Perioperative Medication Management in Elective Plastic Surgery Procedures.

BACKGROUND: Perioperative medication management is vital to maintain patient safety while under anesthesia, as well as to avoid postoperative complications. Plastic surgeons make daily decisions on whether to ask a patient to stop taking medication before their surgery. These important decisions can affect bleeding risk, wound healing, and interactions with anesthetics, which can range from minor to life-threatening. Current plastic surgery literature lacks a comprehensive review of perioperative medication management, with existing reports focusing on specific procedures and specific medication classes. METHODS: A PubMed database search was conducted for articles through July 2021. The bibliographies of included studies were also examined for articles not acquired in the initial search queries. The authors included studies on medication usage and perioperative guidance in patients undergoing elective plastic surgery procedures. The authors excluded studies unrelated to plastic surgery and studies where the medications were used as an intervention. Abstracts, animal studies, studies involving the pediatric population, and book chapters were also excluded, as well as articles not published in English. RESULTS: A total of 801 papers were identified by our search terms. After title and abstract screening, 35 papers were selected for full-text review. After full-text review, 20 papers were selected for inclusion, with an additional 6 papers from cited references added. Of the 26 papers, 6 papers discussed psychotropic drugs, 6 papers discussed medications affecting hemostasis, 4 papers discussed hormone-containing medications, 3 papers discussed antilipid medications, 2 papers discussed antihypertensive medications, 2 papers discussed herbal supplements, 1 paper discussed both psychotropic and herbal supplements, 1 paper discussed medications affecting wound healing, and 1 paper discussed rheumatologic medications. A summary of those recommendations was then compiled together. CONCLUSIONS: The perioperative medication management in elective plastic surgery procedures remains a complex and multidisciplinary process. It is important to manage these patients in a case-by-case manner and to consult a specialist when necessary. Careful medication reconciliation is essential to decrease the likelihood of adverse outcomes and interactions with perioperative anesthetics.

Dangle Protocols in Lower Extremity Reconstruction.

INTRODUCTION: Dangling protocols are known to vary by surgeon and center, and their specific regimen is often largely based on single surgeon or institutional experience. A systematic review was conducted to derive evidence-based recommendations for dangling protocols according to patient-specific and flap-specific considerations. METHODS: A systematic review was performed using PubMed, Embase-OVID and Cochrane-CENTRAL. Study design, patient and flap characteristics, protocol details, dangling-related complications, and flap success rate were recorded. Studies were graded using the Oxford Center for Evidence-Based Medicine Levels of Evidence Scale. Data heterogeneity precluded quantitative analysis. RESULTS: Eleven articles were included (level of evidence (range):IIb-IV; N (range):8-150; age (range):6-89). Dangling initiation, time, and frequency varied considerably. Flap success rate ranged from 94 to 100%. Active smoking, diabetes, and hypertension are associated with characteristic physiologic changes that require vigilance and potential protocol modification. Early dangling appears to be safe across a variety of free flap locations, sizes, and indications. Axial fasciocutaneous flaps may tolerate more aggressive protocols than muscular flaps. While flaps with single venous anastomosis tolerate dangling, double venous or flow-through anastomoses may provide additional benefit. Major limitations included small sample sizes, uncontrolled study designs, and heterogeneous patient selection, dangling practices, monitoring methods, and outcome measures. CONCLUSIONS: Significant heterogeneity persists in postoperative dangling protocols after lower extremity microvascular reconstruction. Patient comorbidities and flap characteristics appear to affect tolerance to dangling. We propose two different standardized pathways based on risk factors. Clinical vigilance should be exercised in tailoring lower extremity protocols to patients' individual characteristics and postoperative course.

Hematoma After Non-Oncologic Breast Procedures: A Comprehensive Review of the Evidence.

BACKGROUND: Hematoma after non-oncologic breast surgery is a common concern requiring expeditious treatment. The purpose of this study is to perform an evidence-based review of perioperative factors that may contribute to hematoma in non-oncologic breast procedures. METHODS: A comprehensive literature review was performed of non-oncologic breast procedures: breast augmentation, single-stage augmentation-mastopexy, mastopexy, and reduction. In total, 28 studies highlighting incidence and potential risk factors for hematoma were included; overall level of evidence was established regarding each perioperative factor examined and hematoma rate. RESULTS: The hematoma rate in breast augmentation ranges from 0.2 to 5.7%. There is inconclusive evidence to support an association between pocket choice or incision location and hematoma rate (Level III) and no evidence of an association between implant type and hematoma (Level V). Single-stage augmentation-mastopexy may have a lower hematoma rate than augmentation alone (Level II). Hematoma may increase the risk of capsular contracture (Level III). In breast reduction, the hematoma rate ranges from 1.0 to 9.3%. Evidence of an association between incision choice and hematoma rate is inconclusive (Level III). Use of epinephrine-containing solution, pedicle choice, and resection weight do not appear to affect hematoma rate (Level V, II, and II, respectively). The use of postoperative drains and ketorolac do not affect the incidence of hematoma (Level I and III, respectively). Intraoperative hypotension may increase the risk of hematoma after breast reduction (Level III). CONCLUSIONS: Breast hematomas are not uncommon complications. Current literature lacks ample evidence for risk factors for hematoma after non-oncologic breast procedures, warranting further, high-powered investigations. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Free-Flap Reconstruction for Diabetic Lower Extremity Limb Salvage.

BACKGROUND: Microsurgical free tissue transfer is an important treatment option for nonhealing lower extremity diabetic wounds. The purpose of this study was to identify factors that affect flap survival and wound complications. METHODS: A retrospective review was conducted of 806 lower extremity free-flap reconstructions performed from 1979 to 2016. A total of 33 free flaps were used for coverage of nonhealing lower-extremity diabetic ulcers. Primary outcome measures were perioperative complications and long-term wound breakdown. RESULTS: The average age was 54 ± 12.3 y. 15.2% of patients were smokers, 12.1% had coronary artery disease and 12.1% had end-stage renal disease. Muscle flaps predominated (75.8%) compared to fasciocutaneous flaps (24.2%). There were 7 patients (21.2%) that underwent a revascularization procedure before (71.4%) or at the same time (28.6%) as the free flap. Immediate complications occurred in 7 flaps (21.2%) with 4 partial losses (12.1%) and 3 total flap failures (9.1%). Major wound complications occurred in 18.2% of patients. An end-to-side (E-S) anastomosis for the artery was used in 63.6% (n = 22) of flaps compared with an end-to-end (E-E) anastomosis. E-S anastomosis was associated with a significantly lower risk of wound complications compared with an arterial E-E anastomosis (0% versus 45.5%, P = 0.001). CONCLUSIONS: The use of microvascular free flaps can be used successfully to cover lower-extremity diabetic wounds. E-E arterial anastomosis should be avoided if possible as it is associated with higher rates of wound breakdown, likely by impairing perfusion to a distal limb with an already compromised vasculature. LEVEL OF EVIDENCE: Level III.

Revisiting the Reverse Sural Artery Flap in Distal Lower Extremity Reconstruction: A Systematic Review and Risk Analysis.

BACKGROUND: The reverse sural artery flap (RSAF) is a popular option for patients with distal lower extremity defects who are not ideal candidates for free flap reconstruction. This is the first systematic review and pooled analysis of surgical characteristics, risk factors, and outcomes of the RSAF. METHODS: A systematic literature review was conducted. All studies reporting on patients undergoing RSAF reconstruction and their outcomes were included. Outcomes were pooled and analyzed using Fisher exact or χ test. RESULTS: Forty-three studies (479 patients, 481 flaps) were analyzed. The majority of patients were male (70.3%), and average ± SD age was 46.9 ± 16.7 years. Rates of smoking, diabetes mellitus (DM), and peripheral vascular disease (PVD) were 34.6%, 35.4%, and 12.3%, respectively. Defect etiologies were largely traumatic (60.4%). The most common defect location was the heel (40.8%). Flap modifications were reported in 123 flaps (25.6%). The most common modification was adipofascial extension (20.3%).Overall, the partial and total flap loss rates were 15.4% and 3.1%, respectively. Partial flap loss was significantly increased in smokers (28.9% vs 12.2% in nonsmokers, P = 0.0195). Technical modifications decreased the odds of partial necrosis by almost 3-fold compared with traditional RSAF reconstruction (7.2% vs 17.9%; odds ratio, 2.8 [1.4-5.8]; P = 0.0035). Patient age, DM, and PVD were not significantly associated with flap loss. CONCLUSIONS: The RSAF remains a safe salvage option for patients with DM or PVD but should be used with caution in smokers. Technical modifications to minimize pedicle compression significantly reduce rates of partial necrosis.

Risk factors for microvascular free flaps in pediatric lower extremity trauma.

PURPOSE: There is a dearth of literature dedicated to specifically evaluating the use of free flap reconstruction in pediatric lower extremity traumas. This study aims to identify specific risk factors for flap failure in pediatric lower extremity trauma reconstruction. METHODS: Retrospective review of 53 free flaps in our lower extremity database (1979-2017) identified all free flaps performed for traumatic reconstruction in children <18 years of age at our institution. RESULTS: Fifty-three free flaps (11.1%) were performed in 49 pediatric patients. The majority of patients were male (69.8%). Arterial injury was present in 19 patients (35.8%) and was associated with significantly higher flap failure rates compared to patients without arterial injury (36.8% vs 8.8%, P = 0.020) with RR = 6.0. This was again found to be true on multivariable logistic regression controlling for age, sex, flap type, and degree of arterial or venous mismatch (RR = 53, P = 0.016). Analysis of anastomotic vessel sizes revealed significantly increased risk of flap failure with increasing degree of arterial size mismatch on logistic regression (RR = 6.1, p = .02). Similar analysis for venous data was performed and revealed trending towards similar findings without reaching statistical significance (P = .086); however, the presence of any venous size mismatch was associated with significantly increased risk of flap failure on χ2 analysis (P = 0.041). CONCLUSION: Free flap reconstruction in the pediatric trauma population is safe with similar survival outcomes when compared to the adult population. Arterial injury and vessel size mismatch were associated with significantly higher flap failure rates in this population. LEVEL OF EVIDENCE: Level III.

Larger free flap size is associated with increased complications in lower extremity trauma reconstruction.

BACKGROUND: Free flap reconstruction after lower extremity trauma remains challenging with various factors affecting overall success. Increasing defect and flap size have been demonstrated to be a surrogate for overall injury severity and correlated with complications. In addition, larger free flaps that encompass more tissue theoretically possess high metabolic demand, and may be more susceptible to ischemic insult. Therefore, the purpose of our study was to determine how flap size affects microsurgical outcomes in the setting of lower extremity trauma reconstruction. METHODS: Retrospective review of 806 lower extremity free flap reconstructions performed from 1979 to 2016 among three affiliated hospitals: a private university hospital, Veterans Health Administration Hospital (VA), and a large, public hospital serving as a level 1 trauma center for the city. Soft tissue free flaps used for below the knee reconstructions of traumatic injuries were included. A receiver operating curve (ROC) was generated and Youden index was used to determine the optimal flap size for predicting flap success. Based on this, flaps were divided into those smaller than 250 cm2 and larger than 250 cm2 . Partial flap failure, total flap failure, takebacks, and overall major complications (defined as events involving flap compromise) were compared between these two groups. Multivariate logistic regression was performed to determine whether flap size independently predicts complications and flap failures, controlling for injury-related and operative factors. RESULTS: A total of 393 patients underwent lower extremity free tissue transfer. There were 229 flaps (58.2%) with size <250 cm2 and 164 flaps (41.7%) ≥ 250 cm2 . ROC analysis and Youden index calculation demonstrated 250 cm2 (AUC 0.651) to be the cutoff free flap for predicting increasing flap failure. Compared to flaps with less than 250 cm2 , larger flaps were associated with increased major complications (33.6% vs. 50.0%, p = .001), any flap failure (11.8% vs. 25.0%, p = .001) and partial flap failure (4.8% vs. 14.6%, p = .001). Logistic regression analysis controlling for age, flap type, era of reconstruction, number of venous anastomoses, presence of associated injuries, presence of a bone gap, vessel runoff, and flap size identified increasing flap size to be independently predictive of major complications (p = .05), any flap failure (p = .001), partial flap failure (p < .001), and takebacks (p = .03). Subset analysis by flap type demonstrated that when flap size exceeded 250 cm2 , use of muscle flaps was associated with significantly increased flap failure rates (p = .008) while for smaller flap size, there was no significant difference in complications between muscle and fasciocutaneous flaps. CONCLUSION: Increasing flap size is independently predictive of flap complications. In particular, a flap size cutoff value of 250 cm2 was associated with significantly increased flap failure and complications particularly among muscle-based flaps. Therefore, we suggest that fasciocutaneous flaps be utilized for injuries requiring large surface area of soft tissue reconstruction.

Perforator Variability of the Anterolateral Thigh Flap Identified on Computed Tomographic Angiography: Anatomic and Clinical Implications.

BACKGROUND: The anterolateral thigh (ALT) flap is a useful flap with minimal donor site morbidity. Preoperative computed tomographic angiography (CTA) for lower extremity reconstruction can determine vessel integrity and plan for recipient vascular targets. This study reviews lower extremity CTAs to further characterize ALT vascular anatomy and associated clinical implications thereof. PATIENTS AND METHODS: Lower extremity CTA studies were retrospectively reviewed, and information on ALT cutaneous perforator location, origin, and course was collected. RESULTS: A total of 58 lateral circumflex femoral artery (LCFA) systems in 31 patients were included. Average age was 38.8 ± 15.9 years with mean body mass index of 27.2 ± 5.7 kg/m2. The majority of patients were females (23, 74.2%). The LCFA most commonly originated from the profunda femoris artery (87.3%), followed by the distal common femoral artery (9.1%). On average, there were 1.66 ± 0.69 cm perforators per extremity, with an average of 5.38 cm between adjacent perforators. Perforators originated from the descending branch of the LCFA in 89.6% of studies. Perforator caliber was <1 mm (29, 30.2%), 1 to 2 mm (55, 57.3%), or >2 mm (12, 12.5%). Mean distance from the most proximal perforator to the anterior superior iliac spine was 20.4 ± 4.82 cm. Perforators were musculocutaneous (46.9%), septocutaneous (34.4%), or septomyocutaneous (18.8%). In 58.1% of patients, only one thigh had easily dissectable septocutaneous and/or septomyocutaneous perforators, in which case preoperative CTA aided in donor thigh selection. CONCLUSION: ALT flap cutaneous perforator anatomy varies considerably. Using CTA, we report on rates of septocutaneous, myocutaneous, and septomyocutaneous perforators and underscore its utility in perforator selection.

Three-Dimensional Affordable Stone Models for Cleft Lip Markings: A Prospective Study of Learner Satisfaction.

INTRODUCTION: Knowledge of surgical markings for unilateral cleft lip (UCL) repair is critical for surgical competency. However, few appropriate models are accessible to residents and affordable and accurately reproduce this 3-dimensional (3D) deformity. We propose that cleft care units have the capability of creating affordable 3D stone models to teach UCL markings. METHODS: Polyvinyl siloxane and SnapStone were used to create UCL stone models. Thirteen plastic surgery residents were prospectively recruited, provided with a textbook chapter and online module for studying surgical markings for UCL repair, and then asked to perform the markings on a UCL stone model and standardized patient photograph. Learner satisfaction was evaluated using a modified survey based on the Student Evaluation of Educational Quality survey. RESULTS: The production time of each model was 10 minutes, whereas the cost was $1.84. Participants reported that the stone model was more stimulating (4.77 ± 0.44 vs 3.92 ± 0.86; U = 38.0; P = 0.008), increased their interest more (4.70 ± 0.48 vs 3.53 ± 1.20; U = 33.5; P = 0.005), allowed better learning (4.61 ± 0.51 vs 3.08 ± 0.86; U = 10.0; P < 0.001), was clearer (4.62 ± 0.51 vs 3.15 ± 0.90; U = 12.5; P < 0.001), and was more effective for learning cleft lip markings (4.77 ± 0.44 vs 3.08 ± 1.04; U = 9.0; P < 0.001). They were also more likely to recommend it (4.85 ± 0.38 vs 3.15 ± 1.07; U = 7.0; P < 0.001). CONCLUSIONS: Plastic surgery residents report that 3D cleft lip stone models are superior training tools to learn cleft lip markings compared with patient photographs. These educational tools have the potential to overcome significant financial, logistic, and time constraints in teaching cleft lip surgery markings.

Flap Reconstruction of Sarcoma Defects in the Setting of Neoadjuvant and Adjuvant Radiation.

BACKGROUND: Limb-sparing treatment of extremity soft tissue sarcomas requires wide resections and radiation therapy. The resulting complex composite defects necessitate reconstructions using either muscle or fasciocutaneous flaps, often in irradiated wound beds. METHODS: A retrospective chart review was performed of all limb-sparing soft tissue sarcoma resections requiring immediate flap reconstruction from 2012 through 2016. RESULTS: Forty-four patients with 51 flaps were identified: 25 fasciocutaneous and 26 muscle-based flaps. Mean defect size, radiation treatment, and follow-up length were similar between groups. More often, muscle-based flaps were performed in younger patients and in the lower extremity. Seventeen flaps were exposed to neoadjuvant radiation, 12 to adjuvant radiation, 5 to both, and 17 to no radiation therapy. Regardless of radiation treatment, complication rates were comparable, with 28% in fasciocutaneous and 31% in muscle-based groups (p < 0.775). Muscle-based flaps performed within 6 weeks of undergoing radiotherapy were less likely to result in complications than those performed after greater than 6 weeks (p < 0.048). At time of follow-up, Musculoskeletal Tumor Society scores for fasciocutaneous and muscle-based reconstructions, with or without radiation, showed no significant differences between groups (mean [SD]: 91% [8%] vs. 89% [13%]). CONCLUSION: The similar complication rates and functional outcomes in this study support the safety and efficacy of both fasciocutaneous flaps and muscle-based flaps in reconstructing limb-sparing sarcoma resection defects, with or without radiotherapy.

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.

Comparing Outcomes for Fasciocutaneous versus Muscle Flaps in Foot and Ankle Free Flap Reconstruction.

BACKGROUND: The distal lower extremity poses unique reconstructive challenges due to its requirements for durability of the load-bearing plantar surface and for thin, pliable contour in the dorsal foot and ankle region. This study compares outcomes between muscle and fasciocutaneous flaps in patients with foot and ankle defects. METHODS: A retrospective review of soft tissue free flaps used for traumatic foot and ankle defects was performed. Outcomes included takebacks, partial flap failure, total flap failure, and wound complications. RESULTS: A total of 165 cases met inclusion criteria, with muscle flaps (n = 110) comprising the majority. Defects involving the non-weight-bearing surface were more common (n = 86) than those of the weight-bearing surface (n = 79). Complications occurred in 56 flaps (33.9%), including 11 partial losses (6.7%) and 6 complete losses (3.6%). There were no differences in take backs, partial flap failure, or total flap failure between muscle and fasciocutaneous flaps; however, fasciocutaneous flaps had significantly fewer wound complications compared with muscle flaps (7.3% vs. 19.1%, p = 0.046). On multivariable regression analysis, defects of the weight-bearing surface had significantly increased risk of wound breakdown compared with those in the non-weight-bearing surface (odds ratio: 5.05, p = 0.004). CONCLUSION: Compared with fasciocutaneous flaps, muscle flaps demonstrated higher rates of wound complications. While the flap selection in foot and ankle reconstruction depends on the nature of the defect, our findings support the use of fasciocutaneous over muscle flaps in this region.

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.

Improving Senescent Wound Healing With Local and Systemic Therapies.

The population is aging, and the prevalence of chronic wounds is increasing. Because neovascularization is essential for tissue repair and both local and systemic factors affect new blood vessel formation, we hypothesize that altering either pathway would reciprocally enhance wound healing in the aged. To test this hypothesis, p53 was locally suppressed and endothelial progenitor cells (EPCs) were systemically mobilized in a murine model of senescent wound healing.Bilateral 6-mm full-thickness stented wounds were made on the dorsum of Zmpste24 mice. Animals received weekly topical p53 small interfering RNA (siRNA) (n = 25), weekly topical nonsense siRNA (n = 25), daily subcutaneous AMD3100 injections (n = 25), or daily subcutaneous saline injections (n = 25). Wounds were photographically assessed and harvested for reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunostaining over 40 days. Circulating EPC levels were measured using fluorescence-activated cell sorting analysis.Local p53 siRNA significantly improved Zmpste24 wound healing (18 ± 2 vs 40 ± 3 days; P ≤ 0.0001). p53 siRNA significantly increased local provasculogenic factors (hypoxia-inducible factor 1 α, stromal cell-derived factor 1 α, and vascular endothelial growth factor; P ≤ 0.05) and decreased local proapoptotic factors (p53, PUMA, and Bax; P ≤ 0.05). Local p53 siRNA also significantly increased the number of circulating EPCs (8 ± 0.2% vs 2.6 ± 0.1%; P ≤ 0.0001). AMD3100 treatment also significantly improved wound healing (20 ± 2 vs 40 ± 3 days; P ≤ 0.0001) and increased EPCs mobilization (7.8 ± 0.4% vs 2.6 ± 0.1%; P ≤ 0.0001). In addition, systemic AMD3100 increased local provasculogenic factors (hypoxia-inducible factor 1 α, stromal cell-derived factor 1 α, and vascular endothelial growth factor; P ≤ 0.05) and decreased local proapoptotic factors (p53, PUMA, and Bax; P ≤ 0.05). Both treatments significantly increased the number of blood vessels in the wound bed (P ≤ 0.0001).The marked delay in Zmpste24 wound healing is significantly improved by local (p53 siRNA) and systemic (AMD3100) treatments. The resulting decrease in proapoptotic factors and increase in provasculogenic factors in the wound bed as well as the increased level of circulating EPCs appear to reverse age-related wound healing impairment by enhancing wound neovascularization.

Skin Paddles Improve Muscle Flap Salvage Rates After Microvascular Compromise in Lower Extremity Reconstruction.

PURPOSE: Free tissue transfer after lower extremity trauma is associated with notoriously high complication rates. Theoretically, the inclusion of a cutaneous paddle on muscle free flaps may improve clinical flap monitoring. The effect of skin paddle presence on muscle free flap salvage outcomes after take-back was examined. METHODS: Retrospective query of our institutional free-flap registry (1979-2016) identified 362 muscle-based flaps performed for soft tissue coverage after below-knee trauma. Primary outcome measures were perioperative complications, specifically take-back indications, timing, and flap salvage rates. Univariate and multivariate regression analyses were performed where appropriate. RESULTS: The most common flaps were latissimus dorsi (166; 45.9%), rectus abdominis (123; 34%), and gracilis (42; 11.6%) with 90 flaps (24.9%) including skin paddles. Take-backs for vascular compromise occurred in 44 flaps (12.2%), of which 39% contained a skin paddle while 61% did not. Overall salvage rate was 20.5%, with 31.8% partial failures and 47.7% total flap losses. Muscle flaps with skin paddles were more likely to return to the operating room within 48 hours postoperatively than those without (57.1% vs 18.2%, P = 0.036). After take-back, significantly more muscle flaps with skin paddles were salvaged compared with muscle flaps without paddles (35.7% vs 4.5%, P = 0.024). Similarly, more muscle-only flaps after take-back failed compared with their counterparts with skin paddles (95.5% vs 65.3%, P = 0.024). CONCLUSIONS: Muscle flaps with a cutaneous paddle were associated with earlier return to the operating room and more successful flap salvage after take-back compared with muscle-only flaps. These findings suggest that skin paddle presence may improve clinical flap monitoring and promote recognition and treatment of microvascular compromise in lower extremity reconstruction.

Limb-sparing sarcoma reconstruction with functional composite thigh flaps.

INTRODUCTION: Innervated muscle transfer can improve functional outcomes after extensive limb-sparing sarcoma resections. We report our experience using composite thigh flaps for functional reconstruction of large oncologic extremity defects. PATIENTS AND METHODS: Between 2011 and 2014, four limb-sparing oncologic resections (3 lower extremities, 1 upper extremity) underwent immediate functional reconstruction with composite thigh free flaps in three males and one female. The age of the patients ranged from 36 to 73 years. There were 3 soft-tissue sarcomas and one giant cell tumor, all required resection of entire muscle compartments. Flap components included fasciocutaneous tissue with sensory nerve, plicated iliotibial band (ITB), and variable amounts of motorized vastus lateralis (VL). RESULTS: All flaps survived without complications. All patients showed VL motor innervation by six months. Follow-up ranged from 20 to 36 months. Motor strength ranged from 2 to 5 out of 5, active range of motion was 25-92% of normal, and Musculoskeletal Tumor Society (MSTS) Scores were between 22 and 29 out of 30. CONCLUSIONS: Limb-sparing techniques for upper and lower extremity sarcomas continue to evolve. Our experience has validated the composite thigh free flap as an excellent option for one-stage functional reconstruction of large limb defects.

Optimizing venous outflow in reconstruction of Gustilo IIIB lower extremity traumas with soft tissue free flap coverage: Are two veins better than one?

PURPOSE: The dependent nature of the lower extremity predisposes to venous congestion, especially following significant trauma. The benefit of a second venous anastomosis, however, remains unclear in lower extremity trauma free flap reconstruction. This study investigated the effect of an additional venous anastomosis on flap outcomes in lower extremity trauma reconstruction. METHODS: Retrospective review between 1979 and 2016 identified 361 soft tissue flaps performed for Gustilo IIIB/C coverage meeting inclusion criteria. Muscle flaps were performed in 287 cases (79.9%) and fasciocutaneous flaps in 72 cases (20.1%). Single-vein anastomosis was performed in 76% of cases and dual-vein anastmoses in 24% of cases. Patient demographics, flap characteristics, and outcomes were examined. RESULTS: Fasciocutaneous flaps were more likely to have two veins performed (P < .001). Complications occurred in 143 flaps (39.8%): 45 take-backs (12.4%), 37 partial losses (10.3%), 31 complete losses (8.6%). Compared to single-vein flaps, two veins reduced major complications (P = .005), partial flap failures (P = .008), and any flap failure (P = .018). Multivariable regression analysis demonstrated two veins to be protective against complications (RR = 2.58, P = .009). Subset regression analysis by flap type demonstrated an even more significant reduction in complications among muscle flaps (RR = 3.92, P = .005). Additionally, a >1 mm vein size mismatch was predictive of total flap failure (RR = 3.02, P = .038). CONCLUSION: Lower extremity trauma free flaps with two venous anastomoses demonstrated a fourfold reduction in complication rates compared to single-vein flaps. Additionally, venous size mismatch >1 mm was an independent predictor of total flap failure, suggesting beneficial effects of both two-vein outflow and matched vessel diameter.

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.

Assessing the Value of a Multimedia-Based Aesthetic Curriculum in Plastic Surgery Residency: A Single-Center Pilot Study.

BACKGROUND: Although global demand for cosmetic surgery continues to rise, plastic surgery residents feel that current models of aesthetic training are inadequate in preparing them for future practice. Digital learning resources offer promising educational possibilities, yet there are no formal studies investigating the integration of these technologies into the aesthetic curriculum. OBJECTIVES: Here, we review the current state of aesthetic training for plastic surgery residents and present a pilot study investigating the value of a dedicated multimedia-based aesthetic curriculum at a single, large academic program. METHODS: Twenty plastic surgery residents participated in an 8-week curriculum consisting of weekly multimedia-based modules covering a specific aesthetic topic. Participants completed pre- and post-intervention surveys at 0 and 10 weeks, respectively. Surveys evaluated resident perspectives of the current state of aesthetic training, confidence in performing surgical and non-surgical aesthetic procedures, perceived efficacy of multimedia interventions for learning, and preferences for inclusion of such approaches in future curricula. RESULTS: 16.7% of participants planned on entering an aesthetic fellowship following residency. The mean number of months of dedicated cosmetic surgery rotations was 1.65 months. Resident confidence level in performing a particular aesthetic procedure significantly increased in 6/14 modules. More than 90% of residents were interested in incorporating the modules into residency. CONCLUSIONS: Technology-based aesthetic training is critical for producing the finest future practitioners and leaders of this specialty. Here, we show that plastic surgery residents can benefit from a multimedia-based aesthetic curriculum, even if they do not plan on pursuing a career devoted to cosmetic surgery.