Faculty Bibliography

Background/UNASSIGNED:Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. Methods/UNASSIGNED:Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments. MHC-I surface expression and knockdown duration were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and natural killer-mediated EC lysis were measured. Using an established VCA rat model, allografts were perfused ex vivo with siMHC-I before transplantation. Allografts were analyzed for MHC-I expression and clinical/histologic evidence of rejection. Results/UNASSIGNED:< 0.05). Conclusions/UNASSIGNED:Ex vivo siMHC-I engineering can effectively modify allografts and significantly prolong rejection-free allograft survival. This novel approach may help reduce future systemic immunosuppression requirements in VCA recipients.

BACKGROUND:Considering that muscle has higher metabolic demand than fasciocutaneous tissue and can be more difficult to monitor clinically, the authors compared take-back salvage rates between fasciocutaneous and muscle free flaps for lower extremity trauma reconstruction. METHODS:The authors conducted a retrospective review of 806 free flaps (1979 to 2016); 481 soft-tissue flaps performed for below-knee trauma met inclusion criteria. Primary outcome measures were perioperative complications, specifically, take-backs and flap salvage rates. Univariate and multivariate regression analysis was performed where appropriate. RESULTS:Take-backs occurred in 71 flaps (muscle, n = 44; fasciocutaneous, n = 27) at an average of 3.7 ± 5.4 days postoperatively. Indications were venous (48 percent), arterial (31 percent), unknown (10 percent), and hematoma (10 percent). Overall outcomes were complete salvage (37 percent), partial failure (25 percent), and total failure (38 percent). Take-backs occurring within 48 hours postoperatively correlated with higher salvage rates (p = 0.022). Fasciocutaneous flaps demonstrated increased take-back rates compared with muscle flaps (p = 0.005) that more frequently occurred within 48 hours postoperatively (relative risk, 13.2; p = 0.012). Fasciocutaneous flaps were successfully salvaged more often than muscle-based flaps (p < 0.001). Multivariable regression strongly demonstrated higher risk of take-back failure for muscle flaps (relative risk, 9.42; p = 0.001), despite higher take-back rates among fasciocutaneous flaps (relative risk, 2.28; p = 0.004). CONCLUSIONS:Compared with muscle-based flaps, fasciocutaneous flaps demonstrated earlier and more frequent take-backs for suspected vascular compromise, with higher successful take-back salvage rates. Furthermore, muscle flaps with skin paddles also demonstrated better salvage outcomes than those without. These findings may reflect a combination of lower metabolic demand and easier visual recognition of vascular compromise in fasciocutaneous tissue. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, III.

BACKGROUND: Wide variations in fat graft survival have been reported. The authors hypothesize that treating the adipose tissue on Telfa gauze creates a processed lipoaspirate with a more functional adipokine profile that improves fat graft survival. METHODS: Suction-assisted lipoaspirate was harvested from humans and was either processed by centrifugation, rolled on Telfa gauze, or left unprocessed. Progenitor cell populations were quantified and characterized by flow cytometry. Glycerol-3-phosphate dehydrogenase assay was used to measure the functional adipocytes. The lipoaspirates were grafted into (n = 45) wild-type mice and harvested to assess fat graft persistence. Vascular endothelial growth factor and platelet-derived growth factor-BB secretions were measured by enzyme-linked immunosorbent assay technique. RESULTS: Centrifuged lipoaspirate had a greater number of progenitor cells per gram of tissue than Telfa-processed and unprocessed lipoaspirate. However, Telfa-processed lipoaspirate had a greater number of functional adipocytes (0.104 U/ml) than centrifuged (0.080 U/ml) and unprocessed lipoaspirate (0.083 U/ml) on glycerol-3-phosphate dehydrogenase assay (p < 0.05). After 10 weeks of grafting, it had greater fat graft persistence (70.9 +/- 6.2 percent) than centrifuged (56.7 +/- 5.5 percent) and unprocessed lipoaspirate (42.2 +/- 2.7 percent) (p < 0.05). It also maintained a greater secretion of vascular endothelial growth factor and platelet-derived growth factor-BB at weeks 1 and 2 than centrifuged and unprocessed lipoaspirate. Furthermore, CD31 staining demonstrated an increase in vascular density of the Telfa-processed lipoaspirate at week 2 compared with the centrifuged lipoaspirate (37 +/- 1 percent and 14 +/- 4 percent per high-power field; p < 0.05). CONCLUSIONS: Lipoaspirate processing technique has a significant impact on fat graft survival rate. Increasing the number of functional adipocytes by processing the fat on Telfa gauze may augment the secretion of angiogenic and mitogenic adipokines within the graft, thereby improving its survivability. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

BACKGROUND: Open tibia fractures are commonly stratified by the Gustilo classification, an orthopedic grading system that does not incorporate the presence of arterial injury when limb perfusion is intact. In the authors' experience, however, the presence of arterial injury appears to negatively impact microsurgical outcomes. METHODS: In a retrospective review of 806 lower extremity reconstructions between 1979 and 2016, 361 soft-tissue flaps performed for Gustilo type IIIB/C coverage met inclusion criteria. Patient demographics, flap characteristics, and outcomes were analyzed. RESULTS: Most patients suffered type IIIB [n = 332 (91.9 percent)] injuries; 29 (8.0 percent) had type IIIC injuries. Preoperative angiography [n = 243 (67.3 percent)] demonstrated arterial injury in 126 (51.8 percent); 27 arterial injuries were identified intraoperatively; and the overall incidence was 153 of 361 (42.4 percent). Complications occurred in 143 flaps (39.6 percent) and included 37 partial losses (10.2 percent) and 31 total losses (8.6 percent). Injured recipient arteries [n = 62 (17.2 percent)] had more complications (p = 0.004); specifically, increased take-backs (p = 0.009). Decreasing vessel runoff increased the risk of complications (p = 0.025), take-backs (p = 0.007), and total flap failures (p = 0.024) accordingly. Specifically, among grade IIIB injuries, controlling for age, sex, time since injury, and vein number, single-vessel runoff was associated with higher rates of complications (relative risk, 3.07; p = 0.012), take-backs (relative risk, 3.43; p = 0.013), and total flap failures (relative risk, 4.80; p = 0.010) compared with three-vessel runoff. CONCLUSIONS: Arterial injury was common among Gustilo type IIIB patients and correlated with increased reconstructive complications. Nonischemic arterial injury appears to negatively impact reconstructive outcomes and should be accounted for when considering free tissue transfer for lower extremity salvage. The authors propose a 3-2-1 modification of the Gustilo type IIIB classification to incorporate degree of arterial injury, as it appears to add prognostic value and certainly influences the reconstructive plan. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Therapeutics utilizing siRNA are currently limited by the availability of safe and effective delivery systems. Cutaneous diseases, specifically ones with significant genetic components are ideal candidates for topical siRNA based therapy but the anatomical structure of skin presents a considerable hurdle. Here, we optimized a novel liposome and protein hybrid nanoparticle delivery system for the topical treatment of diabetic wounds with severe oxidative stress. We utilized a cationic lipid nanoparticle (CLN) composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the edge activator sodium cholate (NaChol), in a 6:1 ratio of DOTAP:NaChol (DNC). Addition of a cationic engineered supercharged coiled-coil protein (CSP) in a 10:1:1 ratio of DNC:CSP:siRNA produced a stable lipoproteoplex (LPP) nanoparticle, with optimal siRNA complexation, minimal cytotoxicity, and increased transfection efficacy. In a humanized murine diabetic wound healing model, our optimized LPP formulation successfully delivered siRNA targeted against Keap1, key repressor of Nrf2 which is a central regulator of redox mechanisms. Application of LPP complexing siKeap1 restored Nrf2 antioxidant function, accelerated diabetic tissue regeneration, and augmented reduction-oxidation homeostasis in the wound environment. Our topical LPP delivery system can readily be translated into clinical use for the treatment of diabetic wounds and can be extended to other cutaneous diseases with genetic components.

BACKGROUND: Patients undergoing implant-based reconstruction in the setting of postmastectomy radiation therapy suffer from increased complications and inferior outcomes compared with those not irradiated, but advances in radiation delivery have allowed for more nuanced therapy. The authors investigated whether these advances impact patient outcomes in implant-based breast reconstruction. METHODS: Retrospective chart review identified all implant-based reconstructions performed at a single institution from November of 2010 to November of 2013. These data were cross-referenced with a registry of patients undergoing breast irradiation. Patient demographics, treatment characteristics, and outcomes were analyzed. RESULTS: Three hundred twenty-six patients (533 reconstructions) were not irradiated, whereas 83 patients (125 reconstructions) received radiation therapy; mean follow-up was 24.7 months versus 26.0 months (p = 0.49). Overall complication rates were higher in the irradiated group (35.2 percent versus 14.4 percent; p < 0.01). Increased maximum radiation doses to the skin were associated with complications (maximum dose to skin, p = 0.05; maximum dose to 1 cc of skin, p = 0.01). Different treatment modalities (e.g., three-dimensional conformal, intensity-modulated, field-in-field, and hybrid techniques) did not impact complication rates. Prone versus supine positioning significantly decreased the maximum skin dose (58.5 Gy versus 61.7 Gy; p = 0.05), although this did not translate to significantly decreased complication rates in analysis of prone versus supine positioning. CONCLUSIONS: As radiation techniques evolve, the maximum dose to skin should be given consideration similar to that for heart and lung dosing, to optimize reconstructive outcomes. Prone positioning significantly decreases the maximum skin dose and trends toward significance in reducing reconstructive complications. With continued study, this may become clinically important. Interdepartmental studies such as this one ensure quality of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

BACKGROUND: The ethical practice of medicine has always been of utmost importance, and plastic surgery is no exception. The literature is devoid of information on the teaching of ethics and professionalism in plastic surgery. In light of this, a survey was sent to ascertain the status of ethics training in plastic surgery residencies. METHODS: A 21-question survey was sent from the American Council of Academic Plastic Surgeons meeting to 180 plastic surgery program directors and coordinators via email. Survey questions inquired about practice environment, number of residents, presence of a formal ethics training program, among others. Binary regression was used to determine if any relationships existed between categorical variables, and Poisson linear regression was used to assess relationships between continuous variables. Statistical significance was set at a P value of 0.05. RESULTS: A total of 104 members responded to the survey (58% response rate). Sixty-three percent were program directors, and most (89%) practiced in academic settings. Sixty-two percent in academics reported having a formal training program, and 60% in private practice reported having one. Only 40% of programs with fewer than 10 residents had ethics training, whereas 78% of programs with more than 20 residents did. The odds of having a training program were slightly higher (odds ratio, 1.1) with more residents (P = 0.17). CONCLUSIONS: Despite the lack of information in the literature, formal ethics and professionalism training does exist in many plastic surgery residencies, although barriers to implementation do exist. Plastic surgery leadership should be involved in the development of standardized curricula to help overcome these barriers.

Background Higher body mass index (BMI) has been shown to increase postoperative complications in autologous breast reconstruction. However, the correlation with flap weight is unknown. Here, we explore the relationship of flap weights and complication rates in patients undergoing microvascular breast reconstruction. Methods Retrospective chart review identified all patients undergoing microvascular breast reconstruction with abdominally based flaps at a single institution between November 2007 and April 2013. Breasts with documented flap weight and 1-year follow-up were included. Patients undergoing stacked deep inferior epigastric perforator flaps were excluded. Breasts were divided into quartiles based on flap weight and examined by demographics, surgical characteristics, complications, and revisions. Results A total of 130 patients undergoing 225 flaps were identified. Patients had a mean age of 50.4 years, mean BMI of 27.1 kg/m2, and mean flap weight of 638.4 g (range: 70-1640 g). Flap weight and BMI were directly correlated. Flaps were divided into weight-based quartiles: first (70-396 g), second (397-615 g), third (616-870 g), and fourth (871-1640 g). There were no associations between flap weight and incidences of venous thrombosis, arterial thrombosis, hematoma, flap loss, fat necrosis, or donor site hernia. However, increased flap weight was associated with increased rate of donor site wound healing problems in both univariate and multivariate analysis. Conclusions Increased flap weight is not associated with added flap complications among patients undergoing microvascular breast reconstruction, however, patients with flaps of 667.5 g or more are more likely to have donor site healing problems. The success and evidence contrary to previous studies may be attributed to surgeon intraoperative flap choice.

In select patients with advanced disease resulting in large composite tissue defects, consideration is often given to multiple flap reconstruction. The authors propose an alternative option. Using virtual surgical planning the authors demonstrate how modest sacrifice in projection translates into a substantial decrease in the volume and surface area of soft tissue needed, in turn maximizing soft tissue coverage with a single fibula free flap. The authors used 3-dimensional virtual surgery to simulate angle-to-angle reconstructions using free fibula flaps. The reference 3-segment reconstruction was done using symphyseal projection to the plane perpendicular to the anterior nasal spine, a customary landmark. Additional simulations were then performed using recessed projections 0.5 mm, 1 cm, 1.5 cm, and 2 cm posterior to anterior nasal spine plane. Program analytics were used to calculate the surface area and volume of the floor of mouth. With projection recessed by 1 cm, surface area decreased 22% to 14 cm. With projection recessed by 2 cm, surface area decreased 44% to 10 cm. With a 3-segment construct converted to a 2-segment construct, surface area decreased 22% to 14 cm. This demonstrates for the first time an official analysis of an intraoperative modification that sacrifices little and gains a lot. Ultimately, 1 compound flap can be used in extensive reconstructions with increased confidence that it will not be overly stressed.