Faculty Bibliography

The scarcity of transplantable organs represents a worldwide public health crisis, and as a result, thousands of people with end-stage kidney disease (ESKD) die waiting for a transplant each year. Xenotransplantation involves transplanting organs from an animal source into humans, offering a potential solution to this significant unmet need. Indeed, if there is a limitless supply of organs, many more patients who do not meet the current criteria for transplant eligibility could also be considered candidates. While there are examples of attempts to transplant animal tissues or organs into humans dating back over 300 years, none were successful due to cross-species immunologic incompatibility. Even so, significant advances in genetic engineering and the emergence of novel immunosuppressive agents have spurred impressive improvements in xenograft survival in preclinical studies involving nonhuman primates. Furthermore, recent reports of genetically modified pig kidney and heart xenotransplants in human decedents and living recipients on a compassionate use basis have provided impetus to advancing the field towards first-in-human trials. However, studies in nonhuman primates and humans thus far have described adaptive as well as innate immune-mediated xenograft injury. Understanding the mechanistic aspects of these responses at the cellular and molecular levels is critical to the development of targeted genetic modifications and innovative therapeutic strategies aimed at preventing rejection and inducing tolerance. Moreover, the physiological components of the bidirectional communication between the human host and pig xenograft must also be understood and manipulated. Here, we review the breakthroughs in renal xenotransplantation in the past few decades and highlight the immunologic hurdles that have yet to be overcome.

Medical ethics education is crucial for medical students and trainees, helping to shape attitudes, beliefs, values, and professional identities. Exploration of ethical dilemmas and approaches to resolving them provides a broader understanding of the social and cultural contexts in which medicine is practiced, as well as the ethical implications of medical decisions, fostering critical thinking and self-reflection skills imperative to providing patient-centered care. However, exposure to medical ethics topics and their clinical applications can be limited by curricular constraints and the availability of institutional resources and expertise. Podcasts, among other Free Open Access Medical Education (FOAMed) resources, are a novel educational tool that offers particular advantages for self-directed learning, a process by which learners engage in asynchronous educational opportunities outside of traditional academic or clinical settings. Podcasts can be readily distributed to wide audiences and played at any time, reducing barriers to access and offering a level of flexibility that is not possible with traditional forms of education and is well-suited to busy schedules. Podcasts can also use real voices and storytelling to make the content memorable and eminently human. This paper describes the development, production process, and impact of Core IM's "At the Bedside," a podcast focusing on issues in medical ethics and the medical humanities, intending to supplement standard bioethics curricula in an accessible, relevant, and engaging way. The authors advocate for broad incorporation of podcasts into medical ethics education.

BACKGROUND:Xenotransplantation clinical trials may begin soon. A persistent risk of xenotransplantation, known for decades, is the possibility that a xenozoonotic infection could be transferred from a xenograft to its recipient and then to other human contacts. Because of this risk, guidelines and commentators have advocated for xenograft recipients to agree to either long-term or lifelong surveillance mechanisms. METHODS:For the past few decades, one solution that has been proposed to ensure that xenograft recipients will comply with surveillance protocols is the use of a heavily modified Ulysses contract, which we review. RESULTS:These contracts are most often used in psychiatry, and their application to xenotransplantation has been espoused several times with minimal criticism. CONCLUSIONS:In this article, we argue against the applicability of Ulysses contracts in xenotransplantation based upon (1) the telos of the advance directive that may not be applicable to this clinical context, (2) the suspect nature of enforcing Ulysses contracts in xenotransplantation, and (3) the ethical and regulatory hurdles that such enforcement would require. Although our focus is on the US regulatory landscape in preparation for clinical trials, there are applications globally.

With decades of pre-clinical studies culminating in the recent clinical application of xenotransplantation, it would appear timely to provide recommendations for operationalizing oversight of xenotransplantation clinical trials. Ethical issues with clinical xenotransplantation have been described for decades, largely centering on animal welfare, the risks posed to the recipient, and public health risks posed by potential spread of xenozoonosis. Much less attention has been given to considerations relating to potentially elevated risks faced by those who may care for or otherwise have close contact with xenograft recipients. This paper examines the ethical and logistical issues raised by the potential exposure to xenozoonotic disease faced by close contacts of xenotransplant recipients-defined herein as including but not limited to caregivers, household contacts, and sexual partners-which warrants special attention given their increased risk of exposure to infection compared to the general public. We discuss implications of assent or consent by these close contacts to potentially undergo, along with the recipient, procedures for infection screening and possible quarantine. We then propose several options and recommendations for operationalizing oversight of xenotransplantation clinical trials that could account for and address close contacts' education on and agency regarding the risk of xenozoonosis.