BACKGROUND:Kidney transplant programs may remove high-risk patients from the national transplant waiting list to mitigate peri-transplant complications and enhance overall post-transplant survival. The phrase "too sick," frequently reported to the Organ Procurement and Transplantation Network (OPTN) as a reason for removal, lacks precision and specificity. Furthermore, there is limited information regarding the survival outcomes of patients who have been delisted and are consequently ineligible for a kidney transplant. In this study, we describe the specific reasons for delisting and investigate subsequent survival outcomes after being removed from the waiting list. METHODS:Data were collected from patients 18 years and older removed from the renal transplant waiting list between January 2011 and December 2015. Delisting categorization divided patients into a medical group (removed for clinical reasons such as cardiovascular disease, malignancy, or severe iliac calcification) and a psychosocial group (removed for issues such as patient request, non-compliance, insurance loss, or loss of contact). The primary endpoints were 5-year survival and restricted mean survival time (RMST) at 5 years. RESULTS:Out of 240 eligible patients, 124 patients (51.7%) were delisted for medical reasons and 116 (48.3%) were delisted for psychosocial reasons. Upon investigation, the primary reason for removal from the transplant waiting list among the medical group was cardiovascular (CV)-related comorbidities (44, 35.5%). 55% of the total number of patients delisted survived for 5 years. Patients delisted for medical reasons exhibited a 5-year survival rate of 43% and a RMST of 3.3 years. Specifically, patients delisted for CV-related reasons had a 5-year survival rate of 44%. In contrast, patients delisted for psychosocial reasons had a higher 5-year survival rate of 70% and a longer RMST of 4.31 years (p-value < 0.001). At 5 years following delisting, patients diagnosed with coronary artery disease (CAD) exhibited a 51% survival rate, which was significantly lower compared to those without CAD with a survival rate of 57% (p = 0.046). CONCLUSION:Cardiovascular disease remains the leading cause of delisting from the kidney transplant waiting list. However, many delisted patients demonstrated longer survival than expected. Further studies are needed to clarify the impact of delisting decisions on outcomes and to guide more informed, patient-centered transplant practices.
Donation after circulatory death (DCD) liver transplantation is increasingly supported by routine use of normothermic machine perfusion (NMP), yet established risk scores, including the UK DCD score, predate widespread NMP adoption. We conducted a retrospective single-center cohort study of adult DCD liver transplants at Mayo Clinic Arizona from January 2019 through December 2024 (n = 586), comparing outcomes of NMP versus static cold storage (SCS) across UK DCD low-, high-, and futile-risk strata. Primary outcomes were early allograft dysfunction (EAD), ischemic cholangiopathy (IC), and graft and patient survival censored at two years. Of 586 transplants, 375 were preserved with NMP and 211 with SCS. Despite older donor age and longer warm ischemia times in the NMP cohort, NMP was associated with lower rates of EAD and IC across all strata. Two-year graft survival was higher with NMP than SCS (91% vs. 80%; p<0.001), and two-year patient survival was 96% versus 89% (p = 0.002). The graft and patient survival advantage was most pronounced in the high-risk (graft survival p = 0.004; patient survival p = 0.02) and futile strata (graft survival p = 0.01; patient survival p = 0.01), whereas graft survival was similar between preservation methods in the low-risk group. These findings support the use of the UK DCD score as a triage tool to guide NMP allocation, with the greatest benefit observed in high-risk and futile grafts for whom NMP should be considered essential rather than optional.
Normothermic machine perfusion (NMP) has enabled increased utilization of high-risk liver allografts; however, real-world data describing use, perfusion logistics, and associated outcomes remain limited. We established the National Organ Perfusion Registry (NOPR), a multicenter collaborative registry designed to capture granular perfusion data not available in the national transplant datasets. Adult liver transplant recipients who underwent transplantation using NMP between 2022 and 2024 at nine U.S. centers were included. Registry data were linked to the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research files to obtain donor and recipient characteristics and post-transplant outcomes. Descriptive analyzes were performed to characterize the indications for NMP use, procurement practices, perfusion timing parameters, and early graft outcomes. A total of 545 NMP liver transplants were analyzed, including 282 donations after circulatory death (DCD) and 263 donations after brain death (DBD). DCD was the most common indication for NMP, and its incidence increased substantially during the study period. Perfusion practices varied, including procurement strategy, device use, time from cross-clamp to NMP initiation, and total perfusion duration. Despite this heterogeneity, early outcomes were favorable, with a 90-day death-censored graft failure rate of 1.7%, and no difference between DCD and DBD grafts. Recipients of DCD grafts had a shorter post-transplant length of stay than DBD recipients. In this multicenter, real-world cohort analysis, NMP was associated with low rates of early graft failure across diverse centers and perfusion practices. These findings support the feasibility of contemporary NMP use and underscore the importance of continued multicenter evaluation to refine perfusion strategies.
Alcohol-associated liver disease (ALD) has become the leading indication for liver transplantation (LT) in the United States. Contemporary practice has shifted toward broader LT access for medically urgent patients with limited pretransplant abstinence or alcohol use disorder (AUD) treatment experience. These patients require AUD treatment post-LT; however, standardized treatment protocols in this setting remain limited. In response to this need, our center implemented a virtual monthly group-based relapse prevention program (RPP) for liver transplant recipients (LTRs) transplanted for ALD. The aim of this quality improvement initiative was to examine the feasibility and acceptability of our program. Sessions were administered virtually by a licensed clinical addiction specialist. We collected data from the electronic health record, patient survey data, and qualitative feedback via a focus group at program completion. Of 46 patients contacted, 41% (n = 19) completed initial enrollment, and 30% (n = 14) attended at least one session. The majority of patients (61%) were male and those who enrolled were transplanted more recently (15 versus 26 months post-LT). Attendance was higher in patients with private insurance and a diagnosis of alcohol-associated hepatitis. Our program was well-received overall by participants, as seen in both patient satisfaction scores and qualitative feedback. Although focus group participants felt the program was not essential for maintaining abstinence, largely due to an already established commitment to abstinence, they valued the sense of community and purpose it provided. With rising ALD burden and broader access to urgent LT, structured and accessible posttransplant AUD interventions remain an important and unmet need.
Fibrosis is common in diverse conditions but has different patterns across tissues and organs despite shared cellular and molecular pathways reasons for which are mostly unexplained. In this review we discuss chronic graft-Versus-host disease (GvHD), progressive systemic sclerosis (PSS), idiopathic pulmonary fibrosis (IPF), primary myelofibrosis (PMF), chronic lung allograft dysfunction (CLAD) and VEXAS syndrome to explore potential mechanisms underlying these patterns of fibrosis. We propose the distribution of fibrosis reflects a complex interplay between aetiology, initiating stimuli, local immune response, tissue-specific micro-environment and host susceptibility. Distinguishing systemic and local drivers of fibrosis is needed to understand and explain these patterns. A deeper understanding of early, tissue-specific events governing fibrotic responses may allow development of preventive and therapeutic strategies.
BACKGROUND:Over 4,500 individuals undergo heart transplantation (HT) in the United States every year. Limited qualitative data exist evaluating challenges and barriers in the evaluation and post-transplant process and their association with primary language spoken. METHODS:We conducted semi-structured interviews with individuals who received HT at a high-volume urban academic medical center between 2015 and 2024. Primary English and Spanish speaking patients were included; interviews were conducted by a certified Spanish speaker. Interviews were audio-recorded and transcribed for thematic analysis. Themes were compared based on primary language spoken. RESULTS:34 HT recipients (median age 61 years, 38% women) participated in this study. Forty-one percent (n = 14) identified Spanish as their primary language. Three key thematic differences emerged based on primary language spoken: (1) perception of the transplant process and emotional needs, (2) financial concerns while awaiting transplant, and (3) methods of communication. Spanish speaking patients more commonly relied on family support, faith, and public assistance programs to navigate the transplant process. English speaking patients, on the other hand, more frequently struggled with the morality of accepting a transplant. Additionally, English speaking patients more commonly had increased financial resources, highlighting the intersection with education and other social determinants of health (SDOH). CONCLUSION:This study identifies key differences in the experiences of HT recipients based on the patient's primary spoken language and inter-related SDOH. This study can inform future studies focused on the impact of health policy changes and the expansion of social support systems on transplant allocation among linguistically diverse communities.
INTRODUCTION:Obesity is a significant barrier to kidney transplantation (KT). KT candidates with obesity are often referred to weight management programs (WMP) but patients' acceptance for WMP referral and their subsequent follow-through are unknown. DESIGN AND METHODS:Using a single-center study, we evaluated the effectiveness of referrals to medical or surgical WMPs among KT candidates to initiate obesity care. We examined factors associated with patients establishing care and any effects of referral acceptance on BMI, KT waitlisting and transplantation. RESULTS:The median age was 57 years, 49% were male, 56% were White, 79% were on dialysis, and 53% were from high social disadvantage areas. Thirty patients (50.8%) accepted WMP referral but only 9 (15.3%) contacted WMP. Patients accepting referral had higher BMI [median 47 vs. 45; p = 0.002] and resided closer to the KT center [20 vs. 48 miles; p = 0.010]. In multivariable models, referral acceptance decreased 2% with each mile away from KT center (OR 0.98; 95%CI: 0.96-1.00) and increased by 22% with every 1 unit increase in BMI (OR 1.22, 95%CI: 1.03-1.45). Among patients accepting referral, every 1-year increase in age reduced odds of contacting WMP by 17% (OR 0.83, 95%CI: 0.74-0.96). CONCLUSION:A large share of KT candidates with obesity do not establish care with WMPs. Increasing age and distance to KT center were contributing factors to low referral acceptance and engagement. Efforts aimed at obesity management in KT should consider these barriers. WMPs integrated within KT programs may overcome barriers to establishing care with WMPs.
BACKGROUND:With increasing use of donation after circulatory death (DCD) donor grafts, the need for accurate risk-stratification tools in liver transplantation has become critical. Machine perfusion has been shown to improve both graft and patient survival. However, existing prediction models were developed in the static cold storage (SCS) era and their accuracy when using machine perfusion remains unknown. Our study aims to study if current scoring systems can predict graft and patient survival for DCD livers preserved using normothermic machine perfusion (NMP). METHODS:This was a retrospective study of patient and graft survival in a two-center U.S. DCD NMP cohort (n = 532) between January 2022 and December 2024. Predicted graft and patient survival rates were obtained from established risk scoring systems, including the United Kingdom DCD risk score (UK-DCD), Early Allograft Dysfunction (EAD) Olthoff score, Liver Graft Assessment Following Transplantation (L-GrAFT7) score, Donor Risk Index (DRI), Balance of Risk (BAR) score, and Survival Outcomes Following Liver Transplant (SOFT) score. Model discrimination was assessed using receiver operating characteristic (ROC) curves (C-statistics). Survival outcomes across risk strata were estimated and compared using Kaplan-Meier (KM) analysis. RESULTS:Across scoring systems, predicted survival consistently underestimated actual graft and patient survival in the NMP DCD cohort. The DRI, SOFT, EAD and L-GrAFT7 did not demonstrate predictive value. UK-DCD predicted ≤85% and <40% 1-year graft survival for its high-risk and "futile" groups, whereas observed rates were 93.7% and 86.8%. BAR low-risk predicted >60% 5-year survival but 94.2% was observed; the high-risk group predicted <60% and observed was 53.3%. Despite underestimations and generally poor C-statistics, in KM stratification, high-risk groups still showed statistical differences in the UK-DCD categories (p = 0.007), and in SOFT score groups (p < 0.001). No statistical difference was seen in BAR (p = 0.36), DRI (p = 0.36), EAD (p = 0.12), or L-GrAFT7 (p = 0.75). CONCLUSION:Existing liver transplant risk scores show limited predictive value for donor-related risk factors in the NMP era, whereas recipient-related factors remain somewhat predictive, despite overestimating risk. Early allograft dysfunction metrics were not reliable predictors of short or long-term outcomes. Future risk models should integrate machine-perfusion parameters and refined donor variables to reflect outcomes more accurately in contemporary DCD liver transplantation.
INTRODUCTION:Dysphagia, gastroesophageal reflux disease (GERD), and delayed gastric emptying (DGE) are foregut risk factors associated with worse lung transplant outcomes. Transplant education varies across centers, and patient awareness of these risk factors could impact treatment adherence and outcomes. METHODS:Pre- and post-lung transplant patients attending pulmonary rehabilitation between 01/2025-06/2025 were invited to complete a questionnaire developed by a multidisciplinary team to assess knowledge, perceived importance, and self-confidence in understanding the evaluation and management of foregut risks. Knowledge and confidence of disease factors were evaluated and assessed. Patient demographics, transplant history, and education preferences were collected. Comparisons were made between pre- and post-transplant groups using Chi-square tests for categorical measures. RESULTS:Among 67 eligible patients, 48 (71.6%) completed the survey. There were no significant differences in age, sex, race, education level, or household income between pre- and post-transplant groups. Recognition of GERD as a risk factor for graft rejection was similar between pre- and post-transplant groups (24, 85.7% vs. 19, 95.0%; p = 0.30), as was overall confidence in understanding DGE as a risk factor (19, 67.9% vs. 13, 65.0%; p = 0.84). Respondents preferred to receive information on risks from the lung transplant team, but most (n = 28, 58.3%) patients indicated gastroenterologists should be most responsible for educating about and managing foregut risks. CONCLUSION:Knowledge of foregut risks and corresponding confidence is high before and after transplant, which may reflect standardized education. Most patients preferred gastroenterology engagement in education on foregut disease, which is currently underutilized and could be an opportunity for multidisciplinary care.
BACKGROUND:Acute kidney injury (AKI) is common following lung transplantation (LTx), and is associated with increased morbidity and mortality. Existing renal injury risk models have not systematically evaluated perioperative variables. We aimed to develop comprehensive preoperative and early postoperative prediction models for AKI and renal replacement therapy (RRT) following LTx. METHODS:Adult LTx recipients at a single Australian tertiary center (January 2016-April 2025) were included in a retrospective cohort study. The KDIGO 2012 serum creatinine criteria were used to define AKI. Stable predictors identified via penalized regression with bootstrap resampling were incorporated into multivariable logistic regression models. Bootstrap internal validation provided optimism-adjusted performance estimates, and decision curve analysis evaluated net clinical benefit. RESULTS:Of 534 patients, 216 (40.4%) developed AKI, and 47 (8.8%) required RRT. The preoperative AKI model, incorporating baseline demographics, comorbidities, and laboratory variables, achieved a C-statistic of 0.632 (95%CI: 0.589-0.679). The postoperative AKI model demonstrated improved discrimination (C-statistic 0.741, 95%CI: 0.697-0.795), incorporating preoperative variables such as chronic lung allograft dysfunction as a transplant indication, alongside procedure duration and novel early postoperative predictors: P/F ratio and cumulative noradrenaline dosage. The RRT models achieved C-statistics of 0.720 (95%CI: 0.643-0.796) and 0.847 (95%CI: 0.781-0.917). Calibration slopes ranged from 0.889-0.949. Decision curve analysis demonstrated net clinical benefit over treat-all strategies across clinically relevant threshold probabilities. CONCLUSIONS:Early postoperative models demonstrated superior discrimination and clinical utility, with timepoint-specific risk stratification capturing distinct perioperative determinants of renal injury. These models provide a foundation for external validation and targeted nephroprotective research in LTx.
INTRODUCTION:Hospitals in the United States are assigned to a designated organ procurement organization (OPO) responsible for managing deceased donors in the designated donation service area (DSA). Hospitals can apply for waivers to work with a different OPO with appropriate justification. We sought to evaluate the impact of hospital waivers on organ donation activity. METHODS:We evaluated Organ Procurement and Transplantation Network (OPTN) data from two OPOs (Donor Network West and Honor Bridge), each with a hospital (Renown Regional Medical Center and North Carolina Baptist Hospital) in its DSA granted a waiver to work with a different OPO beginning in April 2025. We assessed changes in the number of organ donors and organs transplanted pre- and post-granting of a waiver using a difference-in-differences approach based on multilevel mixed-effects models. RESULTS:After switching OPO affiliations, mean monthly donors at intervention hospitals increased from 5.6 pre-waiver to 7.9 post-waiver, while control hospitals remained stable (56.6 vs. 57.5 donors/month). Mean monthly organs transplanted increased from 16.5 to 24.9 at intervention hospitals, while control hospitals were unchanged (170.9 vs. 169.3 organs/month). The difference-in-differences interaction term was statistically significant for both donors recovered (p < 0.1) and organs transplanted (p < 0.1). Reported deaths were stable in both groups. CONCLUSION:With eight months of post-waiver data, hospitals with granted waivers had significant increases in donation activity driven by improved donor conversion rather than changes in referral patterns or organ yield per donor. Although longer-term data are needed to confirm these findings, CMS and the organ transplant community should feel confident that changing donor hospital-OPO affiliations will not negatively impact donation and may lead to significant increases in donation.
BACKGROUND:Despite therapy, some patients with rheumatoid arthritis related interstitial lung disease (RA-ILD) require lung transplantation for progressive disease. We aimed to identify factors associated with lung transplantation and post-transplantation survival in RA-ILD. METHODS:We performed a retrospective observational cohort study using data from Ontario, Canada between 2003 and 2022. RA-ILD patients were identified from the Ontario RA Database. We used a cause-specific hazards model, considering the competing risk of death, to identify factors associated with lung transplantation. A Cox proportional hazards model was used to evaluate post-transplant survival. RESULTS:Among 6470 RA-ILD patients, 77 (1.2%) underwent lung transplantation, equating to 2.40 transplants per 1000 person years. The median time to transplant was 3.7 years. Younger age [HR 0.93 per increasing year (95%CI 0.91-0.95), p < 0.0001], male sex [HR 2.40 (95%CI 1.523.78), p = 0.0002], and comorbid diabetes [HR 1.70 (95%CI 1.06-2.73), p = 0.003], congestive heart failure [HR 1.87 (95%CI 1.15-3.04), p = 0.01] and COPD [HR 2.14 (95%CI 1.25-3.68), p = 0.006] were associated with transplantation. The median survival following transplantation was 4.3 years. CONCLUSION:Lung transplantation is an uncommon, but important therapy for RA-ILD. Select comorbidities are associated with lung transplantation. Post-transplant survival among RA-ILD patients in Ontario was comparable to that reported elsewhere.
BACKGROUND:Normothermic regional perfusion (NRP) is associated with improved posttransplant outcomes in donation after circulatory death (DCD) kidney transplantation. It remains unknown whether hypothermic machine perfusion (HMP) offers additional benefits over static cold storage (SCS) during transport. METHODS:All adult kidney-only transplantations from DCD donors procured by NRP in the OPTN data (10/1/2020-6/30/2025) were identified. Primary exposure was preservation method during transport: NRP combined with HMP (NRP+HMP) or SCS (NRP+SCS). One-to-two propensity score matching (PSM) was performed on fifteen donor and recipient factors. Primary outcomes included delayed graft function (DGF), posttransplant length of stay (LOS), and estimated glomerular filtration rate (eGFR) at 6 months posttransplant. Secondary outcomes were one-year graft and patient survival. RESULTS:Among 4792 NRP cases, HMP was utilized in 85.1%, with its use increasing over time. After 1:2 PSM (685 NRP+SCS matched to 1262 NRP+HMP), NRP+HMP was associated with significantly lower DGF (23.3% vs. 30.5%, p < 0.01). Median LOS (4.0 days in both groups, p = 0.07), 6-month eGFR (58.5 vs. 60.1 mL/min/1.73m2, p = 0.46), one-year graft survival, and one-year patient survival were not significantly different. The association between HMP and lower DGF was observed across KDPI strata, heart recovery status, and cold ischemia time categories, with no significant interactions detected. CONCLUSION:The adoption of HMP after NRP has increased substantially in the United States and was associated with reduced DGF, but no difference was observed for LOS, 6-month eGFR, graft survival, and patient survival. These findings support the routine use of HMP after NRP.
BACKGROUND:As a 6-month waiting period is required to receive exception points to prioritize patients with hepatocellular carcinoma (HCC) for liver transplantation, prompt addition to the waitlist is critical in access to LT. METHODS:Using Epic Cosmos data on patients with HCC referred for LT 1/2018-10/2024, we used modified Poisson regression to calculate rates of waitlisting. Center-level and individual (socioeconomic, geographic, and insurance) factors were measured among those who progressed. RESULTS:Among 11,422 HCC patients referred for LT at 70 centers, with median age 63 [IQR: 58, 68], 71.5% initiated evaluation and, of those who began evaluation, 57.6% were waitlisted for LT. Of those referred, patients who were older (age 70+ vs. 51-60; RR 0.77, 95% CI: 0.65-0.90, p < 0.001), on Medicaid (0.83, 95% CI: 0.71-0.97, p = 0.02), never-married (0.82, 95% CI: 0.73-0.91, p < 0.001), or low SES (Q4: 0.87, 95% CI: 0.77-0.97, p = 0.002) had lower rates of waitlisting. Among waitlisted patients, median time from referral was 3.3 months [IQR: 2.0, 5.3]. Despite adjustment for patient level covariates, there was high center-level variation in rate of waitlisting within 12 months; 13% of centers listed patients at a rate ≥ 20% below the national median. CONCLUSION:Only a fraction of referred patients with HCC are waitlisted for LT. High variation in access to waitlisting based on non-clinical factors suggests barriers to waitlisting that must be addressed. Centers should focus on interventions to reduce barriers to waitlisting in patients with HCC.
Over the years, autologous hematopoietic cell transplantation (auto-HCT) has become one of the most important therapeutic methods of contemporary hematology. However, analyses of survival after treatment are usually limited to 5-10 years. Data on longer survival are limited due to difficulties and loss in follow-up, as well as organizational and personnel changes in transplant centers. Therefore, our study aimed to evaluate the 15- and 20-year overall and progression-free survival of the recipients of auto-HCT in our center without exclusion of salvage indications and patients with comorbidities. During the period ranging from 1999 to 2014, there were 452 recipients of auto-HCT. Survival analyses were performed using Kaplan-Meier curves, the Cox proportional hazards model, and the log-rank test. First, the entire cohort was evaluated for 15- and 20-year overall and progression-free survival. Then, similar analyses were performed for subgroups of patients with more frequent indications, including multiple myeloma, AL amyloidosis, Hodgkin lymphoma (HL), non-Hodgkin lymphomas (NHLs), and acute myeloid leukemia. It was found that after 10 years, both overall and progression-free survival slowly but gradually declined. Still, a significant proportion of transplanted patients survived 20 years following auto-HCT, confirming the ability to cure in at least some cases of these earlier incurable disorders.
Pediatric heart transplant (PHTR) recipients have reduced cardiorespiratory fitness (VO2peak); however, the magnitude of this impairment and its underlying central hemodynamic mechanisms remain poorly characterized. This systematic review and meta-analysis quantified differences in VO2peak and peak exercise central hemodynamics between PHTR recipients and age-matched healthy controls (CON). MEDLINE (PubMed) was searched for studies comparing VO2peak in PHTR recipients and CON. Pooled effect sizes were expressed as weighted mean differences (WMD) using a DerSimonian-Laird random-effects model, and weighted least-squares meta-regression assessed the moderating effects of age and time post-transplant. Seven unique studies (PHTR n = 90; CON n = 118) reported VO2peak and peak HR. PHTR had significantly lower VO2peak (WMD = -9.5 mL/kg/min), peak HR (WMD: -30 bpm), and CO (n = 3 studies, WMD: -2.5 L/min), with no difference in peak SBP (n = 3 studies). Meta-regression revealed no significant moderating effect of age or time post-transplant on the VO2peak deficit. The markedly reduced VO2peak in PHTR recipients is driven primarily by impaired peak CO and persistent chronotropic incompetence, consistent with cardiac allograft sympathetic denervation.
