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.

Severe acute respiratory syndrome novel coronavirus (SARS-CoV-2) has rapidly progressed from an outbreak to a global pandemic, with new variants emerging rapidly. Coronavirus disease 2019 (COVID-19), a disease caused by SARS-CoV-2 infection, can lead to multiorgan damage. Due to the highly contagious and fatal nature of the virus, the priority of medical research has been to find effective treatments. Amid this search, the role of vitamin D in modulating various aspects of the innate and adaptive immune system has been debated.The aim of the work: research on the role of vitamin D in the treatment and prevention of COVID-19. Although there are some conflicting results, the consensus is that vitamin D has a number of immunomodulatory effects that may be beneficial in the context of COVID-19 and that low vitamin D levels may result in dysfunction of key antimicrobial effects, potentially contributing to a poor prognosis. The aim of the paper is to investigate the impact and importance of vitamin D in patients with the corona virus.Work methods: During this retrospective study, data were taken from the Registry of those tested for the presence of the SARS-CoV2 virus, Specialist Center "Health House" in Bijeljina. The research included 30 patients positive for the presence of the SARS-CoV2 virus and 30 patients negative for the presence of the SARS-CoV2 virus. The following parameters were observed in the research: age, gender and vitamin D values, data on the body temperature of the patients and the duration of the disease, as well as the obtained results of the inflammatory parameters (Leukocytes and C- reactive protein CRP). The dana of all patients are anonymous. All patients were tested using the molecular method of polymerase chain reaction known as RT-PCR (Reverse transcription polymerase chain reaction). Separate samples were tested with Arhitectt Vitamin D reagent by the chemiluminescence method (CMIA), manufactured by Abott Arhitectt and 1000sr. Reference values of Vitamin D are from 75 to 150 nmol/L.Results: The concentration of vitamin D was lower in the group of patients with the coronavirus disease (COVID-19) compared to individuals with the absence of the coronavirus disease. There is a tendency towards a negative correlation between the concentration of vitamin D and the duration of the disease in the group of patients with the coronavirus disease (COVID-19), as like as the concentration of vitamin D and body temperature in the group of patients with the coronavirus disease (COVID-19). There is also a tendency towards a negative relationship between the concentration of vitamin D and parameters of inflammation (CRP, Le) in the group of patients with coronavirus disease (COVID-19).

Background: Pancreaticoduodenectomy (PD) known as Whipple procedure is still one of the most complex abdominal surgeries used for treatment of periampullary tumors. PD is often followed with postoperative complications (pancreatic, biliar or intestinal fistula, haemorrhage, intraabdominal abscess, delayed gastric empting. Severe postoperative complications (SPC) can be reason for reoperation and reason of bad outcome of treatment and life treathening condition. Objective: To investigate predicitive value of preoperative hypoalbuminemia for severe postoperative complications (SPC) in patients who have undergone Whipple pancreaticoduodenetomy (PD). However, no similiar study has been ever reported from our country until now. Methods: In this retrospective-prospective study, 100 patients who have had Whipple pancreaticoduodenectomy for malignant periampullary tumors at the Department for Surgery of University Clinic Center Tuzla, Bosnia and Herzegovina were enrolled, from january of 2009 to decembre of 2021. All patients were preoperatively analysed according to serum albumine levels and presensce of hypolabuminemia (serum albumine levels <32g/l). Serum albumine biochemical test were done 1-2 days preoperatively. Clavien Dindo classification was used for determination patients with SPC. Patients who did not have SPC belonged to (I-II) Clavien Dindo group of patients while those who had SPC belonged to( III-V) Clavien Dindo group of patients. Results: Out of 100 patients who have undergone pancreaticoduodenetomy, in 55 (55%) patients postoperative complications were noticed. Mortality rate was 18 (18%) and reoperation has been done in 20 cases (20%). SPC were noticed in 19 patients and most often were: delayed gastric emptying (20%), pancreatic fistula (13%) and intraabdominal collections (9%). Hypoalbuminemic patients had a significantly higher rate of severe postoperative complications ( p<0.05). Using hypoalbuminemia-SPC correlation analaysis, there is confirmed statistically significant correlation between hypoalbuminemia and SPC (ρ= 0.236; p<0.05). Conclusion: Preoperative hypoalbuminemia can be used as predictor and prognostic factor for severe postoperative complications after Whipple pancreaticoduodenectomy. Identification and optimization of serum albumin level prior to Whipple pancreatoduodenectomy may improve surgical outcomes.

Aim: To evaluate the incidence, characteristics, transmission, and outcomes of COVID-19 infection in hospitalized neonates in Tuzla Canton and to emphasize the importance of quality triage in the prevention and control of infection. Material and Methods: A retrospective cohort study, which included all consecutive neonates suspected of COVID-19 infection, and which required screening supervision in the triage department, from those who required hospital treatment at the Pediatric Clinic, University Clinical Center Tuzla for 12 months. (January 1 to December 31, 2020). Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results: In the observed period, in the neonatal triage department, 111 neonates suspected to COVID-19 were treated, with no gender difference. Among them were 92 neonates of mothers suspected of COVID-19 (66 admitted immediately after birth, 26 readmitted after discharge home), and 19 neonates of mothers positive for COVID-19 (16 admitted immediately after birth, 3 readmitted). Cesarean delivery was a more common delivery option, and fever a more common symptom in COVID-19 positive mothers, but without statistical significance. The neonates from COVID-19 suspected mothers formed a heterogeneous group, with common perinatal problems, while neonates from COVID-19 positive mothers, hospitalized immediately after birth, were almost term neonates with appropriate birth weight, without need for a lot of treatment. All neonates hospitalized immediately after birth were negative for COVID-19.  The only three COVID-19 positive neonates were readmitted after previous discharge home, and they had mild symptoms, mostly one-day fever, and they all recovered completely. All of these neonates are under further follow-up after discharge from the hospital, and all are, for now, in good general condition, and all have continued to breastfeed. Conclusion: Neonates born to mothers with positive COVID-19 infection generally have favorable outcomes, with no convincing case of vertical transmission. Neonatal COVID-19 is mostly asymptomatic, acquired postnatally, and associated with favorable outcomes. The importance of quality triage in the prevention and control of infection is crucial, with consistent implementation of safe practices including proper patient isolation and appropriate protective equipment.

Sepsis is a life-threatening condition characterized by a systemic inflammatory response of the body caused by a severe infection. The aim of this study was to examine the importance of hematological parameters and c-reactive protein (CRP) in the diagnosis of sepsis, assessment of disease severity, and prediction of final outcome of these patients. The prospective study included 106 hospitalized patients with a clinical diagnosis of sepsis. Haematological parameters and CRP correlated with sepsis stage, and using ROC (Receiver operating characteristic) analysis were evaluated in the prediction of the final outcome of these patients. Among haematological parameters, patients with sepsis had a significantly higher proportion of total unsegmented neutrophil granulocytes, a lower percentage of lymphocytes, as well as a lower total platelet count (p<0.05 for all measurements). An excellent positive correlation was found between serum CRP concentration and disease stage (r=0.77). The best predictive value for the presence of sepsis was shown by CRP at the cut- off value of 165 mg/L (AUC 0.98), followed by the percentage of unsegmented neutrophil granulocytes for the cut-off value of 15.5 (AUC 0.67), and the percentage of lymphocytes less than 9.9 (AUC 0.66), platelets lower than 118x109/L (AUC 0.63). At the CRP cut-off value of 294.7 mg/L (AUC 0.84; 95% CI 0.74-0.93), death could be predicted in 80.95% of patients with sepsis, with the sensitivity of 43.75% and the specificity of 89.71% (p<0.0001). By monitoring changes in haematological parameters and CRP concentration in combination with other clinical and laboratory indicators, disease severity and final outcome in patients with sepsis can be predicted. Key words: CRP, lymphocytes, platelets, SIRS, sepsis

Aim To determine the degree of accuracy in determining the sex of the skull based on classical morphometric analysis of the mastoid process. Morphometric analysis excluded a subjective approach expressed in osteoscopic analysis. Methods The study was conducted on a sample of 100 macerated skulls of known gender and age from the second half of the 20th century, including the Bosnian population. Of the 100 skulls, 50 (50%) were male and 50 (50%) were female. Male skulls were on average 60 (47-71) years old and female 57 (43-76) years old. At each mastoid process, 3 measurements were made: mastoid length, mastoid width (medio-lateral diameter) ML) and anteroposterior diameter (AP) of the mastoid process. Results Using the univariate method, we found a significant difference between length, width, AP diameter and size of mastoid processes as well as between gender (p <0.05). Multivariate binary logistic regression showed statistically significant differences in AP diameter of the mastoid process (p<0.05). Conclusion The created model "P" ("P"=exp [X]/1+exp [X]) for sex determination based on mastoid process showed sensitivity of 82% correct prediction for female skulls and 65% accurate prediction for male skulls. This discourse with respect of population standards grants most effective anthropological proof and as such may be suggested for forensic expertise based on human skull.

Aim Steady progress in intensive treatment worldwide has increased the survival of immature neonates, but with multiple invasive procedures, which have increased the risk of infection, thus the bacterial resistance to antibiotics. The aim of this study was to analyse the epidemiology of multidrug resistance pathogens as causative agents of neonatal sepsis in the neonatal intensive care unit. Methods A retrospective cohort study conducted at the Intensive care unit of the Paediatric Clinic of Tuzla over a three-year period (2016-2018) analysed epidemiology of neonatal sepsis caused by multidrug resistance pathogens. Statistical analysis applied standard methods, and the research was approved by the Ethics Committee of the institution. Results Of the total of 921 treated neonates, multidrug resistance (MDR) pathogens among causative agents of neonatal sepsis were found in 22 neonates (2.38%) with no gender difference. Prematurity and low birth weight were confirmed as the most significant risk factors. From the maternal risk factors a significant difference was found in the first birth and in vitro fertilization. Clinically, MDR sepsis manifested frequently as late onset sepsis, with longer hospital stay and higher mortality. The findings of leukopenia, thrombocytopenia and coagulation disorders were significant. Gram negative bacteria were frequently isolated, in particular Acinetobacter, which showed the greatest resistance to antibiotics. Conclusion Neonatal MDR sepsis is a threat to life, it complicates the treatment, increases costs and mortality. Outcomes can be improved by preventive strategies, earlier and more accurate diagnosis and rational use of antibiotics.

Introduction: Osteoporosis is a chronic progressive bone disease where the bone tissue resorption exceeds its regenerative capacities. Such a process leads to the reduction of bone mineral density (BMD), and distortion of trabecular microarchitectonics, which creates the basis for an increased fracture risk on a “low trauma” for osteoporosis patients. The notion of low trauma implies a stressor that will not cause a fracture in a healthy person under normal circumstances. BMD is a strong predictor of future fractures. However, many fractures occur in persons with BMD values beyond the defined osteoporosis threshold, and BMD measurement only partially identifies the part of the population with increased fracture risk. Also, it is known that risk factors are influencing the bone mass reduction as predictors of future fractures, and their association may lead to an increased fracture risk irrespective of the bone mass and T-score. Aim: The 10-year individual risk assessment for osteoporotic fracture and the analysis of impact of individual and multiple osteoporosis risk factors on the degree of osteoporotic fracture risk. Methods: The research is a retrospective-prospective study which analyzed 120 patients divided into two groups: 1) asymptomatic patients with known risk factors for osteoporosis in the age group of 40-65 (n=60), 2) asymptomatic patients with known risk factors for osteoporosis in the age group of 65-90 (n=60). FRAX® algorithm was used as a tool for the 10-year hip fracture risk assessment, with prior approval of the Centre for Metabolic Bone Diseases, University of Sheffield from the United Kingdom. Fracture risk assessment was calculated using the online FRAX® calculator. High risk is defined as the hip fracture risk higher than 3% or the risk of a “big” osteoporotic fracture higher than 20%. Results are expressed as mean values with a standard deviation. A comparison between tested patient groups was made applying the student T-test. Results: 32% of patients of average age of 65.8±12.6 years are under high hip fracture risk, 28% of patients are under the hip fracture risk higher than 3%, and the risk for 0.03% patients is higher than 20%. Patients with high fracture risk are of advanced age, female, with lower body weight and height values, lower bone mineral density (BMD) and T score values than patients who are not under a high fracture risk. A positive family anamnesis to osteoporosis and fractures, earlier fractures, smoking, rheumatoid arthritis, and use of glucocorticoids are risk factors that are more represented in patients with high fracture risk and osteoporosis. The impact of the majority of individual risk factors for osteoporosis and fracture is moderate, and their joint effect is significant. The contribution of individual risk factors to the overall 10-year fracture risk depends on the type, number and association of risk factors. Conclusion: This research is a contribution to the resolution of polemics among authors, i.e. a dilemma whether persons with multiple clinical risk factors for osteoporosis with T score values beyond the defined threshold for osteoporosis are candidates for therapy with bisphosphonates, and a dilemma whether persons without any clinical risk factors for osteoporosis with T score values within the defined osteoporosis threshold require therapy with bisphosphonates, or only monitoring is sufficient.