Faculty Bibliography

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.

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.

Radial artery occlusion (RAO), a complication of transradial access, has an incidence of 4.0% to 9.1% in patients with advanced chronic kidney disease (CKD) and may preclude its use creation of arteriovenous fistula. Distal transradial access (dTRA) has lower rates of RAO compared with TRA, but prior studies excluded patients with advanced CKD. This was a single center study of patients with advanced CKD who underwent coronary procedures with dTRA from January 1, 2019 to May 12, 2022 who were retrospectively evaluated for radial artery patency in follow-up with reverse Barbeau testing or repeat access of the artery. Of 71 patients, 66% were on hemodialysis and the remainder had CKD 3 to 5. Access was ultrasound-guided, and all received adequate spasmolytic therapy and patent hemostasis. Proximal radial arteries were patent in 100% of the patients at follow-up. Our data suggest that dTRA is safe for patients with advanced CKD and preserves radial artery patency.

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.