Faculty Bibliography

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.

OBJECTIVE:To develop, implement, and assess the utility of a standardized letter of evaluation (SLOE) for OBGYN residency applicants in the US. DESIGN/METHODS:OBGYN program directors (PDs) were surveyed over 2 consecutive years and asked to estimate the percentage of applicants submitting an SLOE and to indicate its helpfulness compared to traditional letters of recommendation. Sub-group analysis by program type was performed. In 2023, comments for improvement were collected and analyzed for themes using a large language model. SETTING/METHODS:OB/GYN residency programs in the United States. PARTICIPANTS/METHODS:OB/GYN PDs in the United States. RESULTS:The survey was completed by 254 of 293 (86.7%) of PDs in 2022 and 253/293 (86.3%) in 2023. From 2022 to 2023, there was no difference in the estimated percentage of applicants who submitted an SLOE to a program (median 50%-74%), though in 2023, university and combined university-community programs estimated receiving higher percentage of applicants submitting SLOEs compared to community and military programs (p < 0.001). Over the study period, the favorability of the SLOE improved, and feedback indicates a need for continued improvement in the SLOE process, including faculty development, standardization, and more honest assessment of applicants. CONCLUSIONS:An SLOE was submitted by most applicants to OBGYN residency programs. Iterative modification of the SLOE based on PD, applicant, and faculty advisor feedback is needed to assess its utility in the application process.

Stimulant shortages, driven by manufacturing delays, regulatory production quotas, and rising demand, have created significant challenges in the treatment of attention-deficit/hyperactivity disorder. This review provides a systematic framework for medication substitution during shortages, including dose equivalence table and conversion formulas. Critical considerations guiding substitutions include pharmacological distinctions between amphetamine (AMP) and methylphenidate (MPH), isomer composition, dose equivalence, and duration of action. Nonstimulant agents such as atomoxetine and α2-adrenergic agonists are reviewed with attention to their efficacy, tolerability, need for gradual titration, and delayed onset. Patient-specific factors, including age, psychiatric comorbidities, substance use history, and cardiovascular risks, remain essential when selecting alternatives. Systematic monitoring is emphasized to ensure effectiveness and treatment safety during transitions. By integrating pharmacological and patient-centered considerations, this review provides a practical approach for clinicians to maintain treatment continuity during stimulant shortages.

PURPOSE OF REVIEW/OBJECTIVE:Aeroallergens are well established triggers of allergic rhinitis and asthma, yet their contribution to allergic skin diseases such as atopic dermatitis (AD) and chronic urticaria (CU) remains incompletely understood. This article reviews the molecular basis of aeroallergen-driven skin disease in AD and CU as well as management strategies. RECENT FINDINGS/RESULTS:Aeroallergen triggered skin disease involves epithelial barrier disruption, innate immune activation, and neuroimmune amplification. Allergen disruption of the epithelial barrier through PAR-2 and TLR-mediated signaling, induces alarmins that sustain an IL-31-driven itch-scratch cycle. Biologics targeting these pathways reshape these cytokine networks, while checkpoint inhibitors show promise for durable remission. In CU, house dust mite sensitization correlates with basophil hyperreactivity and greater disease severity. Aeroallergen triggered inflammation involves overlapping barrier dysfunction, innate immune activation, and neuroimmune pathways that extend beyond traditional IgE-mediated allergic responses. Future research should prioritize endotype-based patient stratification and quantify the impact of aeroallergen exposure on chronic skin disease trajectory.

IMPORTANCE/UNASSIGNED:Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. OBJECTIVE/UNASSIGNED:To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. EXPOSURES/UNASSIGNED:Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. RESULTS/UNASSIGNED:Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). CONCLUSIONS AND RELEVANCE/UNASSIGNED:These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01915615.

Stereotactic body radiotherapy (SBRT) is established as standard therapy for organ-confined prostate cancer (PC) based on 5-yr phase 2-3 outcomes, but 10-yr data are lacking. Here, we report 10-yr results of a trial conducted at 21 centers. Patients were treated from January 2008 to April 2010. SBRT was delivered on a noncoplanar robotic platform with real-time motion management, to a total dose of 40 Gy in five fractions. Adjuvant hormone therapy was not allowed. Late toxicities (>90 d) were assessed with Common Terminology Criteria for Adverse Events version 3 (CTCAE v3). Biochemical failure is defined as nadir+2. Relapses are defined as biochemical or clinical failure or salvage/systemic PC therapy. Out of 310 evaluable patients, median age 68 yr; 172 were low-risk (LR), and 138 patients were intermediate-risk (IR). Median follow-up was 9 yr. Ten-yr cumulative grade 3 gastrointestinal (GI) or genitourinary (GU) toxicities were 1.4% and 1.5% in the LR and IR cohorts, respectively. There were no grade 4-5 events observed. Ten year grade 2+ GI and GU toxicity rates were 2.1% and 14% respectively. Overall survival in 10 yr was 84%. Overall, relapse-free survival (RFS) was 90%; 94% in the LR cohort, 86% in the IR cohort, and 92% versus 77% in the favorable vs unfavorable intermediate subgroups. In this multi-institutional trial, the 10-yr follow-up demonstrates that prostate SBRT yields minimal toxicity and favorable RFS.