Needs must: living donor liver transplantation from an HIV-positive mother to her HIV-negative child in Johannesburg, South Africa.

The world's first living donor liver transplant from an HIV-positive mother to her HIV-negative child, performed by our team in Johannesburg, South Africa (SA) in 2017, was necessitated by disease profile and health system challenges. In our country, we have a major shortage of donor organs, which compels us to consider innovative solutions to save lives. Simultaneously, the transition of the HIV pandemic, from a death sentence to a chronic illness with excellent survival on treatment required us to rethink our policies regarding HIV infection and living donor liver transplantation . Although HIV infection in the donor is internationally considered an absolute contraindication for transplant to an HIV-negative recipient, there have been a very small number of unintentional transplants from HIV-positive deceased donors to HIV-negative recipients. These transplant recipients do well on antiretroviral medication and their graft survival is not compromised. We have had a number of HIV-positive parents in our setting express a desire to be living liver donors for their critically ill children. Declining these parents as living donors has become increasingly unjustifiable given the very small deceased donor pool in SA; and because many of these parents are virally suppressed and would otherwise fulfil our eligibility criteria as living donors. This paper discusses the evolution of HIV and transplantation in SA, highlights some of the primary ethical considerations for us when embarking on this case and considers the new ethical issues that have arisen since we undertook this transplant.

Donor blood screening and moral responsibility: how safe should blood be?

Some screening tests for donor blood that are used by blood services to prevent transfusion-transmission of infectious diseases offer relatively few health benefits for the resources spent on them. Can good ethical arguments be provided for employing these tests nonetheless? This paper discusses-and ultimately rejects-three such arguments. According to the 'rule of rescue' argument, general standards for cost-effectiveness in healthcare may be ignored when rescuing identifiable individuals. The argument fails in this context, however, because we cannot identify beforehand who will benefit from additional blood screening tests. On the 'imposed risk' argument, general cost-effectiveness standards do not apply when healthcare interventions impose risks on patients. This argument ignores the fact that imposing risks on patients is inevitable in healthcare and that these risks can be countered only within reasonable limits. Finally, the 'manufacturing standard' argument premises that general cost-effectiveness standards do not apply to procedures preventing the contamination of manufactured medical products. We contend that while this argument seems reasonable insofar as commercially manufactured medical products are concerned, publicly funded blood screening tests should respect the standards for general healthcare. We conclude that these particular arguments are unpersuasive, and we offer directions to advance the debate.

Which Donor for Uterus Transplants: Brain-Dead Donor or Living Donor? A Systematic Review.

BACKGROUND: The aim of this systematic review was to evaluate and compare the pros and cons of using living donors or brain-dead donors in uterus transplantation programs, 2 years after the first worldwide live birth after uterus transplantation. METHODS: The Medline database and the Central Cochrane Library were used to locate uterine transplantation studies carried out in human or nonhuman primates. All types of articles (case reports, original studies, meta-analyses, reviews) in English or French were considered for inclusion. RESULTS: Overall, 92 articles were screened and 44 were retained for review. Proof of concept for human uterine transplantation was demonstrated in 2014 with a living donor. Compared with a brain-dead donor strategy, a living donor strategy offers greater possibilities for planning surgery and also decreases cold ischemia time, potentially translating into a higher success rate. However, this approach poses ethical problems, given that the donor is exposed to surgery risks but does not derive any direct benefit. A brain-dead donor strategy is more acceptable from an ethical viewpoint, but its feasibility is currently unproven, potentially owing to a lack of compatible donors, and is associated with a longer cold ischemia time and a potentially higher rejection rate. CONCLUSIONS: The systematic review demonstrates that uterine transplantation is a major surgical innovation for the treatment of absolute uterine factor infertility. Living and brain-dead donor strategies are not mutually exclusive and, in view of the current scarcity of uterine grafts and the anticipated future rise in demand, both will probably be necessary.

Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application.

Mismatch of human leukocyte antigens (HLA) adversely impacts the outcome of patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). This translates into the clinical requirement to timely identify suitable HLA-matched donors which in turn curtails the chances of recipients, especially those from a racial minority, to successfully undergo alloHSCT. We thus sought to broaden the existing pool of registered unrelated donors based on analysis that eliminating the expression of the HLA-A increases the chance for finding a donor matched at HLA-B, -C, and -DRB1 regardless of a patient's race. Elimination of HLA-A expression in HSC was achieved using artificial zinc finger nucleases designed to target HLA-A alleles. Significantly, these engineered HSCs maintain their ability to engraft and reconstitute hematopoiesis in immunocompromised mice. This introduced loss of HLA-A expression decreases the need to recruit large number of donors to match with potential recipients and has particular importance for patients whose HLA repertoire is under-represented in the current donor pool. Furthermore, the genetic engineering of stem cells provides a translational approach to HLA-match a limited number of third-party donors with a wide number of recipients.

An update on liver transplantation: A critical review.

Liver transplantation, although now a routine procedure, with defined indications and usually excellent outcomes, still has challenges. Donor shortage remains a key issue. Transplanted organs are not free of risk and may transmit cancer, infection, metabolic or autoimmune disease. Approaches to the donor shortage include use of organs from donors after circulatory death, from living donors and from those previously infected with Hepatitis B and C and even HIV for selected recipients. Normothermic regional and/or machine perfusion, whether static or pulsatile, normo- or hypothermic, are being explored and will be likely to have a major place in improving donation rates and outcomes. The main indications for liver replacement are alcoholic liver disease, HCV, non-alcoholic liver disease and liver cancer. Recent studies have shown that selected patients with severe alcoholic hepatitis may also benefit from liver transplant. The advent of new and highly effective treatments for HCV, whether given before or after transplant will have a major impact on outcomes. The role of transplantation for those with liver cell cancer continues to evolve as other interventions become more effective. Immunosuppression is usually required life-long and adherence remains a challenge, especially in adolescents. Immunosuppression with calcineurin inhibitors (primarily tacrolimus), antimetabolites (azathioprine or mycophenolate) and corticosteroids remains standard. Outcomes after transplantation are good but not normal in quality or quantity. Premature death may be due to increased risk of cardiovascular disease, de novo cancer, recurrent disease or late technical problems.

Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.

Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation.

[10 Years of Experience in Living Donation for Liver Transplantation in Pediatric Patients - A Single Centre Study].

Living donor liver transplantation poses new issues related to the performance of a major surgery on a healthy person - the living donor. Thus, it requires precise logistics to ensure positive outcome for both the donor and the recipient, outweighing the risks associated with donation and transplantation. For this purpose, we developed an original three phase protocol for evaluation of candidate donors with set of mandatory assays. This paper aims to analyze the outcomes of this protocol. 89 candidates have been examined for the performance of 23 living donor liver transplantations. The procedure was successfully completed by 25 candidates (28.1%), including two cases of procedure suspension due to occurrence of a suitable deceased donor. The majority of exclusions occurred in the third phase, generally due to anatomical variations: arterial (17%), portal (9.68%), venous (18.15%) and biliary (18.15%), and for several reasons simultaneously (6.7%). NO exclusions occurred due to inadequate potential graft or residual volume. All living donors underwent left lateral resection and the measured volumes were enough for both the recipients and the donors. No significant complications occurred in the donors (Clavien 1: 21%, Clavien II: 4%), with no need of transfusion, reoperation or re-hospitalization. The laboratory parameters were restored to normal values within the 10th postoperative day as the average hospital stay was 14.7 days. All donors were discharged with normal laboratory, instrumental and physical parameters. No abnormalities were observed at long-term follow-up. No primary graft dysfunction was observed. The large proportion of declined candidates requires strict adherence to the precise sequence of the evaluation protocol. The main reasons for decline are anatomical variation. Los level of complicatons was registered, with short postoperative stay, normal laboratory results at discharge and normal physiological parameters at long-term follow-up. The concept of donor advocate was introduced for the first time in Bulgaria. His task is to defend the interests of the candidate donor and to provide assistance in making an informed decision.

Pediatric Deceased Donation-A Report of the Transplantation Society Meeting in Geneva.

The Ethics Committee of The Transplantation Society convened a meeting on pediatric deceased donation of organs in Geneva, Switzerland, on March 21 to 22, 2014. Thirty-four participants from Africa, Asia, the Middle East, Oceania, Europe, and North and South America explored the practical and ethical issues pertaining to pediatric deceased donation and developed recommendations for policy and practice. Their expertise was inclusive of pediatric intensive care, internal medicine, and surgery, nursing, ethics, organ donation and procurement, psychology, law, and sociology. The report of the meeting advocates the routine provision of opportunities for deceased donation by pediatric patients and conveys an international call for the development of evidence-based resources needed to inform provision of best practice care in deceased donation for neonates and children.

Seriously ill patients as living unspecified kidney donors: rationale and justification.

BACKGROUND: Between 2000 and December 2013, 106 live donor nephrectomies from anonymous living-donors were performed at the Erasmus MC Rotterdam; five of the donors (5.4%) had a life-threatening disease. The aim of the present report is to give the rational and justification for this procedure. METHODS: All five donors underwent the national standard living-donor screening procedure. Additionally, motivation to donate and psychologic stability were assessed by a psychologist using in-depth interview techniques and a psychologic complaints questionnaire. Post-donor nephrectomy follow-up consisted of standard questionnaires and clinical check-ups. RESULTS: One patient had cerebral and caudal ependymomas, one had severe and progressive emphysema, two had Huntington's disease and one had a grade 2 oligodendroglioma. The psychologic screening revealed genuine motivation, adequate risk perception, and normal sense of reality. No contraindications for donation were found. The five donor nephrectomies made nine kidney transplantations possible. All donors were satisfied with the donation procedure. Three donors died during follow-up (0.6-4.9 years) as a result of their disease. CONCLUSION: In the absence of apparent additional health risks, medical, and psychologic contraindications, we consider it ethically justified to accept an offer from a cognitively competent patient with a life-threatening disease in view of their self-reported satisfaction during follow-up. Although based on a limited number of patients, we conclude that a stricter psychologic screening for seriously ill donors compared to healthy unspecified anonymous donors to unspecified patients is not necessary.

Indicações e seleção do paciente para transplante cardíaco / Indications and patient selection for cardiac transplantation

O transplante cardíaco está indicado para pacientes cominsuficiência cardíaca grave com sintomas incapacitantes, a despeitode estarem recebendo tratamento farmacológico otimizado e deterem se esgotado as possibilidades cirúrgicas de tratamento. Entreoutros fatores, as limitações referentes à disponibilidade de doadoresde coração efetivos, principalmente no Brasil, tornam a escolhacriteriosa do receptor cardíaco, além de um desafio, uma granderesponsabilidade para a prática diária do cardiologista clínico.Hiponatremia, insuficiência renal, caquexia cardíaca, anemia, baixosníveis de colesterol, queda dos níveis de hemoglobina e dependênciade inotrópicos são fatores clínico-laboratoriais associados a mauprognóstico em pacientes com insuficiência cardíaca (IC) avançada.Os escores de risco [HFSS (Heart Failure Survival Score) eSHFM (Seattle Heart Failure Model)] devem ser utilizados comoferramentas acessórias para avaliar a gravidade dos pacientes comIC avançada. VO2 pico < 10 ml/kg/min e VE/VCO2 > 34 no teste doexercício cardiopulmonar estão relacionados com mortalidade empacientes ambulatorialmente avaliados para transplante cardíaco. Ahemodinâmica pulmonar, assim como o perfil imunológico, deveser rotineiramente acessada em pacientes candidatos a transplantecardíaco. Os pacientes com hipertensão pulmonar fixa estão sobrisco de desenvolverem insuficiência cardíaca direita fatal apóso transplante cardíaco. Por sua vez, a presença de anticorposcirculantes contra os antígenos HLA (Human Leukocyte Antigen)é um fator de risco para rejeição do enxerto após o transplantede coração. Finalmente, a indicação do transplante cardíaco emsituações clínicas extremas vem aumentando e se tornando umdesafio na prática clínica cardiológica.

The heart transplantation is indicated for patients with severeheart failure and disabling symptoms despite being receivingoptimal pharmacological treatment and having exhausted thepossibilities of surgical treatment. Among other factors, thelimitations related to the availability of effective heart donor,mainly in Brazil, make a judicious choice of the heart receptorin addition to a challenge, a huge responsibility for the dailypractice of clinical cardiologists. Hyponatremia, renal failure,cardiac cachexia, anemia, low cholesterol levels, decrease inhemoglobin levels and dependence on inotropes are clinical andlaboratory factors associated with poor prognosis in patientswith advanced heart failure. The risk scores [HFSS (HeartFailure Survival Score) and SHFM (Seattle Heart FailureModel)] should be used as ancillary tools to assess the severityof patients with advanced HF. Peak of VO2 < 10 ml/kg/minand VE/VCO2 > 34 during the cardio-pulmonary exercise testare related to mortality in ambulatory patients evaluated forcardiac transplantation. Pulmonary hemodynamics as wellas the immunological profile should be routinely accessed inpatients who are candidates for cardiac transplantation. Patientswith fixed pulmonary hypertension are at risk for fatal rightheart failure after heart transplantation. In turn, the presenceof circulating antibodies to Human Leukocyte Antigen HLA)is a risk factor for graft rejection after heart transplantation.Finally, the indication of cardiac transplantation in extremeclinical situations are increasing and becoming a challenge incardiology clinical practice.

The procurement of cells for the derivation of human embryonic stem cell lines for therapeutic use: recommendations for good practice.

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.

Expanding the live kidney donor pool: ethical considerations regarding altruistic donors, paired and pooled programs.

In renal transplant, there is a well-known deficiency in organ supply relative to demand. Live donation provides superior results when compared with deceased donation including a better rate of graft success and fewer immunologic complications. This deficiency in organs leads to significant morbidity and mortality rates. Alternative avenues have been extensively explored that may expand the live donor pool. They include altruistic donation as well as paired and pooled exchange programs. Altruistic donation is a truly selfless act from a donor unknown to the recipient. Kidney paired donation involves 2 incompatible donor-recipient pairs swapping donors to produce compatibility. Pooled donation involves at least 2 pairs, and can take the form of domino chains in which altruistic input sets up a chain of transplants, in which each recipient's incompatible donor makes a donation for the next recipient. Despite application of these various methods, there lie extensive ethical issues surrounding them. Misconceptions frequently occur; for instance, the perceived benefit that donating an organ to a loved one is greater for a related donor than for an altruistic one. Additionally, it is frequently believed that immunologic incompatibility offers coerced donors liberation from surgery, and that overcoming these barriers by introducing exchange programs provides vulnerable donors less protection. This article explores these and other complex ethical issues surrounding the various methods of expanding the donor pool. The authors offer opinions that challenge the ethical issues and attempt to overcome those views that hinder progress in the field.

Novel approaches to expanding the lung donor pool: donation after cardiac death and ex vivo conditioning.

Two novel approaches have been developed to potentially increase the availability of donor lungs for lung transplantation. In the first approach, lungs from donation after cardiac death (DCD) donors are used to increase the quantity of organ donors. In the second approach, a newly developed normothermic ex vivo lung perfusion (EVLP) technique is used as a means of reassessing the adequacy of lung function from DCD and from high-risk brain death donors prior to transplantation. This EVLP technique can also act as a platform for the delivery of novel therapies to repair injured organs ex vivo.

O itinerário de doadores de sangue: reflexões acerca da micropolítica no cuidado de enfermagem / The blood donors' itinerary: reflections on micro-policy in the nursing care

Estudo qualitativo, desenvolvido à luz da etnometodologia, com o tratamento dos dados a partir da análise do discurso das 26 entrevistas não-estruturadas e dos registros da observação participante em diário de campo. Teve como objetivo analisar o itinerário de candidatos a doadores de sangue num serviço de hemoterapia (SH) do Rio de Janeiro. O itinerário dos doadores de sangue se constitui desde a sensibilização até o transcurso para a doação, envolvendo a saúde e os múltiplos contextos da vida dos candidatos, e toma corpo no espaço micropolítico de trabalho. Prevaleceram os doadores de reposição (65,4 por cento), caracterizados por grupos de familiares, de amigos, colegas de trabalho, vizinhos e, em menor número, por pessoas que doam sem nenhuma relação com o receptor. Destacamos o acesso dos doadores ao SH devido às Áreas Programáticas (AP) em que residem 46,1 por cento dos doadores serem distintas da AP do SH e 23,1 por cento residirem em outros municípios. No itinerário percorrido, existem as etapas antecedentes e as posteriores à triagem clínica, sendo esta destacada pela possibilidade da expressão da tecnologia leve no cuidado de enfermagem. Os significados atribuídos à doação e à motivação são individuais para cada doador. O conhecimento do itinerário possibilita a reflexão sobre o gerenciamento do espaço micropolítico em que usuários e enfermeiras se encontram, tanto apresentando o caminho que o doador percorre no sistema de saúde, como a possível definição de um modelo assistencial à luz das necessidades de saúde dos doadores para o cuidado de enfermagem em hemoterapia.

Qualitative study conducted in the light of ethnomethodology, with the processing of data from the discourse analysis of 26 interviews and unstructured records of participant observation in the field diary. It aimed to examine the route of blood donor candidates at a hematology service (HS) in Rio de Janeiro. The itinerary of blood donors starts with their awareness to the course for the donation, including health and the several contexts of the lives of candidates, and takes shape in the micro-political work. Replacement donors (65.4 percent) prevailed, characterized by groups of relatives, friends, coworkers, neighbors, and in smaller numbers, by people who do not even know the receiver. Among these donors, 46.1 percent live in areas other than where the HS is located, and 23.1 percent live in other cities. Along the itinerary, there are previous and posterior steps leading to the screening clinic, which is highlighted by the possibility of the expression of light technology in nursing care. The meanings attributed to the donation and motivation are individual for each donor. The knowledge of the route allows the reflection on the management of the micro-political space in which users and nurses meet, both showing the path that the donor takes in the health system, and a possible definition of a health care model in the light of the health needs of donors for nursing care in hemotherapy.