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BACKGROUND: Recent randomized trials have demonstrated that for patients with severe tricuspid regurgitation (TR), transcatheter tricuspid valve interventions (TTVI) improve patients’ symptoms, function, and quality of life and that the amount of health status improvement correlates with the extent of TR reduction. Defining this relationship in greater detail can potentially provide insight into device selection and patient-specific treatment goals. We therefore sought to better understand the relationship between both baseline TR severity and change in TR after TTVI and the extent of improvement in health status after TTVI. METHODS: As part of the Tri-QOL (Kansas City Cardiomyopathy Questionnaire Validation in Tricuspid Valve Disease) study, data from 11 studies of TTVI devices were transferred to the US Food and Drug Administration to harmonize and anonymize before analysis by an independent center. This secondary, observational analysis used patient-level data from the 6 single-arm studies of patients who underwent TTVI to explore the association of change in KCCQ-OS with TR grade using multivariable models, adjusted for age, sex, chronic lung disease, and baseline KCCQ-OS. The primary model included TR grade at baseline, TR grade at 1 month, and the interaction between the two. RESULTS: Among 1056 patients with ≥severe TR who underwent TTVI, mean age was 79.1±7.1 years, 60.3% were female, and mean baseline Kansas City Cardiomyopathy Questionnaire-overall summary score [KCCQ-OS] was 49.5±22.3. Baseline TR grade was severe in 33.5%, massive in 35.9%, and torrential in 30.6%. One-month after TTVI, TR was none/trace in 21.7%, mild in 27.2%, moderate in 28.1%, and ≥evere in 23.1%, while the mean change in KCCQ-OS was 17.0±21.3 points. In a multivariable model that included TR grade at baseline, TR grade at 1 month, and their interaction, there was a strong association between reduction in TR and improvement in KCCQ-OS, with no consistent evidence of a threshold of TR grade below which there was no further improvement in KCCQ-OS. However, among patients with baseline torrential TR, the extent of health status improvement plateaued for patients achieving moderate or less TR at 1 month (ie, a 3-grade improvement from baseline). CONCLUSIONS: Health status improvement after TTVI was most strongly associated with the degree of TR reduction, although there was minimal additional improvement for most patients beyond a 3-grade reduction in TR. These findings support the goal of achieving mild or less TR with TTVI, although patients with torrential TR at baseline may be well served if moderate TR can be achieved.

Background and Aims: Older age increases susceptibility to metabolic dysfunction–associated steatotic liver disease (MASLD), but whether it impacts response to therapies, and how the therapies impact regulators of biological aging, are poorly understood. Statins inhibit the mevalonate pathway to block cholesterol biosynthesis and are widely used in MASLD patients to reduce cardiovascular disease. Whether statins prevent progression to cirrhosis is under investigation. However, the molecular effects of statins in human liver, particularly in the context of aging, remain poorly defined. Approach and Results: We analyzed liver transcriptomes and matched clinical data from 368 adults enrolled in the Duke MASLD Biorepository with a focus on age-dependent responses and the interplay between senescence and ferroptosis, a regulated death process that is constrained by the mevalonate pathway. Serum ALT, AST, and LDL cholesterol levels were lower in statin users of both sexes, particularly among older individuals. Transcriptome analyses revealed that statin use is strongly associated with suppression of senescence-related pathways. Statin use is also associated with increased activation of pathways linked to ferroptosis. Both responses persisted after propensity score matching to control for clinical confounders and were validated in an independent obese cohort. Conclusions: Age-dependent transcriptional remodeling in the liver differs in statin users and non-users. Pathways involved in senescence are suppressed while those that promote ferroptosis are induced in statin users. These results suggest that statins may suppress biological aging in MASLD by acting as senolytics and highlight the complex, context-specific roles of senescence in liver adaptation and remodeling.

This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

This Perspective discusses the flaws in the process and methods of institutional external validation in medical education.

Ramdas et al. propose renaming ‘congenital myasthenic syndrome’ as ‘genetic myasthenic syndrome’. They argue that ‘congenital’ misleadingly implies neonatal onset, which may contribute to delayed diagnosis and management, and that revised nomenclature could improve patient outcomes.

Introduction: Porokeratosis is a group of keratinization disorders characterized by the histopathological presence of the cornoid lamella, a hallmark feature across all subtypes. The clinical diagnosis of porokeratosis can be challenging due to its similarity to other dermatological conditions. While polarized light dermatoscopy (PLD) enhances diagnostic accuracy, certain features remain difficult to identify. Ultraviolet-induced fluorescence dermatoscopy (UVFD) is a novel imaging technique that may improve the visualization of porokeratosis features, particularly the peripheral keratin rim. Objectives: This study aimed to assess the diagnostic utility of UVFD compared with PLD in identifying the dermatoscopic features of porokeratosis. Methods: In this retrospective study, dermatologists from five institutions in Chile, Brazil, Poland, and the United States contributed with dermatoscopic images of porokeratosis cases. Both PLD and UVFD images were obtained for each lesion. Two independent investigators evaluated each lesion in PLD and UVFD for the presence of peripheral keratin rim, rim continuity, central scaling, follicular plugs, vascular structures, and photodamaged surrounding skin. A third investigator reviewed discrepancies. Frequencies and means were calculated. McNemar’s chi-square was used for comparison. Results: A total of 136 lesions from 35 patients with biopsy-proven porokeratosis were analyzed. UVFD significantly improved the visualization of the peripheral keratin rim (95.6% vs. 66.2% in PLD; P<0.001) and increased identification rates for central scaling, follicular plugs, and interrupted rims. PLD remained superior for detecting vascular structures(P<0.001). Conclusions: UVFD enhances the visualization of key dermatoscopic features of porokeratosis, particularly the peripheral keratin rim and other keratin-related structures.

Abstract Background: Although hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are inherited disorders expected to display a 1:1 sex ratio, most studies report a strong female dominance. This study analyzed sex differences in 122 self-reported symptoms and comorbidities in patients diagnosed with hEDS or HSD using the 2017 criteria. Methods: Self-reported data was obtained from November 1, 2019, to April 25, 2025, ( n =2,451) from an Intake Questionnaire of adult (≤18 years old) patients diagnosed with hEDS or HSD at the EDS Clinic at Mayo Clinic Florida and analyzed by sex. Results: We found that 90.6% ( n =575) of hEDS patients were female and 9.4% ( n =60) were male, with a sex ratio of 9.6:1 female-to-male, while 95.2% ( n =1,728) of HSD patients were female and 4.8% ( n =88) were male, with a sex ratio of 19.6:1 female-to-male. Females were older than males: hEDS 35 vs. 28 years of age ( p <0.001), HSD 34 vs. 31 years of age ( p =0.004). Overall, females self-reported more symptoms/comorbidities than males: hEDS 31/122 (25.4%), HSD 59/122 (48.4%). In contrast, only 5/122 (4.1%) symptoms/comorbidities were self-reported more often in males including attention deficit disorder/attention deficit hyperactivity disorder, delay in developmental milestones, snoring, autism spectrum disorder, and obstructive sleep apnea. Females with HSD had more mast cell-related symptoms (i.e., hives p <0.001) which were reflected in higher mast cell scores than males ( p <0.001). Patients with higher mast cell scores also had higher serum levels of total IgE ( p =0.029). More females with HSD were diagnosed with fibromyalgia ( p <0.001) and reported symptoms associated with autonomic dysfunction than males. Aside from abuse, which was higher in females (hEDS p =0.039, HSD p <0.001), few sex differences were reported for psychological symptoms/comorbidities. In support for the idea that elevated mast cell activity in females may lead to extracellular matrix remodeling that promotes hypermobility, females with hEDS/HSD had greater serum collagen-4α1 ( p <0.0001) and fibronectin ( p =0.015) than males by ELISA. Conclusions: Females with hEDS and HSD report a higher burden of symptoms/comorbidities than males, providing a possible explanation for fewer males being reported in demographic data. Sex differences in symptoms/comorbidities may reflect sex differences in pathogenic drivers of disease.

Introduction Mitral regurgitation (MR) is a common valvular disease associated with complications such as pulmonary hypertension, atrial fibrillation, and heart failure. However, its full impact on the cardiovascular system, especially on right heart function, is not yet fully understood. Understanding this relationship is important because the right ventricle (RV) is critical for maintaining cardiovascular function. Dysfunction of the RV, which may be contributed by conditions like MR, is strongly associated with poor clinical outcomes. Despite its importance, comprehensively studying MR's effect on the RV has been challenging due to the complex, interdependent nature of cardiovascular dynamics, limited patient data, and the difficulty in synthesizing disparate information to clarify the left heart-right heart connection. Methods The primary goal of this study is to investigate the effects of MR on cardiovascular hemodynamics and RV function by integrating 3D models of the left heart with a closed-loop 0D models of the entire cardiovascular system. We further conduct detailed analyses using patient-specific models to explore how various system modifications impact the RV, providing insights into the nuanced effects of MR on the right heart. Results and Discussion This analysis provides several clinically relevant insights. First, progressive MR markedly increases RV afterload and predisposes the RV to dysfunction, even when intrinsic RV contractility is preserved or enhanced. Second, MR-specific severity indices and left-heart metrics alone fail to capture the true burden on the right heart; RV impairment can progress despite stable or only modestly changing MR descriptors. Finally, these findings highlight the need to incorporate direct assessment of RV structure and function into the evaluation of MR, as RV vulnerability plays a critical role in determining patient risk and guiding management decisions.