BACKGROUND:Although semaglutide 2.4 mg has demonstrated significant weight loss efficacy in clinical trials, real-world data, particularly with regard to clinically complex and underrepresented populations, remain limited. OBJECTIVES:The study aims to assess the real-world effectiveness and patient-reported outcomes associated with the use of semaglutide 2.4 mg in individuals with severe and complex obesity. The study also intends to characterize weight loss response in pre-defined subgroups of patients and to identify predictors of weight loss using machine learning. METHODS:SEMASEARCH is a retrospective multicentric observational cohort embedded within the French early-access program for semaglutide 2.4 mg. A total of 1100 patients with severe obesity (BMI ≥ 40 kg/m2 with at least one treated obesity-related complication) were retrospectively included from 11 expert obesity centers, based on prospectively collected data at baseline, 6 months, and 12 months. Subgroups include patients with a history of bariatric surgery, binge eating disorder, hypothalamic obesity, age ≥ 60 years or altered body composition, BMI ≥ 60 kg/m2, and those receiving psychotropic medications. Assessments include clinical, biological, and body composition data, as well as standardized questionnaires evaluating eating behaviour, physical activity, sleep, quality of life, digestive symptoms, and mental health. PRIMARY OUTCOME:Body weight change since treatment initiation, with assessment at 6 and 12 months. SECONDARY OUTCOMES:Clinically meaningful weight loss (≥ 10%) at 12 months, metabolic improvements, patient-reported outcomes, body composition changes, and tolerance. EXPECTED IMPACT:SEMASEARCH will provide real-world evidence on Semaglutide 2.4 mg use in patients living with severe and complex obesity. It will also address major knowledge gaps in specific populations underrepresented in clinical trials and generate predictive models of weight loss response.

Importance:Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. Objective:To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. Design, Setting, and Participants:Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). Interventions:Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. Main Outcomes and Measures:The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. Results:Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. Conclusions and Relevance:Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. Trial Registration:ClinicalTrials.gov Identifier: NCT03976895.

Background Prognostic factors for systemic outcomes and mortality of sarcoidosis in patients with uveitis have been poorly studied. Methods Multicenter retrospective cohort study of sarcoidosis patients with uveitis. Sarcoidosis diagnosis was established according to the recommendations of the American Thoracic Society. Sarcoid uveitis diagnosis was based on the Standardization of Uveitis Nomenclature classification criteria. Systemic relapse-free survival (RFS) and sequelae-free survival (SFS) were analysed using Kaplan-Meier curves and Cox proportional hazards models. Results 336 patients were included, of whom 208 (61.9%) were female. Median age at sarcoidosis diagnosis was 52 years (range, 10–89 years). Median follow-up was 7.8 years. Systemic relapses occurred in 129 of 334 (38.6%) patients. Shorter systemic RFS was associated with Sub-Saharan African ethnicity (HR, 3.65, 95% CI, 2.26–5.90, P < .001) and anterior uveitis (HR, 1.95, 95% CI, 1.25–3.03, P = .007). Sequelae occurred in 46 of 334 (13.8%) patients. Shorter systemic SFS was associated with neurologic involvement (HR, 5.05, 95% CI, 2.46–10.34, P < .001) and anterior uveitis (HR, 3.10, 95% CI, 1.45–6.66, P = .002). All-cause mortality was 7.7% (24/312) with no sarcoidosis-related deaths. Conclusions Relapses occurred in approximately 40% of patients and were associated with Sub-Saharan African ethnicity and anterior uveitis. One in seven patients developed sequelae of sarcoidosis, which were associated with neurologic involvement and anterior uveitis. These characteristics may help identify patients who could benefit from closer follow-up and consideration of more intensive immunosuppressive therapy. Mortality was approximately 8%, with no sarcoidosis-related deaths.

TPS5640 Background: Patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant platinum-based chemotherapy who are not amenable to complete interval cytoreductive surgery (ICS) due to poor chemosensitivity—defined by a CA-125 KELIM score <1.0—have a particularly poor prognosis, with approximately 20% 5-year overall survival. Ubamatamab is a human IgG4-based bispecific antibody targeting MUC16 (CA-125–expressing ovarian cancer cells) and CD3+ T cells and has demonstrated clinical activity in platinum-resistant recurrent ovarian cancer (Lee et al, Proc ESMO 2025). We hypothesize that adding ubamatamab to standard carboplatin–paclitaxel–bevacizumab may enhance tumor response and improve surgical resectability in patients with advanced high-grade EOC with poor chemosensitivity and disease not amenable to complete ICS after initial neoadjuvant chemotherapy. Methods: RegeNovar (EuCT 2025-524232-20-00) is an academic, multicenter phase I–II trial enrolling patients with stage III–IV high-grade EOC who, after 3–4 cycles of standard neoadjuvant carboplatin–paclitaxel administered every 3 weeks, present two poor prognostic features: (1) unfavorable standardized KELIM score <1.0, and (2) disease considered not amenable to complete ICS. The trial includes two sequential parts: (i) a phase I safety run-in to evaluate the safety of ubamatamab in combination with carboplatin–paclitaxel–bevacizumab and confirm the recommended phase II dose (RP2D); and (ii) a phase II efficacy part assessing the antitumor activity of this combination. Patients receive carboplatin AUC5 ; paclitaxel 175 mg/m²; and bevacizumab 15 mg/kg Q3 weeks for three cycles. Ubamatamab is administered with weekly step-up dosing during cycle 1, followed by a fixed dose of 800 mg Q3 weeks during cycles 2 and 3. Feasibility of complete late cytoreductive surgery is evaluated after three cycles of the study regimen. Subsequent maintenance treatment consists of olaparib plus bevacizumab for patients with BRCA-mutated or HRD-positive tumors, or ubamatamab plus bevacizumab for up to 15 months in patients with HRD-negative tumors. The primary endpoint of phase I is safety, including treatment-related adverse events (NCI CTCAE v6.0), DLT within the first 4 weeks, and RP2D determination using a BOIN design targeting a DLT probability ≤28%. The primary endpoint of phase II is the objective response rate (ORR) after three cycles per RECIST 1.1 (H0 5%, H1 30%, one-sided α=5%, power=80%). Total 31 to 43 patients are required, depending on potential need for dose de-escalation. Secondary endpoints include ORR, duration of response, disease control rate, rate of late cytoreductive surgery, PFS, OS, and progression-free survival during subsequent therapy. The trial is sponsored by ARCAGY-GINECO, conducted in 12 French centers, and funded by Regeneron. Clinical trial information: EuCT 2025-524232-20-00.

Objective To identify predictive factors of remission in patients with sarcoid uveitis and to evaluate recurrence rates and patterns following remission. Methods Multicentre retrospective study of patients with sarcoid uveitis and a minimum follow-up of 3 years. Remission was defined as the absence of clinical symptoms of sarcoidosis for at least 3 years without treatment. Remission-free Kaplan-Meier survival curves were constructed for selected variables. Cox proportional hazards model was then applied. HRs and 95% CIs were estimated for each variable. Statistical significance was set at the p<0.05 level. Rates and patterns of recurrence after remission were collected and compared with initial presentation. Results A total of 329 patients were included (62% female, median age 53 years). Remission occurred in 98 (30%) patients after a median follow-up of 6.5 years. Macular oedema at baseline was associated with a lower likelihood of remission (HR, 0.594, 95% CI 0.342 to 0.996, p=0.043), whereas pulmonary involvement at baseline was associated with a higher likelihood of remission (HR, 1.588, 95% CI 1.047 to 2.419, p=0.032). Recurrence after remission occurred in 6 of 98 patients (6%), with a median time to recurrence of 46 months after remission. At recurrence, patients predominantly had anterior uveitis (83%) and shared similar anatomical patterns with their initial presentation. Conclusions Approximately one in three patients with sarcoid uveitis achieved remission. Macular oedema at baseline was associated with delayed remission, while lung involvement at baseline was associated with faster remission. Recurrence after remission was uncommon and typically mirrored the initial uveitis phenotype.

Background:Advances in colorectal cancer (CRC) screening and endoscopic techniques have led to increased detection of T1 CRC. Patient management relies on histopathological criteria predicting lymph node metastasis (LNM), including submucosal invasion depth (SID) >1000 µm. However, the independent prognostic value of isolated deep invasion remains unclear. Methods:We performed a retrospective multicenter study of patients treated at 18 European centers between 2009 and 2022. Patients with T1 CRC endoscopically resected en bloc and with isolated SID >1000 µm (without other high-risk features) were included. Two groups were analyzed: patients who underwent additional surgery and those who were followed with surveillance. Rates of LNM (surgery group) and recurrence (local and distant; surveillance group) were assessed. Exploratory multivariable analyses were performed to evaluate clinicopathological factors associated with LNM. Results:Among 179 included patients (124 surgery, 55 surveillance), LNM was found in 16/124 surgical specimens (12.9%; 95%CI 7.7-20.4) and recurrence occurred in 2/55 patients undergoing surveillance (3.6%; 95%CI 0.4-12.6). LNM occurred in 1/50 patients (2.0%) with SID <2000 µm and in 15/74 patients (20.3%) with SID ≥2000 µm. Multivariable analysis revealed SID ≥2000 µm (odds ratio [OR] 3.59; 95%CI 1.14-13.71) and colonic (vs. rectal) tumor location (OR 3.63; 95%CI 1.07-16.77) as factors associated with LNM. Conclusion:Isolated deep submucosal invasion in T1 CRC was associated with a non-negligible rate of LNM in this real-world cohort. In exploratory analyses, SID ≥2000 µm was associated with LNM.

OBJECTIVE:To validate whether the 2022 WHO classification improves the prediction of radioactive iodine refractory (RAIR) disease in advanced-stage thyroid carcinomas and to identify associated histological predictive factors. METHODS AND RESULTS:A prospective cohort of 253 patients with pT3, pT4, or M1 thyroid carcinomas (TNM 2010), who underwent surgery between 2009 and 2018 and received at least one radioactive iodine dose, was analysed. Histological slides were reviewed using the 2022 WHO criteria, and clinical data were collected. Cox survival analyses and ROC curve evaluations were performed to identify factors associated with RAIR progression and assess the predictive performance of the new classification. Reclassification identified 28 low-risk neoplasms, all with favourable outcomes. Among the remaining 225 malignant cases, 155 were well-differentiated carcinomas (including 146 papillary carcinomas, 56 of which were aggressive subtypes) and 70 were high-grade carcinomas (39 high-grade differentiated and 31 poorly differentiated carcinomas). Forty patients (17.7%) developed RAIR disease. The 2022 WHO classification showed superior predictive performance compared with the 2004 WHO (AUC: 0.81 versus 0.60, P < 0.001). Multivariate analysis identified tumour necrosis as independent predictive factor of RAIR disease, regardless of the mitotic index. CONCLUSION:The 2022 WHO classification improves RAIR disease prediction, notably by recognizing high-grade carcinomas as a distinct entity. High-grade factors, especially tumour necrosis, which emerges as a key predictive factor, should be systematically reported in thyroid carcinoma pathology reports to enhance patient management and follow-up.

BackgroundTarget trial emulation (TTE) offers a formal framework for causal inference using observational data, but its validity must be evaluated in each research domain by replicating randomised clinical trials (RCTs). We aimed to replicate eight RCTs evaluating the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS) using French registry data. METHODS:This multicentre, retrospective, observational study was conducted using data extracted in December 2023 from the Observatoire Français de la Sclérose en Plaques (OFSEP) database. For each emulated trial, patients were included when they initiated one of the DMT evaluated in the corresponding RCT and met its inclusion criteria. Clinical outcomes were the annualised relapse rate and 3-month confirmed Expanded Disability Status Scale progression. Radiological outcomes were new/enlarged T2-lesions and new gadolinium-enhanced T1-lesions on a brain MRI. A targeted maximum likelihood estimator was used to estimate the treatment effect adjusted for confounding factors between groups and corrected for censoring and missing outcome assessment. RESULTS:14 111 patients were included in eight emulated trials: ASSESS (fingolimod vs glatiramer acetate), BEYOND (interferon beta vs glatiramer acetate), CONFIRM (dimethyl fumarate (DMF) vs glatiramer acetate), OPERA (ocrelizumab vs interferon beta), REGARD (interferon beta vs glatiramer acetate), RIFUND-MS (rituximab vs DMF), TENERE (teriflunomide vs interferon beta) and TRANSFORMS (fingolimod vs interferon beta). Treatment effects estimated in emulated trials were concordant with RCT findings in seven of eight trials for relapse rate, and in all six trials assessing disability progression. Radiological outcomes were more challenging to replicate; concordance was achieved in three of five trials for new T2-lesions, and one of four trials for new gadolinium-enhanced T1-lesions. CONCLUSION:The combined use of a TTE methodology and high-quality registry data is a valid tool to evaluate treatment effectiveness in MS.

Background: Information on the value of circulating methylated nucleosomes for predicting prognosis in non-small cell lung cancer (NSCLC) is limited. We sought to evaluate the association between circulating H3K27Me3-concentrations and overall survival (OS) and progression-free survival (PFS).Methods: A retrospective analysis of plasma samples was performed using specimens collected from patients enrolled in the prospective ONCOPRO study (NCT03787056). Patients with NSCLC were classified into 3 cohorts: Curative intent (radiotherapy or surgery) with or without neoadjuvant treatment; Non-Curative first-line treatment including immunotherapy (NC-Imm); and Non-Curative first-line treatment without immunotherapy (NC-NonImm). Plasma H3K27Me3-nucleosome was quantified by an automated chemiluminescent immunoassay (Nu.Q® H3K27Me3).Results: Sixty-four patients were included: Curative, n=19; NC-Imm; n=21; and NC-NonImm, n=24. Median follow-up ranged from 39.5–61.8 months across cohorts. Median baseline H3K27Me3-nucleosome concentrations were 9.54 ng/mL in the Curative cohort, 11.86 ng/mL in the NC-Imm cohort and 27.07 ng/mL in the NC-NonImm cohort (Curative vs NC-NonImm cohort, p=0.0027). In the NC-NonImm cohort, H3K27Me3-nucleosome levels below the median were associated with prolonged OS (hazard ratio [HR][95% confidence intervals] 0.11 [0.01-0.88], p=0.012). Lower H3K27Me3-nucleosome concentrations were also associated with prolonged PFS (HR 0.22 [0.04–1.08]; p=0.043).Conclusion: These findings suggest a potential prognostic value for circulating H3K27Me3-nucleosomes in metastatic NSCLC. Larger studies are warranted to further validate and refine these observations.

Importance: Prone positioning has been shown to improve respiratory mechanics and oxygenation, but its clinical benefit in infants with acute viral bronchiolitis receiving high-flow nasal cannula (HFNC) support remains unknown. Objective: To investigate whether prone positioning in infants with moderate to severe acute bronchiolitis and HFNC support reduces escalation to noninvasive or invasive ventilation. Design, Setting, and Participants: Multicenter, randomized, open-label trial conducted in 15 pediatric intermediate or intensive care units in France. Infants aged 6 months or younger admitted for 24 hours or less with a diagnosis of acute bronchiolitis with moderate to severe respiratory distress requiring HFNC support were enrolled between January 2021 and November 2023 and followed up until hospital discharge (last patient discharged on December 11, 2023). Interventions: Participants were randomly assigned to the prone position (n = 221) or supine position (n = 230). Infants in the prone position group received prone positioning for 24 hours or longer during the first 48 hours. All participants received standardized HFNC support at 2 L/kg/min. Main Outcomes and Measures: The primary outcome was the need for escalation of care to noninvasive or invasive ventilation within the first 72 hours, according to prespecified criteria. Secondary outcomes included treatment failure, determined by an independent clinical adjudication committee; tolerance of prone positioning; length of hospital stay; duration of respiratory support; infant comfort; and adverse events. Results: Among 451 infants randomized, 446 were included in the primary analysis (median age, 41 [IQR, 19-72] days; 54% male). Escalation of care occurred in 80 infants (17.9%), with no significant difference between the prone position (33/220 [15.0%]) and supine position (47/226 [20.8%]) groups (adjusted odds ratio, 0.66 [95% CI, 0.40-1.07]; P = .09). Secondary outcomes did not differ significantly between the 2 groups. In the safety analysis, serious adverse events occurred in 2 of 180 infants (1.1%) in the prone position group and 2 of 264 (0.8%) in the supine position group. Conclusions and Relevance: Prone positioning in infants with moderate to severe bronchiolitis receiving HFNC support did not significantly reduce escalation of care. However, the wide 95% confidence interval around the observed odds ratio suggests that this study was not definitive and further research is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03976895.

Background:Radioiodine refractory (RAIR) non-anaplastic follicular-cells derived thyroid carcinomas (FCDTC), are responsible for most FCDTC mortality. Although early detection could enable personalised strategies, precise risk factors are largely unknown. We aimed to search for clinical and histopathological predictive factors available at diagnosis for RAIR evolution. Methods:In this single-centre cohort study, patients treated between 2009 and 2018 for a pT3, pT4 or M1 FCDTC (2010 TNM classification), were prospectively enrolled after thyroidectomy. Updated centralised histological review was performed, and a Cox model was used to explore time to RAIR disease. The final multivariable model was then transformed into a 16-point score. Findings:Histopathological review identified 28 patients with low-risk neoplasms and 225 with FCDTC. The median follow-up for FCDTC was 8·3 years (95% CI 7·9-8·9), and 40 patients had RAIR- FCDTC (18%).Univariable analyses identified age ≥55 years, stimulated thyroglobulin ≥20 ng/mL at first radioiodine treatment, tumour size, TERT promoter mutation (not BRAF), un-encapsulated, adipose, muscle and vascular invasion, high Ki67 index, and high-grade follicular cell derived carcinomas (HG-TC) as associated with RAIR evolution at 5 years. On the basis of the final multivariable model with an AUC of 0·90 (0·82-0·97), a 16-point score was constructed: age ≥55 years (hazard ratio 2·05, 95% CI 1·01-4·16; 2 points), stimulated thyroglobulin ≥20 ng/mL at first RAI (5·20, 2·51-10·75; 5 points), TERT promoter mutation (3·22, 1·64-6·33; 3 points), and HG-TC (6·15, 2·86-13·21; 6 points). Interpretation:This score allows early identification of patients at risk of RAIR disease. Recent histological category of HG-TC and TERT promoter mutation are the strongest predictive factors. Funding:Société Française d'Endocrinologie, Ligue Contre le Cancer.

Aim Patients with type 2 diabetes (T2D) and obesity are at increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) with advanced fibrosis (AF), requiring systematic non-invasive assessment using liver stiffness measurement (LSM) or the ELF test. However, access to these biomarkers remains limited in diabetology. We therefore evaluated the diagnostic performance of a new point-of-care ultrasound device, Hepatoscope, for the risk stratification of AF. Methods Participants with T2D and/or obesity and MASLD age 40-80 years, BMI <40 kg/m2 prospectively included in a multi-centre study (NCT04435054) underwent LSM using vibration controlled transient elastography (LSM-VCTE, FibroScan) and 2D-transient elastography (LSM-2DTE) using Hepatoscope version 1 and ELF. Post-acquisition reprocessing of the LSM-2DTE data using the CE approved version 2 (LSM-2DTE-2) was performed in a subgroup of n=120 participants. The area under the ROC curve (AUROC) and 95% confidence interval (CI) were assessed for the detection of intermediate to high-risk of AF, defined by LSM-VCTE ≥ 8 kPa. Results Among 294 participants (83.3% T2D, 42.5% female, 71.4% obesity), 24.8% had LSM-VCTE ≥ 8kPa. Significant correlation was observed between LSM-VCTE and LSM-2DTE-1 r: 0.37 [0.26-0.47], P < 0.001 and was higher between LSM-VCTE and LSM-2DTE-2: r: 0.61 [0.47-0.71], P < 0.001. In the subgroup of 120 participants, the AUROC (95%CI) of LSM-2DTE-2 for the detection of LSM-VCTE ≥ 8kPa was 0.81 (0.72-0.89) compared to 0.64 (0.52-0.75) for ELF. Conclusion This proof-of-concept study provides evidence supporting the role of LSM-2DTE using the Hepatoscope in the risk stratification of AF in diabetology settings. Larger studies are needed to validate its performance.

Objectifs La résection hystéroscopique des fibromes sous-muqueux est une technique efficace pour réduire les ménométrorragies et améliorer la fertilité. Identifier les facteurs prédictifs d’une résection en deux temps est essentiel pour optimiser l’information préopératoire et la planification chirurgicale. L’objectif de ce travail rétrospectif était de vérifier les facteurs déjà rapportés dans la littérature. Méthodes Nous avons analysé 106 patientes opérées d’une résection hystéroscopique de fibrome au CHU Lyon Sud entre janvier 2019 et janvier 2024. Résultats La taille du fibrome était le seul facteur significativement associé à une résection en deux temps. Pour un diamètre ≥3cm, l’odds ratio de seconde intervention était multiplié par 13,3 (risque passant de 4,1 % à 36,4 %). Le taux de complications et le déficit hydrique étaient également plus élevés lors des résections en deux temps. Conclusions La taille du fibrome apparaît comme le principal facteur prédictif d’une résection en deux temps. Ce résultat présente un intérêt clinique direct pour mieux informer les patientes, dont plus d’un tiers nécessiteront une seconde intervention. Des études prospectives multicentriques sont indispensables pour confirmer ces données.

PURPOSE:To describe the factors associated with ocular relapse and visual prognosis in patients with sarcoid uveitis. DESIGN:Multicentric, retrospective cohort study. PARTICIPANTS:A total of 336 patients were included, of whom 208 (61.9%) were female. Median age at uveitis diagnosis was 52 years (range, 10-89 years). METHODS:Ocular relapses and incident visual impairment were recorded over the entire duration of follow-up. Factors associated with ocular relapses and visual impairment were subsequently analyzed. Kaplan-Meier curves for ocular relapse-free survival (RFS) and visual impairment-free survival were constructed for selected variables. Cox proportional hazards model was then applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical significance was set at the P < 0.05 level. MAIN OUTCOME MEASURES:Time to ocular relapse and time to visual impairment. RESULTS:Median follow-up was 7.8 years. Sarcoidosis was histologically proven in 279 patients (83.0%). Ocular relapses occurred in 224 patients (66.7%). The median time to ocular relapse was 2.6 years (interquartile range, 1.6-4.4). Shorter ocular RFS was associated with the presence of macular edema (HR, 1.47, 95% CI, 1.07-2.02, P = 0.020) and persistent inflammation (HR, 1.68, 95% CI, 1.17-2.40, P = 0.004) at baseline. According to World Health Organization definitions, visual impairment was present in 21 of 325 patients (6.5%) at the end of follow-up. Visual impairment was mild in 12 of 325 patients (3.7%), moderate in 6 of 325 patients (1.9%), and severe in 0 of 325 patients (0.0%), and 3 of 325 patients (0.9%) were blind. The main causes of visual impairment were glaucoma in 9 of 20 patients (45.0%), macular edema in 8 of 20 patients (40.0%), and epiretinal membrane in 6 of 20 patients (30.0%). Risk factors for shorter visual impairment-free survival could not be estimated because of the small number of events. CONCLUSIONS:Sarcoid uveitis relapses in approximately two-thirds of patients, and relapses are associated with the presence of macular edema and persistent inflammation at baseline. Most patients with sarcoid uveitis maintain adequate usable vision, with approximately 6% becoming mildly, moderately, or severely visually impaired, and approximately 1% becoming blind after a median follow-up of 7.8 years. FINANCIAL DISCLOSURE(S):The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Background:For chronic lymphocytic leukaemia (CLL) and intermediate risk factors (unmutated IGHV and/or 11q deletion and/or complex karyotype; no TP53 alteration), the best first-line treatment is unclear. We compared an MRD-guided, fixed-duration ibrutinib-venetoclax (IV) regimen to fludarabine-cyclophosphamide-rituximab (FCR) in this population. Methods:The ERADIC randomised, phase 2 trial (NCT04010968), conducted at 35 French hospitals, recruited previously untreated, fit adults with intermediate-risk CLL. Randomisation was 1:1 to: 6x4-weekly cycles of FCR (Months 1-6); or ibrutinib 420 mg/day from Month 1 plus venetoclax (ramp-up to 400 mg/day from Month 4) for a duration depending on the bone marrow measurable residual disease level at Month 9 (if undetectable at a threshold of <0·01% [BM uMRD4] to Month 15; otherwise to Month 27). Primary outcome was the BM uMRD4 rate at Month 27, by assessment oligocentrally (intent-to-treat, worst-case scenario method). Findings:Between 27 September 2019 and 31 January 2021, 120 patients were enrolled (73% male). At Month 27, the BM uMRD4 rate was 37% (22/59; 95% confidence interval [CI] 25, 51) with IV versus 13% (8/61; 95% CI 6, 24) with FCR. The high amount of missing BM MRD data, along with imbalance in missing data between arms, meant that no confirmatory statistics were performed. Best rate of BM uMRD4 plus peripheral blood uMRD5 was 47% (22/47) with IV versus 19% (8/43) with FCR (p = 0·0090). With median 43 months' follow-up, progression-free survival was longer with IV versus FCR (estimated hazard ratio 0·35, 95% CI 0·16, 0·80, p = 0·012). By Month 27, six deaths had occurred (FCR: acute myeloid leukaemia, septic shock, myelodysplastic syndrome; IV: 2 sudden deaths, COVID-19). By the time of follow-up, the most common serious grade 3/4 events were infections and haematological toxicities with FCR, and infections and cardiovascular/metabolic toxicities with IV. Interpretation:Due to the high amount of missing BM MRD data at Month 27, the primary outcome statistical analysis was not deemed feasible. The outcomes reported are secondary and exploratory, and were not been powered for in the study design. A patient profile suitable for an MRD-guided, fixed-duration IV regimen requires consideration of potential toxicities. Funding:Abbvie and Janssen France.

Importance:In women with multiple sclerosis (MS), disease-modifying therapy (DMT) management during pregnancy might impact relapse risk. Objective:To estimate the effect of DMT management during pregnancy on MS relapse rate and compare different therapeutic strategies. Design, Setting, and Participants:This was a multicenter retrospective cohort study using data from January 1990 to December 2023. Data were extracted in December 2023 from the French MS registry. Among 52 955 women in the registry, we included pregnancies identified through childbirths in patients with relapsing-onset MS who were monitored for at least 18 months before delivery and 9 months after. Pregnancies occurring less than 18 months apart or with missing month of birth were excluded. Exposures:Mediation analysis was used to estimate the total, direct, and indirect (mediated by DMT management) effects of pregnancy. Different therapeutic strategies were compared: DMT interruption, switching to or maintaining interferon β or glatiramer acetate, switching to or maintaining natalizumab until the third trimester, and switching to or maintaining intravenous anti-CD20 and interrupting it 3 months before conception. Main Outcomes and Measures:The primary outcome was the annualized relapse rate (ARR) during the preconception, gestation, and postpartum periods. Within a causal inference framework, counterfactual ARRs were estimated using longitudinal g-computation, combining a random forest algorithm for predicting DMTs, and a mixed-effects Poisson model for relapses. Results:We included 6341 pregnancies occurring in 4998 women (mean [SD] age at conception, 31.5 [4.5] years). DMT management during pregnancy significantly increased ARR during gestation (causal rate ratio [cRR], 1.13; 95% CI, 1.06-1.22) and postpartum (cRR, 1.08; 95% CI, 1.01-1.16) periods. This led to a deleterious total effect of pregnancy on ARR, particularly in women receiving natalizumab before pregnancy with prolonged interruption (ie, interruption before the second trimester or resumption more than 3 months after delivery; cRR, 2.18; 95% CI, 1.76-2.69), and in women receiving fingolimod (cRR, 2.15; 95% CI, 1.60-2.93). Compared to DMT interruption, anti-CD20 strategy was the most effective (cRR, 0.38; 95% CI, 0.25-0.52), followed by the natalizumab strategy with short interruption (cRR, 0.80; 95% CI, 0.71-0.90), whereas interferon β (cRR, 0.93; 95% CI, 0.86-0.99) and glatiramer acetate strategies (cRR, 0.91; 95% CI, 0.84-0.99) were less effective. Conclusion:In this study, DMT management during pregnancy significantly increased relapse risk, particularly in patients receiving natalizumab with prolonged interruption or fingolimod. The strategy based on the use of anti-CD20 before pregnancy was the most effective to mitigate this risk.

OBJECTIVES:Hysteroscopic resection of submucosal fibroids is an effective technique to reduce menometrorrhagia and improve fertility. Identifying predictors of two-step resections is essential to optimize preoperative counseling and surgical planning. The objective of this retrospective study was to assess predictive factors previously reported in the literature. METHODS:We analyzed 106 patients who underwent hysteroscopic fibroid resection at Lyon Sud University Hospital between January 2019 and January 2024. RESULTS:Fibroid size was the only factor significantly associated with the need for a two-step resection. For fibroids ≥3cm in diameter, the odds ratio for requiring a second procedure was 13.3, with the risk increasing from 4.1% to 36.4%. Complication rates and fluid deficit were also higher in two-step resections. CONCLUSIONS:Fibroid size appears to be the main predictor of two-step hysteroscopic resection. This finding has direct clinical relevance, as it allows for more accurate preoperative counseling of patients, more than one-third of whom may require a second intervention. Prospective multicenter studies are needed to confirm these results.

BACKGROUND:Cranial radiotherapy for extrapituitary brain tumor is a rare cause of acquired pituitary deficiency. The main objective of the present study was to evaluate the incidence and time onset of pituitary deficit and to investigate predictive factors. MATERIAL AND METHODS:This retrospective cohort study included 246 patients referred to our endocrinology department between 2005 and 2021 for hormone testing after radiotherapy for extrapituitary brain tumor. Incidence of pituitary deficit was reported with 95% confidence intervals [95% CI]. Deficit-free survival was estimated on the Kaplan Meier method. RESULTS:Mean (SD) age at inclusion was 32.2 years (20.3). One hundred and forty-one patients were male (57.3%). One hundred and seventy-five (71.1%) were irradiated after and 71 (28.9%) at or before the age of 15. Mean (SD) follow-up was 10 years (7). At the end of the study, 118 patients (48.0%) had ≥1 hormonal deficit: GH deficit in 88 patients (36.5%), TSH deficit in 61 (24.8%), LH/FSH deficit in 47 (19.5%); ACTH deficit was identified in 12 patients (4.9%), and was never isolated. The overall incidence of pituitary deficits was 10.3 per 100 person-years (95% CI [30.8; 65.3]) and did not differ according to age at irradiation. Pituitary deficits occurred within a mean (SD) 2.6 years (2.5), 4.9 years (3.3), 4.0 years (2.4) and 4.8 years (3.1) for ACTH, TSH, GH and LH/FSH, respectively. The only factor associated with deficit-free survival was pituitary gland D50 (maximum dose received by at least 50% of gland volume): D50 37-44Gy compared to 1-24Gy; HR: 2.51; 95% CI [1.09; 5.80]; P=0.031. CONCLUSION:Half of the patients presented pituitary deficits 10 years after irradiation for extrapituitary brain tumor. However, ACTH deficit was rare, and never isolated, suggesting that it is not necessary to carry out a dynamic test for ACTH if no other deficits are diagnosed.