Meeting the Shortage of Human Cells and Tissues: The Andalusian Quality Assurance Programme for Tissue Donation.

Background A quality assurance programme for the tissue donation process was launched in Andalusia in 2020 to facilitate the integration of tissue donation into end-of-life care, and to respond to the growing need for human tissue for therapeutic purposes. The results of this programme are presented here. Methods After identifying the hospital departments in which to intensify the detection of tissue donors, expanding training activities and designing a specific data collection system for possible tissue donors who do not donate their tissues, the results of the donation activity were quantified and the causes of non-donation were analysed by applying the critical pathway for deceased tissue donation methodology. Results After an initial drop in activity, which coincided with the coronavirus pandemic, the number of tissue donors increased by 48.4% in 2022 compared to 2019. From the eligible donors, 83% were actual tissue donors and 71% were utilised donors. The modifiable causes of tissue donation loss, in order of frequency, were family refusal, followed by organisational or logistical issues, failure to notify or failure to identify possible donors, and failure to complete donor evaluation. Conclusion As a result of the collaboration of the various professionals involved in the programme, tissue donation activity has increased remarkably, the potential and effectiveness of the donation process have been evaluated, and areas for improvement have been identified, which we hope will lead to continuous improvement of the process.

Quality assurance in corneal transplants: Donor cornea assessment and oversight.

The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.

Turning Loss Into Legacy: Opportunities for Tissue and Eye Donation in Community Hospice/Palliative Care.

Organ, tissue, and eye donations provide opportunities to leave a legacy by saving and/or enhancing the quality of life of others. There has been little published related to tissue or eye donation in hospice/palliative care and few initiatives to facilitate donation among hospice patients/families. Donation myths, gaps in knowledge, and, most significantly, lack of donation referral processes result in missed opportunities for patient/families to consider donation. One donor has the potential to impact 75 lives or more through tissue donation and 2 lives through eye donation. Hospice/palliative care providers can play key roles related to education, advocacy, and collaboration. The support of hospice/palliative care organizations and the local Organ Procurement Organization/Tissue and Eye Recovery Agency are essential for facilitating donation opportunities. This article summarizes current literature, examines legislation and regulations related to donation, presents a case that illustrates an opportunity for hospice community based donation, and shares practices that support donation in hospice/palliative care organizations together with the local Organ Procurement Organization/Tissue and Eye Recovery Agency. This article will hopefully provide the impetus for further study and the development of practices to optimize donation in hospice/palliative care, thus providing more patients and families the opportunity to turn loss into legacy.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.