Citations

Background: A growing body of research has connected electronic health record (EHR) workload to physician burnout. In orthopedic surgery, burn-out rates are rising. This study analyzed orthopedic surgeons' EHR use by sex and practice experience. Materials and Methods: EHR activity was analyzed among attending orthopedic surgeons at a single institution from May 2022 to May 2023. Demographic information included self-reported sex and practice years. Outcomes included time spent in notes, orders, clinical review, and in-basket daily; time spent outside of scheduled clinical responsibilities; volume of in-basket messages received daily; and proportion of orders with team contributions. Multivariable linear regression compared outcomes by sex and practice years. Results: A total of 105 orthopedic surgeons were included (91% male; mean 15.5 ± 9.8 practice years). Female surgeons logged 31% more time in the EHR overall (62.2 vs 47.4 minutes daily; P = .05) and on unscheduled days (10.1 additional daily minutes; P = .03), and received more messages from patients (2.4 vs 1.0 messages daily; P = .002) compared to male surgeons. Senior surgeons spent significantly less time on documentation and orders ( P ≤ .048) and on unscheduled days (3.3 less minutes daily per practice decade; P = .013), and had more support with placing orders ( P < .001). Conclusion: Female sex and fewer practice years were associated with increased EHR use. Female orthopedic surgeons tended to have higher patient message volumes, whereas junior surgeons tended to have less team support, spending more time on orders and documentation. Given known factors contributing to burnout, these findings warrant further investigation into targeted interventions to improve physician EHR use.

Introduction Ultra-marathon races present a prolonged cardiopulmonary physiological stress but the magnitude, persistence, and impact of race environment on respiratory function are incompletely understood. The aim of this study is to observe the effect of ultra-marathon trail races on both lung function and airway impedance. Methods Fifty-seven individuals (49/8, M/F) participated in either the Courmayeur-Champex-Chamonix (CCC ® , 101.5km), Ultra Trail du Mont-Blanc (UMTB ® , 171.5 km), or the Hong Kong 100 (HK, 100 km) races. Participant demographics were measured pre-race and included: age (40.7±10.3 yrs); height (175.5±7.1 cm), body mass (69.7±8.3 kg). Spirometry, airway impedance (via forced oscillation technique, FOT), maximal inspiratory (MIP) and expiratory pressure (MEP), and exhaled nitric oxide (ExNO) were assessed before, immediately (18–4 hours after), and 188–24 hours post-race. Mixed effects analysis with Dunnett’s post-hoc correction were conducted to evaluate the effects of race and time. Results Results demonstrated significant effects of time for: forced vital capacity (FVC), forced expiratory flow over one second (FEV 1 ), peak expiratory flow (PEF), forced expiratory flow between 25-75% (FEF25-75), forced expiratory flow at 25% and at 50% (FEF 25 and FEF 50 , respectively), MIP, MEP, airway reactance (X) at all frequencies from FOT (X 5 , X 11 , X 19 ), respiratory rate, and ExNO (all p &lt;0.05). A significant effect of race was also observed for ExNO ( p =0.002). Discussion Findings indicate declines in lung function and airway impedance immediately after ultra-marathon races, some of which, persisted up to 24 hours post-race. Further investigations are required to better understand the etiology of changes in lung function following ultra-endurance events.

Abstract Introduction Here we demonstrate that respiratory infection with Francisella tularensis induces the formation of induced bronchus-associated lymphoid tissue (iBALT) as a protective mechanism against pulmonary tularemia-like disease in mice. While semi-invariant natural killer T (NKT) cells and mucosal-associated invariant T (MAIT) cells are abundant at the lung mucosa, their roles in infectious diseases remain poorly understood. Pulmonary tularemia, the most severe form of tularemia, arises from respiratory infection with F. tularensis. Using C57BL/6 mice infected with the live vaccine strain (LVS) of F. tularensis to model tularemia-like disease, we previously showed that NKT cells exacerbate disease, as NKT-deficient CD1d⁻/⁻ mice were protected. Notably, protected CD1d⁻/⁻ mice developed iBALT structures in the lungs, which were absent in C57BL/6 mice. Methods Molecular immunology methods. Results Respiratory LVS infection in CD1d⁻/⁻ mice induced a robust expansion of IL-17-producing MAIT17 cells and a decrease in regulatory T cells in the lungs compared to C57BL/6 mice. Single-cell RNA sequencing revealed a gene signature in MAIT cells linked to factors that drive iBALT formation. Supporting this notion, adoptive transfer of LVS-activated lung MAIT cells from infected CD1d⁻/⁻ mice conferred protection against tularemia-like disease in RAG2⁻/⁻ recipients, while splenic MAIT cells did not despite the fact that both populations homed to the lungs after transfer. Lung-derived MAIT cells were enriched in IL-17-producing MAIT17 cells, whereas splenic MAIT cells predominantly consisted of interferon-gamma-producing MAIT1 cells. Last, IL-17 was identified as critical for iBALT development during respiratory LVS infection in CD1d⁻/⁻ mice. Conclusion In summary, our findings establish MAIT cells as central mediators of IL-17-dependent protection against pulmonary tularemia-like disease and underscore the potential protective role of iBALT in disease resistance. Funding Source NIH AI137082, VA Merit BX001610, VA SRCS BX004595 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Abstract INTRODUCTION: Pleuropulmonary blastoma (PPB) and Sertoli-Leydig cell tumor (SLCT) are DICER1-related tumors for which novel therapies are urgently needed. A subset of Wilms tumors are also associated with germline or somatic variants in DICER1. Current therapies include cytotoxic chemotherapy, radiation, and surgery, but there are limited options for patients with recurrent disease. Antibody-Drug Conjugates (ADC) have emerged as promising therapies for several solid tumors. Aberrantly expressed cell surface proteins, including Preferentially Expressed Antigen in Melanoma (PRAME), represent potential targets for immunotherapeutic treatments like CAR-T cell and antibody-based therapies in malignant cancers, including DICER1-associated tumors. METHODS: Individuals diagnosed with PPB, SLCT, and Wilms tumor who enrolled in the International PPB/DICER1 Registry, International OTST Registry, and/or UT Southwestern Pediatric Hematology-Oncology Biorepository were selected for analysis. We analyzed ten PPB samples (four PDX, six primary tumor), four SLCT samples (all primary tumor), and 54 Wilms tumor samples (4 PDX, 50 primary tumor). DICER1 hotspot variants were verified in all 14 PPB and SLCT samples, while none of the Wilms tumor samples we analyzed exhibited DICER1 hotspot variants. Mapped and normalized whole-transcriptome sequencing reads were used to examine expression of 73 targets of antibody- or cell-based therapies that are clinically approved or under clinical investigation on clinicaltrials.gov. Genes with a median expression exceeding 2.5 transcripts per million (TPM) were considered expressed in a given tumor type; this threshold was selected to be permissive in identifying potential targets for further evaluation. RESULTS: Of the 73 genes of interest, 21 targetable cell-surface genes met a median expression threshold of 2.5 TPM in at least one tumor type: 11 genes in PPB, 16 in SLCT, and 14 in Wilms. Seven genes (FN1, PRAME, MCAM, CD248, IL11RA, CD276 (B7-H3), and MRC2) were expressed at this level in all three tumor types. Additional genes were expressed above this level in only two of the tumor types; PDGFRA in PPB and SLCT; GPC2 and TYRO3 in SLCT and Wilms tumor; and CSPG4, ERBB2, FZD10 in PPB and Wilms tumor. Six genes were exclusively expressed in SLCT (AXL, GPNMB, PROM1, KDR, ITGA6, FGFR4), and two were unique to Wilms tumor (GPC1, ULBP3). Of these, PRAME was previously reported as frequently expressed in DICER1-associated tumors; little has been reported about the remaining potential targets. CONCLUSION: PPB, SLCT, and Wilms tumor express several potential immunotherapy targets by RNA-seq. Expression of these potential targets should be investigated by immunostaining in a wider panel of tumors. Further study on the potential for ADCs or CAR-T cell therapies to treat DICER1-related conditions is needed. Citation Format: Brenya McNally, BS, Paige H.R. Mallinger, MS, David Huntsman, MD, FRCPC, FCCMG, Yemin Wang, PhD, Joyce Zhang, PhD, Claudette R. Fraire, PhD, Peter J. Schoettler, MD, Kris Ann P. Schultz, MD, Kenneth S. Chen, MD. Identifying potential cell-surface targets for therapeutic treatment of DICER1-related cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Breaking Barriers in the Fight against Rare Cancers; 2026 Jul 18-20; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(14_Suppl):Abstract nr A018.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by lifelong immune dysregulation leading to high rates of autoimmune disorders, elevated risk of complications from infections, immune hypersensitivity, and a unique form of immunodeficiency. It is now appreciated that DS shares key hallmarks with interferonopathies, with vast remodeling of all branches of the immune system, hypercytokinemia, and widespread autoantibody production. Here within, we review the existing literature with an emphasis on clinical considerations toward monitoring, management, and therapeutic opportunities. We highlight recent research advances that illuminate diagnostic approaches to evaluate immune dysregulation in DS. We also discuss the evidence supporting specific immunomodulatory strategies that could have multidimensional benefits in this population, including JAK inhibitors, intravenous immunoglobulin, and B cell–depleting agents.