Public attitudes to xenotransplantation: A national survey in the United States.

Xenotransplantation (XTx) presents a potential clinical alternative to the shortage of human organs for transplantation. Before clinical trials occur in the United States, public assessments are crucial to understand potential barriers to acceptance. The purpose of this study was to explore barriers and identify characteristics associated with attitudes toward XTx. A survey assessing demographic characteristics and attitudes toward XTx was distributed to a nationally representative sample of adults aged ≥18 years in the United States. Regression analysis was employed to identify characteristics associated with attitudes toward XTx. Between May 25 and June 14, 2023, 5008 respondents completed the survey. Importantly, half of the respondents expressed low or no knowledge of either transplantation or XTx. Approximately 40% expressed discomfort with receiving a pig organ for themselves or a loved one. Despite a lack of xenotransplant outcome data, 36% were open to experimental XTx if they needed a transplant. However, 57% rated lack of current evidence of success or fear of complications as top concerns. Regression models consistently associated being younger, female, not needing an organ, or being a member of a racial minority group with lower acceptance. This survey is the largest to date exploring public attitudes toward XTx. Despite overall acceptance, concerns persist. Increasing public acceptance is key as the field advances.

First-in-Human Whole-Eye Transplantation: Ensuring an Ethical Approach to Surgical Innovation.

As innovations in the field of vascular composite allotransplantation (VCA) progress, whole-eye transplantation (WET) is poised to transition from non-human mammalian models to living human recipients. Present treatment options for vision loss are generally considered suboptimal, and attendant concerns ranging from aesthetics and prosthesis maintenance to social stigma may be mitigated by WET. Potential benefits to WET recipients may also include partial vision restoration, psychosocial benefits related to identity and social integration, improvements in physical comfort and function, and reduced surgical risk associated with a biologic eye compared to a prosthesis. Perioperative and postoperative risks of WET are expected to be comparable to those of facial transplantation (FT), and may be similarly mitigated by immunosuppressive protocols, adequate psychosocial support, and a thorough selection process for both the recipient and donor. To minimize the risks associated with immunosuppressive medications, the first attempts in human recipients will likely be performed in conjunction with a FT. If first-in-human attempts at combined FT-WET prove successful and the biologic eye survives, this opens the door for further advancement in the field of vision restoration by means of a viable surgical option. This analysis integrates recent innovations in WET research with the existing discourse on the ethics of surgical innovation and offers preliminary guidance to VCA programs considering undertaking WET in human recipients.

A Comparison of Immunosuppression Regimens in Hand, Face, and Kidney Transplantation.

BACKGROUND: Authors have speculated that vascularized composite allotransplantation (VCA) recipients may require greater maintenance immunosuppression than solid organ transplant (SOT) recipients due to the higher antigenicity of skin. However, detailed comparisons of VCA and SOT immunosuppression regimens have been limited. METHODS: Hand and face VCA recipient immunosuppression data were collected through a systematic literature review. Kidney recipient data were obtained through a retrospective chart review of the authors' institution. Prednisone and mycophenolate mofetil (MMF) doses were compared between VCA and kidney recipients at predefined follow-up intervals (<1, 1-5, and >5 y). Tacrolimus target trough levels (TTTL) were compared at follow-up intervals of 1-5 and >5 y, and stratified into our institution's kidney transplant risk-based target ranges (4-6 ng/mL, 6-8 ng/mL) or higher (>8 ng/mL). RESULTS: Immunosuppression data were available for 57 VCA and 98 kidney recipients. There were no significant differences in prednisone doses between groups at all follow-up intervals. VCA recipient mean MMF dose was significantly greater at <1-y (1.71 ± 0.58 versus 1.16 ± 0.55 gm/d; P = 0.01). For VCA recipients, there was a significant difference (P = 0.02) in TTTL distribution over the three predefined therapeutic ranges (4-6 ng/mL, 6-8 ng/mL, and >8 ng/mL) between 1 and 5 y (24.0%, 20.0%, 56.0%, respectively) and >5 y (28.6%, 42.9%, 28.6%). CONCLUSIONS: At longer follow-up, VCA and kidney recipients receive comparable MMF/prednisone doses, and most VCA recipients are treated with TTTL similar to kidney recipients. Further research may improve our understanding of VCA's complex risk/benefit ratio, and enhance informed consent.

The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects.

Over 115 000 people are waiting for life-saving organ transplants, of whom a small fraction will receive transplants and many others will die while waiting. Existing efforts to expand the number of available organs, including increasing the number of registered donors and procuring organs in uncontrolled environments, are crucial but unlikely to address the shortage in the near future and will not improve donor/recipient compatibility or organ quality. If successful, organ bioengineering can solve the shortage and improve functional outcomes. Studying manufactured organs in animal models has produced valuable data, but is not sufficient to understand viability in humans. Before risking manufactured organ experimentation in living humans, study of bioengineered organs in recently deceased humans would facilitate evaluation of the function of engineered tissues and the complex interactions between the host and the transplanted tissue. Although such studies do not pose risk to human subjects, they pose unique ethical challenges concerning the previous wishes of the deceased, rights of surviving family members, effective operation and fair distribution of medical services, and public transparency. This article investigates the ethical, legal and social considerations in performing engineered organ research on the recently deceased.

Equity in access to facial transplantation.

We examine ethical considerations in access to facial transplantation (FT), with implications for promoting health equity. As a form of vascularised composite allotransplantation, FT is still considered innovative with a relatively low volume of procedures performed to date by a small number of active FT programmes worldwide. However, as numbers continue to increase and institutions look to establish new FT programmes, we anticipate that attention will shift from feasibility towards ensuring the benefits of FT are equitably available to those in need. This manuscript assesses barriers to care and their ethical implications across a number of considerations, with the intent of mapping various factors relating to health equity and fair access to FT. Evidence is drawn from an evolving clinical experience as well as published scholarship addressing several dimensions of access to FT. We also explore novel concerns that have yet to be mentioned in the literature.

Equitable access to ectogenesis for sexual and gender minorities.

As the technology for ectogenesis continues to advance, the ethical implications of such developments should be thoroughly and proactively explored. The possibility of full ectogenesis remains hypothetical at present, and myriad concerns regarding the safety and efficacy of the technology must be evaluated and addressed, while pressing moral considerations should be fully deliberated. However, it is conceivable that the technology may become sufficiently well established in the future and that eventually full ectogenesis might be deemed ethically acceptable as a reproductive alternative to gestation within a human womb under certain circumstances. If the safety and efficacy of full ectogenesis are established, if ethical dilemmas are sufficiently well addressed, and if the technology is offered as a reproductive option to cisgender heterosexual individuals or couples desiring to become parents, there is a moral obligation grounded in social justice to ensure that full ectogenesis be made available to individuals or couples identifying as members of sexual- or gender-minority groups who likewise seek to pursue parenthood. We examine the history of access to current family-building options, including assisted reproductive technology, surrogacy and adoption, for these populations and conclude that in the absence of robust empirical evidence suggesting an increased risk of harm to children of individuals and couples who identify as members of sexual- or gender-minority groups, equitable access to ectogenesis as a pathway to parenthood for sexual and gender minorities must be assured as a matter of reproductive justice.

Analysis of spin in the reporting of studies of topical treatments of photoaged skin.

BACKGROUND: Spin-reporting that distorts the interpretation of results-is not unusual within scientific literature. OBJECTIVE: To appraise strategies of spin among placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. METHODS: A systematic review of the literature was performed to identify placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. A survey of spin strategies was developed and applied to the cohort of identified studies. RESULTS: The systematic review led to the identification of 20 studies in which various types of spin strategies, broadly classified as either inappropriate statistical analyses or inappropriate interpretation of results, were used. The most commonly used strategies included use of multiple primary outcomes (95%), inappropriate extrapolation of results from specific outcomes to global improvements (95%), focus on within-group comparisons (75%), and focus on interim analyses to give more weight to nonsignificant findings (65%). LIMITATIONS: Classification of spin strategies was subjective and might not encompass all the methods used in the published literature. CONCLUSION: Findings in this study inform efforts to reduce spin in the dermatologic literature.

Uterus transplantation in women who are genetically XY.

Uterus transplantation is an emerging technology adding to the arsenal of treatments for infertility; specifically the only available treatment for uterine factor infertility. Ethical investigations concerning risks to uteri donors and transplant recipients have been discussed in the literature. However, missing from the discourse is the potential of uterus transplantation in other groups of genetically XY women who experience uterine factor infertility. There have been philosophical inquiries concerning uterus transplantation in genetically XY women, which includes transgender women and women with complete androgen insufficiency syndrome. We discuss the potential medical steps necessary and associated risks for uterus transplantation in genetically XY women. Presently, the medical technology does not exist to make uterus transplantation a safe and effective option for genetically XY women, however this group should not be summarily excluded from participation in trials. Laboratory research is needed to better understand and reduce medical risk and widen the field to all women who face uterine factor infertility.

Comprehensive Assessment of Vascularized Composite Allotransplantation Patient-Oriented Online Resources.

INTRODUCTION: Online resources have become a major source of medical information for the general public. To date, there has not been an assessment of patient-oriented online resources for face and upper extremity transplantation candidates and patients. The goal of this study is to perform a comprehensive assessment of these resources. METHODS: Our analysis relied on 2 dimensions: comprehensiveness and readability. Comprehensiveness was evaluated using 14 predetermined variables. Readability was evaluated using 8 different readability scales through the Readability Studio Professional Edition Software (Oleander Software, Ltd, Vandalia, Ohio). Data were also collected from solid organ transplantation (SOT), specifically kidney and liver, programs for comparison. RESULTS: Face and upper extremity transplantation programs were significantly more likely to list exclusion criteria (73.9% vs 41.2%; P = 0.02), the need for life-long immunosuppression (87.0% vs 58.8%; P = 0.02), and benefits of transplantation (91.3% vs 61.8%; P = 0.01) compared with SOT programs. The average readability level of online resources by all face and upper extremity transplantation programs exceeded the sixth grade reading level recommended by the National Institutes of Health and the American Medical Association. The average reading grade level of online resources by these programs was also significantly higher than those of SOT with both exceeding the recommended reading level (13.95 ± 1.55 vs 12.60 ± 1.65; P = 0.003). CONCLUSIONS: Future efforts in face and upper extremity transplantation should be directed toward developing standardized, comprehensive, and intelligible resources with high-quality content and simple language.

Women's Experiences and Perceptions of Depression in India: A Metaethnography.

In India, social determinants of health, including poverty, domestic violence, and inadequate social support disproportionately affect women, leaving them more vulnerable to depression than men. We conducted a metaethnography to synthesize qualitative data from 13 studies (1987-2017) that explored women's experiences and perceptions of depression in India. We used a feminist standpoint to critically examine how gender shapes these experiences and perceptions. Indian women's experiences of depression were embedded in their social worlds. Women perceived interpersonal conflict, caregiving burden, domestic violence, financial insecurity, adverse reproductive events and widowhood as causes of depression. Women used cultural expressions to describe physical, emotional, and cognitive distress. The detrimental impact of discriminatory social conditions, gender inequalities, and traditional gender roles on Indian women's mental health highlights the need for gender-sensitive mental health research and practice that can attend to women's sociocultural context and promote values of gender equality and social justice.

The Ethics of Psychosocial Assessment in Vascularized Composite Allotransplantation: A Call for Transparency of Process to Support the Equitable Selection of Patients.

As the field of vascularized composite allotransplantation (VCA) continues to evolve and technological approaches improve, VCA programs must focus on promoting greater consistency in psychosocial assessment across programs to support the equitable selection of patients. Based on a summary of published reports of VCA, we address the ethical considerations raised by the present heterogeneity of approaches to psychosocial assessment, including weighing risks and benefits, informed consent and the role of decisional capacity, and potential or perceived bias in the assessment process. We propose transparency of process across the field and encourage VCA programs to work collaboratively to share approaches to psychosocial assessment both pre- and post-transplant to promote health equity.

Self-Inflicted Gunshot Wound as a Consideration in the Patient Selection Process for Facial Transplantation.

Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.

Perceived Esthetic Outcomes of Face Transplantation: A Survey of the General Public.

Facial transplantation (FT) has attracted the interest of individuals with facial disfigurement as a path to social reintegration. The perception among face transplant recipients and the reconstructive surgery community appears to be that superior functional and esthetic outcomes can be obtained with FT compared to autologous reconstruction (AR). Although lifelong immunosuppression adds well-known risks to FT, its benefits have proven difficult to quantify, especially because of its non-life-saving nature. Evidence that the general public perceives facial allograft recipients as less disfigured than AR patients may dramatically alter the currently accepted risk/benefit ratio of this novel procedure. A survey containing independent images of individuals in nondisfigured (ND), autologous facial reconstruction, and FT groups was administered to the general public in an urban environment. Participants assigned a disfigurement score to each photograph using the Observer-Rated Facial Disfigurement Scale, a validated instrument used to rate facial disfigurement among head and neck cancer patients. One-way analysis of variance was used to calculate differences in mean level of perceived facial disfigurement among the 3 groups. A total of 250 participants completed the survey. Mean perceived disfigurement scores assigned to the ND, FT, and AR groups were 1.2 ±â€Š0.4, 4.9 ±â€Š1.3, and 8.5 ±â€Š0.6, respectively. A significant difference in disfigurement score was observed between all 3 groups (P < 0.001). This pilot study suggests that the general public perceives the esthetic outcome of FT to be superior to those obtained with AR in patients with severe facial defects.

Incorporating Trauma-informed Approaches to Care in Vascularized Composite Allotransplantation.

Since 1998, vascularized composite allotransplantation (VCA) has been a growing area of research in the field of reconstructive surgery. Although conditions treated with VCA often result from a traumatic injury, there has been limited emphasis on incorporating trauma-informed care (TIC) models in VCA. Considering the importance of psychosocial well-being in VCA candidates and recipients, applying best practices in TIC to the face, upper extremity, and penile transplantation may be critical in minimizing retraumatization throughout the perioperative process. There are six main principles of TIC: safety; trustworthiness and transparency; peer support; collaboration and mutuality; empowerment and choice; and cultural, historical, and gender issues, which may be further incorporated in care for VCA patients. Evaluating for PTSD and incorporating TIC may have substantial benefit to postoperative outcomes.

A Delphi Panel Study for Public Education about Vascularized Composite Allograft Donation in the United States.

Introduction: Improving public awareness about the opportunity to become a vascularized composite allograft (VCA) donor is crucial to increasing access to organs. Prior research identified a need for comprehensive and comprehensible public education materials. A 2-round Delphi panel was conducted to garner US expert consensus on the topics and language to include in public education materials via an organ procurement organization-hosted website. Methods: The round 1 survey assessed the importance of educational topics and statements (n = 19) using 5-point Likert scales. The round 2 survey asked experts to rate new and repeated educational topics (n = 27). Open-ended comment boxes elicited experts' feedback and language revisions for educational statements. Responses were analyzed using descriptive statistics and rapid qualitative analysis. Findings: Eighteen experts responded to the round 1 survey and 15 to round 2. After round 2, 20 topics had mean (M) importance greater than neutral (M > 3.00) and were retained in the educational materials. The 5 most important topics by mean Likert ratings were: consent process for donation (M = 4.73), potential recipients (M = 4.73), most common vascularized composite organs transplanted (M = 4.47), purpose (M = 4.47), and definition (M = 4.47). Seven themes emerged from experts' open-ended comments about the importance and language of educational statements. Conclusions: Delphi panel findings identified expert-endorsed topics and educational statements for public education about vascularized composite organ donation via an educational website. Future research should assess the website's impact on public knowledge of VCA donation.

Older Adults' Lived Experience of Kidney Transplantation.

BACKGROUND AND OBJECTIVES: The United States is witnessing a rapid increase in kidney transplantation (KTx) among adults aged 65 and older. Despite this demographic shift, older adults' perspectives on KTx remain notably absent from the discourse on transplant policy and practice, and very little research has examined older adults' perceptions and experiences of KTx. RESEARCH DESIGN AND METHODS: Employing a phenomenological approach, this study explored the lived experiences of 10 KTx recipients aged 65 and older. Fifteen in-depth interviews were conducted, and analyses followed the processes of phenomenological reduction, imaginative variation, and synthesis. RESULTS: Participants reported experiencing an initial disruption of their sense of embodied identity that ranged from mildly unsettling to deeply distressing. However, they described navigating this "liminal" period and eventually incorporating the donor kidney into their sense of embodied self. Notably, most participants viewed their older age as protective and reported that their lived experience over time enabled them to cope more effectively with the challenges they faced during the posttransplant recovery and adaptation period. DISCUSSION AND IMPLICATIONS: Findings from this study can inform more equitable and age-responsive KTx policy, research and clinical practice and may be extended beyond KTx to other forms of solid organ transplantation, vascularized composite allotransplantation, and innovative bioengineered organs.

Technical Feasibility of Whole-eye Vascular Composite Allotransplantation: A Systematic Review.

There are over 43 million individuals in the world who are blind. As retinal ganglion cells are incapable of regeneration, treatment modalities for this condition are limited. Since first incepted in 1885, whole-eye transplantation (WET) has been proposed as the ultimate cure for blindness. As the field evolves, different aspects of the surgery have been individually explored, including allograft viability, retinal survival, and optic nerve regeneration. Due to the paucity in the WET literature, we aimed to systematically review proposed WET surgical techniques to assess surgical feasibility. Additionally, we hope to identify barriers to future clinical application and potential ethical concerns that could be raised with surgery. Methods: We conducted a systematic review of PubMed, Embase, Cochrane Library, and Scopus from inception to June 10, 2022, to identify articles pertaining to WET. Data collection included model organisms studied, surgical techniques utilized, and postoperative functional outcomes. Results: Our results yielded 33 articles, including 14 mammalian and 19 cold-blooded models. In studies performing microvascular anastomosis in mammals, 96% of allografts survived after surgery. With nervous coaptation, 82.9% of retinas had positive electroretinogram signals after surgery, indicating functional retinal cells after transplantation. Results on optic nerve function were inconclusive. Ocular-motor functionality was rarely addressed. Conclusions: Regarding allograft survival, WET appears feasible with no complications to the recipient recorded in previous literature. Functional restoration is potentially achievable with a demonstrated positive retinal survival in live models. Nevertheless, the potential of optic nerve regeneration remains undetermined.

Social support criteria in vascularized composite allotransplantation versus solid organ transplantation: Should the same ethical considerations apply?

The field of vascularized composite allotransplantation (VCA) is evolving, with some procedures poised to transition from highly experimental research toward standard of care. At present, the use of social support as an eligibility criterion for VCA candidacy is at the discretion of individual VCA programs, allowing VCA teams to consider the unique needs of each potential candidate. Yet this flexibility also creates potential for bias during the evaluation process which may disproportionately impact members of certain communities where social configurations may not resemble the model considered "optimal." We examine the extent to which ethical considerations for social support in solid organ transplantation (SOT) may be applied to or adapted for VCA, and the ethically meaningful ways in which VCA procedures differ from SOT. We conclude that VCA programs must retain some flexibility in determining criteria for candidacy at present; however, considerations of equity will become more pressing as VCA procedures evolve toward standard of care, and further empirical evidence will be needed to demonstrate the association between social support and post-operative success. The field of VCA has an opportunity to proactively address considerations of equity and justice and incorporate fair, inclusive practices into this innovative area of transplantation.