The contribution of the donor vascularised hand and face allograft in transplant rejection: An immunological perspective.

Overcoming immunological rejection remains a barrier to the safe adoption of Vascularised Composite Allotransplantation (VCA). To mitigate this risk, clinical protocols have been derived from solid organ transplantation, targeting recipient immunomodulation, yet VCA is unique. Face and hand composite allografts are composed of multiple different tissues, each with their own immunological properties. Experimental work suggests that allografts carry variable numbers and populations of donor leukocytes in an organ specific manner. Ordinarily, these passenger leukocytes are transferred from the donor graft into the recipient circulation after transplantation. Whether alloantigen presentation manifests as acute allograft rejection or transplant tolerance is unknown. This review aims to characterise the immunological properties of the constituent parts of the donor face and hand, the potential fate of donor leukocytes and to consider theoretical graft specific interventions to mitigate early rejection.

Reaching New Heights: A Comprehensive Study of Hand Transplantations in Korea after Institutionalization of Hand Transplantation Law.

PURPOSE: With the revision of the Organ and Transplantation Act in 2018, the hand has become legal as an area of transplantable organs in Korea. In January 2021, the first hand allotransplantation since legalization was successfully performed, and we have performed a total of three successful hand transplantation since then. By comparing and incorporating our experiences, this study aimed to provide a comprehensive reconstructive solution for hand amputation in Korea. MATERIALS AND METHODS: Recipients were selected through a structured preoperative evaluation, and hand transplantations were performed at the distal forearm level. Postoperatively, patients were treated with three-drug immunosuppressive regimen, and functional outcomes were monitored. RESULTS: The hand transplantations were performed without intraoperative complications. All patients had partial skin necrosis and underwent additional surgical procedures in 2 months after transplantation. After additional operations, no further severe complications were observed. Also, patients developed acute rejection within 3 months of surgery, but all resolved within 2 weeks after steroid pulse therapy. Motor and sensory function improved dramatically, and patients were very satisfied with the appearance and function of their transplanted hands. CONCLUSION: Hand transplantation is a viable reconstructive option, and patients have shown positive functional and psychological outcomes. Although this study has limitations, such as the small number of patients and short follow-up period, we should focus on continued recovery of hand function, and be careful not to develop side effects from immunosuppressive drugs. Through the present study, we will continue to strive for a bright future regarding hand transplantation in Korea.

The Nuances of Hand Transplantation After Sepsis.

Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various forms of trauma. However, in the developed world, amputation following severe sepsis seems to be an increasingly common indication for referral to hand transplant programs. Unlike trauma patients with isolated limb injuries, patients with amputations as a complication of sepsis have survived through a state of global tissue hypoperfusion and multisystem organ failure with severe, enduring effects on the entire body's physiology. This article reviews the unique considerations for VCA candidacy in postsepsis patients with upper limb amputation. These insights may also be relevant to postsepsis patients undergoing other forms of transplantation or to VCA patients requiring additional future solid organ transplants.

A Single-Center Retrospective Evaluation of Decision-Making and Factors Motivating Hand Transplant Candidates.

INTRODUCTION: Advancements in vascularized composite allotransplantation have made hand transplants possible for persons living with upper limb loss. Hand transplantation is not a life-saving procedure, but rather a quality-of-life enhancing procedure; hence the risk of morbidity and mortality must be weighed against improvements in function and appearance. This study explored the decision-making process of patients evaluated for hand transplantation. METHODS/APPROACH: A qualitative case series study using retrospective chart data of evaluations was conducted between January 1, 2011 and February 28, 2020. Notes were extracted and read by three reviewers. Each case was summarized noting similarities and differences. FINDINGS: Nine patients underwent evaluation. Eight were no longer under evaluation and did not receive transplant; one was still undergoing evaluation. Patient motivations for evaluation were dissatisfaction with prostheses or self-image, chronic pain, performing activities of daily living, occupation, burden placed on caregivers, and concerns about overuse of non-affected limbs. Patients chose not to pursue transplantation due to rehabilitation time, immunosuppression, alternative treatments, and social and financial challenges. The clinical team discontinued evaluations due to unmet evaluation requirements, medical contraindications, or treatment alternatives. Different modes of shared decision-making were present depending on the party most heavily featured in the charts as driving decisions. DISCUSSION: This was an examination of shared decision-making with hand transplant candidates who did not proceed to transplant. Reasons for choosing alternative strategies for management were multifactorial. Lessons learned regarding patient motivations and shared decision-making can inform future interventions to better support patients.

Vascularized Composite Allotransplantation of the Hand: A Systematic Review of Eligibility Criteria.

BACKGROUND: Hand transplantation (HT) has emerged as an intervention of last resort for those who endured amputation or irreparable loss of upper extremity function. However, because of the considerable effort required for allograft management and the risks of lifelong immunosuppression, patient eligibility is critical to treatment success. Thus, the objective of this article is to investigate the reported eligibility criteria of HT centers globally. METHODS: A systematic review of the HT literature was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, using PubMed, Cochrane, Ovid/Medline, and Scopus. Program Web sites and clinicaltrials.gov entries were included where available. RESULTS: A total of 354 articles were reviewed, 101 of which met inclusion criteria. Furthermore, 10 patient-facing Web sites and 11 clinical trials were included. The most reported criteria related to the capacity to manage the allograft posttransplantation, including access to follow-up, insurance coverage, psychological stability, and history of medical compliance. Other factors related to the impact of immunosuppression, such as active pregnancy and patient immune status, were less emphasized. CONCLUSIONS: Because of the novelty of the field, eligibility criteria continue to evolve. While there is consensus on certain eligibility factors, other criteria diverge between programs, and very few factors were considered absolute contraindications. As the popularity of the field continues to grow, we encourage the development of consensus evidence-based eligibility criteria.

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.

A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response.

Hand transplantation: can we balance the risks and benefits?

Asking 'can we balance the risks and benefits?' implies that a quantification of both risk and benefit in hand transplantation (here the terms hand transplant and hand transplantation refer to allotransplantation of the human hand or hand and part or all of the upper limb or limbs) is possible. Despite all we have learned in recent years about hand transplantation, much remains unknown. Even if reliable methods for quantification of risk and benefit were available, fundamental issues relating to effective communication across the gulf of lived experience between the (presumably) handed surgeon and the handless patient remain. Inherent complexities mean some consider hand transplantation an unsolved problem, but we believe the medical and technical considerations fall within the ambit of a competent multidisciplinary team, and that psychosocial and ethical challenges are open to management through robust frameworks for assessment and decision making, underpinned by an extended period of assessment and dialogue, with candid acknowledgement where uncertainty remains. This respects the patient's autonomy while addressing the need for a prolonged period of informing consent.Level of evidence: V.

Three-Dimensional Computer-Aided Design Modeling and Printing for Accurate Toe-to-Hand Transplantation.

PURPOSE: To introduce toe-to-hand transplantation performed with the assistance of both bone and soft tissue modeling using 3-dimensional printing technology. METHODS: From May 2015 to October 2018, 31 patients (group A, 24 thumbs and 7 fingers) were included. Computed tomography scans were acquired using a spiral computed tomography scanner, and the data were processed with software. Bone, skin, and nail models were created for tailoring the flap taken from the great toe. The impact of foot pathology in terms of pain, disability, and activity restriction was assessed using the Foot Function Index. For comparison, we included 35 patients (group B) who underwent toe-to-hand transplantation without the assistance of 3-dimensional computer-aided modeling. RESULTS: The mean duration of follow-up of groups A and B was 26 months (range, 24-31 months) and 27 months (range, 24-33 months), respectively. The mean Foot Function Index of groups A and B was 5 (range: 0-15) and 17 (range, 0-39), respectively. CONCLUSIONS: Three-dimensional computer-aided modeling and printing provide geometric accuracy in toe-to-hand transplantation. It also may reduce the donor foot morbidity by accurate flap designing and harvesting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Hand Therapy Regimen for Functional Recovery Following Combined Face and Bilateral Hand Transplantation.

Intensive postoperative rehabilitation therapy is associated with positive functional recovery in hand transplants (HTs). Our goal is to share the hand therapy protocol developed for our patient who underwent a combined face and bilateral HT. The patient is a 23-year-old right-hand-dominant male with a history of third-degree burns to 80% of his body following a motor vehicle accident. A multidisciplinary evaluation established his candidacy for a combined face and bilateral HT, and surgery took place in August 2020. Our individualized hand therapy protocol consisted of 4 phases. The pre-surgery phase focused on planning the orthotics and patient/caregivers' education on the rehabilitation process. The intensive care unit (ICU)/acute care phase involved hand allograft protection and positioning via orthotic fabrication, safe limb handling, and edema/wound management. The inpatient rehabilitation phase aimed to prepare the patient for independent living via neuromuscular and sensory re-education, improvement of upper extremities strength/flexibility, training basic activities of daily living, and providing a home exercise program (HEP). Finally, the outpatient phase aimed to maximize our patient's range of motion and independency in performing his routine activities and HEP. The patient's post-transplant functional outcomes showed a significant improvement compared to the pre-operative baseline. We hope this report sheds light on a comprehensive hand therapy program in HT.

The First Successful Combined Full Face and Bilateral Hand Transplant.

BACKGROUND: Vascularized composite allotransplantation has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, the authors present the first successful combined full face and bilateral hand transplant. METHODS: A 21-year-old man presented for evaluation with sequelae of an 80 percent total body surface area burn injury sustained after a motor vehicle accident. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined face and bilateral hand transplantation. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS: Combined full face (i.e., eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (i.e., forearm level) was performed over 23 hours on August 12 to 13, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At 8 months, the patient was approaching functional independence and remained free of acute rejection. He had significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSIONS: Combined face and bilateral hand transplantation is feasible. This was the most comprehensive vascularized composite allotransplantation procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

5-Year Activity and Participation Outcomes of the First Successful Pediatric Bilateral Hand Transplantation: A Case Report.

AIMS: Describe the 5-year outcomes of the first successful pediatric bilateral hand transplantation. METHODS: The child underwent quadrimembral amputation at age two and received bilateral hand allografts at age eight. Rehabilitation included biomechanical, neurorehabilitation, and occupational approaches in acute and outpatient settings. Therapist observed outcomes, patient-reported measures, and parent-reported measures were repeated over a 5-year period. RESULTS: Observation assessments revealed functional dexterity skills and modified independence to full independence with self-care activities. The parent reported the child had moderate difficulty with upper extremity functioning 25-, 41-, and 48-months post-transplantation, and mild difficulty at 60-months; the child reported no difficulties in this domain at 41 months. Five years post-transplantation the child reported enjoying many age-appropriate activities, and high-quality peer relations were endorsed by both parent and child. CONCLUSION: The child developed hand movements for daily activities and was completing daily activities with improved efficiency. Health-related quality of life outcomes were favorable.

Two Decades of Hand Transplantation: A Systematic Review of Outcomes.

ABSTRACT: Hand transplantation for upper extremity amputation provides a unique treatment that restores form and function, which may not be achieved by traditional reconstruction and prosthetics. However, despite enhancing quality of life, hand transplantation remains controversial, because of immunological complications, transplant rejection, and medication effects. This systematic literature review sought to collect information on current experiences and outcomes of hand transplants to determine the efficacy and utility of hand transplants. The databases PubMed, Scopus, and Embase were analyzed with combinations of "hand" or "upper extremity" or "arm" and "transplant" or "allograft," with information collected on recipient characteristics, details of transplant, immunological outcomes, functional outcomes, and complications. Functional outcomes, as measured by Disabilities of Arm, Shoulder and Hand score, were compared between patient groups using Wilcoxon signed-rank test or 1-way analysis of variance test and post hoc Tukey test. Within the 108 articles that fulfilled inclusion and exclusion criteria, there were 96 patients with 148 hand transplants. There were 57 patients who experienced acute rejection and 5 patients with chronic rejection. Disabilities of the Arm, Shoulder and Hand scores significantly decreased after hand transplantation and were significantly lower for distal transplants compared with proximal transplants. There were 3 patients with concurrent face transplantation and 2 patients with simultaneous leg transplants. Sixteen patients experienced amputation of the hand transplant, and there were 5 deaths. This study found that hand transplantation provides significant restoration of function and form, especially for proximal transplants. Reduction in complications, such as rejection and amputation, can be achieved by decreasing medication cost and patient education.

Applying Health Utility Outcome Measures and Quality-Adjusted Life-Years to Compare Hand Allotransplantation and Myoelectric Prostheses for Upper Extremity Amputations.

BACKGROUND: An amputation of the upper extremity not only is devastating for the patient's physical, emotional, and social well-being but also constitutes a financial stress for both the patient and the health care system. The objective of this study was to determine the utility and quality-adjusted life-years of hand allotransplantation versus myoelectric prostheses and to compare these measures in patients afflicted with unilateral versus bilateral amputations. METHODS: A survey was administered on bilateral amputees, unilateral amputees, replantation patients, and healthy controls. Patient demographics, functional patient-reported outcomes, quality-of-life questionnaires, and utility outcome measures were calculated for four different scenarios: hand transplantation and myoelectric prostheses with or without complications. RESULTS: Five bilateral amputees, 12 unilateral amputees, nine replantation patients, and 45 healthy controls completed the survey. The highest quality-adjusted life-years were obtained in the replantation patient group for the scenario of myoelectric prosthesis without complications (mean, 34.8 years). Altogether, there was no statistically significant difference between hand transplantation and myoelectric prostheses (p = 0.36). On subgroup analysis, unilateral amputees reported significantly higher quality-adjusted life-years for myoelectric prostheses rather than hand transplantation (6.4; p = 0.0015), whereas bilateral amputees did not demonstrate a significant difference (-2.4; p = 0.299). CONCLUSIONS: Utility and quality-adjusted life-years do not differ significantly between hand transplantation and myoelectric prostheses, except in unilateral amputees with myoelectric prostheses, who had higher quality-of-life scores. Based on trends from this pilot study, myoelectric prostheses may be considered for unilateral amputees, whereas no superiority can be demonstrated between both treatments in bilateral amputees. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Evaluating Treatment Preferences and Perceptions of a Prosthetic Versus a Transplanted Hand: A Conjoint Analysis-Based Study.

INTRODUCTION: This study used a conjoint analysis-based survey to assess which factors are most influential when considering treatment with a prosthesis or transplant after a unilateral hand amputation. METHODS: Overall, 469 respondents were recruited using Amazon Mechanical Turk and asked to assume that they experienced a hand amputation. To determine preferences for a prosthetic, respondents chose among 11 pairs of alternatives with variations in the following attributes: appearance, function, maintenance, and learning time. Respondents were then presented with descriptions of the risks and outcomes of hand transplantation. The most compelling reasons for and against a transplant were determined and characteristics predictive of support for a transplant were identified. RESULTS: The most important attributes for a prosthesis were "lifelike appearance" and "myolectric function." For hand transplantation, respondents were most concerned about immunosuppression side effects (n = 323, 69%) and the intense nature of surgery (n = 275, 59%), whereas the most positive benefit was the concept of the transplant being "natural" (n = 339, 72%). When faced with the choice of a hand transplant or a prosthetic, approximately 50% of respondents chose a transplantation. Younger age, previous medical experiences, a perceived "familiarity with medical issues," and the regular attendance of religious services were associated with strong support for a hand transplantation (P < 0.01). CONCLUSIONS: When considering a hand prosthesis, respondents are motivated most by appearance and function. Meanwhile, with hand transplantation, the risks of immunosuppression and the intense nature of surgery and recovery are predominant concerns. These findings may help inform patient-physician discussions when considering treatment after unilateral hand amputation.

[Hand Allotransplantation: Care and Challenges].

Hand allotransplantation, a composite tissue allograft, is a time-consuming surgical procedure. This procedure has been shown to significantly improve quality of life in patients with upper extremity loss. The suitability of this procedure must be rigorously evaluated before surgery, and long term antirejection drugs and rehabilitation exercises must be carried out after hand transplantation. Moreover, its success requires close collaboration within the multidisciplinary team. Several related issues are addressed in this article, including the history of hand transplantation surgery, the pros and cons of this procedure, rejection response and immunotherapy, rehabilitation and hand function recovery after hand transplantation, and pre- and post-procedure psychological reactions and evaluations. Response suggestions at the patient and environmental level that reflect the multiple challenges involved in hand transplantation are provided as a reference for clinical decision-makers.

Donor-recipient matching in hand transplantation: a comparison of anthropometric measurements, 3-dimensional virtual models and printed epitheses.

Donor-recipient matching in hand transplantation remains challenging. The usefulness of three-dimensional (3-D) virtual models and printed epitheses were compared with measurements on cadaveric extremities to evaluate the most accurate method of donor-recipient matching for allograft procurement. Ten anthropometric measurements were recorded from 12 human cadaveric upper extremities and matched to printed epitheses and 3-D virtual models. Five circumferential and two longitudinal measurements obtained an intra-class correlation of >0.75 with all three methods, with the Kaplan (0.973) and wrist circumferences (0.942) achieving the highest concordance. Measurement on cadaveric specimens was the most reliable method. Using different combinations of donor hand and recipient forearms, a series of 72 virtual transplantations were then created, and their compatibility rated by ten transplant surgeons. The results confirmed that anthropometric measurements, obtained directly from potential human donor limbs and based on wrist circumference as the primary parameter, provide the best and most clinically relevant donor-recipient match.

Complementary Phenomena: Phantom Hand and Phantom Face.

After tissue or limb loss, the development of sensation and perception of the lost or deafferent tissue is defined as a phantom phenomenon. We investigated the presence of phantom phenomena in individuals who underwent a full face transplant as well as those who had a hand transplant. Specifically, we investigated sensory perception of the face on the fingers and sensory perception of the fingers on the face in three full face and four hand transplant patients. In all seven individuals, we used a brush to separately stimulate the right and left sides of the face or the palmar and dorsal faces of the hand. We then asked the individuals if they felt a sensation of touch on any other part of their body and, if so, to describe their perceptions. Changes in the regions of the primary sensory cortex representing the hand and face were defined using fMRI obtained via tactile sensory stimulation of the clinical examination areas. Two of the full face transplant patients reported sensory perceptions such as a prominent sensation of touch on their faces during sensory stimulation of their fingers. Three of the hand transplant patients reported sensory perceptions, which we referred to as finger patches, during sensory stimulation of the face area. In fMRI, overlaps were observed in the cortical hand and face representation areas. We consider the phantom hand and phantom face phenomena we observed to be complementary due to the neighborhood of the representations of the hand and face in the somatosensory cortex.