Graphical abstract

While clear cell renal cell carcinoma (ccRCC) is curable, advanced metastatic (mRCC) remains a clinical challenge. We analyzed clinical, pathohistological, and molecular data (Receptor Interacting Protein 5—RIP5 and Vestigial Like Family Member 4—VGLL4 expression) of 55 mRCC patients treated with first-line treatment with sunitinib. The trend of linear increase in the protein expression of RIP5 was observed with the progression of tumor grade. Overall, 80% of RIP5-positive cells were in the control kidneys and high-grade mRCC. On the contrary, RIP5 displayed low expression in grade 2 mRCC (5.63%). The trend of linear decrease in the expression of VGLL4 was observed with the progression of tumor grade. The highest protein expression of VGLL4 was observed in grade 2 (87.82%) in comparison to grade 3 and 4 and control. High expression of RIP5 mRNA was associated with longer first-line overall survival and longer progression-free survival in mRCC. In addition, a high VGLL4 mRNA expression showed better overall survival in patients with ccRCC. In conclusion, high mRNA expression of RIP5 and VGLL4 are important markers of better survival rates in mRCC patients.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P< 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registered at Clinicaltrail.gov (NCT04952324).

Background: Painful and damaged nipples are frequently associated with breastfeeding cessation in the early postpartum period. The results of researchers’ studies utilizing different treatments have been inconclusive. Research Aim: To compare the intensity of nipple pain and the healing of damaged nipples during the first 10 days postpartum using either lanolin or human milk treatments. Methods: This single-blind randomized controlled trial included participants (N = 206) who were primiparous with painful and damaged nipples. Participants were recruited from the tertiary teaching hospital within the first 72 hr after delivery and randomized to the intervention group with lanolin (n = 103) and a human milk control group (n = 103). Data were collected in the maternity ward, 3 and 7 days after randomization. The primary outcome was nipple pain intensity and quality measured 3 and 7 days after randomization by the McGill Pain Questionnaire – short form. The nipple damage self-assessment questionnaire was used for the assessment of nipple healing. Breastfeeding self-efficacy, breastfeeding duration, and exclusivity were assessed as secondary outcomes. Results: Participants in both groups reported a statistically nonsignificant reduction in pain (quality and intensity of pain) as well as improved nipple healing 7 days after randomization. Participants in the lanolin group exclusively breastfed their infants 3 days after randomization—significantly more often than participants in the control group (p = .026). The study did not reveal any statistically significant differences for other secondary outcomes. Conclusion: Both lanolin and human milk are equally effective in treating painful and damaged nipples. Registered with Clinicaltrials.gov (NCT04153513)

Background: The aim of this study was to determine and analyze the frequency and obstetric features of preterm birth and neonatal outcomes of infants born before 37 completed weeks of pregnancy. Methods: The retrospective study included 470 premature births. The following data on preterm births were collected from hospital records and analyzed: gestational age, type of preterm birth, multiple pregnancy and maternal parity. The parameters of preterm infants were: Apgar score, intrauterine growth restriction (IUGR), perinatal asphyxia, respiratory distress syndrome (RDS), sepsis, necrotizing enterocolitis, intracranial hemorrhage, neonatal convulsions, hypoglycemia, blood transfusion, the need for surfactant, the need for mechanical ventilation, the length of stay in an Intensive Care Unit and early and late neonatal mortality.Main findings: The frequency of preterm births was 6.48%. The most common type of premature birth was spontaneous premature birth. Most complications occurred in neonates with a gestational age of 28-34 weeks. The most common respiratory complication was RDS (8.1%). Early neonatal mortality was 1.49% and late neonatal mortality was 0.85%.Principal conclusion: Neonatal outcomes of premature infants are directly proportional to their gestational age. The neonatal mortality rate of premature infants at Clinical Hospital Center Mostar (CHC) Mostar is comparable to other developing countries.Key words: preterm birth, gestational age neonatal outcome, perinatal care, neonatal mortality

Background: Placenta accreta spectrum (PAS) is a clinical term used to describe the abnormal trophoblast invasion into the myometrium of the uterine wall and may enter into the serosa or even into adjacent organs. It is associated with severe obstetric haemorrhage and often requires emergency hysterectomy, which is one of the foremost causes of maternal morbidity and mortality. The vast of these conditions are seen in women with a history of previous caesarean section and placenta previa. Cases: In this study we present two cases of a rare type of PAS, placenta percreta, in women with a history of previous caesarean section (CS). Both instances were diagnosed prenatally, using the method of ultrasound and magnetic resonance imaging. They were scheduled for deliveries by CS, and both were hysterectomized. These diagnoses were confirmed in histopathological findings. Conclusion: Considering sparse published data and absence of well conducted studies, optimal management is still undefined. Caesarean hysterectomy is still the gold standard treatment for placenta accreta spectrum proposed by many societies as an absolute and final treatment.

OBJECTIVE Cystatin C (Cys-C) concentration has not been examined sufficiently among healthy newborn population, particularly in terms of reference values. This study aimed to establish gender-, postnatal age- and birth weight-specific Cys-C concentration for healthy term newborns. Its objective was also to examine if there were any differences between our measured concentration and the reference interval established by the CALIPER study. METHODS Serum samples from a total of 90 healthy term newborns were used to determine Cys-C concentration. Cys-C was measured within first three days of birth using particle-enhanced turbidimetric immunoassay (PETIA) on the Architect plus ci8200 analyzer. RESULTS Median concentration of the Cys-C was 2.05 mg/L. There were no statistically significant differences in Cys-C concentration regarding gender (p=0.779), birth weight (p=0.505), postnatal age (p=0.512) or Apgar score (p=0.799). The value of the 2.5th and 97.5th percentile for Cys-C concentrations for girls was 0.93-3.15 mg/L and for boys it was 1.5-3.36 mg/L. CONCLUSION Cys-C concentration in healthy term newborns does not depend on gender, birth weight, postnatal age, or Apgar score. Our measured concentration range of CyS-C in healthy newborns turned out to be slightly wider than the interval determined in the CALIPER study.

Background: Retained placenta is one of the major causes of primary and secondary post-partum hemorrhage (PPH) and active management of the third stage of labor reduces the risk of PPH. Objective: The aim of this paper was to compare the efficacy of intra-umbilical vein injection of carboprost versus oxytocin by time and success rates of total expulsion of the placenta. Methods: This prospective clinical study with quasi-experimental design 2x2x2(risk factors by medication by doses) was conducted at Clinic of Obstetrics and Gynecology, Clinical Center of University of Sarajevo in two-year period. Patients were randomized in 4 groups and 8 subgroupsby different medication doses and risk factors. The main outcome variable was expulsion of retained placenta and second outcome variables were: duration of time from intra-umbilical vein administration of drug to expulsion of retained placenta, the number of cases who required blood transfusion and antibiotics, postpartum hemoglobin after 24h. Statistical significance was accepted for p-values < 0.05. Results: The group B2 (UVI oxytocin 20 IU in 20 mL saline, surgical risk factors) and the group D2 (UVI oxytocin 20 IU in 20 mL saline, non-surgical risk factors) had shorter expulsion time (minutes) (Me=5; IQR=4 to 5; Me=5; IQR=4.3 to 6, respectively) compared with other groups (p<0.001). The success rates of total expulsion of the placenta by groups (A,B,C and D) were not statistically significant (70% vs. 82% vs. 72% vs. 78%, respectively; p=0.483). Post-intervention hemoglobin concentrations was statistically significantly greater in the group B(117.3±1.3) vs. the group A (112.1±1.3), (p =0.028). Conclusion: The time for placental expulsion was significantly shorter and postpartum hemoglobin was significantly higher in the intra-umbilical oxytocin groups than in the carboprost groups.

INTRODUCTION Pregnancy is a unique experience accompanied by significant physiological, biochemical, and psychological changes that may affect a woman's mental health status. With the development of a holistic approach, midwives have become continuous support during pregnancy and childbirth. Childbirth education is an intervention that affects delivery outcomes and the experience of childbirth. Music therapy has been proven to be a safe and effective non - pharmacological method to gain in pregnancy and puerperium. The study aimed to prove the impact of educating pregnant women and listening to classical music on the experience of childbirth pains and the occurrence of psychological symptoms during puerperium. METHODS A prospective randomized controlled trial (n=198) was conducted. The experimental group of pregnant women was educated during pregnancy and listened to classical music the rest of the pregnancy, while the control group received the usual care. The VAS scale was used to assess pain, and the 90 - point scale was used to assess the incidence of psychological symptoms. RESULTS The difference in pain assessment between the experimental and control groups was significant (p<0.001). The experimental group rated their childbirth pain as moderate (M=5.98), while the control group experienced severe pain (M=8.42). A significant difference in the incidence of psychological symptoms between groups was found in the dimensions of interpersonal sensitivity, hostility, phobic anxiety, and paranoid ideations (p=0.042; p=0.014; p=0.013; p=0.008). CONCLUSION This study demonstrated the impact of midwifery education and listening to classical music on the perception of childbirth pain and mental health in the puerperium. The experimental group rated childbirth pain significantly lower compared to the control group and had significantly fewer psychological symptoms 6 weeks after delivery.

Aim To evaluate satisfaction of mothers who gave birth at term with received hospital care and to find areas for improvement at a tertiary hospital. Methods A cross-sectional study at the Department of Obstetrics & Gynaecology at the University Clinical Hospital Mostar was conducted by an anonymous survey using a questionnaire designed exclusively for this study. A total of 100 mothers were included in the study. Results Satisfaction with midwives' communication and their approach to the women during their stay in the delivery room was rated significantly higher (4.7±0.6) when compared to obstetricians-gynaecologists (4.5±0.8) (p=0.02). Midwives were rated better in providing breastfeeding information (4.5±0.8) than for the speed of arrival after a call bell (average grade 4.2±1.0). Respondents were least satisfied with the hygiene (toilet, shower and rooms) and the quality of food (average grades 3.8±1.1 and 3.9±1.0, respectively). Mothers with previous experience in childbirth at the same hospital rated current stay with a similar level of satisfaction. Conclusion Good communication skills of medical and non-medical staff are a recommended step to maintain mothers' childbirth satisfaction, while improvement in quality of nutrition and hygiene should be mandatory.

Introduction Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a biochemical marker significant for early prediction of acute kidney injury in adults. However, it has not been examined sufficiently among the infant population, particularly newborns in terms of reference values. The aim of our study was to determine the concentration of uNGAL in healthy term newborns and to determine if there was a difference in uNGAL concentration according to gender, postnatal age and birth weight. Materials and methods Our study involved 81 healthy term newborns birth (≥ 37 weeks, Apgar score ≥ 8 in the first minute after birth, CRP < 5 mg/L). Urine NGAL was measured using chemiluminescent microparticle immunoassay (CMIA) within 72 hours after birth, on Architect plus ci8200 analyser (Abbott, Chicago, USA). Data were analysed using Statistica software. Results The median concentration of uNGAL in the whole study group of healthy term newborns was 27.1 ng/mL (16.5-56.0 ng/mL) (newborn girls, 27.1 ng/mL (15.8-47.9 ng/mL); newborn boys, 27.9 ng/mL (16.5-61.0 ng/mL), P = 0.941). Median uNGAL concentration according to postnatal age expressed in days was 28.2 ng/mL (11.7-57.2 ng/mL) 1st day, 28.9 ng/mL (16.5-64.2 ng/mL) 2nd day and 23.9 ng/mL (20.2-46.6) 3rd day, P = 0.863. Regarding birth weight for newborns < 3500 g, median concentration was 25.0 ng/mL (16.5-45.4 ng/mL) and for weight ≥ 3500 g 30.6 ng/mL (16.5-64.2 ng/mL), P = 0.455. Conclusions There were no significant difference in uNGAL concentration in relation to gender, postnatal age and birth weight.

In post-war Herzegovina, the health services were significantly devastated and there was a great need for recovery and progress. The Faculty of Medicine was established in 1997 in Mostar. At the same time, in order to raise the level of health care, there was a need to educate nurses and other health workers. In accordance with the Munich Declaration and the Bologna Process, the Governing Board of the University of Mostar adopted a Decision on the establishment of the Health School, which began in October 2000 with the Study of Nursing, with the Study of Physiotherapy in 2001, and with the Study of Radiological Technology in 2002. We tried to make the programs in accordance with the programs of Health Schools in Zagreb, Sarajevo and Maribor, so that students could work in Bosnia and Herzegovina (B&H), Croatia and the European Union after finishing their education in Mostar. Using the experience from the Faculty of Medicine, and the fact that most of the subjects were taught by visiting professors from Sarajevo, Zagreb, Split and Osijek, we introduced classes in shifts from the beginning, ie block teaching, which allows continuous learning. In addition to the three-year professional Study of Nursing, in 2003 the four-year university Study of Nursing also began. Since 2005, students in all studies have been enrolling in undergraduate university studies according to a new curriculum adapted to the Bologna Process. The Study of Sanitary Engineering and the Study of Midwifery were established in 2011 and 2014, respectively. The new building of the Faculty of Health Studies (FZS) on Bijeli brijeg, with modern space and equipment, which, along with the Faculty of Medicine and the University Clinical Hospital, makes up a modern biomedical center in Mostar, was completed in 2009 (Šimi 2016). In addition to being the most numerous and important health professionals, nurses and technicians form a key link in the fight for human health in the world. According to the statistics of the World Health Organization, in the health care of most countries, nurses and midwives make up about 80% of qualified medical staff, and are involved in all life stages of human life. In fact, as much as they are numerical as professional, they are a powerful force that is introducing the changes needed to achieve the goal of ‘health for all people’ in the 21 century. Their scope of work covers a wide range of health services and is the foundation on which more or less most medical teams are based. They work in teams from prevention, enlightenment to the last phase of human life. In the territory of Bosnia and Herzegovina, the combination of previous experiences with new achievements of the European Union is necessary, and this is done by the Faculty of Health Studies of the University of Mostar. Medical science is advancing more and more day by day, which means that doctors are constantly discovering new knowledge, entering previously unknown spheres. Therefore, what is foreseeable and what is already happening, is that the medical profession leaves certain activities to nurses and technicians (Lon ar 2017). In the process of continuous struggle for health, prevention and treatment, the role of a highly educated health worker is becoming increasingly important and he is certainly becoming an irreplaceable link in the process. The goal of our faculty is to educate the best possible health workers who, in addition to quality practical work, will gradually take over our teaching (Babi et al. 2017).

PROBLEM The aim of this study was to quantify and compare the distribution of regulatory CD25+ FOXP3+ and activated CD4+ CD25+ T cells in decidua basalis and parietalis of severe and mild pre-eclampsia (PE) to normal healthy pregnancies. METHOD OF STUDY Decidual tissue (decidua basalis and parietalis) of 13 women with mild PE, 15 women with severe PE and 19 women with healthy term pregnancies were analyzed by immunohistochemistry and double immunofluorescence. RESULTS The total number of CD25+ FOXP3+ cells/mm2 in decidua basalis was decreased in the severe and mild PE versus normal pregnancy group. The total number of CD4+ CD25+ cells/mm2 in decidua basalis was decreased in the severe PE versus normal pregnancy group. The number of CD25+ FOXP3+ and CD4+ CD25+ cells in decidua parietalis was decreased in both PE groups. CONCLUSION Our data suggest that immunological changes of PE reflect on decidua basalis and parietalis and emphasize the importance of characterizing T cells in both decidual departments.

Introduction: Integrated care could be defi ned differently and that is why the following terms can be found in the literature: integrated health, coordinated care, comprehensive care, seamless care, or trans-mural care. It has become a worldwide trend in health care reforms and new organizational arrangements focusing on more coordination between professionals and institutions and integrated forms of care or service provision. The Agency for Quality and Accreditation in Health Care in the Federation of Bosnia and Herzegovina (AKAZ) is using accreditation standards as a tool for quality improvement process aiming to increase the capacity of health care institutions in the Federation of Bosnia and Herzegovina in order to provide safe and quality care for the citizens. In the Agency, it is fi rmly believed that a wisely set and well-organized integrated care can help health professionals deliver health care in accordance with patient needs and even expectations. Aim: The aim of the study was to fi nd out how to implement measures for integration of health care, to fi nd out whether there are any gaps in the health care system, and how to bridge to the application of the best solutions of integrated care in the city of Mostar and Herzegovina-Neretva Canton (HNC). Methods: In this paper, we used feedback and results from the workshop held at the Federal Public Health Institute in Mostar as part of lectures for participants of the course within the Integrated Health Care module held in June 2019. The Integrated Health Care module is part of the Continuous Professional Education for Health Managers in the Federation of Bosnia and Herzegovina. Participants were experienced experts in different fi elds of medicine and pharmacists divided into two groups. Results: Participants identifi ed the most common problems for both primary and hospital physicians, such as unclear referral system to specialist examination, inappropriate patient expectations from primary care, lack of communication between primary care and hospital care, and inadequate use of clinical practice guidelines. To solve these problems, both groups stressed the importance of common strategy documents and guidelines, which should provide clear framework for cooperation and integration including levels of competence and service prices. Furthermore, effi cient information system is crucial for the integration or digitalization of, in strategy documents, agreed mechanisms of coordination and integration. Third, the growing proportion of elderly population should be taken in consideration, including the need of hospice and development of geriatric medicine in the Canton. Participants discussed and compared the results with feedback and results from three workshops held several years before. Discussion: The results of our study stressed the importance of better communication among different sectors, institutions and levels of health care involved in the treatment of patients, pointed to some measures for integration including standardized models of communication, training and education and highlighted priorities for integration. Analysis indicated the necessity for the following: regular analysis of unnecessary or inappropriate referrals and evaluation of such practices, as well as of any duplication of tests and prescriptions (failure to control costs); joint planning of preventive treatments (including the ministry and public health authorities); and clear responsibilities regarding screening programs and patient path analysis. Conclusions: Strong commitment of health care authorities and vision of integrated care and collaborative networks, as well as good communication and leadership were highlighted as key integrated care facilitators. Health care institutions at all levels of care have to organize multidisciplinary teams to work more on better and effective communication and to exchange information among key stakeholders in the system.