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D. Tulumović

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Maida Dugonjić-Taletović, D. Tulumović, M. Aleckovic-Halilovic, Mirha Pjanić, M. Hajder, Alma Halilčević-Terzić, Danijela Lončar, Amila Jašarević

Aim To analyse prevalence of metabolic syndrome (MS) in kidney transplant recipients at the University Clinical Centre Tuzla in Bosnia and Herzegovina (B&H), and determine effects of a modern drug therapy in achieving target metabolic control in kidney transplant patients. Methods A single-centre prospective study that included 142 kidney transplant patients over one year follow-up period was conducted. Patient data were collected during post-transplant periodical controls every 3 months including data from medical records, clinical examinations and laboratory analyses. Results Out of 142 kidney transplant patients, MS was verified in 85 (59.86%); after a pharmacologic treatment MS frequency was decreased to 75 (52.81%). After a one-year period during which patients were receiving therapy for MS, a decrease in the number of patients with hyperlipoproteinemia, decrease in average body mass index (BMI), glycemia and haemoglobin A1C (HbA1C) were observed. Hypertension did not improve during this period, which can be explained by transplant risk factors in the form of immunosuppressive drugs and chronic graft dysfunction. Conclusion A significant reduction in components of the metabolic syndrome after only one year of treatment was recorded, which should be the standard care of kidney transplant patients.

Emir Tulumović, N. Salkić, D. Tulumović

BACKGROUND The incidence and prevalence of inflammatory bowel disease (IBD) vary between regions but have risen globally in recent decades. A lack of data from developing nations limits the understanding of IBD epidemiology. AIM To perform a follow-up review of IBD epidemiology in the Tuzla Canton of Bosnia-Herzegovina during a 10-year period (2009-2019). METHODS We prospectively evaluated the hospital records of both IBD inpatients and outpatients residing in Tuzla Canton for the specified period of time between January 1, 2009 and December 31, 2019. Since all our patients had undergone proximal and distal endoscopic evaluations at the hospital endoscopy unit, we used the hospital’s database as a primary data source, alongside an additional cross-relational search of the database. Both adult and pediatric patients were included in the study. Patients were grouped by IBD type, phenotype, age, and gender. Incidence rates were calculated with age standardization using the European standard population. Trends in incidence and prevalence were evaluated as a 3-year moving average and average annual percentage change rates. RESULTS During the 10-year follow-up period, 651 patients diagnosed with IBD were monitored (of whom 334, or 51.3%, were males, and 317, or 48.7%, were females). Of all the patients, 346 (53.1%) had been diagnosed with ulcerative colitis (UC), 292 (44.9%) with Crohn’s disease (CD), and 13 (2%) with indeterminate colitis (IC). We observed 440 newly diagnosed patients with IBD: 240 (54.5%) with UC, 190 (43.2%) with CD, and 10 (2.3%) with IC. The mean annual crude incidence rates were found to be 9.01/100000 population for IBD [95% confidence interval (CI): 8.17-9.85], with 4.91/100000 (95%CI: 4.29-5.54) for UC and 3.89/100000 (95%CI: 3.34-4.44) for CD. Calculated IBD prevalence in 2019 was 146.64/100000 (95%CI: 128.09-165.19), with 77.94/100000 (95%CI: 68.08-87.70) for UC and 65.77/100000 (95%CI: 54.45-74.1) for CD. The average annual IBD percentage change was 0.79% (95%CI: 0.60-0.88), with -2.82% (95%CI: -2.67 to -2.97) for UC and 6.92% (95%CI: 6.64-7.20) for CD. During the study period, 24,509 distal endoscopic procedures were performed. The incidence of IBD was 3.16/100 examinations (95%CI: 2.86-3.45) or 1.72/100 examinations (95%CI: 1.5-1.94) for UC and 1.36/100 examinations (95%CI: 1.17-1.56) for CD. CONCLUSION Trends in the incidence and prevalence of IBD in Tuzla Canton are similar to Eastern European averages, although there are significant epidemiological differences within geographically close and demographically similar areas.

E. Mesic, M. Aleckovic-Halilovic, D. Tulumović, S. Trnačević

ABSTRACT It has now been more than two decades since the end of the 1992–95 war in Bosnia and Herzegovina. This may well be the proper time to provide the nephrology community with an appraisal of the care of patients with chronic kidney disease in the pre-war, war and post-war periods in the European transitional country. This report on nephrology in Bosnia and Herzegovina draws attention to the hurdles faced for three turbulent years on that burdensome path of providing quality care, and the chance it offered in developing a successful transplant programme while facing the dreadful chaos of war and a migrant crisis. The perception of war and natural disasters is quite different, from the victim’s point of view, from the standardized and well-arranged healthcare systems in the developed world. The guidelines, written in peace, are extremely useful, but are often hard to follow during natural disasters or barbarous wars. Each of the periods described had its specificities as well as its good and bad sides. Despite the unquestionable destructive nature of the war, it was a catalyst for nephrology in Bosnia and Herzegovina to move forward.

Tularemia is a vector-borne zoonosis with a complex epidemiology caused by Francisella tularensis. F. tularensis is a non-motile, obligatory aerobic, facultative intracellular Gram-negative coccobacillus. The bacterium has a broad host range, i.e. mammals, birds and invertebrates. Two types (A, B) and four subspecies (F. tularensis subsp. tularensis (type A), F. tularensis subsp. holarctica (type B), F. tularensis subsp. mediasiatica and F. tularensis subsp. novicida.) are known today. Types A and B are of importance as they cause disease in humans and animals. Type A is present almost exclusively in North America and type B is found all over the Northern hemisphere. F. tularensis is considered to be a class A biological warfare agent, it is notoriously difficult to recognize infections in non-endemic regions and was produced as a weaponized agent by several countries in the 1960ties and 70ties. Humans can acquire tularemia by inhaling dust or aerosols contaminated with F. tularensis bacteria, this type of exposure can result in pneumonic tularemia, one of the most severe forms of the disease. especially farming involving machines that disperse remains of infected animals or carcasses. Rarely, water can become tularemia contaminated through contact with infected animals. Humans who drink contaminated and untreated water may contract oropharyngeal tularemia. The tularemia outbreak in B&H in 1995 showed an unusual number of oropharyngeal cases. As all aspects of this particular tularemia epidemic were not thoroughly investigated and the possible intentional use of agents of biological warfare remained a possibility, we reviewed all available data in order to assess whether the outbreak was natural. Correspondence to: Mirsada Hukić, Institute for Biomedical Diagnostic and Research Nalaz, Sarajevo Bosnia and Herzegovina, Tel: +387-33-651 371; E-mail: mirsadahukic@yahoo.com Received: May 23, 2017; Accepted: June 20, 2017; Published: June 22, 2017 Introduction Tularemia is a vector-borne zoonosis with a complex epidemiology caused by Francisella tularensis. F. tularensis is a non-motile, obligatory aerobic, facultative intracellular Gram-negative coccobacillus. The bacterium has a broad host range, i.e. mammals, birds and invertebrates. Four subspecies are known today; F. tularensis subsp. tularensis (type A), F. tularensis subsp. holarctica (type B), F. tularensis subsp. mediasiatica and F. tularensis subsp. novicida. Types A and B are of importance as they cause disease in humans and animals. Type A is present almost exclusively in North America and type B is found all over the Northern hemisphere [1]. Infections due to tick and deer fly bites usually take the form of ulceroglandular or glandular tularemia. F. tularensis bacteria can also be transmitted to humans via the skin when handling infected animal tissue. This can occur when hunting or skinning infected rodents like rabbits, muskrats and other rodents. Many animals have also been known to become infected and clinically ill from tularemia. Domestic cats are very susceptible and can transmit the bacteria to their owners. Therefore, care should always be taken when handling sick or dead animals. Infection due to handling animals can result in glandular, ulceroglandular and oculoglandular tularemia. Eating of under-cooked meat of infected animal’s tularemia can also result in oropharyngeal tularemia [2]. Humans can acquire tularemia by inhaling dust or aerosols contaminated with F. tularensis bacteria, this type of exposure can result in pneumonic tularemia, one of the most severe forms of the disease. especially farming involving machines that disperse remains of infected animals or carcasses. Rarely, water can become tularemia contaminated through contact with infected animals. Humans who drink contaminated and untreated water may contract oropharyngeal tularemia [3]. Transmission from person to person has so far not been reported. Inhalational tularemia following intentional release of a virulent strain of F. tularensis would have the greatest adverse human Hukić M (2017) Recognizing the possibility of bioterrorism in the face of emerging and reemerging zoonotic pathogens in Bosnia and Herzegovina during the war (1992-1995) Volume 1(3): 2-7 Virol Res Rev, 2017 doi: 10.15761/VRR.1000113 consequence because of its very high infectivity if delivered as an aerosol. It has been estimated that an aerosol dispersal of 50 kg of virulent F. tularensis over a metropolitan area with 5 million inhabitants would result in 250 000 incapacitating casualties, including 19,000 deaths. Outbreaks of pneumonic tularemia, particularly in low incidence areas, should prompt consideration of bioterrorism. F. tularensis has long been considered a potential biological weapon. It was one of the agents studied the Japanese germ warfare research units in Manchuria, China between 1932 and 1945; it was also considered for military purposes in the West [4]. An outbreak of tularemia reported in Soviet and German soldiers during the second world war may have been the result of intentional release [5]. F. tularensis has been studied, weaponized and stockpiled by several countries, including Japan, the USSR and the US [4]. Pathogenesis Francisella tularensis can infect humans through the skin, mucous membranes, gastrointestinal tract, and lungs. The major target organs are the lymph nodes, lungs and pleura, spleen, liver, and kidney. Bacteremia is common in the early phase of infection. The initial tissue reaction to infection is a focal, suppurative necrosis. Suppurative lesions become granulomatous, typical of other granulomatous conditions, i.e. tuberculosis or sarcoidosis. Humans with inhalational exposure also develop early in the course of illness hemorrhagic signs and inflammation of the airways which usually evolves to bronchopneumonia. Clinical manifestations The primary clinical forms of tularemia vary in severity and presentation according to virulence of the infecting organism, the dose, and way of administration. Primary disease presentations can be glandular, ulceroglandular, oculoglandular, oropharyngeal, pneumonic, typhoidal, and septic forms. The onset of tularemia is usually abrupt, with fever (38°C-40°C), headache, chills and rigors, generalized body aches (lower back pain) and sore throat. A dry or slightly productive cough frequently occurs with or without signs of pneumonia. Nausea, vomiting, and diarrhea sometimes occur. Sweats, fever and chills, malaise, progressive weakness and weight loss characterize the continuing illness. In untreated tularemia, symptoms often persist for several weeks or months. Any form of tularemia may be complicated by hematogenous spread, resulting in secondary pleura-pneumonia, sepsis, and meningitis. Prior to the administration of antibiotics, the overall mortality with the more severe type A strains is of 5% to 15%, and in the case of untreated pneumonic and severe systemic forms fatality rates as high as 30% to 60% were reported. Type B infections are in contrast rarely fatal. Ulceroglandular tularemia, after handling a contaminated carcass or due to an infective arthropod bite, a local cutaneous papule appears at the inoculation site together with the onset of generalized symptoms, becomes pustular, and ulcerates within a few days. The ulcer is tender may show an eschar. Antibiotic treatment does not prevent the affected nodes from becoming fluctuant and rupture. Oculoglandular tularemia, which follows direct contamination of the eye, ulceration occurs on the conjunctiva, accompanied by pronounced chemosis, vasculitis, and regional lymphadenitis. Glandular tularemia is characterized by lymphadenopathy without an ulcer. Oropharyngeal tularemia is acquired by drinking contaminated water, ingesting contaminated food, or by inhaling contaminated droplets or aerosols. Affected persons may develop stomatitis but more commonly develop exudative pharyngitis or tonsillitis, sometimes with ulceration. Tularemia pneumonia is the direct result of inhaling contaminated aerosols. Inhalational exposures commonly result in an initial clinical picture of systemic illness without prominent signs of respiratory disease. The earliest pulmonary radiographic findings of inhalational tularemia may be peribronchial infiltrates, typically advancing to bronchopneumonia in one or more lobes. Pulmonary infection can sometimes rapidly progress to severe pneumonia, respiratory failure, and death. Lung abscesses occur infrequently. Typhoidal tularemia is used to describe systemic illness when the site of inoculation or the localization of infection is unclear. Tularemia sepsis is severe and potentially fatal. As in the case of typhoidal tularemia, fever, abdominal pain, diarrhea, and vomiting may be prominent early in the course of illness. The patient typically appears toxic and may develop confusion and coma. Unless treated promptly, septic shock and other complications of systemic inflammatory response syndrome may develop with hemorrhagic signs, acute respiratory distress syndrome and organ failure [4]. The war in Bosnia and Herzegovina (B&H) (1992-1995) As in all conflicts, the inhabitants of Bosnia and Herzegovina were under extreme pressure during the war that took place 1992-1995. Due to the nature of the conflict that sometimes involved hostilities amongst neighbors, there was minimal respect for human rights and civilians, children and old people as well as soldiers suffered the consequences. In particular the weakest individuals, namely women and children suffered the most. Horrific ethnic cleansing campaigns between 1992 and the end of 1995 killed thousands and violently displaced more than two million people in much of B&H. International intervention into the Bosnian conflict led finally to a peace agreement in late 1995 (the Dayton Accords). The Dayton agreement finally ended the war in B&H. In 1995, the conflict between multiple factions was ag

Mersiha Cerkezovic, D. Tulumović, M. M. Umihanic

Introduction: Belching is often reported symptom. It is rarely an isolated disorder and mainly occurs within various gastroduodenal diseases. Aim: The aim is to show the great breadth of clinical symptoms of postcholecystectomy syndrome which should have a multidisciplinary therapeutic approach taking into account all aspects of patient’s life. Case report: We report a case of excessive belching within postcholecystectomy syndrome which disturbs the general psycho-physical condition of the patient, with symptoms of depression and anxiety, and social isolation, which significantly reduces the quality of his life.

Introduction: Starting from the point that the chronic kidney disease (CKD) is chronic, inflammatory and hypercoagulable state characterized by an increase in procoagulant and inflammatory markers high cardiovascular morbidity and mortality in these patients could be explained. Aim: The aim of the research was to monitor inflammatory markers and procoagulants in various stages of kidney disease (stage 1-4). Materials and Methods: The research included 120 subjects older than 18 years with CKD stages 1-4 examined and monitored in Clinic of Nephrology, University Clinical Centre Sarajevo over a period of 24 months. The research included determining the following laboratory parameters: serum creatinine, serum albumin, C-reactive protein, leukocytes in the blood, plasma fibrinogen, D-dimer, antithrombin III, coagulation factors VII (FC VII) and coagulation factor VIII (FC VIII). Results: With the progression of kidney disease (CKD stages 1-4), there was a significant increase of inflammatory and procoagulant markers: CRP, fibrinogen and coagulation factor VIII, and an increase in the average values of leukocytes and a reduction in the value of antithrombin III, but without statistical significance. Also, there were no significant differences in the values of D-dimer and coagulation factor VII. Conclusion: The progression of kidney disease is significantly associated with inflammation, which could in the future be useful in prognostic and therapeutic purposes. Connection of CKD with inflammation and proven connection of inflammation with cardiovascular risk indicates the potential value of some biomarkers, which could in the future identify as predictors of outcome and could have the benefit in the early diagnosis and treatment of cardiovascular disease in CKD.

Aim: The aim of the research was to compare the relationship between inflammatory biomarkers and procoagulants with kidney function assessed by using cystatin C, serum creatinine, and eGFR and determine the sensitivity of cystatin C, serum creatinine and eGFR to total cardiovascular morbidity in patients with CKD stages 1-4. Methods: The research included 120 patients older than 18 years with CKD stages 1-4 monitored over a period of 24 months. Results: Serum cystatin C correlates with fibrinogen (p<0.01), serum albumin (p<0.01), D-dimer (p<0.05), antithrombin III (p<0.01) strongly in relation to the evaluation of kidney function based on serum creatinine and eGFR. By following cystatin C, creatinine and eGFR with comparison of ROC to total cardiovascular morbidity, the highest sensitivity in relation to the presence of cardiovascular morbidity shows cystatin C, then eGFR and the lowest, creatinine, with a significant difference between cystatin C and serum creatinine (p<0.05). Conclusion: Serum cystatin C is more strongly correlated with some biomarkers (fibrinogen, serum albumin, D-dimer, antithrombin III), while simultaneously showing a stronger sensitivity in relation to total cardiovascular morbidity compared with the assessment of kidney function based on serum creatinine and eGFR.

Fahir Baraković, Midhat Tabaković, D. Tulumović, Z. Kusljugic, Elnur Smajić, E. Jasarević, Majda Isabegovic, Larisa Dizdarević Hudić, Ivana Iveljić et al.

The aim of this study was to determine a frequency and a type of early and late surgical complications in kidney transplantation, their impact on renal graft survival among 80 patients, 54 (67.5%) males and 26 (32.5%) females who had undergone a living and cadaveric kidney transplant at the Surgery Center in Tuzla in the period from 15.09.1999 until 31.12.2008. The subjects were divided into two groups according to donor age, younger and older than 55. A significantly higher incidence of early rather than late surgical complications was observed in an experimental group (p=0.001, and p=0.77, respectively). There was a statistically significant difference in the length of graft survival (p=0.004) and the number of deaths (p=0.038). Older age of kidney graft donor had an impact on the occurrence of early surgical complications and no influence on the occurrence of late surgical complications. Fatal outcome after kidney transplantation was significantly higher in patients who received grafts of elderly people.

E. Hodzic, M. Tabaković, E. Mesic, Majda Brcic, Senaid Trnavcević, M. Atić, D. Tulumović, Davor Trojak, Maida Taletovic-Dugonjic et al.

INTRODUCTION Kidney transplantation assures considerably better quality of life than the treatment of end-stage renal disease patients with dialysis. GOAL Authors intended to present results of kidney transplantations that were performed for over 13 years in UCC Tuzla. EXAMINEES AND METHODS Total of 100 transplantations have been done over 13 years. The gender and age structure have been presented, as well as number of transplantations per year, type of transplantation (living related donor, living unrelated donor, deceased donor), number and percentage of donors and results of transplantations expressed as survival of both the patient and transplanted kidney/ renal graft. We also wanted to presented other important events such as dates of introduction of certain drugs, dates of first cadaver transplantation, transplantation with desensitization protocols and dates of first living unrelated (spousal/emotional) transplantation. RESULTS The survival of patients and renal grafts were demonstrated by Kaplan-Meier curve, and obtained results were fully in range of results recommended in other literature and by other authors. One-year survival of graft is 94%, with five-year survival being 75%. One-year survival of patients is 95%, and five-year survival of patients was 84%. DISCUSSION Our results have been compared to those from other studies, gaining suggestions for transplantation improvement. CONCLUSION Among all modifications of renal replacement therapy transplantation is by far the method of choice because, its well known advantages aside, it also has an economical advantage over chronic treatment with dialysis and it should therefore become interesting to healthcare systems.

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