Progress in Transplantation最新文献

Introduction: The antioxidant effects of vitamins may attenuate the oxidative stress on organs imposed by ischemia-reperfusion injury during the process of organ transplantation from brain-dead donors. Circulating levels of vitamins A, C, and E-α in donors after brain death and their relationships to donor demographics, management, organ utilization, and recipient outcomes are largely unknown.

Methods: An observational, prospective, cohort study of 84 consecutive brain-dead organ donors managed at a single organ procurement recovery center was conducted. Vitamin levels were drawn immediately prior to procurement.

Results: Levels of serum vitamins A and E-α and plasma vitamin C were below normal in 80%, 85%, and 92% of donors and deficient in 40%, 62%, and 63%, respectively. Vitamin C deficiency was associated with a longer time between death and specimen collection (P = .004). Death from head trauma and stroke were associated with lower levels of vitamin A than from anoxic causes (P = .003) and smokers had greater vitamin C deficiency (P = .03). During donor management, vitamin C deficiency was associated with longer vasopressor support (P = .03) and normal levels of vitamin E-α were associated with reaching a lower alanine transferase compared to those with subnormal levels (P < .05). Donors deficient in vitamin E-α were less likely to have a liver recovered for transplantation (P = .005). Vitamin levels were not associated with the recipient outcomes examined.

Conclusion: Circulating vitamins A, C, and E-α is profoundly low in brain-dead organ donors, associated with relevant demographic features of the donor, and may influence donor management and organ utilization.

Introduction: Patients are at risk of hospital readmission after kidney and liver transplantation due to the complexity of posttransplant care. Currently, clinical practice relies on providers' prediction since there is a lack of specific strategies. However, the accuracy of clinicians' ability to predict readmissions using clinical judgment alone is unknown. Research Question: What is the accuracy of clinicians' ability to predict readmissions after transplantation using clinical judgment alone? Design: In 2019, clinical providers at a large, urban transplant center were electronically surveyed. Primary surgeons, nephrologists, transplant pharmacists, hepatologists, and nurses were asked, within 24 h of any kidney or liver transplant recipient discharge, to predict whether a patient would be readmitted within 30 days, and the suspected causes of readmission. Prediction accuracy was assessed by sensitivity, specificity, positive and negative predictive value, and F-score. Kappa scores were calculated to assess agreement between transplant surgeons and other providers. Results: Overall, N = 34 unique providers were surveyed about 148 kidney and 63 liver transplant recipients, and 27.0% of kidney recipients and 25.4% of liver recipients were readmitted within 30 days. The positive predictive values were low among clinical providers, ranging from 0.25 to 0.55. Agreements between providers were weak, but higher among kidney transplant providers (range: 0.42-0.44) than for liver transplant providers (range: -0.02-0.26). Conclusion: Clinical judgment alone to predict readmission among transplant recipients may not be sufficient and a combination of clinicians' predictions, multitiered discharge surveillance strategies and data-based predictive models may better identify high-risk patients and guide interventions to reduce readmission.

Introduction: An inverse relationship has been identified between tacrolimus serum concentrations and donor-derived cell-free DNA (dd-cfDNA) levels after lung transplant, but limited data exists on this relationship in the kidney transplant population. Project Aim: The purpose of this evaluation was to examine the relationship between high tacrolimus variability and elevated dd-cfDNA levels in kidney and simultaneous pancreas-kidney transplant recipients at a single center. Design: Single-center, retrospective, descriptive comparative evaluation of kidney and pancreas-kidney transplant recipients who received longitudinal ddcfDNA surveillance. Intrapatient tacrolimus variability was assessed using the coefficient of variation (%CV) measured between 1 and 12 months posttransplant. Pediatrics, retransplant or multiorgan transplant recipients, and pregnant recipients were excluded. Results: One hundred fifteen recipients with 518 dd-cfDNA levels and 3028 tacrolimus troughs were assessed. Pancreas-kidney recipients had significantly higher median dd-cfDNA (0.29% vs. 0.18%, P = .034) and were excluded from analysis. Ninety-nine kidney transplant recipients were included for analysis. Recipients with tacrolimus %CV ≥30 (N = 66) had significantly higher median dd-cfDNA than %CV <30 (0.22% vs. 0.17%, P = .031). Tacrolimus %CV ≥30 demonstrated higher median peak dd-cfDNA than %CV <30, though this was not statistically significant (0.36% vs. 0.28%, P = .058). Conclusion: These data demonstrated that high intrapatient tacrolimus variability may be associated with elevated dd-cfDNA in the first year after kidney transplant.

Alcoholic liver disease (ALD) and alcohol-induced deaths have increased dramatically over the last 2 decades. Patients are often referred to liver transplant programs critically ill with a life expectancy of less than 6 months. Historically, less than 6 months sobriety has been an absolute contraindication for transplant listing as ALD is stigmatized as a choice, as patients are responsible for their condition because they did not stop drinking. It has been recommended that 6 months of sobriety should not be considered the determining factor for access to transplantation. However, changing years of clinical practice involves developing new protocols, finding available resources, reworking systems, transforming team, and institutional culture. Steps taken by a large, urban, academic liver transplant program to develop a program for patients with end stage ALD with less than 6 months of sobriety are outlined.

Introduction: Kidney Allocation System (KAS) was implemented by United Network for Organ Sharing in 2014 to reduce allocation disparities. Research Questions: Outcomes of highly sensitized patients (calculated panel reactive antibody (cPRA) ≥ 97%) before and after KAS were compared to low-risk recipients (cPRA <10%) in the post-KAS era were examined. The impact on racial disparities was determined. Design: This was a retrospective study of national registry data. Two cohorts of adult candidates waitlisted for deceased donor transplantation during 3-year periods before and after KAS were identified. Results: Highly sensitized patients (N = 1238 and 4687) received a deceased donor kidney transplant between January 1, 2011 and December 31, 2013 and between January 1, 2015 and December, 31, 2017. Racial disparity for highly sensitized patients improved, yet remained significant (P < 0.001), with Black patients comprising 40% and 41% of the highly sensitized candidates and 28% and 34% of the recipients pre- and post-KAS. While posttransplant death-censored graft failure for highly sensitized recipients was similar overall, post-KAS was associated with improved graft survival in the first year after transplant (HR 0.56, 95% CI 0.40-0.78). When compared to contemporaneous lowrisk recipients, both death-censored and all-cause graft failure were similar for highly sensitized recipients and was associated with increased risk for death-censored graft failure beyond the first year (HR 1.39, 95% CI 1.11-1.73). Conclusion: The allocation system led to an increase in transplantation in highly sensitized candidates without compromising outcomes. Although KAS has led to more balanced transplant rates between highly sensitized Black and White patients, racial inequalities persist.

Introduction: Neurocognitive and motor impairments are often observed both before and after liver transplantation, resulting in inefficiencies in dual-task performance. Specific aim: The aim of this study was to evaluate the motor-cognitive dual-task performance in liver recipients, with a particular emphasis on cognition, performance status, and the impact of the COVID-19 pandemic. Design: A prospective, cross-sectional, web-based design with a control group was used. The study included 22 liver transplant recipients and 23 controls. Participants completed a motor-cognitive dual-task test (timed up and go test, TUG), a cognitive assessment (mini mental state examination), and a physical performance test (5-repetition sit-to-stand test). The study also used a functional performance status scale (The Karnofsky performance status) and assessed fear of coronavirus disease (fear of COVID-19 scale). Dual-task interference was assessed and the rate of correct responses per second was calculated to assess cognitive performance. Results: The results indicated no statistically significant difference in TUG time and TUG correct responses per second between the groups (group × condition interactions; P > 0.05). There was no significant difference in cognitive and motor dual-task interference during the TUG test between the two groups (P > 0.05). The Karnofsky Performance Status score was significantly correlated with TUG motor dual-task interference (r = -0.424 and P = 0.049). Conclusion: This study suggests that dual-task performance does not differ in cognitive or motor performance between liver recipients and healthy controls under the same dual-task condition. However, further controlled studies are needed to improve the generalizability of these findings.

Introduction: Improving public awareness about the opportunity to become a vascularized composite allograft (VCA) donor is crucial to increasing access to organs. Prior research identified a need for comprehensive and comprehensible public education materials. A 2-round Delphi panel was conducted to garner US expert consensus on the topics and language to include in public education materials via an organ procurement organization-hosted website. Methods: The round 1 survey assessed the importance of educational topics and statements (n = 19) using 5-point Likert scales. The round 2 survey asked experts to rate new and repeated educational topics (n = 27). Open-ended comment boxes elicited experts' feedback and language revisions for educational statements. Responses were analyzed using descriptive statistics and rapid qualitative analysis. Findings: Eighteen experts responded to the round 1 survey and 15 to round 2. After round 2, 20 topics had mean (M) importance greater than neutral (M > 3.00) and were retained in the educational materials. The 5 most important topics by mean Likert ratings were: consent process for donation (M = 4.73), potential recipients (M = 4.73), most common vascularized composite organs transplanted (M = 4.47), purpose (M = 4.47), and definition (M = 4.47). Seven themes emerged from experts' open-ended comments about the importance and language of educational statements. Conclusions: Delphi panel findings identified expert-endorsed topics and educational statements for public education about vascularized composite organ donation via an educational website. Future research should assess the website's impact on public knowledge of VCA donation.

Introduction: Frailty and cognitive function are often measured during kidney transplant evaluation. However, patient perspectives on the ethical considerations of this practice are unclear.

Research question: What are patient perspectives on the use of aging metrics in kidney transplant decision-making?

Design: One hundred participants who were evaluated for kidney transplantation and were enrolled in an ongoing prospective cohort study (response rate = 61.3%) were surveyed. Participants were informed of the definitions of frailty and cognitive impairment and then asked survey questions regarding the use of these measures of aging to determine kidney transplant candidacy.

Results: Participants (75.6%) thought it was unfair to prevent older adults from receiving a kidney transplant based on age, but there was less agreement on whether it was fair to deny frail (46.5%) and cognitively impaired (45.9%) patients from accessing kidney transplantation. Compared to older participants, younger participants had 5.36-times (95%CI:1.94-14.81) the odds of choosing a hypothetical younger, frail patient to list for kidney transplantation than an older, non-frail patient; they also had 3.56-times (95%CI:1.33-9.56) the odds of choosing the hypothetical frail patient with social support rather than a non-frail patient without social support. Participants disagreed on the use of patient age as a listing criterion; 19.5% ranked it as the fairest and 28.7% as the least fair.

Conclusion: The patient views highlighted in this study are an important step toward developing ethical guidelines to ensure fair use of frailty, cognitive function, and chronological age for kidney transplant decision-making.

Introduction: Regulations designed to protect children participating in clinical research often restrict the availability of research data necessary for the development of age-specific therapies and drug dosing. Few data exist on how children experience participation in clinical research, and studies investigating young children undergoing an intensive medical treatment are lacking.

Methods: Mixed methods with semi-structured interviews and DISCO-RC questionnaires were used to explore young children's and their parents' experiences in clinical research participation during a kidney transplantation trajectory.

Findings: Nine children and their parents were interviewed. Children's median age at kidney transplantation was 4 years (IQR 4,7); age at interview was 7 years (IQR 6,9). Thematic content analysis of interviews revealed that most children were unaware of having participated in a study. Both children and their parents frequently were unaware whether procedures were standard care or research related. The additional burden attributed to study participation varied from not at all to heavy in combination with intensive medical treatment. Positive experiences included kind healthcare professionals, effective distraction techniques, educational aspects, contributing to science and extra check-ups. Most reported negative experiences were conflicting communication, spending much time in the hospital, missing school and suboptimal planning. Venous puncture was stressful for all children, whereas the discomfort of other procedures varied.

Conclusion: Pediatric clinical research design should focus on education and fun during research procedures, smart planning, consistent communication, close collaboration between clinical and research team and age appropriate distraction techniques.