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Z. Vukobrat-Bijedic, A. Husic-Selimovic, Lejla Mehinovic, D. Junuzović, N. Bijedić, A. Sofić, Ivana Bjelogrlic, A. Mehmedović

Background: Various complications occur in patients with advanced stages of liver diseases. Renal dysfunction, a parameter included in the MELD score, is the most important prognostic factor. There is a strong need in clinical practice to estimate the GFR in this patients. Objectives: The aim of our study was to detect differences in renal function among patients with different stages of chronic liver diseases caused by HBV and HCV, also to determine the impact of viral etiology and gender on the values of eGFR and renal function. Patients and Methods: This was an observational cross-sectional study performed on patients with HBV and HCV chronic hepatitis, cirrhosis and HCC caused by these viruses hospitalized during period 2009–2014 in the Clinic of Gastroenterohepatology, Clinical Center University of Sarajevo. The estimated GFR (eGFR) was evaluated by the MDRD4 method. For the processing of data SPSS 21.0 statistical software was used. Statistical methods used in this study where: analysis of variance test (ANOVA test), Student’s t-test for independent samples and Pearson coefficient of correlation. The level of significance was p <0.05. Results: Among this three groups of patients there was a statistically significant difference in eGFR (F= 18.79, p<0.05), i.e. increase of degree of liver damage was related with increase of renal impairment, as reflected by a significant reduction in estimated glomerular filtration rate. Gender had no significant effect on eGFR and renal function (p>0.05), except in group of patients with HCC (p<0.05). Etiology had no significant effect on eGFR and renal (p>0.05). There was statistically significant inverse correlation between glomerular filtration rate and liver enzymes AST (-.184) and GGT (-.181). Conclusions: By calculation of GFR, we determined the existence of a significant reduction of kidney function through progression of liver damage from HBV and HCV chronic hepatitis, liver cirrhosis to HCC caused by these viruses, which drawing attention to the importance of the assessment of renal function in patients with this liver pathologies. Gender and etiology had no significant effect on eGFR and impairment of renal function. Given the statistically significant inverse correlation between eGFR and AST and GGT this liver enzymes may have important role as marker for both renal and hepatic injury.

Ivan Boban, Admir Mujkic, I. Dugandžić, N. Bijedić, Indira Hamulic

Paper presents an analysis of a social network using a graph, and also taking into account the 802 post that are created by 114 users representing a social network interaction among the users. Input parameters are represented by the adjacency matrix, which is a kind of relationship between users who are nodes of social networks. Data analysis used the software UCINET 6, which is the adjacency matrix input parameter. Obtained results, as well as their interpretation, are related to the following measures: centrality (degree, betweeness, closeness) clustering coefficient, density, reach, geodesic distance, eigenvector.

Admir Mujkic, Ivan Boban, I. Dugandžić, N. Bijedić

A decision tree is a technique of modeling algorithm for solving classification and prediction problems. The data collected on students and their proficiency as input parameters for the study classifies and predicts outcome for students who will take the exams in the future. The study establishes a correlation between cases as a relationship or correlation between different phenomena represented by values of two variables. Decision tree as a model for classification is presented in the case of predicting the outcome of exams.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, N. Bijedić, Admir Mujkic, A. Sofić, B. Gogov, A. Mehmedović, Ivana Bjelogrlic et al.

Introduction: Colorectal cancer is the major diagnostic and therapeutic problem. The number of patients in the world has increased recently. In our country it is detected late and patients visit doctor in the advanced stage of the disease with already developed metastases. Material and methods: A clinical study was conducted at the Clinic of gastroenterohepatologists, Clinical Center of Sarajevo University on 164 patients. Special attention was given to the symptoms, which are considered to be a macroscopically visible as bleeding, anemia pain, weight loss and disturbance of defecation. Smoking had no effect because a small number of observed patients smoked. Endoscopic examination revealed localization of the tumor in the colon and then underwent targeted biopsy, histological analysis by pathologist, and we determined the concentration of CEA and CA19-9 in the serum. Results: In order to get the most relevant results we used larger data set. The program used to prepare the data was Microsoft Excel 2013, and for the creation of decision trees is a used software RapidMiner version 5. Our research has shown that patients older than 55 years with significant stenosis, metastasis and diarrhea that lasted longer than 3.5 months and bleeding that lasted up to 10 months had cancer of the rectum. Bleeding that lasts longer than 10 months indicated that it was the case of cancer that was localized in the rectum in men and sigma in women. Patients older than 82.5 years and had diarrhea up to 3.5 months developed cancer in the sigma part of the colon. Analyzing pain as a symptom of an alarm, the study found that pain that lasts longer than a few days, is caused by rectal cancer, and occurs after the age of 70.5 years, and in patients younger than 63 years anemia as a alarm symptom, which lasted more than two months in men was caused by cancer of the rectum and in women cancer in other localizations within colon. In patients without stenosis developed bleeding as the most important symptom. We can say that after the age of 74 years cancer of the rectum and sigmoid is more common in men and in women dominate sigma and other locations in the colon. In patients under the 70 years of age with short time of bleeding, cancer predominates in rectum. In patients younger than 63 years can be concluded that weight loss is greater than 8 kg follows rectal cancer. In patients with bleeding that lasted one month or more as classifier occurring the age and gender. Patients younger than 74 years have rectal cancer, while older than 73 years have cancer at other sites. In women these locations are sigma and rectum. Conclusion: Based on this study we can conclude that regardless of the technical advances in medicine must pay special attention to the symptoms that doctors will refer to the localization of the tumor, stenosis of the intestine and possibly metastasis. Key words: Colorectal cancer, diagnostic procedures, concentration of CEA and CA19-9.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, A. Sofić, N. Bijedić, B. Gogov, A. Mehmedović, Aida Saray, Sanjin Glavaš et al.

Introduction: Gastric cancer is one of the most common tumors in humans and is on the 14th place by frequency in the United States and it is at the 8th place by the mortality rate. In the world it takes seventh place by incidence. Today prevail the opinion and the surveys show, that it is twice as common in men as compared to women. Although there are advancements in diagnostics it must be noted that gastric cancer is still discovered late and when it already has metastasized, so that the therapeutic approach is limited and low survival rate. Patients and Methods: The study was retrospective-prospective, which covered the period from 2011 to 2012 and was performed at the Clinic of Gastroenterohepatology, Clinical Center of Sarajevo University. The study included 50 patients with gastric cancer, 34 men and 16 women. All patients underwent gastroscopy and according to tumor lesions localization divided into 3 regions: cardia, corpus and antropyloric region. Tumor lesions were biopted with histologically confirmation of gastric wall cancer. All patients underwent CT of gastric wall, CT of the abdomen and in some cases EUS was performed also. Goal: To prove by available diagnostic methods (endoscopy, CT and EUS) the presence of gastric cancer, histologically validate it and determine localization according to regions. To determine by CT the thickness of the stomach wall or the penetration of tumor lesions, the presence of enlarged lymph nodes and possible metastases. Record by EUS the progression of malignant processes in depth to layers of the wall, surrounding tissue metastases and enlarged lymph nodes. Determine the correlation between the measured parameters. Results: Our study showed that the localization of tumors at the cardia was represented in 15.31%, corpus in 17.36% and antropyloric region 16.33%. Median age he was 65.5 years with a standard deviation of 11.04. We failed to demonstrate a statistically significant difference in verified findings by EUS and age as well as endoscopic findings and age. Also there is no statistically significant difference between the CT scan and endoscopy XT = 5.99 and α = 0.05 = 0.63 XE, XE XT) and endoscopic findings and age (XT = 3.84 at α = 0.01, = 0.01 XE, XE> XT). Conclusion: Our study showed that gastric cancer are more common in men than women, metastases were more common in the elderly population, there were no significant deviations from the endoscopic findings and CT findings. EUS was performed in a small number of patients and showed as a good method because it gave accurate information about the penetration depth. Endoscopy, EUS and CT are ideal methods in diagnostic and staging of gastric cancer before the surgery.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, A. Sofić, N. Bijedić, Ivana Bjelogrlic, B. Gogov, A. Mehmedović

ABSTRACT Introduction: CEA and CA 19-9 are the most common tumor associated antigens used in the staging of patients with rectal cancer and other parts of the colon. Goal: of this study was to evaluate the value of CEA and CA 19-9 in serum of patients with colon cancer and prove its place in the diagnostic staging. Material and Methods: The study was retrospective-prospective performed at the Gastroenterohepatology Clinic, Clinical Center of Sarajevo University. The study included 91 hospitalized patients who had histologically confirmed diagnosis of colon adenocarcinoma in 98% of cases. All patients underwent colonoscopy, targeted biopsy and measurement of CEA and CA 19-9 levels in serum. All of them underwent abdominal CT and MRI of the pelvis in case of rectal cancer. Results: The study analyzed 58 men and 33 women, mean age 66.6 years, with the youngest patient at age of 35 and the oldest at age of 89 years. The largest number of patients was aged 56-75 years. According to localization 77 patients had carcinoma located in the area of the rectum and sigma 37.4 and 37.4 in the rectostigmoid area and sigma. Metastases were observed in 37 patients, with predominance in the liver (22 cases) and both liver and lungs (5 cases). CEA and CA 19-9 were determined in all cases but patients with metastases had high values, especially in the two cases of cecoascendent colon cancer where detected values were extremely high (1789ng/ml and 10780U/ml). Values of CA19 -9 were significantly higher (p<0.05). CEA mean values were highest in patients aged over 75 years. In case of CA 19-9 high mean values have been recorded in patients aged over 75 years with statistically significant differences between the age groups (p<0.05). Conclusion: CEA and CA19-9 are cancer antigens that are late markers of carcinogenesis, with significantly elevated serum concentrations in case of colon cancer with already developed metastases. Older age group of patient has significantly elevated levels of both antigens. Cancer was twice more common in men than in women.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, N. Bijedić, Ivana Bjelogrlic, A. Djuran

INTRODUCTION Ulcerative colitis (UC) is a common disease with a chronic and relapsing presentation requiring regular clinical follow up. Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical presentation and extent of inflammatory bowel disease. GOAL To evaluate the presence of intestinal infections by Entamoeba hystolitica in patients with ulcerative colitis, their impact on clinical outcome, and to identify associated risk factors. MATERIAL AND METHODS A total of 31 patients hospitalized on Gastroenterohepatology Department with patohystologically proved ulcerative colitis were studied. Fresh feces samples taken from 20 patients were examined immediately using Eosin and Lugol-staining methods and analyzing the presence of vegetative and MIFC (Meriolat and Iod staining). RESULTS A total of 16 female and 15 male hospitalized UC patients were analysed in a period of two years (2010-2011). The mean age at diagnosis was 43 years. We analyzed relation of amoeba infection with localization of ulcerative colitis. Our results indicate that amoeba infection is related to extent of disease (they were mostly present in pancolitis). Presence of amoeba is not related to age nor gender. Furthermore, presence of amoeba was not associated with more severe clinical course of disease. Similarly, higher value of serum marker of inflammation was not associated with amoeba infection. DISCUSSION AND CONCLUSION Amoeba infections in UC patients treated at Gastroenterohepatology Department was not related to the grade of disease activity, and other clinical variables such as gender, age and parameters of inflammation. These microorganisms could be a contributing cause of extended localization of disease.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, A. Sofić, N. Bijedić, B. Gogov, A. Djuran, Amila Redzepovic, Aida Saray et al.

Introduction: Colorectal cancer is the third most common tumor which causes high percentage of mortality in the general population. Etiologic factors which cause this disease are various, while diagnostic methods involve very complex protocols from detection of tumor markers to a combination of endoscopic and imaging methods. Goal: To determine the number of patients suffering from colon cancer for a period of two years and with endoscopic methods to verify and localize the tumor and its spread. Histopathological determination of the tumor type. Determine the concentration of CEA and CA 19-9 in the serum. Depending on the tumor location asses its progression, severity and extent by radiological imaging methods. Material and Methods: The study was prospective and retrospective, performed at the Gastroenterohepatology Clinic of the Clinical Center of Sarajevo University. During the two-year follow-up, 91 patients were hospitalized underwent endoscopy, targeted biopsy and histologically proven adenocarcinoma of the colon in which a pathologist determined grade of the cancers. Samples were eosin stained and underwent pathological histological analyzes. All patients according to tumor localization underwent CT scan and MRI of the rectum and pelvis. Results: The most common location of the cancer regardless of sex was in the recto sigmoid colon. Prevalence of colorectal cancer spread to other organs was not related to location. No significant dependence of the localization of the tumor by gender was found (p-value = 0.313). Ca 19-9 had the highest value in localization of tumors in the rectum. There was no statistically significant difference in age between men and women. The largest number of patients has adenocarcinoma grade 2 and the localization at the rectum. Conclusion: The combination of laboratory parameters (CEA and CA 19-9) with endoscopic and radiological imaging methods is essential in diagnosis of colorectal cancer and assessment of the process progression. There is a need to impose additional diagnostic parameters to detect the disease at an earlier stage.

N. Bijedić, Indira Hamulic, Emina Junuz, Ismet Maksumic, D. Radosav

N. Bijedić, Indira Hamulic, Z. Vukobrat-Bijedic, A. Husic-Selimovic

This research is aiming to set higher standards in healthcare research in Bosnia and Herzegovina from the aspect of mathematical and information science methodology. The data on Hepatitis C virus treatment published in previous work was reinvestigated using the Bayesian network methodology. The results are still in the line with the results published worldwide, but this research provides an additional quality, through the conditional probabilities for treatment outcome. Further development of this model may result in an acceptable prediction model for HCV treatment outcome.

Z. Vukobrat-Bijedic, A. Husic-Selimovic, N. Bijedić, Aida Saray, A. Djuran, B. Gogov, Ivana Bjelogrlic

BACKGROUND Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. The majority of GISTs are located in the stomach. Only 3-5% of GISTs are located in the duodenum associated with an increased risk of gastrointestinal bleeding as primary manifestation. AIM The aim of our study was to present frequencies of GIST in patients who underwent endoscopic procedures at Gastroenterohepatology Department due to different reasons. We also investigated the most frequent localization of GIST tumors and pathohistologicall pattern of tissue samples. PATIENTS AND METHODS Twenty two patients examined at gastroenterology department were analyzed in the period from 2005 until 2012. All of the patients were endoscopically examined ( gastroscopy, colonoscopy, endoscopic ultrasound). A few patients were referred from surgery where GIST was diagnosed during surgical procedure. Macroscopically noticed changes were pathohistologically analyzed by immunohistochemical staining (Alpha-smooth muscle actin (SMA), CD34, CD117, Ki-67 antigen, cytokeratin i desmin). RESULTS No significant difference in gender distribution of patients with GIST-s was found. We also analyzed the appearance of GIST with respect to mean patient age and no statistically significant difference was found either. However, investigation of tumor localization related to gender of patients we found a difference in gender distribution of tumor localization. In female GIST-s are more often located in the stomach than in men, with a significance level of 0.05. Immunohistochemical analysis of biopsy samples showed that CD 117 is statistically significant more frequent in men than in woman. CONCLUSION Taking in account the small sample size in our investigation over a period of seven years, we are not able to give a definitive conclusion about GIST. Further studies and observations are necessary to give a definite conclusion.

INTRODUCTION Infection with hepatitis C is often manifested by a mild clinical course, and in many patients it is revealed incidentally, during routine laboratory ests. Progression of the disease often takes 10-20 years with specified high risk of fibrosis and hepatocellular carcinoma. MATERIAL AND METHODS The group of subjects with chronic liver disease of viral C etiology was consisted of 50 patients of both sexes, 38 (75%) were male and 13 (25%) females, aged 20-65 years. Patients were selected according to genotype hepatitis C viral infection and subsequently treated according to two current therapeutic protocols. All patients had prior therapy and after completion of treatment using standard methods of laboratory tests were done the following: functional hepatic tests, serological analysis, nucleic acid detection of hepatitis C virus polymerase chain reaction (PCR), quantitatively and qualitatively with the genotyping of the virus C, which determines the length of therapy. In determining the stage of chronic liver disease, histopathological examination of liver tissue samples obtained by biopsy of the liver was done and we analyzed the fibrosis and architectural changes. RESULTS By analyzing the HCV RNA PCR values at the beginning and end of treatment we tested the effect of treatment on PCR with paired samples t-test logarithm values of the PCR and came to the conclusion that the values after treatment are significantly lower with threshold of significance of 0.01. The results showed that the value of PCR before and after therapy, or achieved a response at the end of therapy, which achieved 77% of patients. The values of ALT in the group of patients with CHC were significantly higher than the values in the group of patients after the therapy. AST values in the patients with CHC were significantly higher than the values in the group of patients after therapy. There was a moderate correlation between ALT values at baseline and ALT values upon completion of treatment (0.5061). There was no correlation between HCV RNA PCR and ALT and AST. CONCLUSION Upon completion of antiviral treatment response at the end of treatment achieved 77% of patients, regardless of the genotype of the virus. Also, regardless of the genotype of the virus antiviral therapy led to statistically significant reduction of AST and ALT, indicating a direct effect of combination therapy on virological and biochemical response with no significant link between these two studied parameters.

A. Husic-Selimovic, Z. Vukobrat-Bijedic, R. Mesihović, J. Huskic, N. Bijedić, S. Radović, A. Sofić

Background and Aims: Hepatic steatosis seems to be a risk factor for poor response to interferon and ribavirin therapy in patients with chronic hepatitis C. The aim of this study was to determine presence of hepatic steatosis in chronic hepatitis C and its influence on early virological response in patients treated with combined antiviral therapy (pegylated interferon and ribavirin). Methods: We studied 96 patients treated at Gastroenterohepatology Department, in the period of four years (2005-2009). There were 71 males and 25 females enrolled in this study. 72 patients had genotype 1, 5 patients had genotype 2, 17 patients had genotype 3 and 2 patients had genotype 4. Liver histology was evaluated in order to establish presence of inflammation, fibrosis and steatosis. HCV RNA levels in sera were measured by real time PCR. Early virological response (EVR) was defined as negative serum HCV RNA at week 12. In order to measure the effect influence of steatosis on early response to therapy, as well as genotype and response to therapy, we calculated relative risk and the corresponding p-value after 12 and 48 weeks. Results: The overall rate of EVR was 70%. The rate was significantly lower in the group with steatosis, regardless of the presence of micro or macrosteatosis, amounting to 60%. Serum cholesterol level was significantly higher in females than in males (7.4±0.7 vs. 5.1±0.3 mg/mL). The values of relative risks (and p-values) for effect of steatosis on the response are RRS12=8.4615 (2.87E-05), and RRS48=0.9844 (0.7399), while the values for the effect of genotype to therapy were RRG12=1.3378 (0.7543), and RRG48=3.5862 (0.2709). Conclusions: Our findings suggested that hepatic steatosis may have a strong influence on interferon therapy response in the sence that it is eight times more probable to not respond in the presence of steatosis. The presence of steatosis was highly associated with progressive disease and failure to achieve the EVR; therefore it can be a predictor of poor response to antiviral therapy.

N. Bijedić, Dževad Zečić

There are various designs for inference about stratified data, based on stratified sampling schemes. The approach in this paper proposes to deploy the methodology of meta-analysis, in particular the combined frequentist and Bayesian model for territorially stratified data. The research presented in this paper uses meta-regression of statistical data collected in Federation of Bosnia and Herzegovina, territorially stratified in administrative units – 10 cantons. In order to show methodologically richer example, we use odds ratio of new versus old passenger versus transport vehicle purchase, so infringing on one aspect of the consumer power in BiH. The proposed estimate is the REM Bayesian regression (log odds), which is impossible to derive without the use of IT. We use the results of FEM and REM frequentist meta-analysis to frame and test the results.

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