Aim To examine whether preoperative tumour size may serve as a biomarker for the occurrence of lymphovascular invasion (LVI) in centrally and peripherally located lung adenocarcinoma. Method The study included 261 patients surgically treated for diagnosed lung adenocarcinoma. A ROC curve was used to determine the biomarker potential of tumour size relative to the occurrence of LVI. Binary logistic regression was used to show changes of tumour size impact on the status of LVI. Result Tumour prevalence according to localization had no statistical significance (p=0.464), while the presence of LVI in central, as well as peripheral positions, was statistically significantly different (p<0.001). The area under the curve of 0.978 highlights the fact that tumour size is an excellent marker of the presence of LVI in centrally located adenocarcinomas of the lung. A similar finding was confirmed in peripherally located lung adenocarcinomas with an area below the curve of 0.943. Binary logistical regression showed that in centrally localized adenocarcinomas of the lung, each additional centimetre of tumour growth represents an increase in the likelihood of LVI+ by 17.14 times. In peripherally located adenocarcinomas of the lung, this increase in likelihood of LVI for each centimetre of growth was 5.46 times. Conclusion With a high degree of sensitivity and specificity, preoperative tumour size may serve as an important biomarker and positive predictor of the presence of LVI in lung adenocarcinoma of any location.

Aim To evaluate vertebral bone marrow adiposity (BMA) using magnetic resonance spectroscopy (MRS) in postmenopausal women and to determine an association of bone density with bone marrow fat content. Methods This cross-sectional study included 120 postmenopausal women referred for osteoporosis screening. All women underwent assessment of bone mineral density by dual X-ray absorptiometry (DXA), who were divided based on T scores into osteoporosis (OST; n=60) and control group (CG; n=60). MRS was used to measure fat fraction (FF), lipid/water ratio (LWR) and fat content (FC) at vertebral spine (L1-L4). Results Mean age, menopause or reproductive period duration was not significantly different between women in OST and control group. Median LWR in OST group was significantly higher compared to CG, 31.5 (22.9-38.8) vs. 28.7 (13.7-37.3) (p=0.039). Median FC was significantly higher in OST compared to the control group, 47.0 (46.3-78.8) and 46.4 (44.3-48.6), respectively (p=0.011). FC was significantly negatively associated with BMD at lumbar spine (Rho=-0.042; p<0.001) and with BMD at hip (Rho=-0.64; p<0.001). In logistic regression model, FC remained independently associated with osteoporosis after controlling for confounders (age, menopause duration, reproductive period duration and body mass index) (OR=1.3; 95% CI 1.1-1.6). Conclusion Bone marrow adiposity is an independent predictor of low bone mass in postmenopausal women suggesting its role as a therapeutic target in postmenopausal osteoporosis management.

Previous research suggested that several genetic polymorphisms are associated with increased risk of ischaemic stroke (IS) in young adults. However, the predictive biomarkers of IS in young adults are still unclear. Our aim was to assess the contribution of modifiable and genetic factors in IS in young adults. In total, 40 stroke patients and 40 healthy controls aged 20 to 50 years were recruited. Data on modifiable factors were collected, then participants were genotyped for seven SNPs linked to thrombophilia: ACE rs1799752, PAI-1 rs1799889, APOE rs1412 and rs429358, FV rs6025 and rs1800595, and FII rs62623459. Significantly increased risk factors: hypertension and dyslipidaemia in stroke patients compared with the controls: 50.0 % vs 27.5 % and 75.0 % vs 40.0% (P = 0.039 and P = 0.002, respectively) were observed. Stroke patients compared with controls did not differ in distribution of ACE, APOE, FV, and FII variants. The 4G4G homozygotes of the PAI-1 gene were significantly more prevalent in stroke patients compared to the controls: 42.5 % vs 17.5 %, (P = 0.033). In the group with the small vessel occlusion subtype of stroke, statistically significant overrepresentation of 4G4G homozygotes and frequency of the 4G allele compared with controls: 57.1 % vs 17.5 % and 0.7 vs 0.45 (P = 0.026 and P = 0.03, respectively) were observed. Independent predictors of stroke incident were: dyslipidaemia (OR (95% CI) = 4.2 (1.4-12.4)) and 4G4G genotype (OR (95% CI) = 3.9 (1.1-13.7)). These results confirm the contribution of dyslipidaemia and 4G4G genotype in the increased risk of IS in young Bosnian adults.

Introduction: Although many predictive tools have already been developed, efforts are still proceeding to identify a reliable biomarker to predict the prognosis of the patients with acute heart disorders. Objectives: The aim was to evaluate the role of renal injury biomarkers (serum cystatin C, serum and urine interleukin-18, IL-18) and heart failure biomarkers (plasma B-type natriuretic peptide, BNP) in the prediction of the postdischarge requirement of renal replacement therapy (RRT) and/or 6-month mortality in patients with acute heart disorders. Patients and Methods: In patients diagnosed with acute heart disorders (acute heart failure [AHF] and/or acute coronary syndrome [ACS]) and admitted to the intensive care units, baseline clinical parameters, renal and cardiac biomarkers were determined. Patients were followed up for 6 months. The composite outcome was the postdischarge requirement of RRT and/or 6-month mortality. Results: Of 120 patients, 5.8% continued RRT after discharge. The 6-month mortality was 20%. Cox logistic regression analysis showed that urine IL-18 (P=0.021), plasma BNP (P=0.046), Acute Physiology and Chronic Health Evaluation (APACHE) II score (P=0.002), and left ventricular diastolic dysfunction (P=0.045) were independent predictors of the postdischarge requirement of RRT and/or 6-month mortality. For predicting RRT and/or 6-month mortality, using urine IL-18 cutoff value of 29.1 pg/mL showed 66.7% sensitivity and 67.7% specificity (area under the curve, AUC 0.70, P=0.003), while using plasma BNP cutoff value of 881.6 pg/mL showed 66.7% sensitivity and 70.8% specificity (AUC 0.76, P<0.001). Conclusion: Urine IL-18 and plasma BNP are independently predictive for the postdischarge requirement of RRT and/or 6-month mortality in patients with acute heart disorders.

OBJECTIVES Although dual-energy X-ray absorptiometry (DXA) is gold standard for osteoporosis diagnosis, several reports have shown discordant T-score values measured by quantitative computed tomography (QCT) and DXA especially in obese subjects, but it is still not clear whether BMD measurement by two modalities is affected by overall obesity or central obesity in postmenopausal females. Therefore, the aims of this study were to compare BMD and T-scores by DXA and QCT and to evaluate whether these two osteoporosis assessment modalities yield different T-score values in postmenopausal females with obesity and central obesity. METHODS This cross-sectional study enrolled 44 postmenopausal females, referred for osteoporosis screening. Anthropometric indices (BMI-body mass index, WC-waist circumference and ICO-index of central obesity) were measured and females underwent assessment of bone mineral density by DXA and QCT. RESULTS Lumbar spine (LS) T-score values were significantly lower by DXA compared to qCT in females with BMI >25 kg/m2, (-1.9±1.5 vs. -2.3±1.2; p=0.039), in females with WC>88 cm(-1.9±1.5 vs. -2.4±1.2; p=0.008) and in females with ICO>0.5(-1.96±1.4 vs. -2.5±1.2; p=0.004). However, in normal weight females and in those without central obesity, LS T-scores by DXA were not different than qCT. DXA at lumbar spine and proximal femur revealed osteoporosis in 47.7% and 11.4% respectively, while QCT detected osteoporosis in 61.4% of females (p<0.001). Measures of central obesity; ICO and WC were not associated with QCT bone mineral density (BMD) (r=0.14 and r=0.21, respectively), but were positively associated both with DXALS BMD (r=0.29 and r=0.31; p<0.05) and DXA proximal femur BMD (r=0.41 and r=0.44; p<0.01). CONCLUSION Our results suggest that obesity is associated with lower T-scores by DXA compared to QCT. Caution is needed when assessing osteoporosis status in obese postmenopausal females. However, further studies with larger sample size are needed to confirm the findings.

Introduction: Hypertension is significantly contributing to global mortality and morbidity and has been identified as the most important modifiable risk factor for early development of cardiovascular diseases (CVD). Aim: The aim of this study was to investigate the efficacy of different combinations of antihypertensive therapy on blood pressure, arterial stiffness and peripheral resistance in patients with essential hypertension using the brachial oscillometric ambulatory blood pressure monitor. Methods: This study was designed as an observational, prospective, multi centric study conducted in eight primary care centers of the Health Center of Canton Sarajevo during the period of six months. The study included 655 participants, both genders, aged between 30 and 75, who were diagnosed with hypertension according to the ESC/ESH guidelines. Participants were divided into six treatment groups based on the hypertensive drug therapy they were using; lisinopril, losartan or valsartan alone or in combination with hydrochlorothiazide (A, B and C group respectively) or combination of lisinopril, losartan or valsartan with/without hydrochlorothiazide together with amlodipine (D, E and F respectively). The participants were monitored at baseline, after 3 and 6 months (1st and 2nd follow-up). Brachial oscillometric ambulatory blood pressure monitor was used for measuring systolic (SBP), diastolic (DBP), pulse pressure (PP), pulse wave velocity (PWV) and peripheral resistance (PR). Results: SBP, DPB, PP, and PWV significantly decreased from baseline to 2nd follow-up in all treatment groups. The mean reductions in SBP were from -11.7 (95%CI; 9.3- 14.1) to -23.2 (95%CI; 18.3-28.1) mmHg and DBP reductions varied from -5.5 (95%CI; 3.9- 7.1) to -13.4 (95%CI; 7.7-19.1) mmHg. PWV decreased in all treatment groups (from -3.3% to -8.2%). Treatment regiment was not associated with significant differences in SBP, DBP, PP or PWV reductions or their values measured at 2nd follow-up. Peripheral resistance significantly decreased only in group C (p=0.011), group D (p=0.009) and group F (p=0.027). Conclusion: These data suggest that lisinopril/lisinopril + hydrochlorothiazide, losartan/losartan + hydrochlorothiazide and valsartan/valsartan + hydrochlorothiazide alone or in combination with amlodipine are equally effective and well tolerated for the reduction of both systolic and diastolic blood pressure and improve arterial stiffness in patients with essential hypertension.

Introduction: Poor glycemic control, assessed by higher glycated hemoglobin (HbA1c) levels, is associated with greater risk of diabetic complications. Aim: The aim of this study was to assess the association of triglyceride - to - HDL cholesterol (TG/HDL-C) ratio and triglyceride glucose (TyG) index with HbA1c and to evaluate their potential role as predictors of glycemic control in patients with diabetes mellitus type 2 (DM2). Patients and methods: This cross-sectional study was conducted in Health Center Banovici and included a total of 113 patients with DM2 classified according to their HbA1c values in two groups: DM2 HbA1c <7% - DM2 patients with good glycemic control (n=39) and DM2 HbA1c ≥7% - DM2 patients with poor glycemic control (n=74). Anthropometric, biochemical parameters and blood pressure values were measured, while TG/HDL-C ratio and TyG index were calculated. Results: TG/HDL-C ratio and TyG index were significantly higher in DM2 HbA1c≥7% compared to DM2 HbA1c<7% group (p=0.003 and p<0.001; respectively). Both TG/HDL-C ratio and TyG index were positively associated with HbA1c levels (Rho=0.29; p=0.002; Rho=0.37; p<0.001; respectively). In linear regression analysis TG/HDL-C ratio and BMI, and also TyG index and BMI were significantly independently associated with HbA1c even after controlling for age, gender, diabetes duration and smoking. When we stratified patients according to BMI values, independent association between TG/HDL-C ratio and HbA1c remained significant only in normal weight subjects (OR 0.21; 95%CI: 0.05-0.37; β=0.65; p=0.017), while independent association between TyG index and HbA1c remained significant only in overweight and obese subjects (OR 0.063; 95%CI: 0.01- 0.12; β=0.24; p =0.027). Conclusion: TG/HDL-C ratio might be a useful predictor of glycemic control in normal weight, and TyG index in overweight and obese patients with DM2.

INCREASED BONE TURNOVER IN OBESE POSTMENOPAUSAL FEMALES

AN IMPACT OF DIABETES DURATION ON SERUM ASYMMETRIC DIMETHYLARGININE CONCENTRATION

Introduction: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. Aim: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. Results: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). Conclusions: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

AIM To assess the utility of gamma-glutamyl transferase (GGT) and C-reactive protein (CRP) in predicting troponin elevation in patients with acute coronary syndrome. PATIENTS The total of 119 patients were divided into troponin-positive (n = 61) and troponin-negative (n = 58) patients. RESULTS CRP cut-off value ≥13.4 mg/l had the sensitivity of 68.1% and specificity of 62.5%, while the GGT cut-off value ≥61.5 IU/l had the sensitivity of 66.0% and specificity of 62.0% and combined use of both CRP and GGT had 71.4% sensitivity and 69.6% specificity in predicting troponin increase in acute coronary syndrome patients. CONCLUSION GGT might be used as an adjuvant marker for risk assessment patients who present with chest pain and are suspected to have acute coronary syndrome.

The relationship between genetic risk factors of thrombophilia and pregnancy loss (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Although, the frequencies of these polymorphisms were reported in different populations, such studies have not yet been performed in Bosnian population. In this study, we determined the prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133) polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (±5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age 31.4 (±6.7) years] with at least one live-born child were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was significantly higher in women with venous thrombosis (VT) compared to women without VT (p = 0.047 and p = 0.001, respectively). There was no significant difference in the distribution of MTHFR genotypes and alleles between these two groups. In addition, we observed no significant differences in the genotype and allele frequencies between the group with PL and control group, for all investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2), and 677T (MTHFR) reported in this study are consistent with the data obtained for other European countries, however, we were not able to confirm the association between the three polymorphisms and PL in Bosnian women.

Aim To investigate total homocysteine (tHcy) serum concentration in patients with probable vascular dementia (VD) and in agematched controls, as well as to determine an association between tHcy serum concentration and cognitive impairment in patients with probable VD. Methods Serum concentration of tHcy was determined by the Fluorescence Polarization Immunoassay on the AxSYM System. Cognitive impairment was tested by the Mini Mental Status Examination (MMSE) score. Body mass index (BMI) was calculated for each subject included in the study. Results Age, systolic, diastolic blood pressure and BMI did not differ significantly between the two groups. Mean serum tHcy concentration in the control group of subjects was 13.35 µmol/L, while in patients with probable VD it was significantly higher, 19.45 µmol/L (p=0.002). A negative but insignificant association between serum tHcy concentration and cognitive impairment in patients with probable VD was found. Conclusion Increased tHcy concentration in patients with probable VD suggests the possible independent role of Hcy in the pathogenesis of VD.

Abstract Background: The ε2, ε3 and ε4 alleles of APOE gene have been associated with several diseases in different populations. Data on the frequency of alleles are used in both a clinical and evolutionary context. Although the data on frequency of these alleles are numerous, there are no reports for the population of Bosnia and Herzegovina. Aim: To estimate the frequency of APOE alleles in a healthy Bosnian population and compare it to data for other European populations. Subjects and Methods: Overall, 170 unrelated Bosnian subjects (108 female and 62 male), aged 53.0 (±5.0) years were included in this study. Genotypes were determined by real-time PCR. Results: In our group the prevalence of heterozygotes E2/E3, E2/E4 and E3/E4 was 20.6%, 3.5% and 12.9%, respectively, while the prevalence of homozygotes E2/E2, E3/E3, E4/E4 was 0.6%, 61.2% and 1.2%, respectively, with a mean frequency of ε2, ε3 and ε4 alleles of 12.6%, 78.0% and 9.4%, respectively. Conclusions: In studied European populations we observed a linear, gradually increasing trend in the frequency of ε4 allele from South to North (Pearson’s test 0,7656, p value <0.00001), and the Bosnian population fits into this pattern perfectly.