Direct endometrial brush cytology in detection of premalignant and malignant lesions of endometrium

CILJ ISTRAŽIVANJA. Procijeniti dijagnostičku vrijednost direktne endometralne brush citologije u detekciji premalignih i malignih lezija endometrija. USTROJ STUDIJE. Retrospektivno presječno poredbeno istraživanje. ISPITANICI I METODE. Retrospektivnim su istraživanjem obuhvaćene ispitanice u kojih je na Kliničkom zavodu za kliničku citologiju KBC-a Osijek od 2002. do kraja 2015. godine izvršen citološki pregled endometralnog brush razmaza, uz uvjet da su u razdoblju od najduže 6 mjeseci nakon citološke dijagnoze imale i patohistološku verifikaciju. Istraživanjem su obuhvaćene i ispitanice s urednim citološkim nalazom koje nisu imale patohistološku verifikaciju citološkog nalaza, a praćene su najmanje tri godine klinički i ultrazvučno. Isključni kriteriji bili su neadekvatni nalazi. Citološke dijagnoze podijeljene su u četiri kategorije: benigno, hiperplazija, hiperplazija s atipijama te suspektna/maligna lezija. Histološki nalazi učinjeni su na Zavodu za patološku anatomiju i sudsku medicinu KBC-a Osijek. Patohistološka je dijagnoza postavljena na kiretmanu ili resekcijskom materijalu, a u skladu s trenutno važećom WHO klasifikacijom. REZULTATI. Osjetljivost endometralne brush citologije najviša je za benigne lezije s uključenim hiperplazijama i iznosi 90 %. Specifičnost je visoka za sve dijagnoze i kreće se od 87,1 % do 99,3 %. Pozitivna prediktivna vrijednost, izuzetno je visoka za benigne lezije (98,4 %) i maligne lezije (89,5 %), a izuzetno je niska za hiperplazije s atipijama (8,6 %). Ukupna dijagnostička točnost iznosi 91,6 %. ZAKLJUČAK. Endometralna brush citologija pouzdana je dijagnostička metoda za diferenciranje benignih od malignih lezija endometrija, a njezina primjena može umanjiti potrebu za drugim invazivnijim i skupljim dijagnostičkim zahvatima.OBJECTIVES. The goal of this research was to determine the value of the direct endometrial brush cytology in the detection of premalignant and malignant lesions of endometrium. STUDY DESIGN. A retrospective cross-sectional comparative study. PARTICIPANS AND METHODS. The study included subjects who were subjected to the direct endometrial brush cytology at the Department of Clinical Cytology, Clinical Hospital Center Osijek, from 2002 to the end of 2015, provided that they were also subjected to the histological verification, over a period of 6 months after the cytological diagnosis. The study also included subjects with normal cytological findings without histological verification, but with clinical and ultrasound follow-up for at least three years. Exclusion criteria were inadequate specimens. Cytology diagnosis were benign lesions, hyperplasia, hyperplasia with atypias and endometrial carcinoma. Cytology brush samples were fixed in 95% alcohol and stained with Papanicolaou method. Histologic analysis was performed at the Department of Pathology and Forensic Medicine, Clinical Hospital Center Osijek. Histopathological analysis was done on formalin fixed, paraffin embedded samples obtained from fractionated curettage or hysterectomy resection material, according to the current WHO classification. RESULTS. The sensitivity of the uterobrush endometrial cytological examination method for benign lesions and hyperplasia was 90%. The specificity was high in detection of all diagnoses and it ranged from 87.1% to 99.3%. Positive predictive value was high for detecting benign lesions (98.4%) and malignant lesions (89.5%) but low for hyperplasia with atypias (86%). The total diagnostic accuracy of the differential cytology was 91.6%. CONCLUSION. The direct endometrial brush cytology is a reliable diagnostic method for differentiation between benign and malignant lesions and its use can minimize the need for other invasive and more expensive procedures. KEYWORDS. OBJECTIVES. The goal of this research was to determine the value of the direct endometrial brush cytology in the detection of premalignant and malignant lesions of endometrium. STUDY DESIGN. A retrospective cross-sectional comparative study. PARTICIPANS AND METHODS. The study included subjects who were subjected to the direct endometrial brush cytology at the Department of Clinical Cytology, Clinical Hospital Center Osijek, from 2002 to the end of 2015, provided that they were also subjected to the histological verification, over a period of 6 months after the cytological diagnosis. The study also included subjects with normal cytological findings without histological verification, but with clinical and ultrasound follow-up for at least three years. Exclusion criteria were inadequate specimens. Cytology diagnosis were benign lesions, hyperplasia, hyperplasia with atypias and endometrial carcinoma. Cytology brush samples were fixed in 95% alcohol and stained with Papanicolaou method. Histologic analysis was performed at the Department of Pathology and Forensic Medicine, Clinical Hospital Center Osijek. Histopathological analysis was done on formalin fixed, paraffin embedded samples obtained from fractionated curettage or hysterectomy resection material, according to the current WHO classification. RESULTS. The sensitivity of the uterobrush endometrial cytological examination method for benign lesions and hyperplasia was 90%. The specificity was high in detection of all diagnoses and it ranged from 87.1% to 99.3%. Positive predictive value was high for detecting benign lesions (98.4%) and malignant lesions (89.5%) but low for hyperplasia with atypias (86%). The total diagnostic accuracy of the differential cytology was 91.6%. CONCLUSION. The direct endometrial brush cytology is a reliable diagnostic method for differentiation between benign and malignant lesions and its use can minimize the need for other invasive and more expensive procedures

Extreme value theory in emerging markets

This paper investigates the performance of extreme value theory (EVT) with the daily stock index returns of four different emerging markets. The research covers the sample representing the Serbian (BELEXline), Croatian (CROBEX), Slovenian (SBI20), and Hungarian (BUX) stock indexes using the data from January 2006 - September 2009. In the paper a performance test was carried out for the success of application of the extreme value theory in estimating and forecasting of the tails of daily return distribution of the analyzed stock indexes. Therefore the main goal is to determine whether EVT adequately estimates and forecasts the tails (2.5% and 5% at the tail) of daily stock index return distribution in the emerging markets of Serbia, Croatia, Slovenia, and Hungary. The applied methodology during the research includes analysis, synthesis and statistical/mathematical methods. Research results according to estimated Generalized Pareto Distribution (GPD) parameters indicate the necessity of applying market risk estimation methods, i.e. extreme value theory (EVT) in the framework of a broader analysis of investment processes in emerging markets

Toxoplasmosis in Serbia: time for an action plan

Known for a century, Toxoplasma gondii has been studied in Serbia half this time, ever since the introduction of the Sabin-Feldman test at the Institute for Medical Research (IMR) in 1959. However, despite 50 years of continuous efforts, exact data on the frequency of acute clinical disease, acute infections in pregnancy and congenital infection in the offspring are still lacking, due to the vague regulatory provision that toxoplasmosis is subject to reporting "in case of epidemiological indications". It is, however, clear that the major Toxoplasma-induced public health issue in Serbia, like elsewhere in Europe, is congenital toxoplasmosis (CT). Continuous monitoring of particular patient groups showed a dramatic decrease in the prevalence of infection over the past two decades, and a consequently increased proportion of women susceptible to infection in pregnancy, suggesting a potential increase in the incidence of CT. Studies of risk factors for infection transmission have provided data to guide national health education campaigns. It is expected that the recent appointment of the National Reference Laboratory for Toxoplasmosis as the focal point for the collection of data from the primary level, will provide the means for accurate assessment of the measure of the problem, which is a prerequisite of an evidence-based nation-wide prevention program. In the meantime, health education of all pregnant women, focused at risk factors of major local significance, is advocated as a sound and financially sustainable option to reduce congenital toxoplasmosis

Prospective Cohort Study of the Kinetics of Specific Antibodies to SARS-CoV-2 Infection and to Four SARS-CoV-2 Vaccines Available in Serbia, and Vaccine Effectiveness: A 3-Month Interim Report

Real-life data on the performance of vaccines against SARS-CoV-2 are still limited. We here present the rates of detection and levels of antibodies specific for the SARS-CoV-2 spike protein RBD (receptor binding domain) elicited by four vaccines available in Serbia, including BNT-162b2 (BioNTech/Pfizer), BBIBP-CorV (Sinopharm), Gam-COVID-Vac (Gamaleya Research Institute) and ChAdOx1-S (AstraZeneca), compared with those after documented COVID-19, at 6 weeks and 3 months post first vaccine dose or post-infection. Six weeks post first vaccine dose, specific IgG antibodies were detected in 100% of individuals fully vaccinated with BNT-162b2 (n = 100) and Gam-COVID-Vac (n = 12) and in 81.7% of BBIBP-CorV recipients (n = 148), while one dose of ChAdOx1-S (n = 24) induced specific antibodies in 75%. Antibody levels elicited by BNT-162b2 were higher, while those elicited by BBIBP-CorV were lower, than after SARS-CoV-2 infection. By 3 months post-vaccination, antibody levels decreased but remained ≥20-fold above the cut-off in BNT-162b2 but not in BBIBP-CorV recipients, when an additional 30% were seronegative. For all vaccines, antibody levels were higher in individuals with past COVID-19 than in naïve individuals. A total of twelve new infections occurred within the first 3 months post-vaccination, eight after the first dose of BNT-162b2 and ChAdOx1-S (one each) and BBIBP-CorV (six), and four after full vaccination with BBIBP-CorV, but none required hospitalization

In Vivo and In Vitro Virulence Analysis of Four Genetically Distinct Toxoplasma gondii Lineage III Isolates

Toxoplasma gondii archetypes II and III are mildly virulent, yet virulence of variant strains is largely unknown. While lineage II dominates in humans in Europe, lineage III strains are present in various intermediate hosts. In Serbia, lineage III represents 24% of the population structure and occurs most frequently in domestic animals, implying a significant presence in the human food web. In this study, the virulence of four genetically distinct lineage III variants was assessed in vivo and in vitro. In vivo, two strains were shown to be intermediately virulent and two mildly virulent, with cumulative mortalities of 69.4%, 38.8%, 10.7%, and 6.8%, respectively. The strain with the highest mortality has previously been isolated in Europe and may be endemic; the strain with the lowest mortality matches ToxoDB#54, while the remaining two represent novel genotypes. Identical alleles were detected at ROP5, ROP16, ROP18, and GRA15. A set of in vitro analyses revealed proliferation and plaque formation as virulence factors. Higher levels of expression of ENO2 in intermediately virulent strains point to enhanced metabolism as the underlying mechanism. The results suggest that metabolic attenuation, and possibly stage conversion, may be delayed in virulent strains

Toxoplasma gondii genotypes circulating in domestic pigs in Serbia

Consumption of undercooked or raw pork is considered a significant risk factor for human infection with Toxoplasma gondii. In this study, we investigated the genetic structure of 18 T. gondii strains obtained from slaughter pigs from Northern Serbia (mainly Vojvodina). The examined samples originated from eight pigs from large commercial farms, six backyard pigs and four free-range Mangalica pigs, all found to be positive for either viable T. gondii or T. gondii DNA. Genotyping was attempted from both pig tissues and mouse brains from the bioassays using a multiplex multilocus nested polymerase chain reaction-restriction fragment length polymorphism (Mn-PCR-RFLP) method with seven markers (GRA6,.lt. SAG2, PK-1, BTUB, C22-8, CS3 and Apico). Identification was achieved for nine T. gondii isolates. Seven isolates were classified as type II and two as type III. These results are consistent with previous studies on animal isolates from Serbia as well as with previous reports that type III is more frequently found in samples from Southern Europe than in those from other parts of the continent

Risk factors for toxoplasma infection in pregnant women in FYR of Macedonia

The aim of the study was to identify risk factors for Toxoplasma gondii infection in pregnant women in FYR of Macedonia. Retrospective analysis of serological and epidemiological data in a series of 235 pregnant women from Macedonia, tested for Toxoplasma infection between January 2004 and December 2005, showed on overall prevalence of infection of 20.4 %. Exposure to transmission factors significantly increased the risk of infection (RR = 1.989, 95 % Cl = 1.041-3.800, p = 0.037). The single infection transmission factor that was a predictor of infection in the whole series was exposure to soil (RR = 1.946, 95 % Cl = 1.026-3.692, p = 0.041). Based on prevalence and the established risk factors for Toxoplasma infection in Macedonia, the health education programme as a sustainable measure for the prevention of congenital toxoplasmosis should focus on educating women of generative age to avoid contact with soil (forming, gardening), and/to adhere to strict hygienic practices afterwards

Trichinella spp. In wild mesocarnivores in an endemic setting

Human trichinellosis and Trichinella infection in pigs are both still endemic in the Balkans, including Serbia. Because of the flow between the sylvatic and the domestic cycle of Trichinella spp., monitoring wildlife has been recommended for the risk assessment of Trichinella spp. infection in swine. We have previously shown the presence of Trichinella infection in wild carnivores including the wolf and the golden jackal, and here we report on Trichinella infection in several other mesocarnivore species. From a total of 469 animals collected between 1994 and 2013, Trichinella larvae were detected in 29 (6.2%, 95% CI = 4.0-8.4) animals, including 14 red foxes (4.7%), 7 wild cats (35%), 5 beech martens (4.8%), 2 pine martens (16.7%), and 1 European badger (6.25%). No Trichinella larvae were detected in the examined specimens of European polecats, steppe polecats and European otters. Species identification of the Trichinella larvae performed for 18 positive samples revealed T. spiralis in 77.8% and T. britovi in 22.2% of the isolates. Both species were detected in red foxes and wild cats. The predominance of T. spiralis in wildlife in Serbia indicates the (past or present) spillover of this pathogen from domestic to wild animals

Investigation of Effects of Inhibitor on Corrosion of Carbon Steel in Water with Biocide

U ovom radu istražen je utjecaj komercijalnog inhibitora (Chemtec FI30) na proces korozije ugljičnog čelika P235 u različitim vodenim otopinama; demineraliziranoj i/ili vodovodnoj vodi uz dodatak komercijalnog biocida (Chemtec BI01). Istraživanja su provedena gravimetrijskom metodom i elektrokemijskim metodama, dok je površina ispitivanog materijala analizirana pomoću optičkog mikroskopa. Analize pokazuju da inhibitor smanjuje brzinu korozije ugljičnog čelika u ispitivanim otopinama, ima visoku djelotvornost te da se može svrstati u anodne inhibitore. Također, uočeno je da inhibitor smanjuje opću i jamičastu koroziju ugljičnog čelika u korozivnim vodenim otopinama. Ovo djelo je dano na korištenje pod licencom Creative Commons Imenovanje 4.0 međunarodna.The effect of a commercial inhibitor (Chemtec FI30) on the corrosion of P235 carbon steel in water (demineralised and/or tap water) with the addition of a commercial biocide (Chemtec BI01) was studied in the present work. This study was carried out by weight loss and electrochemical methods, while specimen’s surface was examined using optical microscope. Results obtained from gravimetric measurement revealed that P235 carbon steel corroded in aqueous solution, i.e., in a solution of demineralised and tap water (50 : 50) and a biocide (Fig. 1), and in tap water with a biocide (Fig. 5). By analysing the surface of carbon steel with an optical microscope, general and pitting corrosion was observed, which was more pronounced in tap water with biocide (Figs. 2 and 6). The addition of a commercial inhibitor significantly reduced the occurrence of corrosion damage on the surface of carbon steel (Figs. 3, 4, 7, and 8) and decreased the rate of carbon steel corrosion in all aqueous solutions (Table 1). Electrochemical investigations performed by open circuit potential measurement, linear polarisation and potentiodynamic polarisation measurement showed that the inhibitor Chemtec FI03 shifted the potential to more positive values (Figs. 9 and 10), increased polarisation resistance (Table 3), decreased the rate of carbon steel corrosion, and had high efficiency in all tested solutions (Table 4). The results obtained showed that this commercial inhibitor could be used as an effective inhibitor for the corrosion of carbon steel in aqueous media. This work is licensed under a Creative Commons Attribution 4.0 International License

Comparative evaluation of three commercial Toxoplasma-specific IgG antibody avidity tests and significance in different clinical settings

Determination of the avidity of specific IgG antibodies has become a generally accepted diagnostic aid for dating Toxoplasma infection. In this study, the Labsystems, VIDAS and EUROIMMUN Toxoplasma IgG avidity assays were compared on a series of 133 Toxoplasma IgG- and IgM-positive sera from symptomatic patients (n=28), from pregnant (n=43) and nonpregnant (n=26) women, and on 18 IgG-positive and IgM-negative sera from chronically infected patients. The results showed excellent concordance between the Labsystems and VIDAS tests in both the IgM-positive (r=0.82, kappa=0.771) and IgM-negative (kappa=0.609) sera, whilst the agreement of the EUROIMMUN assay with both the Labsystems and VIDAS tests in the IgM-positive sera was moderate (kappa=0.575 and kappa=0.525, respectively) and in the IgM-negative sera was poor (kappa=0.000). Analysis of the kinetics of the maturation of avidity in 13 patients in whom follow-up sera were available showed that, despite a general trend of maturation, in two patients the avidity did not become high during 6 and 11 months of follow-up. In view of the clinical setting, in the symptomatic patients, despite one case of complete discrepancy and five cases of partial discrepancy, the Labsystems and VIDAS tests were in almost perfect agreement (kappa=0.812), whilst the agreement in pregnant and non-pregnant women was substantial (kappa=0.754 and kappa=0.708, respectively). In conclusion, the Labsystems and VIDAS tests are equally reliable for the measurement of Toxoplasma IgG avidity; the choice of test should depend on the laboratory setup. The EUROIMMUN test may be an acceptable alternative in resource-limited settings, but should be used prudently