Faculty Bibliography

Normothermic regional perfusion (NRP) is a novel organ procurement strategy used for donation after circulatory death (DCD) involving in situ organ perfusion. This cross-sectional survey study assesses US public attitudes toward organ donation and willingness to donate organs after DCD-NRP, standard DCD and after brain death, comparing registered donors (registrants) and non-registered participants (non-registrants). More registrants agreed with having trust in the medical system and registrants were more likely to agree with donation in every scenario. Almost half of respondents agreed that a person must be dead to donate their vital organs. This study found that willingness to donate was associated with donor registration and trust in the medical system. A secondary finding was that there is not universal understanding of the dead donor rule and implications of first-person authorization. Overall, our findings suggest that public support for donation remains strong, and that NRP utilization does not diminish that support.

BACKGROUND:Medical assistance in dying (MAiD) is legally permitted in a growing number of jurisdictions, and in 6, it can currently be followed by organ donation. Organ donation following MAiD offers patients an opportunity to address transplant needs as a final act of altruism, but it also raises complex ethical questions that require strong safeguards to protect patients, professionals, and public trust. METHODS:We identified key ethical issues and safeguards by analyzing guidelines and protocols from the 6 countries where organ donation following MAiD is performed: Australia, Belgium, Canada, the Netherlands, New Zealand, and Spain. This article was developed under the auspices of the Ethics Committee of The Transplantation Society with medical, ethical, and legal experts from these countries. RESULTS:Three domains of ethical concern emerged: (1) safeguarding the integrity of patients' decision-making (voluntariness, informed consent, and how and when information is presented); (2) ethical governance of donation following MAiD (adherence to the Dead Donor Rule, death determination, and consent for premortem interventions); and (3) implications for care relationships and professional practice (end-of-life impacts, recipient information and donor anonymity, and professional support, including conscientious objection). Key recommendations include clear and consistent policies; a patient-centered, nondirective approach; rigorous eligibility and voluntariness assessments; and strict separation between MAiD and donation/transplantation teams. CONCLUSIONS:These recommendations provide practical guidance for implementing organ donation following MAiD in jurisdictions where it is practiced or being considered. They support patients' end-of-life wishes while safeguarding ethical and legal standards and maintaining trust in both MAiD and organ transplantation.

INTRODUCTION/BACKGROUND:Media messaging offers insight into the informational context that may shape the public's acceptance of xenotransplantation (XTx). The purpose of this study was to characterize the media's portrayal of the initiation of contemporary in-human XTx and assess both the accuracy and the ethical valence of XTx messaging. METHODS:This study employed a summative qualitative content analysis of online print media coverage of the first contemporary experimental pig-to-human transplants in the United States. A comprehensive search of the 50 most-trafficked online news sources in the US was conducted for print articles pertaining to XTx published between July 13, 2021 and July 13, 2022. All articles in the sample were coded using qualitative data analysis software. Using a combined deductive and inductive approach to analysis, codes were grouped into topical categories representing patterns of meaning and subsequently interpreted into overarching themes. RESULTS:The search yielded 208 unique print-based articles. The top five most prevalent codes were "genetically modified," "reference to animal organ," "XTx rejection possibility," "novelty of the procedure," and "XTx as a 'success'/extending life." Code patterns were interpreted into the following overarching themes: (1) value judgments about XTx, (2) justifications for XTx, and (3) emphasis on technical details. CONCLUSIONS:Results suggest that media reporting on XTx during this time period frequently employed incomplete and hyperbolic narratives to support and justify XTx. As the field of XTx evolves with the initiation of human clinical trials, efforts to communicate accurate, balanced information to the general public should be prioritized.

PURPOSE OF REVIEW/OBJECTIVE:The science and practice of xenotransplantation is advancing more rapidly than the regulatory infrastructure that will be necessary to ensure the promise of alleviating the organ shortage can be safely and equitably met. RECENT FINDINGS/RESULTS:While countries leading the way have developed some regulatory guidance to support first in human "compassionate use" xenotransplant interventions and the first clinical trials, existing legislative, regulatory, and operational frameworks for human allotransplantation have not been explicitly extended to nonhuman animal organs. SUMMARY/CONCLUSIONS:To address safety concerns and other ethics challenges unique to xenotransplantation, existing policies must be amended and new policies must be implemented to protect patients and ensure equitable access to xenotransplantation.

With U.S. Food and Drug Administration (FDA) clearance of clinical trials of kidney xenotransplantation (XTx) in living humans, understanding the recipient experience is critical. Semi-structured interviews with the three living XTx recipients identified core domains of the recipient experience, including quality of life (QoL), fears about XTx, and healthcare team communication and support. Transcribed interviews were analyzed by two qualitative researchers using an inductive thematic approach and were mapped onto the Warwick Patient Experience Model, a validated framework to assess key aspects of patient satisfaction with the healthcare experience. All three recipients (53-year-old female; 66-year-old male; 54-year old male) described a restoration of hope, contrasted with their poor quality of life on dialysis. They emphasized that access to XTx and graft survival requires mutual confidence and commitment between recipients and healthcare teams. XTx recipients use dialysis as a point of reference when describing changes in their post-transplant QoL and seemed well-situated to handle the possibility of graft failure. These insights may aid in the creation of decision aids and educational materials tailored to the specific needs of XTx recipients.

Normothermic regional perfusion during controlled donation after circulatory death has emerged as a means to increase the number and viability of organs available for transplant. Because normothermic regional perfusion uses extracorporeal membrane oxygenation, an intervention used for resuscitation under other circumstances, critics have concluded that organ donation using normothermic regional perfusion violates the dead donor rule. As such, the debate about normothermic regional perfusion has been framed as a binary choice between normothermic regional perfusion and the dead donor rule. In this paper, I argue that we should resist this binary framework and instead judge the permissibility of normothermic regional perfusion based on whether it harms organ donors. The obligations owed to organ donors derive from their moral status and include the obligation to prevent harm to donors, protect futures of value and satisfy donors' critical interests. When performed correctly, normothermic regional perfusion does not violate these moral obligations. Therefore, normothermic regional perfusion does not harm organ donors during controlled donation after circulatory death, making it ethically permissible when performed in accordance with standardised protocols.

This article aims to review unresolved ethical issues and raise additional questions to be answered regarding the use of intraoperative brain monitoring during thoracoabdominal normothermic regional perfusion (TA-NRP). We discuss the following ethical questions, as well as offer preliminary recommendations to advance the discourse around use of brain monitoring during TA-NRP: (1) Does brain monitoring admit violation of the dead donor rule? (2) Which monitoring techniques should be implemented during TA-NRP? (3) How should we manage positive findings? (4) How should we manage ambiguous findings on brain monitoring? (5) What procedural and institutional barriers remain to utilizing intraoperative brain monitoring for TA-NRP on a wider scale? We argue that preventing inadvertent brain reperfusion is central to ensuring TA-NRP complies with ethical standards, and that blood flow monitoring is the most direct monitor for reperfusion. We assess potential brain monitors during TA-NRP and suggest that transcranial doppler (TCD) with cerebral oximetry may be the closest existing tests to an ideal monitor for this application. We likewise review remaining questions regarding diagnostic uncertainty around these tests and the implications of this uncertainty or positive findings of brain reperfusion on the donor, their families, and public trust. To begin addressing these questions, necessary first steps include standardization of surgical protocols to include venting and consolidating data around TA-NRP.

The demand for transplant organs far exceeds the available supply. In the United States alone, more than 90,000 patients are currently on the kidney transplant waitlist, yet only about one third of them will ever receive a transplant. Xenotransplantation, organ transplants from gene edited pigs, offers a potential solution to this shortage. Successful investigational transplants of pig kidneys into brain-dead recipients and expanded access cases involving living human recipients have resulted in the green-lighting of the first human clinical trials. Using the benchmark of 2-year survival of non-human primates in pre-clinical studies, we developed a tool that can identify individual wait-listed patients predicted to have a shorter life expectancy than with a xenotransplant, utilizing Random Survival Forest, DeepSurv and Cox Proportional-Hazards models. We found that it is hard to identify patients that reach clinical equipoise unless the expected xenograft survival exceeds two years, with the Random Survival Forest model identifying less than 5% of such patients. Few patients would benefit based on survival alone and potential beneficiaries are spread across more than 200 transplant centers. Several incentives could allow more patients to reach equipoise. At the same benchmark of 2-year xenograft survival, keeping patients inactive on the waitlist while they have a functioning xeno-kidney increases the percentage achieving equipoise by up to 1.7% across cohorts. Granting patients with failed xenografts the same priority as prior living donors increases this by up to 17.9%, while assigning them the highest priority raises it by up to 28.5%. We are able, however, to identify phenotypes that have a high mortality and low transplant rates in the current allocation system that could serve as acceptable candidates; while not achieving equipoise, they would enjoy the benefits of being dialysis free.