Biomarker Phenotypes in Heart Failure with Preserved Ejection Fraction Using Hierarchical Clustering-A Pilot Study.

OBJECTIVES: We hypothesized the existence of distinct phenotype-based groups within the very heterogeneous population of patients of heart failure with preserved ejection fraction (HFpEF) and using an unsupervised hierarchical clustering applied to plasma concentration of various biomarkers. We sought to characterize them as "biomarker phenotypes" and to conclude differences in their overall characteristics. SUBJECTS AND METHODS: A cross-sectional study was conducted on 75 patients with HFpEF. An agglomerative hierarchical clustering was performed using the concentrations of cardiac remodeling biomarkers, BNP and cystatin C. RESULTS: According to the obtained heat map of this analysis, we concluded two distinctive biomarker phenotypes within the HFpEF. The "remodeled phenotype" presented with significantly higher concentrations of cardiac remodeling biomarkers and cystatin C (p < 0.001), higher prevalence of myocardial infarction (p = 0.047), STEMI (p = 0.045), atrial fibrillation (p = 0.047) and anemia: lower erythrocytes count (p=0.037), hemoglobin concentration (p = 0.034) and hematocrit (p = 0.046), compared to "non-remodeled phenotype". Echocardiography showed that patients within "remodeled phenotype" had significantly increased parameters of left ventricular remodeling: left ventricular mass index (p < 0.001), left ventricular mass (p = 0.001), diameters of the interventricular septum (p = 0.027) and posterior wall (p = 0.003) and function alterations, intermediate pauses duration >2.0 seconds (p < 0.006). CONCLUSION: Unsupervised hierarchical clustering applied to plasma concentration of various biomarkers in patients with HFpEF enables the identification of two biomarker phenotypes, significantly different in clinical characteristics and cardiac structure and function, whereas one phenotype particularly relates to patients with reduced ejection fraction. These findings imply distinct underlying pathophysiology within a unique cohort of HFpEF.

Platelet-derived immuno-inflammatory indices show best performance in early prediction of COVID-19 progression.

BACKGROUND: Coronavirus disease 2019 (COVID-19) profoundly affects the immune and hematopoietic systems with various degrees of reactive changes in the blood cell counts. Immuno-inflammatory indices are considered a simple and effective tool in the prediction of COVID-19 outcomes. We aimed to evaluate and compare the usefulness of leukocyte and platelet counts-based immuno-inflammatory indices on admission to hospital in predicting COVID-19 progression and mortality. METHODS: A total of 945 patients were enrolled. In addition to blood cell counts, we assessed hemogram-derived immuno-inflammatory indices in relation to COVID-19 progression and death. The indices were tested by analysis of variance, receiver operating characteristic curve analysis, and binomial logistic regressions. RESULTS: Patients with severe COVID-19 had significantly higher counts of neutrophils, eosinophils, and large immature cells (LIC), while decreased counts of platelets and monocytes. Lymphopenia was found in all of the patients, but without significant association with the outcomes. Patients with a LIC count ≥0.265 x 09 /L had 54.7% more odds of having COVID-19 progression. In multivariable analyses, platelets/neutrophil-to-lymphocyte ratio (P/NLR) and platelets-to-neutrophil radio (P/N) were significant independent predictors of COVID-19 progression and mortality. The odds of a poor outcome were two times higher in cases with P/NLR < 43 x 109 /L and P/N < 29 x 109 /L. CONCLUSION: Indices that include platelet count in combination with neutrophil and/or lymphocyte counts displayed the best discriminatory ability and prognostic value of COVID-19 outcomes. Additionally, LIC showed promising results in the early identification of severe COVID-19.

Temporal Changes in Incidence Rates of the Most Common Gynecological Cancers in the Female Population in Central Serbia.

Background and Objectives: There were 1,335,503 newly diagnosed cases of the most common gynecological cancers in women (cervical, uterine and ovarian cancer) worldwide in 2020. The main objective of this paper was to assess temporal changes in incidence rates of the most common gynecological cancers and to determine the age group with the greatest increase in incidence in the Serbian female population in the period 2003-2018. Material and Methods: Trends and annual percentage change (APC) of the incidence rate with corresponding 95% confidence intervals (CI) were calculated by Joinpoint regression analysis. The trend was considered to be significantly increasing (positive change) or decreasing (negative change) when the p-value was below 0.05 (p < 0.05). Results: The total number of newly registered cancer cases from 2003 to 2018 was 35,799. There was a significant increase of age standardized rate (ASR) for all cancer incidences in women from 2012 to 2018 with APC 6.9% (95% CI from 0.9 to 13.3, p = 0.028) and for uterine cancer during the 2014-2018 period with APC of 16.8% (95% CI: from 4.0 to 31.1, p = 0.014), as well as for ovarian cancer incidence in the 2012-2018 period with APC of 12.1% (95% CI: from 6.7 to 17.8, p < 0.001). A non-significant decrease of ASRs of incidence for cervical cancer was determined from 2003 to 2015 with APC of -0.22% (95% CI: from -3.4 to 3.1, p = 0.887) and a non-significant increase of ASRs incidence from 2015 to 2018 with APC of 14.21% (95% CI: from -13.3 to 50.5, p = 0.311). The most common gynecological cancers were present in all age groups and only ovarian cancer was registered in the youngest age group (0-4 years). Cervical cancer showed a typical increase after the age of 30, with peak incidence in women aged 40-44 and 65-69 years. The increased incidence trend regarding age for cervical cancer (y = 1.3966x + 0.3765, R2 = 0.3395), uterine cancer (y = 1.7963x - 5.4688, R2 = 0.5063) and ovarian cancer (y = 1.0791x - 0.8245, R2 = 0.5317) is statistically significant. Conclusion: Based on our presented results, a significant increase of incidence trend for the most common gynecological cancers in the Serbian female population from 2012 to 2018 was determined. There has been a significant increase in the incidence of uterine cancer from 2014 up to 2018, as well as for ovarian cancer from 2012 up to 2018, while cervical cancer showed a non-significant decrease of incidence trend from 2003 until 2015 and then a non-significant increase. In women below 20 years of age, ovarian cancer was significantly more prevalent, while cervical cancer was significantly more prevalent in the age groups 20-39 and 40-59 years. In the age group of 60-79, uterine cancer had a significantly higher incidence than the other two cancers. Measures of primary prevention, such as vaccination of children against Human Papilloma Virus and screening measures of secondary prevention, for the female population aged 25 to 64 years of age are needed, as well as educating females about healthy lifestyles via media and social networks to help prevent the most common gynecological cancers.

Cancer of unknown primary - incidence, mortality trend, and mortality-to-incidence ratio is associated with human development index in Central Serbia, 1999-2018: Evidence from the national cancer registry.

OBJECTIVES: The aim was to estimate the trend of incidence, mortality and mortality-to-incidence ratio (MIR) in Central Serbia in 1999-2018 and its possible association with the human development index (HDI). METHODS: In this study, cancer of unknown primary (CUP) was included as C77-C80 codes. Trend analysis was performed in the Joinpoint Regression Programme version 4.8.0.1. HDI combines life expectancy, educational attainment and gross national income. HDI values for Serbia are extracted from the global bank site. RESULTS: Joinpoint regression analysis of the age-standardised incidence rate of CUP showed a significantly increasing trend with annual percent change (APC) of 8.5% (95% confidence interval [CI] 3.0-14.3%) in males and 7.8% (95%CI 2.7-13.2) in females. The age-standardised mortality rate of CUP showed a significantly decreasing trend with APC of -1.7% (95%CI -2.8 to -0.5%) in males and -1.4% (95%CI -2.7 to -0.1%) in females. MIR showed a significantly decreasing trend with APC of -9.3% (95%CI -14.6 - -3.6%) in males and -7.1% (95%CI -10.5% to -4.2%) in females. The linear regression showed significant inverse association among HDI and the MIR of CUP in males (r2 = 0.464, p = 0.002) and in females (r2 = 0.612, p < 0.001). CONCLUSIONS: Decline of MIR was associated with HDI, suggesting that CUP prognosis follows socio-economic status.

The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C. Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers. Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%. Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

Cardiac Remodeling Biomarkers as Potential Circulating Markers of Left Ventricular Hypertrophy in Heart Failure with Preserved Ejection Fraction.

Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor (GDF)-15 and syndecan-1 represent biomarkers of cardiac remodeling, involved in heart failure (HF) progression. We hypothesize that their plasma concentrations, together with brain natriuretic peptide (BNP), are different in HF stratified by ejection fraction (EF), demonstrating correlations with echocardiographic parameters that indicate left ventricular (LV) hypertrophy; LV mass index (LVMI) and posterior wall and septum diameters. HF patients (n = 77) were classified according to EF: reduced EF < 40% (HFrEF), mid-range EF = 40-49% (HFmrEF), preserved EF > 50% (HFpEF). We found that plasma concentrations of four cardiac remodeling biomarkers were highest in HFrEF and lowest in HFpEF, p < 0.001. In HFpEF, remodeling biomarkers independently correlated with LVMI: sST2 (p = 0. 002), galectin-3 (p < 0.001), GDF-15 (p = 0.011), and syndecan-1 (p = 0.006), whereas galectin-3 correlated after multivariable adjustments (p = 0.001). Independent correlates of septum and posterior wall diameters, in HFpEF, were sST2 (p = 0.019; p = 0.026), galectin-3 (p = 0.011; p = 0.009), GDF-15 (p = 0.007; p = 0.001), and syndecan-1 (p = 0.005; p = 0.002). In HFrEF, only sST2, adjusted, correlated with LVMI (p = 0.010), whereas BNP correlated with LVMI (p = 0.002) and EF (p = 0.001). GDF-15 correlated with diastolic dysfunction in HFpEF (p = 0.046) and HFrEF (p = 0.024). Cardiac remodeling biomarkers are potential circulating indicators of LV hypertrophy in HFpEF, which may ensure timely recognition of disease progression among high-risk patients.

The partnership between renalase and ejection fraction as a risk factor for increased cardiac remodeling biomarkers in chronic heart failure patients.

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers.Methods: We classified HF patients (n = 76) according to LVEF (preserved/reduced), applied a median plasma renalase (113 ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase (n = 19), HFrEF/low renalase (n = 19), HFrEF/high renalase (n = 32) and HFpEF/high renalase (n = 6). A control group (n = 35) consisted of healthy volunteers.Results: Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF (p < .001, respectively), and renalase's positive correlations were obtained relating to all biomarkers: galectin-3 (r = 0.913; p < .001), sST2 (r = 0.965; p < .001), GDF-15 (r = 0.887; p < .001), syndecan-1 (r = 0.922; p < .001), BNP (r = 0.527; p < .001) and cystatin C (r = 0.844; p < .001) and strong and negative correlation with LVEF (r = -0.456, p < .001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, p < .001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, p < .001, respectively. Results after multivariable adjustments (age/gender) were identical.Conclusion: When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.

Trends in thyroid cancer incidence and mortality in Central Serbia, 1999-2014.

INTRODUCTION: Thyroid cancer (TC) is the most common malignant disease of the endocrine system. The incidence of the TC has been increasing worldwide, especially in female population. However, mortality from TC is low in both males and females. The objective of the paper was to determine and to analyze incidence and mortality trends of TC in males and females in the central Serbia in the period 1999-2014. METHOD: In this descriptive study data from the Serbian Cancer Registry were used. Crude and age-standardized rates (ASRs) of incidence and mortality were calculated. Trend and annual percentage change (APC) of the incidence and mortality rate with corresponding 95% confidence intervals (CI) were calculated by performing Joinpoint regression analyses. RESULTS: A total number of new cases of TC was 3113. TC was diagnosed in 2343 females and 770 males (female-to-male ratio, 3:1). A total number of fatal cases was 770 (while 504 female and 266 male died from TC, female-to-male ratio, 1.9:1). TC was not common before 30 years of age. The highest incidence was recorded both in males and females aged 50-59. Joinpoint regression analysis showed the statistically significant increase of ASRs of TC incidence in males in 1999-2014 period with APC 6.2% (95% CI: 4.2-8.3, p < 0.001) and there was also significant increase of ASRs of TC incidence in females in the same study period with a APC 6.1% (95% CI: 4.2-8.0, p < 0.001). Joinpoint regression analysis showed an insignificant increase of ASRs of TC mortality in males with APC 2.4% (95% CI: -0.5-5.5, p = 0.1). There was an insignificant decrease of ASRs of TC mortality in females with APC -1.3% (95% CI: -4.4-1.9, p = 0.4). CONCLUSION: The increasing trend of age-standardized incidence rates of TC both in males and females and decreasing trend of age-standardized mortality rates during the observed period were registered. Females had higher age-standardized incidence and mortality rates than males. Female to male ratio of incidence was 3:1 and for mortality 1.9:1. Measures of primary and secondary prevention are needed.

Crosstalk of Various Biomarkers That Might Provide Prompt Identification of Acute or Chronic Cardiorenal Syndromes.

INTRODUCTION: Pathophysiological interaction between the heart and kidneys represents the basis for clinical entities called cardiorenal syndromes. The purpose of the study was to assess the relations between acute and chronic cardiorenal syndromes and biomarkers [advanced oxidation protein products, brain natriuretic peptide, malondialdehyde, xanthine oxidoreductase (XOD), xanthine oxidase, xanthine dehydrogenase, interleukin 8, cystatin C, plasminogen activator inhibitor-1, high-sensitive troponin T, C-reactive protein and glomerular filtration rate, measured by the Modification of Diet in Renal Disease (MDRD) formula], to hypothesize biomarkers that might provide a prompt identification of acute or chronic cardiorenal syndromes, and to distinguish acute versus chronic types of these syndromes. METHODS: A total of 114 participants were enrolled in this study, i.e. 79 patients divided into subgroups of acute and chronic cardiorenal syndromes and 35 volunteers. RESULTS: Nonadjusted odds ratio (OR) showed that there was a significant risk for acute cardiorenal syndrome with increased XOD activity (p = 0.037), elevated cystatin C concentration (p = 0.038) and MDRD (p = 0.028). Multivariable adjusted OR, on the other hand, revealed that only glomerular filtration rate measured by the MDRD formula had a significance for acute cardiorenal syndrome (p = 0.046). Nonadjusted OR showed a significant risk for chronic cardiorenal syndrome only in elderly (p = 0.002). Multivariable adjusted OR exhibited that age was the only risk factor for chronic cardiorenal syndrome (p = 0.012). CONCLUSION: Cystatin C, glomerular filtration rate measured by the MDRD equation and XOD were independent risk factors for acute cardiorenal syndrome, while age remained an independent risk factor for chronic cardiorenal syndrome. When comparing ORs of evaluated parameters, the highest significance for acute cardiorenal syndrome was plasma concentration of cystatin C.

The assessment of renalase: searching for the best predictor of early renal dysfunction by multivariate modeling in stable renal transplant recipients.

BACKGROUND: Renal transplant dysfunction has been shown to be an independent risk factor for cardiac, non-cardiovascular, and all-cause mortality in post-transplantation follow-up. MATERIAL AND METHODS: We enrolled 73 renal transplant recipients who were more than 12 months post-renal transplant surgery, had stable graft function, and were on standard immunosuppression. The purpose of the study was to observe the relation between renal dysfunction and endothelial dysfunction parameters (nitrates, asymmetric and symmetric dimethylarginine, and endothelial nitric oxide synthase), and renalase, and to hypothesize the best predictor of early renal dysfunction by multivariate modeling. The other aim was to observe differences with regard to immunosuppression. RESULTS: Non-adjusted odds ratio showed a significant risk of reduced glomerular filtration rate in transplant recipients with increased renalase concentration (p=0.026); age-adjusted odds ratio showed a significant risk of reduced glomerular filtration rate with increased renalase concentration (p=0.042), also after multivariable adjustment (p=0.032). Increased plasma endothelial nitric oxide synthase concentration was a protective factor for glomerular filtration rate (p=0.011). After adjustment for age (p=0.045), and after multivariate modeling, endothelial nitric oxide synthase was shown to be a protective factor for glomerular filtration rate (p=0.014). Significant differences in immunosuppression were found in plasma renalase in patients maintained on cyclosporine (p=0.027). CONCLUSIONS: Renalase was shown to be strong predictor of decreased glomerular filtration rate and was significantly higher in the group of patients on cyclosporine. Endothelial nitric oxide synthase was identified as a strong protective factor for kidney function.

Oxidative and Nitrosative Stress in Stable Renal Transplant Recipients with Respect to the Immunosuppression Protocol - Differences or Similarities?

BACKGROUND: The aim of the study was to evaluate parameters of oxidative and nitrosative stress as well as antioxidative parameters in a group of renal transplant recipients with stable graft function and no clinical signs of cardiovascular disease. We also aimed to determine the correlations among these parameters and to evaluate potential differences in all the biomarkers with regard to the immunosuppression protocol. METHODS: We enrolled 57 renal transplant recipients and 31 controls who were age and sex matched with the renal transplant recipients. All of the patients included in this study had post-renal transplant surgery at least 12 months earlier and were on standard immunosuppressive therapy. In this study, we determined thiobarbituric acid-reactive substances in plasma and red blood cells and advanced oxidation protein products, nitrosative stress parameters (asymmetric and symmetric dimethylarginine - ADMA and SDMA), and antioxidative parameters (total SH groups and catalase activity). RESULTS: The results of our study demonstrated that the levels of oxidative and nitrosative stress were significantly increased compared to the healthy population (p<0.01 except for plasma catalase activity p<0.05). Correlation analysis showed significant positive correlations between: ADMA and SDMA (p<0.01); ADMA and nitrates (p<0.05); SDMA and nitrates (p<0.05); between OS parameters in the experimental group; AOPP and SH groups (p<0.05) and TBARS in plasma and SH groups (p<0.01), SDMA and AOPP (p< 0.05); SDMA and TBARS in plasma (p<0.05); SDMA and SH groups (p<0.01); nitrates and SH groups (p<0.05). CONCLUSION: There was no significant difference in oxidative and nitrosative stress parameters with respect to the immunosuppressive protocol.

Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease.

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p<0.001), while ADP and AMP were significantly increased in both groups of patients compared with control healthy individuals (p<0.001), together with their final degradation product, uric acid (p<0.001). The index of ATP/ADP and ATP/uric acid showed gradual significant fall in both the groups, compared with the control value (p<0.001), near five times in a group on dialysis. Total XOD was up-regulated significantly in a group with essential hypertension, more than in a group on dialysis. The activity of XO, which dominantly contributes reactive oxygen species (ROS) production, significantly increased in dialysis group, more than in a group with essential hypertension. In conclusion, the examination of the role of circulating purine nucleotides and uric acid in pathogenesis of hypertension and possible development of renal disease, together with XO role in ROS production, may help in modulating their liberation and ROS production in slowing progression from hypertension to renal failure.

Glutathione homeostasis disruption of erythrocytes, but not glutathione peroxidase activity change, is closely accompanied with neurological and radiological scoring of acute CNS inflammation.

OBJECTIVES AND METHODS: The levels of glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in the erythrocytes of 50 patients with clinically isolated syndrome of CNS (CIS) and 57 patients with relapsing remitting multiple sclerosis (RRMS). RESULTS: A decrease in GSH content and GPx activity showed significance in both study groups compared to the control values (p = 0.0025 and 0.007 for GSH and p = 0.005 and 0.003 for GPx, in CIS and RRMS patients, respectively). The depletions were more pronounced in RRMS than in CIS patients (p = 0.009 for GSH and p = 0.031 for GPx). The results significantly verify the negative correlations between GSH values and clinical severity (r = -0.513, p = 0.004), radiological findings (r = -0.351, p = 0.008) and disease duration (r = -0.412, p = 0.0025) in CIS patients. The same correlations were observed in RRMS patients between GSH values and clinical severity (r = -0.498, p = 0.004) and patients' radiological features (r = -0.454, p = 0.005). No correlations were observed between GSH values and other patient characteristics, or between GPx activity and all tested patient characteristics (p > 0.01). CONCLUSIONS: The results indicate that GSH content and GPx activity both decreased below the normal range and were accompanied with neuroinflammation, but although both might have great importance in neuroinflammation development, the data presented here confirm that only GSH might serve as a marker which is closely correlated with neurological and radiological scoring of acute CNS inflammation.

Crosstalk of inflammatory mediators and lipid parameters as early markers of renal dysfunction in stable renal transplant recipients with regard to immunosuppression.

BACKGROUND: Kidney transplantation is still the treatment of choice for end-stage renal disease, therefore it is important to establish all modifiable risk factors for initiation of renal dysfunction. MATERIAL/METHODS: We enrolled 73 renal transplant recipients, who were more than 12 months post-renal transplant surgery, had a stable graft function, had no clinically present cardiovascular disease, and were on standard immunosuppressive therapy. The concentrations of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), CRP, lipids, and lipoproteins were measured. We used logistic regression to calculate non-adjusted, age, and multivariable-adjusted ORs and 95% confidence intervals for glomerular filtration rate, GFR <60 ml/min/1.73 m(2). RESULTS: Non-adjusted OR showed that there was a significant risk of reduced GFR in patients with total cholesterol higher than 5.19 mmol/L, LDL cholesterol ≥ 4.1 mmol/L, non- HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. After adjustment for age and in multivariable model, OR showed a significant risk for reduced GFR in patients with total cholesterol ≥ 5.2 mmol/L, LDL ≥ 4.1 mmol/L, non-HDL ≥ 4.2 mmol/L, and higher VCAM-1 concentration. HDL, triglycerides, CRP, and lipoprotein ratios did not have any significance as predictors of renal dysfunction. There were no differences in all evaluated parameters between groups in regard to immunosuppressive therapy. CONCLUSIONS: Total cholesterol, LDL, non-HDL, and VCAM-1 are strong and independent predictors of renal dysfunction in stable renal transplant recipients. In contrast, HDL, CRP, triglycerides, and ICAM-1 did not seem to have any impact on renal dysfunction.