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.

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.

The Lived Experience of Pediatric Gene Therapy: A Scoping Review.

Little is known about patients' and families' lived experiences of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients' and caregivers' perceptions and experiences of social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to (1) provide an overview of existing literature, (2) identify gaps and areas for further research, and (3) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. Four themes emerged, including (1) weighing risks and benefits (2) timing of GT trial participation, (3) value of clear communication, and (4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT-their understanding of its safety, efficacy, and risks-rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations' efforts to develop educational materials tailored to patients' and families' expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.

Gender-affirming hysterectomy in the United States: A comparative outcomes analysis and potential implications for uterine transplantation.

PURPOSE: Hysterectomy is a gynecological procedure sometimes performed as part of the gender-affirming process for transgender and gender-expansive patients assigned female at birth. Our goal was to compare surgical outcomes between patients undergoing gender-affirming hysterectomy and patients undergoing hysterectomy for benign menstrual disorders. We then explored the implications of gender-affirming hysterectomy for uterine transplantation. METHODS: We performed a retrospective cohort study using data from the American College of Surgeons National Surgical Quality Improvement Program database from 2009 through 2018. We identified patients undergoing hysterectomy in the United States based on Current Procedural Terminology code. We used the International Classification of Diseases 9 or 10 codes to identify patients with benign menstrual disorders (non-gender-affirming group) and gender dysphoria (gender-affirming group). We compared patient characteristics and surgical complications. RESULTS: Of the 40,742 patients that met inclusion criteria, 526 (1.3%) patients were individuals with gender dysphoria. Compared to patients who underwent hysterectomy for benign menstrual disorders, gender-affirming patients were younger, were healthier, had a lower prevalence of diabetes, and were more likely to undergo surgery in the outpatient setting, with shorter time to discharge. Complication rates were similar between groups. Logistic regression controlling for the American Society of Anesthesiology classification determined the difference of return to the operating room was not statistically significant (OR 1.082; 95% CI, 0.56-2.10; p = 0.816). CONCLUSION: Gender-affirming hysterectomy has a safety profile similar to hysterectomy performed for benign menstrual disorders. Researchers should further explore the possibility of uterus donation among these patients as they may be suitable candidates.

Should BMI Help Determine Gender-Affirming Surgery Candidacy?

Use of body mass index (BMI) as a health care metric is controversial, especially in candidacy assessments for gender-affirming surgery. When considering experiences of fat trans individuals, it is important to advocate for equitable divisions of responsibility for and recognition of systemic fat phobia. This commentary on a case suggests strategies for increasing equitable access to safe surgery for all body types. If surgeons use BMI thresholds, simultaneous effort must be made to advocate for data collection so that surgical candidacy criteria are evidence-based and equitably applied.

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.

Navigating the Expanded Access Pathway to Investigational Drugs as an Academic Oncologist.

This qualitative study explores academic oncologists' needs and satisfaction with expanded patient access to investigational drugs.

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.

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.

Perspectives of Academic Oncologists About Offering Expanded Access to Investigational Drugs.

Importance: The expanded access (EA) pathway permits patients to be treated with investigational medical products outside clinical trials. Because cancer care is a common indication for which EA is sought and these efforts require physician management, understanding oncologists' perspectives can help illuminate factors influencing patient access. Objective: To learn how oncologists practicing at academic medical centers (AMCs) perceive EA and their role in offering it. Design, Setting, and Participants: This qualitative study used data from semistructured interviews conducted from February 2020 to September 2021 with a purposive sample of oncologists recruited from large, urban AMCs in the northeast United States. Oncologists who had submitted at least 1 single-patient EA request to the institutional review boards at the University of Pennsylvania, Children's Hospital of Philadelphia, NYU Langone Health, and Dana-Farber Cancer Institute from January 1, 2014, through January 31, 2020, were eligible to participate. Data were analyzed from July 2021 to March 2022. Main Outcomes and Measures: Interviews focused on oncologist practice demographics, experience with EA, factors relevant to decisions to pursue EA and comfort with those decisions, perspectives on oncologists' role in EA, perspectives on the FDA's role, and the Right to Try pathway to access investigational drugs. Results: Eligible oncologists were interviewed until thematic saturation was reached, resulting in 25 interviews; most participants were women (15 participants [60%]), reported primarily treating adult patients (15 participants [60%]), had more than 10 years of clinical experience (16 participants [64%]), and had submitted at least 2 single-patient EA requests to their institutional review boards during the relevant period (14 participants [56%]). Oncologists viewed EA as an important tool for securing what they determined to be the best treatment option for their patients based on their own expert assessment of available data. Interviewees reported that they would rather access interventions as commercially available products or through clinical trials; however, if the preferred option was not available through these means, they viewed pursuit of EA as part of their obligation to patients, while often recognizing the potential for inequities in the broader patient population beyond their institutions. Participating oncologists felt confident pursuing investigational drugs for treatment use, despite the absence of FDA marketing approval, and did not necessarily view EA as a last resort. Conclusions and Relevance: These findings indicate that oncologists practicing in large academic settings sought to treat patients with the interventions they deemed most likely to be beneficial, regardless of approval status. As such, they viewed EA as an unexceptional means to obtain promising products, although it remains unclear whether their confidence in evaluating investigational treatments was justified. Future research should examine whether oncologists outside large AMCs share this confidence, as differences may influence patient access to the EA treatment pathway.

Recognizing Racial Disparities in Postoperative Outcomes of Gender Affirming Surgery.

Purpose: Given the increasing frequency with which gender affirming surgery (GAS) is performed, understanding risk factors for poor outcomes is imperative. Recent investigations highlight inferior health outcomes experienced by Black transgender and gender expansive (TGE) individuals. Herein, we evaluate the relationship between race and postoperative outcomes in TGE patients undergoing GAS, utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Methods: We conducted a retrospective review of ACS NSQIP from 2010 to 2018. Patients with a primary diagnosis of gender dysphoria undergoing GAS were identified and grouped by race. Patient characteristics and 30-day postoperative outcomes were recorded. Univariate analysis was used to compare patient characteristics and postoperative outcomes across groups. Multivariate logistic regression was used to determine independent predictors of complications. Results: We included 2308 patients (1780 White, 419 Black, 109 Asian). Gender, body mass index, smoking status, and type of surgery performed differed significantly between groups (p < 0.001). Univariate analysis revealed significant differences in 30-day readmission and organ space surgical site infection (SSI) across groups (p = 0.03). Multivariate logistic regression, adjusted for confounders, revealed that Black patients had higher odds of reoperation (odds ratio [OR] 1.82, p = 0.047), 30-day readmission (OR 2.46, p = 0.003), and organ space SSI (OR 4.65, p = 0.024) than White patients. Conclusion: We found that race was an independent predictor of important short-term postoperative outcomes in GAS. Inclusive clinical research, effective engagement with the TGE community, and surgery-specific enhanced recovery after surgery protocols may help address disparities, but we must acknowledge race as a social determinant of health.

Trends, Gaps, and Collaboration in Facial Transplantation: A Bibliometric Study.

Facial transplantation (FT) has advanced extensively over the past two decades, with over 40 transplants performed to date. Over this time, the FT literature has evolved as well, from early discussions on ethics and feasibility of FT to functional outcomes reports more recently. We aimed to evaluate the entire body of FT literature to identify trends in publications over time in addition to current existing gaps in the field. Methods: We conducted a comprehensive bibliometric analysis of the published FT literature from 1994, the first year FT was mentioned in the literature, through July 2020. Co-authorship and keyword information were analyzed using VOSviewer. Articles were manually categorized based on keywords and their aim to provide insight on trends. Results: A total of 2182 articles were identified. Analysis identified the top 50 publishing authors in the field and demonstrated co-authorship linkage between 84.8% of the top 1000 authors. Clinical surgical techniques, protocols, and experiments were the most frequently published category. Within clinical outcomes, immunologic outcomes were most frequent, while psychosocial were the lowest. Gaps were identified in long-term outcomes reporting and patient-reported outcomes, with physician-reported outcomes heavily outweighing patient-reported outcomes. Conclusions: As the field continues to evolve, rigorous tracking of publication patterns over time will encourage development of a more robust evidence base, identify gaps in the published literature, and highlight opportunities to enhance collaboration in the field. This data will provide surgeons and research institutions with information to further improve this life-changing procedure.

"Postulating Penis: What Influences the Interest of Transmasculine Patients in Gender Affirming Penile Reconstruction Techniques?"

BACKGROUND: The limitations of metoidioplasty and phalloplasty have been reported as deterrents for transgender and other gender expansive individuals (T/GE) desiring gender affirming surgery, and thus penile transplantation, epithesis, and composite tissue engineering (CTE) are being explored as alternative interventions. AIM: We aim to understand the acceptability of novel techniques and factors that may influence patient preferences in surgery to best treat this diverse population. METHODS: Descriptions of metoidioplasty, phalloplasty, epithesis, CTE, and penile transplant were delivered via online survey from January 2020 to May 2020. Respondents provided ordinal ranking of interest in each intervention from 1 to 5, with 1 representing greatest personal interest. Demographics found to be significant on univariable analysis underwent multivariable ordinal logistic regression to determine independent predictors of interest. OUTCOMES: Sexual orientation, gender, and age were independent predictors of interest in interventions. RESULTS: There were 965 qualifying respondents. Gay respondents were less likely to be interested in epithesis (OR: 2.282; P = .001) compared to other sexual orientations. Straight individuals were the least likely to be interested in metoidioplasty (OR 3.251; P = .001), and most interested in penile transplantation (OR 0.382; P = .005) and phalloplasty (OR 0.288, P < .001) as potential interventions. Gay and queer respondents showed a significant interest in phalloplasty (Gay: OR 0.472; P = .004; Queer: OR 0.594; P = .017). Those who identify as men were more interested in phalloplasty (OR 0.552; P < .001) than those with differing gender identities. Older age was the only variable associated with a decreased interest in phalloplasty (OR 1.033; P = .001). No demographic analyzed was an independent predictor of interest in CTE. CLINICAL IMPLICATIONS: A thorough understanding of patient gender identity, sexual orientation, and sexual behavior should be obtained during consultation for gender affirming penile reconstruction, as these factors influence patient preferences for surgical interventions. STRENGTHS AND LIMITATIONS: This study used an anonymous online survey that was distributed through community channels and allowed for the collection of a high quantity of responses throughout the T/GE population that would otherwise be impossible through single-center or in-person means. The community-based methodology minimized barriers to honesty, such as courtesy bias. The survey was only available in English and respondents skewed young and White. CONCLUSION: Despite previously reported concerns about the limitations of metoidioplasty, participants ranked it highly, along with CTE, in terms of personal interest, with sexual orientation, gender, and age independently influencing patient preferences, emphasizing their relevance in patient-surgeon consultations. A. Parker, G. Blasdel, C. Kloer et al. "Postulating Penis: What Influences the Interest of Transmasculine Patients in Gender Affirming Penile Reconstruction Techniques?". J Sex Med 2022;19:385-393.

Navigating Evolving Ethical Questions in Decision Making for Gender-Affirming Medical Care for Adolescents.

As more young people feel safe to outwardly identify as transgender or gender expansive (TGE), meaning that their gender identity does not align with the sex they were assigned at birth, an increasing number of youth who identify as TGE seek gender-affirming medical care (GAMC). GAMC raises a number of ethical questions, such as the capacity of a minor to assent or consent, the role of parents or legal guardians in decisions about treatment, and implications for equitable access to care when differing parental or custodial viewpoints are present. These questions are further complicated by the difficulties in explaining the limits of long-term research in GAMC, with regard to the preservation of fertility, for example. We present two de-identified composite case studies to highlight dilemmas that may arise and offer recommendations to better support patient- and family-centered decision making for GAMC. These include employing a multidisciplinary shared decision-making approach, disentangling informed consent and assent from chronological age, developing a consistent approach to the assessment of decisional capacity, and developing age-appropriate informational materials.

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.

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.