The Evolving Plastic Surgery Applicant: How Far Have We Come in 30 Years?

BACKGROUND: Plastic surgery training has undergone tremendous change and transitioned through many models over the years, including independent, combined, and integrated. This study evaluates how these changes and others have affected plastic surgery applicants' demographics and academic qualifications over the last 30 years. METHODS: Data on applicant demographics and academic qualifications were extracted from multiple sources including the National Resident Matching Program, the American Association of Medical Colleges, and cross-sectional surveys of plastic surgery applicants for the years 1992, 2005, 2011, and 2022. Data were compared using pairwise χ2 goodness of fit tests. RESULTS: The sex distribution of plastic surgery applicants changed significantly over the last 30 years: whereas men predominated in 1992 (86% male vs 14% female), by 2011, the distribution was nearly equal (54% male vs 46% female in both 2011 and 2022, P < 0.001).The racial makeup of applicants also changed over time (P < 0.05). White applicants decreased from 73% in 1992 to 55% in 2011, and 53% in 2022. While there was an increase in Asian (7% to > 17% to > 20%) and other (13% to > 14% to > 21%) applicants over time, whereas the proportion of Black applicants remained stagnant (5% to > 6% to > 8%).Applicants with prior general surgery experience declined precipitously over the years: 96% in 1992, 64% in 2005, 37% in 2011, and 26% in 2022 (P < 0.001). When compared with 1992, Alpha Omega Alpha status increased significantly in 2011 (36% vs 12%, P < 0.05) but did not change considerably in 2005 (22%) and 2022 (23%). Research experience increased dramatically over the years, with the proportion of applicants with at least one publication going from 43% in 1992, to 75% in 2005, to 89% in 2011, and to 99% in 2022 (P < 0.001). Applicant interest in academic plastic surgery did not change considerably over the years at roughly ranging from 30% to 50% of applicants (P = ns). CONCLUSIONS: There has been a shift in the demographics and academic qualifications of plastic surgery applicants over the last 3 decades. Understanding this evolution is critical for reviewing and evaluating the makeup of our specialty, and enacting changes to increase representation where necessary.

The impact of youth-onset type 2 diabetes on postoperative wound healing complications.

Youth-onset type 2 diabetes mellitus is associated with a more rapid decline in ß cells, and earlier onset of medical complications compared to adult-onset diabetes. However, its impact on surgical wounds remains less clear. Therefore, this study aimed to determine whether youth-onset diabetes is a risk factor for wound healing complications in the 30-day postoperative period. To do so, the National Surgical Quality Improvement Program Database years 2012-2019 was analysed. Patients aged 18-24 with non-insulin-dependent diabetes were included. Outcomes assessed included wound infections, wound dehiscence, readmissions, and reoperation. Univariate analysis identified differences between the diabetic and non-diabetic cohorts after which, multivariate logistic regression was employed to control for potential confounding. Analysis included 1589 diabetic and 196,902 non-diabetic patients ages 18-24. The diabetic cohort exhibited a higher proportion of female (83.8% vs. 55.2%, p < 0.001), non-white (22.7% vs. 19.5%, p = 0.001), and Hispanic patients (16.2% vs. 13.6%, p = 0.002). Diabetic patients were less likely to have dirty or contaminated wounds (16.2% vs. 25.2%, p < 0.001); however had increased rates of superficial surgical site infections (SSSIs; 2.0% vs. 0.8%, p < 0.001) and readmission (4.0% vs. 3.0%, p = 0.026). After regression, diabetes remained a significant positive predictor of SSSI (odds ratio: 1.546, p = 0.022); however, it no longer significantly predicted 30-day readmission. Overall, this analysis of a large multicentre surgical outcomes database found that when compared to non-diabetics, youth-onset diabetic patients exhibited a higher proportion of SSSIs in the 30-day postoperative period. These infections were found, despite the diabetic cohort exhibiting lower rates of wound contamination. After controlling for confounding variables, youth-onset diabetes remained a significant predictor of SSSI. Clinically, prevention and treatment of diabetes along with judicious wound care is recommended.

Quantification of Facial Allograft Edema During Acute Rejection: A Software-Based 3-Dimensional Analysis.

BACKGROUND: Acute rejection (AR) is a common complication in facial transplant (FT) patients associated with allograft edema and erythema. Our study aims to demonstrate the feasibility of using software-based 3-dimensional (3D) facial analysis to quantify edema as it resolves during/after AR treatment in an FT patient. METHODS: Our patient is a 23-year-old man who underwent a face and bilateral hand allotransplant in August 2020. The Vectra H1 (Canfield, Fairfield, NJ) portable scanner was used to capture 3D facial images at 8 time points between postoperative day (POD) 392 and 539. The images were analyzed with the Vectra Software using a rejection-free image (POD 539) as a control. RESULTS: Edema increased in the periorbital, lower third, and submandibular regions before AR treatment (POD 392-415). At POD 448, total facial edema was reduced to near baseline values in response to plasmapheresis and thymoglobulin (+156.94 to +28.2 mL). The fastest and most notable response to treatment was seen in the periorbital region, while some edema remained in the submandibular (+19.79 mL) and right lower third (+8.65 mL) regions. On POD 465, after the initial improvement, the edema increased but was resolved with steroid use. Facial edema did not correlate with the histopathological evaluation in our patient. CONCLUSIONS: We demonstrated the feasibility of analyzing 3D facial images to quantify edema during/after AR treatment in an FT patient. Our analysis detected edema changes consistent with AR followed by an improvement after treatment. This technology shows promise for noninvasive monitoring of FT patients.

Predicting postoperative complications following mastectomy in the elderly: Evidence for the 5-factor frailty index.

Understanding the risk factors that contribute to post-mastectomy complications can better inform preoperative discussions. Here, we assess the impact of the 5-Factor Frailty Index Score (mFI-5) in predicting 30-day postoperative complications in patients undergoing mastectomy. A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data base was conducted for patients older than 65 undergoing mastectomy between 2010 and 2015. We assessed each patient's Frailty Index Score using the mFI-5. Primary outcomes included wound complications and overall complications. Multivariate logistic and linear regression analyses were used to determine the ability of the mFI-5 to predict postoperative outcomes. A total of 13,783 patients were analyzed. The rate of wound complications was 3.0%, while the rate of overall complications was 6.0%. An mFI-5 score greater than 2 was an independent risk factor for wound complications and overall complications. Overall, patients undergoing mastectomy with an mFI-5 of 2 or greater experienced higher rates of postoperative complications. The mFI-5 is an accessible tool that can be used to risk-stratify patients undergoing mastectomy and can positively contribute to the informed consent and shared decision-making process.

Hepatic Artery Microvascular Anastomosis in Liver Transplantation: A Systematic Review of the Literature.

BACKGROUND: The operating microscope is used in many centers for microvascular hepatic arterial reconstruction in living as well as deceased donor liver transplantation in adult and pediatric recipients. To date, a systematic review of the literature examining this topic is lacking. METHODS: This systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Three different electronic databases (PubMed, Embase OVID, and Cochrane CENTRAL) were queried. RESULTS: A total of 34 studies were included. The rate of hepatic artery thrombosis (HAT) in noncomparative studies (28) ranged from 0% to 10%, with 8 studies reporting patient deaths resulting from HAT. Within comparative studies, the rate of HAT in patients who underwent arterial reconstruction using the operating microscope ranged from 0% to 5.3%, whereas the rate of HAT in patients who underwent arterial reconstruction using loupe magnification ranged from 0% up to 28.6%, and 2 studies reported patient deaths resulting from HAT. Two comparative studies did not find statistically significant differences between the 2 groups. CONCLUSIONS: Our comprehensive systematic review of the literature seems to suggest that overall, rates of HAT may be lower when the operating microscope is used for hepatic arterial reconstruction in liver transplantation. However, matched comparisons are lacking and surgical teams need to be mindful of the learning curve associated with the use of the operating microscope as compared with loupe magnification, as well as the logistical and time constraints associated with setup of the operating microscope.

Communication Efficiency in a Face Transplant Recipient: Determinants and Therapeutic Implications.

We longitudinally assessed speech intelligibility (percent words correct/pwc), communication efficiency (intelligible words per minute/iwpm), temporal control markers (speech and pause coefficients of variation), and formant frequencies associated with lip motion in a 41-year-old face transplant recipient. Pwc and iwpm at 13 months post-transplantation were both higher than preoperative values. Multivariate regression demonstrated that temporal markers and all formant frequencies associated with lip motion were significant predictors (P < 0.05) of communication efficiency, highlighting the interplay of these variables in generating intelligible and effective speech. These findings can guide us in developing personalized rehabilitative approaches in face transplant recipients for optimal speech outcomes.

Risk Factors for Wound Complications Following Transmetatarsal Amputation in Patients With Diabetes.

BACKGROUND: The goal of our study was to evaluate risk factors for wound complications in patients with diabetes mellitus undergoing transmetatarsal amputations (TMAs), given the paucity of research on this subject. MATERIALS AND METHODS: We used the American College of Surgeons National Surgical Quality Improvement Program database. In this retrospective analysis, all surgical cases with a primary Current Procedural Terminology code for TMA from 2009 to 2015 were reviewed. RESULTS: A total of 2316 patients with diabetes mellitus who underwent TMA were identified. Overall wound complications occurred in 276 (11.9%) of patients. Univariate analysis showed that the operative time was significantly longer in patients who developed complications than those who did not (58.3 ± 39.5 versus 50.6 ± 39.4; P = 0.003). Furthermore, the rate of obesity was significantly higher among patients who developed wound complications than those who did not (47.1% versus 41.5%; P = 0.04). Multivariate analysis demonstrated that a longer operative time (odds ratio = 1.02; 95% confidence interval: 1.01-1.04; P = 0.01) and obesity (odds ratio = 1.60; 95% confidence interval: 1.06-2.40; P = 0.03) were independent risk factors for wound complications in our cohort. CONCLUSIONS: These findings emphasize the importance of having heightened clinical vigilance in obese patients with diabetes mellitus undergoing this procedure, close postoperative follow-up, and limiting operative time when possible.

Impact of Diabetes on 30-Day Complications in Mastectomy and Implant-Based Breast Reconstruction.

BACKGROUND: Diabetic patients are known to be at increased risk of postoperative complications after multiple types of surgery. However, conflicting evidence exists regarding the association between diabetes and wound complications in mastectomy and breast reconstruction. This study evaluates the impact of diabetes on surgical outcomes after mastectomy procedures and implant-based breast reconstruction. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database review from 2010 to 2015 identified patients undergoing total, partial, or subcutaneous mastectomy, as well as immediate or delayed implant reconstruction. Primary outcomes included postoperative wound complications and implant failure. Preoperative variables and outcomes were compared between diabetic and nondiabetic patients. Multivariate regression was used to control for confounders. RESULTS: The following groups were identified: partial (n = 52,583), total (n = 41,540), and subcutaneous mastectomy (n = 3145), as well as immediate (n = 4663) and delayed (n = 4279) implant reconstruction. Diabetes was associated with higher rates of superficial incisional surgical site infection (SSI) in partial mastectomy (odds ratio [OR] = 8.66; P = 0.03). Diabetes was also associated with higher rates of deep incisional SSI (OR = 1.61; P = 0.01) in subcutaneous mastectomy and both superficial (OR = 1.56; P = 0.04) and deep incisional SSI (OR = 2.07; P = 0.04) in total mastectomy. Diabetes was not associated with any wound complications in immediate reconstruction but was associated with higher rates of superficial incisional SSI (OR = 17.46; P < 0.001) in the delayed reconstruction group. There was no association with implant failure in either group. CONCLUSIONS: Evaluation of the largest national cohort of mastectomy and implant reconstructive procedures suggests that diabetic patients are at significantly increased risk of 30-d postoperative infectious wound complications but present no difference in rates of early implant failure.

Diabetes is associated with an increased risk of wound complications and readmission in patients with surgically managed pressure ulcers.

The effect of diabetes on postoperative outcomes following surgical management of pressure ulcers is poorly defined despite evidence showing that patients with diabetes are at increased risk for developing pressure ulcers, as well as postoperative wound complications including delayed healing and infection. This study aimed to examine the impact of diabetes on postoperative outcomes following surgical management of pressure ulcers using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. In this retrospective analysis all CPT codes with ICD-9 diagnoses of pressure ulcers were reviewed. A total of 3,274 patients who underwent surgical management of pressure ulcers were identified, of which 1,040 (31.8%) had diabetes. Overall primary outcomes showed rates of superficial and deep incisional surgical site infection (SSI) were 2.0 and 4.2%, respectively, while the rate of wound dehiscence was 2.1%. Univariate analysis of primary outcomes stratified by diabetes status showed that patients with diabetes had significantly higher rates of superficial incisional SSI (3.9 vs. 2.3%; p = 0.01), deep incisional SSI (7.0 vs. 4.3%; p = 0.001), wound dehiscence (5.2 vs. 2.7%; p < 0.001), as well as significantly higher rates of readmission (12.8 vs. 8.9%; p = 0.001). Multivariate analysis for significant outcomes between groups on univariate analysis demonstrated that diabetes was an independent risk factor for superficial incisional SSI (OR = 2.7; 95% CI: 1.59-4.62; p < 0.001), deep incisional SSI (OR = 1.85; 95% CI: 1.26-2.70; p = 0.002), wound dehiscence (OR = 4.09; 95% CI: 2.49-6.74; p < 0.001), and readmission within 30 days (OR = 1.38; 95% CI: 1.05-1.82; p = 0.02). These findings emphasize the importance of preoperative prevention, and vigilant postoperative wound care and monitoring in patients with diabetes to minimize morbidity and optimize outcomes. Future prospective studies are needed to establish causality between diabetes and these outcomes.

Diabetes is not associated with increased rates of free flap failure: Analysis of outcomes in 6030 patients from the ACS-NSQIP database.

BACKGROUND: Diabetes affects a significant proportion of the population in the United States. Microsurgical procedures are common in this patient population, and despite many conflicting reports in the literature, there are no large studies evaluating the direct association between diabetes and outcomes, specifically failure, following free flap reconstruction. In this study, we sought to determine the impact of diabetes on postoperative outcomes following free flap reconstruction using a national multi-institutional database. METHODS: We reviewed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to identify patients undergoing free flap reconstruction from 2010 to 2015. Preoperative variables and outcomes were compared between diabetic and nondiabetic patients. Univariate and multivariate analyses were performed to control for confounders. RESULTS: We identified 6030 eligible patients. No significant difference in flap failure rates was observed. However, diabetic patients presented significantly higher rates of wound complications, including deep incisional surgical site infection (SSI) (OR = 1.35; P = .01) and wound dehiscence (OR = 1.17; P = .03). Diabetic patients also presented a significantly longer hospital length of stay (LOS) (ß = .62; P < .001). CONCLUSIONS: Our study evaluated the largest national cohort of free flap procedures. These results suggest that diabetes is not associated with increased rates of flap failure. However, diabetic patients are at significantly higher risk of postoperative deep incisional SSI, wound dehiscence, and longer LOS. Our findings provide the most concrete evidence to date in support of free flap reconstruction in diabetic patients, but highlight the need for heightened clinical vigilance and wound care for optimal outcomes.

Incidence of Preventable Nonfatal Craniofacial Injuries and Implications for Facial Transplantation.

INTRODUCTION: The number of patients who may benefit from evaluation for face transplantation in the United States (US) remains largely unknown. The goal of our study was to better delineate the pool of patients who might benefit from face transplant evaluation based on the characteristics and mechanisms of injury of previously reported face transplant recipients. METHODS: The authors utilized data from the National Electronic Injury Surveillance System-All Injury Program in this study. The US Census Bureau data were used for population estimates. Inclusion and exclusion criteria were determined based on the characteristics of face transplant recipients to date, and the mechanisms of injury they sustained ultimately necessitating face transplantation. Statistical significance was reached if P <0.05. RESULTS: The estimated annual incidence of preventable craniofacial injuries from firearms (44,266-58,299; 31.7% increase), burns (5712-19,433; 240.2% increase), and animal attacks (5355-14,666; 173.9% increase) increased from 2005 to 2014, whereas the estimated annual incidence of craniofacial injuries from machinery (3927-2933; 25.3% decrease) decreased between 2005 and 2014. The authors estimate the annual incidence rate to fall between 32.1 per 100,000 and 58.1 per 100,000 among individuals aged 20 to 64 in the US. CONCLUSION: In this study, the authors estimate the annual incidence rate of individuals aged 20 to 64 in the US who may benefit from face transplant evaluation and believe that this quantification has the potential to initiate actionable discussions regarding geographical and financial factors affecting access to care in this patient population.

Comparison of Hand-Sewn versus Coupled Venous Anastomoses in Traumatic Lower Extremity Reconstruction.

BACKGROUND: Microvascular reconstruction of the lower extremity has the highest reported complication and flap failure rates of any anatomical region. Despite widespread adoption of the mechanical anastomotic venous coupler and encouraging results in other anatomical regions, there are limited reports examining its use in the lower extremity. This study compares outcomes between coupled and hand-sewn venous anastomoses in traumatic lower extremity reconstruction. METHODS: Retrospective review of our institutional flap registry from 1979 to 2016 identified soft tissue free flaps performed for the reconstruction of Gustilo type IIIB/IIIC open tibial fractures. Patient demographics, flap characteristics, use of a venous anastomotic coupler, and perioperative outcomes were examined. Analysis was performed using chi-square and Student's t-tests. RESULTS: A total of 361 patients received a microvascular free flap for coverage of a Gustilo type IIIB or IIIC tibial fracture following traumatic injury. After excluding cases that lacked adequate information on coupler use, 358 free flaps were included in the study. There were 72 (20%) free flaps performed using a venous coupler and 286 (80%) performed with hand-sewn venous anastomoses. There were comparable rates of major complications (22.2 vs. 26.1%; p = 0.522), total flap failure (6.5%, vs. 10.2%; p = 0.362), and partial flap failure (9.7 vs. 12.2%; p = 0.579) between venous coupler and hand-sewn anastomoses, respectively. Furthermore, use of the venous coupler was not associated with increased rates of operative take backs (22.8 vs. 23.0%; p = 0.974). However, reconstructions performed using a venous coupler were significantly more likely to have a second venous anastomosis performed (37.5 vs. 21.3%; p = 0.004). CONCLUSION: Complication and flap failure rates were similar between reconstructions performed with a venous coupler and those performed with hand-sewn venous anastomoses. These findings suggest that use of the venous anastomotic coupler is safe and effective in lower extremity reconstruction, with comparable outcomes to conventional sutured anastomoses.

Vein Size Mismatch Increases Flap Failure in Lower Extremity Trauma Free Flap Reconstruction.

BACKGROUND: Venous outflow problems are the most common reasons for perioperative flap complications. Size mismatch in venous anastomoses poses a theoretical problem by promoting turbulent flow and subsequent thrombus formation. The purpose of this study was to determine if increased vein size mismatch is predictive of flap failure. METHODS: Retrospective review of our institutional flap registry from 1979 to 2016 identified 410 free flaps performed for reconstruction of lower extremity trauma. Patient demographics, flap characteristics, and flap outcomes were examined. Venous size mismatch was defined as a difference in size ≥ 1 mm between the recipient vein and flap vein. RESULTS: Vein size mismatch ≥ 1mm was present in 17.1% (n = 70) of patients. The majority of anastomoses were end-to-end (n = 379, 92.4%), and end-to-side anastomoses were preferentially used in the presence of vein size mismatch (p < 0.001). Major complications occurred in 119 (29%) flaps, with 35 (8.5%) partial flap losses and 34 (8.3%) total flap losses. Looking specifically at flaps with end-to-end venous anastomoses, venous size mismatch was associated with increased total flap failure (p = 0.031) and takeback for vascular compromise (p = 0.030). Recipient vein size relative to flap vein size (larger or smaller) had no effect on flap outcomes. Multivariable regression analysis controlling for age, sex, flap type, number of veins, recipient vein size, flap vein size, venous coupler use, and vein size mismatch demonstrated that flaps with ≥ 1 mm vein mismatch were predictive of total flap failure (p = 0.045; odds ratio: 2.58). CONCLUSION: Flaps with vein size mismatch ≥ 1 mm demonstrated increased flap complication rates in the setting of end-to-end venous anastomoses. End-to-side anastomosis was preferentially used in vein size mismatch and carried a higher risk of flap failure. Our results support using veins of similar size for anastomosis whenever feasible to protect against flap complications.

Obesity and Lower Extremity Reconstruction: Evaluating Body Mass Index as an Independent Risk Factor for Early Complications.

BACKGROUND: The prevalence of obesity in the United States continues to grow and is estimated to affect over a quarter of the working-age population. Some studies have identified obesity as a risk factor for flap failure and complications in free flap-based breast reconstruction, but its clinical significance is less clear in nonbreast reconstruction. The role of obesity as a risk factor for failure and complications following lower extremity reconstruction has not been well described, and the limited existing literature demonstrates conflicting results. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed to identify patients undergoing local- or free-flap reconstruction of the lower extremity between 2010 and 2015. Preoperative variables and outcomes were compared between obese (body mass index ≥ 30) and nonobese patients. Chi-square analysis and Fisher's exact test were used for categorical variables and t-tests for continuous variables. Multivariate regression was performed to control for confounders. RESULTS: Univariate analysis of medical and surgical outcomes revealed that obese patients undergoing local flaps of the lower extremity required a significantly longer operative time (187.7 ± 123.2 vs. 166.2 ± 111.7 minutes; p = 0.003) and had significantly higher rates of superficial surgical site infection (SSI; 7.2% vs. 4.5%; p = 0.04). On univariate analysis, there were no significant differences in any postoperative outcomes between obese and nonobese patients undergoing microvascular free flaps of the lower extremity.On multivariate regression analysis, obesity was not an independent risk factor for superficial SSI (odds ratio = 1.01, p = 0.98) or increased operative time (ß = 16.01, p = 0.14) for local flaps of the lower extremity. CONCLUSION: Evaluation of a large, multicenter, validated and risk-adjusted nationwide cohort demonstrated that obesity is not an independent risk factor for early complications following lower extremity reconstruction, suggesting that these procedures may be performed safely in the obese patient population.

Ex vivo allotransplantation engineering: Delivery of mesenchymal stem cells prolongs rejection-free allograft survival.

Current pharmacologic regimens in transplantation prevent allograft rejection through systemic recipient immunosuppression but are associated with severe morbidity and mortality. The ultimate goal of transplantation is the prevention of allograft rejection while maintaining recipient immunocompetence. We hypothesized that allografts could be engineered ex vivo (after allotransplant procurement but before transplantation) by using mesenchymal stem cell-based therapy to generate localized immunomodulation without affecting systemic recipient immunocompetence. To this end, we evaluated the therapeutic efficacy of bone marrow-derived mesenchymal stem cells in vitro and activated them toward an immunomodulatory fate by priming in inflammatory or hypoxic microenvironments. Using an established rat hindlimb model for allotransplantation, we were able to significantly prolong rejection-free allograft survival with a single perioperative ex vivo infusion of bone marrow-derived mesenchymal stem cells through the allograft vasculature, in the absence of long-term pharmacologic immunosuppression. Critically, transplanted rats rejected a second, nonengineered skin graft from the same donor species to the contralateral limb at a later date, demonstrating that recipient systemic immunocompetence remained intact. This study represents a novel approach in transplant immunology and highlights the significant therapeutic opportunity of the ex vivo period in transplant engineering.

Achievements and Challenges in Facial Transplantation.

: The first facial transplantation in 2005 ushered in a new era in reconstructive surgery, offering new possibilities for the repair of severe disfigurements previously limited by conventional techniques. Advances in allograft design, computerized preoperative planning, surgical technique, and postoperative revisions have helped push the boundaries in this new frontier of vascularized composite allotransplantation. Over the past 12 years, 40 of these procedures have been performed across the world, offering the field the opportunity to reflect on current outcomes. Successes achieved in the brief history of facial transplantation have resulted in a new set of obstacles the field must now overcome. In this review, we aim to highlight the achievements, major challenges, and future directions of this rapidly evolving field.

Topical inhibition of PUMA signaling mitigates radiation injury.

Radiation therapy is an effective treatment strategy for many types of cancer but is limited by its side effects on normal tissues, particularly the skin, where persistent and progressive fibrotic changes occur and can impair wound healing. In this study, we attempted to mitigate the effects of irradiation on skin using a novel transcutaneous topical delivery system to locally inhibit p53 up-regulated modulator of apoptosis (PUMA) gene expression with small interfering RNA (siRNA). In an isolated skin irradiation model, the dorsal skin of C57 wild-type mice was irradiated. Prior to irradiation, PUMA and nonsense siRNA were applied via a novel hydrogel formulation to dorsal skin and reapplied weekly. Skin was harvested at multiple time points to evaluate dermal siRNA penetration, mRNA expression, protein expression, dermal thickness, subcutaneous fat, stiffness, vascular hypertrophy, SCAR index, and reactive oxygen species (ROS) generation. Murine skin treated with topical PUMA siRNA via optimized hydrogel formulation demonstrated effective PUMA inhibition in irradiated tissue at 3-4 days. Tissue stiffness, dermal thickness, vascular hypertrophy, SCAR index, ROS levels, and mRNA levels of MnSOD and TGF-ß were all significantly reduced with siPUMA treatment compared to nonsense controls. Subcutaneous fat area was significantly increased, and levels of SMAD3 and Phospho-SMAD3 expression were unchanged. These results show that PUMA expression can be effectively silenced in vivo using a novel hydrogel lipoplex topical delivery system. Moreover, cutaneous PUMA inhibition mitigates radiation induced changes in tissue character, restoring a near-normal phenotype independent of SMAD3 signaling.

Proximal versus Distal Recipient Vessels in Lower Extremity Reconstruction: A Retrospective Series and Systematic Review.

BACKGROUND: Recipient vessels proximal to the zone of injury have traditionally been preferred for lower extremity reconstruction. However, more recent data have shown mixed outcomes when performing anastomoses distal to the zone of injury. We investigated the impact of recipient vessel location on free flap outcomes. METHODS: Retrospective review (1979-2016); 312 soft tissue free flaps for open tibia fractures met inclusion criteria. Flap characteristics and perioperative outcomes were examined. Systematic review identified articles evaluating anastomosis location and flap outcomes; pooled data analysis was performed. RESULTS: More anastomoses were performed proximal to the zone of injury (80.7%) than distal (19.3%). Distal anastomoses were not associated with increased take back rates (19.6%) compared with proximal (23.8%) anastomoses (p = 0.356). Regression analysis comparing proximal and distal anastomoses found no difference in partial flap failures (7.4% vs 11.9%; p = 0.978) or total flap failures (9.3% vs 9.3%; p = 0.815) when controlling for the presence of arterial injury, flap type, and time from injury to coverage. Systematic review yielded 11 articles with 1,245 proximal and 127 distal anastomoses for comparison. Pooled analysis (p = 0.58) and weighted comparative analysis (p = 0.39) found no difference in flap failure rates between proximal and distal groups. CONCLUSION: Our results are congruent with the current lower extremity literature and demonstrate no difference in perioperative complication rates between anastomoses performed proximal or distal to the zone of injury. These findings suggest that anastomotic location choice should be based primarily on recipient vessel quality/flow and ease of access/exposure rather than orientation relative to the zone of injury.

Normalizing dysfunctional purine metabolism accelerates diabetic wound healing.

Diabetic patients exhibit dysfunction of the normal wound healing process, leading to local ischemia by vascular occlusive disease as well as sustained increases in the proinflammatory cytokines and overproduction of reactive oxygen species (ROS). Of the many sources of ROS, the enzyme xanthine oxidase (XO) has been linked to overproduction of ROS in diabetic environment, and studies have shown that treatment with XO inhibitors decreases XO overactivity and XO-generated ROS. This study evaluates the role of XO in the diabetic wound and the impact of specifically inhibiting its activity on wound healing. Treatment of diabetic wounds with siXDH (xanthine dehydrogenase siRNA) decreased XDH mRNA expression by 51.6%, XO activity by 35.9%, ROS levels by 78.1%, pathologic wound burden by 31.5%, and accelerated wound healing by 7 days (23.3%). Polymerase chain reaction analysis showed that increased XO activity in wild-type wound may be due to XDH to XO conversion and/or XO phosphorylation, but not to gene transcription, whereas increased XO activity in diabetic wounds may also be from gene transcription. These results suggest that XO may be responsible for large proportion of elevated oxidative stress in the diabetic wound environment and that normalizing the metabolic activity of XO using targeted delivery of siXDH may decrease overproduction of ROS and accelerate wound healing in diabetic patients.

Epidemiology of distal radius fractures: Elucidating mechanisms, comorbidities, and fracture classification using the national trauma data bank.

BACKGROUND: An update on the epidemiology of distal radius fractures in the United States is necessary, particularly as the elderly population grows. Additionally, age and frailty have been associated with complications following surgical fixation of DRFs. Herein, we utilize the National Trauma Data Bank, a robust nationwide resource, to investigate the relationship between demographics, comorbidities, injury and fracture characteristics, and admission details. METHODS: Patients with isolated distal radius fractures were identified from the National Trauma Data Bank (2016-2019) according to ICD-10 codes. Univariate and multivariate regressions were conducted to determine independent risk factors for bilateral fractures, displaced fractures, open fractures, as well as length of hospital stay and adverse discharge disposition for patients undergoing inpatient surgical fixation. RESULTS: The incidence of DRFs was 3.6/1,000 trauma-related emergency department visits and 10.8/1,000 upper extremity traumas. Trauma mechanism was significantly associated with displaced and open fractures. Age (OR 1.01, 95% CI 1.01-1.01), BMI (OR 1.02, 95% CI 1.01-1.02), smoking (OR 1.34, 95% CI 1.15-1.57), and alcohol level (trace: OR 2.18, 95% CI 1.41-3.29; intoxicated: OR 2.20, 95% CI 1.63-2.95) were significantly associated with open fractures. Machinery (ß=2.04, 95% CI 1.00-3.08) and MVT (ß=0.39, 95% CI 0.08-0.69) mechanisms were independent risk factors for longer length of stay. mFI-5 was an independent risk factor, in a stepwise fashion, for both length of stay and adverse discharge disposition. CONCLUSIONS: High-energy mechanisms and risk factors for poor skin quality were significantly associated with open fractures. mFI-5 was an independent risk factor for longer length of stay and non-routine discharges in patients of all ages, despite controlling for other comorbidities, unrelated complications, and mechanism of injury. Trauma mechanism was an independent risk factor for prolonged length of stay only, particularly in patients younger than 65 years of age.