ABSTRACT
Introduction: Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA. Methods: For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods. Results: In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times. Discussion: Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts.
Subject(s)
Vascularized Composite Allotransplantation , Rats , Humans , Animals , Rats, Inbred Lew , Vascularized Composite Allotransplantation/adverse effects , Vascularized Composite Allotransplantation/methods , Tacrolimus/therapeutic use , Inflammation , Inflammation Mediators , Peripheral NervesABSTRACT
The purpose of this article is to share our institution's experience in optimizing the suitability of composite donor tissue for use in hand transplantation. The centerpiece of this process includes procurement techniques, preservation and timing issues, and anatomical matching. Recovery of the donor hand must proceed in an efficient, organized, and expedient manner. Proper timing of the donor operation not only ensures the quality of donor tissue and outcome for the hand recipient, but also allows surgeons recovering other organs to obtain high quality tissue for those recipients. Timing remains a critical factor in preserving tissue after removal from the donor. We will also consider the factors of temperature and preservation solution during transport.
Subject(s)
Hand Transplantation , Plastic Surgery Procedures/methods , Specimen Handling , Tissue Donors , Tissue Preservation , Tissue and Organ Procurement , Female , Hand/innervation , Humans , Male , Specimen Handling/methods , Time Factors , Tissue Preservation/methods , Tissue and Organ Procurement/methods , Transplantation, HomologousABSTRACT
Amputation induces substantial reorganization of the body part somatotopy in primary sensory cortex (S1 complex, hereafter S1) [1, 2], and these effects of deafferentiation increase with time [3]. Determining whether these changes are reversible is critical for understanding the potential to recover from deafferenting injuries. Earlier BOLD fMRI data demonstrate increased S1 activity in response to stimulation of an allogenically transplanted hand [4]. Here, we report the first evidence that the representation of a transplanted hand can actually recapture the pre-amputation S1 hand territory. A 54-year-old male received a unilateral hand transplant 35 years after traumatic amputation of his right hand. Despite limited sensation, palmar tactile stimulation delivered 4 months post-transplant evoked contralateral S1 responses that were indistinguishable in location and amplitude from those detected in healthy matched controls. We find no evidence for persistent intrusion of representations of the face within the representation of the transplanted hand, although such intrusions are commonly reported in amputees [5, 6]. Our results suggest that even decades after complete deafferentiation, restoring afferent input to S1 leads to re-establishment of the gross hand representation within its original territory. Unexpectedly, large ipsilateral S1 responses accompanied sensory stimulation of the patient's intact hand. These may reflect a change in interhemispheric inhibition that could contribute to maintaining latent hand representations during the period of amputation.
Subject(s)
Cerebral Cortex/physiology , Hand Transplantation , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Time Factors , TouchABSTRACT
Because nearly all the vascularized composite allotransplants performed in the United States have been proposed and carried out as research, the ethical duty to report outcomes pertains. This duty is set forth in several international statements, including the World Health Organization's Statement on Public Disclosure of Clinical Trial Results, the 2013 Helsinki Declaration, and the Singapore Statement on Research Integrity. These international statements call for the reporting of negative and inconclusive outcomes as well as positive outcomes, and for the reporting of results from previously unreported past research. In 2014, the Organ Procurement and Transplant Network vascularized composite allotransplant committee proposed mandatory data collection and submission requirements for transplants, but only for those which took place in September 2015 or later. Reporting of data for the allotransplants which took place before September 2015 was regarded as optional, even though the pre-September 2015 transplants represent the majority of vascularized composite allotransplants in the United States and all the long-term outcome data. We encourage the American Society of Reconstructive Transplantation and the Organ Procurement and Transplant Network committee to embrace the international ethical standards and to hold all vascularized composite allotransplant programs in the United States accountable for reporting data on outcomes of pre-September 2015 transplants.
ABSTRACT
Since the 1960s, skin has been considered to be the most allogenic tissue in humans. This tenet has remained unquestioned in the reconstructive transplant arena, which has led to skin serving as the sole monitor for early rejection in vascularized composite allotransplantation. In this article, the authors question the validity of this belief. The authors' hypothesis is that skin is not always an accurate monitor of rejection in the deep tissues, thus questioning the positive and negative predictive value of the punch biopsy for suspected vascularized composite allotransplantation rejection. A search was carried out identifying vascularized composite allotransplantation publications where the allogenicity of transplanted skin was evaluated. Eighteen publications claimed skin was found to be the most allogenic tissue in humans, justifying its use as a superior monitor for rejection. Eight publications demonstrated skin to be a poor monitor of rejection deeper to the skin. Two vascularized composite allotransplantation animal studies reported skin rejecting simultaneously with the deeper tissues. Finally, three publications discussed a skin and kidney allograft, transplanted simultaneously, indicating skin allogenicity was equivalent to the that of the kidney allograft. Much of the literature in human vascularized composite allotransplantation claims skin to be an excellent monitor of the deep tissues. The conclusion from this study is that skin does not always function as a good monitor for what could be rejecting in the deep tissues. The authors believe continued research is necessary to focus on expanding novel monitoring techniques and technologies to accurately diagnose vascularized composite allotransplantation rejection without tissue destruction.
Subject(s)
Composite Tissue Allografts/physiology , Skin Physiological Phenomena , Animals , Composite Tissue Allografts/immunology , Graft Rejection/physiopathology , Humans , Models, Animal , Terminology as Topic , Transplantation Immunology/physiology , Vascularized Composite Allotransplantation/trendsABSTRACT
BACKGROUND: From 1996 to 2000, Diefenbeck et al. carried out six knee vascularized composite allotransplants. The allotransplants were composed of bone, soft tissue, and femoral vascular pedicle (25 to 40 cm). All rejected between 14 and 56 months. Failures were attributed to chronic rejection. In 2008, the Louisville team lost their fourth patient's hand transplant at 8 months. During the rejection workup, intraoperative findings noted a thickened arterial pedicle attributed to intimal hyperplasia with significant fibrotic perivascular tissue and a near "no-flow phenomenon." No cutaneous rejection was appreciated and failure was attributed to chronic rejection. METHODS: Data were collected from two teams, one in Germany and the other in Louisville, Kentucky. The population under study consisted of the six knee and one hand transplants. The factor of interest was the long donor arterial pedicle. The outcome measurements were transplant survival time and histopathologic results. RESULTS: There are only seven published vascularized composite allotransplant cases where a donor artery longer than 25 cm was used. This cohort represents a 100 percent accelerated failure rate. The cause of these losses remains unexplained. The donor arteries suffered from T-cell-mediated rejection and ischemia-induced media/adventitial necrosis. CONCLUSIONS: We hypothesize that the donor artery rejected at an accelerated rate because of ischemia caused by disruption of the external vasa vasorum in conjunction with intimal hyperplasia induced by T-cell-mediated rejection that led to disruption of the Windkessel effect. Loss of this effect presented as intimal hyperplasia accelerated by ischemia causing an expedited transplant failure. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
Subject(s)
Arteries/physiology , Composite Tissue Allografts/blood supply , Graft Rejection/physiopathology , Ischemia/physiopathology , Vascularized Composite Allotransplantation/adverse effects , Arteries/transplantation , Graft Rejection/prevention & control , Graft Survival/physiology , Hand Transplantation/adverse effects , Humans , Hyperplasia/immunology , Hyperplasia/physiopathology , Ischemia/immunology , Knee/surgery , Regional Blood Flow/physiology , T-Lymphocytes/immunology , Time Factors , Tunica Intima/pathology , Vasa Vasorum/pathologySubject(s)
Graft Rejection/epidemiology , Hand Strength , Hand Transplantation , Hand/innervation , Health Status Indicators , Humans , MaleABSTRACT
PURPOSE: The feasibility of hand allotransplantation has been demonstrated. The purpose of the article is to report the (1) functional return, (2) psychosocial outcomes, (3) clinical and histological assessment for rejection, (4) complications, and (5) graft survival in the 2 American hand transplant recipients. METHODS: We present 2 patients 106 and 81 months, respectively, after unilateral transplantation of an allogeneic hand and forearm. We analyzed clinical course, number of rejection episodes, adverse events, function of the allograft, and quality of life. Clinical laboratory results, biopsy histology, and patient clinical examinations were used to compare the clinical course. Standard hand function tests were used to evaluate function. Psychological interviews were used to assess acceptance and quality of life. RESULTS: Our patients have allograft survival with improvements in intrinsic muscle activity, total active motion and return of functional grip, pinch strength, and sensibility. Rejection episodes were restricted primarily to the first 6 months after transplantation, and all responded to treatment. The major posttransplantation complications were a cytomegalovirus infection in patient 1 and osteonecrosis of the hip requiring both hips to be replaced, 1 at year 4 and the other at year 6, as well as transient immunosuppression-related diabetes in patient 2. Recently we have weaned both patients off maintenance steroids. Current Carroll scores are fair for patient 1 (72/99) and fair for patient 2 (55/99), although patient 2 has not had good recovery of intrinsic function. Both patients are back at work and report an excellent quality of life at nearly 9 and 7 years, respectively, after transplantation. CONCLUSIONS: Our intermediate long-term results of hand transplants have demonstrated functional return similar to that of replants. Graft survival and quality of life after hand transplantation has far exceeded initial expectations. We conclude that allogeneic hand transplant is feasible and holds promise as a treatment modality for catastrophic upper extremity loss. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
Subject(s)
Hand Injuries/surgery , Hand Transplantation , Organ Transplantation , Adult , Graft Rejection/drug therapy , Graft Survival , Humans , Male , Organ Transplantation/psychology , Organ Transplantation/rehabilitation , Recovery of Function , Treatment Outcome , United StatesABSTRACT
Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This report provides a review of all hand transplants performed to date. From September 1998 to February 2006 eighteen male patients underwent 24 hand/forearm/digit transplantations (eleven unilateral and four bilateral hand transplantations, two bilateral forearm transplantations, one thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. Patient average age was 32. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 34 to 85 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date occurred and were caused by severe inflammation and progressive rejection in a non-compliant patient. In addition, 6 hands were lost due to a rejection process as the Chinese recipients did not take their immunosuppressive treatment. These failures were communicated in January 2006. Acute rejection episodes occurred in 12 patients within the first year. Rejection was completely reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. As it would have been very difficult to analyse transplantation functional results in a standardized way, the Registry has performed a functional score system. All patients had achieved protective sensation and in 17 of them also discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities and 90% of the recipients returned to work, and improved manual skills allowed them not only to resume their previous jobs but also, in some cases, to find more suitable employment. Fifteen recipients reported an improvement of their quality of life and we evaluated as a very important point as patient satisfaction and well-being are mandatory goals of hand transplantation.
Subject(s)
Hand Transplantation , Adult , Follow-Up Studies , Graft Rejection , Humans , Immunosuppression Therapy , Male , Middle Aged , Postoperative Complications/etiology , Registries , Transplantation, HomologousABSTRACT
Successful hand transplantation depends upon an extensive, well-coordinated system with resources and experience in both upper extremity and transplant surgery. This description of such a system is drawn from the experience of the Louisville, Kentucky, Hand Transplant Program, which achieved the world's first successful hand transplant in January 1999, and which is the only United States program to date. The personnel and components of this system are outlined, with a detailed description of the roles, responsibilities, and interaction between components. This system ensures optimal management throughout recipient selection, psychiatric screening, education and preparation, donor limb retrieval, transplant surgery, immunosuppression administration and monitoring, and post-transplant rehabilitation therapy. The lessons learned from the experience of the Louisville team, and the experiences of the other teams world-wide, are presented to guide organization of future teams participating in this pioneering endeavor.
Subject(s)
Hand Transplantation , Interprofessional Relations , Program Development , Surgery, Plastic/organization & administration , Humans , Occupational Therapy , Patient Care Team , Psychiatry/methodsABSTRACT
This article reviews the world experience in the newly emerging field of composite tissue allotransplantation. These allografts contain multiple tissues that are usually musculoskeletal structures with a skin or epithelial surface, such as hand, facial structures, larynx, tongue, ear, knee/femur, abdominal wall, and penis. They represent a new transplantation field, with only a 10-year experience and just over 50 clinical cases. This review of the 10-year world experience found uniform technical success, immunologic biology, and immunosuppression regimens very similar to solid organ transplants, and success strongly correlated with adherence to guidelines for psychiatric screening, thorough preparation of patient and families, intense postoperative monitoring, and assurance of medication access. All failures reported have been caused by lapses in these parameters. This early experience shows a great potential for application of these new procedures to the most challenging reconstructive needs.
Subject(s)
Face/surgery , Hand Transplantation , Tissue Transplantation/trends , Transplantation, Homologous/methods , Ear/surgery , Femur/transplantation , Humans , Knee/surgery , Larynx/transplantation , Tongue/transplantationABSTRACT
BACKGROUND: Hand allotransplantation was initially criticized as unethical and unlikely to succeed. The results proved to be better than anticipated, now raising the issue of whether hand transplantation is the standard of care. The purpose of this article is to outline a reasonable methodology for determining whether a surgical procedure is the standard of care, and then to apply that methodology to hand transplantation. METHODS: Publications on ethics and definitions of medical (not legal) standard of care were reviewed. All hand transplantations completed in the United States were evaluated regarding their status as experimental, standard of care, or both. Then, the stakeholders, physicians, public insurers, and regulators were examined to determine whether they accepted hand transplantation as the standard of care. Utility and incremental cost-utility ratio were determined. Hand transplantation was considered the standard of care when stakeholders were using, insuring, and regulating the procedure. RESULTS: The public expresses a desire for hand transplantation. A minority of surgeons consider the procedure the standard of care. Ethical committees, institutional review boards, and scholarly articles deem the procedure ethical. A series of institutions have carried out the procedure with a record of successes. Some institutions perform the surgical procedure as the standard of care. Scholarly work demonstrates beneficial outcomes. Some commercial and federal government insurers are willing to cover the cost of the procedure. Utility determination justifies the procedure. There are no incremental cost-utility ratio analysis studies that justify the procedure. CONCLUSION: Hand transplantation is moving from acceptance as an ethical surgical experiment to the standard of care.
Subject(s)
Hand Injuries/surgery , Hand Transplantation/standards , Standard of Care/organization & administration , Surgeons , Allografts , HumansABSTRACT
BACKGROUND: Hand and face transplantation has established itself as a clinical option for certain reconstructive problems. The purpose of this study was to carry out a rigorous statistical analysis of all hand and face transplantations to determine whether hand and/or face transplantation is the standard of care. METHODS: Data from September of 1998 until March of 2014 on all hand and face transplantations in the world were obtained through publications, news articles, personal communications, and presentations. Data on solid organ transplantation were obtained from the Scientific Registry of Transplant Recipients for comparison with the results of hand transplantation. Resampling and permutation statistical analysis was used to compare structured cohorts of hand, face, and solid organ transplantation. RESULTS: Routine immunosuppression can achieve intermediate- to long-term graft survival in hand transplantation that is empirically superior to solid organ transplantation. Chronic rejection in hand transplantation is statistically significantly less than in solid organ transplantation. Renal failure in hand and face transplantation is empirically less than in solid organ transplantation. Bone marrow transplant with hand transplantation produces both statistically superior and statistically inferior results compared with hand transplantation without bone marrow. In hand transplantation, acute rejection does not seem to increase late allograft loss. The function of hand transplantation is statistically significantly superior to prosthesis yet inferior to hand replantation. Not all hand and face transplants have good results, yet those hand transplants completed within certain parameters obtain excellent results. CONCLUSIONS: Certain hand transplants arguably can be considered the standard of care. Face transplantation requires more time and patient numbers and a clearer definition of inclusion and exclusion criteria before standard of care assessment can be made.
Subject(s)
Facial Transplantation/statistics & numerical data , Graft Survival , Hand Transplantation/statistics & numerical data , Immunosuppression Therapy/methods , Standard of Care , Humans , Transplantation, HomologousABSTRACT
BACKGROUND: Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This inaugural report provides a review of all hand transplants performed to date. METHODS: Between September 1998 and September 2004, 18 male patients underwent 24 hand/forearm/digit transplantations (11 monolateral and 4 bilateral hand transplantations, 2 bilateral forearm transplantations, and 1 thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. The average age of the patient was 32 years. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 17 to 70 months. RESULTS: Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date were caused by severe inflammation and progressive rejection in a noncompliant patient. Acute rejection episodes occurred in 12 patients within the first year. Rejection was reversible in all compliant patients. Side effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. All patients had achieved protective sensation, and 17 patients also achieved discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities. CONCLUSIONS: Despite the enormous antigen load associated with composite tissue allograft, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.
Subject(s)
Arm/transplantation , Fingers/transplantation , Hand Transplantation , Registries , Transplantation, Homologous/physiology , Adult , Amputation, Surgical , Graft Rejection/epidemiology , Humans , International Cooperation , Male , Middle Aged , Opportunistic Infections/epidemiology , Transplantation, Homologous/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: We and others have shown that mixed allogeneic chimerism induces donor-specific tolerance to composite tissue allografts across major histocompatibility complex barriers without the need for immunosuppression. However, a delay period between bone marrow transplantation and limb allotransplantation is required, making such protocols impractical for clinical application. This study eliminates this delay period in a rat hind limb allotransplantation model by performing mixed allogeneic chimerism induction and transplantation "simultaneously." METHODS: Group 1 included controls in which naïve Wistar Furth (WF) hosts received ACI hind limbs. Group 2 included (ACI-->WF) chimeras that received limbs from third-party donors (Fisher), and group 3 included chimeras that received irradiated (1,050 cGy) ACI limbs. In group 4, WF hosts conditioned with 950 cGy received irradiated (1,050 cGy) ACI limbs followed by infusion of 100 x 10(6) ACI T-cell-depleted bone marrow cells and immunotherapy (tacrolimus and mycophenolate mofetil) for 28 days. Group 5 animals received the same treatment as group 4 animals without immunotherapy. RESULTS: The rats in groups 1 and 2 rejected their limbs within 10 days. Only one rat in group 4 survived to the end of the study. Groups 3 and 5 demonstrated long-term limb survival without rejection or graft-versus-host disease. High levels of donor chimerism (>80%) were achieved and maintained throughout the study. Mixed lymphocyte reaction assays in both groups revealed donor-specific hyporesponsiveness with vigorous third-party reactivity. CONCLUSIONS: This study demonstrated that infusion of donor bone marrow cells into conditioned hosts immediately after limb transplantation results in stable mixed chimerism, robust tolerance, and reliable limb allograft survival.
Subject(s)
Hindlimb/transplantation , Mycophenolic Acid/analogs & derivatives , Transplantation Chimera/immunology , Transplantation, Homologous/immunology , Animals , Disease Models, Animal , Drug Therapy, Combination , Graft Survival , Hindlimb/pathology , Immunosuppressive Agents/therapeutic use , Lymphocyte Depletion , Major Histocompatibility Complex , Male , Mycophenolic Acid/therapeutic use , Rats , Rats, Inbred ACI , Rats, Inbred WF , T-Lymphocytes/immunology , Transplantation Conditioning/methods , Transplantation, Homologous/pathology , Whole-Body IrradiationABSTRACT
BACKGROUND: Mixed allogeneic chimerism (MAC) has been shown to induce tolerance to composite tissue allografts (CTA). However, transplantation of unmanipulated donor-specific limbs results in severe graft-versus-host disease (GVHD). This suggests that nontolerant mature donor-derived cells in the CTA may affect the stability of chimerism, potentially resulting in GVHD. The aim of this study was to develop an approach to study and prevent GVHD in a mixed chimeric-rat hind-limb transplantation model. METHODS: [ACI-->WF] chimeras received a limb from Wistar Furth (WF) (syngeneic), Fisher (third-party), or ACI (irradiated [1,050 cGy] or nonirradiated) rats. In vitro tolerance was assessed using mixed lymphocyte reactivity (MLR) assays at the time the animals were killed. RESULTS: [ACI-->WF] chimeras with greater than 85% chimerism exhibited rejection-free survival of donor-specific hind limbs. However, 100% of these animals developed lethal GVHD 22.4+/-2.8 days after limb transplantation. [ACI-->WF] chimeras that underwent transplantation with irradiated ACI or syngeneic WF limbs showed no signs of rejection or GVHD at 5 months. Nonchimeric and third-party controls rejected limbs within 10 days. CONCLUSIONS: Conditioning of the host WF rats with 950 cGy of irradiation (sublethal, myeloablative) led to high levels of MAC without GVHD. The mature T-cell content of nonirradiated donor (ACI) limbs was sufficient to induce lethal GVHD in 100% of tolerant mixed chimeric [ACI-->WF] hosts. Irradiation of donor limbs before transplantation resulted in long-term donor-specific tolerance and prevented GVHD. These data demonstrate that (1) established chimeras could be susceptible to GVHD caused by immunocompetent donor cells transferred with the hind limb, and (2) inactivating these cells with irradiation prevents GVHD and destabilization of chimerism, and permits rejection-free graft acceptance.
Subject(s)
Graft vs Host Disease/prevention & control , Hindlimb/transplantation , Transplantation Chimera , Animals , Cell Line , Graft Survival , Hindlimb/radiation effects , Male , Rats , Rats, Inbred ACI , Rats, Inbred F344 , Rats, Inbred WF , Tissue Donors , Transplantation Tolerance , Transplantation, HomologousABSTRACT
Vascularized composite tissue allotransplantation is a rapidly evolving area that has brought technological advances to the forefront of plastic surgery, hand surgery, and transplant biology. Composite tissue allografts (CTAs) may have profound functional, esthetic, and psychological benefits, but carry with them the risks of life-long immunosuppression and the inadequate abilities to monitor and prevent rejection. Allografts may suffer from additional insults further weakening their overall benefits. Changes in local blood flow, lack of fully restored neurologic function, infection, inflammation with subsequent dysregulated regenerative activity, and paucity of appropriate growth factors may all be involved in reducing the potential of CTAs and therefore serve as new therapeutic targets to improve outcomes. Strategies involving minimized immunosuppression and pro-regenerative therapy may provide a greater path to optimizing long-term CTA function. One such strategy may include mesenchymal stem cells (MSCs), which can provide unique anti-inflammatory and pro-regenerative effects. Insights gained from new studies with MSCs on composite allografts, advances in tissue regeneration reported in other MSC-based clinical studies, as well as consideration of newly described capacities of MSCs, may provide new regenerative based strategies for the care of CTAs.
ABSTRACT
In the last 12 years, the Louisville CTA program has screened more than 600 interested hand transplant candidates and has transplanted 6 patients with 7 hand allografts. The program is a collaborative effort between the surgeons and staff of Kleinert, Kutz and Associates, Jewish Hospital and St. Mary's Healthcare, the Christine M. Kleinert Institute, and the University of Louisville. The functional outcome and long-term results of clinical hand transplantation have exceeded initial expectations both within the program and in the community at large. This report summarizes the successes and challenges of the Louisville CTA experience in composite tissue allotransplantation.
Subject(s)
Hand Transplantation , Adult , Alemtuzumab , Amputation, Traumatic/surgery , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Neoplasm/therapeutic use , Graft Rejection/epidemiology , Hand Injuries/surgery , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kentucky , Male , Middle Aged , Postoperative Complications , Recovery of Function , Sensation , Transplantation, Homologous , Treatment OutcomeABSTRACT
BACKGROUND: The authors examine the information gained from the use of intraoperative nerve recording in the management of suspected brachial plexus root avulsion. METHODS: A retrospective chart review examined 25 patients who had undergone intraoperative nerve recording for a brachial plexus injury. Thirty-seven preganglionic root avulsions were demonstrated by somatosensory evoked potentials, C4 to T1, during intraoperative nerve recording. To measure the information gain derived from intraoperative nerve recording, the authors compared the number of roots diagnosed as preganglionic root avulsions preoperatively to those diagnosed by intraoperative nerve recording. From this, the authors can demonstrate the positive and negative predictive values of their preoperative multimodality assessment for brachial plexus root avulsion and compare this to the result of intraoperative nerve recording to derive the gain of information. In addition, the authors examined the validity of the intraoperative nerve recording somatosensory evoked potentials when this produced a diagnosis of an intact root in this cohort by performing a clinical outcome analysis for those roots used for reconstruction. RESULTS: Twenty-five patients underwent intraoperative nerve recording for unilateral brachial plexus injury; 15 patients were diagnosed with 55 preganglionic root avulsions from C4 to T1 preoperatively by multimodality assessment. Fourteen of 55 roots thought to be avulsed preoperatively were found to be intact with intraoperative nerve recording, representing a gain of information of 25 percent derived from intraoperative nerve recording for roots thought to be avulsed preoperatively. CONCLUSION: Intraoperative nerve recording adds useful information during exploratory brachial plexus surgery.
Subject(s)
Brachial Plexus/surgery , Evoked Potentials, Somatosensory , Monitoring, Intraoperative/methods , Monitoring, Physiologic/methods , Nerve Tissue/injuries , Plastic Surgery Procedures/methods , Radiculopathy/surgery , Adolescent , Adult , Brachial Plexus/injuries , Follow-Up Studies , Hand Injuries/surgery , Humans , Middle Aged , Nerve Tissue/physiopathology , Nerve Transfer/methods , Radiculopathy/diagnosis , Reproducibility of Results , Retrospective Studies , Time Factors , Young AdultABSTRACT
Hand transplantation has proven itself to be a viable treatment option for upper extremity reconstruction. It has grown through advancements in several critical areas: microsurgery, transplant immunology, and hand surgery. The field has also benefited from a global effort with active transplant centers in 3 different continents. The early struggles and breakthroughs of hand transplantation's past have shaped and formed its current state. This article traces the events of the modern era of hand transplantation.