Progress in Transplantation最新文献

Introduction: Posttransplant anemia is a common finding after kidney transplantation. A previous meta-analysis reported an association between anemia and graft loss. However, data on cardiovascular outcomes have not yet been reported. Objective: We conducted an updated meta-analysis to examine the association between posttransplant anemia and outcomes after transplantation including cardiovascular mortality in adult kidney transplant recipients. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to November 2021. Data from each study were combined using the random-effects model. Generic inverse variance method of DerSimonian and Laird was employed to calculate the risk ratios and 95% CIs. Results: Seventeen studies from August 2006 to April 2019 were included (16 463 kidney transplantation recipients). Posttransplant anemia was associated with overall mortality (pooled risk ratio = 1.72 [1.39, 2.13], I² = 56%), graft loss (pooled risk ratio = 2.28 [1.77, 2.93], I² = 94%), cardiovascular death (pooled risk ratio = 2.06 [1.35, 3.16], I² = 0%), and cardiovascular events (pooled risk ratio = 1.33 [1.10, 1.61], I² = 0%). Early anemia (≤6 months), compared with late anemia (>6 months), has higher risk of overall mortality and graft loss with a pooled risk ratio of 2.63 (95% CI 1.79-3.86; I² = 0%) and 2.96 (95% CI 2.29-3.82; I² = 0%), respectively. Discussion: In addition to increased risk of graft loss, our updated meta-analysis demonstrated that posttransplant anemia was significantly associated with poor outcomes after kidney transplantation including overall mortality, graft loss, cardiovascular death, and cardiovascular events. Future studies are required to assess the effects of treatment strategies for posttransplant anemia on posttransplant outcomes including cardiovascular mortality.

Purpose: Malignancy after heart transplantation is associated with poor outcomes. At present, no prediction model exists for any malignancy within the first year after transplant. Methods: We studied adults who underwent heart transplantation included in the multicenter, national Scientific Registry of Transplant Recipients from January 2000 through April 2021. Possible predictors of malignancy were identified based on their known association with malignancy. Multiple imputations were conducted for missing values using predictive mean matching. A multivariable logistic regression model for predicting malignancy development within the first year after transplant was developed and internally validated via 500 bootstrapped samples to estimate the optimism-corrected measures of model accuracy and performance. Results: Among the 47 212 recipients comprising 16% females, 76% whites, 7% with prior malignancy, and a median age of 56 years; 865 (2.3% of those with non-missing data) developed malignancy within the first year after transplant. Prior malignancy, older age at heart transplantation, white race, and nonischemic heart failure etiology were the strongest predictors of new malignancy. The optimism-corrected model had modest discrimination (C-statistic: 0.70, 95% CI: 0.69-0.72) and good calibration and performance (calibration slope: 0.96; Cox-Snell R²: 0.063), particularly at lower predicted risk. A nomogram for the practicing clinician was developed. Conclusions: Using selection variables previously linked to cutaneous malignancy, our model was modestly predictive of the development of any malignancy in the first year after heart transplantation. Future research could identify factors that may improve malignancy prediction, including incorporation of time-to-event data.

Introduction: Limited evidence exists on the effect of isavuconazonium sulfate and posaconazole delayed release tablets on tacrolimus dose-to-concentration ratios in lung transplant recipients.

Project aims: The purpose of this evaluation was to assess the impact of novel triazoles on tacrolimus dose-to-concentration ratios.

Design: This retrospective review included lung transplant recipient ≥18 years of age from January 1, 2017 to October 1, 2020 who received either posaconazole delayed release tablets or isavuconazonium sulfate for. A paired analysis evaluated outcomes pre-triazole and post-triazole initiation.

Results: Forty-one patients met evaluation criteria for inclusion. A total of 34 of 41 patients received posaconazole delayed release tablets. Of these patients, 22 of 34 were transitioned from previous triazole to posaconazole delayed release tablets and experienced a 47% reduction in tacrolimus dose-to-concentration ratio. Twelve patients were newly initiated on posaconazole delayed release tablets and experienced a 50% reduction in tacrolimus dose-to-concentration ratios. Although not statistically significant, a 30% reduction in tacrolimus dose-to-concentration ratio was observed when transitioning to isavuconazonium sulfate from previous triazole therapy.

Conclusion: Limited data exists to provide guidance on tacrolimus dose adjustments with initiation and conversion of novel triazoles, however, this evaluation provides more knowledge on the drug interaction with novel triazoles and tacrolimus.

Introduction: Too small or too big liver grafts for recipient's size has detrimental effects on transplant outcomes. Research Questions: The purpose was to correlate donor-recipient body surface area ratio or body surface area index with recipient survival, graft survival, hepatic artery or portal vein, or vena cava thrombosis. High and low body surface area index cut-off points were determined. Design: There were 11,245 adult recipients of first deceased donor whole liver-only grafts performed in the UK from January 2000 until June 2020. The transplants were grouped according to the body surface area index and compared to complications, graft and recipient survival. Results: The body surface area index ranged from 0.491 to 1.691 with a median of 0.988. The body surface area index > 1.3 was associated with a higher rate of portal vein thrombosis within the first 3 months (5.5%). This risk was higher than size-matched transplants (OR: 2.878, 95% CI: 1.292-6.409, P = 0.01). Overall graft survival was worse in transplants with body surface area index ≤ 0.85 (HR: 1.254, 95% CI: 1.051-1.497, P = 0.012) or body surface area index > 1.4 (HR: 3.704, 95% CI: 2.029-6.762, P < 0.001) than those with intermediate values. The graft survival rates were reduced by 2% for cases with body surface area index ≤ 0.85 but were decreased by 20% for cases with body surface area index > 1.4. These findings were confirmed by bootstrap internal validation. No statistically significant differences were detected for hepatic artery thrombosis, occlusion of hepatic veins/inferior vena cava or recipient survival. Conclusions: Donor-recipient size mismatch affects the rates of portal vein thrombosis within the first 3 months and overall graft survival in deceased-donor liver transplants.

Introduction: A core outcome set (COS) improves the quality of reporting in clinical trials; however, this has not been developed for clinical trials of exercise training among adults undergoing solid organ transplant. Research Question: To explore the perspectives of transplant patients and healthcare professionals on the key outcomes domains that are relevant for clinical trials of exercise in all recipients of transplanted organs. Methods: A Delphi approach was employed with 2 rounds of online questionnaires. Participants rated the importance of outcome domains using a 9-point Likert scale ranging from "not important" to "very important". A score of 7 to 9 (very important) by 70% or more participants and a score of 1 to 3 (not important) by less than 15% participants were required to keep an outcome domain from the first to the second round. Results: Thirty-six participants completed 2 rounds of questionnaires (90% response rate). After Round 1, 8 outcome domains were considered very important in the pretransplant phase; 16 in the early posttransplant; and 17 in the late posttransplant. Only 1 outcome domain, organ rejection in the early posttransplant phase, met the criteria to be considered very important after Round 2. Conclusion: Although consensus was not reached on the core outcome domains, this study provides preliminary information on which domains are higher priority for patients and professionals. Future work should consider a meeting with key stakeholders to allow for deeper discussion to reach consensus on a core outcome set.

Introduction: Lack of knowledge about living donor kidney transplant and difficulties in approaching potential donors constitute barriers for many patients and may contribute to inequality of access. Project Aims: Renal Education and Choices at Home was a UK single-centre pilot of home education; an initiative aiming to overcome barriers by increasing knowledge among patients and support networks and by facilitating living donation discussion in the patient's home. Design: This was a pre-post comparison of knowledge, attitude, and ability to communicate about transplant. Pre-visit knowledge about treatment options and attitudes towards transplant were measured using a validated questionnaire, repeated 4-6 weeks post-visit, to assess the session's impact, along with an evaluation survey, to determine how patients perceived the session. Results: From November 2018 to February 2020, a nurse specialist delivered living donor transplant education sessions in the homes of 86 patients, attended by 141 additional invitees. Home visits led to a significant improvement in knowledge about renal therapies, including living donor transplantation. The evaluation of the home visits by patients and invitees was overwhelmingly positive. Of the 86 patients visited, 46 (53%) had at least one potential donor initiating the assessment process following the visit. Overall, 78 potential donors initiated the assessment process. Conclusion: Home education contributed to addressing recognised barriers, in a way that was well received by patients and was novel in our health system. Home education may be particularly beneficial for patients affected by known barriers to living donor transplantation such as socio-economic deprivation.

Introduction: Digital health interventions may support physical activity among solid organ transplant recipients. These interventions should be designed with users in mind, including healthcare professionals who counsel transplant recipients on physical activity to ensure acceptance and to promote an optimal user experience. The purpose of this study was to explore the perspectives of health care providers on the features of digital health interventions that would be useful in the promotion, implementation, and maintenance of physical activity among solid organ transplant recipients. Methods: This qualitative, cross-sectional study used semistructured interviews that were conducted remotely, via videoconferencing software, with providers who worked with transplant recipients. Interviews were transcribed, and an iterative-inductive, thematic analysis was used to identify common themes. Data were coded using NVivo software. Findings: Thirteen providers participated in this study. Four main themes were identified: (a) physical activity and exercise features (eg, physical activity guidelines, and exercise instructions); (b) credibility; (c) self-management; and (d) user engagement. Potential barriers to using digital health interventions included staffing requirements, professional regulatory issues, cost, perceived low patient motivation to use, and lack of technological literacy or access. Discussion: Digital health interventions were perceived to be a potential adjunct to current physical activity counseling practices, and part of an innovative strategy to address identified barriers to physical activity participation in solid organ transplant recipients.

Introduction: Incidentally detected malignancies in lung explants portend risk of early cancer recurrence and metastases with posttransplant immunosuppression. We present a series of lung transplant recipients with previously unverified malignancies in native lung explants. Design: We reviewed the histopathology, radiographic imaging, and management of lung explant malignancies at our institution over 10 years (2011-2020). Endpoints were survival and allograft rejection. Results: An explant malignancy was found in 1.3% (11/855) of lung transplant recipients (6 [55%] men; median age 68 years; 6 [55%] ex-smokers [median pack-years, 25]). Nine (82%) were adenocarcinoma, 1 (9%) was squamous cell carcinoma (SCC), and 1 (9%) was follicular lymphoma. Three patients (27%) had multifocal involvement (≥3 lobes), 4 (36%) had nodal involvement, and the median (range) tumor size was 2.7 (0.4-19) cm. The median interval between last imaging and transplant was 58 (29-144) days. Mycophenolate mofetil was discontinued or reduced in all; everolimus was used in 2 patients, and cisplatin-pemetrexed chemotherapy was used in 2 patients. The prevalence of acute cellular rejection and chronic rejection was 27% and 9%, respectively. Lung recipients with cancer had significantly lower survival than those without (36.4% vs 67.3%, p = 0.002); median survival was 27 (17, 65) months in 4 recipients who were alive and cancer-free at the end of the study period. Conclusions: Unidentified malignancies, commonly adenocarcinoma, can be detected in explanted native lungs. Pneumonectomy may be curative in SCC, lymphoproliferative disorders, and stage I adenocarcinoma. Modulating immunosuppression to prevent allograft rejection and tumor proliferation is warranted.

Introduction: Donation after circulatory death (DCD) is rapidly increasing in the United States. Detailed data outlining the process from referral to organ transplantation is lacking. Project Aims: We sought to quantify differences at each stage along the referral to donation pathway by donor type. Additionally, we examined factors associated with successful DCD organ utilization. Design: This program evaluation analyzed data from a single organ procurement organization in 2018 to assess demographic and clinical predictors of progression through the donation process, including the role of first-person authorization in DCD. Descriptive statistics were examined by donation stage for demographic characteristics using chi-square; univariate and multivariate logistic regression was used to model predictors of utilization and authorization by organ type, respectively. Results: There were 2466 organ donation referrals during 2018, including 575 donations after brainstem death (DBD), 1890 controlled DCD referrals, and 1 uncontrolled DCD referral. Univariate and multivariate logistic regression models highlighted differences in authorization rates by donor type (DCD vs DBD) and by age, race, and ethnicity. Next-of-kin authorization was declined in 23% of first-person authorized potential DCD, highlighting issues related to the role of donor registration in DCD. Pre-mortem heparin administration was predictive of DCD organ utilization; donor age and warm ischemia time of less than 30 min was statistically significantly associated with DCD extra-renal organ utilization. Conclusion: These results provided insight into strategies for increasing authorization and transplantation of organs from DCD donors and identified areas of improvement for process standardization and policy development.

Background: Body fat and overall weight gain are common after kidney transplantation and are associated with poor clinical outcomes. Therefore, identification of at-risk patients is relevant for preventive interventions. Clinical Question: What variables influence weight and fat gain in patients in the first year after kidney transplantation? Literature Search Prospective and retrospective cohort studies published in or after 2001 naming fat and/or overall weight gain during the first year after kidney transplantation as outcome variable(s) were systematically searched in Medline/Pubmed in November 2018 and March 2022. Clinical Appraisal: We identified 16 studies examining a wide variety of potential factors influencing weight and fat gain over the first posttransplant years. These included genetic, socio-demographic, behavioral, biomedical, psychological and environmental factors. For a number of variables, study results were contradictory: some studies indicated preventive impacts on weight or fat gain; others concluded that the same factors increased it. Cases were discussed with 2 clinical experts. We eventually agreed on 13 potentially relevant risk factors for post-transplant weight/fat gain: age, gender, genes, income, ethnicity, education, eating habits, physical activity, smoking cessation, baseline BMI, baseline fat, depression and perceived overall wellbeing. Integration into Practice Before integration into clinical practice, a critical evaluation of all potential risk factors' suitability for assessment will be necessary. In addition to feasibility, operational definitions and measurement methods must also be considered. Evaluation: To reduce the list of risk factors to the most relevant, a first testing within a prospectively collected data set is planned.