Muayyad Alhefzi

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.

Noninvasive Monitoring of Immune Rejection in Face Transplant Recipients.

Background: Chronic rejection leading to allograft loss remains a significant concern after facial allotransplantation. Chronic rejection may occur without clinical signs or symptoms. The current means of monitoring is histologic analyses of allograft biopsy specimens, which is both invasive and impractical. Prior data suggest that chronic rejection is associated with changes in intima and media thickness of vessels in arms and solid organ allografts; such data have not been published for face transplant recipients. Methods: The authors used a 48-MHz transducer to acquire images of the bilateral facial, radial, dorsalis pedis and, if applicable, sentinel flap arteries in five face transplant recipients (8 months to 4.5 years after transplantation) and five control subjects. The authors assessed the intima, media, and adventitia thickness plus lumen and the total vessel diameter and area. Results: Face transplant recipients had thicker intima in all sites compared with controls, but the ratio of the intimal thickness of facial and radial arteries was similar in face transplant recipients compared with controls (1.00 versus 0.95; p = 0.742). Intraobserver correlation showed reliable reproducibility of the measurements (r = 0.935, p ⩽ 0.001). Interobserver correlation demonstrated reproducibility of intima measurements (r = 0.422, p ⩽ 0.001). Conclusion: The authors demonstrate that ultrasound biomicroscopy is feasible for postsurgical monitoring, and have developed a new benchmark parameter, the facial artery–to–radial artery intimal thickness ratio, to be used in future testing in the setting of chronic rejection. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

A Mobile Extracorporeal Extremity Salvage System for Replantation and Transplantation.

BackgroundTraumatic 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. MethodsBilateral 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. ResultsFive 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. ConclusionsWe 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.

Quality of Life after Face Transplantation: Outcomes, Assessment Tools, and Future Directions.

Background: Face transplantation has emerged as a clinical reality for the restoration of complex facial defects. Critical to the advancement of the burgeoning field of reconstructive transplantation is the quality of the methods used to measure and report the impact of face transplantation on quality of life. Methods: A systematic search using PubMed and EMBASE was conducted for all studies matching the a priori inclusion criteria from 2005 through 2015. Bibliographies of included studies were also reviewed. Two authors (M.A.A and H.K) independently performed screening of titles. Results: The authors identified 17 articles reporting on quality-of-life outcomes among 14 face transplant recipients. Combinations of objective and subjective measures were used to assess quality of life. Instruments used to assess quality of life after face transplantation included over 25 different instruments. Four centers, comprising eight patients, have reported using prospective, systematic data with validated instruments. Overall, there is reported improvement in quality of life after face transplantation. Heterogeneity and a paucity of data between articles preclude a quantitative analysis. Conclusions: Anecdotal and subjective reports of improvements in quality of life after face transplantation constitute the majority of reported outcomes in the English peer-reviewed literature. Improved efforts in methods and standardization of collection and reporting of quality-of-life data after face transplantation are needed to better appreciate the impact of face transplantation on quality of life and justify lifelong immunosuppression and its attendant risks and morbidity.

Guillain-Barré syndrome associated with resistant cytomegalovirus infection after face transplantation

A 39‐year‐old male, who received a facial allograft (cytomegalovirus [CMV] donor‐seropositive, recipient‐seronegative), developed multidrug‐resistant CMV infection despite valganciclovir prophylaxis (900 mg/day) 6 months post transplantation. Lower extremity weakness with upper and lower extremity paresthesias developed progressively 11 months post transplantation, coinciding with immune control of CMV. An axonal form of Guillain–Barré syndrome was diagnosed, based on electrophysiological evidence of a generalized, non‐length‐dependent, sensorimotor axonal polyneuropathy. Treatment with intravenous immunoglobulin led to complete recovery without recurrence after 6 months.

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.

Acellular Hypothermic Extracorporeal Perfusion Extends Allowable Ischemia Time in a Porcine Whole Limb Replantation Model

Background: One of the major challenges in traumatic amputation is the need to keep ischemia time brief (4 to 6 hours) to avoid ischemic damage and enable successful replantation. The current inability to meet this challenge often leads to traumatic limb loss, which has a considerable detrimental impact on the quality of life of patients. Methods: The authors’ team built a portable extracorporeal membrane oxygenator device for the perfusion of amputated extremities with oxygenated acellular solution under controlled parameters. The authors amputated forelimbs of Yorkshire pigs, perfused them ex vivo with acellular Perfadex solution for 12 hours at 10°C in their device, and subsequently replanted them into the host animal. The authors used limbs stored on ice slurry for 4 hours before replantation as their control group. Results: Clinical observation and histopathologic evaluation both demonstrated that there was less morbidity and less tissue damage to the cells during preservation and after replantation in the perfusion group compared with the standard of care. Significant differences in blood markers of muscle damage and tissue cytokine levels underscored these findings. Conclusions: The authors demonstrated the feasibility and superiority of ex vivo hypothermic oxygenated machine perfusion for preservation of amputated limbs over conventional static cold storage and herewith a substantial extension of the allowable ischemia time for replantation after traumatic amputation. This approach could also be applied to the field of transplantation, expanding the potential pool of viable donor vascularized composite allografts.

Transformation of Face Transplants: Volumetric and Morphologic Graft Changes Resemble Aging After Facial Allotransplantation.

Facial allotransplantation restores normal anatomy to severely disfigured faces. Although >30 such operations performed worldwide have yielded promising short‐term results, data on long‐term outcomes remain scarce. Three full‐face transplant recipients were followed for 40 months. Severe changes in volume and composition of the facial allografts were noted. Data from computed tomography performed 6, 18 and 36 months after transplantation were processed to separate allograft from recipient tissues and further into bone, fat and nonfat soft tissues. Skin and muscle biopsies underwent diagnostic evaluation. All three facial allografts sustained significant volume loss (mean 19.55%) between 6 and 36 months after transplant. Bone and nonfat soft tissue volumes decreased significantly over time (17.22% between months 6 and 18 and 25.56% between months 6 and 36, respectively), whereas fat did not. Histological evaluations showed atrophy of muscle fibers. Volumetric and morphometric changes in facial allografts have not been reported previously. The transformation of facial allografts in this study resembled aging through volume loss but differed substantially from regular aging. These findings have implications for risk–benefit assessment, donor selection and measures counteracting muscle and bone atrophy. Superior long‐term outcomes of facial allotransplantation will be crucial to advance toward future clinical routine.

The role of face transplantation in the self-inflicted gunshot wound

BACKGROUND Facial self-inflicted gunshot wounds (SIGSWs) cause a devastating midfacial defect and pose a challenging problem to the reconstructive surgeon. Face transplantation (FT) has the potential for near-normal restoration in otherwise non-reconstructible defects. Two out of 7 FT recipients at Brigham and Womens Hospital (BWH) sustained SIGSWs. In this study, we illustrate the role of FT in the management of SIGSWs through an aesthetic, functional, and psychosocial examination of outcomes. METHODS We performed a retrospective analysis of individuals with SIGSWs who were screened at BWH between 2008 and 2015. We then collected data of the injuries, modes of conventional reconstruction (CR), and deficits. For the FT recipients, we critically reviewed the psychosocial screening process and post-transplantation aesthetic, functional, and psychosocial outcomes. RESULTS A total of six individuals post-SIGSWs were screened for FT. All of them had undergone CR, with five receiving loco-regional flaps and free tissue transfers, and one undergoing serial debridement and primary soft-tissue repair. Following CR, all suffered from residual functional and aesthetic deficits. Two underwent partial FT and one is currently undergoing FT screening. We describe the pre-transplant psychosocial screening process and the aesthetic, functional, and psychosocial outcomes of the SIGSW FT recipients. CONCLUSIONS We examined the facial SIGSW injury, outcomes of CR, and the mechanism of FT to offer a potential solution to the shortcomings of CR. More importantly, we highlight the critical nature of the psychosocial component of the multidisciplinary evaluation given the history of mental illness and suicidal behavior in this subset of patients.

A Retrospective Analysis of Secondary Revisions after Face Transplantation: Assessment of Outcomes, Safety, and Feasibility

Background: Face transplantation has emerged as a viable option for certain patients in the treatment of devastating facial injuries. However, as with autologous free tissue transfer, the need for secondary revisions in face transplantation also exists. The authors’ group has quantified the number of revision operations in their cohort and has assessed the rationale, safety, and outcomes of posttransplantation revisions. Methods: A retrospective analysis of prospectively collected data of the authors’ seven face transplants was performed from April of 2009 to July of 2015. The patients’ medical records, preoperative facial defects, and all operative reports (index and secondary revisions) were critically reviewed. Results: The average number of revision procedures was 2.6 per patient (range, zero to five procedures). The median time interval from face transplantation to revision surgery was 5 months (range, 1 to 10 months). Most interventions consisted of debulking of the allograft, superficial musculoaponeurotic system plication and suspension, and local tissue rearrangement. There were no major infections, allograft skin flap loss, or necrosis. One patient suffered a postoperative complication after autologous fat grafting in the form of acute rejection that resolved with pulse steroids. Conclusions: Secondary revisions after face transplantation are necessary components of care, as they are after most conventional free tissue transfers. Secondary revisions after face transplantation at the authors’ institution have addressed both aesthetic and functional reconstructive needs, and these procedures have proven to be safe in the context of maintenance immunosuppression. Patient and procedure selection along with timing are essential to ensure patient safety, optimal function, and aesthetic outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.