Citations

AIMS: Evidence-based medicine (EBM) is a necessary attribute required for quality medical practice. Despite being integral in advancing medicine and improving patient outcomes, research and quality improvement (QI) rarely integrate into medical education. We present our curricular course design and reveal students' perceptions of the implementation of this course. In addition, we compared physician assistant (PA) student perceptions from the first two traditional cohorts (4 years undergraduate before entry to PA program) to the accelerated 3+2 pathway cohorts (3 years pre-PA coursework followed by 2 years PA program). METHODS: Faculty developed an EBM course taught through student participation in QI projects and assessed students' perceptions of discovery, collaboration, cognitive ownership, and global sense toward general outcomes through the implementation and analysis of validated survey instruments. RESULTS: All students contributed to QI projects, achieved Quality Academy Bronze certification and Silver assessment and disseminated their work at peer-reviewed conferences. Over 56.4% earned Silver certification, and 36.2% of students had their project published in a journal. Student perception of experiential impact was positive overall, with 83.3% of students minimally responding 'true' to the prompts. All students indicated that after the experience, they possessed a basic understanding of QI approaches. The accelerated students selected 'true' for all other prompts more frequently than the traditional student population. DISCUSSION: This manuscript presents vital educational strategies, highlighting an approach and plan to extrapolate EBM principles beyond PA students and to generalize to other healthcare professionals and students. Through course completion, students met educational objectives and reaped additional benefits that positively impacted their resume building and future job prospects. By honing these skills, students are better prepared to contribute to patient care and advance the field of medicine. The accelerated students perceived greater course benefit likely due to the life-experience differences between the two cohorts, whereby the traditional students matriculated into the program with a breadth of prior knowledge obtained through years of contributions to education and careers.

BACKGROUND/OBJECTIVES Pediatric hospital medicine (PHM) is a growing field with a unique scholarly perspective and evolving role in academic leadership. Since the last systematic assessment of PHM research in 2009, predating subspecialty certification in 2016 and fellowship accreditation in 2020, the research infrastructure within PHM has not been reevaluated. We sought to assess the current state of PHM research by assessing the number, scope, and scholarly domains of research faculty, as well as research funding and support. METHODS Using the Pediatrics Research in Inpatient Settings Network, we distributed a cross-sectional survey to PHM group leaders across the United States and Canada. The 16-item instrument, adapted from prior PHM and adult hospital medicine surveys, assessed program demographics, faculty effort allocation, research support, funding, and scholarly domains. Surveys were distributed via REDCap with follow-up reminders. Descriptive statistics were used. RESULTS 49 programs responded (51% response rate), representing 1702 faculty (∼40% of US pediatric hospitalists). Fewer than half of programs (n = 21, 43%) reported faculty with more than 50% research effort. One-hundred and ninety faculty members (11%) had dedicated research time, and 72% of those conducting quality improvement research did so without any protected effort. Most PHM programs (n = 27, 55%) received less than $100 000 in total annual research funding. CONCLUSIONS Despite recent PHM subspecialty designation and pediatric hospitalist desire to conduct research, dedicated time and associated supports are uncommon in PHM groups. Improvements in the PHM research pipeline will require understanding institutional financial constraints and diversifying and strengthening research funding.

Abstract Clinical medical physics is a profession that intersects with various groups as part of a broader healthcare team, including dosimetrists, radiation therapists, radiologic and MRI technologists, IT specialists, and physicians. Success in this field requires academic and technical excellence as well as comprehensive skills for working effectively within an interdisciplinary healthcare team. When hiring medical physics residents, the selection of well‐rounded and highly qualified candidates can be facilitated through a holistic review process that ensures consideration of traditional metrics such as academic performance while also accounting for the importance of various experiences, personal attributes, and intrinsic motivations that impact clinical performance and patient care. The Association of American Medical Colleges (AAMC) emphasizes an overall consideration of Experiences, Attributes, Competencies, and Metrics (EACM) as important for the search process. As part of the healthcare community, medical physics shares the same commitment to high‐quality patient care. By adopting the AAMC's EACM framework, medical physics residency programs can strengthen the fairness, rigor, and overall effectiveness of their application review processes—ultimately benefiting applicants, the medical physics community, and the patients we serve. This Society of Directors of Academic Medical Physics Programs (SDAMPP) task report aims to provide information and resources for applying holistic review to the applicant selection process for medical physics residency programs. Our objective is to enable program directors to reevaluate their selection methods in the context of institutional and program missions and goals and to improve the quality and specificity of recruitment by integrating holistic review concepts into their residency recruitment processes. This initiative can inspire change in recruitment practices, aid programs in hiring well‐rounded and well‐qualified residents, and support the professional growth of our trainees in healthcare. This report provides an overview of holistic reviews and its core principles. We review the current literature and provide evidence from successful implementations of holistic review in other medical fields to illustrate how it can benefit our field. Furthermore, we outline actionable recommendations to facilitate transitioning to a holistic review framework and address potential barriers with practical solutions. A supplemental workbook is provided to guide residency programs in developing their own holistic application review and interview processes. With this report, we aim to provide practical implementation guidelines that will allow residency program directors to implement a selection methodology that comprehensively assesses the full qualifications of individual candidates and ultimately fosters the development of versatile and competent clinical medical physicists who are best equipped to advance the field, meet patient needs, and improve patient care.

Abstract Background Wide-spread mast cell (MC)-associated symptoms and MC activation syndrome (MCAS) are often reported in patients with hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD). The goal of this study was to develop a novel MC score based on 11 self-reported MC-related conditions with clinical and research utility to better understand MC symptoms in hEDS and HSD patients. Methods From November 1, 2019, to June 13, 2025, patients ( n =2,141) filled out an Intake Questionnaire at the Mayo Clinic Florida EDS Clinic that included 11 self-reported questions related to categories of MC-related conditions for a MC score ranging from 0/11 to 11/11. Based on the MC score distribution in hEDS and HSD patients, a MC score of 0-1 was considered a low MC score and ≥5 was considered a high MC score. Symptoms/comorbidities were compared between patients with high vs. low MC scores. Results From the 2,141 hEDS/HSD patients, 535 (25.0%) had a MC score ≥5 (Hi MC). MCAS-specific symptoms such as nausea and vomiting were reported more often in hEDS/HSD patients with a high vs. low MC score ( p <0.0001). Random clinical blood tryptase and urinary MC markers were not elevated in patients with high MC scores ( n =50/group), although high MC scores were found to significantly reduce urinary creatinine levels indicating that the protein used to normalize data was affected by MC activity. In contrast, random blood IgE, tryptase and major basic protein (MBP) by ELISA were increased in patients with high MC scores (e.g., IgE hEDS p =0.0004, HSD p =0.003). Of note, the percentage of patients reporting abuse or post-traumatic stress disorder was nearly doubled in patients with high vs. low MC scores (Abuse and PTSD: hEDS p < 0.0001; HSD p < 0.0001). Overall, 109/135 (80.7%) in hEDS and 129/135 (95.6%) in HSD reported more symptoms/comorbidities if they had a high MC score. Conclusions We found that hEDS/HSD patients with high MC scores self-reported more widespread symptoms/comorbidities and higher MC-related blood markers than patients with low MC scores indicating the utility of this tool to evaluate the level of widespread MC activity in hEDS, HSD and other patients.

Background Marfan syndrome (MFS) is associated with progressive aortic and valvular disease requiring cardiac surgery, but contemporary data on repeat cardiac operations in adults remain limited. Methods We performed a retrospective multicentre cohort study of 783 adults with MFS evaluated across three Mayo Clinic sites. Cardiac operations, postoperative complications, echocardiographic findings and redo sternotomy events were identified by chart review. Multivariate logistic regression was used to evaluate factors associated with redo sternotomy. Results Overall, 454 patients (58.0%) underwent at least one cardiac operation, and 185 patients (23.6% of the total cohort; 41.0% of operated patients) required redo sternotomy. The most common procedures were aortic root intervention (53.4%), aortic valve intervention (39.6%), mitral valve intervention (16.1%) and tricuspid valve intervention (2.6%). Valvular abnormalities were frequent, including mitral regurgitation (51.5%), mitral valve prolapse (41.1%), tricuspid regurgitation (44.6%) and aortic regurgitation (28.5%). Major postoperative complications occurred in 15.3% of patients. On multivariate analysis, hypertension (OR 2.39, 95% CI 1.54 to 3.72), emergent initial operation (OR 3.38, 95% CI 1.97 to 5.80) and postoperative complications (OR 2.59, 95% CI 1.58 to 4.27) were independently associated with redo sternotomy, whereas repair extending beyond the aortic root was associated with lower odds (OR 0.39, 95% CI 0.29 to 0.53). Conclusion In this large multicentre cohort of adults with MFS, cardiac surgery was common, and redo sternotomy occurred frequently among operated patients. These findings provide a contemporary description of the long-term need for cardiac surgery in adults with MFS managed at tertiary referral centres.

ABSTRACT The FDA Modernization Act 3.0 represents a pivotal shift in biomedical research by formally removing the requirement for animal testing and enabling regulatory acceptance of New Approach Methodologies (NAMs). This transition creates an urgent need for robust, human‐relevant biomarkers that can anchor NAM‐generated data within regulatory decision‐making, particularly for first‐in‐human studies. Extracellular vesicles (EVs), owing to their biological stability, accessibility and rich molecular cargo, may be well positioned to fulfil this role. EVs reflect dynamic cellular states and intercellular communication, making them mechanistically informative readouts of pharmacology, toxicity, immune modulation and disease biology across human‐derived model systems. This Perspective outlines how EV‐based biomarkers can support the qualification, standardization, and regulatory acceptance of NAMs, with particular emphasis on ex vivo platforms such as organoids, microtissue systems, organ‐on‐chip devices and perfused tissue slices. We highlight the advantages of EVs for longitudinal, non‐destructive sampling, representation of human variability, and integration with quantitative systems pharmacology and physiologically based pharmacokinetic models. Finally, we discuss the scientific, operational and regulatory challenges that must be addressed and argue that coordinated leadership from the International Society for Extracellular Vesicles (ISEV) is essential. The convergence of regulatory reform and EV science presents a timely call to action to establish EVs as foundational biomarkers in next‐generation, human‐centric drug development.

e20700 Background: Leptomeningeal metastases (LM) are a particularly challenging complication of EGFR-mutant non–small cell lung cancer (NSCLC) and are often associated with rapid neurologic decline. Intrathecal (IT) chemotherapy is frequently used in this setting, but its efficacy and safety have not been well defined. We conducted a systematic review and meta-analysis to assess neurologic response and treatment-related toxicity associated with IT chemotherapy in EGFR-mutant NSCLC with LM. Methods: We performed a PRISMA-guided search of MEDLINE, EMBASE, Cochrane CENTRAL, and targeted grey literature to identify prospective and retrospective studies reporting outcomes of IT chemotherapy in EGFR-mutant NSCLC with LM. Quantitative analyses were restricted to studies with extractable endpoints. Neurologic response and grade ≥3 toxicity were pooled using random-effects generalized linear mixed models with logit transformation. Heterogeneity was assessed using I² and τ². Prespecified sensitivity analyses examined neurologic response by route of administration (lumbar puncture vs Ommaya reservoir), concomitant EGFR-TKI use, and study design or era. Results: Four studies comprising 76 patients reported extractable neurologic response data. The pooled neurologic response rate was 81.9% (95% CI, 64.0%–92.0%), with moderate heterogeneity (I² = 63.4%, p = 0.04). Grade ≥3 toxicity was reported in three studies (n = 59), with a pooled incidence of 11.8% (95% CI, 3.2%–34.9%) and substantial heterogeneity (I² = 71.3%, p = 0.03). Myelosuppression was the most frequently reported severe adverse event, and no consistent signal of severe neurologic toxicity was identified. Exploratory sensitivity analysis suggested higher neurologic response in LP-treated cohorts compared with mixed LP/Ommaya cohorts; however, this finding was driven by a single small study and is likely influenced by limited sample size and selection bias and should be considered hypothesis-generating only. Neurologic response was otherwise consistent across study designs and eras. Stratification by concomitant EGFR-TKI use was limited by incomplete reporting. Median overall survival was variably reported and ranged from approximately 7 to 12 months. Conclusions: In EGFR-mutant NSCLC with leptomeningeal metastases, IT chemotherapy is associated with a high pooled neurologic response and relatively uncommon severe toxicity, although heterogeneity across studies remains substantial. The observed neurologic benefit appears consistent across study designs and is more likely related to underlying EGFR-sensitive disease biology than to a definitive effect of route of administration. These findings support further prospective evaluation of IT chemotherapy as part of multimodal treatment strategies in this high-risk population.

e16377 Background: 1L systemic treatment of mPDAC can lead to severe adverse events (AEs). To contextualize the safety profile of irinotecan-based regimens, real-world data were used to characterize AEs and their management in patients receiving 1L mPDAC treatment with FOLFIRINOX (FFX) or gemcitabine+Nab-paclitaxel (Gem+NabP). Methods: De-identified data from Mayo Clinic electronic health records (all sites; records collected 2010–2023) were used. Natural language processing was leveraged to confirm staging and metastatic classification and to extract treatment data. Adults with mPDAC with stage IV and/or TNM staging of M1 who received ≥ 1 dose of FFX or Gem+NabP were included. Primary endpoint: proportion of patients with AEs of interest (diarrhea, nausea, vomiting, neuropathy, and neutropenia) following initiation of 1L treatment. Secondary endpoints: proportion of patients who received treatment for each AE of interest, median time to resolution and treatment of each AE of interest, and proportion of patients who switched mPDAC treatment or had dose reductions due to AEs. Results: In total, 405 patients (FFX, 197; Gem+NabP, 208) were identified. The proportions of patients who experienced and were treated for any-grade AEs of interest are reported in the Table. Of the AEs of interest, neutropenia resolved most quickly (median time from onset to resolution, FFX: 9.5 days; Gem+NabP: 12.5 days); neuropathy took the longest time to resolve (FFX: 44.0 days; Gem+NabP: 74.0 days). Median time to AE treatment was shortest for nausea and vomiting (both 0.0 days for FFX and for Gem+NabP). Time to treatment was longest for neuropathy (FFX: 158.5 days; Gem+NabP: 70.0 days). Only 5.1% of patients on FFX and 13.4% on Gem+NabP received treatment for neuropathy. Of patients in the FFX group who switched/reduced treatment (n=140), 58.6% received a dose reduction and 7.1% switched to Gem+NabP due to AEs. Conclusions: At the Mayo Clinic sites, incidence of any-grade AEs associated with 1L mPDAC treatment were similar or higher than rates of any-grade or ≥ 2/3–4 grade AEs reported in the literature. Nausea, vomiting and diarrhea were the most commonly treated AEs for both irinotecan-based (FFX) and non-irinotecan-based (Gem+NabP) 1L regimens; neutropenia and neuropathy were less commonly treated. FFX dose reductions were commonly attempted before switching regimens. Proportion experiencing any-grade AE (AE incidence in the literature) Proportion experiencing AE treated for an AE FFX Gem+NabP FFX Gem+NabP Diarrhea 74.6% (50–80%, any grade) 43.8% (< 5%, any grade) 92.5% 56.0% Nausea 81.7% (45%, any grade) 72.1% (20%, grade ≥ 2) 98.8% 96.7% Vomiting 54.8% (10%, any grade) 42.8% (20%, grade ≥ 2) 98.1% 98.9% Neutropenia 58.9% (45%, grade 3–4) 48.1% (12–21%, grade 3–4) 62.1% 46.0% Neuropathy 59.9% (25%, grade 3–4) 32.2% (30%, grade 3–4) 5.1% 13.4%