaceted approach for monitoring the severity, the potential organ failure as well as the risk of death. Monitoring of the efficacy of treatment is also a major issue in the emergency department (ED). The assessment of critically ill conditions and the prognosis of patients with sepsis is currently based on some scoring systems, which are, however, inefficient to provide definite clues about organ failure and prognosis in general. The discretionary and appropriate use of some selected biomarkers such as procalcitonin, inducible protein 10 (IP10), Group IV phospholipase A2 type II (PLA2 II), neutrophil gelatinase-associated lipocalin (NGAL), natriuretic peptides, mature adrenomedullin (ADM), mid-regional pro-adrenomedullin (MR-proADM), copeptin, thrombopoietin, Mer receptor and even red blood cell distribution width (RDW) represent thereby an appealing perspective in the diagnosis and management of patients with sepsis. Nevertheless, at the moment, it is not still clear if it is better to use a multimarkers approach or if a single, most appropriate, biomarker exists. This collective opinion paper is aimed at providing an overview about the potential clinical usefulness of some innovative biomarkers of sepsis in its diagnosis and prognosis, but also in the treatment management of the disease. This manuscript represents a synopsis of the lectures of Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Communicable Diseases; Disease Management; Emergency Medicine; Emergency Service, Hospital; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Humans; Protein Precursors; Sepsis

The aims of this study were to investigate the usefulness of serum C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as postmortem markers of sepsis and to compare C-reactive protein and procalcitonin values in serum, vitreous humor, and cerebrospinal fluid in a series of sepsis cases and control subjects, in order to determine whether these measurements may be employed for the postmortem diagnosis of sepsis. Two study groups were formed, a sepsis group (eight subjects coming from the intensive care unit of two university hospitals, with a clinical diagnosis of sepsis in vivo) and control group (ten autopsy cases admitted to two university medicolegal centers, deceased from natural and unnatural causes, without elements to presume an underlying sepsis as the cause of death). Serum C-reactive protein and procalcitonin concentrations were significantly different between sepsis cases and control cases, whereas serum tumor necrosis factor alpha, interleukin-6, and interleukin-8 values were not significantly different between the two groups, suggesting that measurement of interleukin-6, interleukin-8, and tumor necrosis factor alpha is non-optimal for postmortem discrimination of cases with sepsis. In the sepsis group, vitreous procalcitonin was detectable in seven out of eight cases. In the control group, vitreous procalcitonin was clearly detectable only in one case, which also showed an increase of all markers in serum and for which the cause of death was myocardial infarction associated with multi-organic failure. According to the results of this study, the determination of vitreous procalcitonin may be an alternative to the serum procalcitonin for the postmortem diagnosis of sepsis.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child; Child, Preschool; Female; Forensic Pathology; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Protein Precursors; Sepsis; Tumor Necrosis Factor-alpha; Vitreous Body; Young Adult

High serum procalcitonin (PCT) levels (≥0.5 ng/mL) commonly occur with systemic bacterial and fungal infections. Although several studies suggested that measuring serum PCT levels may serve as a useful marker to distinguish between active antineutrophil cytoplasmic antibodies (ANCA)-associated diseases and invasive infections, there is no information on PCT in myeloperoxidase (MPO)-ANCA-associated glomerulonephritis.. The authors measured serum PCT concentrations before initiation of immunosuppressive therapy in 67 patients with biopsy-proven MPO-ANCA-associated glomerulonephritis. The authors compared complications and clinicopathological parameters between patients with serum PCT levels of <0.5 ng/mL (group A: 58 patients) and ≥0.5 ng/mL (group B: 9 patients).. All 58 patients in group A did not show any clinical sign of systemic infection. On the other hand, 3 of 9 patients in group B had bacterial or fungal infections of the respiratory or urinary tact. One patient had a history of chronic urinary tract infection. In the remaining 5 patients in group B, there were 3 patients with concurrent malignancies and 1 postoperative patient with malignancy. Another in group B had a long history of interstitial pneumonia of unknown origin and severe renal insufficiency. Serum levels of C-reactive protein and creatinine were significantly higher in group B than in group A.. In patients with MPO-ANCA-associated glomerulonephritis, serum PCT levels of ≥0.5 ng/mL are recommended as cutoff for consideration of bacterial and fungal infections. Elevated serum PCT levels could also be observed in some patients with severe injury of the kidneys and/or lungs in the absence of infection.

Topics: Adolescent; Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Autoimmune Diseases; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis; Humans; Immunosuppression Therapy; Male; Middle Aged; Mycoses; Peroxidase; Protein Precursors; Sensitivity and Specificity; Sepsis

To evaluate the diagnostic and prognostic performance of inflammatory markers for septic and non septic (localized) bacterial infections in patients with severe burn.. Data of 145 patients were prospectively included in this study. Serum procalcitonin and other inflammatory markers were measured within 24 h after burn and daily thereafter. Maximum procalcitonin (p=0.004) was independent predictors of outcome in logistic regression analysis. PCT thresholds of 1.5 ng/ml, 0.52 ng/ml and 0.56 ng/ml had adequate sensitivity and specificity to diagnose sepsis, respiratory tract and wound infections respectively. A threshold value of 7.8 ng/ml in PCT concentration on day 3 was associated with the effectiveness of the sepsis treatment with an AUC of 0.86 (95% CI 0.69-1.03, p=0.002). C-reactive protein levels and WBCs showed no significant change over the first 3 days in the patients with successfully treated sepsis (p=0.93).. The maximum procalcitonin level has prognostic value in burn patients. PCT can be used as a diagnostic tool in patients with infectious complications with or without bacteremia during ICU stay. Daily consecutive PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in burn ICU patients.

Topics: Adult; Aged; Bacterial Infections; Biomarkers; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Leukocyte Count; Logistic Models; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Wound Infection

Circulating biomarkers can facilitate sepsis diagnosis, enabling early management and improved outcomes. Procalcitonin (PCT) has been suggested to have superior diagnostic utility compared to other biomarkers.. To define the discriminative value of PCT, interleukin-6 (IL-6), and C-reactive protein (CRP) for suspected sepsis.. PCT, CRP, and IL-6 were correlated with infection likelihood, sepsis severity, and septicemia. Multivariable models were constructed for length-of-stay and discharge to a higher level of care.. Of 336 enrolled subjects, 60% had definite infection, 13% possible infection, and 27% no infection. Of those with infection, 202 presented with sepsis, 28 with severe sepsis, and 17 with septic shock. Overall, 21% of subjects were septicemic. PCT, IL6, and CRP levels were higher in septicemia (median PCT 2.3 vs. 0.2 ng/mL; IL-6 178 vs. 72 pg/mL; CRP 106 vs. 62 mg/dL; p < 0.001). Biomarker concentrations increased with likelihood of infection and sepsis severity. Using receiver operating characteristic analysis, PCT best predicted septicemia (0.78 vs. IL-6 0.70 and CRP 0.67), but CRP better identified clinical infection (0.75 vs. PCT 0.71 and IL-6 0.69). A PCT cutoff of 0.5 ng/mL had 72.6% sensitivity and 69.5% specificity for bacteremia, as well as 40.7% sensitivity and 87.2% specificity for diagnosing infection. A combined clinical-biomarker model revealed that CRP was marginally associated with length of stay (p = 0.015), but no biomarker independently predicted discharge to a higher level of care.. In adult emergency department patients with suspected sepsis, PCT, IL-6, and CRP highly correlate with several infection parameters, but are inadequately discriminating to be used independently as diagnostic tools.

Topics: Adult; Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Infections; Interleukin-6; Length of Stay; Male; Middle Aged; Multivariate Analysis; Patient Discharge; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

Fever suggests the presence of microbial infection in critically ill patients. The aim was to compare the role of old and new biomarkers in predicting absence or presence of microbial infection, its invasiveness and severity in critically ill patients with new onset fever.. We prospectively studied 101 patients in the intensive care unit with new onset fever (>38.3 °C). Routine infection parameters, lactate, procalcitonin (PCT), midregional pro-adrenomedullin (MR proADM), midregional pro-atrial natriuretic peptide (MR proANP) and copeptin (COP) were measured daily for three days after inclusion. Likelihood, invasiveness (by bloodstream infection, BSI) and severity of microbial infection were assessed by cultures, imaging techniques and clinical courses.. All patients had systemic inflammatory response syndrome; 45% had a probable or proven local infection and 12% a BSI, with 20 and 33% mortality in the ICU, respectively. Only peak PCT (cutoff 0.65 ng/mL at minimum) was of predictive value for all endpoints studied, i.e. BSI, septic shock and mortality (high risk infection) and infection without BSI, shock and mortality (low risk infection), at areas under the receiver operating characteristic curves varying between 0.67 (P = 0.003) and 0.72 (P < 0.001). In multivariable analysis, the combination of C-reactive protein and lactate best predicted high risk infection, followed by PCT. For low risk infection, PCT was the single best predictor.. In critically ill patients with new onset fever, plasma PCT as a single variable, among old and new biomarkers, best helps, to some extent, to predict ICU-acquired, high risk microbial infection when peaking above 0.65 ng/mL and low risk infection when peaking below 0.65 ng/mL.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fever of Unknown Origin; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Systemic Inflammatory Response Syndrome

Topics: Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Female; Humans; Infant; Male; Meningitis, Bacterial; Protein Precursors; Sepsis

The reliability of procalcitonin as a predictor of invasive infection in infants <36 months of age with fever and nontoxic appearance was assessed in 868 patients, 15 (1.7%) of whom had invasive infection. The area under the receiver operating characteristic curve for procalcitonin was 0.87 (optimum cutoff 0.9 ng/mL, sensitivity 86.7%, specificity 90.5%), whereas for C-reactive protein it was 0.79 (optimum cutoff 91 mg/L, sensitivity 33.3%, specificity 95.9%). In infants with fever of <8 hours duration, the area under the receiver operating characteristic curve was 0.97 for procalcitonin and 0.76 for C-reactive protein. Procalcitonin was a useful biomarker to predict invasive infection in non-toxic-appearing infants with fever without apparent focus, particularly in febrile episodes of <8 hours duration.

Topics: Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Emergency Medical Services; Female; Fever of Unknown Origin; Humans; Infant; Male; Meningitis, Bacterial; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Sepsis in the early stage is a common disease in emergency medicine, and rapid diagnosis is essential. Our aim was to compare pathogen diagnosis using blood cultures (BC) and the multiplex polymerase chain reaction (PCR) test.Methods. At total of 211 patients admitted to the multidisciplinary emergency department of our university hospital between 2006 and 2009 with suspected severe infection from any origin were studied. Blood samples for BC (aerobic and anaerobic) and multiplex PCR were taken for identification of infectious microorganisms immediately after hospital admission. Results of the BC and PCR correlated with procalcitonin concentration (PCT) and clinical diagnosis of sepsis (≥2 positive SIRS criteria) as well as with severity of disease at admission and with clinical outcome measures.. Results of the BC were available in 200 patients (94.8%) and PCR were available in 119 patients (56.3%), respectively. In total, 87 BC (43.5%) were positive and identified 94 pathogens. In 45 positive PCRs, 47 pathogens (37.8%) were found. Identical results were obtained in 81.4%. In addition, BC identified 9 Gram-positive and 3 Gram-negative bacteria, while PCR added 5 Gram-negative pathogens. Coagulase-negative staphylococci were detected in blood cultures only (n=20, 21.3%), whereas PCR identified significantly more Gram-negative bacteria than BC. In patients with positive PCR results, the PCT level was significantly higher than in patients with negative PCR (15.0±23.3 vs. 8.8±32.8 ng/ml, p<0.001). This difference was not observed for BC (10.6±25.7 vs. 11.6±44.9 ng/ml, p=0.075). The APACHE II score correlated with PCR (19.2±9.1 vs. 15.8±8.9, p<0.05) and was also higher in positive BC (18.7±8.7 vs. 14.4±8.0, p<0.01). Positive PCR and BC were correlated with negative clinical outcomes (e.g., transfer to ICU, mechanical ventilation, renal replacement therapy, death).. In patients admitted with suspected severe infection, a high percentage of positive BC and PCR were observed. Positive findings in the PCR correlate with elevated levels of PCT and high APACHE II scores.

Topics: Adult; Aged; Bacterial Infections; Bacteriological Techniques; Blood; Calcitonin; Calcitonin Gene-Related Peptide; Cooperative Behavior; Culture Media; Early Diagnosis; Emergency Service, Hospital; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Interdisciplinary Communication; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Mycoses; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Sleep, REM; Staphylococcal Infections

The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). We prospectively enrolled patients 18 years or older with severe sepsis from April 2009 to May 2010 at a 2,000-bed university hospital. Patients were eligible if the initial resuscitation according to EGDT protocol was immediately performed at the emergency department. Plasma sTREM-1, C-reactive protein, and procalcitonin concentrations were measured on days 0, 3, 7, and 14. Soluble TREM-1 concentrations were significantly higher at admission and pre-EGDT in nonsurvivors (n = 16) than in survivors (n = 47) (514.1 pg/mL [interquartile range, 412.7-1,749.5 pg/mL] vs. 182.4 pg/mL [interquartile range, 54.3-327.0 pg/mL]; P = 0.001). Procalcitonin and C-reactive protein levels did not significantly differ, whereas central venous oxygen saturation and lactate levels at admission were significantly different between the two groups. The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Emergency Service, Hospital; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Monitoring, Physiologic; Prognosis; Protein Precursors; Receptors, Immunologic; Resuscitation; Sepsis; Severity of Illness Index; Triggering Receptor Expressed on Myeloid Cells-1

The aim of this study was to investigate the presence and concentrations of procalcitonin and C-reactive protein in pericardial fluid and compare these levels to those found in the postmortem serum obtained from the femoral blood. Two groups were formed, a sepsis-related fatalities group and a control group. Postmortem native CT scans, autopsies, histology, neuropathology and toxicology as well as other postmortem biochemistry investigations were performed in all cases. Pericardial fluid procalcitonin levels were significantly different between the cases of sepsis-related fatalities and those of the control group. Postmortem serum procalcitonin levels below the detection limit were also reflected in undetectable pericardial fluid levels. Similarly, a large increase in postmortem serum procalcitonin levels was reflected in a large increase of procalcitonin pericardial fluid levels. Based on these findings, pericardial fluid could be an alternative to postmortem serum for the determination of procalcitonin levels in cases where postmortem serum is not available and measurements of procalcitonin are required to circumstantiate the pathogenesis of death.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Forensic Pathology; Humans; Infant; Male; Middle Aged; Pericardium; Protein Precursors; Sensitivity and Specificity; Sepsis

To determine the prognostic value of the biomarkers procalcitonin, interlukin-6 and C-reactive protein in septic patients.. A cohort of 81 septic patients.. Critical Care Unit. Dr. Peset Hospital. Valencia (Spain).. Divided according to sepsis classification (sepsis, severe sepsis and septic shock), source and two different groups (medical and postsurgical). VARIABLES ANALYZED: Quantitative (procalcitonin, interleukin-6, C-reactive protein, lactate, age, Apache II and SOFA scores upon admission and after 3 and 7 days). Qualitative (ICU mortality, multiorgan failure development and sex).. Mann-Whitney U-test for the comparison of quantitative variables, χ² test for qualitative variables. Multivariate analysis with mortality and multiorgan failure as dependent variables and the described quantitative parameters as independent variables. ROC curves of the variables found to be significant in the multivariate analysis.. Septic shock patients showed greater mortality and more frequent multiorgan failure. Comparison of survivors versus deceased patients showed significant differences in Apache II score, interleukin-6 and lactate (p<0.001) upon admission and after 3 and 7 days. Similar findings applied to the comparison of patients with and without multiorgan failure, and on the same days. Procalcitonin only showed differences on days 3 and 7 (p=0.001). In the multivariate analysis with mortality as dependent variable, interleukin-6 proved significant on day 3 (OR 2.6). With multiorgan failure as dependent variable, only the SOFA score showed significance (OR 2.3). The Apache II and interleukin-6 ROC curves corresponding to day 3 showed areas of 0.80 and 0.86, respectively.. 1) Interleukin-6 is an inflammatory biomarker with mortality prognostic value. 2) None of the biomarkers proved predictive of multiorgan failure.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Sepsis

Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful.. To determine the usefulness of combination biomarkers to diagnose sepsis.. Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center.. Plasma concentrations of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcγRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A "bioscore" combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P < 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort.. This prospective study, including inceptive and validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Logistic Models; Membrane Glycoproteins; Myeloid Cells; Predictive Value of Tests; Prospective Studies; Protein Precursors; Receptors, IgG; Receptors, Immunologic; ROC Curve; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

To investigate the value of procalcitonin (PCT) in the early diagnosis and risk stratification in sepsis.. Among 90 patients, 42 patients suffered sepsis, and 48 patients with severe sepsis. Serum PCT levels, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, the percentage of neutrophils and lactate levels in sepsis and severe sepsis patients were determined. Receive operating characteristic curve (ROC curve) was drawn to evaluate the ability of PCT and related inflammatory parameters in assessing risk factors in patients with sepsis, and to analyze correlation between PCT and sequential organ failure assess (SOFA) score, WBC, lactic acid, and hs-CRP.. Compared with sepsis patients, among severe sepsis patients, the levels of PCT (μg/L), hs-CRP (mg/L), WBC [×10(9)/L] , and SOFA score were significantly higher (PCT: 7.228±2.153 vs. 0.172±0.165, hs-CRP: 102.68±90.99 vs. 29.05±28.76, WBC: 14.15±8.14 vs. 8.15±4.55, SOFA score: 9.87±2.47 vs. 3.09±1.55), with statistical significance (all P<0.01), and the levels of percentage of neutrophils and lactic acid (mmol/L) were slightly increased (percentage of neutrophils: 0.820±0.094 vs. 0.740±0.130, lactic acid: 1.47±0.99 vs. 1.18±0.60), with no statistical significance (both P>0.05). Analysis of ROC curve displayed that area under the curve (AUC) of PCT was 0.808, which was higher than that of WBC, percentage of neutrophils, lactic acid and hs-CRP (AUC was 0.124, 0.042, 0.551 and 0.262, respectively), and when PCT was 1.000 μg/L, the sensitivity was 80.3%, specificity was 72.2%, and they were better than those of other traditional markers of inflammation. Bivariate correlation analysis showed that a positive correlation was found between PCT and SOFA score and WBC [r1=0.418, P1=0.006; r2=0.251, P2=0.011], and there was no correlation between PCT and lactic acid and hs-CRP [r1=0.186, P1=0.155; r2=0.089, P2=0.133].. Serum PCT is a reliable measure in emergency room for early diagnosis of sepsis with high sensitivity and specificity, it could be used as a routine monitoring index in critically ill patients to help assess disease severity in sepsis.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Protein Precursors; Sepsis; Severity of Illness Index

To observe the dynamic changes in serum procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) count in systemic inflammatory response syndrome (SIRS) and their implication in assessment of illness severity and prognosis.. A prospective case control study was conducted. Seventy-two patients with SIRS in Guangdong General Hospital were enrolled in intensive care unit (ICU) from May, 2010 to June, 2011. Parameters including PCT, CRP, and WBC count were determined on the 1st, 3rd, and 5th day after admission. The patients were divided into septic group (n=49) and non-septic group (non-infectious SIRS group, n=23) according to the presence or absence of infectious. Dynamic changes in all parameters were compared between the two groups and correlation analysis was carried out on the basis of differential indexes and sequential organ failure assessment (SOFA). The clinical outcome within 28 days after admission to ICU was observed, and the patients were divided into death group (n=19) and survival group (n=53). Dynamic changes in all parameters between the two groups were compared. Relevant parameters were analyzed with area under receiver operator characteristic curve (ROC curve, AUC) to predict 28-day survival. Logistic regression analysis of the multiple factors was used to screen independent risk factors for predicting death.. PCT level (μg/L) on 1st, 3rd, 5th day after admission were all significantly higher in septic group than those in non-septic group (1st day: 2.5±0.3 vs. 0.9±0.2, 3rd day: 1.9±0.3 vs. 0.6±0.2, 5th day: 0.9±0.1 vs. 0.5±0.1, all P<0.05), while there was no statistically significant difference in CRP and WBC between two groups. PCT level in septic group was gradually decreased with time, there were statistically significant differences between septic group and non-septic group at the different treatment time (all P<0.05), but there was no correlation between PCT and treatment duration in non-septic group. Positive statistical correlation was found between PCT and SOFA score (r=0.979, P<0.05). PCT (μg/L) and CRP levels (mg/L) on 1st, 3rd, 5th day were significantly higher in death group than those of survival group (PCT on 1st day: 2.0±0.8 vs. 0.8±0.3, 3rd day: 2.2±0.7 vs. 0.6±0.3, 5th day: 2.4±1.0 vs. 0.4±0.1; CRP on 1st day: 422±45 vs. 411±44, 3rd day: 418±39 vs. 403±52, 5th day: 392±38 vs. 382±46, all P<0.05), but WBC count showed no statistically significant difference between two groups. PCT level in survival group showed a significant lowering along with treatment duration, and statistical difference was seen by paired comparison between every two time-points (all P<0.05). There was no correlation between PCT level and treatment duration in death group, and it maintained a rather high level. No significant difference was seen in CRP and WBC between two groups with passage of time. AUC was 0.824 and 0.720, respectively, when patient's 28-day survival was predicted by PCT and CRP (both P<0.01). Logistic regression analysis of the multiple factors revealed that PCT>2.23 μg/L was independent risk factor predicting the prognosis [odds ratio (OR) was 1.773, 95% confidence interval (95%CI) 1.033 to 3.214, P=0.015].. Serum PCT evaluation may be helpful in differentiating sepsis and non-sepsis at early stage of disease, and also in predicting the severity of the illness and prognosis of SIRS. PCT may be one of the independent risk factors for 28-day survival.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) has been proposed as a marker of infection and was studied in neutropenic patients. This study investigated its role in non-neutropenic febrile cancer patients (NNCPs).. Between July 2009 and July 2010, a total of 248 NNCPs with fever were studied. PCT was measured in plasma within 24 hours of fever onset and 4 to 7 days thereafter, using a Kryptor system with a lower limit of quantitation of 0.075 ng/mL. Patients' clinical, microbiological, and radiological data were reviewed to make the diagnosis and were correlated with PCT levels.. This study included 30 patients with bloodstream infection (BSI), 60 with localized bacterial infection, 141 with no documented infection, and 8 with tumor-related fever. Most patients (98%) were inpatients or admitted to the hospital during the study. Patients with BSI had significantly higher PCT levels than did those with documented localized infections (P = .048) and no documented infection (P = .011). PCT levels were significantly higher in septic patients than in those without sepsis (P = .012). Patients with stage IV disease or metastasis had significantly higher baseline PCT levels than did those with early stages of cancer (P < .05). PCT levels dropped significantly in patients with bacterial infections in response to antibiotics (P < .0001).. Baseline PCT levels are predictive of BSI and sepsis in NNCPs. They may be predictors of metastasis and advanced cancer. Subsequent decrease in PCT levels in response to antibiotics is suggestive of bacterial infection. Larger trials are needed to confirm the results of this pilot study.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever; Humans; Male; Middle Aged; Neoplasms; Neutropenia; Pilot Projects; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

Sepsis is an increasingly prevalent cause of death, and management in the early stage is a critical issue. However, microbiological findings are generally obtained late during the course of the disease. In this study, we evaluated the clinical utility of procalcitonin (PCT) in improving the diagnosis of bloodstream infections and the potential utility of the SeptiFast (SF) test, a multiplex pathogen detection system, in the etiological diagnosis of immunocompromised patients. Seventy-nine hospitalized immunocompromised patients were included in this study. Our results demonstrate that while the PCT value correlates highly with sepsis, the results do not discriminate adequately enough to justify its independent use as a diagnostic tool. The SF test, combined with blood cultures, improves microbiological data in immunocompromised patients, especially in cases of previous antibiotic therapy and invasive fungal infection.

Topics: Adolescent; Adult; Aged; Bacteriological Techniques; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Immunocompromised Host; Male; Middle Aged; Molecular Diagnostic Techniques; Protein Precursors; Sepsis; Young Adult

Biomarkers, such as C-reactive protein [CRP] and procalcitonin [PCT], are insufficiently sensitive or specific to stratify patients with sepsis. We investigate the prognostic value of pancreatic stone protein/regenerating protein (PSP/reg) concentration in patients with severe infections.. PSP/reg, CRP, PCT, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1-β), IL-6 and IL-8 were prospectively measured in cohort of patients ≥ 18 years of age with severe sepsis or septic shock within 24 hours of admission in a medico-surgical intensive care unit (ICU) of a community and referral university hospital, and the ability to predict in-hospital mortality was determined.. We evaluated 107 patients, 33 with severe sepsis and 74 with septic shock, with in-hospital mortality rates of 6% (2/33) and 25% (17/74), respectively. Plasma concentrations of PSP/reg (343.5 vs. 73.5 ng/ml, P < 0.001), PCT (39.3 vs. 12.0 ng/ml, P < 0.001), IL-8 (682 vs. 184 ng/ml, P < 0.001) and IL-6 (1955 vs. 544 pg/ml, P < 0.01) were significantly higher in patients with septic shock than with severe sepsis. Of note, median PSP/reg was 13.0 ng/ml (IQR: 4.8) in 20 severely burned patients without infection. The area under the ROC curve for PSP/reg (0.65 [95% CI: 0.51 to 0.80]) was higher than for CRP (0.44 [0.29 to 0.60]), PCT 0.46 [0.29 to 0.61]), IL-8 (0.61 [0.43 to 0.77]) or IL-6 (0.59 [0.44 to 0.75]) in predicting in-hospital mortality. In patients with septic shock, PSP/reg was the only biomarker associated with in-hospital mortality (P = 0.049). Risk of mortality increased continuously for each ascending quartile of PSP/reg.. Measurement of PSP/reg concentration within 24 hours of ICU admission may predict in-hospital mortality in patients with septic shock, identifying patients who may benefit most from tailored ICU management.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Health Status Indicators; Hospital Mortality; Humans; Intensive Care Units; Interleukin-1beta; Interleukin-6; Interleukin-8; Lithostathine; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

The aim of the study was to determine whether C-reactive protein (CRP), procalcitonin (PCT), and d-dimer (DD) are markers of mortality in patients admitted to the emergency department (ED) with suspected infection and sepsis.. We conducted a prospective cohort in a university hospital in Medellín, Colombia. Patients were admitted between August 1, 2007, and January 30, 2009. Clinical and demographic data and Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores as well as blood samples for CRP, PCT, and DD were collected within the first 24 hours of admission. Survival was determined on day 28 to establish its association with the proposed biomarkers using logistic regression and receiver operating characteristic curves.. We analyzed 684 patients. The median Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment scores were 10 (interquartile range [IQR], 6-15) and 2 (IQR, 1-4), respectively. The median CRP was 9.6 mg/dL (IQR, 3.5-20.4 mg/dL); PCT, 0.36 ng/mL (IQR, 0.1-3.7 ng/mL); and DD, 1612 ng/mL (IQR, 986-2801 ng/mL). The median DD in survivors was 1475 ng/mL (IQR, 955-2627 ng/mL) vs 2489 ng/mL (IQR, 1698-4573 ng/mL) in nonsurvivors (P=.0001). The discriminatory ability showed area under the curve-receiver operating characteristic for DD, 0.68; CRP, 0.55; and PCT, 0.59. After multivariate analysis, the only biomarker with a linear relation with mortality was DD, with an odds ratio of 2.07 (95% confidence interval, 0.93-4.62) for values more than 1180 and less than 2409 ng/mL and an odds ratio of 3.03 (95% confidence interval, 1.38-6.62) for values more than 2409 ng/mL.. Our results suggest that high levels of DD are associated with 28-day mortality in patients with infection or sepsis identified in the emergency department.

Topics: APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Fibrin Fibrinogen Degradation Products; Humans; Infections; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

Hemolysis can be induced in sepsis via various mechanisms, its pathophysiological importance has been demonstrated in experimental sepsis. However, no data on free hemoglobin concentrations in human sepsis are available. In the present study we measured free hemoglobin in patients with severe sepsis as well as in postoperative patients using four methods. It was our aim to determine the potential value of free hemoglobin as a biomarker for diagnosis and outcome of severe sepsis in critical illness.. Plasma concentration of free hemoglobin was determined in patients with severe sepsis (n = 161) and postoperative patients (n = 136) on day 1 of diagnosis and surgery. For the measurement of free hemoglobin, an enzyme linked immunosorbent assay and three spectrophotometric algorithms were used. Moreover, SAPS II- and SOFA scores as well as procalcitonin concentration and outcome were determined. Kaplan-Meier analysis was performed and odds ratios were determined after classification of free hemoglobin concentrations in a high and low concentration group according to the median. For statistical evaluation the Mann-Whitney test and logistic regression analysis were used.. In non-survivors of severe sepsis, free hemoglobin concentration was twice the concentration compared to survivors. Thirty-day survival of patients, as evidenced by Kaplan-Meier analysis, was markedly lower in patients with high free hemoglobin concentration than in patients with low free hemoglobin concentration. Best discrimination of outcome was achieved with the spectrophotometric method of Harboe (51.3% vs. 86.4% survival, p < 0.001; odds ratio 6.1). Multivariate analysis including free hemoglobin, age, SAPS II- and SOFA-score and procalcitonin demonstrated that free hemoglobin, as determined by all 4 methods, was the best and an independent predictor for death in severe sepsis (p = 0.022 to p < 0.001). Free hemoglobin concentrations were not significantly different in postoperative and septic patients in three of four assays. Thus, free hemoglobin can not be used to diagnose severe sepsis in critical illness.. Free hemoglobin is an important new predictor of survival in severe sepsis.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Erythrocyte Transfusion; Female; Hemoglobins; Hospital Mortality; Humans; Male; Middle Aged; Organ Dysfunction Scores; Postoperative Period; Predictive Value of Tests; Prognosis; Protein Precursors; Risk Factors; Sepsis; Spectrophotometry; Survival Rate

Procalcitonin (PCT), the prohormone of calcitonin, has an early and highly specific increase in response to systemic bacterial infection. The objectives of this study were to determine the natural history of PCT for patients with critical illness and trauma, the utility of PCT as a marker of sepsis versus systemic inflammatory response syndrome (SIRS), and the association of PCT level with mortality.. PCT assays were done on eligible patients with trauma admitted to the trauma intensive care unit (ICU) of a Level I trauma center from June 2009 to June 2010, at hours 0, 6, 12, 24, and daily until discharge from ICU or death. Patients were retrospectively diagnosed with SIRS or sepsis by researchers blinded to PCT results.. A total of 856 PCT levels from 102 patients were analyzed, with mean age of 49 years, 63% male, 89% blunt trauma, mean Injury Severity Score of 21, and hospital mortality of 13%. PCT concentration for patients with sepsis, SIRS, and neither were evaluated. Mean PCT levels were higher for patients with sepsis versus SIRS (p < 0.0001). Patients with a PCT concentration of 5 ng/mL or higher had an increased mortality when compared with those with a PCT of less than 5 ng/mL in a univariate analysis (odds ratio, 3.65; 95% confidence interval, 1.03-12.9; p = 0.04). In a multivariate logistic analysis, PCT was found to be the only significant predictor for sepsis (odds ratio, 2.37; 95% confidence interval,1.23-4.61, p = 0.01).. PCT levels are significantly higher in ICU patients with trauma and sepsis and may help differentiate sepsis from SIRS in critical illness. An elevated PCT level was associated with increased mortality.

Topics: Adult; Aged; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Confidence Intervals; Critical Care; Critical Illness; Diagnosis, Differential; Disease Progression; Female; Hospital Mortality; Humans; Injury Severity Score; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Sensitivity and Specificity; Sepsis; Survival Rate; Systemic Inflammatory Response Syndrome; Trauma Centers; Wounds, Nonpenetrating

To investigate the accuracy of procalcitonin (PCT) as a diagnostic marker of nosocomial sepsis (NS) and define the most accurate cut-off to distinguish infected from uninfected neonates.. Six neonatal intensive care units (NICUs).. 762 neonates admitted to six NICUs during a 28-month observational study for whom at least one serum sample was taken on admission.. Positive and negative predictive values at different PCT cut-off levels.. The overall probability of an NS was doubled or more if PCT was >0.5 ng/ml. In very-low-birth-weight (VLBW) infants, a cut-off of >2.4 ng/ml gave a positive predictive value of NS near to 50% with a probability of a false-positive diagnosis of NS in about 10% of the patients.. In VLBW neonates, a serum PCT value >2.4 ng/ml prompts early empirical antibiotic therapy, while in normal-birth-weight infants, a PCT value ≤2.4 ng/ml carries a low risk of missing an NS.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Likelihood Functions; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

To explore the regularity of changes in total adiponectin (APN) and high molecular bodyweight adiponectin (HAP) in sepsis, and its correlation with infection and its role on predicting prognosis.. A prospective study was conducted. Eighty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medicine University from June to November in 2011 were enrolled in this study. The plasma APN (both total APN and HAP), procalcitonin (PCT), and endotoxin were determined with enzyme linked immunosorbent assay (ELISA) at 2 hours, 2 days, and 6 days after ICU admission. The acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and simplified acute physiology score II (SAPS II) scores were recorded, and insulin resistance index was calculated. Twenty healthy volunteers and 21 patients with systemic inflammation response syndrome (SIRS) were enrolled as controls and SIRS group.. Plasma total APN and HAP in sepsis patients at 2 hours after ICU admission were significantly decreased compared with control group and SIRS group [total APN: 2.87 (2.28, 3.89) mg/L vs. 6.48±1.53 mg/L, 3.72 (2.67, 4.59) mg/L; HAP: 2.64 (2.07, 3.75) mg/L vs. 5.12±1.98 mg/L, 3.33 (2.23, 4.24) mg/L, P<0.05 or P<0.01]. A negative correlation was found between total APN and HAP in plasma and PCT (total APN r=-0.559, HAP r=-0.530, both P<0.01), but no correlation with endotoxin. Those correlations remained significantly in partial correlation analysis controlled by insulin resistance status. There were significances in APN among sepsis, severe sepsis and septic shock groups, and negative correlations were found between APN and APACHE II, SOFA, and SAPS II scores (total APN r value, -0.868, -0.766, -0.725; HAP r value, -0.859, -0.715, -0.692, all P<0.01). Total APN and HAP in plasma of survivors with sepsis (n=41) was gradually increased following the recovery of the disease (total APN χ(2)=34.520, HAP χ(2)=27.802, both P<0.01) and the level in non-survivors (n=7) was decreased (total APN χ(2)=3.938, HAP χ(2)=3.938, both P>0.05). The significantly negative correlations were found between total APN and HAP at 2 hours after ICU admission and ICU duration (total APN r=-0.275, P=0.014; HAP r=-0.299, P=0.007) and ventilation time (total APN r=-0.393, HAP r=-0.519, both P<0.01).. Plasma total APN and HAP was decreased in septic patients, and negatively correlated with PCT. Plasma total APN and HAP played a role in diagnosis of infection and predicting the outcomes, and correlated with severity of sepsis.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Critical Care; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Young Adult

Procalcitonin (PCT) has emerged as a valuable marker of sepsis. The potential role of PCT in diagnosis and therapy monitoring of intravascular catheter-related bloodstream infections (CRBSI) in intensive care unit (ICU) is still unclear and was evaluated.. Forty-six patients were included in the study, provided they were free of infection upon admission and presented the first episode of suspected CRBSI during their ICU stay. Patients who had developed any other infection were excluded. PCT was measured daily during the ICU hospitalization. Primary endpoint was proven CRBSI. Therapy monitoring as according to infection control was also evaluated.. Among the 46 patients, 26 were diagnosed with CRBSI. Median PCT on the day of infection suspicion (D0) was 7.70 and 0.10 ng/ml for patients with and without proven CRBSI, respectively (p < 0.001). The area under the curve (AUC) for PCT was 0.990 (95% CI; 0.972 - 1.000), whereas a cut-off value of 0.70 ng/ml provided sensitivity and specificity of 92.3 and 100% respectively. In contrast, the AUC for white blood cells (WBC) was 0.539 (95% CI; 0.369 - 0.709), and for C-reactive protein (CRP), 0.603 (95% CI; 0.438 - 0.768). PCT was the best predictor of proven infection. Moreover, an increase >0.20 ng/ml of PCT between the D0 and any of the 4 preceding days was associated with a positive predictive value exceeding 96%. PCT concentrations from the D2 to D6 after suspected infection tended to decrease in controlled patients, whereas remained stable in non-controlled subjects. A PCT concentration exceeding 1.5 ng/ml during D3 was associated with lack of responsiveness to therapy (p = 0.028).. We suggest that PCT could be a helpful diagnostic and prognostic marker of CRBSI in critically ill patients. Both absolute values and variations should be considered.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Catheter-Related Infections; Cohort Studies; Critical Illness; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children.. Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis.. Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone.. Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; Critical Illness; Female; Gene Expression; Humans; Infant; Interleukins; Male; Microarray Analysis; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Timely diagnosis and prognostic assessment of ventilator-associated pneumonia remain major challenges in critical care.. To explore the value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin, and the Clinical Pulmonary Infection Score in the diagnosis and prognostic assessment of ventilator-associated pneumonia.. For 92 patients, bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum levels of the receptor and procalcitonin and levels of the receptor in exhaled ventilator condensate were measured, and the Clinical Pulmonary Infection Score was calculated.. On the day of diagnosis, patients who had pneumonia had higher serum levels of the receptor, procalcitonin, and C-reactive protein; higher white blood cell counts; and higher pulmonary infection and Sequential Organ Failure Assessment scores than did patients without pneumonia. White blood cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP. Serum levels of the receptor plus the pulmonary infection score were the most reliable for diagnosis; the area under the receiver operating characteristic curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was 0.95. For 28-day survival, procalcitonin level combined with pulmonary infection score was the most reliable for prognostic assessment (area under the curve, 0.848; 95% CI, 0.672-1.025).. In patients with ventilator-associated pneumonia, serum levels of the receptor plus the pulmonary infection score are useful for diagnosis, and procalcitonin levels plus the pulmonary infection score are useful for prognostic assessment.

Topics: Breath Tests; Bronchoalveolar Lavage Fluid; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Leukocyte Count; Male; Membrane Glycoproteins; Middle Aged; Multivariate Analysis; Odds Ratio; Pneumonia, Ventilator-Associated; Prognosis; Protein Precursors; Receptors, Immunologic; Risk Factors; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Triggering Receptor Expressed on Myeloid Cells-1

To determine the association of procalcitonin (PCT) with trauma severity and post traumatic sepsis in children.. The blood samples of 30 children with acute trauma in a Pediatric unit were collected for four consecutive days. The levels of PCT, IL-6, CRP and WBC were measured. The pediatric trauma score (PTS), length of stay in hospital, incidence of sepsis and clinical outcomes of the children were recorded. The value of PCT for predicting prognosis of children with trauma was compared with other inflammatory markers.. Plasma PCT levels increased significantly in the patients in our study. Sepsis occurred in 23.33% of the patients. The patients with sepsis had higher levels of PCT than those with and without systemic inflammatory response syndrome (SIRS) and the healthy controls (P < 0.05). The peak level of PCT emerged on day 2 after trauma. The plasma PCT levels were positively correlated with trauma severity. The level of PCT on day 2 was an independent predictor for post-trauma sepsis and SIRS.. Plasma PCT levels increase markedly in post trauma children. Plasma PCT of day 2 after trauma is an independent predictor of post-traumatic sepsis and SIRS complications. There is a significant correlation between the severity of injury and plasma PCT.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; China; Female; Humans; Incidence; Interleukin-6; Male; Prognosis; Protein Precursors; Sepsis; Trauma Severity Indices; Wounds and Injuries

To evaluate the diagnostic values of procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA) in septic patients.. This study totally enrolled 390 patients who were admitted to West China Hospital, Sichuan University from March to November 2011 with septic manifestation. The patients were divided into sepsis group (n = 203) and non-sepsis group (n = 187) according to clinical infectious disease standard. PCT and IL-6 were measured by automatic electrochemiluminescence (ECL) analyser. CRP was measured by rate immunonephelometric analyser, SAA was measured by fixed time nephelometric method. The diagnostic powers of these four biomakers were constructed by receiver operating characteristics (ROC) curves.. There were statistically significant differences on the values of PCT, CRP, IL-6, SAA between sepsis group and non-sepsis group. PCT had an AUC value of 0. 919 (P < 0.05) which was higher than that of CRP, IL-6, and SAA (P < 0.05). CRP performed with an AUC of 0.755 (P < 0.05), IL-6 with an AUC of 0.786 (P < 0.05), and SAA with the lowest AUC of 0.645 (P < 0.05). The combination AUC was 0.892 (P < 0.05) and there was no statistically significant difference when compared to PCT. As an early diagnostic indicator of sepsis, the cut-off value of PCT was 1.18 ng/mL, with sensitivity of 84.7%, specific of 83.4%, while Youden index was 0.681, positive predict value was 64.1%, negative predict value was 75.8%, positive likelihood ratio was 5.10, negative likelihood ratio was 0.18, respectively. A statistically significant difference was available on the value of PCT in septic patients between ICU and non-ICU.. PCT as an early independent biomarker for sepsis is superior to immune inflammatory biomarkers (CRP, IL-6, SAA), also is better than the combination of these four biomarkers for economic effect.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Serum Amyloid A Protein

We assessed the diagnostic value of procalcitonin (PCT) in urosepsis on 54 patients with urinary tract infections (UTI), suspected of having urosepsis. The results of urine culture, blood culture, and serum concentrations of PCT were analyzed. Overall, the sensitivity and specificity of PCT for bacteremia were as follows : 100 and 31.6% at concentrations of >0.5 ng/ml and 75.0 and 78.9% at concentrations of >10 ng/ml. we concluded that the PCT level could be a reliable early marker suggestive of urosepsis, and may be helpful when deciding whether to perform immediate urological intervention or not.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Urinary Tract Infections

Procalcitonin (PCT), a prohormone of calcitonin has been described as a specific biomarker of sepsis.. To compare the predictive value of PCT, C reactive protein (CRP) and white blood cell count (WBC) for the diagnosis of late onset sepsis (LOS) in very low birth weight (VLBW) neonates.. We prospectively determined the serum concentration of PCT, CRP and WBC in 53 VLBW newborns with clinical suspicion of LOS. 25 had confirmed sepsis with positive blood culture; 28 had clinical sepsis (negative blood cultures). PCT levels were significantly higher in the infected group (3.0 ng/ml) compared to the non infected group (0.4 ng/ml) (p < 0.05). PCT had the highest area under the ROC curve 0.83 (95% CI 0.70-0.92) p = 0.001 compared to CRP 0.51 (95%CI 0.37-0.65) and WBC 0.53 (95%CI 0.38-0.66) for the diagnosis of LOS .The best PCT cut off value was 0.9 ng/ml. The sensitivity, specificity and negative predictive value were 88%, 72% and 87%, respectively.. The determination of PCT could be more useful than CRP and WBC in the diagnosis of LOS in VLBW newborns.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Leukocyte Count; Male; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Early diagnosis and rapid bacterial identification are of primary importance for outcome of septic patients. SeptiFast® (SF) real-time PCR assay is of potential utility in the etiological diagnosis of sepsis, but it cannot replace blood culture (BC) for routine use in clinical laboratory. Procalcitonin (PCT) is a marker of sepsis and can predict bacteremia in septic patients. The aim of the present study was to investigate whether PCT serum levels could predict SF results, and could help screening febrile patients in which a SF assay can improve the etiological diagnosis of sepsis.. From 1009 febrile patients with suspected sepsis, 1009 samples for BC, SF real-time PCR, and PCT determination were obtained simultaneously, and results were compared and statistically analysed. Receiver operating characteristic (ROC) curves were generated to determine the area under the curve and to identify which cut-off of PCT value produced the best sensitivity to detect SF results.. Mean PCT values of sera drawn simultaneously with samples SF positive (35.42 ± 61.03 ng/ml) or BC positive (23.14 ± 51.56 ng/ml) for a pathogen were statistically higher than those drawn simultaneously with SF negative (0.84 ± 1.67 ng/ml) or BC negative (2.79 ± 16.64 ng/ml) samples (p<0.0001). For SF, ROC analysis showed an area under the curve of 0.927 (95% confidence interval: 0.899-0.955, p<0.0001). The PCT cut-off value of 0.37 ng/ml showed a negative predictive value of 99%, reducing the number of SF assays of 53.9%, still identifying the 96.4% of the pathogens.. PCT can be used in febrile patients with suspected sepsis to predict SF positive or negative results. A cut-off value of 0.37 ng/ml can be considered for optimal sensitivity, so that, in the routine laboratory activity, SF assay should not be used for diagnosis of sepsis in an unselected patient population with a PCT value <0.37 ng/ml.

Topics: Aged; Aged, 80 and over; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Fever; Humans; Male; Middle Aged; Protein Precursors; Real-Time Polymerase Chain Reaction; Sepsis

To evaluate the tendency of the plasma concentration and clearance of procalcitonin (PCT-c) as biomarkers of prognosis of patients with severe sepsis and septic shock, compared to another early prognosis marker, the number of SIRS criteria at sepsis diagnosis.. We conducted a prospective, observational, cohort study, with patients with severe sepsis and septic shock. The serum procalcitonin was determined at diagnosis of sepsis and after 24 and 48 hours. Demographic data, APACHE IV, SOFA score on arrival, number of SIRS criteria at diagnosis, site of infection and microbiological results were recorded.. Twenty-eight patients were included, 19 clinical and nine surgical. In 13 (46.4%) the source of sepsis was pulmonary, abdominal in seven (25.0%), urinary in five (17.9%) and soft tissue in three cases (10.7%). Fifteen patients had severe sepsis and 13 septic shock. Overall mortality was 17.9% (five patients), three with septic shock. Twenty-eight PCT determinations were performed at sepsis diagnosis, 27 after 24 hours and 26 after 48 hours. The initial concentration was not significantly different between survivors and non-survivors groups, but the differences between the two groups after 24 and 48 hours were statistically significant. There was no difference in the number of SIRS criteria. The 24-hour procalcitonin clearance proved to be significantly higher in the group of survivors (-3.0 versus -300.0, p = 0.028). Although the 48-hour procalcitonin clearance has shown to be higher in the group of survivors when compared to non-survivors, the difference did not reach statistical significance.. Persistently high procalcitonin concentrations in plasma, as well as reduced 24-hours PCT clearence, were associated with a significant increase in mortality in patients with severe sepsis and septic shock.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Male; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

To prospectively evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) as percentage of baseline (POB) in predicting hospital survival, we studied 64 consecutive, postoperative patients with severe sepsis.. Plasma PCT, IL-6, and CRP were serially measured from day 1 (onset of sepsis) to day 14 in parallel with clinical data until day 28. Multivariate logistic regression and univariate analysis of predictive accuracy of PCT-, IL-6-, and CRP-POB were performed. Newly derived binary prediction rules were evaluated by calculating sensitivity, specificity, positive predictive value, and negative predictive value.. In survivors, PCT and IL-6 significantly decreased from days 1 to 14, whereas CRP did not. In nonsurvivors, the inflammation markers mostly increased within the second week. At day 7, logistic regression analysis revealed PCT-POB as an independent determinant for survival. Especially, PCT-POB not exceeding 50% and PCT-POB not exceeding 25% with CRP-POB not exceeding 75% on day 7 indicated a favorable outcome with a positive predictive value/sensitivity of 75%/97% and 92%/67%, respectively. In comparison, pretest likelihood to survive by day 28 and observed survival rate were 60% and 67%, respectively.. Prediction rules of decrease in PCT-POB on day 7 in combination with CRP-POB may serve to monitor efficacy and guide duration of therapy in critically ill patients.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Male; Middle Aged; Postoperative Period; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Time Factors

The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis.. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%.. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003).. Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.

Topics: Aged; Aged, 80 and over; Anti-Infective Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Odds Ratio; Practice Guidelines as Topic; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Time Factors; Treatment Outcome

The expression of Fc receptors for IgG (FcγRs) on neutrophils, including CD16, CD32 and CD64, may be modulated in response to sepsis. We investigated the expression of FcγRs on neutrophils and procalcitonin (PCT) as biomarkers of sepsis among critically ill patients.. This prospective study was conducted in a 24-bed respiratory intensive care unit between July 2007 and June 2008. Critically ill patients requiring mechanical ventilation were enrolled and categorized into three groups: those with systemic inflammatory response syndrome (SIRS), those with severe sepsis and those with septic shock. Expression of FcγRs on neutrophils was quantitatively measured by flow cytometry immediately after enrolment of the patient. Serum PCT levels were also measured. Receiver operating characteristic (ROC) curves were used to evaluate the performance of FcγR expression and PCT as biomarkers of sepsis.. Sixty-six patients were enrolled, including 11 with SIRS, 31 with severe sepsis and 24 with septic shock. Nineteen healthy volunteers served as normal controls. CD64 was upregulated, CD16 was downregulated and CD32 remained unchanged during sepsis. CD64 expression and the ratio of CD64/CD16 increased significantly with the severity of sepsis. However, serum PCT levels were not significantly different between SIRS and severe sepsis patients. CD64, CD64/CD16 and PCT all significantly predicted sepsis, septic shock and bacteraemia. As assessed using ROC curves, CD64 was better than PCT for differentiating SIRS from severe sepsis and septic shock. CD64 and CD64/CD16 were associated with mortality.. CD64 and CD16 were differentially modulated by sepsis. CD64, CD64/CD16 and PCT may be biomarkers of sepsis. CD64 was better than PCT for identifying patients who required treatment with antibiotics.

Topics: Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Chronic Disease; Comorbidity; Critical Illness; Female; Flow Cytometry; Humans; Male; Middle Aged; Neutrophils; Prospective Studies; Protein Precursors; Receptors, IgG; Sepsis; Severity of Illness Index

Procalcitonin (ProCT) is increased in serum of septic patients and those with systemic inflammation. Endogenous levels of ProCT might influence the response of polymorphonuclear leukocytes (PMNs), independently of endotoxin, in clinical disease.. Healthy human volunteers.. Recombinant human ProCT (rhProCT).. Whole blood and PMNs were exposed in vitro to exogenous rhProCT. Interleukin (IL)-6, IL-8, IL-10, IL-13, tumor necrosis factor-alpha (TNFα), IL-1β, and macrophage inflammatory protein (MIP)-1β (pg/ml) were measured by multiplex suspension bead-array immunoassay, and migration and phagocytosis were measured in PMNs.. In a whole-blood model, a dose-dependent increase in IL-6, TNFα, and IL-1β of the cell-free supernatant was noted. Pre-incubation with ProCT, at doses consistent with clinical sepsis, resulted in a decrease in PMN migration without alteration in phagocytosis of Staphylococcus aureus or indirect measurements of bacterial killing.. Clinically relevant levels of ProCT influence immunologic responses that may contribute to systemic inflammatory response and septic shock.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Chemotaxis, Leukocyte; Cytokines; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Neutrophils; Protein Precursors; Recombinant Proteins; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

Topics: Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Laboratory Techniques; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Treatment Outcome

To establish reference values in cord blood of the following new sepsis markers: pro-adrenomedullin (MR-proADM), pro-endothelin (CT-proET-1), and pro-atrial natriuretic peptide (MR-proANP).. MR-proADM, CT-proET-1, MR-proANP, and procalcitonin (PCT) were measured in cord blood of newborn infants by Time Resolved Amplified Cryptate Emission (TRACE) technology. The inclusion criteria in the control group (n=194) was the absence of any clinical sign or risk factor of sepsis. A group of 73 newborn infants presenting with risk factors of sepsis at delivery was also studied.. The median values (reference interval) of CT-proET-1, MR-pro-ADM, and MR-proANP measured in cord blood plasma were 72 pmol/L (39-115), 0.84 nmol/L (0.5-1.38), and 163 pmol/L (76-389), respectively. The PCT reference interval was not significantly different from that previously described in cord blood serum.. The reference intervals established will serve as a starting point for further clinical investigations aimed to elucidate the potential prognostic/diagnostic value of these markers in neonatal sepsis management.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Endothelin-1; Female; Fetal Blood; Fetus; Humans; Infant; Infant, Newborn; Photoelectron Spectroscopy; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Protein Precursors; Reference Values; Sepsis

Rapid diagnosis of bloodstream infections (BSIs) in the emergency department (ED) is challenging, with turnaround times exceeding the timeline for rapid diagnosis. We studied the usefulness of procalcitonin as a marker of BSI in 367 adults admitted to our ED with symptoms of systemic infection. Serum samples obtained at the same time as blood cultures were available from 295 patients. Procalcitonin levels were compared with blood culture results and other clinical data obtained during the ED visit. Procalcitonin levels of less than 0.1 ng/mL were considered negative; all other levels were considered positive. In 16 patients, there was evidence of BSI by blood culture, and 12 (75%) of 16 patients had a procalcitonin level of more than 0.1 ng/mL. In 186 (63.1%) of 295 samples, procalcitonin values were less than 0.1 ng/mL, and all were culture negative. With a calculated threshold of 0.1475 ng/mL for procalcitonin, sensitivity and specificity for the procalcitonin assay were 75% and 79%, respectively. The positive predictive value was 17% and the negative predictive value 98% compared with blood cultures. Procalcitonin is a useful marker to rule out sepsis and systemic inflammation in the ED.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Humans; Inflammation; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis

To devise and evaluate quantitative indices of dynamics in lipopolysaccharide-binding protein (LBP), CRP, and procalcitonin concentrations as prognostic markers in sepsis.. Prospective observational cross-sectional study with 5-day follow-up. Simple (Δ(5-1)) and relative (chain indices-based) rates for LBP (ELISA), procalcitonin (immunoluminometry), and CRP were devised.. Admission concentrations of all markers were higher in septic patients than controls. Not the admission levels but markers' time-courses differed between survivors (declining) and non-survivors (persistently high). Simple and relative rates were greater in survivors than non-survivors. Their accuracies as outcome predictors were comparable, higher for LBP and CRP than PCT. At ~95% sensitivity, the highest specificity had LBP relative and simple rates. Except for sepsis severity scores, only LBP was independently associated with lethal outcome.. For outcome prediction, the evaluation of dynamics of sepsis mediators, expressed by simple or relative rates, is a more suitable alternative to markers' peak values.

Topics: Acute-Phase Proteins; Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Cross-Sectional Studies; Female; Humans; Limit of Detection; Male; Membrane Glycoproteins; Middle Aged; Prognosis; Protein Precursors; Reproducibility of Results; Sepsis

To compare semi-quantitative procalcitonin with C-reactive protein in predicting bacteraemia in haematological patients with neutropenic fever.. A total of 77 patients treated with intensive chemotherapy for haematological malignancy at Kuopio University Hospital were candidates for study entry. Eleven of these patients did not fulfil the criteria for neutropenic fever, and 66 patients were finally included. Nineteen patients had acute myeloid leukaemia and 47 had received high-dose chemotherapy supported by autologous stem cell transplant. Ninety neutropenic fever episodes in these 66 patients fulfilled the study entry criteria, with microbiological cultures, procalcitonin and C-reactive protein measurements available. Serum procalcitonin and C-reactive protein were analyzed at the onset of each neutropenic fever episode on day 0, and then daily from days 1 to 4.. Bacteraemia was observed in 21 episodes (23%) and the criteria for severe sepsis were fulfilled in 13 episodes (14%). Half of the bacteraemic episodes were caused by Gram-negative bacteria. The kinetics of procalcitonin and C-reactive protein were similar, with increasing levels for 2 to 4 days after the onset of fever. The procalcitonin level on days 1, 2, 3 and 4 was associated with bacteraemia and Gram-negative bacteraemia, but not with the development of severe sepsis. On day 1, a procalcitonin level above 0.5 ng/ml had a sensitivity of 57% and 70% and specificity of 81% and 77% to predict bacteraemia and Gram-negative bacteraemia, respectively.. An elevated level of procalcitonin within 24 h after the onset of neutropenic fever predicts bacteraemia and Gram-negative bacteraemia in haematological patients.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever of Unknown Origin; Gram-Negative Bacterial Infections; Hematologic Neoplasms; Humans; Male; Middle Aged; Neutropenia; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors; Young Adult

In hantavirus infections levels of serum leukocytes or C-reactive protein are usually elevated to levels found in serious bacterial infections. However, procalcitonin in patients infected with hantavirus has not yet been discussed in the literature. A total of 29 adult patients with hantavirus infection, 30 with sepsis, and 19 with tick-borne encephalitis were included in this observational retrospective study. The median procalcitonin level in patients with hantavirus infection was 0.53 μg/L (range 0.09-11.71 μg/L), in the group with sepsis 4.33 μg/L (range 0.08-161.1 μg/L) and in patients with viral meningitis 0.08 μg/L (range 0.05-0.12 μg/L). The difference between all three groups was statistically significant (p < 0.001). A higher procalcitonin level was found in patients with hemorrhagic fever with renal syndrome caused by Dobrava virus (0.74 μg/L; range 0.09-2.83 μg/L) than in those with Puumala virus infections (0.50 μg/L; range 0.10-11.71 μg/L). However, the difference was not statistically significant (p = 0.895). This study confirmed previous findings demonstrating the association of elevated procalcitonin with bacterial infection. However, increased procalcitonin serum level was also found in hantavirus infections with overlapping results between viral and severe bacterial infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Calcitonin; Calcitonin Gene-Related Peptide; Child; Encephalitis, Tick-Borne; Female; Hantavirus Infections; Humans; Male; Meningitis, Viral; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis; Young Adult

We examined the utility of serum levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for the diagnoses, severity assessments, and predicting the prognoses of patients with sepsis and compared sTREM-1 values with those of C-reactive protein (CRP) and procalcitonin (PCT).. Fifty-two patients with sepsis were included: 15 sepsis cases and 37 severe sepsis cases (severe sepsis + septic shock). Serum levels of sTREM-1, CRP, and PCT were determined on days 1, 3, 5, 7, 10, and 14 after admission to an ICU.. Serum sTREM-1 levels of patients with severe sepsis were significantly higher than for those with sepsis on day 1 (240.6 pg/ml vs. 118.3 pg/ml; P < 0.01), but CRP and PCT levels were not significantly different between the two groups. The area under an ROC curve for sTREM-1 for severe sepsis patients was 0.823 (95% confidence interval: 0.690-0.957). Using 222.5 pg/ml of sTREM-1 as the cut-off value, the sensitivity was 59.5%, the specificity was 93.3%, the positive predictive value was 95.6%, the negative predictive value was 48.3%, the positive likelihood ratio was 8.92, and the negative likelihood ratio was 0.434. Based on 28-day survivals, sTREM-1 levels in the surviving group showed a tendency to decrease over time, while they tended to gradually increase in the non-surviving group. sTREM-1 levels in the non-surviving group were higher than those in the surviving group at all time points, whereas CRP and PCT levels showed a tendency to decrease over time in both groups. sTREM-1 levels and Sequential Organ Failure Assessment (SOFA) scores were positively correlated (r = 0.443; P < 0.001), and this correlation coefficient was greater than the correlation coefficients for both CRP and PCT.. Serum sTREM-1 levels reflected the severity of sepsis more accurately than those of CRP and PCT and were more sensitive for dynamic evaluations of sepsis prognosis.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Membrane Glycoproteins; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sensitivity and Specificity; Sepsis; Serum; Severity of Illness Index; Triggering Receptor Expressed on Myeloid Cells-1

There are no data on serum cortisol of hematological patients at the onset of neutropenic fever and its possible association with the severity of infection. The purpose of this study was to evaluate the association of serum cortisol with the level of C-reactive protein (CRP) and procalcitonin (PCT), widely used markers of infection and inflammation, and with the development of severe sepsis in this patient group. All clinical data were collected prospectively at the hematology ward of Kuopio University Hospital. Altogether, 69 hematological patients with 93 periods of neutropenic fever were included. Nineteen patients received therapy for acute myeloid leukemia, and 50 patients were autologous stem cell transplantation recipients. Each period of neutropenic fever was classified as severe sepsis or not. Serum cortisol, CRP, and PCT were determined at the onset of fever on day 0 and then at 8-9 a.m. on days 1-4. Level of serum cortisol correlated positively with maximal CRP level during days 0 to 4 in neutropenic fever periods without severe sepsis, but no correlation was observed in fever periods with severe sepsis. To conclude, the level of cortisol correlated with the severity of infection measured as maximal CRP or elevated PCT in fever periods without severe sepsis, but in fever periods with severe sepsis, the cortisol response was attenuated.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Hydrocortisone; Inflammation; Male; Middle Aged; Neutropenia; Prospective Studies; Protein Precursors; Sepsis; Young Adult

CD14 is present in macrophage, monocyte, and granulocyte cells and their cell membranes, and it is said to be responsible for intracellular transduction of endotoxin signals. Its soluble fraction is present in blood and is thought to be produced in association with infections. It is called the soluble CD14-subtype (sCD14-ST), and in the following text it is referred to by its generic name, presepsin. We have previously reported that presepsin is produced in association with infection and that it is specifically expressed in sepsis. In the present study we developed a new rapid diagnostic method by using a chemiluminescent enzyme immunoassay that allowed making automated measurements in a shorter time. The results of using this method to measure presepsin values in different pathological conditions were normal, 294.2 ± 121.4 pg/ml; local infection, 721.0 ± 611.3 pg/ml; systemic inflammatory response syndrome, 333.5 ± 130.6 pg/ml; sepsis, 817.9 ± 572.7 pg/ml; and severe sepsis, 1,992.9 ± 1509.2 pg/ml; the presepsin values were significantly higher in patients with local infection, sepsis, and severe sepsis than in patients who did not have infection as a complication. In a comparative study with other diagnostic markers of sepsis based on ROC curves, the area under the curve (AUC) of presepsin was 0.845, and greater than the AUC of procalcitonin (PCT, 0.652), C-reactive protein (CRP, 0.815), or interleukin 6 (IL-6, 0.672). In addition, a significant correlation was found between the APACHE II scores, an index of disease severity, and the presepsin values, suggesting that presepsin values can serve as a parameter that closely reflects the pathology.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Humans; Immunoenzyme Techniques; Interleukin-6; Lipopolysaccharide Receptors; Male; Middle Aged; Protein Precursors; ROC Curve; Sepsis; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

The differential diagnosis of macrophage activation syndrome (MAS) and sepsis must be considered in the clinical course of systemic-onset juvenile idiopathic arthritis (s-JIA) with sudden onset of high-grade fever and abnormal laboratory findings, including leukocytopenia, thrombocytopenia, and coagulopathy. In this report, we describe the case of a 17-month-old girl diagnosed with s-JIA complicated with sepsis. Her serum interleukin (IL)-18 level was significantly elevated throughout the clinical course. Furthermore, compared to other MAS patients, she showed a significantly elevated serum IL-6 level and procalcitonin in sepsis. Therefore, our results suggest that a patient's cytokine profile may be a useful indicator of disease activity and may thus help in the differential diagnosis of sepsis and MAS in s-JIA.

Topics: Arthritis, Juvenile; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Infant; Interleukin-18; Interleukin-6; Macrophage Activation Syndrome; Protein Precursors; Sepsis

The aim of this study was to evaluate the predictive value of resistin and visfatin in neonatal sepsis, and to compare these adipocytokines with C-reactive protein (CRP), procalcitonin and interleukin 6 (IL-6).. A total of 62 term or near term infants with sepsis proven by positivity of blood culture, and 43 healthy infants were included in this study.. There were no statistically significant differences between the two groups as regards birthweight and gestational age. White blood cell count (p= 0.039), CRP levels (p=0.01), procalcitonin levels (p=0.01), IL-6 levels (p= 0.01), visfatin levels (p=0.01) and resistin levels (p=0.01) were significantly higher in septic infants. There was a positive correlation between visfatin, resistin and other markers (WBC, CRP, procalcitonin and IL-6). A cut-off value of 10 ng/mL for visfatin, showed 92% sensitivity and 94% specificity, and a cut-off value of 8 ng/mL for resistin showed 93% sensitivity and 95% specificity for neonatal sepsis.. In the light of these results, visfatin and resistin can be used as a diagnostic marker similar to CRP, procalcitonin and IL-6 in neonatal sepsis. Further studies are needed to better understand the role and predictive value of these molecules in neonatal sepsis.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-6; Nicotinamide Phosphoribosyltransferase; Pregnancy; Protein Precursors; Resistin; Sepsis

A biphasic activated partial thromboplastin time waveform predicts sepsis and disseminated intravascular coagulation in adults. This has not been previously investigated in children. Our aim is to ascertain whether there are changes in the activated partial thromboplastin time waveform in children with meningococcal disease and to compare its diagnostic use with procalcitonin.. Alder Hey Children's National Health Service Foundation Trust, Liverpool, UK.. Thirty-six children admitted to the hospital for the treatment of suspected meningococcal disease had activated partial thromboplastin time waveform and procalcitonin analysis performed at admission. The light transmittance level at 18 secs was used to quantitate the waveform. Severity of disease was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score, Pediatric Risk of Mortality III score, and the Pediatric Logistic Organ Dysfunction score.. Twenty-four children had proven meningococcal disease, 12 had a presumed viral illness, and 20 control subjects were recruited. Transmittance level at 18 secs was lower in children with meningococcal disease and those with a viral illness (p < .0001) and control subjects (p < .0005). Sensitivity and specificity was 0.91 and 0.96 for transmittance level at 18 secs and 0.92 and 1 for procalcitonin in identifying meningococcal disease. There was a significant difference in procalcitonin between children with meningococcal disease and those with a viral illness and control subjects (p < .0005). A negative correlation was found between transmittance level at 18 secs and length of hospital stay (p < .0001), C-reactive protein (p < .0001), procalcitonin (p < .0001), Glasgow Meningococcal Septicaemia Prognostic Score (p < .01), Pediatric Risk of Mortality III score (p < .0001), and Pediatric Logistic Organ Dysfunction score score (p < .0001).. The activated partial thromboplastin time waveform is abnormal in children with meningococcal disease and may be a useful adjunct in the diagnosis and management of sepsis in children.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child, Preschool; England; Female; Hospitals, Pediatric; Humans; Infant; Intensive Care Units, Pediatric; Male; Meningococcal Infections; Neisseria meningitidis; Partial Thromboplastin Time; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis

The aim of this study was to assess the use of neutrophil distribution width (NDW) and to compare it to C-reactive protein (CRP) and procalcitonin (PCT), in the detection of early sepsis in the intensive care unit.. Subjects (N = 166) were divided into 4 groups: healthy, acute inflammatory non-infectious (AINI), localized infection, and systemic infection, according to clinical history and cultures. NDW, CRP, and PCT were compared among the different groups using multivariate analysis of variance (MANOVA). Diagnostic efficacy was assessed using receiver operating characteristic curves and areas under the curves (AUC).. The lowest mean(NDW) was found in the healthy group (n = 41), followed by the AINI (n = 20), localized infection (n = 55), and systemic infection (n = 50) groups. AUC(NDW) was 0.877 for infected (localized + systemic) vs non-infected (healthy + AINI) groups, and 0.965 for systemic infection vs non-infected groups. A cut-off of 21.9 resulted in 90% sensitivity, 92% specificity, 90% positive predictive value, and 92% negative predictive value (AUC(NDW) = 0.965, 95% confidence interval 0.935-0.995). According to MANOVA, only NDW was able to differentiate an acute inflammatory process from early infection in postoperative patients, but not healthy from AINI subjects.. NDW had the highest diagnostic accuracy and is available with the complete blood count with differential (CBC). It may be a promising parameter to aid in the diagnosis of acute infection in adults, provided the possibility of haematological disorders is first ruled out.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Analysis of Variance; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Leukocyte Count; Male; Middle Aged; Neutrophils; Protein Precursors; Reproducibility of Results; Retrospective Studies; ROC Curve; Sepsis; Serologic Tests; Temperature

Timely knowledge of the bacterial etiology and localization of infection are important for empirical antibiotic therapy. Thus, the goal of this study was to evaluate routinely used biomarkers together with novel laboratory parameters in the diagnosis of infection.. In this prospective study, 54 adult patients with bacterial infections admitted to the Department of Infectious Diseases were included. For comparison, 27 patients with viral infections were enrolled. In these patients, white blood cell (WBC) counts, differential blood counts, serum levels of procalcitonin (PCT), IL-1β, IL-6, IL-8, IL-10, IL-12, TNF-α, IFN-γ, soluble CD14 (sCD14), heparin-binding protein (HBP), cortisol (Cort), and monocyte surface expression of TLR2, TLR4, HLA-DR, and CD14 were analyzed. Also, these biomarkers were evaluated in 21 patients with acute community-acquired bacterial pneumonia (CABP), as well as in 21 patients with pyelonephritis and urosepsis.. The highest sensitivity and specificity (expressed as the area under the curve [AUC]) for bacterial infection were observed in serum concentration of PCT (0.952), neutrophil and lymphocyte counts (0.852 and 0.841, respectively), and serum levels of HBP (0.837), IL-6 (0.830), and Cort (0.817). In addition, the serum levels of IFN-γ and Cort were significantly higher and IL-8 levels were lower in CABP when compared to pyelonephritis or urosepsis.. From the novel potential biomarkers, only PCT demonstrated superiority over the routine parameters in the differentiation of bacterial from viral infections. However, some of the novel parameters should be further evaluated in larger and better characterized cohorts of patients in order to find their clinical applications.

Topics: Adult; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Czech Republic; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Pyelonephritis; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Urinary Tract; Virus Diseases

Recognizing infection is crucial in immunocompromised patients with organ dysfunction. Our objective was to assess the diagnostic accuracy of procalcitonin (PCT) in critically ill immunocompromised patients.. This prospective, observational study included patients with suspected sepsis. Patients were classified into one of three diagnostic groups: no infection, bacterial sepsis, and nonbacterial sepsis.. We included 119 patients with a median age of 54 years (interquartile range [IQR], 42-68 years). The general severity (SAPSII) and organ dysfunction (LOD) scores on day 1 were 45 (35-62.7) and 4 (2-6), respectively, and overall hospital mortality was 32.8%. Causes of immunodepression were hematological disorders (64 patients, 53.8%), HIV infection (31 patients, 26%), and solid cancers (26 patients, 21.8%). Bacterial sepsis was diagnosed in 58 patients and nonbacterial infections in nine patients (7.6%); 52 patients (43.7%) had no infection. PCT concentrations on the first ICU day were higher in the group with bacterial sepsis (4.42 [1.60-22.14] vs. 0.26 [0.09-1.26] ng/ml in patients without bacterial infection, P < 0.0001). PCT concentrations on day 1 that were > 0.5 ng/ml had 100% sensitivity but only 63% specificity for diagnosing bacterial sepsis. The area under the receiver operating characteristic (ROC) curve was 0.851 (0.78-0.92). In multivariate analyses, PCT concentrations > 0.5 ng/ml on day 1 independently predicted bacterial sepsis (odds ratio, 8.6; 95% confidence interval, 2.53-29.3; P = 0.0006). PCT concentrations were not significantly correlated with hospital mortality.. Despite limited specificity in critically ill immunocompromised patients, PCT concentrations may help to rule out bacterial infection.

Topics: Adult; Aged; Bacterial Infections; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Immunocompromised Host; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index

This cross sectional observational study was done in the division of neonatology, department of pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) in the year 2007. The study population was 50 newborns in total who needed evaluation of sepsis on clinical suspicion. The main objective of this study was to assess serum procalcitonin (PCT) as a better diagnostic marker than C-Reactive Protein (CRP) in neonatal sepsis. The total study populations were classified into 4 groups like highly probable, probable, and possible and no sepsis group according to the clinical and blood parameters. PCT and CRP were assessed and compared by statistical analysis. For the estimation of PCT and CRP, venous blood was drawn and centrifuged and stored at - 20 degrees C in the refrigerator. Later on PCT was measured by rapid semi quantitative immunochromatographic test. Level of CRP was determined by semi quantitative method (latex). All data were analyzed by SPSS version 10 windows. For statistical analysis appropriate tests were done. In all observations sepsis was found to be more common in male newborns and in those who were delivered by caesarean section. In low birth weight and preterm newborns sepsis was more prevalent. Premature rupture of membrane (PROM) was found to be the commonest maternal clinical condition as a risk factor of sepsis. There was positive correlation between serum PCT and CRP and values of serum PCT as well as CRP differed significantly in the different categories of sepsis indicating relation to the severity of sepsis. PCT is a useful, sensitive and independent biomarker of neonatal sepsis. CRP measurement along with PCT measurement may increase the specificity. Though PCT measurement is comparatively expensive but an easy bed side promt convenient procedure for sick neonates in addition to CRP for rapid evaluation of neonatal sepsis rather than waiting for the report of blood culture.

Topics: Biomarkers; Birth Weight; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Protein Precursors; Risk Factors; Sensitivity and Specificity; Sepsis

To determine the diagnostic values of plasma C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) using an electrochemiluminescence immunoassay (ECLIA) method (Roche Diagnostics GmbH, Mannheim, Germany) to identify severe sepsis in an emergency room (ER) setting.. This was a single-centre prospective follow-up study of 539 consecutive adult patients admitted to the ER with suspected infection. Blood samples were taken concurrently with blood cultures at admission. Patients were divided into 5 groups on the basis of systemic inflammatory response syndrome (SIRS) criteria, documentation of bacterial infection, and organ dysfunction. Fifty-nine patients with no SIRS or bacterial infection, 68 patients with bacterial infection but no SIRS, 54 patients with SIRS but no bacterial infection, 309 patients with sepsis (SIRS and bacterial infection), and 49 patients with severe sepsis (sepsis and organ failure) were evaluated.. In a logistic regression model, the odds ratio (OR) for PCT was 1.58 (95% confidence interval (CI) 1.37-1.82, p < 0.0001), for IL-6 was 1.54 (95% CI 1.32-1.80, p < 0.0001), and for CRP was 1.33 (95% CI 1.01-1.75, p = 0.045). The area under the curve (AUC) was 0.77 (95% CI 0.71-0.84) for PCT, 0.72 (95% CI 0.64-0.80) for IL-6, and 0.60 (95% CI 0.51-0.69) for CRP. PCT emerged as the best marker for severe sepsis, but the difference in AUC was not significant between PCT and IL-6. In multivariate logistic regression analysis, after adjusting for confounders, PCT and IL-6 remained significant independent predictors of severe sepsis.. PCT and IL-6 proved superior to CRP in detecting patients with severe sepsis. The findings thus support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis. The automatic ECLIA method allows even night-shift measurements.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Emergency Service, Hospital; Female; Follow-Up Studies; Germany; Humans; Interleukin-6; Male; Middle Aged; Plasma; Prospective Studies; Protein Precursors; Sepsis; Young Adult

Sepsis is a costly diagnosis in hospitalized patients. Failure to diagnose sepsis in a timely manner creates a potential financial and safety hazard. The use of transthyretin, C-reactive protein and procalcitonin measurement as early markers of systemic inflammatory response syndrome (SIRS) and sepsis in association with admission of emergency department patients to the intensive care unit (ICU) has been studied. In these studies the SIRS criteria as well as the use of an elevated neutrophil count with granulocyte precursors (left shift) have proved to be problematic. Despite the validity of procalcitonin measurement (PCT, Brahms) in the early diagnosis of SIRS the cost and time for testing are limiting considerations. Immature granulocyte (IG) measurement has been proposed as a more readily available indicator of the presence of granulocyte precursors (left shift).. This study calibrates and validates the measurement of granulocyte maturation [Immature granulocytes (IG)] to the identification of sepsis, a study carried out on a Sysmex Analyzer, model XE 2100 (Kobe, Japan). The Sysmex IG parameter is a crucial measure of immature granulocyte counts and includes metamyelocytes and myelocytes, but not band neutrophils.. We found agreement with previous work that designated an IG measurement cut-off of 3.2 as optimal. The analysis was then carried a step further with a multivariable discriminator.

Topics: Area Under Curve; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Flow Cytometry; Granulocytes; Humans; Intensive Care Units; Male; Prealbumin; Protein Precursors; ROC Curve; Sepsis; Systemic Inflammatory Response Syndrome

Multiorgan dysfunction syndrome represents a continuum of cumulative organ dysfunction from very mildly altered function to total and, rarely, irreversible organ failure and is the major cause of death in the intensive care unit (ICU). The terms multiple organ failure syndrome (MOFS), multiple organ system failure (MOSF), and multiple organ failure (MOF) have since been used to describe this syndrome. Infections were initially thought to be the main cause of multiorgan dysfunction; however, other insults, such as severe trauma, burn injuries, and noninfectious inflammatory diseases may precipitate a similar condition. In 2001, several North American and European intensive care societies revisited the definitions for sepsis and related conditions. Additional criteria indicative of physiological derangements were added to the traditional systemic inflammatory response syndrome (SIRS) criteria, including clinical abnormalities (altered mental status, ileus) and biochemical evidence of a sepsis response [procalcitonin (PCT), C-reactive protein (CRP), creatinine, or cytokine levels]. The use of organ failure scores to describe organ dysfunction in ICU patients was encouraged. The pulmonary, cardiovascular, renal, hepatic, hematologic, and central nervous systems are the organs most commonly considered when describing organ dysfunction/failure in the ICU. Scoring systems for organ dysfunction/failure were designed primarily as descriptive tools, aimed at establishing standardized definitions to stratify and compare patients in the ICU in terms of morbidity rather than mortality. Sequential evaluation of organ dysfunction during the ICU stay may track disease progression and may be useful prognostically. We discuss the various scoring systems developed over the past 2 decades and present a rational approach to their role in assessing and following critically ill patients.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Critical Illness; Cytokines; Disease Progression; Humans; Intensive Care Units; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

The clinical signs of early-onset neonatal sepsis (EONS) are nonspecific and indistinguishable from those of noninfectious disorders. The early diagnosis of EONS is difficult, but is essential to improve outcomes. The aim of this study was to determine the diagnostic value of procalcitonin (PCT) at birth and at 24h of age in the prompt diagnosis of EONS.. The patient group consisted of neonates with a Töllner score of ≥ 10 or a Töllner score of 5-10 but with the presence of prolonged rupture of the membranes (> 18 h) or chorioamnionitis or maternal fever (n=171). The control group (n=89) comprised neonates admitted to the neonatal intensive care unit for different disease entities. Procalcitonin levels at birth (first) and at 24h of age (second) were measured for each neonate in both of the study groups.. There was no difference between the two groups in terms of gender, birth weight, or gestational age. The mean (min-max) first PCT level was 0.48 (0.07-3.48)ng/ml in the controls and 0.51 (0.09-28.6)ng/ml in patients. The mean (min-max) second PCT level was 1.72 (0.21-18.23)ng/ml in the controls and 16.17 (0.17-100)ng/ml in patients. There was no statistically significant difference in PCT levels between the patient and control groups at birth. However, at 24h of age, PCT levels were significantly higher in the patient group than in the control group (p<0.001). Serum PCT levels in controls at 24h of age were slightly increased compared to levels at birth, but as a normal reaction. PCT thresholds for the diagnosis of sepsis were 0.59 ng/ml at birth (sensitivity 48.7%, specificity 68.6%) and 5.38 ng/ml at 24h of life (sensitivity 83.3%, specificity 88.6%).. In EONS, PCT measurements at birth may initially be normal; a serial PCT measurement at 24h of age may be more helpful for an early diagnosis. During the first 24h of life PCT is a more sensitive marker of infection than C-reactive protein. Further studies are needed to confirm our findings.

Topics: Age of Onset; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Turkey

Serum macrophage migration inhibitory factor (MIF) and procalcitonin (PCT) concentrations as well as leucocyte numbers were evaluated in a retrospective study with 23 patients with severe burn injuries. The MIF and PCT concentrations as well as the number of leucocytes (LEU) were monitored over a period of 5 days. The total body surface area (TBSA) and sepsis-related organ failure assessment (SOFA) scores were also evaluated. The MIF, PCT concentrations and leucocyte counts were profoundly increased in all patients with severe burn wounds. At the time of admission into the intensive care unit, no significant differences were observed for the MIF and PCT levels between patients with a TBSA<60% (Group 1) and patients with a TBSA>60% (Group 2). After 48 h, however, the MIF and PCT levels reached very high levels in a subgroup of the patients, whereas these levels became normal again in other subgroups. The group of patients with a TBSA>60% was, therefore, subdivided in three groups (subgroups 2a-c). The MIF and PCT data pairs in these subgroups appeared to correlate in an inhomogeneous manner. These levels in the subgroup 2a (i.e., lethal within 5 days) were strongly elevated over those observed in Group 1 (TBSA<60%) and highly increased concentrations of both MIF and PCT correlated with lethal outcome. The combined determination of MIF and PCT might, therefore, be useful to discriminate between post-burn inflammation and systemic inflammatory response syndrome (SIRS) or sepsis with lethal outcome.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Inflammation; Leukocyte Count; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Prognosis; Protein Precursors; Retrospective Studies; Sepsis; Systemic Inflammatory Response Syndrome; Trauma Severity Indices

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Medical Services; Female; France; Hospitalization; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Pyelonephritis; Sepsis

The assay of infection markers can improve diagnostic sensitivity in neonatal sepsis. We determined the levels of neutrophilic CD64 (nCD64), procalcitonin (PCT) and interleukin 10 (IL-10) in infants with neonatal sepsis. Forty-nine newborn infants who met the criteria of sepsis were subjected to a routine sepsis evaluation as well as measurement of PCT and IL-10 levels and nCD64 expression. Of these 49 'infected' infants, 16 had a positive blood culture (culture-positive sepsis) and 33 infants were diagnosed to have clinical sepsis with negative blood cultures (culture-negative sepsis). Another 49 healthy newborn infants were included as a control group. The sensitivity, specificity, positive predictive value and negative predictive value of PCT, IL-10 and nCD64 for the diagnosis of sepsis were determined. IL-10 had the highest sensitivity of 92% and specificity of 84% using a cut-off of > or =17.3 pg/ml. For PCT, the highest sensitivity of 65% and specificity of 60% were found at a cut-off value of > or =36.4 pg/ml. nCD64 had a maximal sensitivity of 92% and specificity of 71% at a cut-off value of 2.6%. Combinations of different markers may improve the sensitivity and specificity of biomarker tests. We found that the best combination was IL-10 and nCD64, which together provided sensitivity of 95% and specificity of 83%, and a negative predictive value of 86%.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Interleukin-10; Neutrophils; Predictive Value of Tests; Protein Precursors; Receptors, IgG; Sensitivity and Specificity; Sepsis

The objective of the paper is to examine the behavior of C-reactive protein (CRP) and procalcitonin (PCT) in the first 12 h of admission and verify which performs better to differentiate children with septic conditions.. Septic children aged between 28 days and 14 years were divided into sepsis (SG; n = 46) and septic shock (SSG; n = 41) groups. CRP and PCT were measured at admission (T0) and 12 h later (T12 h). PCT results were classed as: 0.5 ng/ml = sepsis unlikely; >or=0.5 to <2 = sepsis possible; >or=2 to <10 = systemic inflammation; >or=10 = septic shock.. At T0, there was a higher frequency of SSG with PCT >10 compared to SG [SSG: 30 (73.1%) > SG: 14 (30.4%); P < 0.05]. Similar results were observed at T12 h. Pediatric Risk of Mortality I score was significantly higher for SSG patients with higher PCT than SG patients. CRP levels were not statistically different for groups and time points.. PCT was better than CRP for diagnosing sepsis and septic shock, mainly at admission, and is related to disease severity.

Topics: Adolescent; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

Neopterin (NT) is a compound of low molecule-based pteridine. It is secreted by macrophages as a response to the stimulation of cytokines such as interferon-gamma, interferon-1beta, tumor necrosis factor alpha or bacteria compounds such as lipopolysaccharides. Procalcitonin (PCT) levels may increase in the course of bacterial, parasitic, and fungal infections. Therefore, it can be used for the differential diagnosis of the infection, especially in cases of serious inflammation. In this study, the role of NT, and PCT in sepsis as a prognostic factor, and the relationship between the two parameters are examined.. From November 1, 2005 through December 31, 2005, fifty patients with sepsis admitted to the Department of the Infectious Diseases and Clinical Microbiology and/or Department of Anaesthesiology and Reanimation were enrolled in the study. Patients were divided in two subgroups according to their survival: group I (n=23) nonsurviving patients and group II (n=27) surviving patients.. Serum NT levels have been found to be increased in group I (median: 15 ng/mL, range: 2-69) when compared to group II (median: 5 ng/mL, range: 2-130). The difference was statistically significant (P=0.03). Other laboratory parameters and PCT levels (group I median: 0.13; group II median: 0.08; P<0.05) were not different between the two groups.. NT was found to be a prognostic factor in patients with sepsis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Humans; Male; Middle Aged; Neopterin; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Survival Analysis; Young Adult

Procalcitonin is useful for the diagnosis of sepsis, but its prognostic value regarding mortality is unclear. Our objective was to determine the prognostic value of procalcitonin determined at the onset of sepsis, and to compare it with other markers of inflammatory response, malnutrition and organ dysfunction data.. We studied 253 hospitalized patients (146 men, 107 women) with a median age of 65 years. Sepsis was defined as infection, and at least two SIRS criteria. We assessed co-morbidities, nutritional status, bacteremia, procalcitonin and other inflammatory markers (PCR, TNF-alpha, IL6, TREM-1, IL-10, IL-1ra, CD14 and LBP), and organ function using the SOFA score. Mortality was assessed at 28 days after onset of sepsis.. At day 28, 49 (19%) patients had died. Inflammatory markers showed only moderate predictive value for mortality, with IL-10 and IL-6 being the best predictors. Mortality was mainly related to organ dysfunction indicators (SOFA and Glasgow scores), serum lactate, ferritin and LDH levels, and to nutritional data such as subjective assessment, handgrip strength and serum transferrin levels. The most frequent location of sepsis was the lung, with 140 cases (55%), which showed more comorbidity, worse nutritional status, less frequent bacteremia and lower inflammatory response. When the analysis was limited to patients with non-pulmonary sepsis, organ dysfunction, nutritional status and inflammatory markers showed the best prognostic value. Of the inflammatory markers, procalcitonin showed only moderate predictive value; however it showed the highest correlation with bacteremia and the ability to discriminate non-complicated sepsis from severe forms.. Procalcitonin only showed moderate predictive value for sepsis-related mortality, being surpassed by organ dysfunction, nutritional status, IL-10 and IL-6. However, it proved useful to discriminate between non-complicated and severe forms of sepsis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Humans; Inflammation Mediators; Male; Middle Aged; Nutrition Assessment; Organ Specificity; Prognosis; Protein Precursors; Sepsis; Spain; Young Adult

Rapid and early diagnosis of systemic infections is very important for acting on time with an adequate therapy. The aim of this study is to determine the diagnostic importance of procalcitonin (PCT) and C-reactive protein (CRP) of bacterial infections in different stages of sepsis.PCT and CRP have been determined in 45 newborns, 1-21 days of age, with different stages of sepsis, in the centre for prematurely born neonates. These parameters have also been determined for control group, in which there were 10 healthy newborns. Procalcitonin values were significantly increased in neonates with septic shock (92,5 ng/mL; 6,06-200 ng/mL) compared to the systemic inflammatory response syndrome- SIRS (41 ng/mL; 0,28-200 ng/mL), neonatal sepsis (10,26 ng/mL; 1,08-111,3 ng/mL), neonatal sepsis and purulent meningitis (9,80 ng/mL; 4,3-18,9 ng/mL). The control group values were lower than 0,5 ng/mL. CRP is increased without statistical differences in all stages of sepsis in newborns with septic shock (93,2 mg/L; 6,0-196 mg/L) in cases with SIRS (45,64 mg/L; 6,0-147 mg/L), neonatal sepsis (70,02 mg/L; 6-177 mg/L), neonatal sepsis and purulent meningitis (61,98 mg/L; 24-192 mg/L). The average values for the control group were 4,7 mg/L. Procalcitonin is increased in all stages of sepsis with higher values in the septic shock. The increase of PCT levels is related to the severity, course of infection and prognosis of disease.

Topics: Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Early Diagnosis; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Predictive Value of Tests; Protein Precursors; Sepsis; Severity of Illness Index

To evaluate the value of procalcitonin (PCT) detection in the diagnosis of local infection and sepsis.. PCT, C-reactive protein (CRP), white blood cell count (WBC), neutrophil ratio (neu%) and lymphocyte ratio (lym%) were measured in patients with negative or positive blood culture test. The receiver operating characteristic (ROC) curves were constructed for PCT CRP, WBC, neu%, lym%, and the diagnostic model using SPSS software. Based on the binary logistic regression model, the predictors or probabilities were obtained and applied to establish the empirical and binormal model of the ROC curves to compare the area under the curve (AUC).. A highly significant difference in PCT concentrations was noted between the two groups (chi(2)=52.52, P<0.001), and the diagnostic criteria at <2 of the ROC curves resulted in the greatest Youden index with a sensitivity of 63.3% and specificity of 86.8%. The AUC of PCT, CRP, WBC, neu% and lym% were 0.700, 0.765, 0.636, 0.618 and 0.648, respectively; the combined predicted ROC AUC was 0.776. The maximum Youden index was acquired at the optimal cutoff point of 0.566 with a diagnosis sensitivity and specificity of 63.8% and 84.7%, respectively.. The PCT level is a valuable predictor for a rapid and reliable early diagnosis of sepsis. The diagnostic model based on the laboratory parameters, using the combined predictors of PCT, CRP and lym%, can be a useful means for predicting early-onset sepsis.

Topics: Adolescent; Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Humans; Infections; Male; Middle Aged; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Young Adult

Circulating nucleic acids were discovered more than 60 y ago. With the recent developments in the study of circulating nucleic acids, its application in the diagnostic field has increased. The objective of this study was to assess the usefulness of the quantification of cell-free plasma DNA (CF-DNA) concentration in the diagnosis of infections in febrile patients and as a prognostic marker in septic patients.. Concentrations of CF-DNA, procalcitonin (PCT) and C-reactive protein (CRP) were measured in 110 febrile patients who were clinically diagnosed with fever of unknown origin, localized infection, sepsis or septic shock.. Concentrations of CF-DNA increase according to the severity of the infection. The best cut-off point for predicting infection was 2800 GE (genome equivalents)/mL (sensitivity: 95.0%; specificity: 96.7%) and 14,000 GE/mL for sepsis prediction (sensitivity: 77.8%; specificity: 94.6%). Higher concentrations of CF-DNA were found in exitus septic patients than in survivors. The diagnostic efficiency of CF-DNA was similar to PCT and higher than CRP in infectious processes.. Normal concentrations of CF-DNA can exclude the presence of an infection in febrile patients, and very high concentrations (>10-fold over the normal reference range) stratify the severity of infections, showing a high prognostic value to predict mortality in the absence of other causes for elevated CF-DNA.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; DNA; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Protein Precursors; Seizures, Febrile; Sepsis; Shock, Septic; Young Adult

Topics: Adolescent; Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Male; Middle Aged; Mucositis; Neutropenia; Protein Precursors; ROC Curve; Sepsis; Young Adult

The role of eosinopenia as a marker of sepsis has recently been evaluated. The aim of our study was to test the value of eosinopenia as a diagnostic marker of sepsis in comparison to procalcitonin and C-reactive protein levels.. A prospective study of critically ill adult patients admitted to the medical intensive care unit at an urban hospital. Procalcitonin, C-reactive protein (CRP) levels and eosinophil counts were measured on admission. Patients were classified as non-infected or infected by the medical residents, fellows, and attendings.. A total of 68 patients were enrolled into the study. At a cut-off value of 70 mg/L, the CRP level yielded a sensitivity of 94%, a specificity of 84%, a positive predicted value (PPV) of 83% and a negative predicted value (NPV) of 94%. At a cutoff value of 1.5 μg/L, the sensitivity of the procalcitonin test was 84%, specificity of 92%, PPV 90%, and NPV of 87%. The eosinophil cell count (cutoff of 50 cells/mm(3)) produced a sensitivity of 81%, specificity of 65%, a PPV of 66%, and a NPV of 80%. The comparison of the eosinophil cell count (<50 cells/mm(3)) and procalcitonin levels among the non-infected and infected groups showed a significant statistical difference (Fisher exact test, P = .0239). There was no statistical difference observed when comparisons were made between CRP levels and eosinophil count (Fisher exact test, P = .12). There was also a lack of significant statistical difference when CRP levels were compared to procalcitonin levels (Fisher exact test, P = .49).. Eosinopenia is a very sensitive yet not specific serological marker of sepsis in the intensive care unit and can be utilized to guide physicians in the diagnosis of sepsis.

Topics: Aged; Agranulocytosis; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Eosinophils; Female; Hospitals, Urban; Humans; Intensive Care Units; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Bloodstream infection (BSI) is associated with a high mortality rate. Since the origin of infection is demonstrated in approximately 2/3rds of cases, early and established biomarkers are warranted. We evaluated the clinical performances of automated procalcitonin (PCT) and C-reactive protein (CRP) assays for the quantitative detection of BSI. Analytical performance of the VIDAS(R) BRAHMS PCT assay (bioMérieux, France) was assessed and also compared with the semi-quantitative PCT-Q test (BRAHMS Aktiengesellschaft, Germany).. We prospectively included consecutive patients divided into 3 groups at the Dong-A University Medical Center. Patients were categorized according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference (ACCP/SCCM), and also on the basis of catheter-associated bacteremia.. A total 77 patients were enrolled. All mean values of PCT and PCT-Q were consistent with the reference value. Measured PCT concentrations showed good linearity (r=0.983). The between-run, within-run, and total imprecisions were below 5%. The PCT levels in gram-negative bacteremia were significantly higher than those in gram-positive bacteremia. Furthermore, the PCT concentrations were significantly different among non-infection, bacteremia, sepsis, severe sepsis, and septic shock groups. Our study showed that PCT >0.3 ng/mL had 95.0% sensitivity and 97.3% specificity, whereas CRP >5.46 mg/dL had 85.0% sensitivity and 86.5% specificity for diagnosing sepsis.. We suggest that, compared with CRP, PCT is a better diagnostic and discriminative biomarker of sepsis categorized according to the ACCP/SCCM. Moreover, catheter-associated bacteremia could be discriminated from sepsis using PCT concentration.

Topics: Adult; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Despite recent advances in treatment of severe injured patients, e.g. due to damage control orthopaedics, multi organ dysfunction syndrome (MODS) and sepsis are major complications in daily practice. During one year 94 patients were prospectively collected.. ISS 16, age 18-60 y, primary admission to our level-1 trauma center, survival > 48 hours after trauma. The development of MODS and sepsis were observed and different groups were formed (+/-). Demographic data revealed no significant differences between the subgroups. Comparing groups +MODS and -MODS significant differences on admission day were observed, when PCT showed first on day 2 after trauma differences. Regarding the development of sepsis PCT was advantageous to IL-6 showing significant higher plasma levels in group +sepsis from the first day after trauma. Serum levels of IL-6 and PCT could be useful in early identification of high risk patients to develop posttraumatic MODS. For sepsis PCT is the better prognostic factor.

Topics: Adolescent; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

Sepsis and multiple organ failure remain the leading cause of mortality and morbidity in burns. The aim of our study was to analyse the predictive value of extravascular lung water index (EVLWI) in the development of severe septic complications and mortality. The records of 28 patients with total burned surface area >20% were analysed (EVLWI, procalcitonin (PCT), intrathoracic blood volume index (ITBVI), positive end-expiratory pressure (PEEP), Baltimore Sepsis Scale (BaSS)). Diagnosis of infection (day 0) was based on consensus conference of the American Burn Association. EVLWI correlated with PCT (r=0.597), and PEEP (r=0.501) on day 0 and with BaSS (r=0.524) and MODS (r=0.513) from day 1. EVLWI was elevated (p<0.05) from one day before diagnosis of infection, PCT was higher (p<0.05) from day 0 only. ROC analysis for EVLWI on day -1 and for PCT on day 0 showed similar areas under curve (0.760; 0.766). EVLWI >9 ml kg(-1) on day -1 predicted sepsis (89% sensitivity, 72% specificity). After antibiotic treatment EVLWI remained high in non-survivors, decreased in survivors, whereas PCT decreased in both groups. Our data suggest that EVLWI is an early warning sign of developing infection and its continuous elevation can predict poor prognosis in burns.

Topics: Adult; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Extravascular Lung Water; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis

Neuropeptides arginine-vasopressin (AVP), apelin (APL), and stromal-derived factor-1α (SDF-1α) are involved in the dysfunction of the corticotropic axis observed in septic ICU patients. Study aims were: (i) to portray a distinctive stress-related neuro-corticotropic systemic profile of early sepsis, (ii) to propose a combination data score, for aiding ICU physicians in diagnosing sepsis on admission.. This prospective one-center observational study was carried out in a medical intensive care unit (MICU), tertiary teaching hospital. Seventy-four out of 112 critically ill patients exhibiting systemic inflammatory response syndrome (SIRS) were divided into two groups: proven sepsis and non sepsis, based on post hoc analysis of microbiological criteria and final diagnosis, and compared to healthy volunteers (n = 14). A single blood sampling was performed on admission for measurements of AVP, copeptin, APL, SDF-1α, adrenocorticotropic hormone (ACTH), cortisol baseline and post-stimulation, and procalcitonin (PCT).. Blood baseline ACTH/cortisol ratio was lower and copeptin higher in septic vs. nonseptic patients. SDF-1α was further increased in septic patients vs. normal patients. Cortisol baseline, ACTH, PCT, APACHE II and sepsis scores, and shock on admission, were independent predictors of sepsis diagnosis upon admission. Using the three first aforementioned categorical bio-parameters, a probability score for predicting sepsis yielded an area under the Receiver Operating Curve (ROC) curves better than sepsis score or PCT alone (0.903 vs 0.727 and 0.726: P = 0.005 and P < 0.04, respectively).. The stress response of early admitted ICU patients is different in septic vs. non-septic conditions. A proposed combination of variable score analyses will tentatively help in refining bedside diagnostic tools to efficiently diagnose sepsis after further validation.

Topics: Adrenocorticotropic Hormone; Apelin; Arginine Vasopressin; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Chemokine CXCL12; Female; Glycopeptides; Humans; Hydrocortisone; Intensive Care Units; Intercellular Signaling Peptides and Proteins; Logistic Models; Male; Middle Aged; Patient Admission; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Sepsis; Statistics, Nonparametric; Stress, Physiological

Sepsis and the severe systemic response syndrome are very common illnesses that are responsible for a great amount of morbidity and death. These closely related conditions are characterized by a remarkable increase in the prohormone ProCT (procalcitonin). ProCT is both a marker of sepsis and a harmful mediator of the disease. In the present issue of Clinical Science, in a study in rats with endotoxin shock, Tavares and Miñano used an antibody to a segment of N-ProCT (aminoprocalcitonin) that is part of the ProCT molecule, and confirmed that immunoneutralization of ProCT saves the animals from this severe illness. Furthermore, they extensively studied the epiphenomena associated with this immunoneutralization.

Topics: Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Immunotherapy; Protein Precursors; Rats; Sepsis

Procalcitonin (PCT) was initially described as a calcitonin prohormone and later shown to be a useful marker for identifying bacterial infection and sepsis. We evaluated PCT's clinical efficacy in assessing bacterial infection severity, measuring PCT and systemic inflammatory response syndrome (SIRS) markers in 180 subjects with suspected infection. PCT titer was higher with increasing infection severity. PCT was thus useful in identifying those in critical condition.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Established biomarkers for the diagnosis of sepsis are procalcitonin, interleukin 6, and C-reactive protein. Although sepsis evokes changes of coagulation and fibrinolysis, it is unknown whether thromboelastometry can detect these alterations. We investigated whether thromboelastometry variables are suitable as biomarkers for severe sepsis in critically ill adults.. In the observational cohort study, blood samples were obtained from patients on the day of diagnosis of severe sepsis (n = 56) and from postoperative patients (n = 52), and clotting time, clot formation time, maximum clot firmness, alpha angle, and lysis index were measured with thromboelastometry. In addition, procalcitonin, interleukin 6, and C-reactive protein levels were determined. For comparison of biomarkers, receiver operating characteristic (ROC) curves were used, and the optimal cut-offs and odds ratios were calculated.. In comparison with postoperative controls, patients with sepsis showed an increase in lysis index (97% ± 0.3 versus 92 ± 0.5; P < 0.001; mean and SEM) and procalcitonin (2.5 ng/ml ± 0.5 versus 30.6 ± 8.7; P < 0.001). Clot-formation time, alpha angle, maximum clot firmness, as well as interleukin 6 and C-reactive protein concentrations were not different between groups; clotting time was slightly prolonged. ROC analysis demonstrated an area under the curve (AUC) of 0.901 (CI 0.838-0.964) for the lysis index, and 0.756 (CI 0.666-0.846) for procalcitonin. The calculated cut-off for the lysis index was > 96.5%, resulting in a sensitivity of 84.2%, and a specificity of 94.2%, with an odds ratio of 85.3 (CI 21.7-334.5).. The thromboelastometry lysis index proved to be a more reliable biomarker of severe sepsis in critically ill adults than were procalcitonin, interleukin 6, and C-reactive protein. The results also demonstrate that early involvement of the hemostatic system is a common event in severe sepsis.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Critical Illness; Female; Hemolysis; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Thrombelastography; Up-Regulation

This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care.. PCT was analyzed from blood samples of all patients at baseline, and 155 patients 72 hours later.. The median PCT serum concentration on day 0 was 5.0 ng/ml (interquartile range (IQR) 1.0 and 20.1 ng/ml) and 1.3 ng/ml (IQR 0.5 and 5.8 ng/ml) 72 hours later. Hospital mortality was 25.6% (62/242). Median PCT concentrations in patients with community-acquired infections were higher than with nosocomial infections (P = 0.001). Blood cultures were positive in 28.5% of patients (n = 69), and severe sepsis with positive blood cultures was associated with higher PCT levels than with negative cultures (P = < 0.001). Patients with septic shock had higher PCT concentrations than patients without (P = 0.02). PCT concentrations did not differ between hospital survivors and nonsurvivors (P = 0.64 and P = 0.99, respectively), but mortality was lower in patients whose PCT concentration decreased > 50% (by 72 hours) compared to those with a < 50% decrease (12.2% vs. 29.8%, P = 0.007).. PCT concentrations were higher in more severe forms of severe sepsis, but a substantial concentration decrease was more important for survival than absolute values.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Hospital Mortality; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

Guidelines recommend that two blood cultures be performed in patients with febrile urinary tract infection (UTI), to detect bacteremia and help diagnose urosepsis. The usefulness and cost-effectiveness of this practice have been criticized. This study aimed to evaluate clinical characteristics and the biomarker procalcitonin (PCT) as an aid in predicting bacteremia.. A prospective observational multicenter cohort study included consecutive adults with febrile UTI in 35 primary care units and 8 emergency departments of 7 regional hospitals. Clinical and microbiological data were collected and PCT and time to positivity (TTP) of blood culture were measured.. Of 581 evaluable patients, 136 (23%) had bacteremia. The median age was 66 years (interquartile range 46 to 78 years) and 219 (38%) were male. We evaluated three different models: a clinical model including seven bed-side characteristics, the clinical model plus PCT, and a PCT only model. The diagnostic abilities of these models as reflected by area under the curve of the receiver operating characteristic were 0.71 (95% confidence interval (CI): 0.66 to 0.76), 0.79 (95% CI: 0.75 to 0.83) and 0.73 (95% CI: 0.68 to 0.77) respectively. Calculating corresponding sensitivity and specificity for the presence of bacteremia after each step of adding a significant predictor in the model yielded that the PCT > 0.25 μg/l only model had the best diagnostic performance (sensitivity 0.95; 95% CI: 0.89 to 0.98, specificity 0.50; 95% CI: 0.46 to 0.55). Using PCT as a single decision tool, this would result in 40% fewer blood cultures being taken, while still identifying 94 to 99% of patients with bacteremia.The TTP of E. coli positive blood cultures was linearly correlated with the PCT log value; the higher the PCT the shorter the TTP (R(2) = 0.278, P = 0.007).. PCT accurately predicts the presence of bacteremia and bacterial load in patients with febrile UTI. This may be a helpful biomarker to limit use of blood culture resources.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Bacterial Load; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Fever; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Syndrome; Urinary Tract Infections

To investigate the correlation of hypoproteinemia with inflammation parameters C-reactive protein (CRP), procalcitonin (PCT) and WBC in children with sepsis.. Seventy-three children with sepsis (including 22 severe sepsis) and 40 non-sepsis children (control group) were enrolled. Serum albumin levels were measured on admission. Based on the level of serum albumin, 73 cases of sepsis were classified into three groups: mild hypoproteinemia, severe hypoproteinemia and normal albumin. Blood CRP, PCT and WBC levels were compared in the three groups. The correlation of CRP, PCT and WBC with serum albumin level was evaluated.. Serum albumin levels in the sepsis groups (severe or non-severe) were significantly lower than those in the control group (P<0.05), and the severe sepsis group showed more decreased albumin levels compared with the non-severe sepsis group (P<0.05). Blood CRP, PCT and WBC levels in the mild hypoproteinemia group were higher than those in the normal albumin group (P<0.05), and the severe hypoproteinemia group showed more increased blood CRP, PCT and WBC levels compared with the mild hypoproteinemia group (P<0.05). The incidence of multiple organ failure in the severe hypoproteinemia group was significantly higher than that in the normal albumin group (P<0.05). Serum albumin levels were negatively correlated with blood CRP, PCT and WBC levels.. Serum albumin levels decrease in children with sepsis, and the more serious the illness, the lower serum albumin levels, resulting in a worse prognosis. CRP, PCT and WBC are negatively correlated to serum albumin levels in children with sepsis.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Infant; Leukocyte Count; Male; Protein Precursors; Sepsis; Serum Albumin

Procalcitonin (PCT) is a novel biomarker for diagnosis and severity evaluation of bacterial sepsis. PCT measurement methods provided by Wako Pure Chemical Industries, Ltd. include a fully automated chemiluminescent immunoassay system SphereLight Wako and fully automated immunoanalyzer microTASWako i30 for a quantitative measurement, and immunochromatographic assay method, B R A H M S PCT-Q kit. This time, basic performance of SphereLight Wako and microTASWako i30 was evaluated as quantitative determination methods for PCT. The lower limit of detection for the both methods was 0.02 ng/ml. Correlation coefficients of 0.993 to 0.997 indicated good correlation between the two methods. The both methods allow quick and easy measurement of PCT, therefore they are helpful for diagnosis and severity evaluation of bacterial sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Immunoassay; Luminescent Measurements; Protein Precursors; Sepsis; Severity of Illness Index

The purpose of this study was to determine the role of serum amyloid A (SAA) in diagnosis of neonatal sepsis and evaluation of clinical response to antibiotic therapy. We also aimed to compare the efficiency of SAA with that of C-reactive protein (CRP) and procalcitonin (PCT) in diagnosis and follow-up of neonatal sepsis in preterm infants.. A total of 163 infants were enrolled in this prospective study. The infants were classified into four groups: group 1 (high probable sepsis), group 2 (probable sepsis), group 3 (possible sepsis) and group 4 (no sepsis, control group). Blood samples for whole blood count, CRP, PCT, SAA and culture were obtained before initiating antibiotic treatment. This procedure was repeated three times at 48 h, 7 and 10 days.. Initial CRP, PCT and SAA levels were found to be positive in 73.2, 75.6 and 77.2% of all infants, respectively. Sensitivities of CRP, PCT and SAA at 0 h were 72.3, 74.8 and 76.4%, respectively. Although it was not statistically significant, SAA was found to be more sensitive than CRP and PCT in diagnosis of neonatal sepsis. The area under the curve (AUC) for CRP, PCT and SAA at 0 h were 0.870, 0.870 and 0.875, respectively. Although the AUC for SAA at 0 h was higher than PCT and CRP, the difference was not statistically significant.. SAA is an accurate and reliable marker for diagnosis and follow-up of neonatal sepsis. It is especially useful at the onset of inflammation for rapid diagnosis of neonatal sepsis and can be safely and accurately used in combination with other sepsis markers such as CRP and PCT in diagnosis and follow-up of neonatal sepsis in preterm infants.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Premature; Male; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Serum Amyloid A Protein; Severity of Illness Index

On-demand relaparotomy has been associated with a slightly decreased mortality compared to planned relaparotomy in the surgical treatment of secondary peritonitis. On-demand relaparotomy must be performed without delay to detect progressing sepsis early, before the onset of multiorgan failure. The aim of the study was to evaluate procalcitonin (PCT) as a parameter for early detection of progressing sepsis after operative treatment of the infective source.. In 104 consecutive patients with secondary peritonitis, PCT serum levels were monitored on postoperative days 1 and 2 after initial operative elimination of the septic focus. The PCT ratio between postoperative days 1 and 2 was calculated and correlated to the success of the initial intervention. The latter was considered inadequate if relaparotomies were necessary to eliminate the intraabdominal infection.. Using classification and regression tree analysis, a cutoff could be calculated at 1.03 for the PCT ratio of postoperative day 1 to day 2. Lesser values indicated unsuccessful elimination of the septic source, whereas values above 1.03 represented successful operative treatment of the septic focus. Unsuccessful treatment of the septic process could be detected with a specificity of 63% and a sensitivity of 95%.. The PCT ratio appears to be a valuable aid in deciding if further relaparotomies are necessary after initial operative treatment of an intraabdominal septic focus.

Topics: Aged; APACHE; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Early Diagnosis; Female; Humans; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Protein Precursors; Sepsis; Treatment Outcome

Procalcitonin (PCT) is known to be a reliable biomarker of sepsis and infection. Elevation of serum or plasma PCT has also been observed after major surgery or trauma. The association of PCT with the severity or location of injury in multiple traumatized (polytrauma) patients has not been clearly established, to date. The aim of this study was therefore to evaluate the sensitivity of PCT as a biomarker for the diagnosis of abdominal trauma. In a prospective clinical study, PCT, interrleukin-6, and C-reactive protein were measured in blood (serum) samples obtained in the emergency room (D0) from 74 patients with multiple injuries and in serum samples obtained on the 2 days after trauma (D1, D2). PCT significantly increased during the first two posttraumatic days in patients with severe multiple injuries (n = 24, day 1: 3.37 ng/mL +/- 0.92 ng/mL; day 2: 3.27 ng/mL +/-0.97 ng/mL) as compared with patients with identical Injury Severity Score but without abdominal injury (day 1: 0.6 ng/mL +/- 0.18 ng/mL; 0.61 ng/mL +/- 0.21 ng/mL). Interrleukin-6 and C-reactive protein serum levels were not able to discriminate between patients with and without abdominal injury during the 2-day posttrauma observation period. In a specific evaluation of the abdominal injury pattern, a significant increase of serum PCT concentrations was observed on day 1 after trauma of the liver (4.04 ng/mL +/- 0.99 ng/mL) and the gut (4.63 ng/mL +/- 1.12 ng/mL) compared with other abdominal lesions (0.62 ng/mL +/- 0.2 ng/mL). Markedly elevated PCT concentrations were also evident after severe multiple injuries, including the liver/spleen in combination with thorax trauma (9.37 ng/mL +/- 2.71 ng/mL). Assessment of serum PCT seems to be significantly increased after abdominal trauma in severe multiple traumatized patients and may serve as a useful biomarker to support other diagnostic methods including ultrasound and CT scan. Although elevated levels of PCT during the first 2 days after trauma are more likely to be indicative of traumatic impact than of an ongoing status of sepsis, multiple events such as surgery, massive transfusion, and intensive care therapy might influence the PCT concentration.

Topics: Adolescent; Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Injury Severity Score; Male; Middle Aged; Multiple Trauma; Pilot Projects; Protein Precursors; Sepsis; Viscera

Elevated lactate and interleukin-6 (IL-6) levels were shown to correlate with mortality and multiple organ dysfunction in severely traumatized patients. The purpose of this study was to test whether an association exists between 24-hour lactate clearance, IL-6 and procalcitonin (PCT) levels, and the development of infectious complications in trauma patients.. A total of 1757 consecutive trauma patients with an Injury Severity Score (ISS) > 16 admitted over a 10-year period were retrospectively analyzed over a 21-day period. Exclusion criteria included death within 72 h of admission (24.5%), late admission > 12 h after injury (16%), and age < 16 years (0.5%). Data are stated as the median (range).. Altogether, 1032 trauma patients (76.2% male) with an average age of 38 years, a median ISS of 29 (16-75), and an Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score of 14 (0-40) were evaluated. The in-hospital mortality (>3 days) was 10%. Patients with insufficient 24-hour lactate clearance had a high rate of overall mortality and infections. Elevated early serum procalcitonin on days 1 to 5 after trauma was strongly associated with the subsequent development of sepsis (p < 0.01) but not with nonseptic infections. The kinetics of IL-6 were similar to those of PCT but did differentiate between infected and noninfected patients after day 5.. This study demonstrates that elevated early procalcitonin and IL-6 levels and inadequate 24-hour lactate clearance help identify trauma patients who develop septic and nonseptic infectious complications. Definition of specific cutoff values and early monitoring of these parameters may help direct early surgical and antibiotic therapy and reduce infectious mortality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Injury Severity Score; Interleukin-6; Lactic Acid; Length of Stay; Leukocyte Count; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis; Treatment Outcome; Wounds and Injuries; Young Adult

Serial procalcitonin is reported to be useful to titrate duration of antibiotic therapy in the non critically ill patient with pneumonia. The aim of this study was to examine the relationship between antibiotic therapy and serial serum procalcitonin concentrations in a cohort of critically ill septic patients and examine for any differences between culture positive (CP) and culture negative (CN) sepsis. Seventy-five critically ill patients with suspected sepsis were enrolled in this prospective observational study. Serial procalcitonin and C-reactive protein assays were measured on days one, three, five, seven, 10 and 14. The mean duration of antibiotic therapy was similar in the two groups (10.4 +/- 5.1 (CP) vs. 8.4 +/- 5.1 (CN) days, P = 0.09). Serum procalcitonin concentrations were significantly higher at baseline in the CP than the CN group (14.9 +/- 22.9 vs. 6.8 +/- 21.5 ng/ml, P = 0.04). During the study period, serum concentrations of procalcitonin and C-reactive protein declined in both groups. Serum procalcitonin consistently remained higher in the CP group (P < 0.05) and did not return to normal values. In the CN group, procalcitonin concentrations fell below 0.5 only on day 10. There was no significant difference in C-reactive protein profile between the two groups. Four patients in the CP group (11%) had relapse of sepsis. The mean procalcitonins in the relapsed subgroup were lower than those in the remission subgroup (P = 0.02). Therapy for proven or presumed infections was associated with declining serum procalcitonin and C-reactive protein in critically ill septic patients. The marked variability and overlap in plasma profile of these markers between CP and CN sepsis makes it difficult to define a nadir plasma concentration at which one can recommend discontinuation of antibiotic therapy.

Topics: Anti-Bacterial Agents; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Recurrence; Sensitivity and Specificity; Sepsis; Time Factors

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Immunocompromised Host; Kidney Diseases; Protein Precursors; Sepsis

Procalcitonin (PCT) and C-reactive protein (CRP) are established markers of infection in the general population. In contrast, several studies reported falsely increased PCT levels in patients receiving T-cell antibodies. We evaluated the validity of these markers in patients scheduled for hemopoietic stem cell transplantation receiving anti-thymocyte globulin (ATG) during conditioning. We also assessed renal and liver functions and their relationship to PCT and CRP changes.. Twenty-six patients without clinical signs of infection were prospectively studied. ATG was administered in up to three doses over the course of 5 days. PCT, CRP, white blood cell (WBC) count, urea, creatinine, glomerular filtration rate, bilirubin, alanin amino-transferase (ALT), and gamma-glutamyl transferase (GGT) were assessed daily during ATG administration. Pharyngeal, nose, and rectal swabs and urine samples were cultured twice weekly. Blood cultures were obtained if clinical symptoms of infection were present.. Baseline (BL) levels of both PCT and CRP before ATG administration were normal. WBC count decreased after ATG administration (P = 0.005). One day after ATG administration, both PCT and CRP levels increased significantly, returning to BL levels on day 4. Microbiological results were clinically unremarkable. There was no interrelationship between PCT levels and BL markers of renal or liver functions (P > 0.05 for all comparisons). Bilirubin and GGT were increased on days 2 to 5 and ALT was increased on day 3 (P < 0.05 versus BL). No difference in renal functions was observed. Three patients developed bacterial infection on days 7 to 11 with different dynamics of PCT and CRP. There was no association between the number of ATG doses and PCT levels or between the risk of developing infection and previous PCT levels.. ATG triggered a marked early surge in PCT and CRP followed by a steady decrease over the course of 3 days. The dynamics of both PCT and CRP were similar and were not associated with infection. PCT levels were independent of renal and liver functions and were not predictive of further infectious complications. A direct effect of ATG on T lymphocytes could be the underlying mechanism. Hepatotoxic effect could be a contributing factor. Neither PCT nor CRP is a useful marker that can identify infection in patients receiving ATG.

Topics: Adult; Antilymphocyte Serum; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kidney Function Tests; Liver Function Tests; Male; Middle Aged; Predictive Value of Tests; Preoperative Care; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

Management of the early stage of sepsis is a critical issue. As part of it, infection control including appropriate antibiotic therapy administration should be prompt. However, microbiological findings, if any, are generally obtained late during the course of the disease. The potential interest of procalcitonin (PCT) as a way to assess the clinical efficacy of the empirical antibiotic therapy was addressed in the present study.. An observational cohort study including 180 patients with documented sepsis was conducted in our 15-bed medical intensive care unit (ICU). Procalcitonin measurement was obtained daily over a 4-day period following the onset of sepsis (day 1 (D1) to D4). The PCT time course was analyzed according to the appropriateness of the first-line empirical antibiotic therapy as well as according to the patient outcome.. Appropriate first-line empirical antibiotic therapy (n = 135) was associated with a significantly greater decrease in PCT between D2 and D3 (DeltaPCT D2-D3) (-3.9 (35.9) vs. +5.0 (29.7), respectively; P < 0.01). In addition, DeltaPCT D2-D3 was found to be an independent predictor of first-line empirical antibiotic therapy appropriateness. In addition, a trend toward a greater rise in PCT between D1 and D2 was observed in patients with inappropriate antibiotics as compared with those with appropriate therapy (+5.2 (47.4) and +1.7 (35.0), respectively; P = 0.20). The D1 PCT level failed to predict outcome, but higher levels were measured in the nonsurvivors (n = 51) when compared with the survivors (n = 121) as early as D3 (40.8 (85.7) and 21.3 (41.0), respectively; P = 0.04). Moreover, PCT kinetics between D2 and D3 were also found to be significantly different, since a decrease >or= 30% was expected in the survivors (log-rank test, P = 0.04), and was found to be an independent predictor of survival (odds ratio = 2.94; 95% confidence interval 1.22 to 7.09; P = 0.02).. In our study in an ICU, appropriateness of the empirical antibiotic therapy and the overall survival were associated with a greater decline in PCT between D2 and D3. Further studies are needed to assess the utility of the daily monitoring of PCT in addition to clinical evaluation during the early management of sepsis.

Topics: Aged; Anti-Bacterial Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Female; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; Sepsis; Survival Analysis; Treatment Outcome

This purpose of this study was to determine if serum procalcitonin (PCT) concentration at the time of admission to the ICU is a predictor of all-cause short-term mortality.. This prospective cross-sectional study was conducted over a 16-month period with 86 consecutive critically ill patients. The semi-quantitative PCT-Q test was performed and APACHE II scores and C-reactive protein (CRP) concentrations were determined within 24 h of admission.. PCT-Q test value was a better predictor of all-cause short-term mortality than CRP value or APACHE II score. PCT > or = 10 ng/mL was highly and independently correlated with mortality. Use of PCT-Q > or = 10 ng/mL was superior to use of APACHE II > or = 25 or CRP > or = 10 mg/dL as a predictor of poor outcome.. A PCT-Q value > or = 10 ng/mL obtained at the time of admission to the ICU is a strong predictor of short-term mortality.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Demography; Female; Humans; Intensive Care Units; Male; Middle Aged; Patient Admission; Prognosis; Protein Precursors; ROC Curve; Sepsis; Survival Analysis; Time Factors; Treatment Outcome

The primary aim of this study was to investigate the diagnostic value of procalcitonin (PCT) and C-reactive protein (CRP) in septic complications after major trauma. A secondary aim was to determine whether there was a prognostic value of PCT for severity of injury, organ dysfunction, and sepsis.. Prospective study.. Medical/surgical intensive care unit (ICU).. Ninety-four patients with consecutive trauma >or=16 years who were admitted to the ICU for an expected stay of >24 hours.. None.. PCT and CRP were collected at admission and every day thereafter. The American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definition was used to identify sepsis criteria. The Sequential Organ Failure Assessment score was used to describe the severity of organ dysfunction. We retrospectively analyzed the occurrence of systemic inflammatory response syndrome and sepsis using the collected variables (criteria fulfilled at least during three continuous days).. Patients with trauma presented an early and significant increase in PCT at the moment of septic complications compared with concentrations measured 1 day before the diagnosis of sepsis: 0.85 vs. 3.32 ng/mL for PCT (p < 0.001) and 135 vs. 175 mg/L for CRP (p = not significant). The areas under the respective curve at admission in the diagnosis of sepsis were 0.787 (p < 0.001) and 0.489 for PCT and CRP, respectively.. PCT plasma reinduction marks possible septic complication during systemic inflammatory response syndrome after major trauma. In addition, high PCT concentration at admission after trauma in ICU patients indicates an increased risk of septic complications.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Injury Severity Score; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Wounds and Injuries; Young Adult

Procalcitonin (PCT) is accepted to be a relevant prognostic marker for the development of clinical complications in multiple trauma patients. Therefore, a prospective cohort study was conducted to investigate whether polymorphisms in the calcitonin (CALCA) gene are associated with PCT levels and posttraumatic complications.. During a 14day observation period, blood samples were drawn once daily for systemic PCT concentrations in multiple trauma patients (Injury Severity Score >16). For analysis of allele frequencies, genotype distribution and PCT concentrations polytraumatized patients were separated, according to the development of SIRS, sepsis, septic shock, ARDS, MODS and mortality. Furthermore, association between CALCA polymorphisms and PCT plasma concentrations was assessed.. One hundred thirty seven patients with a mean ISS of 29.2+/-12.1 were included. When trauma patients were grouped according to different posttraumatic complications no association with CALCA SNPs was observed. Additionally, no association was found between CALCA polymorphisms and systemic PCT levels.. CALCA polymorphisms are unlikely to influence clinical outcome in polytraumatized patients. Effects of microbial and inflammatory mediators, as well as other risk factors (gender, age, etc.) seem to have a more significant influence on the transcriptional regulation of CALCA and on PCT plasma concentrations than CALCA polymorphisms.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gene Frequency; Genotype; Haplotypes; Humans; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Protein Precursors; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Protein Precursors; Sepsis; Wounds and Injuries

For over a decade there has been intense interest given to the role of procalcitonin in the diagnosis and management of sepsis in critically ill patients. Early opinions strongly supported the diagnostic role but data accumulating from numerous subsequent studies are less supportive, even when used in very selective settings. Although there remains sufficient reason to support the use of procalcitonin in guiding antibiotic therapy or perhaps providing prognostic information, it may be time to focus our efforts on the early diagnosis of sepsis in the critically care setting on alternative, more promising methods.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Predictive Value of Tests; Protein Precursors; Sepsis

The aim of this study is evaluation of procalcitonin role in the diagnosis of infectious and non infectious inflammation. This cross-sectional study was conducted in one hundred patients in Baqiyatallah Hospital of Iran in 2008. Patients suspected to infection were recruited to study. They were divided to four groups as: systemic inflammatory response syndrome, sepsis, sepsis syndrome and septic shock. Procalcitonin quantitative was assayed by immunoluminometric kit manufactured in Germany. Procalcitonin level was divided to four groups in < 0.5 ng mL(-1) compatible for SIRS, 0.5-2 ng mL(-1) for sepsis and 2-10 ng mL(-1) for sepsis syndrome and > 10 ng mL(-1) for septic shock. Data was analyzed by SPSS 13 for window software; T student test, ANOVA and Chi-square were used. In this study 53(53%) of subjects were men with mean age of 56.16 +/- 19.5 years old. The diagnosis was SIRS in 36%, sepsis in 38%, sepsis syndrome in 14% and septic shock in 12% of cases. Procalcitonin level was less than 0.5 ng mL(-1) in 61% and more than 10 ng mL(-1) in 10% of patients. Procalcitonin level showed significant association with septic shock, positive blood culture and mental dysfunction. Ultimately this study showed that high level of procalcitonin can differentiate septic shock from SIRS and other stages of infection. Dysfunction of mental status and high level of procalcitonin can determine septic shock.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin; Calcitonin Gene-Related Peptide; Child; Cross-Sectional Studies; Diagnosis, Differential; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis syndromes associated with multiple pathogenic factors. Deficient activity of ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a strong rationale for plasma exchange treatment. However, the subset of TMA patients with normal ADAMTS13 activity remains a heterogeneous group of patients in which the appropriate treatment is not well understood. In addition to the common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, the differential diagnosis of TMA may include sepsis, autoimmune disorders, and disseminated intravascular coagulation. Optimal treatment of TMA depends on timely recognition of treatable pathogenic factors. We hypothesized that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA patients. To test this hypothesis, we retrospectively measured the rapid biomarkers of sepsis C-reactive protein (CRP) and procalcitonin (PCT), in a repository of pretreatment plasma samples from 61 TMA patients treated with plasma exchange. Levels were analyzed in 31 severely ADAMTS13-deficient and 30 ADAMTS13-normal patients. None of the 31 patients with severe deficiency of ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non-ADAMTS13-deficient patient samples were strongly positive for PCT. These patient samples also had a >10-fold higher median CRP level than patients with normal PCT. We conclude that rapid assays may help identify sepsis in a subset of TMA patients.

Topics: ADAM Proteins; ADAMTS13 Protein; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Hemolytic-Uremic Syndrome; Humans; Protein Precursors; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Sepsis

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Mucocutaneous Lymph Node Syndrome; Protein Precursors; Sepsis

Rapid identification of infection has a major impact on the clinical course, management, and outcome of critically ill intensive care unit (ICU) patients. We compared the results of PCR and procalcitonin with blood culture for ICU patients suspected of having septicemia. Ninety patients (60 patients meeting the criteria for sepsis and 30 patients not meeting the criteria for sepsis) were evaluated. Compared with blood culture as the gold standard, the sensitivity, specificity, and positive and negative predictive values for PCR were 100%, 43.33%, 46.87%, and 100%, respectively, and for procalcitonin were 100%, 61.66%, 56.6%, and 100%, respectively. The average times required to produce a final result were as follows: PCR, 10 h; blood culture, 33 h; procalcitonin, 45 min. Both PCR and procalcitonin may be useful as rapid tests for detecting septicemia but compared with blood cultures lacked specificity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteria; Calcitonin; Calcitonin Gene-Related Peptide; DNA, Bacterial; Female; Humans; Intensive Care Units; Male; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

The distinctions and interrelationship were established between acute cholangitis and biliary sepsis. Patients with hyperbilirubinemia were divided into four groups according to the developed criteria of inclusion and of using a new strategy of treatment for each group. It determined the result of treatment, i.e. resulted in lower lethality, shorter stay at hospital, less cost of treatment. One of the main criteria for the inclusion into a certain group was considered to be the index of blood plasma procalcitonin.

Topics: Acute Disease; Bile Ducts; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cholangitis; Decompression, Surgical; Follow-Up Studies; Glycoproteins; Humans; Protein Precursors; Retrospective Studies; Sepsis

Every day, critical care physicians around the world face the same challenge of the optimal timing of antimicrobial administration: when to start and when to stop antibiotics. Duration of antibiotic therapy for sepsis is mostly based on expert opinion, but its reduction is arguably the most promising approach to decrease emergence and selection of antibiotic resistance. The study by Hochreiter and colleagues presents another piece of evidence suggesting that procalcitonin may indeed be a valuable diagnostic parameter to guide antibiotic treatment duration, despite the ongoing controversy about the diagnostic accuracy of pro-calcitonin.

Topics: Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Decision Making; Drug Administration Schedule; Evidence-Based Medicine; Humans; Protein Precursors; Sepsis; Time Factors

The Surviving Sepsis Campaign has recommended that antibiotic therapy should be started within the first hour of recognizing severe sepsis. Procalcitonin has recently been proposed as a biomarker of bacterial infection, although the quantitative procalcitonin assay is often time consuming, and it is not always available in many emergency departments (EDs). Our aim is to evaluate usefulness of the semiquantitative procalcitonin fast kit as a guideline for starting antibiotic administration for patients with severe sepsis or septic shock that requires prompt antibiotic therapy in the ED.. We include those patients who were admitted to the ED and who were suspected of having infection. The procalcitonin concentration was determined by semiquantitative PCT-Q strips, and the points of the severity scoring system were calculated. The receiver operating characteristic curve was used to assess the diagnostic value of the PCT-Q strips to predict severe sepsis or septic shock.. Of the 80 recruited patients, 33 patients were categorized as having severe sepsis or septic shock according to the definition. At a procalcitonin cutoff level of 2 ng/mL or greater, the sensitivity of the PCT-Q for detecting severe sepsis or septic shock was 93.94% and the specificity was 87.23. The receiver operating characteristic curve for PCT-Q to predict severe sepsis or septic shock had an area under the curve of 0.916.. PCT-Q is probably a fast, useful method for detecting severe sepsis in the ED, and it can be used as a guideline for antibiotic treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Emergency Service, Hospital; Female; Glycoproteins; Health Status Indicators; Humans; Immunoassay; Infant; Male; Middle Aged; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

Hematopoietic stem-cell transplant is a curative therapy for several malignant and nonmalignant disorders. The purpose of this study was to investigate the association of serum levels of high-sensitivity C-reactive protein and procalcitonin with complications such as acute graft-versus-host disease, veno-occlusive disease, and infection after hematopoietic stem-cell transplant.. Serum high-sensitivity C-reactive protein and procalcitonin levels were sequentially measured with an enzyme-linked immunosorbent assay and a semiquantitative immunochromatographic assay in 35 patients who had undergone hematopoietic stem-cell transplant.. The high-sensitivity C-reactive protein serum level was increased in patients with acute graft-versus-host disease and in those with sepsis. Increased procalcitonin levels were associated only with bacterial infection. Only procalcitonin levels differentiated patients with infection from those with another transplant-related complication. Veno-occlusive disease did not alter C-reactive protein or procalcitonin levels.. Our results support theories that serum levels of high-sensitivity C-reactive protein and procalcitonin are biomarkers for transplantrelated complications such as graft-versus-host disease or infection and that the procalcitonin level can differentiate patients with infection from those with graft-versus-host disease.

Topics: Adolescent; Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Diagnosis, Differential; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Young Adult

The early detection of circulatory failure in patients with sepsis is important for successful treatment. Heparin-binding protein (HBP), released from activated neutrophils, is a potent inducer of vascular leakage. In this study, we investigated whether plasma levels of HBP could be used as an early diagnostic marker for severe sepsis with hypotension.. A prospective study of 233 febrile adult patients with a suspected infection was conducted. Patients were classified into 5 groups on the basis of systemic inflammatory response syndrome criteria, organ failure, and the final diagnosis. Blood samples obtained at enrollment were analyzed for the concentrations of HBP, procalcitonin, interleukin-6, lactate, C-reactive protein, and the number of white blood cells.. Twenty-six patients were diagnosed with severe sepsis and septic shock, 44 patients had severe sepsis without septic shock, 100 patients had sepsis, 43 patients had an infection without sepsis, and 20 patients had an inflammatory response caused by a noninfectious disease. A plasma HBP level > or = 15 ng/mL was a better indicator of severe sepsis (with or without septic shock) than any other laboratory parameter investigated (sensitivity, 87.1%; specificity, 95.1%; positive predictive value, 88.4%; negative predictive value, 94.5%). Thirty-two of the 70 patients with severe sepsis were sampled for up to 12 h before signs of circulatory failure appeared, and in 29 of these patients, HBP plasma concentrations were already elevated.. In febrile patients, high plasma levels of HBP help to identify patients with an imminent risk of developing sepsis with circulatory failure.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimicrobial Cationic Peptides; Biomarkers; Blood Proteins; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Female; Humans; Interleukin-6; Lactates; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Shock; Young Adult

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Creatinine; Enzyme-Linked Immunosorbent Assay; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Thyroid Neoplasms

Systemic inflammatory response syndrome (SIRS) is a frequent condition after cardiopulmonary bypass (CPB) and makes conventional biological tests fail to detect postoperative sepsis. Biphasic waveform (BPW) analysis is a new biological test derived from activated partial thromboplastin time that has recently been proposed for sepsis diagnosis. The aim of this study was to investigate the accuracy of BPW to detect sepsis after cardiac surgery under CPB.. We conducted a prospective study in American Society of Anesthesiologists' (ASA) physical status III and IV patients referred for cardiac surgery under CPB. Procalcitonin (PCT) and BPW were recorded before surgery and every day during the first week following surgery. Patients were then divided into three groups: patients presenting no SIRS, patients presenting with non-septic SIRS and patients presenting with sepsis.. Thirty two patients were included. SIRS occurred in 16 patients (50%) including 5 sepsis (16%) and 11 (34%) non-septic SIRS. PCT and BPW were significantly increased in SIRS patients compared to no SIRS patients (0.9 [0.5-2.2] vs. 8.1 [2.0-21.3] ng/l for PCT and 0.10 [0.09-0.14] vs. 0.29 [0.16-0.56] %T/s for BPW; P < 0.05 for both). We observed no difference in peak PCT value between the sepsis group and the non-septic SIRS group (8.4 [7.5-32.2] vs. 7.8 [1.9-17.5] ng/l; P = 0.67). On the other hand, we found that BPW was significantly higher in the sepsis group compared to the non-septic SIRS group (0.57 [0.54-0.78] vs. 0.19 [0.14-0.29] %T/s; P < 0.01). We found that a BPW threshold value of 0.465%T/s was able to discriminate between sepsis and non-septic SIRS groups with a sensitivity of 100% and a specificity of 93% (area under the curve: 0.948 +/- 0.039; P < 0.01). Applying the previously published threshold of 0.25%T/s, we found a sensitivity of 100% and a specificity of 72% to discriminate between these two groups. Neither C-reactive protein (CRP) nor PCT had significant predictive value (area under the curve for CRP was 0.659 +/- 0.142; P = 0.26 and area under the curve for PCT was 0.704 +/- 0.133; P = 0.15).. BPW has potential clinical applications for sepsis diagnosis in the postoperative period following cardiac surgery under CPB.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Elective Surgical Procedures; Female; Humans; Leukocyte Count; Male; Middle Aged; Partial Thromboplastin Time; Postoperative Complications; Prospective Studies; Protein Precursors; Sepsis; Stroke Volume; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) has been proposed as an interesting marker in the diagnosis, prognosis, and response to treatment of patient with neonatal sepsis. Fifty-nine neonates (34 males and 25 females) with a mean gestational age of approximately 31 weeks and a mean weight of about 1750 g admitted in the Neonatal Intensive Care Unit of Cagliari (Italy) were evaluated in controls and in infected neonates, before and after 48 h of life. From our experience it emerges that PCT is a marker of early and late neonatal sepsis which is reliable in preterm neonates. A cut-off of 0.5 ng/ml starting from the third day of life appears to be capable of ensuring good test sensitivity and specificity.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Protein Precursors; Reference Values; Sensitivity and Specificity; Sepsis

Procalcitonin (PCT) is a relatively new marker for bacterial infections, and its diagnostic utility has been variable across the studies. We investigated the diagnostic utility of PCT for the patients with blood culture-positive sepsis, and compared it with that of C-reactive protein (CRP).. In 1,270 consecutive blood samples, PCT and CRP were simultaneously measured and results were compared according to the five categories of PCT concentrations (<0.05 ng/mL; 0.05-0.49 ng/mL; 0.5-1.99 ng/mL; 2-9.99 ng/mL; > or = 10 ng/mL). In 506 samples, they were further analyzed according to the result of blood culture. PCT and CRP were measured using enzyme-linked fluorescent assay (bioMerieux Co., France) and rate nephelometry (Beckman Coulter Co., USA), respectively. Their diagnostic utilities were compared using ROC curves.. The mean concentrations of CRP in five categories of PCT were 15.4 mg/L, 42.1 mg/L, 101.2 mg/L, 125.0 mg/L, 167.1 mg/L, respectively (P<0.0001). Both PCT and CRP showed significant differences between the two positive and negative groups of blood culture (PCT, 8.47 vs 2.44 ng/mL, P=0.0133; CRP, 110.48 vs 59.78 mg/L, P<0.0001). The areas under the ROC curves (95% confidence interval) for PCT and CRP were 0.720 (0.644-0.788) and 0.558 (0.478-0.636), respectively, and showed a significant difference (P=0.005).. The diagnostic utility of PCT is superior to that of CRP for the patients with blood culture-positive sepsis. PCT seems to be reliable for sepsis diagnosis, and may provide useful information for the critically ill patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Humans; Infant; Infant, Newborn; Middle Aged; Nephelometry and Turbidimetry; Protein Precursors; Reagent Kits, Diagnostic; ROC Curve; Sensitivity and Specificity; Sepsis

Diagnosis of sepsis is difficult, particularly in cases of burn where signs of sepsis may be present in the absence of a real infection. This study compared serum levels of procalcitonin (PCT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and white blood cell (WBC) among 60 burned people with and without infection, in order to assess the value of the information for diagnosis of sepsis. A significantly higher PCT level was observed in the septic group compared to those without sepsis (8.45+/-7.8 vs. 0.5+/-1.0, respectively, p<0.001); no significant differences were found in CRP or WBC levels, neutrophil count or ESR. The area under the receiver operating characteristics curve in the diagnosis of sepsis was 0.97 for PCT (p<0.001) with sensitivity of 100% and specificity of 89.3%. Non-survivors had a mean PCT level significantly higher than that of survivors. Thus the serum PCT level was a highly efficient laboratory parameter for the diagnosis of severe infectious complications after burn, but WBC, neutrophil, ESR and CRP levels were of little value.

Topics: Adult; Biomarkers; Blood Sedimentation; Body Temperature; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Leukocyte Count; Male; Prognosis; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

To examine the behavior of interleukin-6 (IL-6) and procalcitonin (PCT) and verify whether they can be used to differentiate children with septic conditions.. Septic children aged between 28 days and 14 years, prospectively enrolled from 01/2004 to 12/2005, were divided into sepsis (SG; n=47) and septic shock (SSG; n=43) groups. IL-6 and PCT were measured at admission (T0) and 12h later (T12h). PCT results were classed as: 0.5 ng/mL=sepsis unlikely; > or =0.5 to <2=sepsis possible; > or =2 to <10=systemic inflammation; > or =10=septic shock.. Ninety children were included. At T0, there was a higher frequency of SSG with higher PCT compared with SG [SSG: 30 (69.7%)>SG: 14 (29.8%); p<0.05]. Similar results were observed at T12h. PRISM was significantly higher for SSG patients with higher PCT than SG patients. At T0, IL-6 levels were higher in SSG [SSG: 213.10 (10.85-396.70)>SG: 63.21 (0.86-409.82); p=0.001], but not statistically different at T12h. IL-6 levels positively correlated with PRISM score in SSG patients at admission (p=0.001; r=0.86).. PCT and IL-6 appear to be helpful in early assessment of pediatric sepsis, are of diagnostic value at admission, and are related to disease severity.

Topics: Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Interleukin-6; Male; Protein Precursors; Sepsis; Time Factors

Procalcitonin serum level has been recommended as a new marker of bacterial infectious diseases. The aim of this prospective, multicenter study was to determine the clinical usefulness of procalcitonin in differentiating patients with sepsis from those with severe sepsis. Eighty-two patients were enrolled: 20 without systemic inflammatory response syndrome (SIRS), 9 with SIRS, 34 with sepsis, and 19 with severe sepsis. The patients with severe sepsis had significantly higher procalcitonin levels (median, 36.1 ng/ml) than those with sepsis (median, 0.6 ng/ml). With a procalcitonin cutoff value of 2.0 ng/ml, sensitivity for the detection of severe sepsis and specificity for the detection of sepsis were 94.7% and 78.1%, respectively. A good correlation was found between the serum procalcitonin level and the Sepsis-Related Organ Failure Assessment (SOFA) score (r = 0.680), although no correlation was found between the C-reactive protein (CRP) level and the SOFA score. In conclusion, the procalcitonin serum level may be useful not only for aiding the diagnosis of sepsis but also for discriminating between sepsis and severe sepsis.

Topics: APACHE; beta-Glucans; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Glycoproteins; Humans; Interleukin-6; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

To compare the accuracy of procalcitonin (PCT) in early-onset neonatal sepsis (EOS) using standard cut-off values and a multilevel probabilistic approach.. A retrospective study of PCT was performed in 149 newborns at risk of EOS, including preterm or prolonged rupture of membranes, chorioamnionitis or maternal infection, GBS colonization and signs of fetal distress. PCT values were analysed according to time of assay, i.e. at birth and at 24 and 48 h. We estimated sensitivity, specificity, positive (LR+) and negative likelihood ratio (LR-), diagnostic odds ratio (DOR) and number needed to diagnose (NND) using traditional and optimal (derived from ROC analysis) PCT cut-off values.. Using optimal cut-off, the LR+, DOR and NND at birth were 10, 18.9 and 2.2, at 24 h they were 5.3, 11.2 and 2.1, and at 48 h they were 5.6, 18.1 and 1.7, respectively. The multilevel analysis generated three post-test probabilities for each time of assay. At 24 h post-test probabilities of EOS were 78% for PCT >90, 11% for PCT 10.1-90 and 3% for PCT <10.1 mg/L, respectively. Similar results were found in the other time points, with a wide range of intermediate PCT concentrations that did not change the post-test probability.. The multilevel probabilistic approach was more effective in assessing the diagnostic power of PCT in EOS, showing that a wide range of intermediate PCT values was not able to discriminate between presence and absence of infection.

Topics: Age of Onset; Biological Assay; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Infant, Newborn, Diseases; Italy; Likelihood Functions; Models, Statistical; Protein Precursors; Risk Factors; ROC Curve; Sepsis

To assess the clinical value of pro-adrenomedullin (pro-ADM) in the prognosis and risk stratification in sepsis.. Fifty-one critically ill patients admitted to the intensive care unit (ICU) were prospectively stratified into four groups according to internationally recognized criteria: systemic inflammatory response syndrome (SIRS, 25 cases), sepsis (12 cases), severe sepsis (9 cases) and septic shock (5 cases). The levels of plasma pro-ADM was determined in every patient using a new sandwich immunoassay, and compared with procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6 (IL-6), and the acute physiology and chronic health evaluation II (APACHE II) score.. (1) Median pro-ADM concentration was 0.34 microg/L for SIRS, 2.23 microg/L for sepsis, 4.57 microg/L for severe sepsis and 8.21 microg/L for septic shock. The plasma concentration of pro-ADM exhibited a gradual increase, and the median pro-ADM value was highest in the septic shock group (all P<0.05). (2) Compared with the other biomarkers, in the sepsis, severe sepsis and septic shock groups, the plasma concentration of pro-ADM and APACHE II score in the non-survivors was significantly higher than in the survivors (pro-ADM: 2.01 microg/L vs. 9.75 microg/L, APACHE II score: 23.44 scores vs. 38.21 scores, both P<0.05). (3) By the receiver operating characteristic (ROC) curve plot analysis of pro-ADM in sepsis, the area under the ROC curve for pro-ADM (0.87) in survivors was similar to the area under the ROC curve for PCT (0.81) and APACHE II score (0.81), and was significantly higher than the area under the ROC curve for CRP (0.53) and IL-6 (0.71).. The measurement of pro-ADM is a new and useful marker in sepsis prognosis and risk stratification.

Topics: Adrenomedullin; Adult; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Peptide Fragments; Postoperative Complications; Protein Precursors; Risk Assessment; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

The goal of this study was to investigate the role of procalcitonin (PCT) in diagnosis of neonatal sepsis and its correlation with C-Reactive Protein (CRP). One hundred and seventeen neonates with the gestational age > or = 35 weeks with clinically suspected diagnosis of neonatal sepsis were studied during one year from 2007 in Tabriz Children's Hospital. Conventional sepsis workup was done in all cases and the diagnosis of neonatal sepsis was proved based on the results of blood culture. The serum procalcitonin was measured by quantitative Chemo-luminance methods and the results were compared with CRP levels between the neonates with and without proven sepsis. The results showed among in 117 neonates with suspected sepsis 27 (23.1%) cases have positive blood culture (proven sepsis). The mean levels of PCT in neonates with and without proven sepsis was 4.42 +/- 6.66 vs. 2.06 +/- 4.03 ng mL(-1) and CRP 33.98 +/- 36.81 vs. 12.30 +/- 20.42 mg L(-1) were significantly higher in neonates with proven sepsis (p = 0.026 and p < 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of PCT (more than 2 ng mL(-1)) were 66.7, 50, 28.6, 83.3 and CRP (more than 3.5 mg L(-1)) were 70.4, 72.2, 43.2 and 89%, respectively, in diagnosis of neonatal sepsis. There was a meaningful correlation between the level of PCT and CRP in the sepsis group (r = 0.797, p < 0.001). The results of the current study showed that more relying on the level of PCT and CRP for planning the management of neonates with suspected sepsis is not logical, but a negative result may be helpful in ruling it out.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Luminescence; Male; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Elevated procalcitonin (PCT) levels are observed after major surgery, such as orthotopic liver transplantation (OLTx). The aim of this observational study was to evaluate PCT kinetics during the first 5 following days after surgery to establish the prognostic value of PCT changes in the outcome of OLTx, and to predict medical, technical and infectious complications. PCT was also evaluated in the differential diagnosis of infection vs. rejection.. A total of 64 OLTx were performed in 58 patients; they were split into two groups: with and without complications. Out of these patients, 18 developed infection, and nine rejection. PCT was measured before and during surgery, 12 h after transplantation and daily for the 5 following days. PCT was also measured the day when infection or rejection was diagnosed, and on the previous day. PCT was determined by time-resolved amplified cryptate emission (TRACE) technology.. PCT elevation began at 12 h after surgery, reaching a peak on the 1st day in both groups. Significantly higher PCT concentrations were found in the group of patients developing complications, on the 5 postoperative days. It was found that a 24 h PCT value higher than 1.92 microg/L increased by 9.1-time-fold the risk of complications. When infection was diagnosed, a second peak of PCT was observed, but no PCT elevation was shown in rejection.. Daily monitored PCT provides valuable information about the early outcome of OLTx.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

We compared the test characteristics of interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12(p-70), tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT), C-reactive protein (CRP), and full blood count (FBC) in the diagnosis of neonatal sepsis. This prospective cohort study in the Neonatal Intensive Care Unit of Dunedin hospital of patients between July 1, 2002 and February 28, 2007 included 117 neonates commenced on antibiotics for 164 episodes of suspected sepsis. Blood cultures, FBC, CRP, IL-1 beta, IL-6, IL-8, IL-10, IL-12(p-70), TNF-alpha, and PCT were obtained at the time sepsis was first suspected and for the following 3 days. Receiver operator characteristics (ROC) plots and test characteristics were determined using culture-positive sepsis as the gold standard. At the time sepsis was first suspected, the most promising individual test was IL-12(p70) with an area under the curve (95% confidence interval [CI]) for the ROC of 0.74 (0.63 to 0.86), which (with a cutoff at 75 pg/mL) had a sensitivity (95% CI) of 28% (20 to 36%) and a specificity of 98% (96 to 100%). IL-10 had a sensitivity of 17% (10 to 23%) and a specificity of 99% (97 to 100%). IL-10 and IL-12(p70) are promising diagnostic tests that can be used to confirm sepsis in neonates.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Interleukin-10; Interleukin-12; Male; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

Sepsis is an important cause of mortality in newborns. However, a single reliable marker is not available for the diagnosis of neonatal late-onset sepsis (NLS). The aim of this study is to evaluate the value of serum amyloid A (SAA) and procalcitonin (PCT) in the diagnosis and follow-up of NLS.. 36 septic and healthy newborns were included in the study. However, SAA, PCT, TNF-alpha, IL-1beta, and CRP were serially measured on days 0, 4, and 8 in the patients and once in the controls. Töllner's sepsis score (TSS) was calculated for each patient.. CRP, PCT, and TNF-alpha levels in septic neonates at each study day were significantly higher than in the controls (P = .001). SAA and IL-1beta levels did not differ from healthy neonates. The sensitivity and specificity were 86.8% and 97.2% for PCT, 83.3% and 80.6% for TNF-alpha, 75% and 44.4% for SAA on day 0.. Present study suggests that CRP seems to be the most helpful indicator and PCT and TNF-alpha may be useful markers for the early diagnosis of NLS. However, SAA, IL-1beta, and TSS are not reliable markers for the diagnosis and follow-up of NLS.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Interleukin-1beta; Male; Pregnancy; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha

Blood stream infections (BSI) are life-threatening infections in intensive care units (ICU), and prognosis is highly dependent on early detection. Procalcitonin levels have been shown to accurately and quickly distinguish between BSI and noninfectious inflammatory states in critically ill patients. It is, however, unknown to what extent a recent history of sepsis (namely, secondary sepsis) can affect diagnosis of BSI using PCT.. review of the medical records of every patient with BSI in whom PCT dosage at the onset of sepsis was available between 1st September, 2006 and 31st July, 2007.. 179 episodes of either primary (n = 117) or secondary (n = 62) sepsis were included. Procalcitonin levels were found to be markedly lower in patients with secondary sepsis than in those without (6.4 [9.5] vs. 55.6 [99.0] ng/mL, respectively; p < 0.001), whereas the SOFA score was similar in the two groups. Although patients in the former group were more likely to have received steroids and effective antibiotic therapy prior to the BSI episode, and despite a higher proportion of candidemia in this group, a low PCT value was found to be independently associated with secondary sepsis (Odd Ratio = 0.33, 95% Confidence Interval: 0.16-0.70; p = 0.004). Additional patients with suspected but unconfirmed sepsis were used as controls (n = 23). Thus, diagnostic accuracy of PCT as assessed by the area under the receiver-operating characteristic curves (AUROCC) measurement was decreased in the patients with secondary sepsis compared to those without (AUROCC = 0.805, 95% CI: 0.699-0.879, vs. 0.934, 95% CI: 0.881-0.970, respectively; p < 0.050).. In a critically ill patient with BSI, PCT elevation and diagnosis accuracy could be lower if sepsis is secondary than in those with a first episode of infection.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Early Diagnosis; Female; Humans; Leukocyte Count; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis

Topics: Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Diagnostic Tests, Routine; Drug Resistance, Microbial; Humans; Protein Precursors; Sepsis

In this study we tested how a combination of early and late paraclinic markers could predict early onset neonatal sepsis (EONS).. The first 24 hours after the suspicion of EONS, we measured interleukine (IL)-6, IL-8, IL-10, IL-18, tumor necrosis factor-alpha (TNF-alpha), interferon gamma (INF-gamma), procalcitonin (PCT) and C-reactive protein (CRP) at 8-hour intervals on 123 neonates clinically suspected for EONS. The neonates were divided into two groups. The sepsis group: 1A with blood culture verified bacteraemia and 1B strongly suspected sepsis (29 patients). The no sepsis group: 2A treated with antibiotics (37 patients) and 2B not treated with antibiotics (57 patients).. Combined evaluation of each of the early markers with PCT > 25 ng/ml for prediction of EONS at time 0, gave the following sensitivities and specificities: IL-6 > 250 pg/ml: 71% and 88%; IL-8 > 900 pg/ml: 50% and 88%; IL-10 > 40 pg/ml: 43% and 87%; and immature/total (I/T) ratio > 0.35: 59% and 88%. The results of IL-18, TNF-alpha and IFN-gamma did not predict EONS.. IL-6 combined with PCT values is a fair way to evaluate EONS at the time of suspicion of infection. The "old" early marker, I/T ratio, is almost as efficient as IL-6. By combining an early and a late marker it may be possible to reduce the diagnostic "non-conclusive" period of paraclinic values.

Topics: Anti-Bacterial Agents; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Escherichia coli Infections; Female; Humans; Infant, Newborn; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-18; Interleukin-6; Interleukin-8; Leukocyte Count; Male; Neutrophils; Protein Precursors; Retrospective Studies; Sensitivity and Specificity; Sepsis; Staphylococcal Infections; Streptococcal Infections; Streptococcus agalactiae; Tumor Necrosis Factor-alpha

The evaluation of tests for neonatal sepsis is important because the infection may present a very serious threat to the baby. Extensive literature exists on single laboratory test or combinations of tests, as well as tests used together with risk factors and/or clinical signs, to diagnose neonatal sepsis. In many instances, the results of the evaluations have been conflicting. It has recently been suggested that serum procalcitonin (PCT) is of value: in the diagnosis of neonatal sepsis, with varying results. This study was designed to determine the reliability of PCT concentrations as a new marker for the diagnosis of early neonatal sepsis of vertical transmission comparing to the traditional inflammatory mediators, such as interleukin-6 (IL-6) and C-reactive protein (CRP) values. The current study included 69 newborn babies. After full history and clinical examination, they were classified into 2 groups: Group 1, included 27 of asymptomatic newborn infants admitted during the first 24 h of life to the neonatal unit because of prematurity, low birth weight. They had no clinical signs of sepsis during their first week of life and had a negative blood culture, and they did not receive antibiotic treatment. The second group: Group 2, included 42 symptomatic neonates who were admitted to the neonatal care unit and were evaluated for sepsis during the first 48 h of life, they were subclassified into twosubgroups: group 2A; included 22 neonates of confirmed vertical neonatal sepsis, defined as they had at least three clinical signs of infection with culture proven sepsis, and group 2B included 20 neonates of vertical clinical sepsis (they had at least three clinical signs of infection) with negative blood culture. Blood sampling for blood culture, complete blood count, blood gases and blood chemistry, additionally, CRP, serum IL-6 and PCT were measured. The microbial organisms isolated from the blood culture of group 2A; Escherichia coli was isolated from 9 cases, staphylococcus aureus from 6 cases, staphylococcus epidermidis from 2 cases, group B streptococci (GBS) from 2 cases, ureaplasma from 2 cases and one case was GBS positive mother. The comparison between the studied groups revealed that, white blood cell counts (WBCs) and CRP levels were significantly increased in group 2A more than in group 1 and group 2B. While in group 2B the WBCs not differed from group 1 but CRP differed from group 1. IL-6 and PCT values were significantly increased in group 2A mo

Topics: Biomarkers; Birth Weight; Blood; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Gestational Age; Humans; Infant, Newborn; Interleukin-6; Leukocyte Count; Predictive Value of Tests; Protein Precursors; Sensitivity and Specificity; Sepsis; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus agalactiae; Ureaplasma

The prognostic value of procalcitonin (PCT) in patients with sepsis at the emergency department (ED) has not been evaluated. We conducted a prospective observational study to compare the prognostic value of PCT on sepsis and compared with a validated score, Mortality in Emergency Department Sepsis (MEDS) score, and C-reactive protein (CRP) in the setting of ED of an urban, university-based medical center. Five hundred twenty-five consecutive adult patients admitted to the ED fulfilling the American College of Clinical Pharmacists/Society of Critical Care Medicine Consensus Conference definition of sepsis were prospectively enrolled. Serum PCT and CRP were evaluated for each patient. Clinical characteristics and laboratory results on ED admission were recorded using a standardized form. Each patient was followed for at least 30 days. The main outcome was early (5-day) and late (6- to 30-day) mortality. The median age of the study sample was 64.0 (interquartile range, 47-76) years old, and the overall 30-day mortality rate was 10.5%. The c-statistic in the prediction of early mortality was 0.89 for MEDS, 0.76 for PCT, and 0.68 for CRP. The c-statistic in the prediction of late mortality was 0.78 for MEDS, 0.70 for PCT, and 0.63 for CRP. Overall, MEDS score has the best discriminative capability among the three tested markers. Under the best cutoff value, PCT was the most sensitive, and MEDS score was the most specific marker. We suggest further combining the information on PCT and MEDS score to enhance the accuracy in predicting ED sepsis mortality.

Topics: Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

To examine the diagnostic usefulness of procalcitonin (PCT), C-reactive protein and immature to total neutrophil ratio (I : T) in nosocomial sepsis among neonates treated in an intensive care unit.. A retrospective analysis and comparison of diagnostic utility performed in preterm neonates using receiver operating characteristic curves for the diagnosis of culture-proven sepsis.. A total of 78 clinically suspected sepsis episodes in 73 newborns were analysed. The median values of PCT were: 0.56 ng/mL (interquartile range (IQR) 0.33-1.32) in group with aseptic blood culture (n = 15), 2.69 ng/mL (IQR 1.10-5.29) in Gram-positive (n = 47) and 9.36 ng/mL (IQR 3.11-39.35) in Gram-negative sepsis (n = 16). Only PCT values were significantly different (P < 0.01) among all groups. This was also true when correction for differences in blood withdrawal time was implemented. The positive and negative predictive values of PCT in the diagnosis of sepsis equalled 97.5% and 88.9%, respectively, for a cut-off value of 0.99 ng/mL. PCT was significantly better in diagnosis of sepsis than I : T (P = 0.03). No other significant differences in diagnostic efficacy were noted. The diagnostic efficacy was the highest for measurements made two or more hours since the onset of symptoms.. The PCT serum concentration is a valuable tool for early detection of nosocomial sepsis in infants. Highest levels of PCT were observed in Gram-negative infections.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Male; Protein Precursors; Retrospective Studies; ROC Curve; Sepsis; Time Factors

The present study attempted to identify the diagnostic significance of procalcitonin (PCT) in acute abdominal conditions as well as the range of concentrations relating to diagnosis of abdominal sepsis.. This was prospective clinical study. The study included 98 consecutive patients with acute abdominal conditions, divided in sepsis and systemic inflammatory response syndrome (SIRS) group.. PCT concentrations on admission were significantly higher in the sepsis group than in the SIRS group (median [interquartile range] 2.32 [7.41] vs 0.45 ng/ml [2.62]). A cutoff value of 1.1 ng/ml yielded 72.4% sensitivity and 62.5% specificity. In a group of patients with abdominal symptoms lasting for more than 24 h, a cut-off value of 1.1 ng/ml yielded higher sensitivity (82.9%) and higher specificity (77.3%).. Our results suggest that PCT measurements may be useful for early, preoperative diagnosis of abdominal sepsis.

Topics: Acute Disease; Adult; Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Peritonitis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) is a biomarker for the diagnosis of sepsis and bacterial infection diseases.. A new fully automated SphereLight PCT (SL-PCT) assay system for PCT concentration in human serum or plasma by using SphereLight 180 (SL180, Olympus Corp.) analyzer was developed. The SL-PCT assay is based on chemiluminescent enzyme immunoassay.. A linear dose response relationship was observed up to 200 ng/ml PCT concentration. The detection limit of PCT concentration was 0.06 ng/ml. Endogenous substances, anticoagulants, sodium fluoride and drugs did not interfere with assay results. There was a good correlation between the present method and the manual method in serum and plasma samples.. These results indicate that the SL-PCT assay showed good performance in terms of the linearity, detection limit and precision. Use of this PCT measurement may improve the detection of sepsis and infectious disease.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Light; Medical Laboratory Science; Protein Precursors; Sensitivity and Specificity; Sepsis

Sepsis intervention studies need better patient stratification methods, and one way to realize this is the introduction of stable biomarkers. A set of recently developed novel biomarkers, based upon precursor-fragments of short-lived hormones, was previously shown to be increased during sepsis. However, it is not known whether these biomarkers are influenced by sepsis intervention strategies. Therefore we investigated the markers in a model of human endotoxemia intervened by increasing doses of prednisolone.. Prospective, open-label study in a specialized clinical research unit of a university hospital.. Thirty-two healthy male volunteers.. Subjects received prednisolone orally at doses of 0, 3, 10 or 30 mg (n=8 per group) at 2 h before intravenous injection of Escherichia coli lipopolysaccharide (LPS) (4 ng/kg). Blood samples were drawn during 24 h after LPS injection.. LPS injection caused an increase in levels of midregional pro-adrenomedullin (MR-proADM), midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-arginine-vasopressin (CT-proAVP) and procalcitonin (PCT). Prednisolone caused a dose dependent inhibition of MR-proADM, MR-proANP and CT-proAVP levels.. These results show that a set of novel, highly stable sepsis biomarkers was increased during human endotoxemia and was dose-dependently inhibited by corticosteroid pre-treatment.

Topics: Administration, Oral; Adrenomedullin; Adult; Arginine Vasopressin; Atrial Natriuretic Factor; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Dose-Response Relationship, Drug; Endotoxemia; Humans; Inflammation Mediators; Injections, Intravenous; Lipopolysaccharides; Male; Peptide Hormones; Prednisolone; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

To assess the potential role of procalcitonin and tumor necrosis factor-alpha, interleukin-6 and interleukin-8, in the prognosis of patients with sepsis.. Prospective study.. The emergency unit of a teaching hospital.. We included 131 patients with sepsis: 15 (12%) with septic shock, 20 (15%) with severe sepsis and 96 (73%) with sepsis.. Out of the 131 patients, 112 (85.5%) survived and 19 (14.5%) died. These two groups of patients differed with regard to simplified acute physiology score II, severity of infectious disease and underlying disease, bacteremia and type of microorganisms. The mean serum levels of tumor necrosis factor, interleukin-6, interleukin-8, procalcitonin and lactates at study entry were higher in nonsurvivors than in survivors. Multivariate regression analysis showed the most significant of these variables to be serum procalcitonin level (P=0.0007), simplified acute physiology score II (P=0.03) and serum lactate level (P=0.03). Using a model incorporating these three variables, with a cut-off value corresponding to a 15% probability of predicting mortality, death could be correctly predicted in 99.5% of cases and survival in 95%. This cut-off value allowed us to maximize the prediction of death. When serum procalcitonin levels were not taken into account, the best model included simplified acute physiology score II and serum lactate and interleukin-6 levels, but the rate of correct prediction of death then dropped to 84%.. Stepwise multivariate logistic regression analysis showed serum procalcitonin level to be a valuable marker of sepsis severity, compared with the 15 other clinical, biochemical and bacteriologic variables tested.

Topics: Adult; Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Service, Hospital; France; Humans; Interleukin-1; Middle Aged; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic

To study the diagnostic and prognostic value of procalcitonin (PCT), common inflammatory markers combining with scores for estimating organ failure of infection related organs (SOFA) in patients with sepsis in early stage.. Patients were observed continuously in a perspective study with diagnostic tests. According to the definition of ACCP/SCCM Consensus Conference, patients were classified into 5 groups, including non-systemic inflammatory response syndrome (SIRS) (control) group, SIRS group, sepsis group, severe sepsis group and septic shock group. Indexes of inflammation, SOFA and concentration of PCT were determined at 24 hours, and their correlation was analyzed.. Two hundred and eight patients were enrolled, including 59 in non-SIRS group, 57 in SIRS group, 52 in sepsis group, 28 in severe sepsis group and 12 in septic shock group. PCT concentrations were positively correlated with the severity of sepsis. Spearman's correlation coefficient was 0.909 (P=0.000). According to the receiver operating characteristic curves (ROC-curves) analysis principle, ROC curves were drawn and areas under these curves (AUC) was calculated. In the diagnosis of sepsis, AUC values were 0.936+/-0.020 for PCT, 0.973+/-0.011 for SOFA (both P=0.000). The best cutoff values in the diagnosis of sepsis were 0.375 microg/L for PCT, and 3. 5 for SOFA score. The Youden index of PCT and SOFA scores was 0.808 and 0.801, respectively. Binary Logistic regression analysis confirmed that PCT and SOFA score were highly correlated with sepsis (OR=84.794,10.761, respectively, both P=0.000) after eliminating confusion factors including age and C-reactive protein (CRP) etc.. PCT and SOFA score could be used to predict the incidence of sepsis. SOFA score was the best prognostic indicator of sepsis (OR=2.084, P=0.0002).. The traditional inflammatory markers and CRP are useful parameters to differentiate SIRS from non-SIRS, but are not reliable indicators for the early diagnosis in patients with sepsis. PCT is more specific indicator in early diagnosis of sepsis to differentiate from SIRS. PCT combining with SOFA score can be used to predict the incidence of sepsis. SOFA score can be used to define objectively the severity of sepsis according to PCT level and is helpful for estimation of prognosis in patients with sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Humans; Prognosis; Prospective Studies; Protein Precursors; Sepsis

Topics: Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Male; Protein Precursors; Reproducibility of Results; Sepsis

Recent data have suggested that 18 million of new sepsis cases occur each year worldwide, with a mortality rate of almost 30%. There is not consensus on the clinical definition of sepsis and, because of lack of training or simply unawareness, clinicians often miss or delay this diagnosis. This is especially worrying; since there is strong evidence supporting that early treatment is associated with greater clinical success. There are some difficulties for sepsis diagnosis such as the lack of an appropriate gold standard to identify this clinical condition. This situation has hampered the assessment of the accuracy of clinical signs and biomarkers to diagnose sepsis.. Cross-sectional study to determine the operative characteristics of three biological markers of inflammation and coagulation (D-dimer, C-reactive protein and Procalcitonin) as diagnostic tests for sepsis, in patients admitted to hospital care with a presumptive infection as main diagnosis.. There are alternative techniques that have been used to assess the accuracy of tests without gold standards, and they have been widely used in clinical disciplines such as psychiatry, even though they have not been tested in sepsis diagnosis. Considering the main importance of diagnosis as early as possible, we propose a latent class analysis to evaluate the accuracy of three biomarkers to diagnose sepsis.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Colombia; Cross-Sectional Studies; Emergency Service, Hospital; Enzyme-Linked Immunosorbent Assay; Fibrin Fibrinogen Degradation Products; Humans; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis

This study was designed to determine the sensitivity and specificity of a semi-quantitative procalcitonin (PCT) test kit for the diagnosis of neonatal sepsis.. Infants admitted to the neonatal intensive care unit with signs suggestive of sepsis were recruited into the study. Prior to commencement on antibiotics, the following investigations were carried out on each of these infants: blood culture and sensitivity, PCT semi-quantitation and C-reactive protein (CRP) estimation. Infants already on antibiotics, or who developed signs of sepsis within 72 hours of discontinuation of antibiotics, were excluded from the study.. Of the 87 infants recruited, 18 (20.7 percent) were confirmed to have sepsis based on positive blood culture results. At a PCT cut-off level of greater than or equal to 2 ng/ml, the sensitivity of the PCT-Q kit in detecting neonatal sepsis at the onset of symptoms was 88.9 percent and its specificity was 65.2 percent. The sensitivity of CRP for diagnosis of sepsis was 55.6 percent and its specificity was 89.9 percent.. The semi-quantitative PCT test kit is of moderate sensitivity but poor specificity for early diagnosis of neonatal sepsis. A negative PCT test result may help to "rule out", while a raised CRP result helps to "rule in", the possibility of sepsis.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant Welfare; Infant, Newborn; Intensive Care Units, Neonatal; Male; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors

Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery.. Single-center prospective study.. University hospital.. Two hundred seventy-six patients scheduled for elective major aortic surgery.. Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1).. Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection.. Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Female; Humans; Kidney Function Tests; Male; Middle Aged; Postoperative Complications; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Vascular Surgical Procedures

To evaluate the efficacy of procalcitonin PCT to identify critically ill patients with sepsis in comparison with leukocyte count, body temperature, C-reactive protein CRP, erythrocyte sedimentation rate ESR, and interleukin-6 IL-6.. We performed our prospective observational study in 75 patients admitted with acute systemic inflammatory response and suspected infection. The final diagnosis was systemic inflammatory response syndrome SIRS in 38 patients, sepsis in 22, severe sepsis in 10, and suspected viral sepsis in 5. Blood samples were taken on the first day of hospitalization in Al Mwasaa Hospital, Damascus, Syrian Arab Republic, from July 2006 to January 2007. We estimated the relevance of the different parameters by using the t-test, Pearson's correlation coefficient, and area under the receiver operating characteristic curves.. Mean PCT concentrations on admission were 0.37 ng/ml for SIRS n=38, 3.31 ng/ml for sepsis n=22, 40.2 ng/ml for severe sepsis n=10, and significant differences existed in plasma PCT levels among the 3 groups. The PCT was the only distinguisher between sepsis and non-infectious SIRS, whereas it exhibited the best discriminative power between sepsis and severe sepsis with an area under the curve AUC of 0.966 followed by IL-6 with an AUC of 0.836. The PCT also do not correlate with any of the studied parameters within the SIRS group and the sepsis group.. Assessing PCT levels is a more reliable way to indicate sepsis in newly admitted patients with systemic inflammations compared with conventional inflammatory parameters and IL-6.

Topics: Adult; Blood Sedimentation; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Interleukin-6; Leukocyte Count; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Sepsis is a major cause of death in the United States and accounts for approximately 50% of the fatalities in intensive care units. Serum procalcitonin (ProCT) levels are markedly elevated in sepsis and correlate positively with severity of the illness and mortality, however, little is known about the biological activity of ProCT.. To explore the biological activity of purified human ProCT at the calcitonin (CT) family of receptors.. Human ProCT was purified from the TT medullary thyroid carcinoma cell line. Human CTa receptor or human CT receptor-like receptor (CLR) was transiently expressed in COS-7 cells alone or together with individual receptor activity-modifying proteins (RAMPs) to generate the CTa (CT) receptor, the AMY1 (amylin) receptor, the CGRP1 (CT gene-related peptide) receptor, and the AM1 and AM2 (adrenomedullin) receptors. Biological activity of ProCT was assessed by measurement of cAMP accumulation.. ProCT was effectively inert at CTa, AM1, and AM2 receptors. In contrast, it was a potent partial agonist (50-60% of the CGRP efficacy) of the CGRP1 receptor with an EC50 as high as 0.56 nM, although the potency was batch dependent. ProCT also displayed weak partial agonist activity at the AMY1 receptor with an EC50 of approximately 100 nM. Moreover, ProCT also robustly inhibited CGRP-dependent cyclic adenosine monophosphate responses at the CGRP1 receptor.. Our data provide a potential molecular mechanism for the observation that ProCT appears to be toxic while CGRP treatment appears to be beneficial in animal models of sepsis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Receptors, Calcitonin; Sepsis

To assess the diagnostic utility of combining measurement of blood procalcitonin (PCT) concentrations with the presence of a biphasic transmittance waveform (BPW) from the activated partial thromboplastin time (aPTT) to identify sepsis in critically ill patients.. Prospective observational study.. Thirty-one-bed university hospital department of medico-surgical intensive care.. Two hundred consecutive adult patients admitted to the department during a 3-month period.. aPTT waveform analysis was performed on admission and daily throughout the intensive care unit (ICU) stay. Receiver operating characteristic curves were created to determine the best threshold values of BPW and PCT for prediction of sepsis. Of the 200 patients, 63 (32%) had sepsis during the ICU stay; 29 (15%) patients were diagnosed with sepsis at admission. Using a threshold value of BPW slope_1 = -0.075%T/sec, 37 patients (19%) had a BPW at ICU admission and 84 (42%) at some time during the ICU stay. At this threshold, 23 of the patients (62%) with a BPW at admission and 51 (61%) with a BPW during the ICU stay were diagnosed with sepsis. Using a cut-off value of 1 ng/ml, 60 patients (30%) had abnormal PCT at admission, and 86 during the ICU stay. At this threshold, 24 of the patients (40%) with abnormal PCT at admission and 52 (60%) with abnormal PCT during the ICU stay were diagnosed with sepsis. Thirty patients had a BPW and an abnormal PCT, and 23 (77%) of these had sepsis. Of the other 170 patients, only six patients (4%) had sepsis. Hence, the sensitivity of the combination of BPW and PCT at admission was 79% and specificity 96%; the negative predictive value was 96%.. aPTT waveform analysis is an easy and rapid method for identification of sepsis; its combination with PCT increases its specificity.

Topics: Acute Disease; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Humans; Middle Aged; Partial Thromboplastin Time; Prospective Studies; Protein Precursors; Sepsis

Because serum Procalcitonin is reported to be a valid postmortem marker of sepsis, this prospective study was carried out to determine whether the semi-quantitative PCT-Q((R))-Test (B.R.A.H.M.S., Germany) is a reliable indicator of postmortem Procalcitonin (PCT) serum levels, thus enabling a quick "tableside" diagnosis of sepsis. Postmortem PCT-levels of 70 forensic and 78 clinical-pathological autopsy cases (n=148) were examined using the B.R.A.H.M.S-PCT-Q-Test during autopsy. 27 cases were categorized as the cases of sepsis according to the ACCP/SCCM Consensus Conference criteria. 121 cases were assigned to the non-sepsis group. Among the 148 cases, 18 samples could not be analyzed by the reason of strong hemolysis. Using a cut-off point of 2 ng/ml, 20 cases of sepsis were identified (true positive) whereas 3 cases of sepsis were not detected (false negative). In the non-sepsis group (107 cases) 6 cases showed a positive testing (false positive). When applied within 48 h postmortem, the PCT-Q-Test showed a sensitivity of 86.96% and a specificity of 94.39% (at cut-off 2 ng/ml). Likelihood ratios and positive predictive values proved to be lower in the forensic autopsy group (PPV: 59.3% in forensic case vs. 85.1% in clinicopathological cases; NPV: 98.73% in forensic cases vs. 95.2% in clinicopathological cases). The PPVs using a cut-off point of 10 ng/ml were 100% in both groups independent of sepsis prevalences. The results show, that a high NPV for prevalences ranging from 3% to 30% can be reached using a 2 ng/ml cut-off point, whereas a cut-off of 10 ng/ml ensures a high PPV for the respective prevalences in the absence of exclusion criteria. The study provides strong evidence that the introduction of rapid diagnostic test (RDTs) of postmortem PCT serum levels may be useful in achieving rapid distinction between sepsis and non-sepsis-related causes of death, especially in conjunction with the medical case history and further autopsy results. In addition, the use of RDTs enables clinicians to conduct an evidence-based validation of clinical diagnosis, thus facilitating future clinical decision-making.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Child; Forensic Pathology; Humans; Immunoassay; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Severe sepsis is not clinically apparent during the first 24 hours of hospitalization in most children with cancer and febrile neutropenia (FN), delaying targeted interventions that could impact mortality. The aim of this study was to prospectively evaluate biomarkers obtained within 24 hours of hospitalization as predictors of severe sepsis before it becomes clinically evident.. Children with cancer, admitted with FN at high risk for an invasive bacterial infection in 6 public hospitals in Santiago, Chile, were monitored throughout their clinical course for occurrence of severe sepsis. Clinical, demographic and 6 biomarkers [eg, blood urea nitrogen, serum glucose, lactic dehydrogenase, serum C-reactive protein (CRP), interleukin (IL)-8, and procalcitonin] were obtained at the time of admission and after 24 hours. Biomarkers independently associated with severe sepsis diagnosed after the first 24 hours of hospitalization were identified by logistic regression analysis.. A total of 601 high risk FN episodes were enrolled between June 2004 and October 2006; 151 (25%) developed severe sepsis of which 116 (77%) were not clinically apparent during the first 24 hours of hospitalization. Risk factors for severe sepsis were age > or =12 years [odds ratio (OR): 3.85; 95% confidence interval (CI): 2.41-6.15], admission CRP > or =90 mg/L (OR: 2.03; 95% CI: 1.32-3.14), admission IL-8 > or =200 pg/mL (OR: 2.39; 95% CI: 1.51-3.78), 24-hour CRP > or =100 mg/L (OR: 3.06; 95% CI: 1.94-4.85), and 24-hour IL-8 > or =300 pg/mL (OR: 3.13; 95% CI 1.92-5.08).. Age > or =12 years and admission or 24-hour values of CRP > or =90/100 mg/L and IL-8 > or =200/300 pg/mL are predictors of sepsis not clinically apparent during the first 24 hours of hospitalization.

Topics: Adolescent; Age Factors; Biomarkers; Blood Glucose; Blood Urea Nitrogen; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Chile; Female; Fever of Unknown Origin; Hospitalization; Humans; Interleukin-8; L-Lactate Dehydrogenase; Logistic Models; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; Sepsis

Methods for lipopolysaccharide (LPS) (endotoxin) reduction have been proposed as one way to improve the treatment of Gram-negative sepsis. Here we present a case with severe Gram-negative sepsis, treated with a novel device for LPS adsorption (Alteco LPS Adsorber, Alteco Medical AB, Lund, Sweden). After LPS adsorption, the level of LPS in the patient's bloodstream was almost eliminated: from 1.44 EU/ml before treatment to 0.03 EU/ml post treatment). The procalcitonin level and inflammatory cytokines were concurrently reduced. Also, an obvious improvement in the status of the patient's hemodynamics was seen. Forty-five days after treatment the patient is still alive. In conclusion, LPS adsorption may represent a significant improvement in the treatment of Gram-negative sepsis and further studies are planned.

Topics: Abdomen; Acute Disease; Adsorption; Adult; Anticoagulants; Calcitonin; Calcitonin Gene-Related Peptide; Cholecystectomy; Hemoperfusion; Hemorrhage; Heparin; Humans; Lipopolysaccharides; Male; Multiple Organ Failure; Pancreatitis, Acute Necrotizing; Protein Precursors; Pseudomonas aeruginosa; Renal Insufficiency; Respiratory Insufficiency; Sepsis; Severity of Illness Index; Treatment Outcome

The aim of this study was to find the relationship between N-terminal brain natriuretic propeptide (NT-proBNP), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in septic patients. This was a prospective study, performed at Medical University Hospital No. 5 in łódź. Twenty patients with sepsis and severe sepsis were included in the study. N-terminal brain natriuretic propeptide, procalcitonin and C-reactive protein concentrations, and survival were evaluated. In the whole studied group (128 measurements), the mean NT-proBNP, procalcitonin and C-reactive protein concentrations were, respectively: 140.80+/-84.65 pg/ml, 22.32+/-97.41 ng/ml, 128.51+/-79.05 mg/l. The correlations for the NT-proBNP level and procalcitonin and C-reactive protein levels were 0.3273 (p<0.001) and 0.4134 (p<0.001), respectively. NT-proBNP levels correlate with PCT and CRP levels in septic patients. In the survivor subgroup, the mean NT-proBNP plasma concentrations were significantly lower than in the non-survivor subgroup.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Protein Precursors; Sepsis

To estimate the diagnostic value of serum PCT, CRP, leukocyte count and temperature as markers of sepsis in critically ill ICU burn patients.. Prospective, observational study in a four bed Burn Intensive Care Unit.. Forty-three patients admitted in a Burn ICU were included in our study.. Serum PCT, CRP concentrations, WCC (white cell count), neutrophils and temperature were measured within the first 24h after-burn and daily thereafter. Severity of organ failure was estimated by sequential organ failure assessment (SOFA) score. Every day we classified all patients in one of the following three categories: non-systemic inflammatory condition (non-SIRS), SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/-0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and neutrophils did not differ significantly between patients with SIRS non-infected and infected SIRS. CRP was elevated in all three groups but didn't differ significantly between SIRS non-infected and septic patients. Area under receiver operating curves was 0.975 and showed reasonable discriminative power (p = 0.002, 95% CI, 0.91-1.035) in predicting of sepsis only for PCT.. Serum procalcitonin levels can be used as an early indicator of septic complication in patients with severe burn injury.

Topics: Analysis of Variance; Biomarkers; Body Temperature; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Meta-Analysis as Topic; Odds Ratio; Protein Precursors; Reproducibility of Results; Sepsis; Uncertainty

The results of recent studies suggest the usefulness of PCT for early diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to determine the behavior of serum PCT concentrations in both uninfected and infected neonates, and to assess the value of this marker for diagnosis of neonatal sepsis of vertical transmission.. PCT was measured in 827 blood samples collected prospectively from 317 neonates admitted to 13 acute-care teaching hospitals in Spain over one year. Serum PCT concentrations were determined by a specific immunoluminometric assay. The diagnostic efficacy of PCT at birth and within 12-24 h and 36-48 h of life was evaluated calculating the sensitivity, specificity, and likelihood ratio of positive and negative results.. 169 asymptomatic newborns and 148 symptomatic newborns (confirmed vertical sepsis: 31, vertical clinical sepsis: 38, non-infectious diseases: 79) were studied. In asymptomatic neonates, PCT values at 12-24 h were significantly higher than at birth and at 36-48 h of life. Resuscitation at birth and chorioamnionitis were independently associated to PCT values. Neonates with confirmed vertical sepsis showed significantly higher PCT values than those with clinical sepsis. PCT thresholds for the diagnosis of sepsis were 0.55 ng/mL at birth (sensitivity 75.4%, specificity 72.3%); 4.7 ng/mL within 12-24 h of life (sensitivity 73.8%, specificity 80.8%); and 1.7 ng/mL within 36-48 h of life (sensitivity 77.6%, specificity 79.2%).. Serum PCT was moderately useful for the detection of sepsis of vertical transmission, and its reliability as a maker of bacterial infection requires specific cutoff values for each evaluation point over the first 48 h of life.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Follow-Up Studies; Glycoproteins; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Prognosis; Prospective Studies; Protein Precursors; Sepsis

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Leukocyte Count; Protein Precursors; Sepsis; Time Factors

The goal of the study was to analyse plasma procalcitonin (PCT) concentrations during infectious events of burns in ICU. Clinical and laboratory data were collected at admission and twice a week in burned patients admitted with a total body surface area (TBSA) >20%. Procalcitonin was determined using both a semi-quantitative detection (PCT-Q) and a quantitative immunoluminometric method (PCT-Lumi). A total of 359 time points in 25 consecutive patients with 40+/-17% (20-86%) TBSA burned, defined as a procalcitonin concentration associated with an inflammatory status according to society critical care medicine definition, were made. The principal site of infection was the respiratory tract (84% of patients required mechanical ventilation). PCT-Lumi values corresponded to the four semi-quantitative ranges of PCT-Q and statistically reflected the simultaneously observed inflammatory status (Kruskall-Wallis test). The area under the receiver operating characteristic curve for C-reactive protein (CRP) was higher than those for PCT and white blood cell (WBC) count, but this difference was not significant. The optimum PCT cut-off value was 0.534 ng/ml with sensitivity and specificity of 42.4% and 88.8%, respectively. However, PCT does not appear to be superior to C-reactive protein (CRP) and white blood count (WBC) as diagnosis marker of sepsis in burns. PCT is not sufficient to diagnose and to follow infection in burns admitted in ICU.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Cross Infection; Female; Humans; Leukocyte Count; Luminescent Measurements; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis

Procalcitonin (PCT) is a precursor of the hormone calcitonin and has been proposed as a marker of infection in critically ill patients. We evaluated the role of procalcitonin in the early detection of sepsis in an Australian intensive care-high dependency unit (ICU/HDU).. This prospective observational study enrolled 204 consecutive patients admitted to the ICU/HDU of Wollongong Hospital, NSW, over a 3-month period, October to December 2001. Of the 204, 172 (84%) were included in the final analysis. Patient demographic data, serum PCT levels and the vital signs required to score the criteria for systemic inflammatory response syndrome (SIRS) and sepsis were recorded daily until the patient left the ICU. Cultures were obtained when clinically indicated.. PCT measurement appears a useful screening test for sepsis with a cut-off value > 0.85 ng/dL. At levels >10 ng/dL, its diagnostic accuracy improves significantly. PCT level was able to discriminate between sepsis and nonsepsis, and between septic shock and non-septic shock. However, it failed to discriminate well between bacterial and non-bacterial SIRS with a 95% CI for area under the receiver operating characteristic curve of 0.59-0.76.. The use of PCT as a screening test (PCT >0.85ng/dL) in conjunction with traditional criteria is of value in the early diagnosis of bacterial sepsis in suspected cases in the ICU. PCT appears to be a reliable diagnostic test for bacterial sepsis at levels > 10 ng/dL.

Topics: Aged; Anti-Bacterial Agents; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; New South Wales; Prospective Studies; Protein Precursors; Sepsis

Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) and procalcitonin (PCT) are often considered to be specific markers for infection. We evaluated plasma levels of sTREM-1 and PCT in patients with systemic inflammatory response syndrome but no sepsis. Noninfected patients undergoing elective heart surgery with cardiopulmonary bypass (n = 76) and patients admitted after out-of-hospital cardiac arrest (n = 54) were followed up for 3 days. Patients with severe sepsis (n = 55) and healthy volunteers (n = 31) were included as positive and negative controls, respectively. Plasma levels of PCT were higher in sepsis patients than in patients who survived after cardiac arrest or after heart surgery. In contrast, peak plasma levels of sTREM-1 in heart surgery and in cardiac arrest patients overlapped with those measured in patients with sepsis. Both sTREM-1 and PCT were significantly higher in cardiac arrest patients who died of refractory shock than in those who died of neurological failure or survived without major neurological damage. In the cardiac arrest patients with refractory shock, sTREM-1 and PCT levels were similar to those in the patients with severe sepsis. In conclusion, sTREM-1 and PCT are not specific for infection and can increase markedly in acute inflammation without infection.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Heart Arrest; Humans; Male; Membrane Glycoproteins; Middle Aged; Protein Precursors; Receptors, Immunologic; Sepsis; Thoracic Surgery; Triggering Receptor Expressed on Myeloid Cells-1

To develop strategies for the prediction of sepsis outcome systemic procalcitonin (PCT) levels were correlated with various clinical parameters.. PCT levels and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were assessed on the day of sepsis diagnosis in a large series (n = 160) of patients developing sepsis after major visceral surgery.. In multivariate analysis, systemic PCT and the APACHE II score could be identified as independent early predictive indicators of lethal sepsis. Combining both indicators at sepsis onset, a prognosis score could be calculated using binary logistic regression analysis allowing the identification of high- and low-risk groups. While 71% of the high-risk patients died of sepsis, 77% of patients assigned to the low-risk group survived the septic complication (sensitivity 71%, specificity 77%).. Calculation of the prognosis-score allowed for an early prediction of the septic course with high sensitivity and specificity. This information could aid in deciding on adequate treatment strategies.

Topics: Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Postoperative Complications; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

This prospective, non-interventional study was conducted in a medical adult intensive care unit to determine the usefulness of procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) determinations in the diagnosis of nosocomial sepsis. Serum PCT and bronchoalveolar lavage fluid sTREM-1 concentrations were measured in 50 critically ill patients suffering from nosocomial sepsis. Ventilator-associated pneumonia (VAP) was diagnosed in 31 patients and extrapulmonary sepsis in 19. Increase serum PCT concentration (>0.15 ng/ml) was found in 44 (88%) patients and was higher in those suffering from a non-pulmonary sepsis. The concomitant BAL sTREM-1 determination correctly classified pulmonary (VAP) versus non-pulmonary origin in 41 out of 44 cases (93%). Even when PCT concentration remained low, sTREM-1 assessment allowed for the detection of the sepsis (VAP) in 50% of cases. Both PCT and sTREM-1 concentrations were low in only 3 patients (6%) in whom sepsis could have been missed if only diagnosed by the measurement of these 2 biomarkers. We therefore concluded that the combined measurement of serum PCT and BAL sTREM-1 concentrations could be of interest in detecting the presence of a nosocomial sepsis and in discriminating VAP versus extrapulmonary infection.

Topics: Adult; Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Humans; Membrane Glycoproteins; Middle Aged; Pneumonia, Ventilator-Associated; Prospective Studies; Protein Precursors; Receptors, Immunologic; Sepsis; Triggering Receptor Expressed on Myeloid Cells-1

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Meta-Analysis as Topic; Predictive Value of Tests; Protein Precursors; Selection Bias; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Disease Progression; Humans; Meta-Analysis as Topic; Predictive Value of Tests; Protein Precursors; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Meta-Analysis as Topic; Predictive Value of Tests; Protein Precursors; Selection Bias; Sepsis; Systemic Inflammatory Response Syndrome

Possibilities of using C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), lactoferrin (LF) and sorption ability of erythrocytes (SAE) as markers of the severity, prognosis and criteria of effectiveness of treatment were studied in 334 patients with abdominal sepsis. The investigation of the sepsis marker dynamics has shown that fast kinetics of CRP and PCT makes it impossible to assess the prognosis and effectiveness of treatment using these markers. IL-6, LF and SAE are the only ones to be used for this purpose.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Laparotomy; Male; Middle Aged; Peritonitis; Protein Precursors; Sepsis; Severity of Illness Index; Survival Rate

Neonatal infection remains a major diagnostic problem because of non-specific clinical signs and symptoms, as well as low sensitivity and specificity of routine laboratory tests. C-reactive protein (CRP), white blood cell count, absolute neutrophil count and immature/total neutrophil ratio are the most widely used tests in the diagnosis of sepsis and provide useful information, but none of these has demonstrated to be reliable in detecting all septic infants. Procalcitonin (PCT) has been suggested as a potentially useful laboratory test performed in umbilical cord blood when perinatal bacterial sepsis is under investigation.. In this study, the reference interval for umbilical cord blood serum PCT was established for the first time by Time-Resolved Amplified Cryptate Emission (TRACE) technology.. The reference interval for PCT in umbilical cord blood serum ranged from 0.04 to 0.43 microg/L in 168 non-infected newborn infants (95% CI 0.02-0.06 and 0.35-0.60 microg/L, respectively). Cord blood serum PCT correctly classified one infected patient out of 90 newborn infants at risk of vertically transmitted sepsis and identified another neonate as a potentially infected patient despite having negative blood cultures. However, cord blood CRP misclassified 21 out of the 90 patients as infected neonates.. Cord blood PCT measured by TRACE is a potentially more useful early marker of neonatal sepsis than cord blood CRP.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Fetal Blood; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Prospective Studies; Protein Precursors; Reference Values; Sepsis

The main causes of complications of allogenic hematopoietic stem cell transplantation are infections and graft versus host disease.. To assess the predictive value of C reactive protein (CRP) and procalcitonin (PCT) in the diagnosis of invasive bacterial infections in children with febrile neutropenia after an allogenic hematopoietic stem cell transplantation.. Prospective follow up of patients aged 18 years or less, with febrile neutropenia after an allogenic hematopoietic stem cell transplantation. In all patients, cultures from sterile sites, CRP and PCT determinations were done. CRP levels were also measured prior to transplantation and three times per week for 30 days after the procedure. An independent evaluator, blinded to the results of CRP and PCT, classified children as with or without invasive bacterial infection.. Thirty three patients aged 9+/-5 years (21 males) were studied. Eight had an invasive bacterial infection. Sensitivity, specificity, positive and negative predictive values of a CRP > or = 90 mg/L for the diagnosis of invasive bacterial infection were 25, 80, 29 and 77%, respectively. The figures for a PCT > or = 0.7 ng/ml were 43, 78, 38 and 82%, respectively. No differences in repeated CRP values measured during evolution, were observed.. A CRP > or = 90 mg/L or a PCT > or = 0.7 ng/ml had a high specificity and negative predictive value but low sensitivity for the diagnosis of invasive bacterial infections in recipients of allogenic hematopoietic stem cell transplantation.

Topics: Adolescent; Anti-Infective Agents; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Hematopoietic Stem Cell Transplantation; Humans; Infant; Infant, Newborn; Male; Neutropenia; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis; Shock, Septic

To investigate the reliability of serum procalcitonin (PCT) as an early diagnostic test (within the first 12 hours of life) of neonatal sepsis in newborns with maternal or neonatal risk factors for infection.. We performed a prospective study of 123 newborns consecutively admitted to neonatal unit over a 2-year period with at least one risk factor for infection. We constructed a 2x2 table between the validated test (serum PCT by semi-quantitative assay, with several cut-off points: 0.5, 2 and 10 ng/ml) and the reference assay (blood culture or clinical, laboratory and microbiological confirmation of sepsis). The validity (sensitivity, specificity), safety [positive predictive value (PPV) and negative predictive value (NPV)] and likelihood ratios (LR+ and LR-) of the test were calculated.. Serum PCT was measured within the first 12 hours of life in 95% of the patients (mean and median=6 hours). The best cut-off point for serum PCT was 2 ng/ml, and, taking subsequent clinical-laboratory-microbiological confirmation of sepsis as the best reference assay, showed a sensitivity of 100% (95% CI 65-100), specificity of 82% (95% CI 74-88), PPV of 25% (95% CI 13-44), NPV of 100% (95% CI 96-100), LR+ of 5.5 (95% CI 3.7-8.1), and LR- of 0.. Serum PCT levels<2 ng/ml within the first 6-12 hours of life in newborns with risk factors for infection are useful as a screening assay to rule out neonatal sepsis with a sensitivity of 100% (false negatives=0% and NPV=100%). However, for subsequent confirmation a more specific assay (with a low false positive rate and high PPV) should be used, such as C-reactive protein. The higher cost of the serum PCT test should be weighed against shorter admissions as a result of its use.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Male; Prospective Studies; Protein Precursors; Reproducibility of Results; Risk Factors; Sepsis

Systemic inflammatory response syndrome (SIRS), severe infection and sepsis are the problems of present interest in contemporary medicine. The specificity and sensitivity of widespread clinical and laboratory parameters are insufficient for diagnosing these diseases. A new marker for diagnosing of infective etiology of SIRS, severe infection and sepsis which allows early diagnosis and begin specific treatment is procalcitonin (PCT). In severe viral infections or inflammatory reaction of non-infective origin the level of PCT does not elevate or increases moderately. The level of PCT correlates with the severity of SIRS: the more severe the SIRS, the higher the level of PCT. The monitoring of PCT allows a rapid diagnosis of infective complications in patients after severe injuries or operations, in acute respiratory distress syndrome. PCT is considered as a marker of severe bacterial and parasitic infection. However, PCT should not be considered as the only marker we can rely upon in diagnosing of sepsis. The levels of PCT correlate with levels of TNF and IL-6. But the pathophysiological role of PCT in sepsis is not definitely clear yet. The indexes of PCT are most valuable for evaluating treatment efficiency and prognosis.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Protein Precursors; Sepsis

To evaluate whether procalcitonin (PCT) and C reactive protein (CRP) are able to discriminate between sepsis and systemic inflammatory response syndrome (SIRS) in critically ill children.. Prospective, observational study in a paediatric intensive care unit. Kinetics of PCT and CRP were studied in patients undergoing open heart surgery with cardiopulmonary bypass (CPB) (SIRS model; group I1) and patients with confirmed bacterial sepsis (group II).. In group I, PCT median concentration was 0.24 ng/ml (reference value <2.0 ng/ml). There was an increment of PCT concentrations which peaked immediately after CPB (median 0.58 ng/ml), then decreased to 0.47 ng/ml at 24 h; 0.33 ng/ml at 48 h, and 0.22 ng/ml at 72 h. CRP median concentrations remained high on POD1 (36.6 mg/l) and POD2 (13.0 mg/l). In group II, PCT concentrations were high at admission (median 9.15 ng/ml) and subsequently decreased in 11/14 patients who progressed favourably (median 0.31 ng/ml). CRP levels were high in only 11/14 patients at admission. CRP remained high in 13/14 patients at 24 h; in 12/14 at 48 h; and in 10/14 patients at 72 h. Median values were 95.0, 50.9, 86.0, and 20.3 mg/l, respectively. The area under the ROC curve was 0.99 for PCT and 0.54 for CRP. Cut off concentrations to differentiate SIRS from sepsis were >2 ng/ml for PCT and >79 mg/l for CRP.. PCT is able to differentiate between SIRS and sepsis while CRP is not. Moreover, unlike CRP, PCT concentrations varied with the evolution of sepsis.

Topics: Adolescent; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Child; Child, Preschool; Diagnosis, Differential; Female; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Postoperative Complications; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT) and C reactive protein (CRP) concentrations in umbilical cord blood of 197 neonates were measured to evaluate their value as markers of infection. Sixteen of the neonates were infected. The sensitivity, specificity, and negative and positive predictive values were respectively 87.5%, 98.7%, 87.5%, and 98.7% for PCT and 50%, 97%, 67%, and 94% for CRP. Serum PCT in cord blood seems to be a useful and early marker of antenatal infection.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Epidemiologic Methods; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infectious Disease Transmission, Vertical; Protein Precursors; Sepsis

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%-90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Interleukin-6; Interleukin-8; Male; Protein Precursors; Sepsis

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Immunologic Tests; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sepsis

To determine normal concentrations of procalcitonin in preterm infants shortly after birth and to assess its accuracy in detecting bacterial infection.. Blood samples of 100 preterm infants were prospectively drawn during the first 4 days of life for determination of procalcitonin concentration. Infants were classified into four groups according to their sepsis status.. Mean (SD) gestational age and birth weight were 32 (2.9) weeks and 1682 (500) g respectively. A total of 283 procalcitonin concentrations from healthy infants were plotted to construct nomograms of physiologically raised procalcitonin concentration after birth, stratified by two groups to 24-30 and 31-36 weeks gestation. The peak 95th centile procalcitonin concentration was plotted at 28 hours of age; values return to normal after 4 days of life. Only 12 infants were infected, and 13 of their 16 procalcitonin concentrations after birth were higher than the 95th centile, whereas samples taken at birth were lower. In a multivariable analysis, gestational age, premature rupture of membrane, and sepsis status influenced procalcitonin concentration independently, but maternal infection status did not.. The suggested neonatal nomograms of preterm infants are different from those of term infants. Procalcitonin concentrations exceeding the 95th centile may be helpful in detecting congenital infection, but not at birth.

Topics: Aging; Bacterial Infections; Biomarkers; Birth Weight; Calcitonin; Calcitonin Gene-Related Peptide; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Nomograms; Protein Precursors; Reference Values; Sepsis

A 64-year-old male with an APC resistance (factor V mutation Leiden) and interrupted oral anticoagulation due to an erosive gastritis, was admitted to hospital for increasing dyspnoea. Transthoracic echocardiography revealed a floating thrombus via an open foramen ovale in both atria reaching both ventricles. Sonography showed multiple stage thrombosis of the left leg reaching to the V. femoralis superficialis. A few months previously, peripheral pulmonary artery embolization has been confirmed by scintigraphy. The patient was transferred to our hospital and underwent emergency surgery for closure of the atrial septum defect and thrombus removal. On the 4th postoperative day, the patient was transferred to the normal ward, however, on the 10th postoperative day, the patient developed a symptomatic transitory psychotic syndrome and became hypotensive before he was transferred to the ICU. Due to impaired oxygenation and the patient's history, a new pulmonary artery embolization was suspected. After ICU admission, the patient required increasing norepinephrine support and rapidly developed septic fever. However, serum procalcitonin was elevated and a computed tomography (skull, chest and abdomen) was performed for a focus search. Pulmonary artery embolism could be ruled out but an oval structure near to the ampulla recti (ca. 30 x 20 mm) was identified as an abscess and immediate abscess incision was performed. After surgery, the further course was characterized by a steep fall in vasopressor support and body temperature. The patient was transferred to the normal ward on the 2nd postoperative day. This case shows that procalcitonin allows early and reliable diagnosis of sepsis in patients with undefined shock.

Topics: Activated Protein C Resistance; Anticoagulants; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Critical Care; Heart Septal Defects, Atrial; Humans; Male; Middle Aged; Protein Precursors; Psychoses, Substance-Induced; Sepsis; Shock, Septic

Clinicians are in need of better diagnostic markers in diagnosing infections and sepsis. We studied the ability of procalcitonin, lipopolysaccharide-binding protein, IL-6 and C-reactive protein to identify patients with infection and sepsis.. Plasma and serum samples were obtained on admission from patients with suspected community-acquired infections and sepsis. Procalcitonin was measured with a time-resolved amplified cryptate emission technology assay. Lipopolysaccharide-binding protein and IL-6 were measured with a chemiluminescent immunometric assay.. Of 194 included patients, 106 had either infection without systemic inflammatory response syndrome or sepsis. Infected patients had significantly elevated levels of procalcitonin, lipopolysaccharide-binding protein, C-reactive protein and IL-6 compared with noninfected patients (P < 0.001). In a receiver-operating characteristic curve analysis, C-reactive protein and IL-6 performed best in distinguishing between noninfected and infected patients, with an area under the curve larger than 0.82 (P < 0.05). IL-6, lipopolysaccharide-binding protein and C-reactive protein performed best in distinguishing between systemic inflammatory response syndrome and sepsis, with an area under the curve larger than 0.84 (P < 0.01). Procalcitonin performed best in distinguishing between sepsis and severe sepsis, with an area under the curve of 0.74 (P < 0.01).. C-reactive protein, IL-6 and lipopolysaccharide-binding protein appear to be superior to procalcitonin as diagnostic markers for infection and sepsis in patients admitted to a Department of Internal Medicine. Procalcitonin appears to be superior as a severity marker.

Topics: Acute-Phase Proteins; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Community-Acquired Infections; Female; Humans; Interleukin-6; Male; Membrane Glycoproteins; Middle Aged; Prospective Studies; Protein Precursors; Sepsis

To evaluate procalcitonin (PCT) as a diagnostic marker of neonatal sepsis of vertical transmission and to compare the results of PCT with those of the most widely used laboratory tests for sepsis.. A prospective study was conducted in 136 blood samples from 69 newborn infants admitted to a neonatal department. PCT, C-reactive protein (CRP), leukocyte count, and the immature-to-total neutrophil ratio (I/T ratio) were measured. The PCT reference range of controls from 0 to 72 hours of life was constructed, and the diagnostic efficiency of the tests was calculated, with their 95 % confidence intervals (95 % CI).. This study included 35 controls, 24 neonates with noninfectious disorders, and 10 neonates with sepsis (5 with culture-proven sepsis). PCT, CRP, and the I/T ratio discriminated septic from nonseptic patients. Their areas under the ROC curve were 0.696 (p = 0.009), 0.735 (p = 0.002), and 0.703 (p = 0.006), respectively, with no statistically significant differences. The accuracy of PCT, CRP, and leukocyte count improved after 24 hours of life with areas under the ROC curve of 0.813 (p = 0.007), 0.826 (p = 0.005), and 0.841 (p = 0.003), respectively. Overall, PCT detected vertically transmitted sepsis with a sensitivity of 68.4 % (95 % CI: 46.0 %-84.6 %), specificity of 82.4 % (95 % CI: 72.2 %-89.4 %), positive likelihood ratio of 3.89 (95 % CI: 2.18 %-6.96 %), and negative likelihood ratio of 0.38 (95 % CI: 0.19 %-0.76 %), similar to those of CRP.. PCT may be a useful marker for the diagnosis of vertically transmitted sepsis. Studies with larger sample sizes are required to establish the accuracy of PCT.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Nosocomial sepsis is a major problem in neonatal units. Because the clinical signs are nonspecific, highly reliable diagnostic markers are required to guide diagnosis. The aim of this study was to evaluate the utility of procalcitonin (PCT) as a diagnostic marker for nosocomial neonatal sepsis, and to compare the results of PCT with those of the most widely used laboratory tests for sepsis.. Twenty neonates with nosocomial sepsis and 20 controls aged 4-30 days were included in a prospective study performed in a neonatal intensive care unit. PCT, C-reactive protein (CRP), leukocyte count, and the immature-to-total neutrophil ratio (I/T ratio) were measured at onset of signs of infection. The sensitivity, specificity, and likelihood ratio for a positive (LR+) and a negative (LR-) result were calculated.. PCT, CRP, and the I/T ratio discriminated septic from nonseptic patients. Their areas under the ROC curve were 0.849, 0.880, and 0.884, respectively, with no statistically significant differences. Optimal cut-off values were: PCT > or = 0.65 ng/ml (sensitivity 85 %, specificity 80 %, LR 1 4.25, LR- 0.19), PCR > or = 5 .g/ml (sensitivity 80 %, specificity 95 %, LR 1 16, LR- 0.21), and I/T > or = 0.03 (sensitivity 90 %, specificity 75 %, LR 1 3.6, LR- 0.13).. PCT may be a useful marker for the diagnosis of nosocomial neonatal sepsis. Studies with larger samples are required to compare the accuracy of PCT with that of other markers of sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Female; Humans; Infant, Newborn; Male; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described to identify a high-risk intensive care unit population consisting of patients with sepsis or with higher mortality rates than patients with normal aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a diagnostic and prognostic marker of infection.. Prospective, observational study investigating the predictive value of aPTT waveform analysis for the diagnosis and prognosis of sepsis.. Surgical intensive care unit of a university hospital.. We studied 187 consecutive patients who fulfilled at least two or more criteria of the systemic inflammatory response syndrome at admission or during intensive care stay and classified as having systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an 8-month period.. Laboratory analyses including aPTT waveform analysis and procalcitonin and C-reactive protein concentrations were measured at days 1-3.. The final diagnoses were systemic inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and septic shock in 23% of patients. On day 1, the biphasic waveform was significantly more abnormal in patients with severe sepsis or septic shock than in patients with systemic inflammatory response syndrome or sepsis. The biphasic waveform was more accurate than procalcitonin and C-reactive protein for differentiating patients with severe sepsis and septic shock, with 90% sensitivity and 92% negative predictive value. Biphasic waveform values were significantly more abnormal during days 1-3 in septic nonsurvivors than in survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best specificity (91%) and negative predictive value (98%) for the prognosis of sepsis-related mortality on day 3.. In intensive care units, when the analyzer is available, aPTT waveform analysis is an inexpensive, rapid, effective, and readily available tool providing information for the diagnosis of severe sepsis and the prognosis of septic patients.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycoproteins; Humans; Male; Middle Aged; Partial Thromboplastin Time; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Survival Rate

It has recently been suggested that serum procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. The aim of this prospective multicenter study was to assess the usefulness of PCT as a marker of neonatal sepsis of nosocomial origin.. One hundred infants aged between 4 and 28 days of life admitted to the Neonatology Services of 13 acute-care teaching hospitals in Spain over 1-year with clinical suspicion of neonatal sepsis of nosocomial origin were included in the study. Serum PCT concentrations were determined by a specific immunoluminometric assay. The reliability of PCT for the diagnosis of nosocomial neonatal sepsis at the time of suspicion of infection and at 12-24 h and 36-48 h after the onset of symptoms was calculated by receiver-operating characteristics (ROC) curves. The Youden's index (sensitivity + specificity - 1) was used for determination of optimal cutoff values of the diagnostic tests in the different postnatal periods. Sensitivity, specificity, and the likelihood ratio of a positive and negative result with the 95% confidence interval (CI) were calculated.. The diagnosis of nosocomial sepsis was confirmed in 61 neonates. Serum PCT concentrations were significantly higher at initial suspicion and at 12-24 h and 36-48 h after the onset of symptoms in neonates with confirmed sepsis than in neonates with clinically suspected but not confirmed sepsis. Optimal PCT thresholds according to ROC curves were 0.59 ng/mL at the time of suspicion of sepsis (sensitivity 81.4%, specificity 80.6%); 1.34 ng/mL within 12-24 h of birth (sensitivity 73.7%, specificity 80.6%), and 0.69 ng/mL within 36-48 h of birth (sensitivity 86.5%, specificity 72.7%).. Serum PCT concentrations showed a moderate diagnostic reliability for the detection of nosocomial neonatal sepsis from the time of suspicion of infection. PCT is not sufficiently reliable to be the sole marker of sepsis, but would be useful as part of a full sepsis evaluation.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Spain

Topics: Adolescent; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Fever of Unknown Origin; Humans; Infant; Interleukin-6; Male; Neoplasms; Neutropenia; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Statistics, Nonparametric

Procalcitonin (PCT) is widely accepted as an early marker of the severity of sepsis and its prognosis. This study was designed to evaluate the utility of PCT in the early diagnosis of immediate postoperative complications (infectious and non-infectious) following cephalic pancreatoduodenectomy (PD).. Thirty-one patients who underwent elective PD were prospectively analyzed. The patients were divided into two groups according to the presence or absence of postoperative complications. Plasma PCT concentrations were determined by an immunochromatographic method. The correlation between PCT concentrations and the presence of complications, as well as the existence of statistically significant differences in PCT concentrations between the 2 groups of patients, were analyzed. The value of plasma PCT concentrations in predicting complications compared with that of other biochemical variables (C-reactive protein, lactic acid, base excess) and clinical parameters (systemic inflammatory response syndrome) was analyzed.. Significant differences in PCT concentrations were found between the two groups. An inverse correlation between marker levels and patient outcome was observed. The variables that best predicted the development of complications were PCT concentrations and axillary temperature.. Plasma PCT should be taken into account as a useful marker for postoperative clinical course in the follow-up of PD and for the early detection of non-infectious complications.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pancreaticoduodenectomy; Postoperative Care; Postoperative Complications; Predictive Value of Tests; Preoperative Care; Prospective Studies; Protein Precursors; Sepsis

Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation.. More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay.. PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay.. PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Survival Analysis

The diagnostic value of procalcitonin, C-reactive protein, tumor necrosis factor-alpha, and interleukin-10 levels in differentiating sepsis from severe sepsis and the prognostic value of these levels in predicting outcome were evaluated and compared in patients with community-acquired sepsis, severe sepsis, and septic shock in the first 72 h of admission to the hospital. Thirty-nine patients were included in the study. The severe sepsis and septic shock cases were combined in a single "severe sepsis" group, and all comparisons were made between the sepsis (n=21 patients) and the severe sepsis (n=18 patients) groups. Procalcitonin levels in the severe sepsis group were found to be significantly higher at all times of measurements within the first 72 h and were significantly higher at the 72nd hour in patients who died. Procalcitonin levels that remain elevated at the 72nd hour indicated a poor prognosis. C-reactive protein levels were not significantly different between the groups, nor were they indicative of prognosis. No significant differences in the levels of tumor necrosis factor-alpha were found between the sepsis and severe sepsis groups; however, levels were higher at the early stages (at admission and the 24th hour) in patients who died. Interleukin-10 levels were also higher in the severe sepsis group and significantly higher at all times of measurement in patients who died. When the diagnostic and prognostic values at admission were evaluated, procalcitonin and interleukin-10 levels were useful in discriminating between sepsis and severe sepsis, whereas tumor necrosis factor-alpha and interleukin-10 levels were useful in predicting which cases were likely to have a fatal outcome.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Female; Humans; Interleukin-10; Male; Middle Aged; Prognosis; Protein Precursors; Sepsis; Shock, Septic; Tumor Necrosis Factor-alpha

To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.. Prospective observational cohort study.. : Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark.. Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit.. Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level.. Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8).. A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Denmark; Female; Humans; Infant; Leukocyte Count; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Survival Analysis

To evaluate the predictive value of relevant clinical and laboratory parameters (complete blood count (CBC), C-reactive protein (CRP), procalcitonin (PCT) and Staphylococcus-specific polymerase chain reaction (PCR)) in neonates with suspected late-onset sepsis (LOS).. NICU neonates were prospectively followed for septic events. One hundred and eleven neonates developed 148 suspected septic events beyond 3 d of age. We recorded the clinical signs and laboratory abnormalities at onset of sepsis, serum CRP and PCT, Staphylococcus-specific PCR, microbiological data, and empiric antimicrobial therapy.. Variables significantly associated with subsequently confirmed LOS included hypotension (relative risk (RR) = 5.6, 95% CI 3.29-9.53), mechanical ventilation (RR = 2.46, 95% CI 1.24-4.86), immature/total neutrophil ratio (I/T) > 0.2 (RR = 5.13, 95% CI 2.54-10.31), CRP > 1.0 mg/dl (RR = 2.85, 95% CI 1.32-6.15), and small-for-gestational-age (SGA) status (RR = 2.13, 95% CI 1.03-4.38). PCT was not significantly associated with LOS. For detection of staphylococcal bacteremia, Staphylococcus-specific PCR showed: sensitivity 57.1%, specificity 94.7%, positive predictive value 53.3%, and negative predictive value 95.4%.. Hypotension, mechanical ventilation, I/T > 0.2, CRP > 1.0 mg/dl, and SGA status at onset of sepsis are significant predictors of proven neonatal LOS. Staphylococcus-specific PCR might be of value in ruling out staphylococcal sepsis.

Topics: Age of Onset; Blood Cell Count; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Polymerase Chain Reaction; Prospective Studies; Protein Precursors; Sepsis; Staphylococcus

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Denmark; Humans; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To assess the effectiveness of different procalcitonin cutoff values to distinguish non-infected (negative+SIRS) from infected (sepsis+severe sepsis+septic shock) medical and surgical patients.. PCT plasma concentration was measured using an automated chemiluminescence analyzer in 1013 samples collected in 103 patients within 24 h of admission in ICU and daily during the ICU stay. We compared PCT levels in medical and surgical patients. We also compared PCT plasma levels in non-infected versus infected patients and in SIRS versus infected patients both in medical and in surgical groups.. Median values of PCT plasma concentrations were significantly higher in infected than in non-infected groups, both in medical (3.18 vs. 0.45 microg/L) (p<0.0001) and in surgical (10.45 vs. 3.89 microg/L; p<0.0001) patients. At the cutoff of 1 microg/L, the LR+ was 4.78, at the cutoff of 6 microg/L was 12.53, and at the cutoff of 10 microg/L was 18.4.. This study highlights the need of different PCT cutoff values in medical and surgical critically ill patients, not only at the ICU admission but also in the entire ICU stay.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Male; Middle Aged; Protein Precursors; ROC Curve; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

To assess the role of procalcitonin in detecting nosocomial sepsis in preterm infants, after the onset of clinical symptoms.. 100 preterm infants, 24-36 wk of gestation, were followed from the age of 3 d until discharge. Procalcitonin and C-reactive protein (CRP) levels were measured within 3 d of sepsis workup events.. 141 blood samples were drawn from 36 infants during 85 episodes of sepsis workup performed between 4 and 66 d of life. Of these episodes, 51 (60%) were not a result of documented sepsis and thereby served as the negative comparison group. Median procalcitonin levels were higher in the septic group compared with the non-septic group at the time of the sepsis workup (2.7 vs 0.5 ng/ml, p=0.003), at 1-24 h after the sepsis workup (4.6 vs 0.6 ng/ml, p=0.003), and at 25-48 h (6.9 vs 2.0 ng/ml, p=0.016). Using high cutoff levels, both procalcitonin (2.3 ng/ml) and CRP (30 mg/l) had high specificity and positive predictive value (97%, 91% and 96%, 87%, respectively) but low sensitivity (48% and 41%, respectively) to detect sepsis. Areas under the ROC curve for procalcitonin and CRP were 0.74 and 0.73, respectively.. Procalcitonin >2.3 ng/ml or CRP >30 mg/l indicates a high likelihood for neonatal sepsis, and antibiotic therapy should be continued even in the presence of sterile cultures.

Topics: Bacteria; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Humans; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Israel; Protein Precursors; ROC Curve; Sepsis

A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Immunosuppression Therapy; Norepinephrine; Pneumonia, Bacterial; Protein Precursors; Pseudomonas Infections; Sepsis; Shock, Septic

To evaluate the discrimination of serum procalcitonin (PCT) and interleukin-6 (IL-6) between patients with sepsis and non-infectious inflammatory response syndrome (SIRS) and the prediction power of clinical outcome.. A perspective study was performed in 27 patients with sepsis and 30 patients with non-infectious SIRS. The serum concentrations of PCT, IL-6, C-reactive protein (CRP), white blood cell count, percentage of neutrophil, absolute neutrophil count, and maximal body temperature were obtained less than 24 hours after clinical onset of sepsis or SIRS.. The serum levels of PCT and IL-6 and percentage of neutrophil were significantly higher in patients with sepsis than in those with non-infectious SIRS (PCT: 5.54 [1.20, 32.74] microg/L vs 0.77 [0.22, 3.90] microg/L, P=0.001; IL-6: 163.66 [33.60, 505.26] ng/L vs 37.72 [22.52, 110.78] ng/L, P=0.004; CRP [15.28 +/- 8.41] g/L vs [9.51 +/- 7.65] g/L, P=0.010; and percentage of neutrophil: 0.91 +/- 0.04 vs 0.88 +/- 0.04, P=0.010). Receiver operating characteristic curve showed that the power of PCT and IL-6 were the best of all above. There was significant correlation between serum PCT or IL-6 and the acute physiology and chronic health evaluation (APACHE II) or sepsis-related organ failure assessment (SOFA) scores, so was between serum PCT and the intensive care unit (ICU) length of stay.. PCT and IL-6 are more reliable indicators to differentiate sepsis and non-infectious SIRS than the conventional inflammatory markers, and correlate with the disease severity. PCT levels are significantly correlated with ICU length of stay.

Topics: Adult; Aged; APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Interleukin-6; Length of Stay; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

To compare the utility of procalcitonin (PCT) vs C-reactive protein (CRP) as indicators of late-onset neonatal sepsis in very low birth weight (VLBW) infants.. PCT and CRP levels were measured in VLBW infants with suspected sepsis and controls. Comparisons were made between infected vs noninfected infants. Using cutoff values of 0.5 and 1.0 ng/ml for PCT and 0.8 mg/dl for CRP, sensitivity, specificity, positive and negative predictive values were calculated to evaluate these assays as potential predictors of late-onset sepsis.. A total of 67 infants were evaluated. Mean PCT levels were significantly higher in the infected group (5.41 ng/ml) compared to the noninfected group (0.43 ng/ml) (p < 0.001). At a cut off value of 0.5 ng/ml, the sensitivity of PCT was 97%, whereas that of CRP was 73% in predicting late-onset sepsis. At a PCT cutoff of 1.0 ng/ml, sensitivities of PCT and CRP were similar (72% each).. PCT (0.5 ng/ml) is more sensitive than CRP in predicting late-onset sepsis in VLBW infants.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Male; Protein Precursors; Sensitivity and Specificity; Sepsis

The clinical significance of serum procalcitonin (PCT) for discriminating between bacterial infectious disease and nonbacterial infectious disease (such as systemic inflammatory response syndrome (SIRS)), was compared with the significance of endotoxin, beta-D: -glucan, interleukin (IL)-6, and C-reactive protein (CRP) in a multicenter prospective study. The concentrations of PCT in patients with systemic bacterial infection and those with localized bacterial infection were significantly higher than the concentrations in patients with nonbacterial infection or noninfectious diseases. In addition, PCT, endotoxin, IL-6, and CRP concentrations were significantly higher in patients with bacterial infectious disease than in those with nonbacterial infectious disease (P<0.001, P<0.005, P<0.001, and P<0.001, respectively). The cutoff value of PCT for the discrimination of bacterial and nonbacterial infectious diseases was determined to be 0.5 ng/ml, which was associated with a sensitivity of 64.4% and specificity of 86.0%. Areas under the receiver operating characteristic curves (POCs) were 0.84 for PCT, 0.60 for endotoxin, 0.77 for IL-6, and 0.78 for CRP in the combined group of patients with bacterial infectious disease and those with nonbacterial infectious disease, and the area under the ROC for PCT was significantly higher than that for endotoxin (P<0.001). In patients diagnosed with bacteremia based on clinical findings, the positive rate of diagnosis with PCT was 70.2%, while that of blood culture was 42.6%. PCT is thus essential for discriminating bacterial infection from SIRS, and is superior in this respect to conventional serum markers and blood culture.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Japan; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Several reports presented at the 25th International Symposium on Intensive Care and Emergency Medicine held March 21-25 in Brussels, Belgium, have demonstrated the efficacy of using the prohormone procalcitonin (PCT) as a biomarker for severe sepsis. This article reviews some of the most exciting studies.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Clinical Trials as Topic; Humans; Prognosis; Protein Precursors; Sepsis; Severity of Illness Index

This prospective consecutive observational study describes the blood levels of macrophage migration inhibitory factor (MIF), other cytokines, and markers of acute-phase response in 49 consecutive patients who developed the clinical syndrome of sepsis after cardiac surgery. Before starting antimicrobial treatment, all patients underwent microbiologic screening, and blood samples were collected. These samples subsequently were assayed for MIF, macrophage chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and -10, procalcitonin (PCT), and C-reactive protein (CRP). Patients with positive cultures (n = 25) had a higher mortality (P = 0.046) and higher levels of MIF (P < 0.001) than those with negative cultures (n = 24). We could not detect significant difference between the groups concerning the levels of CRP, PCT, IL6, IL10, MCP-1, or TNF-alpha. MIF levels showed an area under receiver operator curve of 0.823 for the prediction of culture-proven bacterial infection, with the best cut-off value at 988.5 pg/mL. In conclusion, circulating levels of MIF could be indicated as a valuable marker of microbiologically documented sepsis in patients after cardiac surgery, which suggests that MIF may be prospectively explored as a useful diagnostic tool in this setting.

Topics: Acute-Phase Reaction; Aged; Anti-Infective Agents; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Chemokine CCL2; Cytokines; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Macrophage Migration-Inhibitory Factors; Male; Middle Aged; Pilot Projects; Postoperative Complications; Protein Precursors; ROC Curve; Sepsis; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha

Prospective examination whether changes in interleukin (IL)-6, IL-10 or procalcitonin (PCT) concentrations correlate with poor outcome in patients with severe sepsis in comparison with APACHE III or SAPS II.. 33 patients who fulfilled the criteria for severe sepsis have been included in the study. Blood samples were collected for cytokine and PCT determinations. The Acute Physiology, Age and Chronic Health Evaluation (APACHE) III score and the Simplified Acute Physiology Score (SAPS) II were calculated for 3 consecutive days.. 14 out of 33 patients died of multiple organ failure. The areas under the ROC-curves for APACHE III and SAPS II indicated a poor discrimination between survivors and non-survivors. Plasma PCT and IL-10 concentrations were higher in non-survivors than in survivors. IL-6 levels showed no differences between groups. The multivariate analysis of the APACHE III, SAPS II, IL-10 and PCT data showed a significant relationship between APACHE III, PCT plasma levels and outcome.. The data suggest that non-surviving patients have higher PCT and IL-10 values. Only APACHE III score and PCT plasma levels correlated with a poor outcome. Therefore, routine measurements of plasma PCT concentrations might be helpful to improve the mortality risk prediction in patients with severe sepsis.

Topics: Adult; Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-10; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis

To evaluate markers of infection in critically ill neonates and children, comparing lipopolysaccharide-binding protein (LBP) with procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP).. Prospective, observational study in the level III multidisciplinary neonatal and pediatric intensive care unit.. Sixty patients with systemic inflammatory response syndrome (SIRS) and suspected infection classified into two groups: SIRS/sepsis ( n=33) and SIRS/no sepsis ( n=27). We included 29 neonates aged less than 48 h (neonates <48 h), 12 neonates older than 48 h (neonates >48 h), and 19 children. Median disease severity was high in neonates aged under 48 h and moderate in neonates aged over 48 h and children.. Serum LBP, PCT, IL-6, and CRP were measured on two consecutive days. Area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, and predictive values were evaluated.. Serum LBP was higher in patients with SIRS/sepsis than in patients with SIRS/no sepsis. AUC for LBP on the first day of suspected infection was 0.89 in the younger neonates, 0.93 in the older neonates, and 0.91 in children.. In critically ill neonates aged under 48 h LBP on the first day of suspected infection is a better marker of sepsis than IL-6 and PCT, and is similar to CRP. In critically ill neonates aged over 48 h and children LBP is a better marker than IL-6 and CRP, and is similar to PCT.

Topics: Acute-Phase Proteins; Adolescent; Age Factors; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Carrier Proteins; Child; Child, Preschool; Critical Illness; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Interleukin-6; Membrane Glycoproteins; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Predictive Value of Tests; Protein Precursors; Sepsis

Levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) in blood are increased as acute phase proteins in patients with inflammatory conditions. Most of the currently used inflammatory markers, such as erythrocyte sedimentation rate and CRP or SAA levels, are non-specific parameters. By contrast, procalcitonin (PCT) has been reported to be selectively induced by severe infection in systemic inflammatory response syndrome (SIRS) and also in sepsis or multiorgan dysfunction syndrome. PCT expression is induced only slightly, if at all, by viral infections, autoimmune disorders, neoplastic disorders and trauma arising from surgical intervention. Serum PCT and SAA levels were compared in 93 patients with a CRP concentration higher than 100 mg/L and in 26 patients with a CRP concentration lower than 1.5 mg/L. In patients with high levels of CRP, all patients with sepsis and severe bacterial infection showed a significantly increased PCT concentration of more than 1.0 microg/L and it was possible to differentiate between the patients with neoplastic disorders and those with other inflammatory diseases. In patients with low levels of CRP, the PCT concentration was less than 0.3 microg/L and an increased PCT level was not seen in patients with autoimmune disorders or viral and fungal infections. These results suggest that determining the serum PCT level may be useful in the differential diagnosis of severe infection.

Topics: Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Glycoproteins; Humans; Inflammation; Neoplasms; Protein Precursors; Sepsis; Serum Amyloid A Protein

To explore the roles of peripheral blood mononuclear cells (PBMCs) and PBMC-derived macrophages in sepsis-related increased procalcitonin and calcitonin gene-related peptide (CGRP) I production.. Prospective, in vitro primary human cell culture study and human tissue samples gene expression analysis.. University hospital research laboratories.. Cells from healthy donors and septic patients.. PBMCs were obtained from healthy donors. Isolation of pure monocyte cultures was performed by magnetic depletion of nonmonocyte cells from PBMCs. Adipose tissue biopsies and circulating leukocytes were collected from septic patients. Expressions of calcitonin messenger RNA and CGRP I messenger RNA were analyzed using reverse transcriptase-polymerase chain reaction and quantitative real-time polymerase chain reaction. Supernatant procalcitonin and CGRP protein content were determined by ultrasensitive chemiluminometric and radioimmunoassays, respectively.. PBMCs expressed and secreted procalcitonin and CGRP within 3-5 hrs after adherence to endothelial cells or plastic surfaces. This induction was transient, as it was not detectable after 18 hrs. No calcitonin or CGRP I messenger RNA was observed in leukocytes obtained from septic patients with markedly increased serum procalcitonin concentrations. Stimulation with cytokines, endotoxin, or Escherichia coli did not induce expression of calcitonin and CGRP I messenger RNA in PBMC-derived macrophages. However, inflammatory factors released from activated macrophages induced a marked expression of procalcitonin and CGRP in co-cultured human adipocytes.. The adhesion-induced, transient expression and secretion of procalcitonin and CGRP in vitro may play an important role during monocyte adhesion and migration in vivo. PBMC-derived macrophages may contribute to the marked increase in circulating procalcitonin by recruiting parenchymal cells within the infected tissue, as exemplified with adipocytes.

Topics: Adipocytes; Calcitonin; Calcitonin Gene-Related Peptide; Cell Culture Techniques; Humans; Leukocytes; Macrophages; Monocytes; Prospective Studies; Protein Precursors; Reference Values; RNA, Messenger; Sepsis

Topics: Animals; Biomarkers; Blood Cells; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Protein Precursors; Sepsis

Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response.. One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection).. PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12).PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann-Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP.. PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Neonatal septicemia is a critical disease in neonatal period. Its incidence among live births is between 1 per thousand and 8 per thousand. Mortality of neonatal septicemia may be as high as 50% for infants who are not treated. The early signs of septicemia in the newborn are generally nonspecific. Blood culture and the other clinical diagnostic measures are not sufficiently sensitive. The present study aimed at evaluating potential use of soluble intercellular adhesion molecule-1 (sICAM-1), procalcitonin (PCT) and C-reactive protein (CRP) in diagnosis of septicemia.. The experimental group consisted of 50 newborns with septicemia who were treated in Hebei Provincial Children's Hospital from April 1, 2002 to December 30, 2002. Thirty of the 50 cases had positive blood culture. The control group included 35 healthy newborns. Fasting blood samples were taken for bacterial cultures and sICAM-1, CRP, PCT determination. PCT and CRP contents were determined immediately after the specimens were collected. Analyses of sICAM-1 were done after inclusion of the last patient. Serum was separated from each specimen and stored at -20 degrees C within 2 hours. The analyses of sICAM-1 were performed by ELISA technique. CRP was analyzed by immunoturbidimetry assay (ITA). Immunochromatographic test was performed for detection of PCT from 200 ul serum. SPSS 10.0 was used to process the data. P values < 0.05 was considered to be statistically significant. One way analysis of variance (ANOVA), multiple comparison, chi-square test, paired-samples T test, linear correlation, Spearman correlation analysis, ROC curve were used for statistical analysis. The sensitivity, specificity, positive and negative predictive values, accuracy, Youden's index for sICAM-1, PCT, CRP and WBC count were calculated. These values were compared with each other.. (1) The content of sICAM-1 in control group varied widely from 79 to 1252 ng/ml. Comparison of the data indicated that there was significant difference among the three groups in the content of sICAM-1, CRP and PCT (P < 0.05), but not in WBC count. These markers are considered positive if sICAM-1 >or= 300 ng/ml, CRP >or= 8 mg/l, PCT >or= 2 ng/ml. Their sensitivity was higher than WBC (P < 0.05). Among these indices, PCT has the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%), accuracy (89.4%), and Youden's index (80.3%). (2) No significant difference was found in sICAM-1 between pre- and post-treatment (P > 0.05); however, there was significant difference in CRP and PCT. (3) sICAM-1 was in direct proportion to CRP (r = 0.339,P < 0.01). PCT is correlated with sICAM-1, CRP (the spearman correlation coefficient 0.569, 0.482, P < 0.01).. Different individual is in different immune status; The level of sICAM-1 is related with neonatal septicemia. sICAM-1 concentration may be used as a diagnostic tool with high sensitivity (85%) and moderate specificity (54.3%) in neonates suspected of infection. The sensitivity and specificity of CRP (>or= 8 mg/l) were accordingly 87.5% and 54.3%. WBC count had low sensitivity for diagnosis (30.0%); Among these indices, PCT had the highest specificity (94.3%), positive predictive (95.6%), negative predictive (82.5%) Values, accuracy (89.4%), Youden's index (80.3%); No correlation was found between sICAM-1 concentration and their ages in day accordingly. CRP, PCT may be used to estimate the effect of therapy. The correlation of the infectious indices indicates that the body may mobilize many organs at the same time to resist the invasion of organism.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Intercellular Adhesion Molecule-1; Protein Precursors; Sepsis

To define whether procalcitonin should be introduced in the diagnostic criteria of sepsis.. Procalcitonin was estimated in sera of 105 critically ill patients by an immunochemiluminometric assay. Diagnosis was settled by 3 types of criteria: A, the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) 1992 criteria; B, the ACCP/SCCM criteria and concentrations of procalcitonin above 1.0 ng/mL as indicative of SIRS/sepsis; and C, the ACCP/SCCM criteria and concentrations of procalcitonin 0.5 to 1.1 ng/mL for SIRS and above 1.1 ng/mL for sepsis.. Criteria A identified 50.5% of patients with SIRS, 18.1% with sepsis, 0.9% with severe sepsis and 22.9% with septic shock; respective diagnosis by criteria B were 26.7%, 9.5%, 10.5% and 25.7%; and respective diagnosis by criteria C were 19.0%, 25.7%, 9.5%, and 25.7%. Sensitivity of concentrations between 0.5 ng/mL and 1.1 ng/mL was 25.6% for Systemic Inflammatory Response Syndrome (SIRS); and above 1.1 ng/mL 92.8% for sepsis. Sepsis-related death was associated with elevated procalcitonin upon presentation of a clinical syndrome.. Despite the limited diagnostic value of procalcitonin for SIRS, concentrations of procalcitonin above 1.1 ng/mL are highly indicative for sepsis without, however, excluding the presence of SIRS.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Severity of Illness Index; Shock, Septic; Systemic Inflammatory Response Syndrome

It has recently been suggested that procalcitonin (PCT) is of value in the diagnosis of neonatal sepsis, with varying results. This study was to evaluate the role of PCT as a single early marker of neonatal sepsis.. Neonatal Unit, Johannesburg Hospital, and Microbiology Laboratory, National Health Laboratory Service (NHLS), South Africa.. Neonates undergoing evaluation for sepsis between April and August 2002 were eligible for inclusion. Patients were categorised into 'no infection', 'possible infection' and 'definite infection' on the basis of C-reactive protein (CRP), white cell count (WCC), platelet count and blood culture results. PCT was correlated with infection categories.. One hundred and eighty-three neonates were enrolled. One hundred and eighteen had no infection, 52 possible infection and 13 definite infection. PCT differed significantly among infection categories (p < 0.0001) and correlated significantly with CRP at presentation (correlation coefficient 0.404, p < 0.001) and CRP at 24 hours (correlation coefficient 0.343, p < 0.001). PCT predicted 89.5% of definite infection. Receiver operating characteristic (ROC) analysis for PCT to predict definite infection showed odds ratio (OR) 1.145 (95% confidence interval (CI): 1.05-1.25) with an area under the curve of 0.778. PCT had a negative predictive value of 0.95 (95% CI: 0.915-0.988) for definite infection.. Although PCT was significantly related to the category of infection, it is not sufficiently reliable to be the sole marker of neonatal sepsis. PCT would be useful as part of a full sepsis evaluation, but is relatively expensive. A negative PCT on presentation may rule out sepsis, but this needs to be evaluated further.

Topics: Bacteremia; Biomarkers; Birth Weight; Calcitonin; Calcitonin Gene-Related Peptide; Gestational Age; Humans; Infant, Newborn; Logistic Models; Platelet Count; Predictive Value of Tests; Protein Precursors; ROC Curve; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Protein Precursors; Sepsis

This prospective study evaluated serum procalcitonin (PCT) and C-reactive protein (CRP) as markers for systemic inflammatory response syndrome (SIRS)/sepsis and mortality in patients with traumatic brain injury and subarachnoid haemorrhage. Sixty-two patients were followed for 7 days. Serum PCT and CRP were measured on days 0, 1, 4, 5, 6 and 7. Seventy-seven per cent of patients with traumatic brain injury and 83% with subarachnoid haemorrhage developed SIRS or sepsis (P=0.75). Baseline PCT and CRP were elevated in 35% and 55% of patients respectively (P=0.03). There was a statistically non-significant step-wise increase in serum PCT levels from no SIRS (0.4+/-0.6 ng/ml) to SIRS (3.05+/-9.3 ng/ml) to sepsis (5.5+/-12.5 ng/ml). A similar trend was noted in baseline PCT in patients with mild (0.06+/-0.9 ng/ml), moderate (0.8+/-0.7 ng/ml) and severe head injury (1.2+/-1.9 ng/ml). Such a gradation was not observed with serum CRP There was a non-significant trend towards baseline PCT being a better marker of hospital mortality compared with baseline CRP (ROC-AUC 0.56 vs 0.31 respectively). This is the first prospective study to document the high incidence of SIRS in neurosurgical patients. In our study, serum PCT appeared to correlate with severity of traumatic brain injury and mortality. However, it could not reliably distinguish between SIRS and sepsis in this cohort. This is in part because baseline PCT elevation seemed to correlate with severity of injury. Only a small proportion of patients developed sepsis, thus necessitating a larger sample size to demonstrate the diagnostic usefulness of serum PCT as a marker of sepsis. Further clinical trials with larger sample sizes are required to confirm any potential role of PCT as a sepsis and outcome indicator in patients with head injuries or subarachnoid haemorrhage.

Topics: Adult; APACHE; Biomarkers; Brain Injuries; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Hospital Mortality; Humans; Male; Middle Aged; Protein Precursors; Sepsis; Subarachnoid Hemorrhage; Survival Rate; Systemic Inflammatory Response Syndrome

Bacterial infections are associated with a high morbidity and mortality rate in patients with acute and chronic renal failure. Because C-reactive-protein (CRP) is elevated in many patients with renal failure, even in the absence of infection, procalcitonin (PCT) might be useful for the detection of systemic bacterial infections. This cross-sectional observation study measured PCT and CRP in several groups of patients with various types, degrees and treatments of kidney diseases, including patients with sepsis treated with renal replacement therapy.. We determined PCT and CRP in 85 renal patients with different stages and treatments of renal insufficiency: chronic renal failure (CRF) n=23, patients undergoing continuous ambulatory peritoneal dialysis (CAPD) n=20, patients undergoing hemodialysis therapy (HD) n=42 and in a group of 40 patients with septic conditions, including 20 patients with acute renal failure (ARF). The infectious status of the patients was monitored.. PCT in serum (reference value in healthy controls < 1 microg/l) was within the normal range in patients with CRF and in patients on both short-term HD (< 1 year) and long-term HD (> 1 year) (median of 0.25 microg/l and 0.61 microg/l). However, PCT was elevated in patients on CAPD (median of 1.18 microg/l). In patients with sepsis, PCT was massively elevated in both the presence and absence of ARF. In contrast, CRP (reference value < 5 mg/l) was markedly increased in patients undergoing short- and long-term HD (medians of 14.5 and 51.1 mg/l) but not in patients on CAPD. In patients with CRF and systemic bacterial infections, both PCT and CRP were markedly elevated (median PCT 63 microg/l, CRP 130 mg/l) but, in contrast to PCT, CRP values overlapped in infected and non-infected patients. There was no relevant decrease in plasma concentrations of PCT by hemofiltration or hemodialysis in patients with sepsis.. With the exception of CAPD patients, PCT levels were not significantly affected by renal diseases or treatments but were markedly elevated in the presence of infections. Thus PCT is a valuable marker for early diagnosis of systemic bacterial infections in patients with CRF or patients undergoing HD. In contrast, CRP is elevated in several groups with renal diseases and has low specificity for the diagnosis of bacterial infections.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross-Sectional Studies; Data Interpretation, Statistical; Diagnosis, Differential; Female; Hemofiltration; Humans; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Protein Precursors; Renal Dialysis; Sensitivity and Specificity; Sepsis; Time Factors

To examine the relationships between procalcitonin, bacterial infection, sepsis-induced multiple organ failure, and mortality rate in children.. Cohort study.. A multidisciplinary, tertiary-care pediatric intensive care unit.. Seventy-eight children meeting criteria for sepsis or septic shock and 12 critically ill children without sepsis.. Venous or arterial blood sampling.. Demographic, epidemiologic, and outcome data were recorded. Plasma from children with sepsis were collected on days 1 and 3, and procalcitonin concentrations were measured by immunoluminometric assay. Organ failure index scores were determined, and multiple organ failure was defined as organ failure index > or = 3. Persistent multiple organ failure was defined by presence of multiple organ failure on day 3. Procalcitonin concentrations (median [25th percentile-75th percentile]) were increased among children with sepsis on day 1 (2.4 ng/mL [0.2-24.2], p < .01) but not on day 3 (0.8 ng/mL [0.1-8.1], p = nonsignificant) vs. controls (0.2 ng/mL [0.1-0.5]). This increase in procalcitonin concentration was particularly robust among children with bacterial sepsis on day 1 (7.1 ng/mL [0.9-44.8], p < .001) and on day 3 (2.9 ng/mL [0.1-32.4], p < .05). Procalcitonin concentrations were not increased among children with fungal, viral, or culture-negative sepsis vs. controls. Procalcitonin concentrations were persistently increased over time among patients with bacterial sepsis who had persistent multiple organ failure (p < .05) and who died (p < .01) but not among patients with nonbacterial sepsis.. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Further study is needed to better delineate this differential procalcitonin response to bacterial vs. nonbacterial sepsis and to characterize any mechanistic role that procalcitonin might play in the development of bacterial sepsis-induced multiple organ failure and mortality.

Topics: Adolescent; Analysis of Variance; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Protein Precursors; Sepsis; Shock, Septic

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units, Pediatric; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic

The reliability of procalcitonin (PCT) and interleukin-6 (IL-6) was determined and compared with that of C-reactive protein (CRP) in the diagnosis of early-onset sepsis of the neonate within the first 12 h of life. ROC analysis of values of 41 neonates with blood-cultures-positive and clinical sepsis compared with those of 27 uninfected neonates revealed sensitivities for PCT (> or = 6 ng/mL), IL-6 (> or = 60 pg/mL), and CRP (> or = 2.5 mg/L) of 77%, 54%, and 69% and specificities of 91%, 100% and 96%, respectively. Sensitivity of CRP at > or = 8 mg/L was 49% (p = 0.012 compared to PCT).. PCT was the most sensitive diagnostic parameter in the diagnosis of early-onset sepsis within 12 h of life.

Topics: Birth Weight; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Gestational Age; Humans; Infant, Newborn; Interleukin-6; Predictive Value of Tests; Protein Precursors; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Sepsis; Time Factors

Circulating levels of calcitonin gene related peptide (CGRP) and calcitonin precursors, including procalcitonin (PCT) and its free aminopeptide N-procalcitonin (N-PCT), have been found dramatically increased in septic patients. PCT is known to attenuate the chemotaxis of monocytes in response to chemoattractants. This study examined whether CGRP and N-PCT modulate the LPS-induced expression of CD11b, which is one of the major integrins involved in monocyte and neutrophil chemotaxis during a response to microbial infections.. In vitro cell culture study in the immunology laboratory of a university hospital.. Healthy volunteers.. We assessed the effects of N-PCT and CGRP on CD11b expression on monocytes and neutrophils after LPS (2 ng/ml) or fMLP (10(-8) M) challenges. We used a human whole blood model, and measurements were made by flow cytometry. Both peptides in a dose-dependent manner decreased the LPS- and fMLP-induced rise in CD11b in monocytes and neutrophils. As these peptides are thought to act by raising cAMP, we also mimicked their effects with the use of rolipram and forskolin and found similar results.. These findings are in line with recent studies demonstrating anti-inflammatory properties for this family of peptides. CGRP and calcitonin precursors may function as factors suppressing the propagation of inflammation through the inhibition of several processes involved during a response to a bacterial stimulus.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; CD11b Antigen; Cells, Cultured; Chemotaxis, Leukocyte; Colforsin; Cyclic AMP; Drug Evaluation, Preclinical; Flow Cytometry; Humans; Inflammation; Lipopolysaccharides; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Protein Precursors; Rolipram; Sepsis; Tumor Necrosis Factor-alpha; Up-Regulation

To investigate the specific characteristics of serum procalcitonin in children with severe infection, to identify relevant factors influencing procalcitonin increase, to assess its prognostic value, and to compare it with C-reactive protein and neutrophil count. A prospective observational study and 48 hrs of follow-up of a cohort of cases.. A pediatric intensive care unit within a children's university hospital in collaboration with a laboratory mainly involved in research in pediatric clinical immunology.. A total of 80 children (median age, 3.1 yrs; range, 1 month to 16 yrs) admitted to a pediatric intensive care unit by suspicion of sepsis.. All patients were treated according to a protocol using antibiotics, fluid resuscitation, inotropic drugs, and mechanical ventilation when they presented with shock or respiratory failure.. Serum procalcitonin and C-reactive protein were measured at admission in all patients and, when possible, repeated 6,12, 24, and 48 hrs later. In most cases, serum procalcitonin was already very high at onset (range, 1.0-722 ng/mL), and it did not increase significantly afterward. Contrary to C-reactive protein, serum procalcitonin did not vary according to the age of patients. The increase of procalcitonin was higher in patients with shock or multiple organ dysfunction syndrome, having a high severity score (Pediatric Risk of Mortality) or in patients who later died.. Serum procalcitonin levels show a rapid increase in children with sepsis, even in infants < 12 month old, and they have a better prognostic value than C-reactive protein or neutrophil count.

Topics: Adolescent; Anti-Bacterial Agents; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Humans; Infant; Intensive Care Units, Pediatric; Leukocyte Count; Male; Neutrophils; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index

Topics: Adolescent; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Infant; Intensive Care Units, Pediatric; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in the detection of infection and sepsis and in the assessment of severity of sepsis.. Prospective study.. Medicosurgical intensive care unit.. Seventy consecutive adult patients who were admitted to the intensive care unit for an expected stay >24 hrs.. None.. PCT and CRP plasma concentrations were measured daily during the intensive care unit stay. Each patient was examined daily for signs and symptoms of infection and was classified daily in one of the following four categories according to the American College of Chest Physicians/Society of Critical Care Medicine criteria: negative, systemic inflammatory response syndrome, localized infection, and sepsis group (sepsis, severe sepsis, or septic shock). The severity of sepsis-related organ failure was assessed by the sepsis-related organ failure assessment score.. A total of 800 patient days were classified into the four categories. The median plasma PCT concentrations in noninfected (systemic inflammatory response syndrome) and localized-infection patient days were 0.4 and 1.4 ng/mL (p <.0001), respectively; the median CRP plasma concentrations were 79.9 and 85.3 mg/L (p =.08), respectively. The area under the receiver operating characteristic curve was 0.756 for PCT (95% confidence interval [CI], 0.675-0.836), compared with 0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median plasma PCT concentrations in nonseptic (systemic inflammatory response syndrome) and septic (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p <.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001), respectively. The area under the receiver operating characteristic curve was 0.925 for PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622-0.733) (p <.0001). The linear correlation between PCT plasma concentrations and the four categories was much stronger than in the case of CRP (Spearman's rho, 0.73 vs. 0.41; p <.05). A rise in sepsis-related organ failure assessment score was related to a higher median value of PCT but not CRP.. PCT is a better marker of sepsis than CRP. The course of PCT shows a closer correlation than that of CRP with the severity of infection and organ dysfunction.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Multiple Organ Failure; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

We prospectively evaluated the capacity of serum procalcitonin (PCT), compared with serum levels of C-reactive protein (CRP) and endotoxin, to identify children at high risk for mortality from sepsis after BMT. Of 47 pediatric bone marrow transplantation patients studied, 22 had an uneventful course post-transplant (Group 1), 17 survived at least one septic event (Group 2), and eight died from multiorgan failure (MOF) following septic shock (Group 3). Median concentrations of PCT over the course of the study were 1.3, 15.2, and 102.8 ng/ml, respectively, in each of the three groups (P<0.002 for each comparison). Median concentrations of CRP were 91, 213, and 260 mg/l, respectively (P<0.001 for Group 1 vs Group 2 and Group 3; P=NS for Group 2 vs Group 3). Median concentrations of endotoxin were 0.21, 0.30, and 0.93 U/l, respectively (P=NS for each comparison). Median concentrations of PCT, in contrast to serum CRP and endotoxin, correlated with the severity of sepsis (8.2 ng/ml in 'sepsis' and 22.3 ng/ml in 'severe sepsis', P=0.028) and provided useful prognostic information during septic episodes.

Topics: Adolescent; Adult; Bone Marrow Transplantation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Endotoxins; Female; Germany; Humans; Infant; Male; Multiple Organ Failure; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock, Septic

Patients in cardiogenic shock (CS) often present with signs of systemic inflammation that mimic infection, especially in the setting of multiple organ failure (MOF). To clarify the usefulness of procalcitonin (PCT) for diagnosing complicating sepsis in patients with CS, especially in the presence of MOF we compared PCT concentrations in patients with CS with and without MOF to those in patients with septic shock (SS).. Retrospective analysis in the cardiovascular ICU at a university hospital.. 40 patients with CS, 15 patients with SS, and 11 noncritically ill patients without infection.. Infection was excluded by clinical and microbiological examination in all CS patients at the time of blood sampling. Nevertheless 35% exhibited CRP concentrations higher than 10 mg/dl and 25% PCT concentrations higher than 2 ng/ml. Median PCT concentrations were higher in CS patients than in controls but lower than in patients with SS. CS patients with MOF at the time of blood sampling exhibited higher PCT concentrations than patients without organ failure. In the pooled population of patients with CS and SS PCT had a higher area under the receiver operating characteristic curve (0.86 vs. 0.83) than CRP and a PCT concentration of 10 ng/ml or higher had greater specificity for sepsis than a PCT concentration of 2 ng/ml or higher but lower negative predictive value.. PCT concentrations above 2 ng/ml are frequently found in CS patients with MOF and do not necessarily indicate infection. PCT was slightly better than CRP for diagnosing sepsis in our study, but a PCT concentration of 10 ng/ml or higher seems to be more appropriate for diagnosing this complication in CS patients than 2 ng/ml.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis; Shock, Cardiogenic

To evaluate the efficacy of using procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate sepsis from non-infectious systemic inflammatory response syndrome (SIRS).. We made a prospective study in a general intensive care unit at Peking Union Medical College Hospital. Twenty patients with sepsis and 31 patients with non-infectious SIRS were enrolled in this study. Serum concentrations of PCT, IL-6 and C-reactive protein (CRP) were determined within 24 h after clinical onset of sepsis or non-infectious SIRS. Leukocyte count, percentage of neutrophils, and absolute neutrophil count, as well as maximal body temperature were also recorded.. Serum concentrations of PCT, IL-6, and CRP, as well as maximal body temperature, were significantly higher in septic patients [3.6 (1.8, 27.5) micro g/L, 810 +/- 516 ng/L, 180 +/- 108 g/L, 38.6 +/- 1.2 degrees C] than non-infectious SIRS patients [0.5 (0.2, 1.8) micro g/L, 235 +/- 177 ng/L, 109 +/- 70 g/L, 37.9 +/- 0.9 degrees C]. IL-6 and PCT exhibited the best discriminative power between sepsis and non-infectious SIRS, with sensitivity above 80% and specificity above 70%. A sepsis score with combination of IL-6 and PCT showed the best discriminative power with the area under the receiver operating characteristic curve of 0.923.. Assessing IL-6 and PCT levels are more reliable ways to differentiate sepsis from non-infectious SIRS, compared with conventional inflammatory parameters.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

One of the most difficult tasks in differential diagnosis of patients with septic syndrome at the Intensive Care Units is to differentiate between infection and non-infection etiology of this syndrome. In the last years, new parameters have played an important role in this area--C-reactive protein, Interleukin-6 and procalcitonin.. Of the investigation was to compare these three parameters in differential diagnosis of the septic syndrome. THE COHORT AND METHODS: The authors examined 56 patients (17 women and 39 men, mean age being 43 and 51 years, respectively) hospitalized at the Intensive Care Units who corresponded to the criteria of the syndrome of inflammatory response, sepsis or septic shock. A total of 99 examinations were done. The samples were taken up to 24 hours after the beginning of clinical symptomatology and submitted to the laboratory within four hours. Immediately afterwards the determination of concentrations of all three parameters--C-reactive protein, interlaukin-6 and procalcitonin, were done. The results of the examinations were compared to each other as well as to the diagnosis of sepsis--the confirmed infection etiology.. In all the evaluated parameters the authors detected significant differences between the values of entry examination and all measurements between the patients with the syndrome of systemic inflammatory response and septic shock as well as among patients with sepsis and the septic shock. Likewise, the authors confirmed significant differences between concentrations of all three parameters in comparing the patients with sepsis and those with the septic shock. Only in the case of procalcitonin there was a significant difference in concentration between patients with the syndrome of systemic inflammatory response of non-infectious etiology and those with sepsis. The concentration of procalcitonin was the only predictive marker of diagnosis with the correlation coefficient r = 0.7263, r2 = 0.5275, P < 0.00005.. Calcitonin proved to be the most specific parameter in demonstrating infection etiology in patients with the septic syndrome, its predictive value being higher than that of C-reactive protein and Interleukin-6. Monitoring of calcitonin dynamism provides important information on efficiency of the applied antibiotic treatment. In patients with diagnostic uncertainties as far as the etiology of the septic syndrome is concerned; procalcitonin is the parameter of choice, while it may be supplemented with the examination of C-reactive protein.

Topics: Adult; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

Circulating levels of calcitonin precursors (CTpr), including procalcitonin (ProCT), increase up to several thousand-fold in human sepsis, and immunoneutralization improves survival in two animal models of this disease. Herein, we analyzed inflammation-mediated calcitonin I gene (CALC I) expression in human adipocyte primary cultures and in adipose tissue samples from infected and noninfected patients with different levels of serum ProCT. In ex vivo differentiated adipocytes, the expression of CT mRNA increased 24-fold (P < 0.05) after the administration of Escherichia coli endotoxin (lipopolysaccharide) and 37-fold (P < 0.05) after IL-1beta administration by 6 h. ProCT protein secretion into culture supernatant increased 13.5-fold (P < 0.01) with lipopolysaccharide treatment and 15.2-fold (P < 0.01) with IL-1beta after 48 h. In coculture experiments, adipocyte CT mRNA expression was evoked by E. coli-activated macrophages in which CT mRNA was undetectable. The marked IL-1beta-mediated ProCT release was inhibited by 89% during coadministration with interferon-gamma (IFNgamma). In patients with infection and markedly increased serum ProCT, CT mRNA was detected in adipose tissue biopsies. Hence, we demonstrate that ProCT, which is suspected to mediate deleterious effects in sepsis and inflammation, is a novel product of adipose tissue secretion. The inhibiting effect of IFNgamma on IL-1beta-induced CT mRNA expression and on ProCT secretion might explain previous observations that serum ProCT concentrations increase less in systemic viral compared with bacterial infections.

Topics: Adipocytes; Adipose Tissue; Calcitonin; Calcitonin Gene-Related Peptide; Cells, Cultured; Gene Expression Regulation; Humans; In Vitro Techniques; Macrophages; Omentum; Protein Precursors; RNA, Messenger; Sepsis

The aim of this prospective cohort study was to address the feasibility of measuring cytokines in serum and urine as early predictor tests for the identification of septic Intensive Care Unit (ICU) patients. The study group consisted of 10 septic and 5 non-septic patients at the onset of sepsis according to modified definitions by the American College of Chest Physicians (ACCP)/Society of Critical Care Medicine (SCCM). Serum and urine samples were taken from septic patients at the onset of sepsis and from non-septic patients, every 12 h for 3 days and thereafter every 24 h until day 10. Levels of TNF-alpha, IL-1beta, IL-6, IL-10, IL-18, IFN-gamma, MCP-1, and PCT (procalcitonin) were measured by ELISA. Apart from serum IL-18 and PCT levels, which were elevated in septic patients (p<0.05), levels of all other cytokines and chemokines in the serum of septic patients did not exceed those of the control group. In urine, in contrast with TNF-alpha, IL-1beta, IL-6, IL-10, IFN-gamma, and MCP-1 in which no differences between the two groups were observed, a distinct trend of elevated IL-18 levels was observed only in the septic group. Whereas elevated serum IL-18 and PCT are clear candidate markers for sepsis criteria, the present data indicating elevated urine IL-18 levels albeit from a limited number of septic patients is an interesting observation. The profile of inflammatory mediators in serum and urine from septic patients herein warrants further investigations in a larger group of patients at the onset of sepsis driven by different infectious foci.

Topics: Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Chemokines; Cohort Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intensive Care Units; Interleukin-18; Male; Middle Aged; Protein Precursors; RNA, Messenger; Sepsis; Time Factors

We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.

Topics: Abbreviated Injury Scale; Adult; Age Factors; Analysis of Variance; Area Under Curve; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Injury Severity Score; Logistic Models; Male; Middle Aged; Models, Statistical; Multiple Organ Failure; Neopterin; Predictive Value of Tests; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Wounds and Injuries

Treatment with antibodies against T-lymphocytes usually triggers a febrile response potentially mimicking or masking infection. Procalcitonin (PCT) is considered a sensitive and specific marker of systemic bacterial and fungal infection. It was the aim of this study to investigate the characteristics of PCT and C-reactive protein (CRP) during treatment with polyclonal or monoclonal anti-T-cell antibodies, in order to examine the ability of these parameters to distinguish between systemic bacterial infection and reaction to antibody treatment. Thus, 15 consecutive febrile episodes after T-cell antibody infusion without clinical signs of infection were compared with nine episodes of Gram-negative sepsis. After T-cell antibody infusion PCT and CRP serum levels increased to a similar extent as in Gram-negative sepsis. Therefore, during T-cell antibody treatment neither PCT nor CRP are adequate for differentiating between fever due to infection or to unspecific cytokine release.

Topics: Adolescent; Antibodies; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Diagnosis, Differential; Female; Fever; Gram-Negative Bacteria; Humans; Infant; Male; Neoplasms; Protein Precursors; Sensitivity and Specificity; Sepsis; T-Lymphocytes

The prognostic value of elevated serum levels of procalcitonin (PCT) in patients early after cardiac surgery on cardiopulmonary bypass (CPB) remains unclear. In a prospective study, we investigated whether PCT is useful as a prognostic marker in cardiac surgery with respect to mortality, complications and infections, and whether PCT is a specific marker for occurrence of infections.. Within 8 months, a subset of 80 high-risk patients (APACHE II-score: 25.1 +/- 4.7 (mean +/- SD)) out of a consecutive cohort of 776 patients was investigated. Demographic data, operative data and clinical endpoints (mortality, infection, severe complication) were documented. Serum levels of PCT were analyzed preoperatively and at postoperative day 1.. Hospital mortality in this high-risk group was 21.3 %, infections occurred in 33.8 % and complications in 58.8 % of the patients. Preoperative PCT was normal in all patients. Postoperative PCT was increased in non-survivors compared to survivors (34.3 +/- 7.0 ng/ml vs. 15.9 +/- 4.9 ng/ml; p < 0.05), in patients with severe complications (30.3 +/- 6.7 ng/ml vs. 5.5 +/- 1.4 ng/ml; p < 0.05) and in patients with infections (38.4 +/- 11.3 ng/ml vs. 10.8 +/- 1.6 ng/ml; p < 0.05). Area under receiver operating characteristic curve for PCT as predictor of mortality, infections and complications was 0.772 (95 %-confidence-interval (CI): 0.651 - 0.894), 0.720 (95 %-CI: 0.603 - 0.837) and 0.861 (95 %-CI: 0.779 - 0.943), respectively. PCT was not different with infectious compared to non-infectious complications.. High levels of PCT are associated with mortality, infections, and severe complications early after cardiac surgery using cardiopulmonary bypass and therefore provide a valuable prognostic marker. However, PCT does not discriminate between infectious and non-infectious complications.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Glycoproteins; Humans; Male; Mediastinitis; Multiple Organ Failure; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

Some mediators of inflammation are associated with sepsis, involving nervous system. Proinflammatory cytokines, TNF-alpha, IL-6, and IL-8, and procalcitonin (PCT), proinflammatory protein, were investigated in patients with neurologic complications in sepsis. TNF-alpha, IL-6, IL-8, and PCT were prospectively investigated in 62 patients with neurologic complications in sepsis. TNF-alpha and IL-6 were studied both in serum as in the CSF, IL-8 and PCT were studied only in serum. TNF-alpha, IL-6, and IL-8 were studied by ELISA (R & D Systems), and the PCT by immunoluminometric assay (BRAHMS). Mean value of TNF-alpha in serum was 578+/-214 pg/ml, and in CSF was 458+/-167 pg/ml (p<0.01). Mean value of IL-6 in serum was 749+/-213 pg/ml, and in CSF was 617.5+/-182 pg/ml (p<0.01). Mean value of IL-8 in serum was 332+/-196 pg/ml (p<0.01). Mean value of PCT in serum was 80+/-16 ng/ml (p<0.01). The investigated parameters do not permit the identifying of cases with neurologic complications. The increased correlation coefficient between cytokines in serum and in CSF suggests the damage of the blood-brain barrier. The raise of PCT in serum, induced by TNF-alpha and IL-6, is an argument of the severity of sepsis.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Interleukin-6; Interleukin-8; Male; Nervous System Diseases; Protein Precursors; Sepsis; Tumor Necrosis Factor-alpha

To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis.. Prospective, cohort study in two university hospital intensive care units.. 61 critically ill patients with suspected sepsis.. The outcome measure was hospital mortality. Hospital survivors ( n=41) and nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D-dimer values. AT III, CRP, and leukocyte count did not differ. The areas under receiver operating curves showed reasonable discriminative power (>0.75) in predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777) values which were comparable to that of APACHE II (0.786), and which remained the only independent predictor of mortality.. Admission and day 2 IL-6, and day 2 PCT, and day 2 D-dimer values differed significantly between hospital survivors and nonsurvivors among critically ill patients with suspected sepsis. However, in prediction of hospital mortality, only the discriminative power of day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis (>0.75).

Topics: Adult; Antithrombin III; APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Fibrin Fibrinogen Degradation Products; Finland; Hospital Mortality; Humans; Interleukin-6; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prognosis; Protein Precursors; Sepsis

High levels of tumor necrosis factor (TNF) alpha messenger RNAs and interleukin (IL) 8 have been reported in leukocytes of patients with sepsis.. Assessment of leukocyte intracytoplasmic levels of proinflammatory and anti-inflammatory cytokines might be clinically more relevant to determine prognosis in patients with severe sepsis.. Cohort study.. Surgical intensive care units of a university hospital.. Leukocyte suspensions obtained from 16 patients, 6 during early sepsis or septic shock and 10 during late sepsis or septic shock, were incubated with anti-CD14 and anti-CD2 or anti-CD3 monoclonal antibodies and then with intracytoplasmic anticytokine antibodies staining for interferon-gamma, TNF-alpha, IL-2, IL-6, IL-8, IL-10, and IL-12 and analyzed with a flow cytometer.. Mann-Whitney test and Spearman correlation test were used in statistical evaluations according to the 28-day all-cause mortality rates and multiple organ dysfunction and sepsis-related organ failure assessment scores.. Higher serum IL-6, IL-8, C-reactive protein, and procalcitonin levels were found in patients with high multiple organ dysfunction and sepsis-related organ failure assessment scores (greater than or equal to the median values [8 and 11, respectively]), in contrast to decreased T-lymphocyte-associated IL-6 and TNF-alpha and monocyte-associated IL-10 and IL-12 proportions. Furthermore, in 28-day all-cause mortality analysis, there were higher levels of C-reactive protein and procalcitonin in nonsurvivors (n = 9) than in survivors (n = 7), while T-lymphocyte-associated IL-2, IL-6, IL-10, and TNF-alpha and monocyte-associated IL-10 and TNF-alpha proportions decreased in the nonsurvivors.. These results suggest that diminished lymphocyte- and monocyte-associated proinflammatory and anti-inflammatory cytokine levels are associated with worse prognosis in patients with severe sepsis.

Topics: APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Glycoproteins; Humans; Interferon-gamma; Interleukins; Leukocytes; Male; Middle Aged; Monocytes; Protein Precursors; Sepsis; Shock, Septic; T-Lymphocytes; Tumor Necrosis Factor-alpha

The 116 amino acid prohormone procalcitonin and some of its component peptides (collectively termed calcitonin precursors) are important markers and mediators of sepsis. In this study, we sought to evaluate the effect of immunoneutralization of calcitonin precursors on metabolic and physiologic variables of sepsis in a porcine model.. A prospective, controlled animal study.. A university research laboratory.. 30-kg Yorkshire pigs.. Sepsis was induced in 15 pigs by intraperitoneal instillation of a suspension of cecal content (1 g/kg animal body weight) and a toxinogenic Escherichia coli solution (2 x 10(11) colony-forming units). During induction of sepsis, seven pigs received an intravenous infusion of purified rabbit antiserum, reactive to the aminoterminal portion of porcine prohormone procalcitonin. Another eight control pigs received an intravenous infusion of purified nonreactive rabbit antiserum. For all 15 animals, physiologic data (urine output, core temperature, arterial pressure, heart rate, cardiac index, and stroke volume index) and metabolic data (serum blood urea nitrogen and creatinine, arterial lactate, and pH) were collected or recorded hourly until death at 15 hrs.. In this large-animal model of rapidly lethal peritonitis, serum calcitonin precursors were significantly elevated. Amino-prohormone procalcitonin-reactive antiserum administration resulted in a significant improvement or a beneficial trend in a majority of the measured physiologic and metabolic derangements induced by sepsis. Specifically, arterial pressure, cardiac index, stroke volume index, pH, and creatinine were all significantly improved, while urine output and serum lactate had beneficial trends. Treated animals also experienced a statistically significant increase of short-term survival.. These data from a large-animal model with polymicrobial sepsis demonstrate the salutary effect of early immunoneutralization of calcitonin precursors on physiologic and metabolic variables. Immunologic blockade of calcitonin precursors may offer a novel therapeutic approach to human sepsis.

Topics: Animals; Antibodies; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Output; Escherichia coli Infections; Hydrogen-Ion Concentration; Immune Sera; Kidney; Lactic Acid; Prospective Studies; Protein Precursors; Rabbits; Sepsis; Swine

To evaluate the efficacy of serun procalcitonin (PCT) and interleukin (IL)-6 in differentiating between severe sepsis and systemic inflammatory response (SIRS) of non-infectious origin.. The serum PCT, IL-6, C-reactive protein (CRP), white blod cell count, percentage of neutrophils, and absolute neutrophil count were determined, and maximal body temperature was recorded among 21 patients was 3.6 (1.8, 27.5) micro g/L, significantly higher than that in SIRS patients (1.3 micro g/L +/- 1.6 micro g/L, P < 0.05). The IL-6 in sepsis patients was 810 ng/L +/- 516 ng/L, significantly higher than that in SIRS patients (235 ng/L +/- 177 ng/L, P < 0.01). However, the differences of CRP, WBC count, percentage of neutrophil, and absolute neutrophil count between the severe sepsis patients and SIRS patients were not statistically significant. PCT and IL-6 showed sensitivity equal or over 80% and specificity equal to or over 70%. The infection score based on PCT and IL-6 showed the best discriminative power to differentiate between severe sepsis and SIRS with the artea under the receiver operating characteristic curve of 0.923.. In comparison with the conventional inflammatory markers, PCT and IL-6 are more reliable indicators to differentiate between sepsis and SIRS.

Topics: Aged; Aged, 80 and over; Blood Cell Count; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Female; Humans; Interleukin-6; Male; Middle Aged; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Raised plasma levels of procalcitonin (proCT) represent an early marker for septicaemia. They are related to disease severity and inversely to outcome and response to treatment. ProCT is presumably synthesised in tIssues other than the thyroid C-cells which are the source of calcitonin (CT) in normal physiology. This study compares proCT and its cleavage products in the serum of patients with septicaemia with those in medullary thyroid carcinoma (MTC).. Immunoreactive proCT and its cleavage products were extracted from the serum of patients with septicaemia or MTC using octadecylsilyl silica columns and characterised by reversed phase HPLC and Western blot analysis. ProCT, CT(1-32) and the flanking peptides PAS-57 and PDN-21 were recognised with antibodies specific for the individual peptides.. ProCT and a 10 kDa polypeptide were recognised with antibodies to PAS-57, CT(1-32) and PDN-21. An 8 kDa proCT fragment was detected with antibodies to CT and PDN-21. However, intact CT(1-32), PAS-57 and PDN-21, found in the serum of MTC patients, were undetectable. The results indicate partial cleavage of proCT in septicaemia different from that in MTC patients.. ProCT and 10 and 8 kDa proCT fragments were recognised in the circulation of septic patients. They were different from the known proCT-processing products PAS-57, CT(1-32) and PDN-21 identified in the serum of normal subjects and of MTC patients. Distinct cleavage of proCT may contribute to the symptoms of septicaemia.

Topics: Aged; Blotting, Western; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoma, Medullary; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Peptide Fragments; Protein Precursors; Sepsis; Thyroid Neoplasms

Procalcitonin (PCT) is increasingly recognised as an important diagnostic parameter in clinical evaluation of the critically ill. This prospective study was designed to investigate PCT as a diagnostic marker of infection in critically ill patients with sepsis. Eighty-five adult ICU patients were studied. Four groups were defined on the basis of clinical, laboratory and bacteriologic findings as systemic inflammatory response syndrome (SIRS) (n = 10), sepsis (n = 16), severe sepsis (n = 18) and septic shock (n = 41). Data were collected including C-reactive protein (CRP), PCT levels and Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores on each ICU day. PCT levels were significantly higher in patients with severe sepsis and septic shock (19.25 +/- 43.08 and 37.15 +/- 61.39 ng/ml) than patients with SIRS (0.73 +/- 1.37 ng/ml) (P < 0.05 for each comparison). As compared with SIRS patients, plasma PCT levels were significantly higher in infected patients (21.9 +/- 47.8 ng/ml), regardless of the degree of sepsis (P < 0.001). PCT showed a higher sensitivity (73% versus 35%) and specificity (83% versus 42%) compared to CRP in identifying infection as a cause of the inflammatory response. Best cut-off levels were 1.31 ng/ml for PCT and 13.9 mg/dl for CRP. We suggest that PCT is a more reliable marker than CRP in defining infection as a cause of systemic inflammatory response.

Topics: Adult; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Humans; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome

This study was designed to assess the value of procalcitonin in establishing the diagnosis and evaluating the prognosis of neonatal sepsis. Thirty-four infants with neonatal sepsis were included in the study. Procalcitonin values of the cases with sepsis were (2.21 +/- 2.48 ng/ml) significantly higher than the values in the control group (0.71 +/- 0.5 ng/ml; p = 0.01). On the 7th day of therapy neonates who had achieved clinical recovery had a significant decrease of procalcitonin levels (0.55 +/- 0.27 ng/ml) compared to the initial values (p = 0.001). Initial mean procalcitonin levels of the cases resulting in death were 4.31 +/- 3.66 g/ml. This was significantly higher than the initial values of the patients who had clinical recovery (1.18 +/- 1.24 ng/ml;p = 0.02). Procalcitonin is a valuable marker for diagnosis, for evaluating prognosis and response to therapy in neonatal sepsis.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Chi-Square Distribution; Female; Humans; Infant, Newborn; Male; Prognosis; Protein Precursors; Radioimmunoassay; Sepsis; Statistics, Nonparametric

To evaluate plasma amino acid concentrations and markers of inflammation in the early stage and the course of septic encephalopathy.. Prospective, case series of patients with well-defined septic encephalopathy.. Surgical department and intensive care unit of a university hospital.. Seventeen patients with sepsis according to the ACCP/SCCM consensus conference criteria and encephalopathy based on neuropsychological tests, compared to a control group undergoing uncomplicated thoracic surgery.. None.. SOFA score, blood samples for plasma amino acids, procalcitonin and interleukin-6. Sepsis was determined to be the cause of encephalopathy in 14 of the 17 patients. Six patients developed septic shock, four died within the study period of 28 days. Within 12 h of the onset of septic encephalopathy, mean values of PCT and IL-6 were elevated ( p<0.001) and the amino acids unbalanced (the ratio of branched-chain to aromatic amino acids was decreased, p<0.001). During the course of sepsis the decreased amino acid ratio was significantly, but moderately, correlated with elevated PCT and IL-6 levels. On study days when PCT was higher than 2 ng/ml, the amino acid ratio was significantly lower. In no patient was severe liver dysfunction seen.. Metabolic disturbances with changes in amino acid levels can occur early in septic patients, without serious liver abnormalities. The present data suggest a possible role of amino acids in the pathogenesis of septic encephalopathy.

Topics: Amino Acids; Biomarkers; Brain Diseases, Metabolic; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Inflammation; Intensive Care Units; Interleukin-6; Liver; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Sepsis

We evaluated procalcitonin (PCT) assay in the emergency diagnosis of neonatal bacterial infection, especially in preterm infants, relative to C-reactive protein (CRP) and fibrinogen.. One hundred and twenty neonates (32 preterm), of whom 21 were infected, were tested.. Concentrations of PCT, CRP and fibrinogen in uninfected infants were not affected by gestational age at birth. Concentrations of CRP and PCT increased rapidly during the first 24 h of life, while fibrinogen concentrations increased gradually from birth. All marker concentrations were significantly greater in neonates with bacterial infection. Receiver-operating characterstic analysis showed that optimum cut-off values for fibrinogen, CRP and PCT were 3.0 g/L, 7.5 mg/L and 2.5 microg/L respectively, for the diagnosis of sepsis at birth.. Determination of PCT is of value in excluding bacterial infection in neonates since it has a negative predictive value of 93%.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Fibrinogen; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Protein Precursors; ROC Curve; Sepsis

To determine the time course of histocompatibility leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells and their relationship to markers of inflammation, organ function, and outcome during severe sepsis.. Prospective, longitudinal study.. University hospital intensive care unit.. Twenty-three postoperative patients with severe sepsis and 26 patients with uneventful postoperative course as well as 24 healthy, age-matched subjects.. Serum procalcitonin was determined by using an immunochemiluminescence assay, and C-reactive protein and leukocyte antigens were determined by using flow cytometry over 14 days in parallel with clinical data collection.. Despite a relative lymphopenia, absolute lymphocyte counts and CD4+/CD8+ T-cell ratio in septic patients were significantly elevated above normal. Particularly, CD4+ and CD8+ T-cell counts in nonsurvivors of sepsis were approximately twice as high as those of survivors. Significantly decreased monocytic HLA-DR expression was observed in both survivors and nonsurvivors at the onset of severe sepsis. Percentages of HLA-DR+ lymphocytes, however, were significantly increased during sepsis, especially in nonsurvivors. Whereas survivors of sepsis showed a continuous recovery of monocytic HLA-DR expression to >or=70% within 10 days, nonsurvivors were characterized by a second decrease in monocytic HLA-DR expression after day 7 or a permanent suppression (<40%). Peak of systemic inflammatory reaction, documented by maximum serum concentrations of procalcitonin and C-reactive protein, coincided with the nadir of monocytic HLA-DR expression. Moreover, procalcitonin and C-reactive protein as well as scores on the Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment were inversely correlated with the monocytic HLA-DR expression.. Decreases in monocytic HLA-DR expression occurred simultaneously with signs of hyperinflammation as early as the onset of severe sepsis and usually developed in opposite directions than inflammatory markers and sepsis severity scores.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Flow Cytometry; HLA-DR Antigens; Humans; Inflammation; Longitudinal Studies; Male; Monocytes; Postoperative Period; Prospective Studies; Protein Precursors; Sepsis; T-Lymphocyte Subsets

A significant decrease of DPP IV activity has been found in patients with severe sepsis in relationship to the increase of procalcitonin. These findings might be explained by the high concentration of other substrates for DPP IV present in these patients. It can be hypothesized that this enzymatic decrease is bound to some changes in immunomodulation. Further studies will be necessary to elucidate the clinical importance of these findings.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Dipeptidyl Peptidase 4; Fluorometry; Humans; Protein Precursors; Sepsis; Statistics as Topic

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Diagnosis, Differential; Humans; Necrosis; Pancreatitis; Protein Precursors; Sepsis; Surgical Procedures, Operative

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Hemofiltration; Humans; Interleukin-1; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Probability; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Survival Analysis; Tumor Necrosis Factor-alpha

We determined the elimination characteristics of procalcitonin (PCT) during continuous veno-venous hemofiltration (CVVHF) and the resulting effect on PCT plasma levels. A prospective study was conducted in patients with sepsis and acute oliguric renal failure, treated with CVVHF using a polysulfone membrane (Baxter Renaflo II PSHF 1200). Patients had sepsis and PCT plasma levels > 4 ng ml(-1) (n = 26). PCT was measured in the pre- and post-filter plasma and the ultrafiltrate at 0, 5, 10, and 15 min and 1, 2, 4, 6, 12, and 24 h after setup of CVVHF. PCT sieving coefficient was 0.24. Elimination of PCT, however, depended on the duration of filtration, because filter adsorption was the main mechanism of PCT clearance during the first hour of hemofiltration, finally increasing to a clearance of PCT into the ultrafiltrate of 2.8-5.5 mL/min after 2 h. PCT plasma levels were not significantly altered during CVVHF (96% of the initial concentration after 24 h, P = 0.72). Similar to what has been observed with cytokines and other proteins of a comparable molecular weight, PCT is removed from the plasma during CVVHF, but plasma PCT levels are unchanged. Thus, PCT can be used as a diagnostic parameter even in patients with acute renal failure undergoing CVVHF.

Topics: Aged; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Hemofiltration; Humans; Male; Middle Aged; Protein Precursors; Renal Replacement Therapy; Sepsis

To evaluate procalcitonin (PCT) as a diagnostic marker of bacterial sepsis in critically ill neonates and children and to compare the results of PCT with those of C-reactive protein (CRP) and serum amyloid (SAA).. Prospective, observational study in neonatal and pediatric intensive care units.. A total of 116 divided into four groups according to age and diagnosis: neonates (aged 3-30 days) with sepsis (n = 20), neonates without sepsis (n = 26), children (aged 2-12 years) with sepsis (n = 32), and children without sepsis (n = 38).. Serum PCT, CRP, and SAA were measured on admission or when a bacterial sepsis was suspected. Area under the receiver operating characteristic (ROC) curve, optimum predictive values, and optimum diagnostic cut off values were evaluated.. Admission PCT was significantly higher in neonates and children with sepsis than in the other groups. In the neonates the area under the ROC curve was 0.99 for PCT, 0.95 for CRP, and 0.98 for SAA; in the children it was 1 for PCT, 0.93 for CRP, and 0.96 for SAA. Cutoff concentrations for optimum prediction of sepsis in the neonates were PCT > 6.1 ng/ml (diagnostic efficiency: 93.8%), CRP > 23.0 mg/l (89.7%), and SAA > 41.3 mg/l (95.3%); in the children they were PCT > 8.1 ng/ml (100%), CRP > 22.1 mg/l (89.8%), and SAA > 67.2 mg/l (94.4%).. In critically ill children PCT concentration is a better diagnostic marker of sepsis than CRP and SAA. In critically ill neonates, however, PCT, CRP, and SAA are similar diagnostic markers of sepsis. A PCT concentration higher than 8.1 ng/ml identified all children with bacterial sepsis.

Topics: Amyloid; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care Units, Pediatric; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

The aim of this prospective study was to investigate whether serum procalcitonin (PCT) can be used as a post-mortem marker of sepsis and to determine whether this biochemical parameter can be employed in the forensic elucidation of death due to sepsis. At least three blood samples were collected between 0.3 and 139 h post-mortem from sepsis-related fatalities (n = 8) and control individuals (n = 53, where death was due to various natural and unnatural causes). Additionally one ante-mortem blood sample was collected shortly before death from the patients in the sepsis group. In the sepsis group, serum PCT concentrations, determined by using an immunoluminometric assay, were elevated in all patients for the whole observation period, whereas in the control group serum PCT was not detectable in 94% of the cases. Measurement of PCT levels seems reasonable until at least approximately 140 h postmortem, depending on the ante-mortem levels. A linear regression model is presented that allows the serum PCT concentration of an individual at the time of death to be estimated on condition that at least two positive post-mortem PCT values have been determined. Ante-mortem PCT values correlated well with the predicted PCT values at the time of death in the sepsis group using the standardized PCT logarithms. According to the results of the present study, PCT is a valuable biochemical parameter for the post-mortem discrimination between sepsis and underlying non-septic causes of death.

Topics: Adolescent; Adult; Aged; Autopsy; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Linear Models; Male; Middle Aged; Postmortem Changes; Prospective Studies; Protein Precursors; Sepsis; Statistics, Nonparametric

The novel inflammatory marker procalcitonin (PCT) was assessed as an index of infection in patients with febrile neutropenia. Blood samples were obtained from 115 patients with febrile neutropenia for determination of PCT levels before onset of fever and daily until the resolution of fever. The median PCT level on the first day of fever was 8.23 ng/mL in patients with bacteremia, compared with 0.86 ng/mL in patients with localized bacterial infections (P=.017). The median PCT level on the first day of fever was 2.62 ng/mL in patients with severe sepsis, compared with 0.57 ng/mL in patients with clinically localized infections (P<.001). A dramatic decrease in PCT levels was documented after resolution of the infection; PCT levels were elevated when the infection worsened. Pronounced PCT levels were also found in patients with fever of unknown origin who were responding to antimicrobial chemotherapy, compared with those not responding to treatment with antibiotics. PCT levels were particularly elevated in patients with bacteremia and severe sepsis. These findings provide new insight into the application of PCT in clinical trials as a diagnostic tool of the severity of an infection in patients with febrile neutropenia and of the need to change antimicrobial regimen.

Topics: Bacteremia; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Protein Precursors; Sepsis

The plasma levels of procalcitonin (PCT) are increased in patients with severe bacterial infections. Its cellular origin and potential pathophysiological function in sepsis is, however, unclear. White blood cells have recently been described to express both PCT mRNA and protein. The aim of this study was to determine whether PCT has any influence on the surface expression of receptors, relevant in inflammation, on human whole blood leukocytes under normal and septic conditions. Venous blood from healthy donors was incubated with PCT (40 ng/ml or 1200 ng/ml) alone or in combination with lipopolysaccharide (LPS, 10 ng/ml) or peptidoglycan (PepG, 10 micrograms/ml) for 6 h. The surface expression of CD14, CD54, CD64, CD80, CD86 and HLA-DR was determined by flow cytometry. We could not detect any influence of PCT on the expression of these receptors. Further studies on potential effects on other cell types during infection seem warranted.

Topics: Analysis of Variance; Calcitonin; Calcitonin Gene-Related Peptide; Flow Cytometry; Humans; Leukocytes; Protein Precursors; Receptors, Immunologic; Sepsis

To assess the diagnostic value of procalcitonin (PCT), interleukin (IL)-6, IL-8, and standard measurements in identifying critically ill patients with sepsis, we performed prospective measurements in 78 consecutive patients admitted with acute systemic inflammatory response syndrome (SIRS) and suspected infection. We estimated the relevance of the different parameters by using multivariable regression modeling, likelihood-ratio tests, and area under the receiver operating characteristic curves (AUC). The final diagnosis was SIRS in 18 patients, sepsis in 14, severe sepsis in 21, and septic shock in 25. PCT yielded the highest discriminative value, with an AUC of 0.92 (CI, 0.85 to 1.0), followed by IL-6 (0.75; CI, 0.63 to 0.87), and IL-8 (0.71; CI, 0.59 to 0.83; p < 0.001). At a cutoff of 1.1 ng/ml, PCT yielded a sensitivity of 97% and a specificity of 78% to differentiate patients with SIRS from those with sepsis-related conditions. Median PCT concentrations on admission (ng/ ml, range) were 0.6 (0 to 5.3) for SIRS; 3.5 (0.4 to 6.7) for sepsis; 6.2 (2.2 to 85) for severe sepsis; and 21.3 (1.2 to 654) for septic shock (p < 0.001). The addition of PCT to a model based solely on standard indicators improved the predictive power of detecting sepsis (likelihood ratio test; p = 0.001) and increased the AUC value for the routine value-based model from 0.77 (CI, 0.64 to 0.89) to 0.94 (CI, 0.89 to 0.99; p = 0.002). In contrast, no additive effect was seen for IL-6 (p = 0.56) or IL-8 (p = 0.14). Elevated PCT concentrations appear to be a promising indicator of sepsis in newly admitted, critically ill patients capable of complementing clinical signs and routine laboratory parameters suggestive of severe infection.

Topics: Adult; Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Diagnosis, Differential; Female; Humans; Interleukin-6; Interleukin-8; Male; Predictive Value of Tests; Prospective Studies; Protein Precursors; Regression Analysis; Sensitivity and Specificity; Sepsis

Procalcitonin (PCT) has proven to be a very sensitive marker of sepsis for non-leucopenic patients. Little is known about its relevance in immunosuppressed and leucopenic adults. Four hundred and seventy-five PCT determinations were carried out in 73 haematological patients: on 221 occasions the white blood cell (WBC) count was < 1.0 x 10(9)/l and on 239 occasions it was > 1.0 x 10(9)/l leucocytes. Patients were classified as: non-systemic infected controls (n = 280), patients with bacteraemia (n = 32), sepsis (n = 30), severe sepsis (n = 3), septic shock (n = 3) and systemic inflammatory response syndrome (SIRS) (n = 62). When the WBC count was > 1.0 x 10(9)/l, gram-negative bacteria induced higher PCT levels (median 9.4 ng/ml) than gram-positives (median 1.4 ng/ml). In cases with a WBC < 1.0 x 10(9)/l, PCT levels were similar for gram-negative and gram-positive bacteria (1.1 ng/ml versus 0.85 ng/ml). Regardless of the leucocyte count, the median PCT level in bacteraemia cases always remained < 0.5 ng/ml. In heavily leucopenic situations, PCT levels were never > 2 ng/ml even in the sepsis and severe sepsis/septic shock groups, whereas a WBC count > 1.0 x 10(9)/l resulted in median PCT values of 4.1 ng/ml and 45 ng/ml respectively. The positive predictive value for sepsis (cut-off 2 ng/ml) was 93% in cases of WBC count > 1.0 x 10(9)/l, but only 66% in leucopenic conditions. The negative predictive value (cut-off 0.5 ng/ml) was 90% when the WBC count was > 1.0 x 10(9)/l and 63% in leucopenic conditions. Procalcitonin is an excellent sepsis marker with a high positive- and negative-predictive value in patients with WBC count > 1.0 x 10(9)/l, but it does not work satisfactorily below this leucocyte count.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Immunosuppression Therapy; Leukocyte Count; Leukopenia; Predictive Value of Tests; Protein Precursors; Sepsis; Shock, Septic; Statistics, Nonparametric

To determine the influence of chorioamnionitis and neonatal sepsis on procalcitonin (PCT) levels in very-low-birth-weight (VLBW) infants within the first week of life.. PCT serum levels were measured in cord blood 1 h after delivery and on day 3 and day 7 of life. Chorioamnionitis and neonatal sepsis within the first week were monitored.. Chorioamnionitis was present in eight of 37 patients (21.6%). PCT on day 3 was increased in both the "No chorioamnionitis" (2.54 ng mL(-1), SEM 0.51) and "Chorioamnionitis" (6.96 ng mL(-1), SEM 2.93) groups of VLBW infants compared with the 1st hour values (0.45 and 0.58 ng mL(-1) SEM 0.07 and 0.11, respectively, P < 0.001) of the same patients. The postnatal gain was higher in the "Chorioamnionitis" group (P < 0.01). Neonatal sepsis was diagnosed (after exclusion) in 12 of 32 patients (37.5%). Mean values of maximum PCT in patients with and without sepsis were 8.41 ng mL(-1) (SEM 1.87) and 3.02 ng mL(-1) (SEM 1.38), respectively (P < 0.05). Sensitivity to sepsis of PCT, ratio of immature to total neutrophils (I : T), and C-reactive protein (CRP) were 75%, 50% and 25%, respectively.. In the group of VLBW infants the PCT level within 72 h of delivery was markedly increased in patients with chorioamnionitis. Compared with I : T and CRP, PCT appears to be a more sensitive marker of neonatal sepsis.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chorioamnionitis; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Pregnancy; Protein Precursors; Sepsis

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin precursors are elevated in the serum of many conditions leading to systemic inflammatory response syndrome. The measurement of PCT in patients suffering from severe bacterial infections is a useful tool for the diagnosis of sepsis. Furthermore, therapeutic decisions are often based on the increase or decline of serum PCT levels. PCT was reported to have 116 amino acids. The aim of our study was the determination of the primary structure of serum PCT from septic patients. Sera containing high PCT-concentrations (>100 ng/ml) were collected from 22 patients with severe sepsis and were pooled for further purification (12.7 microg total concentration of PCT). Pooled PCT was purified on a CT 21-immunoaffinity column, further purified by reversed phase HPLC, and the resulting pure PCT was digested with endoproteinase Asp-N. N-terminal Edman sequencing showed that the first two amino acids (Ala-Pro) of the proposed pro-peptide were missing. Further analyses by MALDI-TOF mass spectroscopy resulted in a distinct mass signal of 12640 Da +/- 0.1%, which is in concordance with the theoretical molecular weight of the N-terminal truncated form (12628 Da). As opposed to previous suggestions, we could not detect any chemical modifications of PCT. In summary, we could demonstrate that PCT in the serum of septic patients is a peptide of only 114 amino acids, instead of the predicted 116 amino acids, lacking the N-terminal dipeptide Ala-Pro. This information on the primary structure of PCT might help in further studies on the physiological role of PCT during sepsis.

Topics: Amino Acid Sequence; Calcitonin; Calcitonin Gene-Related Peptide; Chromatography, Affinity; Humans; Molecular Sequence Data; Peptide Mapping; Protein Precursors; Sepsis; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The levels of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8, and the anti-inflammatory cytokines IL-10 and IL-13 were studied in child patients with sepsis. The changes of the cytokine inhibitors soluble IL-6 receptor and soluble p75 TNF-alpha receptor were also investigated in the patients' sera. An increase of pro- and anti-inflammatory cytokine levels was demonstrated at the time of diagnosis. Pharmacotherapy was accompanied by a decrease of the elevated concentrations of both cytokines and their inhibitors. The time pattern of changes in cytokine and cytokine inhibitor serum concentrations along with the time course of acute phase indices, including procalcitonin and C-reactive protein, allows for an evaluation of the system inflammatory response and may support diagnostic and prognosis methods.

Topics: Anti-Inflammatory Agents; Antigens, CD; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Humans; Infant; Infant, Newborn; Inflammation Mediators; Interleukin-10; Interleukin-13; Interleukin-6; Interleukin-8; Male; Prognosis; Protein Precursors; Receptors, Interleukin-6; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Sepsis

Procalcitonin test (PCT) has been proposed to check severity of generalized infections or sepsis. The authors measured the PCT values with PCT-Q quick test (BRAHMS DIAGNOSTICA GmbH, Berlin) at 14 surgical patients treated in their intensive care unit (7 sepsis, 4 peritonitis, 2 localized pancreatic abscess, 1 postoperative fever). At 3 septic patients (2 pancreatitis, 1 intestinal necrosis) they measured the PCT levels repeatedly during treatment. In 2 patients with localized pancreatic abscess and in 1 patient with postoperative fever without evidence of infection the PCT levels were low (< 0.5 ng/ml). At 4 patients with peritonitis following gastric or colon perforation the PCT levels were highly elevated (> 10 ng/ml). At 7 patients with severe sepsis the PCT values were high (> 2 ng/ml), except for 1 patient with intestinal necrosis. At this patient the PCT levels were repeatedly low. In 2 septic patients with pancreatitis elevated PCT levels indicated the need for surgery. In most patients PCT was a good indicator of generalized infections. PCT levels measured repeatedly in sepsis were lower than in patients with peritonitis.

Topics: Abscess; Adult; Aged; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Female; Humans; Intensive Care Units; Intestinal Diseases; Male; Middle Aged; Necrosis; Pancreatitis; Pancreatitis, Acute Necrotizing; Peritonitis; Predictive Value of Tests; Protein Precursors; Sepsis

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis; Shock, Septic

To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II).. Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period.. A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms.. PCT values were highest in patients with septic shock (12.89+/-4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91+/-3.87 ng/ml vs 0.53+/-2.9 ng/ml;P<0.001, and 0.41+/-3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26+/-1.62, 16.09+/-2.06, and 17.42+/-1.72 points, respectively), but was significantly higher in patients with septic shock (29.27+/-1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock.. In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.

Topics: Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Diagnosis, Differential; Early Diagnosis; Female; Germany; Humans; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

To assess the accuracy of procalcitonin as a measure of severity in patients with septic abdominal illnesses and the sepsis syndrome, to compare measurements with those of other inflammatory mediators, and to predict outcome.. We carried out a prospective clinical study from 246 patients with infective or septic episodes confirmed at laparotomy and 66 patients undergoing elective operations who acted as controls. Specimens of blood for measurement of cytokine concentrations determination were obtained daily from septic patients. In the control group specimens were obtained before operation, at the end of operation, and on each of the following days until normal recovery (day 10). Every two weeks up to 3 months for patients with metastases, who were being followed up.. Compared with other cytokines such as tumor necrosis factor alphaa and interleukin 6 procalcitonin was closely related to the development of infective and septic complications. 59 of 246 patients (24%) with sepsis died. Procalcitonin concentrations preoperatively [median 2.05 compared with 4.2 ng/ml (p=0.08)] (Mann-Whitney U-test) did not differ, but those on the days 1,4 and at the end differed significantly [day 1: 4.9 compared with 13.8 ng/ml (p<0.01); day 4: 4.8 compared with 13.0 ng/ml (p<0.01) and 0.4 compared with 13.25 ng/ml (p<0.01) at the end of the study]. In the control group only 7 (1.6%) of all blood samples, were detected outside the normal range (up to 0.8 ng/ml).. Procalcitonin is a new indicator of infection and sepsis. TNF and IL-6 concentrations always rise after major operations and fall in the absence of infection, indicating operative trauma. Procalcitonin is sensitive in detecting infective complications. Under routine conditions the procalcitonin concentrations seems to be valid, reproducible and detectable.

Topics: APACHE; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Colon; Female; Humans; Intestinal Perforation; Male; Pancreatitis; Peritonitis; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Surgical Wound Infection

To determine accuracy of procalcitonin concentrations for diagnosing nosocomial infections in critically ill neonates.. Case-control study.. Neonatal intensive care unit of a teaching hospital.. Twenty-three neonates with nosocomial infection. Four controls matched for duration of hospital stay and birth date were chosen for each case patient.. PCT concentrations were measured by the LUMItest procalcitonin kit at onset of signs of infection and after recovery. Range of PCT concentrations (ng/ml) was 2.0 to 249.1 in case patients and 0.08 to 1.0 in controls (sensitivity and specificity, 100%). PCT values returned to normal (<1.0 ng/ml) by day 3 to 7 of appropriate antibiotic therapy.. Measurement of PCT concentrations may be useful for early diagnosis and monitoring of infectious complications in neonates during their stay in the neonatal intensive care unit.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Cross Infection; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intensive Care Units, Neonatal; Italy; Male; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis

To determine the correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein (CRP) and procalcitonin (PCT)) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients on randomly chosen days.. Prospective consecutive case series.. Surgical intensive care unit (ICU) of a university hospital.. Two hundred forty-three patients experiencing ICU stays of longer than 48 h categorized for sepsis according to ACCP/SCCM Consensus Conference criteria.. CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area under the curve (AUC) of the receiver operating characteristic (ROC) curves, predictive capability was highest for PCT (0.846 for TNF-alpha>40 pg/ml and 0.837 for IL-6>500 pg/ml), moderate with CRP (0.744 and 0.748, respectively), and lowest for leukocyte count (0.562 and 0.534, respectively) and body temperature (0.570 and 0.623, respectively). Sensitivity, specificity, positive and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest.. PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Germany; Humans; Interleukin-6; Male; Middle Aged; Prognosis; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome; Time Factors; Tumor Necrosis Factor-alpha

Procalcitonin (PCT) plasma concentrations and its kinetic can be used as a diagnostic tool in critically ill patients and patients with sepsis. Since renal dysfunction is a frequent complication in these patients, and PCT is a protein with a low molecular weight, we have measured the half-life time of PCT after peak concentrations in patients with normal and impaired renal function. We also have analyzed the influence of patients age and gender on PCT elimination kinetics.. Prospective clinical study. Renal dysfunction was assessed by plasma creatinine. The half-life time of PCT was evaluated 24 and 48 h after acute induction of PCT, when the focus of PCT induction has rapidly been eliminated.. Intensive care unit of our University hospital, a tertiary health care institution.. 69 patients were included into the study.. None.. The half-life-time of PCT was not significantly altered during renal dysfunction (26.1-33.1 h, 25-50 percentiles, creatinine clearance < 30 ml/min) when compared with normal renal function (22.3-28.9 h). It neither correlated with creatinine clearance (p=0.14), nor age (p=0.99) or gender (p=0.90, Pearson product-moment correlation).. The data of the present study demonstrate that assessment of PCT kinetic can also be used for diagnostic and prognostic reasons in patients with renal dysfunction. It may, however, exceed 24 h also in patients with normal renal function. As to the present knowledge, renal secretion does not contribute as a main pathway to PCT elimination.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Germany; Half-Life; Humans; Intensive Care Units; Kidney Function Tests; Prospective Studies; Protein Precursors; Renal Insufficiency; Sepsis; Severity of Illness Index; Statistics, Nonparametric

Disseminated herpes simplex virus infection is a potentially fatal condition which may be difficult to differentiate from bacterial sepsis. We report the case of a neonate with overwhelming herpes simplex (type 2) viraemia who presented with 'septic shock'.. A low procalcitonin level (1.6 ng/ml), inconsistent with bacteraemia, suggests an alternative aetiology and may strengthen the case for antiviral therapy.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Fatal Outcome; Female; Herpes Genitalis; Humans; Infant, Newborn; Protein Precursors; Sepsis; Shock, Septic

The aim of the study was to investigate whether procalcitonin, soluble CD14 and interleukin-6 show advantages in predicting the outcome and specificity for bacterial infection in patients with sepsis in comparison to common C-reactive protein measurement. Laboratory parameters were measured in plasma of patients during 14 days following the diagnosis of sepsis. Patients fulfilling the ACCP/SCCM criteria for sepsis were admitted to an intensive care unit (n=35). Procalcitonin was measured with an immunoluminometric assay, and soluble CD14 and interleukin-6 were analysed by ELISA. C-reactive protein was determined nephelometrically. Measurements were performed on days 0, 1, 2, 3, 4, 7 and 14. Separating the patients into survivors (n=22) and non-survivors (n=13), it was demonstrated that non-survivors mostly exhibited, after the day of admission, increasing procalcitonin concentrations which peaked around days three and four. In contrast, the procalcitonin concentrations of survivors fell continuously to the value of 2.1 ng/ml which was reported to be important for patients prognosis. The difference between procalcitonin median values of survivors (n=22) and non-survivors (n=13) attained the level of statistical significance on day 7 and on day 14 (p=0.05). When comparing the median values of Creactive protein, soluble CD14 and interleukin-6 between survivors and non-survivors, no significant differences were detectable. In this study, plasma concentrations of soluble CD14 and interleukin-6 showed no predictive value for patients' outcome as compared with established laboratory parameters such as C-reactive protein or leukocyte count. Monitoring of procalcitonin seemed to detect severe episodes of sepsis and may improve the laboratory monitoring of septic patients.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-6; Lipopolysaccharide Receptors; Protein Precursors; Retrospective Studies; Sepsis; Time Factors; Treatment Outcome

To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications.. Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions.. Level I trauma center with emergency room, intensive care unit, and research laboratory.. Four hundred five injured patients with an Injury Severity Score of > or =9 points were enrolled in this study from January 1994 to February 1996.. Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter.. We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients' charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9+/-2.5 ng/mL; day 1) or severe MODS (5.7+/-2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1+/-0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS.. These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Topics: Adult; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Logistic Models; Male; Multiple Organ Failure; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Time Factors; Wounds and Injuries

Sexual hormones are potent regulators of various immune functions. Although androgens are immunosuppressive, estrogens protect against septic challenges in animal models. This study correlates sexual dimorphism with the incidence of posttraumatic complications in severely injured patients.. From January of 1991 to February of 1996, 1,276 consecutive injured patients (Injury Severity Score [ISS] > or = 9 points) were studied. Males (n = 911) did not differ from females (n = 365) with regard to severity of injury (ISS) and injury pattern.. The incidence of posttraumatic sepsis (30.7%) and multiple organ dysfunction syndrome (29.6%) was significantly increased in severely injured males with ISS > or = 25 points in comparison to the equivalent group of females (sepsis, 17.0%; multiple organ dysfunction syndrome, 16.0%). No difference was found in patients with ISS < 25 points. Moreover, plasma levels of procalcitonin and interleukin-6 were elevated (p < 0.05) in severely injured males compared with females.. Sex influences posttraumatic morbidity in severely injured patients and supports the concept that females are immunologically better positioned toward a septic challenge.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Incidence; Injury Severity Score; Interleukin-6; Male; Morbidity; Multiple Organ Failure; Multiple Trauma; Prospective Studies; Protein Precursors; Retrospective Studies; Sepsis; Sex Characteristics; Sex Distribution; Survival Analysis

Topics: Albuminuria; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Critical Care; Critical Illness; Esophagectomy; Follow-Up Studies; Glycoproteins; Humans; Protein Precursors; Sensitivity and Specificity; Sepsis; Time Factors

To evaluate whether plasma concentrations of procalcitonin (PCT), interleukin-6 (IL-6), protein complement 3a (C3a), leukocyte elastase (elastase), and the C-reactive protein (CRP) determined directly after the clinical onset of sepsis or systemic inflammatory response syndrome (SIRS) discriminate between patients suffering from sepsis or SIRS and predict the outcome of these patients.. Prospective study.. Medical intensive care unit at a university hospital.. Twenty-two patients with sepsis and 11 patients with SIRS.. The plasma concentrations of PCT, C3a, and IL-6 obtained < or =8 hrs after clinical onset of sepsis or SIRS but not those of elastase or CRP were significantly higher in septic patients (PCT: median, 16.8 ng/mL, range, 0.9-351.2 ng/mL, p = .003; C3a: median, 807 ng/mL, range, 422-4788 ng/mL, p < .001; IL-6: median, 382 pg/mL, range, 5-1004 pg/mL, p = .009, all Mann-Whitney rank sum test) compared with patients suffering from SIRS (PCT: median, 3.0 ng/mL, range, 0.7-29.5 ng/mL; C3a: median, 409 ng/mL, range, 279566 ng/mL; IL-6: median, 98 pg/mL, range, 23-586 pg/mL). The power of PCT, C3a, and IL-6 to discriminate between septic and SIRS patients was determined in a receiver operating characteristic analysis. C3a was the best variable to differentiate between both populations with a maximal sensitivity of 86% and a specificity of 80%. An even better discrimination (i.e., a maximal sensitivity of 91% and a specificity of 80%) was achieved when PCT and C3a were combined in a "sepsis score." C3a concentrations also helped to predict the outcome of patients. Based on the sepsis score, a logistic regression model was developed that allows a convenient and reliable determination of the probability of an individual patient to suffer from sepsis or SIRS.. Our data show that the determination of PCT, IL-6, and C3a is more reliable to differentiate between septic and SIRS patients than the variables CRP and elastase, routinely used at the intensive care unit. The determination of PCT and C3a plasma concentrations appears to be helpful for an early assessment of septic and SIRS patients in intensive care.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Complement C3a; Diagnosis, Differential; Female; Glycoproteins; Humans; Interleukin-6; Male; Middle Aged; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

The elimination of procalcitonin and the course of plasma concentrations during continuous veno-venous haemodiafiltration were measured in patients with sepsis or multiple organ dysfunction syndrome, because these patients are a main target group for the measurement of procalcitonin and often require renal replacement therapy. Procalcitonin was measured in the prefilter plasma and the filtrate at 5 min, 15 min and 1, 2, 4, 6, 12, 24 h after set-up of continuous veno-venous haemodiafiltration. In a prospective study, 19 patients with plasma levels of procalcitonin > 3 ng mL-1 and acute oliguric renal failure treated with continuous veno-venous haemodiafiltration using a polysulphone membrane, were evaluated for the study of clearance. Twenty-one control patients (procalcitonin < 2 ng mL-1) were studied to determine whether filtration itself induced a procalcitonin response. No interventions were required. In patients with low procalcitonin concentrations (procalcitonin < 2 ng mL-1) continuous veno-venous haemodiafiltration did not cause a rise in procalcitonin. In patients with increased procalcitonin plasma concentrations (> 3 ng mL-1), the protein was removed through the polysulphone membrane, with a final clearance of 4 mL min-1 after the initial adsorption period (clearance 0.4-0.9 mL min-1 during the first hour of continuous veno-venous haemodiafiltration). Thus, on the average, approximately 10% of plasma concentrations were measurable in the filtrate ultimately. However, procalcitonin plasma levels were not significantly altered during continuous veno-venous haemodiafiltration (86% of the initial concentration after 24 h). Although procalcitonin is removed from the plasma during continuous veno-venous haemodiafiltration in measurable amounts plasma procalcitonin concentrations did not change significantly during haemodiafiltration. Procalcitonin thus can also be used as a diagnostic parameter in patients undergoing continuous veno-venous haemodiafiltration.

Topics: Acute Kidney Injury; Adsorption; Aged; Biocompatible Materials; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycoproteins; Hemodiafiltration; Humans; Male; Membranes, Artificial; Middle Aged; Multiple Organ Failure; Polymers; Prospective Studies; Protein Precursors; Renal Replacement Therapy; Sepsis; Shock, Septic; Statistics, Nonparametric; Sulfones

Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections.. Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls).. In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV).. These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

Topics: Aged; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Extracorporeal Circulation; Female; Glycoproteins; Graft Rejection; Heart Transplantation; Humans; Male; Middle Aged; Mycoses; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Virus Diseases

To assess the use of procalcitonin (PCT) for the diagnosis of infection in a medical ICU.. Prospective, observational study.. Seventy-seven infected patients and 24 patients with systemic inflammatory response syndrome (SIRS) due to other causes. Seventy-five patients could be classified into sepsis (n = 24), severe sepsis (n = 27) and septic shock (n = 24), and 20 SIRS patients remained free from infection during the study. Plasma PCT and C-reactive protein (CRP) levels were evaluated within 48 h of admission (day 0), at day 2 and day 4.. As compared with SIRS, PCT and CRP levels at day 0 were higher in infected patients, regardless of the severity of sepsis (25.2 +/- 54.2 ng/ml vs 4.8 +/- 8.7 ng/ml; 159 +/- 92 mg/l vs 71 +/- 58 mg/l, respectively). At cut-off values of 2 ng/ml (PCT) and 100 mg/l (CRP), sensitivity and specificity were 65% and 70% (PCT), 74% and 74% (CRP). PCT and CRP levels were significantly more elevated in septic shock (38.5 +/- 59.1 ng/ml and 173 +/- 98 mg/l) than in SIRS (3.8 +/- 6.9 ng/ml and 70 +/- 48 mg/l), sepsis (1.3 +/- 2.7 ng/ml and 98 +/- 76 mg/l) and severe sepsis (9.1 +/- 18. 2 ng/ml and 145 +/- 70 mg/l) (all p = 0.005). CRP, but not PCT, levels were more elevated in severe sepsis than in SIRS (p<0.0001). Higher PCT levels in the patients with four dysfunctional organs and higher PCT and CRP levels in nonsurvivors may only reflect the marked inflammatory response to septic shock.. In this study, PCT and CRP had poor sensitivity and specificity for the diagnosis of infection. PCT did not clearly discriminate SIRS from sepsis or severe sepsis.

Topics: Analysis of Variance; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Glycoproteins; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Statistics, Nonparametric

To examine the hypothesis that nitrite/nitrate, neopterin, and procalcitonin (PCT) levels can be useful predictors of sepsis-associated mortality and predictors of the postoperative complications after cardiopulmonary bypass (CPB).. Prospective clinical study.. Intensive care unit of the Medical University Hospital.. 41 patients with sepsis, 42 patients subjected to open heart surgery with CPB, and 30 healthy volunteers.. Nitrite/nitrate, neopterin, and PCT levels were measured in septic patients as soon as sepsis was recognized and then on the 2nd, 3rd, and 5th days of treatment. Statistically significant differences between survivors and nonsurvivors were found for neopterin and PCT. The area under receiver operating characteristic curve (AUC) for both parameters as predictors of mortality was above 0.8. The nitrite/nitrate level was also higher in nonsurvivors, but the AUC remained below 0.8, which indicates poor predictive power. The same parameters were measured in patients undergoing cardiac surgery before, during and after CPB establishment. The development of post-operative complications was correlated with increased postoperative neopterin and PCT levels. Additionally, neopterin was found as an early marker for the prognosis of postoperative complications, since patients who developed organ dysfunction had had elevated concentration of this parameter even before surgery (AUC 0.83). Measurement of NO metabolite levels was less specific and less sensitive.. Our results confirm the value of PCT and neopterin measurement as diagnostic tools in monitoring the clinical course of patients in intensive care units.

Topics: Area Under Curve; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Glycoproteins; Humans; Male; Middle Aged; Neopterin; Nitric Oxide; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Statistics, Nonparametric

We prospectively examined 464 febrile patients (median age, 61 years) for predictors of in-hospital death, by use of univariate and multivariate logistic regression using clinical data (age, underlying disease, duration of fever, chills, and shock on admission) and plasma endotoxin, TNF-alpha, IL-6, IL-10, and procalcitonin levels. The mortality rate was 4.6-fold higher (95% confidence interval [CI], 1.8-12) in 31 patients with shock on admission, 7 of whom died; the strongest association with mortality was the endotoxin concentration (relative risk, 13.7; 95% CI, 1. 4-136), which predicted 5 of the deaths with a 5% false-positive rate. For 433 patients without shock on admission, mortality (26 deaths) was associated with age and underlying disease: clinical data predicted 30% of the deaths, whereas IL-6 and procalcitonin levels identified an extra 10% with a 5% false-positive rate. When febrile patients are screened on hospital admission to identify those with a high risk for mortality, clinical judgment on the basis of age, underlying disease, and recent history outweighs the predictive value of endotoxin, cytokine, and procalcitonin levels. Only in patients who present with shock will measurement of endotoxin levels help predict those who will likely die at the cost of few false-positive results.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Bacteria; Calcitonin; Calcitonin Gene-Related Peptide; Community-Acquired Infections; Cytokines; Endotoxemia; Endotoxins; Female; Fever; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock

Infected pancreatic necrosis (IPN) is an absolute indication for surgical intervention, therefore an early and accurate laboratory diagnosis is necessary to confirm the infection. The aim of the study was to analyze the clinical value of procalcitonin (PCT) for the prediction of infected necrosis, in comparison with interleukin-6 (IL-6) and sICAM 1.. A total of 30 patients were investigated; 10 patients with sterile pancreatic necrosis (SPN), 10 with IPN, and 10 with sepsis of different origin. The concentrations of PCT in the patients' sera were measured by immunoluminometric assay (BRAHMS Diagnostica, Berlin, Germany, PCT Lumitest), the IL-6 concentrations by bioassay, applying the B-9 cell line, and the sICAM-1 levels by enzyme-linked immunosorbent assay (ELISA) (R&D). PCT was determined in cell lysates by ECL Western blot.. PCT was found in relatively high concentrations (8.5 +/- 4.8 ng/mL) only in patients with infected pancreatic necrosis, and in patients with sepsis of different origin ( 15 +/- 5.4 ng/mL). Positive values (> 1 ng/mL) preceded positive bacterial results from either blood or surgical samples. None of the serum samples of patients with SPN exhibited PCT concentrations higher than 1.2 ng/mL. In contrast, IL-6 and sICAM-1 were overproduced in both types (infected and sterile) of pancreatic necrosis, and their levels remained elevated for several days even after surgical elimination of the infected focus (widespread necrosectomy and continuous lavage). Sensitivity, specificity, and positive predictive values for discriminating IPN from SPN was 90, 100, and 100% for PCT (p < 0.0001); 100, 20, and 55% for IL-6 (p 0.474 n.s.) and 90, 10, and 50% for sICAM-1 (p 1.000 n.s.). Immunoblotting revealed no PCT in patients' leukocytes, or in human endothelial cell lines.. Elevated serum IL-6 and sICAM-1 levels are characteristic in systemic inflammatory response syndrome (SIRS) of either infectious or noninfectious origin. In contrast, the PCT level is an accurate, readily available parameter that allows the discrimination of IPN, and is a helpful marker facilitating a decision concerning surgical intervention.

Topics: Adult; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Leukocytes; Male; Middle Aged; Pancreatitis, Acute Necrotizing; Prognosis; Protein Precursors; Sensitivity and Specificity; Sepsis

To determine the influence of early-onset neonatal sepsis on interleukin-6 (IL-6) and procalcitonin (PCT) levels in cord blood. To evaluate the significance of usually used infection markers--C-reactive protein (CRP) and immature to total neutrophil ratio (I/T)--and new markers (PCT, IL-6) for the diagnosis of early-onset neonatal sepsis.. Prospective clinical study.. Institute for the Care of Mother and Child, Prague.. The serum levels of IL-6 and PCT were measured in cord blood in 37 low birht weight infants less than 35 week of gestation born in our institute. IL-6 and PCT levels were further evaluated together with CRP and I/T in neonatal blood within 2 hours after delivery. Neonatal sepsis within the first 72 hours of life was monitored.. Differences in mean values of CRP, I/T, IL-6, and PCT between "sepsis proven" and "sepsis not proven" groups were not statistically significant. Only the difference between groups in cord blood PCT was of borderline significance (p = 0.06, higher in "sepsis proven" group). Fisher test showed significant dependence on sepsis in cord blood PCT only (cut-off point 0.4 ng/ml, p < or = 0.05). Other parameters did not show significant dependence on sepsis. Sensitivity for early onset sepsis above 50% was found in cord blood PCT only (sensitivity 60%, specificity 85.2%). PCT predictive accuracy for sepsis expressed as AUC value was 0.74 +/- 0.06.. The only relatively sensitive marker and moderate predictor of early-onset sepsis in premature low birthweight infant was in our study cord blood PCT.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Fetal Blood; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Leukocyte Count; Neutrophils; Prospective Studies; Protein Precursors; Sepsis

To determine the value of procalcitonin (ProCT) as a marker of infection in critically ill patients.. Prospective, observational study.. Medicosurgical department of intensive care (31 beds).. One hundred eleven infected and 79 noninfected patients.. None.. ProCT and C-reactive protein (CRP) concentrations were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and 7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6 vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP increased the specificity for infection to 82.3%. In the infected patients, plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors. Infected patients with bacteremia had higher ProCT concentrations than those without bacteremia, but similar CRP concentrations. ProCT levels were particularly high in septic shock patients.. ProCT is not a better marker of infection than CRP in critically ill patients, but it can represent a useful adjunctive parameter to identify infection and is a useful marker of the severity of infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Female; Hospital Mortality; Humans; Intensive Care Units; Length of Stay; Leukocyte Count; Male; Middle Aged; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Topics: Amino Acid Sequence; Animals; Anti-Inflammatory Agents; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Inflammation Mediators; Mice; Molecular Sequence Data; Protein Precursors; Rats; Sepsis

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.

Topics: Base Sequence; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; DNA; DNA Primers; Gene Expression Regulation; Humans; In Vitro Techniques; Lipopolysaccharide Receptors; Lipopolysaccharides; Molecular Sequence Data; Monocytes; Peptide Fragments; Phytohemagglutinins; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sepsis

To determine correlations and predictive strength of surrogate markers (body temperature, leukocyte count, C-reactive protein [CRP], and procalcitonin [PCT]) with elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in septic patients.. Prospective consecutive case series.. Surgical intensive care unit (ICU) of a university hospital.. A total of 175 patients experiencing intensive care unit stays >48 hrs categorized for sepsis according to ACCP/ SCCM Consensus Conference criteria.. CRP and PCT were both significantly correlated with TNF-alpha and IL-6. Based on the area-under-the-curve of the receiver operating characteristics curves, predicting capability was highest for PCT (0.814 for TNF-alpha >40 pg/mL and 0.794 for IL-6 >500 pg/mL), moderate with CRP (0.732 and 0.716, respectively), and lowest for leukocyte count (0.493 and 0.483, respectively) and body temperature (0.587 and 0.589, respectively). Sensitivity, specificity, positive, and negative predictive values and test effectiveness all followed this same pattern of being highest for PCT followed by CRP, with leukocyte count and body temperature being lowest.. PCT may be an early and better marker of elevated cytokines than the more classic criteria of inflammation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Interleukin-6; Leukocyte Count; Male; Middle Aged; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Tumor Necrosis Factor-alpha

To test the sepsis marker procalcitonin (PCT) for its applicability to discriminate between septic and nonseptic causes of acute respiratory distress syndrome (ARDS).. Prospective study, assessing the course of PCT serum levels in early (within 72 hrs after onset) ARDS. The three other inflammation markers neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) were tested in parallel.. Twenty-four-bed medical intensive care unit of a 1,990-bed primary hospital, providing health care for an estimated 39,000 patients.. Twenty-seven patients, 18 male and nine female, aged 16-85 yrs, with early ARDS of known cause (17 with septic and ten with nonseptic ARDS) were enrolled in a prospective study between May 1994 and May 1995.. Serum samples were drawn every 4-6 hrs for measurement of PCT, neopterin, IL-6, and CRP concentrations. Blood cultures, tracheal aspirates, and urine samples were obtained every 12-24 hrs. In 24 of 27 patients, bronchoscopic cultures were also obtained. Clinical sepsis criteria as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were checked daily.. Assessment of inflammation marker serum levels in septic vs. nonseptic ARDS. PCT serum levels were significantly higher (p < .0005) in the patients with septic ARDS than in patients with nonseptic ARDS within 72 hrs after onset of ARDS. There was no overlap between the two groups. Also, neopterin allowed a differentiation (p < .005), although a substantial overlap between serum levels of septic and nonseptic patients was observed. No discrimination could be achieved by determination of CRP and IL-6 levels.. PCT determination in early ARDS could help to discriminate between septic and nonseptic underlying disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Bacteria; Bacterial Infections; Biomarkers; Biopsy; Bronchoscopy; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Intensive Care Units; Interleukin-6; Male; Middle Aged; Neopterin; Prospective Studies; Protein Precursors; Respiratory Distress Syndrome; Sepsis

Procalcitonin (PCT), a precursor of calcitonin, and endotoxin were determined in the burn wound sepsis model in which 21 Sprague-Dawley rats were scalded approximately 30% on their back. On day 2 post burn, the wounds were inoculated 1 x 10(8) colony-forming units of Pseudomonas aeruginosa. On day 5 post burn P. aeruginosa was detected by blood culture in 10 of the 21 rats (47.6%). The mortality rate 7 days after burn was 90.5%. Significant correlations were observed between serum endotoxin levels and serum PCT levels on day 5 post burn (r = 0.860, p<0.001). It was suggested that endotoxin may induce the release of PCT and that measuring the levels of PCT may be useful in diagnosing burn wound sepsis.

Topics: Animals; Biomarkers; Burns; Calcitonin; Calcitonin Gene-Related Peptide; Disease Models, Animal; Humans; Male; Protein Precursors; Pseudomonas aeruginosa; Pseudomonas Infections; Rats; Rats, Sprague-Dawley; Sepsis; Wound Infection

We evaluated the reliability of serum concentrations of procalcitonin for the diagnosis of early- and late-onset sepsis in a neonatal intensive care unit (NICU) setting. Timed procalcitonin determinations were prospectively obtained during two postnatal periods: 0-48 hours of age (period 1) and 3-30 days of age (period 2). In period 1, we measured procalcitonin concentrations in 83 healthy newborns (group 0) and in 120 NICU patients (14 with culture-proven sepsis, group 1A; 14 with clinical septicemia, group 1B; 75 with no evidence of infection, group 2; and 17 with uncertain findings, group 3). After we established 95% hour-specific reference ranges for group 0, we performed multiple linear regression analyses to determine which maternal, intrapartum, and neonatal complications would affect normal procalcitonin values. Maternal diabetes was the only variable identified in group 2 patients that induced a significant deviation from procalcitonin reference ranges. Analyses of the pooled procalcitonin values obtained for group 1 patients over the 48-hour period after birth yielded a sensitivity of 92.6% and a specificity of 97.5% for procalcitonin concentrations in the detection of early-onset sepsis. In period 2, blood samples from 23 cases with systemic infections were analyzed for procalcitonin concentrations at the onset of signs of infection. The control group was formed by matching four uninfected NICU patients to each infected case. None of the procalcitonin values for the 92 controls overlapped those for the cases (sensitivity and specificity, 100%). Procalcitonin is a promising marker for the diagnosis of early- and late-onset sepsis in neonates at high risk for this infection.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Prospective Studies; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Severity of Illness Index

Topics: Animals; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Protein Precursors; Sepsis

Procalcitonin (ProCT), the precursor to the calcitonin hormone, is abnormally increased in experimental and clinical systemic inflammation, including sepsis. Initially, we investigated the effects of supraphysiologic amounts of ProCT administered to animals with septic peritonitis. Subsequently, we evaluated the efficacy of prophylactic and therapeutic immune blockade of ProCT in this lethal model of sepsis.. Prospective, experimental, controlled study.. Animal research laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at a Veterans Affairs Medical Center.. Young male Golden Syrian hamsters, weighing 90 to 120 g.. In the first study, serum ProCT concentrations were measured in animals at 0, 3, 6, 12, and 24 hrs after induction of sepsis by intraperitoneal implantation of pellets containing Escherichia coli (5 x 10(8) colony-forming units/pellet). In the second study, with mortality as the end point, 30 microg/kg of isolated, purified human ProCT in 10% hamster serum (experimental) or an equal volume of 10% hamster serum (control) were administered intravenously at the time of the E. coli peritoneal implantation. In the third study, experimental animals received intraperitoneal injections of a multiregion-specific goat antiserum reactive to hamster ProCT 1 hr before and 24 hrs after E. coli implantation, while control animals received nonimmune goat serum at the same time points. In the final study, the same antiserum was administered in five divided doses during the 24 hrs after the insertion of E. coli.. In the initial study, ProCT concentrations were increased shortly after induction of sepsis and peaked at 12 hrs. Administration of exogenous ProCT to septic animals significantly increased mortality compared with control animals (93% vs. 43%, p=.02). Prophylactic blockade of ProCT almost completely protected the animals from the lethal effects of sepsis: the 102-hr mortality rate in the experimental group was 6% compared with 62% in the control group (p < .003). In the therapeutic trial, the 102-hr mortality rate was 54% in experimental animals compared with 82% in control animals (p < .045).. These results demonstrate that increased ProCT exacerbates mortality in experimental sepsis, whereas neutralization of ProCT increases survival. Thus, ProCT, in addition to being an important marker of severity of systemic inflammation and mortality, is an integral part of the inflammatory process and directly affects the outcome.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Cricetinae; Escherichia coli Infections; Humans; Immune Sera; Immunization, Passive; Injections, Intraperitoneal; Male; Mesocricetus; Protein Precursors; Sepsis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Diagnosis, Differential; Humans; Infant, Newborn; Infant, Premature, Diseases; Protein Precursors; Sensitivity and Specificity; Sepsis

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Postoperative Complications; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infant, Newborn; Protein Precursors; Sepsis

Procalcitonin (PCT) levels increase in patients with systemic infections; the highest levels have been found in sepsis. This study tested whether plasma procalcitonin level was related to sepsis, CRP, burn size, inhalation injury or mortality in severely burned patients over the entire clinical course. In 27 patients with 51 (20-91)% TBSA, PCT was measured three times weekly from admission over the entire course of stay in a single ICU. Daily scoring by the "Baltimore Sepsis Scale" was performed. The patients were assigned to three groups depending on the clinical course and outcome: A = no septic complications, B = septic complications-survivors, C = septic complications non-survivors. PCT levels were elevated slightly at admission (mean 2.1 ng/ml) except in three patients who suffered electrical burns (mean 15.7 ng/ml). PCT peak levels correlated well with the Scoring values (r = 0.84) while CRP did not (r = 0.64). Peak PCT levels were significantly higher (p < 0.005) in septic patients (B and C) who averaged 49.8+/-76.9 ng/ml, than in non-septic patients (A) who averaged peak levels of 2.3+/-3.7 ng/ml. The highest PCT levels were found immediately before death (86.8+/-97 ng/ml). Seven patients had an inhalation injury 3rd degree. In these patients at 24 h postburn, there was no relationship between PCT levels and inhalation injury but during the later days postburn there were significant differences in PCT levels in patients with versus without inhalation injury. All patients with inhalation injury 3rd degree developed septic complications. There was no positive correlation between the PCT-admission-levels and the TBSA, but there was a positive correlation between the TBSA and the mean peak PCT levels during the later days postburn (r = 0.73; p < 0.05). The cut-off value of 3 ng/ ml we found reliable to indicate severe bacterial or fungal infection. PCT values over 10 ng/ml increasing over the following days were found only in life-threatening situations due to systemic infections. The individual course of PCT in one patient is more important than absolute values. PCT presented in this study as a useful diagnostic parameter in severely burned patients.

Topics: Adolescent; Adult; Bacterial Infections; Body Surface Area; Burns; Burns, Electric; Burns, Inhalation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cause of Death; Critical Care; Follow-Up Studies; Glycoproteins; Humans; Length of Stay; Middle Aged; Mycoses; Patient Admission; Protein Precursors; Reproducibility of Results; Sepsis; Survival Rate

The aim of the study was to investigate the reliability of procalcitonin (PCT), a new potential marker for detection of bacterial, fungal and protozoal infections, in order to differentiate these from viral infections and early rejections in heart, heart-lung and lung transplanted patients. PCT is a propeptide of calcitonin with unknown origin which is not detectable in plasma of healthy subjects. It increases rapidly and significantly under severe microbial infections.. PCT plasma levels were measured using an immuno-luminescence assay. C-reactive protein and white blood cells were quantified to validate the PCT values.. Increased levels of PCT were found in all transplant patients with bacterial, fungal and protozoal infections. The magnitude of the values were clearly associated with the severity of the infection. Trauma of operation or inflammatory events such as viral infections and rejections did not trigger PCT-production. The release of PCT did not depend on the type of pathogens even though Aspergillum resulted in the highest levels measured. Sensitivity, specificity and prognostic value of PCT for systemic infections were higher than of the other parameters investigated.. PCT is a highly specific analyte which shows significant diagnostic validities when nonviral infections are compared with rejection episodes. PCT discriminates between inflammatory events such as rejection or viral infections and nonviral-infections including bacterial, fungal and protozoal infections. The half-life of PCT is 24 h indicating clearly a competent antibiotic treatment. Unnecessary antibiotic therapy can be avoided due to the early exclusion of bacterial and fungal infections.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Female; Graft Rejection; Heart Transplantation; Heart-Lung Transplantation; Humans; Infant; Lung Transplantation; Male; Middle Aged; Protein Precursors; Retrospective Studies; Sepsis

Serum procalcitonin was determined in newborn infants at the time of admission to the pediatrics or obstetrics unit. Increased levels were found in all neonates with bacterial sepsis. Neonates with viral infection, bacterial colonization, or neonatal distress had normal or slightly increased levels. These data suggest that procalcitonin might be of value in diagnosing neonatal sepsis.

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Infant, Newborn; Prospective Studies; Protein Precursors; Sepsis; Virus Diseases

Increased serum concentration of procalcitonin (PCT) in limited number of paediatric patients with acute severe bacterial infections has been described previously. In a prospective study in 337 hospitalised adult patients fulfilling the SIRS-criteria, serum PCT was determined on admission and up to 9 days thereafter. Patients with microbiologically documented infection showed peak values of 30 ng/ml at day 3, which rapidly decreased to normal levels. Patients without sepsis revealed baseline values (0.1 ng/ml or lower). The validity criteria were calculated for several breakpoints of PCT. We detected an interval from 0.1 to 0.5 ng/ml under which a severe microbial infection is unlikely (sensitivity 91%, specificity 25%, positive predictive value 39%, negative predictive value 86%). An infection is most likely above 0.5 ng/ml (sensitivity 60%, specificity 79%, positive predictive value 61%, negative predictive value 78%). Between these two points an infection can neither be confirmed nor excluded. The excellent specificity and negative predictive value at a cut-off point of 0.5 ng/ml suggests that this test might be a useful parameter in the management of infectious diseases.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Predictive Value of Tests; Prospective Studies; Protein Precursors; Reproducibility of Results; Sensitivity and Specificity; Sepsis; Shock, Septic