Cellular recovery after prolonged warm ischaemia of the whole body.

After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death1,2. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology3. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.

Restoration of brain circulation and cellular functions hours post-mortem.

The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.

Reflections on New Evidence on Crisis Standards of Care in the COVID-19 Pandemic.

Crisis standards of care have been widely developed by healthcare systems and states in the United States during the COVID-19 pandemic, and in some rare cases have actually been used to allocate medical resources. All publicly available U.S. crisis standards of care with a mechanism for allocating scarce resources make use of the Sequential Organ Failure Assessment (SOFA) score in hopes of assigning scarce resources to those patients who are more likely to survive. We reflect on the growing body of evidence suggesting that the SOFA score has limited accuracy in predicting mortality among patients hospitalized with COVID-19 and that the SOFA score systematically disfavors Black patients. Use of the SOFA score for allocating scarce resources may therefore result in Black patients with equal likelihood of survival being deprived of life-saving medical resources. There is also a risk of injustice for patients with non-COVID-19 diagnoses, for whom the SOFA score may be a more accurate prognostic score, but who might nevertheless be unfairly (de)prioritized when assessed alongside COVID-19 patients using the same scoring system. For these reasons we recommend that the SOFA score not be used for triage purposes during the COVID pandemic, and that a national effort be made to develop and empirically test crisis standards of care in advance of the next public health emergency.

Addressing Ethical Challenges in US-Based HIV Phylogenetic Research.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

Developing a Triage Protocol for the COVID-19 Pandemic: Allocating Scarce Medical Resources in a Public Health Emergency.

The coronavirus disease-2019 (COVID-19) has caused shortages of life-sustaining medical resources, and future waves of the virus may cause further scarcity. The Yale New Haven Health System developed a triage protocol to allocate scarce medical resources during the COVID-19 pandemic, with the primary goal of saving the most lives possible, and a secondary goal of making triage assessments and decisions consistent, transparent, and fair. We outline the process of developing the triage protocol, summarize the protocol itself, and discuss the major ethical challenges encountered, along with our answers to these challenges. These challenges include (1) the role of age and chronic comorbidities; (2) evaluating children and pregnant patients; (3) racial, ethnic, and socioeconomic disparities in health; (4) prioritization of healthcare workers; and (5) balancing clinical judgment versus protocolized assessments. We conclude with a review of the limitations of our protocol and the lessons learned. We hope that a robust public discussion of such protocols and the ethical challenges that they raise will result in the fairest possible processes, less need for triage, and more lives saved during future waves of the COVID-19 pandemic and similar public health emergencies.

Maximizing biomedical research impacts through bioethical considerations.

Bioethics is the formal study of ethical judgments concerning the advances and applications of biology, medicine and related technologies. In a time of unprecedented biomedical advances, it is critical to integrate bioethical frameworks more fully into biomedical research to align these scientific advances with their intended societal needs. In this Perspective, we describe some motivations and frameworks for cross-disciplinary bioethical training for biomedical researchers, and discuss how actively considering bioethics in research and study design could maximize biomedical researchers' intended impacts in society.

U.S. Lawsuit Claims Federal Law Can Require Emergency Abortions.

In the wake of the U.S. Supreme Court's overruling of Roe vs. Wade, states are passing very strict antiabortion laws that the Biden administration is arguing violate the federal Emergency Medical Treatment and Active Labor Act (EMTALA) because those state laws do not permit emergency life-saving abortions that federal law says must be available to patients. The Biden administration has filed suit against Idaho to have portions of its state law invalidated, and Texas has filed suit against the Biden administration, arguing that its interpretation of EMTALA as requiring that abortions be available to patients in some emergency circumstances amounts to an unconstitutional overreach by the federal government. These suits, and others related to them, may redefine health-related federalism in the United States.

Violations of Suicide-Prevention Guidelines in US Media Coverage of Physician's Suicide Death During the COVID-19 Pandemic.

Background: Healthcare workers are at elevated risk for suicide; though it has yet to be studied, this risk may be exacerbated by the COVID-19 pandemic. News media coverage of high-profile suicide is associated with an increased risk of subsequent suicides. No analysis has yet been published of US media practices for reporting on healthcare worker suicides during the pandemic. Aims: The researchers aimed to evaluate pandemic-era media practices by investigating adherence to best-practice suicide reporting guidelines in coverage of Dr. Lorna Breen's death. Methods: The researchers conducted a content analysis of all unique articles by top outlets reporting Dr. Breen's death between April 26 and 29, 2020, and scored them based on their adherence to the 15 best-practice suicide reporting guidelines. Results: Every media outlet violated an average of at least 5 of 15 suicide guidelines in reporting on Dr. Breen's death; some abided by as few as 2 of 15 recommended guidelines. Seven of 15 guidelines were adhered to by fewer than one third of articles. The National Suicide Prevention Lifeline number, notably easy to include, appeared in only 75% of articles. Limitations: The researchers were limited to reviewing media coverage of one specific instance of COVID-era healthcare worker suicide, making these findings applicable as a prominent case study rather than forming a generalizable claim about suicide reporting during the pandemic or about reporting on healthcare suicides. Conclusion: These violations highlight a range of opportunities to improve suicide prevention in the media, which has a responsibility to ensure reporting does not exacerbate the risk of suicide. Improved adherence to these guidelines could reduce harm for healthcare workers during the pandemic.

The United Kingdom Revisits Its Surrogacy Law.

The United Kingdom is partway through a multiyear process of revising its law on surrogacy, both traditional and gestational. In October of 2019, the Law Commission of England and Wales and the Scottish Law Commission-statutorily created independent bodies charged with keeping the law under review and recommending reforms whenever necessary-completed a public consultation on surrogacy. In June, the commissions published an extensive consultation paper laying out the case for surrogacy reform and making tentative recommendations about how revision should proceed. The commissions are now digesting the public's responses, and they aim to have a final report on their proposed revisions of the law and a draft bill for consideration by Parliament in 2021. The foundation of current U.K. surrogacy law was laid in the Surrogacy Arrangements Act of 1985. There are numerous problems with the existing regime.