Jaimie T. Shores

Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression.

Objective: To minimize maintenance immunosuppression in upper-extremity transplantation to favor the risk-benefit balance of this procedure. Background: Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the risks and side effects of multidrug immunosuppression. We present our experience with upper-extremity transplantation under a novel, donor bone marrow (BM) cell-based treatment protocol (“Pittsburgh protocol”). Methods: Between March 2009 and September 2010, 5 patients received a bilateral hand (n = 2), a bilateral hand/forearm (n = 1), or a unilateral (n = 2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction, followed by tacrolimus monotherapy. On day 14, patients received an infusion of donor BM cells isolated from 9 vertebral bodies. Comprehensive follow-up included functional evaluation, imaging, and immunomonitoring. Results: All patients are maintained on tacrolimus monotherapy with trough levels ranging between 4 and 12 ng/mL. Skin rejections were infrequent and reversible. Patients demonstrated sustained improvements in motor function and sensory return correlating with time after transplantation and level of amputation. Side effects included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, minor wound infection, and hyperuricemia but no infections. Immunomonitoring revealed transient moderate levels of donor-specific antibodies, adequate immunocompetence, and no peripheral blood chimerism. Imaging demonstrated patent vessels with only mild luminal narrowing/occlusion in 1 case. Protocol skin biopsies showed absent or minimal perivascular cellular infiltrates. Conclusions: Our data suggest that this BM cell-based treatment protocol is safe, is well tolerated, and allows upper-extremity transplantation using low-dose tacrolimus monotherapy.

Skin Substitutes and Alternatives: A Review

PURPOSE To provide the specialist in skin and wound care with a review of skin replacement alternatives and their most common uses. TARGET AUDIENCE This continuing education activity is intended for physicians and nurses with an interest in wound care and related disorders. OBJECTIVES After reading this article and taking this test, the reader should be able to: Describe characteristics of skin and skin substitutes for grafting. Identify indications for and uses of common grafting procedures and products.

Negative pressure wound therapy with instillation: a pilot study describing a new method for treating infected wounds

This data review reports the results of 15 patients who were treated with Vacuum‐Assisted Closure® (VAC) negative pressure therapy system in addition to the timed, intermittent delivery of an instilled topical solution for management of their complex, infected wounds. Prospective data for 15 patients treated with negative pressure wound therapy (NPWT)‐instillation was recorded and analysed. Primary endpoints were compared to a retrospective control group of 15 patients treated with our institution‘s standard moist wound‐care therapy. Culture‐specific systemic antibiotics were prescribed as per specific patient need in both groups. All data were checked for normality of distribution and equality of variance and appropriate parametric and non parametric analyses were conducted. Compared with the standard moist wound‐care therapy control group, patients in the NPWT‐instillation group required fewer days of treatment (36·5 ± 13·1 versus 9·9 ± 4·3 days, P < 0·001), cleared of clinical infection earlier (25·9 ± 6·6 versus 6·0 ± 1·5 days, P < 0·001), had wounds close earlier (29·6 ± 6·5 versus 13·2 ± 6·8 days, P < 0·001) and had fewer in‐hospital stay days (39·2 ± 12·1 versus 14·7 ± 9·2 days, P < 0·001). In this pilot study, NPWT instillation showed a significant decrease in the mean time to bioburden reduction, wound closure and hospital discharge compared with traditional wet‐to‐moist wound care. Outcomes from this study analysis suggest that the use of NPWT instillation may reduce cost and decrease inpatient care requirements for these complex, infected wounds.

Hand and Upper Extremity Transplantation: An Update of Outcomes in the Worldwide Experience

Background: Hand/upper extremity transplantation is the most common form of vascularized composite allotransplantation performed to date. An Update of worldwide outcomes is reported. Methods: The authors summarize the international experience with 107 known transplanted hand/upper extremities in 72 patients. Data from published medical literature, national and international meetings, lay press reports, and personal communications were utilized to provide the most up-to-date summary. Results: Although 24 losses (including four mortalities) are known, three of the four reported mortalities and eight of 24 limb losses were caused by multiple type vascularized composite allotransplantations (combined upper and lower limb or upper limb and face). Seven more losses were attributable to 15 patients in the early experience in China. In the United States and Western Europe, only three other non-acute graft losses have been reported, resulting in a patient survival rate for unilateral or bilateral hand transplantation in isolation of 98.5 percent and an overall graft survival rate of 83.1 percent. Conclusions: Published functional outcomes continue to demonstrate improvement in function and quality of life. The international experience supports the idea that, for properly selected individuals, hand and upper extremity transplantation should be considered an important treatment option.

A clinical review of infected wound treatment with Vacuum Assisted Closure (V.A.C.) therapy: experience and case series.

Over the last decade Vacuum Assisted Closure® (KCI Licensing, Inc., San Antonio, TX) has been established as an effective wound care modality for managing complex acute and chronic wounds. The therapy has been widely adopted by many institutions to treat a variety of wound types. Increasingly, the therapy is being used to manage infected and critically colonized, difficult‐to‐treat wounds. This growing interest coupled with practitioner uncertainty in using the therapy in the presence of infection prompted the convening of an interprofessional expert advisory panel to determine appropriate use of the different modalities of negative pressure wound therapy (NPWT) as delivered by V.A.C.® Therapy and V.A.C. Instill® with either GranuFoam™ or GranuFoam Silver™ Dressings. The panel reviewed infected wound treatment methods within the context of evidence‐based medicine coupled with experiential insight using V.A.C.® Therapy Systems to manage a variety of infected wounds. The primary objectives of the panel were 1) to exchange state‐of‐practice evidence, 2) to review and evaluate the strength of existing data, and 3) to develop practice recommendations based on published evidence and clinical experience regarding use of the V.A.C.® Therapy Systems in infected wounds. These recommendations are meant to identify which infected wounds will benefit from the most appropriate V.A.C.® Therapy System modality and provide an infected wound treatment algorithm that may lead to a better understanding of optimal treatment strategies.

Composite tissue allotransplantation: hand transplantation and beyond.

Recent advances in transplant immunology are shifting the focus from immunosuppression to immunoregulation, making composite tissue allotransplantation with novel and less potent immunosuppressive regimens a possibility. Hand transplantation has been the most frequently performed human composite tissue allotransplantation, with more than 50 upper extremity-based transplants done worldwide. Further research is needed regarding immunomodulating protocols, and careful oversight and individualized screening procedures will be required as patients seeking improved quality of life through human composite tissue allotransplantation come to accept a certain level of risk in these experimental procedures. Still, composite tissue allotransplantation offers to advance transplant medicine and reconstructive surgery.

Outcomes of vacuum-assisted closure for the treatment of wounds in a paediatric population: case series of 58 patients.

OBJECTIVE This retrospective case series describes our experiences and outcomes using the vacuum-assisted closure (VAC) Therapy System for the management of difficult acute and chronic wounds in paediatric patients. SUMMARY BACKGROUND DATA Difficult wounds that cannot be closed primarily can create major challenges in paediatric patient care. Decreasing the time to wound closure is especially critical when managing paediatric patients. METHODS A retrospective review of medical records for 58 consecutive paediatric patients treated with VAC therapy was performed. Demographics, diagnosis, length of therapy, time to closure, time to discharge, type of VAC dressing used, dressing change schedule, therapy settings, and complications were recorded for each patient. RESULTS The median age of all 58 patients was 10 years (range, 10 days to 16 years). Fifty-four of the 58 wounds reached full closure. Patients were divided into five different groups according to diagnosis. The median time to closure for each group follows: Group 1 (abdominal wounds) 10 days (range, 3-99 days); Group 2 (surgical soft tissue deficit) 12 days (range, 3-30 days); Group 3 (trauma wounds) 7 days (range, 3-10 days); Group 4 (stage III/IV pressure ulcers) 15 days (range, 14-15 days); Group 5 (fasciotomy wounds) 5 days (range, 5-10 days). No complications were recorded for any of the patients. CONCLUSIONS The results demonstrate that VAC therapy may be a viable, safe and effective method of managing this difficult-to-treat population.

Tendon coverage using an artificial skin substitute

BACKGROUND Soft tissue deficits associated with exposed tendon and absent paratenon pose difficult reconstructive problems due to tendon adhesions, poor range of motion, poor cosmesis, and donor site morbidity. Integra Bilayer Matrix Wound Dressing (Integra Lifesciences Corp Plainsboro, NJ) is a skin substitute widely used in reconstructive surgery, including the incidental coverage of tendons. However, Integras post-operative functionality of the tendons has not been well documented. We report the results of using Integra for soft tissue reconstruction overlying tendons with loss of paratenon in upper and lower extremity soft tissue defects. METHODS Forty-two patients (35 men and 7 women) with exposed tendons due to trauma (37), cancer excision (2) or chronic wounds (3) were reconstructed using Integra. Results were compiled in a prospective manner, including age, gender, wound location, wound size, time to final closure, operative time, follow-up length, split-thickness skin graft percentage take and active post-operative range of motion. Likewise using Medline, a literature search of current surgical techniques for the treatment of exposed tendons and the results from the literature were compared with these study results. RESULTS All patients healed with an average split-thickness skin graft take rate of 92.5% ± 6.1 (range, 80-100%). The thirty-two patients not lost to follow-up achieved an average range of motion of 91.2% ± 6.5 (range, 80-100%). CONCLUSION Integra offers a convenient, efficient operative procedure with minimal morbidity, demonstrating good cosmesis and tendon function. Thus, Integra may offer an alternative option for immediate tendon coverage in both the upper and lower extremities.

Surgical and technical aspects of hand transplantation: is it just another replant?

The ultimate goal of hand allotransplantation is to achieve graft survival and useful long-term function. To achieve these goals, selection of the appropriate patient, detailed preoperative planning, and precise surgical technique are of paramount importance. Transplantation should be reserved for motivated consenting adults in good general heath, who are psychologically stable and have failed a trial of prosthetic use. While the key surgical steps of transplantation are similar to those of replantation, there are major differences. This article describes the steps in hand allotransplantation, and the importance of patient selection as well as preoperative and postoperative care.

Using the dorsal, cavernosal, and external pudendal arteries for penile transplantation: technical considerations and perfusion territories.

Background: Penile transplantation may provide improved outcomes compared with autogenous phalloplastic reconstruction. The optimal approach to vascularizing penile allografts is unknown. In penile replantation, typically only the dorsal arteries are repaired, but using the cavernosal and external pudendal arteries may improve erectile function and shaft skin perfusion, respectively. The authors sought to demonstrate the technical feasibility of using the dorsal, cavernosal, and external pudendal vessels for penile transplantation and to assess differences in their perfusion territories. Methods: Cadaveric penile transplantation was performed. Different colored dyes were injected at physiologic pressure into the dorsal, cavernosal, and external pudendal arteries, and tissue perfusion territories were assessed visually. Results: Cavernosal artery exposure and repair required minimal dissection of the corpora cavernosa; extra length taken from the donor compensated for resultant shortening of the proximal shaft stump. The external pudendal system was easily accessed in the groin. Dye injected into the cavernosal artery strongly perfused the corpora cavernosa, with minimal communication to skin. The dorsal artery principally perfused the glans and corpus spongiosum. The external pudendal artery perfused the shaft and surrounding skin. Conclusions: Anastomosing the cavernosal arteries may augment corporal inflow, which is necessary for erection. Although the dorsal arteries are critical for distal penile skin perfusion, the external pudendal artery should be used in proximal transplantation to ensure adequate shaft skin perfusion. Each of these arteries has a distinct and seemingly important perfusion territory that should be considered in the setting of penile transplantation.