Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver-Kidney Transplantation.

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Racial disparities in access to HLA-matched unrelated donor transplants: a prospective 1312-patient analysis.

Availability of 8/8 HLA-allele matched unrelated donors (URDs) is a barrier for ethnic and racial minorities. We prospectively evaluated receipt of 8/8 HLA-allele matched URD or either 7/8 URD or cord blood (CB) transplants by patient ancestry from 2005 to 2017. Matched URDs were given priority if they were available. Of 1312 patients, 723 (55%) received 8/8 URD, 219 (17%) 7/8 URD, 319 (24%) CB, and 51 (4%) had no 7/8 or 8/8 URD or CB graft. Europeans were more likely to receive an 8/8 URD transplant than non-Europeans (67% vs 33%) and less likely to have no URD or CB graft (1% vs 9%). Southern Europeans received 8/8 URD transplants (41%) at rates similar to those of Asians (34%) and white Hispanics (35%); Africans were the least likely (18%) to undergo 8/8 URD transplantation. CB and 7/8 URDs extended transplant access to all groups. In 742 recent patients, marked racial disparity in 8/8 URD access between groups observed in earlier years persisted with only a modest increase in the percentage of 8/8 URD transplants. Of 78 recent African patients, 46% received a CB transplant and 14% had no 7/8 or 8/8 URD or CB graft. Increasing registry size has not resolved the racial disparity in URD access, which emphasizes the importance of alternative graft sources.

Emerging Ethical Challenges Raised by the Evolution of Vascularized Composite Allotransplantation.

BACKGROUND: Despite early skepticism, the field of vascularized composite allotransplantation (VCA) has demonstrated feasibility. The ethics of VCA have moved past doubts about the morality of attempting such transplants to how to conduct them ethically. METHODS: Leaders of each program performing and/or evaluating VCA in the United States were invited to participate in a working group to assess the state and future of VCA ethics and policy. Four meetings were held over the course of 1 year to describe key challenges and potential solutions. RESULTS: Working group participants concluded that VCA holds great promise as treatment for patients with particular injuries or deficits, but the field faces unique challenges to adoption as standard of care, which can only be overcome by data sharing and standardization of evaluation and outcome metrics. CONCLUSIONS: Adequate attention must be given to concerns including managing the uniquely intense physician-patient relationship, ethical patient selection, ensuring patients have adequate representation, informing and earning the trust of the public for donation, standardizing metrics for success, and fostering an environment of data sharing. These steps are critical to transitioning VCA from research to standard of care and to its insurance coverage inclusion.

The Battle Ground between Two Giants: Toe Transfer and Hand Allotransplantation.

A few severe hand injuries represent a gray zone for the reconstructive surgeon, for which autologous tissue transfer and allotransplantation can yield satisfactory results, but not without downsides or morbidity.This article is written to address the dilemma of application of both techniques in those selected cases.

Medical and ethical considerations on hematopoietic stem cells mobilization for healthy donors.

Hematopoietic stem cell transplantation is a common procedure potentially beneficial to many individuals with cancer, hematological, or inherited disorders, and has highlighted the need of related or unrelated donors to perform allograft. Donation of hematopoietic stem cells, either through bone marrow harvest or peripheral blood stem cell collection, is well-established and widespread. Over the past two decades, the peripheral blood stem cell collection by aphaeresis has become the main source of hematopoietic stem cells for transplantation, due to faster engraftment and practicability and lower risk of relapse for high-risk patients. For peripheral blood stem cell donation, donors require mobilization of hematopoietic stem cells from bone marrow into the blood stream. This is performed by growth factors injections. This article is a review of reported applications of growth factors (original granulocyte colony stimulating factor and its biosimilars), for healthy donors' peripheral blood stem cell mobilization, in terms of toxicity, side effects, efficacy and follow-up. There is still an ethical dilemma for clinicians involved in allograft, because they expose healthy donors to drugs. It is important to dispel some of the critical concerns regarding their use in healthy volunteers, particularly because they receive no personal therapeutic benefit from this procedure.

Lessons learned from the world's first successful penis allotransplantation.

We performed a successful penis allotransplantation on 11 December 2014. Sharing the lessons learned might help more patients in need to be treated this way. We divided the project into manageable segments that was each overseen by an expert. The ethical review and conduct paved the way for a publically acceptable and successful project. Screening for a psychological stable recipient is important. The most difficult part of the project was finding a donor penis. This was successfully negotiated with the family of a brain dead donor by creating a neo-phallus for the donor, thereby maintaining the dignity of the donor. Working with transplant coordinators that are sympathetic to aphallic men is crucial. Surgeons versed in microvascular techniques is a critical part of the team. Transplant immunologists have to adapt to treat composite tissue transplantation patients.

Surgical, ethical, and psychosocial considerations in human head transplantation.

Transplanting a head and brain is perhaps the final frontier of organ transplantation. The goal of body-to-head transplantation (BHT) is to sustain the life of individuals who suffer from terminal disease, but whose head and brain are healthy. Ideally BHT could provide a lifesaving treatment for several conditions where none currently exists. BHT is no ordinary experiment, to transfer a head to another body involves extraordinarily complex medical challenges as well as ethical and existential dilemmas that were previously confined to the imagination of writers of fiction. The possibility of replacing an incurably ill body with a healthy one tests not only our surgical limits, but also the social and psychological boundaries of physical life and alters what we recognize life to be. The purpose of this target article, the complementary manuscript focused on immunological issues in BHT, and the accompanying Commentaries by scholars and practitioners in medicine, immunology, and bioethics is to review major surgical and psychosocial-ethical and immunological considerations surrounding body-to-head transplantation. We hope that together these ideas will provide readers with a comprehensive overview of the possibilities and challenges associated with BHT and initiate professional discussion and debate through which this new frontier in medicine is considered and approached.

Ethical questions raised by the first allotransplantations of the face: a survey of French surgeons.

INTRODUCTION: More than any other allograft, the allotransplantation of the face has a symbolic character, which raises a large number of questions. The objective of this article is to make an analysis through a survey carried out among French surgeons. METHODS: A file of 909 e-mail addresses of surgeons was created so as to send out a questionnaire regarding 10 ethical issues. RESULTS: Beyond the technical prowess, the surgeons ethical reflection initially focused on the notion of consent to donation and care. They attached equal importance to all ethical questions. They spontaneously raised the issue of over-mediatization of these first transplants and the place of the transplant surgeons and their patients in the medical information. CONCLUSION: Over two thirds of the surgeons attached importance to ethical issues regarding the donor and recipient of a facial allograft. Some of the principal questions facing facial transplantation is of an ethical nature as it is an unprecedented procedure that is challenged by the axiom to first do no harm and the need of modern medicine to limit risk to as close to zero as possible. For the non-specialist, accepting psychologically the face of another individual appears to be a real issue. Contrary to that, the main demand expressed by the facial transplant recipients appears to be related to facial functions rather than appearance.

The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation.

Absolute uterine factor infertility (UFI) refers to the refractory causes of female infertility stemming from the anatomical or physiological inability of a uterus to sustain gestation. Today, uterine factor infertility affects 3-5% of the population. Traditionally, although surrogacy and adoption have been the only viable options for females affected by this condition, the uterine transplant is currently under investigation as a potential medical alternative for women who desire to go through the experience of pregnancy. Although animal models have shown promising results, human transplantation cases have only been described in case reports and a successful transplant leading to gestation is yet to occur in humans. Notwithstanding the intricate medical and scientific complexities that a uterine transplant places on the medical minds of our time, ethical questions on this matter pose a similar, if not greater, challenge. In light of these facts, this article attempts to present the ethical issues in the context of experimentation and standard practice which surround this controversial and potentially paradigm-altering procedure; and given these, introduces "The Montreal Criteria for the Ethical Feasibility of Uterine Transplantation", a set of proposed criteria required for a woman to be ethically considered a candidate for uterine transplantation.

The ongoing charity of organ donation. Contemporary English Sunni fatwas on organ donation and blood transfusion.

BACKGROUND: Empirical studies in Muslim communities on organ donation and blood transfusion show that Muslim counsellors play an important role in the decision process. Despite the emerging importance of online English Sunni fatwas, these fatwas on organ donation and blood transfusion have hardly been studied, thus creating a gap in our knowledge of contemporary Islamic views on the subject. METHOD: We analysed 70 English Sunni e-fatwas and subjected them to an in-depth text analysis in order to reveal the key concepts in the Islamic ethical framework regarding organ donation and blood transfusion. RESULTS: All 70 fatwas allow for organ donation and blood transfusion. Autotransplantation is no problem at all if done for medical reasons. Allotransplantation, both from a living and a dead donor, appears to be possible though only in quite restricted ways. Xenotransplantation is less often mentioned but can be allowed in case of necessity. Transplantation in general is seen as an ongoing form of charity. Nearly half of the fatwas allowing blood transfusion do so without mentioning any restriction or problem whatsoever. The other half of the fatwas on transfusion contain the same conditional approval as found in the arguments pro organ transplantation. CONCLUSION: Our findings are very much in line with the international literature on the subject. We found two new elements: debates on the definition of the moment of death are hardly mentioned in the English Sunni fatwas and organ donation and blood transfusion are presented as an ongoing form of charity.

Ethical issues in penile transplantation.

This article provides an overview of the ethical issues associated with penile transplantation, a form of composite tissue allografting. There is only one reported case of human penile transplantation, and, as such, this technique is considered to be experimental. The ethical issues at stake involve both the graft donor and the graft recipient. With regard to the recipient, there are significant concerns relating to surgical risks and benefits, informed consent, body image (including surgical expectations and outcomes) and compliance. Donor issues may include family consent and privacy, as well as graft harvesting (leaving the donor cadaver without a penis). Many of these ethical issues can be explored during the recipient's assessment and consent process. Because no medium-term or long-term outcome data for this procedure exist-only one such operation has ever been performed-the burdens and ethical issues concerning penile transplantation remain unknown.

[To cure: to become oneself or become different?]. / Guérir : devenir soi ou devenir autre ?

The parallel evolution of lifestyles and medicine calls into question the objectives of the therapeutical relationship. Leading-edge technology, the allotransplant radically questions what curing means: is it about becoming oneself again or another person? This paper studies this dilemma from three standpoints. First, in an aesthetics perspective, the transplant surgery refers to an implicit definition of what is an acceptable body, which introduces a tension between vascular supply, immunology and beauty. How far can we favour one or the other? Secondly, in a religious perspective, transplant contributes to the mimetic desire: how can we regulate this desire in a society that increasingly values the body? Finally, from a philosophical standpoint, allotransplant questions my personal relationship with my body: beyond its technological requirements, we have to determine, in the public and private spheres, if individuals have or are bodies. What responsibility does medicine assume, as an institution and a community of agents, in this anthropological choice?

Supporting facial transplantation with the pillars of bioethics.

Facial transplantation has recently been offered to patients with severely disfigured faces not amenable to functional reconstruction with autologous tissues. Arguments against this procedure include risks of immunosuppression, the concern that it will be done for cosmesis, the belief that acceptable reconstruction can be achieved with autologous tissues, the potential impact on the patient of graft failure, and the concern that the procedure may be adopted by unqualified centers. If we look to bioethics to help us dissect the question of whether or not facial transplantation should be performed, we see that the majority of the arguments have been proscriptive rather than prescriptive. There are valid arguments in favor of facial transplantation based on the prescriptive pillars of bioethics: autonomy, justice, and beneficence. This article attempts to reframe the dialogue in a prescriptive manner.

Facial allograft transplants: where's the catch?

Face transplantation--or, more properly, facial allograft transplantation (FAT)--generates much public interest and academic debate. In this paper, we suggest that it is up to opponents of FAT to make the case for its impermissibility. We allow that there is a number of apparently strong arguments that might be deployed against FAT. However, all but one of these turn out not to be compelling after examination. The remaining argument is not so easily dismissed--but its central point is fairly workaday and certainly does not tell us anything about FAT in particular. Therefore, qua argument about facial transplant surgery, it fails to hit its target. Overall, we conclude that a compelling case against FAT remains to be made.

[Philosophical and ethics aspects of the composite tissues allotransplantations (CTA)]. / Aspects éthicophilosophiques des allotransplantations de tissus composites (ATC).

The first successes of total hand and partial face transplants raise several philosophical and ethical questions. This paper examines the perspective of the recipient, the donor and the social aspect. The question of the identity remains unsolved. Philosophical point of view shows an historical continuity in the desire of the human being for improving his condition.

Facial allograft transplantation, personal identity and subjectivity.

An analysis of the identity issues involved in facial allograft transplantation is provided in this paper. The identity issues involved in organ transplantation in general, under both theoretical accounts of personal identity and subjective accounts provided by organ recipients, are examined. It is argued that the identity issues involved in facial allograft transplantation are similar to those involved in organ transplantation in general, but much stronger because the face is so closely linked with personal identity. Recipients of facial allograft transplantation have the potential to feel that their identity is a mix between their own and the donor's, and the donor's family is potentially likely to feel that their loved one "lives on". It is also argued that facial allograft transplantation allows the recipients to regain an identity, because they can now be seen in the social world. Moreover, they may regain expressivity, allowing for them to be seen even more by others, and to regain an identity to an even greater extent. Informing both recipients and donors about the role that identity plays in facial allograft transplantation could enhance the consent process for facial allograft transplantation and donation.