Faculty Bibliography

Chronic hyperglycemia impairs intracellular redox homeostasis and contributes to impaired diabetic tissue regeneration. The Keap1/Nrf2 pathway is a critical regulator of the endogenous antioxidant response system and its dysfunction has been implicated in numerous pathologies. Here, we characterize the effect of chronic hyperglycemia on Nrf2 signaling within a diabetic cutaneous regeneration model. We characterized the effects of chronic hyperglycemia on the Keap1/Nrf2 pathway within models of diabetic cutaneous wound regeneration. We assessed reactive oxygen species (ROS) production and antioxidant gene expression following alterations in the Nrf2 suppressor, Keap1, and the subsequent changes in Nrf2 signaling. We also developed a topical siRNA-based therapy to restore redox homeostasis within diabetic wounds. Western blot demonstrated that chronic hyperglycemia-associated oxidative stress inhibits nuclear translocation of Nrf2 and impairs activation of antioxidant genes, thus contributing to ROS accumulation. Keap1 inhibition increased Nrf2 nuclear translocation, increased antioxidant gene expression, and reduced ROS production to normoglycemic levels, both in vitro and in vivo. Topical siKeap1 therapy resulted in improved regenerative capacity of diabetic wounds and accelerated closure. We report that chronic hyperglycemia weakens the endogenous antioxidant response and the consequences of this defect are manifested by intracellular redox dysregulation, which can be restored by Keap1 inhibition. Targeted siRNA-based therapy represents a novel, efficacious strategy to reestablish redox homeostasis and accelerate diabetic cutaneous tissue regeneration.

Background The internal mammary vessels are the most commonly used recipients for microsurgical breast reconstructions. Often, the costal cartilage is sacrificed to obtain improved vessel exposure. In an effort to reduce adverse effects associated with traditional rib sacrifice, recent studies have described less-invasive, rib-sparing strategies. Methods After obtaining institutional review board's approval, a retrospective review of all patients undergoing microsurgical breast reconstruction at a single institution between November 2007 and December 2013 was conducted. Patients were divided into two cohorts for comparison: rib-sacrificing and rib-sparing internal mammary vessel harvests. Results A total of 547 reconstructions (344 patients) met inclusion criteria for this study. A total of 64.9% (n = 355) underwent rib-sacrificing internal mammary vessel harvest. Cohorts were similar in baseline patient characteristics, indications for surgery, and cancer therapies. However, patients undergoing rib-sparing reconstructions had significantly shorter operative times (440 vs. 476 minutes; p < 0.01), and significantly less postoperative pain on postoperative day (POD) 1 (2.8/10 vs. 3.4/10; p = 0.033) and POD2 (2.4/10 vs. 3.0/10; p = 0.037). Furthermore, patients undergoing rib-sparing techniques had greater incidence of fat necrosis requiring excision (12.5 vs. 2.8%; p < 0.01) and a trend toward higher incidence of hematoma, venous thrombosis, and arterial thrombosis when compared with rib-sacrificing patients. Conclusions Rib-sparing harvest of internal mammary vessels is a feasible technique in microsurgical breast reconstruction. However, given the significant increase in fat necrosis requiring surgical excision, the trend toward increased postoperative complications, and no significant difference in postoperative revision rates, the purported benefits of this technique may fail to outweigh the possible risks.

Background This study aims to characterize the evolution and trends in free flap breast reconstruction at our institution. Methods The authors reviewed and analyzed a registry of free flap breast reconstructions performed at a large urban academic center. Results Between 1979 and mid-2014, a total of 920 patients underwent breast reconstruction with 1,254 flaps. The mean age was 47.7 years (range, 16-79 years). Over the past 10 years, patients were older than all patients seen in the prior decade (average age 48.9 vs. 46.1 years, p = 0.002). Overall, 82% of flaps were performed at our university hospital, 17% at a major urban county hospital, and < 1% at other sites. A total of 99% patients received postmastectomy reconstruction for an existing cancer diagnosis or prophylaxis. There has been a significant increase in reconstructions, with 579 flaps performed over the past 5 years alone. There has been a fundamental shift in the predominant flap of choice over time. Perforator flaps have increased in popularity at our institution, with 74% of all reconstructions over this past 5 years being perforator based. Perforator flaps were more likely to be chosen over nonperforator flaps in older versus younger patients (p = 0.0008). There has been a steady increase in bilateral reconstructions since the first one was performed in 1987 (p = 0.002). Conclusions Over the past 35 years, our institution has seen a significant evolution in free flap-based breast reconstruction. Besides a massive increase in flap numbers we have seen a significant trend toward bilateral reconstructions and perforator-based flaps.

BACKGROUND: Acellular dermal matrices are used in implant-based breast reconstruction. The introduction of contour fenestrated AlloDerm (Life-Cell, Branchburg, N.J.) offers sterile processing, a crescent shape, and prefabricated fenestrations. However, any evidence comparing reconstructive outcomes between this newer generation acellular dermal matrices and earlier versions is lacking. METHODS: Patients undergoing implant-based breast reconstruction from 2010 to 2014 were identified. Reconstructive outcomes were stratified by 4 types of implant coverage: aseptic AlloDerm, sterile "ready-to-use" AlloDerm, contour fenestrated AlloDerm, or total submuscular coverage. Outcomes were compared with significance set at P < 0.05. RESULTS: A total of 620 patients (1019 reconstructions) underwent immediate, implant-based breast reconstruction; patients with contour fenestrated AlloDerm were more likely to have nipple-sparing mastectomy (P = 0.0001, 0.0004, and 0.0001) and immediate permanent implant reconstructions (P = 0.0001). Those with contour fenestrated AlloDerm coverage had lower infection rates requiring oral (P = 0.0016) and intravenous antibiotics (P = 0.0012) compared with aseptic AlloDerm coverage. Compared with sterile "ready-to-use" AlloDerm coverage, those with contour fenestrated AlloDerm had similar infection outcomes but significantly more minor mastectomy flap necrosis (P = 0.0023). Compared with total submuscular coverage, those with contour fenestrated AlloDerm coverage had similar infection outcomes but significantly more explantations (P = 0.0001), major (P = 0.0130) and minor mastectomy flap necrosis (P = 0.0001). Significant independent risk factors for increased infection were also identified. CONCLUSIONS: Contour fenestrated AlloDerm reduces infections compared with aseptic AlloDerm, but infection rates are similar to those of sterile, ready-to-use AlloDerm and total submuscular coverage.