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F. Nišić, Aida Pidro, O. Lepara, Almir Fajkić, Ajla Pidro Mioković, E. Suljic, Aida Nišić, I. Kovačević

Objective: This study aimed to determine the intravitreal concentration of VEGF in eyes with PDR and to evaluate the effects of previous PRP on its level. Methods: It was a cross-sectional study performed at the Clinical Centre University. It included 90 eyes surgically treated with PPV, divided into three groups, group A - patients with PDR with previous PRP, group B - patients with PDR without previous PRP, and group C - PPV performed due to the indication unrelated to diabetes. A vitreous sample was obtained during PPV, and the VEGF concentration was determined using an Enzyme-linked immunosorbent assay test (ELISA). Shapiro-Wilk, nonparametric tests Kruskal-Wallis, Mann-Whithney U test, ANOVA and Spearman’s correlation test were used. Results: The highest vitreous VEGF concentration was in group B - 972.96 (743.33-1149.13) and was higher than in group A - 69.22 (37.33-225.15) and in group C - 19.93 (1.15-32.17) (p<0.001). There was a positive correlation between VEGF vitreous concentration and glucose level in group A patients (Rho=0.410; p=0.027). Conclusion: As a treatment before PPV surgery, PRP showed to be effective in the reduction of VEGF levels, which also highlighted a decrease in complications during and postoperatively. Abbreviations: DRS = Diabetic Retinopathy Study, PDR = proliferative diabetic retinopathy, VEGF = vascular endothelial growth factor, PRP = pan-retinal photocoagulation, PPV = pars plana vitrectomy, HbA1c = glycosylated hemoglobin, ETDRS = Early treatment diabetic retinopathy study, ESR = erythrocyte sedimentation rate, BCVA = best corrected visual acuity, OCT = optical coherent tomography, ILM = internal limiting membrane, PHACO = phacoemulsification, IOL = intraocular lens, ELISA = Enzyme-linked immunosorbent assay test, AUC = area under the curve, DME = diabetic macular oedema, TDR = tractional retinal detachment, VMT = vitreomacular traction

Asija Začiragić, A. Dervišević, N. Avdagić, N. Babic, A. Valjevac, O. Lepara, J. Huskic

Abstract Objective. The present study assessed the impact of type 2 diabetes mellitus (T2DM) duration on the serum asymmetric dimethylarginine (ADMA) and C-reactive protein (CRP) concentration in Bosnian patients. Methods. Participants for this cross-sectional study were randomly selected from the Family Medicine Clinic (Sarajevo, Bosnia and Herzegovina). Serum ADMA concentration was determined by ELISA. Serum high-sensitivity (hs-CRP) was determined by particle-enhanced immunonephelometry. ANOVA test followed by Scheffe post-hoc test or Kruskal-Wallis test followed by Man-Whitney test were used for statistical analysis. Results. The study included 38 patients in up to 10 years diabetes duration (≤10 years T2DM) group, 22 patients in greater than 10 years diabetes duration (>10 years T2DM) group, and 60 controls. Serum ADMA concentration in the >10 years T2DM group (1.81±0.15 μmol/L) was significantly higher compared to serum ADMA concentration in the ≤10 years T2DM group (1.38±0.41 μmol/L; p<0.001) and in controls (0.62±0.15 μmol/L; p<0.001). A significant difference in serum ADMA concentration was found between the <10 years T2DM group and the controls (p<0.001). The serum CRP concentration in the >10 years T2DM group [5.95 (4.20–9.12) mg/L] was significantly higher compared to serum CRP concentration in the <10 years T2DM group [2.35 (1.40–4.30) mg/L; p<0.001] and controls [0.85 (0.50–1.30) mg/L; p<0.001]. Significant difference in serum CRP concentration was observed between the <10 years T2DM group and controls (p<0.001). Conclusions. The present study showed an increase in the serum ADMA and CRP concentrations with the advancement of T2DM. These results suggest that ADMA and CRP may serve as indicators of endothelial dysfunction and chronic low-grade inflammation progression in patients with T2DM. Larger prospective studies are required to confirm the observed findings.

Asija Začiragić, A. Valjevac, A. Dervišević, Almir Fajkić, Selma Spahić, R. Jadric, I. Hasanbegović, O. Lepara

Background: Conflicting data exist on traditional lipid profiles in patients with Alzheimer’s disease (AD) and vascular dementia (VD), whereas scarce number of studies evaluated non-traditional lipid profiles in patients with AD and VD. Studies have shown that ethnic background may affect lipid profile. Objective: The aim of the present study was to conduct comparative assessment of traditional and non-traditional lipid profiles in Bosnian patients with AD and VD. Methods: A controlled, cross-sectional study was performed with 66 patients with AD, 50 patients with VD, and 60 control subjects. The Montreal Cognitive Assessment (MoCA) test was used for an evaluation of the global cognitive function. The Hachinski ischemic score was used to distinguish patients with VD from those with AD. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with ANOVA followed by the Tuckey posthoc test or with the Kruskal Wallis test followed by the Mann-Whitney test. Results: Results of the present study have shown that patients in AD group had significantly lower level of TC, TG, LDL-C, VLDL-C, Non-HDL-C and significantly lower atherogenic index compared to the control group (CG) and compared to the VD patients. Significant difference in values of TG and VLDL-C was observed between VD and the CG, whereas no significant difference in values of TC, LDL-C, atherogenic index and Non-HDL-C was observed between these two groups. Our results have also shown that TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratios were significantly lower in AD patients compared to the VD and CG. Moreover, TG/HDL-C ratio was significantly lower in VD compared to the CG. However, a significant difference in TC/HDL-C and LDL-C/HDL-C was not observed between VD and the CG. Conclusion: Based on the results of the present study it can be deduced that there is a difference in traditional and non-traditional lipid profiles between AD and VD patients of Bosnian descent. Obtained results suggest that lipids are decreased in AD and in VD to a certain extent. However, since there is an inconsistence in literature whether there is an association between cholesterol and cognition, large prospective studies are required to elucidate this controversy.

A. Mujaković, B. Paralija, O. Lepara, Almir Fajkić, Avdo Kurtović, B. Prnjavorac, E. Begić, Nejra Gondžetović-Ćorić

Aim To investigate infl uence of neutrophil-to-lymphocyte ratio (NLR) and proatherogenic risk factors to improve the accuracy of pneumonia severity index (PSI) in the prediction of community acquired pneumonia (CAP) outcome in healthy individuals. Methods A retrospective observational cross-sectional study conducted at the Clinic for Pulmonary Diseases and Tuberculosis "Podhrastovi", University Clinical Centre Sarajevo, included 83 patients with the diagnosis of CAP during the period March 2019-March 2021. Once diagnosed with CAP, PSI score was calculated and according to its value the need for hospital treatment was identifi ed. Patients were divided in two groups: low risk of CAP (PSI <90), and high risk of CAP (PSI> 90). Results The overall average hospital stay was 22.76±10.154 days. In the patients diagnosed with CAP, a positive correlation was established between the following parameters PSI score and age (r=0.670; p<0.01), C-reactive protein-CRP (rho=0.287; p<0.01), leukocytes (rho=0.406; p<0.01), NLR (rho=0.313; p<0.01) and platelet to lymphocyte ratio (PLR) (0.296; p<0.05). CRP, leukocytes, NLR and PLR were statistically signifi cantly higher in patients with high risk of CAP compared to patients with low risk of CAP. Diastolic blood pressure, lymphocytes, eosinophils were signifi cantly lower in patients with high risk of CAP (p<0.05;) compared to patients with low risk of CAP (p<0.01). The optimal cut-off value of NLR for CAP patients was 3.089 with an estimated area under curve (AUC) of 0.664. Conclusion Proatherogenic parameters such as age, systolic blood pressure and leukocytes in combination with neutrophil-lymphocyte count ratio could improve accuracy of the pneumonia severity index in community acquired pneumonia outcome.

E. Begić, A. Iglica, R. Gojak, R. Baljic, Z. Begić, A. Durak-Nalbantić, M. Halilčević, A. Džubur et al.

Aim The aim of this study was to link the values of D-dimer and C-reactive protein (CRP), with the occurrence of pericardial effusion in patients who had coronavirus disease 2019 (COVID-19) and have preserved systolic function of the left ventricle (LV). Methods This was a prospective study and included 146 patients who underwent echocardiographic examination 30 days after the acute phase of COVID-19. Patients who were placed on mechanical ventilation, patients who had pulmonary thromboembolism or acute coronary syndrome during the acute period of the disease, patients who had an ejection fraction of the LV <50%, patients who were diagnosed with pericarditis during acute illness or clinical signs of heart failure (or had elevated N-terminal-pro hormone B-type natriuretic peptide value), with verified renal or hepatic dysfunction were excluded from the study, including patients with diabetes mellitus Type 1, patients with cancer, connective tissue disease, or pregnant women. The existence of cardiovascular risk factors (hypertension, diabetes mellitus Type 2, and hyperlipidemia), the presence of previous ischemic heart disease, maximum values of D-dimer, and CRP (during the first 15 days of the disease) was taken into the analysis. Results Effusion was verified around the right atrium (RA) in 104 patients (3.85 ± 1.75 mm), in 135 patients next to the free wall of the right ventricle (RV) (5.24 ± 2.29 mm), in front of the apex of the LV in 27 patients (2.44 ± 0.97 mm), next to the lateral wall of LV in 35 patients (4.43 ± 3.21 mm), and behind the posterior wall of LV in 30 patients (2.83 ± 1.62 mm). Mean CRP values during the acute phase of the disease were 43.0 mg/L (8.6–76.2 mg/L), whereas D-dimer mean value was 880.00 μg/L (467.00 –2000.00 μg/L). CRP values correlated with effusion next to the free wall of RV (rho = 0.202; P = 0.018). The D dimer correlated with effusion around RA (rho = 0.308; P = 0.0001). Conclusion The clinical picture of the post-COVID patients could be explained by the appearance of pericardial effusion. D-dimer value correlates with the occurrence of effusion around RA, whereas CRP value correlates with effusion next to the free wall of RV.

Asija Začiragić, A. Dervišević, A. Valjevac, Almir Fajkić, Selma Spahić, I. Hasanbegović, R. Jadric, O. Lepara

Background: Lipids and lipoproteins are significantly involved in maintaining structural and functional components of the human brain and neurons, but their role in the development of Alzheimer’s disease (AD) and vascular dementia (VD) remains unclear. Objective: The aim of the present study was to explore the differences in the standard and novel lipid profile parameters in patients with AD and VD, stratified by the degree of cognitive impairment (CI). Methods: Present study included 66 patients with AD, 50 patients with VD, and 60 control subjects. For an evaluation of the global cognitive function the Montreal Cognitive Assessment (MoCA) test was used. In order to distinguish patients with VD from those with AD the Hachinski ischemic score was used. Plasma total cholesterol (TC), high-density lipoprotein -cholesterol (HDL-C), and triglycerides (TG) levels were determined using standard enzymatic colorimetric techniques, whereas the Friedewald formula was used to calculate low-density lipoprotein-cholesterol (LDL-C) levels. The non-traditional lipid indices such as TG/HDL-C, TC/HDL-C, and LDL-C/HDL-C ratio were separately calculated. The differences between the groups were analyzed with the Kruskal Wallis test followed by the Mann-Whitney test or with ANOVA followed by the Tuckey posthoc test. Results: Results of the conducted study have found that the patients in AD group with moderate CI and patients in AD group with severe CI exhibited significantly lower levels of serum TC, TG, LDL-C, VLDL-C, Non- HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C and LDL-C/HDL-C compared to cognitively normal control subjects. Moreover, patients in VD group with severe and moderate CI had significantly lower level of TG compared to control group of subjects. Our results have also shown that patients in AD group with moderate CI had significantly lower level of TC, TG, LDL-C, Non-HDL-C, atherogenic index, TG/HDL-C, TC/HDL-C compared to VD patients with moderate CI. In addition, patients in AD group with severe CI had significantly lower level of TC, LDL-C, Non-HDL-C and TC/HDL-C compared to VD patients with severe CI. Conclusion: The results of this study have shown dysregulation of lipid metabolism in AD and VD patients with different degree of CI. In both moderate and in severe CI, patients with AD had lower levels of majority of standard and novel lipid parameters compared to patients with VD. Further larger prospective studies are required to elucidate the accuracy of standard and novel lipid parameters in the assessment of different degree of CI in AD and VD.

Ajla Pidro, Aida Pidro, Amra Nadarević-Vodenčarević, Meliha Halilbašić, O. Lepara, F. Nišić

Objectives: The aim of this study was to determine the possible correlation between the short- and long-term effects of intravitreal bevacizumab on macular oedema after branch retinal vein occlusion (BRVO). Material and methods: This prospective clinical study included fifteen eyes of patients with macular oedema after BRVO. Corrected distance visual acuity (CDVA), recorded in LogMAR units, central foveal thickness (CFT) and maximum foveal thickness (MFT) were evaluated at one month after first application and at least every 2 months for one year. PRN treatment protocol was used for all patients. Statistical calculation was performed with SPSS for Windows and Microsoft Excel. Results: Mean CFT decreased significantly (p<0,0001) from baseline 471,2 ± 151,7 μm to 285,9 ± 79,82 μm at 12 months. CDVA improved significantly (p<0,0001) from baseline 0,58 ± 0,34 to 0,1 ± 0,25 at the end of follow up period. Change from baseline in the CDVA after one month was significantly positively correlated with the change in CDVA after 12 months (r=0,76, p=0,001). Change in CFT after one month had a strong positive correlation (r=0,78, p=0,001) with change after 12 months. There was no statistically significant correlation between the number of injections and the changes in CDVA, CFT, MFT after a single injection. Conclusions: Single injection effects of bevacizumab may indicate long-term results on macular oedema after BRVO, but further and larger studies are necessary. Abbreviations: BRVO = Branch retinal vein occlusion, RVO = Retinal vein occlusion, CFT = Central foveal thickness, MFT = Maximum foveal thickness, VEGF = Vascular endothelial growth factor, MO = Macular oedema, CDVA = Corrected distance visual acuity, PRN = Pro-re-Nata, SD-OCT = Special-domain optical coherence tomography, FT = Foveal thickness, LogMAR = Logarithm of the Minimum Angle of Resolution, WHO = World Health Organization, RPE = Retinal pigment epithelium

A. Džubur, Delila Lisica, Emir Hodžić, E. Begić, O. Lepara, Almir Fajkić, Ena Gogić, M. Ejubović

Aim To examine the prevalence of depression in patients after acute myocardial infarction (AMI), as well as the relationship between the depression and quality of life. Methods The survey was conducted via sociodemographic questionnaire, Beck Depression Inventory (BDI), and Short Form 36 Health Survey questionnaire (SF-36). The result of SF-36 is expressed in subscales that make up the health status profile, i.e. physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Results The study included 120 patients, of which 70 males and 50 females aged between 41 and 88 years (mean 64.73±11.218). All patients were hospitalized at the Clinical Centre of the University of Sarajevo, Clinic for Cardiovascular Disease and Rheumatism, due to complications caused by AMI. After AMI 59 (49.17%) patients had depression. Depression was negatively associated with physical functioning, physical role, emotional role, social functioning, mental health, vitality, pain and general health. Physical functioning (r= -0.701; p<0.01) and physical role (r = -0.538; p<0.01) had the highest correlation with depression. Conclusion The evaluation of depressive symptoms after AMI is imperative, because the appearance of symptoms could have an effect on the patient's quality of life.

K. Grbić, J. Alić, O. Lepara, S. Omić, J. Heljić, F. Krupic, F. Krupic

Background For many patients with end-stage disease, organ transplant often provides the only chance for survival. Organ donation (OD) is affected by legislation, cultural and ethnic background, and knowledge and attitudes play a crucial role in promoting that concept. The present study aimed to assess differences in education level, perception, and willingness towards OD among Bosnian immigrants living in Sweden and respondents living in Bosnia and Herzegovina. Study design We performed a quantitative cross-sectional study using a self-administered questionnaire among 204 participants. Methods The questionnaire provided demographic characteristics, information about opinions, awareness, and knowledge on the donation process and religious approach to the subject, willingness to donate/receive organs, and possession of a donor card. Results All respondents supported OD, regardless of their education level. Only 2% of university-educated individuals from Bosnia and Herzegovina claimed to be donor card owners (p<0.001). Most of the university-educated respondents in Sweden, compared to Bosnia and Herzegovina, agreed that OD is needed and should be promoted (73.8% vs. 46.9%, p=0.007), opposite to the non-university-educated (51.4% vs. 66.0%, p=0.024). University-educated respondents stated that the donor card was informative enough (p=0.014) and considered self-perceived knowledge about OD to be sufficient or excellent (p<0.001). Most respondents were married and employed, practicing Muslims. Most of non-university-educated respondents from both countries believe their religion does not oppose OD (p=0.032). However, university-educated individuals strongly believe that OD does not have to be within the same religious group (p=0.016), while other participants did not have a definitive opinion. Conclusions Public behavior towards OD is affected by the social environment and the educational level. The study highlights the importance of achieving a suitable social climate for donation. Also, it suggests that more efforts are needed to harvest the benefits of the substantial support for OD among the Bosnian population.

Azra Metović, J. Mušanović, N. Ramic, O. Lepara, D. Šečić, E. Pepić, S. Zec, S. Šljuka

Background: Breast cancer in women is the second most common and accounts for approximately 18% of all malignant tumors in women worldwide. The etiology of breast cancer is not clear enough. Starting from the assumption that the manifestation of breast cancer may have a multifactorial model, this article compares the population-genetic structure of patients (experimental group) with the population-genetic structure of healthy population (control group). Objective: The aim of the study was to examine the possible genetic basis of the Rh factor relationship with selected homozygous-recessive traits of females with breast cancer, and to diagnose the probability (assess the risk) of developing the disease in healthy women by analyzing homozygous-recessive traits (HRT). Methods: This are an anthroposcopic-qualitative study that included two groups of subjects, experimental and control (a total of 80 subjects). An analysis of the percentages within each group was performed using the Chi-square test. The results are presented in tables, and the accepted level of significance is at the level of p <0.05. Results: In the group of Rh+ subjects, the correlation of this type of Rh factor with the breast cancer was proven, given the frequency of the phenotype of homozygous-recessive traits in them. A statistically significant difference was found for 4 traits, and three are also close to the set significance level. In subjects with Rh- factor, a statistically significant difference was found for only one trait (absence of mallets on the phalanges). Conclusion: Although the number of subjects was relatively small, we can conclude that in the experimental group a higher frequency of recessive phenotypes for the examined traits was recorded, which indicates the genetic load of the subjects from this group. Correlation with Rh factor was observed in the case of subjects of the experimental group with Rh+ factor.

Introduction Although extracorporeal shock wave lithotripsy (ESWL) is minimally invasive and highly efficient for the management of kidney stones, adverse effects have been described. Available indicators of renal function exhibit insufficient sensitivity in acute renal injury (AKI). We aimed to evaluate the severity of the kidney tissue response to ESWL injury by measuring the urinary neutrophil gelatinase-associated lipocalin (uNGAL), which can indicate AKI in its early phase. Material and methods The prospective, controlled study included 62 patients with nephrolithiasis undergoing single ESWL treatment. uNGAL level was measured before the procedure, and 6 h and 12 h after. Results The median uNGAL level increased by 126.0%, 6 h after ESWL (p <0.001). The growth rate continued and 12 h after was higher by 583.7%, compared to the pre-treatment level (p <0.001). The median value of estimated glomerular filtration rate (eGFR) dropped by 15.3% 12 h after the treatment (p <0.001). It increased by 5.0% in the period 7 days to 3 months after (p <0.001) and after 3 months it was lower by 10.1% compared to pre-ESWL values (p <0.001). uNGAL level after 12 h was significantly negatively associated with eGFR, 12 h, 7 days and 3 months after the ESWL. The sensitivity of uNGAL 12 h after ESWL was 60.6%; its specificity was 75.0%, with a positive predictive value of 74.0% and negative predictive value of 61.7%. Conclusions uNGAL appears to be a useful biomarker for the assessment and prediction of AKI. It was noticed that uNGAL had the highest predictive value 12 h after the ESWL treatment.

F. Zvizdić, E. Begić, M. Dilić, Š. Sokolović, O. Lepara

Aim To investigate the benefit of high-dose lipophilic statin therapy on cardiac remodelling, function and progression of heart failure (HF) in patients with ischemic heart disease. Methods A total of 80 patients with ischemic HF diagnosis were followed during 6 months, and they were divided in two groups. First group (n=40) was treated by high-dose lipophilic statin therapy (atorvastatin 40 mg) and conventional therapy for HF, while the second group (n=40) had no atorvastatin in the therapy. Results In the beginning of study, from all of the observed parameters, only the ratio of flow rates in early and late diastole (E/A ratio) differed between the test groups (p=0.007). After six months, a statistically significant increase in left ventricular end-diastolic diameter (LVIDD) in patients who had not been treated with atorvastatin was found. In the patients treated with atorvastatin, there was a significant reduction in basal right ventricle diameter in diastole and systole (p<0.001 and p<0.001, respectively), and in tricuspid annular plane systolic excursion (TAPSE) (p<0.001); there was a reduction in LVIDD (p<0.001), and an increase of ejection fraction of the left ventricle according to Teicholtz and Simpson (p<0.001 and p<0.001, respectively). Also, there was an increase of deceleration time of early diastolic velocity (DTE) (p<0.05) and a decrease of isovolumic relaxation time (IVRT) (p<0.001). Conclusion The reduction in the right and left ventricle diameters was noted after the six-month atorvastatin therapy. Atorvastatin in the therapy resulted in increased EFLV and better systolic function and should be a part of a therapeutic modality of HF.

K. Grbić, A. Mujaković, O. Lepara, Z. Lepara, E. Begić, F. Krupic

Introduction: The invasion of blood and lymph vessels with tumor tissue represents a negative prognostic factor of the disease course in patients with non-small cell lung cancer. Aim: The aim of the study was to determine the marker value of a preoperatively determined size of pulmonary squamous cell carcinoma and adenocarcinoma and its impact on lymphovascular invasion (LVI) in resected lung tissue. Materials and Methods: The conducted observational cross-sectional study included 322 patients with a complete resection of confirmed squamous cell lung carcinoma and lung adenocarcinoma. Preoperative size and type of tumor were determined by a preoperative chest computed tomography scan and cytological/histological analysis of obtained samples, while LVI status was determined by pathohistological analysis of resected tumor lung tissue. Receiver operating characteristic (ROC) curve analysis was performed to assess whether tumor size could serve as a reliable marker for LVI. P < 0.05 was considered statically significant. Results: A statistically significant difference in the frequency of tumor size (P = 0.580) along with LVI (P = 0.656) was not established between the patients with squamous cell lung cancer and lung adenocarcinoma. A ratio between the size of lung adenocarcinoma and LVI status (P < 0.001) was determined as statistically significant, while such a difference was not established in squamous cell lung cancer (P = 0.052). The ROC analysis revealed that tumor size >39 mm in patients with lung adenocarcinoma has obtained a sensitivity of 70.8% and a specificity of 60.9% to differentiate patients with a LVI (areas under the curve [AUC] = 0.70; 95% CI 0.60‒0.79; P < 0.001). A tumor size >4.6 cm in patients with squamous cell lung cancer obtained a sensitivity of 56.5% and a specificity of 60.3% to differentiate patients with a LVI (AUC = 0.59; 95% CI 0.50‒0.67; P = 0.043). Conclusion: The preoperative size of lung adenocarcinoma could be an acceptable marker of LVI presence in resected lung tissue, while in the squamous cell lung cancer, a potential biomarker role of the preoperative size of the tumor was inadequate.

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