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.

The Seven Step Neck Lift Z-Plasty.

Patients with large amounts of neck skin redundancy who do not desire or are not candidates for traditional face and neck lifts can be managed with direct neck lifts. There are many existing surgical techniques to address central neck laxity. In this article, we aim to clarify our surgical technique in a clear video format to showcase how to address central neck laxity in seven steps with neck lift Z-plasty.

Dead Space - The Final Frontier in Rhinoplasty: Review and 10 Key Recommendations.

SUMMARY: Mitigating dead space has been recognized as an essential step towards ensuring a more predictable and aesthetically pleasing outcome in rhinoplasty. The current body of literature leaves a discernible gap in offering a unified, systematic approach to dead space management in rhinoplasty. The aim of our article is to bridge this gap by presenting an integrative approach to surgical and post-surgical techniques.

Productivity and Efficiency of a Department Resident Aesthetic Plastic Surgery Clinic.

Background: There has been increasing demand for aesthetic surgery procedures in the United States, highlighting the critical importance of the competence of plastic surgery residents and rigorous methods of aesthetic surgery training. Objectives: The objective of this study was to review procedures and outcomes from our plastic surgery resident aesthetic clinic. Outcomes and costs were compared to national averages and reports from the literature. Methods: A retrospective chart review identified all adult patients who presented to the Resident Aesthetic Surgery Clinic at NYU Langone Health in 2021. Patient demographics, comorbidities, procedural data, postoperative complications, revisions, and surgeon fees were compiled. A brief confidence survey was distributed to participating residents before and after their clinic rotation. Data were analyzed using IBM SPSS software (Armonk, NY). Results: In 2021, 144/379 consultations led to an operation (38.0% conversion rate), resulting in 420 distinct surgical procedures. The majority (53.3%) of procedures involved the head and neck. Complication and revision rates were 5.5% and 1.0%, respectively, with surgeon fees consistently below the national average. Residents reported being significantly more confident performing face lifts, rhinoplasties, and aesthetic surgery in general following their clinic rotation. Conclusions: These data represent the largest annual reported study of plastic surgery resident aesthetic procedures and outcomes, demonstrating the high volume and productivity of the NYU Resident Aesthetic Surgery Clinic. These results further support resident aesthetic clinics as a robust training modality.

Vascularized Composite Allotransplantation: Alternatives and Catch-22s.

Technical success has been achieved in several forms of vascularized composite allotransplantation, including hand, face, penis, and lower extremity. However, the risks of lifelong immunosuppression have limited these procedures to a select group of patients for whom nontransplant alternatives have resulted in unsatisfactory outcomes. Recent reports of facial allograft failure, and subsequent reconstruction using autologous tissues, have reinforced the idea that a surgical contingency plan must be in place in case this devastating complication occurs. Interestingly, backup plans in the setting of vascularized composite allotransplantation consist of the nontransplant alternatives that were deemed suboptimal in the first place. Moreover, these options may have been exhausted before transplantation, and may therefore be limited in the case of allograft loss or reamputation. In this article, the authors describe the surgical and nonsurgical alternatives to hand, face, penis, and lower extremity transplantation. In addition, the authors explore the ethical implications of approaching vascularized composite allotransplantation as a "last resort" or as a "high-risk, improved-outcome" procedure, focusing on whether nontransplant options eventually preclude vascularized composite allotransplantation, or whether vascularized composite allotransplantation limits future nontransplant reconstruction.

Use of Computerized Clinical Decision Support Systems to Prevent Venous Thromboembolism in Surgical Patients: A Systematic Review and Meta-analysis.

Importance: Health care professionals do not adequately stratify risk or provide prophylaxis for venous thromboembolism (VTE) among surgical patients. Computerized clinical decision support systems (CCDSSs) have been implemented to assist clinicians and improve prophylaxis for VTE. Objective: To evaluate the effect of implementing CCDSSs on the ordering of VTE prophylaxis and the rates of VTE. Data Sources: PubMed, MEDLINE via OVID, EMBASE via OVID, Scopus, Cochrane CENTRAL Register of Controlled Trials, and clinicaltrials.gov were searched in June 2016 for articles published in English from October 15, 1991, to February 16, 2016. A manual search of references from relevant articles was also performed. Study Selection: Clinical trials and observational studies among surgical patients comparing CCDSSs with VTE risk stratification and assistance in ordering prophylaxis vs routine care without decision support were included. Of the 188 articles screened, 11 (5.9%) were eligible for meta-analysis. Data Extraction and Synthesis: Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Two reviewers extracted data and assessed quality independently. Main Outcomes and Measures: Rates of prophylaxis for VTE and VTE events. Random- and fixed-effects models were used to summarize odds ratios and risk ratios. Results: Eleven articles (9 prospective cohort trials and 2 retrospective cohort trials) comprising 156 366 individuals (104 241 in the intervention group and 52 125 in the control group) were included. The use of CCDSSs was associated with a significant increase in the rate of appropriate ordering of prophylaxis for VTE (odds ratio, 2.35; 95% CI, 1.78-3.10; P < .001) and a significant decrease in the risk of VTE events (risk ratio, 0.78; 95% CI, 0.72-0.85; P < .001). Conclusions and Relevance: Use of CCDSSs increases the proportion of surgical patients who were prescribed adequate prophylaxis for VTE and correlates with a reduction in VTE events.

Does prophylactic mesh placement in elective, midline laparotomy reduce the incidence of incisional hernia? A systematic review and meta-analysis.

BACKGROUND: Operative intervention to correct incisional hernia affects 150,000 patients annually, with 1 in 3 repairs recurring within 9 years. The aim of this study was to compare the incidence of incisional hernia and postoperative complications in elective midline laparotomy patients after the use of prophylactic mesh placement and primary suture closure. METHODS: A systematic review was performed to identify studies comparing prophylactic mesh placement to primary suture closure in elective, midline laparotomy at index abdominal aponeurosis closure. The primary outcome was incisional hernia. Secondary outcomes included postoperative complications. RESULTS: Fourteen studies were included (2,114 patients), with 1,152 receiving prophylactic mesh placement. Prophylactic mesh placement decreased the risk of incisional hernia overall when compared to primary suture closure (relative risk = 0.15; P < .00001) and in trials using only polypropylene mesh versus 4:1 primary suture closure (relative risk = 0.15; P = .003). Prophylactic mesh placement reduced the risk of incisional hernia regardless of mesh location or composition: onlay (relative risk = 0.07; P < .0001), retrorectus (relative risk = 0.04; P = .002), and preperitoneal (relative risk = 0.18; P = .02). Prophylactic mesh placement increased risk of seroma overall (relative risk = 1.95; P < .0001), onlay (relative risk = 2.43; P = .01) and preperitoneal (relative risk = 1.47; P = .01) but not retrorectus plane (relative risk = 1.55; P = .26). Polypropylene mesh increased seroma risk only in the onlay position (relative risk = 2.77; P = .04). Prophylactic mesh placement patients are at increased risk for chronic wound pain compared to primary suture closure (relative risk = 1.70; P = .03). CONCLUSION: Prophylactic mesh placement is associated with an 85% postoperative incisional hernia risk reduction when compared to primary suture closure in at-risk patients undergoing elective, midline laparotomy closure. This technique appears to be safe with comparable complication profiles, barring an increased risk of seroma, especially with the onlay technique, and the possibility for an increased risk of chronic pain. Despite this verification, evidence from large domestic trials that sufficiently addresses major knowledge gaps is simply lacking.

Novel lipoproteoplex delivers Keap1 siRNA based gene therapy to accelerate diabetic wound healing.

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.

Tissue Liquefaction Liposuction for Body Contouring and Autologous Fat Transfer: A Retrospective Review Over 3 Years.

Objective: Tissue liquefaction lipoplasty is a novel, low-energy method cleared for use in aesthetic body contouring and autologous fat transfer. This is a retrospective review of the clinical effectiveness and safety of a liquefaction lipoplasty system for liposuction and autologous fat transfer. Methods: A retrospective review was done evaluating all liquefaction lipoplasty procedures with or without autologous fat transfer performed by a single surgeon (March 2013 to June 2016). Patient demographics, operative details, and any complications were tabulated from patient charts. A typical case reported is presented with pre-/postoperative photographs. Results: Two hundred fifty-five consecutive liquefaction lipoplasty procedures were performed over 39 months. The average lipoaspirate volume was 1208 ± 991 mL and the average fat graft volume was 322 ± 277 mL. The overall complication rate was 9 of 255 (3.52%). There were 2 episodes of seroma (0.78%) that were aspirated and 2 episodes of cellulitis (0.78%) that responded to oral antibiotics. In the autologous fat transfer cohort, there were 5 of 103 (4.85%) cases of mild to moderate fat necrosis, with 1 patient requiring return to the operating room for removal of an oil cyst. No revisions of donor sites were required. Conclusions: Liquefaction lipoplasty appears safe for liposuction and autologous fat transfer, with a complication profile that is comparable with other widely used forms of suction-assisted liposuction. The liquefaction lipoplasty technology also provides potential time savings in the operating room that can minimize surgeon fatigue when harvesting large volumes of high-quality fat. Liquefaction lipoplasty appears to have advantages for both the patient and the surgeon, and further studies are underway.