Performance Evaluation of a Novel Non-Invasive Test for the Detection of Advanced Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to advanced liver fibrosis (ALF). We evaluated the diagnostic accuracy of a novel Liver Fibrosis Risk Index (LFRI) in MAFLD subjects using transient elastography (TE) as the reference method for liver fibrosis measurement and then the diagnostic performance of a new two-step non-invasive algorithm for the detection of ALF risk in MAFLD, using Fibrosis-4 (FIB-4) followed by LFRI and comparing it to the reference algorithm based on FIB-4 and TE. We conducted a prospective study on 104 MAFLD European adult subjects. All consenting subjects underwent TE and measurements of FIB-4 and LFRI. For FIB-4 and TE, validated cut-offs were used. An ROC analysis showed that LFRI diagnosed severe fibrosis with moderate accuracy in MAFLD subjects with a negative predictive value above 90%. Using the new algorithm with LFRI thresholds recommended by the manufacturer, the number of subjects classified into ALF risk groups (low, intermediate, or high) differed significantly when compared with the reference algorithm (p = 0.001), with moderate agreement between them (weighted kappa (95% CI) = 0.59 (0.41-0.77)). To improve the performance of the LFRI-based algorithm, we modified cut-off points based on ROC curves obtained by dividing the study population according to the reference algorithm and observed no difference between algorithms (p = 0.054) in categorizing ALF risk, with a slight increase in the total agreement (weighted kappa (95% CI) = 0.63 (0.44-0.82)). Our findings suggest that using the novel LFRI as a second-line test may represent a potential alternative for liver fibrosis risk stratification in MAFLD patients; however, modified cut-offs are needed to optimize its performance.

Reference values and biological determinants for cardiac myosin-binding protein C concentrations assessed with an enzyme-linked immunosorbent assay.

Background: Cardiac myosin-binding protein C (cMyC) is a novel cardio-specific biomarker of potential diagnostic and prognostic value for cardiovascular events. This study aims to determine reference values for cMyC and identify biological determinants of its concentration. Methods: A population of 488 presumably healthy adults were enrolled to define biological determinants which affect cMyC concentrations in serum. Concentrations of cMyC were assessed using enzyme-linked immunosorbent assays from commercially available kits. Eligibility for inclusion in this study evaluated all subjects' anthropometric, demographic and laboratory measurements. After applying strict inclusion criteria, a reference population (n=150) was defined and used to determine reference values. Reference values were derived using a robust method.

The Differences in the Level of Anti-SARS-CoV-2 Antibodies after mRNA Vaccine between Convalescent and Non-Previously Infected People Disappear after the Second Dose-Study in Healthcare Workers Group in Poland.

(1) Background: In many infections, antibodies play a crucial role in controlling infection. In COVID-19, the dynamics of the immune system response to SARS-CoV-2 is not fully understood. (2) Methods: The study was conducted on 120 healthcare workers from Dr. Antoni Jurasz University Hospital No. 1 in Bydgoszcz, between June and December 2020. In all participants, IgA and IgG antibody serum concentrations were measured using the semi-quantitative Anti-SARS-CoV-2 ELISA test (Euroimmun). After vaccination, in January and February 2021, antibody levels were examined using the quantitative IgG Anti-SARS-CoV-2 Quantivac ELISA test (Euroimmun). (3) Results: During the whole study period, the SARS-CoV-2 infection was confirmed in 29 (24.2%) participants. In all infected participants, IgA and IgG antibodies were detectable after infection by semi-quantitative serological tests. Levels of antibodies were higher one month after the first dose in the convalescents than in the non-previously infected participants. In this second group, the level of antibodies increased significantly after the second dose of vaccines compared to the first dose. (4) Conclusions: The level of antibodies after the first dose of vaccine in the convalescents' group is higher than in the SARS-CoV-2 non-infected group, but the differences disappear after the second vaccination.

Chosen Vascular Risk Markers in Pseudoexfoliation Syndrome: An Age-Related Disorder.

PURPOSE: To evaluate lipids and C-reactive protein serum levels in patients with pseudoexfoliation syndrome (PEX) in the Polish population. METHODS: 96 patients were studied with PEX and 79 control subjects. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, non-HDL-cholesterol and CRP serum levels, and TG/HDL-C and TC/HDL-C indexes were assessed. RESULTS: There were no significant differences in concentration of lipids and values of TC/HDL-C, TG/HDL-C, and non-HDL-C between PEX and control groups. High-sensitivity C-reactive protein was not increased in patients with PEX. CONCLUSIONS: Our results cast doubt on the opinion on the possible PEX and vascular diseases relation. Further studies on this subject are mandatory.

Gamma-glutamyltransferase activity as a surrogate biomarker of metabolic health status in young nondiabetic obese women.

AIM: We investigated the association of gamma-glutamyltransferase (GGT) activity with atherogenic risk factors and metabolic health status in young nondiabetic obese women. METHODS & RESULTS: In 140 obese women GGT activity was independently associated with BMI, triglyceride to high-density cholesterol ratio and homeostasis model assessment. Metabolically healthy but obese women had significantly lower GGT activity, associated with a normal insulin sensitivity, favorable lipid profile and apolipoprotein B to apolipoprotein AI ratio. GGT activity showed good diagnostic accuracy to distinguish between metabolically healthy but obese and obese women at risk (77.8% sensitivity and 60% specificity). GGT activity >17 U/l can predict atherogenic risk and insulin resistance. CONCLUSION: GGT activity may serve as a potential surrogate biomarker of atherogenic risk and metabolic health status.

Amyloid ß Peptides and Cognitive Functions in Patients with Pseudoexfoliation Syndrome.

PURPOSE: The aim of this study was to evaluate if there is any relation between the Alzheimer's peptides (amyloid ß-40 and ß-42) concentration in plasma and aqueous humor as well as cognitive functions with pseudoexfoliation syndrome (PEX). METHODS: One-hundred forty-two patients with PEX have been included for this study; median age: 75 years (Q1 = 71,5; Q3 = 80,0). Control group comprised 93 subjects aged 74 years (Q1 = 68,0; Q3 = 80,0). Amyloid ß-40 and ß-42 (Aß-40, Aß-42) concentrations were assessed in plasma in 73 PEX patients and 49 controls. Aß-40 concentration in aqueous humor was measured in 31 patients from each group. Mini Mental State Examination (MMSE) and Clock Drawing Tests were performed in 83 PEX patients and 36 controls. RESULTS: The differences between amyloid concentrations both in plasma and in aqueous humor in PEX and control groups were not statistically significant. There were no differences in MMSE and Clock Drawing Tests between groups. CONCLUSION: Our results do not indicate any relation between PEX and Alzheimer's amyloids or cognitive functions in cataract patients.

Serum inhibin A and inhibin B levels in epithelial ovarian cancer patients.

THE AIM: of our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival. MATERIAL AND METHODS: We enrolled 90 epithelial ovarian cancer patients in our study, aged 45-81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery. RESULTS: In the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96-10.09) and inhibin B was 13.9 pg/mL (5.1-45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p=0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p=0,00625, log-rank test). CONCLUSION: 1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.

25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension.

BACKGROUND: The mechanism that underlies the association between low 25-hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to involve regulation of the renin-angiotensin-aldosterone system and the impact on endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D supplementation presents an ambiguous effect on endothelial function and arterial stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP], homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed untreated hypertension. METHODS: Patients were classified based on ambulatory blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose, insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media thickness (IMT), and left-ventricular mass (LVM) measurements were performed. RESULTS: 25(OH)D3 was significantly lower in hypertensive patients. The logistic regression analysis indicated that 25(OH)D3 reduced the probability of hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in those with hypertension correlated significantly with systolic BP (SBP; r = -0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted for up to 27% of SBP variation after adjusting for age, BMI, and smoking. 25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of 25(OH)D3 was 10%. CONCLUSION: The impact of 25(OH)D3 on SBP variation, mediated by its effect on endothelial dysfunction and subclinical organ damage, is modest but significant.

A-FABP and its association with atherogenic risk profile and insulin resistance in young overweight and obese women.

AIM: We evaluated the association of A-FABP with proatherogenic risk profile and insulin resistance (IR) in young, nondiabetic, overweight/obese women. MATERIALS & METHODS: Serum A-FABP, high-sensitivity CRP, adiponectin, glucose, insulin, lipids and apolipoproteins were measured in 104 women (aged 20-45 years; BMI ≥25 kg/m(2)) and age-matched healthy controls (n = 76; BMI <25 kg/m(2)). All patients underwent blood pressure and anthropometric measurements. RESULTS: A-FABP concentration was related to IR, and anthropometric and atherogenic indices. A-FABP was an independent predictor of triglyceride:high-density lipoprotein cholesterol, explaining 42% of its variation in overweight/obese women. At a cutoff level of 16 ng/ml, A-FABP discriminated between controls and overweight/obese (area under curve = 0.96) with high sensitivity and specificity. A-FABP predicted atherogenic risk, with an odds ratio of 11.2 (95% CI: 3.7-34.2), 7.1 (1.9-27.2) and 6.7 (2.6-17.2) for having elevated triglyceride:high-density lipoprotein cholesterol, apoB and CRP, respectively, and IR with an odds ratio 5.6 (1.8-17.2). CONCLUSION: A-FABP seems to be a valuable predictor of atherogenic risk profile; if elevated it contributes to cardiovascular disease beyond its effect on IR.

Serum anti-müllerian hormone levels in patients with epithelial ovarian cancer.

Objectives. The aim of our study was to examine serum anti-Müllerian hormone (AMH) concentration in ovarian cancer patients in relation to clinicopathological features, such as a pathological subtype of the tumor, (FIGO) stage, grading, and overall 5-year survival. Material and Methods. We enrolled 72 epithelial ovarian cancer patients in our study, aged 45-79 years, who underwent optimal cytoreductive surgery. In all patients, serum AMH concentration was measured using a two-step sandwich type enzyme immunoassay before surgery. As a reference value for women over 45 years we accepted anti-Müllerian hormone concentration below 1 ng/mL. Results. In the whole group of patients with ovarian cancer, median serum concentration of AMH was 0.07 (0.0-0.37) ng/mL, whereas in the group of those with positive AMH values (≥0.14 ng/mL) it was 0.31 (0.15-0.73) ng/mL. No significant correlation was found between serum AMH levels and FIGO stage, histological subtype, or grading (P > 0.05). The analysis of five-year survival rate related to AMH levels showed no statistically significant differences. There were no differences in survival rates between patients with positive or negative serum AMH levels. Conclusion. Measurement of serum anti-Müllerian hormone levels was not useful in predicting clinicopathological features and survival in patients with ovarian cancer.