Facial Vascularized Composite Allograft Research Articles

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.

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.

Partial Loss of Nasal Tissue in a Facial Vascularized Composite Allograft Patient.

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Characteristics of postmortem organ donors in N.V. Sklifosovsky Research Institute for Emergency Medicine and the donor hospitals of FMBA of Russia (2008–2017)

Rationale.There have been only single studies conducted in the Russian Federation to characterize the posthumous donor population.Objective:Identifying the main characteristics of the donor pool in N.V. Sklifosovsky Research Institute for Emergency Medicine of Moscow Healthcare Department and in the State Research Center – A.I. Burnasyan Federal Medical Biophysical Center, FMBA, for the period from 2008–2017.Material and methods.The clinical records of 429 actual and effective posthumous donors were analyzed retrospectively. The following characteristics were studied: gender, age, permanent place of residence, cause of death, the duration of mechanical lung ventilation, type of donation, total number of harvested organs, and number of organs recovered per donor.Results.There were 281 male and 148 female donors. The increase in the mean age of donors from 37 to 48.5 years was noted. Cerebrovascular disease and traumatic brain injury became the main causes of death. Since 2012, the rate of cerebrovascular diseases as the cause of donor death has increased from 30% to 70%. Of 429 actual donors, the brain death was diagnosed in 366 (85.3%). Four hundred eight deceased became effective donors. A total of 1,247 donor organs (744 kidneys, 220 livers, 42 pancreas, 2 intestines, 180 hearts, 58 lungs, and 1 facial vascularized composite allograft) were obtained. The mean number of donor organs recovered per donor was 3.06.Conclusions.The results obtained can be used to develop unified protocols and results of posthumous donors and to assess the possible volume of transplant care. In the period 2008–2017 an increase in the average age of posthumous donors (from 38.1 to 48.7 years) due to the proportion of donors in the 18–29 age group (from 29 to 4%) and an increase in the proportion of donors in the age group over 60 (from 3 to 15%). From 2012 to 2017 (from 68 to 29%) due to an increase in the number of donors who died as a result of cerebrovascular diseases (from 30 to 71%). Among the posthumous donors delivered by ambulance teams directly to the intensive care units, 69% of the consciousness level was depressed to 5 and lower on the Glasgow coma scale.

Outcomes of Solid Organ Transplants After Simultaneous Solid Organ and Vascularized Composite Allograft Procurements

Current knowledge of the impact of facial vascularized composite allograft (VCA) procurement on the transplantation outcomes of the concomitantly recovered solid organs is limited to isolated case reports and short-term results. Here we report on a nationwide analysis of facial allograft donor surgery experience and long-term outcomes of the concomitantly recovered solid organs and their recipients. There were 10 facial VCA procurements in organ donors between December 2008 and October 2014. We identified the population of subjects who received solid organs from these 10 donors using the Scientific Registry of Transplant Recipients. We retrospectively reviewed operative characteristics, intraoperative parameters, and postoperative outcomes. Six of 10 donor surgeries were performed at outside institutions, all on brain-dead donors. Mean operative duration for facial VCA recovery was 6.9 hours (range, 4-13.25 hours). A total of 36 solid organs were recovered and transplanted into 35 recipients. Survival rates for kidney and liver recipients were 100% and 90% at a median follow-up of 33 and 27.5 months, respectively (range, 6-72 months). Graft survival rates for kidneys and livers were 15 of 16 (94%) and 9 of 10 (90%), respectively. Recipient and graft survival rates for hearts and lungs were 75% (n = 4) and 100% (n = 3) at mean follow-up time of 14.75 and 16 months, respectively. A liver recipient died at 22 months from unknown causes and a heart recipient died of leukemia at 10 months. Facial VCA procurement does not appear to adversely affect the outcomes of transplant recipients of concomitantly recovered solid organ allografts.

Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant Research Procurement: A Translational Simulation Model.

Cadaveric face transplant models are routinely used for technical allograft design, perfusion assessment, and transplant simulation but are associated with substantial limitations. The purpose of this study was to describe the experience of implementing a translational donor research facial procurement and solid organ allograft recovery model. Institutional review board approval was obtained, and a 49-year-old, brain-dead donor was identified for facial vascularized composite allograft research procurement. The family generously consented to donation of solid organs and the total face, eyelids, ears, scalp, and skeletal subunit allograft. The successful sequence of computed tomographic scanning, fabrication and postprocessing of patient-specific cutting guides, tracheostomy placement, preoperative fluorescent angiography, silicone mask facial impression, donor facial allograft recovery, postprocurement fluorescent angiography, and successful recovery of kidneys and liver occurred without any donor instability. Preservation of the bilateral external carotid arteries, facial arteries, occipital arteries, and bilateral thyrolinguofacial and internal jugular veins provided reliable and robust perfusion to the entirety of the allograft. Total time of facial procurement was 10 hours 57 minutes. Essential to clinical face transplant outcomes is the preparedness of the institution, multidisciplinary face transplant team, organ procurement organization, and solid organ transplant colleagues. A translational facial research procurement and solid organ recovery model serves as an educational experience to modify processes and address procedural, anatomical, and logistical concerns for institutions developing a clinical face transplantation program. This methodical approach best simulates the stressors and challenges that can be expected during clinical face transplantation. Therapeutic, V.

Algorithm for Total Face and Multiorgan Procurement From a Brain-Dead Donor

Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time–intensive, “simultaneous–start” procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain–dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO2 remained normal. All organs had good postoperative function. We propose an algorithm that allows “face first, concurrent completion” recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.

Multi-Organ and Complex Full Facial Segment Procurement from a Brain Dead Donor

The procurement of facial vascularized composite allografts (VCA) is complicated by highly variable recipient defects, in contrast to more standardized recovery of solid organ and hand VCA. In donors undergoing facial VCA recovery, coordination with multi-organ recovery is essential to preserve functional outcomes of solid organ allografts. Methods: We performed coordinated procurement of a full facial VCA with abdominal organ recovery for transplantation from a brain dead donor. The facial VCA included all facial skin, mimetic muscles, multiple sensory and motor nerve branches, the anterior tongue and segments of the maxilla and mandible. Abdominal organ recovery included liver and kidneys. Close monitoring of arterial blood gases, urine output, transfusion requirements, and key steps of facial VCA dissection guided timing of abdominal organ recovery. Results: Recovery of the facial VCA required ˜10.5 hours, with tracheostomy and silicone mask impression performed prior to procurement. Transfusion of 9 units packed red blood cells, 6 units fresh frozen plasma, 1 pooled unit platelets, and 7 L crystalloid were required to maintain stable hemodynamics (MAP 70.1±8.4mmHg) and adequate urine output (0.7 mL/kg/Hr). Donor coagulopathy increased transfusion requirements and the majority of blood loss occurred after mid-face dissection and the initiation of abdominal organ recovery. Oxygenation (192-254 mmHg) and blood pH (7.30-7.35) were normal throughout recovery. Abdominal organ recovery was initiated 6.5 hours into the procedure and prior to performing facial VCA osteotomies; abdominal and facial recovery teams were able to operate concurrently thereafter. After heparinization, the facial VCA was explanted for backtable flushing with University of Wisconsin solution. Abdominal organ recovery immediately followed without complication and good recipient graft function. Conclusions: Facial VCA procurement entails additional blood loss and substantial extension of donor recovery operations. Close monitoring of the donor allows for delayed solid-organ recovery after facial skeletal dissection and potential greatest blood loss. Coordinated care between anesthesia, solid-organ, and facial VCA teams allows for procurement of a complicated facial VCA while preserving solid organ outcomes.

Infused Bone Marrow Fails to Prolong Vascularized Composite Allograft Survival in Nonhuman Primates

Introduction: Clinical protocols for hand and face vascularized composite allografts (VCA) have included varying amounts donor bone marrow cell (BMC) infusion after lymphocyte depletion as an immunomodulatory strategy. We previously demonstrated that vascularized bone marrow (VBM) protects facial VCA from rejection in unconditioned nonhuman primates. To investigate the potential immunologic benefit of infused BMC, we substituted infused BMC for VBM in the transplanted facial segment. Methods: Three cynomolgus macaques underwent heterotopic facial segment transplantation with mandibular segment removed, followed by central venous infusion of BMC from the same MHC-mismatched donor on postoperative day 1. Bone marrow cells were collected from the donor lumbar vertebrae following euthanasia. Cells counts and viability were confirmed using trypan blue and automated complete blood count. Donor BMC were infused at 200 million cells per kg of recipient weight, a standard for bone marrow transplantation. CD34+ hematopoeitic stem and progenitor cells were identified using a modified ISHAGE gating strategy. Immunosuppression was maintained with tacrolimus and mycophenolate mofetil. Rejection episodes were not treated. Chimerism was measured in blood samples using flow cytometry. Results: Mean cell content of the mandibular segments set aside before transplantation was 48.2 million cells/kg of donor weight. Hematopoeitic stem and progenitor cells comprised 5.63% of vertebral bone marrow BMC and 7.60% of mandibular BMC. Animals in the previous VCA+VBM treatment group had no graft loss while on immunosuppression. Additionally, graft survival was longer vs. VCA alone (205-430 vs. 9-42 days), as was rejection-free survival (44-358 vs. 7-15 days). In the VCA + BMC group all animals developed acute rejection (Banff grade I or higher) by day 14. One progressed to grade IV rejection and graft loss by day 28, while another resolved but progressed to chronic rejection by day 50 and endpoint at day 115 for post-transplant lymphoproliferative disease with chronic rejection. Only one animal receiving BMC demonstrated transient macrochimerism days 85-98. Chimerism was similarly observed transiently in only one animal receiving VCA without either VBM or BMC. In contrast, 3 of 4 animals with VBM demonstrated macrochimerism.Figure: [Graft Survival]Conclusion: Despite larger cell counts, BMC infusion failed to prolong facial VCA survival compared to VBM. These data support that VBM is a more effective immunomodulatory strategy than infusion of donor BMC without depletional pre-conditioning. The addition of irradiation and T cell depletion therapies to VBM may further enhance the amount and durability of chimerism, and potentially allow for the development tolerance.

Total Face, Double Jaw, and Tongue Transplant Simulation

With the transplantation of more extensive facial vascularized composite allografts, fundamental craniofacial and aesthetic principles become increasingly important. In addition, computer-assisted planning and intraoperative navigation may improve precision and efficiency in these complex procedures. Ten mock face transplants were performed in 20 cadavers. The vascularized composite allograft consisted of all facial skin, mimetic muscles, the tongue, the midface by means of a Le Fort III osteotomy, and the mandible by means of sagittal split osteotomies. Craniofacial computed tomographic scans were obtained before and after the mock transplants. Surgical planning software was used to virtually plan the osteotomies, and a surgical navigation system guided the osteotomies intraoperatively. Cephalometric analyses were compared between the virtually planned transplants and the actual postoperative results. The combination of preoperative computerized planning and intraoperative guidance consistently produced a vascularized composite allograft that could be easily fixated to the prepared recipient, with only minimal burring of osteotomy sites necessary. Satisfactory occlusion was maintained, and postoperative computed tomography confirmed accurate skeletal fixation. Insignificant differences with regard to cephalometric analyses were noted when predicted and actual postoperative data were compared. The authors' experience treating severe craniofacial injury allowed consistent transfer of facial vascularized composite allografts, maintaining proper occlusion. Preoperative computer planning and intraoperative navigation ensured precise osteotomies and a good donor-recipient skeletal match, which greatly reduced the need for intraoperative adjustments and manipulation. This total facial vascularized composite allograft represents one of the most extensive described and is intended to represent a typical central facial demolition pattern.

Total Face, Double Jaw, and Tongue Transplant Research Procurement

Transplantation of a facial vascularized composite allograft is a highly complex procedure that requires meticulous planning and affords little room for error. Although cadaveric dissections are an essential preparatory exercise, they cannot simulate the true clinical experience of facial vascularized composite allograft recovery. After obtaining institutional review board approval to perform a facial vascularized composite allograft research procurement, a 66-year-old, brain-dead donor was identified. The family graciously consented to donation of a total face, double jaw, and tongue allograft and multiple solid organs. A craniofacial computed tomographic angiogram was obtained preoperatively to define the vascular anatomy and facilitate virtual computerized surgical planning. The allograft was procured in 10 hours, with an additional 2 hours required for an open tracheostomy and silicone facial impression. The donor was coagulopathic throughout the recovery, resulting in an estimated blood loss of 1500 ml. Fluorescence angiography confirmed adequate perfusion of the entire allograft based on lingual and facial arterial and external jugular and thyrolinguofacial venous pedicles. The solid organ transplant team initiated abdominal organ isolation while the facial allograft procurement was in progress. After completion of allograft recovery, the kidneys and liver were recovered without complication. Before conducting a clinical face transplant, adequate preparation is critical to maximize vascularized composite allotransplantation outcomes and preserve solid organ allograft function. As more centers begin to perform facial transplantation, research procurement of a facial vascularized composite allograft offers a unique educational opportunity for the surgical and anesthesia teams, the organ procurement organization, and the institution.

Infrared Fluorescence Imaging of Lymphatic Regeneration in Nonhuman Primate Facial Vascularized Composite Allografts

Clinical vascularized composite allografts (VCA), although performed with good success, have been characterized by rejection episodes and postoperative graft edema. We investigated lymphatic donor-recipient reconstitution and lymphatic regeneration in a nonhuman primate facial VCA model. Heterotopic partial face (n = 9) VCAs were performed in cynomolgus macaques. Grafts were monitored for rejection episodes and response to immunosuppressive therapies as previously described. Donor and recipient lymphatic channels were evaluated using a near-infrared handheld dual-channel light-emitting diode camera system capable of detecting fluorescence from indocyanine green injections. Graft lymphatic channels were serially evaluated from postoperative day 0 to 364. Preoperative imaging demonstrated superficial lymphatic anatomy similar to human anatomy. Initial resolution of facial allograft swelling coincided with superficial donor-recipient lymphatic channel reconstitution. Reconstitution occurred despite early acute rejection episodes in 2 animals. However, lymphatic channels demonstrated persistent functional and anatomic pathology, and graft edema never fully resolved. No differences in lymphatic channels were noted between grafts that developed transplant vasculopathy (n = 3) and those that did not (n = 6). Dynamic changes in patterns of lymphatic drainage were noted in 4 animals following withdrawal of immunosuppression. Donor-recipient lymphatic channel regeneration following VCA did not result in resolution of edema. Technical causes of graft edema may be overcome with alternative surgical techniques, allowing for direct investigation of the immunologic relationship between VCA graft edema and rejection responses. Mechanisms and timing of dynamic donor-recipient lymphatic channel relationships can be evaluated using fluorescent imaging systems to better define the immunologic role of lymphatic channels in VCA engraftment and rejection responses, which may have direct clinical implications.