Citations

Abstract Background Opportunistic bilateral salpingectomy (OBS), the removal of fallopian tubes during hysterectomy or instead of tubal ligation, is recommended to reduce ovarian cancer risk. However, data on the effectiveness of prophylactic OBS is limited. Methods This population-based retrospective cohort included individuals aged 18–80 in Ontario, Canada, who underwent OBS or comparator surgeries (hysterectomy with ovarian and tubal conservation or tubal ligation) from 2011 to 2023. Individuals with gynecologic cancer before or within six months of surgery were excluded. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Sensitivity analyses varied the time between surgery and cancer diagnosis to account for pre-existing serous tubal intraepithelial carcinomas. Results Among 196,839 individuals, 57,941 underwent OBS and 138,898 underwent comparator surgeries. 142 epithelial ovarian cancers were diagnosed (19 in the OBS group and 123 in the comparator surgery group). OBS was associated with reduced risk of any ovarian carcinoma, with an adjusted hazard ratio (aHR) of 0.60 (95% CI, 0.36 to 0.98). For serous ovarian carcinoma (high- and low-grade combined due to missing grade data), the aHR was 0.47 (95% CI, 0.22 to 0.99). Sensitivity analyses with 12- and 18-month intervals showed aHRs of 0.59 (95% CI, 0.35 to 0.99) and 0.60 (95% CI, 0.35 to 1.01) for all ovarian carcinomas, and 0.49 (95% CI, 0.23 to 1.01) and 0.47 (95% CI, 0.22 to 0.99) for serous ovarian carcinoma, respectively. Conclusions OBS was associated with reduced risk of ovarian carcinoma, supporting its role as a primary prevention strategy.

Background The management of osteochondral lesions of the talus (OLT) is challenging, with 2 main options being conservative and surgical management. Orthobiologic therapies come to bridge the gap between these 2 options; however, inconsistencies in indication, composition, and heterogeneous evidence limit clinical decision-making. To address these challenges, 3 International Congress Meetings on Cartilage Repair of the Ankle were convened in Pittsburgh, USA (2017), Dublin, Ireland (2019), and New York, USA (2025) to establish agreement on the role of conservative management and injectable orthobiologic strategies in the treatment of OLT. Methods Seventy-five multidisciplinary experts from over 25 countries and 1 territory participated in a structured Delphi-based consensus process. Blinded surveys, structured questionnaires, and in-person discussions were used to develop and refine statements, supported by literature review and graded evidence (A1–E). Consensus strength was defined as consensus (51%-74%), strong consensus (75%-99%), or unanimous (100%) Results In total, 29 consensus statements were achieved across the 3 meetings. Strong agreement was reached regarding indications and expected outcomes of conservative management, including the role of immobilization and appropriate timing for surgical intervention. Orthobiologic injections, including platelet-rich plasma, concentrated bone marrow aspirate, and hyaluronic acid, were considered appropriate in select patients with persistent symptoms, although no superiority was demonstrated among formulations, preparation methods, or injection strategies. When used as adjuncts to surgical procedures, orthobiologics may improve radiological outcomes, with limited evidence for improvement in clinical outcomes. Technical considerations, including preferred harvest sites and a lack of standardized preparation protocols, were identified, along with key principles for patient counseling Conclusion These international consensus statements establish a standardized framework for the conservative management and use of injectable orthobiologic therapies in OLT. By clarifying indications, technical considerations, and current limitations, this work aims to improve consistency in clinical practice, guide treatment decision-making, and inform future research.

Importance Limited granular data exist on breast cancer in transgender, nonbinary, and/or gender-diverse (TGD) individuals. Objective To describe patient demographic and tumor clinicopathological variables, clinically relevant risk factors, method of breast cancer detection, treatment characteristics, and locoregional outcomes and to estimate a 5-year breast cancer–specific survival (BCSS). Design, Setting, and Participants This cohort study obtained data on patients treated from 1990 to 2023 from 22 US academic medical centers using institutional databases, electronic medical records, and tumor registries. Included participants were TGD individuals 18 years or older with stage 0 to IV breast cancer. A comparative breast cancer cohort was selected from the 2016 to 2021 Surveillance, Epidemiology, and End Results Program (SEER) breast cancer dataset. Data were analyzed from January to October 2025. Exposure Breast cancer. Main Outcomes and Measures Estimated 5-year BCSS and locoregional recurrence rates. Wilcoxon rank sum and χ 2 tests were used to compare continuous and categorical variables. Kaplan-Meier analysis was used to estimate 5-year BCSS. Results A total of 112 TGD persons (median [IQR] age at diagnosis, 42.5 [36.5-51.0] years; 104 individuals [92.9%] were assigned female at birth) with breast cancer and 1 with bilateral disease were included in the analysis. Forty-three patients (38.4%) used gender-affirming hormone therapy before diagnosis. Among the entire cohort, 58 patients (51.8%) detected their own breast cancer, 68 (60.7%) had a familial breast cancer history, and 16 (14.3%) had a pathogenic germline variant. Tumors were predominantly hormone receptor positive (96 [85.7%]) and early stage (29 [25.7%] ductal carcinoma in situ [DCIS]; 51 [45.1%] stage I). The TGD cohort, compared with patients with breast cancer in the SEER dataset (N = 480 915), was younger (median [IQR] age, 42.5 [36.5-51.0] years vs 62.0 [52.0-72.0] years), had a higher proportion of persons assigned male at birth (8 [7.1%] vs 3522 [0.7%]), more often had progesterone receptor–positive disease (89 [79.5%] vs 335 491 [69.8%]), and presented with earlier-stage disease (eg, DCIS: 29 [25.9%] vs 79 604 [16.6%]). With a median (IQR) follow-up time for the TGD cohort of 38 (24-74) months, 5-year BCSS was favorable at 96.2% (95% CI, 85.3%-99.0%). Conclusions and Relevance This cohort study of TGD patients with breast cancer found that this population was young and often detected their own tumors via self-examination, suggesting opportunities to improve early detection through screening for individuals at elevated risk. Although short-term BCSS appeared favorable, prospective research is essential to define evidence-based guidelines and elucidate long-term outcomes.

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.

Under the auspices of the International Society of Vascularized Composite Allotransplantation (ISVCA), a section of the Transplantation Society (TTS) that promotes and encourages research and training in the field of vascularized composite allotransplantation (VCA), the 4th Chauvet Workshop was convened in conjunction with the biennial meeting of the ISVCA from 27–29th June 2025 in Helsinki, Finland. The Chauvet workgroup recognizes the importance of psychological evaluation and management in VCA and works to provide an interdisciplinary platform for the development of psychosocial guidelines for the field. For the first time this workshop was conducted jointly with the ISVCA biennial congress, facilitating wider attendance, and discussions between different units and across disciplines. Three main areas were discussed; outcomes and lessons learned, qualitative research approaches and patient reported outcome measures (PROMS), and the role of team science in complex care models. We also heard an update from patient advocate Vasyly Rohovyy, on the progress being made to develop a VCA patient support and advocacy community. Here we summarize these discussions.

Abstract Introduction Intracerebral hemorrhage (ICH) carries higher morbidity and mortality than ischemic stroke. Recent studies have demonstrated improved patient outcomes by applying ultra-early bundled interventions including blood pressure management, coagulopathy reversal, and osmotic therapy. Effective strategies to deliver these ultra-early treatment options are currently being explored. On December 19th, 2022, the Mayo Clinic Comprehensive Stroke Center (CSC) launched the “ICH Phases” communication system to accelerate ICH patient care. Objective To evaluate adherence to the AHA/ASA guidelines in acute ICH care following the implementation of our novel-tiered paging system. Methods We retrospectively reviewed patients admitted with spontaneous ICH during 2024 and 2025. We excluded traumatic cases. We extracted clinical data such as time to imaging, documentation of ICH score, blood pressure control, reversal of anticoagulation, venous thrombo-embolism (VTE) prophylaxis and discharge disposition. Results Among 67 patients, 68.7% underwent CT imaging within 25 minutes. We documented the ICH score within 6 hours in 82.9% of patients. Nearly 94.7% of patients with SBP>140 mm Hg received antihypertensive therapy, yet only 18% reached target BP within 60 minutes. We completed the reversal of anticoagulation within 120 minutes in 75% of patients. VTE prophylaxis was initiated within 24 hours in 91% of patients. Discussion Our novel system demonstrated adherence to the AHA/ASA guidelines, and time sensitive benchmarks in neuroimaging, reversal of anticoagulation, and VTE prophylaxis. Early BP control remains a challenge, that highlights the discrepancy between guidelines and real-ground implementation. Conclusion A novel tiered paging system is effective for enhancing early ICH care. Such a holistic system remains critical for sustained improvement in quality of care.

Abstract Background aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

Background: Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure (HF) cases and remains diagnostically challenging due to nonspecific symptoms and a lack of accessible noninvasive screening tools, leading to widespread underdiagnosis and delayed treatment. The electrocardiogram (ECG) is a low-cost, widely available tool that reflects myocardial electrical remodeling. We previously developed and externally validated an ECG-based artificial intelligence (ECG-AI) model capable of classifying ECGs into four categories: reduced ejection fraction (rEF), mid-range ejection fraction (mEF), HFpEF, and controls. In this study, we evaluate the ability of this ECG-AI model to predict future HFpEF diagnosis using real-world data from a large integrated health system. Methods: We applied the validated ECG-AI model to an independent cohort of 7713 patients from Wake Forest Baptist Health (WFBH), using one ECG per patient recorded before the clinical diagnosis of HFpEF. Model discrimination was evaluated across multiple prediction windows from six months up to ten years before diagnosis using the area under the receiver operating characteristic curve (AUC), with comparisons performed using DeLong’s test. Performance was also compared head-to-head with the H2FPEF score, a validated clinical score for HFpEF, in the subset of patients with complete data for score calculation. ECG-AI outputs were stratified into quartiles and evaluated using Kaplan–Meier survival analysis and multivariable Cox proportional hazards regression adjusted for demographics and major comorbidities. Results: Of the 7713 patients, 283 (3.7%) were subsequently diagnosed with HFpEF. The ECG-AI model achieved an AUC of 0.79 (95% CI, 0.72–0.86) using ECGs recorded within six months before diagnosis. Discrimination remained stable across prediction windows extending up to ten years before diagnosis (AUC range, 0.78–0.80; all DeLong p > 0.01 vs. the six-month window). Compared with the H2FPEF score, ECG-AI demonstrated superior discrimination, improving the AUC by 0.06–0.07 across the evaluated prediction windows. Patients in the highest ECG-AI risk quartile had an unadjusted hazard ratio (HR) of 11.18 (95% CI, 7.27–17.21; C-index, 0.75) and an adjusted HR of 6.60 (95% CI, 4.24–10.28; C-index, 0.82). Adding clinical covariates to ECG-AI improved the C-index by 0.07 and 0.09 for the five- and ten-year prediction windows, respectively. Conclusions: An independently validated ECG-AI model predicted incident HFpEF up to ten years before clinical diagnosis and outperformed the H2FPEF score using ECG alone, indicating that ECG-derived signatures precede clinical recognition of the syndrome. ECG-AI shows promise as a prognostic, risk-stratification tool to prioritize further evaluation; prospective validation and single-lead assessment are needed before screening or wearable deployment.

This protocol paper details a single-center, randomized trial to compare greater occipital nerve blocks (GONBs) to multiple peripheral nerve blocks (MPNBs) for acute headache relief and prophylaxis in episodic migraine. GONBs are effective for the treatment and prevention of migraine, but a combination of trigeminal and occipital nerve blocks can be effective when GONBs alone have failed. To test this hypothesis, 60 adult participants will be randomized to receive either bilateral GONB or MPNBs of the bilateral greater occipital, lesser occipital, auriculotemporal, supraorbital, and supratrochlear nerves during an acute migraine with 0.5–1.25 mL bupivacaine 0.5%. Methylprednisolone 10–20 mg will be added only for the occipital nerves. Anesthesia in the distribution of each nerve block will be tested, and reinjection with bupivacaine will be performed until anesthesia is achieved. The primary endpoint will be pain freedom 20 min after injections. Secondary endpoints include pain freedom at 2 and 24 h, headache relief at 2 h, frequency and severity of subsequent migraine, and absenteeism from work/school/life events due to headaches over a 12-week follow-up period compared to a four-week run-in period. Trial Registration: The trial is registered at ClinicalTrials.gov (NCT04278573).

Abstract The mutation status of isocitrate dehydrogenase (IDH) in glioma patients has diagnostic and prognostic significance but is available only after surgery. Rapid and sensitive intraoperative molecular diagnosis is essential for distinguishing tumor from infiltrative and from normal brain tissue to maximize safe resection. IDH-mutant (mut)tumors produce high concentrations of 2-hydroxyglutarate (2HG), which serves as a surrogate marker of IDH mutation. Here, we use desorption electrospray ionization-multiple reaction monitoring (DESI-MRM), a form of mass spectrometry (MS), for rapid prediction of IDH mutation status. A set of 30 human brain smears was analyzed using DESI-MRM experiments to predict the mutation status of IDH and quantify 2HG in glioma samples within 2 min (endogenous reference molecule) or 7 min (external standard). Nanoelectrospray ionization (nESI) was employed as a validation method. An isotopically labeled surrogate internal standard allowed quantitative measurement of 2HG and clear separation between IDH-mut and IDH-wildtype (wt) samples, showing 100% agreement with clinical diagnosis. 2HG concentrations in IDH-mut samples ranged from 88 to 1445 ng mg–1, while IDH-wt samples exhibited 2HG concentrations of 9–15 ng mg–1. Calibration curves showed method accuracy within ≤15%. The quantitative results obtained using isotopically labeled standards showed a strong correlation between IDH mutation score and 2HG concentrations, as did an earlier semiquantitative (ratiometric, endogenous standard) method. These findings highlight the standalone capability of DESI-MRM for making measurements to justify assessments for intraoperative diagnosis and to support surgical decision-making to improve patient outcomes.