Re-cognizing the new self: The neurocognitive plasticity of self-processing following facial transplantation.

The face is a defining feature of our individuality, crucial for our social interactions. But what happens when the face connected to the self is radically altered or replaced? We address the plasticity of self-face recognition in the context of facial transplantation. While the acquisition of a new face following facial transplantation is a medical fact, the experience of a new identity is an unexplored psychological outcome. We traced the changes in self-face recognition before and after facial transplantation to understand if and how the transplanted face gradually comes to be perceived and recognized as the recipient's own new face. Neurobehavioral evidence documents a strong representation of the pre-injury appearance pre-operatively, while following the transplantation, the recipient incorporates the new face into his self-identity. The acquisition of this new facial identity is supported by neural activity in medial frontal regions that are considered to integrate psychological and perceptual aspects of the self.

Update on long-term mental health outcomes in eight face transplant recipients from a single center.

OBJECTIVE: Face transplantation is a groundbreaking and complex surgical intervention offering profound physical and psychological benefits to patients with severe facial disfigurements. This report provides an update on the long-term psychosocial outcome of eight face transplant recipients. METHOD: All transplant recipients were initially transplanted at Brigham and Women´s Hospital (Boston, USA) between 2011 and 2020 and seen as outpatient patients at Yale New Haven Hospital (New Haven, USA). A mixed-methods approach was used to assess the psychological and social well-being of these patients. The Short-Form 12, Brief-COPE, EQ-VAS and CES-D were administered between October 2022 and October 2023. RESULTS: Older age of face transplant recipients was significantly and positively associated with better mental health and increased use of both emotional and instrumental support (Brief-COPE). The initial enhancement in patients' self-reported quality of life, as assessed by the EQVAS, declined on the EQ-VAS score at the last follow-up. Similarly, an increase in depression score was observed (CES-D score) up through the last follow-up assessment. Both of the latter results, however, did not reach statistical significance. CONCLUSIONS: These results underscore the importance of ongoing psychological support throughout the long-term journey of recovery for face transplant recipients. These findings emphasize the need for a comprehensive, patient-centered approach that also addresses the complex psychological dimensions and contributes to our understanding of the mental health dynamics involved in face transplantation, stressing the need for guidelines and continued research in this evolving field.

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.

Self-Inflicted Gunshot Wound as a Consideration in the Patient Selection Process for Facial Transplantation.

Facial transplantation is emerging as a therapeutic option for self-inflicted gunshot wounds. The self-inflicted nature of this injury raises questions about the appropriate role of self-harm in determining patient eligibility. Potential candidates for facial transplantation undergo extensive psychosocial screening. The presence of a self-inflicted gunshot wound warrants special attention to ensure that a patient is prepared to undergo a demanding procedure that poses significant risk, as well as stringent lifelong management. Herein, we explore the ethics of considering mechanism of injury in the patient selection process, referring to the precedent set forth in solid organ transplantation. We also consider the available evidence regarding outcomes of individuals transplanted for self-inflicted mechanisms of injury in both solid organ and facial transplantation. We conclude that while the presence of a self-inflicted gunshot wound is significant in the overall evaluation of the candidate, it does not on its own warrant exclusion from consideration for a facial transplantation.

Looking the World in the Face: The Benefits and Challenges of Facial Transplantation for Blind Patients

Total bilateral blindness in the setting of facial transplantation is a controversial matter. Some transplant teams exclude these candidates, while others accept them onto their facial transplant waiting list. Using 3 cases, the clinical and ethical complexity of total bilateral blindness is explored. Guidance (medical, psychological, and social) for total bilateral blindness as both an inclusion and exclusion criterion is provided, with the stipulation that total bilateral blindness should not be an automatic exclusion criterion for facial transplantation. Additionally, guidance for corneal transplant in facial transplant candidates is discussed. Suggestions for posttransplant disability assistance for patients with total bilateral blindness are also provided.

Facial transplantation surgery introduction.

Severely disfiguring facial injuries can have a devastating impact on the patient's quality of life. During the past decade, vascularized facial allotransplantation has progressed from an experimental possibility to a clinical reality in the fields of disease, trauma, and congenital malformations. This technique may now be considered a viable option for repairing complex craniofacial defects for which the results of autologous reconstruction remain suboptimal. Vascularized facial allotransplantation permits optimal anatomical reconstruction and provides desired functional, esthetic, and psychosocial benefits that are far superior to those achieved with conventional methods. Along with dramatic improvements in their functional statuses, patients regain the ability to make facial expressions such as smiling and to perform various functions such as smelling, eating, drinking, and speaking. The ideas in the 1997 movie "Face/Off" have now been realized in the clinical field. The objective of this article is to introduce this new surgical field, provide a basis for examining the status of the field of face transplantation, and stimulate and enhance facial transplantation studies in Korea.

Long-term skeletal, cephalometric, and volumetric changes in two Helsinki bimaxillary face transplant patients.

Analysis of skeletal, cephalometric, and volumetric changes and occlusion during long-term follow-up was performed for two patients who underwent bimaxillary facial transplantation (FT). The study material consisted of the follow-up data of two bimaxillary composite FT performed in Helsinki University Hospital, one in 2016 and the other in 2018. Serial three-dimensional computed tomography scans obtained during follow-up (6 years for patient 1, 4 years for patient 2) were analyzed. The position of the maxilla remained stable in both patients. At 4 and 6 years, the changes in the anterior maxilla were ≤1 mm, while the anterior mandible had moved 2.6-4 mm anteriorly and the mandibular midline 0.4-3.7 mm to the left side. Patient 1 underwent re-osteosynthesis 4 months after transplantation due to mandibular non-union. Patient 2 had a sagittal mandibular osteotomy at 15 months after FT due to lateral crossbite and tension created by temporomandibular joint rotation. Thereafter both patients had a stable occlusion. A continuous bone volume reduction in the mandible was noticed in both patients (6% and 9% reduction of the transplanted volume). The volume of the transplanted maxilla decreased during the early postoperative period but increased back to the original transplanted volume during the follow-up.

Review of two immunosuppressants: tacrolimus and cyclosporine.

Immunosuppressants are vital in organ transplantation including facial transplantation (FT) but are associated with persistent side effects. This review article was prepared to compare the two most used immunosuppressants, cyclosporine and tacrolimus, in terms of mechanism of action, efficacy, and safety and to assess recent trials to mitigate their side effects. PubMed and Google Scholar queries were conducted using combinations of the following search terms: "transplantation immunosuppressant," "cyclosporine," "tacrolimus," "calcineurin inhibitor (CNI)," "efficacy," "safety," "induction therapy," "maintenance therapy," and "conversion therapy." Both immunosuppressants inhibit calcineurin and effectively down-regulate cytokines. Tacrolimus may be more advantageous since it lowers the likelihood of acute rejection, has the ability to reverse allograft rejection following cyclosporine treatment, and has the potential to reinnervate nerves. Meanwhile, graft survival rates seem to be comparable for the CNIs. To avoid nephrotoxicity, various immunosuppressants other than CNIs have been studied. Despite averting nephrotoxicity, these medications show increases in acute rejection or other types of adverse effects compared to CNIs. FT has been a topic of interest for oral and maxillofacial surgeons, and the postoperative usage of immunosuppressants is crucial for the long-term prognosis of FT. As contemporary transplantation regimens incorporate novel medications along with CNIs, further research is required.

Correlation between facial vascularized composite allotransplantation rejection and laboratory markers: Insights from a retrospective study of eight patients.

BACKGROUND: The field of facial vascularized composite allotransplantation (fVCA) is still new and a limited number of patients have undergone the procedure. This has led to a lack of understanding about the impact of fVCA rejection on standard laboratory markers (e.g., CBC, BMP, CRP) for the acute management of these patients. It is not clear if rejection elicits a systemic inflammatory response that influences common inflammatory markers such as WBC and CRP. A comprehensive understanding of changes in these markers could help in the management of fVCA patients in the acute setting. METHODS: The medical records of 8 fVCA patients with a total of 9 transplants were reviewed retrospectively, and data on standard laboratory values (CBC, BMP, LFTs, CRP) and vital signs were extracted. To examine the relationship between laboratory values and rejection status, linear mixed models were used to analyze the data, taking into account their longitudinal nature (repeated measures). RESULTS: A statistically significant relationship was found between the Banff grade of rejection and the relative number of basophils in the patient's blood during rejection (p = 0.005). In addition, in patients with clinical signs of rejection (e.g., facial erythema, edema) and skin biopsy showing Banff ≥ II, CRP was found to be significantly elevated (p = 0.03). The WBC count remained stable during rejection, and the relative number of neutrophils was lower at the time of rejection, indicating possible consumption at the site of rejection. CONCLUSION: During fVCA rejection, most standard laboratory parameters and vital signs appear to be stable. However, the levels of CRP and basophils were elevated during rejection, while the neutrophil count was lower. Leukocytosis can likely be used as a marker of microbial infection in fVCA patients, as WBC does not seem to increase at the time of allograft rejection.

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 in vivo. 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 in vitro, which inhibited pro-inflammatory cytokines and in vivo 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 T cells (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.

Longitudinal Recovery of Speech Motor Function Following Facial Transplantation: A Prospective Observational Study.

OBJECTIVES: Although facial transplantation is considered effective for restoring facial appearance, research on speech outcomes following surgery is limited. More research is critically needed to inform patients of expected rates and extent of recovery, and to develop interventions aimed at improving speech outcomes. METHODS: Four patients in early recovery (3 weeks-24 months postsurgery) and three patients in late recovery (36-60 months postsurgery) were included. Clinical measures of speech recovery, including speech intelligibility measured using the Sentence Intelligibility Test, a lip strength testing device (Iowa Oral Performance Instrument), and kinematic measures of lip and jaw function measured using high-resolution 3D optical motion capture were used to describe the rate and extent of functional speech and lip recovery, describe and compare the rate of functional speech recovery and kinematic lip and jaw changes in early and late stages of recovery, and explore the association between kinematic measures and functional speech. RESULTS: Speech intelligibility, speaking rate, and lip strength were below normative values in the first 2 years of postsurgery. Participants in the first 2 years of recovery demonstrated steeper slopes of improvement in clinical and kinematic measures than participants in the later stages of recovery (36-64 months). Gains in jaw range of movement and gains in lip speed and range of movement were significantly correlated with rates of sentence intelligibility improvement. Gains in lip strength were not associated with functional speech improvement. CONCLUSIONS: These findings motivate ongoing work aimed at developing interventions for improving motor speech function in this population. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:2359-2367, 2022.

Facial Transplantation.

Facial transplantation is a vascularized composite allotransplantation, which may be considered in patients with extensive and challenging facial defects for which conventional reconstructive approaches fail to provide satisfactory functional and esthetic outcomes. Facial transplantation has the advantage of replacing defective or absent structures with anatomically identical tissues. Facial transplantation may provide functional, esthetic, and psychosocial benefits, but must be weighed against risks such as lifelong immunosuppression. Success is reliant on patient understanding, motivation, consent and compliance, and a multidisciplinary approach with careful team planning and organization. This review highlights the achievements, challenges, and future directions of this rapidly evolving field.

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.

Pre-transplant management and sensitisation in vascularised composite allotransplantation: A systematic review.

INTRODUCTION: Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody formation and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-transplant management strategies influence immunological outcome following VCA. METHODS: A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-transplant, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis. RESULTS: The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients were sensitised prior to reconstructive transplantation with an 80%%incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies. CONCLUSIONS: Currently employed acute management strategies may predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. To determine whether association between pre-transplant management and outcomes exists, further refinement of international registries is required.

The Helsinki approach to face transplantation.

AIM: We herein describe the establishment of the Helsinki Vascularized Composite Allotransplantation (VCA) program and its execution in the first two face transplant cases. METHODS & PATIENTS: The Helsinki VCA program initially required the fulfillment of legal, hospital, financial, and ethical requirements. Thereafter, the assembling of a multidisciplinary team commenced. A team of Plastic, maxillofacial and ENT surgeons comprise the facial VCA team. The protocol involves collaboration with the Solid Organ Transplant (SOT) team, transplant immunology, immunosuppression, microbiology, psychiatric evaluation, well-defined VCA indications and informed consent. Between 2011 and 2017 two patients were selected for transplantation. Both patients had a severe composite facial deformity involving the maxilla and mandible following earlier ballistic injury. RESULTS: Patient 1 was a 35 year-old male who underwent successful near total face transplantation in February 2016 and at 30 months he has a good aesthetic outcome with symmetrical restoration of the central face and good sensory and symmetrical motor functional outcomes. Patient 2 was a 58 year-old male who underwent full face transplantation in March 2018 and at 5 months he has recovered without major problems. CONCLUSION: A successful facial VCA program requires a well-prepared research protocol, experts from multiple specialties and careful patient selection. The establishment of the Helsinki VCA program required long and thorough planning and resulted in the first two Nordic face transplantation cases. This protocol now forms the platform (as a proof of concept) for other types of vascularized composite allotransplantations.

[A sociological perspective on facial transplant]. / Greffe de visage, regard sociologique.

Is disfigurement a medical or social problem? Trajectories of people in facial surgery services reveal the privilege of normality. Since 2005, four out of ten transplant patients in France have died. In England, a charity campaigns for the right to live with a facial disfigurement.

Long-distance care of face transplant recipients in the United States.

Promising aesthetic and functional outcomes in facial transplantation have fueled the interest of patients and providers alike. However, there are currently only 11 active face transplant centers in the United States, and only five have accumulated operative experience to date, resulting in an extremely unbalanced geographical distribution of providers. Since face transplant recipients must receive life-long follow-up, this presents unique challenges for face transplant candidates and provider teams, as long-distance travel may add considerable difficulty to pre- and post-transplant care. Furthermore, by compromising follow-up, this burden of travel may impact the ability of experienced face transplant centers to collect data, share knowledge as these patients are followed, and continue to advance the field. This article highlights the unique logistical and ethical implications of the highly probable long-distance nature of face transplant care in the United States, a challenging aspect of management that has not been previously discussed in the literature. Furthermore, we review current strategies in the long-distance management of solid organ transplantation (SOT) recipients, and propose several possibilities to help address these challenges in facial transplantation based on SOT experience.

Dental considerations and the role of prosthodontics and maxillofacial prosthetics in facial transplantation.

BACKGROUND: Facial transplantation (FT) is a challenging reconstructive endeavor that requires the expertise of a multidisciplinary team. The specific role of maxillofacial prosthodontists has not yet been reported in detail. METHODS: This review considers the contributions of prosthodontists throughout the FT process, from patient selection and dental evaluation to long-term dental rehabilitation of the transplant patient postoperatively. Moreover, considerations of dental management are evaluated. RESULTS: In the almost 40 FT reported in the literature, the most consistently documented contribution by prosthodontists is the fabrication of a donor mask to maintain donor integrity. Though infrequently reported, prosthodontists have the potential to plan and perform a variety of dental procedures and follow-up plans. CONCLUSIONS: When applicable, facial transplant teams are tasked with providing optimal stomatognathic function and dental occlusion to recipients with severe facial disfigurement. The maxillofacial prosthodontist's contribution is crucial to the long-term dental restoration of the edentulous facial transplant candidate, in addition to the fabrication of the donor mask which fulfills the team's ethical responsibilities. PRACTICAL IMPLICATIONS: Maxillofacial prosthodontists play a pivotal role in facial transplantation, particularly when jaw segments are intended for transplantation.

Preoperative clinical management of patients who are candidates for facial transplantation / Manejo clínico pré-operatório de pacientes candidatos ao transplante facial

Introduction: Face transplantation has gained recognition, changing the clinicalsurgical scenario for restoring complex facial defects, as it attributes functional and aesthetic recovery to patients who have suffered serious accidents. At the time of writing this article, in official publications, 43 patients had already undergone facial transplantation worldwide. Face transplantation has numerous pieces of evidence that can irrefutably provide improvements to the patient. For this, preoperative care for the patient must be carefully established so that there is good surgical performance. Case Report: Male patient, 46 years old, reports that, at the age of 6, he had burns due to exposure to gasoline, with 72% of his body surface burned, showing sequelae of burns and surgical reconstructions on the face, with redundant and ptotic skin flap on the left cheek, absence of upper and lower lip and exposure of lower teeth. Conclusion: It is important to publicize this innovative procedure in different medical specialties and preoperative care through a thorough investigation, which attributes better surgical effectiveness, allowing the rescue of their facial identity, once stigmatized.

Introdução: O transplante de face adquiriu reconhecimento, alterando o panorama clínico-cirúrgico para a restauração de defeitos faciais complexos, visto que atribui recuperação funcional e estética a pacientes que sofreram acidentes graves. Até o momento da redação deste artigo, em publicações oficiais, 43 pacientes já haviam realizado o transplante facial em todo mundo. O transplante de face possui inúmeras evidências que podem fornecer melhorias ao paciente de forma irrefutável. Para isso, cuidados pré-operatórios ao paciente devem ser cuidadosamente estabelecidos para que haja um bom desempenho cirúrgico. Relato de Caso: Paciente sexo masculino, 46 anos, relata que, aos 6 anos de idade, teve queimadura por exposição à gasolina, com 72% de superfície corporal queimada, apresentando sequelas de queimaduras e reconstruções cirúrgicas na face, com retalho cutâneo redundante e ptótico em bochecha esquerda, ausência de lábio superior e inferior e exposição dos dentes inferiores. Conclusão: Ressalta-se a importância da divulgação desse procedimento inovador em diferentes especialidades médicas e dos cuidados pré-operatórios através de uma investigação minuciosa, que atribuem uma melhor eficácia cirúrgica, possibilitando o resgate de sua identidade facial, uma vez estigmatizada.