Daniel J. Ceradini

Vascularized composite allotransplantation (VCA) restores form and function in patients with severe disfigurement, but long-term success remains limited by acute rejection (AR). Most induction protocols emphasize T-cell depletion with antithymocyte globulin (ATG) and corticosteroids. Given the immunogenicity of skin-containing allografts and growing recognition of B-cell contributions to alloimmunity, our institution incorporated rituximab, a CD20-directed monoclonal antibody, into induction therapy. We characterized B- and T-cell reconstitution through the first episode of AR in 4 VCA recipients transplanted at a single institution, all of whom underwent induction with rituximab, ATG, and methylprednisolone, followed by maintenance therapy with tacrolimus, mycophenolate mofetil, and prednisone. Serial peripheral blood samples were analyzed by flow cytometry for absolute counts of CD3+ T cells and CD19+ B cells. All recipients demonstrated near-complete CD19+ B-cell depletion after induction. In Patients 1 to 3, CD19+ counts remained suppressed for ∼200 days; these patients subsequently experienced their first AR on postoperative day (POD) 914, 536, and 282, respectively. Patient 4 demonstrated rapid depletion and persistent suppression of CD19+, remaining rejection-free throughout follow-up. In contrast, CD3+ reconstitution was heterogeneous: Patients 1 and 2 demonstrated gradual recovery, Patient 3 had marked fluctuations, and Patient 4 exhibited persistent suppression. Rituximab-based induction produced durable B-cell depletion across all recipients, while T-cell recovery was heterogeneous and appeared temporally associated with rejection. The absence of rejection in the single recipient with persistently low CD3+ and CD19+ counts suggests that delayed global immune reconstitution may contribute to prolonged graft stability. These observations support longitudinal monitoring of lymphocytes and warrant validation in larger cohorts.

Vascularized composite allotransplantation carries a persistently high burden of acute rejection, and standardized strategies for treatment-refractory disease remain undefined. The authors report the course of a combined face and bilateral hand transplant recipient, transplanted for sequelae of an 80% total body surface area burn, who experienced 11 episodes of acute rejection over ∼4 years despite standard triple immunosuppression and sequential adjunctive therapy with sirolimus and everolimus. Eight episodes were cellular, and 3 met criteria for antibody-mediated rejection on the basis of elevated angiotensin II type 1 receptor (AT1R) antibody rather than donor-specific antibody, which remained undetectable throughout the patient’s course. After exhausting conventional adjuncts, belatacept was added to continued calcineurin-inhibitor therapy. Over the subsequent 26 months, 4 confirmed rejection episodes occurred within the first 9 months, overlapping the loading phase and everolimus withdrawal; no episode thereafter required plasmapheresis, thymoglobulin, or rituximab, and 2 later presentations were ultimately classified as inflammatory rather than confirmed rejection. Simultaneous biopsies of the hand and facial allograft components showed discordant Banff grades, and dermal sclerosis was a recurring histologic finding across the treatment course. Renal function remained stable despite continued calcineurin-inhibitor exposure, and Epstein-Barr virus DNA remained undetectable on serial surveillance despite a donor-positive, recipient-negative serostatus mismatch. This case, among the longer-reported courses of adjunctive belatacept in this population, suggests that costimulation blockade, added to ongoing calcineurin-inhibitor therapy, may reduce the severity and treatment intensity of recurrent rejection in a previously treatment-refractory vascularized composite allograft recipient.

Vascularized composite allotransplantation (VCA) literature has been constrained by incomplete registry reporting, and acute rejection (AR) in skin-containing grafts remains poorly characterized despite its clinical importance. The authors performed a retrospective cohort study using OPTN VCA transplant and follow-up data sets, encompassing the complete available registry history (1998–2025) rather than restricting to the postoversight window used in prior OPTN/SRTR reports. Baseline characteristics were summarized for all 152 VCA recipients (64 uterus, 88 nonuterus), and AR burden, timing, and baseline correlates were analyzed among 87 nonuterus, skin-containing recipients using univariable Cox regression and log-rank testing. Nonuterus transplant activity extended back to 1998, well before formal OPTN oversight began in 2014, and data completeness varied substantially by variable, organ subtype, and era; several key fields, including donor age, diagnosis, race/ethnicity, and blood type, were disproportionately missing among the earliest nonuterus recipients. Among skin-containing recipients with follow-up, 56.5% experienced at least 1 AR episode, with a median time to first rejection of 25 days and frequent recurrence (median 5 episodes per rejector). Rejection incidence and timing varied by graft type, and a higher baseline calculated panel-reactive antibody (cPRA) was associated with earlier first rejection (HR=1.015, P =0.024). These findings demonstrate that the US VCA outcomes are shaped by both heterogeneous, graft-type-specific rejection burden and longstanding gaps in registry reporting. Meaningful comparison across VCA subtypes will require standardized definitions, mandatory reporting, and systematic longitudinal follow-up, particularly for rejection-related and immunologic variables.

Bone-containing facial vascularized composite allotransplantation (VCA) requires precise skeletal reconstruction to restore facial projection, occlusion, orbital support, and the face's structural framework. Virtual surgical planning (VSP) and patient-specific surgical devices facilitate donor-recipient skeletal alignment, but long-term maintenance of the planned skeletal relationships has not been well quantified. We performed a retrospective longitudinal analysis of surface deviations on computed tomography (CT) images in 3 facial VCA recipients with osseous allograft components. For each recipient, early and delayed postoperative CT scans were compared with the final VSP using PROPLAN CMF. The primary outcomes were changes in surface agreement within ±1 mm for upper skull/midface and full mandible; additional skeletal subunits were evaluated as secondary outcomes. Early imaging was obtained at a mean of 23.7 days post-transplantation (range: 2–52 d), and delayed imaging at a mean of 3.12 years (range: 2.02–5.27 y). The mean upper skull/midface agreement was 86.0% at early and 83.0% at delayed follow-up, corresponding to a mean change of −3.0 percentage points (range: −7 to −1). The mean mandibular agreement increased from 50.0% to 57.7%, a mean change of +7.7 percentage points (range: −1 to +13). Secondary regional analyses demonstrated greater heterogeneity among individual skeletal subunits. These findings demonstrate sustained longitudinal concordance between postoperative skeletal position and the original VSP over multiyear follow-up. VSP provides both a reproducible framework for precise osseous reconstruction and a durable reference for longitudinal assessment of skeletal outcomes after facial VCA. Standardized regions of interest and serial imaging protocols will be important for future comparisons across recipients and centers.

Outcome assessment after face transplantation remains heterogeneous, limiting comparison of recovery, patient benefit, and treatment burden across programs. We sought to define a face-specific core outcome set for longitudinal postoperative assessment, informed by the NYU Langone experience and its published outcome literature. We performed a methodological inventory of postoperative assessments used across 4 NYU Langone face transplant recipients treated between 2015 and 2023 and reviewed face-relevant peer-reviewed publications available through September 2026. Recipient-level outcome values were not reanalyzed. Measures were prioritized for clinical relevance, repeatability, and suitability for longitudinal comparison. Twenty-three relevant publications from the NYU program informed the framework. The proposed core outcome set comprises 6 domains: (1) allograft integrity and surgical outcomes; (2) rejection, immunologic surveillance, and immunosuppression-related morbidity; (3) facial sensory and motor recovery; (4) speech, swallowing, and oral function; (5) structural and region-specific facial outcomes; and (6) patient-reported outcomes, rehabilitation, and treatment burden. This face-specific framework provides a clinically focused minimum data set for longitudinal outcome assessment after face transplantation. Consistent use may improve patient tracking and facilitate more meaningful comparison across programs, while prospective multicenter implementation will be necessary to refine and validate the proposed core set.

Many surgical and nonsurgical options are available to patients seeking facial rejuvenation. In this review, we aim to provide an overview of the current trends in facelift and necklift procedures while simultaneously highlighting the utility of nonsurgical treatments. A comprehensive literature review was performed using the PubMed, Google Scholar, and Cochrane Library databases, with the objective of including recent literature published on facelift and necklift procedures from 2015 to 2025. Articles were selected based on relevance, with a specific focus on including a wide breadth of techniques. A considerable body of literature has been published to further classify the soft-tissue anatomy of the face and neck. In particular, these studies focus on the characterization of the three-dimensional anatomy of the facial nerve with emphasis on safe planes of dissection to avoid inadvertent facial nerve injury. The current literature continues to debate both the theoretical and practical advantages and disadvantages of various facelift techniques. Broadly speaking, facelift techniques can be divided into those that manipulate the superficial musculoaponeurotic system (SMAS) layer on its superficial surface and those that undermine the SMAS to varying extents. Numerous approaches are available to improve the contour of the neck and jawline, including manipulation of the platysma muscle and subplatysmal volume reduction. Other surgical procedures and nonsurgical treatments should be considered to optimize and enhance facelift and necklift results. Advancements in patient safety include a focus on minimizing complications while reducing the length of recovery. Facelift and necklift procedures remain the foundational pillars for facial rejuvenation. With attention to patient-specific anatomy, surgeons can work collaboratively with patients to provide global facial optimization by choosing appropriate facelift and necklift techniques in combination with other ancillary procedures. Doing so will deliver enduring, elegant results.

Introduction: The aging neck is a prevalent aesthetic concern, with over 160,000 neck procedures performed in 2020. It is characterized by increased soft tissue laxity and displacement of cervical structures. While nonsurgical interventions like cryoablation and laser resurfacing show promise, their variable responses highlight the necessity for surgical solutions. Traditional neck lifts address superficial structures but often neglect the subplatysmal plane. Recently, deep plane neck lifts have gained attention for addressing deeper anatomical structures. This paper systematically reviews the literature on subplatysmal modifications in cervicoplasty, aiming to clarify the risks and benefits of these evolving surgical techniques. Methods: On February 20, 2024, a systematic review adhering to Preferred Reporting Items for Systematic Review and Meta-Analyses 2020 guidelines was performed. MEDLINE, PubMed, Cochrane, and Scopus databases were searched for terms related to neck rejuvenation. Independent reviewers screened titles, abstracts, and full texts, including all relevant studies. Data extracted included patient numbers, procedures, outcomes, and complications. Results: From an initial 771 articles, 57 studies encompassing 8648 patients met inclusion criteria. The most commonly altered anatomical structures during “deep plane” neck lift (DPNL) were the submandibular gland (69.9%), digastric muscles (58.6%), and subplatysmal fat (48.6%). Postoperative complications were reported in 59.6% of studies, with nerve palsy (0.2%–12%) and hematoma (0.2%–4%) being most common. Aesthetic outcomes were less frequently reported (56% of studies); patient satisfaction ranged from 81.6% to 98.6%, while objective measures were reported in only 12% of studies. Conclusions: Recent surveys indicate a growing concern over excess laxity under the chin, with patients increasingly seeking neck rejuvenation. Our review found that DPNL techniques vary widely, with the submandibular gland and digastric muscles being the most frequently altered structures. Despite a general lack of standardized outcome measures, patient satisfaction was high. However, DPNL showed a higher rate of postoperative nerve palsy compared to traditional neck lift. Overall, while DPNL demonstrates potential aesthetic benefits, the increased risk necessitates thorough patient counseling and further studies for standardization and comparison.

Background.: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens. Methods.: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling. Results.: Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5, CD8A, KLRK1, and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention. Conclusions.: The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation.