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.