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Background: Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated., Methods: We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed., Results: The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction., Conclusions: Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: This study examines the effect of belatacept based salvage regimens on kidney transplant outcomes., Methods: This single-center retrospective study included all adult kidney transplant recipients between 2011 and 2022 who were converted to belatacept salvage therapy during their follow up. eGFR, graft survival, incidence of infections and neoplasia, histology and DSA data were collected through systematic review of the medical record., Results: Patients were divided into 3 groups based on salvage regimen: Mycophenolate mofetil/belatacept (MMF/Bela) (n = 28), low-dose Calcineurin inhibitors/belatacept (CNI/Bela) (n = 22), and low-dose Calcineurin inhibitors/ Mycophenolate mofetil /belatacept (CNI/MMF/Bela) (n = 13). Patients with antibody-mediated rejection were more likely to receive CNIs in addition to belatacept (low-dose CNI/MMF/Bela 54%, low-dose CNI/Bela 45%, MMF/Bela 3.6%, p < 0.001). DSA decreased in all groups after transition to belatacept by 15.67% (p = 0.15). No difference in Glomerular filtration rate (eGFR) over time was observed between the groups, and eGFR remained stable over the first year after transition to belatacept. The incidence of death and allograft failure was similar between the groups (low- dose CNI/MMF/Bela n = 3, low-dose CNI/Bela n = 7, MMF/Bela n = 4; p = 0.41). Patients in the low-dose CNI/Bela cohort who were transitioned to belatacept within 6 months from transplant showed a decline in eGFR over the first year after transition, while the other treatment cohorts demonstrated stable or slight increase in eGFR., Conclusions: The present study demonstrates comparable transplant outcomes in terms of eGFR, graft survival, incidence of infections and neoplasia, rejection rate and donor specific antibody (DSA) in three belatacept-based maintenance immunosuppression regimens supporting the safety and efficacy of these therapeutic options., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Impacts of ischemic time (IT) on pediatric heart transplant outcomes are multifactorial. We aimed to analyze the effect of prolonged IT on graft loss after pediatric heart transplantation. We hypothesized that graft survival with prolonged IT has improved across eras., Methods: Patients <18 years old in the Pediatric Heart Transplant Society database were included (N=6,765) and stratified by diagnosis and era (1993-2004, 2005-2009, and 2010-2019). Severe graft failure (SGF) was defined as death, retransplant, or need for mechanical circulatory support in the first 7 days post-transplant. Descriptive statistical methods were used to compare differences between patient characteristics and IT. Kaplan-Meier survival analysis compared freedom from graft loss, rejection, and infection. Multivariable analysis was performed for graft loss and SGF (hazard and logistic regression modeling, respectively)., Results: Diagnoses were cardiomyopathy (N = 3,246) and congenital heart disease (CHD; N = 3,305). CHD were younger, more likely to have an IT ≥4.5 hours, and more likely to require extracorporeal membrane oxygenation or mechanical ventilation at transplant (all p < 0.001). Median IT was 3.6 hours (interquartile range 2.98-4.31; range 0-10.5). IT was associated with early graft loss (HR 1.012, 95% CI 1.005-1.019), but not when analyzed only in the most recent era. IT was associated with SGF (OR 1.016 95%CI 1.003-1.030)., Conclusions: Donor IT was independently associated with an increased risk of graft loss, albeit with a small effect relative to other risk factors. Graft survival with prolonged IT has improved in the most recent era but the risk of SGF persists., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: Delayed graft function (DGF) is a common condition that necessitates dialysis during the first week after transplantation. Although DGF rarely occurs following living-donor kidney transplantation (LDKT), it may eventually lead to acute or chronic graft rejection. This study aimed to assess the risk factors for DGF in patients who underwent LDKT., Methods: A systematic review and meta-analysis of studies published before August 2022 was conducted using the PubMed, Science Direct, Cochrane, and Directory of Open Access Journal (DOAJ) databases. The review included studies that assessed the incidence of DGF following LDKT, and examined its risk factors, while excluding studies involving deceased donors. Potential risk factors were analyzed using pooled mean differences or odds ratios with 95% confidence intervals (CIs). Review Manager 5.3 was used for the meta-analysis., Results: Among the 13 included studies, 3685 cases of DGF were identified in a total of 113,261 patients (3.25%). Potential risk factors for DGF following LDKT were examined across several aspects, including donor, recipient, donor/recipient relationship, and immunological and intraoperative factors. The identified risk factors included older donors (P = 0.07), male recipients (P < 0.0001), higher recipient body mass index (BMI) (P < 0.0001), non-white recipients (P < 0.0001), pre-existing diabetes (P < 0.0001), pre-existing hypertension (P = 0.01), history of dialysis (P < 0.0001), re-transplantation (P = 0.004), unrelated donor/recipient (P = 0.02), ABO incompatibility (P < 0.0001), higher panel reactive antibody (PRA) levels (P < 0.0001), utilization of right kidney (P < 0.0001), and longer cold ischemia time (CIT) (P = 0.004)., Conclusion: Several factors related to the donor, recipient, donor/recipient relationship, and immunological and intraoperative aspects were identified as potential risk factors for the development of DGF following LDKT. Addressing and optimizing these factors may improve the long-term outcomes of LDKT., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multiorgan transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multiorgan heart transplants in the contemporary era., Methods: We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary end-point was the development of angiographic CAV within 5 years of follow-up., Results: Among 20,591 patients included in the analysis, 1,279 (6%) underwent multiorgan heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ), and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years, and 74% were male. There were no significant between-group differences in cold ischemic time. The incidence of acute rejection during the first year after transplant was significantly lower in the multiorgan group (18% vs 33%, p < 0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multiorgan group (p < 0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multiorgan heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio = 0.76, 95% confidence interval: 0.66-0.88, p < 0.01)., Conclusions: Simultaneous multiorgan heart transplantation is associated with a significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients., Methods: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes., Results: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection., Conclusions: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes., Methods: All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics., Results: A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays., Conclusions: A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of graft failure in pediatric heart transplant recipients (HTRs). Early statin use has been shown to reduce CAV incidence and all-cause mortality in adult HTRs. We sought to evaluate the contemporary prevalence and trends of statin use in pediatric HTRs and the association between statin use with CAV development and graft failure., Methods: Patients aged <17 years at the time of primary heart transplant who survived to ≥3 years without CAV were identified from the Pediatric Heart Transplant Society database (2001-2018). Statin use in the first 3 years posttransplant was defined as consecutive, intermediate, or absent. Kaplan-Meier survival, multivariable modeling, and propensity score-matched analyses evaluated associations between statin use and CAV incidence and graft survival, with subanalyses performed on subjects aged ≥10 years at transplant., Results: Among 3,485 (of which 1,086 aged ≥10 years) HTRs, 584 (17%) received consecutive statin therapy, 647 (19%) received intermediate use, and 2,254 (65%) received no statin therapy. Statin use varied widely between sites, with increasing use in the ≥10-year-old cohort over time. By multivariate analysis, statin use was not associated with graft loss. Consecutive statin use was also not associated with graft survival or freedom from CAV development when compared to absent statin use in unmatched or propensity-matched analyses., Conclusions: While statins remain commonly utilized in pediatric HTRs, early consecutive statin therapy did not decrease CAV incidence or graft loss. The differing effects of statins on CAV development and progression in pediatric vs adult HTRs suggest differing risk and mediating factors and require further study., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The relationship between sarcopenia and prognosis in solid organ transplantation recipients (SOTr) remains unverified. We aimed to quantify the prevalence of pretransplant sarcopenia and its effect on patient and graft survival in SOTr. We used PubMed, EMBASE, Cochrane Library and Web of Science to search relevant studies published in English (from inception to December 31, 2021). Prospective and retrospective cohort studies that reported the prevalence of sarcopenia before transplant or the association between sarcopenia and clinical outcomes in SOTr were included. Primary outcomes were the prevalence of sarcopenia and its impact on patient and graft survival. Secondary outcomes included perioperative complications, acute rejection, length of hospital stay, length of intensive care unit stay (ICU LOS) and early readmission. Thirty-nine studies involving 5792 patients were included. Pooled prevalence of sarcopenia amongst SOTr candidates was 40 % (95 % confidence interval [CI]: 34%-47 % and I 2  = 97 %). Sarcopenia was associated with increased risk of death (hazard ratio [HR] = 1.87, 95 % CI: 1.46-2.41 and I 2  = 60 %), poor graft survival (HR = 1.71, 95 % CI: 1.16-2.54 and I 2  = 57 %) and increased liver graft loss (HR = 1.43, 95 % CI: 1.03-1.99 and I 2  = 38 %). Patients with sarcopenia demonstrated increased incidence of perioperative complications (risk ratio [RR] = 1.34, 95 % CI: 1.17-1.53 and I 2  = 40 %), long ICU LOS (mean difference = 2.31 days, 95 % CI: 0.58-4.04 and I 2  = 97 %) and decreased risk of acute rejection (RR = 0.61, 95 % CI: 0.42-0.89 and I 2  = 0 %). In Conclusion, sarcopenia is prevalent in SOTr candidates and associated with death and graft loss. Identifying sarcopenia before transplantation and intervening may improve long-term outcomes., Competing Interests: Declaration of competing interest No conflict of interest with respect to research, authorship and publication of the article., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background & Aims: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US., Methods: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates., Results: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant., Conclusions: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC., Impact and Implications: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The significance of atypical infiltrates (eosinophils or plasma cells) on endomyocardial biopsy (EMB) after pediatric heart transplant (HTx) is not known. We hypothesized that atypical infiltrates are associated with worse post-HTx outcomes., Methods: We performed a retrospective cohort study of consecutive patients <21 years old who underwent primary HTx between 2013 and 2017. Multiorgan transplants were excluded. The presence of atypical infiltrates and burden of atypical infiltrates (rare vs predominant) on EMB were recorded. Primary outcome was a composite of cardiac allograft vasculopathy, graft failure (relisting or retransplant), or death. Presence of atypical infiltrates was evaluated: (1) overall using Cox regression with time-dependent covariates and (2) if present by 1 year post-HTx using Kaplan-Meier analysis., Results: Atypical infiltrates were present in 24 out of 95 patients (25%) and were associated with a higher likelihood of reaching the composite outcome (hazard ratio (HR) 6.22, 95% confidence interval (CI) 2.60-14.89, p < 0.0001). This persisted when controlling for rejection in multivariable analysis. There was also a greater risk of the composite outcome if ≥2 nonconsecutive EMBs had atypical infiltrates (HR 11.80, 95%CI 3.17-43.84, p = 0.0002) or if atypical infiltrates were the predominant feature on EMB (HR 30.58, 95%CI 9.34-100.06, p < 0.0001). Patients with atypical infiltrates by 1-year post-HTx had a 5-year freedom from the composite outcome of 48%, compared to 90% if no atypical infiltrates had been present by this timepoint (log rank p = 0.002)., Conclusions: The presence of atypical infiltrates on EMB is associated with significantly worse outcomes in children following HTx. These patients require closer follow-up to assess for developing graft dysfunction., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The relationship between social determinants of health and outcomes after heart transplantation has not been examined. The social vulnerability index (SVI) uses United States census data to determine the social vulnerability of every census tract based on 15 factors. This retrospective study seeks to examine the impact of SVI on outcomes after heart transplantation. Adult heart recipients who received a graft between 2012 and 2021 were stratified into SVI percentiles of <75% and SVI of ≥75%. The primary endpoint was survival. The median SVI was 48% (interquartile range: 30%-67%) among 23 700 recipients. One-year survival was similar between groups (91.4 vs 90.7%, log-rank P = .169); however, 5-year survival was lower among individuals living in vulnerable communities (74.8% vs 80.0%, P < .001). This finding persisted despite risk adjustment for other factors associated with mortality (survival time ratio 0.819, 95% confidence interval: 0.755-0.890, P < .001). The incidences of 5-year hospital readmission (81.4% vs 75.4%, P < .001) and graft rejection (40.3% vs 35.7%, P = .004) were higher among individuals living in vulnerable communities. Individuals living in vulnerable communities may be at increased risk of mortality after heart transplantation. These findings suggest there is an opportunity to focus on these recipients undergoing heart transplantation to improve survival., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alejandro Suarez-Pierre reports financial support was provided by American Association for Thoracic Surgery., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Belatacept may provide benefit in delayed graft function, but its association with infectious complications is understudied. We aim to assess the incidence of CMV and BK viremia in patients treated with sirolimus or belatacept as part of a three-drug immunosuppression regimen after kidney transplantation., Materials and Methods: Kidney transplant recipients from 01/01/2015 to 10/01/2021 were retrospectively reviewed. Maintenance immunosuppression was either tacrolimus, mycophenolate and sirolimus (B 0 ) or tacrolimus, mycophenolate, and belatacept (5.0 mg/kg monthly) (B 1 ). Primary outcomes of interest were BK and CMV viremia which were followed until the end of the study period. Secondary outcomes included graft function (serum creatinine, eGFR) and acute rejection through 12 months., Results: Belatacept was initiated in patients with a higher mean kidney donor profile index (B 0 :0.36 vs. B 1 :0.44, p = .02) with more delayed graft function (B 0 :6.1% vs. B 1 :26.1%, p < .001). Belatacept therapy was associated with more "severe" CMV viremia >25,000 copies/mL (B 0 :1.2% vs. B 1 :5.9%, p = .016) and CMV disease (B 0 :0.41% vs. B 1 :4.2%, p = .015). However, there was no difference in the overall incidence of CMV viremia >200 IU/mL (B 0 :9.4% vs. B 1 :13.5%, p = .28). There was no difference in the incidence of BK viremia >200 IU/mL (B 0 :29.7% vs. B 1 :31.1%, p = .78) or BK-associated nephropathy (B 0 :2.4% vs. B 1 :1.7%, p = .58), but belatacept was associated with "severe" BK viremia, defined as >10,000 IU/mL (B 0 :13.0% vs. B 1 :21.8%, p = .03). The mean serum Cr was significantly higher with belatacept therapy at 1-year follow up (B 0 :1.24 mg/dL vs. B 1 :1.43 mg/dL, p = .003). Biopsy-proven acute rejection (B 0 :1.2% vs. B 1 :2.6%, p = .35) and graft loss (B 0 :1.2% vs. B 1 :0.84%, p = .81) were comparable at 12 months., Conclusions: Belatacept therapy was associated with an increased risk of CMV disease and "severe" CMV and BK viremia. However, this regimen did not increase the overall incidence of infection and facilitated comparable acute rejection and graft loss at 12-month follow up., Competing Interests: Declaration of Competing Interest The authors report no financial or other conflicts of interest. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Patients are usually maintained on at least 2 immunosuppressive drugs (ISDs) after the first year post heart transplant. Anecdotally, some children are switched to single-drug monotherapy (a single ISD) for various reasons and varying durations. Outcomes associated with differences in immunosuppression after heart transplantation are unknown for children., Objectives: A priori we defined a noninferiority hypothesis for monotherapy compared to ≥2 ISDs. The primary outcome was graft failure, a composite of death and retransplantation. Secondary outcomes included rejection, infection, malignancy, cardiac allograft vasculopathy and dialysis., Methods: This international, multicenter, retrospective, observational cohort study used data from the Pediatric Heart Transplant Society. We included patients who underwent first-time heart transplant <18 years of age between 1999 and 2020 with ≥1 year of follow-up data available., Results: Our analysis included 3493 patients with a median time post-transplant of 6.7 years. There were 893 patients (25.6%) switched to monotherapy at least once with the remaining 2600 patients always on ≥2 ISDs. The median time on monotherapy after the first year post-transplant was 2.8 years (range 1.1-5.9 years). We found an adjusted hazard ratio (HR) of 0.65 (95%CI: 0.47-0.88) favoring monotherapy compared to ≥2 ISDs (p = 0.002). There were no meaningful differences in the incidence of secondary outcomes between groups, except for a lower rate of cardiac allograft vasculopathy in patients on monotherapy (HR 0.58, 95%CI: 0.45-0.74)., Conclusions: For pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was noninferior to standard therapy with ≥2 ISDs in the medium term., Condensed Abstract: Some children are switched to a single immunosuppressive drug (ISD) for various reasons after heart transplant, but outcomes associated with differences in immunosuppression are unknown for children. We assessed graft failure in children on a single ISD (monotherapy) compared to ≥2 ISDs in a cohort of 3493 children with a first heart transplant. We found an adjusted hazard ratio of 0.65 (95%CI: 0.47-0.88) favoring monotherapy. We concluded that for pediatric heart transplant recipients placed on monotherapy, immunosuppression with a single ISD after the first year post-transplant was non-inferior to standard therapy with ≥2 ISDs in the medium term., Competing Interests: Disclosure statement This study was partially funded by an unresticted grant from the Foundation of Stars, Montreal, Canada. F.D. is a research scholar with salary support from the Fonds de recherche du Québec – Santé (grant #281946). The authors have no conflicts of interest to disclose., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients., Methods: All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors., Results: 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p = 0.002), but with lower CAV grades (p = 0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss., Conclusions: ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Donors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients., Methods: Adults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor-recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used., Results: Meeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41)., Conclusions: Use of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate whether symptomatic atherosclerotic vascular disease (SAVD) was associated with graft survival in primary kidney transplant recipients., Summary Background Data: Recipient atherosclerotic vascular disease is associated with increased mortality rates amongst renal transplant patients. However, its relationship with graft survival has not been well studied., Methods: This retrospective observational analysis was performed using data for adult kidney transplant recipients between 11/09/2000 and 28/02/2020 extracted from the UNOS national organ transplantation database. Patients were divided into two groups based on recipient history of symptomatic atherosclerotic disease (angina or peripheral vascular disease). Risk-adjusted outcomes were assessed by multivariate Cox regression analysis adjusting for both donor and recipient characteristics., Results: 11,771 adult kidney transplant recipients from the UNOS database were eligible for analysis (1543 had a history of SAVD, 10,228 did not have a history of SAVD). After adjusting for confounders, positive SAVD status was associated with an adverse effect on graft survival at both 1 year (HR 1.35, p < 0.001) and 10 years (HR 1.15, p < 0.001)., Conclusions: SAVD should be considered an independent risk factor for poor prognosis in patients undergoing kidney transplant., (Copyright © 2022. Published by Elsevier B.V.)

Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p < .001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p = .008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4-6.3; p = .003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Introduction: Despite survival rates after pediatric kidney transplantation (KT) are on the rise it is still likely that most pediatric recipients will require more than one retransplant in their lifetime. The earlier the age at the first KT the higher is the risk of repeat pediatric kidney transplantation (RPKT)., Objective: The current study aims to analyze the outcomes of repeat pediatric kidney transplantation (RPKT) among pediatric kidney transplant recipients focusing on surgical complications and compare the outcomes of second and subsequent grafts with those of the first kidney graft., Materials and Methods: Retrospective study of RPKT (<18 years) undertaken between January 2000-2020. We analyzed primary etiology of renal disease, time to graft loss (GL), etiology of initial graft failure, history of acute rejection, previous delayed graft function, HLA-mismatches at the initial transplant, surgical complications and outcomes. Additionally, we compared the characteristics and outcomes of patients who underwent RPKT (group 1) with those who received a first kidney graft (group 2)., Results: Out of 229 kT, 59 patients underwent RPKT (26 females/33 males). At the time of RPKT median age was 11.37 years (SD:5.7). The most frequent primary renal disease was congenital nephrotic syndrome in 11 (18.6%). Fifty-four (91.5%) were on renal replacement therapy at the time of transplant. Fourty-one patients received their second KT (69.5%), 14 (23.7%) the third, 3 (5.1%) the fourth and 1 (1.7%) the fifth. Transplant graft nephrectomy (GN) was performed in 26 patients (44.1%) prior to retransplantation. Fifty-four (91.5%) received a cadaveric graft and 5 (8.5%) a living-related graft. An extraperitoneal approach was achieved in 53 patients (89.8%), whereas in the remaining 6 (10.2%) the graft was placed intraperitoneally. We observed 10 surgical complications (16.9%): 9 major which required reintervention and 1 minor (perirenal hematoma). No vascular complications were observed and none of the surgical complications were involved in graft loss. Graft survival at 1,3 and 5 years was 91%, 84% and 73% respectively. The most frequent cause of GL was chronic graft nephropathy in 15 (25.4%). After a mean follow-up of 9.40 years (SD: 4.7) only 2 patients died (3.4%), both with functioning grafts., Discussion: Pediatric recipients of second and subsequent kidney grafts constitute a remarkable high-risk population but are becoming more frequent at reference pediatric transplant centers., Conclusions: RPKT is technically challenging but can yield good results. In our series overall the incidence of surgical complications and particularly vascular complications was low., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: Black race is associated with worse outcomes across solid organ transplantation. Augmenting immunosuppression through antithymocyte globulin (ATG) induction may mitigate organ rejection and graft loss. We investigated whether racial and socioeconomic outcome disparities persist in children receiving ATG induction., Methods: Using the Pediatric Heart Transplant Society registry, we compared outcomes in Black and White children who underwent heart transplant with ATG induction between 2000 and 2020. The primary outcomes of treated rejection, rejection with hemodynamic compromise (HC), and graft loss (death or re-transplant). We explored the association of these outcomes with race and socioeconomic disparity, assessed using a neighborhood deprivation index [NDI] score at 1-year post-transplant (high NDI score implies more socioeconomic disadvantage)., Results: The study cohort included 1,719 ATG-induced pediatric heart transplant recipients (22% Black, 78% White). There was no difference in first year treated rejection (Black 24.5%, White 28.1%, p = 0.2). During 10 year follow up, the risk of treated rejection was similar; however, Black recipients were at higher risk of HC rejection (p = 0.009) and graft loss (p = 0.02). Black recipients had a higher mean NDI score (p < 0.001). Graft loss conditional on 1-year survival was associated with high NDI score in both White and Black recipients (p < 0.0001). In a multivariable Cox model, both high NDI score (HR 1.97, 95% CI 1.23-3.17) and Black race (HR 2.22, 95% CI 1.40-3.53) were associated with graft loss., Conclusion: Black race and socioeconomic disadvantage remain associated with late HC rejection and graft loss in children with ATG induction. These disparities represent important opportunities to improve long term transplant outcomes., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: ABO-incompatible heart transplant is a method to increase the infant donor pool. However data on long-term survival and rejection after ABO-incompatible heart transplant in recent era are limited., Methods: The United Network for Organ Sharing database was queried for infant heart transplants performed from January 2008 to March 2020. Patient demographics and known risk factors for posttransplant mortality were collected. Statistical analysis using Bayesian additive regression trees was performed to evaluate the association of ABO incompatibility and overall survival, graft survival, acute rejection episodes, and length of stay., Results: Of 1368 included infants (age < 1 year), 280 (20.47%) were ABO incompatible. ABO incompatibility was not associated with increased all-cause mortality, acute rejection episodes, or length of stay, whereas extracorporeal membrane oxygenation and intubation status of the recipient at the time of transplantation were associated with increased all-cause mortality and graft failure. Idiopathic cardiomyopathy was associated with a decreased likelihood of posttransplant all-cause mortality. One-, 5-, and 10-year survival rates among compatible vs incompatible transplants were estimated to be 90% vs 88%, 82% vs 79%, and 77% vs 73%, respectively., Conclusions: ABO-incompatible infant heart transplant does not affect posttransplant survival, incidence of rejection, or postoperative length of stay. Therefore it remains a viable and important strategy to increase the infant donor pool., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Black patients suffer higher rates of antibody-mediated rejection and have worse long-term graft survival after heart transplantation. Donor-derived cell free DNA (ddcfDNA) is released into the blood following allograft injury. This study analyzed %ddcfDNA in 63 heart transplant recipients categorized by Black and non-Black race, during the first 200 days after transplant. Immediately after transplant, %ddcfDNA was higher for Black patients (mean [SE]: 8.3% [1.3%] vs 3.2% [1.2%], p = 0.001). In the first week post-transplant, the rate of decay in %ddcfDNA was similar (0.7% [0.68] vs 0.7% [0.11], p = 0.78), and values declined in both groups to a comparable plateau at 7 days post-transplant (0.46% [0.03] vs 0.45% [0.04], p = 0.78). The proportion of Black patients experiencing AMR was higher than non-Black patients (21% vs 9% [hazard ratio of 2.61 [95% confidence interval: 0.651-10.43], p = 0.18). Black patients were more likely to receive a race mismatched organ than non-Black patients (69% vs 35%, p = 0.01), which may explain the higher levels of early allograft injury., (Copyright © 2022. Published by Elsevier Inc.)

Background: Retransplantation is rare and associated with worse survival and more morbidity. The study aim is to describe an updated cohort of pediatric retransplants, determine if there has been an era effect on outcomes, and understand if identified trends are explained by changes in patient selection., Methods: Pediatric Heart Transplant Society database analysis of retransplantation patients <18 years of age (Era 1: 1993-2001, Era 2: 2002-2010, Era 3: 2011-2018). Multivariate analysis identified risk factors for graft loss. Multiphase parametric hazard modeling was used to depict era and risk factor effect., Results: Survival was lower (p < .0001) for retransplant (n = 222) compared to primary transplant (n = 6548) (median 9.3 vs 20.2 years). Median survival increased from Era 1 to 2 (4.8 vs 9.3 years; p < .0001) with no incremental change in Era 3. Era 2 and 3 retransplants had a longer inter-transplant interval (p < .0001), were less frequently for early graft failure (p = .0004) or acute rejection (p = .007), more frequently from a ventricular assist device (p = .0014), and less frequently from extracorporeal membrane oxygenation (p = .0024). Predictors of graft loss included Era 1 (HR 10.55, p = .001), congenital heart disease (HR 4.42, p = .01), inter-transplant interval <1 year (HR 5.34, p = .002), and mechanical support (ventricular assist device HR 7.47, p = .0042; extracorporeal membrane oxygenation HR 10.09, p < .0001). For each 1-year increase in inter-transplant interval, graft loss risk decreased by 1.15 (p = .0002). Retransplantation was associated with more rejection, infection, and allograft vasculopathy., Conclusions: Graft survival has improved in pediatric retransplants making it a viable option in select patients. Retransplantation should be avoided in the setting of early graft failure especially requiring mechanical support., Competing Interests: Disclosure statement The authors have no conflicts of interest to disclose., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Bu et al. report that elevated donor-derived cell-free DNA detected on serial measurements performed for both surveillance and assessment of kidney allograft dysfunction was associated with rejection, future de novo donor-specific antibodies, and decline in estimated glomerular filtration rate. Their data suggest that donor-derived cell-free DNA may be a useful indicator of kidney allograft health. In this commentary, we discuss the expanding role of donor-derived cell-free DNA for allograft surveillance and highlight potential limitations., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Evidence regarding the utility of routine induction therapy on outcomes is not clear. This study aims to evaluate whether induction therapy is associated with a reduced risk of treated rejection and improved overall survival., Methods: We retrospectively analyzed all adult patients (age ≥ 18 years) that are included in the UNOS database who underwent heart transplantation between 2000 and 2017. Patients with prior transplants and dual organ transplants were excluded. 34,361 patients were included in the final analysis. We assessed the impact of induction therapy with T cell depleting agents (TC-DA), IL2 receptor antagonists (IL2R antagonist) and compared that to no induction therapy using Cox regression models adjusted for propensity scores. The primary outcome measure was all-cause mortality, whereas treated rejection at one year was analyzed as a secondary outcome measure (available in 77% of patients)., Results: A total of 52% of the cohort did not receive any induction therapy. A total of 27% received IL2R antagonist and the rest received TC-DA. Median age of the recipients was 55 (IQR: 46-62) years. A total of 25% of the population were women and 39% were supported on left ventricular assist device therapy at the time of transplantation. Median follow-up was 4.2 (IQR: 1.1-8.5) years with 32% reported mortality. Multivariate analysis with propensity score adjustment showed that TC-DA induction did not have any effect on mortality (HR = 0.98, 95% CI 0.93-1.03, p = 0.48). However, IL2R antagonist was associated with a modestly increased risk of all-cause mortality compared to no induction (HR = 1.06, 95% CI 1.01-1.11, p = 0.02, respectively). A total of 25% of patients were found to have treated rejection at one year, TC-DA induction was associated with reduced odds of rejection at one year (OR = 0.82, 95% CI 0.76-0.88, p < 0.001). However, induction with IL2R antagonist was not found to have a significant impact (OR = 1.03, 95% CI 0.96-1.11, p = 0.36)., Conclusions: Compared to no induction therapy, induction with TC-DA was associated with reduction in risk of treated rejection at 1 year with no effect on mortality and IL2R antagonist was associated with a small but statistically significant increase in mortality without any impact on risk of rejection., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Previous studies in solid organ transplantation have shown a relationship between circulating eosinophil (EOS) counts and the presence of acute cellular rejection (ACR). However, the relationship between this potential biomarker and ACR in lung transplant (LTx) patients remains unclear., Objective: To assess the association between EOS and the presence of acute cellular rejection in lung transplant recipients., Materials and Methods: Retrospective study of 583 transbronchial biopsies (TBB) performed in 256 lung transplant patients between 2012 and 2018. We analyzed age, sex, underlying pathology, date of transplant, indications for TBB, presence and degree of ACR, and the simultaneous absolute and relative EOS., Results: ACR were observed in 170 of 583 TBB (29.2%). EOS in patients with ACR were higher than in patients without ACR (203.6 ± 248/mm 3 vs 103.1 ± 153/mm 3 ; p < 0.001). High levels of both absolute and relative EOS were associated with the presence of ACR regardless of the underlying disease (odds ratio [OR] 1.003; 95% confidence interval [CI], 1.002-1.004; OR 1.226; 95% CI, 1.120-1.342) and time after transplant (OR 1.003; 95% CI, 1.002-1.004 and OR 1.239; 95% CI, 1.132-1.356). Moreover, both absolute and relative EOS were strongly associated with moderate and severe grades of ACR (OR 3.55; 95% CI, 3.00-4.10 and OR 3.56; 95% CI, 3.00-4.12)., Conclusions: EOS are elevated in ACR, especially in moderate or severe ACR. Increased vigilance for ACR is therefore advisable in lung transplant recipients with elevated EOS., Competing Interests: Disclosure statement The authors have no conflicts of interest to declare., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Lung volume reduction surgery (LVRS) is treatment option for chronic obstructive pulmonary disease, the second most common indication for lung transplantation (LTx) in the United States. Lung volume reduction surgery before LTx is controversial. Single-institution studies report contradicting results, and the impact of undergoing LVRS before LTx on outcomes after LTx is unclear., Methods: We reviewed the United Network for Organ Sharing database for all adults (aged more than 18 years) who underwent first-time LTx for chronic obstructive pulmonary disease in the lung allocation score era. We used patient demographic and clinical characteristics and lung allocation score to propensity match patients who did and patients who did not undergo LVRS before LTx. The primary exposure was prior LVRS. The primary outcome was graft failure after LTx. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards models were used to assess outcomes., Results: A total of 4905 patients with chronic obstructive pulmonary disease underwent LTx between May 2005 and March 2017. Of them, 107 patients (2.2%) underwent LVRS before LTx. Propensity matching generated 212 matches (106 LVRS+LTx, and 106 LTx only). Median survival was significantly longer in the LTx only cohort (6.5 vs 3.4 years, P = .034). Lung volume reduction surgery before lung transplantation was associated with significantly increased risk of graft failure after lung transplant (hazard ratio 1.72; 95% confidence interval, 1.13 to 2.60; P = .01)., Conclusions: In this national, propensity-matched analysis of LVRS before LTx, we show that LVRS is associated with a significantly increased risk of graft failure. Patients who undergo LVRS and remain in need of LTx should be carefully assessed and followed postoperatively., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background/objective: This study is to assess immunological and graft survival outcomes after pancreas transplant at a single institute in Asia., Methods: Patients undergoing pancreas transplant with enteric drainage were included. Clinical data and outcomes were evaluated and compared between each subgroup., Results: There were 165 cases of pancreas transplant, including 38 (23 %) simultaneous pancreas-kidney transplant (SPK), 24 (15 %) pancreas after kidney transplant (PAK), 75 (46 %) pancreas transplant alone (PTA), and 28 (17 %) pancreas before kidney transplant (PBK). The overall surgical complication rate was 46.1 %, with highest (62.5 %) in PAK and lowest (32.0 %) in PTA, P = 0.008. The late complications included 32.7 % infection and 3.6 % malignancy. Overall rejection of pancreas graft was 24.8 % including 18.2 % acute and 9.7 % chronic rejection. Rejection was highest in PTA group (36.0 %) and lowest in PBK (3.6 %). There were 56 cases (33.9 %) with graft loss in total, with highest graft loss rate in PTA (38.7 %). The 1-year, 5-year and 10-year pancreas graft survivals for total patients were 98.0 %, 87.7 % and 70.9 % respectively., Conclusions: Enteric drainage in pancreas transplant could be applied safely not only in SPK but also in other subgroups. Enteric drainage itself would not compromise the immunological and graft survival outcomes., (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Background: Heart transplant programs and regulatory entities require highly accurate performance metrics to support internal quality improvement activities and national oversight of transplant programs, respectively. We assessed the accuracy of publicly reported performance measures., Methods: We used the United Network for Organ Sharing registry to study patients who underwent heart transplantation between January 1, 2016 and June 30, 2018. We used tests of calibration to compare the observed rate of 1-year graft failure to the expected risk of 1-year graft failure, which was calculated for each recipient using the July 2019 method published by the Scientific Registry of Transplant Recipients (SRTR). The primary study outcome was the joint test of calibration, which accounts for both the total number of events predicted (calibration-in-the-large) and dispersion of risk predictions (calibration slope)., Results: 6,528 heart transplants were analyzed. The primary test of calibration failed (p <0.0001), indicating poor accuracy of the SRTR model. The calibration-in-the-large statistic (0.63, 95% confidence interval [CI] 0.58-0.68, p < 0.0001) demonstrated overestimation of event rates while the calibration slope statistic (0.56, 95% CI 0.49-0.62, p <0.0001) indicated over-dispersion of event rates. Pre-specified subgroup analyses demonstrated poor calibration for all subgroups (each p <0.01). After recalibration, program-level observed/expected ratios increased by a median of 0.14 (p <0.0001)., Conclusions: Risk models employed for publicly-reported graft survival at U.S. heart transplant centers lack accuracy in general and in all subgroups tested. The use of disease-specific models may improve the accuracy of program performance metrics., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Elderly liver transplant (LTx) recipients at a lower risk of acute rejection compared to younger recipients due to immunosenescence. As such, they may benefit from reduced immunosuppression (IS) to minimize infectious and malignant complications. We aimed to evaluate outcomes in LTx recipients ≥60 years compared to a younger group of LTx recipients aged 18-59 years maintained on a similar level of IS. This was a single-center retrospective evaluation of adult LTx recipients from 2013 to 2018 who received methylprednisolone induction and were maintained on tacrolimus, mycophenolate mofetil (MMF), and a prednisone taper. A total of 143 LTx recipients were evaluated. Mean age in the older group was 65 ± 3.8 compared to 49 ± 10.4 years in the younger group (p < 0.0001). Mean tacrolimus levels and the duration of MMF and steroids were comparable. Both groups had a similar incidence of first rejection within 1 year (19.2% in the elderly group vs. 23.1% in the younger group, p = 0.57). There were no statistical difference in terms of infection, malignancy, or patient survival. In conclusion, our data suggests that elderly LTx recipients, when treated with a similar level of IS, had similar 1 year incidence of rejection, infection, malignancy, and patient survival as younger LTx recipients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro 12M ), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients., Methods: We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro 12M as the mean of the 2 prebronchodilator FEV 1 measurements 12-month post-transplant. Normal spirometry was defined as FEV 1 /FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro 12M , survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro 12M RESULTS: One hundred and eleven (51%) lung transplant recipients normalized their Spiro 12M . Normal Spiro 12M was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV 1 increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro 12M (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro 12M ., Conclusions: Abnormal Spiro 12M is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: ABO-incompatible liver transplantation (ABOi-LT) is increasingly used to overcome donor shortage. Evidence about disadvantage and advantage in comparison with ABO-compatible liver transplantation (ABOc-LT) needs to be performed in the early and late periods. Herein, We compared the short-term and long-term outcomes between ABOi-LT and ABOc-LT cohorts., Methods: We performed a meta-analysis based on the observation studies which included outcomes at ≥1 year after ABOi-LT and ABOc-LT procedures, based on the MEDLINE (via Pubmed), the Cochrance Central Register of Controlled Trials (CENTRAL), and EMBASE (via Ovid) systems. Two researchers independently screened each study according to the pre-established inclusion and exclusion criteria to assess the quality of each study and extracted data from published studies. The primary outcome indicators were all-cause mortality and graft survival at 1, 3 and 5 years after transplantation. In the meta-analysis, we based on the value of heterogeneity using a fixed-effect and a random-effect. A fixed-effect model was used if the value of I2 was less than or equal 50%; and a random-effect model was used if the value of I2 was greater than 50%., Findings: Out of 335 identified records, 29 records with 10,783 patients with liver transplants; 2137 of them were ABOi-LTs and the remaining 8646 were ABOc-LTs. There was no significant difference at 1-year, 3-year, and 5-year in all-cause mortality, death-censored graft survival and complication incidence rate between ABO-incompatible living donor liver transplantation (ABOi-LDLT) group and ABO-compatible living donor liver transplantation (ABOc-LDLT) group. Compared with ABO-compatible deceased donor liver transplantation (ABOc-DDLT), ABO-incompatible deceased donor liver transplantation (ABOi-DDLT) had a higher 1-year all-cause mortality, and the value of totally pooled odds ratio (OR) was 1.89 (1.28,2.80). However, there was no significant difference at 3-year and 5-year all-cause mortality between ABOi-DDLT and ABOc-DDLT groups. ABOi-DDLT group had a lower 1-year and 5-year death-censored graft survival than ABOc-DDLT, as the value of totally pooled OR was 1.91 (1.41,2.60) and 1.52 (1.12,2.05), respectively. No significant difference was detected at 3-year death-censored graft survival between ABOi-DDLT and ABOc-DDLT groups. ABOi-DDLT group had a higher complication incidence rate than ABOc-DDLT, and the value of totally pooled OR was 2.26 (1.53,3.33). We found no obvious bias except for the complication of living donor liver transplantation (LDLT; P = 0.038)., In Conclusion: The short-term and long-term outcomes were worse after ABOi-DDLT than ABOc-DDLT in the all-cause mortality, death-censored graft survival, and complication incidence rate. However, the same outcomes were essentially comparable between ABOi-LDLT vs. ABOc-LDLT cohorts. Considering the current shortage of liver donors, we believe that ABOi-LT from living donor and deceased donors can save lives under emergency situations., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Barth Syndrome (BTHS) is a rare, X-linked disease characterized by cardioskeletal myopathy and neutropenia. Comparative outcomes after heart transplantation have not been reported., Methods: We identified BTHS recipients across 3 registries (Pediatric Heart Transplant Study Registry [PHTS], Barth Syndrome Research Registry and Repository, and Scientific Registry of Transplant Recipient-Pediatric Health Information System) and matched them 1:4 to non-BTHS, male heart transplant (HT) recipients listed with dilated cardiomyopathy in PHTS. Demographics and survival data were analyzed for all recipients, whereas post-HT infection, malignancy, allograft vasculopathy, and acute rejection were only available for analysis for individuals with PHTS data., Results: Forty-seven BTHS individuals with 51 listings and 43 HTs (including 2 re-transplants) were identified. Age at primary HT was 1.7 years (IQR: 0.6-4.5). Mechanical circulatory support at HT was common (ventricular assist device 29%, extracorporeal membrane oxygenation 5%). Over a median follow-up of 4.5 years (IQR 2.7-9.1), survival for BTHS HT recipients was no different than non-BTHS HT recipients (HR 0.91, 95% CI 0.40-2.12, p = 0.85). Among those with PHTS data (n = 28), BTHS HT recipients showed no difference in freedom from infection (HR 0.64, 0.34-1.22; p = 0.18), malignancy (HR 0.22, 0.02-2.01, p = 0.18), and allograft vasculopathy (HR 0.58, 0.16-2.1, p = 0.41). Freedom from acute rejection (HR 0.39, 0.17-0.86, p = 0.02) was greater for BTHS HT recipients despite similar use of induction (61 vs 73%, p = 0.20), steroids at 30-days (75 vs 62%, p = 0.27), and dual/triple drug immunosuppression at 1-year (80 vs 84%, p = 0.55)., Conclusions: In this largest cohort yet reported, individuals with BTHS have equivalent survival with less acute rejection and no difference in infection or malignancy after HT. When indicated, HT for individuals with BTHS is appropriate., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Fine particulate matter (PM 2.5 ), a common form of air pollution which can induce systemic inflammatory response, is a risk factor for adverse health outcomes. Kidney transplant (KT) recipients are likely vulnerable to PM 2.5 due to comorbidity and chronic immunosuppression. We sought to quantify the association between PM 2.5 and post-KT outcomes. For adult KT recipients (1/1/2010-12/31/2016) in the Scientific Registry of Transplant Recipients, we estimated annual zip-code level PM 2.5 concentrations at the time of KT using NASA's SEDAC Global PM 2.5 Grids. We determined the associations between PM 2.5 and delayed graft function (DGF) and 1-year acute rejection using logistic regression and death-censored graft failure (DCGF) and mortality using Cox proportional hazard models. All models were adjusted for sociodemographics, recipient, transplant, and ZIP code level confounders. Among 87 233 KT recipients, PM 2.5 was associated with increased odds of DGF (OR = 1.59; 95% CI: 1.48-1.71) and 1-year acute rejection (OR = 1.31; 95% CI: 1.17-1.46) and increased risk of all-cause mortality (HR = 1.15; 95% CI: 1.07-1.23) but not DCGF (HR = 1.05; 95% CI: 0.97-1.51). In conclusion, PM 2.5 was associated with higher odds of DGF and 1-year acute rejection and elevated risk of mortality among KT recipients. Our study highlights the importance of considering environmental exposure as risk factors for post-KT outcomes., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The clinical use of post-transplant risk scores is limited by their poor statistical performance. We hypothesized that developing specific prognostic models for each type of circulatory support at transplant may improve risk stratification., Methods: We analyzed the UNOS database including contemporary, first, non-combined heart transplantations (2013-2018). The endpoint was death or retransplantation during the first year post-transplant. Three different circulatory support statuses at transplant were considered: no support, durable mechanical support and temporary support (inotropes, temporary mechanical support). We generated 1,000 bootstrap samples that we randomly split into derivation and test sets. In each sample, we derived an overall model and 3 specific models (1 for each type of circulatory support) using Cox regressions, and compared, in the test set, their statistical performance for each type of circulatory support., Results: A total of 13,729 patients were included; 1,220 patients (8.9%) met the composite endpoint. Circulatory support status at transplant was associated with important differences in baseline characteristics and distinct prognosis (p = 0.01), interacted significantly with important predictive variables included in the overall model, and had a major impact on post-transplant predictive models (type of variables included and their corresponding hazard ratios). However, specific models suffered from poor discriminative performance and significantly improved risk stratification (discrimination, reclassification indices, calibration) compared to overall models in a very limited proportion of bootstrap samples (<15%). These results were consistent across several sensitivity analyzes., Conclusion: Circulatory support status at transplant reflected different disease states that influenced predictive models. However, developing specific models for each circulatory support status did not significantly improve risk stratification., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes., Method: This is a retrospective national database analysis of children <19 years of age at time of heart transplantation (HT) from 05/2008-01/2018. Use of IT or no IT, use of steroids, calculated panel reactive antibodies (cPRA) and outcomes (Mortality, post-transplant lymphoproliferative disease (PTLD), rejection rates) were studied within a mean follow-up period of 2.9 years (0.2-8.1 years)., Results: All 32 patients (12♂, 20♀), median age at HT of 6.4 years (24 days - 18 years) received IT using either polyclonal antibodies (ATG; 72%) or interleukin-2 receptor antagonist (anti-IL-2R mAb; 28%). Length of treatment was median of 4 (1-63) days. At time of HT all patients received steroids, while at discharge 32% and one year after HT 19%. Kaplan-Meier analysis of survival revealed a one-year survival of 86%. Three out of 7 patients with elevated cPRA (43%) died. Median time to first treated rejection was 19.4 months (±60.5 SD) without significant difference if treated with anti-IL-2R mAb or ATG (p:0.5). No development of PTLD, chronic renal failure needing ongoing renal replacement therapy or diabetes mellitus were recorded., Discussion: This is the first report of the national practice use of IT within Switzerland. It reveals a high use of IT, no development of PTLD and a low use of steroids at one-year post HT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transplant glomerulopathy is established as a hallmark of chronic antibody-mediated rejection in kidney transplant patients with donor-specific HLA antibodies (HLA-DSA). The clinical importance of transplant glomerulopathy in the absence of HLA-DSA is not well established. To help define this, 954 patients (encompassing 3744 biopsies) who underwent kidney transplantation 2004-2013 were studied with retrospective high-resolution HLA genotyping of both donors and recipients. The risk factors, histopathological appearance and prognosis of cases with transplant glomerulopathy in the absence of HLA-DSA were compared to those cases with HLA-DSA, and the impact of the PIRCHE-II score and eplet mismatches on development of transplant glomerulopathy evaluated. In this cohort, 10.3% developed transplant glomerulopathy, on average 3.2 years post-transplant. At the time of glomerulopathy, 23.5% had persistent pre-transplant or de novo HLA-DSA, while 76.5% were HLA-DSA negative. Only HLA-DSA was identified as a risk factor for glomerulopathy development as eplet mismatches and the PIRCHE-II score did not associate. HLA-DSA negative biopsies with glomerulopathy had less interstitial inflammation, less glomerulitis, and less C4d deposition in the peritubular capillaries compared to the HLA-DSA positive biopsies with glomerulopathy. While graft function was comparable between the two groups, HLA-DSA positive glomerulopathy was associated with a significantly higher risk of graft failure compared to HLA-DSA negative glomerulopathy (Hazard Ratio 3.84; 95% confidence interval 1.94-7.59). Landmark analysis three-years post-transplant showed that HLA-DSA negative patients with glomerulopathy still had a significant increased risk of graft failure compared to patients negative for glomerulopathy (2.62; 1.46-4.72). Thus, transplant glomerulopathy often occurs in the absence of HLA-DSA, independent of HLA molecular mismatches, and represents a different phenotype with less concomitant inflammation and better graft survival compared to that developed in the presence of HLA-DSA., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The impact of donor sex on heart transplantation outcomes irrespective of recipient sex remains unclear. The objective of this study was to evaluate the impact of donor sex on heart transplantation outcomes in the United States., Methods: From 1987 to March 2019, 63,775 adult patients who underwent heart transplantation were matched to 27,509 male and 11,474 female donors in the United States. Data were prospectively collected by the United Network for Organ Sharing (UNOS). Patients without missing data were stratified by donor sex and donor menopause status. The groups were matched 1:1 using the propensity score of each patient. Kaplan-Meier survival and cox proportional hazards regression analyses were performed. The primary endpoint was all-cause mortality. Secondary endpoints were postoperative complications., Results: Propensity matching generated 15,506 and 1,094 patients based on donor sex and menopause status, respectively. Recipients who received female donor allografts were more likely to have acute rejection episodes requiring anti-rejection medical treatment (11.9% vs 10.1%, p = .007) and require post-transplant dialysis (10.9% vs 9.3%, p = .001) than those who received male donor allografts. Overall survival using female vs male donor allografts was similar (p = .34). Recipients who received pre- vs post-menopausal female donor hearts had similar postoperative outcomes and overall survival (p = .23)., Conclusions: Analysis of the UNOS database showed similar median survival using female vs male donor hearts in adult heart transplantation, irrespective of donor menopause status. Female donor allografts are used far less frequently, thus these results represent an opportunity to maximize usage by better utilization of suitable female donor organs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary embolism (PE) is unexpectedly detected in some donor lungs during organ procurement for lung transplantation. Anecdotally, such lungs are usually implanted; however, the impact of this finding on recipient outcomes remains unclear. We hypothesized that incidentally detected donor PE is associated with adverse short-term and long-term outcomes among lung transplant recipients., Methods: We analyzed a prospectively maintained database of all lung donors procured by a single surgeon and transplanted at our institution between 2009 and 2018. A standardized approach was used for all procurements and included antegrade and retrograde flush. Pulmonary embolism was defined as macroscopic thrombus seen in the pulmonary artery during the donor procurement operation., Results: A total of 501 consecutive lung procurements were performed during the study period. The incidence of donor PE was 4.4% (22 of 501). No organs were discarded owing to PE. Donors with PE were similar to donors without PE in baseline characteristics and Pao 2 . Recipients in the two groups were also similar. Pulmonary embolism was associated with a higher likelihood of acute cellular rejection grade 2 or more (10 of 22 [45.5%] vs 120 of 479 [25.1%], P = .03). Multivariable Cox modeling demonstrated an association between PE and the development of chronic lung allograft dysfunction (hazard ratio 2.02; 95% confidence interval, 1.23 to 3.30; P = .005)., Conclusions: Lungs from donors with incidentally detected PE may be associated with a higher incidence of recipient acute cellular rejection as well as reduced chronic lung allograft dysfunction-free survival. Surgeons must use caution when transplanting lungs with incidentally discovered PE. These preliminary findings warrant corroboration in larger data sets., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Vitamin D (VitD) deficiency is associated with several diseases such as multiple sclerosis, rheumatoid arthritis, respiratory infection, and so forth. In the field of transplantation (kidney transplantation), some studies reported that patients with VitD deficiency are of increased chance of acute rejection, but other studies did not show such a chance. On the other hand, since VitD is a modulatory factor and can reduce the inflammatory response, understanding the exact role of it in transplantation may contribute to tolerance condition in these patients., Methods: The electronic databases, including PubMed, Scopus, Embase, ProQuest, Web of Science, and Google Scholar, were searched for eligible studies. In general, 14 studies with a total of 4770 patients were included in this meta-analysis. Regarding the methodological heterogeneity, we selected a random-effects combination model. Moreover, OR was chosen as an effect size for this study., Results: After the combination of 14 studies, we showed that patients in the VitD-deficient group had an 82% increased chance of acute rejection compared with patients in the VitD-sufficient group, and this effect was significant (OR 1.82; 95% confidence interval [CI] [1.29, 2.56]; I 2  = 52.3%). This result was significant, and, regarding the narrow CI, it can be a conclusive result. Study quality and gender variables were the main sources of inconsistent results in the primary studies. Moreover, using meta-regression, we showed that VitD deficiency (independent from the estimated glomerular filtration rate (eGFR) of patients) increased the chance of acute rejection., Conclusion: The normal VitD status of patients a few days before and after transplantation can reduce the chance of acute rejection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: ABO-incompatible (ABOi) heart transplantation (HT) in infants has been used to reduce waiting list time and mortality with outcomes comparable to ABO compatible (ABOc). We sought to assess trends in ABOi listing and transplantation for infants within the United Network for Organ Sharing registry and to evaluate its influence on outcomes., Methods: We reviewed infants listed for HT in the United Network for Organ Sharing registry (2007-2018). We compared demographic and clinical characteristics, waiting list duration, graft survival, and 1-year freedom from rejection between patients listed for ABOi and ABOc. Cochran-Armitage trend test, univariate nonparametric statistical methods, and Kaplan-Meier curves were used to analyze the data., Results: During the study period, 2787 patients were listed for HT, 53% of whom were listed for ABOi. Median waiting list time for patients in blood group O receiving an ABOi transplant was significantly shorter (P < .0001). Among the 1862 patients who received HT, 15% were ABOi. The incidence of ABOi HT also increased over time. The pretransplant anti-A and anti-B titers in the ABOi group did not significantly affect outcomes. There was no difference in the incidence of rejection in the first year after transplant and no significant difference in posttransplant survival CONCLUSIONS: The number of infants listed and transplanted as ABOi has gradually increased over the past decade, with a significantly decreased waiting list time for ABOi transplants in blood group O. At 1 year after transplant, rejection was comparable between the ABOi and ABOc groups and there was no significant difference in survival., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Several patient-related factors have been identified with regard to the safety and efficacy of breast reconstructions. This study analyzed the largest series of microsurgical breast reconstructions in Germany using deep inferior epigastric perforator (DIEP) flaps, with a focus on the impact of patient body mass index (BMI)., Patients and Methods: A total of 3911 female patients underwent 4561 free DIEP flap breast reconstructions across 22 different centers. The cases were divided into five groups using World Health Organization BMI criteria: underweight group (BMI <18.5 kg/m 2 ), normal weight/ control group (BMI: 18.5-24.9 kg/m 2 ), overweight group (BMI: 25-29.9 kg/m 2 ), moderately obese group (BMI: 30-34.9 kg/m 2 ), and severely obese group (BMI ≥ 35 kg/m 2 ). Surgical complications were accounted for and the five BMI groups were then compared., Results: Overall, there was no significant difference regarding the rate of partial- and total flap loss between all BMI groups (p > 0.05). However, overweight and obese patients showed significantly higher rates of postoperative infections at the donor and recipient sites than the control group (donor site infections: overweight 0.6%; moderately obese 0.9%; severely obese 2.4% vs control 0.1%; all p<0.01; recipient site infections: overweight 0.5%; moderately obese 0.8%; severely obese 1.4% vs control 0.1%; all p < 0.05). The rate of medical complications also differed significantly between groups, with the highest rates in moderately and severely obese women (moderately obese: 8.4%; severely obese: 13.0% vs. control: 5.1%; p < 0.01)., Conclusion: Our findings suggest that successful free tissue transfer can be achieved even in an underweight and severely obese population with acceptable risk for complications., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest. There was no funding., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Despite growing interest in donor-specific antibodies (DSAs) and antibody-mediated rejection (AMR) in lung transplantation (LTx), no study evaluating the outcomes in recipients with de novo DSAs (dnDSAs) in living-donor lobar LTx (LDLLT) exists. We compared various characteristics of DSAs in LDLLT with those in cadaveric LTx (CLT) based on prospectively collected data., Methods: Between October 2009 and September 2019, 211 recipients underwent LTx (128 CLTs and 83 LDLLTs). We reviewed 108 CLTs and 74 LDLLTs to determine the characteristics and clinical impact of dnDSAs. Eighteen data-deficient cases, 7 cases with preformed DSAs, and 4 re-transplants were excluded., Results: There were significant differences between CLT and LDLLT patients in age, primary disease, ischemic time, and number of human leukocyte antigen mismatches per donor. The dnDSA incidence in LDLLT (6.8%) was significantly lower than that in CLT (19.4%, p = 0.02). The dnDSAs appeared later in LDLLT (mean 1,256 days) than in CLT (mean 196 days, p = 0.003). According to Cox models analyzed using dnDSA as a time-dependent covariate, dnDSA positivity was significantly associated with a poor overall survival (OS; hazard ratio [HR] 3.46, 95% confidence interval [CI] 1.59-7.57, p = 0.002) and poor CLAD-free survival in case of CLT (HR: 2.23, 95% CI: 1.08-4.63, p = 0.003). However, no such significant associations were noted in case of LDLLT., Conclusions: The dnDSA occurrence was significantly lower and later in LDLLT than in CLT. Furthermore, dnDSA-positivity was significantly associated with worse OS and CLAD-free survival after CLT but not after LDLLT., Competing Interests: Conflicts of interest The authors have no conflicts of interest or funding to disclose., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the use of cryopreserved arterial allografts (CAA) as a substitute for infected infrarenal aortic prostheses, and its outcomes., Methods: A single centre retrospective study of consecutive patients receiving an abdominal aortic CAA after removal of an infected graft was conducted between January 1997 and December 2013. The primary outcome was the rate of allograft related revision surgery. Secondary outcomes were the 30 day mortality rate, survival, primary patency, limb salvage, and infection recurrence. Allograft ruptures secondary to infection and risk factors for allograft failure were also investigated., Results: Two hundred patients (mean age 64.2 ± 9.4 years) were included. In 56 (28%) cases, infection was related to an enteric fistula. The mean follow up duration was 4.1 years. The 30 day mortality rate was 11%. Early revision surgery was needed in 59 patients (29.5%). Among them, 15 (7.5%) were allograft related and led to the death of three patients (1.5%), corresponding to a 7.5% 30 day allograft related revision surgery rate. During the first six months, 17 (8.5%) patients experienced 21 events with complete or partial rupture (pseudo-aneurysm) of the allograft responsible for five (2.5%) deaths, corresponding to a re-infection rate of 8.5%. The multivariable analysis showed that diabetes and pseudo-aneurysm of the native aorta on presentation were predictive factors for short term allograft rupture. After six months, 25 (12.5%) patients experienced long term allograft complications (rupture, n = 2, 1%; pseudo-aneurysm, n = 6, 3%; aneurysm, n = 2, 1%; thrombosis, n = 11, 5.5%; stenosis, n = 4, 2%;) requiring revision surgery resulting in one death. The five year rates of survival, allograft related revision surgery, limb salvage, primary patency, and infection recurrence were 56%, 30%, 89%, 80%, and 12%, respectively., Conclusion: CAAs provide acceptable results to treat aortic graft infection with few early graft related fatal complications. Long term allograft related complications are quite common but are associated with low mortality and amputation rates., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Surveillance of allograft health after transplantation has traditionally relied on biopsy procedures that enable pathologic assessment for acute rejection. Noninvasive methods to assess for graft injury have been developed and tested over the past decade, and now offer a convenient way to reduce reliance on invasive testing and improve patient satisfaction. Emerging evidence suggests that detection of allograft injury via donor-derived cell-free DNA (dd-cfDNA) may, in fact, have better sensitivity compared to traditional biopsy-based strategies. This state-of-the-art review describes the development, testing, and current use of dd-cfDNA assays for acute rejection monitoring after heart transplantation, and discusses innovative ways that such assays can be used for personalized patient management., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients., Methods: 40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients' CAV risk. Analyses were based on OPTN data (June 30, 2019)., Results: Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p < 0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%., Conclusions: In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk., Competing Interests: Declaration of Competing Interest AMB has received honoraria from Abbott, Abiomed, AstraZeneca, BerlinHeart, Medtronic and Novartis (unrelated to the submitted work). BS has received speakers fee from AstraZeneca and Abiomed (unrelated to the submitted work). CM reports speaker fees from AstraZeneca, Novartis and Loewenstein Medical (unrelated to the current work). RBS has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union’s Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239)(unrelated to the submitted work). RSP has received honoraria from the Abiomed Advisory Board and the Medtronic Advisory Board (unrelated to the submitted work). SB has received received speaker fees from Medtronic, Pfizer, Roche, Novartis and Siemens Diagnostics (unrelated to the submitted work)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The transplantation field requires the identification of specific risk factors associated with the level of immunosuppression. Here, our aim was to analyze the association between the number of circulating lymphocytes, monitored routinely by complete blood cell counts during outpatient visits, and patient and graft survival. In total, 2,999 kidney or combined kidney-pancreas recipients transplanted between 2000 and 2016, from two University hospitals, were enrolled. We investigated the etiological relationship between time-dependent lymphocyte count beyond one year after transplantation and patient and graft survival, viral infection and cancer risk using time-dependent multivariate Cox models. Model 1 considered kidney function at one year and model 2 as time-dependent variable. At the time of inclusion (one year after transplantation), 584 patients (19.4%) had deep lymphopenia (under 750 /mm 3 ) and 1,072 (35.7%) had a normal count (over 1,500 /mm 3 ). A patient with deep lymphopenia at a given follow-up time had significantly higher risks of graft failure, death and viral infection than comparable patients with a normal lymphocyte count at the same time point. Thus, after the first year of transplantation, the occurrence of deep lymphopenia within a patient's follow-up is a risk factor for long-term graft failure, death and viral infection., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)