Postmortem Donation Research Articles

Harmonization of postmortem donations for pediatric brain tumors and molecular characterization of diffuse midline gliomas

Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers. Recent molecular studies have resulted in the discovery of recurrent driver mutations in many pediatric brain tumors. However, despite these molecular advances, the clinical outcomes of high grade tumors, including H3K27M diffuse midline glioma (H3K27M DMG), remain poor. To address the paucity of tissue for biological studies, we have established a comprehensive protocol for the coordination and processing of donated specimens at postmortem. Since 2010, 60 postmortem pediatric brain tumor donations from 26 institutions were coordinated and collected. Patient derived xenograft models and cell cultures were successfully created (76% and 44% of attempts respectively), irrespective of postmortem processing time. Histological analysis of mid-sagittal whole brain sections revealed evidence of treatment response, immune cell infiltration and the migratory path of infiltrating H3K27M DMG cells into other midline structures and cerebral lobes. Sequencing of primary and disseminated tumors confirmed the presence of oncogenic driver mutations and their obligate partners. Our findings highlight the importance of postmortem tissue donations as an invaluable resource to accelerate research, potentially leading to improved outcomes for children with aggressive brain tumors.

Enthesis of the Calcaneal Tendon ‐ A morphological Analysis

IntroductionThe enthesis of the Achilles tendon (ASE) is an example of a fibrocartilaginous osteotendinous insertion. It shows a complex ultrastructure and is surrounded by various attachment tissues. For various pathologies, caused by degeneration, rheumatoid diseases and excessive strain, the ASE is the site of manifestation. Therefore, the visualization of its ultrastructure is of great clinical interest in order to diagnose diseases early or monitor their course of therapy. Magnetic resonance imaging (MRI) is considered the gold standard for soft tissue imaging and is used in this study in the form of a three‐dimensional MRI‐sequence, capable of generating variable echo times (3D‐vTE‐sequence). To verify the correctness of the results obtained, it is necessary to prepare a corresponding histological compound. Thus, this study serves to design a manufacturing protocol for a holistic histological preparation of the ASE. Additionally, the potential of the 3D‐vTE‐sequence for imaging ultrastructural details of the ASE is to be investigated based on this histological preparation. A special feature of this study is that a holistic, morphological comparison of the ASE is to be achieved by the used techniques, which, to our current knowledge, has not yet been carried out in this form.MethodsIn total five ASE were extracted from post‐mortem donations. Initially, proof of concept was performed with two ASE by using Giemsa stained cutting‐thin section‐technique by Plenk. Subsequently, three further ASE were subjected to MRI using a T2*‐weighted 3D‐vTE‐sequence in a 7 Tesla magnetic resonance tomograph. Measurements with a total of 12 different echo times were performed. Additionalliy, after the cutting‐thin section‐preparation, individually microradiographies (MRG) were manufactured.ResultsThe proof of concept showed satisfactory results regarding the histological imaging of the ASE and its ultrastructure. The holistic, high‐resolution images of the MRI‐examination showed ultrastructural details of the ASE, which correlated morphologically with the depiction of the ASE in the cutting‐thin section‐preparations. At the same time, some ultrastructural details are not reflected in MRI. The same applies in some cutting‐thin section‐preparations of the ASE: Due to artifact formation and other reasons, not all components of the ultrastructure can be determined. The MRG provided reliable information about the architecture of the bone tissue and were additionally used for the comparison between MRI and histological compounds. Seite | 7ConclusionThe used cutting‐thin section‐technique by Plenk and the 3D vTE MRI‐sequence showed great potential for the holistic representation of ASE and its ultrastructure. Nevertheless, certain deficits can be identified in both forms of presentation. Regarding to the detailed reproduction of the ultrastructure, the cutting‐thin section‐technique by Plenk is superior to the used MRI‐sequence. The manufactured MRG warranted a detailed depiction of the hard tissue architecture and have been useful for the performed holistic comparison. For further trials of this kind, it is necessary to take alternative depiction techniques into account to check their potential and compare it with the techniques used in this study.

Your data will never die, but you will: A comparative analysis of US and UK post-mortem data donation frameworks

Posthumous medical data donation (PMDD) for the purpose of legitimate, non-commercial and, potentially, very beneficial medical research has been sparsely discussed in legal scholarship to date. Conversely, quite an extensive social science and humanities research establishes benefits of this practice. It also finds that PMDD enables individuals to employ their altruistic motivations and aspirations by helping them participate in ‘citizen's science’ and medical research, thus supporting efforts in finding cures for some of the acutest diseases of today. There appears to be no jurisdiction where a regulatory framework supports and enables PMDD. This paper analyses whether and to what extent law and policy should enable this practice. We take a comparative approach, examining the position under both US and UK law, providing the first comparative legal account of this practice. We do not aim to suggest a detailed legal solution for PMDD, but rather key considerations and principles for legislative/policy reforms, which would support the practice of PMDD. We discuss organ donation and provide a comparative outlook with the aim of drawing lessons from this practice, and applying them to the regulation of PMDD. Our analysis is both normative and black letter since we consider arguments regarding the necessity of organ and data donation, as well as the law that regulates these practices.

Join the Lone Kidney Club: incentivising live organ donation

Given the dramatic shortage of transplantable organs, demand cannot be met by established and envisioned organ procurement policies targeting postmortem donation. Live organ donation (LOD) is a medically attractive option,...

The ethical case for non-directed postmortem sperm donation

In this article we outline and defend the concept of voluntary non-directed postmortem sperm donation. This approach offers a potential means of increasing the quantity and heterogeneity of donor sperm....

Modeling Lay People's Ethical Attitudes to Organ Donation: A Q-Methodology Study.

BackgroundOrgan donation is commonly evaluated by biomedical ethicists based largely on principlism with autonomy at the top of the “moral mountain.” Lay people may differ in the way they invoke and balance the various ethical interests. We explored lay people’s ethical attitudes to organ donation.MethodsRespondents (n=196) ranked 42 opinion-statements on organ donation according to a 9-category symmetrical distribution. Statements’ scores were analyzed by averaging-analysis and Q-methodology.ResultsRespondents’ mean (SD) age was 34.5 (10.6) years, 53% were women, 69% Muslims (30% Christians), 29% Saudis (26% Filipinos), and 38% healthcare-related. The most-agreeable statements were “Acceptable if benefit to recipient large,” “Explicit donor consent and family approval for live donation,” “Acceptable if directed to family member,” and “Explicit donor consent and family approval for postmortem donation.” The most-disagreeable statements were “Donor consent and family approval not required for postmortem donation,” “Acceptable with purely materialistic motivation,” and “Only donor no-known objection for postmortem donation.” Women, Christians, and healthcare respondents gave higher rank to “Explicit donor consent and family approval for live donation,” “Only donor family consent required for postmortem donation,” and “Acceptable if organ distribution equitable,” respectively, and Muslims gave more weight to donor/family harm (p ≤0.001). Q-methodology identified various ethical resolution models that were associated with religious affiliation and included relatively “motives-concerned,” “family-benefit-concerned,” “familism-oriented,” and “religious or non-religious altruism-concerned” models. Of 23 neutral statements on averaging-analysis, 48% and 65% received extreme ranks in ≥1 women and men Q-methodology models, respectively.Conclusion1) On average, recipient benefit, requirement of both explicit donor consent and family approval, donor-recipient relationship, and motives were predominant considerations; 2) ranking of some statements was associated with respondents’ demographics; 3) Q-methodology identified various ethical resolution models that were partially masked by averaging-analysis; and 4) strong virtue and familism approaches in our respondents provide some empirical evidence against principlism adequacy.

Desire, duty and medical gifting: how it became possible to long for a useful death

ABSTRACT It is common in social science critique of medical uses of the body to portray donation of the dead body as a sacrifice. In contemporary Denmark, however, some people claim to desire post-mortem utility. Here we argue that the articulated desires for utility should not be written off as false consciousness hiding a ‘real’ sacrifice. People use medical promises to reinvent the meaning of death; and, in turn, they make promises to medical institutions by signing up as donors. Registrations of post-mortem donations serve to uphold a sense of control; ensure post-vital dignity, and to align people with wider socially engrained ideals of productivity and agency. We build our argument on interviews conducted in Denmark 2007–2018.

Cardiac arrest and multi-tissue donation: interview with relatives

The interview with the relatives of a deceased for a post-mortem and cardiac death multi-tissues donation is a complex and delicate act of care performed by hospital coordination nurses for organ and tissue donation. The desirable exercise in face to face can also be done by telephone.

Body donation for research and teaching purposes: the contribution of blood donation units in the progress of anatomical science.

Cadaver's dissection has a fundamental role in teaching and understanding the anatomy. Postmortem body donation (PMBD) is an important source of cadavers and provides an opportunity to carry out research or educational activities in medicine and surgery. The objective of the current study is to determine the perspectives and attitudes toward PMBD among blood donors (BLD) and elderly people. These data are fundamental to highlight the PMBD extent and individual factors that might influence PMBD. Six hundred and fifty questionnaires were distributed to 500 (327 male and 173 female, mean age 39.9 ± 9.6 years) blood donors (BLD) and 150 elderly people (62 males and 88 females, mean age 74 ± 9.4 years). A specially designed self-administered questionnaire covering demographic data, knowledge and attitude of the participants concerning body donation (BD) was used. Concerning the perception of BD among BLD and elderly people, the most common reason for BD in both study groups was the contribution in research, while the commonest reason for hesitating about BD was the lack of information, following by personal reasons. The BLD were more likely to be interested in BD for contribution in research and personal reasons. Additionally, BLD were less likely than the elderly to hesitate about BD for religious and personal reasons and more likely to hesitate about BD for not being informed. BLD who were interested in BD for contribution in research were significantly older. Elderly people who hesitated about BD for personal reasons were significantly older. In the BLD group, those who responded that blood and body donation are the same were significantly younger, while in the elderly group - significantly older. The proportion of BLD who declared that blood and body donation is the same was significantly higher in more educated people. A need for well-organised and informative BD programmes is evident. Orientating the public towards this practice is of high moral and medical value, since with this important promotion the altruistic act of BD will expand globally.

Attitudes and Knowledge Regarding Postmortem Cornea Donation among Young and Elderly People in Germany: Sufficient for Decision Making?

Objectives: To evaluate the knowledge of and attitudes toward postmortem cornea donation in living young and elderly potential donors in a German city. Method: High-school students and seniors participated in a nonrandomized prospective survey focusing on willingness to donate corneas postmortem and factors that might influence underlying specific attitudes. Statistical analysis was descriptive and included logistic regression. Results: The survey showed that 73.3% of the high-school students and 41.6% of the seniors, 53.2% of whom had already signed an advanced medical directive, felt insufficiently informed about donation. High-school students were significantly less willing to donate their corneas postmortem (p < 0.001), and fewer of them possessed a donor card (p < 0.001). High-school students specified the internet as their favored source of information about donation in 82.7% of cases, while the family physician was the first preference for 47.8% of the seniors. Conclusions: The willingness to donate and the proportion of donor card ownership were significantly lower in the high-school students than among the seniors, corresponding to their respective knowledge in matters of donation. Young people should be systematically informed about cornea donation at school, as soon as they reach the legal minimum age for donation, and primary-care physicians should provide relevant information to every new patient to aid their decision making concerning postmortem cornea donation.

Autonomia na doação de órgãos post mortem no Brasil

Resumo Desde 1964, ano da primeira lei brasileira de doação de órgãos, muitos avanços da medicina aumentaram a qualidade e expectativa de vida, dentre eles o aprimoramento das técnicas de transplante. Este estudo teve como objetivo analisar a legislação brasileira para verificar a supremacia do consentimento do paciente na doação de órgãos post mortem. A partir da revisão da literatura e das normas jurídicas e éticas brasileiras relacionadas à autorização de transplantes, constatou-se que, mesmo após alteração da Lei 9.434/1997, é necessário adequar a legislação vigente aos princípios constitucionais e às regras do direito civil do país. Assim, conclui-se que é preciso atualizar a Lei de Transplantes, incluindo no texto a prevalência da vontade do paciente doador, mesmo diante da recusa de seus familiares.

The US Transuranium and Uranium Registries (USTUR): A Five-Decade Follow-Up Of Plutonium and Uranium Workers.

Dedication: The research of the US Transuranium and Uranium Registries relies heavily upon postmortem autopsy findings and radiochemical analysis of tissues. The enormous debt owed to those now-deceased registrants who unselfishly voluntarily participated in the US Transuranium and Uranium Registries program through postmortem donation of their tissues and to those still-living registrants who have volunteered to be future postmortem tissue donors is hereby acknowledged with gratitude. The scientific findings derived from postmortem analysis of these tissues have been instrumental in advancing our understanding of the actinide elements in humans and have led to refinement, validation, and confidence in safety standards for those who work with these elements as well as for the general public. To these generous and anonymous persons who made this ultimate contribution, this paper is dedicated with great thanks and admiration.

The 100-plus Study of cognitively healthy centenarians: rationale, design and cohort description

Although the incidence of dementia increases exponentially with age, some individuals reach more than 100 years with fully retained cognitive abilities. To identify the characteristics associated with the escape or delay of cognitive decline, we initiated the 100-plus Study (www.100plus.nl). The 100-plus Study is an on-going prospective cohort study of Dutch centenarians who self-reported to be cognitively healthy, their first-degree family members and their respective partners. We collect demographics, life history, medical history, genealogy, neuropsychological data and blood samples. Centenarians are followed annually until death. PET–MRI scans and feces donation are optional. Almost 30% of the centenarians agreed to post-mortem brain donation. To date (September 2018), 332 centenarians were included in the study. We analyzed demographic statistics of the first 300 centenarians (25% males) included in the cohort. Centenarians came from higher socio-economic classes and had higher levels of education compared to their birth cohort; alcohol consumption of centenarians was similar, and most males smoked during their lifetime. At baseline, the centenarians had a median MMSE score of 25 points (IQR 22.0–27.5); most centenarians lived independently, retained hearing and vision abilities and were independently mobile. Mortality was associated with cognitive functioning: centenarians with a baseline MMSE score ≥ 26 points had a mortality percentage of 17% per annual year in the second year after baseline, while centenarians with a baseline MMSE score < 26 points had a mortality of 42% per annual year (p = 0.003). The cohort was 2.1-fold enriched with the neuroprotective APOE-ε2 allele relative to 60–80 year-old population controls (p = 4.8 × 10−7), APOE-ε3 was unchanged and the APOE-ε4 allele was 2.3-fold depleted (p = 6.3 × 10−7). Comprehensive characterization of the 100-plus cohort of cognitively healthy centenarians might reveal protective factors that explain the physiology of long-term preserved cognitive health.

The beginning of the program of multiorgan postmortem donation and transplantation in the Republic of Sakha (Yakutia)

The article is devoted to the main aspects of organization of multiorgan donation from donors with brain death in the Republic of Sakha (Yakutia). Transplant services to the population of this region have been in place since 2001, and until 2016 only kidney transplants or liver fragments from a living related donor have been performed. The presence of an effective postmortem donation program will allow to meet the high demand of this region for high-tech assistance by organ transplantation.

Lifting the Price on Human Life

The increasing number of patients in need of organtransplantation has fostered the growth of an internationalblack market in which the wealthy purchase kidneys, liver,or other tissue from vulnerable persons. Oftentimes, victimsendure substandard care and are forced to consent to lifethreatening procedures for little to no compensation. Since voluntary donation alone is unable to reconcile supply with demand, more economically developed countries have begun to experiment with reimbursing donors for incurred expenses and creating procedural barriers for those who would prefer to opt out of post-mortem donation.1 However, poverty can be equally as problematic as the shortage of organs itself. In this regard, the ideal solution should eliminate the initial need for people to donate out of desperation. After relating the organ trade to issues of substandard care and criminal exploitation, it becomes evident that nonfinancial donor compensation, in the form of housing, tuition, insurance, or employment, could be an effective means of suppressing the illegal organ marketand restoring basic rights to disadvantaged donors.

Criminalization of Acts in the Sphere of Lifetime and Postmortem Donation

The present article is devoted to questions of improvement of the criminal legislation regarding a regulation of responsibility for the crimes connected with an illegal removal of organs and fabrics of the person in the Russian Federation. The specification of a problem of criminal and legal responsibility for some acts in this sphere demands very close attention and the optimum decision.

Chapter 3 - Autism BrainNet: A network of postmortem brain banks established to facilitate autism research

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators.

Cadaveric Donation and Post-mortem Reuse of Pacemakers and Defibrillators in Nepal: Medical, Legal and Ethical Challenges

Cardiovascular diseases (CVDs) are the number one cause of death globally. An estimated 17.5 million people died from CVDs in 2012, representing 31% of all global deaths. Over three quarters of all deaths related CVDs take place in low- and middle-income countries (LMICs). Studies have estimated that 1 to 2 million people worldwide die each year due to lack of access to cardiac rhythm management devices (CRMDs) i.e. implantable cardiac defibrillator (ICD) or a pacemaker. The principal challenge is the high cost of these devices and the resource constraint in LMICs. A growing body of literature, mostly single center, uncontrolled and retrospective studies has suggested reuse of CRMDs from deceased donors as a safe and effective alternative. This paper seeks to propose the concept of post-mortem CRMD donation and reutilization program within Nepal as a life-saving initiative. Though the spirit of the program is in line with the ethical principles of respect for persons, beneficence, justice, and the common good, it is challenged with several logistical barriers and legal concerns. In this paper we have discussed the clinical, legal and ethical perspectives with a literature review on similar programs.

Managing Social Inequality: Confraternal Charity in Portugal and Its Overseas Colonies

When the first misericórdia was created in 1498, Lisbon was trying to erase the wounds of the violent expulsion of the Jewish communities from the kingdom, and the confraternity was born under the concern of reuniting baptized persons who wanted to exercise charity. The misericórdias were soon to be founded all over the kingdom and its empire, acting as prebanking institutions and rivaling with local institutions like the municipality or the bishopric. Their importance was based mainly upon moral authority, as they tended to cater for most situations of poverty. Even if other local institutions practised charity, they were not generally able to attain the same scale of human or economic resources, as the misericórdias relied on the voluntary work of their members and attracted substantial postmortem donations. They responded directly to the king and were largely out of the control of competitors. By contrast, royal authority was too weak to impose an effective control; the first serious attempts to do so date from the marquis of Pombal's consulate (1750–77). In spite of misunderstandings and conflicts with the Crown, it is undeniable misericórdias gave an important contribution to the formation of local communities, participating in the dynamics between center and periphery. In spite of the variety of their geographic and demographic contexts, they could always be recognizable by central powers as abiding to the same principles. However, the elites who governed them were free to transform misericórdias into institutions capable of motivating their participation. Between obedience to the king and local management of resources, there was ample space for social action.

Iranian kidney market in limbo: a commentary on “The ambiguous lessons of the Iranian model of paid living kidney donation”

Sigrid Fry-Revere's The Kidney Sellers: A Journey of Discovery in Iran, an allegedly first-hand examination of the Iranian paid kidney donation model, has been criticized by Koplin in an essay formerly published in the Monash Bioethics Review. Koplin especially challenges Fry-Revere's claim that financially compensating kidney vendors might facilitate altruistic kidney donation. The current situation in Iran, according to Koplin, suggests that the market model has undermined altruistic donation. On this point, this commentary tries to show that healthcare policymakers in Iran no longer see the Iranian paid kidney donation model as a sustainable and ethically justifiable status quo. Briefly touching on the criticisms that have been made even by some positive commentators of the Iranian model, this commentary aims to call attention to the fact that the current dynamic within healthcare policymaking in Iran seeks primarily to decrease its reliance on the organ market instead of revising and modifying it. This complicates the plausibility of any kind of extrapolation, replication or extracting empirical support from the Iranian model to create organ markets in other countries, for example, as Fry-Revere suggests to conduct a trial of a financially incentivized kidney donation scheme in the US. The conclusion is that the Iranian healthcare system should tackle the organ shortage through increasing altruistic living and postmortem kidney donations. This might also provide, finally, a space for conducting extensive and long-term follow-up studies on well-being, satisfaction and social integration of Iranian kidney vendors.