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The aim of the study was to evaluate thyroid-stimulating hormone (TSH) concentration in a reference group and to compare it with the TSH in subjects with high probability of thyroid dysfunction. The study population consisted of 852 subjects. The reference group consisting of 316 subjects was obtained by the exclusion of the subjects having thyroid disease, taking thyroid influencing drugs, having increased thyroid peroxidase (TPO) antibodies, or having abnormal thyroid ultrasound. 42 high probability of thyroid dysfunction subjects were defined by the association of increased TPO antibody concentration, changed echogenicity, and changed echosonographic structure of thyroid parenchyma. In the reference group TSH reference range was 0.45 mU/l (95 % CI 0.39-0.56 mU/l) to 3.43 mU/l (95 % CI 3.10-4.22 mU/l). To distinguish reference and high probability of thyroid dysfunction group a TSH threshold was calculated. At a threshold value of 3.09 mU/l (95 % CI 2.93-3.38 mU/l), specificity was 95 % and sensitivity 38.1 %. Using 2 different approaches to find upper limit of the TSH reference range we obtained similar results. Using reference group only a value of 3.43 mU/l was obtained. Using both reference group and subjects with the high probability of thyroid dysfunction we obtained 95 % CI for the upper reference limit between 2.93 and 3.38 mU/l. Based on these premises, it could be argued that conservative estimate of the TSH upper reference range should be 3.4 mU/l for both sexes. [ABSTRACT FROM AUTHOR]

Context. Insulin-like growth factor-1 (IGF-1) is main serum surrogate marker of growth hormone (GH) secretion, used in diagnostics and treatment of GH deficiency (GHD) and acromegaly. Regional, ethnic, racial or nutritional factors obscure cross-population applicability of IGF-1 reference values. Establishment of population- and assayspecific reference values requires sizable representative cohort of healthy subjects. Subjects and Methods. In representative sample of healthy adult population of Serbia (N=1200, 21-80 years, 1:1 male:female) serum IGF-1 was analyzed by Siemens Immulite 2000 assay under uniform laboratory conditions. Upper and lower limit of reference range (5th - 95th percentile) were calculated for each of the 12 quinquennial age intervals. IGF-1 distribution was normalized and standard deviation score (SDS) calculated by Logarithmic and LMS methods. Results. IGF-1 and age correlated significantly, with most prominent decline at 21-50 years, followed by a plateau up to age of 70. Gender differences were not significant overall. Plateau in age-related IGF-1 decline was less prominent in women. Correlations of IGF-1 with body mass index (BMI) or waist to hip ratio (WHR) were insignificant. Superior IGF-1 SDS transformation was achieved with LMS method, while logarithmic method was simpler to use. Conclusions. Normative age-specific serum IGF-1 reference values were established on a representative cohort of healthy adults in Serbia. Our results support recommendations against necessity for gender-specific or BMI- and WHR-specific reference ranges. Populationbased data serve to generate IGF-1 SDS, which is valuable in rational application of consensus guidelines, proper longitudinal follow-up, advancement in efficacy and safety and personalization of treatment targets. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance represents the emerging problem of modern medicine. Despite the fact that Enterobacter spp. is one of the most resistant pathogens, there has been a paucity of data on molecular epidemiology and antimicrobial susceptibility of community isolates in European countries as well as in Serbia. This study was conducted in 2016 and 2017 with the aim to investigate the prevalence of carbapenem-resistant Enterobacter spp. community isolates, molecular determinants of carbapenem resistance, and their genetic relatedness. Seventeen (1.6%) of 1,040 isolates that were positive for carbapenemase screening in accordance with European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations were included in the study. Minimum inhibitory concentrations for selected antimicrobials were determined by broth microdilution and by disk diffusion for chloramphenicol. Multiplex polymerase chain reactions (PCRs) for blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48-like carbapenemase genes were performed. Clonality was assessed by enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis. All isolates were multidrug resistant. The most frequent carbapenemase gene found was blaNDM (70.6%), followed by isolates coharboring blaNDM and blaOXA-48-like genes (23.5%) and a single isolate with the blaOXA-48-like gene (5.9%). ERIC-PCR molecular typing showed six different clusters (A-F) with clonal relatedness among isolates from the same institution and association of clusters E and F with the blaNDM carbapenemase gene. Our results indicate the need for Enterobacter spp. surveillance both in the community and hospitals to prevent spreading of multiresistant clones.

Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT) polymorphism and risk of preeclampsia (PE). The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestational-age (SGA) complicating PE., Methods: The study included 47 early-onset PE patients and 47 control cases. Forty-seven early-onset PE patients were grouped by disease severity (33 patients with a severe form and 14 patients without severe features) and secondly by size for gestational age (12 patients with appropriate-for-gestational-age (AGA) and 35 patients with SGA size). p.Val158Met polymorphism was genotyped by PCR-RFLP analysis., Results: Allele analysis showed significant difference in COMT allele distribution between early-onset PE and control group as well as early-onset PE SGA and controls (p=0.04057 and p=0.0411 respectively). A statistically significant distribution difference between the severe form and form without severe features of early-onset PE patients was not observed (p>0.05). The highest difference observed was in the allele recessive model where COMT MetMet genotype was associated with decreased risk of early-onset PE (OR=0.281; 95%CI = 0.092-0.7836) and PE complications including severe early-onset PE (OR= 0.304; 95%CI=0.086-0.944) and SGA early-onset PE (OR=0.284; 95%CI=0.081-0.874)., Conclusions: COMT may be used as a candidate gene for early-onset PE and its severe form and SGA complications., Competing Interests: The authors stated that they have no conflicts of interest regarding the publication of this article.

Introduction: A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity., Objective: Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes., Methods: A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated., Results: Participants were 58.65 ± 7.62 years of age with a body mass index of 35.06 ± 5.15 kg/m², waist circumference of 115.04 ± 15.5 cm, and the duration of diabetes of 4.11 ± 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged., Conclusion: Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.

Complete examination of 21 patients with IgA nephropathy included determination urine and serum IL-6, TNF alpha and INF gamma levels by ELISA (Luzernachen, Luzern Switzerland). Control group included 15 healthy volunteers. Urine IL-6 levels ranging 37-274.1 pg/ml were detected in 15 (71.2%) patients with IgA nephropathy. IL-6 serum levels were undetectable. In the control group serum and urine levels were also undetectable. Correlation between the IL-6 level and proteinuria degree and endogenous creatinine clearance rate has not revealed statistically significant relationship. In relation to histologic groups (minimal changes, focal glomerulonephritis, mesangial proliferative, diffuse sclerosing) patients with minimal changes had (statistically) significantly higher IL-6 urine levels than the third and fourth group. Average the urine levels were 145.8 +/- 166.6 pg/ml and the serum ones were 148 +/- 101 pg/ml. In relation to the control group (statistically) significant difference was not found. Correlation between TNF alpha level and proteinuria degree and creatinine clearance rate has revealed (statistically) significant relationship (p < 0.05). Average interferon gamma serum levels in lgA nephropathy patients were 312.0 +/- 111.8 and in comparison with the control group (statistically) significant difference was found (p < 0.01). The obtained results suggest the important role of cytokine production disregulation associated with the pathogenesis of IgA nephropathy.

Several studies have suggested that the measurement of urinary interleukin-6 (IL-6) is a helpful tool for diagnosis and monitoring the progression of glomerulonephritis. The aim of this study was to determine if IL-6 level might reflect the histological type of glomerular lesions. We performed a prospective study of 43 patients who underwent renal biopsy in our hospital. There were 35 male and 8 female patients with median age of 30.5 years (range 19-50). Included among these were 13 cases of IgA nephropathy, 11 cases of membranoproliferative glomerulonephritis, 6 cases of poststreptococcal glomerulonephritis, 6 cases of mesangial proliferative glomerulonephritis, 5 cases of membranous nephropathy and 2 cases of C3 nephritis. IL-6 was measured by ELISA (Lucernachem, Switzerland). IL-6 was not detected in the serum and rine of 15 healthy controls. IL-6 was elevated in the urine of 30 patients with different histological types of glomerular lesions (range 3.7 to 433.3 pg/ml) but was not detected in the urine of remaining 13 patients. The presence of IL-6 in the urine in absence of raised serum IL-6 suggests that urinary IL-6 was produced by the kidney. We have concluded that urinary IL-6 level can be considered as a marker of glomerulonephritis but not one that is very specific for any particular histological type of primary glomerulonephritis. Thus, the urinary IL-6 level is not a useful tool in the differential diagnosis of primary glomerulonephritis. We need further studies to determine whether urinary IL-6 level could by considered for monitoring of disease activity and therapy.