Faculty Bibliography

BACKGROUND/UNASSIGNED:During the last 20 years, the novel and highly visible nature of facial transplantation (FT) has posed a dual and potentially conflicting obligation for FT programs: to disseminate findings for scientific advancement while respecting recipients' preferences for privacy, given the significant public and media attention. The individually identifying nature of FT is not present in other forms of vascularized composite allotransplantation, making it unique. Despite extensive ethical discourse on FT, implications for privacy are largely absent from ethical analyses. METHODS/UNASSIGNED:This conceptual analysis assesses the complex ethical implications associated with privacy in FT and offers guidance to FT programs for navigating concerns related to donors, recipients, and their families. A literature review was performed and supplemented by our institutional experience. RESULTS/UNASSIGNED:Ethical approaches to privacy require balancing the conflicting ethical principles at the center of this dual obligation. Patient-centered strategies should include comprehensive psychological screening to understand patients' goals for care, informed consent that clearly addresses the dissemination of information and media involvement, and control of media coverage until the recipient is ready and willing. Public relations support for recipients has been helpful in our institution's experience. Additional community-based strategies include educational outreach interventions to satisfy public curiosity. CONCLUSIONS/UNASSIGNED:Findings from published reports alongside our institution's experience suggest that a nuanced, multifaceted approach is essential to navigate the ethical complexities of privacy in FT. Aligning key stakeholders to support FT recipients' well-being while maintaining scientific integrity reflects the ethical tension between duties to patients and obligations to advance transplant science.

BACKGROUND/UNASSIGNED:Advancements in surgical techniques and immunosuppressive therapies have transformed care for patients through vascularized composite allotransplantation (VCA). However, lifelong systemic immunosuppression (SI) carries significant risks, specifically during acute rejection (AR), which typically requires increasing SI dosages. Mitigating such risks may be achieved through topical tacrolimus (TT). Although TT shows promise for VCA in preclinical studies, robust clinical data are lacking. This systematic review aims to evaluate the clinical use of TT in VCA. METHODS/UNASSIGNED:A systematic review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines using Cochrane, PubMed, Scopus, and Web of Science. Studies included patients who underwent VCA and received TT treatment. Study details, patient demographics, VCA characteristics, Banff grade, induction and SI maintenance protocols, complications, AR episodes, and treatment plans following these episodes were collected. RESULTS/UNASSIGNED:The search yielded 271 articles; 11 met inclusion criteria, encompassing 15 VCA recipients (mean age 39.9 y). Thirty-two AR episodes were reported; 22 (68.8%) involved TT. TT was mostly used in Banff grade I-II AR episodes. Resolution occurred in 65.5% of TT-treated episodes, though this finding was not statistically significant. TT was frequently used with steroids and adjunct therapies. CONCLUSIONS/UNASSIGNED:This systematic review highlights the potential role that TT may play in mitigating the need for increased doses of SI during AR episodes. As clinical data continue to grow, further research is essential to establish the potential benefits and efficacy of TT use in VCA.

BACKGROUND/UNASSIGNED:Vascularized composite allotransplantation (VCA) restores complex defects when conventional reconstruction is not feasible. However, lifelong immunosuppression introduces substantial risks, including posttransplant malignancies. This study aims to characterize the incidence, timing, management, and outcomes of posttransplant malignancies in VCA recipients to inform future surveillance and management guidelines. METHODS/UNASSIGNED:A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines using PubMed, Scopus, Web of Science, and Cochrane. Eligible studies included patients who underwent VCA and developed a subsequent malignancy. Collected data included demographics, transplant and malignancy details, and survival. RESULTS/UNASSIGNED:Fifteen studies comprising 15 unique VCA recipients were included. Transplants involved the face (37.5%), upper extremity (37.5%), scalp (12.5%), lower extremity (6.25%), and abdominal wall (6.25%). Median time to first malignancy was 1.89 years posttransplant. Across all cases, 24 malignancies were reported, most commonly nonmelanoma skin cancer (60%) and posttransplant lymphoproliferative disorder (33%). Notably, 85% of skin cancers developed at nonallograft sites. Overall survival was 53.3%. All patients with skin cancer alone survived, whereas posttransplant lymphoproliferative disorder carried a 50% mortality rate. Median time from malignancy to death was 5.5 years, and from transplant to death, 10.1 years. CONCLUSIONS/UNASSIGNED:Recipients of VCA demonstrate increased malignancy risk, particularly nonmelanoma skin cancers and lymphoma, with a typical onset of 2 years posttransplant. Dermatologic surveillance focusing on native skin, Epstein-Barr virus viral load monitoring in high-risk recipients, and regular follow-up are essential and may aid early detection.

BACKGROUND/UNASSIGNED:Vascularized composite allotransplantation (VCA) restores form and function in patients with severe disfigurement, yet acute rejection remains common within the first year. In solid organ transplantation, rituximab, a B cell-depleting agent, has been shown to reduce rejection in highly sensitized recipients, and donor-specific antibodies (DSAs) are established biomarkers of rejection. The impact of rituximab and DSAs in VCA remains unclear. This study examined rejection-free survival following rituximab induction and the relationship between positive DSA levels and rejection in VCA recipients. METHODS/UNASSIGNED:This retrospective review analyzed 4 patients who underwent facial transplantation between 2015 and 2023 at our institution. All patients received rituximab and antithymocyte globulin as part of their induction immunosuppression. Rejection-free survival was the primary outcome, with DSA levels assessed at baseline and throughout follow-up. A generalized linear mixed-effects model was used to evaluate the relationship between DSA positivity and rejection. RESULTS/UNASSIGNED:= 0.693). Some patients were DSA-negative during clinical rejection, and some were DSA-positive without signs of rejection. CONCLUSIONS/UNASSIGNED:This is the first study to evaluate rituximab-based induction in a cohort of VCA recipients, demonstrating median rejection-free survival exceeding one and a half years. Although some patients were DSA-positive during rejection episodes, no significant correlation was observed, challenging the predictive value of DSAs as seen in solid organ transplantation and highlighting the need to explore alternative biomarkers for rejection in VCA.

Vascularized composite allotransplantation (VCA) involves immunologically heterogeneous tissues with a high incidence of acute rejection. Reliable and timely detection of rejection onset remains a major unmet challenge in VCA management. This longitudinal exploratory case study assessed blood- and tissue-derived biomarkers for acute rejection monitoring in a full-face and bilateral hand transplant recipient over 4.6 years. Of these biomarkers, donor-derived cell-free DNA (dd-cfDNA) and short tandem repeats (STR) showed trends toward elevated recipient levels during acute rejection, though differences were not statistically significant. CD8⁺ T-cell percentages increased before acute rejection onset, highlighting a temporal association. Anti-angiotensin II type 1 receptor antibody (AT1R-Ab) levels did not differ significantly between acute rejection and non-rejection episodes, possibly due to prophylactic immune cell depletion. While dd-cfDNA and STR levels correlate with rejection episodes and reflect key graft cellular events, CD8⁺ T-cell dynamics demonstrated the strongest temporal association with rejection episodes in this patient, though no biomarker showed statistically significant differences. These exploratory findings support the need for further longitudinal, multi-patient studies to validate emerging biomarkers and refine rejection monitoring strategies in VCA.

BACKGROUND:Facial transplantation offers transformative solutions for patients with severe facial disfigurements. Minimizing ischemia time is critical for preserving tissue viability, and prioritizing facial allograft recovery during multiorgan procurement aims to optimize outcomes. This study evaluates whether prioritizing facial allograft procurement affects the outcomes of non-vascularized composite allotransplantation (VCA) organ transplants. METHODS:This retrospective study analyzed 4 VCA donor recoveries and face transplants at our center. Perioperative data, including operation times, blood pressure, oxygenation, urine output, and blood product administration, were recorded. Donor data were verified using the United Network for Organ Sharing database, institutional records, and data from LiveOnNY and Gift of Life organ procurement organizations to assess recipient and graft survival. RESULTS:Twenty-one allografts (VCAs and organs) were transplanted into 16 patients. The 1-year patient survival rate was 92% (11 of 12) among non-VCA recipients. One patient died during surgery, and 2 patients died more than 3 years after transplantation from unrelated causes. Three non-VCA graft failures occurred within the first year, resulting in an 87% graft survival rate. The median ischemia time for face transplants was 3 hours 18 minutes. Preoperative planning, including cadaveric rehearsals, computerized surgical plans, and 3-dimensionally printed cutting guides, contributed to stable perioperative parameters and reduced blood loss. CONCLUSIONS:This study suggests that prioritizing facial allograft procurement is feasible and does not appear to compromise non-VCA organ transplant outcomes. Further multicenter studies are needed to validate these findings and further refine protocols.

PURPOSE/OBJECTIVE:To describe the first successful whole eye transplantation (WET) in a human, performed with concurrent partial face transplantation, and to characterize postoperative outcomes. DESIGN/METHODS:Case report. PARTICIPANT/METHODS:A 46-year-old male with severe facial and ocular deficits following high-voltage electrical injury, including left eye enucleation and extensive soft tissue and aesthetic deformities. METHODS:Comprehensive preoperative evaluation, precise microsurgical techniques including vascular anastomosis and optic nerve coaptation, and serial postoperative assessments with optical coherence tomography (OCT), fluorescein angiography (FA), electroretinography (ERG), and visual evoked potentials (VEP). MAIN OUTCOME MEASURES/METHODS:Sustained globe viability, vascular perfusion, retinal structural integrity, and electrophysiological function. RESULTS:The transplanted globe demonstrated robust vascular perfusion and structural preservation over 12 months. Outer retinal function was maintained, as indicated by ERG, despite retinal nerve fiber layer loss and optic nerve transection. VEP confirmed absence of visual perception. The procedure achieved substantial aesthetic restoration. CONCLUSIONS:This study establishes the feasibility of WET in humans, with sustained globe viability and preserved outer retinal function. These findings serve as a critical step toward future exploration of ocular transplantation.

INTRODUCTION/UNASSIGNED:Pretransplant access varies, but whether pretransplant steps vary regionally across dialysis facilities remains unclear. METHODS/UNASSIGNED:We identified 62,467 adults (aged 18-80 years) referred from 2471 dialysis facilities and 27,171 initiating transplant evaluation from 2188 facilities in New England, New York, Southeast, and Ohio River Valley within the Early Steps to Transplant Access Registry (E-STAR) (January 1, 2015-December 31, 2023), linked with US Renal Data System (USRDS) and the Scientific Registry of Transplant Recipients data, followed-up through March 2, 2024. We examined dialysis facility-level proportions of evaluation start within 6 months of referral and waitlisting within 1 year of evaluation start. Descriptive statistics using analysis of variance and chi-square tests summarized outcome distributions and baseline characteristics within tertiles of outcome proportions, overall and by region. RESULTS/UNASSIGNED:Evaluation start within 6 months across 2471 facilities varied from 0% to 100%; median within-facility proportion was 50% (interquartile range: 33.3%-64.3%), ranging from 33.3% (18.2%-50%) in the Ohio River Valley to 66.7% (50%-76.7%) in New York. Waitlisting within 1 year of evaluation start varied from 0% to 100% across 2188 facilities; median within-facility proportion was 41.2% (26.0%-60%), lowest in the Southeast (31.9% [20%-43.8%]) and similar across other regions (50%). Facilities in the lowest tertile of evaluation start proportions (< 39.13%) more often treated patients from high-poverty neighborhoods (36.8% vs. 29.2%) and were for-profit (82.4% vs. 73.5%) than the highest tertile (> 58.33%). These characteristics varied by region. Facility-level clustering explained 12.2% (95% confidence interval [CI]: 10.5%-13.5%) of variation in evaluation and 8.2% (6.7%-9.2%) in waitlisting. CONCLUSION/UNASSIGNED:Substantial regional variation in pretransplant access across dialysis facilities reinforces the need for region-specific strategies to improve access.

BACKGROUND:Whole eye transplantation (WET) has long been looked to as a potential solution for the aesthetic and functional deficits caused by severe ocular pathology and trauma. Here, we describe the first successful combined face and whole eye transplantation (FT/WET), highlighting the logistical, ethical, and technical considerations that enabled this milestone. METHODS:A 46-year-old male with severe facial and ocular deficits underwent multidisciplinary evaluation and was deemed a candidate for FT/WET. Subsequently, a surgical algorithm was developed through rigorous preoperative planning and team based surgical simulations. This process focused on techniques that would allow for efficient graft procurement and inset, while simultaneously limiting trauma to the globe and its adnexa. RESULTS:Longitudinal monitoring demonstrated maintained graft viability throughout the postoperative period. Fluorescein angiography and ICG angiography confirmed robust retinal and choroidal perfusion. Diffusion-weighted MRI revealed structural preservation of the optic tracts, despite inner retinal atrophy. The patient has also experienced significant improvement in facial aesthetics and functionality with no episodes of graft rejection to date. CONCLUSIONS:This case demonstrates the feasibility of addressing deficits once deemed irreparable through advanced surgical techniques, preoperative planning, and multidisciplinary collaboration. Although functional vision recovery has not been observed, this innovation expands the reconstructive options available for patients with severe facial and ocular deficits, paving the way for future advancements in vascularized composite allotransplantation.

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.