Association of ACE2 and TMPRSS2 genes variants with disease severity and most important biomarkers in COVID-19 patients in Bosnia and Herzegovina.

AIM: To assess the association of single nucleotide polymorphisms (SNPs) in the ACE2 and TMPRSS2 genes with COVID-19 severity and key biomarkers. METHODS: The study involved 750 COVID-19 patients from Bosnia and Herzegovina, divided into three groups: mild, moderate, and severe cases. Genetic variations within the ACE2 (rs2285666) and TMPRSS2 (rs2070788) genes were examined with real-time polymerase chain reaction. Biochemical markers were determined with standard procedures. RESULTS: There was a significant difference in the rs2070788 genotype distribution between patients with mild and moderate symptoms, but not between other groups. For the rs2285666 polymorphism, no significant difference in genotype distribution was found. In patients with mild symptoms, carriers of the GG genotype of rs2070788 had significantly higher total bilirubin levels than carriers of the AA genotype. Similarly, carriers of the TT genotype of rs2285666 had significantly higher activated partial thromboplastin time and international normalized ratio, and lower lactate dehydrogenase levels compared with the CC genotype. Among patients with severe symptoms, carriers of the GG genotype showed significantly higher potassium levels than carriers of the AA genotype, while carriers of the TT genotype showed significantly higher erythrocyte count as well as hemoglobin and hematocrit levels compared with the CC genotype. CONCLUSION: This study highlights the role of genetic factors, particularly SNPs in the ACE2 and TMPRSS2 genes, in determining COVID-19 severity, aiding patient risk assessment and prognosis.

Testing of Anesthesia Machines and Defibrillators in Healthcare Institutions.

To improve the quality of patient treatment by improving the functionality of medical devices in healthcare institutions. To present the results of the safety and performance inspection of patient-relevant output parameters of anesthesia machines and defibrillators defined by legal metrology. This study covered 130 anesthesia machines and 161 defibrillators used in public and private healthcare institutions, during a period of two years. Testing procedures were carried out according to international standards and legal metrology legislative procedures in Bosnia and Herzegovina. The results show that in 13.84% of tested anesthesia machine and 14.91% of defibrillators device performance is not in accordance with requirements and should either have its results be verified, or the device removed from use or scheduled for corrective maintenance. Research emphasizes importance of independent safety and performance inspections, and gives recommendations for the frequency of inspection based on measurements. Results offer implications for adequacy of preventive and corrective maintenance performed in healthcare institutions. Based on collected data, the first digital electronical database of anesthesia machines and defibrillators used in healthcare institutions in Bosnia and Herzegovina is created. This database is a useful tool for tracking each device's performance over time.

Effect of Cigarette Smoking on Haematological Parameters in Healthy Population.

OBJECTIVE: Tobacco cigarette smoking is one of the major leading causes of death throughout the world. Smoking has both acute and chronic effect on haematological parameters. The aim of the present study was to assess the extent of adverse effects of cigarette smoking on biochemical characteristics in healthy smokers. SUBJECTS AND METHOD: One hundred and fifty six subjects participated in this study, 56 smokers and 100 non-smokers. The smokers were regularly consuming 10-20 cigarettes per day for at least 3 years. Complete blood cell count was analyzed by CELL-DYN 3700 fully automatic haematological analyzer. RESULTS: The smokers had significantly higher levels of white blood cell (p<0,001), hemoglobin (p=0,042), mean corpuscular volume (p=0,001) and mean corpuscular hemoglobin concentration (p<0,001). All other measured parameters did not differ significantly. Cigarette smoking caused a significant increase (p<0,001) in red blood cells, white blood cells (p=0,040), hemoglobin (p<0,001), hematocrit (p=0,047) and mean corpuscular hemoglobin (p<0,001) in males in comparison to female smokers. CONCLUSION: In conclusion, our study showed that continuous cigarette smoking has severe adverse effects on haematological parameters (e.g., hemoglobin, white blood cells count, mean corpuscular volume, mean corpuscular hemoglobin concentration, red blood cells count, hematocrit) and these alterations might be associated with a greater risk for developing atherosclerosis, polycythemia vera, chronic obstructive pulmonary disease and/or cardiovascular diseases.

Y Chromosome Story-Ancient Genetic Data as a Supplementary Tool for the Analysis of Modern Croatian Genetic Pool.

Due to its turbulent demographic history, marked by extensive settlement and gene flow from diverse regions of Eurasia, Southeastern Europe (SEE) has consistently served as a genetic crossroads between East and West and a junction for the migrations that reshaped Europe's population. SEE, including modern Croatian territory, was a crucial passage from the Near East and even more distant regions and human populations in this region, as almost any other European population represents a remarkable genetic mixture. Modern humans have continuously occupied this region since the Upper Paleolithic era, and different (pre)historical events have left a distinctive genetic signature on the historical narrative of this region. Our views of its history have been mostly renewed in the last few decades by extraordinary data obtained from Y-chromosome studies. In recent times, the international research community, bringing together geneticists and archaeologists, has steadily released a growing number of ancient genomes from this region, shedding more light on its complex past population dynamics and shaping the genetic pool in Croatia and this part of Europe.

Principal component analysis of the oxidative stress, inflammation, and dyslipidemia influence in patients with different levels of glucoregulation.

Background: The aim of the study was to explore the mutual relationship between oxidative stress, inflammation and metabolic biomarkers in subjects with prediabetes (PRE), newly diagnosed type 2 diabetes patients (NT2D) and overt type 2 diabetes (T2D) using principal component analysis (PCA) as a thorough statistical approach. Methods: Glycated hemoglobin, lipid parameters, inflammation (IL-6, CRP and fibrinogen) and oxidative stress markers pro-oxidants (AOPP, PAB, TOS) and antioxidants (PON1, tSHG, TAS) were measured. PCA was applied to explore the factors that the most strongly influenced glucoregulation. Results: A total of 278 subjects were (i.e., 37 PRE, 42 NT2D and 99 T2D) were compared with 100 healthy subjects as a control group (CG). PCA emphasized 4 different factors explaining 49% of the variance of the tested parameters: oxidative stress-dyslipidemia related factor (with positive loading of TG and tSHG, and with negative loading of HDL-c and TAS), dyslipidaemia related factor (i.e., total cholesterol and LDL-c, both with positive loading), Anthropometric related factor (i.e., waist and hip circumference, both with positive loading) and oxidative stressInflammation related factor (i.e., PAB, fibrinogen, and CRP all with positive loading). Out of these 4 factors, only oxidative stress - dyslipidaemia related factor showed a significant predictive capability towards poor glucoregulation. An increase in this factor by one unit showed a 1.6 times higher probability for poor glucoregulation. Conclusions: Redox imbalance (determined with lower TAS and higher tSHG), in addition to higher TG and lower HDLc was associated with poor glucoregulation.

Evaluation of the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols Using Inflammatory Markers.

Background: The pathophysiology and therapy of coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are a dilemma for scientists and health professionals, and the fact that patients show different symptoms and severity of the clinical picture also contributes to that. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of immunomodulators) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring inflammatory markers (ESR and CRP), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Inflammatory markers [ESR (erythrocyte sedimentation rate), CRP (C-reactive protein)] were examined on three occasions: twice during hospitalization and once after hospital discharge. Immunomodulators used intrahospital were corticosteroids (methylprednisolone, dexamethasone, methylprednisolone + dexamethasone), tocilizumab or metenkefalin/tridecactide. Posthospital, patients were taking either methylprednisolone or did not use any immunomodulators. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis and Wilcoxon Signed-Rank) were applied and effect size (ES) was calculated. Results: Three corticosteroid therapies used intrahospital caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture, but the ES was the biggest with methylprednisolone + dexamethasone, then dexamethasone, and lastly methylprednisolone. Posthospital, methylprednisolone caused a significant decrease in both inflammatory markers, especially in patients with a severe clinical picture. The most common comorbidity in all patients, as well as in patients with a severe clinical picture, was hypertension. There was no statistically significant impact of the number of comorbidities patients had on ESR and CRP, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of immunomodulators, especially methylprednisolone + dexamethasone intrahospital and methylprednisolone posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the immune response. There is also a positive correlation between the number of comorbidities patients have and the severity of the clinical picture.

The Use of Coagulation Markers to Evaluate the Effectiveness of Coronavirus Disease (COVID-19) Therapeutic Protocols.

Background: Patients infected by coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), display various symptoms and severity of the clinical picture. Thus, the therapy and pathophysiology of this disease are a dilemma for health professionals and scientists. Objective: This paper aims to evaluate the effectiveness of therapeutic protocols (the use of anticoagulants) in the treatment of COVID-19 patients of various severity of the clinical picture by monitoring coagulation markers (PT, INR, aPTT and D-dimer), as well as the impact of the type and number of comorbidities patients had on these markers. Methods: A total of 200 patients with a mild (n=76), moderate (n=70) or severe (n=54) clinical picture was included. Coagulation markers [PT (prothrombin time), INR (international normalized ratio), aPTT (activated partial thromboplastin time), D-dimer] were examined on three occasions: twice during hospitalization and once after hospital discharge. Anticoagulants used intrahospital were fraxiparine, rivaroxaban or unfractionated heparin. Posthospital, patients were taking either rivaroxaban or did not use any anticoagulants. For statistical analysis, SPSS 26.0 and Microsoft Excel 2019 were used, with a level of significance of α=0.05. Nonparametric tests (Kruskal-Wallis, Wilcoxon Signed-Rank and Bonferroni) were applied and effect size (ES) was calculated. Results: Three anticoagulants used intrahospital caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture, but the ES was the biggest with fraxiparine, then rivaroxaban, and lastly unfractionated heparin. Posthospital, rivaroxaban caused a significant decrease in PT, INR and D-dimer and a significant increase in aPTT, especially in patients with a severe clinical picture. Hypertension was the most common comorbidity in all patients, as well as in patients with a severe clinical picture. There was a statistically significant impact of the number of comorbidities patients had on D-dimer, and none on PT, INR and aPTT, but the highest number of comorbidities was in patients with a severe clinical picture. Conclusion: The use of anticoagulants, especially fraxiparine intrahospital and rivaroxaban posthospital, is justified in most COVID-19 cases as there is a significant correlation between this disease's pathophysiology and the coagulation process. There is also a positive correlation between the severity of the clinical picture and the number of comorbidities patients have.

Application of artificial intelligence for the classification of the clinical outcome and therapy in patients with viral infections: The case of COVID-19.

BACKGROUND: With the end of the coronavirus disease 2019 (COVID-19) pandemic, it becomes intriguing to observe the impact of innovative digital technologies on the diagnosis and management of diseases, in order to improve clinical outcomes for patients. OBJECTIVE: The research aims to enhance diagnostics, prediction, and personalized treatment for patients across three classes of clinical severity (mild, moderate, and severe). What sets this study apart is its innovative approach, wherein classification extends beyond mere disease presence, encompassing the classification of disease severity. This novel perspective lays the foundation for a crucial decision support system during patient triage. METHODS: An artificial neural network, as a deep learning technique, enabled the development of a complex model based on the analysis of data collected during the process of diagnosing and treating 1000 patients at the Tesanj General Hospital, Bosnia and Herzegovina. RESULTS: The final model achieved a classification accuracy of 82.4% on the validation data set, which testifies to the successful application of the artificial neural network in the classification of clinical outcomes and therapy in patients infected with viral infections. CONCLUSION: The results obtained show that expert systems are valuable tools for decision support in healthcare in communities with limited resources and increased demands. The research has the potential to improve patient care for future epidemics and pandemics.

Knowledge and Attitudes regarding Covid-19 Vaccination among Medical and Non-medical Students in Bosnia and Herzegovina.

OBJECTIVE: The aim of this study was to investigate students' knowledge, attitudes and hesitancy regarding COVID-19 vaccination. METHODS: A cross-sectional questionnaire-based survey was conducted among a total of 1282 medical students and 509 non-medical students at four public universities in Bosnia and Herzegovina: Tuzla, Sarajevo, Banja Luka, and Mostar. RESULTS: A significantly higher rate of vaccination was observed in the group of medical students as well as a higher level of knowledge about vaccination in general and vaccines against the COVID-19 disease. Students who received the COVID-19 vaccine had a higher level of knowledge about vaccination in general and COVID-19 vaccines in particular compared to the non-vaccinated students in the medical and non-medical groups, respectively. Furthermore, vaccinated students, regardless of the course they are taking, showed generally stronger positive attitudes compared to non-vaccinated students, regarding the safety and effectiveness of the COVID-19 vaccine. Both groups of students believe that the rapid development of the vaccine is contributing to refusal or hesitancy to receive a vaccine against COVID-19. Social media/networks were the main sources of information about the COVID-19 vaccine. We did not find any contribution of social media to the reduced level of COVID-19 vaccine coverage. CONCLUSION: Education of students about the benefits of the COVID-19 vaccine will lead to its better acceptance as well as the development of more positive attitudes towards vaccination in general, especially having in mind that students are the future population of parents, who will make decisions about vaccinating their children.

Identification of human genetic variants modulating the course of COVID-19 infection with importance in other viral infections.

Introduction: COVID-19 has been a major focus of scientific research since early 2020. Due to its societal, economic, and clinical impact worldwide, research efforts aimed, among other questions, to address the effect of host genetics in susceptibility and severity of COVID-19. Methods: We, therefore, performed next-generation sequencing of coding and regulatory regions of 16 human genes, involved in maintenance of the immune system or encoding receptors for viral entry into the host cells, in a subset of 60 COVID-19 patients from the General Hospital Tesanj, Bosnia and Herzegovina, classified into three groups of clinical conditions of different severity ("mild," "moderate," and "severe"). Results: We confirmed that the male sex and older age are risk factors for severe clinical picture and identified 13 variants on seven genes (CD55, IL1B, IL4, IRF7, DDX58, TMPRSS2, and ACE2) with potential functional significance, either as genetic markers of modulated susceptibility to SARS-CoV-2 infection or modifiers of the infection severity. Our results include variants reported for the first time as potentially associated with COVID-19, but further research and larger patient cohorts are required to confirm their effect. Discussion: Such studies, focused on candidate genes and/or variants, have a potential to answer the questions regarding the effect of human genetic makeup on the expected infection outcome. In addition, loci we identified here were previously reported to have clinical significance in other diseases and viral infections, thus confirming a general, broader significance of COVID-19-related research results following the end of the pandemic period.

Association of trace element status in COVID-19 patients with disease severity.

Caused by the new SARS-CoV-2 coronavirus, COVID-19 (coronavirus disease 2019) evolves with clinical symptoms that vary widely in severity, from mild symptoms to critical conditions, which can even result in the patient's death. A critical aspect related to an individual response to SARS-CoV-2 infection is the competence of the immune system, and it is well known that several trace elements are essential for an adequate immune response and have anti-inflammatory and antioxidant properties that are of particular importance in fighting infection. Thus, it is widely accepted that adequate trace element status can reduce the risk of SARS-CoV-2 infection and disease severity. In this study, we evaluated the serum levels of Cu, Zn, Se, Fe, I and Mg in patients (n = 210) with clinical conditions of different severity ("mild", "moderate", "severe" and "exitus letalis", i.e., patients who eventually died). The results showed significant differences between the four groups for Cu, Zn, Se and Fe, in particular a significant trend of Zn and Se serum levels to be decreased and Cu to be increased with the severity of symptoms. For Mg and I, no differences were observed, but I levels were shown to be increased in all groups.

IgG N-glycome changes during the course of severe COVID-19: An observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation. METHODS: Using ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78). FINDINGS: Multiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19. INTERPRETATION: The IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19. FUNDING: This work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Interaction between Omeprazole and Gliclazide in Relation to CYP2C19 Phenotype.

The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4-1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.

Clinical use of an analysis of oxidative stress and IL-6 as the promoters of diabetic polyneuropathy.

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.

Chest x-ray resolution after SARS-CoV-2 infection.

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.

Relevance of uric Acid in progression of type 2 diabetes mellitus.

Recent studies have introduced serum uric acid (UA) as a potential risk factor for developing diabetes, hypertension, stroke, and cardiovascular diseases. The value of elevated levels of UA in serum as a risk factor for diabetes development is still under scrutiny. Recent data suggest that clearance of UA is being reduced with increase in insulin resistance and UA as a marker of prediabetes period. However, conflicting data related to UA in serum of patients with Type 2 diabetes prompted us to study the urine/serum ratio of UA levels (USRUA) in these patients and healthy controls. All subjects included in the study were free of evidence of hepatitis B or C viral infection or active liver and kidney damage. Patients receiving drugs known to influence UA levels were also excluded from this study. Analysis of glucose and uric acid were performed on Dade Behring analyzer using standard IFCC protocols. Interestingly, our data demonstrated about 2.5 fold higher USRUA values in diabetic patients as compared to control subjects. Furthermore, there was a trend of correlation of USRUA value with the blood glucose levels in diabetic patients, which was more prominent in diabetic men than in women. With aging, levels of uric acid increased in serum of diabetic patients, and this effect was also more profound in male than in female diabetics. In conclusion, this study showed significantly elevated USRUA levels in patients with Type 2 diabetes, a negative USRUA correlation with the blood glucose levels in diabetic patients, and an effect of sex and age on the uric acid levels. Since literature data suggest a strong genetic effect on UA levels, it would be pertinent to perform further, possibly genetic studies, in order to clarify gender and ethnic differences in UA concentrations.

Use of chest CT scan scoring system for diagnostic and therapeutic decision making in pleural effusion.

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.

Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes.

The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.

Association of FTO Gene Variant (rs8050136) with Type 2 Diabetes and Markers of Obesity, Glycaemic Control and Inflammation.

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 Tesanj 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.

Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina.

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.