Citations

Abstract Introduction Combat casualty care requires standardized proficiency criteria to ensure readiness in austere environments, yet gaps persist in defining performance thresholds for critical trauma skills. The Combat Medical Skills Sustainment Consortium (CMSSC), a novel military-civilian collaboration, aimed to validate competency thresholds for 21 Department of Defense-identified trauma skills. Materials and Methods A prospective cohort study (2022-2025) enrolled 1,495 military and civilian personnel across five academic centers, stratified by experience (novice, intermediate, expert). Skills, including cricothyroidotomy, whole blood transfusion, and ultrasound-guided vascular access, were assessed using validated checklists in Role 2-congruent simulations. Statistical analysis compared checklist performance against participant experience with a priori checklist scores estimated at 40% (novices) and 90% (experts). Results Competency thresholds were established, ranging from 77% (mechanical ventilation) to 100% (handoff). Experts achieved 85%-98% proficiency across most skills, with novices at 34%-97%. A ceiling effect was observed for less complex skills consistent with the power law of practice. Conclusion The Combat Medical Skills Sustainment Consortium validated standardized assessment tools, with potential to address readiness gaps through military-civilian synergy. Findings support consortium-guided curriculum development and highlight the need for longitudinal skill decay studies. Impact This study sets a benchmark for trauma care skills assessment, facilitating rapid adoption across military and civilian settings.

Abstract Glioblastoma (GBM) is an aggressive, high-grade glioma with a near-universally fatal prognosis. Therapeutic failure is often attributed to the highly selective blood brain barrier (BBB), the diffuse infiltrative nature of the tumor, and the marked intratumoral heterogeneity of GBM. Although antibody drug conjugates ADCs have shown promise for high grade gliomas such as GBM, efficacy is limited by ADC size. Aptamers—short, synthetic, single-stranded DNA or RNA molecules—can be ∼6-fold lower in molecular weight than IgG antibodies and have the potential to cross the intact BBB. Unlike other nucleic acid-based therapies, aptamer function arises from three-dimensional shape rather than genetic coding. Here we aim to replace the targeting component of the ADC paradigm with a DNA aptamer, thus creating an aptamer-drug conjugate (ApDC). We employed in vivo SELEX using an orthotopic patient-derived xenograft (PDX) GBM mouse model and a vast (∼100 trillion 80-mer sequences) ApDC library. We report the results from this first in vivo ApDC selection of its kind. We characterize target tissue binding ex vivo , cell association, biodistribution, and pharmacokinetics from this selection. This study exemplifies an unbiased approach to a problem that rational design has yet to overcome, offering a new direction for GBM therapeutic development.

Obesity is increasingly prevalent among living kidney donor candidates, presenting complex clinical, ethical, and logistical challenges. Although obesity is linked to increased post-donation hypertension, diabetes, proteinuria, and chronic kidney disease, the overall absolute risks are modest and may differ depending on metabolic health and patterns of fat distribution. Current reliance on body mass index alone fails to capture the full spectrum of obesity-related risks, leading to inconsistent donor selection practices and potential inequities. This review examines the pathophysiological mechanisms of obesity-related kidney injury and available evidence on comorbidities and postdonation outcomes related to obesity. We discuss tools for better risk stratification, such as imaging-based adiposity assessment and personalized weight management strategies, and note that some risks may remain after weight loss. Barriers such as rigid body mass index cutoffs, limited access to treatment, and lack of long-term follow-up exacerbate disparities in access to donation. We argue for a shift toward individualized, risk-based evaluation supported by multidisciplinary care. We underscore the importance of donor counseling and advocate for a comprehensive, rather than paternalistic approach to living kidney donor selection. Advancing safe and equitable living donation in the context of rising obesity rates will necessitate revised guidelines, improved access to treatment, and an ongoing commitment to donor well-being.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

Abstract Purpose This study explores how new residents experienced the transition to residency, examines factors that made the transition process more or less difficult, and identifies potentially modifiable program features that enhanced or would have enhanced transition experiences. Method The authors conducted a qualitative interview study of postgraduate year (PGY) 1 residents in emergency medicine, family medicine, general surgery, internal medicine, obstetrics and gynecology, pediatric and adolescent medicine, and psychiatry at Mayo Clinic sites in Arizona, Florida, Minnesota, and Wisconsin between December 2020 and March 2021. Open-ended questions explored residents’ transition experiences. Interviews were audio-recorded, transcribed, coded inductively, and analyzed iteratively using general thematic analysis from an epistemologically constructivist perspective. Results Forty-five residents (25 women, 20 men) from 12 programs, 7 specialties, and 4 states participated. PGY-1 residents experienced the transition to residency as a confluence of overlapping and interconnected transitions that unfolded over time, spanned multiple life domains, and generated numerous personal and professional demands. Residents appraised demands based on their effects on patient care, professional growth, and personal well-being and struggled when coincident demands forced tradeoffs among these concerns. Residents who experienced many difficulties during the transition to residency reported high demands (eg, due to transition-related discontinuities, depleted resources from prior transitions or a difficult match experience, structural and systemic barriers, coincident personal or situational stressors) and/or fewer resources (eg, insufficient residency or life skills, limited social support, financial strain). Preparedness and supportive relationships eased the transition process. Residency program features that enhanced or would have enhanced the transition experience included monitoring and limiting overall demands, minimizing unhelpful and harmful demands, calibrating constructive demands, and increasing holistic support. Conclusions Study findings illuminate transition experiences of PGY-1 residents, reveal person-centered considerations to inform ongoing improvement efforts, and identify potentially actionable steps programs can take to improve resident transition experiences.

Background In pediatric patients presenting after blunt trauma, the incidence of clinically significant cervical spine injury (CSI) is approximately 1%. Although multidetector CT (MDCT) is widely accepted for cervical spine clearance in adults, its utility in children remains uncertain. The purpose of this study is to evaluate the sensitivity of MDCT in identifying clinically significant CSI in pediatric patients, stratified by age groups: adolescents (12 years to 17 years) and children (0 years to 11 years). Methods We designed a national, multicenter, prospective observational study to assess the diagnostic performance of MDCT in detecting clinically significant CSI in pediatric trauma patients. Data are being collected from participating centers on imaging findings, clinical outcomes, and the presence of confirmed CSIs after blunt trauma. The analysis plan includes stratification by age group and calculation of sensitivity, specificity, and predictive values of MDCT for CSI. Results This abstract outlines the background, methodology, and analytical framework of the study. Data collection and analysis are ongoing. This study represents the largest known cohort of pediatric patients undergoing cervical spine imaging after blunt trauma and is the first prospective study of its kind focused exclusively on this population. Conclusions This study will provide critical data to inform guidelines for pediatric cervical spine clearance after blunt trauma. By evaluating the sensitivity of MDCT in detecting clinically significant CSI, the findings aim to support evidence-based imaging strategies and improve the safety and efficiency of pediatric trauma care.

Individuals with congenital heart disease are living well into adulthood, resulting in a growing population at risk for neurocognitive and psychosocial challenges. Numerous studies have described these risks in childhood, but significant gaps remain in our understanding of how those challenges evolve across stages of adulthood and how to optimally integrate neurocognitive and psychosocial care for adults with congenital heart disease. A multidisciplinary group of experts and patient partners assembled in April 2024 in Atlanta, GA, forming 3 working groups: (1) Genetics and Brain Health, (2) Characterizing Neuropsychological and Psychological Outcomes, and (3) Neuropsychological and Psychosocial Interventions. Current knowledge was reviewed, knowledge gaps were identified, and recommendations to address these gaps were formulated. Five critical questions regarding the characterization of neuropsychological and psychological outcomes of adults with congenital heart disease were prioritized for discussion: which neurocognitive and psychosocial domains should be prioritized in research and clinical care, what are the trajectories of neurocognitive and psychosocial functioning over the lifespan, how should neurocognitive and psychosocial screening be deployed, what should neurocognitive and psychosocial assessments include, and how do we make comprehensive neurocognitive and psychosocial care a reality. Although many gaps in knowledge were identified, particularly around characterizing neurocognitive trajectories throughout adulthood, there is substantial evidence of increased risk for poor psychosocial outcomes among adults with with congenital heart disease. Clinical and research advances must progress in tandem to address these risks. Specific recommendations for advancing this field over the next decade are offered.

817 Background: Universal germline sequencing is increasingly utilized in practice, but existing evidence and guidelines are based on studies in predominantly white populations. This study aims to compare the prevalence of genetic alterations in white vs underrepresented minority (URM) populations and assess incremental findings discovered with universal testing beyond current guidelines. Methods: This prospective, multicenter study analyzed genetic alterations in white and URM cohorts with primary GI malignancies receiving care at Mayo Clinic cancer centers between April 2018 and April 2025. Patients underwent germline sequencing using a next-generation sequencing (NGS) platform targeting over 80 genes. We compared the distribution of results between white and URM populations. Concordance with NCCN testing guidelines and incremental findings were assessed. Results: A total of 1128 patients were studied, of which 758 were white and 370 were URM, (47.6% Hispanic, 22.7% Black, 13.8% Asian, 10.5% American Indian, 0.8% Pacific Islander, and 6.8% other). Pathogenic variants (PGV) were more common in the white population (16.1% vs 9.2% P < 0.001). Variants of uncertain significance (VUS) were more common in the URM population (53.2 vs 43.5%, P<0.001). A total of 156 patients were found to have a PGV. PGVs outside primary cancer genes were more common in white patients (57.4% vs. 32.4%; p=0.0241). Incremental findings from universal testing were higher in white patients (66.4% vs 35.3%; p=0.0011). Conclusions: This study reveals a significant difference in the prevalence of PGV and VUS between white and URM patients with primary GI malignancies. The higher rate of PGVs in white patients and VUS in URM patients highlights potential inequities in both detection and interpretation of genetic results. These findings emphasize the need for broader representation in genetic databases to ensure equitable access to precision oncology. Screening guidelines met by patients with PGV. White (N=122) URM (N=34) Total (N=156) p value Did they meet NCCN testing guidelines for their primary cancer? 0.0991 Yes 87 (71.3%) 29 (85.3%) 116 (74.4%) No 35 (28.7%) 5 (14.7%) 40 (25.6%) Was the PGV outside of the primary genes recommended for their primary cancer? 0.0241 Yes 70 (57.4%) 11 (32.4%) 81 (51.9%) No 47 (38.5%) 22 (64.7%) 69 (44.2%) Incremental Finding 0.0011 Yes 81 (66.4%) 12 (35.3%) 93 (59.6%) No 41 (33.6%) 22 (64.7%) 63 (40.4%)

566 Background: FGFR inhibitors (FGFRi) have an established role in treating FGFR2-altered (alt) cholangiocarcinoma (CCA). Tinengotinib, a novel FGFRi, has shown promising activity overcoming acquired resistance to prior FGFRi. We present biomarker analyses evaluating tinengotinib’s ability to overcome prior FGFRi resistance and to elucidate mechanism of resistance to tinengotinib. Methods: Eligible patients (pts) with advanced/metastatic CCA who had received ≥ 1 prior systemic chemotherapy were treated with tinengotinib 10 mg daily across 4 Cohorts: A1: FGFR2 fusion (fus) with primary progressive disease (PD) on prior FGFRi; A2: FGFR2 fus with PD after prior response to FGFRi; B: FGFR alt without FGFR2 fus; C: FGFR wild-type. Efficacy was assessed by RECIST v1.1. All pts underwent liquid biopsy for circulating tumor DNA (ctDNA) at baseline; additional timepoints include cycle 3 day 1 (C3D1), time of PD, and end of treatment (EOT). Samples were analyzed using FoundationOne Liquid panel. Results: 27 out of 55 enrolled pts had biomarker samples collected at baseline and C3D1. Among them, pts in A1 (n=10, 107 mutations (mut)), B (n=8, 90 mut) and C (n=5, 74 mut) showed a significant decrease in short variant allele frequencies (VAF) from baseline to C3D1 by a median relative VAF reduction of 100% (p<0.0001) for each of the three cohorts. Although a median relative VAF reduction of 33.3% was seen in A2 (n=4, 15 mut), this was not significant (p=0.6093) likely due to low baseline mutation burden. A ≥50% reduction in ctDNA was associated with improved progression free survival (p<0.0014). Additionally, 100% of median relative reductions in FGFR2 kinase domain (KD) mut were seen in A1 and B (p<0.0001, 95% CI 100-100% and p=0.0156, 95% CI 83.6-100%, respectively), with 92% and 57% clearance of initial FGFR2 KD mut by C3D1. In a subgroup of 10 pts with biomarker sampling at baseline and EOT, 3 pts in A1 with acquired resistance showed emergence of novel FGFR2 mut, loss of FGFR-sensitive mut and new mut in alternate pathways (e.g., AKT, EGFR, RAS/MAPK) while retaining the original FGFR2 fus. 1 pt from B developed resistance due to new FGFR2 rearrangements and FGFR2 mut. 4 FGFR wild-type pts from C developed resistance involving mut in TP53, KRAS, and other oncogenic drivers. Conclusions: These findings provide genomic evidence that tinengotinib may overcome resistance to prior FGFRi treatment in FGFR2 fus-positive CCA, as reflected by significantly reductions in ctDNA VAFs and frequent clearance of FGFR2 KD mutations. The emergence of resistance alterations including de novo FGFR2 mutations and bypass pathways activations indicates acquired resistance that may limit long-term benefit. These results support further investigation with expanded biomarker sampling to better characterize resistance evolution and guide therapy optimization in an ongoing Phase 3 trial. Clinical trial information: NCT04919642 .