Fixed flexion deformity (FFD) of the elbow is a recognized sequela of obstetric brachial plexus palsy (OBPP). Physiotherapy, stretching, and extension splinting are commonly used, but established contractures may persist despite these measures. This study evaluated the outcomes and complications of serial casting and hinged elbow bracing for OBPP-related elbow FFD. A retrospective case series of 89 treatment courses in 73 patients with OBPP-related elbow FFD treated between 1996 and 2014 was performed. There were 80 serial casting courses, 8 hinged elbow brace courses, and 1 combined course. Outcomes were analyzed at the treatment-course level. The primary outcome was the change in active elbow FFD measured before and after treatment. Treatment duration, number of casts, complications, premature termination, and recurrence requiring repeat treatment were recorded. The mean age at treatment was 12.2±4.9 years. Mean treatment duration was 6.2±3.7 weeks. Mean pretreatment active FFD was 45.8±19.9 degrees and improved to 20.7±15.1 degrees after treatment, giving a mean improvement of 25.2 degrees (95% CI: 21.6-28.8 degrees; P<0.001; Cohen dz=1.49). The recorded range of pretreatment FFD was 15 to 120 degrees. Fifty-eight treatment courses (65.2%) achieved a post-treatment FFD of 20 degrees or less. Eight treatment courses (9.0%) were terminated prematurely because of complications, discomfort, travel burden, or noncompliance. Sixty-two of 73 patients (84.9%) required only 1 treatment course. Recurrence requiring repeat treatment occurred in 11 patients (15.1%), who underwent 27 treatment courses in total. Serial casting and hinged elbow bracing produced clinically meaningful improvement in elbow extension in patients with OBPP-related elbow FFD, with a low rate of complications and premature termination. Most patients required only 1 treatment course. Recurrence occurred in a minority of patients, but repeat treatment remained effective, supporting these techniques as repeatable nonoperative options for selected patients. Level IV, case series, retrospective.
To evaluate the impact of a formalized uterine manipulator training program on medical students' operating room experiences during their obstetrics and gynecology clerkship. Prospective cohort study with pre- and post-intervention surveys and a hands-on skills evaluation. Uterine manipulator simulation training was delivered during obstetrics and gynecology clerkship orientation at the Larner College of Medicine at University of Vermont. The sessions included a didactic video and hands-on simulation using a low-fidelity pelvic trainer. Eighty-eight third-year medical students rotating through the obstetrics and gynecology clerkship during the 2024-2025 academic year. Prior to the intervention, 69.4% of students reported discomfort assisting with laparoscopic surgery. Following the intervention, over 75% of students agreed that formalized training improved their ability to participate effectively as surgical team members, increased the educational value of laparoscopic hysterectomy cases, and enhanced their comfort assisting in surgery. There was a statistically significant improvement in uterine manipulator knowledge scores between pre- and post-simulation surveys (p < 0.001). Students scored an average of 91% on the end-of-rotation technical skills evaluation. A formalized uterine manipulator simulation training program implemented during clerkship orientation improved medical students' comfort assisting with laparoscopic hysterectomy, enhanced the educational value of operative cases, and increased their effective participation as surgical team members.
Leigh syndrome is a rare mitochondrial disorder characterized by progressive psychomotor regression. Due to high childhood mortality and rare adult-onset cases, there are no guidelines for the obstetric management of this population. In these patients, physiological stress from labor may precipitate acute decompensation, manifesting with metabolic acidosis and multiorgan failure. We report the obstetric anesthetic management of a patient with adult-onset Leigh syndrome who required an emergent intrapartum cesarean delivery after labor induction. This case highlights the necessity of tailored anesthetic strategies to mitigate mitochondrial dysfunction and supports the potential safety of essential peripartum medications previously undocumented in this population.
Emerging arboviral infections, a heterogeneous group with varied mechanisms of action and effects, pose a constant challenge in obstetric practice in overseas departments, with a potential risk of extension to mainland France. Teratogenic emerging arboviral infections such as Zika virus (ZIKV), Venezuelan equine encephalitis virus (VEEV), and more recently Oropouche virus are particularly alarming. Given climate change and globalization, these infections have the potential to spread geographically. Beyond their impact on maternal health, some infections can lead to obstetric complications, fetal and/or neonatal infections, and malformations that may result in long-term neurological and neurosensory sequelae. Their real impact seems to be underestimated. It is crucial to develop a coordinated international response within a global approach that includes human, animal, and environmental health to address the challenges posed by emerging and re-emerging infectious diseases. This may involve vaccine research, improved surveillance methods, and the development of rapid diagnostic tools. Les arboviroses émergentes, un groupe d’infections hétérogène avec des mécanismes d’action et des effets très variés, constituent un défi constant dans la pratique obstétricale dans les départements d’outre-mer, avec un potentiel risque d’extension en France métropolitaine. Les arboviroses émergentes tératogènes, comme le virus Zika, le virus de l’encéphalite équine vénézuélienne ou encore récemment le virus Oropouche, sont particulièrement alarmantes. Compte tenu du changement climatique, de l’urbanisation, de la mobilité, ces infections ont le potentiel de se propager géographiquement. Au-delà de leur impact sur la santé maternelle, certaines infections peuvent entraîner des complications obstétricales, des infections fœtales ou/et néonatales, des malformations et provoquer des séquelles de type troubles neurologiques et neurosensoriels à long terme. Leur impact réel semble sous-estimé. Il est crucial de développer une réponse internationale coordonnée, dans une approche globale incluant la santé humaine, animale et l’environnement, pour relever les défis posés par les maladies infectieuses émergentes et réémergentes. Cela peut inclure, notamment, la recherche de vaccins, l’amélioration des moyens de surveillance et la création d’outils de diagnostic rapide.
Serological testing during pregnancy is an integral part of obstetric monitoring. This screening is essentially based on the detection and dosage of specific antibodies (IgM and IgG) of a virus, bacteria or parasite. Currently in France, 4 serologies are mandatory (toxoplasmosis, rubella, syphilis and hepatitis B) but others are recommended and systematically offered (HIV, HCV, CMV). Determination of immune status should ideally be done in the pre-conception period or as soon as possible after the diagnosis of pregnancy. In the absence of immunity (IgM-, IgG-), hygienic and dietary measures are recommended, and the monitoring methods vary with the pathogen concerned. If seroconversion is suspected (IgM+, IgG+), the patient must be referred to a specialized fetal medicine unit to discuss the need for additional testing and to begin treatment if necessary. If there is any doubt about the interpretation of the serology result, it is essential to refer the patient to a prenatal center or to seek advice from a national reference laboratory. Le dépistage sérologique durant la grossesse fait partie intégrante du suivi obstétrical. Ce dépistage repose essentiellement sur la détection et le dosage d’anticorps spécifiques (IgM et IgG) d’un virus, d’une bactérie ou d’un parasite. Actuellement en France, seules quatre sérologies sont obligatoires (toxoplasmose, rubéole, syphilis et hépatite B), mais d’autres sont recommandées et systématiquement proposées (virus de l’immunodéficience humaine [VIH] et virus de l’hépatite C [VHC], cytomégalovirus [CMV]). La détermination du statut immunitaire doit être réalisée idéalement en période préconceptionnelle ou le plus précocement possible après le diagnostic de grossesse. En absence d’immunité (IgM-, IgG-), des mesures hygiénodiététiques sont recommandées, et les modalités de surveillance varient en fonction du pathogène concerné. Devant une suspicion de séroconversion (IgM+, IgG+), la patiente doit être adressée à un centre spécialisé afin de discuter de l’intérêt de réaliser des examens complémentaires et de débuter un traitement. En cas de doute sur l’interprétation du résultat de la sérologie, il est indispensable d’adresser la patiente à un centre de diagnostic prénatal ou de prendre un avis auprès d’un centre de référence.
Children, neonates, and pregnant women are particularly vulnerable during disasters. Fragmentation between specialized pediatric-perinatal systems and general disaster response frameworks can hinder coordinated care. Following lessons from the 2011 Great East Japan Earthquake, Japan established the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM) to embed specialists within disaster command structures. However, large-scale activation under prolonged infrastructure disruption has not been systematically evaluated. We conducted a structured retrospective descriptive analysis of DLPPM operational records during the first month after the 2024 Noto Peninsula Earthquake. Activities were reviewed across five pre-specified domains to examine how the liaison framework functioned during the acute and subacute phases. DLPPM was integrated into the prefectural disaster headquarters and consolidated maternal-child health information, enabling centralized identification of 83 pregnant women, estimated to represent most pregnant women in the severely affected region. Twenty-one obstetric transfers were coordinated. Pediatric transfers and evacuation of medically dependent children were facilitated through established networks. During the subacute phase, DLPPM initiated maternal-child support measures, including a "Children's Conference" and a support website. These findings suggest that DLPPM functioned as a centralized coordination hub linking specialized clinical networks with disaster governance, although real-time identification of vulnerable families in shelters remained limited. Embedding pediatric and perinatal specialists within disaster headquarters can support structured medical coordination for vulnerable populations. Earlier and more systematic integration with public health and welfare systems is essential to extend this hub function beyond hospital-centered care.
Foot pain and symptoms affect 42% of pregnant women and extend beyond gestation, but the associations between foot morphology and these symptoms are not well understood. We sought to identify changes in foot shape throughout pregnancy and postpartum, using a novel multiplane digital camera-based system and to determine whether these alterations are associated with clinically important changes in the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Physical Function scores. (1) How does foot width, length, dorsum height, Arch Height Index, and medial foot area change throughout pregnancy and postpartum? (2) Are there relationships between foot shape and changes in foot shape over time with clinically important changes in PROMIS Pain Interference and Physical Function scores during pregnancy and postpartum? Between December 2023 and November 2024, we recruited patients scheduled for an obstetrics visit at Penn Medicine clinics in the Philadelphia, PA, USA, area who were between the gestational ages of 6 to 15 weeks, older than 18 years of age, had a BMI less than 45, had no history of connective tissue disorders or trauma to the lower extremities, and could understand and provide written consent. Of 2067 contacted patients, 40 consented and scheduled a laboratory visit; 78% (31 of 40) had complete datasets and were available for analysis. Pregnant participants (mean ± SD age of 35 ± 4 years, mean ± SD BMI of 68.8 ± 11.8 kg) visited the laboratory between 9 and 15 weeks (early pregnancy), 23 and 27 weeks (mid-pregnancy), and 34 and 39 weeks (late pregnancy) of gestation as well as between 9 and 15 weeks postpartum for foot shape assessment and completion of PROMIS scores. We developed a multiplane digital imaging approach designed to capture the top and medial views of the foot simultaneously to allow rapid quantification of foot shape while eliminating exposure to ionizing radiation. We validated this system by longitudinally monitoring foot shape in a control group of 18 nonpregnant participants (mean ± SD age of 28 ± 4 years, mean ± SD BMI of 62.7 ± 6.4 kg) assessed 12 weeks apart. This control group included female patients who had no previous pregnancies, were older than 18 years of age, had a BMI less than 45, had no history of connective tissue disorders or trauma to the lower extremities that resulted in medical intervention, and could provide written consent. We collected PROMIS Pain Interference and Physical Function score assessments during pregnancy and postpartum. Both scores are standardized T-scores and range from 20 to 80, with higher Pain Interference and lower Physical Function scores indicating worse outcomes. Minimum clinically important differences for pain interference and physical function in foot and ankle orthopaedics range between 5.5 and 9.8 T-score points; therefore, we used a conservative threshold of > 10, which represents 1 SD, to identify clinically important changes in pain interference and physical function during pregnancy. We found that foot shape changed from early to late pregnancy, with median (range) increases in left foot width (9.14 cm [8.42 to 11.50] versus 9.30 cm [8.55 to 10.57], median difference +0.21 cm [95% CI 0.06 to 0.25]; p = 0.02), left dorsum height (6.22 cm [5.52 to 7.12] versus 6.33 cm [5.67 to 7.78], median difference +0.17 cm [95% CI 0.01 to 0.46]; p = 0.03), and right dorsum height (6.30 cm [5.51 to 7.58] versus 6.50 cm [5.52 to 7.64], median difference +0.23 cm [95% CI 0.13 to 0.38]; p = 0.008). There were mean ± SD increases in left foot length (24.37 ± 1.24 cm versus 24.66 ± 1.12 cm, mean difference +0.29 cm [95% CI 0.09 to 0.49]; p = 0.03), left medial foot area (83.08 ± 7.12 cm2 versus 87.30 ± 7.15 cm2, mean difference +4.22 cm2 [95% CI 2.19 to 6.25]; p = 0.001), and right medial foot area (84.02 ± 7.71 cm2 versus 88.10 ± 8.53 cm2, mean difference +4.08 cm2 [95% CI 2.21 to 5.94]; p < 0.001). In addition, median (range) left foot width increased from early pregnancy to the postpartum period (9.14 cm [8.42 to 11.50] versus 9.42 cm [8.29 to 10.77], median difference +0.10 cm [95% CI 0.09 to 0.37]; p = 0.01). We found associations between foot shape and patient-reported pain during pregnancy. Pregnant participants with clinically important increases in pain interference from early to late pregnancy had increased right medial foot area during late pregnancy (median [range] 11.37 cm2/shoe size [9.72 to 15.97], median difference +1.02 cm2/shoe size [95% CI 0.42 to 1.73]; p = 0.005) and postpartum (11.26 cm2/shoe size [9.88 to 15.47], median difference +0.91 cm2/shoe size [95% CI 0.04 to 2.57]; p = 0.01) compared to the control group of nonpregnant participants (10.35 cm2/shoe size [8.76 to 11.54]). Pregnant participants with clinically important increases in pain interference from early to late pregnancy also demonstrated an increase in right foot length from early to late pregnancy when compared with nonpregnant participants who had no changes in pain interference (0.49 ± 0.59 cm versus -0.14 ± 0.49 cm, mean difference 0.63 cm [95% CI 0.21 to 1.06]; p = 0.005). Pregnant participants with clinically important declines in physical function had a greater increase in right medial foot area from early to late pregnancy than pregnant participants without a physical function decline (6.62 ± 4.94 cm2 versus 1.98 ± 4.00 cm2, mean difference 4.64 cm2 [95% CI 1.14 to 4.64]; p = 0.01). This study identified potential morphological risk factors for musculoskeletal pain and reduced function in pregnant patients. Patient-reported pain and function were predominantly associated with pregnancy-induced lower extremity edema. These findings have potential clinical impact to guide interventions (such as compression socks, massage, or foot elevation) aimed at managing foot changes during pregnancy to reduce musculoskeletal pain and disability.Level of Evidence Level III, prognostic study.
This study aims to thoroughly investigate the protective effects of various breastfeeding rates on bronchopulmonary dysplasia (BPD), clarify the relationship between them, and further determine the minimum protective threshold. This prospective study enrolled 276 preterm infants who were born in the obstetrics department of a tertiary Grade A hospital in Zhejiang, China, and were directly admitted to the NICU. This study involved 276 infants, categorized into three breastfeeding groups based on proportion: low (100 infants, 36.2%), medium (98 infants, 35.5%), and high (78 infants, 28.3%). Notably, the incidence of BPD in the high-proportion breastfeeding group (19.5%) was significantly lower than that in the medium-proportion group (44.5%) and the low-proportion group (55%) (p < 0.05); however, there was no statistically significant difference in the incidence of BPD between the medium-proportion group and the low-proportion group (p > 0.05). Exploratory nonlinear analyses suggested a possible candidate inflection point around 0.31, above which the inverse association between breastfeeding proportion and BPD appeared stronger. Breastfeeding plays a crucial role in protecting premature infants from BPD. However, this protective effect does not increase linearly but becomes significant only when the breastfeeding rate reaches 31%. However, this threshold-related finding should be interpreted cautiously and requires validation in larger studies with more comprehensive confounder adjustment.
Partial molar pregnancy co-existing with a live fetus is a rare obstetric condition posing diagnostic and management challenges.
Antiphospholipid antibodies (aPL) may directly affect placentation and trigger local complement-mediated inflammation/thrombosis. Obstetric complications in the antiphospholipid syndrome (APS) are still frequent despite therapy/close monitoring, and the identification of new risk biomarkers is an unmet need. We aimed to prospectively investigate the prognostic value of classification/non-classification laboratory APS criteria and markers of complement activation for pregnancy complications, in particular preterm delivery (PTD). We followed 60 women prospectively during pregnancy and postpartum: 33 aPL-positive (20 APS and 13 aPL-carriers) and 27 aPL-negative [5 systemic lupus erythematosus (SLE), 11 rheumatoid arthritis (RA) and 11 undifferentiated connective tissue diseases (UCTD)]. aPL criteria tests, anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG/IgM and anti-β2glycoprotein I-Domain I (anti-β2GPI-DI) IgG, complement products (C3, C4, C3a, C5a, sC5b-9, MBL) and complement pathway activity [Classical (CP), Alternative (AP), and Lectin (LP)] were measured in 231 available specimens. PTD was experienced in 21% of aPL-positive and 15% of aPL-negative women. Anti-PS/PT IgG/IgM titers were significantly higher in PTD vs. non-PTD women (p<0.05) at almost all time-points. At variance with CP and AP, LP activity in aPL-positive PTD was lower than in non-PTD, reaching a statistically significant difference compared with aPL-negative PTD patients (p<0.05). Moreover, LP activity significantly correlated with anti-PS/PT IgG/IgM titers, both measured in the first trimester (p<0.05), and all of them significantly correlated with the week of gestation at delivery (p<0.05). The reduced LP activity and the higher anti-PS/PT IgG/IgM titers in PTD aPL-positive women during the first trimester suggest their use as early prognostic tools for PTD in aPL-positive pregnant women.
Ovarian cancer (OC) is one of the most common gynecological cancers, representing the abnormal and uncontrolled growth of ovarian cells leading to the formation of tumors. It is one of the leading causes of death in the majority of nations. A wide range of factors, such as lifestyle, environmental factors, genetic factors, hormonal changes, and repeated miscarriages, influence the emergence of OC. Contrary to these factors, breastfeeding, pregnancy, oral contraceptive pills (OCP), and tubal ligation lower the risk of getting OC. The classification of OC as early-stage, advanced-stage, low-grade, or high-grade cancer mainly depends on the histological subtype present at the time of detection. There are various classification systems used to classify OC, but the two most commonly used ones are the International Federation of Gynaecology and Obstetrics (FIGO) staging system and the tumor-node-metastasis (TNM) staging system. The present case is of a 63-year-old female patient diagnosed with high-grade serous carcinoma of the ovary with a TNM staging grade of T1a N0 M0 and an FIGO A1 grade, managed effectively with staging laparotomy. The case study concludes that early identification and care of OC can prevent disease progression, resulting in a better quality of life and prolonging the patient's life. It is crucial to conduct frequent evaluations of a specific age group in the older population to avoid such occurrences.
Placenta Accreta Spectrum (PAS) is a severe obstetric disorder characterized by excessive trophoblast invasion into the uterine myometrium, leading to life-threatening hemorrhage at delivery. While closely monitored, the molecular drivers of its progression remain poorly defined, hindering predictive and therapeutic strategies. Here, we employed longitudinal quantitative proteomics on maternal plasma from five PAS patients across gestation. We identified Keratin 6A (KRT6A) as a key biomarker whose plasma levels increase with PAS progression. Immunohistochemistry confirmed the specific upregulation of KRT6A in trophoblasts at the maternal-fetal interface in PAS. Functional studies demonstrated that KRT6A overexpression significantly enhances the migration and invasion capabilities of trophoblast cell lines in vitro, without affecting proliferation or apoptosis. Integrative bioinformatics analysis linked KRT6A to the activation of the MYC signaling pathway, a known driver of invasiveness. Our data establish KRT6A as a plasma biomarker correlating with PAS severity and a functional regulator of trophoblast invasiveness. These findings suggest a novel mechanism wherein KRT6A-mediated enhancement of trophoblast invasion, potentially via MYC signaling, contributes to PAS pathogenesis. This work provides a potential circulating biomarker for monitoring PAS progression and implicates KRT6A as a candidate therapeutic target for mitigating excessive placental invasion.
Biological tools are essential in obstetrical infectious diseases for determining immune status, systematic screening, or confirming a primary infection in pregnant women. Early detection of fetal-risk infections, even asymptomatic, is key. Expert centers and multidisciplinary prenatal diagnostic centers are recommended for complex cases.Serological analysis, particularly IgM and IgG testing, is vital for identifying primary infections. Timing and patient history (clinical, vaccination, travel) must be considered. In specific cases, follow-up tests (IgG avidity or PCR) are required for confirmation. Serological testing should be conducted early in pregnancy and within the same laboratory to ensure consistency. IgG avidity tests help differentiate recent from older infections, especially in CMV, rubella, and toxoplasmosis, where gestational timing is critical. Techniques like immunoblot and western blot are used for confirming equivocal or inconsistent serology results.PCR provides highly sensitive detection of infectious agents' DNA or RNA and can be useful before antibodies become detectable. It is particularly useful for diagnosing viral infections from lesion samples, such as HSV or VZV, and plays a key role in prenatal diagnosis on amniotic fluid after maternal infection. Les outils biologiques sont essentiels en infectiologie obstétricale pour déterminer le statut immunitaire, effectuer un dépistage systématique ou confirmer une primo-infection chez la femme enceinte. La détection précoce des infections à risque fœtal est déterminante, même en l’absence de symptômes. Dans les cas complexes, il est recommandé de consulter les centres experts (centres nationaux de référence, laboratoires spécialisés) et les centres pluridisciplinaires de diagnostic prénatal (CPDPN).Les analyses sérologiques, notamment les dosages d’IgM et IgG, sont indispensables pour identifier les primo-infections. Il est important de tenir compte du contexte clinique, des antécédents et de l’âge gestationnel. Des tests complémentaires (avidité des IgG ou PCR) sont parfois nécessaires pour confirmation. Les analyses doivent être réalisées précocement et dans le même laboratoire pour garantir la cohérence entre les résultats. Les tests d’avidité des IgG permettent de distinguer les infections récentes des plus anciennes, notamment pour la rubéole, le cytomégalovirus (CMV) et la toxoplasmose. Les techniques comme l’immunoblot et le western blot sont utilisées pour confirmer des résultats sérologiques équivoques ou discordants.La PCR offre une détection très sensible de l’ADN ou de l’ARN d’agents infectieux, utile avant l’apparition des anticorps. Elle joue un rôle clé pour diagnostiquer des infections virales (CMV, virus de l’herpès simplex) et, en contexte prénatal, elle est réalisée sur le liquide amniotique après une infection maternelle.
Placenta accreta spectrum (PAS) disorders are associated with substantial maternal morbidity and remain one of the most challenging conditions in modern obstetrics. Although cesarean hysterectomy with the placenta left in situ is widely regarded as the standard treatment, uterus-preserving surgical strategies have emerged as viable alternatives in carefully selected cases managed in specialized centers. Building on our recently published systematic review and meta-analysis, this expert-illustrated review provides a comprehensive and critical appraisal of conservative surgical approaches for PAS, with a particular focus on operative techniques, patient selection, and short- and long-term outcomes. We clearly differentiate two fundamentally distinct conservative strategies: myometrial resection techniques and leaving the placenta in situ. For each approach, we synthesize current evidence, describe procedural nuances, highlight technical prerequisites, and discuss expected intraoperative and delayed complications. The most commonly performed myometrial resection techniques-including one-step conservative surgery, the Triple-P procedure, and the Kasr Alainy technique-are detailed step-by-step and illustrated to emphasize key surgical principles. Expectant management with the placenta left in situ is also reviewed, with particular attention to indications, postoperative surveillance, delayed morbidity, and fertility outcomes. Data from 50 studies encompassing 2659 patients undergoing myometrial resection and 552 managed with the placenta left in situ are integrated to contextualize reported outcomes and failure rates. This expert review aims to support clinical decision-making by clarifying the indications, limitations, and risks of conservative PAS management. We argue that uterus-preserving strategies can be safely and effectively implemented in selected patients when performed by experienced multidisciplinary teams, while emphasizing that readiness to convert to hysterectomy remains essential. By distinguishing techniques and aligning them with patient-specific factors, this review provides practical guidance for maternal-fetal medicine specialists managing PAS in contemporary clinical practice.
Endometriosis is associated with chronic pelvic pain, largely due to immune dysregulation within the peritoneal cavity. The activation status of peritoneal immune cells is not well understood, and comparisons with systemic immune cells may provide insights for diagnosing and treating inflammation and pain in endometriosis. To investigate immune cell activation and inhibition status in peritoneal fluid and blood in endometriosis patients using full-spectrum flow cytometry. This study included patients undergoing laparoscopy for diagnosis or treatment of peritoneal endometriosis or for unrelated conditions; peritoneal fluid was collected from n = 6 endometriosis patients and n = 8 controls, and matched blood from n = 5 endometriosis patients and n = 7 controls. Immune cells were analysed using a 20-marker full-spectrum flow cytometry panel. Data were analysed for statistical significance using the Kruskal-Wallis or Mann-Whitney U test, with a p value below 0.05 considered significant. The main differences between endometriosis and control samples were found in lymphoid populations in peritoneal fluid and myeloid populations in blood. Contrary to our expectations, the expression of PD-1 on peritoneal fluid NK and T cell populations was significantly lower in endometriosis than in controls (p < 0.05). The significant decrease in immune checkpoint PD-1 expression represents a novel immunopathological feature of endometriosis and highlights potential therapeutic targets for managing inflammation and pain through immune checkpoint modulation.
Accurate nodal staging in early-stage cervical cancer remains challenging. Although preoperative imaging is mandatory in the preoperative workup, its limited sensitivity for small-volume disease, together with the suboptimal performance of intraoperative frozen section, may result in undetected lymph node metastases. We report a case from the ongoing RHINOCERUS study (NCT06906705) exploring the feasibility of intraoperative high-frequency ultrasound for sentinel lymph node evaluation. A patient with cervical cancer clinically staged as FIGO 2018 stage IB1, with no evidence of nodal involvement at preoperative imaging, was selected for radical hysterectomy with sentinel lymph node biopsy. After surgical excision, sentinel lymph nodes were intraoperatively assessed ex vivo using a 33 MHz high-frequency linear ultrasound probe and classified according to standardized ultrasound criteria. Ultrasound classified one sentinel node as malignant (LN5) and the other as probably malignant (LN4). Histopathological examination subsequently confirmed metastatic involvement in both sentinel lymph nodes. Qualitative comparison demonstrated concordance between ultrasound features and the histopathological correlates. These preliminary findings suggest that high-frequency ultrasound may provide real-time intraoperative morphological assessment of lymph nodes. Intraoperative identification of nodal metastases could inform surgical decision-making. Further prospective evaluation is ongoing to define its diagnostic accuracy and clinical applicability.
Vitamin K deficiency bleeding in infants is a rare but potentially life-threatening condition that is effectively prevented by newborn intramuscular vitamin K prophylaxis. Despite this, there are reports of increasing parental refusal of vitamin K prophylaxis globally. To evaluate temporal trends of prophylactic newborn vitamin K administration and its association with bleeding diagnoses during infancy. This was a nationwide cohort study of births between January 1, 2003, and December 31, 2021, followed up until 6 months of age. The study setting was in Sweden and included all live-born infants born at 35 or more weeks' gestation during the study period. Data analysis was performed from June 1 to December 19, 2025. The exposure was nonreceipt of intramuscular vitamin K administration at birth. The primary outcome was a bleeding diagnosis within the first 6 months of life. Data from the Swedish Medical Birth Register was linked to multiple Swedish national registers. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% CIs. Among 2 020 302 live births, 24 089 infants (mean [SD] gestational age, 40.0 [1.6] weeks; 12 472 male [51.8%]) had no record of intramuscular vitamin K administration at birth. The rate of nonreceipt decreased during the first study years from 1.32% (1242 of 94 214 newborns) in 2003 to 0.66% (667 of 100 429 newborns) in 2006, and then gradually increased and more than doubled to 1.50% (1619 of 107 915 newborns) in 2021. Infants without intramuscular vitamin K administration had 1.54-fold higher odds (aOR, 1.52; 95% CI,1.27-1.81) of bleeding and 3.18-fold higher odds (aOR, 2.91; 95% CI, 2.13-3.96) of an intracranial bleeding episode during infancy, compared with infants with intramuscular vitamin K. This cohort study shows that the number of infants in Sweden who do not receive intramuscular vitamin K administration at birth to prevent bleeding episodes continues to be low but is increasing, and these infants have a significantly higher associated risk of bleeding episodes, including intracranial hemorrhages. These findings suggest the importance of intramuscular vitamin K administration in the newborn period to prevent bleeding episodes and the need for continued education of parents and caregivers on its significance.
The NATALEE and monarchE trials showed significant invasive disease-free survival benefits with the addition of a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to endocrine therapy (ET) in patients with hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer (EBC). This study evaluates outcomes in real-world patients prior to widespread availability of adjuvant CDK4/6is, depending on nodal status, including N0 disease with and without high-risk features. Anonymized data from the Flatiron Health US electronic health record database (2011 to 2023) were analyzed. Adults with American Joint Committee on Cancer anatomic stage I-III HR+/HER2- EBC who underwent surgery and adjuvant ET were included. Overall and distant recurrence and all-cause mortality risks were assessed descriptively across nodal subgroups using Cox proportional hazards models. Recurrence-free survival, distant recurrence-free survival (DRFS), and overall survival were evaluated using Kaplan-Meier methods in the NATALEE- and monarchE-eligible populations. Among 7481 analyzed patients, 5387 (72.0%) had N0 disease, including 604 (11.2%) with high-risk features and 4783 (88.8%) without. Additionally, 1626 (21.7%) had N1 and 468 (6.3%) had N2-N3 disease. At a potential median follow-up of 78.0 months, the N0 high-risk subgroup showed overall and distant recurrence and mortality risks similar to those in the N1 subgroup. Overall, 2534 patients (33.9%) were NATALEE-eligible, and 1157 (15.5%) were monarchE-eligible. Both populations showed relatively high 5-year distant recurrence rates (DRFS, 83.1% and 74.6%, respectively). This contemporary real-world analysis highlights a meaningful recurrence risk in the broader HR+/HER2- EBC population, irrespective of nodal status, and emphasizes the need for effective treatment strategies.
Women with polycystic ovary syndrome (PCOS) and insulin resistance (IR) commonly have elevated serum advanced glycation end-products (AGEs) that accumulate in their ovaries, potentially altering ovarian function. AGEs have been shown to interfere with insulin signaling in granulosa cells (GCs) by suppressing the translocation of glucose transporters. Additionally, PCOS has been associated with insulin receptor substrate (IRS)-1 polymorphisms and upregulation in IRS-1 gene expression in GCs. We hypothesize that AGEs are partly responsible for ovarian IR by altering IRS-1 in human GCs. Cumulus granulosa cells from women undergoing IVF were cultured in control media or media containing human glycated albumin (HGA) as a source of AGEs. The quantification of mRNA expression was compared using RT-PCR for receptors for AGEs (RAGE), IRS-1, IRS-2, Glucose Transporter Type (GLUT)-1, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). In addition, IRS-1 protein intensity was assessed by immunofluorescence. Compared to the control group, HGA-treated GCs showed a statistically significant upregulation in RAGE mRNA by 314% and in IRS-1 mRNA by 423%. Even though there was a 183% increase in GLUT-1 mRNA, it did not reach statistical significance. There was no change in IRS-2 or NF-κB mRNA expression levels. Immunofluorescence showed that IRS-1 deposition was visualized in GCs, and the addition of HGA resulted in a significant increase in the intensity of IRS-1 protein compared to control cells. The AGE-induced upregulation in IRS-1, the primary insulin receptor substrate, in GCs could indicate compensation for insulin action deficiency and potentially IR. Additionally, immunofluorescence analysis of GLUT-4 revealed a statistically significant reduction in cytoplasmic GLUT-4 signal in HGA-treated GCs compared to controls (2.10 ± 0.21 vs. 3.81 ± 0.22 arbitrary units; p = 0.010), consistent with AGE-mediated disruption of glucose transporter localization. These results suggest that AGE exposure may initiate early molecular changes consistent with altered insulin signaling, but do not establish insulin resistance per se.
Regulatory T cells (Tregs) are key mediators of immunosuppression in ovarian cancer, yet strategies for selectively targeting tumor-infiltrating Tregs remain limited. CD4+CCR8+ Tregs have been proposed as a highly suppressive subset, but their functional relevance and therapeutic potential require further investigation. Here, we demonstrate that CCR8 is preferentially expressed on tumor-infiltrating CD4+ Tregs in syngeneic ID8 and B16 tumor models, accounting for a significantly higher proportion compared with CD4+ conventional T cells and CD8+ T cells (p < 0.001). Functionally, CD4+CCR8+ Tregs exhibited enhanced suppressive activity, markedly inhibiting IFN-γ production by CD8+ T cells (p < 0.01). The antagonist AZ084 significantly impaired Treg differentiation and alleviated Treg-mediated suppression in vitro (p < 0.01). In vivo, AZ084 treatment effectively suppressed tumor growth in both ovarian cancer and melanoma models (p < 0.01), accompanied by a reduction in tumor-infiltrating CD4+CCR8+ Tregs and an increase in CD8+ T cell infiltration and effector function (p < 0.05). Importantly, AZ084 had minimal impact on splenic immune cell composition (p > 0.05), suggesting limited systemic immunotoxicity. Collectively, our findings identify CCR8 as a selective marker and functional regulator of tumor-infiltrating Tregs. Targeting CCR8 with AZ084 represents a promising strategy to enhance antitumor immunity while preserving peripheral immune homeostasis, providing a potential therapeutic approach for ovarian cancer.