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.

The immunologic considerations in human head transplantation.

The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient.

Factors associated with non-reimbursable activity on an inpatient pediatric consultation-liaison service.

The aim of this study was to identify factors contributing to clinician time spent in non-reimbursable activity on an inpatient pediatric consultation-liaison (C-L) service. A retrospective study was conducted using inpatient C-L service data on 1,246 consecutive referrals. For this patient population, the strongest predictor of level of non-reimbursable clinical activity was illness chronicity and the number of contacts with C-L service clinicians during their hospital stay. Patients with acute life-threatening illnesses required the highest mean amount of non-reimbursable service activity. On average, 28 % of total clinician time in completing a hospital consultation was spent in non-reimbursable activity. Effective C-L services require a proportion of time spent in non-reimbursable clinical activity, such as liaison and coordinating care with other providers. Identifying referral and systemic factors contributing to non-reimbursable activity can provide insight into budgeting/negotiating for institutional support for essential clinical and non-clinical functions in providing competent quality patient care.

Plastic surgeon's risk acceptance in facial transplantation.

BACKGROUND: A great deal of ethical debate has accompanied the introduction of facial tissue allotransplantation into the clinical arena. Critics contend that the risks of lifelong immunosuppression do not justify the benefits of this new non-life-saving reconstructive procedure, whereas proponents argue that they do. Absent from this debate are the opinions of individuals with real-life experiences with the risks and benefits associated with this new treatment. METHODS: In this study, the authors question facially disfigured individuals (n = 33) and the reconstructive surgeons who treat them (n = 45), organ transplant recipients (n = 42) and the professionals who manage their immunosuppression medication (n = 37), and healthy volunteer controls (n = 148) to determine the amount of risk they are willing to accept to receive facial tissue allotransplantation. A survey with psychometrically reliable and validated questions was administered to the above five groups, and appropriate statistical analysis was used to analyze and compare the data within and between groups. RESULTS: Of the five groups studied, reconstructive surgeons would accept the least amount of risk for a facial tissue allotransplant, followed by transplant specialists, then kidney transplant recipients, then facially disfigured individuals, and finally healthy control volunteers, who would accept the most amount of risk. CONCLUSIONS: The authors' data indicate that reconstructive surgeons are the least tolerant of risks compared with the other groups studied concerning facial tissue allotransplantation. This is particularly important because they are the primary caregivers to facially disfigured patients and, as such, will be the ones to lead the effort to move this new reconstructive treatment into the clinical arena.

Ethical considerations in human facial tissue allotransplantation.

BACKGROUND: Human facial tissue allotransplantation is now a clinical reality. Proponents of this new treatment contend that the benefits outweigh the risks, while the critics argue they do not. This debate has been presented in great detail in the bioethics literature but has not been brought to the attention of the plastic surgery community. METHODS: The purpose of this paper is to provide a synopsis of the key issues being debated in facial transplantation by presenting to the plastic surgery community a synopsis of an ethical debate published in the 2004 summer issue of the American Journal of Bioethics. RESULTS: Presented is a set of ethical guidelines for facial transplantation in the form of a "target article." Alongside this are written commentaries from 15 experts in related fields, along with responses to these commentaries. Together, this discussion makes up a landmark exercise in open display and public and professional discussion and evaluation and serves as a comprehensive list of the major ethical issues being debated today in the field of facial tissue allotransplantation. CONCLUSIONS: Plastic surgeons play a central role in the care of facially disfigured patients and will therefore lead the introduction of facial tissue allotransplantation into the clinical arena. Consequently, it is important that they be aware of, and indeed that they play a key role in forming, the debate surrounding this new treatment. It is with this in mind that we present this synopsis to the plastic surgery readership.

Ethical considerations in face transplantation.

Human face transplantation is now a clinical reality. The surgical techniques necessary to perform these procedures have been used routinely in reconstructive microsurgery for many years. From an immunological standpoint since face and hand contain mostly the same tissues it is reasonable to assume that the same immunosuppressive regimen found to be effective in human hand transplants should also work in face transplantation. It is the ethical issues associated with the risks and benefits of performing facial transplantation that have posed the greatest challenges leading up to performing this new procedure. In this editorial, we will review some of the main events that have led to the recently performed human face transplants, specifically focusing on the key ethical issues at the center of this debate. We will discuss how the research and clinical experience in human hand transplantation laid the foundation for performing face transplantation and describe the research and the ethical guidelines upon which a team at the University of Louisville based their position "to move ahead" in spite of much criticism. Finally we will outline some of the key arguments against face transplantation, and conclude with a discussion on what comes next now that the first human face transplants have been performed.

Risk assessment of immunosuppressive therapy in facial transplantation.

BACKGROUND: Immunosuppression-related risks are foremost among ethical concerns regarding facial transplantation. However, previous risk estimates are inaccurate and misleading, because they are based on data from studies using different immunosuppression regimens, health status of the transplant recipients, tissue composition, and antigenicity. This review provides a comprehensive risk assessment for facial transplantation based on comparable data of immunosuppression, recipient health status, and composition and antigenicity of the transplanted tissue. METHODS: The risk estimates for face transplantation presented here are based on data reported in clinical kidney (10-year experience) and hand transplantation (5-year experience) studies using tacrolimus/mycophenolate mofetil/corticosteroid therapy. Mitigating factors including ease of rejection diagnosis, rejection reversibility, infection prophylaxis, patient selection, and viral serologic status are taken into account. RESULTS: Estimated risks include acute rejection (10 to 70 percent incidence), acute rejection reversibility (approximating 100 percent with corticosteroid therapy alone), chronic rejection (<10 percent over 5 years), cytomegalovirus disease (1 to 15 percent), diabetes (5 to 15 percent), hypertension (5 to 10 percent), and renal failure (<5 percent). CONCLUSIONS: A review of these data indicates that previously reported estimates of immunosuppression-related risks are outdated and therefore should no longer be used. These updated risk estimates should be used by facial transplant teams, institutional review boards, and potential recipients when considering the immunologic risks associated with facial transplantation.

Research and events leading to facial transplantation.

Facial transplantation has long captured the interest and imagination of scientists, the media, and the lay public. Facial transplantation could provide an excellent alternative to current treatments for facial disfigurement caused by burns, trauma, cancer extirpation, or congenital birth defects. This article discusses the major technical, immunologic, psychosocial and ethical hurdles that have been overcome to bring facial transplantation from an idea to a clinical reality by providing the reader with a chronologic overview of the research and events that have led this exciting new treatment into the clinical arena.

Composite tissue allotransplantation of the hand and face: a new frontier in transplant and reconstructive surgery.

Each year an estimated 7-million people in the USA need composite tissue reconstruction because of surgical excision of tumors, accidents and congenital malformations. Limb amputees alone comprise over 1.2 million of these. This figure is more than double the number of solid organs needed for transplantation. Composite tissue allotransplantation in the form of hand and facial tissue transplantation are now a clinical reality. The discovery, in the late 1990s, that the same immunotherapy used routinely in kidney transplantation was also effective in preventing skin rejection made this possible. While these new treatments seem like major advancements most of the surgical, immunological and ethical methods used are not new at all and have been around and routinely used in clinical practice for some time. In this review of composite tissue allotransplantation, we: (i) outline the limitations of conventional reconstructive methods for treating severe facial disfigurement, (ii) review the history of composite tissue allotransplantation, (iii) discuss the chronological scientific advances that have made it possible, (iv) focus on the two unique clinical scenarios of hand and face transplantation, and (v) reflect on the critical issues that must be addressed as we move this new frontier toward becoming a treatment in mainstream medicine.

Risk acceptance in laryngeal transplantation.

PURPOSE: Advancements in the fields of head and neck surgery and immunology have paved the way for new quality of life-improving procedures such as larynx transplantation. To quantitatively assess the risks versus benefits in larynx transplantation, we used a questionnaire-based survey (Louisville Instrument For Transplantation [LIFT]) to measure the degree of risk individuals are willing to accept to receive different types of transplantation procedures. METHODS: The LIFT contains 237 standardized questions incorporating standard gamble and time tradeoff outcome measures as well as questions assessing body image perception, depression, self-esteem, optimism, socially desirable responding, and demographics. Respondents were questioned on the extent to which they would trade off specific numbers of life-years, or sustain other costs, in exchange for receiving seven different types of transplant procedures. For this study, we questioned 243 individuals in three study populations with differing life experiences: healthy individuals, organ transplant recipients, and laryngectomees. RESULTS: All populations questioned perceived risks differently based on their varied life experiences and would accept differing degrees of risk for the different transplant procedures. Organ transplant recipients were the most risk-tolerant group, whereas laryngectomees were the least risk-tolerant. CONCLUSIONS: By questioning individuals with life experiences directly relevant to the risks and benefits associated with larynx transplantation, this study provides an empiric basis for assessing risk versus benefit in this new quality of life-improving procedure.

Investigation of risk acceptance in facial transplantation.

BACKGROUND: The surgical techniques necessary to transplant a human face are well established, and the early success of human hand transplants suggests that the immunological hurdles of transplanting human facial tissues have largely been overcome. Therefore, it is the ethical barriers that pose the greatest challenge to performing facial transplantation. At the center of the ethical debate is the question, "Do the risks posed by the life-long immunosuppression that a recipient would have to take justify the benefits of receiving a face transplant?" In this study, the authors answer this question by assessing the degree of risk individuals would be willing to accept to receive a face transplant. METHODS: To quantitatively assess risks versus benefits in facial transplantation, the authors developed the Louisville Instrument for Transplantation, or LIFT, which contains 237 standardized questions. Respondents in three study populations (healthy individuals, n = 150; organ transplant recipients, n = 42; and individuals with facial disfigurement, n = 34) were questioned about the extent to which they would trade off specific numbers of life-years, or sustain other costs, in exchange for receiving seven different transplant procedures. RESULTS: The authors found that the three populations would accept differing degrees of risk for the seven transplant procedures. Organ transplant recipients were the most risk-tolerant group, while facially disfigured individuals were the least risk tolerant. All groups questioned would accept the highest degree of risk to receive a face transplant compared with the six other procedures. CONCLUSIONS: This study presents an empirical basis for assessing risk versus benefit in facial transplantation. In doing so, it provides a more solid foundation upon which to introduce this exciting new reconstructive modality into the clinical arena.

Risk acceptance in composite-tissue allotransplantation reconstructive procedures.

Composite-tissue allotransplantation (CTA) is a new therapeutic modality to reconstruct major tissue defects of the face, larynx, and extremities. Unlike most life-saving organ-transplantation procedures, CTA is considered to improve quality of life. Therefore, the question arises, do the risks posed by the immunosuppression drugs that patients must take to prevent rejection justify the benefits of these procedures? The purpose of this study was to assess the relative risk that individuals are willing to accept in order to receive the benefits of CTA procedures. We used a psychometrically reliable and valid instrument to question two primary populations of individuals: those who live with the risks of immunosuppression, and healthy individuals. The level of risk acceptance for the seven transplant procedures tested (foot, single hand, double hand, larynx, kidney, hemiface, and full face) showed significant differences in research participants' risk acceptance for the different transplant procedures, but no significant differences between groups. Based on these findings, we conclude that certain CTA procedures convey benefits to recipients that are perceived by subjects, including individuals who live with the risks of immunosuppression, to warrant the risks of these procedures.

A comparison of influences on attitudes towards mental health service use in an African-American and White community.

The purpose of this study was to examine the attitudes toward mental health service (MHS) use within a sample of African-American and White adults (N = 739) and to identify correlates associated with those expressed attitudes. African-Americans (n = 132) and Whites (n = 607) were interviewed using the Louisville Metropolitan Survey that included the Attitudes Toward Seeking Professional Psychological Help Scale. Findings from this study indicated that responses regarding seeking mental health services were positively correlated with educational attainment and gender In addition, further findings also suggested that while race was significantly associated with attitudes toward seeking mental health services, it was also associated with prior familiarity with mental health services African-Americans reported both less willingness to seek mental health services and less familiarity with mental health services. The unexpected finding of the association between familiarity and attitudes toward mental health services use has value in furthering scientific inquiry. Investigation into the role of familiarity with mental health services and the decision-making process leading to mental health services use in diverse populations holds potential.