Software-based video analysis of functional outcomes of face transplantation.

INTRODUCTION: Assessment of outcomes after face transplantation (FT) is necessary to provide sound evidence on the benefits of this life-giving surgery. Current methods for outcomes assessment, however, are imprecise or prone to subjectivity. Software-based video analysis may allow fast, objective and retrospective assessment of restoration of facial movements and functions after FT. PATIENTS AND METHODS: We recorded videos of 7 subjects before as well as every 3-6 months after facial transplantation. Patients performed the same sequence of facial movements in every video: smile, open mouth, purse lips, wrinkle nose, frown, close eyes, and lift eyebrows. The videos were retrospectively analyzed using EMOTIENT software, which is capable of automatic tracking and detailed measurements of facial movements and expressions. These measurements were subsequently compared to the same patient at different time points, as well as to the normal population. RESULTS: Open mouth, wrinkle nose and smile functions significantly improved in all patients when compared to pre-transplant functions; this improvement was significant at 3, 6, and 12 months after transplant, respectively. Lip purse, eye closure and frown functions improved by 6, 9, and 18 months after transplantation, respectively; however, improvement in these particular functions was not significantly with respect to pre-transplant. Face transplantation did not improve any of the patients' ability to lift their eyebrows. Most remarkably, mouth opening and smiling functions both reached values comparable to the normal population at 3 and 12 months after transplantation, respectively. CONCLUSION: Software-based video analysis provides a valuable assessment tool capable of objective, precise and reproducible analysis of facial movements and functions after FT.

Reduced Hypoxia-Related Genes in Porcine Limbs in Ex Vivo Hypothermic Perfusion Versus Cold Storage.

BACKGROUND: Ischemia-reperfusion injury remains the major limiting factor for limb replantation and transplantation. Static cold storage (SCS) on ice currently represents the standard mode of preservation but is limited to 6 h of duration. Ex vivo machine perfusion has evolved as a potential alternative to safely extend the duration of ex vivo preservation by providing continuous supply of oxygen and nutrients. This study aims to evaluate underlying molecular mechanisms of both preservation modalities. METHODS: We assessed molecular changes in amputated porcine forelimbs stored on ice at 4°C for 2 h (n = 2) and limbs perfused with Perfadex solution at 10°C for 2 h (n = 3) or 12 h (n = 3) before replantation. Muscle biopsies were examined for histological changes and gene expression levels using H&E staining and a hypoxia-related PCR gene array, respectively. RESULTS: Histology revealed only minor differences between the ice (SCS) and perfusion groups after 2 h of preservation, with decreased muscle fiber disruption in the perfusion groups compared with the ice (SCS) group. Perfused limbs demonstrated downregulation of genes coding for glycolytic pathways and glucose transporters after 2 h and 12 h when compared with SCS after 2 h. Similarly, genes that induce angiogenesis and those that are activated on DNA damage were downregulated in both perfusion groups as compared with SCS. CONCLUSIONS: Perfusion of porcine limbs resulted in less activation of hypoxia-related gene families when compared with SCS. This may indicate a state more closely resembling physiological conditions during perfusion and potentially limiting ischemic injury. Our study confirms ex vivo perfusion for up to 12 h as a viable alternative for preservation of vascularized composite tissues.

Face transplantation-current status and future developments.

More than thirty-five facial allograft transplantations (FAT) have been reported worldwide since the pioneering case performed in France in the year 2005. FAT has received tremendous interest by the medical field and the general public while gaining strong support from multiple disciplines as a solution for reconstructing complex facial defects not amenable/responsive to conventional methods. FAT has expanded the frontiers of reconstructive microsurgery, immunology and transplantation, and established its place in the cross section of multiple disciplines. The procedure introduces complex scientific, ethical, and societal issues. Patients and physicians are called to deal with a variety of-sometimes everlasting-challenges, such as immunosuppression management and psychosocial hurdles. This review reflects on the surgical and scientific advancements in FAT and milestones reached in the last 12 years. It aims to encourage active discussion regarding the current practices and techniques used in FAT and suggest future directions that may allow transitioning into the next phase of FAT, which we describe as safe, reliable, and accessible standard operation for selected patients.

Trismus in Face Transplantation Following Ballistic Trauma.

BACKGROUND: Trismus can be a challenging consequence of ballistic trauma to the face, and has rarely been described in the setting of face transplantation. Almost half of all current face transplant recipients in the world received transplantation to restore form and function after a ballistic injury. Here we report our experience and challenges with long standing trismus after face transplantation. METHODS: We reviewed the medical records of our face transplant recipients whose indication was ballistic injury. We focused our review on trismus and assessed the pre-, peri- and postoperative planning, surgery and functional outcomes. RESULTS: Two patients received partial face transplantation, including the midface for ballistic trauma. Both patients suffered from impaired mouth opening, speech intelligibility, and oral competence. Severe scarring of the temporomandibular joint (TMJ) required intraoperative release in both patients, and additional total condylectomy on the left side 6 months posttransplant for 1 patient. Posttransplant, both patients achieved an improvement in mouth opening; however, there was persistent trismus. One year after transplantation, range of motion of the jaw had improved for both patients. Independent oral food intake was possible 1 year after surgery, although spillage of liquids and mixed consistency solids persisted. Speech intelligibility testing showed impairments in the immediate postoperative period, with improvement to over 85% for both patients at 1 year posttransplant. CONCLUSIONS: Ballistic trauma to the face and subsequent reconstructive measures can cause significant scarring and covert injuries to structures such as the TMJ, resulting in long standing trismus. Meticulous individual planning prior to interventions such as face transplantation must take these into account. We encourage intraoperative evaluation of these structures as well as peri- and postoperative treatment when necessary. Due to the nature of the primary injury, functional outcomes after face transplantation in these patients may differ substantially from those of other indications.

Experience With Patient Referrals for Upper Extremity Transplantation at a U.S. Academic Medical Center.

PURPOSE: To date, there have been over 100 upper extremity transplantations (UET) performed worldwide. However, little data are available regarding institutional screening practices or description of the population of patients that seek transplantation as a treatment modality for their upper extremity disabilities. We performed a review of our institutional experience in an attempt to better understand our referral patterns and identify factors that may be associated with successful screening. METHODS: Contact demographic data, injury characteristics, and mode of referral were retrospectively reviewed from 2010 through 2015. Differences in demographic data, injury-related characteristics, and clinical trial outcomes were assessed with the Chi-square test or Fisher exact test. RESULTS: There were a total of 89 UET contacts. The average age was 35.2 years, with most contacts being white (n = 24). The majority were male (n = 66; 75.0%) and the most common indication for referral was trauma (n = 43; 55.8%). Of the 89 contacts, 20 (22.5%) were physician referrals and 69 (77.5%) were self-referrals. Physician referrals led to the most screened and accepted contacts, whereas self-referrals more often led to immediate exclusion. CONCLUSIONS: This study gives an overview of the demographic composition of our UET contacts, with a specific emphasis on mode of referral. We have identified that physician referrals have led to more screened and accepted patients versus self-referred individuals. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

Long-Term Effects of the Collagenase of the Bacterium Clostridium histolyticum for the Treatment of Capsular Fibrosis After Silicone Implants.

BACKGROUND: Capsular contracture remains the most frequent long-term complication after augmentation mammoplasty with silicone implants. Thereby, the main part of the fibrotic capsule is collagen. The collagenase of the bacterium Clostridium histolyticum is approved for the treatment of fibrotic diseases and has been demonstrated to be effective for capsular fibrosis treatment in the short term. However, long-term effectiveness is currently unknown but mandatory for clinical utilization. MATERIALS AND METHODS: Forty-eight rats received miniature silicone implants and an injection with either collagenase (treatment group) or plain solvent solution (control group) 120 days post insertion. Ten and 60 days after the injections, the rats underwent 7-Tesla magnetic resonance imaging (MRI) and high-resolution ultrasound (HR-US). Capsule tissue was harvested, and capsule thickness and collagen density were evaluated through histology. Furthermore, the expression levels of inflammatory (CD68, IL4, IL10, IL12, IL13), pro-, and anti-fibrotic (TGFb1, TGFb3, Smad3, Col1-4) genes were analyzed using qRT-PCR. RESULTS: On days 10 and 60 after injection of collagenase, histology showed that capsule thickness was significantly reduced in the treatment group when compared with the control (p < 0.05). Thickness measurements were verified by MRI and HR-US analysis. Skin perforation occurred in two cases after collagenase injection. The initial up-regulation of pro-fibrotic and inflammatory genes 10 days after collagenase injection did not persist in the long term. Contrarily, on day 60, a slight trend towards lower expression levels with a significant down-regulation of TGFb3 was detected in the treatment group. CONCLUSION: The collagenase of the bacterium C. histolyticum effectively degrades capsular fibrosis around silicone implants with stable outcomes throughout 60 days post injection. Skin perforation and adequate and uniform drug distribution within the implant pocket are issues that need to be addressed. Further studies are warranted to clarify whether collagenase injections have the potential to become a viable treatment option for capsular contracture. NO LEVEL ASSIGNED: This journal requires that authors 46 assign a level of evidence to each article. For a full 47 description of these Evidence-Based Medicine ratings, 48 please refer to the Table of Contents or the online 49 Instructions to Authors. www.springer.com/00266 .

Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration.

The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation (VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes.

A Mobile Extracorporeal Extremity Salvage System for Replantation and Transplantation.

BACKGROUND: Traumatic amputation is the second leading cause of limb loss in the United States. The preferred treatment is salvage and replantation of the amputated limb, whenever possible, and allotransplantation is a novel procedure whereby healthy limbs are procured from deceased organ donors and transplanted into the amputee recipient. A major restriction for both procedures is the irrecoverable muscle damage occurring due to ischemia. We investigated the feasibility of using a novel lightweight, mobile perfusion device specifically designed to perfuse amputated porcine limbs with an acellular perfusion solution to delay ischemic muscle damage prior to transplantation or replantation. METHODS: Bilateral hind limbs of Yorkshire pigs were amputated; one of the limbs was preserved by perfusion in the mobile perfusion device, and the other by storage in ice slurry for 12 hours. RESULTS: Five sets of bilateral limbs were preserved as described previously. A defined pressure of 30 mm Hg was reliably maintained in the arterial system without loss of flow. Comparison of the perfusate composition before and after limb passage revealed significant differences. Muscle biopsies showed a consistent progression of clusters of hypoxic cells in the control limbs with time. Similar changes could not be observed in the perfused tissue. CONCLUSIONS: We have designed and built a small, mobile perfusion device that is operational and that more closely mimics the normal physiological environment when compared with the current standard of preservation in ice slurry. This project may have far-reaching implications for the treatment of limb loss through replantation and transplantation.

Surgical Optimization of Motor Recovery in Face Transplantation.

BACKGROUND: Face transplantation (FT) has emerged as a viable option for treating devastating facial injuries. Most reported outcomes have demonstrated satisfactory motor and sensory restoration despite differences in technique. The authors have developed an algorithm of facial nerve management in these challenging patients. Our principles of management are illustrated by 2 specific patients. METHODS: A retrospective analysis of prospectively collected data on 2 full face transplants was performed. Both patients required nerve grafting during full FT. Patient 1 due to short donor facial nerve stumps and patient 2 due to intraoperative soft tissue swelling. Patient 2 required a nerve transfer 11 months after full FT due to impaired motor recovery opposite the side of nerve grafting. Follow-up examinations consisting of manual muscle testing and Sunnybrook Facial Grading System 6 to 42 months after full FT with selected video examinations were critically reviewed. RESULTS: Patient 1 had symmetrical motor recovery with gradual improvements noted throughout. At 6 months, Patient 2 had asymmetrically improving motor function. After nerve transfer, the patient showed gradual improvement in motor recovery, symmetry, and tone. Videos for each patient demonstrate the evolution of the patients' ability to smile from 6 to 42 months. DISCUSSION: The authors describe their assessment of motor recovery and management of facial nerve reconstruction as it pertains to FT. Finally, the authors illustrate the principles of nerve transfer are applicable to FT recipients.

Three patients with full facial transplantation.

Unlike conventional reconstruction, facial transplantation seeks to correct severe deformities in a single operation. We report on three patients who received full-face transplants at our institution in 2011 in operations that aimed for functional restoration by coaptation of all main available motor and sensory nerves. We enumerate the technical challenges and postoperative complications and their management, including single episodes of acute rejection in two patients. At 6 months of follow-up, all facial allografts were surviving, facial appearance and function were improved, and glucocorticoids were successfully withdrawn in all patients.

Biomarker evaluation of face transplant rejection: association of donor T cells with target cell injury.

This series of 113 sequential biopsies of full facial transplants provides findings of potential translational significance as well as biological insights that could prompt reexamination of conventional paradigms of effector pathways in skin allograft rejection. Serial biopsies before, during, and after rejection episodes were evaluated for clinicopathological assessment that in selected cases included specific biomarkers for donor-versus-recipient T cells. Histologic evidence of rejection included lymphocyte-associated injury to epidermal rete ridges, follicular infundibula, and dermal microvessels. Surprisingly, during active rejection, immune cells spatially associated with target cell injury consisted abundantly or predominantly of lymphocytes of donor origin with an immunophenotype typical of the resident memory T-cell subset. Current dogma assumes that skin allograft rejection is mediated by recipient T cells that attack epidermal targets, and the association of donor T cells with sites of target cell injury raises questions regarding the potential complexity of immune cell interactions in the rejection process. A more histopathologically refined and immune-based biomarker approach to assessment of rejection of facial transplants is now indicated.

Vascularized composite tissue allotransplantation--state of the art.

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including - but not limited to - trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.

Vascularized composite allotransplantation and tissue engineering.

For many living with the devastating aftermath of disfiguring facial injuries, extremity amputations, and other composite tissues defects, conventional reconstruction offers limited relief. Full restoration of the face or extremities with anatomic equivalents recently became possible with decades of advancements in transplantation and regenerative medicine. Vascularized composite allotransplantation (VCA) is the transfer of anatomic equivalents from immunologically and aesthetically compatible donors to recipients with severe defects. The transplanted tissues are "composite" because they include multiple types essential for function, for example, skin, muscle, nerves, and blood vessels. More than 100 patients worldwide have benefited from VCA, the majority receiving hand or face transplants. Despite its demonstrated results, the clinical practice of VCA is limited by center experience, public awareness, donor shortage, and the risks of lifelong immune suppression. Tissue engineering (TE) is the generation of customized tissues in the laboratory using cells, biomaterials and bioreactors. Tissue engineering may eventually supersede VCA in the clinic, because it bypasses donor shortage and immune suppression challenges. Billions of dollars have been invested in TE research and development, which are expected to result in a myriad of clinical products within the mid- to long-term. First, tissue engineers must address challenges such as vascularization of engineered tissues and maintenance of phenotype in culture. If these hurdles can be overcome, it is to be hoped that the lessons learned through decades of research in both VCA and TE will act synergistically to generate off-the-shelf composite tissues that can thrive after implantation and in the absence of immune suppression.

Craniofacial principles in face transplantation.

BACKGROUND: Face transplantation allows the reconstruction of the previously nonreconstructible injury. Anthropometric landmarks are fixated to corresponding cephalometric landmarks to restore function and appearance, with emphasis on phonation, mastication, and functional upper airway. Currently, only a few face transplantations have been performed worldwide. A portion of these reconstructions involves combinations of hard and soft tissues of the midface. METHODS: Craniofacial and orthognathic considerations should be emphasized for functional effect in the planning and execution of face transplants that include both bone and soft tissue elements. These steps are taken to restore normal anatomy by fixating the midface into proper relationship with the skull base. Traditional orthognathic planning, using cephalometric parameters, often involves a line through sella and nasion as a reference for the skull base. Intraoperatively though, without a cephalograph, the sella-nasion plane is not accessible as a reference point. RESULTS: Postoperative analysis of our first face transplant recipient revealed that the Frankfort horizontal plane can alternatively serve as an accessible skull base reference point to guide the positioning of the midface. We have developed a technique to ensure fixation of the midface donor allograft in a proper functional relationship with the skull base, within 1 SD of Bolton normative data. CONCLUSIONS: "Reverse craniofacial planning" allows for precise fixation of the hard tissue components of the face transplant in relation to the skull base, as opposed to a "best fit" approach. We believe that this relationship results in the most anatomical restoration of occlusion, speech, and airway function.

All hands on deck: Hand replantation versus transplantation.

OBJECTIVES: Our hands play a remarkable role in our activities of daily living and the make-up of our identities. In the United States, an estimated 41,000 individuals live with upper limb loss. Our expanding experience in limb transplantation-including operative techniques, rehabilitation, and expected outcomes-has often been based on our past experience with replantation. Here, we undertake a systematic review of replantation with transplantation in an attempt to better understand the determinants of outcome for each and to provide a summary of the data to this point. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted PubMed searches from 1964 to 2013 for articles in English. In total, 53 primary and secondary source articles were found to involve surgical repair (either replantation or transplantation) for complete amputations at the wrist and forearm levels. All were read and analyzed. RESULTS: Hand replantations and transplantations were compared with respect to pre-operative considerations, surgical techniques, post-operative considerations and outcomes, including motor, sensation, cosmesis, patient satisfaction/quality of life, adverse events/side effects, financial costs, and overall function. While comparison of data is limited by heterogeneity, these data support our belief that good outcomes depend on patient expectations and commitment. CONCLUSION: When possible, hand replantation remains the primary option after acute amputation. However, when replantation fails or is not possible, hand transplantation appears to provide at least equal outcomes. Patient commitment, realistic expectations, and physician competence must coincide to achieve the best possible outcomes for both hand replantation and transplantation.

OPTIMIZING COLLAGEN TRANSPORT THROUGH TRACK-ETCHED NANOPORES.

Polymer transport through nanopores is a potentially powerful tool for separation and organization of molecules in biotechnology applications. Our goal is to produce aligned collagen fibrils by mimicking cell-mediated collagen assembly: driving collagen monomers in solution through the aligned nanopores in track-etched membranes followed by fibrillogenesis at the pore exit. We examined type I atelo-collagen monomer transport in neutral, cold solution through polycarbonate track-etched membranes comprising 80-nm-diameter, 6-µm-long pores at 2% areal fraction. Source concentrations of 1.0, 2.8 and 7.0 mg/ml and pressure differentials of 0, 10 and 20 inH(2)O were used. Membrane surfaces were hydrophilized via covalent poly(ethylene-glycol) binding to limit solute-membrane interaction. Collagen transport through the nanopores was a non-intuitive process due to the complex behavior of this associating molecule in semi-dilute solution. Nonetheless, a modified open pore model provided reasonable predictions of transport parameters. Transport rates were concentration- and pressure-dependent, with diffusivities across the membrane in semi-dilute solution two-fold those in dilute solution, possibly via cooperative diffusion or polymer entrainment. The most significant enhancement of collagen transport was accomplished by membrane hydrophilization. The highest concentration transported (5.99±2.58 mg/ml) with the highest monomer flux (2.60±0.49 ×10(3) molecules s(-1) pore(-1)) was observed using 2.8 mg collagen/ml, 10 inH(2)O and hydrophilic membranes.

Living Donation of Vascularized Composite Allografts.

Living donation has become a medically and ethically accepted practice in solid organ transplantation. Published proceedings from the international kidney transplant community and from the Ethics Committee of The Transplantation Society articulated the general principles and specific recommendations for living donation, which remain the backbone of Centers for Medicare and Medicaid Services and Organ Procurement and Transplantation Network requirements and policies. Meanwhile, there have been major advancements in another revolutionary field of transplant medicine: vascularized composite allotransplantation. Recent interventions have demonstrated potential for superior functional and aesthetic outcomes in a single operation when compared to staged conventional reconstructions. In view of these successes, the indications for vascularized composite allotransplantation are expected to broaden to include less extensive types of transplants, which would introduce the possibility of using living vascularized composite allotransplantation donors. In this article, the authors discuss the feasibility and ethics associated with living donation of vascularized composite allografts. The authors explore the current guidelines and policies set by the Organ Procurement and Transplantation Network regarding living organ donation. In addition, the authors provide several clinical scenarios in which living donation of vascularized composite allotransplantation could be used to augment the reconstructive ladder currently used by reconstructive surgeons to guide their reconstructive strategies.

Enhancing cell seeding of scaffolds in tissue engineering through manipulation of hydrodynamic parameters.

The seeding of cells onto biocompatible scaffolds is a determinant step in the attainment of functional properties of engineered tissues. Efficient, fast and spatially uniform cell seeding can improve the clinical potential of engineered tissue templates. One way to approach these cell seeding requirements is through bioreactor design. In the present study, bovine chondrocytes were seeded (2.5, 5.0 or 10.0 million cells per scaffold) onto polyglycolic acid scaffolds within the hydrodynamic environments of wavy-walled and spinner flask bioreactors. Previous characterizations of the hydrodynamic environment in the vicinity of constructs cultivated in these bioreactors suggested decreased flow-induced shear stress as well as increased recirculation and magnitude of the axial fluid velocities in the wavy-walled bioreactor. Here we report more efficient and spatially uniform cell seeding in the wavy-walled bioreactor, and at intermediate initial cell densities (5 million cells per scaffold). This study constitutes an important step towards the achievement of functional tissue-engineered implants by (i) increasing our understanding of the influence of hydrodynamic parameters on the efficiency and spatial distribution of cell attachment to scaffolds and the production of extracellular matrix and (ii) introducing a comprehensive approach to the investigation of the effects of bioprocessing conditions on tissue morphology and composition.

First Lower Two-Thirds Osteomyocutaneous Facial Allograft Perfused by a Unilateral Facial Artery: Outcomes and Vascularization at 1 Year after Transplantation.

BACKGROUND: Facial allotransplantation provides a unique opportunity to restore facial form and function in severely disfigured patients. Using a single unilateral facial artery for vascularization can significantly reduce surgical duration and thus facilitate the practice of face transplantation. METHODS: A 33-year-old man with a history of high-energy ballistic trauma received a facial allograft comprising the lower two-thirds of the face, including maxilla and mandible. Vascular anastomoses involved one unilateral facial artery and two veins. Vascularization patterns, airway volume, and facial functions were assessed before and 1 year after transplantation. In addition, immunosuppressive therapy and rejection episodes were recorded. RESULTS: One year after transplantation, the facial allograft is well perfused and gradually improving in function. Unilateral facial artery anastomosis remains patent and collateralization with the contralateral side is taking place through collaterals of the submental arteries. Bony perfusion of the maxilla and mandible is provided periosteally. Bilateral venous outflow is evident. Airway volume is significantly increased compared with before transplantation, and gastrostomy and tracheostomy tubes have been securely removed. The recipient has gained the abilities to smell, speak, feel, and grimace 1 year after transplantation. Steroids were successfully weaned after 9 months, leaving the patient on dual immunosuppressive therapy with tacrolimus and mycophenolate mofetil. Two rejection episodes occurred, of which one was treated by steroid pulse and the other by adjusting the maintenance therapy. CONCLUSIONS: In this patient, a facial allograft comprising the lower two-thirds of the face including the maxilla and mandible is sufficiently perfused by one unilateral facial artery. Bilateral venous outflow, however, seems to be necessary. Facial allotransplantation can significantly and securely improve facial form and function. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

The Effects of Lip-Closure Exercise on Lip Strength and Function Following Full Facial Transplantation: A Case Report.

PURPOSE: Facial transplantation is a relatively new option for individuals with severe facial disfigurements. Clinical case studies on existing patients indicate many instances of persistent facial motor impairment for facial expression, speech, and swallowing. These preliminary findings motivate additional research on the impact of lip-strengthening exercises following facial transplantation. METHOD: In this study, we assessed the efficacy of an 8-week, biofeedback-driven, lip closure-strengthening exercise program in a single patient 1-year status post-full facial transplantation. Exercise was at 60% of peak strength. Outcome measures included instrumental measures of lip strength and mobility, clinical measures of speech, and patient-reported outcomes in feeding and facial expression. RESULTS: Results revealed improvements in labial strength, speed of lip movement, and range of motion during speech. A 3-point improvement in sentence speech intelligibility was also observed following strength-training exercise. The patient reported improvements in her ability to drink from a straw and communicate via facial expression. CONCLUSION: These preliminary findings motivate additional research on the efficacy of lip-strengthening exercises following facial transplantation.