Damon S. Cooney

Donor age negatively affects the immunoregulatory properties of both adipose and bone marrow derived mesenchymal stem cells.

PURPOSE Age negatively impacts the biologic features of mesenchymal stem cells (MSCs), including decreased expansion kinetics and differentiation potential. Clinically, donor-age may be within a wide spectrum; therefore, investigation of the role of donors age on immunoregulatory potential is of critical importance to translate stem cell therapies from bench to bedside. METHODS Adipose and bone marrow derived MSCs (ASCs and BMSCs) were isolated in parallel from Lewis and Brown Norway rats of young (less than 4-week old) and senior groups (older than 15-month). The presentation of cells and time required for growth to 90% confluence was recorded. FACS sorting based on the expression of CD90 and CD29 double positive and CD45 CD11 double negative quantified the proportions of MSCs. After expansion, ASCs and BMSCs from different age groups were co-cultured in mixed lymphocyte reaction (MLR; Lewis vs. Brown Norway) assays. The suppression of CD3(+)CD4(+) and CD3(+)CD8(+) T cell populations by different sources of MSCs were compared. RESULTS The kinetics of cell growth was slower in old animals (17.3±2days) compared with young animals (8.8±3days), and cell morphology was irregular and enlarged in the senior groups. The yield of MSCs by FACS sorting was significantly higher in young groups compared to senior groups (p<0.02). With regard to immunoregulatory potential, senior ASCs failed to induce any CD3(+)CD4(+) T cell suppression (p>0.05). In addition, young BMSCs-induced suppression was more prominent than seniors (p<0.05). CONCLUSIONS Donor age should be taken into consideration when using recipient MSC of either bone marrow or adipose origin in clinical applications.

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.

Abdominally based free flap planning in breast reconstruction with computed tomographic angiography: systematic review and meta-analysis.

Background: Computed tomographic angiography is often used for preoperative mapping. The authors aimed to systematically assess breast reconstruction outcomes after abdominally based free flaps planned with preoperative computed tomographic angiography versus Doppler ultrasonography. Methods: A search of the PubMed, EMBASE, and Scopus databases and an additional hand-search of relevant articles until June of 2012 rendered 442 English-language citations. Three authors independently reviewed these citations and included all the studies comparing preoperative computed tomographic angiography versus Doppler ultrasonography with regard to short-term postoperative outcomes and operative times. A meta-analysis was performed to evaluate the incidence of flap-related complications (seven studies), donor-site morbidity (four studies), and operative times (five studies) between preoperative computed tomographic angiography and Doppler ultrasonography. A pooled relative risk was calculated using a random-effect model to compare complication rates between the computed tomographic angiography and Doppler ultrasonography groups. Results: A total of 13 studies met inclusion criteria. Preoperative computed tomographic angiography was associated with significantly fewer flap-related complications (relative risk, 0.87; 95 percent CI, 0.78 to 0.97), reduced donor-site morbidity (relative risk, 0.84; 95 percent CI, 0.76 to 0.94), and shorter reconstruction operative time by 87.7 minutes (mean difference, 87.7 minutes; 95 percent CI, 78.3 to 97.1 minutes). Conclusions: The use of preoperative computed tomographic angiography reduces the operative time, postoperative flap-related complications, and donor-site morbidity compared with Doppler ultrasonography. Preoperative computed tomographic angiography has the potential to reduce operative cost and increase efficiency in the operating room. Thus, preoperative mapping by computed tomographic angiography should be strongly considered for abdominally based free flap breast reconstruction.

Current concepts and systematic review of vascularized composite allotransplantation of the abdominal wall

Abdominal wall vascularized composite allotransplantation (AW‐VCA) is a rarely utilized technique for large composite abdominal wall defects. The goal of this article is to systematically review the literature and current concepts of AW‐VCA, outline the challenges ahead, and provide an outlook for the future.

Mesenchymal Stem Cells Enhance Nerve Regeneration in a Rat Sciatic Nerve Repair and Hindlimb Transplant Model

This study investigates the efficacy of local and intravenous mesenchymal stem cell (MSC) administration to augment neuroregeneration in both a sciatic nerve cut-and-repair and rat hindlimb transplant model. Bone marrow-derived MSCs were harvested and purified from Brown-Norway (BN) rats. Sciatic nerve transections and repairs were performed in three groups of Lewis (LEW) rats: negative controls (n = 4), local MSCs (epineural) injection (n = 4), and systemic MSCs (intravenous) injection (n = 4). Syngeneic (LEW-LEW) (n = 4) and allogeneic (BN-LEW) (n = 4) hindlimb transplants were performed and assessed for neuroregeneration after local or systemic MSC treatment. Rats undergoing sciatic nerve cut-and-repair and treated with either local or systemic injection of MSCs had significant improvement in the speed of recovery of compound muscle action potential amplitudes and axon counts when compared with negative controls. Similarly, rats undergoing allogeneic hindlimb transplants treated with local injection of MSCs exhibited significantly increased axon counts. Similarly, systemic MSC treatment resulted in improved nerve regeneration following allogeneic hindlimb transplants. Systemic administration had a more pronounced effect on electromotor recovery while local injection was more effective at increasing fiber counts, suggesting different targets of action. Local and systemic MSC injections significantly improve the pace and degree of nerve regeneration after nerve injury and hindlimb transplantation.

Increased cutaneous nerve fibers in female specimens.

Background: The control of pain is critical to performing surgery. All surgical procedures cause some degree of pain, and the ability to minimize pain often affects a patients perception of surgical outcome. Although the development of surgery was boosted by the advent of anesthesia, inadequate pain control continues to plague modern medicine. The mechanism of pain induction is an important area of research in the health care industry. To date, few studies have demonstrated increased perception of pain and lower tolerance for pain in female patients when compared with male patients. The authors hypothesized about whether these differences were related to increased density of nerve fibers in female as compared with male patients. Methods: The density of nerve fibers at a specific location (the skin directly overlying the infraorbital nerve foramen) was measured to test this hypothesis. Twenty cadaver skin specimens (1 cm2) were harvested, prepared using immunohistochemistry (S-100 polyclonal antibody), and counted using 45× high-powered microscopy. Results: Female specimens (n = 10) demonstrated increased nerve fiber density (34 ± 19 fibers/cm2 skin) when compared with male specimens (n = 10; 17 ± 8 fibers/cm2 skin; p = 0.038). Conclusion: Although preliminary and limited in scope, these findings favor a physical (organic) rather than a psychosocial explanation for more pronounced pain perception in female patients.

Comprehensive Observations of Resident Evolution: A Novel Method for Assessing Procedure-Based Residency Training

Background: Assessment of surgical skills in the operating room remains a challenge. Increasing documentation requirements of the Accreditation Council for Graduate Medical Education are necessitating mechanisms to document trainee competence without hindering operative turnover. The authors created a comprehensive electronic resource to facilitate plastic surgery training program compliance with changes mandated by Next Accreditation System Milestones and the ACGME. Methods: In 2013, the authors implemented the Comprehensive Observations of Resident Evolution, or CORE, a Web-based tool to assess plastic surgery residents. It comprises a rapid electronic assessment of resident operating room performance completed after each surgery; a data dashboard displaying graphical summaries of resident progress by case, Milestone, or current procedural terminology code; and an electronic Milestones tracker (MileMarker), which enables ongoing trainee assessments. Results: From January through October of 2014, 24 residents completed nearly 1300 Operative Entrustability Assessments. Thirty-eight percent of residents reported more immediate feedback regarding operative performance. The assessment demonstrates construct validity, which distinguishes novice residents from experienced residents. Individual case data identify resident-specific operative strengths and weaknesses. Using assessment data, the first two Clinical Competency Committee reviews were 81 percent and 87 percent shorter than Milestones pilot test site reports (average, 11.5 and 8 minutes versus 60 minutes per resident, respectively). Conclusions: Comprehensive Observations of Resident Evolution is capable of capturing operative performance data on all operating room cases by primary current procedural terminology code. It increases immediate attending/trainee feedback and assessment transparency, enables trainee self-monitoring, and informs end-of-rotation reviews, programwide assessments, and tailoring of training to address specific needs. It is a valuable resource for tracking resident progress in real-time while maintaining compliance with evolving ACGME requirements.

Pyoderma Gangrenosum After Breast Surgery: Diagnostic Pearls and Treatment Recommendations Based on a Systematic Literature Review.

BackgroundPyoderma gangrenosum (PG) is a rare cutaneous disorder that poses a diagnostic challenge in the postoperative period. A systematic literature review was performed to determine distinguishing characteristics of PG in the setting of breast surgery that can facilitate timely diagnosis and appropriate treatment. MethodsPubMed, EMBASE, Scopus, and Web of Science databases were systematically searched for articles with cases of PG occurring after breast surgery. Forty-three relevant articles, including 49 case reports, were identified. ResultsPG manifested bilaterally in 30 of 34 cases (88%) in which bilateral surgery was performed. Abdominal wounds were present in 6 of 7 cases in which an abdominal donor site was used for breast reconstruction. Nipples were spared from wound involvement in 33 of 37 cases (89%) in which nipples were present after surgery. Presence of fever was noted in 27 cases (55%) and leukocytosis in 21 cases (43%). A total of 33 patients (67%) underwent wound debridement. Successful medical treatment most commonly involved steroids (41 cases, 84%) and cyclosporine (10 cases, 20%). ConclusionsPertinent clinical features were identified that may aid in timely diagnosis and treatment of PG after breast surgery. Appearance of discrete wounds involving multiple surgical sites that surround but spare the nipples should raise suspicion for PG rather than infection or ischemia, even with concomitant fever and leukocytosis. Wound debridement should be minimized and skin grafting considered only after medical therapy is initiated. Cognizance of these features may enable prompt therapeutic intervention that minimizes morbidity and improves outcomes.

Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury.

Background: Therapies to improve outcomes following peripheral nerve injury are lacking. Prolonged denervation of muscle and Schwann cells contributes to poor outcomes. In this study, the authors assess the effects of growth hormone therapy on axonal regeneration, Schwann cell and muscle maintenance, and end-organ reinnervation in rats. Methods: Male Sprague-Dawley rats underwent sciatic nerve transection and repair and femoral nerve transection without repair and received either daily subcutaneous growth hormone (0.4 mg/day) or no treatment (n = 8 per group). At 5 weeks, the authors assessed axonal regeneration within the sciatic nerve, muscle atrophy within the gastrocnemius muscle, motor endplate reinnervation within the soleus muscle, and Schwann cell proliferation within the denervated distal femoral nerve. Results: Growth hormone–treated animals demonstrated greater percentage increase in body mass (12.2 ± 1.8 versus 8.5 ± 1.5; p = 0.0044), greater number of regenerating myelinated axons (13,876 ± 2036 versus 8645 ± 3279; p = 0.0018) and g-ratio (0.64 ± 0.11 versus 0.51 ± 0.06; p = 0.01), greater percentage reinnervation of motor endplates (75.8 ± 8.7 versus 38.2 ± 22.6; p = 0.0008), and greater muscle myofibril cross-sectional area (731.8 ± 157 &mgr;m versus 545.2 ± 144.3 &mgr;m; p = 0.027). Conclusions: In male rats, growth hormone therapy accelerates axonal regeneration, reduces muscle atrophy, and promotes muscle reinnervation. Growth hormone therapy may also maintain proliferating Schwann cells in the setting of prolonged denervation. These findings suggest potential for improved outcomes with growth hormone therapy after peripheral nerve injuries.

Follicular Anatomy of the Anterior Temporal Hairline and Implications for Rhytidectomy

Background: Incisions made perpendicular to the hair follicles during anterior frontal hairline brow lifts or forehead shortening procedures help produce an inconspicuous forehead scar. The success of this “hidden” incision relies on the anteriorly directed frontal hairline follicles and their growth vector. The authors hypothesized that a similar incision could be made perpendicular to the hair follicles in the temple region during rhytidectomy. A well-designed anterior hairline beveled incision over the temple would allow for improved leverage during soft-tissue repositioning and a concealed hairline incision in the temple region. Methods: Anterior temporal hairline strips 4 cm in length at the level of the lateral canthus were excised from 16 fresh cadavers. Hairline follicles (n = 227) were assessed for direction and angle of growth after appropriate tissue preparation and staining (hematoxylin and eosin). The hair follicle angle was analyzed microscopically as it approached the epidermis. Results: The anterior temporal hairline follicles were oriented at a mean angle with the epidermis of 16 ± 3 degrees anteriorly and inferiorly. Conclusions: The anterior temporal hairline follicles of the scalp are oriented anteriorly and inferiorly with the epidermis, providing the surgical rational for using a beveled hairline incision angled 30 to 45 degrees to the external skin surface to undercut the distal flap. This incision is perpendicular to and transects the temporal hair follicles during rhytidectomy, permitting hair growth through and anterior to the scar. This modified anterior temporal hairline incision reduces visibility of the scar at the hairline for patients in whom scar show and hairstyle versatility are important concerns.