Faculty Bibliography

INTRODUCTION/BACKGROUND:Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical challenges, including key knowledge gaps related to understanding and measuring aspects of language deficit in MS (i.e., WFD). Further investigations of possible correlates of deficits with other symptoms of MS (i.e., such as depression, fatigue and cognitive impairment) were also carried out as part of this study to find out if WFD is a standalone symptom or is a part of a broader and complex symptom of MS. METHODS:In this cohort study, all data from 586 consecutive Persons with MS (PwMS) (137 males and 449 females), with a mean age of 47.1 (SD±10.34) and a median EDSS score of 2.0, were included. A standardized naming task was used as part of a computerized cognitive assessment battery (CAB, NeuroTrax™) with computer-based administration and off-site scoring that has been validated for use in PwMS to determine the associations between cognitive impairment (CI), fatigue, and depression in WFD. RESULTS:A significant correlation (r = 0.327) was noted in this study between cognitive impairment and WFD (p < 0.001). PwMS with CI had a higher rate of WFD (i.e., 43.2%) as compared to individuals with WFD despite not having CI (i.e., 13.9%). Disability (EDSS), disease duration, depression and fatigue, were not correlated with WFD. CONCLUSION/CONCLUSIONS:WFD are most likely part of a larger underlying problem (i.e., CI), but there is a small group of persons with MS and WFD who have isolated WFD. Findings of this study have implications for activities of daily living (ADLs) and therapy for rehabilitation professionals working with PwMS.

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.

Sepsis is a systemic inflammatory disorder marked by dysregulated inflammation and coagulopathy. Annexin A2 (A2), a profibrinolytic protein, assembles plasminogen and tissue plasminogen activator on cell surfaces, thereby maintaining vascular patency. However, its role in human sepsis has remained poorly defined. We investigated whether A2 undergoes qualitative or quantitative modification during human sepsis with associated end-organ dysfunction. Peripheral blood mononuclear cells and plasma were collected from 65 patients with sepsis and 27 healthy controls. A2 expression and integrity were evaluated with cell surface plasmin generation using immunoblot and fluorometric assays. Both A2 integrity and plasmin generation were significantly reduced in patients with sepsis and with septic shock. A2 underwent sepsis-related membrane-associated proteolysis mediated by a serine protease. A2 reduction correlated with interleukin-18 levels and was significantly associated with renal, pulmonary, cardiovascular, and neurologic dysfunction. A2 proteolysis may represent a novel biomarker and therapeutic target for sepsis-related microvasculopathy.

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.

INTRODUCTION/UNASSIGNED:Pseudofolliculitis barbae (PFB) is a chronic inflammatory condition of hair follicles characterized by inflamed papules and pustules, with increased risk in individuals with curly or coarse hair. While psychiatric comorbidities in acne are well studied, limited research exists on PFB's psychological impact. METHODS/UNASSIGNED:dataset, which includes EHR data from US adults since 2018. RESULTS/UNASSIGNED:= 0.15). DISCUSSION/UNASSIGNED:Our study demonstrated a significant association between PFB and mood disorders like depression or anxiety. Future studies should examine PFB severity and treatment efficacy on psychological outcomes.

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.