Luis Landin

The International Registry on Hand and Composite Tissue Transplantation.

Background. The International Registry on Hand and Composite Tissue Transplantation was founded in May 2002, and the analysis of all cases with follow-up information up to July 2010 is presented here. Methods. From September 1998 to July 2010, 49 hands (17 unilateral and 16 bilateral hand transplantations, including 1 case of bilateral arm transplantation) have been reported, for a total of 33 patients. They were 31 men and 2 women (median age 32 years). Time since hand loss ranged from 2 months to 34 years, and in 46% of cases, the level of amputation was at wrist. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, sirolimus, and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was also used in several cases. Follow-up ranges from 1 month to 11 years. Results. One patient died on day 65. Three patients transplanted in the Western countries have lost their graft, whereas until September 2009, seven hand grafts were removed for noncompliance to the immunosuppressive therapy in China. Eighty-five percent of recipients experienced at least one episode of acute rejection within the first year, and they were reversible when promptly treated. Side effects included opportunistic infections, metabolic complications, and malignancies. All patients developed protective sensibility, 90% of them developed tactile sensibility, and 82.3% also developed a discriminative sensibility. Motor recovery enabled patients to perform most daily activities. Conclusions. Hand transplantation is a complex procedure, and its success is based on patients compliance and his or her careful evaluation before and after transplantation.

CD3+-Mediated Rejection and C4d Deposition in Two Composite Tissue (Bilateral Hand) Allograft Recipients After Induction With Alemtuzumab

Background. New therapies are being introduced in reconstructive transplant surgery to enhance composite tissue allograft survival. Methods. Alemtuzumab was used in two bilateral hand allograft recipients to cause lymphocyte depletion. Results. Although profound leukopenia and lymphopenia developed, several episodes of acute rejection occurred both in the early and late posttransplant period. Cell-mediated rejection was diagnosed during acute rejection episodes. Intraluminal C4d deposits were found in the capillaries not only accompanying cellular rejection, but also in the absence of clinical rejection. However, their significance is unclear because donor-specific antibodies were absent, there were no pathological signs of injury, allograft function was not impaired, and clinical signs of rejection resolved. Conclusion. These findings suggest that alemtuzumab may not prevent cell-mediated rejection of a hand allograft transplant. Furthermore, C4d deposition warrants attention in clinical composite tissue allotransplants.

Treatment of Recalcitrant Distal Tibial Nonunion Using the Descending Genicular Corticoperiosteal Free Flap

BACKGROUND Recalcitrant nonunions of the distal tibia without bone defect are severe problems whose treatment is difficult. Stable internal fixation and osteogenetic enhancement are required. The thin corticoperiosteal flap based on the descending genicular artery has been previously described to treat nonunions in the upper extremity without bone defect. The use of this flap to treat distal tibial nonunions is reported in the present article. METHODS Twenty-five patients with recalcitrant nonunion of the distal tibial metaphysis without segmental bone defect or evidence of infection were treated with revision of the internal fixation and a corticoperiosteal free flap from the medial condyle of the femur. The number of previous surgical procedures was two to five. The flaps were compound, including muscle or fat, for wound coverage in seven cases. RESULTS All compound flaps survived. Bony union was achieved in all cases, with bone formation at the nonunion site by the fourth month in all cases but one. In this case bone union took 7 months. Donor morbidity was negligible. Two tibiotalar arthrodeses were performed secondarily for posttraumatic osteoarthritis. CONCLUSIONS Treatment of recalcitrant distal tibial nonunions without bone defect with removal of previous hardware, stable internal fixation, and free corticoperiosteal flap transfer is safe and effective in noninfected cases.

Outcomes with respect to disabilities of the upper limb after hand allograft transplantation: a systematic review

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.

Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm allograft: functional follow-up at 32 months post transplantation.

Allografts of the forearm are still uncommon in the field of composite tissue allograft transplantation. In November 2007, a right-hand allograft and a left-hand/full-length forearm allograft were transplanted in a 30-year-old man who lost both hands and the vision in his left eye due to an explosion. The patient underwent alemtuzumab and steroid induction therapy. Tacrolimus, mycophenolate mofetil, and low doses of steroids were given to prevent rejection. The allografts were rejected 3 times, but these episodes were controlled successfully. The immunosuppressive regimen was switched from tacrolimus to sirolimus because of increased serum creatinine. The left allograft showed a flexion contracture due to muscle fibrosis that was conjectured to be associated with a perioperative ischemic injury and permitted only a Moberg-type key pinch. In contrast, an excellent grade of function was observed in the right allograft. The Disabilities of the Shoulder, Arm, and Hand score improved from 70.83 to 36.6 and intrinsic musculature returned to both allografts. The patient was able to work 2 years after transplantation. This is the first report of an ischemic injury related to the successful allotransplantation of a composite tissue.

Kidney transplants in HIV-positive recipients under HAART. A comprehensive review and meta-analysis of 12 series

BACKGROUND Kidney transplantation is being introduced gradually for the treatment of end-stage renal disease in patients who are human immunodeficiency virus (HIV) positive. Our aim was to review the outcomes of kidney transplantation in HIV-positive recipients who were being treated with highly active antiretroviral therapy (HAART). METHODS Eligible papers were English language manuscripts, published between July 2003 and April 2009 and available through Medline, that described three or more recipients of kidney transplants who were HIV positive and undergoing HAART. The regimens for induction and maintenance therapy, organ rejection, patient survival, CD4 counts, HIV progression, infectious complications and deaths were recorded. The survival at 1 year, organ rejection and infectious complications were evaluated using a random effects model with 95% confidence intervals (CI). RESULTS Twelve case series met the defined criteria. Induction therapy consisted most commonly of the administration of anti-CD25 monoclonal antibodies, and triple immunosuppressive therapy was used most commonly for maintenance. Among the 254 patients, 1-year survival was 0.93 (95% CI, 0.90-0.96), organ rejection was diagnosed in 0.36 (95% CI, 0.25-0.49) and infectious complications occurred in 0.29 (95% CI, 0.17-0.43). The CD4 counts decreased after transplantation but recovered later. Acquired immune deficiency syndrome (AIDS)-defining infections occurred in three patients. CONCLUSIONS Kidney transplantation appears to be safe in patients undergoing HAART. However, larger series of patients are needed to determine the best protocols for the induction and maintenance of immunosuppression.

Bilateral Hand Transplantation: Result at 20 Months

On November 2006, a bilateral hand allotransplantation was performed for a 47-year-old female who had suffered radiocarpal amputations 28 years before. Technical aspects of the operation are detailed. Alemtuzumab induction, and triple therapy of tacrolimus, mycophenolate mofetil and prednisone were used to control rejection. The evolution of the result and functioning at 20 months are presented in detail. Two acute rejection episodes occurred and were successfully treated with steroids. In addition the patient developed a factitious visual disorder and a facial basal cell carcinoma. Functionally, at 20 months, the patient had a Hand Registry Functional Score of 69 (good), and a DASH score of 19.

Standardizing skin biopsy sampling to assess rejection in vascularized composite allotransplantation

Over 70 hands and 20 faces have been transplanted during the past 13 yr, which have shown good to excellent functional and esthetic outcomes. However, (skin) rejection episodes complicate the post‐operative courses of hand and face transplant recipients and are still a major obstacle to overcome after reconstructive allotransplantation. This article summarizes all relevant information on the skin component and rejection of a vascularized composite allograft. As more and more centers plan to implement a vascularized composite allotransplantation (VCA) program, we further develop guidelines and recommendations on collection and processing of skin biopsies from hand and face allograft recipients. This will help to standardize post‐operative monitoring, avoid pitfalls for those new in the field and facilitate comparison of data on VCA between centers.

Management of soft-tissue complications of the lateral approach for calcaneal fractures.

Background: Soft-tissue complications after using the lateral approach for internal fixation of calcaneal fractures are relatively frequent, even in skilled hands. The global management of these wounds has never been standardized. Methods: The authors present a series of 24 patients with wound edge necrosis of lateral approaches for displaced intra-articular calcaneal fractures. Follow-up ranged from 5 to 52 months. The wound was covered with a local subcutaneous transverse flap in six cases, a sural subcutaneous flap in 12 cases, and a distal vastus lateralis free flap in six cases. Hardware was removed only if gross malalignment of the fracture was present. A treatment algorithm is proposed. Results: All the transverse local flaps were successful. Two sural flaps had complications that were salvaged with a free flap. All free flaps were successful, and all fractures healed. No chronic infections developed. Conclusions: The authors’ algorithm proved useful. For minor necroses (<1.5 cm wide) with supple tissues and no infection, the transverse local subcutaneous flap was effective. For moderate-sized wounds (1.5 to 5 cm) with no infection, a sural subcutaneous flap was used. In infected wounds with good fracture reconstruction, a free flap was used without hardware removal. If unsatisfactory bone reconstruction and infection were present, hardware removal and a sural flap were appropriate. For extensive defects (>5 cm) or when regional flaps failed, a free flap was useful.

Factors Influencing Acute Rejection of Human Hand Allografts: A Systematic Review

AbstractAcute rejection (AR) of human hand allografts (HHAs) may carry a risk of graft loss and leads to the need for immunosuppressive treatment. The literature on HHAs was reviewed to determine and evaluate the factors that trigger AR of HHAs. Clinical case reports of hand allograft transplantation published between 1999 and 2011 in English, French, or German were reviewed systematically. The number of AR episodes was the main outcome measure. Sixty-eight episodes of AR were described in 28 recipients. Calcineurin inhibitor-based maintenance regimens were associated with significantly fewer AR episodes than non–calcineurin inhibitor-based regimens (mean 1.9 vs 3.2; P = 0.018). In recipients who experienced cytomegalovirus infection, the mean number of episodes of AR was 4, whereas in those who did not experience cytomegalovirus infection it was 2.25 (P = 0.024). The planning of hand allograft transplantation should take these factors into account to minimize the risk of AR.