Development and Validation of a Risk Score Predicting Death Without Transplant in Adult Heart Transplant Candidates.

Importance: The US heart allocation system prioritizes medically urgent candidates with a high risk of dying without transplant. The current therapy-based 6-status system is susceptible to manipulation and has limited rank ordering ability. Objective: To develop and validate a candidate risk score that incorporates current clinical, laboratory, and hemodynamic data. Design, Setting, and Participants: A registry-based observational study of adult heart transplant candidates (aged ≥18 years) from the US heart allocation system listed between January 1, 2019, and December 31, 2022, split by center into training (70%) and test (30%) datasets. Adult candidates were listed between January 1, 2019, and December 31, 2022. Main Outcomes and Measures: A US candidate risk score (US-CRS) model was developed by adding a predefined set of predictors to the current French Candidate Risk Score (French-CRS) model. Sensitivity analyses were performed, which included intra-aortic balloon pumps (IABP) and percutaneous ventricular assist devices (VAD) in the definition of short-term mechanical circulatory support (MCS) for the US-CRS. Performance of the US-CRS model, French-CRS model, and 6-status model in the test dataset was evaluated by time-dependent area under the receiver operating characteristic curve (AUC) for death without transplant within 6 weeks and overall survival concordance (c-index) with integrated AUC. Results: A total of 16 905 adult heart transplant candidates were listed (mean [SD] age, 53 [13] years; 73% male; 58% White); 796 patients (4.7%) died without a transplant. The final US-CRS contained time-varying short-term MCS (ventricular assist-extracorporeal membrane oxygenation or temporary surgical VAD), the log of bilirubin, estimated glomerular filtration rate, the log of B-type natriuretic peptide, albumin, sodium, and durable left ventricular assist device. In the test dataset, the AUC for death within 6 weeks of listing for the US-CRS model was 0.79 (95% CI, 0.75-0.83), for the French-CRS model was 0.72 (95% CI, 0.67-0.76), and 6-status model was 0.68 (95% CI, 0.62-0.73). Overall c-index for the US-CRS model was 0.76 (95% CI, 0.73-0.80), for the French-CRS model was 0.69 (95% CI, 0.65-0.73), and 6-status model was 0.67 (95% CI, 0.63-0.71). Classifying IABP and percutaneous VAD as short-term MCS reduced the effect size by 54%. Conclusions and Relevance: In this registry-based study of US heart transplant candidates, a continuous multivariable allocation score outperformed the 6-status system in rank ordering heart transplant candidates by medical urgency and may be useful for the medical urgency component of heart allocation.

Caracterização do processo de doação de órgãos em uma região do nordeste brasileiro / Caracterización del proceso de donación de órganos en una región de Brasil / Caracterization of the organ donation process in a region of northeast Brazil

Introdução: O processo de doação de órgãos e tecidos é definido por ações a fim de transformar um Potencial Doador (PD) em doador efetivo e inicia-se com o diagnóstico de morte encefálica. Objetivo: Analisar o perfil clínico e sociodemográfico dos potenciais doadores de órgãos, como também os fatores que influenciam na doação de órgãos. Métodos: Trata-se de uma pesquisa quantitativa, transversal, retrospectiva e analítica realizada através da coleta de dados de 455 prontuários de pacientes com diagnóstico de Morte Encefálica, de uma Região do Nordeste brasileiro, utilizando formulário estruturado. Posteriormente realizaram-se análises descritivas e nas associações entre as variáveis independentes e dependente, utilizou-se o teste qui-quadrado de Pearson Resultados: As faixas etárias de maior incidência foram entre 21 a 40 anos e 41 a 60 anos, com 33,8% cada, prevalecendo o sexo masculino (64,1%). Em relação à causa da morte, predominou o Trauma Cranioencefálico com 36,5%. Foram entrevistados 83,3% dos familiares e desses, 53,5% autorizaram a doação. Quanto à relação das respostas das entrevistas com os familiares e o sexo dos PD o sexo masculino se destacou com 59,01% das entrevistas positivas, quanto a entrevista e faixa etária, não foram encontradas diferenças significativas. Correlacionando o resultado das entrevistas familiares e a causa da morte, 40,63% destas tinham como causa o trauma cranioencefálico, e desse total, 63,63% tiveram a doação autorizada. Conclusão: A maioria dos doadores efetivos foram jovens e do sexo masculino, com prevalência do trauma craneoencefálico como causa da morte encefálica e da aceitação familiar para a doação.

Introducción: El proceso de donación de órganos y tejidos se define por las acciones encaminadas a transformar a una persona donante potencial (DP) en donante efectiva. Este proceso comienza con el diagnóstico de muerte encefálica. Objetivo: Analizar el perfil clínico y sociodemográfico de potenciales donantes de órganos, así como los factores que influyen en la donación de órganos. Métodos: Se trata de una investigación cuantitativa, transversal, retrospectiva y analítica realizada a partir de la recopilación de datos de 455 prontuarios de pacientes con diagnóstico de muerte encefálica, en una región del Nordeste de Brasil, utilizando un formulario estructurado. Posteriormente, se realizaron análisis descriptivos y, en las asociaciones entre las variables independiente y dependiente, se utilizó la prueba chi-cuadrado de Pearson Resultados: Los grupos de edad con mayor incidencia fueron de 21 a 40 años y de 41 a 60 años, con un 33.8 % cada uno, con predominio del sexo masculino (64.1 %). En cuanto a la causa de muerte, predominó el trauma craneoencefálico con un 36.5 %. Se entrevistó al 83.3 % de familiares y, de este grupo, el 53.5 % autorizó la donación. En cuanto a la relación entre las respuestas de las entrevistas a familiares y el sexo del TP, se destacó el sexo masculino con un 59.01 % de las entrevistas positivas; en cuanto a la entrevista y grupo de edad no se encontraron diferencias significativas. Correlacionando los resultados de las entrevistas familiares y la causa de muerte, el 40.63 % fue por trauma craneoencefálico y, de ese total, el 63.63 % tenía autorizada la donación. Conclusión: Los donantes más efectivos fueron jóvenes y varones, con predominio del traumatismo craneoencefálico como causa de muerte encefálica y aceptación familiar de la donación.

Introduction: The process of organ and tissue donation is defined by actions to transform a Potential Donor (PD) into an effective donor and begins with the diagnosis of brain death. Objective: To analyze the clinical and sociodemographic profile of potential organ donors, as well as the factors that influence organ donation. Methods: This is a quantitative, cross-sectional, retrospective, and analytical research carried out in a region of Northeast Brazil by collecting data from 455 medical records of patients with brain death, who were diagnosed using a structured form. Subsequently, descriptive analyzes were carried out and for the associations between the independent and dependent variables, the Pearson's chi-square test was used. Results: The age groups with the highest incidence were between 21 to 40 years old and 41 to 60 years old, with a 33.8 % each, with a predominance of males (64.1%). Regarding the cause of death, traumatic brain injury was the most common with a 36.5% of the sample. From the 83.3% of the family members that were interviewed, 53.5% of them authorized the donation. Male potential donors constituted the 59.01% of the authorized donations (positive interviews). There was no relationship between the interview results and the age group of the PD. When correlating the results of family interviews and the cause of death, 40.63% of them were caused by traumatic brain injury and, out of this total, 63.63% had the donation authorized. Conclusion: The most effective donors were young and male whose cause of brain death was traumatic brain injury and whose families allowed the donation.

Time to Abolish Metrics That Sustain Systemic Racism in Kidney Allocation.

This Viewpoint discusses how the Kidney Donor Profile Index (KDPI) in its current form is not fit to guide kidney allocation because it devalues organ donation by Black donors based on a weak association between donor race and kidney transplant failure.

Impact of donor kidney biopsy on kidney yield and posttransplant outcomes.

Procurement biopsy is performed to determine kidney quality, but evidence supporting such association is poor. We investigated the impact of glomerulosclerosis percentage (GS%) on kidney yield and patient outcomes. Information on deceased kidney donors from July 1, 2017, to June 30, 2019, was collected. Association between GS% and kidney yield (number of kidneys procured per donor) and posttransplant graft and patient outcomes were studied. Maximal GS% and minimal GS% were calculated to determine the relationship between GS% and kidney yield; minimal GS% only for correlation with posttransplant outcomes. Multinomial logistic regression and Cox models with least absolute shrinkage and selection operator were used to analyze the association of GS% with kidney yield and posttransplant outcomes, respectively. The kidney yield was 1.63 when maximal GS% and minimal GS% were <5%, but was 0.88 when both GS% were >20%. The hazard ratio for graft failure 1 year after transplant was 1.05 when minimal GS% was 16% to 20%, but was 1.3 for GS% of >20%. The hazard ratio for mortality increased from 1 to 1.2 when minimal GS% reached >20%. In summary, higher GS% was associated with lower kidney yield and inferior posttransplant outcomes. Incorporation of GS% into Scientific Registry of Transplant Recipients models may reassure organ procurement organizations and transplant centers pursuing kidneys with relatively high GS% levels, thereby reducing kidney discard rates.

[Organ donation after determination of brain death : Legal aspects and practical approach]. / Organspende nach irreversiblem Hirnfunktionsausfall : Rechtliche Aspekte und praktisches Vorgehen.

The prerequisites for post-mortem organ donation in Germany include the determination of irreversible loss of brain function, consent to organ donation, and the exclusion of medical contraindications. In addition, mainly because of the shortage of donor organs in Germany and the sometimes controversial social and media discussions on the topic of organ donation, all physicians involved in the donation process must be familiar with the relevant laws, guidelines, and procedural instructions. This applies especially to those who are to carry out the verification of irreversible brain death. Only then, can they act safely in this challenging situation and serve as competent consultants for all involved.

Temporal trends in the use and outcomes of temporary mechanical circulatory support as a bridge to cardiac transplantation in Spain. Final report of the ASIS-TC study.

BACKGROUND: We aimed to describe recent trends in the use and outcomes of temporary mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx) in Spain. METHODS: Retrospective case-by-case analysis of 1,036 patients listed for emergency HTx while on temporary MCS in 16 Spanish institutions from January 1st, 2010 to December 31st, 2020. Patients were classified in 3 eras according to changes in donor allocation criteria (Era 1: January 2010/May 2014; Era 2: June 2014/May 2017; Era 3: June 2017/December 2020). RESULTS: Over time, the proportion of candidates listed with intra-aortic balloon pumps decreased (Era 1 = 55.9%, Era 2 = 32%, Era 3 = 0.9%; p < 0.001), while the proportion of candidates listed with surgical continuous-flow temporary VADs (Era 1 = 10.6%, Era 2 = 32%, Era 3 = 49.1%; p < 0.001) and percutaneous VADs (Era 1 = 0.3%, Era 2 = 6.3%; Era 3 = 17.2%; p < 0.001) increased. Rates of HTx increased from Era 1 (79.4%) to Era 2 (87.8%), and Era 3 (87%) (p = 0.004), while rates of death before HTx decreased (Era 1 = 17.7%; Era 2 = 11%, Era 3 = 12.4%; p = 0.037) Median time from listing to HTx increased in patients supported with intra-aortic balloon pumps (Era 1 = 8 days, Era 2 = 15 days; p < 0.001) but remained stable in other candidates (Era 1 = 6 days; Era 2 = 5 days; Era 3 = 6 days; p = 0.134). One-year post-transplant survival was 71.4% in Era 1, 79.3% in Era 2, and 76.5% in Era 3 (p = 0.112). Preoperative bridging with ECMO was associated with increased 1-year post-transplant mortality (adjusted HR=1.71; 95% CI 1.15-2.53; p = 0.008). CONCLUSIONS: During the period 2010 to 2020, successive changes in the Spanish organ allocation protocol were followed by a significant increase of the rate of HTx and a significant reduction of waiting list mortality in candidates supported with temporary MCS. One-year post-transplant survival rates remained acceptable.

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.

Saúde atualiza critérios para gerenciamento de risco da Covid-19 para doação e transplantes de órgãos

Garantir a continuidade aos processos relacionados a atividades como doações e transplantes de órgãos

Resultados del trasplante renal con donante en asistolia controlada expandido / Kidney transplant outcome of expanded criteria donors after circulatory death

El incremento en el número de pacientes en lista de espera de trasplante renal ha llevado a intentar aumentar el número de posibles donantes incorporando candidatos que anteriormente no se habrían considerado óptimos, incluyendo entre estos a los donantes de pacientes de asistolia (DA) y aquellos con criterios «expandidos» (DCE). Los receptores de injertos de DA controlada (DAc) sufren más función retrasada del injerto, pero presentan una evolución a largo plazo equiparable a los de donantes de muerte encefálica, lo que ha permitido un aumento en el número de trasplantes de DAc en distintos países en los últimos años. De forma paralela, el uso de DAc con criterios expandidos (DAc/DCE) se ha incrementado en los últimos años en diferentes países, permitiendo acortar la lista de espera del trasplante renal. El uso de estos injertos, aunque se relaciona con una mayor frecuencia de función retrasada del injerto, ofrece supervivencias del injerto a largo plazo similares o solo ligeramente inferiores a las de los donantes de muerte encefálica con criterios expandidos. Distintos estudios han observado que los receptores de injertos DAc/DCE tienen peor función renal que los DAc/estándar y que los donantes de muerte encefálica/DCE. La mortalidad asociada al trasplante de injertos de DAc/DCE se relaciona principalmente con la elevada edad del receptor. Los pacientes que reciben un trasplante renal de DAc/≥ 60 años presentan mejor supervivencia que los que continúan en la lista de espera, aunque este hecho no se ha demostrado en los receptores de DAc/> 65 años. La utilización de este tipo de órganos debe llevar pareja la optimización de los tiempos quirúrgicos y el menor tiempo de isquemia fría posible. (AU)

The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with “expanded” criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and brain death/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia. (AU)

Increasing Living Donor Liver Transplantation Using Liver Paired Exchange.

BACKGROUND: Living donor liver transplantation (LDLT) continues to be the primary modality of liver transplantation in Asia, but it accounts for about 5% of all liver transplantations in the US. ABO incompatibility is the primary reason motivated donors are declined. Although kidney paired exchanges are common, liver paired exchange (LPE) is still evolving in the US. STUDY DESIGN: This is a retrospective review (between January 1, 2019, and July 31, 2021) of our initial experience with LPE. RESULTS: A total of 10 LPEs (20 LDLTs) were performed during the study period. Seven LPEs were initiated by a nondirected O donor. The other 3 pair sets involved 1 ABO compatible and 1 ABO incompatible pair. Transplantations in a pair set were completed within a mean of 4.8 (range 1-14) days of each other. All 20 donors are doing well with no major complications at 12.7 (range 1-20) months. Seventeen of 20 recipients are alive and have good allograft function. One recipient died in the early postoperative period. Two late deaths of patients with functioning allografts were due to COVID-19 (at 8 months) and peritoneal carcinomatosis and gram-negative sepsis (at 9 months). CONCLUSIONS: LPE is feasible in a high-volume LDLT center and is a useful option to increase LDLT by overcoming ABO incompatibility. Nondirected donors can be utilized to initiate an LPE.

Optimal Sequencing of Deceased Donor and Live Donor Kidney Transplant Among Pediatric Patients With Kidney Failure.

Importance: In the US, live donor (LD) kidney transplant rates have decreased in pediatric recipients. Pediatric patients with kidney failure will likely need more than 1 kidney transplant during their lifetime, but the optimal sequence of transplant (ie, deceased donor [DD] followed by LD or vice versa) is not known. Objective: To determine whether pediatric recipients should first receive a DD allograft followed by an LD allograft (DD-LD sequence) or an LD allograft followed by a DD allograft (LD-DD sequence). Design, Setting, and Participants: This decision analytical model examined US pediatric patients with kidney failure included in the US Renal Data System 2019 Report who were waiting for a kidney transplant, received a transplant, or experienced graft failure. Interventions: Kidney transplant sequences of LD-DD vs DD-LD. Main Outcomes and Measures: Difference in projected life-years between the 2 sequence options. Results: Among patients included in the analysis, the LD-DD sequence provided more net life-years in those 5 years of age (1.82 [95% CI, 0.87-2.77]) and 20 years of age (2.23 [95% CI, 1.31-3.15]) compared with the DD-LD sequence. The net outcomes in patients 10 years of age (0.36 [95% CI, -0.51 to 1.23] additional life-years) and 15 years of age (0.64 [95% CI, -0.15 to 1.39] additional life-years) were not significantly different. However, for those aged 10 years, an LD-DD sequence was favored if eligibility for a second transplant was low (2.09 [95% CI, 1.20-2.98] additional life-years) or if the LD was no longer available (2.32 [95% CI, 1.52-3.12] additional life-years). For those aged 15 years, the LD-DD sequence was favored if the eligibility for a second transplant was low (1.84 [95% CI, 0.96-2.72] additional life-years) or if the LD was no longer available (2.49 [95% CI, 1.77-3.27] additional life-years). Access to multiple DD transplants did not compensate for missing the LD opportunity. Conclusions and Relevance: These findings suggest that the decreased use of LD kidney transplants in pediatric recipients during the past 2 decades should be scrutinized. Given the uncertainty of future recipient eligibility for retransplant and future availability of an LD transplant, the LD-DD sequence is likely the better option. This strategy of an LD transplant first would not only benefit pediatric recipients but allow DD kidneys to be used by others who do not have an LD option.

Trends in Survival for Pediatric Transplantation.

OBJECTIVES: Progress in pediatric transplantation measured in the context of waitlist and posttransplant survival is well documented but falls short of providing a complete perspective for children and their families. An intent-to-treat analysis, in which we measure survival from listing to death regardless of whether a transplant is received, provides a more comprehensive perspective through which progress can be examined. METHODS: Univariable and multivariable Cox regression was used to analyze factors impacting intent-to-treat survival in 12 984 children listed for heart transplant, 17 519 children listed for liver transplant, and 16 699 children listed for kidney transplant. The Kaplan-Meier method and log-rank test were used to assess change in waitlist, posttransplant, and intent-to-treat survival. Wait times and transplant rates were compared by using χ2 tests. RESULTS: Intent-to-treat survival steadily improved from 1987 to 2017 in children listed for heart (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.96-0.97), liver (HR 0.95, 95% CI 0.94-0.97), and kidney (HR 0.97, 95% CI 0.95-0.99) transplant. Waitlist and posttransplant survival also improved steadily for all 3 organs. For heart transplant, the percentage of patients transplanted within 1 year significantly increased from 1987 to 2017 (60.8% vs 68.7%); however, no significant increase was observed in liver (68.9% vs 72.5%) or kidney (59.2% vs 62.7%) transplant. CONCLUSIONS: Intent-to-treat survival, which is more representative of the patient perspective than individual metrics alone, steadily improved for heart, liver, and kidney transplant over the study period. Further efforts to maximize the donor pool, improve posttransplant outcomes, and optimize patient care while on the waitlist may contribute to future progress.