Prognostic Value of Routine Biomarkers in the Early Stage of COVID-19.

Various biomarkers like certain complete blood cell count parameters and the derived ratios including neutrophil-lymphocyte ratio are commonly used to evaluate disease severity. Our study aimed to establish if baseline levels of complete blood cell count-derived biomarkers and CRP, measured before any treatment which can interfere with their values, could serve as a predictor of development of pneumonia and the need for hospitalization requiring oxygen therapy. We retrospectively analyzed the laboratory data of 200 consecutive patients without comorbidities, who denied usage of medications prior to blood analysis and visited a COVID-19 ambulance between October and December 2021. Multivariate regression analysis extracted older age, elevated CRP and lower eosinophil count as significant independent predictors of pneumonia (p = 0.003, p = 0.000, p = 0.046, respectively). Independent predictors of hospitalization were higher CRP (p = 0.000) and lower platelet count (p = 0.005). There was no significant difference in the neutrophil-lymphocyte and platelet-lymphocyte ratios between examined groups. Individual biomarkers such as platelet and eosinophil count might be better in predicting the severity of COVID-19 than the neutrophil-lymphocyte and platelet-lymphocyte ratios.

COVID-19 Breakthrough Infections among Patients Aged ≥65 Years in Serbia: Morbidity and Mortality Overview.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 have shown effectiveness in the prevention of COVID-19. Breakthrough infections occur, and age has been shown to be one of the dominant risk factors for poorer outcome. This research focuses on characteristics of breakthrough infections in older adults. METHODS: This retrospective study was conducted for four months (March−June 2021) in the autonomous province of Vojvodina in Serbia on 11,372 patients using reverse-transcription polymerase chain reaction or antigen-detection rapid diagnostic tests verifying COVID-19 in those aged ≥65 years. Demographics, comorbidities, disease severity, and final outcomes were evaluated in fully vaccinated compared to unvaccinated individuals. Individuals were divided into younger-old (65−74 years) and older-old (≥75 years) age groups and differences between those groups were further evaluated. Binary logistic regression was performed to identify independent predictors of poor outcome. RESULTS: By the end of the research, 51.3% of the population of APV 65−74 years, as well as 46.2% of those older than 74 years, were vaccinated. From the acquired sample, 17.4% had breakthrough infection. Asymptomatic forms were higher in both age groups of vaccinated vs. unvaccinated (3.9%­younger-old, 6.3%­older-old vs. 2.9%­younger-old, 3.9%­older-old). The same results were registered with mild symptoms (82.1%­younger-old, 68.1%­older-old vs. 76.3%­younger-old, 57.5%­older-old) (p < 0.001). The case fatality ratio of the vaccinated population was smaller than the unvaccinated population in both groups (3.1% vs. 7.9%­younger-old; 11.4% vs. 22.5%­older-old) (p < 0.001). The odds ratio for poor outcome in unvaccinated individuals was 2.3 (95% confidence interval, p < 0.001) for the total sample. CONCLUSIONS: An increase in asymptomatic and mild forms, as well as decrease in severe or critical forms and poor outcomes, were noted in the vaccinated population. Choosing to avoid vaccination against SARS-CoV-2 may increase the chance of poor outcome in older individuals.

Clinical Presentations, Predictive Factors, and Outcomes of Clostridioides difficile Infection among COVID-19 Hospitalized Patients­A Single Center Experience from the COVID Hospital of the University Clinical Center of Vojvodina, Serbia

Background: This study aimed to investigate the clinical form, risk factors, and outcomes of patients with COVID-19 and Clostridioides difficile co-infections. Methods: This retrospective study (2 September 2021-1 April 2022) included all patients with Clostridioides difficile infection (CDI) and COVID-19 infection who were admitted to the Covid Hospital of the University Clinical Center of Vojvodina. Results: A total of 5124 COVID-19 patients were admitted to the Covid Hospital, and 326 of them (6.36%) developed hospital-onset CDI. Of those, 326 of the CDI patients (88.65%) were older than 65 years. The median time of CDI onset was 12.88 days. Previous hospitalizations showed 69.93% of CDI patients compared to 38.81% in the non-CDI group (p = 0.029). The concomitant antibiotics exposure was higher among the CDI group versus the non-CDI group (88.65% vs. 68.42%, p = 0.037). Albumin levels were ≤ 25 g/L among 39.57% of the CDI patients and 21.71% in the non-CDI patients (p = 0.021). The clinical manifestations of CDI ranged from mild diarrhea (26.9%) to severe diarrhea (63.49%) and a complicated form of colitis (9.81%). Regarding outcomes, 79.14% of the CDI patients recovered and 20.86% had fatal outcomes in-hospital. Although a minority of the patients were in the non-CDI group, the difference in mortality rate between the CDI and non-CDI group was not statistically significant (20.86% vs. 15.13%, p = 0.097). Conclusions: Elderly patients on concomitant antibiotic treatments with hypoalbuminemia and with previous healthcare exposures were the most affected by COVID-19 and CD co-infections.

Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter.

The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.

Unexpected TBEV Seropositivity in Serbian Patients Who Recovered from Viral Meningitis and Encephalitis.

The tick-borne encephalitis virus (TBEV) causes a life-threatening disease named Tick-borne encephalitis (TBE). The clinical symptoms associated with TBE range from non-specific to severe inflammation of the central nervous system and are very similar to the clinical presentation of other viral meningitis/encephalitis. In consequence, TBE is often misclassified by clinical physicians, mainly in the non-identified high-risk areas where none or only a few TBE cases have been reported. Considering this situation, we hypothesized that among persons from northern Serbia who recovered from viral meningitis or encephalitis, there would be evidence of TBEV infection. To test this hypothesis, in this observational study, we evaluated the seroreactivity against TBEV antigens in patients from northern Serbia who were hospitalized due to viral meningitis and/or viral encephalitis of unknown etiology. Three cases of seroreactivity to TBEV antigens were discovered among convalescent patients who recovered from viral meningitis and/or encephalitis and accepted to participate in the study (n = 15). The clinical and laboratory findings of these patients overlap with that of seronegative convalescent patients. Although TBE has been a notifiable disease in Serbia since 2004, there is no active TBE surveillance program for the serologic or molecular screening of TBEV infection in humans in the country. This study highlights the necessity to increase the awareness of TBE among physicians and perform active and systematic screening of TBEV antibodies among patients with viral meningitis and/or encephalitis.

Epidemiological study on the incidence of haemorrhagic fever with renal syndrome in five Western Balkan countries for a 10-year period: 2006-2015.

BACKGROUND: Large-scale epidemics of haemorrhagic fever with renal syndrome (HFRS) have been reported mostly in Asia and Europe, with around 100,000 people affected each year. In the Southeast Europe, Balkan region, HFRS is endemic disease with approximately 100 cases per year. Our aim was to describe epidemiological characteristics of HFRS in five Western Balkan (WB) countries and to describe correlation between HFRS incidence and major meteorological event that hit the area in May 2014. METHODS: National surveillance data of HFRS from Bosnia and Herzegovina, Croatia, Montenegro, North Macedonia and Serbia obtained from 1 January 2006 to 31 December 2015 were collected and analysed. RESULTS: In a 10-year period, a total of 1,065 HFRS patients were reported in five WB countries. Cumulative incidence rate ranged from 0.05 to 15.80 per 100.000 inhabitants (in North Macedonia and Montenegro respectively). Increasing number of HFRS cases was reported with a peak incidence in three specific years (2008, 2012, and 2014). Average incidence for the entire area was higher in males than females (5.63 and 1.90 per 100.000 inhabitants respectively). Summer was the season with the highest number of cases and an average incidence rate of 1.74/100.000 inhabitants across 10-year period. Haemorrhagic fever with renal syndrome incidence was significantly increased (7.91/100.000 inhabitants) in 2014, when a few months earlier, severe floods affected several WB countries. A strong significant negative correlation (r = -.84, p < .01) between the monthly incidence of HFRS and the number of months after May's floods was demonstrated for the total area of WB. CONCLUSION: Our findings demonstrate that the HFRS incidence had similar distribution (general, age, sex and seasonality) across majority of the included countries. Summer was the season with the highest recorded incidence. Common epidemic years were detected in all observed countries as well as a negative correlation between the monthly incidence of HFRS and the number of months after May's cyclone.

Changing epidemiology of catheter-related bloodstream infections in neutropenic oncohematological patients.

BACKGROUND: We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality. MATERIALS/METHODS: All consecutive episodes of CRBSIs were prospectively collected (1994-2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs. RESULTS: 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (p<0.001). CRBSIs epidemiology has been changing: the rate of GNB increased over time (from 11.9% to 29.4%; p<0.001), as well as the absolute number and rate of multidrug-resistant (MDR) GNB (from 9.5% to 40.0%; p = 0.039). P. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004-1.011), older age (OR 1.016; 95%CI 1.001-1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306-5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001-3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003). CONCLUSION: A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time.

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study.

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Endothelial biomarkers in the light of new sepsis definition.

The aim of our study was to compare usefulness of endothelial biomarkers for severity and outcome prediction in patients with positive Sepsis-3 criteria with traditionally used biomarkers. A total of 150 patients were included in our study. Patients were divided into two groups: patients with sepsis and those with infectious systemic inflammatory response syndrome. Development of septic shock and 28-day mortality were assessed. Endocan and thrombomodulin showed better discriminative power than procalcitonin for the presence of sepsis. Endocan showed good discriminative power for septic shock prediction. Addition of endocan significantly contributed to sequential (sepsis-related) organ failure assessment score in logistic regression model. Conclusion: Endothelial biomarkers have a good diagnostic potential for sepsis. Endocan is useful as a predictor of the severity and fatality of sepsis.

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study.

Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS). Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20-29 years old), group 2 (30-39), group 3 (40-49) and group 4 (50-59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. Results: The NAA/Cr ratios were decreased in the 20-29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50-59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations. Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART. Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.

Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers.

INTRODUCTION: The aim of this study was to investigate the role of C3 and C4 complement components in prediction of sepsis outcome. The secondary aim was to determine relationship between complement components and other inflammatory parameters, and parameters of hemostasis. METHODS: One-hundred-thirty-seven patients with sepsis (Sepsis-3 criteria) were included in the study. Routine laboratory markers, predictive APACHEII and SOFA scores, concentrations of C3 and C4, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), endogenous thrombin potential (ETP), thrombomodulin, and D-dimer were available. Concentrations of C3 and C4 were correlated with the disease outcome, predictive scores, inflammatory markers and parameters of hemostasis. Statistical analysis was performed using the non-parametric approach and significance was set at p < 0.05. RESULTS: A significant depletion of the complement was observed in non-survivors (AUCROCC3 = 0.692, pC3 < 0.001,AUCROCC4 = 0.672, pC4 = 0.001). There was a significant negative correlation of C3and C4with APACHEII and SOFA (C3-APACHEII ρ = -0.364, p = 0.011, C3-SOFA ρ = -0.460, p < 0.001), aPTT (ρ = -0.407, p < 0.001), PT (ρ = -0.408, p < 0.001), and D-dimer (ρ = -0.274, p = 0.001). A significant positive correlation was observed with natural anticoagulants (C3-AT ρ = 0.493, p < 0.001; C3-PC ρ = 0.450, p < 0.001; C3-PS ρ = 0.345, p < 0.001), fibrinogen (ρ = 0.481, p < 0.001),and ETP (ρ = 0.384, p < 0.001). C3 and C4 correlated significantly only with CRP (ρ = 0.207, p = 0.015), while no significant correlations with procalcitonin and WBC were detected. Results were similar for C4 and C3, although C3 presented higher correlation coefficients. CONCLUSION: In septic patients with poorer outcome, a significant depletion of the complement system was observed. Concentrations of complement components demonstrated stronger correlations with coagulation parameters than with inflammatory biomarkers.

The role of TNF-α superfamily members in immunopathogenesis of sepsis.

BACKGROUND: Members of TNFα superfamily, A proliferation inducing ligand (APRIL), B-cell activating factor (BAFF) and Transmembrane activator and calcium cyclophylin interactor (TACI) are main regulators of B-cell function. The aim of this study was to evaluate concentrations of APRIL, BAFF and soluble TACI (sTACI) receptor in septic patients compared to healthy controls and compare concentrations of these biomarkers depending on sepsis severity and outcome. MATERIALS AND METHODS: A total of 115 septic patients and 30 healthy volunteers were included and concentrations of APRIL, BAFF and sTACI were determined in all subjects at the admission (ELISA R&D Systems tests). Concentrations of these biomarkers in function of sepsis severity (sepsis n = 94 and septic shock n = 21) and outcome (lethal n = 40, recovery n = 75) were tested, as well as correlations with APACHE II and SOFA scores, immunoglobulins, complement, PCT and CRP concentrations. RESULTS: Concentrations of all three biomarkers were significantly increased in septic patients compared to controls (AUCAPRIL = 0.982, AUCBAFF = 0.873, AUCsTACI = 0.683). Higher concentrations of APRIL and sTACI (p = 0.033, p = 0.037), and lower concentrations of BAFF (p = 0.005) were observed in patients with septic shock compared to sepsis. BAFF concentrations correlated positively with IgM, C3 and C4 levels. sTACI and APRIL were shown to be predictors of lethal outcome (p = 0.003, p = 0.049). CONCLUSIONS: Concentrations of observedTNFα superfamily members are significantly increased in septic patients, confirming their role in sepsis pathogenesis.Higher concentrations of anti-inflammatory sTACI receptor correlated with severity of sepsis and poorer prognosis, thus potentially indicating domination of anti-inflammatory response in septic patients with worse outcome.

APRIL and sTACI could be predictors of multiorgan dysfunction syndrome in sepsis.

Although the role of B cells in sepsis immunoregulation has become an interesting topic, there is lack of data on the role of B cell function regulators in prediction of multiorgan dysfunction syndrome (MODS). The aim of this study was to evaluate the prognostic value of A Proliferation Inducing Ligand (APRIL) and soluble Transmembrane Activator and CAML Interactor Protein (sTACI), the main B cell function regulators, in prediction of MODS development within the first 48 h after admission to intensive care unit, among septic patients. We included 112 patients with sepsis, treated at Clinic for Infectious Diseases and Emergency Center, Clinical Center of Vojvodina, Novi Sad, Serbia. Plasma concentrations of APRIL and sTACI were determined at the admission and potential development of MODS was confirmed in the first 48 h. Concentrations of APRIL (p = 0.003) and sTACI (p<0.001) were higher in patients who developed MODS (n = 30). ROC curve analysis showed that AUC for sTACI (AUC = 0.764) was greater than that for procalcitonin (AUC = 0.719) and APRIL (AUC = 0.673) in MODS development prediction. Multivariate regression analysis showed that sTACI, as an anti-inflammatory biomarker stimulating the apoptosis of B cells, was the only independent predictor of MODS, beside SOFA score. Elevated level of sTACI could be the alarm for the increased B cell apoptosis and development of immune paralysis. Including these biomarkers into predictive scores specific for septic patients may potentially improve their sensitivity and specificity. Measurement of their concentrations dynamics could contribute to better assessment of sepsis evolution and timely introduction of immunomodulatory therapy.

Neuroendocrine disorder in chronic fatigue syndrome

Background/aim: Neuroendocrine disorders are considered a possible pathogenetic mechanism in chronic fatigue syndrome (CFS). The aim of our study was to determine the function of the hypothalamic-pituitary-adrenal axis (HPA) and thyroid function in women of reproductive age suffering from CFS. Materials and methods: The study included 40 women suffering from CFS and 40 healthy women (15-45 years old). Serum levels of cortisol (0800 and 1800 hours), ACTH, total T4, total T3, and TSH were measured in all subjects. The Fibro Fatigue Scale was used for determination of fatigue level. Results: Cortisol serum levels were normal in both groups. The distinctively positive moderate correlation of morning and afternoon cortisol levels that was observed in healthy women was absent in the CFS group. This may indicate a disturbed physiological rhythm of cortisol secretion. Although basal serum T4, T3, and TSH levels were normal in all subjects, concentrations of T3 were significantly lower in the CFS group. Conclusion: One-time hormone measurement is not sufficient to detect hormonal imbalance in women suffering from CFS. Absence of a correlation between afternoon and morning cortisol level could be a more representative factor for detecting HPA axis disturbance.

HIV-associated neurodegeneration and neuroimmunity: multivoxel MR spectroscopy study in drug-naïve and treated patients.

OBJECTIVES: The aim of this study was to test neurobiochemical changes in normal appearing brain tissue in HIV+ patients receiving and not receiving combined antiretroviral therapy (cART) and healthy controls, using multivoxel MR spectroscopy (mvMRS). METHODS: We performed long- and short-echo 3D mvMRS in 110 neuroasymptomatic subjects (32 HIV+ subjects on cART, 28 HIV+ therapy-naïve subjects and 50 healthy controls) on a 3T MR scanner, targeting frontal and parietal supracallosal subcortical and deep white matter and cingulate gyrus (NAA/Cr, Cho/Cr and mI/Cr ratios were analysed). The statistical value was set at p < 0.05. RESULTS: Considering differences between HIV-infected and healthy subjects, there was a significant decrease in the NAA/Cr ratio in HIV+ subjects in all observed locations, an increase in mI/Cr levels in the anterior cingulate gyrus (ACG), and no significant differences in Cho/Cr ratios, except in ACG, where the increase showed trending towards significance in HIV+ patients. There were no significant differences between HIV+ patients on and without cART in all three ratios. CONCLUSION: Neuronal loss and dysfunction affects the whole brain volume in HIV-infected patients. Unfortunately, cART appears to be ineffective in halting accelerated neurodegenerative process induced by HIV but is partially effective in preventing glial proliferation. KEY POINTS: • This is the first multivoxel human brain 3T MRS study in HIV. • All observed areas of the brain are affected by neurodegenerative process. • Cingulate gyrus and subcortical white matter are most vulnerable to HIV-induced neurodegeneration. • cART is effective in control of inflammation but ineffective in preventing neurodegeneration.

Endogenous thrombin potential as marker of procoagulant response that can be useful in early stage of sepsis.

: Sepsis is associated with complex procoagulant and anticoagulant changes that modify inflammatory response. Identification of coagulation markers that can differentiate useful procoagulant response from adverse alteration of clotting mechanism in patient with sepsis. In total, 150 patients who fulfilled criteria for diagnosis of sepsis were included in this study. Patients were categorized in two groups according to sepsis severity in the first 24 h from intensive care unit admission: sepsis and septic shock. In total, 28-day mortality was assessed. Platelet count, activated partial thromboplastin time, prothrombin time, D-dimer, fibrinogen, protein C, protein S, antithrombin levels, and endogenous thrombin potential were determined within first 24 h from ICU admission. Differences between groups of septic patients were assessed by Mann-Whitney U test. Categorical variables were compared using χ test. Receiver operating characteristic curves were plotted to determine predictive values of variables for sepsis severity prediction. Activated partial thromboplastin time and prothrombin time were significantly prolonged with higher D-dimer, lower fibrinogen, and natural anticoagulant levels (protein C, protein S, and antithrombin) in patients with more severe form of the disease and worse outcome (P < 0.05). Endogenous thrombin potential [area under the curve (AUC) %] was significantly decreased in patients with more severe form of sepsis (66.01 ±â€Š41.51 vs. 83.21 ±â€Š28.83; AUC 0.76) and in patients with worse outcome (67.66 ±â€Š37.79 vs. 81.79 ±â€Š32.15; AUC 0.68; P < 0.05). Evaluation of initial thrombin generation is useful to distinguish between beneficial coagulation activation and hazardous haemostatic alteration, and to predict multiorgan dysfunction development and poor outcome in septic patients.

Chronic Hepatitis C and Alcohol Abuse: The Single Center Experience of Novi Sad - Serbia.

BACKGROUND: Chronic ethyl alcohol consuming is well known independent negative predictor of unfavorable natural course and therapy outcome of Chronic Hepatitis C (CHC) infection. OBJECTIVE: The aim of the present study was to clarify the impact of alcohol consumption on fibrosis rate progression in patients with CHC and Sustained Virologic Response (SVR) rates in patients undergoing treatment with pegylated interferon and ribavirin. METHOD: This cross sectional retrospective study included 807 CHC patients underwent liver biopsy and hospitalized at Clinical center of Vojvodina, Novi Sad, Serbia. According to the alcohol consumption equal or greater than 50 g/day prior to liver biopsy, patients were divided into two groups. We compared demographic, clinical, virologic and histopathological markers of CHC, as well as response to antiviral therapy. RESULTS: We find statistically significant difference (p=0.001) in gender, but not in age (p=0.081), estimated duration of the CHC (p=0.470) and hepatitis C genotype (p=0.545) between two groups. Among patients with CHC who consume alcohol ≥50 g/day there were significantly higher incidence of intravenous drug users (p=0.000). Binary logistic regression showed that the only independent predictors of moderate to severe fibrosis (fibrosis ≥2) were age (p=0.000) and alcohol use (p=0.027). There was not statistically significant difference in SVR rate between two groups (p=0.810). CONCLUSION: We believe that this good result in treatment outcome was the consequence of proper selection of patients based primarily on regulations of Republic of Serbia on the necessity of abstinence from the use of alcohol and psychoactive substances at least one year before starting antiviral therapy.

Non-cirrhotic Portal Hypertension Associated with Didanosine and Streptococcus agalactiae Infection: A Case Report.

BACKGROUND: Non-Cirrhotic Portal Hypertension (NCPH) is a rare but potentially fatal liver disorder described in patients treated with anti-retroviral therapy for Human Immunodeficiency Virus (HIV). In particular, the most important predisposing factor to its development has been identified as prolonged exposure to Didanosine (ddI). The clinical entity of NCPH is characterized by an increase in portal pressure due to pre- or intra-hepatic causes, in absence of liver cirrhosis. However, the exact pathogenesis remains poorly understood, and due to its rarity, the diagnosis is often delayed. OBJECTIVE: We herein report a case in which ddI administration, with concomitant spontaneous bacterial peritonitis by Streptococcus agalactiae, has induced NCPH in a HIV male patient. CONCLUSION: NPCH should be suspected when HIV patient with an history of ddI treatment presents liver decompensation.

Prognostic value of hemostasis-related parameters for prediction of organ dysfunction and mortality in sepsis.

BACKGROUND/AIM: Clinical manifestations of sepsis are not caused directly by the invading pathogens, but rather mostly by systemic inflammation that leads to activation of the coagulation system. The aim of this study was to determine whether levels of hemostasis- related parameters measured in intensive care unit admissions are associated with mortality and severity in patients with sepsis. MATERIALS AND METHODS: Eighty-five patients who fulfilled criteria for a diagnosis of sepsis were included in our study. Platelet count, activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time, D-dimer, and fibrinogen levels were determined within the first 24 h from sepsis onset. Differences between groups of septic patients were assessed by Mann-Whitney U test and Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. RESULTS: Prolonged aPTT and PT with higher D-dimer concentrations in patients with sepsis are associated with more severe forms of the disease, aPTT was prolonged in nonsurvivors, while platelet count and fibrinogen levels were higher in survivors. Platelet count and aPTT ratio are independent predictors of fatal outcome in our logistic regression model. CONCLUSION: Hemostasis-related parameters have a significant impact on severity and outcome in sepsis.