Foch Hospital

PURPOSE: Women remain underrepresented in clinical trials despite increasing evidence of sex and gender-related differences. METHODS: We conducted an exploratory qualitative study based on seven semi-structured interviews with French psychiatrist-researchers to examine how women’s inclusion in clinical trials is perceived and managed. RESULTS: Participants described precautionary exclusion of pregnant and breastfeeding women, organizational constraints related to umbrella protocols, and indirect communication with Research Ethics Committees. CONCLUSIONS: These findings suggest that women’s underrepresentation may be shaped by precautionary practices and institutional structures rather than explicit opposition to inclusion.

BACKGROUND:No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS:In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS:Median age at presentation was 48 years (first to third quartile, 34-59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%-48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis-associated form (13.1%) at 3 years (P=0.15). CONCLUSIONS:Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06447935.

STUDY QUESTION:What have been the activities, characteristics, and outcomes of uterus transplantation (UTx) performed worldwide from 2000 through 2024? SUMMARY ANSWER:In 91 UTx cases, 67 involved live donors and 80 of the recipients had Mayer-Rokitansky-Küster-Hauser syndrome, with 12-month graft survival of 74%, enabling pregnancy attempts that yielded 44 healthy singleton deliveries with a live birth rate per embryo transfer of 30.3%. WHAT IS KNOWN ALREADY:UTx is the only treatment for women with absolute uterine factor infertility who wish to carry a pregnancy. According to a comprehensive report including data up to 2020 on 45 UTx cases, 19 live births occurred (35.8% per embryo transfer) at a mean of 35.3 weeks gestation. STUDY DESIGN, SIZE, DURATION:Data were extracted from the web-based registry of the International Society of Uterus Transplantation (ISUTx). This registry captures information on donor and recipient characteristics, transplantation procedures, postoperative complications, immunosuppression, complications including rejections, and reproductive outcome. Analyses were undertaken of the 91 transplants performed between 6 April 2000 and 31 December 2024, that were recorded in the registry. PARTICIPANTS/MATERIALS, SETTING, METHODS:Twenty-four medical centers in five continents registered their uterus transplants by entering data from the day of transplantation until 3 months after graft removal. The following variables were assessed: the demographic and laboratory characteristics of donors and recipients, the source of graft (live versus deceased donor), surgical specifics including technique, duration, ischemic times, and post-op complications, immunosuppression, rejection data, pregnancy with live birth(s), and hysterectomy. MAIN RESULTS AND THE ROLE OF CHANCE:In 91 uterus transplantations (67 from live donors, 24 from deceased donors), the overall surgical success rate, defined as graft viability by 12 months, was 75%. Most recipients (88%) had Mayer-Rokitansky-Küster-Hauser syndrome, with mothers being the most frequent (64%) live donors. Live donor hysterectomies were performed by laparotomy (54%), robotics (28%), or laparoscopy (18%). Total ischemic time was shorter in live- versus deceased-donor UTx procedures. Rejection episodes that were treated with escalations of immunosuppression were more frequent during months 1-5 (44%) than during months 6-10 (28%) post-UTx. Graft survival during the first 12 months was superior when grafts from premenopausal donors were used as compared to from postmenopausal donors. Forty-four singleton live births (mean gestational length of 34.5 weeks), including eight second births, were reported, with a live birth rate per embryo transfer of 30%. Preeclampsia was the most common pregnancy complication, occurring in 23% of live-birth pregnancies. Major postnatal complications occurred in 11 infants, 9 with respiratory distress syndrome; no major malformations were observed. LIMITATIONS, REASONS FOR CAUTION:Data in the registry are self-reported and not subjected to validation. Although the ISUTx registry represents the most comprehensive quality registry of UTx activity in the world, cases from at least four centers are excluded as they were not entered into the registry. Birth outcomes from some registry cases are as yet unknown as these ongoing cases have not yet reached the endpoint of hysterectomy. WIDER IMPLICATIONS OF THE FINDINGS:This study presents the most comprehensive analysis to date of UTx, the only fertility treatment for absolute uterine factor infertility. The registry serves as the prime source for quality assessment and process improvement in UTx. STUDY FUNDING/COMPETING INTEREST(S):The establishment and operation of the registry were funded by the Swedish Research Council (2024-03487 to M.B.) and Jane and Dan Olsson Foundation (2024-11 to M.B.). There was no competing interest. TRIAL REGISTRATION NUMBER:Not applicable.

The future of personalized medicine requires moving beyond isolated data streams toward integrated, multi-scale representations of human health. Digital twins (DTs) have emerged as promising solutions, offering dynamic, individualized simulations of biological systems. However, current implementations often rely on narrow data sources, limiting predictive power, adaptability, and clinical utility. The next generation of digital twins must integrate molecular, cellular, tissue, organ, clinical, behavioral, and environmental data to accurately model health trajectories and disease evolution. This review synthesizes the conceptual foundations, technical architectures, clinical applications, and ethical challenges associated with multi-scale digital twins (MSDTs). Key enabling technologies include multimodal data fusion, graph neural networks, causal inference frameworks, reinforcement learning, and hybrid mechanistic–AI modeling approaches. Clinical applications can illustrate the potential of MSDTs to personalize interventions dynamically. Significant barriers persist regarding data integration, ethical governance, bias mitigation, and regulatory adaptation.

Blood pressure (BP) variability, particularly arterial hypotension during mechanical thrombectomy (MT) for acute ischemic stroke (AIS), has been associated with unfavorable outcomes. This variability in BP is notably present during induction in general anesthesia (GA). This study seeks to assess the effectiveness of a personalized BP management protocol during MT under general GA in mitigating hypotension and its impact on functional outcomes at 90 days. We conducted a monocentric before-after study involving two retrospective cohorts of patients who underwent MT for AIS under GA, before and after implementing the protocol. The protocol aimed to maintain the mean arterial pressure (MAP) within 10