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Background Premature and early menopause involve ovarian hormone deprivation, which may contribute to later-life vulnerability to cognitive decline and neurodegenerative diseases. Multimodal neuroimaging biomarkers provide a means of detecting structural, microstructural, functional, and molecular brain changes before clinical symptoms emerge. Methods Following PRISMA guidelines, we conducted a systematic search of PubMed. Study quality was assessed using the Newcastle–Ottawa Scale. Results Neuroimaging modalities included in vivo structural magnetic resonance imaging (MRI) ( n = 16), functional MRI ( n = 2), diffusion tensor imaging ( n = 4), and positron emission tomography ( n = 3). Women with premature or early menopause showed regionally specific structural and microstructural brain abnormalities, including lower gray-matter volume or cortical thickness in medial temporal, frontal, and basal forebrain regions; white-matter microstructural abnormalities in the anterior corona radiata, corpus callosum, and fronto-occipital tracts; and reduced posterior hippocampal activation during memory encoding. In one study, earlier age at menopause was associated with higher amyloid- β (Aβ) burden in women who underwent premenopausal bilateral oophorectomy (PBO), and elevated tau deposition was reported predominantly among women with higher Aβ levels. Conclusion Converging multimodal neuroimaging evidence suggests that premature and early menopause may be associated with Alzheimer’s disease-relevant brain changes. However, findings remain heterogeneous, and longitudinal studies are needed to clarify the temporal relationships between ovarian hormone deprivation and neurodegeneration, and to determine the clinical implication of these findings.

Background/Objectives: Characterizing spinal cord multiple sclerosis (MS) lesions in MRI is critical for diagnosis, monitoring, and treatment evaluation. However, current automated approaches for lesion detection and segmentation are typically designed for specific MRI contrasts or acquisition sites, limiting their generalizability in real-world clinical settings where imaging protocols vary widely. This work proposes a robust multi-site, multi-contrast segmentation framework for spinal cord lesions. Methods: The segmentation model was trained and evaluated on a large-scale dataset comprising 4428 annotated images from 1849 persons with MS across 23 imaging centers, encompassing six MRI contrasts (T1w, T2w, T2*w, PSIR, STIR, and UNIT1) acquired at 1.5 tesla (T), 3 T, and 7 T. Results: Likert-type assessment performed by neuroradiologist ratings demonstrated superior generalization of the model compared to existing contrast-specific pipelines ( p < 0.01). Additional experiments evaluated robustness across spinal levels, acquisition resolutions, binarization thresholds, and quantitative evaluation on external labeled datasets. Conclusions: The proposed model can achieve accurate and reliable spinal cord MS lesion segmentation across heterogeneous MRI data, addressing a key barrier to clinical translation. The model is available in the Spinal Cord Toolbox v7.2 and higher. Code repository: https://github.com/ivadomed/seg-sc-ms-lesion-multicontrast

Abstract Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P &lt; .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P &lt; .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

Importance Sex differences are increasingly recognized as modifiers of Alzheimer disease and related dementias, with women exhibiting greater tau burden and faster cognitive decline than men. Even though α-synuclein copathology frequently occurs in Alzheimer disease, its contribution to sex differences in disease progression is unclear. Objective To test whether α-synuclein positivity, measured using cerebrospinal fluid seed amplification assay (SAA), is differentially associated with tau accumulation in women vs men across the Alzheimer disease continuum. Design, Setting, and Participants This cohort study used longitudinal tau positron emission tomography from the Alzheimer’s Disease Neuroimaging Initiative collected between 2015 and 2023, with a median (IQR) follow-up of 1.23 (0.00-3.84) years. Participants were stratified by cerebrospinal fluid α-synuclein seed amplification assay status and sex. Participants were cognitively unimpaired or cognitively impaired (mild cognitive impairment or dementia) at baseline. Exposure Cerebrospinal fluid α-synuclein status determined by SAA and dichotomized as SAA negative or SAA positive. Main Outcomes and Measures Tau burden was quantified as standardized uptake value ratio (SUVr) in the medial temporal composite region of interest. Linear mixed-effects models tested SAA by sex by time interactions on longitudinal tau accumulation, adjusting for baseline age, baseline cognitive status, apolipoprotein E ε4 carrier status, and site. Sample size estimates were calculated to detect 25% and 50% treatment effects with 80% power in those with cognitive impairment. Results Among 415 participants (mean [SD] age, 72.3 [7.6] years; 220 women [53%]; 69 SAA positive [17%] and 346 SAA negative [83%]), there was a significant interaction between SAA status, sex, and time on tau accumulation (β, 0.061; 95% CI, 0.030-0.093; P &amp;lt; .001). Women with positive SAA results exhibited the fastest tau accumulation compared with other groups (0.066 SUVr per year; 95% CI, 0.043 to 0.089 SUVr per year; P &amp;lt; .001). Clinical trials targeting tau pathology in cognitively impaired individuals with 18-month follow-up would require 129 SAA-positive women to detect a 25% treatment effect with 80% power, compared with 518 SAA-negative women. Conclusions and Relevance In this cohort study of participants across the Alzheimer disease continuum, α-synuclein copathology was associated with faster tau accumulation in women than men. These findings may inform sex-specific interpretation of α-synuclein biomarkers and trial design.

Abstract Background The associations between bilateral oophorectomy or hysterectomy with ovarian conservation and the risk of Parkinson's disease (PD) remain inconclusive. Objectives To evaluate the evidence on these two associations. Methods We conducted a systematic search across Embase, PubMed, Scopus, MEDLINE, and Web of Science through May 15, 2024. Data were extracted independently by two reviewers, and random‐effects meta‐analyses were performed. Results Eight studies with a total of 242,275 women were included. For bilateral oophorectomy, the effect size (ES) was greater than 1.0 in 5 of 8 studies. The pooled analysis showed a significant association between premenopausal bilateral oophorectomy and an increased risk of PD in cohort studies (hazard ratio [HR] 1.32; 95% CI 1.12–1.56) but not in case–control studies or combining both cohort and case–control studies. There was a suggestive trend of increasing risk with younger age at bilateral oophorectomy. For hysterectomy with ovarian conservation, the ES was greater than 1.0 in all six studies. The pooled analysis showed a non‐significant association in cohort studies and in case–control studies; however, the association was significant when combining both cohort studies and case–control studies (ES 1.19; 95% CI 1.01–1.41). Conclusions Current studies provided low to moderate evidence for the associations between bilateral oophorectomy and hysterectomy with ovarian conservation and increased risk of PD. However, the evidence was only observational and there was important heterogeneity across the case–control studies. Future studies should focus on surgeries performed at younger ages and on the possible effects of estrogen replacement therapy.

Abstract Objective To compare the long‐term risk of subsequent abdominopelvic surgery in women who underwent hysterectomy with ovarian conservation (H‐OC) versus referent women, and in women who underwent abdominal H‐OC versus vaginal H‐OC. Methods We conducted a population‐based cohort study in Olmsted County, Minnesota, USA including 1573 women who underwent H‐OC for a benign indication at age 18–44 years between January 1, 1980, and December 31, 2002, and 1573 age‐matched (±1 year) referent women who had not undergone hysterectomy or any oophorectomy as of the matching date. For both the H‐OC women and the referent women, we defined the index date as the H‐OC or matching date plus 6 months. The index date served as the starting point for follow‐up. Results Overall, we found an increased risk of subsequent lysis of adhesions in women who underwent H‐OC compared to referent women (hazard ratio [HR], 1.57 [95% confidence interval [CI]: 1.09–2.27]). Women undergoing H‐OC also had an increased risk of subsequent gastrointestinal tract procedures (HR, 1.18 [95% CI: 1.05–1.31]) compared to referent women. When comparing surgical route of H‐OC, we identified an increased risk of subsequent adnexal surgeries in women undergoing abdominal compared with vaginal H‐OC (HR, 1.91 [95% CI: 1.40–2.61]). Conclusion Women who underwent H‐OC have an increased risk of subsequent abdominopelvic surgeries compared to referent women. In addition, women who underwent abdominal H‐OC have an increased risk of subsequent adnexal procedures compared to women who underwent vaginal H‐OC.

Abstract Introduction Obecabtagene autoleucel (obe-cel) and brexucabtagene autoleucel (brexu-cel) are CD19 targeted chimeric antigen receptor T cell (CAR-T) therapies, approved for the treatment of adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (ALL). Mechanistic differences between obe-cel and brexu-cel including differing costimulatory domains (4-1BB vs. CD28), CD19 binding domains (intermediate vs. high affinity) and split dose (Days 1 and 10) vs. single infusion may impact in-vivo cellular kinetics that translate into variant clinical outcomes. In pivotal trials, obe-cel resulted in lower rates of severe cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) compared to brexu-cel with comparable efficacy (Roddie et al., NEJM 2025; Shah et al., Lancet 2021). Real-world utilization and outcomes with obe-cel are unknown given the relatively recent approval. Methods The ROCCA database, comprising real world data from patients (pts) with r/r ALL treated at 40 North American institutions was utilized in this analysis. Pts with r/r ALL were eligible if they were apheresed for obe-cel since its approval (11/8/2024) or brexu-cel over a comparable period (since 8/1/24) and had at least 30 days of follow up. Data cut off was 7/15/2025. CRS/ICANS were graded per ASTCT criteria. Measurable residual disease (MRD) was assessed by flow cytometry and/or next generation sequencing per institutional standards. Results 38 pts have undergone apheresis for obe-cel (36 infused, all received both infusions) and 54 (53 infused) for brexu-cel over the study period. Pts in the obe-cel and brexu-cel cohorts had the following baseline characteristics: median age, 47 vs. 39 years; ECOG 2+, 15% vs. 26%; Ph+ disease, 24% vs 13%; KMT2Ar, 0 vs. 4%; TP53m, 11% vs 11%, and hypodiploid karyotype, 5% vs 6%. The following prior treatment patterns were observed: median lines of therapy before CAR-T 3 vs. 3; prior SCT 24% vs. 30%, prior blinatumomab 68% vs. 46%, prior inotuzumab 45% vs. 30%. At apheresis, active disease (&gt;5% bone marrow blasts) was present in 47% vs. 55% of obe-cel and brexu-cel pts, respectively; the remainder were in CR (with 18% vs. 22% in MRD- CR, respectively). Among obe-cel (n= 35 [92% of cohort]) and brexu-cel (21 [38% of cohort] pts with disease re-assessment prior to lymphodepletion (LD), 31% vs. 43% had active BM disease, respectively; few pts (24% vs. 17%) had &gt;20% marrow disease burden prior to LD. CAR-mediated toxicity differed significantly between the cohorts. CRS occurred in 56% of obe-cel pts compared to 94% of brexu-cel pts (p &lt; 0.0001). There were no Gr3+ CRS events among the obe-cel pts; 3 (6%) brexu-cel pts had Gr3+ CRS (p = 0.27). ICANS occurred in 17% of obe-cel pts vs. 51% of brexu-cel pts (p = 0.001). Gr3+ ICANS occurred in 6% of obe-cel vs. 32% of brexu-cel pts (p = 0.0027). Among the obe-cel pts, CRS occurred in 31% after the first infusion and 46% after the second; ICANS occurred in 3% after the first infusion and 15% after the second. Prolonged Gr4 neutropenia (ANC &lt; 500 cells/uL beyond day 30 from infusion) occurred in 24% of obe-cel vs. 28% of brexu-cel pts (p = 0.73). Deaths within the first 28 days of infusion occurred in 0 obe-cel pts and 4 brexu-cel pts (2 of infection, 1 of infection/brain bleed, and 1 of liver failure in the setting of Gr4 CRS and HLH). Response rates were high and did not significantly differ between cohorts (p = 0.85). Among the 31 obe-cel pts with available response data, 25 (81%) achieved an MRD- CR/CRi, 3 (10%) had an MRD+ CR/CRi, 2 (6%) had a CR/CRi with unknown MRD, and 1 (3%) did not respond. Among 41 brexu-cel pts with available response data, 33 (80%) had an MRD- CR/CRi, 4 (10%) an MRD+ CR/CRi, and 4 (10%) CR/CRi with unknown MRD. Conclusion Pts selected for obe-cel apheresis were similar to those for brexu-cel over the study period (noting that not all centers had access to obe-cel during this time). Similar to clinical trial results, obe-cel was associated with lower rates of CRS/ICANS. Rates of MRD-negative CR were high and did not differ between cohorts. A larger sample and longer follow up are required for further analyses; we anticipate a cohort of ~75 obe-cel treated pts by the annual meeting and will provide updated data.

Objectives: To determine the risk of developing de novo carpal tunnel syndrome (CTS), arthritis, or rheumatoid arthritis in women who underwent hysterectomy with bilateral ovarian conservation (H-OC) before reaching spontaneous menopause. Methods: We identified 1,573 women undergoing H-OC for a benign indication at age 18 to 44 years between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman who had not undergone hysterectomy or oophorectomy before the matching date (index date). Diagnostic codes for CTS and arthritis were extracted from the Rochester Epidemiology Project medical records-linkage system through 2019. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models and the two cohorts were balanced for 19 chronic conditions and for several potential confounders present at index date. Results: Over a median 25.8-year follow-up, women undergoing H-OC had an increased risk of developing CTS (HR: 1.33; 95% CI: 1.13-1.56) compared with referent women. The risk was similar in strata by age at H-OC and was higher for women with endometriosis and menstrual disorders indications. Women undergoing H-OC also had an increased risk of developing arthritis (HR: 1.34; 95% CI: 1.23-1.47). The risk was similar in strata by age at H-OC and by indication. Rheumatoid arthritis considered separately was also associated with H-OC (HR: 1.55; 95% CI: 1.05-2.30). Conclusions: H-OC was associated with an increased risk of de novo CTS, arthritis (all types), and rheumatoid arthritis. Further studies are needed to confirm these associations and to explore potential biological mechanisms.

Abstract Aims Patients with end-stage renal disease (ESRD) and atrial fibrillation present a challenge for thromboembolic prevention, given their elevated risks of both thromboembolism and bleeding. Anticoagulants carry a higher bleeding risk in this population without clear evidence of thromboembolic benefit. This study aims to define the role of left atrial appendage occlusion (LAAO) as a preventive strategy for patients with ESRD. Methods and results A systematic literature review was conducted to identify studies reporting outcomes in patients with ESRD who underwent LAAO. Meta-analyses of aggregate and individual patient data were performed to evaluate acute and long-term outcomes and compare them with those of patients without ESRD. Seventeen studies reporting data from 24 127 patients, including 1047 with ESRD, were included. Procedural complications were more common in patients with ESRD (RR 2.23; P = 0.02), with a pooled rate of 4% (95% CI, 1–9%). There was no significant difference in thromboembolic event rates during follow-up between the groups (IRR 1.44; P = 0.16), but major bleeding incidence was higher among patients with ESRD (IRR 1.84; P &lt; 0.01). Individual patient-level data from seven studies comprising 4745 patients (268 with ESRD) were obtained and analysed. Similarly, there was no significant association between ESRD and stroke/TIA incidence (HR, 1.22; 95% CI, 0.66–2.26), but major bleeding was higher on patients with ESRD (HR, 1.65; 95% CI, 1.01–2.69). Conclusion LAAO represents a feasible option for thromboembolic prevention in patients with ESRD, although these patients have an increased risk of complications and bleeding.

Objective To study the reliability and validity of adverse childhood experiences (ACE) scores measured using a questionnaire versus abstraction of medical records, and to test whether the scores vary by history of bilateral oophorectomy, or by age and presence of anxiety or depressive symptoms at the time of questionnaire administration. Design The study involved a reliability component and a predictive validity component. Setting A population-based sample in Olmsted County, Minnesota, was derived from the Mayo Clinic Cohort Study of Oophorectomy and Aging-2. Participants We included 198 women who underwent premenopausal bilateral oophorectomy for a non-malignant indication between 1988 and 2007 and 174 referent women of the same age randomly sampled from the general population (total of 372 women). At a later time (median of 22.7 years later), the women were contacted and invited to self-administer the ACE questionnaire during an inperson visit. Independent of the visit, their medical records were abstracted for ACE by a physician. Interventions Questionnaire and abstraction-based ACE scores. Main outcome measures Agreement between the two ACE scores (reliability; weighted kappa statistics) and comparison of incidence of multimorbidity in women with ACE scores ≥1 vs 0 (predictive validity; survival analyses). Data were analysed in March and April 2024. Results The 372 women in the study had a median age of 65 years at the time of ACE questionnaire self-administration (IQR, 62–69). Questionnaire-based ACE scores showed moderate agreement with abstracted ACE scores (weighted kappa 0.44 (95% CI 0.34 to 0.54)). The cut-off score of ACE ≥1 showed an overall fair agreement between the two scores (kappa 0.33 (95% CI 0.24 to 0.43)). A comparison of the cumulative incidence of multimorbidity in women with an ACE score ≥1 versus women with ACE score of 0 yielded a HR of 1.13 (95% CI 1.00 to 1.27) for abstracted ACE and 1.13 (95% CI 1.01 to 1.27) for questionnaire-based ACE. The best predictive validity was for ACE measured by both methods combined (either or) with a HR of 1.29 (95% CI 1.13 to 1.46). Conclusions and relevance Questionnaire-based ACE scores have moderate agreement with medical records abstracted ACE scores. However, both sets of ACE scores are predictive of the accumulation of multimorbidity at older age and should be considered complementary.