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Objectives: To assess the prognostic value of pentraxin 3 (PTX3) in patients with ST-elevation myocardial infarction (STEMI) after bare-metal stent (BMS) implantation. Methods: In this prospective study, PTX3, interleukin (IL-6), IL-10, high-sensitivity c-reactive protein (hsCRP), and cardiac troponin I (cTnI) plasma values were determined before and 24 hours after BMS implantation in 97 consecutively enrolled patients with STEMI who were admitted to University Clinical Center Tuzla, Tuzla, Bosnia and Herzegovina between February 2016 and February 2017. Patients were followed for 24 months to assess major adverse cardiovascular events (MACEs). Results: At 24 hours after percutaneous coronary intervention (PCI), plasma values of PTX3, IL-6, hsCRP, and cTnI were significantly increased; and IL-10 levels were significantly decreased compared with the values determined before PCI. Patients with MACEs had significantly higher plasma PTX3 levels at 24 hours after BMS-PCI than in patients without MACEs. Patients with PTX3 plasma values ≥5042 ng/ml had a significantly higher risk of MACEs than patients with PTX3 levels

This is the first report of molecular and epidemiology findings from Bosnia and Herzegovina related to ongoing severe acute respiratory syndrome coronavirus 2 epidemic. Whole genome sequence of four samples from coronavirus disease 2019 (COVID-19) outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, and England). The constructed phylogenetic tree indicates possible multiple independent introduction events. The data presented contribute to a better understanding of COVID-19 in the current reemergence of the disease.

INTRODUCTION: European guidelines recommend treatment of chronic Hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe.METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum HBV-DNA in European tertiary referral centres.RESULTS: Data of 1568 patients was included. The majority (73.8%) was exposed to lamivudine monotherapy. Drug resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n=102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load and lamivudine exposure (pCONCLUSION: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.

Background HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32–3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P

Introduction: Intensive care units (ICUs) are associated with a greater risk of developing nosocomial infections (NIs) than other departments. Aim: The aim of this study was to determine the rate, the site and causative organisms of NIs in the surgical ICU at University Clinical Center Tuzla. Methods: All patients admitted to the surgical ICU were followed prospectively, for the development of NIs (January-December 2010). Determination of NIs was performed using standardized the Centers for Disease Control and Prevention (CDC) criteria. Results: 94 out of 834 patients (11.27%) developed NIs. Respiratory tract infections were seen in 56 (60%), urinary tract infections in 15 (16%) and gastrointestinal tract infections in 8 (9%) patients. Other infections identified were surgical site, bloodstream and skin infections. Gram-negative organisms were reported in approximately 75% of cases (78.7% extended-spectrum beta-lactamase (ESBL)-producers). Klebsiella pneumoniae was the commonest (51.0%), followed by Proteus mirabilis (21.3%) and Pseudomonas aeruginosa (10.6%). Methicillin-resistant Staphylococcus aureus (MRSA) (16%), and Clostridium difficile (9.6%) were the commonest among gram-positive bacteria. Conclusion: Respiratory and urinary tract infections made up the great majority of NIs. ICU patients are more susceptible to NIs, emphasizing the importance of continuous surveillance and enforcement of specific infection control measures.

Objective – Outbreaks of sepsis caused by multidrug-resistant Acinetobacter baumannii in neonatal intensive care units have been reported, but rarely from our country. We describe such an outbreak in the Department of Paediatrics of the University Clinical Centre Tuzla in 2012 to investigate risk factors, the mode of transmission and to assess control measures. Setting – An 18 bed, level 3 neonatal intensive care unit in a university affiliated teaching hospital. Patients and methods – Seventeen neonates who developed multidrug-resistant Acinetobacter baumannii nosocomial infection were matched to 17 neonates who were admitted to the same unit without infections, during the outbreak period. Cases and controls were compared for possible risk factors (birth weight, gender, intubation, antibiotic use, etc.). Surveillance cultures were collected from health care personnel and the environment. Results – Six out of the 17 neonates (35.3%) died. Surveillance cultures were negative. Seventeen isolates from newborns had the same patterns of resistance. Multidrug-resistant Acinetobacter baumannii was brought into the unit by an infected infant who was transferred from the neurosurgery hospital. Risk factors significantly associated with the infection were: incubator care (OR 6.66; p =0.034), exposure to a central venous catheter (OR 13.75; p=0.004), mechanical ventilation (OR 5.25;p =0.031) and exposure to a patient with Acinetobacter baumannii infection (OR 38.40; p =0.02). Conclusion – Surveillance cultures for all newborns transferred from other hospitals and isolation measures are important to prevent nosocomial infections and outbreak. Negative environmental and health care worker cultures have to be meticulously analyzed. Cohorting of affected newborns and nursing staff, contact isolation, and environmental cleaning are crucial to control the outbreak.

Introduction: Acinetobacter baumannii is a frequent cause of infections in hospitals around the world, which is very difficult to control and treat. It is particularly prevalent in intensive care wards. Aim: The main objective of the research was to establish the application of epidemiological monitoring of nosocomial infections (NIs) caused by A. baumannii in order to determine: the type and distribution of NIs, and to investigate antimicrobial drug resistance of A. baumannii. Material and Methods: 855 patients treated at the Clinic of Anesthesiology and Reanimation, University Clinical Center Tuzla during 2013 were followed prospectively for the development of NIs. Infections caused by A. baumannii were characterized by the anatomical site and antibiotics resistance profile. Results: NIs were registered in 105 patients (12.3%; 855/105). The predominant cause of infection was A. baumannii with an incidence of 51.4% (54/105), followed by ESBL-producing Klebsiella pneumoniae with 15.2% (16/105) of cases, methicillin-resistant Staphylococcus aureus with 8.6% (9/105), and ESBL-producing Proteus mirabilis with 7.6% (8/105). According to the anatomical site, and type of NIs caused by A. baumannii, the most frequent were respiratory infections (74.1%; 40/54). Infections of surgical sites were registered in 11.1% (6/54) of cases, while bloodstream infections in 9.2% (5/54). A. baumannii isolates tested resistant against most antibiotics examined, but showed a high degree of susceptibility to tobramycin (87%; 47/54) and colistin (100%; 54/54). Conclusion: The increasing incidence of multi- and extensively drug-resistant Acinetobacter spp. emphasizes the importance of administration of an adequate antibiotic strategy and the implementation of strict monitoring of the measures for controlling nosocomial infections.

Duality between N=1 supersymmetric gauge theories(Seiberg's duality) isgeometrized, in the framework of AdS/CFT correspodences. It is shown thatSeiberg's duality corresponds to monodromy of wrapped D5 branes on the homologycycles of a generalized conifold where D3 branes are located. The celebrated\tilde{N}_c=N_f-N_c, \tilde{N}_f=N_f rule is reproduced and a braid groupstructure in a sequence of dualities, is found.

Introduction: The prevalence of human brucellosis in Bosnia and Herzegovina and the Tuzla Canton reached its peak in 2008, with a reported total of 994 cases within country, and with 104 cases within the Tuzla Canton. Aim: to analyze the clinical and epidemiological features of human brucellosis in patients hospitalized at the University Clinical Center Tuzla during the period from 01/01/2000 till the 31/12/2010. Methods: We retrospectively analyzed the clinical symptoms, the laboratory and X-ray findings, the treatments, and the course and outcome of the disease. The diagnosis of brucellosis was based on anamnesis, clinical presentation, in correlation with a positive blood-culture, and/or serological tests. Results: The majority of patients (93.18%) were from rural regions. There were more males (79.54%) than females. Most of the patients were aged between 30 to 39 years (21% cases). Contact with infected animals was registered for 83.40% of the patients. The main symptoms and signs were fever, joint-pains, night sweating, anorexia, headaches, and hepatosplenomegaly. The important laboratory findings were increased erythrocyte sedimentation rates, increased values of C-reactive protein, and anemia. Adult patients were treated with a combination of gentamicin or streptomycin with doxycycline, and the children with a combination of gentamicin, and trimethoprim-sulfametaxasol, over at least 6 weeks. Complications were documented in 20.45% of the patients. Relapses were observed in 14.20%, and a chronic form of brucellosis in 5.11% of patients. There were no cases with lethal outcomes. Conclusion: Brucellosis is a growing public health problem, not only within the Tuzla Canton, but throughout Bosnia and Herzegovina.

A measles outbreak with two epidemic waves involving 4649 probable and laboratory-confirmed cases was recorded in six out of ten cantons of the Federation of Bosnia and Herzegovina between February 2014 and April 2015. The majority of the patients had never received measles vaccination (3115/4649, 67.00%), and the vaccination status of another 23% was unknown (1066/4649). A total of 281 blood samples were tested serologically. Virus detection was performed using 44 nasopharyngeal swabs. About 57% (161/281) of the laboratory-investigated sera were immunoglobulin M positive, and 95% (42/44) of the swabs were reverse transcriptase-PCR positive. Phylogenetic analysis of sequences obtained from 30 swab samples showed circulation of two variants of genotype D8, but no genotype D4 strains as detected in 2007. Similar involvement of all age groups indicates a problem with vaccine refusal resulting from antivaccination activities in addition to gaps in immunization coverage during the war and postwar period (1992-1998). Differences in ethnicity, vaccine coverage, compliance with review policies of vaccination records and potentially also travel habits may partially explain why only six of ten cantons were affected by the outbreak. The second epidemic wave may in part be due to large-scale migrations due to catastrophic floods in 2014. As a result of the epidemic, 6- to 12-month-old children may now be vaccinated against measles during outbreaks, and public health recommendations for interventions have been strengthened. Additional efforts are required to implement the measures throughout the cantons.

The use of central venous catheters (CVC) carries a risk from local and systemic infectious complications, with prevalence of 6% in patients in Intensive care unit. Microorganisms colonizing the CVC usually originate from patient's or staff member's skin, but the source can also be a contaminated infusion solution or hematogenous dissemination from a distant focus. The infective agents often show increased resistance to antibiotics, which is an additional therapeutic problem. There is no knowledge of the frequency of the colonization of CVC by microorganisms in hospitals in Bosnia and Herzegovina, neither of the types of microorganisms which usually colonize CVC, nor their sensitivity to antimicrobial agents.During the period 2004-2008, the analysis of 188 CVC samples was performed in patients in ICU at which the doubt for CVC connected infection was present. The microorganism identification was performed by standard microbiological antibiotics sensitivity methods.Out of 188 checked samples, 101 (54%) had positive cultures and 87 (46%) were sterile. Out of 101 positive microbiological cultures, in 33 (32.67%) the gram-positive bacteria had been found, gram-negative in 62 (61.37%) and Candida albicans in 6 (5.94%) cultures. Gram-ne-gative bacteria were 93.55% sensitive to imipenem, and Gram-positive bacteria were sensitive to vancomycin.Gram-negative bacilli and Coagulase-negative staphylococci are the most frequent micro-organisms which colonize the CVC. The increase of bacteria antibiotics resistance represents a big problem. All those facts leads to the need for bigger control and supervision over the CVC implantation, its proper maintenance and rational use.

Prevalence of hepatitis C virus (HCV) genotypes in Bosnia and Herzegovina (B&H) is an issue that is not sufficiently researched and there is a need for studies that would explore this in detail.The aim of this study was to determine the distribution of HCV genotypes in the group of patients with chronic hepatitis C and also in the group of first time blood donors that tested positive for anti HCV antibodies during the blood screening process. Our secondary goal was to compare the proportions of HCV genotypes between these two groups.We analyzed 75 blood samples of patients with confirmed chronic hepatitis C. We also analyzed 13/16082 blood samples of first time blood donors found to be HCV positive during the blood screening process. We also determined HCV genotype in HCV RNA positive samples.We have found that genotype 1b was more prevalent in chronic hepatitis C patients (52/75; 69,3%) than in first time blood donors (6/13; 46,1%), however this difference was not statistically significant (c2=1,721; df=1; p=0,19). Genotype 1a was more prevalent in the group of first time blood donors (3/13; 23,1%) than in the group of chronic hepatitis C patients (3/75; 4%), but this was also with limited statistical significance (c2=3,71; df=1; p=0,054). We have not found any significant difference in prevalence of genotypes 1a (p=0,2) and genotypes 3 (p=0,70) when compared between chronic patients (3/75 and 16/75; respectively) and first time blood donors (3/13 and 4/13; respectively). Our study confirmed domination of genotype 1b in the region of northeastern B&H which is in accordance with HCV genotype prevalence in other countries in our part of Europe.

Since its foundation in 1992, the Croatian Medical Journal (CMJ) has followed the strict standards of quality in the scientific publishing. However, the Journal has been aware that its specific position demands more than just following the already established rules. From the very beginning, the Journal declared an “author-helpful policy,” stating that “journal editors should have a major role in training authors in science communication, especially in smaller and developing scientific communities. Journal authors usually send scientifically acceptable but poorly prepared articles and it is a pity to lose valid data because of their poor presentation.” (1,2). In brief, the editors and editorial staff of the CMJ have been well aware that the skills of scientific reporting and publishing in our academic community are not developed and that valuable research results and valid data are being lost because of poor presentation. To be perfectly honest, ten years ago this statement looked like a nice promise, one of the many we in academic medicine learnt not to take too seriously.

Introduction: The finding of reduced value of immunoglobulin A (IgA) in children is frequent in daily medical practice. It is important to correctly interpret the findings as adequate further diagnostic evaluation of the patient in order to make the determination on the significance of such findings. In children younger than 4 years always consider the transient impairment of immunoglobulins, maturation of child and his immune system can lead to an improvement in the clinical picture. In older children decreased IgA may lead to serious illnesses that need to be recognize and acknowledge through the appropriate diagnostic methods. Material and methods: Research was realized at the University Clinical Center Tuzla. Children with suspected deficient immune response due to reduced values of IgA observed and , goes through further diagnostic evaluation at the Polyclinic for Laboratory Medicine, Department of Immunology and Department of Microbiology, as well as the Clinic of Radiology. In the period of year 2013, there were a total of 91 patients with reduced values of IgA, age up to 13 years, of which 55 boys and 36 girls. Results: Our study followed 91 patients, for the year 2013, through their medical charts and made evaluation of diagnostic and screening tests. The significance of this paper is to draw attention to the importance of diagnostic approach to IgA deficient pediatric patient and relevance of knowledge of individual diagnostic methods as well as to the proper interpretation of the results thereof.

Hepatitis C infection is important global health problem with wide spectrum of health, social and economic consequences. The goal of this research was to estimate prevalence of hepatitis C virus infection in risk groups, and to determine association hepatitis C virus (HCV) infection and risk factors. Research included 4627 subjects divided in two groups. Test group included 2627 subjects divided in 4 subgroups with risk for HCV infection: those who received blood transfusion without screening on HCV (it was introduced in 1995) (700); intravenous drug users (60); patients on hemodialysis (168) and health care workers (1699). Control group included 2000 healthy volunteer blood donors. In all subjects anti-HCV antibodies were tested with third generation ELISA test. Positive serum samples were tested for presence of HCVRNA, using reaction of reverse transcription and polymerase chain reaction. In all anti-HCV positive subjects further epidemiological and clinical workup was performed. Prevalence of HCV infection in risk groups was: 4.6% in subjects who have received blood transfusions without HCV blood screening, 35% in intravenous drug users, 58.9% in patients on chronic dialysis, and 0.4% in health care workers. In control group prevalence was low (0.2%). In the group of 158 anti-HCV positive subjects, 73.4% had HCVRNA. The largest number of subjects with HCV infection was in the age group of 30-49 years (45.8%). This study showed that multiple blood transfusions before introducing the blood screening for HCV, longer duration of intravenous drug abuse, longer duration of hemodialysis treatment, larger number of accidental injuries in health care workers are independent and statistically significant risk factors for those groups examined. Results of this study confirm that general screening for HCV infection is recommended in risk groups for HCV infection in order to identify to prevent and to treat it.

Objectives Hepatitis C virus (HCV) infection is spread worldwide with significant geographical differences in the prevalence and genotypes. The aim of this study was to analyse HCV infection in hemodialysis (HD) units in Bosnia and Herzegovina (BH), through genotypes and routes of transmission. Design and Methods We analysed data from Renal Registry of BH for the years 2002 and 2003 in order to estimate prevalence and incidence of anti-HCV positive patients in 23 HD units in BH (ELISA III). Then we tested 88 anti-HCV positive patients from Tuzla for HCV RNA using reverse transcription polymerase chain reaction (Amplicor Roche diagnostic commercial test) and genotype with method of reverse hibridization of amplified sample material (Innolipa HCV II commercial test). Results In 2002 we registered a prevalence of 39.1 and an incidence of 3.1% of anti-HCV positive HD patients in 23 HD units, and in 2003 a prevalence of 29.3 and an incidence of 2.04% in 24 HD units. Prevalence of anti-HCV positive patients was significantly different in HD units, from 14.3 to 69.1%. From 88 tested anti-HCV positive HD patients in Tuzla HD unit, we found 76 HCV RNA positive patients (87.36%). The genotype of HCV was analysed in 59 of these patients and we found, unusual for Europe, genotype 4 in 37 (62.7%), genotype 1b in 17 (28.8%) and 1a in five patients (8.5%). A total of 61% of seroconversions happened in 1999, 2000 and 2001. In 2001, we separated dialysis machines for anti-HCV positive and anti-HCV negative patients, and in 2003 we had nine seroconversions (genotype 4 in five patients). These patients had no blood transfusions. Conclusions Prevalence and incidence of anti-HCV positive hemodialysis patients is still high in BH and origin of genotype 4 HCV is not clear. Nosocomial spreading of HCV plays a significant and probably the most important role in transmission of HCV in HD units.

Introduction: Clostridium difficile (C. difficile) is currently the leading cause of healthcare-associated diarrhea, but almost nothing is known about the extent of C. difficile infection (CDI) in Bosnia and Herzegovina. Goal: We aimed to retrospectively analyze CDI in hospitalized patients at University Clinical Center (UCC) Tuzla, Bosnia and Herzegovina from January 2009 through June 2012. Methods: We analyzed all patients (except children ages 0-2), diagnosed with CDI based on anamnestic and epidemiological, clinical picture and microbiological tests (proof of toxins in the stool by enzyme-linked immunosorbent assay). Results: From a total of 989 patients tested for C. difficile toxin (60.2 per 10,000 inpatient days) 347 (35.08%) were positives. The mean incidence rate of CDI was 2.23 per 10,000 inpatient days (range 1.32-2.87). Annual rates of hospitalization were 15.68 per 10,000 admissions (range 8.99-20.35). Most patients had a previously identified risk profile of old age, comorbidity and recent use of antibiotics. 41/276 (14.86%) patients had died, and 11/41 (26.82%) were CDI-associated deaths. Complicated CDI were registered in 53/276 (19.21%) patients, and recurrent infections in 65/276 (23.55%). Conclusion: Our data suggest that CDI is largely present in our setting which represents a serious problem and points to the importance of international surveillance, detection and control of CDI.