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Reassessing Ethical Considerations in Pediatric Facial Transplantation: Where Are We Now?
Laspro, Matteo; Thys, Erika; Stead, Thor S; Onuh, Ogechukwu C; Wyatt, Hailey P; Gursky, Alexis K; Rodriguez, Eduardo D; Kimberly, Laura L
BACKGROUND/UNASSIGNED:Many strides have been made in the field of vascular composite allotransplantation, and some vascular composite allotransplantation procedures, including upper extremity and facial transplantation, are arguably nearing the standard of care for adult recipients. Although centers devoted to pediatric upper extremity transplantation have been established, very little recent scholarship has addressed the advisability of initiating pediatric facial transplantation (PFTx). METHODS/UNASSIGNED:This conceptual ethical analysis assesses the present risks and benefits associated with PFTx based on a review of the literature combined with our team's clinical experience. RESULTS/UNASSIGNED:Considerations for PFTx include anticipated improvements in quality of life and social integration during a critically important formative developmental phase, ongoing risks associated with immunosuppression and known challenges with nonadherence in adolescent and young adult populations, unknowns about facial growth and continued incorporation of the allograft, the likelihood of need for retransplantation, and issues around decisional capacity and the ability to provide informed consent. CONCLUSIONS/UNASSIGNED:Weighing the risks and benefits of PFTx, particularly the risks associated with long-term immunosuppression and the likely need for retransplantation, we believe that the reservations are such that pediatric patients should not be considered candidates for PFTx at this time.
PMCID:13363335
PMID: 42444768
ISSN: 2169-7574
CID: 6066602
Is There an Increasing Interest in Vascular Composite Allotransplantation? A Search Trends Analysis
Laspro, Matteo; Diaz, Allison L; Gursky, Alexis K; Chinta, Sachin R; Wyatt, Hailey P; Shah, Alay R; Rodriguez, Eduardo D
BACKGROUND/UNASSIGNED:Vascular composite allotransplantation (VCA) offers a surgical option for patients with defects unamenable to standard reconstruction. The most recognized VCA allografts include transplants of the face (FTx), hand (HTx), uterus (UTx), and penis (PTx). As the field evolves, public interest and perception may influence its transition into the standard of care. Formal studies assessing public interest in VCA are limited. Given the public's role as a stakeholder, this study explores global trends in public interest in VCA over time. METHODS/UNASSIGNED:A worldwide Google Trends search was carried out from January 1, 2004, to December 31, 2024. Search terms representing all major VCA allografts were queried to analyze for annual trends. Related terms and queries were captured to examine public associations. PubMed searches for each allograft were conducted through February 3, 2025, to assess scientific interest. RESULTS/UNASSIGNED:Public interest in VCA has generally increased over time, with variation by allograft type. UTx showed the largest increase in Google search volume since 2004, with all allograft types experiencing positive trend lines. UTx received the greatest number of total searches, followed by PTx, FTx, and HTx. PubMed analysis also showed an overall positive increase in publication history across allografts. CONCLUSIONS/UNASSIGNED:Interest across VCA interventions has increased, with variations by allograft type. Media exposure, recipient stories, and outcomes data likely shape these patterns. Future research should seek to determine the drivers of public interest and how to meet their informational needs. As VCA becomes the standard of care, continued public interest will promote donation efforts.
PMCID:13363035
PMID: 42444771
ISSN: 2169-7574
CID: 6066632
A Systematic Review of the Clinical Application of Topical Tacrolimus in Vascularized Composite Allotransplantation
Wyatt, Hailey P; Belisario, Maxwell N; Gursky, Alexis K; Chinta, Sachin R; Shah, Alay R; Gelb, Bruce E; Rodriguez, Eduardo D
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.
PMCID:13363039
PMID: 42444765
ISSN: 2169-7574
CID: 6066572
A Decade of Innovation: A 10-year Institutional Review of Advancements in Vascularized Composite Allotransplantation
Shah, Alay R; Chinta, Sachin R; Tran, David L; Gursky, Alexis K; Ceradini, Daniel J; Rodriguez, Eduardo D
BACKGROUND/UNASSIGNED:Vascularized composite allotransplantation (VCA) has achieved significant advancements in reconstructive surgery through pioneering efforts in face, upper extremity, and whole-eye transplantations. The VCA program at New York University Langone Health has pursued these efforts since its inception in 2013. METHODS/UNASSIGNED:This review documents the evolution of the VCA program, highlighting 4 critical cases that demonstrate the program's innovative approach to surgical challenges and patient care. Each case study reveals the integration of computerized surgical planning, meticulous preoperative preparations, postoperative outcomes, and key institutional metrics. RESULTS/UNASSIGNED:Notable achievements include the first successful combined face and bilateral hand transplantation, and the first combined face and whole-eye transplantation, with improved procedural efficiencies such as reduced hospital and intensive care unit length of stay and operative durations over time. Furthermore, the program's focus on multidisciplinary collaboration has enhanced patient outcomes and operational procedures. CONCLUSIONS/UNASSIGNED:These efforts not only mark significant milestones in VCA but also contribute to the broader surgical and microsurgical fields by refining techniques that minimize resource use and optimize patient recovery and quality of life.
PMCID:13363115
PMID: 42444761
ISSN: 2169-7574
CID: 6066532
Transforming the Face of Medical Education: A 5-year Experience Enhancing an Anatomy Curriculum With the Principles of Facial Transplantation
Alfonso, Allyson R; Wyatt, Hailey P; Gursky, Alexis K; Kantar, Rami S; Oh, So-Young; Harnik, Victoria; Rodriguez, Eduardo D
BACKGROUND/UNASSIGNED:As anatomy curricula in medical schools transition from cadaveric dissection to digital alternatives, medical educators must seek novel strategies to maintain student engagement. To address this challenge, we aimed to integrate an online module and lecture on facial transplantation (FT) into the head and neck anatomy medical school curriculum and assess its effectiveness. METHODS/UNASSIGNED:An online learning module paired with a lecture was created, with shared learning objectives based on the principles of FT. Through multimedia learning, clinically relevant content was used to teach anatomy through surgical videos supplemented with animations. Knowledge assessments followed National Board of Medical Examiners guidelines and were validated by 4 experts. Pre- and posttests evaluated confidence, knowledge, and satisfaction. RESULTS/UNASSIGNED:< 0.001). Students agreed that the module was stimulating, interesting, clear, effective, and allowed for better learning, and stated that they would recommend it to others. Eighty-five percent of students rated the lecture overall as excellent. CONCLUSIONS/UNASSIGNED:FT provides an engaging and effective application for preclinical medical students to integrate curricular content. Involvement of plastic surgeons in the curriculum can create motivating opportunities for students to enhance their medical education and anatomical knowledge, while receiving an early introduction to fundamental principles of plastic and reconstructive surgery.
PMCID:13363126
PMID: 42444769
ISSN: 2169-7574
CID: 6066612
The State of Posttransplant Malignancies in Vascularized Composite Allotransplantation
Gursky, Alexis K; Horn, Allison N; Wyatt, Hailey P; Chinta, Sachin R; Shah, Alay R; Gelb, Bruce E; Ceradini, Daniel J; Rodriguez, Eduardo D
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.
PMCID:13362853
PMID: 42444763
ISSN: 2169-7574
CID: 6066552
Rituximab-based Induction in Vascularized Composite Allotransplantation: Prolonged Rejection-free Survival and the Role of Donor-specific Antibodies
Gursky, Alexis K; Chinta, Sachin R; Wyatt, Hailey P; Shah, Alay R; Lu, Samantha; Mangiola, Massimo; Gelb, Bruce E; Ceradini, Daniel J; Rodriguez, Eduardo D
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.
PMCID:13362945
PMID: 42444766
ISSN: 2169-7574
CID: 6066582
Heterotopic Hindlimb-to-Neck Transplantation in the Mouse: A Supermicrosurgical Model of Vascularized Composite Allotransplantation
Hirayama, Haruyuki; Polak, Lisa; Delliturri, Marisa; Bouaoud, Jebrane; Ceradini, Daniel J; Rabbani, Piul S; Rodriguez, Eduardo D; Lupon, Elise; Lu, Catherine Pei-Ju
Vascularized composite allotransplantation (VCA) is increasingly recognized as a reconstructive option that offers substantial benefits for patients with severe tissue loss, including injuries affecting the face and hand. Despite its clinical promise, VCA remains limited by surgical complexity, the need for long-term immunosuppression, and associated morbidity. Preclinical models are therefore essential for refining surgical techniques, testing novel immunomodulatory approaches, and investigating ischemia/reperfusion injury. Compared with large-animal models, rodent models offer advantages in accessibility and cost while adhering more closely to the 3Rs principles of Replacement, Reduction, and Refinement. Among them, the mouse offers unique advantages, including the availability of humanized strains, a broad panel of well-characterized antibodies, and compatibility with advanced immunological assays. These features make the mouse particularly valuable for translational VCA research. Murine VCA, however, requires demanding supermicrosurgical skills, as vascular anastomoses are performed on vessels measuring approximately 0.3-0.5 mm in diameter. To enhance reproducibility, we provide technical tips that have proven critical to the success of these procedures. These include the insertion of a nylon filament into the vessel lumen to stabilize the anastomosis, careful separation of the artery and vein over a sufficient distance along the pedicle, precise anesthetic dosing, and specific maneuvers to prevent pedicle twisting. We also highlight common pitfalls and errors, offering practical guidance to improve outcomes. Here, we describe a comprehensive, stepwise protocol for mouse heterotopic hindlimb-to-neck transplantation, accompanied by instructional video material. This non-functional model minimizes postoperative morbidity compared with orthotopic transplantation while providing robust and reproducible results. It is ideally suited for training in supermicrosurgery and for addressing key experimental questions in VCA, including immune tolerance, graft preservation, and ischemia/reperfusion mechanisms. This methodology provides investigators with a reliable murine platform to advance translational VCA research and to develop innovative strategies aimed at improving outcomes in reconstructive transplantation.
PMID: 42044141
ISSN: 1940-087x
CID: 6029072
Exploratory biomarkers for acute rejection in vascularized composite allotransplantation
Pullmann, Dominika; Rifkin, William J; Hirayama, Haruyuki; Gelb, Bruce E; Moshiri, Ata S; Mangiola, Massimo; Rodriguez, Eduardo D; Lu, Catherine P; Rabbani, Piul S
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.
PMCID:13079665
PMID: 41993136
ISSN: 2813-2440
CID: 6028202
Outcomes of Multiorgan Donation Recipients following Prioritized Facial Vascular Composite Allograft Procurement
Huang, Ren-Wen; Gelb, Bruce E; Ceradini, Daniel J; Rodriguez, Eduardo D
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.
PMID: 40920479
ISSN: 1529-4242
CID: 6017692