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Background: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. Objective: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. Methodology: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. Results: After a minimum of 24 months follow‐up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy‐dependent by 6 months and all had normal or near‐normal swallowing by the end of year two after transplantation. Median follow‐up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. Conclusions: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end‐stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. Level of Evidence: 4 Laryngoscope, 134:4313–4320, 2024 [ABSTRACT FROM AUTHOR]

The revision of the Korea Organ Transplantation Act (KOTA) in 2018 included hand/arm among the organs that can be transplanted. The first hand transplantation since the revision of KOTA took place in January 2021. A 62-year-old male patient experienced hand amputation on July 13, 2018, by a catapult injury. The patient first visited our institute 3 months after the injury. After serial interviews and an overall evaluation, the patient was registered on the hand transplantation waiting list in January 2020. On January 9, 2021, the patient underwent hand transplantation at the right distal forearm level. The total operation time was 17 hours 15 minutes, and the cold ischemic time was 4 hours 9 minutes. Postoperative immunosuppression was administered based on the protocol used for kidney transplantation. Two acute rejection episodes occurred, on postoperative days 33 and 41. Both rejection episodes were reversible with rescue therapy of a higher tacrolimus trough level, steroid pulse therapy, and topical immunosuppressants. Controlled passive range of motion exercise was started on postoperative day 10. Dynamic splint was applied on postoperative day 18. At 1 year, graft maintenance and functional improvement were satisfactory, and the patient showed a Disabilities of Arm, Shoulder and Hand score of 25.8. We successfully performed the first hand transplantation surgery under the KOTA amendment. It came from the organic and effective cooperation of plastic, orthopaedic, and transplantation departments and we believe it will guarantee the future ongoing success.

Background: The aim of this study is to establish an in vivo large mammalian model that can form the basis for future immunosuppression research, nerve recovery research, surgical applicability, and training studies. Materials and Methods: An 18‑month‑old, 40 kg, curly breed sheep was used.Awhole‑eye autotransplantation was planned, including the upper and lower eyelids, lacrimal gland, and extraocular muscles. Intracranial intervention and inclusion of the bone segment were not considered. The frontozygomatic approach was used in the operation. Circulation was established by anastomoses of the internal ophthalmic vein and artery with elongated superficial temporal artery and vein with vein grafts. The optic nerve was repaired last. Blood circulation and the retina were checked by means of postoperative bleeding and indirect ophthalmoscope. Results: Using the internal carotid system, circulation of the entire eye and its appendages was achieved in the early period. The frontozygomatic approach facilitated nerve and vessel repairs and therefore shortened the ischemia time (16 min). Although circulation was established in the retina, local bleeding foci were detected. Pupillary, corneal, and palpebral reflexes could not be obtained from the animal. The animal died on the 10th day. Circulation of the autotransplanted tissue was present at this time, including the eyelids and appendages of the eye. Conclusion: The composite whole‑eye autotransplantation model was successfully planned in vivo in a large mammal, the sheep, without the need for intracranial intervention, and by including all of the eye attachments based on the internal ophthalmic artery. [ABSTRACT FROM AUTHOR]

The revision of the Korea Organ Transplantation Act (KOTA) in 2018 included hand/arm among the organs that can be transplanted. The first hand transplantation since the revision of KOTA took place in January 2021. A 62-year-old male patient experienced hand amputation on July 13, 2018, by a catapult injury. The patient first visited our institute 3 months after the injury. After serial interviews and an overall evaluation, the patient was registered on the hand transplantation waiting list in January 2020. On January 9, 2021, the patient underwent hand transplantation at the right distal forearm level. The total operation time was 17 hours 15 minutes, and the cold ischemic time was 4 hours 9 minutes. Postoperative immunosuppression was administered based on the protocol used for kidney transplantation. Two acute rejection episodes occurred, on postoperative days 33 and 41. Both rejection episodes were reversible with rescue therapy of a higher tacrolimus trough level, steroid pulse therapy, and topical immunosuppressants. Controlled passive range of motion exercise was started on postoperative day 10. Dynamic splint was applied on postoperative day 18. At 1 year, graft maintenance and functional improvement were satisfactory, and the patient showed a Disabilities of Arm, Shoulder and Hand score of 25.8. We successfully performed the first hand transplantation surgery under the KOTA amendment. It came from the organic and effective cooperation of plastic, orthopaedic, and transplantation departments and we believe it will guarantee the future ongoing success. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to establish an in vivo large mammalian model that can form the basis for future immunosuppression research, nerve recovery research, surgical applicability, and training studies. Materials and Methods: An 18-month-old, 40 kg, curly breed sheep was used. A whole-eye autotransplantation was planned, including the upper and lower eyelids, lacrimal gland, and extraocular muscles. Intracranial intervention and inclusion of the bone segment were not considered. The frontozygomatic approach was used in the operation. Circulation was established by anastomoses of the internal ophthalmic vein and artery with elongated superficial temporal artery and vein with vein grafts. The optic nerve was repaired last. Blood circulation and the retina were checked by means of postoperative bleeding and indirect ophthalmoscope. Results: Using the internal carotid system, circulation of the entire eye and its appendages was achieved in the early period. The frontozygomatic approach facilitated nerve and vessel repairs and therefore shortened the ischemia time (16 min). Although circulation was established in the retina, local bleeding foci were detected. Pupillary, corneal, and palpebral reflexes could not be obtained from the animal. The animal died on the 10th day. Circulation of the autotransplanted tissue was present at this time, including the eyelids and appendages of the eye. Conclusion: The composite whole-eye autotransplantation model was successfully planned in vivo in a large mammal, the sheep, without the need for intracranial intervention, and by including all of the eye attachments based on the internal ophthalmic artery.

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. [ABSTRACT FROM AUTHOR]

Reconstruction of long tracheal defects still proves to be a challenge. Free fasciocutaneous flaps with cartilaginous struts or an allotransplant trachea have been reported but not been widely performed. This article reports with the experience of using a tracheal allotransplant in such a defect. A 43-year-old lady presented with adenoid cystic carcinoma involving the entire trachea from subglottic area up to the carina, leading to a life-threatening airway occlusion. After preliminary stenting, allotransplant trachea obtained from a brain-dead individual was revascularized in the forearm of the patient after mechanical decellularization to reduce the immune load and fulfil the need for immunosuppression in the background of active cancer. Subsequently, the trachea and larynx were resected. The vascularized neotrachea was transferred successfully into the neck. The patient did well initially but succumbed to a fatal hemorrhage due to innominate vein aneurysmal rupture on the 22nd day after the transplant. The technical details of resection, fabrication of the neotrachea, its transfer, and the lessons learnt in this tracheal allotransplant are described.

Within the past two decades, vascularized facial composite allotransplantation has evolved into a viable option in the reconstructive surgeons' armamentarium for patients with extensive facial disfigurements. As it has expanded the frontiers of microsurgical reconstructive techniques, facial transplantation has come to garner widespread interest within both the medical community and the general public. The procedure has established itself as an amalgamation of the forefronts of reconstructive microsurgery, immunology, and transplantation science. Therein too lies its complexity as multifaceted scientific developments are met with ethical and social issues. Both patients and physicians are faced with the everlasting challenges of immunosuppression regimens and their inherent complications, long-term aesthetic and functional considerations, the role of revision procedures, and the inevitable psychosocial implications. This article reflects on the medical and surgical advancements in facial transplantation surgery and highlights anticipated future challenges. It aims to encourage discussion regarding anticipated barriers to current practice and suggest future directions as we transition into the next phase of facial allograft transplantation. [ABSTRACT FROM AUTHOR]

The functional and sociocultural role of the auricle has been prevalent in art, literature and history for millennia. It is no surprise, therefore, that auricular anomalies can be associated with affective disorders and impaired academic performance in children. The challenge of auricular reconstruction has captured the attention of surgical innovators for millennia with the earliest records of auricular reconstruction documented in the Edwin Smith Surgical Papyrus dating back to 3000 BCE. Since the 19th century, however, the interest in the ambition partial and total auricular reconstruction witnessed a rebirth, with refinements in frame construction, projection and skin coverage improving exponentially over the last two centuries. The gold standard auricular reconstruction practices today have their roots in these historical milestones, and form a solid foundation for the introduction of technological advancements such as 3D bioprinting and composite tissue allotransplantation into future auricular reconstruction practice. The aim of this review is to outline the sociocultural role of the auricle, the history and evolution of auricular reconstruction surgery and to provide an insight into potential future avenues of restoring auricular form and function. [ABSTRACT FROM AUTHOR]

Background: Distal digital nerve repairs can present unique challenges for hand surgeons due to their sensitive location and ongoing difficulty obtaining soft tissue coverage in this region. Although autografts and nerve conduits have been shown to be of benefit with nerve gaps, they can have morbidities associated with their use. Nerve allografts have become a viable option over the past decade as their use has increased and data are now showing similar outcomes, particularly in short gap segments. Flaps and skin grafts are traditional coverage options for full thickness wounds but can pose challenges with multiple digit involvement, depth of wound, and critical structures exposed. Methods: We present a case where nerve allograft was used for distal digital nerve repair. Due to the distal nature of the nerve repair in the index digit distal to the trifurcation, the distal end of the nerve graft was connected to multiple small nerve ends. Dermal substitute was placed to achieve distal coverage of the affected digits. Results: At 6-month follow-up, the patient demonstrated improved strength, normal sensation, and full return of digital function. Conclusion: Nerve allograft can be used in combination with dermal skin substitute to achieve normal sensation and return of digital function following distal digital nerve injuries. [ABSTRACT FROM AUTHOR]

Background: Upper extremity transplantation is a quality-of-life enhancing treatment for select patients with upper extremity loss. This article reviews the preoperative, intraoperative, and postoperative challenges in the upper extremity transplantation process and the lessons learned from the first 2 decades of hand transplantation. Methods: Key components of the author's hand transplantation protocol including patient selection, donor screening, surgical rehearsal, donor procurement, transplantation, immunosuppression, and patient outcome reporting/follow-up are reported to assist other teams who wish to establish a hand transplantation program. Results: There have been many advancements in the first 20 years of hand transplantation including better patient selection criteria, the recent addition of pediatric patients, improved surgical techniques such as the use of virtual surgical planning, and improved immunosuppression protocols. Improvement has also taken place in the tracking and reporting of hand transplant outcomes, but more work is clearly needed to fully define the benefits of transplantation, especially for pediatric patients. Conclusions: Over the past 20 years, significant progress has been made in upper extremity transplantation although a number of challenges remain including how to best document and share outcome measures, optimize immunosuppression, and diagnose/treat rejection. The authors encourage upper extremity transplant programs to report their experience and protocols to advance hand transplantation as standard of care for properly selected individuals. [ABSTRACT FROM AUTHOR]

Abstract With growing number of cases in recent years, composite tissue allotransplantation (CTA) has been improving the quality of life of patient who seeks reconstruction and repair of damaged tissues. Composite tissue allografts are heterogeneous. They are composed of a variety of tissue types, including skin, muscle, vessel, bone, bone marrow, lymph nodes, nerve, and tendon. As a primary target of CTA, skin has high antigenicity with a rich repertoire of resident cells that play pivotal roles in immune surveillance. In this regard, understanding the molecular mechanisms involved in immune rejection in the skin would be essential to achieve successful CTA. Although scientific evidence has proved the necessity of immunosuppressive drugs to prevent rejection of allotransplanted tissues, there remains a lingering dilemma due to the lack of specificity of targeted immunosuppression and risks of side effects. A cumulative body of evidence has demonstrated T regulatory (Treg) cells have critical roles in induction of immune tolerance and immune homeostasis in preclinical and clinical studies. Presently, controlling immune susceptible characteristics of CTA with adoptive transfer of Treg cells is being considered promising and it has drawn great interests. This updated review will focus on a dominant form of Treg cells expressing CD4+CD25+ surface molecules and a forkhead box P3 transcription factor with immune tolerant and immune homeostasis activities. For future application of Treg cells as therapeutics in CTA, molecular and cellular characteristics of CTA and immune rejection, Treg cell development and phenotypes, Treg cell plasticity and stability, immune tolerant functions of Treg cells in CTA in preclinical studies, and protocols for therapeutic application of Treg cells in clinical settings are addressed in this review. Collectively, Treg cell therapy in CTA seems feasible with promising perspectives. However, the extreme high immunogenicity of CTA warrants caution.

Introduction: Vascularized composite tissue allotransplantation is a relatively new concept, which was unavailable in the Indian subcontinent till a bilateral hand transplant was carried out successfully in January 2015. Materials and Methods: The setting up of the transplant programme involved obtaining legal clearances, creating public awareness, harnessing the institutional facilities, drawing up protocols, assembling the surgical team, managing immunological issues, rehabilitation and preparing the ancillary services. Results: Both, the first and second bilateral hand transplants were resounding successes with both the recipients getting back to their original daily routines. Conclusions: The organisation of the hand transplant programme was a large task, which necessitated intensive planning, and cooperation from various teams within and outside the institution. Exemplary team-work was the key to the phenomenal success of these path breaking endeavors in the subcontinent.

Introduction: This report covers the strategies adopted for rehabilitation for the first and second dual hand transplants performed in India. Materials and Methods: The team, under a trained physiatrist, including physiotherapy and occupational therapy personnel, was involved in the management of both these patients. The management protocol was developed considering previous reports as well as our management strategies in the rehabilitation of the replanted hands. The involvement of the team with the patients started in the 1st week itself and continued on a daily basis for the entire year. Results: Outcome analysis was performed at 6 months and 1 year using the disability of shoulder and hand evaluation and hand transplant scoring system. Functional magnetic resonance imaging was done at the end of 1 year to assess the cortical integration of the transplanted hand. Conclusion: Despite more than 110 hands being transplanted worldwide, hand transplant remains an experimental procedure. It is still not considered the “standard of care” for hand amputees. Outcome analyses performed worldwide do indicate that the procedure can provide a substantial improvement in the quality of life for the hand amputee, especially the bilateral amputees.

Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the ‘self’ from the ‘non-self’. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as ‘non-self’. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC). Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy. Results: Both the recipients were managed by the standard triple drug therapy and have had only minor episodes of rejections thus far which have been managed appropriately. Discussion: Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy. Various groups have tried various other formulations and regimes as well. Conclusion: A comprehensive plan has to be drawn up for immunological screening, selection and the post-operative immunosuppressant usage. The ultimate goal of these immunosuppression modalities is to achieve a state of donor-specific tolerance.

Introduction: This article deals with two patients who underwent bilateral hand transplantation following amputation of both upper limbs at the distal third of the foream. Materials and Methods: The first patient had a history of loss of hands in a train accident, with possiblity of a run over element during the injury. The second patient lost his both hands in a mine blast. The preoperative work up included detailed clinical and psychological evaluation. The donor retrieval was similar in both the cases and the donors were housed in our own instittution. The donor preparation, recipient preparation and the transplant procedure was similar except for the need of primary tendon transfers in the left hand of the first patient. Results: The first patient needed a free flap transfer to cover compromised skin flap on the left hand on the second day. The second hand transplant was uneventful. Both the recipients are now back to their normal daily routines. Conclusions: Hand transplantation is a potentially life altering procedure, but to optimise the results, it is imperative that there is a meticulous planning and diligent execution with utmost importance to the detail coupled with a synchronised team effort.

Reconstruction of long tracheal defects still proves to be a challenge. Free fasciocutaneous flaps with cartilaginous struts or an allotransplant trachea have been reported but not been widely performed. This article reports with the experience of using a tracheal allotransplant in such a defect. A 43-year-old lady presented with adenoid cystic carcinoma involving the entire trachea from subglottic area up to the carina, leading to a life-threatening airway occlusion. After preliminary stenting, allotransplant trachea obtained from a brain-dead individual was revascularized in the forearm of the patient after mechanical decellularization to reduce the immune load and fulfil the need for immunosuppression in the background of active cancer. Subsequently, the trachea and larynx were resected. The vascularized neotrachea was transferred successfully into the neck. The patient did well initially but succumbed to a fatal hemorrhage due to innominate vein aneurysmal rupture on the 22nd day after the transplant. The technical details of resection, fabrication of the neotrachea, its transfer, and the lessons learnt in this tracheal allotransplant are described. [ABSTRACT FROM AUTHOR]

Abstract Background Ischemia-reperfusion injury remains the major limiting factor for limb replantation and transplantation. Static cold storage (SCS) on ice currently represents the standard mode of preservation but is limited to 6 h of duration. Ex vivo machine perfusion has evolved as a potential alternative to safely extend the duration of ex vivo preservation by providing continuous supply of oxygen and nutrients. This study aims to evaluate underlying molecular mechanisms of both preservation modalities. Methods We assessed molecular changes in amputated porcine forelimbs stored on ice at 4°C for 2 h (n = 2) and limbs perfused with Perfadex solution at 10°C for 2 h (n = 3) or 12 h (n = 3) before replantation. Muscle biopsies were examined for histological changes and gene expression levels using H&E staining and a hypoxia-related PCR gene array, respectively. Results Histology revealed only minor differences between the ice (SCS) and perfusion groups after 2 h of preservation, with decreased muscle fiber disruption in the perfusion groups compared with the ice (SCS) group. Perfused limbs demonstrated downregulation of genes coding for glycolytic pathways and glucose transporters after 2 h and 12 h when compared with SCS after 2 h. Similarly, genes that induce angiogenesis and those that are activated on DNA damage were downregulated in both perfusion groups as compared with SCS. Conclusions Perfusion of porcine limbs resulted in less activation of hypoxia-related gene families when compared with SCS. This may indicate a state more closely resembling physiological conditions during perfusion and potentially limiting ischemic injury. Our study confirms ex vivo perfusion for up to 12 h as a viable alternative for preservation of vascularized composite tissues. [ABSTRACT FROM AUTHOR]

Background  Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression. Method  A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results. Result  Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy. Conclusion  Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance. [ABSTRACT FROM AUTHOR]

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Introduction: Being able to counter immune-mediated rejection has for decades been the single largest obstacle for the progress of vascular composite allotransplantation (VCA). The human immune system performs the key role of differentiating the 'self' from the 'non-self'. This, although is quintessential to eliminate or resist infections, also resists the acceptance of an allograft which it promptly recognises as 'non-self'. Materials and Methods: Pre-operative evaluation of the recipient evaluation included immunological assessment in the form of panel reactive antibodies (PRA), human leucocyte antigen (HLA) typing, donor-specific antibody detection assays (DSA) and complement-dependent cytotoxicity assays (CDC). Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy. Results: Both the recipients were managed by the standard triple drug therapy and have had only minor episodes of rejections thus far which have been managed appropriately. Discussion: Induction immunosuppression was by thymoglobulin and the maintenance by the standard triple-drug therapy. Various groups have tried various other formulations and regimes as well. Conclusion: A comprehensive plan has to be drawn up for immunological screening, selection and the post-operative immunosuppressant usage. The ultimate goal of these immunosuppression modalities is to achieve a state of donor-specific tolerance. [ABSTRACT FROM AUTHOR]

Introduction: This report covers the strategies adopted for rehabilitation for the first and second dual hand transplants performed in India. Materials and Methods: The team, under a trained physiatrist, including physiotherapy and occupational therapy personnel, was involved in the management of both these patients. The management protocol was developed considering previous reports as well as our management strategies in the rehabilitation of the replanted hands. The involvement of the team with the patients started in the 1st week itself and continued on a daily basis for the entire year. Results: Outcome analysis was performed at 6 months and 1 year using the disability of shoulder and hand evaluation and hand transplant scoring system. Functional magnetic resonance imaging was done at the end of 1 year to assess the cortical integration of the transplanted hand. Conclusion: Despite more than 110 hands being transplanted worldwide, hand transplant remains an experimental procedure. It is still not considered the "standard of care" for hand amputees. Outcome analyses performed worldwide do indicate that the procedure can provide a substantial improvement in the quality of life for the hand amputee, especially the bilateral amputees. [ABSTRACT FROM AUTHOR]

Introduction: This article deals with two patients who underwent bilateral hand transplantation following amputation of both upper limbs at the distal third of the foream. Materials and Methods: The first patient had a history of loss of hands in a train accident, with possiblity of a run over element during the injury. The second patient lost his both hands in a mine blast. The preoperative work up included detailed clinical and psychological evaluation. The donor retrieval was similar in both the cases and the donors were housed in our own instittution. The donor preparation, recipient preparation and the transplant procedure was similar except for the need of primary tendon transfers in the left hand of the first patient. Results: The first patient needed a free flap transfer to cover compromised skin flap on the left hand on the second day. The second hand transplant was uneventful. Both the recipients are now back to their normal daily routines. Conclusions: Hand transplantation is a potentially life altering procedure, but to optimise the results, it is imperative that there is a meticulous planning and diligent execution with utmost importance to the detail coupled with a synchronised team effort. [ABSTRACT FROM AUTHOR]

Introduction: Vascularized composite tissue allotransplantation is a relatively new concept, which was unavailable in the Indian subcontinent till a bilateral hand transplant was carried out successfully in January 2015. Materials and Methods: The setting up of the transplant programme involved obtaining legal clearances, creating public awareness, harnessing the institutional facilities, drawing up protocols, assembling the surgical team, managing immunological issues, rehabilitation and preparing the ancillary services. Results: Both, the first and second bilateral hand transplants were resounding successes with both the recipients getting back to their original daily routines. Conclusions: The organisation of the hand transplant programme was a large task, which necessitated intensive planning, and cooperation from various teams within and outside the institution. Exemplary team-work was the key to the phenomenal success of these path breaking endeavors in the subcontinent. [ABSTRACT FROM AUTHOR]

The idea of head transplantation appears at first as unrealistic, unethical, and futile. Here we discuss immunological considerations in human head transplantation. In a separate accompanying article we discuss surgical, ethical, and psychosocial issues concerned in body-to-head transplantation (BHT) [1]. The success of such an unusual allograft, where the donor and the recipient can reject each other, depends on prevention of complex immunologic reactions, especially rejection of the head by the body (graft-vs-host) or probably less likely, the possibility of the head rejecting the total body allograft (host-vs-graft). The technical and immunologic difficulties are enormous, especially since rapid nerve and cord connections and regeneration have not yet been possible to achieve. In this article we begin by briefly reviewing neuro-immunologic issues that may favor BHT such as the blood brain barrier (BBB) and point out its shortcomings. And we touch on the cellular and humoral elements in the brain proper that differ in some respects from those in other organs and in the periphery. Based on recent successes in vascular composite allografts (VCAs), we will elaborate on potential specific advantages and difficulties in BHT of various available immunosuppressive medications already utilized in VCAs. The risk/benefit ratio of these drugs will be emphasized in relation to direct brain toxicity such as seizure disorders, interference, or promotion of nerve regeneration, and potentiation of cerebral viral infections. The final portion of this article will focus on pre-transplant immunologic manipulation of the deceased donor body along with pretreatment of the recipient. [ABSTRACT FROM AUTHOR]

Transplanting a head and brain is perhaps the final frontier of organ transplantation. The goal of body-to-head transplantation (BHT) is to sustain the life of individuals who suffer from terminal disease, but whose head and brain are healthy. Ideally BHT could provide a lifesaving treatment for several conditions where none currently exists. BHT is no ordinary experiment, to transfer a head to another body involves extraordinarily complex medical challenges as well as ethical and existential dilemmas that were previously confined to the imagination of writers of fiction. The possibility of replacing an incurably ill body with a healthy one tests not only our surgical limits, but also the social and psychological boundaries of physical life and alters what we recognize life to be. The purpose of this target article, the complementary manuscript focused on immunological issues in BHT, and the accompanying Commentaries by scholars and practitioners in medicine, immunology, and bioethics is to review major surgical and psychosocial-ethical and immunological considerations surrounding body-to-head transplantation. We hope that together these ideas will provide readers with a comprehensive overview of the possibilities and challenges associated with BHT and initiate professional discussion and debate through which this new frontier in medicine is considered and approached. [ABSTRACT FROM AUTHOR]

Background: 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., Methods: 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., Results: 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., Conclusions: Focusing on optimizing psychosocial variables in transplant candidates may help improve hand transplant success.

Rats are the most frequently used animals in composite tissue allotransplantation (CTA) studies and most craniofacial composite tissue transplantation models are described in rats. During the last 10 years, a total of 8 different craniofacial composite tissue allotransplantation (CCTA) models have designed and developed in rats. These models include full face/scalp transplants, hemiface transplants, composite hemiface/calvarium transplants, rat maxilla allotransplants, composite osteomusculocutaneous hemiface/mandible/tongue flap transplants, composite midface allotransplants, total osteocutaneous hemifacial allotransplantation model and composite face and eyeball allotransplant model with optic nerve. All these models provide a basic and scientific foundation for future success in CTA in the clinical setting. This review presents different experimental models of CCTA in rats which are relevant to observed in clinical scenario cases of severe facial deformities. [Arch Clin Exp Surg 2012; 1(3.000): 181-187]

Background: Trauma often co-occurs with cardiac arrest and hemorrhagic shock. Skin and muscle injuries often lead to significant inflammation in the affected tissue. The primary mechanism by which inflammation is initiated, sustained, and terminated is cytokine-mediated immune signaling, but this signaling can be altered by cardiac arrest. The complexity and context sensitivity of immune signaling in general has stymied a clear understanding of these signaling dynamics. Methodology/Principal findings: We hypothesized that advanced numerical and biological function analysis methods would help elucidate the inflammatory response to skin and muscle wounds in rats, both with and without concomitant shock. Based on multiplexed analysis of inflammatory mediators, we discerned a differential interleukin (IL)-1α and IL-18 signature in skin vs. muscle, which was suggestive of inflammasome activation in the skin. Immunoblotting revealed caspase-1 activation in skin but not muscle. Notably, IL-1α and IL-18, along with caspase-1, were greatly elevated in the skin following cardiac arrest, consistent with differential inflammasome activation. Conclusions/Significance: Tissue-specific activation of Caspase-1 and the NLRP3 inflammasome appear to be key factors in determining the type and severity of the inflammatory response to tissue injury, especially in the presence of severe shock, as suggested via data-driven modeling.

The advent of more potent immunosuppressants led to the first successful human upper extremity transplantation in 1998. At this time, >100 upper extremity transplants, 30 face transplants, and a variety of other vascularized composite allotransplantation ( VCA) procedures have been performed around the world. VCA recipients present unique challenges for transplantation. The incidence of acute rejection exceeds 80% in hand and face transplantation and is well documented, whereas reports about antibody-mediated rejection and chronic rejection remain scarce. Immunosuppression protocols commonly used at US centers are derived from solid organ transplantation protocols. Novel approaches to minimize rejections in VCA may include improved HLA matching and considerations toward cytomegalovirus infection status. New graft preservation techniques may decrease immunogenicity prior to transplant. Novel monitoring methods such as valid biomarkers, ultrasound biomicroscopy, and sentinel flaps may enable earlier diagnosis of rejection. Cell-based therapies are being explored to achieve immunosuppressive regimen minimization or even tolerance induction. The efficacy of local immunosuppression in clinical VCA remains controversial. In conclusion, although immunosuppressive strategies adapted from SOT have demonstrated good midterm results, focusing on the unique features of VCA grafts may enable additional, more specific treatment strategies in the future and improved long-term graft outcomes. [ABSTRACT FROM AUTHOR]