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The Omicron variant of SARS-CoV-2 is associated with milder symptoms and lower hospitalization and mortality rates than Delta variants, although the impact of Omicron on immunocompromised patients, especially solid organ transplant (SOT) recipients, is still unclear. This study compares the hospitalization rate and outcomes between immunocompromised, immunocompetent, and SOT patients during the Delta and Omicron periods. We included adult patients who tested positive for SARS-CoV-2 on PCR or nasopharyngeal antigen test between 26 June 2021 to 8 September 2022, at our institution. A total of 12,401 COVID-19 patients were included, of which 11,055 were immunocompetent, and 1346 were immunocompromised (375 SOT recipients). Throughout the Delta and Omicron outbreaks, immunocompromised patients exhibited higher comorbidities and 30-day hospitalizations, but rates of mechanical ventilation and ICU-level care were like immunocompetent patients. During the Omicron wave, immunocompromised patients had higher unadjusted relative risk estimates (RR = 2.37, 95% CI 1.96–2.87, p < 0.05) than Delta (RR = 1.58, 95% CI 1.24–2.01, p < 0.05), with higher adjusted relative risk for hospitalization in Omicron (RR = 1.50, 95% CI 1.10–2.03, p = 0.01). Analyses show increased hospitalization risk in immunocompromised during the Omicron wave compared to the Delta wave, with no significant difference in hospitalization outcomes. The relative risk of hospitalization for SOT patients was higher in both waves.

Background Ketamine has demonstrated efficacy in treatment-resistant depression, primarily in psychiatric or outpatient populations. Its use in ICU patients remains underexplored, with limited data beyond case reports and small series. This study evaluated the association between subanesthetic ketamine infusions and improvement in depressive symptoms and hemodynamic changes in ICU patients. Methods We conducted a retrospective study of adults admitted to the ICU who received IV ketamine (0.3-0.75 mg/kg over 40 min on three consecutive days) for depressive symptoms. Changes in depressive symptoms were assessed using routine clinical documentation by physicians, nurses, and occupational and physical therapists. Hemodynamic parameters (blood pressure and heart rate) were recorded before and up to 120 min after infusion. The primary outcome was to evaluate depressive symptoms while the secondary outcome was to assess hemodynamic changes post transfusion. Results Thirty-four patients met criteria, including 18 solid organ transplant recipients. Median age was 59 years; 61.8% were male. Ketamine was associated with improvement in apparent sadness (90.0% vs 52.2%, P < .05) and reported sadness (95.0% vs 59.1%, P < .05). In transplant recipients, improvement in apparent sadness remained significant (80.0% vs 41.7%, P < .05). Hemodynamic parameters remained stable; heart rate increased transiently at 15-30 min post-infusion, returning to baseline by 60-90 min. Adverse effects observed were anxiety (12.5%), restlessness and/or agitation (10.4%), and dissociation (8.16%). Conclusion Subanesthetic ketamine improved specific depressive symptoms in critically ill ICU patients without significant hemodynamic instability. These findings support its potential as a rapid-acting antidepressant in the ICU, warranting further prospective trials.

Critically ill patients frequently require intrahospital transport (IHT) to diagnostic exams or procedures and must remain connected to life-sustaining medical lines. During IHT, the risk of tangled medical lines is unavoidable. The idea for a novel medical line securement device was inspired by a patient transport nurse due to frustrations and workflow inefficiencies managing tangled medical lines. The study aim was to explore the correlation between the utilization of a single-use securement device to manual or accidental disconnections of medical lines during IHT, and nurses’ perception of efficiency, compared to the current practice of no utilization of a securement device. In 2019, a randomized, descriptive, correlational study was conducted on 142 progressive and intensive care hospitalized patients. Study coordinators measured the number of times either IV lines or monitor cords were accidentally or manually disconnected to detangle during or after transportation and the perception of transport efficiency. Results revealed fewer manual disconnections among intervention group compared to the control. Nurses’ perception regarding the efficiency between the intervention and control group was statistically significant when the device was utilized to secure the lines and cords during transport. Nurses reported much higher satisfaction rates of transport efficiency when the device was used. This finding showed the device’s utility for improving nurse satisfaction during IHT of critically ill patients. Utilization of the medical line securement device may be generalizable across other healthcare settings and disciplines where the complexity of medical lines may exist.

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.

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%)

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH. METHODS: Participants were recruited from 3 geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Participants underwent Exome+ sequencing (dba Helix, San Mateo, CA) and return of results for specific genetic findings in APOB , LDLR , or PCSK9 . A chart review was performed to collect demographics, personal, and family cardiovascular history. RESULTS: At the time of the study, 84 413 participants were enrolled in the Tapestry study. Annotation and interpretation of all variants in genes for FH resulted in the identification of 419 likely pathogenic and pathogenic variants (prevalence, 0.50%), which included 116 APOB , 298 LDLR , and 5 PCSK9 . Sixty-six percent were female, the mean body mass index was 27.3, with 12.3% reporting a history of diabetes. Hypertriglyceridemia (≥150 mg/dL) was present in 39.5% and reduced HDL (<50 mg/dL) was present in 56.7% of patients. 27.5% of patients were not on cholesterol-lowering medications, and only 10% of FH carriers were at goal low-density lipoprotein cholesterol levels. A history of coronary artery disease was reported in 22.4% of the cohort. Nearly 90% of these participants were newly diagnosed carriers of FH. Only 30.8% of confirmed genetic diagnoses of FH satisfied clinical (Dutch lipid clinic network) criteria for a diagnosis. CONCLUSIONS: Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have familial hypercholesterolemia. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05212428.

Introduction Despite growing evidence to characterise cancer-associated cognitive decline (CACD) in women with breast cancer, interventions to mitigate CACD are limited. Emerging evidence suggests aerobic exercise may enhance cognition after breast cancer diagnosis and treatment; yet, CACD remains an understudied outcome of exercise, and few high-quality studies have been conducted. In addition to knowledge gaps in effectiveness, the translation of exercise interventions to community settings remains challenging. The Breast cancer Reasoning and Activity INtervention (BRAIN) investigates the effectiveness of aerobic exercise training, delivered in a community-based setting, for improving cognitive function in women with breast cancer and gathers information on the implementation success of the intervention. Methods and analysis This Hybrid Type I effectiveness–implementation study is conducted at an academic medical centre in the southwestern United States in partnership with a non-profit, community health and wellness organisation. The study enrols 160 women diagnosed with stage I–IIIa breast cancer and within 3–36 months of treatment completion into a 1:1 randomised controlled trial. Individuals randomised to the exercise group receive a 6-month, individually tailored aerobic exercise programme delivered by exercise trainers employed at local community fitness centres. The programme is progressive in nature and designed to help participants achieve aerobic exercise levels consistent with guidelines for cancer survivors. Individuals randomise to the control group receive a 6-month health education control intervention delivered virtually by hospital-based health educators. Cognitive performance (primary), self-reported cognition, patient-reported outcomes, physical activity and cardiorespiratory fitness are measured at baseline, 6 months (postintervention) and 12 months (follow-up). Brain structure and function are measured via magnetic resonance imaging (MRI) at baseline and 6 months. Implementation outcomes are defined by the RE-AIM framework, which includes reach, effectiveness, adoption, implementation and maintenance. RE-AIM outcomes are measured at baseline, 6 months, 12 months and ongoing during the study. Ethics and dissemination This study was approved by the Mayo Clinic Institutional Review Board (#23-000020). All participants provide informed consent prior to participation. Findings will be disseminated to scientific, clinical and community audiences through manuscripts, presentations and newsletters. Trial registration number NCT04816006.

Sarcomas are rare heterogenous mesenchymal tumors with over seventy-five different subtypes, with varying biology and outcomes, with no clear inciting factor in the vast majority. To determine the prevalence of pathogenic germline variants (PGV) in patients with sarcomas, we undertook a prospective multi-site study of germline sequencing using an 84-gene next-generation sequencing panel among patients receiving care at the four Mayo Clinic Cancer Centers. Of 115 patients with bone and soft tissue sarcoma, the median age was 60 years, 49.6% were female, 82.6% were White. The anatomical location of the primary tumor included extremities (34.8%), retroperitoneum (19.1%), trunk (13.0%), and head and neck (7.8%). Family history of cancer was present in 62.6% of the study population. Ten patients (8.7%) had a pathogenic/likely pathogenic variant (PGV). Of these, three had stage IV sarcoma, and seven had earlier-stage sarcoma (stages I–III). Among the 55 (48.7%) patients who had variant of uncertain significance (VUS), 41.1% (22/55) had stage IV sarcoma and 58.9% (33/55) had earlier-stage disease. Of the ten patients with PGV, high-to-moderate penetrance gene abnormalities were identified in eight patients (80%) involving TP53 (3), BRCA1 (1), SDHA (1), ATM (2), and NBN (1) genes. The vast majority of the PGVs (70%) would not have been detected using the current guidelines. Because of the paucity of sarcomas and lack of effective treatment options for advanced disease, germline testing in sarcomas represents a potentially impactful strategy to assess therapeutic options and for assessment of familial risk.