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An Ebola virus outbreak in the Democratic Republic of the Congo has been declared a Public Health Emergency of International Concern. In recent years, substantial advances in evidence-based clinical guidelines, vaccines, and therapeutics have been made, leading to improved outcomes. Our understanding regarding pregnancy outcomes has evolved; maternal mortality rates appear lower than previously believed, but vertical transmission and neonatal death rates remain high. Information gaps persist, particularly regarding infection with Bundibugyo ebolavirus, the species responsible for the current outbreak. No licensed therapeutics or vaccines are available, although candidates are promising. Including pregnant individuals in trials is critical to generating evidence on safety and efficacy of therapeutics during pregnancy. Here we provide an update regarding Ebola virus disease and implications for pregnancy.
Isolated torsion of a hydrosalpinx is an exceptionally rare gynaecological emergency that often presents with vague and non-specific symptoms, leading to delays in diagnosis. Hydrosalpinx is a known predisposing factor for tubal torsion, yet isolated involvement without ovarian pathology is uncommon. We report the case of a 22-year-old woman presenting with acute right lower abdominal pain and vomiting, in whom ultrasonography demonstrated a cystic adnexal lesion distinct from the ovary. Laparoscopic evaluation confirmed isolated torsion of the right hydrosalpinx with necrosis, necessitating salpingectomy. Early laparoscopic intervention enabled prompt recovery and preservation of ovarian function. This case highlights the importance of maintaining a high index of suspicion for isolated tubal torsion in reproductive-aged women presenting with acute pelvic pain.
To compare postoperative pain, opioid use, and recovery outcomes between transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and total laparoscopic hysterectomy (TLH). Prospective randomized controlled trial. Tertiary care university-affiliated hospital. Ninety female patients (18-75 years, ASA I-II) undergoing elective hysterectomy for benign indications. Patients were randomized to undergo hysterectomy via vNOTES (n=45) or TLH (n=45) under standardized anesthesia and analgesia protocols. Pain scores were significantly lower in the vNOTES group (p<0.001), with median NRS scores of 3 vs. 7 at 12 hours and 2 vs. 4 at 24 hours (both p<0.001). No participants in the vNOTES group received postoperative rescue opioids, whereas all TLH patients did (p<0.001); median tramadol consumption was 0 (0-0) mg vs. 200 (200-300) mg (p<0.001). Recovery was faster with vNOTES, including earlier return of bowel function, oral intake, mobilization (p=0.001), and shorter hospital stay (all p≤0.001). QoR-15 scores were higher (adjusted mean difference 10.8, 95% CI 5.9-15.7; p<0.001), while fatigue scores were lower (-3.9; p<0.001). Hemoglobin decrease was slightly greater in the vNOTES group (-1.92 ± 0.64 vs. -1.65 ± 0.55 g/dL; p=0.045), although this difference was not considered clinically significant. Postoperative nausea, shoulder pain, and respiratory distress were less frequent, with similar complication rates. vNOTES was associated with lower postoperative pain scores, reduced postoperative rescue opioid use, and improved immediate postoperative recovery compared with TLH, supporting its potential as a patient-centered minimally invasive approach. ClinicalTrials.gov (NCT07306507).
This global consensus conference was designed to define best practice for the controversial aspects of primary surgical management of uterovaginal pelvic organ prolapse (U-POP), to identify unanswered clinical questions, and to educate junior researchers on systematic review and meta-analysis methodology. Eleven committees were created with geographically diverse representation and tasked with answering pragmatic questions specific to U-POP surgical decision making. A systematic search of MEDLINE, Embase, and ClinicalTrials.gov from 2000 through December 2025 was performed with specific search terms for each committee. Relevant abstracts and full texts were doubly screened and included articles were doubly extracted. Guided by literature, consensus statements were created and assigned high, moderate, and low levels of evidence. Statements with low levels of evidence were presented and voted upon in-person at a consensus conference, hosted by the Department of Urology at Wake Forest University School of Medicine in Winston Salem, NC, USA. Contributions from 154 participants (including 33 junior researchers) from 19 countries led to 29 systematic searches, screening of 51,143 abstracts and 3,869 full-text manuscripts. There were 133 consensus statements presented at the conference; 6 were supported by high-quality, 28 by moderate-quality, and 99 by low-quality or no evidence respectively, and required Delphi process consensus. Among expert opinion statements, 58 were accepted, 32 were rejected, and 9 were eligible for revision. A total of 92 statements are presented here to guide clinical decision making and best practices in surgical management of primary U-POP.
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Crigler-Najjar syndrome (CNN) type I is a rare autosomal recessive disorder caused by complete deficiency of uridine 5'-diphosphate glucuronosyltransferase 1A1, leading to severe unconjugated hyperbilirubinemia and a high risk of kernicterus. We describe the case of a 7-year-old girl with CNN type I and kernicterus who presented with fever and breakthrough seizures during an upper respiratory infection, with severe neurodevelopmental impairment, including spastic quadriplegic cerebral palsy, epilepsy, global developmental delay, and failure to thrive. This case highlights the devastating, irreversible neurological sequelae of untreated neonatal hyperbilirubinemia and emphasizes the importance of early diagnosis and aggressive management. RésuméLe syndrome de Crigler-Najjar (CNN) de type I est une maladie autosomique récessive rare causée par un déficit complet en uridine-5′-diphosphate glucuronosyltransférase 1A1, entraînant une hyperbilirubinémie non conjuguée sévère et un risque élevé de kernictère. Nous décrivons le cas d’une fille de 7 ans atteinte du CNN de type I et d’un kernictère, qui présentait de la fièvre et des crises épileptiques de rupture lors d’une infection des voies respiratoires supérieures, ainsi qu’un retard neurodéveloppemental sévère, comprenant une paralysie cérébrale spastique tétrapléjique, une épilepsie, un retard global du développement et un retard de croissance. Ce cas met en évidence les séquelles neurologiques dévastatrices et irréversibles d’une hyperbilirubinémie néonatale non traitée et souligne l’importance d’un diagnostic précoce et d’une prise en charge agressive.
The d emographic shift toward an older population is accelerating the prevalence of age-related diseases. Precision geromedicine represents a paradigm shift in targeting the biological processes of ageing to optimise health and healthspan, which likely requires multimodal tailored interventions. PROMETHEUS, as part of the XPRIZE healthspan semi-finalist competition, is an 8-week feasibility and exploratory study including 20 middle-aged-to-older participants who received a multimodal intervention comprising fundamental and augmented interventions. The fundamental interventions include sleep and dietary recommendations; supplementation with whey protein, creatine, and fucoidan; supervised exercise with an exergaming component (dual-task cognitive-physical training); motivational interviewing; and cognitive behavioural therapy. The augmented intervention is further personalised based on predefined gerotypes, reflecting individual ageing patterns beyond chronological age. At baseline, urolithin A, nicotinamide mononucleotide, and/or multivitamin-multimineral were prescribed to participants based on their muscle mass, VO2peak, and cognitive performance. At mid-intervention, interventions were adjusted based on individual response, including dose escalation and/or the addition of ergothioneine for inadequate improvement in cognition. Primary outcomes include measures of muscle strength and mass, immune function and cognitive performance, and feasibility indicators such as adherence and trial completion. Secondary outcomes include assessments of other biological, clinical, and digital biomarkers of ageing, as well as qualitative indicators of motivation and personal values. This study is aimed at investigating the recruitment feasibility, safety, adherence, and exploratory outcome trajectories of a multimodal, personalised precision geromedicine intervention protocol based on individual participant's baseline characteristics and interim responses. These findings will also inform the design of a subsequent 12-month, randomised controlled trial evaluating personalised lifestyle and nutraceutical strategies with the potential to incorporate repurposed pharmacological agents to optimise age-related health outcomes.
To assess attachment patterns and stress coping strategies in patients with NIH and non-NIH phenotypes of PCOS. Additionally, to explore the correlations between attachment and stress coping, as well as the correlations between BMI, hirsutism, and psychological variables. 62 patients with NIH phenotypes and 32 patients with non-NIH phenotypes were enrolled into the study. Each patient underwent gynecological and endocrinological diagnostics. Attachment Styles Questionnaire was used to assess attachment, and Mini-Cope Inventory was applied to assess stress coping. The anxious-ambivalent attachment pattern was more pronounced in patients with "classic" NIH phenotypes. Patients with NIH phenotypes were less likely to use active coping, planning, and acceptance as coping mechanisms for stress. Furthermore, we observed a statistical trend in the differences in the following avoidance coping strategies: denial (p = 0.066), behavioral disengagement (p = 0.084), and self-blame (p = 0.066). In both phenotypes secure attachment correlated positively with seeking emotional support, whereas anxious-avoidant correlated negatively with this mechanism. In turn, anxious-ambivalent attachment in both phenotypes correlated negatively with acceptance and positively with behavioral disengagement and self-blame. Attachment patterns did not correlate with either BMI or the severity of hirsutism. Patients with different PCOS phenotypes differ in their attachment patterns and stress coping strategies. Attachment styles are correlated with specific coping mechanisms for stress. Personalized approach that takes into account the clinical variability of PCOS and differences in psychological functioning should be applied.
Postoperative pain and anxiety remain common concerns after minimally invasive gynecologic surgery despite advances in surgical techniques and analgesic strategies. Virtual reality (VR) has been investigated as a potential nonpharmacological intervention for pain management; however, evidence in gynecologic postoperative settings is limited. This study aims to evaluate the efficacy and safety of VR technology compared with standard postoperative analgesia for pain and anxiety management in patients undergoing minimally invasive gynecologic surgery. This randomized controlled trial was conducted at Sun Yat-sen Memorial Hospital of Sun Yat-sen University in China. A total of 131 patients undergoing laparoscopy or combined hysteroscopy for benign gynecologic diseases were randomly assigned in a 1:1 ratio to either a VR group (n=68) or a control group (n=63). All patients received a standardized general anesthesia protocol intraoperatively. The control group received conventional analgesic therapy after surgery, and the VR group received a 20-minute VR intervention 6 hours postoperatively. The pain and anxiety levels were evaluated using a visual analog scale at 6 and 7 hours postoperatively. The primary outcome was the change in pain scores between 6 and 7 hours. Secondary outcomes included maximum pain score, anxiety score changes, length of hospital stay, hospitalization costs, and occurrence of adverse events. Analyses were performed according to the intention-to-treat principle. There was no statistically significant difference in the primary outcome between the VR and control groups (mean difference 0.169, 95% CI -0.271 to 0.608; P=.45). Similarly, no significant differences were observed in the maximum pain score (mean difference 0.839, 95% CI -0.101 to 1.779; P=.08), and no improvement was observed in the anxiety score (mean difference 0.042, 95% CI -0.365 to 0.449; P=.84). No significant differences were found in length of hospital stay, hospitalization costs, or incidence of adverse events, including dizziness, nausea, and vomiting (all P>.05). A single 20-minute VR intervention did not provide additional analgesic or anxiolytic benefit compared with standard postoperative care after minimally invasive gynecologic surgery. VR was well tolerated, and its role in postoperative recovery requires further investigation. Chinese Clinical Trial Registry ChiCTR2400091244; https://tinyurl.com/4b92a9td.
This study aims to investigate the methylation status and mRNA expression of key apoptotic genes, including death-associated protein kinase (DAPK 1), tumor necrosis factor receptor superfamily member 6 (FAS), SMAC, and tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and its association with clinicopathological factors in cervical cancer cases. Methylation analysis was performed on 110 cervical cancer patients using qualitative methylation-specific polymerase chain reaction (MSP). Real-time PCR was used to analyze expression levels of selected genes. All samples were also analysed for the presence of high-risk HPV types (HPV 16 and 18) with specific primer. Additionally, association with clinicopathological and risk factors were evaluated. In-silico analysis was also done for further validation. The methylation status of DAPK, TRAIL R1, SMAC, and FAS was significantly different between cancer tissues and normal tissues. DAPK (0.001), FAS (0.001), and TRAIL R1 (0.02) were hypermethylated, and SMAC was found to be hypomethylated with the highest significance of < 0.0001. HPV 16 + samples were highly significant with DAPK (0.007) and FAS (0.013), and HPV 18 + samples were significant with DAPK (0.024), FAS (0.002) and TRAIL R1 (0.009). No HPV association was found with SMAC. Methylation was found to be inversely proportional to DAPK, TRAIL R1, and FAS expression. Aberrant promoter methylation of key apoptotic genes is significantly associated with cervical cancer and may contribute to its progression. Significant correlations with HPV infection and clinicopathological factors highlight their possible potential as predictive biomarkers. However, larger studies and functional validation are needed to confirm these findings and their clinical applicability.
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Calcium oxalate (CaOx) kidney stones are the most common form of urolithiasis and are characterized by high incidence and recurrence rates. 4-Octyl itaconate (4-OI), an itaconate derivative, has been shown to exert broad protective effects in various disease models owing to its anti-inflammatory and antioxidant properties. However, its role in CaOx kidney stone formation remains largely unknown. A CaOx kidney stone model was established in 6-week-old male C57BL/6 mice by glyoxylic acid induction, followed by treatment with 4-OI at 50 mg/kg. Renal tissues were subjected to HE, TUNEL, DHE, Prussian blue, and von Kossa staining to evaluate renal tissue injury, apoptosis, reactive oxygen species (ROS) production, iron deposition, and CaOx crystal deposition. Mechanistically, we observed that 4-OI exerts its effects through the NRF2-HO-1/SLC7A11 pathway in HK-2 cells. Our results suggest that 4-OI prevents CaOx crystal formation, attenuates oxidative stress, and mitigates ferroptosis both in vitro and in vivo via the NRF2-HO-1/SLC7A11 pathway. 4-OI attenuates renal CaOx formation, reduces oxidative stress, and alleviates ferroptosis through the NRF2-HO-1/SLC7A11 pathway. These findings suggest that 4-OI has significant therapeutic potential for the treatment of CaOx kidney stones.
Platelets can undergo at least two distinct types of regulated cell death, apoptosis and mPTP-driven necrosis. Apoptosis is believed to be responsible for platelet clearance, while strong platelet activation by physiological agonists leads to necrosis, producing procoagulant platelet remnants that are essential for blood coagulation during thrombosis and hemostasis. To thoroughly compare morphological and functional features of apoptotic and necrotic-like procoagulant platelets in vitro, their procoagulant activity, ability to bind coagulation proteins, and adhesive protein composition were evaluated. Confocal and electron microscopy were used to analyze morphology. Both apoptotic and necrotic-like procoagulant platelets had balloon-shaped morphology with phosphatidylserine-enriched "caps", as well as similar abilities to bind blood coagulation factors and participate in procoagulant reactions. However, apoptotic platelets did not release their alpha-granules and, consequently, did not have the "coat" of alpha-granular proteins such as P-selectin, fibrin(ogen), and von Willebrand factor on their surface, which was characteristic for the necrotic-like procoagulant ones. They were completely unable to bind external fibrinogen. They were completely unable to bind external fibrinogen. During storage of platelet concentrates, PS-positive platelets of both apoptotic (PS+/CD62P-) and necrotic-like procoagulant (PS+/CD62P+) phenotypes were observed to accumulate.
Tubo-ovarian abscess is a serious complication of pelvic inflammatory disease that often requires surgical management. Diabetic ketoacidosis is a life-threatening metabolic emergency most seen in Type 1 diabetes but can rarely occur in Type 2 diabetes. The simultaneous occurrence of TOA and DKA is extremely rare, highlighting a clinically important association. We report a 37-year-old woman with poorly controlled Type 2 diabetes mellitus who presented with severe abdominal pain, fever, and metabolic decompensation diagnosed as DKA. On workup, CT scan revealed bilateral tubo-ovarian abscesses. She was admitted to the intensive care unit and managed appropriately. Persistent fever with elevated CRP prompted laparoscopic drainage of both abscesses, resulting in clinical improvement. Bilateral tubo-ovarian abscess can precipitate diabetic ketoacidosis in women with Type 2 diabetes mellitus. Recognizing gynecologic sepsis as a potential precipitant is crucial for timely management.
Sub-Saharan Africa bears a high burden of both malaria in pregnancy and hypertensive disorders of pregnancy including preeclampsia, a leading cause of maternal and perinatal deaths. Increasing evidence suggests that infection with Plasmodium falciparum, which causes placental malaria, is associated with increased preeclampsia risk. Here we discuss how epidemiologic and biological evidence link malaria to preeclampsia by examining shared pathways, including placental inflammation and vascular disruptions, which culminate in the unifying phenomenon of placental dysfunction in both syndromes. With these shared mechanisms in mind, we discuss how malaria prevention strategies could reduce the risk of preeclampsia and related long-term cardiovascular disease in endemic settings. We also outline key research and implementation priorities to support integrated prevention approaches in affected settings.
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Massive perivillous fibrinoid deposition (MPFD) is an extremely rare placental pathology associated with recurrent pregnancy loss and adverse perinatal outcomes. We present the case of a 41-year-old woman with systemic autoimmune disorders and a history of ten pregnancy losses, with histologically confirmed perivillous fibrinoid deposition in two available previous placental specimens and no evidence of chronic histiocytic intervillositis in the reviewed material. A personalized immunomodulatory protocol combining intravenous immunoglobulin (IVIg), corticosteroids, hydroxychloroquine, and antithrombotic therapy was associated with a successful full-term pregnancy, culminating in the live birth of a healthy infant by C-section. This case highlights the potential utility of tailored immunotherapy in complex recurrent pregnancy loss (RPL) cases associated with MPFD, although causal attribution to any single agent cannot be established given the single-case design, incomplete histological documentation of prior losses, and the simultaneous use of multiple interventions.
Maternal fever during labor analgesia may arise from infectious causes (such as chorioamnionitis) or noninfectious causes (such as epidural-related maternal fever [ERMF]). While chorioamnionitis is associated with neonatal outcomes, the impact of isolated ERMF remains controversial. This is due, in part, to the potential for occult intrauterine infection, which may not be clinically apparent during labor. Consequently, inadequate consideration of histological chorioamnionitis has limited the scope and validity of previous studies. This study aimed to evaluate the effects of ERMF on neonatal outcomes by excluding confirmed histological chorioamnionitis and minimizing suspected infection using predefined clinical criteria. This retrospective study included women with singleton term deliveries under labor analgesia between January 2017 and July 2023. Cases with fetal anomalies or growth restriction were excluded. Placental pathological examination was performed when any of the predefined risk-based criteria were met, irrespective of maternal fever: clinical suspicion of chorioamnionitis, prolonged rupture of membranes, and neonatal asphyxia. Among febrile cases, short-term neonatal outcomes were first compared between those with and without histological chorioamnionitis. Subsequently, outcomes were compared between mothers with intrapartum fever (≥38 °C) and those without fever using propensity score matching. Long-term infant development was assessed using a Maternal and Child Health Handbook-based questionnaire. Overall, 186 matched pairs were included. All matched covariate standardized mean differences were <0.1, confirming acceptable balance. Compared with the nonfever group, the fever group had longer mean ± standard deviation durations from rupture of membranes to delivery (12.9 ± 9.4 vs 8.7 ± 10.9 hours; difference 4.2 hours; 95% confidence interval [CI], 2.17-6.33), first stage of labor (13.2 ± 6.7 vs 9.6 ± 6.3 hours; difference 3.6 hours; 95% CI, 2.32-4.99), and duration of labor analgesia (14.9 ± 9.6 vs 8.6 ± 6.7 hours; difference 6.3 hours; 95% CI, 4.62-8.01), along with a higher incidence of fetal tachycardia (36.0 vs 10.7%; absolute risk difference 25.3%; 95% CI, 12.3-37.2). In contrast, maternal fever was not associated with adverse neonatal outcomes, including umbilical artery pH <7.2, Apgar score <7 at 1 and 5 minutes, or neonatal intensive care unit admission. Growth and developmental milestones assessed at long-term follow-up using the Maternal and Child Health Handbook questionnaire were within the normal range in both groups. Following exclusion of histological chorioamnionitis, ERMF was associated with prolonged labor and fetal tachycardia but was not associated with adverse short-term neonatal outcomes or impaired long-term development.
This systematic review will aim to evaluate the effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) on implantation rate, clinical pregnancy rate, live birth rate, and clinical miscarriage rate compared to standard in vitro fertilization/intracytoplasmic sperm insemination (IVF/ICSI) in women with recurrent implantation failure. Recurrent implantation failure is a complex condition in assisted reproductive technology, attributed to multifactorial causes, with chromosomal aneuploidy being a leading contributor. PGT-A has been proposed as a strategy for selecting euploid embryos, but its effectiveness on reproductive outcomes remains unclear due to conflicting evidence. This review will include clinical trials and observational studies comparing PGT-A to standard IVF/ICSI in women with recurrent implantation failure. The review will assess the implantation rate, clinical pregnancy rate, live birth rate, and clinical miscarriage rate as outcomes. This review will follow the JBI methodology for systematic reviews of effectiveness. A systematic search will be conducted in PubMed, Scopus, and Embase (Embase.com). Two reviewers will independently screen titles, abstracts, and full texts. Data will be extracted using Excel software, and methodological quality will be assessed. Meta-analysis will be performed using a random effects model, with heterogeneity assessed by I2, and publication bias will be evaluated. Evidence certainty will be rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. English-language studies will be included from the earliest searchable date of each database until January 19, 2026. PROSPERO CRD420251029623.
As an update to the 2021 guidelines, the 2025 endometrial carcinoma risk classification by the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) combines grade 3 endometrioid and nonendometrioid carcinomas into a single "high-grade" category and indicates that, within the mismatch repair-deficient (MMRd) molecular subgroup, tumor grade has limited relevance. We evaluated the prognostic value of tumor grade within the 2025 ESGO-ESTRO-ESP framework in a retrospective, single-center cohort of 1115 patients (median follow-up: 69 mo). Molecular classification and estrogen receptor status were determined by immunohistochemistry and polymerase-ε (POLE) sequencing. A 3-category histopathologic classification (grade 1-2 endometrioid, grade 3 endometrioid, and nonendometrioid) was associated with survival within MMRd, no-specific-molecular-profile (NSMP), and p53-abnormal subgroups. Analyses were not feasible in POLE ultramutated carcinomas. Within the MMRd and NSMP groups, disease-specific survival did not differ between grade 3 endometrioid and nonendometrioid carcinomas, supporting their combination into a single high-grade category for adjusted analysis. In localized MMRd tumors, deep myometrial invasion, cervical stromal invasion, and focal or substantial lymphovascular space invasion (LVSI) were associated with poor survival. In localized NSMP tumors, the pooled high-grade category and substantial LVSI predicted poor survival, with similar outcomes observed in stage IIB and IIC tumors. We confirm the lack of independent prognostic impact of grade in MMRd, as reflected in the guidelines. In NSMP, substantial LVSI but not estrogen receptor status has prognostic value beyond grade, supporting refinement of risk stratification in clinical practice.