Background: In situ cellular reprogramming offers the possibility of regenerating functional cardiomyocytes directly from scar fibroblasts, obviating the challenges of cell implantation. We hypothesized that pretreating scar with gene transfer of the angiogenic vascular endothelial growth factor ( VEGF ) would enhance the efficacy of this strategy. Methods and Results: Gata4, Mef2c, and Tbx5 ( GMT ) administration via lentiviral transduction was demonstrated to transdifferentiate rat fibroblasts into (induced) cardiomyocytes in vitro by cardiomyocyte marker studies. Fisher 344 rats underwent coronary ligation and intramyocardial administration of an adenovirus encoding all 3 major isoforms of VEGF (Ad VEGF ‐All6A ⁺ ) or an AdNull control vector (n=12/group). Lentivirus encoding GMT or a GFP control was administered to each animal 3 weeks later, followed by histologic and echocardiographic analyses. GMT administration reduced the extent of fibrosis by half compared with GFP controls (12±2% vs 24±3%, P <0.01) and reduced the number of myofibroblasts detected in the infarct zone by 4‐fold. GMT ‐treated animals also demonstrated greater density of cardiomyocyte‐specific marker beta myosin heavy chain 7 ⁺ cells compared with animals receiving GFP with or without VEGF ( P <0.01). Ejection fraction was significantly improved after GMT vs GFP administration (12±3% vs −7±3%, P <0.01). Eight (73%) GFP animals but no GMT animals demonstrated decreased ejection fraction during this interval ( P <0.01). Also, improvement in ejection fraction was 4‐fold greater in GMT / VEGF vs GMT /null animals (17±2% vs 4±1%, P <0.05). Conclusions: VEGF administration to infarcted myocardium enhances the efficacy of GMT ‐mediated cellular reprogramming in improving myocardial function and reducing the extent of myocardial fibrosis compared with the use of GMT or VEGF alone.

BACKGROUND: Closed-suction drains, implants, and acellular dermal matrix (ADM) are routinely used in tissue expander-based immediate breast reconstruction (TE-IBR). Each of these factors is thought to increase the potential for surgical site infection (SSI). Although CDC guidelines recommend only 24 hours of antibiotic prophylaxis after TE-IBR, current clinical practices vary significantly. This study evaluated the difference in SSI between 2 different prophylactic antibiotic durations. STUDY DESIGN: A noninferiority randomized controlled trial was designed in which TE-IBR patients received antibiotics either 24 hours postoperatively or until drain removal. The primary outcome was SSI, as defined by CDC criteria. Operative and postoperative protocols were standardized. Secondary endpoints included clinical outcomes up to 1 year and all implant loss, or reoperation. RESULTS: There were 112 TE-IBR patients (180 breasts) using ADM who were randomized into 2 study arms, with 62 patients in the 24-hour group and 50 in the extended group. Surgical site infection was diagnosed in 12 patients in the 24-hour group and 11 in the extended group (19.4% vs 22.0%, p = 0.82). The extended group had 7 patients who required IV antibiotics and an overall implant loss in 7 patients (14.0%). The 24-hour group had 4 patients who required IV antibiotics, with 3 requiring removal (4.8%). Patients with diabetes, postoperative seroma, or wound dehiscence were all more likely to develop SSI (p < 0.02). CONCLUSIONS: In a randomized controlled noninferiority trial, 24 hours of antibiotics is equivalent to extended oral antibiotics for SSI in TE-IBR patients. Additional multicenter trials will further assess this important aspect of TE-IBR postoperative care.

The primary aim of this study was to evaluate the outcomes of a series of patients with Charcot neuroarthropathy (CN) who were evaluated in a tertiary care setting. We hypothesized that those patients with CN who presented with a Charcot-related foot wound would have lower rates of successful limb salvage than patients who presented without a wound. Two hundred forty-five patients (280 feet) were identified with diabetic CN during the time period from January 1, 2005, to June 1, 2015. This consecutive cohort of patients was treated by a single surgeon and had a mean age of 57.9 ± 10.0 years. Our CN patients were divided into 2 groups for the purpose of our analysis. Our study group included those patients who presented to our clinic with a Charcot-related foot wound. Our control group was composed of CN patients who presented without a Charcot-related foot wound. Overall, 78 feet (27.9%) were successfully treated nonoperatively and 202 feet (72.1%) required some type of surgery. Of the 202 feet that received surgery, 22 (10.9%) were not felt to be suitable for reconstruction and underwent a definitive transtibial amputation without an attempt at reconstruction. An additional 18 patients underwent soft tissue surgery, which included drainage of infection, posterior muscle group lengthening, or soft tissue reconstructive flap surgery. The remaining 162 feet underwent osseous surgery, which included ostectomies for osteomyelitis, exostectomies, osteotomies, and arthrodesis. Eighteen of the 180 limbs (10.0%) that underwent soft tissue or osseous reconstruction ultimately required a transtibial amputation, resulting in a successful limb salvage rate of 90.0%. Thirty-five amputations were performed in 164 feet (21.3%) with Charcot-related foot wounds compared with 5 amputations in 116 feet (4.5%) without Charcot-related foot wounds (OR 6.02, 95% CI 2.28-15.91, P < .0001). The presence of a Charcot-related foot wound at presentation increased the likelihood of a major lower extremity amputation by a factor of 6. Other risk factors that were associated with major amputation in patients included active infection at presentation, nonunion/instability after reconstruction, and a postoperative wound problem. The overall rate of successful limb salvage in patients deemed reconstructive candidates was 90%. Level III, retrospective, case-control study.