OBJECTIVES:To evaluate the long-term impact of oophoropexy on pelvic pain symptoms and fertility outcomes in women with recurrent ovarian torsion. DESIGN:Retrospective case-control study. PARTICIPANTS:Thirty women who underwent oophoropexy for recurrent ovarian torsion were matched in a 1:2 ratio with 60 women who experienced a single episode of ovarian torsion treated with detorsion alone. SETTING:Tertiary university-affiliated medical center. METHODS:Demographic, clinical, surgical, and follow-up data were obtained from medical records and structured telephone interviews. Long-term outcomes included dysmenorrhea, dyspareunia, and non-menstrual pelvic pain assessed using a numeric rating scale. Reproductive outcomes were also evaluated. Conditional logistic regression was performed to account for the matched case-control design. RESULTS:Median follow-up was 48 months (IQR 16-60). Women who underwent oophoropexy had significantly higher rates of worsening dysmenorrhea (46% vs. 10%), dyspareunia (23.3% vs. 1.7%), and non-menstrual pelvic pain (36.7% vs. 11.7%) compared with controls (all p < 0.01). In adjusted conditional logistic regression accounting for the matched design, oophoropexy remained independently associated with worsening dysmenorrhea [aOR 4.11, 95% CI 1.15-14.66, p=0.030]. Fertility outcomes were comparable between groups. LIMITATIONS:The retrospective design and limited sample size may affect the generalizability of the findings, and long-term symptoms were assessed using patient-reported measures. CONCLUSIONS:Oophoropexy following recurrent ovarian torsion may be associated with long-term pelvic pain symptoms without compromising fertility. These potential risks should be discussed with patients during preoperative counselling.
INTRODUCTION:Endometriosis (EMs) is a chronic inflammatory disorder involving ectopic endometrial-like tissue. Semaphorin 3C (SEMA3C), a secreted guidance protein regulating cell survival, migration, and tissue remodeling, may contribute to EMs. This study examined SEMA3C expression and its relationship with ferroptosis in human endometrial stromal cells (HESCs). METHODS:SEMA3C expression was assessed in tissues from 30 patients with EMs and 30 controls by immunohistochemistry, Western blotting, and quantitative real-time PCR. Primary HESCs were subjected to SEMA3C overexpression or siRNA-mediated knockdown. Cell viability, migration, iron content, lipid peroxidation, antioxidant activity, inflammatory cytokines, and ferroptosis regulators were analyzed. Ferrostatin-1 was used for rescue experiments. RESULTS:SEMA3C was upregulated in ectopic tissues versus controls (P < 0.001) and correlated with disease severity (stage III-IV vs. I-II, P < 0.01). Ectopic lesions also showed higher SEMA3C mRNA than matched eutopic endometrium (P < 0.001). Ectopic tissues and SEMA3C-overexpressing HESCs showed increased ferroptosis-related oxidative and inflammatory changes. SEMA3C overexpression enhanced HESC viability and migration, increased ACSL4, and decreased Nrf2, GPX4, and SLC7A11 expression (P < 0.001). SEMA3C knockdown or Ferrostatin-1 attenuated these alterations and suppressed HESC viability and migration (P < 0.01). CONCLUSION:SEMA3C promotes HESC viability and migration through ferroptosis-related oxidative and inflammatory mechanisms, identifying the SEMA3C-ferroptosis axis as a potential pathogenic pathway in EMs.
OBJECTIVES:Cecoappendiceal endometriosis is rare and frequently mimics colorectal neoplasia, making preoperative diagnosis challenging. We report the first documented case of a cecal traction true diverticulum caused directly by endometriosis-associated smooth muscle hypertrophy and subserosal fibrosis. CASE PRESENTATION:A 42-year-old nulliparous woman presented with an incidentally discovered malignant-appearing polypoid cecal mass on colonoscopy. Abdominal CT demonstrated a 1.5-cm enhancing lesion at the proximal appendix. Laparoscopic wedge resection of the cecum and appendix was performed. Histology revealed deep endometriosis (>5 mm) with dramatic smooth muscle hypertrophy (muscularis propria 12 mm vs. normal ∼0.37 mm; >30-fold increase) in both the cecum and appendix. A true traction diverticulum-confirmed histologically to contain all three bowel wall layers-had formed as a direct mechanical consequence of progressive endometriosis-driven hypertrophy and fibrosis. Immunohistochemistry demonstrated estrogen-receptor-positive glands and CD10-positive stroma; beta-catenin negativity excluded mesenteric fibromatosis. CONCLUSION:This is the first documented case of endometriosis-induced cecal traction diverticulum, establishing a new mechanistic concept in intestinal endometriosis. Endometriosis-driven myoproliferation combined with subserosal fibrosis may generate sufficient mechanical traction to invert the cecal wall into a diverticular configuration. Endometriosis should be included in the differential diagnosis of cecal diverticular lesions in reproductive-aged women, and pelvic MRI should be considered for preoperative characterization before attributing such lesions to neoplasia or diverticulitis.
OBJECTIVE:Postpartum depressive symptoms are a common psychiatric condition with multifactorial aetiology. Haematological inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) have been proposed as indicators of systemic inflammation in mood disorders. This study aimed to investigate the association, rather than causality, between these markers and postpartum depressive symptoms in a homogeneous sample of first-time mothers. METHODS:In this cross-sectional observational study, 92 primiparous women attending a routine two-week postpartum follow-up were evaluated. Inclusion criteria included age ≥18 years, singleton term pregnancy, and attendance at postpartum follow-up. Depressive symptoms were assessed using the validated Turkish Edinburgh Postnatal Depression Scale (EPDS), with a cut-off score of 12 or higher. Complete blood count parameters were analysed, and NLR, PLR and MLR were calculated. Statistical analyses included independent samples t-tests, Mann-Whitney U tests, chi-square tests, and binary logistic regression analysis. RESULTS:Maternal and neonatal characteristics were comparable between groups. NLR, PLR and MLR values did not differ significantly. Logistic regression analysis showed that none of these markers were independent predictors of postpartum depressive symptoms (all p > 0.05). CONCLUSION:In this study, NLR, PLR and MLR were not associated with postpartum depressive symptoms. These findings suggest that simple blood count-derived ratios may have limited utility as standalone indicators of postpartum depressive symptoms.
BACKGROUND:Premenstrual Syndrome (PMS) has become a prevalent public health issue among reproductive-age women. However, comprehensive analyses of the temporal trends in PMS disease burden in China remain limited. OBJECTIVE:To investigate the trends in the disease burden of Premenstrual Syndrome (PMS) among reproductive-age women in China and globally from 1990 to 2021, and to predict the burden up to 2035. DESIGN:Secondary analysis of data from the Global Burden of Disease (GBD) 2021 study. Participants/Materials: Women of reproductive age (15-49 years). SETTING:China and global populations. METHODS:We analyzed temporal trends in PMS burden using the number of cases, years lived with disability (YLDs), crude prevalence rate (CPR), crude YLDs rate (CYR), age-standardized prevalence rate (ASPR), and age-standardized YLDs rate (ASYR). Joinpoint regression was used to analyze temporal trends, and a Bayesian age-period-cohort model was used to predict disease burden from 2022 to 2035. RESULTS:From 1990 to 2021, the ASPR and ASYR of PMS in China were both lower than the global levels. In 2021, the ASPR and ASYR of PMS in China were 43,631.94 per 100,000 and 370.48 per 100,000, respectively, representing decreases of 1.70% and 1.21% compared with 1990. Globally, the corresponding rates were 45,504.28 per 100,000 and 379.98 per 100,000, showing increases of 1.23% and 1.18% compared with 1990. Moreover, the global number of prevalent cases and YLDs rose substantially by 49.88% and 49.46%, respectively. In 2021, the peak numbers of prevalent cases and YLDs of PMS in both China and the world occurred in the 35-39-year age group, while the CPR and CYR peaked in the 40-44-year age group. Projection results indicated that the burden of PMS in China, as measured by ASPR and ASYR, would intensify from 2022 to 2035, with the rates expected to increase to 44,969.08 per 100,000 and 380.07 per 100,000, respectively. Globally, the ASPR was projected to rise to 45,786.66 per 100,000, whereas the ASYR was expected to decrease to 377.10 per 100,000. CONCLUSION:This study revealed that, in contrast to the upward trend in the global burden of PMS among women of reproductive age, the PMS burden in China exhibited a slight decline. However, the PMS burden in both China and the world is likely to face growth challenges over the next decade, highlighting the urgency of implementing targeted public health interventions.
OBJECTIVES:This study aims to systematically assess the association between exposure to endocrine-disrupting heavy metals (Pb, Hg, or Cr) and the risk of polycystic ovary syndrome (PCOS) through a meta-analysis of observational studies. DESIGN:Meta analysis Materials, Setting, Methods: We thoroughly explored PubMed, Embase, and the Cochrane Library for studies released until April 2023, using MeSH terms and keywords related to heavy metals and PCOS. Inclusion criteria encompassed observational studies reporting blood or urinary concentrations of Pb, Hg, or Cr in PCOS cases versus healthy controls. RESULTS:Seven Asian studies involving 897 reproductive-aged women were included. Whole-blood levels of Pb were significantly higher in PCOS (SMD=0.494, 95% CI: 0.227-0.761, p = 0.0003; I² = 99%), while serum or urinary levels showed no difference. Whole blood analysis provided more biologically relevant data for Pb exposure assessment due to its high binding affinity for hemoglobin. No statistically significant associations were observed for Hg exposure across biological matrices: serum (SMD = 2.047, 95% CI: -2.382 to 6.476, p = 0.365), whole blood (SMD = 0.831, 95% CI: -0.740 to 2.401, p = 0.300), or urine (SMD = 0.110, 95% CI: -0.253 to 0.473, p = 0.553). PCOS women had significant increased Cr across biological matrices (serum: SMD=0.287, 95%CI: 0.085-0.632, p <0.001; whole blood: SMD=0.506, 95% CI: 0.184-0.828, p =0.002) with minimal heterogeneity (I² = 0%). CONCLUSIONS:This meta-analysis identifies Pb and Cr exposure as a potential risk factor for PCOS in Asian populations. In contrast, Hg exhibited no statistically significant associations. These findings highlight the need for metal-specific prevention strategies in reproductive health.
OBJECTIVES:The aim of the study was to evaluate whether endometrial polyp localization is associated with premalignant/malignant histopathology and to compare clinical and morphological characteristics between benign and premalignant/malignant polyps. DESIGN:This is a single-center retrospective observational study. Participants/Materials: A total of 580 women who underwent hysteroscopic polypectomy with subsequent histopathological evaluation were included. SETTING:The study was conducted at a tertiary referral center between January 2010 and December 2024. METHODS:Polyps were categorized according to hysteroscopic localization (fundal, anterior wall, posterior wall, cornual, lower uterine segment). Cases were grouped as benign versus premalignant/malignant based on histopathology. Demographic variables (age, menopausal status), clinical presentation (abnormal uterine bleeding), and morphological parameters (polyp size, endometrial thickness) were compared. A multivariate logistic regression model including age, menopausal status, abnormal uterine bleeding, polyp size, endometrial thickness, and polyp localization was used to identify independent predictors. RESULTS:Most polyps were fundal (31.0%), anterior wall (24.3%), or posterior wall (21.0). Premalignant/malignant pathology was detected in 6.4% of cases and occurred more frequently in fundal and cornual localizations. Compared with the benign group, the premalignant/malignant group had a higher mean age (56.7 ± 8.1 vs. 48.9 ± 9.4 years) and a higher proportion of postmenopausal women (78.9 vs. 37.5%). Abnormal uterine bleeding was more common in premalignant/malignant cases (94.7 vs. 61.3%). Median polyp size was larger (18 mm [7-38] vs. 12 mm [4-34]) and mean endometrial thickness was greater (15.2 ± 5.1 mm vs. 10.1 ± 4.6 mm). In multivariate analysis, fundal (OR 2.18, 95% CI: 1.02-4.66) and cornual localization (OR 2.87, 95% CI: 1.21-6.79) remained independently associated with premalignant/malignant pathology. LIMITATIONS:This is a retrospective, single-center design; results depend on the completeness and accuracy of hysteroscopic records. Data regarding tamoxifen and hormone replacement therapy use were not available. CONCLUSIONS:Beyond established risk factors, fundal and cornual localization of endometrial polyps is independently associated with premalignant/malignant pathology. Localization may add clinical value to risk stratification during hysteroscopic assessment.
Background: Recurrent urinary tract infections (rUTIs) are common in peri- and postmenopausal women and impose substantial symptom, quality of life, and antimicrobial stewardship burdens, with particularly high incidence and hospitalization costs documented in England and UK primary care populations. Vaginal estrogen, by restoring urogenital epithelium and the Lactobacillus-dominant microbiome, is recommended in several guidelines for preventing rUTI, including UK antimicrobial prescribing guidance for rUTIs and European Association of Urology recommendations. However, most formulations are licensed only for genitourinary syndrome of menopause, not for urinary tract infection (UTI) prophylaxis. This creates a mismatch between the growing clinical evidence base and the absence of a specific regulatory indication for rUTI prevention across major regulatory agencies, including the US Food and Drug Administration (FDA), the European Medicines Agency, and the UK Medicines and Healthcare products Regulatory Agency, which may contribute to underuse and clinician uncertainty. Objectives: The objective of this review is to summarize the evidence on vaginal estrogen for prevention of rUTIs in peri- and postmenopausal women, with a particular focus on its use alone and in combination with antibiotic therapy, and on the gap between clinical guideline recommendations and regulatory product labeling. Methods: We conducted a structured narrative review focusing on randomized controlled trials (RCTs) and clinical practice guidelines evaluating intravaginal estrogen for the prevention of rUTI in peri- and postmenopausal women. PubMed and Embase searches were performed using key terms for estrogen, UTI, and menopause, and were supplemented with targeted searches of major guidelines. Data were described in terms of study design, participant characteristics, estrogen formulations and dosing regimens, timing of initiation, comparators, outcome measures, and reported safety outcomes. Outcome: Evidence from five RCTs reported that low-dose vaginal estrogen, administered as creams, tablets, rings, or gels, reduced culture-confirmed rUTI episodes and improved vaginal health indices, with no head-to-head trials comparing estrogen formulations directly, precluding conclusions about the relative superiority of any single preparation, and a favorable local safety profile. One trial found estriol pessaries less effective than antibiotic prophylaxis for rUTI prevention, suggesting that estrogen alone may be insufficient in some women and that combined regimens warrant further investigation, although no trial has directly evaluated concurrent antibiotic and estrogen therapy. Initiation was predominantly prophylactic or post-antibiotic, and no identified trial evaluated co-initiation of vaginal estrogen with antibiotics at the onset of acute UTI, highlighting a persisting evidence gap regarding optimal timing of therapy. Conclusions and Outlook: Vaginal estrogen is an evidence-based yet underutilized strategy for rUTI prevention in peri- and postmenopausal women, supported by RCT data and guideline recommendations, but not recognized in current FDA-approved indications for vaginal estrogen products. Addressing this evidence-to-approval gap will require regulatory reassessment informed by existing trial data, alongside pragmatic studies to optimize timing, dosing, and formulation, and to evaluate the efficacy of combined estrogen and antibiotic therapy. Once these therapeutic parameters are established, patient-centered research should further explore women’s preferences, acceptability, and shared decision-making, as treatment characteristics are likely to shape patient experience and outcomes.
Introduction Investigation of the number of oocytes recovered from different ovarian stimulation (OS) protocols is essential, as oocyte number is positively associated with the number of good-quality embryos obtained; however, there are few data comparing the number of oocytes retrieved following OS with recombinant or urinary gonadotropins. Methods A systematic review and meta-analysis of published evidence was performed to compare the number of oocytes retrieved with recombinant human follicle stimulating hormone:recombinant human luteinizing hormone (r-hFSH:r-hLH) in a 2:1 ratio versus highly purified human menopausal gonadotropin (HP-hMG) alone from Day 1 of OS. The literature search was conducted according to PRISMA guidelines (https://www.prisma-statement.org/) using Medline, EMBASE, Biosis, Scisearch, and TOXCENTER on STN. Studies were included if they reported on r-hFSH:r-hLH in a 2:1 ratio versus HP-hMG alone, both administered from Day 1 of OS, and the results for the number of oocytes retrieved were presented for both interventions. Data were extracted from the full articles independently by two reviewers (JES and BH). Results were analyzed using a random-effects meta-analysis model. Any potential risk of bias was assessed using the ROBINS-I tool. Secondary outcomes were the number of mature (MII) oocytes, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. Results Six studies were included in the meta-analysis (5287 cycles): four non-interventional studies, one non-interventional cross-over study and one randomized controlled trial. The number of oocytes per cycle was significantly higher in women treated with r-hFSH:r-hLH 2:1 compared with those treated with HP-hMG alone (mean difference 1.43, 95% CI 0.18–2.69; P = 0.025). Clinical pregnancy rate per started cycle was significantly higher with r-hFSH:r-hLH 2:1 compared with HP-hMG (rate ratio 1.18, 95% CI 1.06 to 1.33; P = 0.004; five studies). There were insufficient data to draw any firm conclusions on the other secondary outcomes. Conclusions The higher number of oocytes retrieved with r-hFSH:r-hLH is a pertinent finding, owing to the well-established positive association between oocyte number and reproductive outcomes. Although we report a higher clinical pregnancy rate for r-hFSH:r-hLH, limited data prevented us from drawing firm conclusions regarding live birth outcomes.
OBJECTIVES:The aim of the study was to investigate whether data collected from wearable devices, such as heart rate, step count, and sleep-related parameters, can reduce uncertainty in cardiovascular disease (CVD) risk prediction among apparently healthy women aged 40-69 years when blood pressure and blood lipid values required for the SCORE2 risk calculator are unavailable. A secondary objective was to identify wearable-derived features that contribute most to reducing uncertainty in CVD risk prediction. DESIGN:This was a monocentric, exploratory, cross-sectional observational study. Participants/Materials: Women aged 40-69 years with and without cardiovascular risk factors were invited to participate. Eligible participants were biologically female, fluent in German, owned a smartphone, and provided written informed consent. Women with diagnosed CVD, diabetes mellitus, chronic kidney disease, or familial hypercholesterolemia were excluded. The study uses clinical assessments, blood sampling, validated questionnaires, and 7-day continuous monitoring with a Garmin® Vivosmart 5 wearable device. SETTING:The study was conducted at the Department of Obstetrics and Gynecology, University Hospital of Bern, Inselspital, Switzerland. METHODS:Participants attended two study visits scheduled 7 to 10 days apart. At baseline, anthropometric measures, blood pressure, pulse, waist circumference, blood samples for lipid profile and HbA1c, and questionnaire data on medical history, nutrition, menopausal symptoms, psychosocial health, anxiety, depression, stress, sleep, and quality of life were collected. Participants wore a Garmin® wearable device for 7 days, generating data on heart rate, physical activity, sleep, and related digital biomarkers. Statistical analyses will explore probabilistic approaches to impute systematically missing SCORE2 input parameters, particularly blood pressure and blood lipids, using auxiliary variables such as age, BMI, and wearable-derived features. Model performance will be evaluated by comparing probabilistic CVD risk predictions with SCORE2 estimates based on complete clinical input data. RESULTS:As this manuscript describes the study design and methodology, no outcome results are reported. The planned sample size is 250 participants, accounting for an estimated dropout rate of approximately 10%. LIMITATIONS:The exploratory design and monocentric setting may limit generalizability. The sample size may be limited for selecting predictors from high-dimensional wearable data, and identified surrogate features will require external validation. In addition, adherence to wearing the device and potential recording or transmission errors may affect the completeness and quality of wearable data. CONCLUSIONS:The Frauenherzen study provides a methodological framework for evaluating whether wearable-derived digital biomarkers can support CVD risk prediction in middle-aged women when conventional clinical parameters are missing. By combining clinical, questionnaire-based, and wearable data, the study aimed to inform future sex-specific cardiovascular risk stratification and the development of accessible preventive digital health tools.
OBJECTIVE:The aim of the study was to compare the effectiveness, complications, and treatment preference parameters of long-term pessary therapy versus vaginal obliteration (colpocleisis) in elderly, sexually inactive female patients with severe pelvic organ prolapse (POP). DESIGN:This study was a single-center, retrospective observational study. Participants/Materials: In our study, we included elderly, sexually inactive women treated for advanced POP between January 2015 and November 2023. Long-term pessary therapy was applied in 30 cases, while 46 patients underwent vaginal obliteration. The mean follow-up duration was 41.9 ± 31.9 vs. 61.9 ± 40.1 months, respectively. SETTING:The study was performed at the department of urology of our university (n = 76). METHODS:Data collection was carried out based on clinical patient documentation and telephone interviews. We used a standardized, non-validated questionnaire specifically designed for this study covering four domains: patient characteristics; POP-related symptoms; treatment effectiveness and complications; socioeconomic and health-related parameters, including treatment preferences. Pre- and post-treatment parameters and intergroup differences were statistically analyzed. RESULTS:The mean age of the patients was 74 ± 5.6 years, and the mean BMI was 25.6 ± 4.4. Following both pessary therapy and surgery, high rates of symptom resolution were observed regarding vaginal foreign body sensation, discomfort, and/or palpable bulge (93.5% vs. 95.5%) and obstructive voiding difficulty (100% vs. 96.4%). The rate of patient satisfaction was high in both groups (90% vs. 97.8%, p = 0.15); however, symptom improvement was significantly greater following vaginal obliteration (VAS: 8.9 ± 1.1 vs. 7.7 ± 1.7, p < 0.001). Pessary therapy was discontinued in 23.3% of cases, and 20% later required surgical POP intervention. No reoperations due to recurrence were required following obliterative surgery. Adverse events occurred in 26.6% of pessary patients, and complications occurred in 17.3% of surgically treated patients. The most frequent reason for choosing pessary therapy was fear of surgery (76.6%), while the most common reason for choosing surgery was refusal of pessary therapy (58.5%). LIMITATIONS:The retrospective design and relatively small sample size limit the generalizability of the findings. CONCLUSIONS:In elderly, sexually inactive women requiring treatment for advanced POP, both vaginal obliteration and long-term pessary therapy provide excellent therapeutic alternatives. The two modalities demonstrate comparable outcomes, high effectiveness, and an acceptable rate of non-severe complications, making both options suitable for appropriately selected patients.
OBJECTIVES:The aim was to evaluate the therapeutic effects of dehydroepiandrosterone (DHEA) and DT56a (Femarelle®) on systemic and genitourinary symptoms of menopause in postmenopausal women. DESIGN:A comparative effectiveness research study of seventy postmenopausal women (mean age: 53 years), experiencing postmenopausal symptoms, was designed. PARTICIPANTS:Seventy patients were randomly assigned to receive either DHEA (60 mg/day) or Femarelle® (644 mg/day) for 3 months. MATERIALS, SETTING, METHODS:Subjects were assessed for serum estradiol, luteinizing hormone, follicle-stimulating hormone, Greene Climacteric Scales Scores, female urinary symptoms, and female sexual function index (FSFI). RESULTS:Both DHEA and Femarelle® demonstrated comparable efficacy in reducing total Greene Climacteric Scale scores. No significant differences in serum follicle-stimulating hormone and E2 levels were observed between the 2 groups. Within-group analyses showed that DHEA was associated with significant improvements in urinary symptoms (overactive bladder symptom score, urinary distress inventory-6, incontinence impact questionnaire-7, international consultation of incontinence questionnaire, and pelvic organ prolapse distress inventory) and sexual function measures (FSFI domains including desire, arousal, lubrication, orgasm, and satisfaction), whereas Femarelle® did not show significant changes over the 3-month period. Between-group comparisons of change scores suggested a trend toward greater improvement in the DHEA group; however, these findings should be interpreted with caution, given the exploratory design and limited sample size. LIMITATIONS:The absence of testosterone measurements limits the assessment of the androgenic effects of DHEA. Femarelle® has never been studied for sexual function; our findings are preliminary and require long-term validation. CONCLUSIONS:While both DHEA and Femarelle® were effective in improving climacteric symptoms, DHEA was associated with improvements in genitourinary symptoms in this cohort. However, given the exploratory design and absence of a placebo control, these findings should be interpreted as hypothesis-generating.
INTRODUCTION:Endometriosis is characterized by a persistent inflammatory process and is commonly shown to be associated with pelvic pain, dysmenorrhea, and a deterioration in overall quality of life. Due to limitations and side effects of current medical and surgical treatments, nutrition-based adjunctive strategies have gained attention. The purpose of this research was to critically examine the latest scientific evidence based on randomized controlled trials about dietary supplement treatment and the therapeutic management of endometriosis-related symptoms. METHODS:The conduct of this systematic review adhered to PRISMA methodological principles, with prior registration of the protocol in PROSPERO (CRD42024624094). PubMed, Scopus, and Web of Science databases were comprehensively explored. RESULTS:Eleven randomized controlled trials involving 739 participants were included. The mean intervention duration was 12.3 ± 6.03 weeks. Eight trials evaluated vitamin supplementation, and three assessed herbal or bioactive compounds. Combined vitamin C and E supplementation consistently demonstrated reductions in pain-related outcomes across five trials. In contrast, findings regarding vitamin D were inconsistent, with only one of three studies reporting significant improvement compared to placebo. Among herbal interventions, two of three trials reported significant reductions in pain-related symptoms. CONCLUSION:Overall methodological quality ranged from good to fair. However, the available literature restricts conclusions due to limited sample sizes and methodological differences. Larger, well-designed trials with standardized protocols and biomarker-guided approaches are needed.
Objectives: This prospective study aimed to evaluate whether β-human chorionic gonadotropin (β-hCG) levels in uterine cavity lavage fluid can serve as a diagnostic tool to differentiate ectopic pregnancy from failed intrauterine pregnancy in patients with pregnancy of unknown location (PUL). Design: This prospective interventional study was conducted at a tertiary referral center, enrolling a total of 113 hemodynamically stable patients with PUL. Materials and Methods: All enrolled patients underwent endometrial aspiration (EA), which was performed using a flexible Karman cannula to obtain tissue samples for histopathological examination. Based on histopathological results combined with clinical follow-up data, participants were subsequently categorized into two groups: those diagnosed with ectopic pregnancy and those with failed intrauterine pregnancy. Prior to performing EA, uterine lavage was performed to collect fluid samples from the endometrial cavity, and β-hCG levels were quantitatively measured in the lavage specimens. The primary outcome measure was the comparison of lavage β-hCG concentrations between the ectopic and failed intrauterine pregnancy groups, with the intent to establish a diagnostic cutoff value for clinical application. Secondary outcome measures included comparisons of serum β-hCG levels, endometrial thickness assessed via imaging, and clinical and demographic parameters between the groups. Results: After exclusion criteria and incomplete data removal, 103 patients were included in the final analysis, comprising 81 individuals diagnosed with ectopic pregnancy and 22 with failed intrauterine pregnancies. Statistical analysis showed that the mean age was significantly higher in the failed intrauterine pregnancy group versus the ectopic pregnancy group (p = 0.03), while other demographic and clinical variables did not differ significantly between the groups. β-hCG concentrations in uterine lavage fluid were lower in the ectopic group compared to the failed intrauterine pregnancy group. This difference was significant in absolute terms (mean ± SD: 122.78 ± 115.41 mIU/mL vs. 321.09 ± 495.19 mIU/mL, p = 0.008) and after normalization to total protein content in the lavage fluid (100.67 ± 208.19 mIU/mg vs. 294.32 ± 510.69 mIU/mg, p = 0.001). In contrast, serum β-hCG levels and endometrial thickness did not show statistically significant differences between the two groups. Conclusion: Lavage β-hCG appears promising as a tool for early PUL assessment by identifying the pregnancy location. This standardized methodology could expedite the diagnosis of high-risk pregnancies through a less invasive approach, thereby enhancing ectopic pregnancy management. Further research is needed to improve accuracy.
This paper shows that it is possible to quickly determine the velocity field of coronary blood flow and wall shear stress using a very fast image-based approach on a routine coronary angiogram, which is an alternative approach to reconstructing a target arterial model and performing time-consuming computational fluid dynamics simulations. The method analyzes two frames from a short contrast washout sequence acquired 0.1 s apart and applies a convection-dominant transport model to estimate local projected velocity and instantaneous projected wall shear stress. In four patients with stenoses in the middle third of the left anterior descending coronary artery, the peak wall shear stress within the stenotic segment showed a mean relative difference of 10.3% compared with a same-geometry two-dimensional ANSYS computational fluid dynamics reference. These results suggest that rapid image-only wall shear stress estimation may be used as an adjunctive hemodynamic assessment tool to provide additional information to clinicians when time is critical. However, further studies are still needed for broader validation and for evaluation at multiple time points during the cardiac cycle.
For the current noninvasive lung cancer screening methods based on volatile organic compounds (VOCs) using electronic noses (e-noses), existing approaches still face limitations in modeling the long-range dependencies of sensor responses, the cross-channel global correlations, and the long-term trend features during the steady-state phase. Moreover, the associated deep learning models are often structurally complex and rely heavily on manual feature engineering, which restricts the engineering application and clinical translation of e-nose systems. To address these issues, this study proposes a lightweight global-local feature fusion framework for complex VOC sensing tasks and designs an efficient, lightweight feature extraction module (LFE) to achieve high-efficiency gas classification. For quantitative analysis of gas components, a GBDT-GRU Joint Prediction Model (JGPM) is introduced, effectively modeling the temporal evolution characteristics of sensor response signals. The above models were systematically validated using an e-nose experimental platform with synthetic gases of acetone, ethanol, isopropanol, and their mixtures at the ppm level as a proof-of-concept (PoC) study. The experimental results show that the proposed models outperform the comparative methods in both gas classification accuracy and concentration prediction performance, while maintaining low model complexity. Although current validation is at the preclinical stage, this framework provides a robust algorithmic foundation for future intelligent gas sensing and clinical breath-based disease screening.
Accurate decoding of motor imagery electroencephalogram signals plays a critical role in brain-computer interfaces for neurorehabilitation and assistive technologies. However, existing multi-scale temporal methods often overlook scale-specific importance and fail to jointly capture transient and long-term neural dynamics, we propose a Weighted Multi-scale Attention-enhanced Temporal Convolutional Network (WMA-TCNet). The model employs parallel multi-scale temporal convolutions to capture neural patterns associated with distinct EEG rhythms. A global-aware scale attention mechanism adaptively weights each branch to emphasize task-relevant temporal information. A weighted Channel-Preserving Prior Path is introduced to maintain channel-wise dependencies and enhance spatial modeling stability across cortical regions. In addition, a temporal attention-guided TCN jointly captures local and long-range temporal dependencies. Experiments on BCI Competition IV 2a and 2b datasets show that WMA-TCNet achieves accuracies of 85.8% and 90.0% in subject-dependent settings, and 68.6% and 79.5% in cross-subject scenarios. These results demonstrate improved decoding performance and robustness, while providing a biologically meaningful framework for modeling multi-scale neural dynamics, with potential applications in brain-computer interfaces and neurorehabilitation.
OBJECTIVES:Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age and is associated with significant metabolic, reproductive, and psychological morbidity. Although international evidence-based guidelines exist, patient reports continue to indicate unmet needs, particularly in areas that most affect quality of life. The primary objective of this study was to assess PCOS-related knowledge, as well as general practitioners' (GPs) perceptions and interdisciplinary communication practices. A secondary objective was to examine whether identified knowledge gaps among GPs align with symptom domains reported by patients as most bothersome. DESIGN:This study employed a cross-sectional survey design targeting practicing GPs. Quantitative findings were descriptively analyzed and contextualized using published data from an independent, large-scale patient survey. Participants/Materials: A total of 918 GPs practicing in the federal state of Hesse, Germany, were invited to participate. The final analytical sample comprised 118 GPs who completed the survey. The GP questionnaire included demographic and professional characteristics as well as a 21-item knowledge assessment derived from the 2018 International PCOS Guideline. To contextualize GP findings, data from a published patient survey including 1,926 individuals with PCOS were used to identify patient-prioritized symptom domains. SETTING:The study was conducted in primary care settings across Hesse, Germany. METHODS:The GP survey assessed awareness of PCOS prevalence, familiarity with guideline recommendations, perceived relevance of guidelines to daily practice, and interdisciplinary collaboration, particularly with gynecologists. Knowledge accuracy scores were calculated as the percentage of correct responses across the 21 items. Subgroup analyses explored associations between GP characteristics and knowledge levels. Published patient survey data were used to determine symptom burden and domains perceived as most distressing, allowing comparison with GP knowledge gaps. RESULTS:A total of 93.2% of GPs estimated PCOS prevalence in their practice below 5% and 69.5% considered the International PCOS Guideline irrelevant to routine practice. PCOS-related knowledge among participants showed a mean accuracy of 54.6% (95% CI: 50.4-58.8) across all domains, with the lowest scores in reproductive aspects (45.5%, 95% CI: 40.6-50.4) and hyperandrogenism (43.7%, 95% CI: 38.7-48.7). Notably, cosmetic manifestations of hyperandrogenism were identified by patients as among the most burdensome symptoms. Furthermore, 45.8% of GPs reported suboptimal communication with gynecologists, highlighting deficiencies in interdisciplinary care pathways. LIMITATIONS:Limitations include a low response rate with potential nonresponse bias, the newly developed questionnaire without formal psychometric validation, and reliance on self-reported data. In addition, variation in patient populations across practices and the lack of linkage between physician responses and patient outcomes may limit generalizability. CONCLUSIONS:PCOS-related knowledge gaps among GPs are most pronounced in clinical domains that patients perceive as most distressing, highlighting a critical mismatch between care provision and patient needs. These findings underscore the necessity for targeted educational interventions, improved dissemination and implementation of PCOS guidelines in primary care, and strengthened interdisciplinary collaboration to enhance patient-centered PCOS management.
The CROSSBRAIN EU project aims to address the heterogeneous nature of brain pathologies by developing wireless implantable microbots (µBots, planned dimensions 100 × 100 × 100 μm3) for highly localized neuromodulation. These devices are designed to precisely modulate brain activity with minimal invasiveness, enabling targeted resolution of specific spatiotemporal events, capabilities not currently achieved by existing neuromodulation technologies. A crucial step involves visualizing and ensuring the optimal placement of the µBots in the brain tissue, to study their functionality after implantation. In this preliminary ex vivo study, we used non-functional µBot silicon (Si) dummies matching the lateral dimensions of the intended µBots, with reduced thickness (100 × 100 × 50 μm3) to simplify fabrication and handling. Due to the intrinsic MRI incompatibility of the µBot platform, encompassing both the dummies used in this study and the future functional devices under development, and the limitations of standard histological approaches in reliably identifying and preserving the implant site during processing, we developed an integrated imaging workflow combining 2D and 3D techniques. While standard histological methods and tissue clearing presented substantial limitations in preserving the position of the dummies within the brain tissue, combining histological techniques with 3D X-ray tomography provided a robust strategy. In particular, synchrotron radiation-based X-ray Phase Contrast Tomography (XPCT), with its intrinsic high contrast and resolution, enabled detailed visualization of dummies within the surrounding vascular and cellular architecture. In contrast, conventional micro-Computed Tomography (micro-CT), although more widely accessible, enabled non-destructive guidance for targeted sectioning. Importantly, and in line with the scope of a Brief Research Report, this study presents a preliminary but technically robust investigation conducted within the CROSSBRAIN project, aimed at identifying and establishing an optimized imaging strategy for the visualization of implanted µBots in brain tissue. This methodological framework is intended as an initial step toward future in vivo studies, in which the validated imaging pipeline will be applied to track both dummy and functional devices and to enable subsequent evaluation of foreign body response under physiologically relevant conditions. This ex vivo workflow therefore provides the essential technical foundation for such future investigations and supports the clear positioning of this work as a feasibility and optimization study. This approach could be particularly valuable for new generations of implantable technologies incompatible with MRI and could support future development of personalized neuromodulation therapies by enabling precise device localization and structural tissue assessment.
Islet transplantation hold promises as a cell therapy for managing type 1 diabetes, but its effectiveness remains limited due to early graft loss caused by hypoxia and associated stressors. Identifying strategies to enhance islet resilience is imperative for improving clinical outcomes. We hypothesized that mitigating this injury requires shifting focus from augmenting oxygen supply to reducing the cellular metabolic demand. Adenosine (AD), an endogenous purine nucleoside with immunomodulatory and metabolic regulatory roles, emerges as a candidate to mitigate these challenges. This study evaluates the impact of AD on human islet (HI) viability, function, and metabolic suppression under hypoxic stress (1% O2). Results demonstrated that AD at 1 mM induced a transient reduction in insulin content without impairing viability or functional indices (stimulation index, insulin secretion). These changes were reversible within 96 h of withdrawal. Preconditioning HI with 1 mM AD prior to 48-h hypoxia preserved both viability and glucose-stimulated insulin secretion, mitigating functional losses up to 48 h post-reperfusion. These findings establish AD preconditioning as an effective, reversible approach to reduce islet metabolic demand and enhance hypoxia tolerance during the early post-transplantation period. Furthermore, AD can be readily integrated into various stages of beta-cell replacement workflow, including islet culture, encapsulation, and 3D bioprinting. Overall, AD-mediated metabolic downregulation offers a novel strategy for mitigating ischemia-reperfusion injury, paving the way for more efficient and resilient cell-based therapies for beta-cell replacement.
