Extremity Transplantation Research Articles

Establishing an upper extremity transplantation program: lessons learnt over 12 years.

As one of the early hand transplant programs in the world, we are often asked to educate other programs on the lessons we have learned and on how to set up a successful hand transplantation program. Two decades of global experience with vascularized composite allotransplantation (VCA) of the upper limb have demonstrated improved functional outcomes and quality of life for carefully screened patients. Despite initial reticence about VCA, over 30 patients in the USA have benefited from hand transplantation, with around 80% long-term successes. We have experience with four bilateral upper extremity patients who have undergone bilateral upper extremity allotransplants. This review article highlights our personal experience and lessons with respect to VCA team assembly, logistics, patient selection, perioperative planning, the operative procedure, and postoperative management. Continual learning and critical evaluation are crucial to maintaining a successful upper extremity VCA program. This will ensure that patients who stand to benefit most from this life-enhancing procedure are identified and are others optimized to achieve the best possible outcomes.

A World Update of Progress in Lower Extremity Transplantation: What's Hot and What's Not.

The field of vascularized composite allotransplantation (VCA) is the new frontier of solid organ transplantation (SOT). VCA spans life-enhancing/life-changing procedures such as upper extremity, craniofacial (including eye), laryngeal, tracheal, abdominal wall, penis, and lower extremity transplants. VCAs such as uterus transplants are life giving unlike any other SOT. Of all VCAs that have shown successful intermediate- to long-term graft survival with functional and immunologic outcomes, lower extremity VCAs have remained largely underexplored. Lower extremity transplantation (LET) can offer patients with improved function compared to the use of conventional prostheses, reducing concerns of phantom limb pain and stump complications, and offer an option for eligible amputees that either fail prosthetic rehabilitation or do not adapt to prosthetics. Nevertheless, these benefits must be carefully weighed against the risks of VCA, which are not trivial, including the adverse effects of lifelong immunosuppression, extremely challenging perioperative care, and delayed nerve regeneration. There have been 5 lower extremity transplants to date, ranging from unilateral or bilateral to quadrimembral, progressively increasing in risk that resulted in fatalities in 3 of the 5 cases, emphasizing the inherent risks. The advantages of LET over prosthetics must be carefully weighed, demanding rigorous candidate selection for optimal outcomes.

Advancing vascularized composite allotransplantation: essential factors for upper extremity transplant program development.

Vascularized Composite Allotransplantation (VCA) offers a unique option to restore form and function after limb loss or facial trauma that cannot be satisfactorily accomplished through traditional prosthetics or reconstructions. Establishing a successful Upper Extremity Transplantation (UET) program requires strong leadership and a structured surgical team, and extensive interdisciplinary collaboration. We conducted a qualitative study among 12 health care professionals and patients. Informed consent was obtained per protocol, and semi-structured interviews were conducted online and recorded. Participants reported their perceptions of factors that either favored or hindered a successful outcome, including functional status before and after surgery, preparation for transplant, shared decision-making, rehabilitation, and psychosocial support. Thematic analysis revealed that it is essential to establish a team comprising various disciplines well before performing VCA procedures. Defining a common goal and choosing a defined leader is a key factor in procedural success and requires open collaboration beyond what is typical. Primary described categories are interdisciplinary collaboration and skills of the VCA team, building and leading a VCA team, pre-transplant procedures, post-transplant course, and factors to consider when establishing a program. The basic roles of team science play an outsized role in establishing a VCA program. Transplantation medicine involves various overlapping scientific and medical categories requiring health professionals to consciously work together to establish complex vertical and horizontal communication webs between teams to obtain positive outcomes. In addition to medical considerations, patient-specific factors such as transparent communication, therapy plan establishment, plan adherence, and continual follow-up are significant factors to overall success.

Crowdsourcing Opinions and Awareness of Upper Extremity Transplantation in the United States.

Introduction As of 2008, the United States had 41,000 people living with upper extremity amputation. This number is projected to reach300,000 by 2050. Human upper extremity transplantation (HUET) may become a more common treatment option with the potential to significantly improve the quality of life for certain amputees. Awareness and opinions regarding HUETamong Americans, particularly in Veterans/Service Members (VSM) affiliates, are largely unknown. Materials and methods We administered a survey on Amazon Mechanical Turk (MTurk) workers. Eligible participants were US citizens aged ≥18 years; MTurk worker selection targeted workers who self-reported being a VSM. We used descriptive statistics to summarize study findings and Fisher's exact and Wilcoxon's rank-sum tests for between-group comparisons. Results The survey was completed by 764 individuals, 604 (79.1%) of whom reported being aware of HUET. Among those familiar versus unfamiliar, a significantly higher proportion were aged ≤35 years (n=385, 64.0% vs. n=86, 53.7%; p=0.017), employed (n=523, 86.6% vs. n=114, 71.3%; p<0.001), and aware of their religion's stance on organ/tissue donation (n=341, 54.5% vs. n=62, 38.8%; p<0.001). Amputees and/or respondents related to an amputee were more likely to be aware of HUET than individuals who were amputation naive (n=211, 90.6% vs. n=393, 74.0%, respectively; p<0.001), as were individuals with a personal or familial military affiliation (n=286, 85.4% with vs. n=318, 74.1% with no affiliation; p<0.001). The most reported HUET information sources were digital media (n=157, 31.2%) and internet (n=137, 27.2%). Conclusions Our survey of MTurk workers found greater awareness of HUET among individuals with a VSM or amputee connection. Our additional findings that the internet and academic sources, such as journals or reputable medical publications, were respondents' preferred sources of HUET information emphasize the importance of vascularized composite allotransplantation (VCA) centers' involvement in creating accurate and accessible content to help educate the public about this treatment.

Crowdsourcing Attitudes and Beliefs About Upper Extremity Donation in the United States.

Introduction To date, upper extremity transplantation (UET) is the most frequently performed vascularized composite allotransplantation (VCA). Perceptions regarding upper extremity donation among Americans, particularly in veterans and service members (VSMs), are largely unknown. Materials and methods We administered a one-time survey to United States (US)-resident Amazon Mechanical Turk (MTurk) workers aged ≥18 years. Descriptive statistics were used to summarize study data; frequencies and percentages were calculated for categorical variables analyzed by Fischer's exact test and using a two-tailed test assessing the statistical significance of p<0.05. Results A total of 860 respondents completed the study survey. Among these, 529 (61.5%) reported willingness to donate an upper extremity, 152 (17.7%) were undecided, and 179 (20.8%) were unwilling. A significantly higher proportion of those willing to donate were female (66.7%, p=0.009), non-Hispanic (63.9%, p=0.000), White (64.0%, p=0.004), non-religious (71.3%, p=0.001), not a VSM (62.8%, p=0.000), or non-amputees (62.9%, p=0.000). Conclusions Our survey found that being female, non-Hispanic, White, non-religious, non-VSM, or non-amputee was significantly associated with donation willingness. These findings may help guide VCA programs, organ procurement organizations, and researchers in efforts to develop targeted educational materials to broaden the public's knowledge and awareness of VCA donation to further benefit all patients in need of or desiring transplantation.

Replantation versus transplantation: Where do we stand?

Despite advances in extremity trauma care and reconstructive microsurgery, management of the traumatic amputations remains a challenge. The majority of patients will forever experience some level of disability even with replantation or advanced prosthetics. The goal of this article is to familiarize hand and reconstructive surgeons with the current state of upper extremity transplantation, so they better can educate their amputee patients regarding this as an option following limb loss. Current literature, in addition to the international registry on hand and composite tissue transplantation, was reviewed to assemble a summary of outcomes in upper extremity replantation and transplantation. Sensory and functional outcomes of replantation and transplantation are comparable. Reported complications of immunosuppression are similar to those of other solid organ transplants. The financial cost of hand transplantation is high, but comparable to the lifetime cost of prosthesis use. While the risk of immunosuppression is a serious consideration for patients pursuing hand transplantation, in the well-selected and informed patient, hand transplantation can dramatically improve patient reported to outcomes and quality of life.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

Poor outcomes in functional recovery after upper extremity transplantation are largely attributable to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells, and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. Rats underwent orthotopic forelimb transplantation across a full major histocompatibility complex mismatch and received either porcine-derived growth hormone or no treatment ( n = 18 per group). Functional recovery was measured using electrically stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals ( P = 0.005, P = 0.08, respectively). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, or axon counts between groups. The rates of clinical and histologic rejection did not differ significantly between groups. The findings alleviate concern for increased risk of transplant rejection during GH therapy and support the translation of GH as a therapeutic method to promote improved functional recovery in upper extremity transplantation. The authors' findings suggest that growth hormone is a promising therapeutic option to improve motor functional recovery in upper extremity transplantation without increased risk of rejection.

Psychosocial Risk Stratification in Upper Extremity Transplantation Candidates.

Candidate selection for upper extremity transplantation remains an inherently subjective process. This work evaluated the effect that psychosocial factors have on outcomes, both to standardize evaluation of potential candidates and in optimizing these factors prior to transplantation. Our goal was to measure and quantify the risk that various psychosocial factors have on transplant outcomes. Given that we do not have sufficient post-transplant patients to examine specific factors, we chose to have experts in the field evaluate hypothetical patients based on their experience. We used a Generalized Estimating Equation to estimate and compare surgical candidacy scores using patient scenario vignettes based on the presence or absence of permutations of the following: (1) depression; (2) participation in occupational therapy (OT); (3) expectation of post-transplant function; (4) punctuality; and (5) family support were given to experts in the field. This work suggests there is a decrease in predicted success with increasing numbers of negative factors with participation in OT and realistic expectations of outcomes being most important. An increase in the summarizing risk score from 0 to 1.7 was associated with a decrease in the outcome surgical candidacy score from 8.6 to 5.3, meaning candidates with 2 risk factors would often observe a large drop in surgical candidacy score. Focusing on optimizing psychosocial variables in transplant candidates may help improve hand transplant success.

Assessment of quality of life after upper extremity transplantation: Framework for patient-reported outcome scale domains.

Upper extremity transplantation offers the promise of restored function and regained quality of life (QOL) for individuals who have sustained hand or arm amputation. However, a major challenge for this procedure becoming an accessible treatment option for patients is the lack of standard measures to document benefits to QOL. Patient-reported outcomes (PRO) measures are well-suited for this kind of intervention, where the perspective of the patient is central to defining treatment success. To date, qualitative work with experts, clinicians, and patients has been used to identify the most important domains of QOL for PRO item development. Specifically, our group's qualitative work has identified several domains of QOL that are unique to individuals who have received upper extremity transplants, which are distinct from topics covered by existing PRO measures. These include emotional and social aspects of upper extremity transplant, such as Expectations and Perceived Outcomes, Integration and Assimilation of Transplant, Fitting in, and Post-Surgical Challenges and Complications. The broad topic of Satisfaction with Transplant was subdivided into three subtopics: Function, Sensation, and Aesthetics. Satisfaction with Sensation was also identified as a unique domain not evaluated by existing PRO measures. This report operationalizes these eight QOL domains by presenting scoping definitions. This manuscript describes the work that has been completed for domain characterization as an early step toward developing standardized PRO measures to evaluate these important outcomes specific to upper extremity transplantation.

Development of a rat forelimb vascularized composite allograft (VCA) perfusion protocol.

Vascularized composite allografts (VCAs) refer to en bloc heterogenous tissue that is transplanted to restore form and function after amputation or tissue loss. Rat limb VCA has emerged as a robust translational model to study the pathophysiology of these transplants. However, these models have predominately focused on hindlimb VCAs which does not translate anatomically to upper extremity transplantation, whereas the majority of clinical VCAs are upper extremity and hand transplants. This work details our optimization of rat forelimb VCA procurement and sub-normothermic machine perfusion (SNMP) protocols, with results in comparison to hindlimb perfusion with the same perfusion modality. Results indicate that compared to hindlimbs, rat forelimbs on machine perfusion mandate lower flow rates and higher acceptable maximum pressures. Additionally, low-flow forelimbs have less cellular damage than high-flow forelimbs based on oxygen uptake, edema, potassium levels, and histology through 2 hours of machine perfusion. These results are expected to inform future upper extremity VCA preservation studies.

Identifying Health-Related Quality of Life Domains After Upper Extremity Transplantation

ObjectiveTo identify the most important health-related quality of life (HRQOL) domains and patient-reported outcomes after upper extremity transplantation (UET) in individuals with upper extremity amputation. DesignVerbatim audio-recordings of individual interviews and focus groups were analyzed using qualitative, grounded theory-based methods to identify important domains of HRQOL and provide guidance for outcomes measurement after UET. SettingIndividual interviews were conducted by phone. Focus groups were conducted at 5 upper extremity vascularized composite allotransplantation (VCA) centers in the US and at an international conference of VCA experts. ParticipantsIndividual phone interviews were conducted with 5 individuals with lived experience of UET. Thirteen focus groups were conducted with a total of 59 clinical professionals involved in UET. InterventionsNot applicable. Main Outcome MeasuresNot applicable. ResultsTwenty-eight key HRQOL domains were identified, including physical functioning and medical complications, positive and negative emotional functioning, and social participation, relations, and independence. We identified key constructs for use in evaluation of the potentially substantial physical, medical, social, and emotional effects of UET. ConclusionsThis study provides an overview of the most important issues affecting HRQOL after UET, including several topics that are unique to individuals with UET. This information will be used to establish systematic, comprehensive, and longitudinal measurement of post-UET HRQOL outcomes.

Psychosocial and bioethical challenges and developments for the future of vascularized composite allotransplantation: A scoping review and viewpoint of recent developments and clinical experiences in the field of vascularized composite allotransplantation.

Vascularized Composite Allotransplantation (VCA) has evolved in recent years, encompassing hand, face, uterus, penile, and lower extremity transplantation. Accordingly, without centralized oversight by United States Organ Procurement and Transplantation Network (OPTN) or European Programs, centers have developed their own practices and procedures that likely vary, and accordingly, present different levels of rigor to the evaluation process, internationally. The importance of psychosocial factors in the selection process and treatment course has been widely recognized, and therefore, several approaches have been developed to standardize and guide care of VCA candidates and recipients. We propose to develop an international multidisciplinary platform for the exchange of expertise that includes clinical, patient, and research perspectives. Patient perspectives would derive from peer education and the assessment of patient-reported outcomes. To establish a foundation for such a platform, future research should review and combine current VCA protocols, to develop the ethical framework for a standardized psychosocial evaluation and follow-up of VCA candidates and recipients. This review presents a comprehensive overview of recent results in the field of VCA, developments in structural aspects of VCA, and provides viewpoints driven from clinical experience.

107. Attitudes and Beliefs Towards Upper Extremity Donation in The United States

Purpose: To date, upper extremity transplantation (UET) is the most frequently performed type of Vascularized Composite Allotransplantation (VCA). UET can most closely restore form, function, and sensation in upper extremity amputees. With 300,000 projected upper extremity amputees living in the United States by 2050, UET may become more common. Few studies have assessed the general US population’s attitudes and beliefs towards VCA transplantation and donation. We performed this study to characterize attitudes and beliefs of upper extremity donation by surveying Amazon Mechanical Turk (MTurk) workers who identified as US residents, with an emphasis on MTurk workers with a US Armed Forces (USAF) affiliation. Methods: In May 2020, we administered a one-time Qualtrics survey to Amazon MTurk workers. Eligible participants were US residents aged ≥18 years who completed a study-specific survey. The study survey was further targeted within the MTurk system towards workers who self-reported an affiliation with the USAF. The 28-item survey included a brief description of UET followed by questions regarding opinions on organ and upper extremity transplantation and donation; whether respondents were aware that upper extremity is not included in state ID organ donor designations; and workers’ military affiliation, amputee status, and sociodemographic characteristics. Descriptive statistics were used to summarize study data; frequencies and percentages were calculated for categorical variables. Comparative statistical analysis by Monte Carlo was used to analyze categorical variables. Statistical significance was assessed at 2-sided significance of p < 0.05. Results: A total of 860 respondents completed the study questionnaire. Among these, 529 (61.5%) reported willingness to donate an upper extremity, 152 (17.7%) were undecided, and 179 (20.8%) were unwilling. Among those willing to donate, a significantly higher proportion were female (66.7%, p=0.009), non-Hispanic (63.9%, p=0.000), non-religious (71.3%, p=0.001), non-USAF affiliated (62.8%, p=0.000), and non-amputee or amputee-related (61.7%, p=0.008). Nearly half (n=429, 49.9%) of respondents felt that donating an organ such as a kidney or liver was different from donating a hand or arm with the most common explanation being that upper extremities are an external/visible part of the body. The majority of respondents (n=549, 63.8%) reported being designated organ donors as indicated on their state ID and 411 (47.8%) believed upper extremity donation is already included in this designation. Of those who were state ID designated organ donors, 395 (65.4%) were willing to donate both organs and upper extremities. Conclusions: Our Amazon MTurk survey found that being female, non-Hispanic, non-USAF affiliated, or not being an amputee were significantly associated with willingness to donate upper extremities. Descriptive studies characterizing the reasons that opinions of upper extremity donation differ from solid organ donation may help guide VCA programs, organ procurement organizations, and researchers in their efforts to develop targeted educational materials to broaden the public’s knowledge and awareness of VCA donation to further benefit all patients in need of or desiring transplantation.

Ex Vivo Normothermic Perfusion of Human Upper Limbs.

Ischemia-reperfusion injury remains a primary concern in upper extremity transplantation. Ex vivo normothermic perfusion (EVNP) enables near-physiological organ preservation, avoiding the deleterious effects of hypoxia and cooling. We investigated the effectiveness of human limb EVNP compared with static cold storage (SCS). Twenty human upper extremities were procured. Ten were perfused at 38 °C with an oxygenated red blood cell-based solution, and contralateral limbs served as SCS control (4 °C). EVNP was terminated with systolic arterial pressure ≥115 mm Hg, compartment fullness, or a 20% decline in oxygen saturation. Weight, contractility, compartment pressure, tissue oxygen saturation, and uptake rates were assessed. Perfusate fluid dynamics, gases, electrolytes, and metabolites were measured. Myocyte injury scores and liquid chromatography-mass spectrometry analysis were performed. EVNP duration was 41.6 ± 9.4 h. Vascular resistance averaged 173.0 ± 29.4 mm Hg × min/L. Weight change and compartment pressures were 0.4 ± 12.2% ( P = 0.21) and 21.7 ± 15.58 mm Hg ( P = 0.003), respectively. Arterial and venous carbon dioxide partial pressure, oxygen saturation, and pH were 509.5 ± 91.4 mm Hg, 15.7 ± 30.2 mm Hg, 87.4 ± 11.4%, and 7.3 ± 0.2, respectively. Oxygen uptake rates averaged 5.7 ± 2.8 mL/min/g. Lactate reached 20 mmol/L after 15 (interquartile range = 6) h. Limb contractility was preserved for 30.5 (interquartile range = 15.8) h ( P < 0.001) and negatively correlated with perfusate potassium (ρ = -0.7, P < 0.001). Endpoint myocyte injury scores were 28.9 ± 11.5% (EVNP) and 90.2 ± 11.8% (SCS) ( P < 0.001). A significant increase in taurine ( P = 0.002) and decrease in tryptophan ( P = 0.002) were detected. Infrared thermography and indocyanine green angiography confirmed the presence of peripheral perfusion. EVNP can overcome the limitations of cold preservation by extending preservation times, enabling limb quality assessment, and allowing limb reconditioning before transplantation.

Noninvasive evaluation of intragraft immune responses in upper extremity transplantation.

In vascularized composite allotransplantation (VCA), invasive tissue biopsies remain the gold standard in diagnosing rejection carrying significant morbidity. We aimed to show feasibility of tape-stripping for noninvasive immune monitoring in VCA. Tape-stripping was performed on allografts and native skin of upper extremity transplant recipients. Healthy nontransplanted individuals served as controls. The technique was also used in swine on naïve skin in nontransplanted animals, native skin of treated, transplanted swine, nonrejecting VCAs, and rejecting VCAs. Extracted protein was analyzed for differences in cytokine expression using Luminex technology. Significantly decreased levels of INFγ and IL-1Ra were seen between human allograft samples and native skin. In swine, rejecting grafts had increased IL-1Ra compared to naïve and native skin, decreased levels of GM-CSF compared to native skin, and decreased IL-10 compared to nonrejecting grafts. Unsupervised hierarchical clustering revealed rejecting grafts separated from the nonrejecting (P=0.021). Variable importance in projection scores identified GM-CSF, IL-1Ra, and IL-2 as the most important profiles for group discrimination. Differences in cytokine expression are detectable in human VCA patient native skin and VCA graft skin using a noninvasive tape-stripping method. Swine studies suggest that differences in cytokines between rejecting and nonrejecting grafts are discernable.

Public Perceptions of Cross-Sex Vascularized Composite Allotransplantation

Cross-sex vascularized composite allotransplantation has been performed in cadaveric facial transplantation and clinical extremity transplantation. Understanding the challenge of appropriate donor-recipient matching, this study sought to characterize the public's perception of cross-sex vascularized composite allotransplantation. Participants were surveyed in New York City. Data collected included demographics and willingness to donate vascularized composite allografts (VCAs) of various types. Similar questions were asked in the context of same-sex and cross-sex donation. A total of 101 participants (male: 56.4%; age ≤35 years: 62.4%) were surveyed. The majority expressed willingness to donate to recipients of a different sex (hand: 78.2%, face: 56.4%, penis or uterus: 69.3%, lower limb: 81.2%, abdominal wall: 80.2%, larynx: 81.2%, and solid organs: 85.2%). Among VCAs, willingness to donate facial allografts was significantly different in same-sex versus cross-sex contexts (64.4% vs 56.4%; P = 0.008). Participants were also significantly more likely to donate VCAs to same-sex recipients on behalf of themselves versus loved ones (P < 0.05). There was significantly lower willingness to receive cross-sex versus same-sex facial (P = 0.022) and genital allografts (P = 0.022). Education on the preservation of recipient masculinity or femininity in cross-sex facial transplantation increased participants' willingness to receive a cross-sex face transplant from 56.4% to 71.3% (P = 0.001). This study highlights the urban public's acceptance of VCA donation or reception regardless of sex mismatch. There is increased willingness to receive a cross-sex face transplant after education, highlighting opportunities for future focused interventions to increase public awareness and ultimately the donor pool.

Special Considerations for Secondary Surgery After Upper Extremity Transplantation.

Upper extremity (UE) transplantation is a complex undertaking that may require emergent or elective secondary surgery (SS) days to years following transplant. Various patient and transplantation may help determine what SS is needed. In this study, we characterize the SS needed by our UE transplant patients. We retrospectively reviewed 6 patients who underwent hand and UE transplantation by one of the authors. Transplantation and SS details were obtained from medical records. Hand and arm function was quantified both subjectively (patient-reports) and objectively (Disabilities of the Arm, Shoulder, and Hand Score; Carroll test; Action Research Arm Tests; Box and Block test). Six patients underwent transplantation for a total of 10 transplanted limbs. Five transplants were performed below and 5 above the elbow. Mean time post-transplantation at last follow-up was 5 years (range: 1-9 years). In all, 66.7% of the patients required SS: total 7 surgeries comprising 13 procedures. The most common procedures were to improve hand function-nerve decompressions and tendon transfer, both in above-elbow transplant. Both patients showed a mean improvement of 15 points on Carroll scores. One above-elbow transplant had a brachioplasty for excess skin and another had a hematoma evacuation immediately after transplantation. Procedures in the below-elbow transplants included multiple incision and drainages for a septic wrist and an open reduction and internal fixation for a forearm fracture. Patients receiving UE transplantation often require one or more secondary procedures which may vary with level of transplantation. Secondary surgery should be an important aspect of pretransplant planning and cost-effectiveness determinations. Level IV.

Graft vasculopathy in upper extremity allotransplantation: Results of a retrospective high-resolution ultrasonographic study.

Graft vasculopathy (GV) is the most severe pathologic change of chronic rejection in vascularized composite allotransplantation. Since 2012, the intimal media thickness (IMT) of radial and ulnar arteries was annually monitored by high-resolution ultrasonography in seven bilateral upper extremity transplant (UET) patients. We also investigated the IMT of seven matched healthy subjects (controls). No significant difference between IMT values of controls and UET patients was found. The median IMT values of recipient radial and ulnar arteries were 0.23mm and 0.25mm, respectively, while the median IMT values of grafted radial and ulnar arteries were 0.27mm and 0.30mm, respectively. There was a statistically significant difference in the IMT values of the grafted and recipient ulnar arteries (p=.043), but this difference was no longer significant when patient #2 was excluded. He showed a significant difference between recipient and grafted arteries and significantly higher IMT values (p=.001) of his grafted arteries compared with those of all transplanted patients. This patient developed GV leading to graft loss 11years after the transplantation. In conclusion, this study showed a significant IMT increase in an UET recipient who developed GV.

Pediatric Upper Extremity Vascularized Composite Allotransplantation—Progress and Future

Since 1998, over 120 upper extremity transplants have been successfully performed around the world; however, the field of vascularized composite allotransplantation (VCA) continues to face various medical challenges and ethical controversies. This article summarizes the worldwide experience with transplantation of vascularized composite upper extremities in children and discusses the unique considerations facing potential pediatric VCA recipients. Three children have successfully received composite upper or lower extremity transplants, of which two involved isografts and one involved allografts. Numerous research and clinical advances relevant to VCA have been made, including patient screening, perioperative rehabilitation, allograft preservation and transportation, enhancement of nerve regeneration, understanding of cortical plasticity, and immunomodulatory strategies. Ethical and psychosocial issues remain at the forefront when evaluating potential pediatric VCA recipients. For ethically and rigorously screened pediatric patients with debilitating upper extremity absence, VCA is a compelling option to restore form and function and has a promising future.

Vascularized Composite Allotransplantation in Burn Reconstruction: Systematic Review and Meta-analysis

Vascularized composite allotransplantation has been successfully employed for burn reconstruction since 2003. However, its safety in this population has been questioned due to high levels of alloimmunization from burn care-related tissue exposures. To investigate this, a systematic review of vascularized composite allotransplantation employed for burn reconstruction was conducted, evaluating literature from January 2000 to September 2019. Articles containing vascularized composite allotransplantation, composite tissue allotransplantation, and burn reconstructive surgery were included; articles without published outcomes were excluded. Observational meta-analysis of pooled mortality and acute rejection episodes relative to allograft type (face vs extremity) and reconstruction type (burn vs non-burn) was performed. Twenty-four of the 63 identified articles met the criteria for inclusion, with 5 more articles added after secondary review. To date, 152 allotransplantations have been performed in 117 patients: 45 face transplants and 107 extremity transplants. Of these, 34 (22%) were performed for burn reconstruction in 25 patients (21%) with an overall higher 1-year mortality rate (12.0% vs 1.1%, P = .030). Of these deaths, 75% received three or more simultaneous allografts. Additionally, more episodes of acute rejection occurred compared to non-burn patients (4.4 vs 2.4, P = .035). Vascularized composite allotransplantation performed for burn reconstruction was found to be associated with a greater risk of 1-year mortality and nearly twice the number of episodes of acute rejection. Future studies should seek to identify unique risk factors of burn patients undergoing this operation and evaluate the relationship between antigenic burden and surgical outcomes.