Background Socioeconomic disparities in lung transplantation outcomes have been well described, but little is known about the impact of community-level disparities amongst waitlisted patients. This study examines the relationship between community-level socioeconomic advantage, measured by the Distressed Communities Index (DCI), and the risk of adverse waitlist events, defined as waitlist removal for death or clinical deterioration. Methods The Scientific Registry of Transplant Recipients was used to retrospectively review 13,792 adult lung transplantation candidates listed between 2016 and 2020. Each patient was associated with a composite DCI score based on education, housing vacancy, unemployment, poverty, median income, and changes in employment and establishments. Clinical data were paired with socioeconomic data using zip codes. Statistical analysis was conducted using descriptive statistics and logistic regression methods. Results No difference in risk of adverse waitlist events was identified across DCI score quintiles after adjustment. Compared to the least socioeconomically distressed lung transplant waitlist patients, the most distressed patients were more likely to be female (47.77% vs 39.22%), non-White (26.08% vs 10.18%), younger (55.97 vs 58.67), publicly insured (60.43% vs 50.45%), and not complete college education (78.06% vs 56.42%), all p < 0.0001. Conclusions No difference was found in the risk of adverse events on the lung transplantation waitlist between different composite community distress quintiles. Future research needs to elucidate the effects of disparities present prior to listing for lung transplantation.

BACKGROUND:Pulmonary arterial hypertension (PAH) is a rare, progressive disease characterised by elevated pulmonary vascular resistance that can lead to right ventricular failure and premature death. Ralinepag is an oral, once-daily, selective prostacyclin IP receptor agonist developed to treat PAH. We aimed to evaluate the efficacy and safety of ralinepag in patients with PAH. METHODS:ADVANCE OUTCOMES was a randomised, double-blind, placebo-controlled, event-driven, phase 3 trial of ralinepag in patients with PAH. Eligible patients were aged 18 years or older and PAH was diagnosed on the basis of the 2022 European Society of Cardiology and European Respiratory Society guidelines (mean pulmonary artery pressure >20 mm Hg, pulmonary artery wedge pressure ≤15 mm Hg, and pulmonary vascular resistance of >2 Wood units). Patients were randomly assigned (1:1) to ralinepag or placebo, initiated at a dose of 50 μg once daily and titrated weekly until the highest tolerated individualised dose was reached. Randomisation was stratified by baseline 6-minute walk distance (6MWD), PAH aetiology, and oral background therapy. A block size of four was used within each combination of stratification factors. The sponsor, patients, and all personnel directly involved with the conduct of the study were masked to study drug identity and randomisation assignments. The primary outcome was time to first clinical worsening event, a composite of death from any cause, admission to hospital due to worsening PAH or right heart failure, initiation of parenteral or inhaled prostacyclin-pathway therapy, disease progression, or unsatisfactory long-term clinical response. Efficacy analyses were done in the full analysis set and safety analyses in the safety set; both sets comprised 687 patients after exclusion of 41 randomly assigned and treated patients from sites in China (exclusions due to regulatory challenges and data integrity concerns). This study is registered with ClinicalTrials.gov (NCT03626688) and euclinicaltrials.eu (2023-509304-16-00) and is complete. FINDINGS:Patients were enrolled between Jan 24, 2019, and June 20, 2025. Of 1037 patients screened for eligibility, 728 were randomly assigned and received at least one dose of ralinepag or placebo; 687 were included in the full analysis and safety sets, of whom 350 received ralinepag and 337 received placebo. Median follow-up from randomisation to clinical worsening event, censoring, or study closure was 85·0 weeks (IQR 27·6-160·9) in the ralinepag group and 78·4 weeks (34·6-137) in the placebo group. At baseline, patients had a mean 6MWD of 438·9 m (SD 104·8) and 548 (80%) of 687 patients were receiving dual background PAH therapy. Overall, 64 (18%) of 350 patients in the ralinepag group and 121 (36%) of 337 patients in the placebo group had a first clinical worsening event (hazard ratio 0·45 [95% CI 0·33-0·62]; p<0·0001). The largest numerical between-group differences in components of the composite outcome were observed for disease progression, initiation of parenteral or inhaled prostacyclin-pathway therapy, and unsatisfactory long-term clinical response. Adverse event was the primary reason for treatment discontinuation in 65 (19%) of 350 patients in the ralinepag group and ten (3%) of 337 patients in the placebo group. Serious adverse events occurred in 98 (28%) patients in the ralinepag group and 104 (31%) patients in the placebo group. Adverse events leading to death occurred in 15 (4%) and 14 (4%) patients, respectively. INTERPRETATION:In patients with PAH receiving contemporary background therapy, ralinepag significantly reduced the risk of first clinical worsening compared with placebo, but was associated with more adverse-event-related treatment discontinuations. These results support the use of ralinepag as an oral, once-daily prostacyclin-pathway treatment option for PAH. FUNDING:United Therapeutics Corporation.

INTRODUCTION:Acute respiratory distress syndrome (ARDS) requiring venovenous extracorporeal membrane oxygenation (VV ECMO) support is associated with chest radiograph changes commonly referred to as "drowning ECMO lung" ECMO lung presents as white-out of both lung fields, involving all lobes of the bilateral lungs. While the clinical significance of chest radiograph findings over time has been described in the general ARDS population, it has not been evaluated specifically in VV ECMO patients. This subpopulation suffers the most severe disease as well as the confounding effects of ECMO support. MATERIALS AND METHODS:We identified 28 patients requiring VV ECMO cannulation for influenza-related ARDS between September 2009 and January 2018. Interpretation of chest X-ray images was divided into zones that correspond to anatomical lobes on computed tomography. Progression of radiologic injury was assessed by analysing the number of zones involved on the chest radiograph (X-ray) at days 1, 3, 7, 14, and 21 from cannulation and discharge. The primary endpoint was survival to hospital discharge. RESULTS:The majority of patients had complete opacification on days 1, 3, and 7 after VV ECMO cannulation. Patients with persistent complete opacification on chest X-ray infiltrate by day 14, following cannulation had an increased mortality. Survival to hospital discharge was increased in patients demonstrating improvement in radiological findings at day 19 compared to patients without significant radiologic improvement (100% vs 53%, log-rank P = 0.003). CONCLUSION:The evolution and recovery of lung injury reflected by serial chest X-ray imaging studies after influenza-related ARDS requiring VV ECMO support is associated with improved survival in this single centre, retrospective cohort.

BACKGROUND:Calcineurin inhibitor (CNI) related kidney dysfunction is common and associated with worse outcomes after lung transplantation (LTx). To mitigate that risk, belatacept use in a CNI-sparing regimen is an alternative in LTx. We aim to describe our experience using belatacept as a CNI-sparing regimen in LTx. METHODS:A multi-institutional retrospective review of LTx patients who received belatacept (1/2018-8/2023) was performed. The primary outcome is the change in estimated glomerular filtration rate (eGFR) after initiation of belatacept. Secondary outcomes were compared with a control group of patients transplanted during 1/2018-8/2023 that did not receive belatacept. Secondary outcomes include acute cellular rejection (ACR), denovo donor specific antibodies (DSA), antibody mediated rejection (AMR), infections, malignancy, chronic lung allograft dysfunction (CLAD) and mortality. RESULTS:A total of 170 LTx patients who received belatacept were included for the primary outcome. To investigate the secondary outcomes an additional 288 LTx controls were used. The median (IQR) eGFR at the time of belatacept initiation, six months, and one year post belatacept initiation was 43 (34-52), 46 (37-53) and 43 (36-53) mL/min/1.73 m2, respectively (p = 0.21). There was no significant difference in ACR, DSA, AMR, infections, malignancy, CLAD or mortality between both groups. CONCLUSIONS:Belatacept CNI-sparing therapy was well tolerated and feasible in LTx recipients, with renal function appearing to stabilize over time and no apparent safety signal for acute rejection, infection, malignancy, CLAD, or mortality.

Background: Telemedicine has become essential for maintaining post-transplant care while reducing exposure risks during the SARS-CoV-2 pandemic. Lung transplant recipients require frequent monitoring due to chronic immunosuppression and comorbidities. This study evaluates patient satisfaction and the feasibility of a lung transplant telemedicine program using a multidimensional, patient-centered survey. Methods: We conducted an observational study at the University of Maryland Lung Transplant Center between March and November 2020. A customized telemedicine satisfaction survey, developed with expert and patient input, was distributed via e-mail to lung transplant recipients, with a follow-up 6 months later. Key domains included quality of care, technology usability, cost burden, and overall experience. Results: Of 148 patients surveyed, 106 responded, with 53 completing the follow-up survey. In the initial and follow-up surveys, 94% and 89% rated telemedicine care as "very good" or "excellent." Technology usability was high, with 96% and 94% reporting good understanding. Most patients (90% initially, 84% at follow-up) noted decreased travel costs. However, while patients appreciated these benefits, preference for in-person visits increased from 45% initially to 65% at follow-up. Conclusion: Lung transplant patients reported high satisfaction with telemedicine, benefiting from reduced costs and COVID-19 exposure risk. The survey captured the complexities of post-transplant care while addressing technological barriers. Future research should validate telemedicine satisfaction tools across multiple centers and assess its impact on clinical outcomes in transplant populations.

Rationale: Few studies have outlined the impact of donor mechanism of death (MoD) on lung transplant (LTx) outcomes. This study aims to analyze all available data from the Organ Procurement and Transplant Network (OPTN) to identify the impact of changing trends in donor MoD on LTx outcomes. Method: This retrospective study analyzed 46,997 de-identified LTx records from January 1990 to April 2024 in the OPTN database. Transplants were stratified by donor mechanism of death and those with either electrical or sudden infantile death syndrome were excluded due to low volume. Survival was measured at 30,90, 180 day and 1,2,5, and 10 years. Results: Overall, intracranial hemorrhage was the most common donor mechanism of death followed by blunt injury and gun-shot wounds (n = 15,688, 11,644, 8,736, respectively). Stab wound donor MoD had the longest median survival time (6.779 years), followed by cardiovascular (6.190 years), while intracranial hemorrhage/stroke (5.309 years) and drowning (5.342 years) had the shortest. Short term survival until 180 days was significantly higher in drug intoxication MoD LTx followed by asphyxiation compared to all other MoD (180-day survival, 92.7% and 91.9% respectively). Short term survival was lowest amongst stab wound related MoD (180-day survival 88.62%). Survival at 1 and 2 years was highest amongst donor MoDs of natural causes (88.77%) and drug intoxication (79.4%) respectively. Survival at 5 years was highest amongst those with stab wounds (61.9%) followed by seizures (57.8%). In contrast, survival was lowest amongst those with donor MoD of intracranial hemorrhage (52%). 10-year survival is highest amongst those with cardiovascular related MoD LTx followed by stab wounds and lowest amongst drowning donor MoD. All findings were statistically significant with log-rank p-value <0.0001. Conclusion: Survival outcomes of recipients may be dependent on the MoD of the donor with drug intoxication and natural causes associated with higher short and medium-term survival rates. In contrast, stab wounds have the highest overall median survival. More data should be explored to understand the potential prognostic and donor selection implications of donor MoD on LTx recipient survival.

BACKGROUND:Lung transplant (LT) recipients with high-risk cytomegalovirus (CMV) mismatch donors (donor seropositive, recipient seronegative) have worse early and late outcomes. We sought to describe the outcomes among high-risk mismatch patients managed using proactive monitoring and multimodality prophylaxis and management protocol. METHODS:We included patients with single or bilateral lung transplants between January 2012 and December 2016 (n = 324). The patients were classified into two groups: high-risk CMV mismatch (R-/D+): n = 83 (25.6%) and non-high-risk CMV mismatch (n = 241). Post-LT follow-up period ranged from 8 to 12 years. Post-transplant survival was analyzed as the primary outcome variable. RESULTS:There was no difference in LT recipients' baseline and post-transplant characteristics with and without CMV-mismatch donors. The mismatch group experienced a significantly higher frequency and burden of CMV viremia (p < 0.001) and resistant viremia (p < 0.001). Regardless, the two groups had similar long-term outcomes with no statistically significant difference in CLAD-free survival at 3 years or overall post-transplant survival. On Cox proportional hazard analysis, transplant indication was the only independent predictor of post-transplant survival (p = 0.004). CONCLUSIONS:A proactive multimodality CMV management protocol consisting of antiviral agents (ganciclovir/valganciclovir) and immune augmentation with CMV immune globulin may improve outcomes among high-risk CMV mismatch LT recipients.

INTRODUCTION:Access to transplantation is not entirely equitable with several studies demonstrating racial and socioeconomic disparities affecting the transplant process and thereby outcomes. Notably, few studies have focused on disparities prior to waitlisting. This study aimed to characterize the impact of community socioeconomic factors as measured by the Distressed Community Index (DCI) on acceptance for lung transplant waitlisting. METHODS:A retrospective review was performed on 463 patients evaluated for lung transplant waitlisting at our institution between 2016 and 2020. Community distress was calculated using the DCI, which yields a composite Distress Index (cDI) and includes data on various community characteristics. Statistical analysis was done using descriptive statistics and logistic regression methods. RESULTS:Of the 463 patients included, 333 (71.9%) were accepted and 130 (28.1%) were denied for waitlisting. The mean cDI was 42.5 (±30.0) and 44.8 (±30.8) (p = 0.45) for the accepted and declined groups, respectively, indicating mid-tier distress for both groups by DCI metrics. The cDI was not found to be associated with odds of waitlist acceptance (OR 0.997, CI 0.99-1.004, p = 0.455). Furthermore, there was no association between sex, race, ethnicity, public insurance coverage, or any of the subcomponents of the DCI and the odds of successful waitlisting at our institution. CONCLUSION:This single-center retrospective evaluation found that cDI, as calculated by the DCI, and the DCI subcomponents were not associated with transplant waitlist acceptance. Future studies should be done evaluating community-level socioeconomic disparities and the utility of community disadvantage indexing tools in the lung transplant waitlisting process, with the intentions of conceptually expanding our understanding of the link between transplant outcomes and biopsychosocial candidacy.

BACKGROUND:Belatacept use in renal transplant is associated with similar graft survival and elimination of preexisting donor-specific antibodies (DSA). We aim to describe the impact of Belatacept use on de novo DSA in lung transplant (LTx). METHODS:A multi-institutional retrospective review of LTx patients with de novo DSA who received Belatacept (January 2018-August 2023) was performed. The primary outcome is the change in DSA post Belatacept initiation. Changes in mean fluorescence intensity (MFI) before and after Belatacept administration were analyzed using a linear mixed-effects model. Secondary outcomes included antibody-mediated rejection (AMR). RESULTS:Forty-four patients with DSA received Belatacept. Most DSA were class II (n = 41, 93%), with a median (IQR) MFI of 4000 (2500-7000) at Belatacept initiation. Following Belatacept initiation, DSA resolved in (n = 25, 57%) patients, decreased in (n = 7, 16%), and remained unchanged in (n = 12, 27%). No de novo DSA developed during Belatacept therapy. There was no significant change in MFI pre Belatacept administration (change = -38, 95% CI: -267 to 191, p = 0.745), whereas MFI decreased significantly post Belatacept administration (change = -334, 95% CI: -449 to -219, p < 0.001). A total of (n = 25, 57%) patients experienced AMR prior to initiating Belatacept. None of the patients developed AMR while on Belatacept. CONCLUSION:This is the largest cohort to date of LTx patients with DSA who received Belatacept. Belatacept use was associated with a reduction in DSA.