Snezana Brkic

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.

Lipid and protein oxidation in female patients with chronic fatigue syndrome

Introduction Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS. Material and methods Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined. Results The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol. Conclusions The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Cystatin C in pre-eclampsia.

Objective: To evaluate diagnostic value of cystatin C serum levels as alternative marker of renal function in pre-eclamsia (PE) and compare it with the traditional markers of renal function, creatinine and uric acid. In order to investigate the possible influence of inflammation on biochemical markers of renal function, serum levels of high sensitive CRP were measured (hsCRP). Methods: In this prospective study markers of kidney function were investigated in two groups of pregnant women: one with PE (n = 32) and the other of healthy pregnant women (n = 60). Serum cystatin C levels were measured as well as levels of traditional renal markers creatinin and uric acid and levels of high sensitive C-reactive protein. Results: Serum levels of cystatin C, creatinine and uric acid were significantly higher in the PE group than in the control group. Serum levels of hsCRP were higher in approximately the same number of patients with PE (50%) as in normal pregnancies (40%), without significant differences in CRP values between the two groups of patients. Conclusions: Cystatin C serum level may have significant role as a marker of pre-eclampsia specially when used in combination with uric acid levels.

Multivitamin mineral supplementation in patients with chronic fatigue syndrome.

Background Chronic fatigue syndrome (CFS) is characterized by medically unexplained persistent or reoccurring fatigue lasting at least 6 months. CFS has a multifactorial pathogenesis in which oxidative stress (OS) plays a prominent role. Treatment is with a vitamin and mineral supplement, but this therapeutic option so far has not been properly researched. Material/Methods This prospective study included 38 women of reproductive age consecutively diagnosed by CDC definition of CFS and treated with a multivitamin mineral supplement. Before and after the 2-month supplementation, SOD activity was determined and patients self-assessed their improvement in 2 questionnaires: the Fibro Fatigue Scale (FFS) and the Quality of Life Scale (SF36). Results There was a significant improvement in SOD activity levels; and significant decreases in fatigue (p=0.0009), sleep disorders (p=0.008), autonomic nervous system symptoms (p=0.018), frequency and intensity of headaches (p=0.0001), and subjective feeling of infection (p=0.0002). No positive effect on quality of life was found. Conclusions Treatment with a vitamin and mineral supplement could be a safe and easy way to improve symptoms and quality of life in patients with CFS.

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

AbstractObjectivesThe 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).MethodsWe 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.ResultsConsidering 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.ConclusionNeuronal 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.

Thrombomodulin is a Strong Predictor of Multiorgan Dysfunction Syndrome in Patients With Sepsis

Background: Biomarkers of endothelial dysfunction are not recommended for routine laboratory investigation of the outcome prognosis and prediction of the course of sepsis. Methods: A total of 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Development of multiorgan dysfunction syndrome (MODS) in the first 48 hours was assessed. Differences between groups of patients with sepsis were assessed by Mann-Whitney U test and by Kruskal-Wallis test. Logistic regression analysis was performed to test the joint effect of different predictors. Results: Level of thrombomodulin was significantly higher in group of patients with MODS than without MODS (P = .015). Levels of antithrombin (P = .026) and protein C (P = .035) were significantly lower in patients with MODS. Level of thrombomodulin was the strongest predictor in MODS development in first 48 hours (P = .028). Conclusion: The level of thrombomodulin not only was able to distinguish the severity of sepsis but also was a significant predictor of MODS development.

Lipid peroxidation in the first trimester of pregnancy.

Aim: To determine the existence and level of oxidative stress caused by lipid peroxidation in pregnancy. Methods: The research was conducted as prospective examination that included 60 healthy women (age 18–45). The women included in the examination were divided into two groups. The group I (N-31) included women in the first trimester of normal, healthy pregnancy. The group II included healthy nongravid women (N-29). Concentrations of markers of lipid peroxidation malondialdehyde (MDA) and thiobarbituric acid (TBARS) were determined using commercial ELISA tests OxiSelect™ TBARS Assay Kit and OxiSelect™ MDA ELISA Kit. Results: The results of this research indicate that the concentrations of the markers of lipid peroxidation TBARS and MDA are detectable in both groups. Higher mean values of MDA (>20 pmol/mg) were measured in the group of pregnant women, than in the group of nongravid women. The results indicate that mean values of TBARS markers are lower in pregnant women (≤50 µM) than in nongravid women (>100 µM). Conclusion: The marker of lipid peroxidation MDA proved to be a sensitive marker for following lipid peroxidation during pregnancy, therefore it can be considered as a good predictor of possible complications during pregnancy.

Mid-pregnancy interleukins levels in serum and amniotic fluid as predictors of preterm delivery.

Abstract Objectives: To find out if determination of IL-4, IL-13 and IL-6 in amniotic fluid (AF) and serum in mid-pregnancy can be used as predictors of preterm delivery. Material and methods: The research has comprised 88 pregnant women at 16-24 weeks of gestation, who were subjected to early amniocentesis. Levels of interleukins were determined by ELISA tests. Pregnant women had been monitored untill termination of pregnancy and divided in two groups: 68 term and 20 preterm deliveries. Results: IL-13 was not detectable at all in serum and amniotic fluid samples. IL-4 was not detectable in serum samples of both groups of women and it was detectable only in small number (20 % - 27 %) of AF samples. There was no statistically significant difference (p=0.665) in the mean values of AF IL-4 levels between the examined groups of women. Detectability for IL-6 was very low in serum specimens, while in AF it was detectable in 100% of cases and its levels was significantly higher (p<0.001) in preterm delivery group. Conclusions: The results obtained in this study suggest that the AF mid-pregnancy levels of IL-6 higher than 132 pg/ml may indicate preterm delivery.

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

&NA; 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 &khgr;2 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 ± 41.51 vs. 83.21 ± 28.83; AUC 0.76) and in patients with worse outcome (67.66 ± 37.79 vs. 81.79 ± 32.15; 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.

Fever of Unknown Origin in Elderly Patients

INTRODUCTION Causes of fever of unknown origin are different. It is considered that it can be caused with over 200 different clinical entities. Aetiological causes differ according to different categories of age. Febricity in the elderly is at most the result of autoimmune processes, malignancies, bacterial infections and vasculitis. OBJECTIVE The aim of this study was to determine the most common characteristics of fever, the most common laboratory, bacterial and viral tests and to analyze applied therapy in patients with unknown febrile state, and to affirm final diagnosis in elderly patients, as well as younger than 65 years old, and to define outcome of disease in both groups of patients. METHODS Research comprised 100 patients who had been treated at the Infectious Disease Clinic of the Clinical Centre of Vojvodina in Novi Sad, during a three-year period, and in whom fever of unknown origin had been diagnosed. Patients were divided into two homogenous groups of 50 people. The first one (S) consisted of patients older than 65 years, and the second, control group (K) was constituted of patients younger than the age of 65. All of them were chosen by random sample method. RESULTS Average results of standard laboratory parameters of infection were obtained, such as erythrocyte sedimentation rate (ESR), fibrinogen, CRP, and especially leukocyte, and those were significantly higher in the group of elderly patients. The cause had not been found in 10% of elderly patient group, and in the younger group, not even in the third of patients. Among known causative agents dominant were infections, usually of respiratory and urinary tract, in both tested groups. Even 28% of the elderly had sepsis, and 10% endocarditis. Malignant diseases were more frequent in group of the elderly patients, and immune i.e. systematic disorders were evenly noticed in both groups of patients. CONCLUSION Despite advanced studies in medicine, and existence of modern diagnostic procedures, fever of unknown origin is still today differential diagnostic problem.