Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies.

Background: The benefits of physical activity during pregnancy include lower maternal weight gain, a lower likelihood of gestational diabetes, low back pain, preeclampsia, preterm delivery, caesarian delivery, and macrosomia. This study aimed to examine the factors associated with insufficient leisure-time physical activity (LTPA) during the first trimester. Methods: A cross-sectional study was conducted at the Clinic for Obstetrics and Gynecology of Clinical Center of Serbia, Belgrade, between January and June of 2018. The final analyses included 162/175 pregnant women. The questionnaire was used to obtain social characteristics, pregnancy, and lifestyle characteristics (Pregnancy Risk Assessment Monitoring System—PRAMS), pre-pregnancy LTPA (International Physical Activity Questionnaire—IPAQ), and LTPA during the first trimester (Pregnancy Physical Activity Questionnaire—PPAQ). Women were classified into two groups of sufficient and insufficient LTPA during the first trimester based on the recommendations of the World Health Organization. Multivariate logistic regression analysis was applied. Results: A total of 27.2% of the women had insufficient LTPA during pregnancy. Insufficient LTPA during pregnancy was associated with <12 years of education (OR: 2.3, 95% CI: 1.05–5.04), self-rated financial status as poor (OR: 0.34, 95% CI: 0.14–0.79), and hours spent walking before pregnancy (OR: 0.87, 95% CI: 0.77–0.99). Conclusions: Our results can help direct health care professionals advice for women who are planning pregnancy towards walking as it seems to be sustained during pregnancy.

The aim of this study was to examine the differences in pregnancy complications, delivery characteristics, and neonatal outcomes between women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). This study included all pregnant women with diabetes in pregnancy in Belgrade, Serbia, between 2010 and 2020. The total sample consisted of 6737 patients. In total, 1318 (19.6%) patients had T1DM, 138 (2.0%) had T2DM, and 5281 patients (78.4%) had GDM. Multivariate logistic regression with the type of diabetes as an outcome variable showed that patients with T1DM had a lower likelihood of vaginal delivery (OR: 0.73, 95% CI: 0.64–0.83), gestational hypertension (OR: 0.47, 95% CI: 0.36–0.62), higher likelihood of chronic hypertension (OR: 1.88, 95% CI: 1.55–2.29),and a higher likelihood ofgestational age at delivery before 37 weeks (OR: 1.38, 95% CI: 1.18–1.63) compared to women with GDM. Multivariate logistic regression showed that patients with T2DM had a lower likelihood ofgestational hypertension compared to women with GDM (OR: 0.37, 95% CI: 0.15–0.92).Our results indicate that the highest percentage of diabetes in pregnancy is GDM, and the existence of differences in pregnancy complications, childbirth characteristics, and neonatal outcomes are predominantly between women with GDM and women with T1DM.

The present study purposed to determine characteristics of ovarian carcinoma and to analyze predictors of survival in patients with ovarian carcinoma. A retrospective cohort study was conducted including the patients with diagnosed ovarian carcinoma treated at the Clinic for Operative Oncology, Oncology Institute of Vojvodina in the period from January 2012 to December 2016. Seventy-two women with ovarian carcinoma were included in the analysis. The data about the histological type of tumor, disease stage, treatment, lymphatic infiltration, and surgical procedure were collected retrospectively, using the database of the institution where the research was conducted (BirPis 21 SRC Infonet DOO ‒ Information System Oncology Institute of Vojvodina). Descriptive statistics and multivariate analysis using Cox proportional hazards model were performed. The univariate Cox regression analysis identified histology, tumor grade, FIGO (International Federation of Gynecology and Obstetrics) stage, NACT (Neoadjuvant Chemotherapy), number of therapy cycles, type of surgery, and chemotherapy response as independent predictors of mortality. Finally, the type of tumor and chemotherapy response had an increased hazard ratio for mortality in the multivariate Cox regression model. Herewith, the percentage of high-grade, advanced-stage ovarian cancer patients with complete response to chemotherapy, absence of recurrent disease, and lymphovascular space invasion were significant predictors of survival in patients with ovarian carcinoma. Herein, emerging data regarding precision medicine and molecular-based personalized treatments are promising and will likely modify the way the authors provide multiple lines of treatments in the near future.

Background and Objectives: The aim of this study was to assess the differences in Doppler indices of the uterine (Ut), umbilical (UA), and middle cerebral artery (MCA) in diabetic versus non-diabetic pregnancies by conducting a comprehensive systematic review of the literature with a meta-analysis. Materials and Methods: PubMed, Web of Science, and SCOPUS were searched for studies that measured the pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio index (S/D ratio) of the umbilical artery, middle cerebral artery, and uterine artery in diabetic versus non-diabetic pregnancies. Two reviewers independently evaluated the eligibility of studies, abstracted data, and performed quality assessments according to standardized protocols. The standardized mean difference (SMD) was used as a measure of effect size. Heterogeneity was assessed using the I2 statistic. Publication bias was evaluated by means of funnel plots. Results: A total of 62 publications were included in the qualitative and 43 in quantitative analysis. The UA-RI, UtA-PI, and UtA-S/D ratios were increased in diabetic compared with non-diabetic pregnancies. Subgroup analysis showed that levels of UtA-PI were significantly higher during the third, but not during the first trimester of pregnancy in diabetic versus non-diabetic pregnancies. No differences were found for the UA-PI, UA-S/D ratio, MCA-PI, MCA-RI, MCA-S/D ratio, or UtA-RI between diabetic and non-diabetic pregnancies. Conclusions: This meta-analysis revealed the presence of hemodynamic changes in uterine and umbilical arteries, but not in the middle cerebral artery in pregnancies complicated by diabetes.

One of the risk factors for vascular obstetric complications, such as intrauterine growth restriction (IUGR), is inherited thrombophilias. Nevertheless, routine screening for thrombophilias is not endorsed in pregnant women due to their low prevalence and conflicting results of published studies regarding the usefulness of screening in these patients. The cause of IUGR remains unknown in almost 1 quarter of cases. There are no published studies evaluating the association of inherited thrombophilias and IUGR in patients with IUGR of unknown origin. Understanding and preventing IUGR is an important public health concern, as IUGR has been associated with fetal mortality and neonatal morbidity, as well as adverse long-standing consequences. This study aimed to evaluate the prevalence of inherited thrombophilias in IUGR of unknown cause and to test the association between the inherited thrombophilias and IUGR of unknown cause. This study included 33 cases of IUGR of unknown cause tested for inherited thrombophilias and 66 controls individually matched for age, ethnicity, and smoking status. Patients with plasminogen activator inhibitor 1 (PAI-1) and methylenetetrahydrofolate reductase (MTHFR) had significantly higher odds for IUGR of unknown cause (P < .001 and P = .002, respectively) with OR 13.546 (CI 95% 3.79–48.37) and 8.139 (CI 95% 2.20–30.10), respectively. A positive association between other inherited thrombophilias (homozygous 20210 prothrombin gene mutation and homozygous factor V Leiden) and IUGR of unknown cause was also found, P = .096, OR 6.106 (CI 95% 0.72–51.30), although it was not statistically significant (P = .096, OR = 6.106, CI 95% 0.72–51.30). Our results indicate that PAI-1 and MTHFR thrombophilias represent risk factors for IUGR of otherwise unidentified cause.