Citations

Abstract Enfortumab vedotin (EV), pembrolizumab, and EV plus pembrolizumab (EV/P) have rapidly reshaped the treatment landscape of advanced urothelial carcinoma, but toxicity increasingly determines treatment delivery, treatment continuity, and real-world benefit. As EV/P moves into broader clinical use, clinicians must distinguish adverse events related to antibody-drug conjugate exposure from immune-mediated toxicities and recognize syndromes in which both mechanisms may contribute. In this practical, mechanism-informed review, we synthesize pivotal trials, mature follow-up reports, and representative real-world cohorts describing the safety of EV monotherapy, pembrolizumab monotherapy, and EV/P in urothelial carcinoma. Because adverse-event reporting and ascertainment are heterogeneous across studies, including differences in preferred terms, composite categories, grading frameworks, and treatment-related versus all-cause reporting, we emphasize clinically interpretable patterns rather than pooled estimates. EV monotherapy is characterized by cutaneous toxicity, peripheral neuropathy, hyperglycemia, dysgeusia, and ocular events, including early epithelial/metabolic events and cumulative neuropathy. Pembrolizumab monotherapy has a lower overall high-grade toxicity burden but is defined by immune-mediated endocrinopathies, pneumonitis, hepatitis, colitis, and nephritis. Combination therapy produces a predictable overlap of these toxicity domains, creating diagnostic and management challenges for syndromes such as skin toxicity, diarrhea, fatigue, and pulmonary symptoms. We provide comparative visual toxicity signatures, regimen-specific summary tables, temporal toxicity mapping, and a pragmatic attribution framework that classifies events as EV-predominant, immune-predominant, overlap/indeterminate, or high-risk requiring initial interruption of both agents. This review aims to support bedside recognition, provisional attribution, early management, and safer implementation of EV/P in contemporary urothelial carcinoma practice.

Follicular occlusion disorders (FOD) represent a tetrad of chronic, recurrent inflammatory conditions united by a common pathophysiologic mechanism: follicular hyperkeratosis leading to occlusion, rupture, and subsequent abscess or sinus tract formation. First conceptualized as a triad in the 1950s and later expanded to a tetrad in the 1970s, this grouping includes hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal sinus (PS). Despite their shared pathogenesis, each condition carries distinct clinical features, epidemiological profiles, and management considerations. This article aims to provide a comprehensive review of FOD, with a primary emphasis on HS (the most prevalent of the disorders). Hidradenitis suppurativa is a debilitating disease affecting ∼1% of the global population, predominantly in females, and the diagnosis is often delayed by 7 or more years. Multiple genes are linked to FOD patients with a positive familial history in 35% to 40%, along with lifestyle factors (smoking, alcohol consumption, and obesity). Key inflammatory mediators, including TNF-α, IL-1β, and IL-17, drive the chronic tissue destruction characteristic of FOD, frequently resulting in scarring, lymphedema, and significant psychosocial impairment. Wound care is critical and often underemphasized in disease management. This article outlines evidence-informed wound care strategies for both nonsurgical and postsurgical presentations, including dressing selection, exudate and odor management, pain and itch control, infection management, and the emerging role of intravenous ertapenem as rescue therapy. An interprofessional approach, integrating dermatology, surgery, wound care nursing, and psychosocial support, is emphasized throughout as essential to improving patient outcomes and quality of life. GENERAL PURPOSE: To increase clinicians’ understanding of follicular occlusion disorders including the associated risk factors, clinical manifestations, and evidence-based approaches for management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will: Assess clinical characteristics of each follicular occlusion disorder Evaluate the basic disease mechanisms for follicular occlusion disorders Describe principal disease burdens that require wound care attention Identify the unique wound care strategies and follicular occlusion disorder challenges JOURNAL/aswca/04.03/00129334-202610000-00004/figure1/v/2026-09-18T181327Z/r/image-jpeg

Background Disruption in rest‐activity rhythm (RAR) is an emerging risk factor for cardiovascular disease (CVD) and mortality, but the strength of evidence is unclear. Therefore, we conducted a systematic review and meta‐analysis to assess associations between RAR characteristics and cardiovascular disease incidence or prevalence, cardiovascular mortality, and all‐cause mortality. Methods A systematic search was conducted in PubMed, Web of Science, Cochrane Library, and Embase for cohort or cross‐sectional studies published up to August 2025. The exposure variables were nonparametric RAR parameters, including interdaily stability (describing day‐to‐day stability of the RAR), intradaily variability (a measure of RAR fragmentation), and relative amplitude (indicating robustness or strength of the RAR). The primary outcomes were cardiovascular mortality and all‐cause mortality. The secondary outcomes included cardiovascular disease prevalence and incidence. Results Seven studies involving 109 365 participants were included. Pooled results showed that higher intradaily variability was associated with a significantly increased risk of all‐cause mortality (hazard ratio [HR], 1.05 [95% CI, 1.02–1.09]) and cardiovascular disease prevalence (odds ratio, 1.73 [95% CI, 1.21–2.47]). Lower relative amplitude was significantly associated with higher cardiovascular mortality (HR, 1.50 [95% CI, 1.13–1.98]) and all‐cause mortality (HR, 1.46 [95% CI, 1.27–1.68]). Interdaily stability showed no significant associations with any outcome. Conclusions Measures of disrupted rest‐activity rhythms were associated with increased cardiovascular mortality, and all‐cause mortality. These findings support using RAR metrics as early, noninvasive risk indicators. Future work should investigate whether appropriately timed physical activity and sleep, as well as other interventions targeting RAR can mitigate cardiovascular risk.

BACKGROUND: Ventricular fibrillation (VF) remains a leading cause of sudden cardiac death with an incompletely characterized electrophysiological substrate. Traditional large-animal VF models are limited by hemodynamic collapse and myocardial ischemia. This study establishes a reproducible swine model using dual mechanical circulatory devices to enable high-density electroanatomic mapping under nonischemic conditions. METHODS: Five Yorkshire swine (55–65 kg) underwent sustained VF supported by venoarterial extracorporeal membrane oxygenation (2.5–3.0 L/min) and percutaneous left ventricular unloading (Impella CP, P-2–P-4). High-density electroanatomic mapping using CARTO 7 was performed at baseline and after defibrillation. Bipolar voltage was acquired from 7 predefined ventricular regions (21 measurements per animal per time point; n=210 paired observations). Unipolar voltage mapping and continuous surface ECG monitoring were used to assess acute ischemic injury. Systemic perfusion was maintained at systolic arterial pressure ≥80 mm Hg. Linear mixed-effects modeling was used to analyze voltage changes from pre-VF to post-VF. RESULTS: Sustained VF (10±1 minutes) was reproducibly induced and maintained with consistent hemodynamics (systolic arterial pressure, 90±5 mm Hg; extracorporeal membrane oxygenation flow, 2.5±0.5 L/min). All animals were successfully defibrillated. High-density mapping was feasible in all experiments (1000±300 points per chamber). Bipolar voltage showed no change from pre-VF (5.86±2.56 mV) to post-VF (6.53±2.22 mV; mean difference, 0.67 mV [95% CI, –0.31 to 1.65]; P =0.15). Both left ( P =0.17) and right ventricles ( P =0.08) demonstrated voltage preservation. Regional analysis showed no significant changes (all P >0.05); post-VF voltages remained above viability thresholds (>1.5 mV). Unipolar voltage maps recovered toward baseline, with no ECG injury pattern identified after defibrillation. CONCLUSIONS: Dual mechanical circulatory support with venoarterial extracorporeal membrane oxygenation and Impella CP enables reproducible, high-fidelity electroanatomic mapping and preserves myocardial substrate after sustained VF in a large-animal model. This platform overcomes key technical barriers in VF research, providing a nonischemic foundation for future mechanistic and translational studies.