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.

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.

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.

Endocan is useful biomarker of survival and severity in sepsis.

INTRODUCTION: Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined. MATERIALS AND METHODS: 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test. RESULTS: Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure. CONCLUSIONS: Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores.