Kodi Azari

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.

rhBMP-2 Delivered in a Calcium Phosphate Cement Accelerates Bridging of Critical-Sized Defects in Rabbit Radii

BACKGROUND Treatment of segmental bone loss remains a challenge in skeletal repairs. This study was performed to evaluate the efficacy of the use of recombinant bone morphogenetic protein-2 (rhBMP-2) delivered in an injectable calcium phosphate cement (alpha bone substitute material [alpha-BSM]) to bridge critical-sized defects in the rabbit radius. METHODS Unilateral 20-mm mid-diaphyseal defects were created in the radii of thirty-six skeletally mature New Zealand White rabbits. The defects in twelve rabbits each were filled with 0.166 mg/mL rhBMP-2/alpha-BSM cement, 0.033 mg/mL rhBMP-2/alpha-BSM cement, or buffer/alpha-BSM cement. Six rabbits from each group were killed at four weeks, and six were killed at eight weeks. Serial radiographs were made to monitor defect-bridging and residual alpha-BSM carrier. A semiquantitative histological scoring system was used to evaluate defect-bridging. Histomorphometry was used to quantify residual alpha-BSM; trabecular bone area; trabecular bone volume fraction; and cortical length, width, and area. RESULTS At four weeks, there had been more rapid resorption of alpha-BSM and filling of the defects with trabecular bone in the group treated with 0.166 mg/mL rhBMP-2/alpha-BSM than in the other two groups. Histomorphometry confirmed an increased trabecular area and volume fraction in this group compared with the other two groups. In both rhBMP-2/alpha-BSM-treated groups, the majority of the trabecular bone was formed by a direct process adjacent to the resorbing alpha-BSM. At eight weeks, complete cortical bridging and regeneration of the marrow space were present in all of the defects treated with 0.166 mg/mL rhBMP-2/alpha-BSM. That group also had reduced residual alpha-BSM and trabecular area and volume, compared with the other two groups, at eight weeks as a result of a rapid remodeling process. CONCLUSIONS Treatment of a critical-sized defect in a rabbit radius with 0.166 mg/mL rhBMP-2/alpha-BSM injectable cement can result in bridging with cortical bone and a regenerated bone-marrow space by eight weeks. Site-specific remodeling appears to be responsible for corticalization and marrow regeneration. CLINICAL RELEVANCE RhBMP-2 delivered in a calcium phosphate cement may be useful to achieve bridging of critical-sized defects in patients. Its injectable properties may allow minimally invasive use. Delayed percutaneous administration would also be possible when augmentation is desired following an initial surgical procedure or when soft-tissue injuries preclude adequate initial treatment.

Anti-TGF-beta2 antibody therapy inhibits postoperative resynostosis in craniosynostotic rabbits.

Background: Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)-β2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF-β2 function with the use of neutralizing antibodies may inhibit resynostosis. The present study was designed to test this hypothesis. Methods: New Zealand White rabbits with bilateral coronal suture synostosis were used as suturectomy controls (group 1, n = 9) or given suturectomy with nonspecific, control immunoglobulin G antibody (group 2, n = 9) or suturectomy with anti-TGF-β2 antibody (group 3, n = 11). At 10 days of age, a 3 × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slowly resorbing collagen gel mixed with either immunoglobulin G (100 &mgr;g per suture) or anti-TGF-β2 (100 &mgr;g per suture). Three-dimensional computed tomography scan reconstructions of the defects were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histomorphometric analysis. Results: Computed tomography scan data revealed that the suturectomy sites treated with anti-TGF-β2 showed significantly (p < 0.05) greater areas through 84 days of age compared with controls. Histomorphometry also showed that suturectomy sites treated with anti-TGF-β2 had patent suturectomy sites and more fibrous tissue in the defects compared with sites in control rabbits and had significantly (p < 0.001) less new bone area (by approximately 215 percent) in the suturectomy site. Conclusions: These data support the initial hypothesis that interference with TGF-β2 function inhibited postoperative resynostosis in this rabbit model. They also suggest that this biologically based therapy may be a potential surgical adjunct to retard postoperative resynostosis in infants with craniosynostosis.

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.

Metastatic adenocarcinoma of the colon presenting as a mass in the mandible.

Metastatic adenocarcinoma of the colon is a frequently encountered medical situation. Metastasis to the mandible from adenocarcinoma of the colon is very unusual and rarely reported. We report the case of a 73‐year‐old man with metastatic adenocarcinoma to the mandible.

Technical aspects of the recipient operation in hand transplantation

The goal of hand allotransplantation is to achieve graft survival and useful long-term function. To achieve these goals, precise surgical technique is of critical importance. The key surgical steps and sequence of events in hand allotransplantation are similar to major upper extremity replantations, but are modified to accommodate major conceptual differences that exist between the two procedures.

Microsurgical reconstruction for canalicular laceration using Monostent and Mini-Monoka.

Many surgical techniques are available for repairing a lacerated canaliculus, such as, Worst pigtail probing, and monocanalicular or bicanalicular procedures involving silicone intubation. Despite this, controversy still exists regarding the best surgical method in terms of subjective and objective outcomes. We report the experience of microscopic canalicular repair using monocanalicular stents; Monostent (Eagle Vision Inc., Memphis, TN) and Mini-Monoka stents (FCI Ophthalmics, Marshfield Hills, MA) and compare these 2 products. Seventeen cases of canalicular lacerations in 15 consecutive patients underwent microscopic canalicular repair using a monocanalicular procedure with either a Monostent (Eagle Vision Inc.) (5 cases) or a Mini-Monoka stent (FCI Ophthalmics) (12 cases). Microscopic anastomosis of the canalicular mucosa was performed following the placement of a juxta canalicular suture to reduce tension. Subjective and objective flows of repaired lacrimal drainage systems were checked by saline injection using a Healon needle (Advanced Medical Optics, Inc., Santa Ana, CA) and dacryocystogram. Patent lacrimal drainage systems were achieved in 16 of the 17 cases, and mild epiphora was acceptable in 14 patients during follow-up. No cases of spontaneous punctal plug migration, stent displacement, eyeball irritation or inflammation, or granuloma formation were encountered. However, in one case, a Mini-Monoka stent (FCI Ophthalmics) was repeatedly extruded or clogged internally and replaced by Monostent (Eagle Vision Inc.). Although the latter had a larger conduit diameter, it was more flexible and had potentially folded on itself in the lacrimal sac, thus, obstructing flow in this case. Microscopic canalicular reconstruction using a Monostent (Eagle Vision Inc.) or Mini-Monoka stent (FCI Ophthalmics) offers a safe, effective, and straightforward means of acute lacrimal system injury treatment.

Successful composite graft for fingertip amputations using ice-cooling and lipo-prostaglandin E1

In distal fingertip amputations where microanastomosis may not be possible, composite grafting might offer the possibility of maintaining digital length and function using the patients own tissue. Many trials such as ice-cooling, pharmacologic enhancement and hyperbaric oxygenation have been reported to improve the survival rate of the composite graft. Twenty-four cases of unreplantable fingertip amputation were classified as types I to III according to the level of injury. We performed the composite grafting followed by immediate ice-cooling for 2 weeks and intravenous lipo-prostaglandin E(1) (lipo-PGE(1)) injection for 8.8 days each on average. Twenty-two fingertips in 24 patients survived completely with acceptable appearance and sensibility over the 8 month follow-up period. Confirming that therapeutic angiogenesis using ice-cooling and lipo-PGE(1) can increase the survival rate of the composite graft in unreplantable fingertip amputation, we describe the procedures and postoperative care in detail.

Bone morphogenetic proteins: A review for cranial and maxillofacial surgery

Kodi Azari, MD, John S. Doctor, PhD, Bruce A. Doll, DDS, PhD, Jeffrey O. Hollinger, DDS, PhD* Division of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA Bone Tissue Engineering Center, Carnegie Mellon University, 125 Smith Hall, 5000 Forbes Avenue, Pittsburgh, PA 15213, USA Department of Biological Sciences, Duquesne University, Pittsburgh, PA, USA School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

Cost comparison of open fasciectomy versus percutaneous needle aponeurotomy for treatment of Dupuytren contracture.

BackgroundMany surgical options exist for the treatment of Dupuytren contracture. Little has been written regarding their financial implications. The purpose of this study was to compare the immediate direct costs of open fasciectomy to percutaneous needle aponeurotomy (NA) for the surgical treatment of Dupuytren contracture. Materials and MethodsA retrospective review was performed comparing patients treated with open fasciectomy (group 1) to patients treated with percutaneous NA (group 2) for the treatment of Dupuytren disease from 2008 to 2010. Financial and medical records were reviewed. Direct cost of treatment was calculated from hospital billing records, including surgical, anesthesia, and facility fees. Statistical analysis was performed using unpaired t test. ResultsTwenty-four patients received open segmental palmar and/or digital fasciectomy (group 1). Average preoperative metacarpophalangeal joint flexion contracture was 30 degrees, and proximal interphalangeal joint flexion contracture was 42 degrees. Group 2 consisted of 24 patients. Average preoperative metacarpophalangeal flexion contracture was 31 degrees, and proximal interphalangeal flexion contracture was 27 degrees. Mean cost for group 1 was