AIMS: The aim of the study was to investigate the prognostic value of Ki-67 and histological grade in patients with estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative early breast cancer. Although the proliferation activity of different tumors assessed with antigen Ki-67 was extensively studied in the last decade and showed that Ki67 expression was a useful prognostic factor in breast cancer, there is still a controversy about the utility value of Ki-67. METHODS: The retrospective study covered the period from 2016 to 2022. Year included 106 patients from Brcko District, with early estrogen-positive and HER2 receptors-negative breast cancer. The average patients’ age was 62.37 ± 11.65 years. Patients were divided into groups with high/low Ki-67 and high/low histological grade. Multiple linear regression analysis was performed for disease relapse and mortality. RESULTS: Patients with high Ki-67 were more frequent postmenopausal, had higher histological grade, cancer ˂2 cm, more frequent lymph nodes’ metastases, more frequently underwent to axillary surgery, and had a higher mortality rate. Patients with high histological grade were older, more frequent postmenopausal, had more frequent metastases to the lymph nodes, more frequent occurrence of high Ki-67, more frequent relapse of disease, and more frequent of death. CONCLUSION: Combination of high Ki-67 with high histological grade in ER positive and HER2-negative early breast cancer is an important prognostic factor.

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.

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 Tešanj, 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.

Background: Pregabalin is a first-line therapy of pain with additional positive effects on the states of depression and anxiety that often occur in patients with chronic pain, thus improving their quality of life. Objective: The aim of this study was to demonstrate the efficacy of pregabalin in reducing neuropathic pain and improving quality of life in patients with peripheral and central chronic neuropathic pain in Bosnia and Herzegovina. Also, the aim was to monitor the safety of therapy with pregabalin. Methods: The study included patients with neuropathic pain lasting more than 3 months. Based on the underlying disease, patients were divided into 5 groups: DM–patients with diabetes mellitus, M–patients after stroke, D–patients with lower back pain, MS–patients with multiple sclerosis, and P group–patients with spinal cord injury. During the baseline visit, the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) was used to assess neuropathic pain. During two follow-up visits (1.5 and 3 months after baseline), the 36-Item Short-Form Health Survey (SF 36) was used to assess the effectiveness of therapy on quality of life. The safety of the treatment was evaluated by monitoring the incidence of adverse drug reactions. Results: The study included 125 patients. During treatment with pregabalin, there was a statistically significant reduction in pain intensity in the DM, M, D and MS groups. In group P, the decrease in pain intensity was not statistically significant (p = 0.070). There was a significant improvement in different parameters of the quality of life in all analyzed groups, with the most prominent effects in the DM group. The effectiveness of treatment was rated as “good” and “very good” in more than 70% of subjects in each group. The expected side effects of treatment were recorded in 27.1% of patients in the DM group, in 20.0% in the M group and in 22.2% in the MS group. Unexpected side effects of treatment were observed in one patient (2.1%) in the DM group. Assessment of tolerability of the applied treatment showed “good” and “very good” response in 68.7% of patients in DM group, 73.3% in M group, 74.5% in D group, 88.9% in MS group and 85.8% in P group. Conclusion: Pregabalin is a safe and effective drug in treatment of neuropathic pain of different etiology.

Aim To identify clinical and laboratory parameters on admission and/or during a hospital stay that would predict prolonged hospital stay in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods A retrospective cross-sectional study was conducted at the Clinic for Pulmonary Diseases and Tuberculosis, Clinical Centre University of Sarajevo for the period 2019-2021 accounting patients admitted due to AECOPD. The need for hospitalization was evaluated according to the current GOLD criteria and certain clinical parameters. Spirometry testing and laboratory analysis were performed for all patients on the day of admission and on the 10th day of hospital stay. Linear regression was used to show the relationship between multiple independent predictor variables and LOS. Results A total of 50 patients were evaluated during their hospital stay due to AECOPD. Median of LOS was 22.02±1.06, with 90% hospital survival rate. Due to AECOPD the median of LOS in the intensive care unit (ICU) was 4±0.68 days with pH<7.35 in 34% of hospitalized patients. According to spirometry classification on the day of admission, 56% of patients were assigned to group 3 and 16% to group 4 with significant improvement identified on spirometry findings on discharge. Platelets on the day of admission were the only statistically significant positive predictors of the length of hospital stay. Conclusion Identifying chronic obstructive pulmonary disease patients at risk of frequent exacerbations and appropriate disease management could reduce the disease burden.

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.

Background: Cardiovascular diseases (CVD) are the cause of 17 million deaths a year worldwide, of which 25% are sudden cardiac deaths (SCD). In Europe cardiovascular diseases (CVD) remains a leading cause of death in Europe accounting for 3.9 million deaths each year. Even with well-known risk factors and the current standards of health care, improvement of health and quality of life of CVD patients are still remains one of the biggest public health challenges we must overcome. Objective: The aim of this study was to analize of current strategic documents and relevant facts of WHO and other appropriate institutions regarding CVDs prevention and control for potentialy use in Bosnia and Herzegovina (B&H). Methods: Authors made a narrative review to provide a brief overview of the recent and relevant documents of good practice in prevention, diagnostic and therapeutic approaches of cardiovascular diseases that should be consider as milestones for the health authorities in the Federation of B&H. Results and Discussion: Bosnia and Herzegovina is among the countries with a high risk of CVD together with Albania, Croatia, Czech Republic, Estonia, Hungary, Kazakhstan, Poland, Slovakia, and Turkey. The main public health challenge in Bosnia and Herzegovina is reducing noncommunicable diseases (NCDs): heart disease, stroke, cancer, diabetes and chronic respiratory disease. NCDs are estimated to account for 80% of the country’s annual deaths, and addressing them is the foremost public health priority in the country. Cardiovascular diseases still represent a worldwide public health problem, with some new dimensions caused by challenges caused through pandemic of COVID-19. The well-known cardiovascular risk factors require new and more efficient public health approaches to the prevention and control. Conclusion: Due to the recently developed cardiovascular guidelines that were made by the European Society of Cardiology and World Heart Federation, key priority for health authorities should be is to update the existing CVD guidelines in the Federation of BiH in accordance with the international good practice to support healthcare professionals in their efforts to reduce the burden of cardiovascular disease in both individual patients, as well as at a population level..

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.