Citations

The 2025 American College of Cardiology/American Heart Association/American College of Emergency Physicians/National Association of Emergency Medical Services Physicians/Society for Cardiovascular Angiography & Interventions acute coronary syndrome guideline focuses on strategies to reduce bleeding risk with antiplatelet therapy yet lacks any recommendation related to CYP2C19 genotyping. The impact of CYP2C19 loss‐of‐function alleles on the effectiveness of clopidogrel is well documented, and although prasugrel and ticagrelor more effectively reduce the risk for atherothrombotic events compared with clopidogrel in patients with a CYP2C19 loss‐of‐function allele, clopidogrel reduces bleeding risk without an increase in atherothrombotic events compared with prasugrel or ticagrelor in those without a loss‐of‐function allele. Accordingly, an American Heart Association Scientific Statement supports CYP2C19 genetic testing before oral P2Y 12 inhibitors are prescribed. This commentary summarizes the evidence in support of CYP2C19 ‐guided P2Y 12 inhibitor selection in the context of other 2025 acute coronary syndrome guideline recommendations and urges future guidelines to incorporate recommendations for CYP2C19 genotyping, especially for those at high bleeding risk.

Morel-Lavallee lesions (MLLs) are traumatic closed degloving injuries with operative intervention (OI), especially excisional debridement, remaining the mainstay of treatment. However, high-quality evidence describing operative techniques and outcomes remains limited. This study aimed to characterize current OI practices and associated outcomes, especially among patients undergoing excisional debridement, hypothesizing an increased risk of wound complications with this approach for MLLs. Methods This prospective (2021-2024), multicenter, observational study was conducted across 15 trauma centers and included patients diagnosed with MLL who underwent OI. The association between operative technique (eg, excisional debridement) and the primary outcome of wound complications was evaluated. Wound complications were defined as cellulitis, deep wound infection, skin necrosis, necrotizing soft tissue infection (NSTI), and/or organized hematoma. Results Of 88 MLL patients undergoing OI, 36 (40.9%) had excisional debridement, with 4 (11.1%) limited excision to skin, 20 (55.6%) extended to subcutaneous tissue, and 12 (33.3%) down to muscle. Excisional debridement had higher rates of skin necrosis (22.2% vs. 1.9%, P = .002). Although overall rates of wound complications were statistically similar between cohorts (33.3% vs. 17.3%, P = .098), univariate analysis demonstrated excisional debridement had increased risk of wound complications (OR 2.52, CI 1.07-5.97, P = .035). Conclusion This prospective multicenter study over three years demonstrated that a fifth of MLLs undergoing excisional debridement developed postoperative skin necrosis. Excisional debridement also had a more than two-fold increased risk of wound complications compared to other OIs. These findings underscore the importance of investigating alternative operative techniques, such as incision and drainage or minimally invasive debridement methods.

Objective To estimate the prevalence, incidence, and disease burden of autoimmune seizures and epilepsies in Olmsted County. Methods We conducted a retrospective, population‐based study using the Rochester Epidemiology Project (1996–2019). Age‐ and sex‐standardized rates (2019 United States standard population) per 100,000 were calculated with 95% confidence intervals (95% CIs). Temporal trends in incidence were assessed over 3 consecutive 8‐year intervals (1996–2003, 2004–2011, and 2012–2019) using Poisson regression to estimate rate ratios per period and trend. Disability‐adjusted life years (DALYs), years of life lost (YLL), and years lived with disability (YLD) and 95% uncertainty intervals (95% UIs) were estimated for 2019. Results Twenty‐three patients were identified between 1996 and 2019. In 2019, the standardized prevalence of all autoimmune seizures and epilepsies was 9.81 (95% CI, 5.59–15.21) per 100,000, including autoimmune‐associated epilepsy (AAE) 7.27 (3.74–11.95) and acute symptomatic seizures secondary to autoimmune encephalitis (ASSAE) 2.55 (0.69–5.60). From 1996 to 2019, the standardized incidence was 0.50 (0.29–0.77) per 100,000 person‐years overall, with AAE 0.36 (0.19–0.59) and ASSAE 0.15 (0.05–0.30). By period, the standardized incidence of all autoimmune seizures and epilepsies suggested a rising trend from 0.28 (95% CI, 0.06–0.68) in 1996 to 2003 to 0.60 (95% CI, 0.24–1.12) in 2004–2011, then plateaued at 0.53 (95% CI, 0.21–1.00) in 2012 to 2019 (rate ratio per 8‐year interval 1.30, 95% CI, 0.71–2.38), largely driven by the seropositive subgroup. The standardized DALY rate was 26.27 (95% Uncertainly intervals [UI], 5.30–67.09) per 100,000 (YLL 20.07 [0.00–60.21] and YLD 6.20 [5.06–7.39]). Interpretation Although autoimmune seizures and epilepsies remain rare, they result in a disproportionately high disease burden. ANN NEUROL 2026;100:74–83

BACKGROUND: Morel-Lavallée lesions (MLLs) are closed degloving injuries that occur throughout the body and present treatment challenges due to their rarity and variability in management. We aimed to compare characteristics and outcomes for MLL patients undergoing early (less than 48 hours) vs late (more than 48 hours) surgical intervention, hypothesizing decreased length of stay (LOS) with early intervention. STUDY DESIGN: Fifteen centers participated in this prospective observational study, including all adult patients who sustained a MLL and underwent surgery. No patients were excluded. Bivariate comparisons for early vs late intervention cohorts were performed. RESULTS: Of 150 MLL patients, 101 (67.3%) underwent early intervention. Both cohorts had comparable ages, BMI, vitals, Charlson Comorbidity Index, and injury severity scores (all p > 0.05). However, early intervention patients more commonly had abdominal (37% vs 6.3%, p < 0.001) MLLs, whereas late intervention patients more often had hip (16.7% vs 3.0%, p = 0.01) and thigh (41.7% vs 22%, p = 0.03) MLLs. Early patients had shorter ICU LOS (2 vs 5, p = 0.003) but statistically similar hospital LOS (12 vs 20, p = 0.06). There was no difference in wound-related complications (19.8% vs 24.5%, p = 0.51) or mean number of additional surgeries (p = 0.41) between cohorts. CONCLUSIONS: Over two-thirds of MLL patients underwent early operation. These patients had decreased ICU LOS and a statistically similar albeit clinically shorter overall LOS, despite similar demographics, comorbidities, injury severity, and number of additional surgeries. Therefore, early operation appears beneficial and should be pursued in MLL patients when clinically indicated and feasible.

369 Background: MRI-guided transurethral ultrasound ablation (TULSA) uses MRI to target, monitor, and control thermal ablation of prostate tissue with high intensity directional ultrasound, demonstrating favorable histologic control and preservation of genitourinary function in single-arm studies [1,2]. CAPTAIN (NCT05027477) is a post-market, multi-center randomized controlled trial (RCT) of TULSA vs RARP for intermediate-risk prostate cancer, and is the first such study to meet its enrolment target. Here we compare baseline patient characteristics, treatment parameters, and periprocedural outcomes. Methods: CAPTAIN enrolled men with treatment-naïve, organ-confined, Grade Group 2 or 3 prostate cancer at 23 centers including academic and private clinics in the USA (20), Canada (2), and Finland (1). Patients were randomized 2:1 to TULSA or RARP, without crossover. Endpoints include pad-free urinary continence (EPIC) and erections sufficient for penetration (IIEF Q2) at 1 year, salvage treatment at 3 years, and survival to 10 years. Periprocedural metrics include length of stay, blood loss, catheter time, and 30-day patient diary (EQ-5D-5L, NRS pain score). Results: 211 patients were treated from Jan 2022 to Aug 2025 (70% TULSA, 30% RARP), surpassing the enrolment target of 201. Arms had similar baseline characteristics: median (IQR) age for TULSA vs. RARP was 63 (58–68) vs 65 (60–69) years (p=0.12), PSA was 6.5 (4.9–9.6) vs 7.2 (5.6–9.7) ng/mL (p=0.63), Grade Group 2/3 proportions were 76%/24% vs 77%/23% (p=0.88). RARP involved bilateral, unilateral, or no nerve sparing in 89%, 5.7%, and 5.7% of cases. TULSA ablation plans included whole-gland (68%) and ≥hemi-ablation (32%). Median (IQR) blood loss was lower during TULSA vs RARP: 0 (0–0) vs 100 (100–200) mL (p<0.001). Hospital stay was shorter for TULSA: 0.29 (0.27–0.32) vs 1.24 (1.12–1.36) days (p<0.001). Catheter duration was longer post-TULSA: 13 (11–15) vs 8 (8–10) days (p<0.001). Patients reported lower NRS pain scores after TULSA to post-operative day 6, and less decline in overall health on the EQ-5D-5L 0-100 visual analog scale over 30 days (p<0.05). Fewer patients reported extreme inability on EQ-5D-5L after TULSA vs RARP over the first month for mobility (0% vs 15%), self-care (1% vs 18%), and usual activities (18% vs 38%) (all p<0.05). Conclusions: CAPTAIN is the first multicenter RCT comparing ablation to radical prostate cancer treatment to meet its enrollment target. Early perioperative results from CAPTAIN demonstrate that TULSA had no blood loss or overnight hospitalization, reduced post-procedural pain, and faster return to baseline activities and overall health. Data collection to 1 and 3 years post-treatment continues to readout of the primary safety and oncological outcomes. [1] Klotz et al 2021, JUrol 205(3):769-779. [2] Eggener et al 2024, UrolOnc 42:S83. Clinical trial information: NCT05027477 .

Abstract Background Loss-of-function variants in TTN-encoded titin are the most common genetic cause of dilated cardiomyopathy (DCM). In addition, titin truncating variants (TTNtvs) are over-represented in early-onset atrial fibrillation (AF) and unexplained sudden cardiac arrest/death (SCA/SCD) suggesting that in rare circumstances TTNtvs may cause arrhythmias in a pre-cardiomyopathic electrical phase. Purpose To compare the prevalence of AF, sustained ventricular arrhythmias (VAs) and SCA/SCD between TTNtv-positive patients with genotype-positive but phenotype-negative (G+/P-) disease, non-dilated left ventricular cardiomyopathy (NDLVC) and DCM. Methods Retrospective review of 1,229 patients in our Arrhythmogenic/Dilated Cardiomyopathy Registry was used to identify those with TTNtvs in high proportion spliced-in (&gt;90%) exons classified as pathogenic or likely pathogenic according to current American College of Medical Genetics and Genomics variant classification guidelines. Demographic, electrocardiographic, imaging and outcome data were extracted from the electronic record. After exclusion of those without satisfactory imaging data, each TTNtv-positive patient was classified as having G+/P- disease, NDLVC, or DCM according to the 2023 European Society of Cardiology Guidelines for the management of cardiomyopathies. The prevalence of AF, non-SCA major VA events (sustained VT and appropriate VT/VF-terminating ICD therapies), and SCA/SCD was then compared between the three left ventricular morphofunctional subgroups. Results Overall, 232 TTNtv-positive patients (mean age of 44 ± 17 years; 57% male) were included (average LVEF of 39 ± 17%; 32% with a history of AF; 23% with a history of non-SCA VA event and 6% with a history of SCA). Forty-nine (21%) were G+/P-, 45 (19%) had NDLVC, and 138 (59%) had DCM at the time of their most recent clinical evaluation. As expected, the prevalence of AF was higher in TTNtv-DCM patients when compared to both TTNtv-NDLVC [56/138 (41%) vs. 11/45 (24%); p=0.04] and G+/P- disease [56/138 (41%) vs. 5/49 (10%); p&lt;0.001]. Similarly, the number of patients who experienced a non-SCA major VA event was higher in TTNtv-DCM than either TTNtv-NDLVC [44/138 (32%) vs. 6/45 (9%); p=0.01] or G+/P- disease [44/138 (31%) vs. 4/49 (8%); p&lt;0.001]. Interestingly, no difference in the number of TTNtv-positive patients who experienced a SCA/SCD was observed across subgroups [2/49 (4%) for G+/P-; 2/45 (4%) for NDLVC; and 8/138 (6%) for DCM; p=ns for all comparisons]. Conclusion In patients with TTNtv substrates who were evaluated at a quaternary medical center, the prevalence of AF and major VA events correlates with left ventricular morphology/function with the greatest risk observed in those with DCM. However, the prevalence of AF and major VA events, including SCA, in TTNtv-positive patients with G+/P- and NDLVC disease is not trivial and highlights the ability of TTNtvs to present in a pre-cardiomyopathic electrical phase.

Abstract Background Common genetic variation has been linked to an increased risk of developing dilated cardiomyopathy (DCM) in case-control studies. However, the phenotypic profile and biological mechanisms by which genetic background may predispose individuals to DCM and outcomes in the general population remain unclear. Aim The primary objectives of this study were twofold: (1) to validate a DCM polygenic score (PRS-1) based on a prior meta-analysis of case–control genetic association studies [Tadros R et al. Nat Genet (2021)]; and (2) To apply this PRS, along with two recently developed PRSs for DCM [PRS-2 from Zheng SL et al. Nat Genet (2024) and PRS-3 from Jurgens SJ et al. Nat Genet (2024)] to a general population that underwent comprehensive longitudinal phenotypic assessments and had long-term outcomes available. Methods While the PRS-1 was derived from only 13 SNPs, PRS-2 and PRS-3 were generated from 709,534 and 1,072,247 SNPs, respectively with significant overlap between them. These DCM-PRSs were applied to an unselected community-based cohort (n=1897) aged &gt;45 years, who underwent a physical examination, echocardiogram, and blood sample at baseline. Subsequent clinical outcomes were collected over a median 16 year follow-up (IQR: 15-17). Results No significant differences between the quartiles were present in terms of age, sex (48% male), and cardiovascular risk factors (CV-RF) (such as hypertension, diabetes, and coronary artery disease). However, linear regression models demonstrated a significant correlation between all DCM-PRSs and left ventricular (LV) parameters, including LV ejection fraction, LV end-systolic diameter, and LV end-diastolic diameter (Table). Multivariable regression analysis confirmed that these correlations were independent of age, sex, CV-RF, and population stratification (adjusted for the first 10 principal components [PCs]). During follow-up, 47 individuals developed DCM. A logistic regression analysis, using a 3:1 matched cohort of non-DCM vs. DCM individuals based on age and sex and adjusted for the same 10 PCs, found a significant correlation between DCM development and both PRS-1 [OR=2.27 (1.06–4.85), p=0.03] and PRS-3 [OR=2.63 (1.20–5.75), p=0.02], while PRS-2 did not show a significant association [OR=1.85 (0.84–4.06), p=0.12]. No association was found between the DCM-PRSs and heart failure (HF) biomarkers (aldosterone, natriuretic peptides, ST2, Galectin-3) or HF outcomes (all-cause mortality/HF hospitalization). Conclusion PRS-1 for DCM despite being derived from only 13 risk alleles, performs at least as well as the newer and more extensive PRSs, in its correlation with LV function, dimensions, and DCM development (except for PRS-2) in a general population. The absence of correlation between these DCM-PRSs and the renin-angiotensin-aldosterone system or natriuretic peptides suggests that genetic background influences LV traits through mechanisms independent of these biological pathways.

This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.