The American Heart Association's PREVENT equations offer a contemporary, race-free alternative to the Pooled Cohort Equations (PCE), incorporating kidney function to estimate 10- and 30-year risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, and total CVD. PREVENT-ASCVD is now recommended for primary-prevention risk assessment in the 2026 multisociety dyslipidemia guidelines, replacing the PCE, making its real-world performance immediately consequential. PREVENT generally preserves discrimination, but calibration varies across populations, with possible overestimation or underestimation. It often lowers estimated risk and modeled eligibility for statin or antihypertensive therapy versus the PCE. Performance is favorable in several general and older-adult cohorts, but underestimation is concerning in people with HIV, rheumatoid arthritis, selected international cohorts, and statin-naïve adults. Coronary artery calcium can refine selected estimates, though no trial has shown PREVENT-guided care improves outcomes. This narrative review appraises external validation, calibration, and reclassification behavior, evaluates effects on treatment eligibility, and identifies evidence gaps, concluding that implementation should remain population-sensitive with local validation and recalibration when appropriate.

Markedly increased risk of thrombosis has been described as a key clinical feature of the recently described VEXAS (vacuoles, E1 enzyme, X linked, autoinflammatory, somatic) syndrome. Critically however, the pathological mechanisms underlying VEXAS-associated hypercoagulability remain poorly understood. We addressed this question in a cohort of 40 VEXAS patients referred to the National Institutes of Health with defined pathological UBA1 sequence variants. In keeping with previous reports, twenty-one (52.5%) VEXAS patients in our cohort experienced thrombotic events. Plasma VWF and FVIII activity levels were both increased in VEXAS compared to age-matched controls. Consistent with endothelial cell (EC) activation and Weibel Palade body exocytosis, plasma VWF propeptide and angiopoietin II levels were also significantly elevated in VEXAS subjects. Furthermore, an accumulation of high molecular weight VWF multimers was seen in VEXAS patients. In keeping with ongoing endotheliopathy, plasma levels of soluble Vascular Cell adhesion Molecule-1 (VCAM-1) and soluble thrombomodulin (sTM) were significantly higher in VEXAS patients compared to controls. Finally, significantly increased thrombin generation and activated protein C resistance (APCR) were also observed in plasma from VEXAS patients. In conclusion, our novel findings demonstrate that VEXAS syndrome is associated with significant EC activation and endotheliopathy. This results in both quantitative and qualitative alterations in plasma VWF levels, increased FVIII levels, enhanced thrombin generation and an APCR phenotype. Further studies will be required to determine whether therapeutic interventions targeted at EC and/or the VWF-ADAMTS13 axis may be useful in VEXAS management.

Septic arthritis is an important cause of morbidity in calves, and radiographic interpretation may vary between observers, especially when structured scoring systems are used by less experienced readers. This single-center retrospective reader study evaluated whether general-purpose multimodal large language models (LLMs) could support rubric-based radiographic scoring of presumptive septic carpal arthritis in calves. Fifty calves aged 0-3 months with clinical findings consistent with presumptive septic carpal arthritis were included, and one carpal radiograph per case was assessed. Two novice veterinary surgeons and three multimodal LLMs, ChatGPT-5, Gemini-2.5 Pro, and Claude Sonnet-4, independently scored each case using a Constant-based ordinal radiographic scoring framework. Expert consensus served as the operational reference standard. Agreement with the reference was assessed using exact agreement, agreement within one score category, and quadratic weighted kappa. Novice 1 showed the highest concordance, with a mean exact agreement of 55.6%, mean ±1 agreement of 89.8%, and substantial agreement (mean κw = 0.68; 95% CI, 0.56-0.80). ChatGPT-5 was the best-performing model, achieving moderate agreement (mean exact agreement, 53.0%; mean ±1 agreement, 82.6%; mean κw = 0.58; 95% CI, 0.41-0.72). Claude Sonnet-4 and Gemini-2.5 Pro showed slight agreement overall. The best-performing novice reader remained more reliable than the evaluated models, although ChatGPT-5 performed comparably to, or better than, one novice evaluator in selected parameters. Selected LLMs may have limited adjunctive value for structured review or training, but not as replacements for human interpretation.

Understanding diagnosis and management of specific autoimmune diseases is based on existing classifications or diagnostic criteria. However, patients frequently present with broad, multisystem features that mimic multiple autoimmune diseases. Recognizing clinical mimicry is crucial because overclassifying these features as distinct coexisting diseases often presents a diagnostic challenge. We report the case of a 36-year-old man who presented with progressive weakness. The patient initially complained of facial rash and skin lesions, which then developed into tetraparesis, arthralgia, and difficulty swallowing. Physical examination revealed various skin and musculoskeletal manifestations, including erythematous plaques on the face without involving the nasolabial folds, discoid rash, heliotrope rash, Gottron's sign, and multiple ulcers. Neurological examination showed decreased muscle strength and motor lesions. Laboratory results showed an increase in inflammatory markers, positive antinuclear antibodies (ANAs) as well as positive myositis-specific antibodies for melanoma differentiation-associated protein (MDA)-5. Electromyography (EMG) examination showed findings consistent with myogenic lesions. Chest CT scan showed interstitial lung disease (ILD), and hand radiography showed juxta-articular wrist osteopenia consistent with early signs of inflammatory arthritis. Based on these findings, the patient was diagnosed with MDA-5 dermatomyositis (DM) with lupus-like features and inflammatory arthritis, representing a high-risk DM phenotype that clinically mimics a triple overlap syndrome, rather than three distinct confirmed diseases. Initial treatment involved the administration of high-dose methylprednisolone followed by a gradual dose reduction, hydroxychloroquine, and mycophenolate sodium after the secondary skin infection resolved. The patient received multidisciplinary care involving various specialties. After treatment, the patient's motor weakness improved. Distinguishing severe phenotypes of connective tissue diseases (CTDs) from true overlapping syndromes is a diagnostic challenge due to overlapping symptoms and laboratory findings. Accurate diagnosis requires a comprehensive clinical and serological evaluation, as well as a deep understanding of the classification criteria for each disease to avoid overclassification. Early diagnosis and aggressive treatment targeting the primary driving pathology can improve the prognosis and quality of life of patients.