Upper Extremity Transplantation Research Articles

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

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

Case Report: Post-transplant lymphoproliferative disorder as a serious complication of vascularized composite allotransplantation

Vascularized composite allotransplantation (VCA) is an emerging field in transplant surgery. Despite overall positive outcomes, VCA confers risk for multiple complications related to the procedure and subsequent immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders occurring after solid organ and hematopoietic stem cell transplant. A patient with PTLD after bilateral upper extremity transplantation is presented as well as a review of all known cases of PTLD after VCA, with a focus on the unique epidemiology, presentation, and treatment in this population.

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 following upper extremity transplantation are largely due 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 MHC-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). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

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.

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.

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.

Psychosocial Predictors of Upper Extremity Transplantation Outcomes: A Review of the International Registry 1998-2016.

Upper extremity transplantation (UET) is becoming increasingly common. This article attempts to collate data from cases contributing to the International Registry on Hand and Composite Tissue Transplantation (IRHCTT), define psychosocial themes perceived as predictors of success using statistical methods, and provide an objective measure for optimization and selection of candidates. The IRHCTT provided anonymous data on UET recipients. A supplementary psychosocial survey was developed focusing on themes of depression, posttraumatic stress disorder (PTSD), anxiety, interpersonal functioning and dependence, compliance, chronic pain, social support, quality of life, and patient expectations. We determined the risk of transplant loss and psychological factors associated with higher risk of transplant loss. Sixty-two UET recipients reported to the IRHCTT. Forty-three psychosocial surveys (68%) were received, with 38 (88%) having intact transplants and 5 (12%) being amputated. Among recipients with a diagnosis of anxiety (N = 29, 67%), 5 (17%) reported transplant loss (P = 0.03). Among those with depression (N = 14, 33%), 2 recipients (14%) has transplant loss (P = 0.17); while 4 recipients (22%) with PTSD (N = 18, 42%) had transplant loss (P = 0.01). Of participants active in occupational therapy (N = 28, 65%), 2 (7%) reported transplant loss (P = 0.09). Of recipients with realistic functional expectations (N = 34, 79%), 2 (6%) had transplant loss versus 3 (34%) who were felt to not have realistic expectations (N = 9, 21%, P = 0.05). Recipients with strong family support (N = 33, 77%) had a lower risk of transplant loss compared with poor or fair family support (N = 10, 23%), but did not reach statistical significance (6% versus 30%, P = 0.14). Anxiety, depression, PTSD, participation in occupational therapy, expectations for posttransplant function, and family support are associated with postsurgical transplant status.

Evolution of the rat hind limb transplant as an experimental model of vascularized composite allotransplantation: Approaches and advantages.

As clinical experience with surgical techniques and immunosuppression in vascularized composite allotransplantation recipients has accumulated, vascularized composite allotransplantation for hand and face have become standard of care in some countries for select patients who have experienced catastrophic tissue loss. Experience to date suggests that clinical vascularized composite allotransplantation grafts undergo the same processes of allograft rejection as solid organ grafts. Nonetheless, there are some distinct differences, especially with respect to the immunologic influence of the skin and how the graft is affected by environmental and traumatic insults. Understanding the mechanisms around these similarities and differences has the potential to not only improve vascularized composite allotransplantation outcomes but also outcomes for all types of transplants and to contribute to our understanding of how complex systems of immunity and function work together. A distinct disadvantage in the study of upper extremity vascularized composite allotransplantation recipients is the low number of clinical transplants performed each year. As upper extremity transplantation is a quality of life rather than a lifesaving transplant, these numbers are not likely to increase significantly until the risks of systemic immunosuppression can be reduced. As such, experimental models of vascularized composite allotransplantation are essential to test hypotheses regarding unique characteristics of graft rejection and acceptance of vascularized composite allotransplantation allografts. Rat hind limb vascularized composite allotransplantation models have been widely used to address these questions and provide essential proof-of-concept findings which can then be extended to other experimental models, including mice and large animal models, as new concepts are translated to the clinic. Here, we review the large body of rat hind limb vascularized composite allotransplantation models in the literature, with a focus on the various surgical models that have been developed, contrasting the characteristics of the specific model and how they have been applied. We hope that this review will assist other researchers in choosing the most appropriate rat hind limb transplantation model for their scientific interests.

Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation.

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5mg/kg) for 14days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1×106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500µL ip, POD 1, 5). Banff grade III or 120days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28days in CTRL (n=7), 34 in ASC (n=6), and 27.5 in ASC-CYP (n=4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.

Hand transplantation in the United States: A review of the Organ Procurement and Transplantation Network/United Network for Organ Sharing Database.

Hand transplantation is the most common application of vascularized composite allotransplantation (VCA). Since July 3, 2014, VCAs were added to the definition of organs covered by federal regulation (the Organ Procurement and Transplantation Network (OPTN) Final Rule) and legislation (the National Organ Transplant Act). As such, VCA is subject to requirements including data submission. We performed an analysis of recipients reported to the OPTN to have received hand transplantation between 1999 and 2018. Forty-three patients were identified as having been listed for upper extremity transplantation in the United States. Of these, 22 received transplantation prior to July 3, 2014 and 10 from then to December 31, 2018. Of patients transplanted after 2014, posttransplant functional scores included a decrease in Disabilities of the Arm, Shoulder and Hand questionnaire in 3 of 10 patients, Carroll test scores ranging from 9 to 60 of 99, and monofilament testing with protective sensation achieved in 4 of 6 patients. Complications included rejection in nine recipients with Banff scores from II-IV. One patient experienced graft failure 5days after transplantation. Of the remaining patients, two were reported as receiving monotherapy and seven receiving dual or triple immunosuppression therapy. The inclusion of VCA in the OPTN Final Rule standardized parameters for safe implementation and data collection.

Clinical Significance of Alloantibodies in Hand Transplantation: A Multicenter Study.

Donor-specific antibodies (DSAs) have a strong negative correlation with long-term survival in solid organ transplantation. Although the clinical significance of DSA and antibody-mediated rejection (AMR) in upper extremity transplantation (UET) remains to be established, a growing number of single-center reports indicate their presence and potential clinical impact. We present a multicenter study assessing the occurrence and significance of alloantibodies in UET in reference to immunological parameters and functional outcome. Our study revealed a high prevalence and early development of de novo DSA and non-DSA (43%, the majority detected within the first 3 postoperative y). HLA class II mismatch correlated with antibody development, which in turn significantly correlated with the incidence of acute cellular rejection. Cellular rejections preceded antibody development in almost all cases. A strong correlation between DSA and graft survival or function cannot be statistically established at this early stage but a correlation with a lesser outcome seems to emerge. While the phenotype and true clinical effect of AMR remain to be better defined, the high prevalence of DSA and the correlation with acute rejection highlight the need for optimizing immunosuppression, close monitoring, and the relevance of an HLA class II match in UET recipients.

Indian Subcontinent's First Proximal Forearm Level Double Upper Extremity Transplantation.

Introduction Vascularized composite allotransplantation (VCA) has added another step to the reconstructive ladder, leading to a paradigm shift in the approach toward management of cases of upper limb amputations. In this article, we discuss in detail the technical aspects of proximal forearm level transplantation, as well as the immediate posttransplant monitoring and immunosuppression protocols. Materials and Methods A 24-year-old male victim of an electric injury presented with a bilateral proximal forearm level amputation. After the mandatory preoperative psychiatric and immunological evaluation, the patient underwent a proximal forearm level double upper extremity transplantation. He was then put on a stringent immunosuppression and physical rehabilitative regime. Discussion Conceptually, the proximal forearm level transplantation is significantly different from distal forearm level transplant. This transplant “reestablishes” the “donor extremity length,” maintains the normal functional length of the donor muscles, and the functional return happens only after the newly transplanted donor muscles are reinnervated over a period of time. Conclusion As the sequence of surgical repair and associated decision making could be quite confusing for this level of transplantation, it is highly advisable to do mock cadaver surgical dissections in order to standardize the procedure and make the team familiar with it.

Comprehensive Assessment of Vascularized Composite Allotransplantation Patient-Oriented Online Resources.

Online resources have become a major source of medical information for the general public. To date, there has not been an assessment of patient-oriented online resources for face and upper extremity transplantation candidates and patients. The goal of this study is to perform a comprehensive assessment of these resources. Our analysis relied on 2 dimensions: comprehensiveness and readability. Comprehensiveness was evaluated using 14 predetermined variables. Readability was evaluated using 8 different readability scales through the Readability Studio Professional Edition Software (Oleander Software, Ltd, Vandalia, Ohio). Data were also collected from solid organ transplantation (SOT), specifically kidney and liver, programs for comparison. Face and upper extremity transplantation programs were significantly more likely to list exclusion criteria (73.9% vs 41.2%; P = 0.02), the need for life-long immunosuppression (87.0% vs 58.8%; P = 0.02), and benefits of transplantation (91.3% vs 61.8%; P = 0.01) compared with SOT programs. The average readability level of online resources by all face and upper extremity transplantation programs exceeded the sixth grade reading level recommended by the National Institutes of Health and the American Medical Association. The average reading grade level of online resources by these programs was also significantly higher than those of SOT with both exceeding the recommended reading level (13.95 ± 1.55 vs 12.60 ± 1.65; P = 0.003). Future efforts in face and upper extremity transplantation should be directed toward developing standardized, comprehensive, and intelligible resources with high-quality content and simple language.

Hand Transplantation: The Benefits, Risks, Outcomes, and Future.

The field of transplantation came to fruition in 1954 when Joseph Murray, an American plastic surgeon, performed the first kidney transplant in the world.1 Subsequently, most early transplantations in the U.S. were of solid homogeneous organs. Then, in 1964, a hand transplant was performed in Ecuador on a sailor who had lost both arms in an explosion,2 and the possibility of composite tissue allotransplantation (CTA) with heterogeneous tissues then emerged. However, the patient's graft was rejected and was explanted at week 3. The field was stagnant until the 1980s, when the discovery of calcineurin inhibitors improved immunotherapy and made limb transplantation viable. In 1999, a hand was transplanted with long-term success in Louisville, Kentucky,3 reawakening interest in CTA and reconstructive transplantation. By 2009, 53 successful hand transplants had been performed worldwide.4In reconstructive transplantation for catastrophic limb and tissue loss, a one-year graft-survival rate of 96% has been reported5—notable because upper-extremity transplantation is extremely complex. The steps include bone approximation and plating of both the radius and ulna, extensive vessel anastomoses, extensor and flexor tendon repairs, and limb innervation.Hand and arm transplantation optimally restores full motor and sensory function. Investigators6 reported better functional outcomes after tissue transplants than after using prosthetic devices: quantitative testing7 in multiple recipients revealed that CTA methods enabled patients to resume most daily activities, including eating, driving, and writing.6 In one registry,5 all transplant recipients developed protective sensibility against pain, 90% regained tactile sensibility, and 82.3% achieved discriminative (fine) sensibility. However, the greatest benefit was improved quality of life, reported by 75% of recipients.5Despite the benefits of CTA, debate continues on whether the potential for improving a patient's quality of life outweighs the risks: limb transplants are usually elective procedures, yet they necessitate intensive surgery and the same lifelong immunosuppressive therapy as do solid-organ transplants. Risks include opportunistic infection (chiefly cytomegalovirus), metabolic disorders such as diabetes mellitus and Cushing syndrome, and malignancies (skin cancers and lymphoproliferative disease).5,8,9 The graft itself might also fail consequent to infection, acute rejection, intimal hyperplasia, or noncompliance with immunosuppressive medications.5 Acute rejection, which reportedly occurs in 85% of recipients within the first year, typically manifests itself with cutaneous lesions.5,10 Therefore, healthcare providers disagree about when and whether hand transplantation should be offered.11 On the bright side, acute rejection can be reversed with prompt treatment, and we found no reports of graft-versus-host disease or chronic rejection in recipients of hand grafts.Satisfactory survival rates after CTA indicate that the field of reconstructive transplantation will continue to expand. Risk reduction will be crucial, particularly in association with immunotherapy. The Baylor Comprehensive Hand Transplant Program team has developed a protocol for using donor bone marrow and stem cells to modulate the immune system in place of typical immunosuppression during clinical reconstructive transplantation. Success in these efforts may transform the care of patients who experience catastrophic limb loss.We thank Sebastian J. Winocour, MD, FRCSC, and Shayan A. Izaddoost, MD, PhD, Division of Plastic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, for their contributions to the manuscript.