Vu T. Nguyen

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.

Comparison of biodegradable conduits within aged rat sciatic nerve defects.

Background: Considering that little is known about the peripheral nerve regenerative capacity of elderly patients, the authors studied nerve regenerative capacity in aged rats and compared the effect of three synthetic nerve guides with different material characteristics and porosity. The authors hypothesized that the use of a biodegradable composite nerve guide (CultiGuides) would promote nerve regeneration and functional recovery in a manner similar to treatment with autografts or U.S. Food and Drug Administration–approved polyglycolic acid Neurotubes in an aged rat sciatic nerve defect model. Methods: Aged Sprague-Dawley rats (11 months old) underwent a 1-cm sciatic nerve resection in the right leg [group 1, control (contralateral leg samples), n = 10; group 2, negative (nerve gap defect), n = 6; group 3, autograft, n = 10; group 4, polycaprolactone, n = 10; group 5, CultiGuides, n = 10; and group 6, Neurotube, n = 10]. Results: After 12 weeks, the negative group did not demonstrate any nerve regeneration. In the regenerated and distal nerve, all treated groups had increased myelinated areas compared with the negative control. In the regenerated nerve, there was a significant increase in myelination in the Neurotube group compared with the polycaprolactone group (p < 0.001). However, in the distal nerve, there were no differences among the treatment groups. Walking track analyses and gastrocnemius muscle weight ratios were not different among treatment groups 3 through 6. Conclusions: The results showed differences in myelination; Neurotubes promoted the highest degree of myelination (p < 0.001) as compared with all groups. The authors found no improvement in function of the repaired nerve as measured by percentage of autotomy, the sciatic function index, and gastrocnemius muscle weight. No group was able to recover function in this aged model.

Prolongation of composite tissue allograft survival by immature recipient dendritic cells pulsed with donor antigen and transient low-dose immunosuppression.

Background: Composite tissue allograft transplantation is limited by risks of long-term immunosuppression. The authors investigated whether short-term immunosuppression combined with recipient immature dendritic cells pulsed with donor antigens promotes composite tissue allograft survival. Methods: Orthotopic hind-limb transplants were performed (day 0) from Wistar-Furth (RT1u) to Lewis (RT1l) rats. Recipient dendritic cells were propagated from bone marrow with granulocyte-macrophage colony-stimulating factor (bone marrow–derived dendritic cells) and pulsed with or without donor splenic cell lysate. Recipients were as follows: group I, control; group II, cyclosporine (10 mg/kg/day, days 0 through 6, intraperitoneally); group III, antilymphocyte serum plus cyclosporine (days −4 and +1, intraperitoneally); and groups IV and V, cyclosporine plus antilymphocyte serum, combined with 7 × 106 untreated or donor cell lysate-pulsed bone marrow–derived dendritic cells (days +7 and +14, intravenously), respectively. Epidermolysis/desquamation of donor skin defined rejection. Mixed leukocyte reaction determined recipient T-cell reactivity to donor. Tissue samples were obtained at 3 weeks and on the day of rejection. Groups comprised six or seven rats. Results: Donor alloantigen-pulsed bone marrow–derived dendritic cells (group V) significantly prolonged median composite tissue allograft survival time (32.0 days) compared with groups II (18.0 days, p = 0.0012), III (22.5 days, p = 0.0043), and IV (26.5 days, p = 0.0043). Splenic T cells in group V exhibited hyporesponsiveness to donor alloantigen in mixed leukocyte reaction. Interestingly, the graft muscle component in the bone marrow–derived dendritic cell–treated group (group V) showed significant reduction in mononuclear cell infiltration relative to group II (p = 0.0317). Conclusions: Donor alloantigen–pulsed recipient bone marrow–derived dendritic cells combined with transient T-cell–directed immunosuppression significantly prolonged composite tissue allograft survival across a full major histocompatibility complex barrier. This may represent the basis for a novel, clinically applicable strategy to promote composite tissue allograft survival with reduced systemic immunosuppression.

Time- versus Competency-Based Residency Training.

Summary: Graduate medical education is at the brink of a paradigm shift in educating the next generation of physicians. Over 100 years ago, the Flexner report helped usher in the Halstedian residency, based on timed exposure and knowledge assessment as the cornerstones of medical education. The addition of operative case logs and respective board examinations to the current model of surgical education has served to establish practice minimums; however, they do not provide any assessment of actual operative capability or clinical competence. Although these facets have been tempered over time, one could argue that they currently exist only as surrogates for the true goal of all graduate medical education: the development of competent, graduating physicians, capable of independent and ethical practice. There now exists a growing body of evidence that competency-based medical education is this century’s Flexnerian revolution. By the objective, subjective, and global assessment of competence, it is thought that we can more effectively and efficiently educate our trainees, provide much needed accountability to our individual patients and to the public as a whole, and establish a lasting model of self-motivated, lifelong learning.

A National Curriculum of Fundamental Skills for Plastic Surgery Residency: Report of the Inaugural ACAPS Boot Camp.

Background The Inaugural American Council of Academic Plastic Surgeons Plastic Surgery Boot Camp program was developed in response to ongoing changes in graduate medical education. The Boot Camp is a hands-on, practicum-based, 3-day course to introduce core concepts in plastic surgery for new plastic surgery residents (in both integrated and independent tracks). Methods The course was held in Pittsburgh in July to August 2015. There were 43 attendees (35 integrated/8 independent) representing 22 residency programs across 15 states. Faculty was composed of 8 local personnel and 5 visiting. Lecture topics and practical sessions covered the full spectrum of plastic surgery. All trainees completed an online survey evaluation both during the course and at 6 months. Results Participant responses were overwhelmingly positive. A total of 72% of respondents rated the Boot Camp ≥ 8 on a 1 to 10 scale (10 is excellent) for the overall course rating; 79% of respondents agreed or strongly agreed with the statement that the simulation scenarios were realistic; and 75% of participants agreed or strongly agreed with the statement that they found simulation-based training to be a valuable way to teach this material. Respondents reported an increase in comfort and confidence across topics after attending the Boot Camp at both 0- and 6-month time points. Instructors received positive evaluations across all topics. Conclusions This successful inaugural course serves as a benchmark for development of a logistical blueprint, business plan, and curriculum for a proposed expansion to regional centers, to potentially encompass all incoming residents in plastic surgery.

Development of a reliable model of total abdominal wall transplantation

Background: Among the most common complications associated with abdominal organ transplantation are issues with abdominal wall closure. This difficulty, along with the recent rise in the use of vascularized composite allotransplantation, has led surgeons to the notion of abdominal wall transplantation. Methods: The authors have developed a novel surgical model for a full-thickness total abdominal wall transplant based on a unilateral pedicle between fully major histocompatibility complex–mismatched rat strains. An established cuff technique was used to anastomose the donor’s common iliac vessels to the recipient’s femoral vessels. Three groups (n = 6 per group) received FK506 monotherapy, 0.25, 0.50, or 0.75 mg/kg per day. The transplants were assessed daily for evidence of rejection by visual inspection. Hematoxylin and eosin skin biopsies and fluorescence-activated cell sorting analysis of the recipients’ peripheral blood were performed. Results: No signs of rejection were observed in the animals receiving FK506, 0.50 or 0.75 mg/kg per day. Those receiving 0.25 mg/kg per day, however, displayed a mixed rejection response. Flow cytometric analysis did not show evidence of donor-specific chimerism. Conclusions: A full-thickness abdominal wall graft based on a unilateral pedicle is a technically feasible and reliable small-animal surgical model. The use of greater than or equal to 0.50 mg/kg per day FK506 results in 100 percent graft survival. Future plans are to use this model to investigate the immunologic interaction of a concomitant solid organ and an abdominal wall allograft, as would likely occur in the clinical situation.

The ACAPS Plastic Surgery Boot Camp Program: Evaluation of the University of Pittsburgh 3-year Experience

BACKGROUND The American Council of Academic Plastic Surgeons sponsored Plastic Surgery Boot Camp program was developed in response to ongoing changes in graduate medical education. The purpose of this new program was to facilitate the transition of both Integrated and Independent residents into Plastic Surgery training, as current trainees are required to rapidly assimilate knowledge and gain clinical skills to which they have had limited and/or inconsistent exposure during their prior education. The Boot Camp program was introduced in July 2015 in Pittsburgh, PA, and has subsequently expanded to 4 regional sites across the United States due to the use of standardized presentations, increased practical sessions, and streamlined evaluations. The aim of this study was to evaluate the Pittsburgh Plastic Surgery Boot Camp experience over the past 3 years and its impact on participant performance.

Craniofacial Surgery Fellowship Selection Criteria: A National Program Director Survey

Background: Candidate characteristics for craniofacial fellowship training still remain unknown, as no data are available in the literature. This study aims to provide information on the criteria that are used to select and rank applicants for the craniofacial surgery fellowship match. Method: A 38-question survey was sent in April 2015 to all craniofacial surgery fellowship program directors (n = 29) involved in the US match using QuestionPro Survey Software. The survey investigated factors used for selection of applicants, including medical school, residency training, research experience, fellowship interview, and candidate characteristics. A 5-point Likert scale was used to grade 33 factors from “not at all important” (1) to “essential in making my decision” (5); or for 5 controversial factors from “very negative impact” (1) to “very positive impact in making my decision” (5). Results: A total of 62% (18 out of 29) of responses were received from craniofacial surgery program directors. The most important factors were professionalism and ethics (4.7 ± 0.5), perceived commitment to craniofacial surgery (4.6 ± 0.8), interactions with faculty and staff (4.5 ± 0.5), interpersonal skills (4.5 ± 0.5), and overall interview performance (4.4 ± 0.6). Factors that have a negative impact on the selection process include graduation from a nonplastic surgery residency program (1.9 ± 0.7) or a non-US plastic surgery residency program (2.2 ± 0.6), and visa requirement (2.2 ± 0.5). Conclusion: This study provides data on craniofacial surgery program directors’ perception on the criteria important for fellowship applicant selection. It is our hope that program directors, residency programs, and applicants find this data useful as they prepare for the craniofacial fellowship match.

Hand Surgery Fellowship Selection Criteria: A National Fellowship Director Survey

Background Candidate characteristics for hand surgery fellowship training remains unknown, as very little data is available in the literature. This study aims to provide information on the criteria that are employed to select candidates for the hand surgery fellowship match. Methods A 38-question survey was sent in April 2015 to all Accreditation Council for Graduate Medical Education recognized hand surgery fellowship program directors (n=81) involved in the U.S. match. The survey investigated factors used for the selection of applicants, including medical school, residency training, research experience, fellowship interview, and candidate characteristics. A 5-point Likert scale was used to grade 33 factors from “not at all important” (1) to “essential in making my decision” (5); or for five controversial factors from “very negative impact” (1) to “very positive impact in making my decision” (5). Results A total of 52% (42 out of 81) of responses were received from hand surgery fellowship program directors. The most important influential factors were interactions with faculty during interview and visit (4.6±0.6), interpersonal skills (4.6±0.5), overall interview performance in the selection process (4.6±0.6), professionalism and ethics (4.6±0.7), and letters of recommendation from hand surgeons (4.5±0.7). Factors that have a negative impact on the selection process include visa requirement (2.1±1.2), graduate of non-plastic surgery residency program (2.4±1.3), and graduate of a foreign medical school (2.4±1.1). Conclusions This study provides data on hand surgery fellowship directors’ perception on the criteria important for fellowship applicant selection, and showed that interview-related criteria and letters of recommendation are the important factors.

Role of Components Separation in War-Related Pediatric Abdominal Trauma

INTRODUCTION: Trauma and reconstruction surgeons in the deployed military theater are often exposed to devastating and signifi cant pediatric war-related injuries.1 While extremity and craniofacial injuries are important considerations in the care of these children, the associated abdominal injuries secondary to penetrating ballistics and blast exposure can be immediately life-threatening, and careful management of such abdominal injuries are critical in the impact of survival for these children. The purpose of this review is to report our collective experience in managing pediatric abdominal trauma within the austere, battlefi eld environment with careful considerations to lessons learned during the last decade of war-related pediatric trauma.