calca-protein--human and Heart-Diseases

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and conse

Topics: Adrenomedullin; Algorithms; Atrial Natriuretic Factor; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Emergency Medicine; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Precision Medicine; Protein Precursors; Respiratory Tract Diseases; Switzerland; Triage; Troponin

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

Therapeutic plasma exchange (TPE) plays a key role in the management of various diseases, from thrombotic thrombocytopenic purpura and Goodpasture's syndrome to cardiac allograft rejection. In many of these disease states cardiac and inflammatory involvement is common and biomarkers are routinely used for diagnosis or assessment of therapeutic success. The effect of TPE on biomarkers used in the clinical routine has not been investigated.. TPE was initiated for established clinical conditions in 21 patients. Troponin T, NT-proBNP, C-reactive protein, procalcitonin and routine chemistry were drawn before and after TPE, as well as before and after the 2(nd) TPE. The total amount of these markers in the waste bag was also analyzed.. In 21 patients 42 TPEs were performed. The procedure reduced plasma levels of the examined biomarkers: 23% for NT-proBNP (pre vs. post: 4637±10234 ng/l to 3565±8295 ng/l, p<0.001), 64% for CRP (21.9±47.0 mg/l vs. 7.8±15.8 mg/l, p<0.001) and 31% for procalcitonin (0.39±1.1 µg/l vs. 0.27±0.72 µg/l, p=0.004). TPE also tended to reduce plasma levels of troponin T by about 14% (60.7±175.5 ng/l vs. 52.2±141.3 ng/l), however this difference was not statistical significant (p=0.95). There was a significant correlation between the difference of pre TPE levels to post TPE levels of all examined biomarkers and the total amount of the removed biomarker in the collected removed plasma.. TPE significantly reduces plasma levels of inflammatory and cardiac biomarkers. Therefore, post TPE levels of cardiac and inflammatory biomarkers should be viewed with caution.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Heart Diseases; Humans; Inflammation; Kinetics; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Plasma Exchange; Protein Precursors; Time Factors; Troponin T

Postoperative infections and cardiac events are the major morbidity factors after thoracic surgery and dominating causes of death. Therefore, a sensitive blood marker is needed for an early diagnosis of complications. Twenty-two patients admitted with lung cancer were enrolled in this study. Procalcitonin, brain natriuretic peptide, C-reactive peptide and interleukin-6 levels were recorded preoperatively and postoperatively on days 1-5. Laboratory values of patients with cardiac or infectious complications were compared to patients without complications. During postoperative course procalcitonin and brain natriuretic peptide levels elevated in all patients, but both had higher peak levels in patients with infectious or cardiac complication than without these complications. Interleukin-6 levels were increased on day one and showed a slower decrease in case of complications than without complications. In general, brain natriuretic peptide and procalcitonin levels are increased in the postoperative course after major pulmonary resection, but cardiac and infectious complications are associated with higher levels and a slower decrease than without complications. Interleukin-6 levels showed a slower decrease in patients with complications in the postoperative course than without complications. So the combination of procalcitonin, brain natriuretic peptide, and interleukin-6 seems to be useful for an optimized postoperative monitoring.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Follow-Up Studies; Heart Diseases; Humans; Interleukin-6; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Pneumonectomy; Predictive Value of Tests; Prospective Studies; Protein Precursors; Surgical Wound Infection; Time Factors; Treatment Outcome

Due to the combination of local trauma, extracorporeal circulation (ECC), and pulmonary and myocardial reperfusion, cardiac surgery leads to substantial changes in the immune system and possibly to post-operative complications. Procedures without ECC, however, have failed to demonstrate clear advantages. We hypothesized that ECC is far less important in this context than the reperfusion/reventilation of the lung parenchyma and the surgical trauma. We therefore conducted a prospective observational study to compare immune reactions after cardiac operations with those after thoracic surgery.. Serum levels of pro-inflammatory interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha as well as C-reactive protein (CRP), lipoprotein-binding protein (LBP) and procalcitonin (PCT) were measured pre-operatively (d0), at the end of the operation (dx), 6h after the operation (dx+), on the 1st (d1), 3rd (d3), and 5th (d5) post-operative days in 108 patients (pts) undergoing elective coronary artery bypass grafting (CAB) with ECC (n=42, CPB CAB), off-pump coronary artery bypass surgery (n=24, OP CAB) without ECC or thoracic surgery (n=42, TS).. After cardiac surgery (CS), IL-6 and IL-8 increased and reached a maximum on dx+. IL-6 returned to baseline values at d3, whereas IL-8 remained elevated until d5. No difference was found between OP CAB and CPB CAB patients. In the TS patients, IL-6 increased later (dx+) and absolute levels were lower than in the CS patients. No increase in IL-8 was noted in the TS patients. Due to the high variation in the results obtained in all three groups, there was no significant change in TNF-alpha. A comparison of TS, OP CAB, and CPB CAB revealed that the CS patients had higher levels on d0, dx, d3, and d5. Serum levels of CRP, LBP, and IL-2R increased from dx+ to d5 in all groups and reached maximum values on d3. Whereas we found no difference in CRP and IL-2R between the groups, LBP levels were significantly higher from dx+ to d3 after OP CAB. PCT was elevated from dx+ to d3 in all pts. Similar levels were noted for the TS and OP CAB patients. The CPB CAB patients showed the highest levels.. Surgical trauma and reperfusion injury appear to represent the predominant factors resulting in immunologic changes after cardiac surgery. Cardiopulmonary bypass (CPB) may be less important for immune response and acute-phase reactions than previously suspected. In addition, our data indicate a relationship between IL-6 synthesis and the degree of surgical trauma. IL-8 appears to be elevated only after cardiac surgery whereas PCT liberation depended on the use of ECC.

Topics: Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cell Division; Coronary Artery Bypass; Coronary Artery Bypass, Off-Pump; Cytokines; Extracorporeal Circulation; Heart Diseases; Humans; Immunity, Innate; Interleukin-6; Interleukin-8; Lymphocyte Activation; Lymphocytes; Middle Aged; Prospective Studies; Protein Precursors; Thoracic Neoplasms; Thoracic Surgical Procedures; Tumor Necrosis Factor-alpha

To investigate procalcitonin (PCT) levels in patients undergoing cardiopulmonary bypass (CPB) in order to assess the prevalence and prognostic capacity of elevated PCT levels following CPB in open heart surgery.. prospective observational study in consecutive patients.. Twenty-four-bed ICU, department of thoracic and cardiovascular surgery, university hospital.. Seven hundred and twenty two patients, 691 of whom underwent CPB, i.e., 476 had coronary bypass surgery (CABG), 130 valve replacement, 34 combined CABG and valve replacement and 23 thoracic aortic surgery.. Standard perfusion techniques were used with cardioplegic arrest and mild hypothermia (28-32 degrees C). With the exception of thoracic aortic procedures, full-flow perfusion was performed.. PCT was measured prior to surgery and daily thereafter until ICU discharge or death. PCT significantly increased at day 1 postoperatively compared to baseline values (0.25+/-1.65 vs 6.49+/-22.0 ng/ml, p<0.005). However, in 55.1% of patients PCT was below 1.0 ng/ml. In 12.8% of CABG patients PCT was increased to >5.0 ng/ml, compared to 39% in valve patients and 35% of patients with aortic surgery. An elevated PCT level >1.0-5.0 ng/ml at day 1 was highly predictive of mortality (P<0.03, vs<1.0 ng/ml), with an additional accuracy when levels >5.0 ng/ml were measured (P<0.002 vs<1.0 ng/ml).. These results provide evidence that PCT might serve as an early prognostic marker in patients undergoing CPB in open heart surgery. It may be worth considering immunomodulating approaches in patients presenting elevated PCT levels in the early phase after CPB.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Heart Diseases; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Protein Precursors; Sensitivity and Specificity

One hundred and ten patients were investigated prospectively in a study aimed at creating reference curves for inflammation markers (serum C-reactive protein (CRP), blood leukocyte count, iron, transthyretin and procalcitonin). Blood samples were taken daily and the patients were monitored for signs of infection. Ninety-six patients had no postoperative infections. CRP and leukocyte counts peaked on the third and second postoperative days, respectively. Neither patients operated on off-pump (n = 4) nor patients with minor infections (n = 11) differed from the non-infected group. Two out of three patients with major postoperative infection exhibited a secondary peak in CRP and leukocyte count. Iron and transthyretin decreased initially, followed by a slow increase without any difference between the groups. Procalcitonin was high in some non-infected patients and low in some infected patients. CRP and leukocyte count had a predictable course with a secondary peak in major infections but the other markers did not provide any valuable information.

Topics: Adult; Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Heart Diseases; Humans; Inflammation Mediators; Iron; Leukocyte Count; Male; Middle Aged; Postoperative Complications; Prealbumin; Predictive Value of Tests; Prospective Studies; Protein Precursors; Surgical Wound Infection; Systemic Inflammatory Response Syndrome

To determine the value of procalcitonin (PCT) as a marker of postoperative infection after cardiac surgery.. A prospective single institution three phase study.. University cardiac surgical intensive care unit (31 beds).. Phase 1: To determine the normal perioperative kinetics of PCT, 20 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass were included. Phase 2: To determine whether PCT may be useful for diagnosis of postoperative infection, 97 consecutive patients with suspected infection were included. Phase 3: To determine the ability of PCT to differentiate patients with septic shock from those with cardiogenic shock, 26 patients with postoperative circulatory failure were compared.. Phase 1: Serum samples were drawn for PCT determination after induction of anesthesia (baseline), at the end of surgery, and daily until postoperative day (POD) 8. Baseline serum PCT concentration was 0.17 +/- 0.08 ng/mL (mean +/- SD). Serum PCT increased after cardiac surgery with a peak on POD 1 (1.08 +/- 1.36). Serum PCT returned to normal range on POD 3 and remained stable thereafter. Phase 2: In patients with suspected infection, serum PCT was measured at the same time of C-reactive protein (CRP) and bacteriologic samples. Among the 97 included patients, 54 were infected with pneumonia (n = 17), bacteremia (n = 16), mediastinitis (n = 9), or septic shock (n = 12). In the 43 remaining patients, infection was excluded by microbiological examinations. In noninfected patients, serum PCT concentration was 0.41 +/- 0.36 ng/mL (range, 0.08-1.67 ng/mL). Serum PCT concentration was markedly higher in patients with septic shock (96.98 +/- 119.61 ng/mL). Moderate increase in serum PCT concentration occurred during pneumonia (4.85 +/-3.31 ng/mL) and bacteremia (3.57 +/- 2.98 ng/mL). Serum PCT concentration remained low during mediastinitis (0.80 +/- 0.58 ng/mL). Five patients with mediastinitis, two patients with bacteremia, and one patient with pneumonia had serum PCT concentrations of <1 ng/mL. These eight patients were administered antibiotics previously and serum PCT was measured during a therapeutic antibiotic window. For prediction of infection by PCT, the best cutoff value was 1 ng/mL, with sensitivity 85%, specificity 95%, positive predictive value 96%, and negative predictive value 84%. Serum CRP was high in all patients without intergroup difference. For prediction of infection by CRP, a value of 50 mg/L was sensitive (84%) but poorly specific (40%). Comparing the area under the receiver operating characteristic curves, PCT was better than CRP for diagnosis of postoperative sepsis (0.82 for PCT vs. 0.68 for CRP). Phase 3: Serum PCT concentration was significantly higher in patients with septic shock than in those with cardiogenic shock (96.98 +/- 119.61 ng/mL vs. 11.30 +/- 12.3 ng/mL). For discrimination between septic and cardiogenic shock, the best cutoff value was 10 ng/mL, with sensitivity of 100% and specificity of 62%.. Cardiac surgery with cardiopulmonary bypass influences serum PCT concentration with a peak on POD 1. In the presence of fever, PCT is a reliable marker for diagnosis of infection after cardiac surgery, except in patients who previously received antibiotics. PCT was more relevant than CRP for diagnosis of postoperative infection. During a postoperative circulatory failure, a serum PCT concentration >10 ng/mL is highly indicative of a septic shock.

Topics: Adult; Aged; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Diagnosis, Differential; Female; Heart Diseases; Heart Failure; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Shock, Cardiogenic; Shock, Septic; Surgical Wound Infection

Cardiopulmonary bypass generally leads to an unspecific increase of inflammatory parameters after cardiac operations. Increased Procalcitonin (PCT)-levels in serum, particularly after contamination with bacterial endotoxines, can be used as a marker for specific infections. The objective of this prospective study was to evaluate the course of PCT after cardiac surgery for the differential diagnosis of infections/unspecific inflammatory reactions, compared to routine infection parameters.. Serum PCT levels were measured in 400 routine cardiosurgical patients preoperatively and at 1., 2., 4. and 6. postoperative days with a luminescence immunoassay. PCT-values were compared to the patient's clinical infection status, body temperature, leukocyte count and C-reactive protein (CRP).. 364 patients had an infection-free postoperative course, 27 patients developed infections. All of these patients showed elevated infection parameters at 1-2. postoperative days. In patients without infection, these parameters decreased after 2. postoperative day. Patients predisposed to an infection had continuously high temperature, leukocytes, CRP and PCT until 4.postoperative day with leukocytes and CRP decreasing after 4.postoperative day. PCT however showed a divergent course with a second increase in these patients between 4.-6. postop day (p<0.001). At this time, no clinical sign of an infection was evident. The increase of PCT was independent of infection type, but most apparent in bacteriemia/sepsis.. Based on its different course from other parameters in infection development between 4.-6. days, PCT can probably be used as a predictive marker in bacterial infections after cardiac surgery. The cost of the used immunoassay however will set the limits for a routine application.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Body Temperature; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Female; Heart Diseases; Humans; Immunoassay; Leukocyte Count; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; Surgical Wound Infection