Medicine and Pharmacology

Abstract: Introduction: Ovarian cancer remains the most lethal gynecological malignancy worldwide, primarily due to late-stage diagnosis, extensive molecular heterogeneity, and the development of therapeutic resistance. Although advances in cytoreductive surgery and platinum-based chemotherapy have improved short-term disease control, durable long-term survival improvements remain modest, particularly in patients with recurrent or platinum-resistant disease. Rapid progress in molecular profiling, targeted therapeutics, and artificial intelligence–based diagnostic tools has transformed the understanding and management of ovarian cancer. However, translating these scientific advances into consistent clinical benefit remains challenging due to therapeutic resistance, limited validation of emerging biomarkers, and disparities in access to precision oncology. Methods: This narrative review synthesizes current evidence from peer-reviewed clinical trials, translational studies, and systematic reviews examining molecular pathogenesis, early detection strategies, and therapeutic developments in ovarian cancer. Literature was identified through structured searches of major biomedical databases, focusing on studies evaluating molecular biomarkers, artificial intelligence–driven diagnostic approaches, targeted therapies—including poly (ADP-ribose) polymerase inhibitors and anti-angiogenic agents—and emerging treatment modalities such as immunotherapy, antibody–drug conjugates, and cellular therapies. Particular emphasis was placed on identifying conflicting findings, methodological limitations, and translational barriers affecting clinical implementation. Results: Advances in genomic and molecular characterization have established ovarian cancer as a biologically heterogeneous disease comprising multiple histological and molecular subtypes with distinct clinical behavior and therapeutic responsiveness. Targeted therapies, particularly PARP inhibitors, have significantly improved progression-free survival in patients with homologous recombination deficiency; however, long-term efficacy is frequently limited by acquired resistance mechanisms, including restoration of homologous recombination function and activation of alternative DNA repair pathways. Emerging diagnostic technologies—including circulating tumor DNA, multi-omics biomarker panels, and artificial intelligence–based predictive models—demonstrate promising diagnostic accuracy for early-stage disease detection. Nevertheless, many of these technologies remain in early clinical development and require large-scale prospective validation before routine adoption in clinical practice. Discussion: Despite substantial scientific progress, several translational gaps continue to limit the real-world impact of precision oncology in ovarian cancer. Variability in biomarker performance across populations, heterogeneity in study design, and reliance on retrospective datasets complicate interpretation of current evidence. In addition, the relatively modest response rates observed with immunotherapy highlight the importance of understanding tumor immune evasion mechanisms and optimizing combination treatment strategies. Emerging therapies, including antibody–drug conjugates and chimeric antigen receptor T-cell therapies, show encouraging early clinical activity but remain under active investigation. Addressing these challenges will require interdisciplinary collaboration, standardized biomarker validation frameworks, and integration of computational tools into routine clinical workflows. Conclusion: Ovarian cancer management is undergoing a paradigm shift toward precision oncology driven by advances in molecular biology, biomarker discovery, and targeted therapeutics. However, durable improvements in survival will depend on overcoming therapeutic resistance, validating early detection strategies in diverse populations, and ensuring equitable access to advanced diagnostics and personalized treatments. Future research should prioritize prospective validation of emerging technologies, development of biomarker-guided treatment strategies, and translation of scientific innovation into sustainable clinical outcomes.

Abstract: Background/Objectives: Pregnancy is associated with anatomical, hormonal, and immunological changes that may increase susceptibility to infections and metabolic disturbances. Adequate hygiene practices and balanced nutrition, including appropriate supplementation, may help reduce maternal and fetal complications. This study aimed to describe hygiene and nutrition behaviors among women aged 18–40 years in Romania and to evaluate their association with pregnancy outcome, complications, and infections during gestation. Methods: An observational, descriptive, and analytical cross-sectional study was conducted using an anonymous online questionnaire distributed through Google Forms. Eligible participants were women aged 18–40 years from Romania who were currently pregnant or had experienced at least one previous pregnancy ending in birth or miscarriage. The questionnaire assessed socio-demographic characteristics, hand, oral, and intimate hygiene behaviors, nutritional supplementation, pregnancy-related infections and complications, and the outcome of the most recent pregnancy. Data from 61 respondents collected over a 6-month period were analyzed using descriptive statistics and Chi-square tests. Results: Most participants reported favorable hygiene practices and relatively balanced or balanced diets. Term delivery was the most frequent pregnancy outcome (75.4%), while 72.1% reported no diagnosed infection during pregnancy. A significant association was found between intimate hygiene frequency and vaginal candidiasis (χ² = 8.92; p = 0.011), with occasional intimate hygiene linked to a higher frequency of infection. Perceived diet quality was also significantly associated with pregnancy complications (χ² = 8.81; p = 0.012), and a higher level of supplementation was significantly associated with more favorable pregnancy outcomes (χ² = 28.29; p < 0.001). No significant association was found between hand-washing frequency and urinary tract infections (χ² = 2.32; p = 0.314). Conclusions: The findings suggest that adequate intimate hygiene, balanced nutrition, and appropriate nutritional supplementation during pregnancy may contribute to better maternal and fetal out-comes. These results support the importance of prenatal education and preventive strategies focused on hygiene and nutrition. Larger studies are needed to confirm these associations.

Abstract: Chronic stress, circadian disruption, sedentary behavior, industrialized diets and disturbances in the gut microbiome have created an evolutionary mismatch between ancestral physiology and the modern environment. Generation X (Gen X) women (born between 1965–1980) are the first cohort to enter midlife having lived their entire adult lives within these conditions while also carrying distinct cohort-specific factors shaped by major economic and cultural transitions. The interaction of evolutionary mismatch and Gen X pressures destabilizes hormonal regulation, increases allostatic load and impairs mitochondrial function, contributing to fatigue, metabolic inflexibility and cognitive dysfunction during perimenopause and menopause, with implications for postmenopausal health and long-term disease risk. Women with polycystic ovary syndrome have reduced insulin sensitivity and a heightened proinflammatory response that makes them more susceptible to Gen X evolutionary mismatch pressures. This paper synthesizes evidence from evolutionary biology, endocrinology, neuroscience and lifestyle medicine to present an integrated model explaining the mechanisms driving midlife symptomatology in Gen X women. The model places midlife dysfunction within an evolutionary mismatch context, where modern environmental exposures and cohort-specific demands interact with hormonal, immune and metabolic changes to drive convergent pathophysiological mechanisms. A tiered recovery framework is proposed, targeting allostatic load reduction, circadian realignment, restoration of metabolic flexibility, and integration of mitochondrial, musculoskeletal and gut–brain–endocrine signaling systems.

Abstract: Background and Objectives: Augmented reality (AR) is increasingly being explored as an adjunct to image-guided minimally invasive surgery. In gynecology, its potential may be particularly relevant in fertility-preserving procedures, where the surgeon must balance adequate disease treatment with preservation of uterine architecture, reproductive anatomy, and future fertility potential. The aim of this review was to examine the current evidence on AR in minimally invasive reproductive gynecologic surgery, with a particular focus on myomectomy, adenomyomectomy, and endometriosis surgery, and to critically evaluate its limitations and future clinical role. Materials and Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and Google Scholar from database inception to March 2026. Search terms included combinations of “augmented reality”, “mixed reality”, “image-guided surgery”, “myomectomy”, “fibroid”, “leiomyoma”, “adenomyosis”, “adenomyomectomy”, “endometriosis”, “deep infiltrating endometriosis”, “fertility-preserving surgery”, and “reproductive surgery”. Eligible studies included original clinical studies, pilot studies, feasibility studies, case series, case reports, technical reports, and translational studies directly relevant to reproductive gynecologic surgery. Results: The available evidence is limited and consists mainly of feasibility studies, proof-of-concept reports, technical notes, and small observational series. The most developed reproductive applications of AR are currently found in myomectomy and adenomyomectomy, where MRI-based uterine modeling has been used to improve lesion localization and support tissue-sparing dissection. In endometriosis surgery, AR remains less mature as an intraoperative tool but appears promising for lesion mapping, anatomical orientation, and dissection planning. Across procedures, AR appears most clinically plausible as a tool for technical refinement and complication prevention rather than as a technology with proven superiority in perioperative or reproductive outcomes. Conclusions: AR is a promising adjunct in fertility-preserving minimally invasive gynecologic surgery, particularly in anatomically complex procedures requiring accurate lesion localization and tissue-preserving dissection. However, the current evidence base remains insufficient to support routine implementation. Future research should determine whether AR can improve operative precision, reduce complications, preserve uterine integrity, and ultimately influence fertility-related outcomes.

Abstract: Background/Objectives: Endometriosis is a chronic, estrogen-dependent inflammatory disease affecting approximately 10% of reproductive-age individuals and is associated with pelvic pain, infertility, and reduced quality of life. Despite its high prevalence, diagnosis is often delayed for years and current therapies primarily focus on hormonal suppression rather than disease modification. Recent work has clarified several biological pathways involved in endometriosis, including altered estrogen signaling, immune dysregulation, and neuroangiogenesis. These insights have prompted development of new diagnostic strategies and targeted therapies. This review aims to synthesize current evidence on advances in the diagnosis and treatment of endometriosis and to highlight emerging targeted therapies that may improve patient outcomes. Methods: A narrative review was carried out using PubMed, Scopus, and Web of Science, focusing on peer-reviewed work from the last two decades on endometriosis diagnosis and treatment. Clinical trials, systematic reviews, consensus recommendations, and observational studies were included to assemble a broad picture of established care and developing strategies. Results: Advances in diagnostic approaches include improvements in imaging modalities, development of candidate biomarkers, and exploration of non-invasive diagnostic tools aimed at reducing diagnostic delay. Therapeutic innovations include oral gonadotropin-releasing hormone (GnRH) antagonists, selective progesterone receptor modulators, aromatase inhibitors, and emerging immunomodulatory and anti-inflammatory treatments targeting key molecular pathways involved in disease progression. These developments reflect a shift toward more individualized and mechanism-based treatment strategies. Conclusions: Emerging diagnostic tools and targeted therapies represent promising advances in endometriosis care. Continued research integrating molecular insights with clinical practice may facilitate earlier diagnosis, improve symptom control, and support more personalized treatment approaches for individuals affected by endometriosis.

Abstract:

Background: Produced by indoor Stachybotrys and Trichoderma spp., macrocyclic trichothecenes (MTs), cytotoxic respirable molecules(<0.01–0.03µm) inhibit protein/DNA/RNA production, damage mitochondria, and induce apoptosis. Dust-bound MTs remain toxic despite remediation/disinfection. Upon inhalation, they cross tissue barriers spreading widely, plausibly injurious to placentae and the unborn. Methods: Retrospective epidemiological study of pregnant females and offspring exposed to indoor MTs, Stachybotrys or Trichoderma, correlating professional indoor testing, medical outcomes, exposure variables, mold species, and urine/milk MTs excretion. Results: In eight women from seven MT/mold contaminated homes, with 21 pregnancies, complications occurred in 19 (90%) pregnancies including miscarriages (38%), premature labor (33%). Placental abnormalities in 2 women (25%) from the same home (calcification, chronic villitis, placental infarcts, double placenta, gritty membranitis). Birth defects in infants (38%) included renal hypertrophy, levocardia, patent foramen ovale, ventriculoseptal defect, ptosis, teeth, “goosebump” black/grey skin discoloration. Later abnormalities included developmental delay (46%), oropharyngeal hypotonic dysphagia, refractory eczema, refractory perirectal rash progressing to intussusception. Lactation difficulties included grey-black oronasal drainage, thrush, projectile vomiting, choking, oropharyngeal neurologic damage, apnea, respiratory arrest. Aspergillus +/- Penicillium exposure was documented for all 8 women, Stachybotyrs (75%), Chaetomium (50%) Trichoderma (37%) and indoor MT contamination exposure (75%). Conclusions: In-utero indoor MTs and Stachybotrys exposure correlates strongly with adverse gestational, neonatal complications, including miscarriage, congenital defects, and placental abnormalities. Exposure timing and severity correlate with adverse outcomes. Breastfeeding with indoor exposure appears hazardous. Environmental/human MTs testing appears useful identifying contamination +/or exposure.

Abstract: Introduction: Premenstrual syndrome (PMS) and its more severe form - premenstrual dysphoric disorder (PMDD) constitute a significant health problem among women of reproductive age. These disorders include emotional, physical, and behavioral symptoms that occur in the late luteal phase and disappear with the onset of menstrual bleeding. Objective: The aim of the study was to present the symptomatology of PMS and PMDD, their epidemiology, pathogenesis and treatment, and to discuss their comorbidity with female sexual dysfunctions (FSD) and sexual pain disorders. Material and Methods: Five independent researchers conducted a review of the literature from the last ten years using the following databases: PubMed, Web of Science, and Google Scholar, employing the keywords “pms”, “pmdd” together with: “sexual dysfunction” and “sexology”. Results: PMS and PMDD are associated with an increased risk of sexual dysfunctions such as: hypolibidemia, anorgasmia and dyspareunia. The comorbidity is presumably due to shared hormonal predictors, dysregulation of the serotonergic system and psychosocial factors. Treatment includes a multidisciplinary approach, including pharmacotherapy, dietary interventions, and physiotherapeutic methods. Conclusions: PMS and PMDD may significantly affect women’s psychosexual functioning. Early diagnosis and comprehensive, interdisciplinary treatment may improve patients’ quality of life and reduce the negative health consequences of these disorders.

Abstract: Background and Objectives: Endometrial polyps are common in women presenting with subfertility, yet uncertainty persists regarding which lesions warrant removal and how best to integrate hysteroscopic management with contemporary fertility treatment pathways. This narrative review synthesizes current evidence on pathophysiological mechanisms, diagnostic approaches, fertility outcomes, and practical clinical management for women under 40 years of age. Materials and Methods: PubMed/MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library were searched for English-language human studies published between January 2005 and December 2024. From 2352 records identified, 83 studies were included (8 randomized controlled trials, 12 systematic reviews/meta-analyses, 21 prospective cohort studies, 34 retrospective cohort studies, 5 case-control studies, and 3 clinical guidelines). Evidence was synthesized thematically using a narrative approach. Results: Across treatment modalities, hysteroscopic polypectomy was consistently associated with improved fertility outcomes. The landmark Pérez-Medina randomized trial reported a relative risk of 2.1 (95% CI 1.5–2.9) for pregnancy after polypectomy before intrauterine insemination. For IVF/ICSI, reported clinical pregnancy rates after polypectomy range from 53–72% and live birth rates from 43–66%. Proposed mechanisms include mechanical interference, chronic inflammation with cytokine dysregulation, altered endometrial receptivity (including HOXA10/HOXA11 dysregulation), and impaired decidualization. Conclusion: Current evidence supports hysteroscopic polypectomy as an effective intervention to improve fertility outcomes in subfertile women with endometrial polyps, particularly prior to intrauterine insemination and IVF/ICSI. Contemporary guidance (including the 2024 SOGC guideline) favors polypectomy regardless of polyp size. Future research should clarify molecular predictors of polyp-associated infertility, optimal timing relative to fertility treatment, and long-term reproductive outcomes.

Abstract: Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways—including JAK/STAT, PI3K/AKT, NF-κB, and MAPK—that integrate immune and decidual responses. The bidirectional embryo–endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine.

Abstract:

Background/Objectives: Inguinal hernia and hydrocele are common pediatric surgical conditions resulting from failed obliteration of the processus vaginalis during fetal development. Although prenatal exposure to fine particulate matter (PM2.5) has been linked to adverse perinatal outcomes and congenital anomalies, its role in structurally defined pediatric surgical diseases remains unclear. We examined the association between maternal PM2.5 exposure during pregnancy and the risk of inguinal hernia or hydrocele in offspring. Methods: We performed a retrospective cohort study of 1,093 mother–offspring pairs delivering at a tertiary referral center (July 2016–June 2019). Monthly residential PM2.5 levels were estimated at geocoded maternal addresses using kriging interpolation from fixed-site monitoring stations. Offspring diagnosed with inguinal hernia or hydrocele through March 2024 were identified using ICD-10 codes. Perinatal characteristics were compared using t-tests and chi-square tests, and multivariable logistic regression assessed trimester-specific PM2.5 exposure and risk. Results: During follow-up, 53 offspring (4.85%) developed inguinal hernia or hydrocele. Male sex (odds ratio [OR], 24.71; 95%CI, 5.95–102.54; p<0.001) and second-trimester PM2.5 exposure (OR, 1.07 per µg/m³; 95%CI, 1.01–1.14; p=0.028) were independent risk factors. A dose–response pattern was observed across quartiles of second-trimester exposure; interquartile range increase was associated with a 64% higher risk (OR, 1.64). The model showed good discrimination (AUC, 0.804). Conclusions: Elevated maternal PM2.5 exposure during the second trimester was independently associated with increased risk of inguinal hernia or hydrocele in offspring. Prenatal air pollution may contribute to persistence of the processus vaginalis and represents a potentially modifiable environmental risk factor.

Abstract: Background: Enhanced Recovery After Cesarean (ERAC) protocols increasingly incorporate preoperative carbohydrate (CHO) loading to mitigate surgical stress and improve maternal recovery. However, concerns persist regarding its potential impact on neonatal metabolic and acid–base status. Methods: A narrative review of randomized controlled trials, observational studies, and meta-analyses published between 2019 and 2025 was conducted, focusing on neonatal outcomes following maternal preoperative CHO loading before elective cesarean delivery. Primary outcomes included Apgar scores and umbilical cord arterial pH, while secondary outcomes addressed neonatal glucose homeostasis and metabolic biomarkers. Results: Across available studies, preoperative CHO loading was not associated with adverse Apgar scores or clinically relevant neonatal acidosis. Minor statistically significant differences in umbilical cord pH reported in some cohorts remained within physiological ranges. Conversely, CHO loading consistently reduced the incidence of neonatal hypoglycemia, albeit with an increased rate of transient, clinically benign hyperglycemia. Emerging evidence also suggests reduced neonatal metabolic stress at a cellular level, reflected by lower purine degradation products in umbilical cord blood. Conclusions: Preoperative CHO loading within ERAC protocols appears metabolically safe for the neonate and confers clinically meaningful protection against neonatal hypoglycemia. While its superiority over liberal clear-fluid strategies for maternal comfort remains debated, its metabolic benefits support its role as a targeted nutritional intervention in elective cesarean delivery.

Abstract: Background: Restoration of apical support is a primary objective in pelvic organ prolapse surgery; however, postoperative pelvic floor biomechanics and vaginal axis orientation are increasingly recognized as relevant determinants of clinical outcome. Laparoscopic pectopexy may be performed using synthetic mesh or non-absorbable sutures (wire), yet the influence of fixation material on postoperative vaginal axis remains insufficiently explored. This study aimed to evaluate vaginal axis orientation after mesh versus wire pectopexy using magnetic resonance imaging (MRI). Methods: A prospective non-randomized comparative cohort study included 100 women with symptomatic apical pelvic organ prolapse (POP-Q stage ≥ II). Fifty patients underwent mesh pectopexy and fifty wire pectopexy. All patients underwent standardized postoperative pelvic MRI at one-year follow-up using a 1.5 Tesla scanner with dynamic Valsalva sequences. MRI measurements included vaginal PS3L axis angle, H-line, and M-line. Clinical outcomes were assessed by gynecological examination. Statistical analysis included ANOVA, logistic regression, and ROC curve evaluation. Results: No cases of apical prolapse recurrence were observed. Vaginal axis orientation was significantly associated with postoperative clinical findings (F = 3.867, p = 0.019). Logistic regression identified vaginal axis angle as an independent predictor of normal clinical outcome (β = −0.257, p = 0.008; AUC = 0.819). A more physiological vaginal axis was more frequently observed following wire pectopexy Conclusions: Postoperative vaginal axis orientation assessed by MRI represents a relevant parameter after apical prolapse repair. Wire pectopexy was associated with a more physiological vaginal axis alignment, suggesting potential biomechanical advantages that may influence postoperative pelvic floor stability.

Abstract: Objective: To compare fetal MAPSE and TAPSE values in preeclamptic pregnancies with those in healthy pregnancies and to examine the changes in these parameters according to the severity of preeclampsia. Methods: This prospective case–control study enrolled 77 women with preeclampsia and 81 healthy pregnant controls. Fetal MAPSE and TAPSE were obtained under standardized conditions by experienced operators using M-mode ultrasonography. Results: Fetal mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) values were found to be significantly lower in the preeclampsia group compared with the control group (p < 0.001). In analyses evaluating preeclampsia cases within themselves, fetal MAPSE and TAPSE values were found to be more significantly reduced in the preeclampsia with severe features group compared to the preeclampsia without severe features group. Conclusion: Fetal MAPSE and TAPSE values, measured by M-mode ultrasonography, were found to be significantly lower in the preeclampsia group compared to the control group. The more pronounced decrease in these values, particularly in preeclampsia with severe features cases, suggests that MAPSE and TAPSE measurements may be early indicators of fetal cardiac adaptation to the impaired intrauterine environment.

Abstract: (1) Background: Access to reliable medicines information is essential to support safe medi-cine use during pregnancy and breastfeeding, where concerns regarding fetal and neonatal safety complicate clinical decision-making. Analgesics are widely used during these peri-ods, yet uncertainty regarding safety persists due to evolving evidence, regulatory changes, and inconsistent information sources. Obstetric medicines information services play a critical role in addressing these information needs. This study aimed to evaluate patterns and characteristics of analgesic-related enquiries to a specialist obstetric medicines infor-mation service over a 20-year period. (2) Methods: A retrospective observational study was conducted using enquiry data from the King Ed-ward Memorial Hospital Obstetric Medicines Information Service (KEMH OMIS), Western Australia. All enquiries recorded between 1 January 2001 and 31 December 2020 were ex-tracted from the Microsoft Access® database. Records with incomplete data were excluded. Data were standardised, coded, and analysed using Microsoft Excel® and SPSS® Version 25. Descriptive statistics were used to summarise enquiry characteristics, caller type, tim-ing of exposure, and analgesic medicines involved. Trends over time were analysed. (3) Results: A total of 48,458 enquiries were analysed, of which 4,978 (10.3%) related to anal-gesics, making this the third most common medicine class. Most enquiries related to breastfeeding (62.1%), followed by pregnancy (32.7%). The public accounted for 60.9% of calls, while health professionals contributed 39.1%. The highest frequency of breastfeeding enquiries occurred within the first four weeks postpartum, and pregnancy enquiries were most common in the second trimester. Paracetamol was the most frequently enquired an-algesic (24.5%), followed by codeine (19.8%), ibuprofen (14.4%), diclofenac (7.2%), and tramadol (9.3%). Analgesic-related enquiries declined significantly over time (p< 0.001), particularly codeine-related enquiries following regulatory safety warnings. (4) Conclusion: Analgesics represent a substantial proportion of medicines information enquiries in preg-nancy and breastfeeding, reflecting widespread use and ongoing safety concerns. Pharma-cist-led medicines information services play a critical role in supporting safe analgesic use. Continued surveillance and targeted education are essential to optimise maternal and in-fant medication safety.

Abstract: Background. The preoperative differential diagnosis of myometrial lesions remains a significant challenge when using conventional imaging techniques, such as ultrasound (US) and magnetic resonance imaging (MRI). Radiomics and machine learning, which leverage quantitative features beyond human visual perception, are increasingly recognized as promising tools for improving differential diagnosis in gynecology. Methods. This retrospective study included patients who underwent surgery for uterine masses and had preoperative MR. A machine learning model was developed to analyze radiomic features extracted from T2-weighted and diffusion-weighted MR images. Results. 44 subjects were included: 19 (43.2%) classified as "sarcoma" and 25 (56.8%) as "fibroid" based on histology after surgery. This dataset was used for training and cross-validation of different models. Three models, comprising ensembles of machine learning classifiers (random forests, support vector machines, and k-nearest neighbors), were developed for binary classification using histological diagnosis as reference standard. The best-performing model achieved the following results: AUC 90%, accuracy 82%, sensitivity 95%, specificity 72%, PPV 72%, and NPV 95%. Conclusions. Our model demonstrated high sensitivity and moderate accuracy, suggesting its potential as a valuable tool for assisting clinicians in the preliminary assessment of myometrial lesions and guiding decision-making toward conservative management in cases of non-suspicious masses.

Abstract:

Objective: Bevacizumab (BEV) and Olaparib (OLA) have demonstrated clinical efficacy as maintenance therapies for first platinum-sensitive recurrent ovarian cancer. However, direct comparisons between these agents independent of homologous recombination deficiency (HRD) and BRCA status, remain limited and the clinical validity of OLA dose reduction has not yet been confirmed. This study aimed to compare the efficacy and safety of BEV, standard-dose OLA, and dose-reduced OLA as maintenance therapy and to evaluate the clinical utility of OLA dose reduction. Methods: This retrospective multicenter study included 101 patients with first platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer who received maintenance therapy after achieving a response to chemotherapy. Patients were classified into three groups: BEV (n = 34), standard-dose OLA (n = 31), and dose-reduced OLA (n = 36). The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and adverse events. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: Median PFS was 16 months in the BEV group, 16 months in the standard-dose OLA group, and 24 months in the dose-reduced OLA group, with significantly longer PFS in the dose-reduced OLA group (p < 0.001). In the multivariate Cox analysis, treatment remained an independent prognostic factor for PFS (HR 0.67, 95% CI 0.46–0.96, p = 0.030). Median OS was 44, 45, and 64 months, respectively, with no significant differences among groups; PFI ≥12 months was the only independent prognostic factor for OS. Grade ≥3 hematologic toxicities were more frequent in the OLA groups but were manageable. Conclusions: Dose-reduced OLA was associated with prolonged PFS while maintaining manageable toxicity, supporting its clinical validity as a maintenance option independent of HRD and BRCA status.

Abstract: Background: Gynecologic cancers constitute a major public health burden worldwide, with marked regional and temporal variations influenced by demographic changes, healthcare access, and screening practices. In Turkey, contemporary nationwide data capturing recent temporal trends—particularly during the COVID-19 pandemic—remain limited. Methods: This nationwide, retrospective observational study integrated six independent gynecologic cancer datasets obtained from the İstinye University Dataset Sharing Platform, comprising 22,468 adult patients (≥18 years) diagnosed between 2014 and 2024 across 33 hospitals in Turkey. Cancer types included ovarian, endometrial, cervical, vulvar, vaginal, and fallopian tube malignancies. Annual case counts were analyzed, and normalized admission rates were calculated per 100,000 unique patient admissions to account for variations in healthcare utilization. Cancer-type–specific analyses and descriptive pandemic-period sensitivity analyses were performed. Results: The mean age of the study population was 62.75 ± 13.95 years, with most patients aged over 60 years (60.9%). Ovarian cancer was the most frequent diagnosis (40.8%), followed by endometrial (34.7%) and cervical cancers (20.7%), while rarer malignancies accounted for less than 4% of cases. Annual diagnoses increased progressively from 2014 to 2019, followed by a marked rise in 2020 and a pronounced peak in 2021, during which 30.6% of all cases were recorded. When normalized to total unique patient admissions, gynecologic cancer admission rates ranged from 45.2–55.1 per 100,000 in the pre-pandemic period and peaked sharply in 2021 at 239.1 per 100,000 admissions. Cancer-type–specific normalization revealed parallel temporal patterns across all malignancies, with the most pronounced increases observed for ovarian (104.1 per 100,000) and endometrial cancers (77.4 per 100,000) in 2021. Overall mortality was 2.8%, with a mean survival of 13.13 ± 17.79 months among exitus patients, and no significant differences in survival duration across cancer types. Conclusions: This nationwide multicenter analysis demonstrates a substantial increase in gynecologic cancer presentations in Turkey over the past decade, with a pronounced, system-wide surge during the COVID-19 pandemic period. Normalized analyses indicate that this increase exceeded overall healthcare utilization, suggesting pandemic-related diagnostic delays and backlog effects. Continuous surveillance using utilization-adjusted metrics is essential to accurately interpret temporal trends and to guide future cancer control and healthcare resilience strategies.

Abstract: Study Objective: To perform a thorough bibliometric analysis of the scientific literature on radiofrequency ablation (RFA) for uterine fibroids, mapping the research landscape, identifying important contributors, and tracking the development of research themes with an emphasis on patient-centered outcomes such as long-term symptom control, fertility, and quality of life. Design: A bibliometric and science mapping study using CiteSpace. Setting: N/A Patients or Participants: N/A Interventions: Analysis of peer-reviewed literature indexed in the Web of Science Core Collection. Measurements and Main Results: We analyzed 156 publications from 2015-2025 using CiteSpace to identify collaborative networks, citation patterns, and research hotspots. The analysis revealed 11 major research clusters with high structural coherence (Modularity Q=0.8123; Mean Silhouette=0.8405). The largest and most impactful clusters centered on patient-centered outcomes: Health Utility (Cluster 0, n=48, mean year 2018), Long-Term Outcome (Cluster 3, n=39, mean year 2019), and Treatment Outcome (Cluster 9, n=11, mean year 2020). Technology-specific clusters confirmed two distinct RFA approaches: transcervical (Sonata System, Cluster 2, n=45) and laparoscopic (Symptomatic Myoma, Cluster 8, n=13). Citation burst analysis identified Bradley LD (burst strength 5.26) as the most impactful recent author, representing a landmark 2019 systematic review that catalyzed the field. Betweenness centrality analysis revealed artery embolization (centrality 0.26) as the primary intellectual bridge, demonstrating that RFA research is firmly anchored to the established uterine artery embolization literature. Key opinion leaders included Stewart EA (67 citations), Spies JB (46 citations), and Berman JM (40 citations). Emerging research fronts focus on fertility outcomes, with Rabinovici J (burst 3.77) and Berman JM (sigma 1.24) identified as pivotal contributors to reproductive outcomes research. Conclusion: This bibliometric analysis confirms that RFA for uterine fibroids is a rapidly maturing field with a clear trajectory from technical feasibility studies toward rigorous assessment of long-term, patient-centered outcomes. The mapping of collaborative networks and research themes provides clinicians and researchers with a valuable roadmap of the field's intellectual structure and identifies opportunities for future investigation, particularly in standardized reproductive outcome reporting and comparative effectiveness research against myomectomy and UAE.

Abstract: Background: Population ageing is accelerating worldwide, accompanied by a rising prevalence of multimorbidity and polypharmacy. Medicines with anticholinergic properties are commonly prescribed to older adults for a wide range of conditions, including depression, urinary incontinence, Parkinson’s disease, allergies, and respiratory disorders. While short-term anticholinergic effects such as dry mouth and constipation are well recognised, increasing evidence suggests that cumulative anticholinergic exposure may contribute to adverse cognitive outcomes in older populations.Objective: This review aims to discuss the concept of anticholinergic burden, outline commonly used tools to quantify exposure, and examine the evidence linking cumulative anticholinergic exposure with cognitive decline and other adverse health outcomes. It also explores strategies to identify and mitigate anticholinergic burden in clinical practice.Methods: Relevant literature on anticholinergic medications, burden scales, and associated clinical outcomes was reviewed. Attention was given to validated measurement tools such as the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Risk Scale (ARS), and Anticholinergic Drug Scale (ADS), as well as studies examining associations between anticholinergic exposure and cognitive and functional outcomes.Results: Evidence from observational studies indicates that higher cumulative anticholinergic burden is associated with increased risks of cognitive impairment, delirium, falls, functional decline, and possibly dementia. Measurement tools allow clinicians and researchers to estimate cumulative exposure, with several studies identifying clinically meaningful risk at moderate to high burden scores. Conclusion: Anticholinergic burden represents a potentially modifiable contributor to adverse outcomes in ageing populations. Routine assessment of anticholinergic exposure, careful medication review, and deprescribing strategies where appropriate may help reduce avoidable cognitive and functional harm in older adults. Integrating burden assessment into prescribing systems and clinical decision support tools may further support safer pharmacotherapy in an ageing society.

Abstract: Polycystic ovary syndrome (PCOS) is a prevalent endocrine–metabolic disorder affecting 5.5–11.5% of women of reproductive age. While reduced adiponectin levels have been con-sistently demonstrated in adult women with PCOS, findings in adolescents remain less clearly defined. A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Google Scholar were searched from inception to October 31, 2025. Observational studies comparing adiponectin levels in post-pubertal adolescents with PCOS and controls were included. A random-effects model with REML estimator was applied. Study heterogeneity and publication bias were as-sessed. Eighteen studies comprising 1,590 participants (679 PCOS; 911 controls) were in-cluded. Adolescents with PCOS demonstrated significantly lower adiponectin levels com-pared to controls (mean difference [MD] −3.17 µg/mL; 95% CI −4.27 to −2.07; p = 0.001), I² = 94.6%. Egger’s (p = 0.81) and Begg’s (p = 0.16) tests indicated no evidence of publication bias. Adolescents with PCOS exhibit significantly reduced circulating adiponectin levels, suggesting that adipose tissue dysfunction and metabolic dysregulation are present early in the disease course. These findings support the role of adiponectin as a potential early biomarker of cardiometabolic risk in adolescent PCOS and underscore the importance of early metabolic screening and intervention.