Citations

Abstract Rationale Pulmonary hypertension (PH) develops in up to 50% of patients with advanced interstitial lung disease (ILD) and is associated with increased morbidity, mortality, and impaired quality of life. Early recognition is essential, as available therapy for ILD-PH has been shown to improve outcomes. Identifying physiologic markers of PH may facilitate earlier referral for right heart catheterization (RHC) and initiation of targeted treatment. Thus, this study aimed to (1) compare functional parameters between ILD patients with and without RHC-confirmed PH, and (2) assess the applicability of previously proposed ILD-PH screening criteria. Methods We retrospectively analyzed ILD transplant candidates with available pre-transplant pulmonary function tests (FVC%, DLCO%), echocardiographic right-ventricular systolic pressure (RVSP), six-minute walk distance (6MWD) with oxygen requirement, and RHC data. PH was defined according to the 2022 ESC/ERS criteria. Functional parameters were compared between patients with and without PH. Among those without a prior PH diagnosis, screening thresholds derived from previously published tools were applied (RVSP ≥ 35 mmHg, DLCO < 40%, FVC/DLCO > 1.6, 6MWD < 350 m, or oxygen use during 6MWD). Results Of 107 ILD patients evaluated, 90 had complete RHC data (48 ILD-PH, 42 ILD without PH). Group comparisons are summarized in Table 1. Patients with PH had lower DLCO% (median 18.5 [11.5-26.7] vs 26.5 [20.0-34.7], p = 0.08), higher FVC/DLCO ratios (2.68 [2.1-3.4] vs 1.7 [1.4-2.6], p = 0.08), and higher RVSP (55 [39.7-63.2] vs 39.5 [29-48] mmHg, p = 0.002). Oxygen requirement during 6MWD was more frequent in ILD-PH (79.2% vs 61.9%, p = 0.08). Among patients with PH, 38 (79.16%) had no formal diagnosis prior to pre-transplant RHC. Of these cases, all (100%) met ≥3 screening criteria, most commonly DLCO < 40% (n = 38, 100%), FVC/DLCO > 1.6 (n = 37, 97.3%), and 6MWD < 350 m (n = 33, 86.8%). Additionally, 32 patients (84.21%) met ≥4 criteria and 8 (21.05%) met all five criteria. Conclusion In ILD transplant candidates, patients with PH had worse functional profiles when compared to those without PH, and nearly 80% of PH cases were previously undiagnosed. Systematic application of validated PH screening tools in ILD populations may facilitate earlier recognition, potentially improving patient outcomes. This abstract is funded by: None

Abstract Rationale Endobronchial valve (EBV) placement is an established bronchoscopic lung volume reduction (BLVR) therapy for advanced emphysema. Although randomized trials have shown improvements in lung function, real-world data on predictors of response and complications remain limited. This study evaluated physiological and clinical outcomes after EBV placement and explored predictors of treatment response and adverse events. Methods We retrospectively analyzed 75 patients who underwent EBV placement for severe emphysema at Mayo Clinic Florida between 2018 and 2023. Demographics, comorbidities, pulmonary function test and complications data were collected before and after procedure. Responders were defined as those achieving a ≥ 15% relative increase in forced expiratory volume in one second (FEV1), ≥10% reduction in residual volume (RV), ≥25-meter increase in six-minute walk distance (6MWD), or ≥ 1-point decrease in modified Medical Research Council (mMRC) dyspnea score. Results The mean age was 70.4 ± 7.1 years, 59% were female, and the mean Body Mass Index was 25.6 ± 4.9 kg/m². Most patients were non-Hispanic White (96%) and ever-smokers (97%, median 40 pack-years). Following EBV placement, FEV1 increased by + 0.10 L (p < 0.001), forced vital capacity by + 0.17 L (p = 0.001), RV decreased by -0.69 L (p < 0.001), while total lung capacity decreased by -0.35 L (p < 0.001). Diffusing capacity, 6MWD, and mMRC did not significantly change. Responder analysis showed FEV1 improvement in 52% (34/65), RV reduction in 65% (42/65), 6MWD gain in 33% (18/55), and mMRC improvement in 33% (21/63). Complete lobar atelectasis occurred in 59% (44/75) and was significantly associated with FEV1 improvement (p < 0.01). 30-day follow up complications included pneumothorax (26.7%), COPD exacerbation (21%), and pneumonia (20%). 15% pneumothoraces were managed conservatively, 55% required chest tube, 30% needed valve removal due to persistent air leak. Valve migration and replacement occurred in 2.6% each, and valve removal in 26.6% patients. Median hospital stay was longer in patients with complications (5 vs 4 days, p = 0.003). In-hospital mortality was 5.3% but no procedure-related deaths were identified. Conclusions EBV placement is a safe and effective BLVR approach yielding significant improvements in FEV1 and reductions in hyperinflation. Pneumothorax and valve-related events were the most frequent complications. Complete lobar atelectasis strongly correlated with functional improvement, suggesting that early reassessment should be considered when collapse is not achieved to prevent complications and unnecessary valve retention. This abstract is funded by: None

Abstract Rationale Treatment of hematologic malignancies has been revolutionized by Chimeric antigen receptor T -cell (CAR-T) therapy. Pulmonary complications are increasingly being reported, however, there are no standardized timelines for pulmonary function test (PFTs) assessment before or after the infusion. We aimed to evaluate changes in lung function (TLC, RV, FEV1, and FEV1/FVC) pre- and post-CAR-T therapy and examine whether these parameters correlate with the development of specific pulmonary complications. Methods We conducted a retrospective chart review of patients above the age of 18 with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Pre-CAR-T PFTs were obtained closest to the infusion date, and post-CAR-T PFTs were recorded at the earliest available time following infusion. Pre- and post-CART pulmonary function tests were compared using non-parametric paired tests. In addition, we examined the relationship between baseline PFTs and the subsequent occurrence of pulmonary complications after CAR-T infusion. The Wilcoxon signed-rank test was applied to assess both the magnitude and direction of change while Sign test was used to evaluate only the direction to confirm the consistency of results. These tests were chosen due to small sample size and non-normal distribution of data. Results Among the 68 patients in our cohort, paired pre- and post- CAR-T measurements of pulmonary function were available for 18 patients. FEV1 declined significantly post-infusion (2.70 ± 0.81 L vs 2.28 ± 0.74 L; Z= -2.55, p = 0.011), the FEV1/FVC ratio remained stable (77.8 ± 8.0 vs 80.9 ± 12.2, p = 0.53). Mean TLC and RV remained stable (TLC 5.70 ± 1.18 L vs 4.66 ± 1.02 L, p = 0.17 and 2.13 ± 0.62 L vs 2.00 ± 0.70 L, p = 0.58). There was no significant correlation between the baseline lung function and the development of pulmonary complications. Conclusion Only the pattern of FEV1 decline following CAR-T therapy infusion demonstrates a significant decline, whereas other PFTs, although reduced, did not show significance. While these findings may suggest a restrictive ventilatory pattern, additional data on lung volumes are required to accurately characterize the underlying type of pulmonary function impairment. Although limited by small sample size and non-uniform timing of PFT assessments, this highlights the need for a routine pre-CAR-T pulmonary function evaluation to inform patient selection and baseline risk stratification. This abstract is funded by: None

Abstract RATIONALE There are limited studies evaluating the association between chimeric antigen receptor T-cell (CAR-T) therapy and interstitial lung abnormalities (ILA). Our study aims to investigate this potential relationship to better understand pulmonary complications following CAR-T therapy. Methods We conducted a retrospective chart review of patients aged 18 or older with any malignancy who received CAR-T therapy between June 12, 2018, and December 26, 2023. Chest imaging, including PET or CT scans, was reviewed for each patient; the closest scan before CAR-T therapy and the most recent scan afterward. We identified ILA based on findings that included ground-glass opacities, reticular abnormalities, traction bronchiectasis, honeycombing, or non-emphysematous cysts involving more than 5% of lung zones. We excluded dependent atelectasis, paraspinal fibrosis, aspiration-related changes, mild focal or unilateral abnormalities, and smoking-related centrilobular nodularity without other findings. Results A total of 66 patients had adequate imaging data both before and after CAR-T infusion. Before therapy, 17 patients (25.8%) demonstrated ILA, while 49 (74.2%) did not. Following CAR-T therapy, the overall prevalence of ILA increased to 31 patients (47.0%). Among those who did not have ILA before CAR-T, 16 of 49 (32.7%) developed new ILA following therapy. Conversely, among those with pre-existing ILA, 14 of 17 (82.4%) showed persistent or progressive ILA post-CAR-T. This distribution demonstrated a statistically significant association between pre- and post-CAR-T ILA status (χ² = 10.8, p = 0.001), indicating that pre-CAR-T ILA status strongly predicted post-CAR-T ILA persistence or worsening. When evaluating post-CAR-T ILA in relation to clinical outcomes, among those with pre-CAR-T ILA, 52.9% (n = 9) were deceased at follow-up, compared to 55.1% (n = 27) among patients without ILA. The difference in mortality between the groups was not statistically significant (χ² = 2.34, p = 0.31). 19 of 31 patients (61.3%) with post-CAR-T ILA were deceased at last follow-up, compared with 17 of 37 (45.9%) in those without ILA. Although mortality was numerically higher among patients with post-CAR-T ILA, this difference did not reach statistical significance (χ² = 1.04, p = 0.308). Conclusion Our study demonstrates a statistically significant association between pre- and post-CAR-T interstitial lung abnormalities, suggesting that CAR-T therapy may contribute to the progression or development of ILAs. These findings highlight the need for closer pulmonary monitoring during CAR-T treatment. This abstract is funded by: None

Abstract Summary A retrospective cohort study of 113,729 IBD patients with low cardiovascular (CV) risk using the US National TriNetX database. Anti-TNF and anti-integrin therapies were linked to reduced major adverse cardiovascular events (MACE), while JAK inhibitors showed no increased risk. Background Due to underlying chronic inflammation, inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). There is limited data on the role of cardiovascular (CV) risk factors and IBD medications on MACE. We aim to determine the association between MACE and IBD medications in a large national cohort of IBD patients with low baseline CV risk. Methods We conducted a retrospective cohort study between January 1, 2015—November 15, 2023 using the TriNetX database. Using logistic regression analysis, IBD patients exposed to biologics and small molecules were assessed for outcomes of individual and composite MACE [myocardial infarction (MI), ischemic stroke, percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG)]. Outcomes were adjusted for demographics, non-advanced IBD therapies, statin use, CV risk factors, and prior history of coronary artery disease (CAD). Results We identified 113,729 IBD patients with an average age of 42 years and low prevalence of CV risk factors (5-6%). Anti-TNF therapy was associated with a statistically significant decreased risk of composite MACE [adjusted OR (aOR) 0.795, 95% CI 0.670-0.930, p = 0.005] and PCI/CABG [aOR 0.56, 95% CI 0.274-0.562, p = 0.002] and anti-integrin therapy was associated with a decreased risk of composite MACE [aOR 0.76, 95% CI 0.580-0.980, p = 0.035]. Anti-IL12/23 and JAK inhibitors showed no increased risk of MACE. Conclusion In a cohort of young IBD patients with low CV risk, use of anti-TNF and anti-integrins is associated with a decreased risk of MACE and there was no increased risk of MACE with JAK inhibitors.

Importance Transcatheter tricuspid valve replacement (TTVR) demonstrated superior outcomes over medical therapy in patients with severe tricuspid regurgitation (TR) in the Edwards EVOQUE Transcatheter Tricuspid Valve Replacement: Pivotal Clinical Investigation of Safety and Clinical Efficacy Using a Novel Device II (TRISCEND II) randomized clinical trial, and received regulatory approval in the US in 2024. Contemporary real-world data on its effectiveness and safety remain limited. Objective To evaluate 30-day clinical, echocardiographic, and health status outcomes of TTVR in real-world use. Design, Setting, and Population Retrospective cohort study of all consecutive patients who underwent TTVR in the US from February 2024 through March 2025 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients had symptomatic, severe TR despite optimal medical therapy and TTVR was deemed appropriate by a heart team. Statistical analysis was conducted from September 2025 to February 2026. Exposure Device-enabled TTVR. Main Outcomes and Measures Thirty-day event rates (all-cause death, stroke, bleeding, new cardiac implantable electronic device [CIED] implantation, heart failure hospitalizations), TR reduction, and changes in health status (New York Heart Association [NYHA] functional class and Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS] score) are reported. Subgroup analyses examined the impact of baseline CIED status on outcomes. Results Among 1034 attempted procedures at 82 centers (mean [SD] age, 77.1 [10.6] years; 69.1% female; 73.2% NYHA functional class III/IV), a valve was successfully implanted in 1017 patients (98.4%). Mild or less TR was achieved in 98.4% of patients post procedure and in 97.7% at 30 days. At 30 days, all-cause mortality was 3.1%; stroke, 0.2%; bleeding, 7.9%; new CIED, 15.9% in CIED-naive patients; and heart failure hospitalization, 3.1%. There were significant improvements in NYHA functional class (class I/II, 82.7%; P < .001) and mean KCCQ-OS score (22.4 points; P < .001) from baseline to 30 days. There were no significant differences in 30-day mortality ( P = .47), heart failure hospitalization ( P > .99), and functional outcomes ( P = .55) when patients were stratified by baseline CIED status. Conclusions and Relevance Early US real-world experience with TTVR confirms safety and effectiveness in patients with severe TR. Thirty-day outcomes are consistent with the TRISCEND II pivotal trial, demonstrating acceptable safety, near-complete TR elimination, and significant health status improvements in an older, comorbid population. Rates of new CIED implantation and bleeding were lower than randomized clinical trial experience.

Abstract Background Pediatric patients undergoing hematopoietic cell transplantation (HCT) may develop life-threatening complications and need for ICU admission (ICU). They may display more severe and/or unique manifestations of organ dysfunction syndromes, including acute respiratory failure, sepsis and delirium, compared to the general pediatric In this interim analysis of the POEM study, the utility of a p-MODS screening tool as a predictor of endotheliopathies and/or ICU is reported. Methods: NCT05090345 is a prospective multi-center registry/biorepository trial of children and adolescents/young adults (AYA) undergoing HCT to assess the impact of endotheliopathies on morbidity and mortality. Patients undergoing all HCT types are prospectively monitored for 100 days post-HCT for sinusoidal obstructive syndrome (SOS), thrombotic microangiopathy (TMA), capillary leak syndrome (CLS), diffuse alveolar hemorrhage (DAH) and ICU. The risk of p-MODS was assessed within 7 days of HCT admission and weekly for 4 weeks, to dynamically evaluate organ function across 8 systems: respiratory, cardiovascular, renal, hepatic, hematologic, neurologic, immune, and gastrointestinal. Each system was graded on a 0–5 scale based on clinical and laboratory parameters, with total pMODS calculated using the worst score per organ. Descriptive statistics were used to compare p-MODS score between groups with “events” (defined as endotheliopathy or ICU) versus “no events”. The “no event” comparison group was matched 1:1 by diagnosis, age, gender and HCT type. Results: Among all subjects (n=151), the median age was 11.3 (range: 0.2–26.9) years and the majority (64%) male and Caucasian ( 60%) and 20% Black. Most patients (86.8%) underwent allogeneic HCT. Common indications were hematologic malignancy (45%), solid tumors (19%) and hemoglobinopathies (8.6%).Events (n=50) were observed in 35 of 151 patients, including ICU (n=26), SOS (n=19), TMA (n=3) CLS (n=1) and DAH (n=1). Events occurred at a median of 16 (range: –7 to 85) days post-HCT. Median time to ICU was 15 (range: –7 to 82) days post-HCT. The median pMODS score at the time of ICU was 10 (range: 1–22). All three patients with TMA had preceding ICU admissions and 4 of 19 patients with SOS required ICU management. The median time to onset of endotheliopathy was 17 (range: 6–33) days post-HCT. The median pMODS score at the time of event was 11 (range: 7–18), compared to a median of 8 (range: 5–21) the week prior to onset. Patients who developed events exhibited progressively higher scores compared to matched controls starting at week 1 (p < 0.05). This difference became more pronounced over time, reaching statistical significance at week 2 (p < 0.001). Since physiologic decline may precede overt events, we next analyzed pMODS score change between Day 0 and week 1. A significant difference was observed with median increase of 2 (range: –2 to 16) in the event group versus 1 (range: –3 to 7) in the control group (p = 0.01). Analysis of individual organ system scores revealed notable differences between the event and control groups by Week 1, prior to median event onset. The event group had higher rates of indicators of organ dysfunction in 6 of 8 organ system. The event group had more subjects with acute kidney injury, elevated delirium scores, need for respiratory support, increased bilirubin, moderate to significant weight gain and infections. However, rates of neutropenia and lymphopenia were comparable between groups. Conclusion In this interim analysis, a significant increase in pMODS between Day 0 and week 1 post-HCT may reflect early physiologic decline, with notable changes in respiratory status, acute kidney injury, elevated CAPD scores, and infectious burden. These findings highlight the potential utility of pMODS as an early screening tool to identify pediatric HCT recipients at risk for clinical deterioration. Prospective and dynamic monitoring of pMODS may support timely intervention and improve outcomes in this vulnerable population.

Environmental degradation due to industrial groundwater contamination is an emerging cardiovascular disease (CVD) risk factor. Our study examines the elevated CVD prevalence, including heart failure (HF) risk factors, in rural Punjab, India, near which a private distillery was linked to long-term groundwater contamination and environmental degradation. Our team primarily focused on CVD prevalence and its associations with environmental toxins. We also explored the role of socio-economic disparities on health outcomes. A cross-sectional study of 4,885 residents in three villages adjacent to the distillery (Mahianwala Kala, Ratol Rohi, Mansoorwaal Kalan) was conducted from October 2022 to August 2023. Health camps with follow-up door-to-door surveys by trained medical personnel collected medical histories, environmental exposure details, and socio-demographic data. Key outcomes included both communicable and non-communicable diseases, such as hypertension, ischemic heart disease, heart failure, and cancer. Logistic regression assessed associations between CVD prevalence, socio-economic status, and pollution exposure, with groundwater testing for heavy metals and chemical oxygen demand (COD). The cohort demonstrated a high CVD burden, with 39% having hypertension (exceeding national averages by more than 50%), 34% having diagnosed CVD, and 21.3% of households reporting an immediate family history of myocardial infarction. Adjusted models highlighted elevated odds of heart disease (OR 1.42; 95% CI 1.31–1.51) and stroke (OR 1.29; 95% CI 1.16–1.38), with higher clustering in low-income families. Concurrent systemic toxicity was also evident, as 60.5% reported dermatological conditions, 10.5% familial cancer, 20.8% with no history of smoking cited COPD-related dyspnea. We also observed elevated miscarriage rates and developmental disabilities in the studied population. Groundwater analysis confirmed contamination with cyanide (0.3 mg/L), lead (0.16 mg/L), and COD (320 mg/L), correlating with self-reported water discoloration and irregularities in taste. Families with polluted water access had a 1.5-fold increased CVD risk. Industrial contamination was linked to higher cardiovascular morbidity and multi-organ health effects in our study's cohort in rural India. The link was exacerbated by socio-economic inequities. These findings highlight the role of environmental degradation in rise in CVD, particularly in low-resource settings.

Abstract The velocity data presented demonstrate the complicated flow behavior of nanocrystalline cellulose (NCC) suspensions even when standard rheometry shows only subtle effects. Rheo-nuclear magnetic resonance (NMR) velocimetry with spatial and temporal resolution indicates that NCC suspensions undergo varying flow behavior, which correlates with bulk rheology and includes wall-slip, shear banding, and yielding. Large-velocity fluctuations in a chiral nematic liquid crystal-phase suspension (5% w/v) indicate particle director orientation tumbling and flow. The results provide details of the mesoscale velocity distributions in space and time, which can be used to inform the interpretation of rheology data, as well as processing flow conditions to control NCC suspension microstructure and impact properties of composite and other materials.

Background/Objectives: Our study examined 5-year patient and graft survival outcomes among non-smokers, former smokers, and active smokers at the time of liver transplantation (LT) and immediate post-operative complications and short-term outcomes following LT. Methods: This was a retrospective study that examined all liver transplants occurring at Cleveland Clinic Main Campus between January 2015–October 2022. Kaplan–Meier curves examined survival outcomes, and Cox’s multivariate regression analysis was performed. Results: Over the 5-year period, patient survival did not differ statistically between patient groups (all p-values >0.05). However, graft survival was significantly lower in active smokers (p = 0.012). In the multivariate analysis, age (HR = 1.03, 95% CI 1.01–1.05, p = 0.002) and admission to the ICU (HR 1.68, 95% CI 1.13–2.50, p = 0.01) were positively associated with overall mortality. Immediate and short-term complications did not differ statistically between patient groups. Cardiovascular disease (22.5%) was the most common cause of death among all patients. Conclusions: Though our study did not show decreased patient survival outcomes, our findings are in line with previous studies that have shown that pre-transplant smoking is associated with overall reduced graft survival. Combined with the risk for de novo malignancy and cardiovascular events post transplant, smoking cessation before LT should be encouraged to ensure graft longevity.