Citations

Abstract Background Polycystic ovary syndrome (PCOS) affects 10% to 13% of individuals assigned female at birth (AFAB), although a greater prevalence is reported in transgender/gender diverse individuals (TGD) (23.8-38.8%). Testosterone therapy (TT) in TGD individuals is linked to worsening cardiovascular risk factors (CVRFs). Whether TT induces more adverse cardiometabolic changes in TGD with PCOS than TGD without PCOS remains uncertain. Objective To compare the effects of TT on CVRF in TGD with and without PCOS. Methods We retrospectively reviewed 373 records to identify 62 TGD with PCOS (withestablished guideline criteria) and 132 age-matched TGD without PCOS. Data included longitudinal anthropometric measurements, hormone and metabolic parameters, and CVRF before and after TT. Group comparison of PCOS vs without PCOS before and after TT was conducted via independent t-tests, Mann–Whitney-U, and Chi-square. Results At baseline, TGD with PCOS had significantly greater body mass index (BMI), obesity prevalence, and, after controlling for BMI, baseline metformin use. There were no significant differences between TGD with and without PCOS when comparing intra-participant changes after TT. Controlling for BMI, TGD with PCOS on TT exhibited significantly greater hyperlipidemia prevalence, alanine transaminase (ALT) levels, and bioavailable testosterone concentrations than TGD without PCOS on TT. Conclusion Greater baseline cardiometabolic risk was largely BMI-related in TGD with PCOS compared to TGD without PCOS. Only hyperlipidemia and elevated ALT were more prevalent during TT after adjusting for BMI. These findings support cardiometabolic monitoring during TT in all TGD individuals without significant increased risk with PCOS history.

Early allograft failure (EAF) after living donor liver transplantation (LDLT) remains a clinical challenge. Existing prediction models developed for deceased donor transplantation poorly apply to LDLT due to distinct surgical and physiological factors. This study identifies clinical determinants of EAF and develops an LDLT-specific prediction model. We conducted a multicenter retrospective cohort study from 17 high-volume LDLT centers (January 2016–December 2020) with external validation at a tertiary center in Saudi Arabia (January 2015–December 2022). The primary outcome was EAF (graft loss or patient death ≤90 d). Multivariable mixed-effects logistic regression identified preoperative/intraoperative risk factors. The EAGLE-LDLT model was constructed using postoperative laboratory values. Performance was compared against established models (EAD, MEAF, A2ALL) using ROC analysis and decision curve analysis. The development cohort included 2944 adult LDLT recipients (67.7% male; median age 55 y; median MELD 14) with a 5.5% EAF rate. External validation included 1020 recipients (median MELD 21, 6.7% EAF). Independent risk factors for EAF were MELD (OR 1.06, 95% CI 1.04–1.08), donor BMI (OR 1.05, 95% CI 1.00–1.10), portal vein thrombosis (OR 1.73, 95% CI 1.13–2.63), and hepaticojejunostomy (OR 1.58, 95% CI 1.06–2.36). The EAGLE-LDLT model incorporating peak ALT (>468 U/L), peak INR (>1.9), and bilirubin (>3.5 mg/dL) and INR (>1.3) at POD7, demonstrated superior discrimination (AUC=0.81) compared with MEAF (AUC=0.77, p =0.004), EAD (AUC=0.67, p <0.001), and A2ALL (AUC=0.65, p <0.001). EAGLE-LDLT achieved balanced sensitivity (75.0%) and specificity (73.7%), effectively stratifying patients into high-risk (15% of patients; 40.4% EAF incidence) and low-risk groups. Preoperative and intraoperative clinical factors predict EAF in LDLT. The EAGLE-LDLT model accurately identifies LDLT recipients at the highest risk for EAF postoperatively.

Ameloblastomas are locally aggressive odontogenic tumors that most commonly arise in the mandible and maxilla and often harbor BRAF V600E mutations. While rare extragnathic ameloblastomas have been reported, primary pulmonary cases have not been documented. We identified 3 pulmonary neoplasms with features of ameloblastoma that were submitted for consultation between 2022 and 2025 at 3 academic institutions and performed detailed clinicopathologic and molecular analysis. The tumors presented as 5.4 to 7.3 cm peribronchial solitary lung masses. All resected tumors exhibited a predominant stellate reticulum-like component composed of loosely arranged p40-reactive bland squamoid-to-spindled cells with long intercellular bridges, and streaming and swirling architecture, surrounded by palisaded columnar cells with focal reverse nuclear polarity at the interface with myxoid stroma. All tumors were immunoreactive for BRAF V600E IHC, and BRAF V600E mutations were confirmed by molecular assays, including broad next-generation sequencing on 2 cases. Florid hyperplasia of entrapped pneumocytes initially suggested a biphasic neoplasm, but the absence of BRAF V600E IHC labeling confirmed pneumocyte entrapment. Occult gnathic primary tumors were excluded by subsequent clinical examination, including negative panoramic dental x-rays. No recurrences or metastases have been observed to date. This first series of primary pulmonary ameloblastomas highlights a distinctive tumor with histologic and molecular features identical to gnathic counterparts. We discuss the potential histogenesis of these unusual tumors.

Abstract Exercise training improves cardiovascular health and reduces the risk for future cardiovascular events and mortality. However, emerging evidence suggests that Masters athletes may have a higher prevalence of cardiovascular abnormalities, such as atrial arrhythmias, coronary atherosclerosis, aortic dilatation, and myocardial fibrosis, compared to their less active peers. The clinical management of Masters athletes may be challenging as available guidelines for such conditions are generally based on data derived from symptomatic sedentary patients, limiting their applicability to highly trained individuals. Other unique challenges in the clinical assessment of Masters athletes include differences in symptomatic presentations compared to sedentary individuals, potential resistance to the initiation of pharmacologic treatment, and the increasing availability of consumer wearable health data that may provide relevant information on their cardiovascular health status. The purpose of this joint EAPC/ESC and ACC Clinical Consensus Statement is to provide an in-depth update on the current state of knowledge on abnormal cardiovascular findings in Masters athletes. We present an expert-based approach on the diagnostic assessment, management, and prognosis of (i) atrial fibrillation, (ii) bradyarrhythmias, (iii) ventricular arrhythmias, (iv) coronary atherosclerosis, (v) aortic dilatation, (vi) myocardial fibrosis, and (vii) exercise-induced arrhythmogenic cardiomyopathy. Clinical challenges, areas of ongoing controversy, and uncertainty and the potential underlying mechanisms are discussed. We also present future perspectives and research directives to further refine current best practice strategies. This includes the need for clinical outcome studies, dedicated randomized controlled trials in athletes, and international registries with diverse populations and longitudinal follow-up to evaluate the natural history of cardiac abnormalities and facilitate development of evidence-based approaches in the clinical management of Masters athletes with cardiovascular abnormalities.

Abstract Aims Coronary angiography might contain clinically relevant information, beyond its traditional role in delineating coronary artery disease. We sought to explore the role of deep learning (DL) in detecting right ventricular dysfunction from routinely acquired cine images during coronary angiography. Methods and results 3D-convolutional neural networks (CNN) were trained to identify right ventricle (RV) dysfunction from diagnostic angiography of the right coronary artery (RCA). The model’s input was two cine angiograms from LAO and RAO projections. The model’s output was normal vs. abnormal RV function. Ground truth on RV function was obtained from the nearest transthoracic echocardiogram to the coronary angiogram. Two analyses were performed to identify (i) any RV dysfunction (≥mild) and (ii) significant RV dysfunction (≥mild–moderate). A total of 10 336 coronary angiograms from 9849 patients (mean age 66, 36% women) were included. The cohort was split into training (70%), validation (15%), and testing (15%) sets. In the testing sets, the models attained an area under the ROC curve (AUC), sensitivity, and specificity of 0.82 (95% CI: 0.80–0.84), 0.75, and 0.74, for detecting any RV dysfunction, and 0.83 (95% CI: 0.80–0.86), 0.82, and 0.70 for detecting significant (≥mild–moderate) RV dysfunction. Combining an ECG-driven AI model with the angio-driven model improved the AUC values to 0.83 and 0.87 for detecting any or advanced RV dysfunction, respectively. Conclusion A novel deep learning algorithm yielded acceptable classification accuracy in detecting RV dysfunction from routine cine angiography of the RCA. The model’s performance improved further by adding ECG to its inputs.

830 Background: Immune checkpoint inhibitors (ICIs) are standard therapy for MSI-H GI cancers. Lynch syndrome, caused by germline mutations in mismatch repair (MMR) genes, leads to MSI-H tumors and robust ICI responses, but its effect on irAEs remains poorly defined. Clarifying this risk may inform treatment selection and toxicity monitoring. Methods: We retrospectively reviewed MSI-H or MMR-deficient (dMMR) GI cancer patients (pts) treated with ICIs across Mayo Clinic (AZ, MN, FL) from January 2017 to June 2025. Eligible pts were identified using Mayo Data Explorer. Demographics, treatment, and irAEs (graded per CTCAE v5.0) were collected. Lynch status was determined by germline testing when available. Logistic regression estimated odds ratios (ORs) for any grade and grade ≥3 irAEs, adjusting for age, cancer type, prior chemotherapy, and treatment regimen. Results: A total of 209 pts with dMMR/MSI-H GI cancer were included: 61 with Lynch syndrome and 148 without. Lynch pts were younger (median 58 vs 76 years, p < 0.001) and more likely to have received prior chemotherapy (62% vs 43%, p = 0.009). Colorectal cancer was the predominant cancer type (74%), but Lynch pts had proportionally more non-colorectal GI cancers (15% vs 2.7%, p = 0.007). Overall, 29% of pts experienced an irAE, with rates significantly higher in Lynch vs non-Lynch pts (43% vs 24%, p = 0.005). The most frequent irAEs were gastrointestinal, endocrine, and dermatologic, followed by hepatic and pulmonary events. Grade ≥3 irAEs occurred in 16% overall, with no significant difference between groups (p = 0.124). In adjusted models, Lynch syndrome was independently associated with a higher risk of any grade irAE (OR 2.14, 95% CI 1.09 - 4.19, p = 0.026), while risk of severe irAEs was not increased (OR 1.55, 95% CI 0.64 - 3.59, p = 0.316). Lynch syndrome pts were more likely to have combination therapy (17% vs 6.8%, p = 0.029). However, there were no differences observed in any grade irAE between monotherapy and combination immunotherapy (OR 1.36, 95% CI 0.49 - 3.54, p = 0.535). Conclusions: Lynch syndrome is associated with a higher prevalence of any-grade irAEs among dMMR/MSI-H GI cancer pts treated with ICIs, though severe events were not increased. Incorporating Lynch status into immunotherapy planning may improve risk stratification and guide regimen selection.

ABSTRACT Obstructive sleep apnea (OSA) is a common, heritable disorder with diverse clinical presentations and etiologies. We conducted a genome-wide association meta-analysis of 492,107 individuals, including 46,028 OSA cases, identifying 14 genome-wide significant loci, eight of which are novel. Analyses adjusting for body mass index (BMI) revealed three loci independent of obesity, implicating alternative biological pathways contributing to disease. Integrative functional analyses, including chromatin interaction mapping, fine-mapping, and eQTL colocalization, prioritized candidate effector genes. Notably, implicated genes in chondrocytes were associated with craniofacial morphology in both mouse and human multivariate genotype-phenotype mapping, supporting a role for craniofacial structure in OSA risk. These findings highlight key genetic pathways (obesity-related, neurological, and craniofacial) underlying the development of OSA, offering new insights into its complex etiology.

Living donor liver transplantation (LDLT) is an established therapy with curative intent for pediatric and adult patients with acute liver failure and end-stage liver disease. Donor safety remains paramount and commences during preoperative evaluation and assessment. Given the importance of the topic, the International Liver Transplantation Society and International Living Donor Liver Transplantation Group consensus conference on Living Liver Donor Safety was convened in March 2025 (Toronto, Canada). Recommendations were based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system for assessment of recommendations, and the Danish model of consensus was followed. This report presents 28 recommendations from the working group focused on addressing clinically relevant questions related to the preoperative aspects of living donor safety including assessment of donor acceptability (age, body mass index and hepatic steatosis; medical conditions and contraindications), medical and surgical workup (liver function and procoagulant workup; anatomical considerations and safe remnant), and psychosocial evaluation (timing and team; underlying conditions; non-directed, paired, and anonymous directed donors; urgent living donor workups for acute liver failure).