rome and Inflammation

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in adults and children. Along with obesity, diabetes and insulin resistance, genetic factors strongly impact on NAFLD development and progression. Dysregulated bile acid metabolism and the fibroblast growth factor 19 (FGF19) pathway play a pivotal role in NAFLD pathogenesis. However, the mechanism through which the FGF19 receptor system is associated with liver damage in NAFLD remains to be defined.. We evaluated the impact of the rs17618244 G>A β-Klotho (KLB) variant on liver damage in 249 pediatric patients with biopsy-proven NAFLD and the association of this variant with the expression of hepatic and soluble KLB. In vitro models were established to investigate the role of the KLB mutant.. The KLB rs17618244 variant was associated with an increased risk of ballooning and lobular inflammation. KLB plasma levels were lower in carriers of the rs17618244 minor A allele and were associated with lobular inflammation, ballooning and fibrosis. In HepG2 and Huh7 hepatoma cell lines, exposure to free fatty acids caused a severe reduction of intracellular and secreted KLB. Finally, KLB downregulation obtained by the expression of a KLB mutant in HepG2 and Huh7 cells induced intracellular lipid accumulation and upregulation of p62, ACOX1, ACSL1, IL-1β and TNF-α gene expression.. In conclusion, we showed an association between the rs17618244 KLB variant, which leads to reduced KLB expression, and the severity of NAFLD in pediatric patients. We can speculate that the KLB protein may exert a protective role against lipotoxicity and inflammation in hepatocytes.. Genetic and environmental factors strongly impact on the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). The FGF19/FGFR4/KLB pathway plays a pivotal role in the pathogenesis of NAFLD. The aim of the study was to investigate the impact of a genetic variant in the KLB gene on the severity of liver disease. Our data suggest that the KLB protein plays a protective role against lipotoxicity and inflammation in hepatocytes.

Topics: Adolescent; Alleles; Carcinoma, Hepatocellular; Case-Control Studies; Child; Down-Regulation; Female; Fibroblast Growth Factors; Hep G2 Cells; Humans; Inflammation; Klotho Proteins; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Membrane Proteins; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Receptor, Fibroblast Growth Factor, Type 4; Rome

Obesity was recently identified as a major risk factor for worse COVID-19 severity, especially among the young. The reason why its impact seems to be less pronounced in the elderly may be due to the concomitant presence of other comorbidities. However, all reports only focus on BMI, an indirect marker of body fat.. To explore the impact on COVID-19 severity of abdominal fat as a marker of body composition easily collected in patients undergoing a chest CT scan.. Patients included in this retrospective study were consecutively enrolled among those admitted to an Emergency Department in Rome, Italy, who tested positive for SARS-Cov-2 and underwent a chest CT scan in March 2020. Data were extracted from electronic medical records.. 150 patients were included (64.7% male, mean age 64 ± 16 years). Visceral fat (VAT) was significantly higher in patients requiring intensive care (p = 0.032), together with age (p = 0.009), inflammation markers CRP and LDH (p < 0.0001, p = 0.003, respectively), and interstitial pneumonia severity as assessed by a Lung Severity Score (LSS) (p < 0.0001). Increasing age, lymphocytes, CRP, LDH, D-Dimer, LSS, total abdominal fat as well as VAT were found to have a significant univariate association with the need of intensive care. A multivariate analysis showed that LSS and VAT were independently associated with the need of intensive care (OR: 1.262; 95%CI: 1.0171-1.488; p = 0.005 and OR: 2.474; 95%CI: 1.017-6.019; p = 0.046, respectively).. VAT is a marker of worse clinical outcomes in patients with COVID-19. Given the exploratory nature of our study, further investigation is needed to confirm our findings and elucidate the mechanisms underlying such association.

Topics: Aged; Aged, 80 and over; Betacoronavirus; Body Composition; Body Mass Index; C-Reactive Protein; Comorbidity; Coronavirus Infections; COVID-19; Critical Care; Female; Humans; Inflammation; Intra-Abdominal Fat; L-Lactate Dehydrogenase; Lung; Male; Middle Aged; Obesity; Pandemics; Pneumonia, Viral; Retrospective Studies; Risk Factors; Rome; SARS-CoV-2; Tomography, X-Ray Computed; Treatment Outcome

Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers.. From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribution width (RDW %)]. Model-based punctual estimates, as average of all patients' values, and differences between survivors and non-survivors, overall, and by co-morbidities, at specific times after symptoms, with relative 95% CI and P-values, were obtained by marginal prediction and ANOVA- style joint tests. All analyses were carried out by STATA 15 statistical package.. 379 COVID-19 patients [273 (72% were male; mean age was 61.67 (SD 15.60)] were enrolled and 1,805 measures per parameter were analysed. Neutrophils' counts were on average significantly higher in non-survivors than in survivors (P<0.001) and lymphocytes were on average higher in survivors (P<0.001). These differences were time dependent. Average platelets' counts (P<0.001) and median platelets' volume (P<0.001) were significantly different in survivors and non-survivors. The differences were time dependent and consistent with acute inflammation followed either by recovery or by death. Anaemia with anisocytosis was observed in the later phase of COVID-19 disease in non-survivors only. Mortality was significantly higher in patients with diabetes (OR = 3.28; 95%CI 1.51-7.13; p = 0.005), obesity (OR = 3.89; 95%CI 1.51-10.04; p = 0.010), chronic renal failure (OR = 9.23; 95%CI 3.49-24.36; p = 0.001), COPD (OR = 2.47; 95% IC 1.13-5.43; p = 0.033), cardiovascular diseases (OR = 4.46; 95%CI 2.25-8.86; p = 0.001), and those >60 years (OR = 4.21; 95%CI 1.82-9.77; p = 0.001). Age (OR = 2.59; 95%CI 1.04-6.45; p = 0.042), obesity (OR = 5.13; 95%CI 1.81-14.50; p = 0.002), renal chronic failure (OR = 5.20; 95%CI 1.80-14.97; p = 0.002) and cardiovascular diseases (OR 2.79; 95%CI 1.29-6.03; p = 0.009) were independently associated with poor clinical outcome at 30 days after symptoms' onset.. Increased neutrophil counts, reduced lymphocyte counts, increased median platelet volume and anaemia with anisocytosis, are poor prognostic indicators for COVID19, after adjusting for the confounding effect of obesity, chronic renal failure, COPD, cardiovascular diseases and age >60 years.

Topics: Biomarkers; Blood Cell Count; Cohort Studies; COVID-19; Demography; Erythrocyte Indices; Female; Humans; Inflammation; Leukocyte Count; Longitudinal Studies; Lymphocytes; Male; Mean Platelet Volume; Middle Aged; Neutrophils; Prognosis; Rome; Survivors

Severe carotid stenosis is a frequent cause of stroke in both men and women. Whereas several sex-related comparisons are available on coronary atherosclerosis, there are few data appraising gender-specific features of carotid plaques. We aimed to systematically compare the pathology and inflammatory features of carotid plaques in men vs women.. Carotid plaque specimens were collected from patients undergoing surgical endarterectomy for asymptomatic or symptomatic carotid stenosis. Histologic analysis was performed, as well as measurements of plaque composition and inflammation.. A total of 457 patients were included (132 women, 325 men). Baseline analyses showed a greater prevalence of hypercholesterolemia, hypertension, and former smoking status in women, despite a higher Framingham Heart Score in men (all P < .05). Women had a lower prevalence of thrombotic plaques, smaller percentage area of necrotic core, and hemorrhage extension (all P < .05). Plaque inflammation analysis showed a lower concentration of inflammatory and, in particular, of macrophage foam cells in the plaque cap of women (both P < .05). These differences were, however, no longer significant at multivariable analysis, including several baseline features, such as symptom status and stenosis severity.. Carotid plaques seem significantly different in women and men, but the main drivers of such pathologic differences are baseline features, including stenosis severity and symptom status.

Topics: Aged; Asymptomatic Diseases; Carotid Arteries; Carotid Stenosis; Chi-Square Distribution; Endarterectomy, Carotid; Female; Foam Cells; Hemorrhage; Humans; Hypercholesterolemia; Hypertension; Inflammation; Linear Models; Male; Middle Aged; Multivariate Analysis; Necrosis; Plaque, Atherosclerotic; Prevalence; Risk Assessment; Risk Factors; Rome; Severity of Illness Index; Sex Factors; Smoking; Thrombosis

Topics: General Surgery; Greece; History, Ancient; History, Medieval; Humans; Inflammation; Rome