Placental expression of inflammatory Galectin-12 is associated with gestational diabetes.

OBJECTIVES: Gestational diabetes mellitus (GDM) is a growing health concern. Since members of the galectin-family are identified to play a role in the pathogenesis of GDM, we determined galectin-12 as an essential protein due to its influence in lipolysis and inflammation processes. This study investigates the expression of galectin-12 in the placentas of women with GDM. STUDY DESIGN: The study population includes 40 expectant women suffering from GDM and 40 healthy controls. The expression of galectin-12 in the syncytiotrophoblast (SCT) and the extra villous trophoblast (EVT) of the placenta was analyzed by immunohistological staining and double immunofluorescence. Immunoreactivity Score (IRS) was used for evaluation. RESULTS: The results demonstrate a significant overexpression of galectin-12 in the nucleus of the SCT and the EVT of placentas with GDM compared to the healthy control group. Additionally, double immunofluorescence visualizes corresponding results with an overexpression of galectin-12 in the extra villous trophoblast of GDM placentas representing maternal cells. CONCLUSION: This study identifies galectin-12 to be associated with the process of gestational diabetes mellitus. These findings are in correspondence with the involvement of galectin-12 in inflammatory processes. Maternal BMI and male sex seem to be confounder for the expression of galectin-12 in the nuclear syncytiotrophoblast, but not in other parts of the investigated placental areas. Further investigations are necessary to verify the correlation between gestational diabetes mellitus and the expression of galectin-12 in the placenta and to further elucidate its distinct role.

Use of the Gene Expression Test Prosigna® in Premenopausal Patients with HR+, HER2- Early Breast Cancer: Correlation of the Results with the Proliferation Marker Ki-67.

Introduction: In hormone receptor-positive (ER+/PR+) and human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (EBC), gene expression tests such as the Prosigna are increasingly used since classic clinicopathological parameters and the proliferation factor Ki-67 often do not allow a definite therapy decision regarding an adjuvant chemotherapy. While the Prosigna test has been validated for postmenopausal patients, few data are available regarding its use in premenopausal patients. The present study compared the Prosigna test with the Ki-67 index in premenopausal patients. Materials and Methods: Premenopausal patients with HR+ HER2-, pN0-1, G1-2 EBC were retrospectively enrolled (n = 55). The Prosigna assay was performed in formalin-fixed paraffin-embedded tumor samples of surgical resection specimens. Ki-67 was reassessed in original diagnostic core needle biopsy specimens and defined as low, intermediate, or high with the threshold of <10%, 10-24%, ≥25%. Results: According to Ki-67, patients were in the low (LR)-, intermediate (IR)-, and high-risk (HR) groups in 40%, 36%, and 24% of the cases. The Prosigna gene signature assay assessed the risk of recurrence as LR for 45% of the patients, IR for 35%, and HR for 20%. The most frequent intrinsic subtypes were luminal A in 73% and luminal B in 24% of the patients. A moderate correlation was found between Prosigna and Ki-67 scores with a Pearson correlation coefficient of 0.51. In the overall cohort, 47% of the Ki-67-based therapy decision would correspond to those based on the Prosigna score. After exclusion of IR patients, matching of low/low or high/high results was observed in 57% of the cases. Conclusion: According to the present study, there is only limited concordance regarding the risk group stratification between Ki-67 and Prosigna-based risk assessment. The relevance and frequency of premenopausal breast cancer emphasizes the need for further evaluation of gene expression analyses in this setting and the correlation with classic clinicopathological parameters regarding therapy decision-making.

Changes in the rate of preterm infants during the COVID-19 pandemic Lockdown Period-data from a large tertiary German University Center.

PURPOSE: After living with the COVID-19 pandemic for more than 2 years, the impact of lockdown measures on preterm birth rates is inconsistent according to data from different countries. In this study, rates of preterm-born infants during the time of COVID-19-related lockdowns were analyzed in a tertiary perinatal center at Munich University, Germany. METHODS: We analyzed the number of preterm births, infants, and stillbirths before 37 weeks of gestation during the German COVID-19 lockdown period compared to the same time periods in the years 2018 and 2019 combined. Additionally, we expanded the analysis to Pre- and Post-Lockdown Periods in 2020 compared to the respective control periods in the years 2018 and 2019. RESULTS: Our database shows a reduction in the rate of preterm infants during the COVID-19 lockdown period (18.6%) compared to the combined control periods in 2018 and 2019 (23.2%, p = 0.027). This was mainly based on a reduced rate of preterm multiples during the lockdown period (12.8% vs. 28.9%, p = 0.003) followed by a reversed effect showing a threefold rise in multiple births after the lockdown. In singletons, the rate of preterm births was not reduced during the lockdown. The rate of stillbirths was not affected by the lockdown measures as compared to the control period (0.9% vs. 0.7%, p = 0.750). CONCLUSION: During the COVID-19 pandemic lockdown period, we found a reduced rate of preterm-born infants compared to a combined control period in the years 2018 and 2019 in our large tertiary University Center in Germany. Due to the predominant reduction in preterm multiples, we postulate that less physical activity might have led to the protective effect by lockdown measures.

Galectin-10 Expression in Placentas of Women with Gestational Diabetes.

Galectins are known to play an important role in immunoregulatory processes and autoimmune diseases. Galectin-10 is a cytoplasmic protein of human eosinophils and is involved in various eosinophilic diseases. Since increased galectin expression is already detected in the placentas of mothers with gestational diabetes mellitus (GDM), this study focuses on the specific role of galectin-10 and hints at consequences for the diagnosis and therapeutic options of GDM. It is hypothesized that the difference in galectin-10 expression will raise the pathophysiological understanding of gestational diabetes. The study population consists of 80 women: 40 healthy mothers and 40 women suffering from gestational diabetes mellitus. The expression of galectin-10 was analyzed in the syncytiotrophoblast (SCT) and the decidua of the placenta via immunohistochemistry and immunofluorescence double staining. The immunoreactivity score (IRS) was used for evaluation. The results in this study were significant for an overexpression of galectin-10 in GDM placentas compared with the control group. The syncytiotrophoblast showed overexpression in the nucleus and the cytoplasm, whereas expression of galectin-10 in the decidua was significant in the cytoplasm only. This study identified the expression changes in galectin-10 in placental tissue between healthy and GDM mothers and intensified the understanding of gestational diabetes. Assuming that gestational diabetes mellitus is involved in inflammatory processes, galectin-10 might play a role in the development and maintenance of GDM. Further investigation is required to strengthen these findings.

Breastfeeding Behavior Within the Covid-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: The SARS-CoV-2 pandemic and its influence on peripartum processes worldwide led to issues in breastfeeding support. RESEARCH AIM: The aim of this study was to describe breastfeeding behavior and peripartum in-hospital management during the pandemic in Germany and Austria. METHODS: This study was a descriptive study using a combination of secondary longitudinal data and a cross-sectional online survey. Registry data from the prospective multicenter COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS) cohort study (longitudinal, medical records of 1,815 parent-neonate pairs with confirmed SARS-CoV-2 infection during pregnancy) and a cross-sectional online survey of CRONOS hospitals' physicians (N = 67) were used for a descriptive comparison of feeding outcomes and postpartum management. RESULTS: In 93.7% (n = 1700) of the cases in which information on the neonate's diet was provided, feeding was with the mother's own milk. Among neonates not receiving their mother's own milk, 24.3% (n = 26) reported SARS-CoV-2 infection as the reason. Peripartum maternal SARS-CoV-2 infection, severe maternal COVID-19 including the need for intensive care unit (ICU) treatment or invasive ventilation, preterm birth, mandatory delivery due to COVID-19, and neonatal ICU admission were associated with lower rates of breastfeeding. Rooming-in positively influenced breastfeeding without affecting neonatal SARS-CoV-2 frequency (4.2% vs. 5.6%). CRONOS hospitals reported that feeding an infant their mother's own milk continued to be supported during the pandemic. In cases of severe COVID-19, four of five hospitals encouraged breastfeeding. CONCLUSION: Maintaining rooming-in and breastfeeding support services in the CRONOS hospitals during the pandemic resulted in high breastfeeding rates.

Clinical relevance of potential self-medication drug interactions in antineoplastic and immune-modulating therapy among online pharmacy customers.

Background: Modern oral antineoplastic and immune-modulating drugs offer an array of therapeutic advantages, and yet pose challenges in daily use for patients, physicians and pharmacists. In contrast to intravenous administration, these drugs are not subject to direct medical control. Recently, we have seen a huge rise in sales of non-prescription over-the-counter (OTC) medicines via the internet without any advice from a healthcare professional. Objectives: The aim of this study was to investigate whether the risk of known potential drug-drug interactions between modern oral antineoplastic and immune-modulating drugs and OTC drugs differs between sales in traditional community pharmacies versus online pharmacies. Design: Real-life sales data from community and online pharmacies were used as basis for the analysis. Methods: We determined the most frequently purchased antineoplastic and immune-modulating drug-substances in 14 local community pharmacies within the Munich area, Germany and identified the OTC substance groups that could potentially cause interactions with oncological therapies. Using sales data from 11 local community pharmacies and three online pharmacies, we investigated whether OTC purchases differed between the two sales channels. Results: We identified 10 relevant OTC substance classes and detected significant variations in patients' preferred sales channels between the drug classes. Certain OTC drugs, which seem to be bought more often over the internet, pose risks during antineoplastic and immune-modulating therapy. Conclusion: Patients should therefore be proactively made aware of the corresponding risks in order not to jeopardize the activity of the antineoplastic and immune-modulating drugs and thus the success of their therapy.

Comparing Community and Online Pharmacies: Investigating Potential Interactions Between Cancer and Immune-Modulating Drugs with Over-the-Counter Medications, and the Importance of Patient Awareness and Healthcare Professional Guidance in Minimizing Adverse Effects and Maintaining Treatment Efficacy Modern anticancer and immune-modulating drugs have the advantage of often being taken orally, but they present other challenges in daily use. Unlike intravenously administered drugs, these are usually not administered by a physician but taken by the patient at home. In these cases, patients may be more likely to buy and take self-medicating drugs over-the-counter (OTC) without consulting a healthcare professional. This study aimed to investigate whether there is a different risk of drug interactions between cancer or immune-modulating drugs and OTC drugs when bought in a community pharmacy versus an online pharmacy. Therefore, we looked at the most common cancer and immune-modulating drugs purchased in 14 local community pharmacies in Munich and identified which OTC drugs could cause problems when used simultaneously. Additionally, we analyzed the sales data from 11 local and 3 online pharmacies to determine if people were more likely to buy different OTC drugs from the two types of pharmacies. As a result, this study showed 10 relevant OTC drug types that potentially cause problems and influence effectiveness when used with cancer or immune-modulating drugs. Furthermore, we observed that some of these OTC drugs were purchased more often online than in community pharmacies and thus are more distant from the control of a physician or pharmacist. It is therefore essential for patients to be aware of the risks associated with easily accessible OTC drugs in combination with their cancer or immune-modulating medication, as serious side effects or decreased efficacy may develop. Patients should remember to consult their doctor or pharmacist if there is any uncertainty about potential drug interactions. At the same time, healthcare professionals should proactively draw their patients' attention to these potential risks, especially when purchasing online.

Nuclear receptor co-repressor NCOR2 and its relation to GPER with prognostic impact in ovarian cancer.

PURPOSE: The significance of the non-classical G-protein-coupled estrogen receptor (GPER) as positive or negative prognostic factor for ovarian cancer patients remains still controversial. Recent results indicate that an imbalance of both co-factors and co-repressors of nuclear receptors regulates ovarian carcinogenesis by altering the transcriptional activity through chromatin remodeling. The present study aims to investigate whether the expression of the nuclear co-repressor NCOR2 plays a role in GPER signaling which thereby could positively impact overall survival rates of ovarian cancer patients. METHODS: NCOR2 expression was evaluated by immunohistochemistry in a cohort of 156 epithelial ovarian cancer (EOC) tumor samples and correlated with GPER expression. The correlation and differences in clinical and histopathological variables as well as their effect on prognosis were analyzed by Spearman's correlation, Kruskal-Wallis test and Kaplan-Meier estimates. RESULTS: Histologic subtypes were associated with different NCOR2 expression patterns. More specifically, serous and mucinous EOC demonstrated a higher NCOR2 expression (P = 0.008). In addition, high nuclear NCOR2 expression correlated significantly with high GPER expression (cc = 0.245, P = 0.008). A combined evaluation of both high NCOR2 (IRS > 6) and high GPER (IRS > 8) expression revealed an association of a significantly improved overall survival (median OS 50.9 versus 105.1 months, P = 0.048). CONCLUSION: Our results support the hypothesis that nuclear co-repressors such as NCOR2 may influence the transcription of target genes in EOC such as GPER. Understanding the role of nuclear co-repressors on signaling pathways will allow a better understanding of the factors involved in prognosis and clinical outcome of EOC patients.

Updates of placental macrophages: Origins, molecular markers, functions, and related diseases.

Placental macrophages are highly heterogeneous cells with differential phenotypes and functions defined by differential origins and modulated by the changing placental environment. During pregnancy, placental macrophages play a critical role in embryo implantation, placenta formation and homeostasis, fetal development and parturition. This review summarizes recent findings on the cellular origin of placental macrophages, and provide a comprehensive description of their phenotypes, corresponding molecular markers and functions in human placenta. Finally, alterations of placental macrophages in pregnancy-related diseases are discussed.

Increase of the T-reg-recruiting chemokine CCL22 expression in a progressive course of cervical dysplasia.

PURPOSE: An increasing infiltration of FoxP3-positive T-regs is associated with a higher grade of cervical intraepithelial neoplasia. The T-reg-recruiting chemokine CCL22 is expressed in various tumour entities. Aim of our study was to investigate the role of CCL22 in the progression and regression of cervical intraepithelial neoplasias, especially in patients with intermediate cervical intraepithelial neoplasias (CIN II). Furthermore, our aim was to characterize the CCL22-producing cells and explore the role of innate immunity in the process of cells recruitment. METHODS: CCL22 expression was analyzed immunohistochemically in 169 patient samples. The immunoreactive score as well as the median numbers of positive cells were calculated in each slide and correlated with the histological CIN grade and FoxP3 expression. Additionally, CD68/CCL22 as well as CD68/PPARγ and CD68/FoxP3 expression were examined by double immunofluorescence. Statistical analysis was performed by SPSS 26. RESULTS: A significantly higher expression of epithelial CCL22 in CIN II with progression in comparison to CIN II with regression (p = 0.006) could be detected. CCL22 was correlated with FoxP3 (Spearman's Rho: 0.308; p < 0.01). In 88%, CCL22-positive cells were positive for CD68, and 71% of CD68-positive macrophages expressed PPARγ. Colocalization of CD68 and FoxP3 was detected in 12%. CONCLUSION: We could demonstrate that increased expression of CCL22, mainly produced by macrophages, correlates with elevated potential of malignancy. CCL22 expression could act as a predictor for regression and progression in cervical intraepithelial neoplasia, and it may help in the decision process regarding surgical treatment versus watchful waiting strategy in order to prevent conisation-associated risks. Furthermore, our findings support the potential of CCL22-producing cells as a target for immune therapy in cervical cancer patients.

A20 and the noncanonical NF-κB pathway are key regulators of neutrophil recruitment during fetal ontogeny.

Newborns are at high risk of developing neonatal sepsis, particularly if born prematurely. This has been linked to divergent requirements the immune system has to fulfill during intrauterine compared with extrauterine life. By transcriptomic analysis of fetal and adult neutrophils, we shed new light on the molecular mechanisms of neutrophil maturation and functional adaption during fetal ontogeny. We identified an accumulation of differentially regulated genes within the noncanonical NF-κB signaling pathway accompanied by constitutive nuclear localization of RelB and increased surface expression of TNF receptor type II in fetal neutrophils, as well as elevated levels of lymphotoxin α in fetal serum. Furthermore, we found strong upregulation of the negative inflammatory regulator A20 (Tnfaip3) in fetal neutrophils, which was accompanied by pronounced downregulation of the canonical NF-κB pathway. Functionally, overexpressing A20 in Hoxb8 cells led to reduced adhesion of these neutrophil-like cells in a flow chamber system. Conversely, mice with a neutrophil-specific A20 deletion displayed increased inflammation in vivo. Taken together, we have uncovered constitutive activation of the noncanonical NF-κB pathway with concomitant upregulation of A20 in fetal neutrophils. This offers perfect adaption of neutrophil function during intrauterine fetal life but also restricts appropriate immune responses particularly in prematurely born infants.

PLA2G7/PAF-AH as Potential Negative Regulator of the Wnt Signaling Pathway Mediates Protective Effects in BRCA1 Mutant Breast Cancer.

Past studies have confirmed that aberrant activation of the Wnt/ß-catenin signaling is associated with tumorigenesis and metastasis in breast cancer, while the role of platelet-activating factor acetylhydrolase (PLA2G7/PAF-AH) in this signaling pathway remains unclear. In this study, we analyze the functional impact of PAF-AH on BRCA1 mutant breast cancer and explore its relationship to the Wnt signaling pathway. By performing immunohistochemistry, PAF-AH expression and ß-catenin expression were examined in both BRCA1 WT and BRCA1 mutant breast cancer specimens. The BRCA1 mutant breast cancer cell line HCC1937 was used for in vitro experiments to assess the impact of PAF-AH on cellular functions. The intracellular distribution of ß-catenin depending on PLA2G7/PAF-AH expression was investigated by immunocytochemistry. Significantly higher nuclear expression levels of PAF-AH were found in BRCA1 mutant tissue specimens than in BRCA1 WT samples. Cell viability, proliferation, and the motility rate of HCC1937 were significantly enhanced after PLA2G7 silencing, which indicated a protective role of PAF-AH in breast cancer. Nuclear PAF-AH expressed correlatedly with membranous ß-catenin. PLA2G7 silencing provoked the ß-catenin translocation from the membrane to the nucleus and activated Wnt signaling downstream genes. Our data showed a protective effect of high PAF-AH expression in BRCA1 mutant breast cancer. PAF-AH may achieve its protective effect by negatively regulating the Wnt pathway. In conclusion, our research sheds new light on the regulatory pathways in BRCA1 mutant breast cancer.

Pelvic inlet area is associated with birth mode.

INTRODUCTION: To determine whether a pelvis is wide enough for spontaneous delivery has long been the subject of obstetric research. A number of variables have been proposed as predictors, all with limited accuracy. In this study, we use a novel three-dimensional (3D) method to measure the female pelvis and assess which pelvic features influence birth mode. We compare the 3D pelvic morphology of women who delivered vaginally, women who had cesarean sections, and nulliparous women. The aim of this study is to identify differences in pelvic morphology between these groups. MATERIAL AND METHODS: This observational study included women aged 50 years and older who underwent a CT scan of the pelvis for any medical indication. We recorded biometric data including height, weight, and age, and obtained the obstetric history. The bony pelvis was extracted from the CT scans and reconstructed in three dimensions. By placing 274 landmarks on each surface model, the pelvises were measured in detail. The pelvic inlet was measured using 32 landmarks. The trial was registered at the German Clinical Trials Register DRKS (DRKS00017690). RESULTS: For this study, 206 women were screened. Exclusion criteria were foreign material in the bony pelvis, unknown birth mode, and exclusively preterm births. Women who had both a vaginal birth and a cesarean section were excluded from the group comparison. We compared the pelvises of 177 women between three groups divided by obstetric history: vaginal births only (n = 118), cesarean sections only (n = 21), and nulliparous women (n = 38). The inlet area was significantly smaller in the cesarean section group (mean = 126.3 cm2 ) compared with the vaginal birth group (mean = 134.9 cm2 , p = 0.002). The nulliparous women were used as a control group: there was no statistically significant difference in pelvic inlet area between the nulliparous and vaginal birth groups. CONCLUSIONS: By placing 274 landmarks on a pelvis reconstructed in 3D, a very precise measurement of the morphology of the pelvis is possible. We identified a significant difference in pelvic inlet area between women with vaginal delivery and those with cesarean section. A unique feature of this study is the method of measurement of the bony pelvis that goes beyond linear distance measurements as used in previous pelvimetric studies.

Risk of postpartum depressive symptoms is influenced by psychological burden related to the COVID-19 pandemic and dependent of individual stress coping.

PURPOSE: There are different studies worldwide, which have shown a higher risk of mental disorders due to the COVID-19 pandemic. One aim of this study was to identify influencing factors of the psychological burden related to the COVID-19 pandemic and the impact on the development of postpartum depression. Further, the role of individual stress and coping strategies was analyzed in this context. MATERIALS AND METHODS: Between March and October 2020, 131 women in obstetric care at the LMU Clinic Munich completed a questionnaire at consecutive stages during their perinatal period. The times set for the questionnaire were before birth, 1 month, 2 months, and 6 months after birth. The questionnaire was designed to evaluate the psychological burden related to the COVID-19 pandemic. For this a modified version of the Stress and coping inventory (SCI) and the Edinburgh Postnatal Depression Scale (EPDS) was used. RESULTS: We could show that the psychological burden related to the COVID-19 pandemic influenced the EPDS score 1, 2 and 6 months after birth. In addition, the prenatal stress and individual coping strategies affected the EPDS and the burden related to the COVID-19 pandemic before and after birth significantly. CONCLUSION: An association of the psychological burden related to the COVID-19 pandemic with the risk of developing postpartum depressive symptoms could be shown in this study. In this context, the separation of the partner and the family was recognized as an important factor. Furthermore, the SCI was identified as an effective screening instrument for identifying mothers with an increased risk of postpartum depression. Hereby allowing primary prevention by early intervention or secondary prevention by early diagnosis.

Trends among patients with endometriosis over a 7-year period and the impact of the COVID-19 pandemic: experience from an academic high-level endometriosis centre in Germany.

PURPOSE: Endometriosis is known to be an underestimated disease. Lately the awareness of the disease seems to have improved. Aim of this analysis is to provide an overview of the development of treatment of patients diagnosed with endometriosis. This includes a special scope on implications of the COVID-19 pandemic since in multiple settings postponed treatments resulting in negative impact on prognosis were reported. MATERIALS AND METHODS: We analysed the development of numbers of patients treated for endometriosis in an academic centre within a 7-year period, 01/2015-12/2021, performing a systematic analysis of ICD-10-Codes from our computer system used in clinical routine. RESULTS: Treatment numbers increased over the past 7 years, i.e., 239 treated cases in 2015 vs. 679 in 2021. Following restrictions for outpatient evaluation and surgical capacity at our centre, during COVID-19 pandemic the numbers of treated patients were reduced, especially in the first lockdown period (03/22/2020-05/05/2020 vs. same period in 2019: outpatient clinic (9 vs. 36; p < 0.001), patients surgically treated (27 vs. 52; p < 0,001)). The comparison of 2020 to 2019 showed a reduction in April 2020 of - 37% in outpatient department and up to - 90% for surgically treated patients. Comparing to 2019, we found a reduction of surgical interventions in 2020 by - 9% and an increase by 83% in 2021. CONCLUSIONS: Raising numbers of patients treated for endometriosis point to a new awareness for the disease. After the decline during the lockdown period numbers raised again, leading to a delay, but not an omission of treatment. A certified endometriosis centre with established and well-organized structures is required to improve not only treatment results but also quality of life of those affected.

High RIG-I and EFTUD2 expression predicts poor survival in endometrial cancer.

PURPOSE: Endometrial cancer is the most common gynecological malignancy. The helicase RIG-I, a part of the innate immune system, and EFTUD2, a splicing factor which can upregulate RIG-I expression, are shown to influence tumor growth and disease progression in several malignancies. For endometrial cancer, an immunogenic cancer, data about RIG-I and EFTUD2 are still missing. The aim of this study was to examine the expression of RIG-I and EFTUD2 in endometrial cancer. METHODS: 225 specimen of endometrial cancer were immunohistochemically stained for RIG-I and EFTUD2. The results were correlated to clinicopathological data, overall survival (OS) and progression-free survival (PFS). RESULTS: High RIG-I expression correlated with advanced tumor stages (FIGO: p = 0.027; pT: p = 0.010) and worse survival rates (OS: p = 0.009; PFS: p = 0.022). High EFTUD2 expression correlated to worse survival rates (OS: p = 0.026; PFS: p < 0.001) and was determined to be an independent marker for progression-free survival. CONCLUSION: Our data suggest that the expression of RIG-I and EFTUD2 correlates with survival data, which makes both a possible therapeutic target in the future.

Gender Bias in Urology: How Do Patients Really Choose Their Urologist?

Purpose: The present study aimed to investigate the influence of patients' and urologists' gender when choosing a urologist. With rising population diversity through immigration and generational differences, patient-centered healthcare has recently moved to the focus of European healthcare systems. As healthcare in urology often concentrates on sensitive topics, and often involves gender-specific diseases, research on the influence of gender on decision-making processes is of high importance. Understanding influence of gender on patients' choices in real life would provide patients, and physicians alike, with the means to provide better resources to achieve greater satisfaction from visits to a urologist. Patients and Methods: A questionnaire was prepared, and patients at our tertiary referral center were given the opportunity to voluntarily participate in our survey. We collected questionnaires from 1012 patients during their visits from June 2021 to October 2021. Results: Patients were divided into groups according to their gender: male (n=763), female (n=246), and non-binary (n=3). Our patient cohort consisted of more men than women (75% vs 24%), with only three patients identifying as non-binary. Irrespective of the patients' own gender, patients preferred a male urologist when problems were considered embarrassing, limiting daily activities, or when worrisome. When problems were considered painful, all patients preferred a female urologist. When patients had had a previous positive experience with a female or male urologist, they preferred to be treated by a female or male urologist, respectively. Overall, 65% of patients stated a gender preference for at least one given situation, or consultation scenario. Conclusion: As the majority of our patients stated a gender preference, urological departments should be considerate of potential patients' preferences for urologist gender that may be based on the individual patient's history, taking a comprehensive approach to fulfill the patients' need for same gender urologists in educational hospitals and health care services.

Permixon®, hexane-extracted Serenoa repens, inhibits human prostate and bladder smooth muscle contraction and exerts growth-related functions in human prostate stromal cells.

AIMS: Recently, the European Association of Urology recommended hexane-extracted fruit of Serenoa repens (HESr) in their guidelines on management of non-neurogenic male lower urinary tracts symptoms (LUTS). Despite previously lacking recommendations, Permixon® is the most investigated HESr in clinical trials, where it proved effective for male LUTS. In contrast, underlying mechanisms were rarely addressed and are only marginally understood. We therefore investigated effects of Permixon® on human prostate and detrusor smooth muscle contraction and on growth-related functions in prostate stromal cells. MAIN METHODS: Permixon® capsules were dissolved using n-hexane. Contractions of human prostate and detrusor tissues were induced in organ bath. Proliferation (EdU assay), growth (colony formation), apoptosis and cell death (flow cytometry), viability (CCK-8) and actin organization (phalloidin staining) were studied in cultured human prostate stromal cells (WPMY-1). KEY FINDINGS: Permixon® inhibited α1-adrenergic and thromboxane-induced contractions in prostate tissues, and methacholine-and thromboxane-induced contractions in detrusor tissues. Endothelin-1-induced contractions were not inhibited. Neurogenic contractions were inhibited in both tissues in a concentration-dependent manner. In WPMY-1 cells, Permixon® caused concentration-dependent breakdown of actin polymerization, inhibited colony formation, reduced cell viability, and proliferation, without showing cytotoxic or pro-apoptotic effects. SIGNIFICANCE: Our results provide a novel basis that allows, for the first time, to fully explain the ubiquitous beneficial effects of HESr in clinical trials. HESr may inhibit at least neurogenic, α1-adrenergic and thromboxane-induced smooth muscle contraction in the prostate and detrusor, and in parallel, prostate stromal cell growth. Together, this may explain symptom improvements by Permixon® in previous clinical trials.

Presence of regulatory T-cells in endometrial cancer predicts poorer overall survival and promotes progression of tumor cells.

PURPOSE: Endometrial cancer (EC) is one of the most common gynaecologic malignancies. Tumor infiltrating regulatory T-cells (Treg) have been reported to have a prognostic impact in many malignancies. Immunotherapeutic strategies are gaining interest for advanced and recurrent EC cases, where treatment options are rare. Our study was aimed at determining the value of Treg in EC progression. METHODS: EC specimens from 275 patients and 28 controls were screened immunohistochemically for the presence of Treg represented by FoxP3. Correlations with clinicopathological and survival parameters were performed. Functional assays were performed using EC cell lines Ishikawa + and RL95-2 after co-culturing with isolated CD4 + CD25 + CD127dim Treg. To assess the influence of EC on the composition of peripheral blood mononuclear cells (PBMC), flow cytometric analyses were performed. RESULTS: We found that an increased infiltration of Treg was associated with high grades and a reduced overall survival. Treg were almost absent in endometrium tissues from healthy control patients. Co-culture of tumor cells with CD4 + CD25 + CD127dim Treg led to functional changes: enhanced invasion, migration and viability indicated that increased levels of Treg in the tumor microenvironment may promote tumor growth. Furthermore, we found that the presence of EC cells led to phenotypic changes in PBMC, showing significantly increased levels of CD25 and FoxP3. CONCLUSION: Our results indicate that the presence of Treg in the EC tumor environment is associated with a poorer outcome. A remarkable impact of Treg on tumor cell behaviour and vice versa of tumor cells on PBMC subpopulations support this notion mechanistically. Our findings provide a basis for focusing on Treg as potential future therapeutic targets in EC.