Facial Allograft Research Articles

Long-term Posttransplant-Related Bone Volumetric Changes in Eight Face Transplant Recipients – a Single Center Retrospective Case Series

BackgroundThe long-term stability of allograft or native bone in facial vascularized composite allograft (fVCA) recipients is unclear. This study quantified long-term bone volume changes in facial transplants MethodsComputed tomography scans of eight fVCA recipients (2011-2023) were analyzed with Materialise Mimics. Native bone (soft tissue-only VCAs, n=4) and allo-transplanted bone (n=4) were compared. Median bone volumes were assessed for significance using the Wilcoxon -Ranked Sum Test. ResultsMean follow up was 10 years (range 5-13). A significant median decrease in both mandibular (-6,520 mm3; p=0.0078) and maxillary (-3,548 mm3; p=0.0078) bone volumes were seen in all patients, irrespective of bone origin. Median bone volume loss was -9.92% in the bony allograft cohort and -22.60% in the soft tissue only cohort, respectively. The histopathological analysis of the limited samples available (n = 2) showed physiological bone even after ten years. ConclusionPatients with allotransplanted bone showed less pronounced volume loss compared to those with native bone receiving soft tissue-only allografts. This finding suggests that allotransplanted vascularized bone in fVCAs may not be a primary target of chronic rejection processes that compromise bone volume stability and functionality. Bone volume changes are likely influenced by multiple factors, such as tooth loss, nutrition, chronic immunosuppression (e.g., steroids), mechanical stress/load, varying bone remodeling rates, and other medical comorbidities. Further research is needed to clarify the factors affecting bone volume and remodeling after fVCA.

Combined Face and Whole Eye Transplantation: Cadaveric Rehearsals and Feasibility Assessment.

In properly selected patients, combined face and whole eye transplantation (FWET) may offer a more optimal aesthetic and potentially functional outcome while avoiding the complications and stigma of enucleation and prosthetics. This study presents the most comprehensive cadaveric assessment for FWET to date, including rehearsal allograft procurement on a brain-dead donor. Over a 2-year period, 15 rehearsal dissections were performed on 21 cadavers and one brain-dead donor. After identification of a potential recipient, rehearsals assessed clinical feasibility and enabled operative planning, technical practice, refinement of personalized equipment, and improved communication among team members. Operative techniques are described. Facial allograft procurement closely followed previously described face transplant techniques. Ophthalmic to superficial temporal (O-ST) vessel anastomosis for globe survival was assessed. Craniectomy allowed for maximal optic nerve and ophthalmic vessel pedicle length. Appropriate pedicle length and vessel caliber for O-ST anastomosis was seen. Research procurement demonstrated collateral blood flow to the orbit and surrounding structures from the external carotid system as well as confirmed the feasibility of timely O-ST anastomosis. Personalized cutting guides enabled highly accurate bony inset. This study formalizes an approach to FWET, which is feasible for clinical translation in judiciously selected patients. O-ST anastomosis seems to minimize retinal ischemia time and allow perfusion of the combined allograft on a single external carotid pedicle. Although restoration of vision likely remains out of reach, globe survival is possible.

Mid-Cheek Reconstruction after a Dog Bite: Case Report and Literature Review

The incidence of animal bite injuries affecting the anatomical regions of the head and neck is notably prevalent, particularly among individuals within the younger demographic. Canine species have been identified as the primary source of the majority of bite injuries in the human population, the spectrum of injuries encompasses a range of traumatic manifestations, which may encompass uncomplicated lacerations or punctures, as well as more complex avulsions characterized by the presence or absence of accompanying tissue. The anatomical regions most frequently affected by the condition under investigation include the buccal region, nasal area, and labial region. The acquisition of comprehensive data regarding the vaccination status of both the animal and the patient is of paramount significance in the realm of medical research. Furthermore, it is imperative to duly administer prophylactic measures such as tetanus or rabies prophylaxis, contingent up on the presence of any indications warranting such interventions. The aforementioned wounds necessitate comprehensive assessment, meticulous cleansing, and, on occasion, surgical debridement or reconstruction within the confines of the operating theater. The selection of the appropriate reparative intervention is contingent upon a comprehensive assessment of the precise anatomical site and magnitude of the inflicted trauma, thereby encompassing a spectrum of potential modalities including primary closure, microsurgical replantation, dermal grafting, tissue flaps, and in rare instances, facial allograft transplantation.

Maximizing Solid Organ and Face Transplant Procurement Team Coordination: The Posterior Tibial Artery Flap as an Ideal Sentinel Flap

Face transplantation became a reality with the first case performed in 2005. Facial tissue allograft procurement is technically complex and time-intensive. Brain-dead deceased donors are frequently, if not always, multiorgan donors. Every effort should be made during face allograft recovery to minimize any risk to the recovery of lifesaving solid organs. Some programs require the procurement of a myofascial vascularized skin graft to function as a sentinel flap allowing frequent monitoring for rejection without negatively impacting the esthetics of the face graft. Up till now, the flap used has been the radial forearm flap. Procuring the radial forearm flap places the procuring team in close proximity to the head and torso, where the face recovery and the solid organ recovery teams would require unhindered access. Here, we present the posterior tibial artery flap as an alternative flap that would provide benefits to the coordination of the multiple teams working to procure organs from a deceased donor.

Sentinel flaps correlate with pro-inflammatory and immunoregulatory mediators of human face transplantation rejection

Abstract Early diagnosis and treatment of immune rejection is critical for face transplants (vascularized composite allografts, VCA). VCA rejection is diagnosed by histologic evaluation of skin biopsies, yet repeated biopsies are a considerable aesthetic problem. Sentinel flaps, fasciocutaneous radial forearm flaps, have been used for remote-site rejection monitoring, but the concordance between tissues during rejection remains unclear. With access to the world’s largest cohort of VCA patients at a single center worldwide, we studied 14 paired skin biopsies from sentinel flaps (SF) and facial allografts (FA) during rejection and non-rejection. We previously identified 15 pro-inflammatory genes (including GZMB, HLA-DPB1, IFNG) and 15 immunoregulatory genes (including SOCS1, CTLA4, IDO1) upregulated in VCA rejection. SF and FA had an average correlation coefficient of 0.88 and 0.76 for pro- and anti-inflammatory gene sets, respectively. During rejection, there was no significant difference in expression of the 15 pro-inflammatory genes between tissue type (SF versus FA), and only one immunoregulatory gene (PDCD1) was significantly different. Across all samples, there were 64 differentially expressed genes (DEG) between rejection and non-rejection, 13 DEG between tissue types, and only 2 DEG when statistically accounting for differences in tissue type driven by rejection status (log2FC>1, p<0.05). High throughput sequencing (HTS) of the CDR3 of TCR-β genes from 4 matched pairs during rejection identified a mean of 9.5 expanded shared T cell clones, indicating that shared antigens drove rejection in both tissues. Together, these data indicate that SF could serve as effective remote-site monitoring for face transplant rejection. NIH T32 Training Grant 2T32AR007098-47 Dept. of Dermatology, Harvard Medical School RT170025 (P.I. Rachael A. Clark) Department of Defense - congressionally Directed Medical Research Programs; "T cells and Rejection in Vascularized Composite Allografts).

Local Delivery of Adipose Stem Cells Promotes Allograft Survival in a Rat Hind-Limb Model of Vascularized Composite Allotransplantation.

Adipose stem cells (ASCs) are a promising cell-based immunotherapy because of their minimally invasive harvest, high yield, and immunomodulatory capacity. In this study, the authors investigated the effects of local versus systemic ASC delivery on vascularized composite allotransplant survival and alloimmune regulation. Lewis rats received hind-limb transplants from Brown Norway rats and were administered donor-derived ASCs (passage 3 or 4, 1 × 10 6 cells/rat) locally in the allograft, or contralateral limb, or systemically at postoperative day 1. Recipients were treated intraperitoneally with rabbit anti-rat lymphocyte serum on postoperative days 1 and 4 and daily tacrolimus for 21 days. Limb allografts were monitored for clinical signs of rejection. Donor cell chimerism, immune cell differentiation, and cytokine expression in recipient lymphoid organs were measured by flow cytometric analysis. The immunomodulation function of ASCs was tested by mixed lymphocyte reaction assay and ASC stimulation studies. Local-ASC-treated recipients achieved significant prolonged allograft survival (85.7% survived >130 days; n = 6) compared with systemic-ASC and contralateral-ASC groups. Secondary donor skin allografts transplanted to the local-ASC long-term surviving recipients accepted permanently without additional immunosuppression. The increases in donor cell chimerism and regulatory T-cells were evident in blood and draining lymph nodes of the local-ASC group. Moreover, mixed lymphocyte reaction showed that ASCs inhibited donor-specific T-cell proliferation independent of direct ASC-T-cell contact. ASCs up-regulated antiinflammatory molecules in response to cytokine stimulation in vitro. Local delivery of ASCs promoted long-term survival and modulated alloimmune responses in a full major histocompatibility complex-mismatched vascularized composite allotransplantation model and was more effective than systemic administration. ASCs are a readily available and abundant source of therapeutic cells that could decrease the amount of systemic immunosuppression required to maintain limb and face allografts.

IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism

Vascularized composite allotransplantation has great potential in face transplantation by supporting functional restoration following tissue grafting. However, the need for lifelong administration of immunosuppressive drugs still limits its wide use. Modified mRNA (modRNA) technology provides an efficient and safe method to directly produce protein invivo. Nevertheless, the use of IL-10 modRNA-based protein replacement, which exhibits anti-inflammatory properties, has not been shown to prolong composite facial allograft survival. In this study, IL-10 modRNA was demonstrated to produce functional IL-10 protein invitro, which inhibited pro-inflammatory cytokines and invivo formation of an anti-inflammatory environments. We found that without any immunosuppression, C57BL/6J mice with fully major histocompatibility complex (MHC)-mismatched facial allografts and local injection of IL-10 modRNA had a significantly prolonged survival rate. Decreased lymphocyte infiltration and pro-inflammatory T helper 1 subsets and increased anti-inflammatory regulatory Tcells (Tregs) were seen in IL-10 modRNA-treated mice. Moreover, IL-10 modRNA induced multilineage chimerism, especially the development of donor Treg chimerism, which protected allografts from destruction because of recipient alloimmunity. These results support the use of monotherapy based on immunomodulatory IL-10 cytokines encoded by modRNA, which inhibit acute rejection and prolong allograft survival through the induction of donor Treg chimerism.

Facial Allograft Donation: An Interpretative Phenomenological Analysis of the Experiences of Family Members.

Facial allograft transplantation can be regarded as a particular and complex type of donation because of its perceptibility and the importance of the face as an identity characteristic. As research on this topic is currently lacking, the objective of this study is to explore the experiences of the family members of the donor in facial allograft donation. In-depth, semi-structured interviews were conducted separately with the donor's family members and analyzed using interpretative phenomenological analysis. Six themes were identified: (1) Contrasting facial donation to that of more commonly donated organs; (2) Consenting to facial donation; (3) Expectations towards the recipient of the facial graft; (4) Expectations and consequences of restoration of the donor's face; (5) Relationship with the medical team during the process; and (6) Media attention. The findings of our study help to better support donor families through the facial donation process and to improve facial transplantation procedures.

Validating a Novel Device to Improve Skin Color Matching for Face Transplants.

A prospective study of 100 individuals was conducted. All participants were photographed and scanned with the Nix Color Sensor. Sixty pairwise comparisons were randomly generated. Skin color analysis was performed using photographs and the Nix Color Sensor. Delta E2000 values were compared to mean evaluator ratings using a Spearman correlation analysis. One hundred patients were included. A Spearman's correlation demonstrated a strong inverse correlation between Delta E2000 values and the mean evaluator ratings. The higher the mean evaluator rating for likeness, the lower the delta. A correlation coefficient of -0.850 demonstrates a statistically significant relationship (P < 0.01). When the Delta E2000 rises above 5 there is a significant drop in the mean evaluator ratings. As mean evaluator ratings of 5 and above would be considered adequate for face transplant amongst most plastic surgeons, an E2000 value of 5 or lower should be targeted when matching donors with recipients for face transplant. The Nix Color Sensor positively correlates to the plastic surgeon's perception of skin color and can serve as an adjunct in donor selection for facial VCAs.

The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism.

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

Software-based Detection of Acute Rejection Changes in Face Transplant.

An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking. A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons. Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79-18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43-21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96-27.28). This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

Facial Transplantation: Principles and Evolving Concepts.

After studying this article, the participant should be able to: 1. Appreciate the evolution and increasing complexity of transplanted facial allografts over the past two decades. 2. Discuss indications and contraindications for facial transplantation, and donor and recipient selection criteria and considerations. 3. Discuss logistical, immunologic, and cost considerations in facial transplantation, in addition to emerging technologies used. 4. Understand surgical approaches and anatomical and technical nuances of the procedure. 5. Describe aesthetic, functional, and psychosocial outcomes of facial transplantation reported to date. This CME article highlights principles and evolving concepts in facial transplantation. The field has witnessed significant advances over the past two decades, with more than 40 face transplants reported to date. The procedure now occupies the highest rung on the reconstructive ladder for patients with extensive facial disfigurement who are not amenable to autologous reconstructive approaches, in pursuit of optimal functional and aesthetic outcomes. Indications, contraindications, and donor and recipient considerations for the procedure are discussed. The authors also review logistical, immunologic, and cost considerations of facial transplantation. Surgical approaches to allograft procurement and transplantation, in addition to technical and anatomical nuances of the procedure, are provided. Finally, the authors review aesthetic, functional, and psychosocial outcomes that have been reported to date.

Successful Treatment of Life-Threatening COVID-19 Infection in a Face Transplant Recipient.

Recent literature suggests that severe COVID-19 is associated with an exaggerated immune response during viral infection, resulting in cytokine storm. Although elevated plasma interleukin 6 (IL-6) has been reported in severe COVID-19 infections, and treatment with anti–IL-6 (tocilizumab) has demonstrated promising outcomes both domestically and abroad, reports remain limited and therapeutic regimens vary considerably. Furthermore, research pertaining to transplant recipients, COVID-19 infection, and anti–IL-6 therapy remains underdeveloped. Herein, we report the successful treatment of the only reported facial vascularized composite allograft (VCA) recipient who contracted severe COVID-19 and the first reported VCA recipient with COVID-19 infection that received anti–IL-6 immunotherapy resulting in an excellent recovery despite his multiple preexisting and COVID-19–related comorbidities—adult respiratory distress syndrome, acute renal failure requiring hemodialysis, and concomitant sepsis due to extensive drug-resistant bacterial pneumonia upon presentation. To date, he has not demonstrated any anti-IL-6 drug-related adverse effects. This preliminary report also suggests that our immunosuppressed VCA patients can indeed demonstrate a robust cytokine response during COVID-19 infection and may also respond favorably to emerging anticytokine immune therapies. We hope that our experience proves helpful to other centers that might encounter critically ill VCA recipients in the ongoing COVID-19 pandemic and in the years to follow.

Neuromotor Speech Recovery Across Different Behavioral Speech Modifications in Individuals Following Facial Transplantation.

Despite signs of facial nerve recovery within a few months following face transplantation, speech deficits persist for years. Behavioral speech modifications (e.g., slower-than-normal speaking rate and increased loudness) have shown promising potential to enhance speech intelligibility in populations with dysarthric speech. However, such evidence-based practice approach is lacking in clinical management of speech in individuals with facial transplantation. Because facial transplantation involves complex craniofacial reconstruction and facial nerve coaptation, it is unknown to what extent individuals with face transplant are capable of adapting their motor system to task-specific articulatory demands. The purpose of this study was to identify the underlying articulatory mechanisms employed by individuals with face transplantation in response to speech modification cues at early and late stages of neuromotor recovery. In addition, we aimed to identify speech modifications that conferred improved speech clarity. Participants were seven individuals who underwent full or partial facial vascularized composite allografts that included lips and muscles of facial animation and were in early (~2 months) or late (~42 months) stages of recovery. Participants produced repetitions of the sentence “Buy Bobby a puppy” in normal, fast, loud, and slow speech modifications. Articulatory movement traces were recorded using a 3D optical motion capture system. Kinematic measures of average speed (mm/s) and range of movement (mm3) were extracted from the lower lip (± jaw) marker. Two speech language pathologists rated speech clarity for each speaker using a visual analog scale (VAS) approach. Results demonstrated that facial motor capacity increased from early to late stages of recovery. While individuals in the early group exhibited restricted capabilities to adjust their motor system based on the articulatory demands of each speech modification, individuals in the late group demonstrated faster speed and larger-than-normal range of movement for loud speech, and slower speed and larger-than-normal range of movement for slow speech. In addition, subjects in both groups showed overreliance on jaw rather than lip articulatory function across all speech modifications, perhaps as a compensatory strategy to optimize articulatory stability and maximize speech function. Finally, improved speech clarity was associated with loud speech in both stages of recovery.

More than skin deep: Mucosal pathology in facial vascularized composite allografts. Commentary on “Pathologies of oral and sinonasal mucosa following facial vascularized composite allotransplantation”

The susceptibility of transplanted mucosa to rejection has been recognized since early in the facial vascularized composite allotransplantation experience (fVCA),1 but the appreciation of mucosal pathologies following face transplantation and the understanding of the pathophysiology and clinical importance of mucosal lesions remain secondary to those of skin.

Public Perceptions of Cross-Sex Vascularized Composite Allotransplantation

Cross-sex vascularized composite allotransplantation has been performed in cadaveric facial transplantation and clinical extremity transplantation. Understanding the challenge of appropriate donor-recipient matching, this study sought to characterize the public's perception of cross-sex vascularized composite allotransplantation. Participants were surveyed in New York City. Data collected included demographics and willingness to donate vascularized composite allografts (VCAs) of various types. Similar questions were asked in the context of same-sex and cross-sex donation. A total of 101 participants (male: 56.4%; age ≤35 years: 62.4%) were surveyed. The majority expressed willingness to donate to recipients of a different sex (hand: 78.2%, face: 56.4%, penis or uterus: 69.3%, lower limb: 81.2%, abdominal wall: 80.2%, larynx: 81.2%, and solid organs: 85.2%). Among VCAs, willingness to donate facial allografts was significantly different in same-sex versus cross-sex contexts (64.4% vs 56.4%; P = 0.008). Participants were also significantly more likely to donate VCAs to same-sex recipients on behalf of themselves versus loved ones (P < 0.05). There was significantly lower willingness to receive cross-sex versus same-sex facial (P = 0.022) and genital allografts (P = 0.022). Education on the preservation of recipient masculinity or femininity in cross-sex facial transplantation increased participants' willingness to receive a cross-sex face transplant from 56.4% to 71.3% (P = 0.001). This study highlights the urban public's acceptance of VCA donation or reception regardless of sex mismatch. There is increased willingness to receive a cross-sex face transplant after education, highlighting opportunities for future focused interventions to increase public awareness and ultimately the donor pool.

Editorial introductions

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Didier A. MandelbrotDidier A. MandelbrotDr Mandelbrot is currently Medical Director of Kidney and Pancreas Transplantation at UW Health and Professor of Medicine at the University of Wisconsin School of Medicine. He was an undergraduate at Harvard College, medical student at the University of Pennsylvania, resident in Medicine at the Hospital of the University of Pennsylvania, and renal fellow at Brigham and Women's Hospital. He has a background in basic transplant immunology and a longstanding interest in the diagnosis and treatment of solid organ rejection. He has participated in numerous single and multi-center clinical trials in kidney transplantation, and has published almost 200 papers and chapters. He has made important contributions on the role of donor-specific antibodies in the context of kidney transplantation, pancreas transplantation and simultaneous liver-kidney transplantation. He also has a particular interest in living kidney donation, and has been active in describing and improving practices in the US. He was co-PI of the NIH-funded Kidney Donor Outcomes Cohort study and recently finished serving as Chair of the American Society of Transplantation's Living Donor Community of Practice. He is currently a member of the United Network of Organ Sharing Medical and Professional Standards Committee, the American Transplant Congress Program Planning Committee, and the Medical Board of the National Kidney Registry. He is an Associate Editor of Clinical Transplantation. Maria SiemionowMaria SiemionowDr Siemionow, a world-renowned scientist and microsurgeon, is Professor of Orthopedics and Director of Microsurgery Research at The University of Illinois at Chicago. She specializes in microsurgery, hand surgery, peripheral nerve surgery, transplantation, and microsurgery research. She is pioneering development of new technology for minimal immunosuppression in transplantation and enhancement of nerve and muscle regeneration. She served as a President of the American Society for Reconstructive Transplantation, President of the International Hand and Composite Tissue Allotransplantation Society and President of the American Society for Peripheral Nerve. She is a member of the academic-industry team, Warrior Restoration Consortium, focusing on development of clinical therapies and new technologies for wounded soldiers as part of the second phase of the Armed Forces Institute for Regenerative Medicine (AFIRM II). She has received numerous honors, including high praise as Principal Investigator for the world's first IRB approval for Facial Allograft Transplantation protocol; in 2008, she led the team that performed the first near-total face transplantation in the United States. Dr Siemionow has over 330 scientific publications. She has edited three plastic surgery textbooks, two popular science books, and has contributed to over 120 published book chapters. Dr Siemionow received numerous awards including the Polish Order of Merit (2009), the Commander's Cross Polonia Restituta Award from the President of Poland (2009), the Outstanding Achievement in Clinical Research Award from the Plastic Surgery Educational Foundation (2010); the 2011 American Society of Plastic Surgeons’ Board of Trustees Special Achievement Award and Casimir Funk National Science Award (2013). In 2014 she received the Great Immigrants Award from the Carnegie Foundation of New York. In 2016 Dr Siemionow was awarded the Heritage Award granted by the Polish American Congress. In 2019 she received Golden Otis Award. Prior to her UIC appointment, she was Director of Plastic Surgery Research and Head of Microsurgical Training for Cleveland Clinic's Department of Plastic Surgery. Jeffery A. KahnJeffery A. KahnDr Jeffrey A. Kahn completed his undergraduate training at the University at Albany, State University of New York, medical school training at the State University of New York, Upstate Medical University and internal medicine residency at Emory University. He then went on to fellowship training in gastroenterology at the University of Southern California and transplant hepatology training at Cedars Sinai-Sinai Medical Center. He has been the medical director of the Keck School of Medicine of USC Liver Transplant Program since 2011, with a special interest in living donor liver transplantation and transfusion-free liver transplantation. His research interests include liver transplant waitlist disparities, liver transplant outcomes and has ongoing translational research related to occult hepatitis C infection.

Facial Transplantation: Complications, Outcomes, and Long-Term Management Strategies.

Within the past two decades, vascularized facial composite allotransplantation has evolved into a viable option in the reconstructive surgeons' armamentarium for patients with extensive facial disfigurements. As it has expanded the frontiers of microsurgical reconstructive techniques, facial transplantation has come to garner widespread interest within both the medical community and the general public. The procedure has established itself as an amalgamation of the forefronts of reconstructive microsurgery, immunology, and transplantation science. Therein too lies its complexity as multifaceted scientific developments are met with ethical and social issues. Both patients and physicians are faced with the everlasting challenges of immunosuppression regimens and their inherent complications, long-term aesthetic and functional considerations, the role of revision procedures, and the inevitable psychosocial implications. This article reflects on the medical and surgical advancements in facial transplantation surgery and highlights anticipated future challenges. It aims to encourage discussion regarding anticipated barriers to current practice and suggest future directions as we transition into the next phase of facial allograft transplantation.

Enhancing Face Transplant Outcomes: Fundamental Principles of Facial Allograft Revision.

Background:Facial transplantation (FT) has become a feasible reconstructive solution for patients with devastating facial injuries. Secondary revisions to optimize functional and aesthetic outcomes are to be expected, yet the optimal timing and approach remain to be determined. The purpose of this study was to analyze all facial allograft revisions reported to date, including the senior author’s experience with 3 FTs.Methods:A literature review was performed, with 2 reviewers independently conducting title and abstract screening, followed by a full-text review. All articles mentioning FT revision surgeries were evaluated. The medical records of the senior author’s 3 FT recipients were additionally reviewed.Results:Initially, 721 articles were captured and 37 were included in the final analysis. Thirty-two FTs were reported to have involved posttransplant allograft revisions, with FT recipients undergoing a mean of 4.8 ± 4.6 revision procedures. The mean duration between FT and the first revision procedure was 149 ± 179 days. A wide spectrum of revisions was identified and categorized as involving the soft tissues, craniofacial skeleton, dentition, oronasal cavity, salivary glands, facial nerve, or ocular region. In the senior author’s experience, when indicated, posttransplant occlusal changes and integrity of the donor–recipient intraoral interface were successfully addressed with secondary procedures without allograft compromise or loss.Conclusions:The worldwide experience shows that secondary procedures are nearly ubiquitous after FT and can be safely performed at various timepoints. The authors thereby establish 5 distinct categories of facial allograft revisions and define 7 critical principles to optimize posttransplant procedures.

Anesthetic Considerations in Facial Transplantation: Experience at NYU Langone Health and Systematic Review.

Background:Anesthetic considerations are integral to the success of facial transplantation (FT), yet limited evidence exists to guide quality improvement. This study presents an institutional anesthesia protocol, defines reported anesthetic considerations, and provides a comprehensive update to inform future directions of the field.Methods:An institutional “FT Anesthesia Protocol” was developed and applied to 2 face transplants. A systematic review of 3 databases captured FTs in the peer-reviewed literature up to February 2020. Two reviewers independently screened titles and abstracts to include all clinical articles with FT recipient and/or donor-specific preoperative, intraoperative, and relevant postoperative anesthetic variables. Data charting guided a narrative synthesis, and quantitative synthesis reported variables as median (range).Results:Our institutional experience emphasizes the importance of on-site rehearsals, anticipation of patient-specific anesthetic and resuscitative requirements, and long-term pain management. Systematic search identified 1092 unique records, and 129 met inclusion criteria. Reports of 37 FTs in the literature informed the following anesthetic axes: donor pre- and intraoperative management during facial allograft procurement, recipient perioperative care, immunotherapy, antimicrobial prophylaxis, and pain management. Quantitative synthesis of 30 articles showed a median operative time of 18 hours (range, 9–28) and fluid replacement with 13 L (5–18) of crystalloids, 13 units (0–66) of packed red blood cells, 10 units (0–63) of fresh frozen plasma, and 1 unit (0–9) of platelets.Conclusions:Anesthetic considerations in FT span the continuum of care. Future efforts should guide standard reporting to establish evidence-based strategies that promote quality improvement and patient safety.