Faculty Bibliography

PURPOSE/OBJECTIVE:The various physiological profiles comprising vascularized composite allografts (VCAs) pose unique challenges to preservation. Minimizing ischemia, reperfusion injury, and rejection remains a primary focus of graft pretreatments (PTs). Currently, the gold standard PT consists of flushing the graft and placing it in static cold storage in the University of Wisconsin solution. With this method, graft viability is limited to 4 to 6 hours. Prolonging this time limit will increase donor allocation radius, access to care, and positive patient outcomes. We aimed to evaluate novel PTs that could potentially enhance and lengthen VCA viability. METHODS:Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, we conducted a comprehensive literature search of EMBASE, Cochrane, and PubMed. Studies had to be published prior to June 15, 2022. PTs had to target cell physiology, rather than immunogenicity. We extracted data including study design, PT details, evaluation metrics, and outcomes. RESULTS:We identified 13 studies, categorized into 3 groups: solution-based alterations to the gold standard, ex vivo perfusion, and other novel techniques. The incorporation of hydrogen sulfide and Perfadex as solutions in the gold standard protocol demonstrated a 6-day delay in rejection and limited reperfusion injury markers, respectively. In an ex vivo perfusion study, after 24 hours of PT and 12 hours posttransplant, VCA muscle contractility remained close to normal. The gold standard PT did not demonstrate the same success. However, graft weight gain, up to 50% of baseline among the reviewed articles, is a prominent adverse effect of perfusion. Another technique, cryopreservation, displayed 90% graft failure by venous thrombosis, despite high free graft viability following 2 weeks of storage. CONCLUSIONS:This study of PT modalities found a variety of encouraging preservation techniques for grafts with high levels of tissue diversity. Ex vivo perfusion dominated PT innovation with promising results in preserving the viability and functionality of muscle, which is central to the restoration of movement. Future studies are necessary to evaluate long-term graft outcomes and to optimize PT protocols for extended preservation times to ensure clinical relevance.

PURPOSE/UNASSIGNED:There is limited literature reporting swallowing outcomes in the pre- and postoperative period for patients undergoing facial transplantation. This case report aims to utilize a combination of objective and patient-reported outcome measures to highlight swallowing improvements following the world's first face with whole-eye transplantation. METHOD/UNASSIGNED:Outcome measures in jaw range of motion, anterior containment, texture progression, airway protection, and pharyngeal swallow function were collected pretransplantation by two speech-language pathologists (SLPs) and at multiple postoperative visits after the procedure was completed. Specific outcome measures included the Gothenburg Trismus Questionnaire, Maximal Incisor Opening, Modified Teachers Drooling Scale, Functional Oral Intake Scale, Eating Assessment Tool-10, The Penetration-Aspiration Scale, and the Modified Barium Swallow Study Impairment Profile. Measures were then compared over a 1-year time period to assess changes in swallow function. RESULTS/UNASSIGNED:Improvements in jaw range of motion, anterior containment, and airway protection were observed. The patient's stated goal of returning to full PO diet following face transplant was achieved within 1 year. CONCLUSIONS/UNASSIGNED:Swallowing and trismus outcome measures are an important tool for monitoring progress along a patient's recovery journey, especially following unique procedures such as face transplantation. Based on this single patient case study, facial transplantation can lead to improvements in both objective and patient-reported outcomes. Future goals for research should continue to explore this unique population due to the limited literature available for SLPs, as well as include development of valid and reliable assessment tools specific to the face transplantation population.

BACKGROUND:Uterus transplantation (UTx) is the sole clinical treatment for patients with a diagnosis of uterine infertility factor to experience gestation and delivery. Following UTx, candidates who have been largely healthy must agree to extensively interface with the healthcare system and practice strict adherence to an immunosuppressive regimen to protect the allograft until delivery of a live birth. Aside from the risks associated with immunosuppression, UTx recipients often face complicated pregnancies, with a possibility of pregnancy loss and allograft failure. Therefore, appropriate recipient eligibility criteria are central to transplantation success. The objective of this study is to investigate eligibility criteria reported by UTx programs globally. METHODS:A systematic review of UTx literature was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, using PubMed, Cochrane, Ovid/MEDLINE, and Scopus. ClinicalTrials.gov entries and program websites were queried for eligibility criteria as well. RESULTS:Two hundred ninety-six studies were identified, 79 of which were included in the final review. Twenty-one clinical trials and 6 patient-facing websites were included. Most reported eligibility criteria included females of reproductive age, excellent in vitro fertilization candidacy, psychological stability, absence of systemic infection, and willingness to comply with all treatment protocols. The importance of factors such as social support and recipient relationship with their partner varied between centers. CONCLUSION/CONCLUSIONS:Although consensus exists across certain eligibility criteria, the importance of other criteria presents greater ambiguity across centers. As UTx programs expand, and more patients gain access to the procedure, the evolution of eligibility criteria must be documented to optimize best practices across centers.

IMPORTANCE/UNASSIGNED:There is an urgent need for a validated gender-affirming care-specific patient-reported outcome measure (PROM). OBJECTIVE/UNASSIGNED:To field test the GENDER-Q, a new PROM for gender-affirming care, in a large, international sample of transgender and gender diverse (TGD) adults and evaluate its psychometric properties. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This international cross-sectional study was conducted among TGD adults aged 18 years and older who were seeking or had received gender-affirming care within the past 5 years at 21 clinical sites across Canada, the United States, the Netherlands, and Spain; participants were also recruited through community groups (eg, crowdsourcing platform, social media). The study was conducted between February 2022 and March 2024. Participants had to be capable of completing the instrument in English, Danish, Dutch, or French-Canadian. Eligible participants accessed an online REDCap survey to complete sociodemographic questions and questions about gender-affirming care they had received or sought (ie, to look, function, or feel masculine, feminine, gender fluid, or another way). MAIN OUTCOME AND MEASURES/UNASSIGNED:Branching logic was used to assign relevant instrument scales. Rasch measurement theory (RMT) analysis was used to examine the fit of the observed data to the Rasch model for each scale. Test-retest reliability and hypothesis-based construct validity of instrument scales were examined. The hypothesis was that instrument scale scores would increase with better outcomes on corresponding categorical questions. RESULTS/UNASSIGNED:A total of 5497 participants (mean [SD] age, 32.8 [12.3] years; 1837 [33.4%] men; 1307 [23.8%] nonbinary individuals; and 2036 [37.0%] women) completed the field test survey. Participants sought or had the following types of gender-affirming care: 2674 (48.6%) masculinizing, 2271 (41.3%) femininizing, and 552 (10.0%) other. RMT analysis led to the development of 54 unidimensional scales and 2 checklists covering domains of health-related quality of life, sexual, urination, gender practices, voice, hair, face and neck, body, breasts, genital feminization, chest, genital masculinization, and experience of care. Test-retest reliability of the scales (intraclass correlation coefficient [average] >0.70) was demonstrated. Only 1 item (phalloplasty donor flap) had an ICC less than 0.70. As hypothesized, scores increased incrementally with better associated self-reported categorical responses. For example, among 661 participants who reported poor psychological well-being, the mean (SD) scale score was 45 (18) points; for those who reported excellent psychological well-being, the mean (SD) scale score was 85 (16) points (P < .001). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cross-sectional study of 5497 TGD adults, the instrument demonstrated reliability and validity. The instrument was validated in an international sample and is designed to collect and compare evidence-based outcome data for gender-affirming care from the patients' perspective.

BACKGROUND:Vascularized composite allotransplantation (VCA) holds significant promise for patients with complex structural defects, providing solutions unattainable through traditional methods. Despite technical successes, graft rejection and ischemia-reperfusion injury (IRI) present major challenges, with high rejection rates even under modern immunosuppression protocols. This review synthesizes current literature on immunologic pretreatments (IPTs) designed to mitigate these issues, focusing on interventions applied to donor tissues between procurement and transplantation. METHODS:A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines identified 11 relevant studies, categorizing IPTs into donor tissue modification (DTM), deoxygenated perfusate, and oxygenation methods. RESULTS:DTM, the most common IPT method, shows promise in reducing immunogenicity and prolonging graft survival, primarily through techniques such as recipient bone marrow-derived cell conditioning and MHC-I knockdown using small interfering RNA (siRNA). Deoxygenated perfusate studies highlighted mitomycin C's potential in reducing immune response and extending graft viability. Oxygenation methods, aimed at minimizing IRIs, utilized perfusion techniques to maintain graft viability ex vivo. CONCLUSIONS:Although IPTs for extending graft survival have seen moderate clinical translation, those targeting immunogenicity remain largely experimental. This review underscores the potential of these IPT modalities to improve VCA outcomes by reducing rejection and IRIs. However, it also highlights the need for further research, particularly multi-center clinical trials, to validate these techniques for broader clinical adoption. This comprehensive synthesis aims to guide future studies and enhance clinical strategies for VCA, ultimately improving patient outcomes.

BACKGROUND/UNASSIGNED:In vascularized composite allotransplantation, face transplantation stands as a transformative intervention for patients with severe facial disfigurement. Monitoring of graft rejection, however, remains a critical challenge. This study aimed to investigate the role of lymphocyte subsets in the early detection and monitoring of graft rejection in face transplantation. METHODS/UNASSIGNED:We conducted a retrospective chart review of 3 face transplant recipients who underwent face transplantation at our institution. Peripheral blood samples were analyzed for lymphocyte subsets at multiple time points posttransplantation. A linear mixed-effects model was used, aiming to identify any upregulation associated with episodes of graft rejection. RESULTS/UNASSIGNED:= 0.0015, respectively). CONCLUSIONS/UNASSIGNED:Our study demonstrates that monitoring specific lymphocyte subsets offers a promising adjunct for graft surveillance that is less invasive when compared with traditionally used punch biopsies. This approach not only enhances the precision of rejection monitoring but also improves patient comfort and compliance, thereby contributing to better long-term graft outcomes.

IMPORTANCE/UNASSIGNED:Since 2005, a total of 50 face transplants have been reported from 18 centers in 11 countries. The overall survival of the grafts has not yet been established. OBJECTIVE/UNASSIGNED:To assess the survival of the face transplant grafts and evaluate factors potentially influencing it. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Data on all the transplants included in this multicenter cohort study were collected at participating transplant centers for updated nonpublished data, supplemented with literature review for nonparticipating centers. Data from 2005 until September 2023, were included. Data were analyzed from November 11, 2005, through September 18, 2023. Patients included the first 50 patients in the world to have received a face transplant. EXPOSURE/UNASSIGNED:Face transplant graft. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was the overall survival of the face transplant graft, defined as either transplant loss or patient death. The secondary outcome was the number of acute rejection episodes per year. RESULTS/UNASSIGNED:The 50 transplants were performed on 39 men (81%) and 9 women (19%) with a median age of 35 (range, 19-68) years at the time of the transplant. The median follow-up time was 8.9 (range, 0.2-16.7) years. During the follow-up, 6 transplants were lost with 2 patients retransplanted. There were 10 patients who died, 2 of whom had lost a transplant. The 5- and 10-year survival of the transplants was 85% (SD, 5%) and 74% (SD, 7%), respectively. The sequential number of the transplant in the world was a significant predictor of survival (hazard ratio, 95; 95% CI, 90-100; P < 05). The median number of acute rejection episodes per year was 1.2 (range, 0-5.3) for the transplants that were lost and 0.7 (range, 0-4.6) for the transplants that survived. No correlation with patient and transplant variables was detected for either the transplant survival or the number of rejection episodes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, the overall survival of the face transplants is encouraging. These data suggest that the acceptable long-term survival of face transplants makes them a reconstructive option for extensive facial defects.

IMPORTANCE/UNASSIGNED:Catastrophic facial injury with globe loss remains a formidable clinical problem with no previous reports of reconstruction by whole eye or combined whole eye and facial transplant. OBJECTIVE/UNASSIGNED:To develop a microsurgical strategy for combined whole eye and facial transplant and describe the clinical findings during the first year following transplant. DESIGN, SETTING, AND PARTICIPANT/UNASSIGNED:A 46-year-old man who sustained a high-voltage electrical injury with catastrophic tissue loss to his face and left globe underwent combined whole eye and face transplant using personalized surgical devices and a novel microsurgical strategy at a specialized center for vascularized composite allotransplantation. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reperfusion and viability of the whole eye and facial allografts, retinal function, and incidence of acute rejection. RESULTS/UNASSIGNED:The patient underwent a combined whole eye and face transplant from an immunologically compatible donor with primary optic nerve coaptation and conventional postoperative immunosuppression. Globe and retinal perfusion were maintained throughout the immediate postoperative period, evidenced by fluorescein angiography. Optical coherence tomography demonstrated atrophy of inner retinal layers and attenuation and disruption of the ellipsoid zone. Serial electroretinography confirmed retinal responses to light in the transplanted eye. Using structural and functional magnetic resonance imaging, the integrity of the transplanted visual pathways and potential occipital cortical response to light stimulation of the transplanted eye was demonstrated. At 1 year post transplant (postoperative day 366), there was no perception of light in the transplanted eye. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This is the first report of whole eye transplant combined with facial transplant, demonstrating allograft survival including rejection-free graft survival and electroretinographic measurements indicating retinal response to light stimuli. These data highlight the potential for clinical allotransplantation for globe loss.

OBJECTIVE:Facial feminization surgery (FFS) treats gender dysphoria in transfeminine patients by addressing the facial bony and soft tissue components. Individuals seeking FFS may be taking gender-affirming hormone replacement therapy [gender-affirming hormone therapy (GAHT)]. This study aims to better characterize the GAHT's impact on venous thromboembolism (VTE) risk, surgical planning, and outcomes. METHODS:A systematic review and meta-analysis of the literature were carried out to assess the effect of perioperative GAHT continuation on VTE. Cochrane Q and I2 statistics measured study heterogeneity with the following meta-regression exploring these results. Simultaneously, a retrospective review of the senior author's FFS cohort was conducted to investigate GAHT duration's impact on FFS revision rate, complication incidence, and facial structures operated on. RESULTS:Eleven articles were included: 602 patients stopped GAHT, of whom 3 VTEs were recorded (0.49%). This is compared with one episode among the 925 who continued GAHT perioperatively (0.11%). Study heterogeneity was low (0%), but limited VTE sample size precluded meta-analytic conclusions. Gender-affirming hormone therapy duration does not impact the incidence of all-cause complications (P = 0.478), wound infection (P = 0.283), hematoma (P = 0.283), or VTE (P = 1). The only procedures significantly less associated with higher GAHT were tracheal shaving (P = 0.002) and mandibuloplasty (P = 0.003). Finally, the FFS revision rate was not associated with GAHT duration (P = 0.06). CONCLUSION/CONCLUSIONS:There is a paucity of data to assess the safety or harm of continuing GAHT in the FFS perioperative period. Thus, a shared provider-patient decision-making process examining the risks and benefits of GAHT perioperative continuation is warranted. As patients seeking gender-affirming care are diverse, a "one-protocol-fits-all" is not appropriate.