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Aim To analyse the resolution of chest X-ray findings in relation to laboratory parameters in patients infected with acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a two- month followup. Analysis of chest X-ray findings in the first few months after the disease is the main goal of our work. Methods Out of the total of 343 patients chest X-ray findings were followed in 269 patients. Patients were divided into groups according to the severity of findings. D-dimer, inflammatory markers, blood cell count, neutrophil lymphocyte ratio (NLR) were analysed. Chest X-ray was analysed during the hospitalization on the day of admission, on the third, the seventh and the fourteenth day (scoring method was used). After discharge chest X-ray was performed in a two-week follow-up, then after one and two months, and after three months if necessary. Results Incomplete chest X-ray resolution was identified in 24 (39.34%) patients with severe, 27 (22.31 %) patients with moderate and in three (3.91%) patients with mild findings. Statistical significance was established in overall score by comparison between all groups (p<0.001), and in the moderate compared to the mild group (p=0.0051). The difference of NLR in the severe compared to the moderate group was observed (p=0.0021) and in the severe group compared to the mild group (p=0.00013). Conclusion Chest X-ray findings persisted mostly in the severe group followed by the moderate and mild ones. Long-term followup is necessary for the appropriate treatment and prevention of fibrosis, and reduction of symptoms.

Aim To investigate interleukin 6 (IL-6) values depending on duration of diabetes mellitus (DM) and evaluate possible correlation with diabetic polyneuropathy. Methods The research study included 90 patients with DM divided into three groups (30 patients each) according to the duration of DM: group A - patients who had DM for less than 10 years, group B - duration of DM was 10 to 20 years, and group C - patients with DM over 20 years. Control group (K) included 30 healthy participants. Results IL-6 was significantly higher in the healthy control group, 180.318 pg/mL±94.18, than in group A, 47.23pg/ml±34.8, group B, 43.31pg/ml±33.17, and group C, 70.39 pg/ml±59.26 (p=0.0001). All groups had significantly different values of IL-6 between each other (p=0.0001). Level of IL-6 was in correlation with diabetic polyneuropathy in the group A (the youngest participants) (p=0.0001). In other groups there was no significant correlation between IL-6 and diabetic polyneuropathy. Conclusion The level of IL-6 was in correlation with neuropathy among younger patients. A higher level of IL-6 in the control group than in diabetic groups is a sign of stronger inflammatory response among younger and healthy people than in patients with DM.

E. Jusufovic, V. Žugić, M. Košnik, M. Drvenica, S. Hromis, J. Nurkić, M. Al‐Ahmad, L. B. Kardum et al.

Aim To investigate the usage of chest computed tomography (CT) scan score for improvement in diagnostic and treatment efficacy of repetitive pleural effusion. Methods CT scan scoring system was used as a part of diagnostic procedures in patients with repetitive pleural effusion. Patients with at least two pleurocentesis were included in the study. Chest and abdominal ultrasound, chest x-ray, bronchoscopy, biochemical, microbiological and cytological analysis of pleural fluid specimen were performed for all patients. Results In a two-year period (during 2017-2018) 79 patients were analysed, 27 (34.17%) female and 52 (65.82%) male patients. Malignant pleural diseases were confirmed in 32 cases (40.5%), nonmalignant pleural effusions in 38 (48.1 %) cases, and nine (11.4%) patients rested without exact cause of pleural effusion after two pleurocenteses. Binary regression model showed odds ratio of 1.314; CI 95% 1.119-1.543) (p=0.00088). Confirmed malignancies with pleural effusion were in high correlation with the number of points in CT scan score. Conclusion CT scan scoring system was helpful for diagnostic and treatment decision making in patients with repetitive pleural effusion.

E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. Bulat-Kardum, M. Bećarević, M. Osmić et al.

Despite multistep efforts many asthma patients remain symptomatic. Anti-inflammatory activities of curcumin were shown. Aim was to analyse the add-on therapy with curcumin on inflammatory parameters, lung function, disease control and quality of life in asthma patients. 150 non-smokers with moderate partially controlled asthma were treated during 3 months with stable moderate dose of inhaled glucocorticoids and divided into three groups (n=50): curcumin group (receiving curcumin 500 mg per os twice daily), placebo and control group. Before study, sputum eosinophils (sEo), blood eosinophils (bEo), high sensitive C-reactive protein (hsCRP), predicted forced expiratory volume in first second (FEV1%), Asthma Control Test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) were similar between groups. After study, FEV1%, ACT and AQLQ were improved in all groups, but these improvements were more prominent in curcumin group than in placebo and control. Additionally curcumin group only showed improvement in sEo, bEo and hsCRP. Furthermore, curcumin group showed also more frequent clinically significant improvement in ACT score (change>3) and in AQLQ score (change≥0.5) when compared to placebo and control. However, placebo and control showed similar distribution in FEV1%, ACT, AQLQ, hsCRP, sEo and bEo after study. This is the first placebo controlled and single-blind study to suggest that add-on therapy with curcumin could improve lung function, disease control and quality of life in moderate partially controlled asthma. Future studies may benefit from a larger sample size, longer study duration, double blind design, different dose of curcumin and/or improvements in oral bioavailability.

E. Jusufovic, M. Košnik, J. Nurkić, N. Arifhodzic, M. Al‐Ahmad, L. B. Kardum, M. Bećarević, M. Osmić et al.

Sputum eosinophils might predict response to inhaled corticosteroids (ICS) in patients with advanced chronic obstructive pulmonary disease (COPD). Induction of sputum requires expertise and may not always be successful. Aim was to investigate correlation and predictive relationship between peripheral blood eosinophils (bEo) and sputum eosinophils (sEo), and impact of peripheral blood eosinophilia on outcome of COPD exacerbation. 120 current smokers with COPD (GOLD group C) (57.4 ± 0.92 years, M/F ratio 1.4), with no blood (≥7% or >0.43x109/L) nor sputum (≥3%) eosinophilia, were treated with moderate dose of ICS and long-acting bronchodilatator during stable disease, but systemic corticosteroids and antibiotics during exacerbation. According to sputum eosinophilia (≥4%) during exacerbation, patients were divided into eosinophilic (n=45) and non-eosinophilic group (n=75). In stable disease, bEo and sEo were similar in both groups (p>0.05). During exacerbation, bEo and sEo were significantly higher in eosinophilic group (eosinophilic vs. non-eosinophilic: blood: 1.42 ± 0.39 x109/l vs. 0.23 ± 0.02 x109/l, p<0.001; sputum: 8% (4, 19) vs. 1% (0, 3), p<0.0001), but bEo correlated with sEo in both groups (eosinophilic: r=0.52, p<0.001; non-eosinophilic: r=0.25, p<0.05). Relative bEo predicted sputum eosinophilia (area under the curve=0.71, standard error=0.05; 95% confidence interval [CI] =0.61-0.81; p<0.001) and enabled identification of the presence or absence of sputum eosinophilia in 82% of the cases at a threshold of ≥4% (specificity=83.56%, sensitivity=93.83%, positive likelihood ratio=3.67). Eosinophilic group during exacerbation showed less frequent hospitalisations and shorter exacerbation (eosinophilic vs. non-eosinophilic: hospitalisations: 26.7% vs. 60.0%, p<0.001; duration of exacerbation (days): 8.1±0.35 vs. 10.13±0.31, p<0.0001). In COPD exacerbation, relative peripheral blood eosinophils ≥4% might identify sputum eosinophilia. Blood eosinophilia indicate better outcome of COPD exacerbation. Further investigations are needed to predict eosinophilic exacerbation in COPD patients, with prior absence of sputum or blood eosinophilia.

F. Zvizdić, E. Begić, A. Mujaković, E. Hodžić, B. Prnjavorac, O. Bedak, F. Čustović, Haris Bradaric et al.

Introduction: The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients. Aim: To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages. Patients and methods: The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration. Results: Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577. Conclusion: Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.

Summary Background FTO, a gene recently discovered in genomewide associated studies for type 2 diabetes mellitus (T2D), play an important role in the management of energy homeostasis, nucleic acid demethylation and regulation of body fat mass by lipolysis. The aim of this study was to analyze the association of FTO rs8050136 A>C genetic variant with clinical and biochemical parameters of T2D in the population of West Balkan region (Bosnians and Herzegovinians and Kosovars). Methods The study included 638 patients with T2D and prediabetes and 360 healthy controls of both genders, aged from 40 to 65 years. Patients were recruited at the Clinical Centre University of Sarajevo, University Hospital of Clinical Centre in Banja Luka, General Hospital in Tešanj and Health Centre in Prizren. Genotyping of analyzed FTO polymorphism rs8050136 A>C was performed by qPCR allelic discrimination. Results Genotype frequencies of the analyzed polymorphism were comparable between patients with T2D, prediabetic patients, and healthy population. Logistic regression analyses didn’t show significant association of FTO rs8050136 A allele with increased risk of T2D. However, risk A allele was significantly associated with higher levels of HbA1c, insulin, HOMA-IR index, diastolic blood pressure, and inflammatory markers (fibrinogen and leukocytes) as well as showed tendency of association with increased values of obesity markers (BMI, waist and hip circumference). Conclusions Results of our study showed a significant association of FTO genetic variant rs8050136 A>C with the major markers of insulin resistance, obesity and inflammation, opening new avenues for solving many unclear questions in the pathogenesis of T2D.

Lejla Mahmutović, T. Bego, M. Sterner, Gabriella Gremsperger, E. Ahlqvist, Zelija Velija Asimi, B. Prnjavorac, N. Hamad et al.

Abstract Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], padd = 0.025; B = 0.079, 95% CI [0.006, 0.150], padd = 0.033, respectively) in T2D, and with HbA1c (B = 0.034, 95% CI [0.003, 0.065], pdom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = −0.17, 95% CI [−0.03, −0.002], padd = 0.030) and HbA1c (B = 0.03, 95% CI [0.002, 0.06], pdom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA1c levels in Bosnia and Herzegovina’s population.

Title of Days of AMNuBiH 2018” and “SWEP 2018” is “Ethical Dilemmas in Science Editing and Publishing”. Why? If one wants to create a scientific work, must have on his mind that creating a scientific work requires creativity and openness, honesty, trust, and obeying the ethical principles for writing a scientific paper. While working on a an biomedical research involving human subjects medical workers should have on mind that it is the duty of the physician to remain the protector of the life and health of that person on whom biomedical research is being carried out. The World Medical Association (WMA) has developed the Declaration of Helsinki as a statement of ethical principles to provide guidance to physicians and other participants in medical research involving human subjects.

Una Suljić, B. Prnjavorac, T. Bego, M. Malenica, T. Dujic, I. Prnjavorac, A. Causevic, L. Šaranović

Aim To investigate whether or not additional treatment of ischemic heart disease with trimetazidine could improve effort tolerance and overall quality of life of patients with ischemic heart disease. Methods The study included 200 patients with ischemic heart disease. The sample was divided into 2 randomly selected groups: experimental and control group. The diagnostic procedures included: trade-mill test according to Bruce protocol, heart ultrasound for assessment of ejection fraction, test for the assessment of quality of life and subjective problems (Short Form SF 36). Patients were tested for time of discharge from hospital, after 6 and 12 months, including re-evaluation of the overall condition of the previous period. Results Patients have been tested for the tolerance of effort with the measurement Metabolic Equivalent of TASK (METs), which is the equivalent of physical labor. Patients treated with trimetazidine since the time of hospital discharge achieved an average of 3.68, after 6 months 5.68, and after 12 months 7.79 METs. The control group achieved 3.68, 3.59 and 3.87 METs, respectively. Using Mann-Whitney test no difference at discharge time (p=0.880), but after six and twelve months there was some difference (p<0.001). Results of ejection fraction measured by echocardiography were similar. No difference between the two groups with regard to time of discharge (p=0.821, but p<0.001 after six and twelve months, respectively). Conclusion Patients treated with conventional therapy including trimetazidine have better tolerance to effort and better ejection fraction on heart ultrasound examination in comparison with those treated without trimetazidine, so trimetazidin improve the metabolic balance of heart muscle.

Sehveta Mustafić, S. Brkić, B. Prnjavorac, Albina Sinanović, Humera Porobić Jahić, Sabina Salkić

Aim To investigate predictive value of procalcitonin in diagnosis of sepsis in predicting positive blood culture, and possibility to predict final outcome in septic patients. Method This prospective study involved 106 hospitalized patients who met two or more criteria for systemic inflammatory response syndrome (SIRS). In comparison to Sepsis Related Organ Failure Assessment score (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II score procalcitonin (PCT), C-reactive protein and lactate levels were used to predict final outcome in septic patients (recorded as 28-day survival or non-survival). Using Receiver operating characteristic (ROC) curve the area under the curve (AUC) was calculated for diagnostic value and accuracy of different parameters with the best sensitivity and specificity for given cut-off values. Result Fifty-two out of 82 patients with documented sepsis had positive blood culture. Procalcitonin showed the best predictive value for both diagnosis of sepsis and bacteraemia with the cut-off value of 0.57 ng/mL (AUC 0.99) and 4.68 ng/mL (AUC 0.94), respectively. Serum lactate level showed the best 28-day mortality predictive value with the cut-off value of 3.25 mmol/L (AUC 0.95), and procalcitonin with the cut-off value of 15.05 ng/mL (AUC 0.92), followed by SOFA (AUC 0.92), CRP (AUC 0.84) and APACHE II score (AUC 0.83). Conclusion Monitoring of PCT in SIRS-positive patients raises possibility to distinguish between patients with sepsis and those with non-infectious SIRS. A significant correlation between PCT and SOFA, and APACHE II score in non-surviving septic patients indicates that PTC combined with clinical score could be useful for assessing severity of infection.

1Department of Biochemistry and Clinical Analysis, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina 2Clinics for Endocrinology, Diabetes and Metabolism Diseases, University Clinical Centre of Sarajevo, Sarajevo, Bosnia and Herzegovina 3General Hospital of Tesanj, Tesanj, Bosnia and Herzegovina 4Department of Pathophysiology, Faculty of Pharmacy; University Sarajevo, Sarajevo, Bosnia and Herzegovina 5The Chair of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia 6Institute for Clinical Biochemistry and Diagnostics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic 7Faculty of Engineering and Natural Sciences, International University of Sarajevo, Sarajevo, Bosnia and Herzegovina

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