Citations

Background Native American (NA) patients experience persistent inequities in advance care planning (ACP) and often present to tertiary centers with critical illness; culturally respectful serious-illness communication is therefore essential in emergency and intensive care settings. Intervention We developed and implemented a nursing-led, multidisciplinary educational initiative at a large academic medical center serving patients from >50 tribal nations. Informed by a literature review, local practice needs, and expert input from a Native American Patient Experience Ambassador, we created (1) an “Honoring Your Choices” (HYC) communication card with culturally sensitive prompts for serious illness conversations and (2) a quick reference guide (QRG) outlining key cultural considerations and unit-specific resources. Tools were disseminated to seven intensive care units and the emergency department through nurse leader engagement, unit rounding, and staff education, and the initiative was presented at departmental Grand Rounds/didactics with pre/post surveys to assess impact. Results Twenty-seven pre-session and twenty-four post-session surveys were collected from clinicians and trainees. Prior to the session, >80% of respondents reported being not or only slightly confident discussing end-of-life issues with NA patients/families; post-session surveys demonstrated increased self-reported confidence in recognizing when cultural beliefs may influence care and in conducting end-of-life discussions. Conclusions This initiative demonstrates how culturally congruent approaches to serious illness conversations may support more meaningful engagement with NA patients and families. Our experience suggests that developing and evaluating a brief, point-of-care communication tool like Honoring Your Choices may be accomplished with existing interdisciplinary partnerships, offering a practical model that other institutions can readily mirror.

ABSTRACT Background Hidradenitis suppurativa (HS) is an inflammatory condition associated with cysts of the folliculopilosebaceous unit primarily affecting intertriginous areas. HS has been correlated with smoke exposure in the adult population, but there is a knowledge gap in understanding its effect in pediatric and adolescent patients. This study assesses correlations between active and passive smoke exposure and the development of HS in the pediatric and adolescent population. Methods A retrospective case–control study was conducted at Mayo Clinic (2010–2023) of patients diagnosed with HS before the age of 18 years who were age‐, sex‐, and race‐matched to healthy controls in a 1:3 ratio, analyzed using Fisher exact for categorical variables and Kruskal–Wallis for continuous. Results One hundred and seventy‐four cases and 522 controls met inclusion criteria. The prevalence of active and passive smoke exposure was significantly higher in patients with HS compared to controls ( p = 0.001), with passive smoke accounting for 64.6% ( N = 31/48) of smoke exposure in patients with HS. Smoke exposure was associated with a significant increase in the odds of an HS diagnosis, with an odds ratio of 4.8 (95% CI: 3.06–7.61) for passive and/or active exposure, and 1.64 (95% CI: 1.01–2.61) for passive exposure alone. Smoke exposure was associated with a later age of diagnosis than those with no smoke exposure ( p < 0.001). Conclusion Prevalence of active and passive smoke exposure was higher in pediatric and adolescent patients with HS compared to age, sex, and race‐matched healthy controls. Smoke exposure increased the odds of having HS and was associated with a later age at diagnosis.

ABSTRACT Extracellular vesicles (EVs) are increasingly recognized as mediators of intercellular communication in cancer. We previously demonstrated that re‐expression of the leucine‐rich domain (LRD) of neurofibromin (NF1) suppresses glioblastoma (GBM) invasion and limits microglia/macrophage infiltration into the tumor microenvironment (TME). Given the central role of tumor‐associated microglia/macrophages (TAMs) in GBM progression, we investigated whether NF1‐LRD‐containing EVs (NF1‐LRD‐EVs) could modulate TAM function and remodel the TME. Our results showed that NF1‐LRD‐EVs attenuated microglia and macrophage recruitment in migration assays, consistent with reduced microglia/macrophage recruitment observed in vivo . In parallel, treatment with NF1‐LRD‐EVs enhanced phagocytic activity of both microglia and iPSC‐derived macrophages, accompanied by induction of pro‐inflammatory cytokines TNF‐α, IL‐6, and IL‐1β, and downregulation of immunosuppressive mediators such as Arginase‐1 and IL‐10. Mechanistically, NF1‐LRD‐EVs induced ADAM17‐associated inflammatory signaling, accompanied by NF‐κB activation. Pharmacological inhibition of ADAM17 reduced TNF‐α release and attenuated NF‐κB activation, supporting a role for ADAM17‐dependent signaling in amplifying this inflammatory response. Together, these findings show that NF1‐LRD‐EVs reprogram TAMs toward a pro‐inflammatory phenotype and modulate the GBM immune microenvironment. These results provide a framework for understanding NF1‐LRD‐EV‐mediated immune regulation and support further investigation of EV‐mediated immune modulation of the TME.

ACCESS is a prospective, multicenter phase II trial evaluating peripheral blood stem cell (PBSC) transplantation using 4-7/8 HLA-mismatched unrelated donors (MMUD) with post-transplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate. Adults undergoing first HCT with myeloablative (MAC) or reduced-intensity/nonmyeloablative (RIC/NMA) conditioning were enrolled, with donors aged 18-35 years and matched at 4/8-7/8 HLA loci by high-resolution typing. This expanded analysis includes all enrolled adult PBSC recipients, including the protocol-specified RIC/NMA cohort expansion, to improve precision of outcome estimates and provide descriptive analyses by HLA match level. Among 268 adults, 183 received 7/8 and 85 received &lt;7/8 MMUD grafts; 82.4% of the &lt;7/8 cohort received 6/8 grafts. Median follow-up among survivors was 11.9 months. At 1-year, overall survival was 78.6% (95% CI, 71.9-83.9) in the 7/8 cohort and 85.6% (95% CI, 76.0-91.5) in the &lt;7/8 cohort. One-year relapse, non-relapse mortality, and GVHD-free relapse-free survival were 17.1%, 13.7%, and 51.1% versus 22.8%, 8.4%, and 54.6%, respectively. The cumulative incidence of grade II-IV and grade III-IV acute GVHD by day 100 was 36.6% and 7.7% in the 7/8 cohort versus 28.3% and 5.9% in the &lt;7/8 cohort. Moderate-to-severe chronic GVHD at 1 year was 11.3% versus 7.7%, respectively. Among adult ACCESS recipients treated on a uniform young-donor PBSC/PTCy platform, short-term outcomes with predominantly 6/8 MMUD transplantation were encouraging. Because donor match level was not prospectively assigned and between-group comparisons were exploratory, these findings are descriptive and should not be interpreted as establishing equivalence with 7/8 MMUD transplantation. (Registered as NCT04904588 at CT.gov)

Abstract Glioblastoma (GBM) remains the most lethal primary brain cancer due to its remarkable metabolic plasticity and therapeutic resistance. Here, we identify cholesterol dependency as a therapeutically exploitable vulnerability in GBM using two FDA-approved drugs: the H1 histamine antagonist clemastine and the retinoid X receptor agonist bexarotene. Combined treatment induces potent synergistic anti-tumor activity across patient-derived glioma models, suppressing proliferation, stemness, and survival at sub-IC50 concentrations. Mechanistically, this therapy disrupts cholesterol biosynthesis, transport, and homeostasis, triggering endoplasmic reticulum stress and activation of the unfolded protein response, ultimately leading to autophagy and apoptotic cell death. Orthotopic patient-derived glioma models recapitulate these mechanisms in vivo, where local intracranial administration significantly reduces tumor progression and prolongs survival using fourfold lower doses than systemic intraperitoneal delivery. Single-cell RNA sequencing revealed activation of regeneration and plasticity programs, accompanied by immune microenvironment remodeling and enhanced inflammatory signaling. Importantly, syngeneic models preserved immune cell composition, supporting future integration with immunotherapeutic strategies. Together, these findings establish cholesterol dysregulation–induced metabolic collapse as a promising therapeutic approach for GBM.

Background: Telomeres are repetitive sequences at the end of linear chromosomes that preserve genetic information. Patients with telomere biology disorders (TBDs) are subject to multiorgan manifestations, which include the liver. However, due to the rare nature of the disorder, these manifestations are not fully characterized. Methods: Here, we describe the hepatic manifestations of patients with TBD at a large tertiary center within a specialized TBD clinic; 121 consecutive patients with TBD seen from 2017 to 2024 were included. The median age of the TBD diagnosis was 43 years old, with 60% male. The most common pathogenic/likely pathogenic variant was TERT (25%), followed by RTEL1 (10%) and TERC (7%). Results: Evidence of hepatic involvement in TBD was observed in 60% of patients (73 of 121), as determined by imaging studies or abnormal liver chemistries. Hepatic steatosis was the most prevalent imaging finding (56%), while a cholestatic pattern of liver injury was the predominant laboratory abnormality (73%). Biopsy-proven portosinusoidal vascular disorder was present in 4 patients. Findings of portal hypertension were observed in 25 patients (34%), with decompensation observed in 12 patients (16%). Traditional liver imaging modalities (computer tomography, ultrasound, and MRI) were compared with magnetic resonance elastography in 41 patients. Of these, 7 patients had abnormal magnetic resonance elastography with normal traditional imaging (17%), indicating higher sensitivity of magnetic resonance elastography to detect liver involvement. Conclusions: This study describes the liver manifestations within a cohort of patients with TBD with findings of portosinusoidal vascular disorder and hepatopulmonary syndrome similar to other cohorts and a noted higher prevalence of hepatic steatosis as compared with the general population. Liver stiffness measurements, integrated with imaging and laboratory testing, further improve characterization of hepatic manifestations in TBD.

Background: The Accreditation Council for Graduate Medical Education (ACGME) case log system establishes minimum clinical experiences for anesthesiology residency. While core program requirements were last updated in 2016, case log minimums themselves have not undergone a major revision in approximately two decades. Consequently, current requirements may not fully reflect changes in anesthetic practice and the evolving scope of perioperative medicine. In anticipation of major ACGME revisions in 2027, this study aimed to develop consensus-driven recommendations for modernizing residency case logs. Methods: A three-round modified Delphi study was conducted with a nationally representative panel of 60 stakeholders, including anesthesiology residency program directors and academic and private practice anesthesiologists. Panelists evaluated a comprehensive list of potential case categories across three domains: technical skills, surgical case characteristics, and patient demographics. In Round 1, panelists proposed minimum numbers or suggested that no requirement was necessary. Rounds 2 and 3 utilized iterative feedback to determine consensus on the necessity of requirements and specific minimum thresholds. Consensus was defined as at least two-thirds agreement. Results: Sixty invited experts completed all three rounds (100% response rate). The panel reached consensus to recommend new minimum requirements across several areas not currently tracked with minimums, including arterial lines (40), central lines (20), fiberoptic intubation (10), one-lung ventilation (10), neuromonitoring (10), POCUS (10 Cardiac, 10 Lung), and NORA (20 cases). Regarding existing requirements, consensus was reached to recommend increasing total peripheral nerve blocks from 40 to 60, with added requirements for anatomic specificity, and cardiac case minimums from 20 to 25. The panel also established consensus definitions for life-threatening pathologies to standardize reporting. The panel did not achieve consensus on several areas, including, for example, whether a minimum requirement for patients younger than 3 months should be maintained. Conclusion: These findings provide stakeholder-validated recommendations to inform upcoming ACGME requirement revisions.

This study examines the patient- and hospital-level variation in time to initiation of inpatient management among patients admitted to general medical services.

Background: Traditional educational methods often require protected time away from clinical duties, can be difficult to attend because of staffing or scheduling constraints, and may not consistently engage learners or meet individual learning needs. This article describes a gamified in situ microlearning approach to nursing professional development within the clinical practice setting that was designed to improve confidence and knowledge retention while maintaining staff satisfaction. Method: The educational intervention was provided in the clinical setting to avoid scheduling conflicts and interruptions in care. Results: Education on 18 topics was provided over 12 months. The gamified microlearning was associated with increased self-reported confidence without negatively impacting satisfaction. Conclusion: Gamified in situ microlearning can serve as a valuable adjunct to nursing professional development.