Citations

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 Introduction Burkholderia, Achromobacter, and Stenotrophomonas species are associated with worse clinical outcomes in cystic fibrosis (CF),1 though little is known about their prevalence or pathogenicity in non-CF bronchiectasis (pwBE). Herein we describe the prevalence and clinical characteristics of pwBE who isolated each of these three organisms. Methods We conducted a retrospective cross-sectional analysis of baseline data from the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR). Adult bronchiectasis patients with known Achromobacter, Burkholderia cepacia complex (BCC), or Stenotrphomonas maltophilia culture results were included. Patients were stratified according to the presence of at least one positive culture among the gram-negative species. Demographics, clinical characteristics, and first annual follow-up culture results were summarized descriptively for the overall study population and between groups. No inferential analyses or hypothesis testing was performed. Results 5003 pwBE met the inclusion criteria, of which 39 (0.78%) isolated Achromobacter species, 11 isolated Burkholderia (0.22%), and 288 isolated Stenotrophomonas maltophilia (5.8%). Patients with Achromobacter were older, with a median age (interquartile range) of 76 (73.0-79.0) years, compared to the overall bronchiectasis cohort (69.0 years). Those with Burkholderia or Stenotrophomonas were younger, at 69.0 (53.0-75.0) and 71.0 (63.0-77.0) years, respectively. A high proportion of those with Achromobacter were male (31%) versus those with Burkholderia (9%) and Stenotrophomonas (24%), were current or former smokers (46%), were more likely to have had one or more exacerbations in the 2 years prior to enrollment (87%) than the overall BE cohort (57%), and were more likely to have had pulmonary-related hospitalization than those with either Burkholderia or Stenotrophomonas (46% vs. 27% and 19%, respectively). PwBE who isolated Burkholderia were less likely to have co-colonization with Pseudomonas aeruginosa or NTM species (9% each). At first annual follow-up, no patients with baseline Burkholderia isolated them at follow-up, and only 31% with baseline Stenotrophomonas isolated it at follow-up. Conclusion Overall prevalence of Achromobacter, Burkholderia, and Stenotrophomonas species in the BE cohort was low. Patients who isolated Achromobacter species were older, more likely to be current or former smokers, and more likely to experience pulmonary exacerbation and hospitalization. 15 patients who had not previously isolated Achromobacter, and 3 patients who had not previously isolated Burkholderia did so at annual follow-up. Interestingly, no patients with baseline Burkholderia isolates went on to isolate it at annual follow-up, which contradicts earlier studies in pwCF.2 The number of patients isolating Burkholderia in the U.S. BRR is very low, thereby limiting interpretation. This abstract is funded by: None

Abstract Introduction Aminoglycoside antibiotics are well known to cause cochlear and vestibular toxicity when used systemically. Inhaled tobramycin was developed to reduce systemic exposure and is considered safer with only rare reports of ototoxicity have been reported in patients with renal dysfunction. We describe a case of bilateral sensorineural hearing loss (SNHL) and tinnitus associated with inhaled tobramycin in a patient without renal impairment, emphasizing that even inhaled formulations can induce significant auditory toxicity in susceptible individuals. Case A 85 year old woman with Sjogren’s related interstitial lung disease and bronchiectasis who was chronically colonized by Pseudomonas aeruginosa was treated with inhaled tobramycin for recurrent infections. She had normal renal function and no prior aminoglycoside exposure. After approximately three months of inhaled therapy, she noted progressive bilateral hearing decline and high pitched tinnitus without vertigo or otalgia. Physical examination revealed clear ear canals and intact tympanic membranes. Baseline audiometry one year ago had demonstrated mild to moderately-severe bilateral SNHL. Repeat testing after tobramycin exposure showed worsening thresholds and reduced word recognition bilaterally. MRI of the brain and internal auditory canals was unremarkable. Serum creatinine remained normal throughout treatment. Inhaled tobramycin was discontinued, after which hearing loss stabilized. No further progression was observed on follow-up audiometry. Discussion Although systemic absorption from inhaled tobramycin is typically low, elderly and low-body-weight patients may accumulate sufficient serum levels to cause cochlear injury. Mechanisms include reactive oxygen species mediated hair cell toxicity and possible genetic susceptibility involving the mitochondrial 12S rRNA mutation. Prior reports of vestibulotoxicity and cochleotoxicity from inhaled tobramycin primarily involved patients with renal dysfunction, however, this case report demonstrates that toxicity can occur despite preserved renal function. Clinicians should maintain vigilance for otologic symptoms in patients receiving inhaled aminoglycosides. Baseline and periodic audiometric monitoring should be incorporated into chronic treatment protocols. This abstract is funded by: None

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 Gastroesophageal reflux disease (GERD) is a common comorbidity in non-cystic fibrosis bronchiectasis (NCFB), yet its impact on clinical outcomes remains poorly defined. We sought to determine whether GERD is associated with worse clinical outcomes in patients with NCFB using a large, real-world database. Methods We conducted a retrospective cohort study using the TriNetX platform, identifying patients with NCFB (ICD-10 J47*) with and without concurrent GERD (ICD-10 K21*), excluding those with cystic fibrosis (ICD-10 E84*). Propensity score matching (PSM) was performed using 1:1 nearest neighbor matching without replacement, controlling for age, sex, race/ethnicity, obesity, socioeconomic risk factors, and tobacco use. Primary outcomes included pneumonia, bronchiectasis exacerbations, intensive care unit admission, mechanical ventilation, and mortality. Statistical analyses included risk ratios and Cox proportional hazards modeling for survival outcomes. Results Out of 421,710 patients with NCFB in the dataset from January 2000 to September 2025, 186,874 (44%) had a diagnosis of GERD. After propensity score matching, 179,753 patients with NCFB+GERD and 179,753 patients with NCFB-only were included (mean age 74.0±13.1 years, 58.8% female, 67.1% White). Baseline characteristics were well-balanced after matching. Median follow-up was approximately 2.5 years for both cohorts (898 vs 889 days; similar means and IQR), ensuring balanced observation time. Compared to NCFB-only, NCFB+GERD was associated with increased risks for mortality (risk ratio 1.04, 95% CI 1.02-1.05; p < 0.001), pneumonia (risk ratio 1.06, 95% CI 1.05-1.08; p < 0.001), bronchiectasis exacerbations (risk ratio 1.03, 95% CI 1.01-1.06; p = 0.006), and mechanical ventilation (risk ratio 1.14, 95% CI 1.10-1.18; p < 0.001). Intensive care unit admission rates were comparable between groups (risk ratio 1.00; p = 0.65). Conclusions In this large propensity score-matched analysis, concurrent GERD in NCFB is independently associated with increased mortality, pneumonia, bronchiectasis exacerbations, and mechanical ventilation requirements. These findings suggest GERD may represent a modifiable risk factor warranting aggressive management in NCFB patients. Study limitations include retrospective design, reliance on ICD-10 coding accuracy, and potential unmeasured confounders. Our results support systematic screening and treatment of GERD in NCFB, but whether targeted GERD management can modify the natural history of NCFB future investigation. This abstract is funded by: None

Abstract Background Sputum color is a visual marker of airway inflammation and disease activity in bronchiectasis, ranging from clear or light gray (mucoid) to yellow-green (purulent), the latter largely reflecting neutrophil myeloperoxidase release. This study evaluated associations between sputum color and common clinical markers of disease activity to determine which parameters differed most between color categories. Methods Forty spontaneous sputum samples were analyzed from 80 consecutive adults with non-cystic fibrosis bronchiectasis (median age 70 years [IQR 12]; 74% female) enrolled between January 2024 and April 2025 in an observational study. Sputum color was graded using the Murray Sputum Color Chart and classified as mucoid (color #1) or purulent (colors #2-4). Clinical parameters, including blood cell counts, C-reactive protein (CRP), fractional exhaled nitric oxide (FeNO), and results of bacterial and acid-fast bacillus cultures (induced or bronchoscopic), were obtained from medical records if available within one month of enrollment. Categorical variables were analyzed using chi-square or Fisher’s exact tests and continuous variables with the Mann-Whitney U test. A secondary analysis compared patients who could versus could not produce spontaneous sputum. Results Of 40 samples, 20 (50%) were purulent. Blood neutrophil counts (median 4.5 vs. 3.9 x109/L), neutrophil-to-lymphocyte ratios (2.5 vs. 2.6), and eosinophil counts (1.7 vs. 1.7 x109/L) did not differ significantly between groups (n = 26). FeNO was normal in all 10 patients with available data and was not analyzed further. CRP was higher among patients with purulent sputum (4.6 vs. <3 mg/L; n = 20; p = 0.044). Bacterial growth was more frequent in purulent than mucoid samples (73% vs. 31%; n = 31; p = 0.032). Isolates in the purulent group included Klebsiella, Pseudomonas, Staphylococcus, and Streptococcus (n = 2 each), and single isolates of Acetobacter, Acinetobacter, Chryseobacterium, Delftia, Enterobacter, Escherichia, and Moraxella. In the mucoid group, Pseudomonas, Staphylococcus (n = 2 each), and Stenotrophomonas (n = 1) were identified. Mycobacterial growth did not differ significantly (20% vs. 12.5%; n = 31; p = 0.65). Patients unable to produce spontaneous sputum had a higher rate of mycobacterial isolation on induced/bronchoscopic samples (43% vs. 16%; n = 54; p = 0.027), though other parameters were similar. Over 90% of measurements were obtained within three days of enrollment, and freezing did not appear to alter sputum color. Conclusions Even within a small cohort, purulent sputum was associated with higher CRP and greater bacterial growth, supporting sputum color as a rapid, inexpensive marker of disease activity in bronchiectasis. Further research should clarify whether sputum color primarily reflects bacterial colonization, airway inflammation, or both. 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 Rationale Bronchopulmonary dysplasia (BPD) is a chronic lung disease that significantly affects premature infants, leading to impaired lung development, inflammation, and fibrosis due to sustained exposure to high oxygen levels in the Neonatal Intensive Care Unit (NICU). In BPD, airway narrowing and hyperreactivity are common, making bronchodilation beneficial. Caffeine, a respiratory stimulant typically used for apnea of prematurity, also has bronchodilatory properties. This study investigates caffeine’s impact on airway remodeling (fibrosis and cellular proliferation) in fetal airway smooth muscle cells (fASMs) exposed to mild hyperoxic stress. By inhibiting phosphodiesterase, caffeine increases cyclic adenosine monophosphate (cAMP) levels, thereby relaxing airway smooth muscle. Caffeine’s influence on calcium (Ca2+) kinetics is essential for muscle contraction and relaxation. The goal is to better understand caffeine’s therapeutic role in bronchodilation and reducing fibrosis and proliferation in BPD. Methods Ca2+ imaging, proliferation assay, and immunofluorescence imaging (IF) were performed. fASMs were exposed to normoxia (21% O2) or mild hyperoxia (∼40% O2) for 48 hours, with or without caffeine treatment. Results Acute caffeine exposure (25 mM) decreased Ca2+ amplitude (corresponding to a dilatory effect) after addition of acetylcholine (10 μM) in normoxia. Caffeine treatment reduced cell proliferation in both normoxic and hyperoxic groups. Caffeine decreased both Ki67 (marker of proliferation) and Col1a1 (marker of fibrosis) protein expression under hyperoxic conditions. Conclusions Caffeine influences Ca2+ signaling, reduces cell proliferation and fibrosis, and, thus, may modulate airway remodeling and hyperreactivity under hyperoxic stress, suggesting its potential as a therapeutic strategy for BPD. This abstract is funded by: NIH R01 HL56470, R01 HL177837

Abstract Rationale Long COVID (LC) has affected approximately 400 million people worldwide, with about 20 million in the US. LC is characterized by a host of new symptoms, including neuropsychiatric disorders including cognitive impairment. Disruption of the gut microbiome has been correlated with symptoms of LC. This study examined whether gut microbiome modulation via intake of probiotic fermented foods mitigated psychiatric and cognitive impairments. Methods This was a pilot trial performed at a single academic medical center that enrolled and randomized patients with LC 1:1 into the treatment vs. control arm. Those enrolled into the treatment arm received teaching on the gut microbiome, its relationship to LC, and were encouraged to eat a diet high in probiotic fermented foods for 12 weeks. Those in the control arm did not receive the teaching and were encouraged to eat their normal diet. Diets were tracked using the Mayo Clinic Diet application on a smart phone at least three days per week, and those in the treatment arm received routine calls to discuss protocol adherence and gather subjective feedback on the trial. Neuropsychiatric questionnaires (HADS, IES-R, EQ-5D-5L, and MoCA Blind) were completed at enrollment and upon completion of the trial. Questionnaire scores were evaluated for changes using a paired t-test, with statistical significance defined as a p-value <0.05. Correlation between the fermented food intake and improvements in questionnaires was completed using the Spearman test. Results 43 patients were enrolled; 18 patients in the treatment arm and 20 patients in the control arm completed the trial. Groups did not differ by age, race, education, or baseline neuropsychiatric testing. There was a significant increase in fermented food intake in the treatment arm over the duration of the study. Those in the treatment arm had improvements in questionnaires related to anxiety, PTSD, and quality of life. Those in the control arm only had improvements in reported overall quality of life. Intra-group changes can be seen in Table 1. Correlations between fermented food intake and change in questionnaire scoring showed numerical but not statistically significant improvements in many of the questionnaires, except for the MOCA questionnaire and EQ-5D-5L Self-Care question. Conclusion Implementing a diet high in fermented foods in patients with LC appears to have some signal for improvement in neuropsychiatric symptoms. Completing a larger trial would help clarify if changes would be statistically significant. This abstract is funded by: Mayo Clinic Critical Care Research Committee