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Career Plans Among Graduating US Emergency Medicine Residents
No full textIMPORTANCE: The emergency medicine (EM) workforce is undergoing complex change, including a potential projected physician surplus, the volatile and evolving interests of medical students, and the continued high rates of burnout. Understanding the career intentions of graduating residents is critical to inform workforce planning.
OBJECTIVE: To examine the career plans, anticipated career durations, and key factors associated with the career decisions of graduating US EM residents.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study, which sampled graduating residents from all Accreditation Council for Graduate Medical Education-accredited categorical EM programs, was conducted after the 2023 American Board of Emergency Medicine In-Training Examination. Resident-level characteristics, including gender, race and ethnicity, educational debt, and burnout status, were examined. Data were obtained from June 20 to August 18, 2024, and analysis occurred from December 16, 2024, to August 12, 2025.
MAIN OUTCOMES AND MEASURES: Primary outcomes included immediate postresidency career plans, intended practice setting, anticipated years of clinical practice, and importance of 10 career decision factors.
RESULTS: Of 2782 eligible residents, 2711 (97.4%; 1394 men [51.4%]) responded to at least 1 survey item. Most respondents (1654 [61.0%]) reported educational debt exceeding 200 000 or more in debt (1376 [50.7%]) were significantly more likely to cite salary as a major factor (299 000: odds ratio [OR], 2.01 [95% CI, 1.39-2.89]; 399 000: OR, 2.31 [95% CI, 1.58-3.39]; ≥$400 000: OR, 1.58 [95% CI, 1.05-2.42]).
CONCLUSIONS AND RELEVANCE: In this survey study of graduating EM residents in 2023, most respondents planned to practice clinical EM for 2 decades primarily in community or hybrid settings, with a minority of residents interested in rural practice. Career decisions are overarching and encompass career factors; lifestyle, location, professional fulfillment, and salary were the strongest career factors. Burnout, educational debt, and demographic characteristics were associated with career decisions. These findings have implications for workforce modeling, retention strategies, and policies to support the EM workforce
STAT-Independent Functions of Janus Kinases 1 and 2 Are Obligatory for the Postnatal Development of Mammary Epithelial Ducts
No full textJanus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation of mammary ducts is unaffected by the lack of expression and activation of all seven STAT proteins. Additionally, STAT deficiency impairs the cytokine-induced autophosphorylation of JAK1/2. These findings suggest that mammary duct development is orchestrated by STAT-independent signaling mechanisms of JAK1 and JAK2, potentially beyond their roles as tyrosine kinases
Evaluation of Large Language Models as Decision Support Tools for Head and Neck Cancer Management: A Blinded Multidisciplinary Simulation Study
No full textBACKGROUND: The management of head and neck cancer relies on multidisciplinary expertise; however, access to tumor boards remains variable. Large language models (LLMs) may support guideline-based decision-making, although performance in complex oncologic scenarios is not well defined.
METHODS: Fourteen synthetic cases based on real tumor board encounters were evaluated. Five blinded comparator arms produced recommendations: a human expert, Non-RAG-GPT-4, Non-RAG-GPT-5, RAG-GPT-4, and RAG-GPT-5. Eight head and neck oncologic surgeons scored each recommendation for appropriateness, clarity, specificity, and feasibility using 5-point Likert scales. Paired permutation testing and inter-rater reliability were assessed.
RESULTS: LLM outputs showed close alignment with expert recommendations. RAG-based models achieved the highest mean scores across domains, with some statistically significant differences versus the expert comparator in appropriateness and clarity; however, absolute differences were modest. Inter-rater reliability was strong (ICC 0.73-0.87).
CONCLUSIONS: Advanced LLMs can generate guideline-concordant management recommendations in simulated head and neck cancer cases, supporting potential utility for decision support and education; prospective validation and expert oversight remain essential
Clinical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay
No full textBACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays performed in the central laboratory have long turnaround times. This study evaluates the clinical performance of a novel bedside point-of-care (POC) hs-cTnI assay (i-STAT® hs-TnI) to aid in the diagnosis of myocardial infarction (MI).
METHODS: A prospective multisite cohort study involving emergency department (ED) patients with symptoms suggestive of acute coronary syndrome was conducted at 28 sites across the United States. Serial whole blood samples were collected at 0-1 h and \u3e1-3 h from ED presentation. Primary outcome was MI or non-MI. Sensitivity, specificity, and negative predictive value (NPV) for MI were calculated with 97.5% lower confidence limits (LCL) using the female, male, and overall 99th percentile upper reference limit (URL, 13, 28, and 21 ng/L, respectively). Post hoc analysis was also conducted for initial measurements below the limit of quantification (LoQ, 2.9 ng/L) and \u3c 5.0 ng/L.
RESULTS: The cohort included 3582 patients, median age 59 y, 64% female. MI incidence was 8.6%. Sensitivity and specificity at \u3e1-3 h were 96.6% (LCL 91.7%) and 82.1% (80.2%) using the female URL; 90.7% (LCL 84.1%) and 83.9% (LCL 81.4%) using the male URL; and 92.4% (LCL 88.3%) and 85.6% (LCL 84.2%) using the overall URL. NPVs for MI of initial hs-cTnI measurements
CONCLUSIONS: The whole blood POC i-STAT hs-TnI assay demonstrated performance characteristics similar to other hs-cTn assays and achieved high sensitivity and NPV for initial measurements
CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT05629572
Characterizing the Effects of Antimuscarinics on RhoA Signaling
No full textPurpose: Airway hyperresponsiveness in asthma is driven by acetylcholine-mediated activation of the muscarinic acetylcholine 3 receptor (M3R), promoting bronchoconstriction, mucus hypersecretion, and airway remodeling. Despite directly targeting this pathway, antimuscarinics remain adjunctive rather than first-line therapy, suggesting a disconnect between biological rationale and clinical efficacy. Recent work from the Scott Lab at Thomas Jefferson University demonstrates that M3R in human airway smooth muscle (HASM) cells drives muscle shortening through G12/13–driven RhoA signaling rather than through Gq/11-dependent calcium flux. We therefore investigated whether clinically prescribed antimuscarinics effectively inhibit G12/13-dependent RhoA signaling in HASM cells.
Methods: Human telomerase reverse transcriptase immortalized HASM cells with Renilla luciferase under the control of a serum response element (hTERT-SRE) were used to evaluate ligand-dependent RhoA activation. Cells were stimulated for 5 hours with drug, either alone or combined with 100 µM acetylcholine. Luciferase activity was measured and normalized to the maximal acetylcholine response, using 3-parameter nonlinear regression to determine residual RhoA activation.
Results: Ipratropium bromide, revefenacin, tiotropium bromide and umeclidinium bromide exhibited partial agonism of the M3R-dependent RhoA signaling pathway that governs HASM contraction. In preliminary studies, glycopyrrolate appears to behave as a neutral antagonist of M3R signaling. Partial agonism by erstwhile muscarinic antagonists may sustain pro-contractile signaling despite receptor blockade.
Conclusions: These findings suggest that many anticholinergics inadvertently preserve G12/13–RhoA signaling, limiting their bronchoprotective efficacy. Defining this signaling bias across antimuscarinic agents provides a framework for developing next-generation therapies that more effectively suppress the G12/13–RhoA axis to control airway hyperresponsiveness and hypertrophy.https://jdc.jefferson.edu/aoa_research_symposium_posters/1026/thumbnail.jp
Elucidating the Binding Site of the Arrestin-Biased Agonist ICL1-20
No full textBackground and Purpose: 6.7 million Americans live with congestive heart failure (CHF). In CHF, catecholamines are released into cardiac tissue, bind β-adrenergic receptors (βARs), and activate G-protein signaling cascades, causing ischemia and apoptosis. Accordingly, β-blockers are used to antagonize catecholamine binding to βARs and suppress apoptotic downstream effects. However, β-blockers have dose-limiting hypotension, bradycardia and fail to stimulate the cardioprotective β-arrestin signaling pathway. These limits create opportunities for the development of drugs that selectively stimulate β-arrestin signaling while suppressing cardiotoxic G protein signaling. We have previously reported a biased agonist of the β-arrestin pathway (ICL1-20) that selectively stimulates β-arrestin recruitment to the β2AR, but not the β1AR. The mechanism through which ICL1-20 recruits β-arrestin to the β2AR is unclear.
Methods: This project aims to identify residues on the β2AR critical for ICL1-20 function through chimera mutagenesis. For this method, a series of chimeric receptors were created in which secondary structural elements from β2AR were replaced with corresponding ones from β1AR (e.g., intracellular loop 1 (ICL1), extracellular loop 1 (ECL1), etc). Chimeric receptors were tested for sensitivity to ICL1-20. Loss of ICL1-20 agonism of β-arrestin recruitment to chimeric receptors indicates loss of β2AR sequence important for ICL1-20 recognition or function.
Results: Preliminary mutagenesis results suggest that intracellular loop 1 (ICL1) of the β2AR contributes to ICL1-20 recognition by the β2AR and subsequent β-arrestin recruitment.
Conclusion: Results from comprehensive chimera mutagenesis studies should define structural determinants of ICL1-20 function and inform the development of drug-like molecules that can promote arrestin-biased agonism of the β2AR.https://jdc.jefferson.edu/aoa_research_symposium_posters/1028/thumbnail.jp
Use of Hybrid Versus Video-Only Teledermatology Varies by Condition: A Cross-Sectional Study of 2064 Encounters
No full textOutcomes and Implications of Patients Included vs. Excluded for Extracorporeal Cardiopulmonary Resuscitation After Initial Activation
No full textBACKGROUND: The aim of this study is to describe the implementation of a new Extracorporeal Cardiopulmonary Resuscitation (ECPR) program in Cleveland, Ohio, USA. We also provide a novel comparison of outcomes between patients cannulated vs excluded from cannulation for ECPR after initial field activation.
METHODS: A prospective observational study of ECPR activations between September 2021 and February 2025. Patients meeting initial eligibility criteria for out-of-hospital cardiac arrest (OHCA)-namely based on age, bystander-CPR, and initial shockable rhythm-were transported to the emergency department where the ECPR team completed cannulation based on further biochemical criteria. Medical records were used to collect data after every ECPR activation.
RESULTS: 45 ECPR activations were identified. Among these, 13 patients were cannulated for ECMO, while 32 patients did not meet cannulation criteria. Among those cannulated, 10 of 13 (76.9 %) survived to hospital discharge vs 5 of 32 (15.6 %) who did not receive ECMO (p \u3c 0.001). Among patients who underwent ECPR, there was no incidence of brain death or significant access site bleeding complications. The most common reason for aborted cannulation was due to the biochemical exclusion criteria of pH \u3c 7 or lactate \u3e15 mmol/L.
CONCLUSION: The implementation of ECPR with strict eligibility criteria resulted in a small number of cannulations but a high survival rate. Strict criteria may lead to missed opportunities for successful ECPR and occasionally trigger activation of the ECPR team without ultimately performing cannulation. As institutions develop their ECPR programs, they should carefully consider eligibility criteria in order to balance survival rate and case volume
