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An increasing number of institutions and companies is recently showing increasing interest in supersonic and hypersonic flight with particular focus on sub-orbital flight and high-speed point-to-point transportation. In this scenario, the University of Naples “Federico II” is currently studying advanced concepts of supersonic/hypersonic aircraft and suitable high-speed propulsion system integration for efficient travel in the Mach 4-5 speed range. Within this framework, a collaboration is in progress with the SME Blue Engineering. In the present work a study is undertaken to investigate the performances along with aerodynamic design of the supersonic intake for the turboramjet engines and the engine-airframe integration for a Mach 4 supersonic business jet. Firstly, attention is focused on directional stability and trimmability enhancement acting on aircraft configuration. The following section is dedicated to the aerodynamic design of a high-efficiency intake adapted to different flight conditions. To conclude, the last section addresses the sensitive issue of airframe-engine integration. The configuration analysis has been carried out with the quick and low-cost software Missile DATCOM, well suited for aircraft preliminary design. For the supersonic intake aerodynamic design and the airframe-engine integration analysis, the commercial Navier-Stokes solver Siemens STAR CCM+ has been used. An improved configuration has been proposed, actioning on vertical tail and wing for the directional stability enhancement, while the trim conditions have been improved using a canard. As for the supersonic intake aerodynamic design, the choice fell on mixed-compression variable-geometry. In particular, a total spike forward translation of 0.65 m guarantees adaptive operations along the supersonic trajectory. In addition, the choice of mixed-compression configuration ensured high efficiency values thanks to the multiple shock waves’ reflection in the supersonic diffuser. For what concerns the engine-airframe integration, the engine location above the wing has been shown to be not suitable due to the strong aerodynamic interference that reflects in a completely off-design intake functioning. Therefore, the configuration has been upgraded integrating the engine with the wing avoiding the issues experienced in the previous case

Analysis of all upper extremity (UET) and face allotransplantations (FT) reported to the International Registry on Hand and Composite Tissue Transplantation (IRHCTT) by May 2017. The IRHCTT includes 66 cases of UET (18 unilateral and 38 bilateral) and 30 of FT. Acute and chronic rejections were reported in the presence of immunosuppression. Complications similar to those reported in solid organ transplantation occurred. UET patient survival was 96.7% at 1, 5, and 10 years after transplantation; graft survival was 90.4% at 1 year and 86.6% at 5 and 10 years. FT patient survival was 96.6% at 1 year and 96.2% at 5 years; graft survival was 96.6% at 1 and 5 years. The majority of UET and FT recipients were satisfied of their graft. UET and FT are complex procedures requiring long-life immunosuppression; their success requires the patients’ careful selection, through evaluation, follow-up and compliance to the immunosuppression.

20-Year Follow-up of Two Patients with Bilateral Hand Transplants This letter reports the 20-year results in two men who underwent bilateral hand transplantation. Each of the patients can perform a...

Summary Whereas vascularized composite allografts often undergo acute rejections early in the postgraft period, rejection manifesting with severe vascular changes (graft vasculopathy) has only been observed on three occasions in humans. We report a hand-allografted patient who developed severe rejection following discontinuation of the immunosuppressive treatment. It manifested clinically with erythematous maculopapules on the skin and pathologically with graft vasculopathy that affected both large vessels and smaller cutaneous ones. The observation that graft vasculopathy can affect skin vessels shows that it is amenable to diagnosis with usual skin biopsy as recommended for the follow-up of these allografts. Graft vasculopathy developing in the setting of vascularized composite allografts likely represents chronic rejection due to under-immunosuppression and, if confirmed, should be included in a future update of the Banff classification of vascularized composite allograft rejection.

Summary The aim of this work is to compare disabilities of the upper limb before and after hand allograft transplantation (HAT), and to describe the side effects of immunosuppressive (IS) agents given to recipients of hand allografts. Clinical cases of HAT published between 1999 and 2011 in English, French, or German were reviewed systematically, with emphasis on comparing disabilities of the arm, shoulder and hand (DASH) scores before and after transplantation. Duration of ischemia, extent of amputation, and time since amputation were evaluated for their effect on intrinsic musculature function. Infectious, metabolic, and oncological complications because of IS therapy were recorded. Twenty-eight patients were reported in 56 clinical manuscripts. Among these patients, disabilities of the upper limb dropped by a mean of 27.6 (±19.04) points on the DASH score after HAT (P = 0.005). Lower DASH scores (P = 0.036) were recorded after secondary surgery on hand allografts. The presence of intrinsic muscle function was observed in 57% of the recipients. Duration of ischemia, extent of transplantation, and time since amputation were not associated statistically with the return of intrinsic musculature function. Three grafts were lost to follow-up because of noncompliance with immunosuppression, rejection, and arterial thrombosis, respectively. Fifty-two complications caused by IS agents were reported, and they were successfully managed medically or surgically. HAT recipients showed notable functional gains, but most complications resulted from the IS protocols.

Composite tissue allotransplantations (CTAs) have clinically shown little, if any, evidence of chronic rejection. Consequently, the effect of chronic rejection on bones, joints, nerves, muscles, tendons and vessels may still have undescribed implications. We thoroughly assessed all allograft structures by histology, magnetic resonance imaging, ultrasonography and high resolution peripheral quantitative computed tomography scan in four bilateral hand-grafted patients (10, 7, 3 and 2 years of follow-up, respectively) and in one facial allotransplantation (5 years of follow-up). All the recipients presented normal skin structure without dermal fibrosis. Vessels were patent, without thrombosis, stenosis or intimal hyperplasia. Tendons and nerves were also normal; muscles showed some changes, such as a variable degree of muscular hypotrophy, particularly of intrinsic muscles, accompanied by fatty degeneration that might be related to denervation. In the majority of hand-grafted patients graft radius and recipient tibia showed a decrease in trabecular density, although in the graft radius the alterations also involved the cortices. No deterioration of graft function was noted. In these cases of CTA no signs of chronic graft rejection have been detected. However, the possibility that chronic rejection may develop in CTA exists, highlighting the necessity of close continuous follow-up of the patients.

Nonunion and avascular necrosis of the proximal pole of the scaphoid remain one of the most difficult problems in wrist reconstructive surgery. A number of interpositional vascularized bone grafts have been proposed for scaphoid nonunion, in order to promote faster union at the contact site with both fragments. However, once the proximal pole has undergone avascular changes and is completely necrotic, there is no alternative other than to remove it. At present, more radical operations have been advocated in these cases, such as proximal row carpectomy or intercarpal arthrodesis. We present a case where the necrotic proximal pole of the scaphoid was removed and replaced with a remodeled osteochondral-free vascularized graft from the rib based on the inferior and superior intercostal arteries, branches of the internal mammary artery. © 2009 Wiley-Liss, Inc. Microsurgery 2009.

We have designed and constructed force measurement equipment to assess hand–finger function in pressing tasks. The equipment was used for monitoring the follow-up of five hand-transplanted subjects. Interactive software was integrated into the instrument to monitor the functionality of the hand and fingers during exercises in realtime. The interactive software included biofeedback to provide realtime quantitative responses for the patient and the therapist. Acceptance of the system was investigated with patients and therapists: the system was found to be user-friendly and effective; it was practical both for patients and therapists. The system could be used in a telerehabilitation centre or in a patient's home.

Donor leukocytes administered at the time of transplantation may prolong organ allograft survival. Delayed administration of calcineurin inhibitors, such as FK506 or cyclosporine, may enhance their efficacy. Herein the effectiveness of this strategy to promote limb transplant survival was investigated in the strong histocompatibility barrier of Brown-Norway donor to Lewis recipients. Donor leukocytes (6 × 107 intravenously) were injected on the day of transplantation followed on day 1 to 14 with mycophenolate mofetil (MMF; 15 mg/kg/d) and prednisone, (0.5 mg/kg/d) which were then tapered by 20% each week and stopped at week 7. Administration of of FK506 (2 mg/kg/d) was started on day 4 and continued for 8 weeks, then tapered for 4 weeks to a maintenance dose of 0.8 mg/kg/d, which was continued for 12 weeks (group A; n = 8). A control group (n = 8) underwent identical treatment save for donor leukocyte injection but rather commencement of FK506 on day 1. Rejection was common during FK506 tapering in both groups. However group A showed a significantly later onset, a shorter period for reversal of the first rejection, and a significantly lower dosage of FK506 at the time of rejection. After the completion of immunosuppression, rejection occurred significantly later in group A than the control group with one animal surviving without immunosuppression on day 344. This is the first trial of a donor leukocyte injection combined with delayed FK506 administration in limb transplantation, which suggested that it could produce a modest but significant improvement in outcome.

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.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.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.Despite the enormous antigen load associated with composite tissue allograft, hand transplantation became a clinical reality with immunosuppression comparable to transplantation of solid organs.

Studies in animals and humans suggest that sympathetic activity exerts a stiffening influence on large and middle-sized artery walls. We sought to obtain further evidence on this issue by measuring radial artery distensibility in an allotransplanted and thus denervated hand using the contralateral artery as control. In 2 men, blood pressure was measured by a semiautomatic device (Dinamap). Diastolic diameter, systo-diastolic diameter excursion (ultrasound Wall Track system), and distensibility (Reneman formula) of both radial arteries were measured at a level corresponding to 4 cm below the suture of the transplanted hand 40 days after surgery and every 4 weeks for the next 6 months. After surgery, systo-diastolic diameter excursion and distensibility were much greater in the transplanted radial artery than in the contralateral vessel, reaching values similar to the contralateral ones after 4 months, when signs of reinnervation of the transplanted hands had appeared. Radial deinnervation was accompanied by an increased arterial distensibility, which provides further evidence of the sympathetic stiffening effect on arterial wall in humans.

Far-field methods for aerodynamic drag calculation and breakdown around aircraft configurations by Computational Fluid Dynamics are widely adopted. Recent improvements and advances of one of these algorithms are discussed. Because these methods rely for breakdown purposes on the detection of the boundary-layer region around the body, an analysis of possible alternatives to the currently adopted boundary-layer sensor is proposed. Furthermore, a recently published study in the case of inviscid flow on the influence of the accuracy of the numerical solution at far field has been repeated in viscous flow. It shows how a far-field solution influences the computation of near-field drag, in particular, in high-lift conditions. Finally, an application to a complex high-lift three-dimensional configuration of an alternative method for the computation of the lift-induced drag is discussed. The method is based on the integration of the Lamb-vector field.

In this study the three components of an immunosuppressive combination therapy were gradually withdrawn in a rat limb transplantation model to evaluate the effects on long-term survival of the grafted limbs, rejection rate, and functional recovery. The procedure was performed in 16 rats across a strong Brown Norway to Fischer 344 histocompatibility barrier. Eight animals served as a control group that was not given any antirejection therapy and rejected their limb within a few days. The remaining eight animals were administered a 2-week course of immunosuppressive therapy including tacrolimus (TRL; 2 mg/kg/d), mycophenolate mofetil (MMF; 15 mg/kg/d), and prednisolone (Pred; 0.5 mg/kg/d). At 2 weeks, Pred and MMF were simultaneously tapered by 20% of the dosage every week; by week 7 the animals were on TRL only. TRL was then tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d at week 12. After 6 months the immunosuppression was stopped. Four of 8 animals did not reject throughout the study up, to the 1-year endpoint. At this stage they show excellent functional outcomes, evaluated by clinical tests and walking tract analysis. The remaining four rats developed a rejection at an average of 267 days postoperatively (range 224 to 302 days), corresponding to an average of 87 days (range 44 to 122 days) without any immunosuppression. They were sacrificed as soon as rejection was confirmed for histological examination of the various tissues. This study showed that a triple combination therapy provides excellent long-term functional outcomes of the transplanted limbs, with no rejection episodes, no side effects, or complications, even 6 months after withdrawal of all immunosuppressive components, suggesting the possible emergence of tolerance.

Hand transplantation may become an important procedure for upper limb functional restoration. To date, 18 patients have been undergone 24 hand operations in the world. Initial results are extremely promising; the functional results are apparently superior to those obtained with prostheses. We report on the combined French and Italian experience of six patients (eight hands), which is based on a jointly devised protocol and represents the largest available clinical series. Six male patients aged 43, 33, 35, 32, 33, and 22 years received either a single right hand–dominant transplantation (four cases) or a simultaneous double hand transplantation (two cases). The time since the amputation ranged from 3 to 22 years. The level of transplantation was at the wrist in five cases (six hands) and at the distal forearm in two cases (two hands). Cold ischemia averaged 11.5 hours. Three patients simultaneously received additional full-thickness skin taken from the donor and transplanted onto their left hip area. This skin served as a source for biopsies and as an additional area to monitor rejection (distant sentinel skin graft). The immunosuppressive protocol included polyclonal antibodies (three patients) or monoclonal anti-CD 25 antibody (three patients), tacrolimus, mycophenolate mofetil, and prednisolone. No surgical complications occurred. Skin rejection occurred at least once in all patients at a mean of 40 days postoperatively. Three patients recovered protective and some discriminative sensation in their palm and fingers. Two patients are recovering sensation, but are still in the early phases of the regenerative process, due to the short time since the transplantation. One patient was not compliant with the immunosuppressive therapy, and underwent uncontrolled rejection and reamputation.

Based on the results achieved in single human hand transplantations, we decided to perform the first double hand transplantation with a conventional immunosuppressive protocol in a patient with a high potential for functional recovery. Two years after transplantation the efficacy and the safety of this immunosuppressive protocol are evaluated. The recipient was a 33-yr-old man suffering from a traumatic amputation of both hands in 1996. Five HLA-A, -B, and -DR mismatches were present with the donor; T and B cell cross-match was negative. Immunosuppressive protocol included tacrolimus, prednisone, mycophenolate mofetil and, for induction, antithymocyte globulins and then anti CD25 monoclonal antibody. Reconstitution of lymphocyte populations proceeded normally. Neither anti-HLA antibodies nor chimerism in peripheral blood were detected. Two episodes of acute rejection characterized by maculopapular lesions occurred on days 53 and 82 after transplantation. Skin biopsies revealed a dermal lymphocytic infiltrate. Both episodes were completely and rapidly reversed by topical clobetasol and increased systemic corticosteroid therapy. The only side-effects related to treatment were reversible serum sickness and hyperglycemia. No infectious complications and malignancies occurred. No signs of graft-versus-host disease have been detected. This case of double hand transplantation shows that conventional immunosuppression is effective and safe to ensure survival and functional recovery of the grafted limb.

Objective of this study was to analyze fifteen months after surgery the sensorimotor recovery of the first human double hand transplantation.As for any organ transplantation the success of composite tissue allografts such as a double hand allograft depends on prevention of rejection and its functional recovery.The recipient was a 33-year-old man with bilateral amputation. Surgery included procurement of the upper extremities from a multiorgan cadaveric donor, preparation of the graft and recipient's stumps; then, bone fixation, arterial and venous anastomoses, nerve sutures, joining of tendons and muscles and skin closure. Rehabilitation program included physiotherapy, electrostimulation and occupational therapy. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil and, for induction, antithymocyte globulins and then CD25 monoclonal antibody were added. Sensorimotor recovery tests and functional magnetic resonance imaging (fMRI) were performed to assess functional return and cortical reorganization. All the results were classified according to Ipsen's classification.No surgical complications occurred. Two episodes of skin acute rejection characterized by maculopapular lesions were completely reversed increasing steroid dose within 10 days. By fifteen months the sensorimotor recovery was encouraging and the life quality improved. fMRI showed that cortical hand representation progressively shifted from lateral to medial region in the motor cortex.Even though at present this double hand allograft, treated using a conventional immunosuppression, allowed to obtain results at least as good as those achieved in replanted upper extremities, longer follow-up will be necessary to demonstrate the final functional restoration.

Hand transplantation is a model of composite tissue allografting ( a A ) . The immunological issues in CTA are extremely complex, as different tissues are involved, each of which has to be considered both individually and as a part of a unit while each has a different time and intensity of rejection. Cartilage, ligaments and fat present low antigenicity, and consequently they lead to a weak rejection; bone, muscles, nerves and vessels show a moderate rejection profile in spite of various degrees of immunogenicity; skin, a complex immunological structure, is the component that develops the most severe rejection, because of the abundance of dentritic cells within epidermis and dermis. Finally, bone marrow, a source of immunocompetent cells, is a major target for rejection, but also a source of contaminating donor T cells that could induce a graft-versus-host disease in a strongly immunosuppressed recipient, and a source of stem cells that might contribute to the development of a microchimerism. Limb transplantation, the most common experimental model of CTA, has met with varying degrees of success; however, results have improved with the introduction of new immunosuppressants, especially tacrolimus and mycophenolic acid [l-71. In humans few cases of isolated muscle [8], bone, joint [9, lo], nerve [ l l ] or vascular allografts [12] have been reported. The first vascularized human hand transplantation was performed on 23 September 1998 in Lyon, and it is described in the present report [13].

A new sutureless technique to successfully anastomose the abdominal aorta of rats (1.3 mm in diameter) by using a fully biodegradable, laser-activated protein solder is presented. A total of 90 rats were divided into two groups randomly. In group one, the anastomoses were performed by using conventional microsuturing technique, whereas in group two, the anastomoses were performed by using a new laser welding technique. In addition, each of the two groups were divided into five subgroups and evaluated at different follow-up periods (10 minutes, 1 hour, 1 day, 1 week, and 6 weeks). At these intervals, the anastomoses were evaluated for patency and tensile strength. Three anastomoses in each subgroup were processed for light and electron microscopy. All anastomoses were found to be patent. The mean clamp time of the anastomoses performed with conventional suturing was 20.6 minutes compared with 7.2 minutes for the laser-activated welded anastomoses (p < 0.001). The strain measurements showed a stronger mechanical bond of the sutured anastomoses in the initial phase. However, at 6 weeks the tensile strength of the laser-welded anastomoses was higher compared with the conventional suture technique. Histologic evaluations revealed a near complete resorption of the solder after 6 weeks. The junction site of the vessel ends cannot be determined on the luminal side of the artery. In conclusion, a resorbable protein used as a solder, activated by a diode laser, can provide a reliable, safe, and rapid arterial anastomosis, which could be performed by any microsurgeon faster than conventional suturing after a short learning curve.

Ulnar nerve lesions around the elbow often carry an unfavorable prognosis due to insufficient sensory and intrinsic muscle recovery. We present a series of 7 cases in which restoration of ulnar innervated intrinsic muscles of the hand and of skin sensibility was achieved. This was accomplished by a distal connection of the anterior interosseous nerve and the superficial sensory palmar branch of the median nerve to the motor and sensory components of the ulnar nerve at Guyon's canal. The length of the follow-up period ranged from 1 to 3.5 years. Results were graded by the Highet-Zachary scale. Good motor and sensory recovery was obtained in 6 cases; only return of protective sensation occurred in the remaining case.

The first hand allograft was performed on September 23, 1998. The right distal forearm and hand of a brain dead donor was transplanted to a 48 year old recipient who had undergone a traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with organ preservation solution (UW) and transported to Lyon in a cool container. Two teams simultaneously dissected the donor's limb and the recipient's stump to identify anatomical structures. Transplantation involved bone fixation, arterial and venous anastomoses, nerve sutures, joining of the muscles and tendons, and skin closure. Immunosuppression consisted of anti-lymphocyte, polyclonal and monoclonal antibodies, tacrolimus, mycophenolic acid, and prednisone. Mild clinical and histological signs of rejection occurred at week 9 after surgery. They disappeared with adjustments of the immunosuppressant doses. Seven months after surgery the patient was in good general condition. Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress is excellent, reaching the fingertips. A longer follow-up is necessary to appreciate the final result. In the absence of further rejection, the functional prognosis of the graft should be similar to that reported after successful autoreconstruction.

Summary Background Long-term survival of animal limb allografts with new immunosuppressant combinations and encouraging results of autologous limb replantations led us to believe that clinical application of hand transplantation in human beings was viable. Methods On Sept 23, 1998, we transplanted the right distal forearm and hand of a brain-dead man aged 41 years on to a man aged 48 years who had had traumatic amputation of the distal third of his right forearm. The donor's arm was irrigated with UW organ preservation solution at 4°C, amputated 5 cm above the elbow, and transported in a cool container. We dissected the donor limb and the recipient's arm simultaneously to identify anatomical structures. Appropriate lengths of viable structures were matched. Transplantation involved bone fixation, arterial and venous anastomoses (ischaemic time 12·5 h), nerve sutures, joining of muscles and tendons, and skin closure. Immunosuppression included antithymocyte globulins, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and prednisone. Follow-up included routine post-transplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. Findings The initial postoperative course was uneventful. No surgical complications were seen. Immunosuppression was well tolerated. Mild clinical and histological signs of cutaneous rejection were seen at weeks 8-9 after surgery. These signs disappeared after prednisone dose was increased (from 20 mg/day to 40 mg/day) and topical application of immunosuppressive creams (tacrolimus, clobetasol). Intensive physiotherapy led to satisfactory progress of motor function. Sensory progress (Tinel's sign) was excellent and reached the wrist crease (20 cm) on day 100 for the median and ulnar nerves, and at least 24 cm to the palm by 6 months when deep pressure, but not light touch sensation, could be felt at the mid palm. Interpretation Hand allotransplantation is technically feasible. Currently available immunosuppression seems to prevent acute rejection. If no further episode of rejection occurs, the functional prognosis of this graft should be similar to if not better than that reported in large series of autoreconstruction.

Using the technique of radioactive 51Cr-labeled biological microspheres, this study evaluated arterial blood flow following small vessel anastomosis by CO2 laser welding and a dissolvable stent in the lumen. A total of 30 Sprague-Dawley rats were divided into two groups. Group A: 11 rats had their femoral arteries ligated on one side. The contralateral side served as a control, with the artery transected and repaired using conventional microsuturing. Group B: 19 rats had their femoral arteries transected and repaired using CO2 laser welding and an intraluminal dissolvable stent technique. The contralateral side was again used as a control using conventional microsuturing. At 1 hr postoperatively, 51Cr-labeled biological microspheres were injected centripetally into the left common carotid artery and the legs and thighs immediately harvested for measurement of radioactivity. All repaired arteries were patent (30/30 in the microsuturing group and 19/19 in the stented welding group), with no detectable stenosis or dilation at the repaired site. Statistical analysis showed that tissue radioactivity (cpm/g) in the ligated group (3,972 +/- 384 in thighs and 3,142 +/- 742 in legs) was significantly lower than in the microsuturing group (7,132 +/- 1,723 in thighs and 6,557 +/- 1,469 in legs) (P 0.05) and legs (6,386 +/- 1,703 and 6,288 +/- 1,757, respectively; P > 0.05). This study provided evidence that the dissolvable stent placed intraluminally does not impair blood circulation and that when coupled with CO2 laser welding offers a high-quality alternative to conventional small vessel anastomosis.

This study evaluates the use of sutureless laser welding for vasovasostomy. In 14 rodents, the left vas deferens underwent vasovasostomy using an albumin-based solder applied to the adventitia of the vas deferens. The solder contained the dye, indocyanine green, to allow selective absorption and denaturation by a fiber-coupled 800-nm diode laser. The right vas deferens served as a control, receiving conventional layered microsurgical repair. We used a removable 4/0 nylon stent and microclamps to appose the vas deferens during repair, with no need for stay sutures. The mean time to perform laser solder repair (23.5 min) and conventional repair (23.3 min) were not significantly different (P = 0.91). However, examination after 8 weeks showed that granuloma formation (G) and patency (P) rates for the conventional suture technique (G, 14%; P, 93%) were significantly better than observed for the laser solder technique (G, 57%; P, 50%). © 1998 Wiley-Liss, Inc. MICROSURGERY 18:414–418, 1998

In thumb reconstruction, the wrap-around free flap has many advantages; however, delayed wound healing, pain, and skin ulcerations at the donor site can be a problem. In 5 patients, a free lateral forearm fasciocutaneous flap was successfully used for immediate resurfacing of the donor defect of the big toe during wrap-around procedures. This flap was selected after preliminary anatomic studies that showed that it could be safely raised if based on the anterior terminal division of the posterior radial collateral artery. The average follow-up period was 2 years. The time required for healing of the great-toe defect was less than 1 month. All patients were satisfied with the outcome of the procedure. The skin of this flap is very pliable and thin, and the subcutaneous tissue is about half the thickness of that of the lateral arm flap. This technique is especially indicated for closure of moderate to big skin defects at the great-toe level, whenever a larger than usual amount of skin is required, during wrap-around procedures for thumb reconstruction.

To assess the efficacy, role, and limitations of diagnostic ultrasound in the hand and wrist, the results of 98 examinations performed for a variety of surgical conditions were retrospectively analyzed. Ultrasound was shown to be reliable in evaluating radiolucent foreign body, tendon rupture versus tendon adhesion, tendinitis, peritendinitis, and ganglion cyst (specificity, 1; positive predictive value, 1). A correct suggestion of soft tissue mass histology was offered in six of eight operated cases. Tumor size and extent was accurately assessed in all but one case. The observed limitation of ultrasound was a small false negative rate in each category, which related to a variety of factors, including operator dependence, resolution threshold in the submillimeter range, image degradation due to postoperative edema, a narrow field of view, and one instance of indiscrete tumor margination. More work is needed to determine the role (if any) of ultrasound in the evaluation of peripheral nerve, triangular fibrocartilage, dorsal carpal ligament, and bone pathology.

When using microvascular polytetrafluoroethylene (PTFE) vascular grafts, the best results in terms of patency rate and neoendothelialization are obtained with prostheses with thin walls and long fibril length (i.e., 90 μm). A complete internal neoendothelial lining is usually achieved at 12 weeks after implantation. Clinically, this period can be too long. In this study, 1-mm internal diameter PTFE prostheses with optimal physical characteristics were pretreated with basic fibroblast growth factor in fibrin glue, a potent endothelial cell mitogen, and chemoattractant. Rate, speed, extent, quality, and origin of neoendothelium were compared with two control groups, using Evans Blue dye, immunohistochemical localization of factor VIII von Willebrand factor protein, and scanning electron microscopy. Prostheses (8 mm long) were implanted in the infrarenal rat aorta and harvested after 3 weeks. In treated grafts, the amount of endothelial regeneration was greater than in untreated grafts (75% of the internal surface compared with 30%). However, patency rate in the experimental group was lower than in the control groups. This study provides new data on neoendothelial regeneration in small-diameter PTFE grafts. © 1998 Wiley-Liss, Inc.

Fibre-optic technology combined with confocality produces a microscope capable of optical thin sectioning. In this original study, tibial nerves have been stained in a rat model with a vital dye, 4-(4-diethylaminostyryl)-N-methylpyridinium iodide, and analysed by fibre-optic confocal microscopy to produce detailed images of nerve ultrastructure. Schwann cells, nodes of Ranvier and longitudinal myelinated sheaths enclosing axons were clearly visible. Single axons appeared as brightly staining longitudinal structures. This allowed easy tracing of multiple signal axons within the nerve tissue. An accurate measurement of internodal lengths was easily accomplished. This technique is comparable to current histological techniques, but does not require biopsy, thin sectioning or tissue fixing. This study offers a standard for further in vivo microscopy, including the possibility of monitoring the progression of nerve regeneration following microsurgical neurorraphy.

This paper reports on the first clinical case where a polytetrafluoroethylene (PTFE) graft of less than 3 mm in diameter was implanted in the arterial system of a patient to bridge a vascular defect. A 1.5 cm long, 1.5 mm diameter prosthesis was interposed in the superficial palmar arch of a man who sustained a laceration of the palm of his dominant hand. The graft was implanted by means of the 3M Precise Microvascular Anastomotic System on one end, and by conventional microsurgical technique on the other end. There were no postoperative complications. The patient resumed his pre-injury activities 9 weeks after trauma. Serial Doppler ultrasound examinations showed normal blood flow and complete patency of the graft. An angiogram performed 12 weeks postoperatively confirmed the patency of the prosthesis. Twelve months post-operatively the patient is free from complications. The use of small diameter PTFE prostheses may be considered when planning grafting procedures for microvascular defects.

BACKGROUND The muscle fibers in a transplanted hand remain denervated for a long period of time after the transplant. This prolonged inactivity may change the electrophysiological membrane properties of muscle fibers, as observed in long-term denervation. We investigated whether electrophysiological properties of the muscle fibers are preserved in a transplanted hand even after several months of denervation. Specifically, we assessed the dependence of muscle fiber conduction velocity (CV) on discharge rate in motor units of the abductor digiti minimi muscle. METHODS Surface electromyography signals were recorded from the transplanted hand of a patient who was 35 years of age at the time of the transplant. In each of 11 experimental sessions performed over a period of 23 months after the transplant, the subject was asked to linearly increase the activation or to maintain a maximum activation of the abductor digiti minimi muscle for 60 sec. Individual motor unit action potentials were identified from the electromyography recordings and muscle fiber CV was estimated for each action potential as a function of the time interval separating the action potential from the preceding discharge (interspike interval [ISI]). RESULTS The baseline (ISI >1000 msec) CV was 3.8±0.3 m/sec. CV decreased monotonically with increasing ISI (R=0.95). For ISI in the range 0 to 10 msec, muscle fiber CV was 24.9%±16.3% higher than the baseline value (P

The International Registry on Hand and Composite Tissue Transplantation (IRHCTT) was founded in 2002 and its purpose was to collect detailed information from every case of hand and face transplantation providing a unique opportunity for the teams to share their experiences and to keep abreast of the latest developments. The registry of face transplantation presents some peculiar characteristics as face is considered a complex “organ” constituted of anatomic parts with different functions. In the Registry facial deficits are expressed as “aesthetic units,” adding also the depth of the defect; and in the procedure section, it is not only important to report the transplanted aesthetic units but also to detail all the grafted tissues, vascular anastomoses, nerve repairs, and eventual additional surgical procedures. Immunosuppressive regimen, rejection episodes, side effects, or other complications are fully reported. The evaluation of outcomes is difficult as disfigurement involves different parts of face with loss of various functions. Consequently, it is important to evaluate both aesthetic and functional results, detailing the recovered functions, such as swallowing, eating and drinking, speaking, or opening and closing eyelids. Two items, such as “Psychological and social acceptance” and “Patient satisfaction and general well-being” are also reported as the goal of face transplantation is to allow the patient to have a social life and improved quality of life.

The 3M Precise Microvascular Anastomotic System has had an experimental long-term testing for the first time in polytetrafluoroethylene (PTFE) 1-mm diameter arterial grafts. The grafts were placed in the infrarenal aorta of 48 rats. At different time intervals (2 weeks, 16 weeks and 1 year), each section containing a graft and its pair of anastomotic devices was removed and processed for light and scanning electron microscopy, with the aid of a newly-designed device. Eighty-three percent of the mechanically anastomosed grafts were found to be patent. Only 14.8 percent of the grafts harvested at 16 weeks or 1 year showed neo-endothelial lining on the inner surface of the graft. A constant finding of this study was the marked atrophy of the aortic media within the devices, that was progressively evident from 2 weeks to 1 year. A network of capillaries within the graft walls was present at 16 weeks. In one case, a large capillary was found to traverse the graft wall and to reach the luminal surface, suggesting that transmural capillaries may contribute to the formation of neo-intima in 1-mm PTFE grafts.

The 3M Precise Microvascular Anastomotic System has been tested experimentally in long-term studies of arteries of 1 mm in diameter for the first time. The device was placed, using a newly described technique, in the infrarenal aorta of 25 rats. At different intervals (2 weeks, 16 weeks, and 1 year), the section containing the 3M Precise Microvascular Anastomotic System was removed and processed for light microscopy and scanning electron microscopy. All the anastomoses were found to be patent. Using a new device to process the material, both light microscopy and scanning electron microscopy at 2 weeks showed a perfect reparative process at the junction site and the presence of a continuous endothelial layer. Media atrophy was responsible for wall thinning within the device. At 16 weeks, the atrophy of the media was even more marked, reducing the vessel wall thickness within the device to one-third of normal. At 1 year, this atrophy of the media was complete; smooth muscle cells disappeared and were replaced by fibrous tissue. Adventitia was not present over the long term within the device. The continuous endothelial layer, however, was still viable. These long-term results suggest that scar tissue forms within the device, while a continuous endothelial layer remains viable internal to this.

We present a case in which an open wound involving the ulnar collateral ligament of the metacarpophalangeal joint of the little finger was treated by ligament reconstruction using a strip of Dacron material, nerve grafting and coverage by a posterior interosseous artery pedicled flap. At a long term follow-up of 4 years, the joint was stable and had a full range of movement.

Human cytomegalovirus (HCMV) infection is the major viral complication in solid organ transplant recipients. Seronegative recipents (R-) of organs from seropositive donors (D+) appear to be at higher risk of developing symptomatic HCMV infection. To what extent systemic life-threatening complications can be risked for non-life-saving transplant procedures? A case report describing successful treatment of repeated episodes of active HCMV infection in a D+R- hand recipient in the absence of HCMV-specific T-cell immunity is presented. In the attempt to save both the patient and the transplanted hand, a preemptive treatment strategy was adopted with the aim to boost the constitution of the virus-specific T-cell immune response and simultaneously avoid onset of disease. Careful monitoring of HCMV load in blood and HCMV-specific T-cell immunity guided administration of repeated courses of antiviral treatment and avoided emergence of HCMV-related symptoms. Following establishment of HCMV-specific CD4+ and CD8+ T-cell response, preemptive treatment was no longer required due to sustained HCMV disappearance from blood. The patient is now well, and his hand too. In conclusion, evaluation of virus-specific T-cell immunity is of crucial importance in D+R- transplant recipients and careful monitoring of HCMV-specific T cell mediated response should always parallel monitoring of HCMV load in transplant recipients.

Skin rejection after hand transplantation is characterized by a maculopapular erythematous rash that may be diffuse, patchy or focal, and distributed over forearms and dorsum of the hands. This 'classical' pattern of rejection usually spares the skin of the palm and does not affect the nails. Herein, we report the experience on four cases presenting with an 'atypical' pattern of rejection that is novel in involving the palmar skin and the nails. All patients were young and exposed to repetitive and persistent mechanical stress of the palm. Characteristic features of rejection included a desquamative rash associated with dry skin, red papules, scaling and lichenification localized to the palm. Skin lesions were associated with nail dystrophy, degeneration, deformation or loss. Histology of the skin and nail bed revealed a lymphocytic infiltrate with predominance of T cells (CD3+, CD4+ and CD8+), with small numbers of B cells (CD20+ and CD79a+) and a low number of Forkhead transcription factor 3 (FOXP3)-positive cells in one patient. The lesions persisted over weeks to months, responded poorly to steroid treatment and were managed with antithymocyte globulin (ATG; Thymoglobulin, Genzyme, Cambridge, MA), alemtuzumab and/or intensified maintenance immunosuppression.

Administration of donor bone marrow (BM) cells can improve the outcome of transplantation. The ability of donor vascularized bone marrow transplantation (VBM) to provide an ongoing source of donor cells and improve survival in a rigorous rat model of hind limb transplantation (HLTX) was investigated. HLTX were performed between Brown Norway (BN) donors and Lewis recipients in three groups: HLTX; HLTX plus intravenous donor BM cells and HLTX plus simultaneous VBM transplantation. Animals received 12 weeks triple immunosuppression. Survival was compared at 4 months and donor chimerism was evaluated. Simultaneous VBM transplantation led to slight but nonsignificant prolongation of survival (P=0.056). Donor cells in the VBM were eventually replaced by recipient and there was no long-term increase in chimerism. Few donor cells were observed in thymus. Simultaneous VBM transplantation showed a trend for improved survival of HLTX however the VBM failed to provide a sustained increase in chimerism.

Hand surgeons and reconstructive microsurgeons have been “transplanting” composite tissues for a long time. Every time we perform a free flap, we are actually performing a true transplant. Most of the time there is no choice other than to adapt a flap coming from a certain donor area to a recipient area with different characteristics. Normally this happens in cases of complex multitissue defects or when the tissue that needs reconstruction carries some unique features. So while we are now exploring the area of prefabrication or prelamination of flaps, we are aware that we are far from perfection, hence the need to look at using possible allogeneic tissues [1]. With the advent of microsurgery, the long-term results of autologous replantation of the upper extremity, especially after a clean-cut amputation, have become extremely good. In a recent long-term review study, it was shown that replanted hands and forearms had a mean loss of range of motion of 17.5% [2].

From a surgical point of view, hand transplantation is technically not very different from a hand replantation. However, the procedure presents unique requirements, especially from an organization point of view. In our experience, there is no doubt that there are more differences than similarities between hand transplantation and replantation, so that the two operations must be considered quite different and a completely different approach must be followed [1].

Human hand transplantation became a reality on 23 September 1998 when the first successful case was performed, with long-term transplant survival and promising functional recovery [1]. Twenty-four hand transplantations have been performed until the writing of this book (12 unilateral and 6 bilateral). However, there remains considerable debate over the ethical consequences of hand allotransplantation, and many questions must be answered before it becomes a routine procedure.

Herpes virus infections are common causes of morbidity and mortality in solid organ and haematopoietic stem cell transplant recipients. Recent innovations in diagnosis, prophylaxis and treatment have reduced the incidence of herpes virus infections during the early posttransplant period, but they continue to significantly influence the outcome after transplantation [1].

While an internal organ is hidden but works immediately after the transplantation, a hand is fully visible and takes many months to gradually recover sensation and movement [1, 2]. Assessment of viability of transplanted internal organs is usually done by measuring function, either by biochemical evaluations or routine biopsies [3, 4]. In case of a hand, monitoring is largely based on visual inspection [5, 6, 7]. This is a definite advantage compared with internal organs, where an initial rejection may go undetected for some time until the next scheduled biochemical tests or biopsy are carried out. Methods for monitoring rejection in human hand transplantation include visual inspection of skin changes and histological analysis of biopsies. However, repetitive skin biopsies on a relatively small area may pose the problem of leaving multiple visible scars, especially if these procedures must be carried out over a period of many years.

The first hand transplantation was performed in Lyon, France, on 23 September 1998 by an international team of surgeons. Since then, hand transplantation programmes have been launched in the United States, China, Italy, Austria and Belgium. Since 1998, 11 patients have received a single hand transplant, four a double hand transplant and two a double forearm transplant.

Patients suffering from intestinal failure and total-parenteral-nutrition-derived complications can be treated with either intestinal or multivisceral abdominal transplantation. These operations have greatly increased in number in the last decade (more than 1,000 reported cases) because of the improved survival rate due to advances in surgical technique, better immunosuppressive regime, donor selection and recipient care [1]. However, there are cases where achieving primary closure of the abdominal wall at the end of the surgical procedure is very difficult. Patients requiring intestinal transplantation have often previously undergone intestinal resection, with loss of the small-bowel domain. Their abdominal wall structure may be severely altered because of laparotomies, enterocutaneous fistulae, infections and tumours.

Microsurgery was developed in the twentieth century by combining techniques of vascular surgery with an operating microscope, fine instruments, microsuture and new operative strategy and techniques. The first vascular anastomosis was performed by J.B. Murphy in 1897, but Alexis Carrel [1] originated the method for triangulation of blood vessels to perform arterial and venous repairs in 1902. He performed an end-to-end anastomosis. It was in 1960 that Jules Jacobson [2], a vascular surgeon, described microsurgical anastomoses in vessels as small as 1.4 mm using an operating microscope.

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.