Harriet Kiwanuka

Evolution of ethical debate on face transplantation.

Background: Face transplantation can provide improved quality of life to severely disfigured individuals. The unique challenges of face transplantation prompted much ethical discussion even before the first clinical case. Many deemed it unethical, because of issues ranging from the need for potentially harmful immunosuppression to the potential transfer of identity. Over time, the ethical debate surrounding face transplantation has evolved. Methods: In August of 2012, the authors performed a review of the scientific literature on the ethics of face transplantation, focusing on the evolution of the discussion from before to after the first clinical case in 2005. The authors conducted a primary search (73 peer-reviewed publications) in PubMed using combinations of the terms “ethics” and “face transplantation” and “opinions,” and a secondary search (37 peer-reviewed publications) retrieving publications cited in some of the primary search findings. In total, the authors reviewed 110 articles. Results: A series of 15 issues were addressed repeatedly throughout the reviewed articles. The authors observed an evolution of the general opinion regarding face transplantation: initially seen almost unanimously as an outlandish and morally objectionable procedure, it began to be accepted as a feasible and necessary treatment option for the most significant facial defects. Conclusion: With growing clinical experience globally, new ethical questions have arisen that must be addressed to move the field of face transplantation forward in an ethically sound manner.

Common Postburn Deformities and Their Management

This article describes a practical, clinically based approach to classification of postburn deformities. Burn scar contractures are of either the broad diffuse type or linear band-like type. The former generally respond well to release and insertion of a skin graft or substitute, whereas the latter are generally repaired using a simple or modified Z-plasty or a transpositional flap technique. The pulsed dye laser is a promising technique used to reduce scar thickness and redness. Postburn deformities of the face, upper and lower extremities, and trunk are discussed, in addition to novel techniques for vascularized composite allotransplantation of the face.

Vascularized composite allotransplantation and tissue engineering.

Abstract 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.

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.

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.

Perceived social support among patients with burn injuries: A perspective from the developing world

BACKGROUND Social support is among the most well-established predictors of post-burn psychopathology after burn. Despite a disproportionately large burden of burns in the developing world, the nature of social support among burn patients in this context remains elusive. We, therefore, seek to investigate social support and its biopsychosocial determinants among patients with burn injuries in Pakistan. METHODS A cross-sectional study of 343 patients presenting with burn injuries at four teaching hospitals in the Punjab province of Pakistan was conducted. Patient evaluation consisted of a multi-part survey of demographic status, clinical features, and social support as measured by the validated Urdu translation of the Multidimensional Scale of Perceived Social Support (MSPSS). Multiple regression analysis was performed to evaluate associations between patient characteristics and MSPSS score. RESULTS Mean overall MSPSS score was 57.64 (std dev 13.57). Notable positive predictors of social support include male gender, Punjabi ethnicity, burn surface area, and ego resiliency. CONCLUSION Our study reveals a troubling pattern of inadequate social support among certain subgroups of Pakistani burn patients. Addressing these inequities in the provision of social support must be prioritized as part of the global burn care agenda.

Tissue conservation for transplantation

Abstract Pathophysiological changes that occur during ischemia and subsequent reperfusion cause damage to tissues procured for transplantation and also affect long-term allograft function and survival. The proper preservation of organs before transplantation is a must to limit these injuries as much as possible. For decades, static cold storage has been the gold standard for organ preservation, with mechanical perfusion developing as a promising alternative only recently. The current literature points to the need of developing dedicated preservation protocols for every organ, which in combination with other interventions such as ischemic preconditioning and therapeutic additives offer the possibility of improving organ preservation and extending it to multiple times its current duration. This review strives to present an overview of the current body of knowledge with regard to the preservation of organs and tissues destined for transplantation.

2544: Patient recruitment and referral patterns in face transplantation

2544: Patient recruitment and referral patterns in face transplantation Harriet Kiwanuka, Mario A. Aycart, MD, Ericka Bueno, Muayyad Alhefzi, Nicco Krezdorn, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Promising short term results raise an important question regarding its patient population—are centers that perform face transplantation effectively reaching individuals from the targeted facial disfigurement population? Our center reviewed our face transplantation contacts to assess patient recruitment and outreach performance. Methods We performed a retrospective review of subjects who requested screening for face transplantation (aka: “Contacts”) between the time of our IRB protocol approval (February 2008) to October 2015. We investigated the relationship between referral mode (physician vs self) with the Contact’s demographic characteristics (age, gender, race, mechanism of injury, geographic location) and clinical trial status. Results There were a total of 72 face transplantation Contacts The average age of the Contacts was 38 years, and the majority of them were male (n D 41, 569%) The predominant race of Contacts was White (n D 33) and the most prevalent mechanism of injury was burns (n D 32) The majority of our Contacts resided within the US (n D 47), with the majority from the Northeastern US (n D 21) Of the 72 Contacts, 35 (486%) were physician referrals and 37 (514%) were self referrals Physician referrals led to the most screened and transplanted Contacts in our center, whereas self-referral often led to immediate exclusion. Conclusions In this study, we show the diversity of patient characteristics and referral patterns in our clinical trial Furthermore, we describe the relationship of characteristics to outcomes in our cohort and identify areas of improvement, such as patient and physician education. Lastly, we are reminded of face transplantation’s potential impact. Figure 1. Overall clinical status of contacts -no (%). CONTACT Harriet Kiwanuka hkiwanuka@partners.org

2536: Ex vivo hypothermic perfusion of amputated porcine forelimbs promotes reduced molecular damage to skeletal muscle when compared with conventional cold storage

2536: Ex vivo hypothermic perfusion of amputated porcine forelimbs promotes reduced molecular damage to skeletal muscle when compared with conventional cold storage Nicco Krezdorn, Dharaniya Sakthivel, Mario A. Aycart, MD, Muayyad Alfhefzi, Thet-Su Win, Harriet Kiwanuka, Ericka Bueno, Indranil Sinha, and Bohdan Pomahac Brigham and Women’s Hospital, Boston, MA, USA Background Limb allotransplantation is largely limited by the allowable ischemia time in limbs Muscle makes up most of the volume of isolated limbs, and its maximum allowable ischemia time is currently in the order of 4–6–h Extracorporeal perfusion devices may support safe extension of the allowable ischemia time for limb tissues The aim of this study was to assess the effect of different storage modalities on gene expression in porcine forelimbs. Methods Porcine forelimbs were amputated and either perfused with oxygenated acellular supplemented perfusion solution (Perfadex ) for 12 h at 10 C (treatment; n D 3) or stored on ice slurry at 4 C (control; n D 2) before replantation Gene expression profiles in muscle tissues from the amputated limb were analyzed after 2 h on ice as well as after 2–h and 12–h perfusion using a hypoxia gene expression qPCR array of 84