INTRODUCTION:Patients often receive propofol for sedation and clevidipine for hypertension in the intensive care unit. Both agents are formulated as a lipid emulsion, which may increase the risk of hypertriglyceridemia and acute pancreatitis with their coadministration. We aimed to determine the incidence of hypertriglyceridemia and acute pancreatitis with concurrent administration of propofol and clevidipine and identify patient risk factors for hypertriglyceridemia. METHODS:This was a multicenter retrospective study of adult patients (≥ 18 years old) receiving concurrent propofol and clevidipine infusions for ≥ 6 h. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and acute pancreatitis. The secondary outcome was risk factors associated with hypertriglyceridemia during concurrent propofol and clevidipine infusions until both infusions had been discontinued. Univariable and multivariable logistic regression analyses were used to assess risk factors of hypertriglyceridemia in patients receiving concurrent propofol and clevidipine infusions. RESULTS:Across 1,226 patients, the median duration of infusion overlap was 12.4 [interquartile range (IQR) 8.3, 22.7] hours. The mean age of the cohort was 59.6 [standard deviation (SD) 14.9] years, and 59.4% were male. Assuming those without a triglyceride level drawn did not have hypertriglyceridemia, hypertriglyceridemia after initiation of propofol and clevidipine infusion was found in 7.7% [95% confidence interval (CI) 6.3% to 9.3%] of the entire cohort. Twenty-six patients (2.1%) had a diagnosis of pancreatitis after initiation of lipid infusions, of which 12 cases were possibly infusion-related, and one case was likely infusion-related. After calculating the Naranjo Scale, all 13 cases of pancreatitis were possibly related to propofol or clevidipine infusions. Based on a multivariable logistic regression of those with a triglyceride level available, risk factors for hypertriglyceridemia included pancreatitis within the past 5 years [adjusted odds ratio (aOR) 2.77, 95% CI, 1.23 to 6.23] and statin use (aOR 1.94, 95% CI, 1.13 to 3.34). CONCLUSIONS:In our cohort of patients receiving concurrent propofol and clevidipine, the frequency of hypertriglyceridemia and acute pancreatitis was low. Further comparative studies are warranted to assess the risk of pancreatitis with the addition of clevidipine to propofol.

Sixty years after its initial description, the epidemiology and pathophysiology of acute respiratory distress syndrome (ARDS) have evolved substantially. This narrative review examines whether ARDS is a preventable disease, evaluating the evidence for successful prevention of iatrogenic phenotypes and the challenges that remain for noniatrogenic causes. We reviewed the published literature on ARDS prevention, including evidence from clinical trials, population-based epidemiologic studies, implementation research, and biological subphenotyping studies, synthesized through the framework of the multiple hit hypothesis. For iatrogenic phenotypes, ARDS prevention has substantially succeeded. Transfusion-related acute lung injury has declined dramatically following male-predominant plasma policies. Lung-protective ventilation initiated in emergency departments and operating rooms has reduced both ARDS incidence and mortality. Bundled care approaches combining restrictive fluid and transfusion strategies, aspiration precautions, and early antimicrobials have further reduced iatrogenic lung injury. What remains under the ARDS label is an increasingly heterogeneous collection of conditions driven by upstream host–pathogen interactions and biological phenotype. Pharmacologic prevention trials in unselected populations have been consistently disappointing, likely because biologically distinct subphenotypes respond differently to treatment. Additionally, the population-attributable fraction of death from ARDS is modest, suggesting that even successful prevention may not translate into proportional mortality reduction. Extending prevention beyond iatrogenic causes will require precision approaches: phenotype-targeted pharmacotherapy, individualized mechanical ventilation, and systematic implementation of evidence-based practices across the care continuum.

Rationale: Critically ill lung cancer patients are a growing, high-risk population. However, prognostic tools to guide intensive care unit (ICU) decision-making are limited. Objectives: To identify oncologic and critical illness factors associated with 90-day mortality following ICU admission in patients with lung cancer. Methods: We conducted a retrospective cohort study of lung cancer patients admitted to the ICU across Mayo Clinic Health System between 2018 and 2024. The primary outcome was 90-day mortality. Two complementary Cox proportional hazards models were developed: a focused model including cancer-specific variables (stage, time since diagnosis, time since last systemic therapy, prior thoracotomy, Eastern Cooperative Oncology Group [ECOG] performance status prior to admission, body mass index, cause of critical illness, code status at admission) and a full model that added broader clinical factors (age and Sequential Organ Failure Assessment [SOFA] score). We also evaluated discharge disposition and transitions in code status. Results: Among 528 patients, 90-day mortality was 58.7%. In the focused model (C-index 0.67), independent predictors of mortality included late-stage disease, cancer-specific reason for ICU admission, limitations in resuscitation orders, and ECOG >1. In the full model (C-index 0.95), only age and SOFA score remained significant. Among early-stage patients, recent targeted or combination therapy was associated with higher mortality, though this association may reflect underlying disease characteristics or treatment selection rather than direct treatment effects. Patients who changed code status during admission had high mortality (83%) and a low rate of discharge home (11%). Conclusion: Lung cancer patients admitted to ICU experience high short-term mortality, with outcomes shaped by both oncologic status and the severity of acute illness. A dual-model approach suggests a risk hierarchy: Cancer-specific factors inform baseline mortality risk with an ICU admission, but age and physiologic derangement are the dominant drivers of survival once critical illness develops. These findings support dynamic, multidisciplinary prognostication and underscore the need to integrate oncology and critical care expertise in ICU decision-making.

BACKGROUND:Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of pulmonary chronic graft vs host disease (cGvHD) that occurs in around 10% of allogeneic hematopoietic cell transplant (HCT) recipients and confers poor prognosis, with survival rates at 5 years of < 50%. Posttransplant cyclophosphamide (PTCy) has emerged as an effective GvHD prophylaxis that reduces overall cGvHD incidence, but its specific impact on BOS risk remains unclear. RESEARCH QUESTION:How does PTCy affect the rate of BOS among patients undergoing allogeneic HCT? STUDY DESIGN AND METHODS:We conducted a retrospective multicenter cohort study across 3 US centers between 2015 and 2023 comparing BOS incidence between patients receiving PTCy vs non-PTCy GvHD prophylaxis. BOS was defined as either meeting strict National Institutes of Health criteria (4 of 4) or meeting 3 of 4 criteria with clinical BOS diagnosis. We used competing risk regression accounting for death and performed mediation analysis to evaluate whether cGvHD reduction mediates PTCy's protective effect. RESULTS:Among 900 patients (276 with PTCy, 624 without PTCy), PTCy was associated with a 75% reduction in BOS risk (adjusted hazard ratio [HR], 0.25; 95% CI, 0.09-0.74; P = .012) when adjusted for age, immunologic matching status, and baseline FEV1 and stratified by conditioning strategy. Mediation analysis demonstrated that when cGvHD was added to the model, the PTCy HR attenuated from 0.26 to 0.41 (57% attenuation toward the null; P = .108), indicating that cGvHD prevention mediates PTCy's protective effect. Results remained robust after excluding haploidentical transplants (HR, 0.24; 95% CI, 0.07-0.77; P = .016). INTERPRETATION:Our results show that PTCy significantly reduces BOS risk through prevention of cGvHD, expanding current evidence of PTCy's benefits beyond overall cGvHD reduction to include protection against this often fatal pulmonary complication. These findings support consideration of PTCy-based regimens for patients at high risk of BOS and may inform risk stratification strategies in posttransplant monitoring.

Mucormycosis is an uncommon but severe invasive fungal infection in hematopoietic stem cell transplant recipients. Contemporary cases may occur outside the classic early neutropenic post-transplant window and during antifungal prophylaxis. We performed an International Classification of Diseases code-screened retrospective case series using the institutional denominator of adult hematopoietic stem cell transplant recipients at Mayo Clinic from January 1, 2008, through December 1, 2025. Cases were adjudicated using 2020 European Organization for Research and Treatment of Cancer and Mycoses Study Group Education and Research Consortium criteria. We analyzed transplant characteristics, immune and pulmonary host factors, prophylaxis and therapeutic drug monitoring, diagnostic evidence, management, critical care use, and outcomes. Among 6,340 adult transplant recipients, 13 met criteria for invasive mucormycosis; eleven had allogeneic transplant and 2 had autologous transplant. Median age was 61 years, and median onset was 681 days after transplant. Underlying conditions included acute myeloid leukemia in 4 patients, chronic lymphocytic leukemia and chronic myeloid leukemia in 2 each, and diffuse large B-cell lymphoma, T-cell lymphoma, acute lymphoblastic leukemia, multiple myeloma, and VEXAS syndrome in one each. All patients were receiving systemic antifungal prophylaxis; 11 were receiving mold-active azoles and 6 were receiving posaconazole. Five patients had pre-diagnosis azole levels available. Neutropenia was present in 4 patients, while lymphopenia, low helper T-cell counts when measured, graft-versus-host disease, targeted or immunomodulatory therapies, and pulmonary host-defense abnormalities were frequent. Pulmonary or mixed pulmonary involvement occurred in 8 patients, disseminated disease in 3, and 9 cases were proven. Liposomal amphotericin B was used in 12 patients, source-control surgery in 6, intensive care unit admission in 6, mechanical ventilation in 5, and all-cause mortality was 5 of 13 at 30, 42, and 90 days. This series describes mucormycosis in adult transplant recipients rather than establishing causal attribution to transplantation in every case. The findings support diagnostic vigilance for Mucorales infection in chronically immunocompromised transplant recipients, including those remote from transplant, receiving prophylaxis, and without neutropenia.

BACKGROUND:Lung transplant recipients (LTRs) are highly susceptible to invasive mold infections (IMIs). In clinical practice, diagnostic codes for IMI serve as claims-based markers of suspected infection that often prompt antifungal therapy, but their real-world clinical and economic impact remains incompletely defined. RESEARCH QUESTION:Among LTRs, are IMI-coded diagnoses associated with increased health care utilization, costs, and mortality? STUDY DESIGN AND METHODS:We conducted a retrospective cohort study using the OptumLabs Data Warehouse (2005-2023). Adult LTRs were identified by procedure codes and followed from transplant until disenrollment, death, or December 2023. IMIs were defined by International Classification of Diseases, Ninth Revision/International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Risk factors were assessed using multivariable logistic regression. A 1:2 matched cohort (age, sex, and transplant length of stay) evaluated health care utilization, costs, and mortality. Utilization and costs were calculated per patient-month (PPM) and stratified by payer. Mortality was assessed using Cox models. RESULTS:Among 1,120 eligible LTRs, 343 (30.6%; 95% CI, 27.9%-33.4%) had an IMI-coded diagnosis, most commonly aspergillosis (88%). Male sex (OR, 1.52; 95% CI, 1.16-1.99) and cystic fibrosis (OR, 1.93; 95% CI, 1.14-3.28) were independently associated with IMI coding, whereas higher comorbidity burden was associated with lower odds (OR, 0.65; 95% CI, 0.43-0.98). In the matched cohort (IMI: n = 243; non-IMI: n = 486), IMI coding was associated with greater emergency department use (0.13 vs 0.10 visits/PPM; P = .018) and longer inpatient stay (3.28 vs 2.23 days/PPM; P = .031). Cost patterns diverged: commercially insured recipients with IMI-coded diagnoses had lower pharmacy costs ($3,416 vs $4,504/PPM; P = .006), whereas Medicare Advantage recipients incurred significantly higher inpatient, medical, and overall costs. IMI coding was associated with nearly 2-fold higher mortality (hazard ratio, 1.83; 95% CI, 1.33-2.51; P < .001). INTERPRETATION:Our results show that IMI-coded diagnoses are common after lung transplant and are associated with greater acute care utilization, higher costs among Medicare Advantage recipients, and increased mortality. These findings underscore the clinical and economic burden of suspected mold infections in LTRs and highlight the need for integrated claims and clinical data to refine risk reduction strategies.

Pretransplant pulmonary function testing (PFT) is standard before hematopoietic cell transplantation (HCT), but few centers complement it with objective functional capacity assessment. At our institution, a 3-min step exercise test is performed at the time of PFTs, generating two distinct measures: exercise duration (a functional capacity surrogate) and oxygen desaturation (a gas exchange measure). Whether either component adds prognostic value beyond PFTs is unknown. The primary objective of the study was whether step-derived variables added predictive value beyond a baseline model containing age, sex, transplant type, FEV1z-score, DLCO z-score, and hemoglobin. Outcomes of interest were overall survival, ICU admission within 120 d, and invasive mechanical ventilation within 120 d. This is a single-center retrospective cohort of 3458 adult HCT recipients (2648 autologous, 810 allogeneic) who underwent a 3-min step exercise test before HCT between 2005 and 2024. Pulse oximetry and heart rate were recorded during the step test. Pretransplant PFTs were interpreted using Global Lung Initiative reference equations and reported as z-scores. Overall survival was analyzed using Cox proportional hazards regression, and ICU admission and invasive mechanical ventilation were analyzed using logistic regression. Additive value of exercise variables was evaluated with a prespecified baseline model containing established predictors of HCT outcomes. Median follow-up was 4.5 yr. During follow-up, 1149 patients (33.2%) died, 495 (14.3%) were admitted to the ICU within 120 d, and 131 (3.8%) required invasive mechanical ventilation. Of 3431 patients with exercise time recorded, 718 (20.9%) stopped before completing the 3-min protocol. Exercise time predicted all three outcomes after full adjustment: each additional minute was associated with lower mortality (HR 0.90, 95% CI 0.82 to 0.99, P = .025), lower odds of ICU admission (OR 0.80, 95% CI 0.69 to 0.92, P = .003), and lower odds of invasive mechanical ventilation (OR 0.70, 95% CI 0.55 to 0.89, P = .004). Model fit improved with the addition of exercise time for all three outcomes. In contrast, oxygen desaturation did not predict any outcome after hemoglobin adjustment (overall survival HR 0.99, 95% CI 0.96 to 1.02, P = .53). An apparent association between desaturation and mortality without hemoglobin adjustment (HR 0.96, P = .003) was fully absorbed by measured hemoglobin, confirming confounding by oxygen-carrying capacity. Exercise duration during a brief pretransplant step test independently predicts overall survival, ICU admission, and invasive mechanical ventilation after HCT, capturing a dimension of pretransplant fitness not measured by resting PFTs or hemoglobin. Oxygen desaturation does not add prognostic value, and the apparent signal in unadjusted analyses reflects hemoglobin confounding. These findings support emphasizing exercise capacity assessment before HCT.

Introduction Community-acquired pneumonia (CAP) is common and remains the leading infectious cause of death worldwide. Antibiotics remain the mainstay of treatment, but organisms are often not identified, necessitating empirical treatment. Current treatment guidelines recommend combination therapy with beta-lactams and macrolides or monotherapy with fluoroquinolones for non-severe CAP. However, rising antibiotic resistance and safety concerns have led to increased doxycycline use, despite limited evidence supporting its efficacy. Our goal is to conduct a pragmatic, open-label, randomised clinical trial comparing the effectiveness of azithromycin with that of doxycycline in combination with beta-lactam therapy in adult patients hospitalised for CAP.Methods and analysis Patients presenting to the emergency department or directly referred to the hospital with a clinical presentation concerning for CAP and need for hospitalisation are eligible. We plan to enrol 1120 adults hospitalised at six hospitals across four states, including rural, suburban and urban settings and academic and community hospitals. Randomisation will be 1:1 using an electronic health record (EHR)-embedded screening and randomisation tool triggered by the treating clinician’s orders for azithromycin or doxycycline. Outcomes will be ascertained pragmatically via EHR-based data retrieval and will not require additional study visits. Our primary outcome is days alive and out of the hospital through day 28. Secondary outcomes include oxygen-free days; a composite of a need for advanced respiratory support or in-hospital mortality with analyses of each component separately; an ordinal measure of clinical deterioration defined by a prespecified severity scale; and 60-day and 180-day mortality. Safety outcomes are the incidence of Clostridioides difficile infection and QT prolongation. Analyses will follow an intention-to-treat framework, with per-protocol analyses for sensitivity. The primary endpoint will be compared between groups using a stratified van Elteren test, with supportive analyses using proportional odds regression and analysis of covariance adjusted for key covariates.Ethics and dissemination The Mayo Clinic Institutional Review Board reviewed and approved this protocol with a waiver of written consent, requiring verbal consent to be obtained by the clinician initiating the antibiotics (IRB# 24–0 06 503). Findings will be disseminated through peer-reviewed publications and international conference presentations.Trial registration number NCT07164131.

BACKGROUND:The impact of psychosocial health and socioeconomic status (SES) on long-term lung transplant survival remains unclear. METHODS:We conducted a single-center, retrospective 2:1 matched case-control study of adult lung transplant recipients (1999-2019). Cases survived ≥6 years post-transplant; controls survived <6 years. Matching was based on transplant year (±5 years) and indication. Psychosocial health and SES were assessed using the Psychosocial Assessment of Candidates for Transplant (PACT) score, Mayo Clinic Housing-Based Socioeconomic Status (HOUSES) index, and Area Deprivation Index (ADI). Secondary covariates included insurance, marital status, employment, caregiver relationship, and proximity to the transplant center. Conditional logistic regression adjusted for age and gender was used. RESULTS:Among 189 patients (63 cases, 126 controls), PACT score, HOUSES index, and ADI were not significantly associated with long-term survival. Patients with non-family caregivers had lower odds of survival compared to those with a spouse or partner (OR = 0.16, p = 0.022). Regional residents had lower odds of long-term survival compared to local recipients (OR = 0.55, p = 0.001). CONCLUSIONS:Pre-transplant psychosocial and SES measures were not significantly associated with long-term survival. Caregiver relationships and geographic proximity may have a greater impact on outcomes, highlighting the importance of support systems and access to care.

Rationale: Hematopoietic cell transplantation (HCT) risk scores have seen minimal updates over the past 20 years, despite advancements in clinical practice. Pulmonary function test (PFT) thresholds, initially based on NHANES reference equations, now have alternative reference standards from the Global Lung Function Initiative (GLI) 2012 and GLI-Global, which may reclassify patients and affect outcomes. This study investigates the impact of GLI reclassification on outcomes in HCT, comparing traditional fixed thresholds with continuous (z-score) risk assessment models. Methods: A retrospective review of 3,120 adult patients who underwent autologous HCT at MD Anderson Cancer Center from 1999 to 2015 was conducted. Primary endpoints were ICU admission, mechanical ventilation (IMV), and survival within 120 days post-transplant. PFT measures (FEV1, FVC, DLCO) were calculated using GLI-2012 and GLI-Global reference equations, analyzed both continuously (z-scores) and categorically by ATS/ERS guidelines. Cox proportional hazards and logistic regression models were employed, with AUROC comparisons to evaluate predictive performance. Results: The cohort had a mean age of 49 years (SD 14), with 41% female and 77% White. Of the 3,120 patients included in the study, the cohort consisted of 77% White, 5.4% Black, 3.3% Asian, and 14% identifying as other ethnicities. At 120 days, mortality was 1% (n=41), ICU admission 5% (n=169), and IMV 2% (n=70). Continuous DLCO was associated with a lower risk of mortality (HR: 0.75; p=0.03), ICU admission (OR: 0.83; p=0.01), and IMV (OR: 0.80; p=0.02). GLI-Global's FEV1 z-scores were also significant for mortality (HR: 0.70; p=0.01), ICU admission (OR: 0.74; p<0.0001), and IMV (OR: 0.70; p=0.0003). Categorical analyses showed significant mortality reduction with normal DLCO (HR: 0.46; p=0.01) and ICU admission reduction with normal FEV1 GLI-2012 (OR: 0.63; p=0.02). Reclassification by race, as shown in Figure 1, indicated that race-specific equations overestimated PFT values in Black patients and underestimated them in Asian patients. Conclusion: Reclassification by GLI reference equations, particularly using continuous z-scores, significantly influences post-HCT outcomes, suggesting that continuous assessment may improve risk stratification. Including race does not improve the model's performance. These findings support integrating updated PFT references and continuous risk models into HCT prognostic tools for enhanced clinical decision-making.

INTRODUCTION:Lung transplant recipients (LTRs) are susceptible to invasive candidiasis (IC). This study aimed to assess the incidence, risk factors, and impact of IC on mortality in LTRs using a national insurance claims cohort. METHODS:We conducted a retrospective cohort study using administrative claims data from the OptumLabs® Data Warehouse. We identified LTRs from January 1, 2005, to December 31, 2023, using procedural codes. Exclusion criteria included re-transplantations and pre-transplant IC. We employed multivariable logistic regression to identify risk factors for IC and Cox Proportional Hazard models to assess the impact of IC on mortality. RESULTS:Among 1279 LTRs, 131 (10.2%) developed IC, primarily during the initial hospitalization for lung transplantation (index hospitalization). The median time to IC diagnosis was 32.0 days following transplant. Post-transplant extra-corporeal membrane oxygenation (ECMO) for more than 8 days was associated with IC (OR: 2.34; 95% CI 1.03 to 5.34). Mortality was higher in LTRs with IC (HR: 2.31; 95% CI: 1.45 to 3.67; p < 0.001). LTRs with IC also had longer hospital stays (median 26.0 days vs. 20.0 days; p < 0.001) and more re-operations (36.7% vs. 27.3%; p = 0.003) compared to those without IC. CONCLUSION:Invasive candidiasis affects approximately 10% of lung transplant recipients, most often during the initial hospitalization. It is associated with increased mortality, prolonged hospital stays, and a greater need for surgical re-intervention. These findings highlight the importance of early identification and targeted preventive strategies to improve outcomes in this high-risk population.

Acute respiratory failure is the leading reason for intensive care unit (ICU) admission among critically ill patients with cancer. We aimed to describe the clinical characteristics, risk factors, and outcomes of patients with cancer and acute respiratory distress syndrome (ARDS) and to evaluate associations of venovenous extracorporeal membrane oxygenation (ECMO) with outcomes in the subgroup with severe ARDS. We conducted a multinational, prospective, observational cohort study of patients with cancer and ARDS in 13 countries in Europe and North America. The primary endpoint was 90-day mortality. Among 715 included patients, 73.4

Background: Pulmonary function tests, forced expiratory volume in 1 s (FEV₁) and diffusing capacity for carbon monoxide (DLCO), are integral to pre-transplant evaluation of allogeneic hematopoietic cell transplantation (HCT) candidates because they estimate the risk of early post-HCT death and respiratory failure. Interpretation has historically relied on race-specific Global Lung Function Initiative equations from 2012 (GLI-2012). In 2021 the Initiative released race-neutral equations (GLI-Global). The influence of adopting GLI-Global on risk stratification, outcome prediction, and transplant eligibility is unknown. Methods: We retrospectively analyzed 8808 adults who underwent first allogeneic HCT at four United States centers between 1999 and 2021. FEV₁ values were converted to z-scores with both GLI-2012 and GLI-Global, whereas DLCO z-scores were calculated with GLI-2017 which is a race neutral equation. Pulmonary impairment was graded with the Lung Function Score (LFS); each component [FEV₁ and DLCO] receives 1 to 6 points based on percent predicted (> 80 % = 1, 70-79 % = 2, 60-69 % = 3, 50-59 % = 4, 40-49 % = 5, < 40 % = 6) and the sum of 2 to 12 maps to grades I (2), II (3-5), III (6-9), and IV (10-12). Primary endpoints were non-relapse mortality (NRM) at 120 days and 2 years, intensive care unit admission, and invasive mechanical ventilation. Prediction was assessed with Cox proportional hazards models and Harrell c-statistics. Results: Switching to GLI-Global reclassified 4.2 % of patients (368 of 8808) across LFS strata. Reclassification was racially asymmetric: 12.2 % of Black patients moved to higher-risk grades whereas 3.9 % of White patients moved to lower-risk grades. C-statistics for FEV₁ z-scores were nearly identical with GLI-Global versus GLI-2012: 2-year NRM 0.544 vs 0.542, 120-day NRM 0.566 vs 0.568, intensive care admission 0.545 vs 0.538, and mechanical ventilation 0.605 vs 0.605; confidence intervals overlapped for every comparison. Continuous z-score models consistently outperformed categorical cut-offs for each outcome: 2-year NRM 0.544 vs 0.518, 120-day NRM 0.566 vs 0.523, intensive care admission 0.545 vs 0.515, and mechanical ventilation 0.605 vs 0.529; confidence intervals did not overlap for every comparison. The composite LFS outperformed models that used FEV₁ or DLCO alone. Extrapolating cohort reclassification rates to 38,606 adults aged 40 to 84 who received allogeneic HCTs reported to the Center for International Blood and Marrow Transplant Research between 2009 and 2018 predicts that 1521 patients, including 509 Black adults, would shift LFS grades and could face altered transplant eligibility. Conclusions: Race-neutral GLI-Global equations modestly change pulmonary risk categorization, disproportionately raising scores for Black HCT candidates, yet maintain predictive accuracy for early mortality, respiratory failure, and intensive care use. Continuous dual-variable models and the composite LFS provide superior prediction. Although race-neutral interpretation aligns with current society guidelines, its tendency to classify Black individuals as higher risk highlights the need for refined continuous models that limit unnecessary reclassification and increased disparities in transplant eligibility.

RATIONALE: Long-term survival after lung transplantation is challenging, with limited research on risk and protective factors. Clinical factors such as younger age, female sex, fewer acute rejection hospitalizations, and double lung transplants are associated with better outcomes. However, the role of psychosocial health and socioeconomic status (SES) remains underexplored. This study aimed to assess the influence of pre-transplant psychosocial health and SES on long-term survival in adult lung transplant recipients. METHODS: We conducted a single-center, retrospective case-control study using the Mayo Clinic Rochester lung transplant registry. Cases (survivors ≥ 6 years) and controls (survivors <6 years) were matched by transplant date (+/- 5 years) and indication for transplant, resulting in 190 subjects (63 cases, 127 controls). We assessed the impact of pre-transplant psychosocial health and SES on long-term survival using initial PACT scores (<2), the HOUSES index, and the national/state area deprivation index (ADI). Additional factors included proximity to the transplant center, insurance type, marital status, primary caregiver status, and employment status. Statistical analyses used the paired Wilcoxon rank-sum test for continuous variables and McNemar's test for categorical variables, with results reported as median (IQR) or percentages. RESULTS: Donor characteristics (age, sex, smoking history, risk criteria, cause of death) and recipient characteristics (age at transplant, sex, BMI, medical condition, functional status, type of transplant) were similar between cases and controls, with no statistically significant differences (all p>0.05). CMV mismatch, waitlist time, and transplant hospital length of stay were also comparable (all p>0.05). Psychosocial health indicators, including proximity to the transplant center, pre-transplant initial PACT score, insurance type, marital status, primary caregiver, and employment status, did not differ significantly between groups (all p>0.05). The HOUSES index was similar between cases and controls (p=0.179). However, long-term survivors had significantly higher national and state ADI scores than controls (national ADI: p=0.029; state ADI: p=0.019). CONCLUSIONS: Pre-transplant psychosocial health indicators, including proximity to the transplant center, initial PACT score, and caregiver support, did not differ significantly between long-term lung transplant survivors and those with shorter survival. Although SES measured by the HOUSES index was not associated with long-term survival, higher national and state ADI scores were linked to increased long-term survival, suggesting unique protective factors for patients from socioeconomically deprived areas. These findings highlight the complex role of socioeconomic factors in lung transplant outcomes and underscore the need for further research into how specific socioeconomic and environmental factors influence long-term survival.

RATIONALE Propofol is the first-line sedative for critically-ill, mechanically-ventilated patients, but it can increase serum triglyceride levels. Machine-learning (ML) offers a promising approach for individualized risk stratification of propofol-associated hypertriglyceridemia, enabling proactive triglyceride monitoring and sedation optimization. This study aims to develop and validate ML models to predict hypertriglyceridemia risks in critically-ill patients receiving propofol. METHODS We analyzed retrospective data from adult ICU patients on mechanical ventilation receiving continuous propofol infusion for ≥24 hours across four Mayo Clinic sites from May 2018 to June 2023. The primary outcome was hypertriglyceridemia, defined as serum triglycerides >400 mg/dL within 10 days of starting propofol. Ten-fold cross-validation and leave-one-site-out nested cross-validation (LOSO-CV) were used for model tuning and external validation of our modeling process, respectively. Feature selection was conducted through a union of Boruta and least absolute shrinkage and selection operator (LASSO). While COVID status was a strong predictor of hypertriglyceridemia, we concurrently developed non-COVID models to ensure future relevance in non-pandemic settings. Six ML algorithms (logistic regression, support vector machines, random forests, LightGBM, XGBoost, and multilayer perceptrons) were tuned using Bayesian optimization to minimize cross-entropy loss. Classification thresholds were set to target sensitivity ≥80%. Model performance was evaluated using AUC-ROC, Brier score, sensitivity, and specificity. Models with the highest Youden's Index were designated the best-performing model. Model explainability was assessed using permutation importance and SHapley Additive exPlanations (SHAP). RESULTS We included 3922 eligible patients with triglyceride measurements. Of these, 3042 patients were COVID-negative and used for non-COVID modeling. The best-performing non-COVID models achieved an average AUC-ROC of 0.69 (95% confidence interval [CI] 0.68-0.70), Brier score of 0.12 (95% CI 0.09-0.14), sensitivity of 0.79 (95% CI 0.75-0.83), and specificity of 0.48 (95% CI 0.44-0.52) during LOSO-CV. The best-performing models that included COVID status achieved an average AUC-ROC of 0.71 (95% CI 0.70-0.72), Brier score of 0.13 (95% CI 0.10-0.16), sensitivity of 0.78 (95% CI 0.71-0.84), and specificity of 0.51 (95% CI 0.45 to 0.56) during LOSO-CV. The permutation importance results of the final non-COVID model are shown in the figure. CONCLUSION We have developed sensitive ML models for predicting hypertriglyceridemia risks in critically-ill patients receiving propofol. Although developed during the COVID-19 pandemic, the non-COVID models are more likely to have future relevance, and they have similar performance as models including COVID status. These models will be integrated into a web-based clinical calculator and undergo further validation in prospective studies.

INTRO:A three-drug immunosuppression regimen to prevent graft loss is the cornerstone of therapy following lung transplantation. Direct comparisons between maintenance regimens including mycophenolate (MMF) and azathioprine (AZA) are limited in the lung transplant population. METHODS:We completed a retrospective cohort study of adult (≥18 years of age) lung transplant recipients at Mayo Clinic (Rochester, MN) from January 1, 2009 through July 1, 2022 and compared outcomes in patients on AZA vs MMF. Our primary outcome was clinically significant acute cellular rejection. Secondary outcomes included graft loss, drug interruption, chronic lung allograft dysfunction (CLAD), and infection. Analyses were performed with Multivariable Cox Regression with transplant era and induction immunosuppression agent as covariables. RESULTS:224 patients were included, 88 on AZA and 136 on MMF. The risk of clinically significant rejection was greater in the AZA group compared to the MMF group (HR, 1.76; 95 % CI 1.12-2.79; P = 0.02). Medication interruption was also higher in the AZA (HR, 1.47; 95 % CI 1.04-2.08; P = 0.026). Rates of CLAD, graft loss, and infection were similar between the groups. CONCLUSION:In this cohort, MMF was associated with lower risk of clinically significant acute cellular rejection and drug interruption when compared to AZA. Similar rates of CLAD, graft loss, and infection were observed.