UK guidelines on transplantation from deceased donors after circulatory death

Transplantation offers patients with end-stage organ failure a cost-effective treatment that can improve quality of life and increase life expectancy. Prior to the introduction of guidance defining the concept of brain death in the 1970s, all organs donated for transplantation were from donation after circulatory death (DCD) donors. Following the introduction of neurological testing to diagnose death, the majority of organs donated for transplantation were from donation after brain death (DBD) donors or living donors.

Differential donor management of pediatric vs adult organ donors and potential impact on pediatric lung transplantation.

BACKGROUND: Despite clinical progress over time, a shortage of suitable donor organs continues to limit solid organ transplantation around the world. Lungs are the organs most likely to be assessed as unsuitable during donor management among all transplantable organs. Although the number of lung transplants performed in children is limited, death on the wait list remains a barrier to transplant success for many potential transplant candidates. Optimizing organ donor management can yield additional organs for transplant candidates. METHODOLOGY: We accessed the Donor Management Goal (DMG) Registry to evaluate the efficiency and efficacy of donor management in the procurement of lungs for transplantation. Further, we stratified donors by age and compared pediatric age cohorts to adult cohorts with respect to attainment of donor management target goals and successful pathway to transplantation. We utilized recipient data from the Organ Procurement Transplantation Network (OPTN) to put this data into context. The DMG bundle consists of nine physiologic parameters chosen as end-points guiding donor management for potential organ donors. The number of parameters fulfilled has been regarded as an indication of efficacy of donor management. RESULTS: We noted a markedly lower number of organ donors in the pediatric age group compared to adults. On the other hand, the number of donors greatly exceeds the number of infants, children and adolescents who undergo lung transplantation. Organs transplanted per donor peaks in the adolescent age group. At initial donor referral, DMG bundle attainment is lower in all age groups and improves during donor management. With respect to oxygenation, there is less overall improvement in younger donors compared to older donors during donor management. When donors who yield lungs for transplantation are compared to those whose lungs were not transplanted, oxygenation improved more substantially during donor management. Furthermore, improved oxygenation correlated with the total number of organs transplanted per donor. CONCLUSIONS: In the face of continued wait list mortality on the pediatric lung transplant wait list, the number of young donors may not be a limiting factor. We believe that this dataset provides evidence that management of young pediatric donors is not as consistent or efficient as the management of older donors, potentially limiting the number of life-saving organs for pediatric lung transplant candidates. Across all ages, optimizing donor lung management may increase the potential to transplant multiple other organs.

Outcomes of Heart Transplantation Using a Temperature-controlled Hypothermic Storage System.

BACKGROUND: The SherpaPak Cardiac Transport System is a novel technology that provides stable, optimal hypothermic control during organ transport. The objectives of this study were to describe our experience using the SherpaPak system and to compare outcomes after heart transplantation after using SherpaPak versus the conventional static cold storage method (non-SherpaPak). METHODS: From 2018 to June 2021, 62 SherpaPak and 186 non-SherpaPak patients underwent primary heart transplantation at Stanford University with follow-up through May 2022. The primary end point was all-cause mortality, and secondary end points were postoperative complications. Optimal variable ratio matching, cox proportional hazards regression model, and Kaplan-Meier survival analyses were performed. RESULTS: Before matching, the SherpaPak versus non-SherpaPak patients were older and received organs with significantly longer total allograft ischemic time. After matching, SherpaPak patients required fewer units of blood product for perioperative transfusion compared with non-SherpaPak patients but otherwise had similar postoperative outcomes such as hospital length of stay, primary graft dysfunction, inotrope score, mechanical circulatory support use, cerebral vascular accident, myocardial infarction, respiratory failure, new renal failure requiring dialysis, postoperative bleeding or tamponade requiring reoperation, infection, and survival. CONCLUSIONS: In conclusion, this is one of the first retrospective comparison studies that evaluated the outcomes of heart transplantation using organs preserved and transported via the SherpaPak system. Given the excellent outcomes, despite prolonged total allograft ischemic time, it may be reasonable to adopt the SherpaPak system to accept organs from a remote location to further expand the donor pool.

Ethical Solutions to the Problem of Organ Shortage.

Organ shortage is a major survival issue for millions of people worldwide. Globally 1.2 million people die each year from kidney failure. In this paper, we critically examine and find lacking extant proposals for increasing organ supply, such as opting in and opt out for deceased donor organs, and parochial altruism and paired kidney exchange for live organs. We defend two ethical solutions to the problem of organ shortage. One is to make deceased donor organs automatically available for transplant without requiring consent from the donor or their relatives. The other is for society to buy nonvital organs in a strictly regulated market and provide them to people in need for free.

Impact of the 2018 change in US allocation policy on adults with congenital heart disease.

BACKGROUND: The US adult heart allocation policy was changed on October 18, 2018. This study aims to evaluate its impact on orthotopic heart transplantation (OHT) for adults with congenital heart disease (ACHD). METHODS: The United Network for Organ Sharing database was used to perform 2 comparisons: waitlist outcomes among listed ACHD candidates, and post-transplant outcomes in those transplanted. Waitlisted candidates were stratified by date of waitlisting: Period 1: 2010 to 2013; Period 2: 2014 to October 17, 2018 and Period 3: October 18, 2018 to March 20, 2020. Transplanted ACHD patients were similarly stratified but by date of transplantation. Competing risk regression for waitlist outcomes was performed. Post-transplant survival was analyzed using the Kaplan-Meier method and multivariable Cox regression. RESULTS: Nine hundred and seventy-six patients with ACHD were waitlisted for OHT in our study: 343(35.1%), 466(47.8%), and 167(17.1%) in periods 1, 2, and 3. Post-policy change, 1-year cumulative incidence of waitlist mortality or deterioration decreased (p = 0.02). Six hundred and forty-eight patients were transplanted: 221(34.1%), 329(50.8%) and 98(15.1%) respectively. In those transplanted, post-policy median waitlist time (174, 161 and 38 days, p < 0.001) decreased and the use of intra-aortic balloon pumps increased (1.4%, 4.9% and 19.4%, p < 0.001). Compared to periods 1 and 2, risk-adjusted post-transplant 1-year mortality was similar to period 3 (HR 1.10, 95% CI 0.52-2.32; p = 0.81) (HR 1.19, 95% CI 0.58-2.46, p = 0.63). CONCLUSIONS: The recent US allocation policy change may have resulted in reduced waitlist times and 1-year waitlist mortality for OHTs in ACHD patients. Early post-transplant outcomes appear comparable post-policy change.

Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.

BACKGROUND: The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. METHODS: We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. RESULTS: Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. CONCLUSIONS: Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.

Outcomes of living liver donors are worse than those of matched healthy controls.

BACKGROUND & AIMS: Donor death is the most serious complication of living liver donation but is reported rarely. We investigated the actual mortality of living liver donors (LLDs) compared with matched control groups based on analysis of the Korean National Health Insurance Services (NHIS) database. METHODS: This cohort study included 12,372 LLDs who donated a liver graft between 2002 and 2018, and were registered in the Korean Network for Organ Sharing. They were compared to 3 matched control groups selected from the Korean NHIS and comprising a total of 123,710 individuals: healthy population (Group I); general population without comorbidities (Group II); and general population with comorbidities (Group III). RESULTS: In this population, 78.5% of living liver donors were 20-39 years old, and 64.7% of all donors were male. Eighty-nine donors (0.7%) in the LLD group died (68 males and 21 females), a mortality rate (/1,000 person-years) of 0.91 (0.74-1.12). Mortality rate ratio and the adjusted hazard ratio of the LLD group was 2.03 (1.61-2.55) and 1.71 (1.31-2.25) compared to Control Group I, 0.75 (0.60-0.93) and 0.63 (0.49-0.82) compared to Control Group II, and 0.58 (0.46-0.71) and 0.49 (0.39-0.60) compared to Control Group III. LLD group, depression, and lower income were risk factors for adjusted mortality. The incidence of liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the LLD group was significantly higher than in Control Group I. CONCLUSIONS: Outcomes of the LLD group were worse than those of the matched healthy control group despite the small number of deaths and medical morbidities in this group. LLDs should receive careful medical attention for an extended period after donation. LAY SUMMARY: The incidence of mortality, liver failure, depression, cancer, diabetes, hypertension, brain infarction, brain hemorrhage, and end-stage renal disease in the living liver donor group was significantly higher than in the matched healthy group. Careful donor evaluation and selection processes can improve donor safety and enable safe living donor liver transplantation.

A challenge to equity in transplantation: Increased center-level variation in short-term mechanical circulatory support use in the context of the updated U.S. heart transplant allocation policy.

BACKGROUND: The United States National Organ Procurement Transplant Network (OPTN) implemented changes to the adult heart allocation system to reduce waitlist mortality by improving access for those at greater risk of pre-transplant death, including patients on short-term mechanical circulatory support (sMCS). While sMCS increased, it is unknown whether the increase occurred equitably across centers. METHODS: The OPTN database was used to assess changes in use of sMCS at time of transplant in the 12 months before (pre-change) and after (post-change) implementation of the allocation system in October 2018 among 5,477 heart transplant recipients. An interrupted time series analysis comparing use of bridging therapies pre- and post-change was performed. Variability in the proportion of sMCS use at the center level pre- and post-change was determined. RESULTS: In the month pre-change, 9.7% of patients were transplanted with sMCS. There was an immediate increase in sMCS transplant the following month to 32.4% - an absolute and relative increase of 22.7% and 312% (p < 0.001). While sMCS use was stable pre-change (monthly change 0.0%, 95% CI [-0.1%,0.1%]), there was a continuous 1.2%/month increase post-change ([0.6%,1.8%], p < 0.001). Center-level variation in sMCS use increased substantially after implementation, from a median (interquartile range) of 3.85% (10%) pre-change to 35.7% (30.6%) post-change (p < 0.001). CONCLUSIONS: Use of sMCS at time of transplant increased immediately and continued to expand following heart allocation policy changes. Center-level variation in use of sMCS at the time of transplant increased compared to pre-change, which may have negatively impacted equitable access to heart transplantation.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

BACKGROUND & AIMS: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy. METHODS: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss. RESULTS: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss. CONCLUSIONS: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes. CLINICAL TRIAL NUMBER: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes.

Epidemiology of corneal transplantation before achieving the Zero Queue / Epidemiologia do transplante de córnea antes de atingir a Fila Zero

ABSTRACT Objective: To outline the epidemiological profile of cornea donors and recipients before reaching queue zero. Methods: Epidemiological study, of quantitative approach, with transversal, analytical design, analyzing database records from the Health Secretary of the State of Ceará, from 2013 to 2015. Results: We obtained 1,558 cornea donors and 2,287 cornea recipients from 2013 to 2015. Most donors were male, capital residents, from 21 to 40 years old. Of donated eyeballs, 14.52% were disposed, due to poor condition, infiltration or positive serology. The recipients were predominantly women over 60 years old. The procedures were mostly elective, due to bullous keratopathy (28%). Regarding emergency transplants, ulcer (38.51%) and retransplant (35.14%) were most prevalent. Predominantly, transplants were funded by the Unified Health System. Conclusion: The majority of patients who were submitted to corneal transplantation are senile, especially females, therefore should be cautiously observed. On the other hand, donors are mainly male and young, reflecting the high number of tragic accidents. The surgery for bullous keratopathy is the most frequent among elective transplants, while the ulcer surgery is the main cause of emergency procedures. The fact that most surgeries were financed by the Unified Health System reflects the importance of this system.

RESUMO Objetivo: Traçar o perfil epidemiológico dos doadores e receptores de córnea antes de atingir a Fila Zero. Métodos: Estudo epidemiológico, de abordagem quantitativa, com delineamento transversal e analítico, analisando registros da base de dados da Secretaria de Saúde do Estado do Ceará, de 2013 a 2015. Resultados: Foram obtidos 1.558 doadores de córnea e 2.287 receptores de córnea, de 2013 a 2015. A maioria dos doadores era homem, procedente da capital, de 21 a 40 anos. Dentre os globos oculares doados, 14,52% foram descartados por má condição, infiltração ou sorologia positiva. Os receptores eram predominantemente mulheres acima de 60 anos de idade. Os procedimentos foram majoritariamente eletivos, devido à ceratopatia bolhosa (28%). Já para transplantes de emergência, a úlcera (38,51%) e o retransplante (35,14%) foram os mais prevalentes. Em geral, os transplantes foram custeados pelo Sistema Único de Saúde. Conclusão: A maioria dos pacientes submetidos a transplantes de córnea foram do grupo etário senil, principalmente do sexo feminino, devendo esse grupo ser observado com cautela. Em contrapartida, os doadores eram, principalmente, homens e jovens, refletindo o alto número de pessoas que morrem devido a acidentes trágicos. A cirurgia de ceratopatia bolhosa foi a mais frequente dentre os transplantes eletivos; já a de úlcera foi a principal causa dos procedimentos de emergência. O fato de a maioria das cirurgias ter sido financiada pelo Sistema Único de Saúde reflete a importância desse sistema.

Associations Among Different Domains of Quality Among US Liver Transplant Programs.

Importance: US liver transplant programs have traditionally been evaluated on 1-year patient and graft survival. However, there is concern that a narrow focus on recipient outcomes may not incentivize programs to improve in other ways that would benefit patients with end-stage liver disease. Objective: To determine the correlation among different potential domains of quality for adult liver transplant programs. Design, Setting, and Participants: This retrospective cohort study was conducted from 2014 to 2019 among adult liver transplant programs included in the United Network for Organ Sharing and Scientific Registry of Transplant Recipients program-specific reports. Liver transplant programs in the United States completing at least 10 liver transplants per year were included. Data were analyzed from March 2 to August 13, 2020. Main Outcomes and Measures: The potential domains of quality examined included recipient outcomes (1-year graft and patient survival), aggressiveness (ie, marginal graft use, defined as the rate of use of donors with body mass index [calculated as weight in kilograms divided by height in meters squared] greater than 40, age older than 65 years, or deceased by cardiac death), and waiting list management (ie, waiting list mortality). The correlation among measures, aggregated at the center level, was evaluated using linear regression to control for mean Model for End Stage Liver Disease-Sodium score at organ allocation. The extent to which programs were able to achieve high quality across multiple domains was also evaluated. Results: Among 114 transplant programs that performed a total of 44 554 transplants, the mean (SD) 1-year graft and patient survival was 90.3% (3.0%) with a total range of 75.9% to 96.6%. The mean (SD) waiting list mortality rate was 16.7 (6.1) deaths per 100 person-years, with a total range of 6.3 to 53.0 deaths per 100 person years. The mean (SD) marginal graft use rate was 15.8 (8.8) donors per 100 transplants, with a total range of 0 to 49.3 donors. There was no correlation between 1-year graft and patient survival and waiting list mortality (ß = -0.053; P = .19) or marginal graft use (ß = -0.007; P = .84) after correcting for mean allocation Model for End Stage Liver Disease-Sodium scores. There were 2 transplant programs (1.8%) that performed in the top quartile on all 3 measures, while 4 transplant programs (3.6%) performed in the bottom quartile on all 3 measures. Conclusions and Relevance: This cohort study found that among US liver transplant programs, there were no correlations among 1-year recipient outcomes, measures of program aggressiveness, or waiting list management. These findings suggest that a program's performance in one domain may be independent and unrelated to its performance on others and that the understanding of factors contributing to these domains is incomplete.

Why are there so many liver transplants from living donors in Asia and so few in Europe and the US?

Acceptance of liver transplantation (LT) as an established treatment modality for end-stage liver disease has led to an exponential increase in the demand for organs, resulting in an ever-increasing gap between the availability of organs and the number of sick patients waiting for them. Interestingly, influenced by cultural, socio-economic and other constraints, the West and the East have attempted to address this problem of shortage in different ways. Living donor LT (LDLT) became polarised to the East with over 90% of LT in this region being LDLT. On the other hand, the West chose to concentrate their efforts on optimising the use of cadaveric livers with techniques such as split LT, or by using extended criteria donors (including donation after cardiac death donors) and machine perfusion devices etc. Consequently, LDLT did not find the widespread acceptance it did in the East and hence over 90% of all LT are DDLT in this region. We review each regions' perspective and attempt to provide a globally viable roadmap to bridge the widening gap between the demand and availability of livers for LT.

Impact of the COVID-19 Pandemic on Keratoplasty and Corneal Eye Banking.

PURPOSE: The purpose of this study was to assess the impact of COVID-19 guidelines for corneal donor tissue screening and the utility of routine postmortem COVID-19 testing of donors intended for surgical use at a single eye bank. METHODS: A retrospective analysis of referrals to and eligible donors from an eye bank between March 1, 2020, and June 30, 2020, was performed, with the same time period in 2019 as a control. Referrals who were not procured because of Eye Bank Association of America COVID-19 guidelines and eye bank-specific restrictions were noted. The results of 1 month of routine postmortem testing performed by the eye bank were examined. Analysis of variance tests were performed to assess the change between donors from 2019 to 2020. RESULTS: There was a significant reduction in both the number of total referrals to the eye bank (P = 0.044) and donors eligible for surgical transplantation (P = 0.031). Eye Bank Association of America COVID-19 guidelines reduced the number of referrals over this period by 4% to 14%. Of the 266 surgically eligible donors who received postmortem COVID-19 testing in June by the eye bank, 13 resulted positive (4.9%). CONCLUSIONS: Despite a reduction in referrals and eligible corneal transplant donors at a single eye bank, there was a surplus of surgically suitable corneal tissue during the first wave of the COVID-19 pandemic. Eye banks should consider routine postmortem COVID-19 testing to identify asymptomatic infected donors although the risk of transmission of COVID-19 from infected donors is unknown.

Canadian Society of Transplantation White Paper: Ethical and Legal Considerations for Alcohol and Cannabis Use in Solid Organ Listing and Allocation.

Alcohol and cannabis use as a contraindication to organ transplantation is a controversial issue. Until recently, patients in Canada with alcohol-associated liver disease were required to demonstrate abstinence for 6 mo to receive a liver transplant. There is no equivalent rule that is applied consistently for cannabis use. There is some evidence that alcohol and cannabis use disorder pretransplant could be associated with worse outcomes posttransplantation. However, early liver transplantation for patients with alcohol-associated liver disease in France and in the United States has led to challenges of the 6-mo abstinence rule in Canada in the media. It has also resulted in several legal challenges arguing that the rule violates human rights laws regarding discrimination in the provision of medical services and that the rule is also unconstitutional (this challenge is still before the court). Recent legalization of cannabis use for adults in Canada has led to questions about the appropriateness of limiting transplant access based on cannabis use. The ethics committee of the Canadian Society of Transplantation was asked to provide an ethical analysis of cannabis and alcohol abstinence policies. Our conclusions were as follows: neither cannabis use nor the 6-mo abstinence rule for alcohol use should be an absolute contraindication to transplantation, and transplant could be offered to selected patients, further research should be conducted to ensure evidence-based policies; and the transplant community has a duty not to perpetuate stigma associated with alcohol and cannabis use disorders.

Is donation after circulatory determination of death feasible for pediatric patients in italy?

To determine the potential effect of a donation after cardiac death active program on the number of organ donors in a Italian Pediatric Intensive Care Unit (PICU). We conducted a retrospective study of all deaths in PICU of an academic Children Hospital between 2012 and 2020, tracing the organ donation activity. Patients were categorized as brain deaths, deaths despite maximal resuscitation, and deaths after withdrawal or limitation of life support. Patient demographics, premortem physiology, end-of-life circumstances, and functional warm ischemia time were recorded. Eligible donors after cardiac death were identified by the absence of medical contraindication and functional warm ischemia time <60 minutes. Of 124 deaths that occurred during the study period, 34 met criteria for brain death, 23 were potential donors, and 13 became actual donors. Of the remaining 90 patients that met criteria for cardiac death, 66 died despite maximal resuscitation, 24 died after withdrawal or limitation of care and between them 13 were identified as theoretically eligible DCD donors. Of these, 5 patients had a functional warm ischemia time of <1 hour and were potential candidates for DCD of 10 kidneys and 2 lungs. Even if few children could have been eligible for DCD in the study period, an active program could have been able to increase the number of potential organ donors by 20% in the last eight years at our institution. DCD deserves to be explored in Italy as a new option for children.

Cord blood beyond transplantation: can we use the experience to advance all cell therapies?

Unrelated cord blood (CB) units, already manufactured, fully tested and stored, are high-quality products for haematopoietic stem cell transplantation and cell therapies, as well as an optimal starting material for cell expansion, cell engineering or cell re-programming technologies. CB banks have been pioneers in the development and implementation of Current Good Manufacturing Practices for cell-therapy products. Sharing their technological and regulatory experience will help advance all cell therapies, CB-derived or not, particularly as they transition from autologous, individually manufactured products to stored, 'off-the shelf' treatments. Such strategies will allow broader patient access and wide product utilisation.

Refitting the Model for End-Stage Liver Disease for the Eurotransplant Region.

BACKGROUND AND AIMS: The United Network for Organ Sharing's Model for End-Stage Liver Disease (UNOS-MELD) score is the basis of liver allocation in the Eurotransplant region. It was constructed 20 years ago in a small US cohort and has remained unchanged ever since. The best boundaries and coefficients were never calculated for any region outside the United States. Therefore, this study refits the MELD (reMELD) for the Eurotransplant region. APPROACH AND RESULTS: All adult patients listed for a first liver transplantation between January 1, 2007, and December 31, 2018, were included. Data were randomly split in a training set (70%) and a validation set (30%). In the training data, generalized additive models with splines were plotted for each MELD parameter. The lower and upper bound combinations with the maximum log-likelihood were chosen for the final models. The refit models were tested in the validation data with C-indices and Brier scores. Through likelihood ratio tests the refit models were compared to UNOS-MELD. The correlation between scores and survival of prioritized patients was calculated. A total of 6,684 patients were included. Based on training data, refit parameters were capped at creatinine 0.7-2.5, bilirubin 0.3-27, international normalized ratio 0.1-2.6, and sodium 120-139. ReMELD and reMELD-Na showed C-indices of 0.866 and 0.869, respectively. ReMELD-Na prioritized patients with 1.6 times higher 90-day mortality probabilities compared to UNOS-MELD. CONCLUSIONS: Refitting MELD resulted in new lower and upper bounds for each parameter. The predictive power of reMELD-Na was significantly higher than UNOS-MELD. ReMELD prioritized patients with higher 90-day mortality rates. Thus, reMELD(-Na) should replace UNOS-MELD for liver graft allocation in the Eurotransplant region.

Kidney transplantation after rescue allocation-meticulous selection yields the chance for excellent outcome.

BACKGROUND: The small number of organ donors forces transplant centres to consider potentially suboptimal kidneys for transplantation. Eurotransplant established an algorithm for rescue allocation (RA) of kidneys repeatedly declined or not allocated within 5 h after procurement. Data on the outcomes and benefits of RA are scarce to date. METHODS: We conducted a retrospective 8-year analysis of transplant outcomes of RA offers based on our in-house criteria catalogue for acceptance and decline of organs and potential recipients. RESULTS: RA donors and recipients were both older compared with standard allocation (SA). RA donors more frequently had a history of hypertension, diabetes or fulfilled expanded criteria donor key parameters. RA recipients had poorer human leucocyte antigen (HLA) matches and longer cold ischaemia times (CITs). However, waiting time was shorter and delayed graft function, primary non-function and biopsy-proven rejections were comparable to SA. Five-year graft and patient survival after RA were similar to SA. In multivariate models accounting for confounding factors, graft survival and mortality after RA and SA were comparable as well. CONCLUSIONS: Facing relevant comorbidities and rapid deterioration with the risk of being removed from the waiting list, kidney transplantation after RA was identified to allow for earlier transplantation with excellent outcome. Data from this survey propose not to reject categorically organs from multimorbid donors with older age and a history of hypertension or diabetes to aim for the best possible HLA matching and to carefully calculate overall expected CIT.

Islets Transplantation at a Crossroads - Need for Urgent Regulatory Update in the United States: Perspective Presented During the Scientific Sessions 2021 at the American Diabetes Association Congress.

Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place. The BLA process is costly and lengthy. However, despite the application of drug manufacturing technology and regulations, the final islet product sterility and potency cannot be confirmed, even when islets meet all the predetermined release criteria. Therefore, further regulation of islets as drugs is obsolete and will continue to hinder clinical application of islet transplantation in the US. The Organ Procurement and Transplantation Network together with the United Network for Organ Sharing have developed separately from the FDA and BLA regulatory framework for human organs under the Human Resources & Services Administration to assure safety and efficacy of transplantation. Based on similar biologic characteristics of islets and human organs, we propose inclusion of islets into the existing regulatory framework for organs for transplantation, along with continued FDA oversight for islet processing, as it is for other cell/tissue products exempt from BLA. This approach would reassure islet quality, efficacy and access for Americans with diabetes to this effective procedure.