Faculty Bibliography

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

As of this writing, twenty-one states have passed laws barring transgender youth-athletes from competing on public-school sports teams in accordance with their gender identity. Proponents of these regulations claim that transgender females in particular have inherent physiological advantages that threaten a "level playing field" for their cisgender competitors. Existing evidence is limited but does not support these restrictions. Gathering more robust data will require allowing transgender youth to compete (rather than preemptively barring them), but even if trans females are shown to retain some advantage, this would not have greater moral significance than the many other "fair" physical and economic advantages found across sports. These regulations deprive transgender youth, an exceptionally vulnerable population, from the vast physical, mental, and social benefits of sports. While we advocate for transgender inclusion under our current, gender-segregated model of sport, we propose changes to the overarching structure that would promote a more inclusive and fairer athletic environment.

Use of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary resuscitation, termed eCPR, offers the prospect of improving survival with good neurological function after cardiac arrest. After death, ECMO can also be used for enhanced preservation of abdominal and thoracic organs, designated normothermic regional perfusion (NRP), before organ recovery for transplantation. To optimize resuscitation and transplantation outcomes, healthcare networks in Portugal and Italy have developed cardiac arrest protocols that integrate use of eCPR with NRP. Similar dissemination of eCPR and its integration with NRP in the USA raise novel ethical issues due to a non-nationalized health system and an opt-in framework for organ donation, as well as other legal and cultural factors. Nonetheless, eCPR investigations are ongoing, and both eCPR and NRP are selectively employed in clinical practice. This paper delineates the most pressing relevant ethical considerations and proposes recommendations for implementation of protocols that aim to promote public trust and reduce conflicts of interest. Transparent policies should rely on protocols that separate lifesaving from organ preservation considerations; robust, centralized eCPR data to inform equitable and evidence-based allocations; uniform practices concerning clinical decision-making and resource utilization; and partnership with community stakeholders, allowing patients to make decisions about emergency care that align with their values. Proactively addressing these ethical and logistical challenges could enable eCPR dissemination and integration with NRP protocols in the USA, with the potential to maximize lives saved through both improved resuscitation with good neurological outcomes and increased organ donation opportunities when resuscitation is unsuccessful or not in accordance with individuals' wishes.

Over the past year, three scientific teams conducted experiments of genetically-edited porcine organs into human recipients, three of whom were deceased and one living. In this editorial, we describe challenges for the design of initial xenotransplantation clinical trials and focus on patient selection, consent, and requisite post-transplant follow-up. Given the uncertain clinical benefit of xenotransplantation, we propose that patient selection criteria might include novel elements such as approaching patients who have low quality of life and strong aversion to continued dialysis therapy. We set expectations related to the importance of informing and protecting family members and medical teams who could be exposed to zoonotic viral infection from the donor organ and/or receive unwanted publicity. Meeting these challenges in trial design and oversight will require multidisciplinary expertise, a conceptual model that extends beyond the individual patient, and creative collaboration between scientists and regulatory agencies.

Precision nutrition is an emerging concept that aims to develop nutrition recommendations tailored to different people's circumstances and biological characteristics. Responses to dietary change and the resulting health outcomes from consuming different diets may vary significantly between people based on interactions between their genetic backgrounds, physiology, microbiome, underlying health status, behaviors, social influences, and environmental exposures. On January 11-12, 2021, the National Institutes of Health convened a workshop entitled "Precision Nutrition: Research Gaps and Opportunities" to bring together experts to discuss the issues involved in better understanding and addressing precision nutrition. The Workshop proceeded in three parts: Part I covered many aspects of genetics and physiology that mediate the links between nutrient intake and health conditions such as cardiovascular disease, Alzheimer's disease, and cancer. Part II reviewed potential contributors to interindividual variability in dietary exposures and responses such as baseline nutritional status, circadian rhythm/sleep, environmental exposures, sensory properties of food, stress, inflammation, and the social determinants of health. Part III presented the need for systems approaches, with new methods and technologies that can facilitate the study and implementation of precision nutrition, and workforce development needed to create a new generation of researchers. The workshop concluded that much research will be needed before more precise nutrition recommendations can be achieved. This includes better understanding and accounting for variables such as age, sex, ethnicity, medical history, genetics, and social and environmental factors. The advent of new methods and technologies and the availability of considerably more data bring tremendous opportunity. However, the field must proceed with appropriate levels of caution and make sure the factors listed above are all considered, and systems approaches, and methods are incorporated. It will be important to develop and train an expanded workforce with the goal of reducing health disparities and improving precision nutritional advice for all Americans.

Donation after circulatory determination of death (DCDD) has increased organ donation rates in the US over the past decade within an established legal framework, which is consistent with and supports individual and family decisions regarding organ donation in the context of end-of-life care. A new application, controlled DCDD donation utilizing thoracoabdominal normothermic regional perfusion (NRP) protocols (cDCDD-NRP), provides the opportunity to maximize a donation decision by recovering additional organs for transplant, including the heart, and to limit the detrimental impact of warm ischemic time by perfusing organs in situ following the declaration of circulatory death. In this viewpoint, we narrate our rationale for why cDCDD-NRP is consistent within the existing legal framework for organ donation in the United States and recommend no changes to the Uniform Determination of Death Act.