Citations

Abstract Purpose Diagnostic bronchoscopy plays a critical role in management for immunocompromised patients hospitalized with new pulmonary infiltrations. Most existing data on bronchoscopy in immunocompromised patients are derived from ICU cohorts or mixed inpatient/outpatient populations. This study aimed to assess the relationship between specific immunosuppression types-classified per the 2025 IDSA guidelines-and bronchoscopy yield and its impact on hospital management among non-ICU patients with new pulmonary infiltrates compared to non-immunocompromised. Methods A retrospective review of 447 hospitalized (immunocompromised and non-immunocompromised) patients who underwent bronchoscopy for new pulmonary infiltrates was completed between January 2022 and December 2024 in a single center tertiary care center. Data collected included demographics, immunosuppression type, and bronchoscopy results (cell count, differential, cultures, biopsies). Post-bronchoscopy management changes were also recorded. Multivariate logistic regression was used to correlate immunosuppression subtypes to diagnostic yield and management impact. Results The overall positivity rate for significant findings was 46% (n = 205). 367 of 447 (82%) met criteria for immunosuppressed. The immunosuppressed positivity rate was 46% vs 45% for non-immunosuppressed (P=.43). Broken down by subtype, positivity rates were: Active immunotherapy 33%, active chemotherapy 45%, hematologic malignancy 45%, hematopoietic stem cell transplant 44%, solid organ transplant 43%, active HIV 66%, primary immunodeficiency 78%, autoimmune modulator therapy 45%, daily prednisone use >20 mg 45%. Only primary immunodeficiency was associated with a statistical higher likelihood of a positive bronchoscopy (Odds ratio 4.69; P = 0.025).The overall rate of a significant change in management as a direct result of the bronchoscopy was 26%. Immunosuppressed was 26% compared to 22% for non-immunosuppressed (p = 0.5). Broken down by subtype management change rates were: Active immunotherapy 66%, active chemotherapy 18%, hematologic malignancy 19%, hematopoietic stem cell transplant 26%, solid organ transplant 32%, active HIV 100%, primary immunodeficiency 78%, autoimmune modulator therapy 70%, and daily prednisone use >20 mg 23%. Active immunotherapy and active immunomodulator therapy were correlated with a significant change in management (OR 8.9; P = 0.02, OR 3.6; P = 0.02, respectively). Conclusions Bronchoscopy yield and management impact were similar between immunosuppressed and non-immunosuppressed hospitalized patients. However, bronchoscopy more frequently influenced management in patients receiving active immunotherapy or immunomodulators, supporting earlier diagnostic use in these populations. This abstract is funded by: None

Abstract Background Spinal cord ischemia (SCI) is an uncommon but devastating complication of Veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Peripheral femoral cannulation, while rapidly deployable, may compromise spinal cord perfusion. We report a case of thoracolumbar spinal cord ischemia presenting as paraplegia with cauda equina enhancement in a patient on femoral VA-ECMO. Case Presentation A 57-year-old man with nonischemic cardiomyopathy (EF 30%), atrial fibrillation on apixaban, and ICD (2023) suffered a witnessed out-of-hospital cardiac arrest requiring 45 minutes of CPR before return of spontaneous circulation. Peripheral femoral-femoral VA-ECMO was initiated, complicated by left femoral artery injury requiring repair. He was supported with the right axillary Impella 5.5 and listed UNOS Status 1 for heart transplantation. On ECMO day 5, the patient developed acute bilateral lower extremity weakness with preserved sensation and allodynia of the soles. Neurologic exam demonstrated flaccid paralysis below the quadriceps, consistent with a T12 motor level (ASIA C). Given his prolonged low-flow state and ECMO configuration, spinal cord ischemia was suspected. Hemodynamic augmentation and conversion of ECMO drainage from femoral to left subclavian were performed, along with corticosteroids. Following orthotopic heart transplantation on 8/8/2025, MRI of the thoracic and lumbar spine showed thickening, clumping, and enhancement of the cauda equina nerve roots without cord infarction. CSF analysis was negative for infection or inflammation, supporting an ischemic etiology. Despite rehabilitation and neuropathic pain management with pregabalin, lower extremity weakness persisted. He was discharged to inpatient rehabilitation with residual paraplegia. Discussion SCI is a rare neurological complication of femoral VA-ECMO, likely resulting from compromised spinal perfusion due to retrograde aortic flow, vascular injury, or systemic hypoperfusion during cardiac arrest. Post-ischemic cauda equina enhancement may reflect reperfusion-related breakdown of the blood-nerve barrier. Conclusion This case underscores the need for early recognition of spinal cord ischemia in ECMO-supported patients with new-onset paraplegia. Maintaining adequate mean arterial pressure, minimizing femoral arterial compromise, and early reevaluation of cannulation strategy may mitigate irreversible neurologic injury. This abstract is funded by: None

Abstract Introduction Critical aortic stenosis causing cardiogenic shock has very high mortality, particularly in patients with end-stage renal disease (ESRD) and multivalvular involvement. options for surgical aortic valve replacement (SAVR) are often limited by prohibitive perioperative risk. Transcatheter aortic valve replacement (TAVR) has emerged as a lifesaving alternative in select high-risk populations. We describe a patient with ESRD who presented in cardiogenic shock due to critical aortic stenosis (AS) and experienced dramatic reversal of left ventricular (LV) dysfunction following TAVR. Case A 62-year-old male with ESRD on peritoneal dialysis and hypertension presented with acute chest pain and dyspnea. Laboratory findings revealed elevated Troponin T (353ng/L) and Pro-BNP (70,000 pg/mL). He was admitted for non-ST elevation myocardial infarction; however, coronary angiography demonstrated no coronary artery disease. Transthoracic echocardiogram (TTE) revealed a left ventricular ejection fraction (LVEF) of 15-20%, sever global akinesis, eccentric left ventricular hypertrophy, and severe aortic stenosis (mean gradient 34 mmHg, valve area 0.53 cm²). Additional findings included severe aortic regurgitation and severe mitral regurgitation. Overnight, he developed altered mentation, cold extremities and lactic acidosis (14.5 mmol/L), Pulmonary artery catheter readings were consistent with cardiogenic shock. Repeat TTE redemonstrated critical aortic stenosis (peak velocity 5.3 m/s, mean gradient 71 mmHg, valve area 0.73 cm²). An urgent TAVR was performed with deployment of a 26 mm Edwards Sapien 3 pericardial prosthesis. A post-procedure TTE demonstrated LVEF improvement to 50-55%, with only mild residual LV hypokinesis. The patient showed rapid clinical recovery and was weaned off inotropes. Discussion Severe aortic stenosis imposes a fixed obstruction to left ventricular outflow, leading to excessive afterload and secondary systolic dysfunction. The rapid improvement in ejection fraction following TAVR supports the concept of afterload-induced myocardial stunning rather than irreversible cardiomyopathy. Although TAVR was traditionally avoided in unstable or shock patients, particularly those with ESRD, growing evidence supports its use as a rescue therapy in carefully selected cases. By reducing afterload, TAVR restores forward cardiac output, enhances coronary perfusion, and can reverse shock. Emerging registry data demonstrates that patients with severe AS and cardiogenic shock can achieve meaningful recovery following TAVR when performed expeditiously. This case underscores the expanding role of TAVR in managing cardiogenic shock due to severe valvular disease. The magnitude of left ventricular recovery in this case underscores the reversibility of left ventricular dysfunction once the mechanical obstruction is relieved, it highlights the importance of early recognition and intervention before irreversible myocardial remodeling occurs. This abstract is funded by: NA

Abstract Primary Ciliary Dyskinesia (PCD) is a rare, genetically heterogenous disorder of motile cilia, leading to impaired mucociliary clearance and chronic respiratory disease. Its clinical presentation often overlaps with common conditions, including obstructive pulmonary diseases, contributing to diagnostic delays. Mutations in the DNAH11 gene are associated with PCD, but patients frequently lack the classic ultrastructural ciliary defects. We present a case which highlights the importance of considering rare ciliopathies in patients with refractory respiratory symptoms and the evolving role of genetic testing in diagnosis. A 44-year-old woman with early onset asthma was referred for evaluation of recurrent pneumonias, occurring biannually in recent years. She had been affected by respiratory disease since childhood. Despite aggressive asthma management, including long-term mepolizumab, she reported frequent pneumonias and persistent respiratory symptoms. Pulmonary function tests demonstrated obstructive physiology with bronchodilator responsiveness. Chest CT revealed diffuse cylindrical bronchiectasis, small airway disease, and a tree-in-bud pattern. Initial genetic testing identified heterozygous variants in DNAH11 and AP3D1. Whole genome sequencing later revealed a maternally inherited, likely pathogenic, DNAH11 variant and a paternally inherited variant of uncertain significance (VUS), suggesting a compound heterozygous state. Although not definitively diagnostic, this genetic profile, combined with lifelong respiratory symptoms, and imaging findings, raised strong clinical suspicion for PCD. She was treated targeting both asthma and PCD. Her regimen included a combination inhaler of fluticasone, umeclidinium, and vilanterol, as-needed albuterol, mepolizumab, and the addition of airway clearance focused techniques, including nebulized hypertonic saline, flutter valves, and chest physiotherapy. She demonstrated significant symptomatic improvement and a dramatic reduction in pneumonias or exacerbations. This case underscores the diagnostic complexity of chronic respiratory disease in young adults. PCD should be considered in patients with early-onset, persistent respiratory symptoms and recurrent infections, particularly when standard asthma therapies fail. DNAH11 mutations are known to cause PCD, often without detectable ciliary ultrastructural abnormalities, making diagnosis reliant on clinical features, nasal nitric oxide levels, high-speed video microscopy, and genetic testing. Compound heterozygosity involving a pathogenic variant and a VUS, as seen in this case, is not definitively diagnostic per current ATS/ERS guidelines, but may support a clinical diagnosis when aligned with phenotype and imaging findings. This case illustrates the importance of a multidisciplinary approach, including pulmonology, allergy, genetics, and immunology, in evaluating complex respiratory presentations. Early recognition and tailored therapy, including airway clearance and infection prevention, are critical to improving patient outcomes and quality of life in patients with suspected PCD. This abstract is funded by: None

Abstract Rationale Glucagon-like peptide 1 (GLP-1) receptor agonists are novel antihyperglycemic drugs that have shown benefit in various disease states, namely in cardiovascular and renal disease. GLP-1 agonists in murine models of obstructive lung diseases have been shown to decrease airway inflammation and hyperresponsiveness. In humans, some observational studies show an association between GLP-1 agonist use and reduced exacerbations of chronic obstructive pulmonary disease (COPD). In a meta-analysis, GLP-1 agonist use decreased the risk of several respiratory disorders including bronchitis (3). Bronchiectasis is another chronic airway disease, characterized by abnormal airway dilation leading to impaired mucous clearance and increased risk of infection (4). Data on the association between GLP-1 agonist use and bronchiectasis is sparce. We, therefore, examined the effects of GLP-1 agonists on the mortality of patients with bronchiectasis in a large sample size. Methods In this retrospective case control study, we identified patients with bronchiectasis from a single-center database of patients at our institution. We identified patients with bronchiectasis who received a GLP-1 agonist and compared them to patients who never received a GLP-1 agonist. Data was displayed as median with interquartile range and a Kaplan-Meier curve was used for mortality analysis. Results We identified a total of 256,777 patients with bronchiectasis. Of these, 249911 patients with bronchiectasis had not received a GLP-1 agonist and 6866 patients had received a GLP-1 agonist. The median age for patients in the GLP-1 group was 63 vs. 64 for the control group. 54.5 % of patients in the GLP-1 group were female compared to 52.9% in the control. Patients who received a GLP-1 agonist had improved survival at 1 month (99.9% for the GLP-1 group vs. 98.7% for the control group), 5 months (98.9% for the GLP-1 group vs. 95.9% for the control group), 10 months (97.9% for the GLP-1 group vs. 93.5% for the control group), 30 months (91.9% for the GLP-1 group vs. 86.8% for the control group) and 60 months (81.8% for the GLP-1 group vs. 79.3% for the control group), p < 0.001, Hazard ratio 0.56 (95% CI 0.50 - 0.62). Conclusion Our study showed that GLP-1 agonists are associated with improved survival in patients with bronchiectasis. Several mechanisms may contribute to this effect, including weight loss and reduction of cardiovascular mortality. Further studies are needed to investigate GLP-1 agonists as a potential therapeutic option for bronchiectasis, and to elucidate the mechanisms behind this association. This abstract is funded by: none

Abstract Hairy cell leukemia (HCL) and HCL variant (HCLv) are distinct, rare, and chronic splenic B-cell lymphomas/leukemias that partially overlap in clinicopathologic presentation but differ in genetic basis, prognosis, and management. HCL is caused by the BRAF-V600E kinase–activating mutation in >95% of the patients, usually has excellent responses to chemotherapy with purine analogues, and is also amenable to BRAF inhibitor–based targeted treatments. In contrast, HCLv lacks BRAFV600E mutation, requires combined therapy with purine analogues in addition to rituximab, and generally shows less durable responses. Here, an international team of hematologists, experts on these rare diseases, was convened by the Hairy Cell Leukemia Foundation to update the previous guidelines (published in 2017) by providing a summary of current methods to diagnose and manage patients with HCL and HCLv as well as a prospective on newer targeted therapies to further improve outcomes.

Abstract Prognostic indices such as the CLL International Prognostic Index (CLL-IPI) and the International Prognostic Score for Early-stage CLL (IPS-E) can predict time to first treatment (TTFT) in patients with early-stage CLL. Their ability to predict risk of infection - a leading contributor to morbidity and mortality in CLL - remains uncertain. The CLL-TIM is a machine-learning model developed in Europe that integrates clinical, laboratory, and infection-related data to predict TTFT or infection risk within 2-years of diagnosis, Receiver Operating Characteristic - Area Under the Curve (ROC-AUC) 0.74; Agius et al., Nat Comm 11, 363 2020. We conducted the first validation of CLL-TIM in a US cohort of newly diagnosed CLL patients and compared its performance with the CLL-IPI and IPS-E indices. Adults with newly diagnosed CLL (2000-2020) were identified through the Rochester Epidemiology Project using International Classification of Disease (ICD) codes; all diagnoses were confirmed. We replicated the variable selection from the original CLL-TIM model and applied it to our cohort. The primary endpoint was a 2-year composite of either TTFT or incident infection (defined as having blood cultures drawn). Model performance was evaluated using ROC-AUC consistent with the original CLL-TIM methods. CLL-IPI and IPS-E performance was assessed using time-dependent ROC-AUC; pairwise differences in discrimination were tested using DeLong. We identified 454 CLL patients with a median age of 72 years [range, 30-97], 166 (37%) were female, Rai Stage was 0-II in 399 (92%) patients. IGHV genes were unmutated in 130/305 (42%) patients and TP53 disruption (either del17p by FISH or TP53 mutation) was present in 24/329 (8%) patients. At 2-years, 55 (12%) patients received CLL therapy, and 56 (12%) patients had an infection. The 2-year composite endpoint was observed in 94 (21%) patients. The ROC-AUC was 0.74 (95% CI 0.68-0.80) for CLL-TIM, 0.69 for CLL-IPI (95% CI 0.63-0.75, p=0.11 compared to CLL-TIM) , and 0.68 for IPS-E (95% CI 0.62-0.74, p=0.02 compared to CLL-TIM). We also evaluated the ROC-AUC using all the prognostic models for each individual endpoints. The corresponding ROC-AUC for TTFT at 2 years were 0.79, 0.74, and 0.76 for CLL-TIM, CLL-IPI, and IPS-E, respectively; and for infection at 2 years were 0.68, 0.57, and 0.52, respectively. This is the first validation of the CLL-TIM in a US-based cohort of newly diagnosed CLL patients. Although the CLL-TIM model exceeded the minimally meaningful discrimination threshold (AUC >0.7) for individual patient-level risk prediction, there was no statistical difference in AUC between CLL-TIM and CLL-IPI, suggesting either model can predict the composite endpoint at 2 years. Most of the observed discrimination was driven by prediction of TTFT rather than infection, underscoring the need to develop more infection-specific risk models for newly diagnosed CLL. Citation Format: Raphael Mwangi, Tait D. Shanafelt, Soren Basnet, Emily L. West, Owen Keegan, Timothy G. Call, Yao Yuan, Bryan Alexis Vallejo, Paul J. Hampel, Lindsey E. Roeker, Yucai Wang, Saad J. Kenderian, Sara J. Achenbach, Aaron D. Norman, Kari G. Rabe, Neil E. Kay, James R. Cerhan, Curtis A. Hanson, Susan L. Slager, Sameer A. Parikh. Validation of the CLL treatment infection model (CLL-TIM) in patients with newly diagnosed chronic lymphocytic leukemia (CLL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4228.

Introduction/Objectives: House call programs provide care for homebound patients. We conducted a case-control study to compare hospitalization and/or emergency department (ED) use by patients enrolled in a primary care house call program versus ambulatory (community-dwelling) patients. Methods: Program enrollees (cases) were matched by age and self-reported gender to community-dwelling patients (controls). The primary exposure was the combination of hospitalization and/or ED visits for 1 year before the index date (October 1, 2024). We used unadjusted and adjusted conditional logistic regression to determine differences in health care use. Results: We identified 26 cases (median [range] age, 84 [66-98] years; 16 [62%] female) and 130 controls. All cases had 4 or more chronic diseases, as compared with 87 (67%) of controls ( P = .003). A higher proportion of cases than controls had previous hospitalization and/or ED visits (84.6% vs 27.7%; P < .001). After adjusting for the number of chronic illnesses, no differences in previous hospitalization and/or ED use were identified between groups. Conclusions: Cases had more chronic illnesses and more hospitalizations and/or ED visits than community-dwelling controls. The comorbid health burden of participants in the house call program drove greater health care use and justifies a higher level of care for this medically complex patient population.