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Diabetes is Associated with an Increased Risk of Wound Complications and Readmission in Patients with Surgically Managed Pressure Ulcers

Alfonso, Allyson R; Kantar, Rami S; Ramly, Elie P; Daar, David A; Rifkin, William J; Levine, Jamie P; Ceradini, Daniel J
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 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.
PMID: 30663823
ISSN: 1524-475x
CID: 3610362

From "Coordinated" to "Integrated" Residency Training: Evaluating Changes and the Current State of Plastic Surgery Programs

Rifkin, William J; Cammarata, Michael J; Kantar, Rami S; DeMitchell-Rodriguez, Evellyn; Navarro, Carla M; Diaz-Siso, J Rodrigo; Ceradini, Daniel J; Stranix, John T; Saadeh, Pierre B
BACKGROUND:Since the inception of the integrated model, educational leaders have predicted its ongoing evolution, as the optimal plastic surgery curriculum remains a source of debate. With the now complete elimination of the "coordinated" pathway, the total number of integrated programs has arguably reached a plateau. As such, this study examines the current state of training in integrated residencies and re-evaluates the variability in the first 3 years of training observed previously. METHODS:Program information was obtained for all 68 integrated plastic surgery programs, of which rotation schedules were available for 59. Plastic surgery, general surgery, and surgical subspecialty exposures were quantified and compared. Inclusion of rotations "strongly suggested" by the Residency Review Committee and the American Board of Plastic Surgery was also examined. RESULTS:PGY1-3 plastic surgery exposure ranged from 3.5-25 months (mean 13.9 ± 5.4). General surgery rotations ranged from 5-22.5 months (mean 12.8 ± 4.7). Surgical subspecialty rotations ranged from 0-8 months (mean 3.6 ± 1.8). There was no difference in mean plastic surgery exposure between programs based within departments versus divisions (15.4 vs. 13.3 months; p=0.184). There remained significant variability in the inclusion of 18 non-plastic surgery rotations including the "strongly suggested" rotations. CONCLUSIONS:Plastic surgery exposure remains highly variable with over a 7-fold difference between programs. This suggests that programs are still sorting out the "ideal" curriculum. However, there is an overall trend towards earlier and increased plastic surgery exposure in PGY1-3, which now exceeds the average time spent on general surgery rotations.
PMID: 30624340
ISSN: 1529-4242
CID: 3579912

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

Rifkin, William J; Kantar, Rami S; Daar, David A; Alfonso, Allyson R; Cammarata, Michael J; Wilson, Stelios C; Diaz-Siso, J Rodrigo; Levine, Jamie P; Stranix, John T; Ceradini, Daniel J
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:-tests for continuous variables. Multivariate regression was performed to control for confounders. RESULTS: = 0.14) for local flaps of the lower extremity. CONCLUSIONS: 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.
PMID: 30579287
ISSN: 1098-8947
CID: 3560272

Dysregulation of Nrf2/Keap1 Redox Pathway in Diabetes Affects Multipotency of Stromal Cells

Rabbani, Piul S; Soares, Marc A; Hameedi, Sophia G; Kadle, Rohini L; Mubasher, Adnan; Kowzun, Maria; Ceradini, Daniel J
The molecular and cellular level reaches of the metabolic dysregulations that characterize diabetes are yet to be fully discovered. As mechanisms underlying management of reactive oxygen species (ROS) gain interest as crucial factors in cell integrity, questions arise about the role of redox cues in regulation and maintenance of bone marrow-derived multipotent stromal cells (BMSCs) that contribute to wound healing, particularly in diabetes. Through comparison of BMSCs from wild type and diabetic mice, with a known redox and metabolic disorder, we found that the cytoprotective Nrf2/Keap1 pathway is dysregulated and functionally insufficient in diabetic BMSCs. Nrf2 is basally active, but in chronic ROS we found irregular inhibition of Nrf2 by Keap1, altered metabolism and limited BMSC multipotency. Forced upregulation of Nrf2-directed transcription, through knockdown of Keap1, restores redox homeostasis. Normalized Nrf2/Keap1 signaling restores multipotent cell properties in diabetic BMSCs through Sox2 expression. These restored BMSCs can resume their role in regenerative tissue repair and promote healing of diabetic wounds. Knowledge of diabetes and hyperglycemia-induced deficits in BMSC regulation, and strategies to reverse them offers translational promise. Our study establishes Nrf2/Keap1 as a cytoprotective pathway, as well as a metabolic rheostat that affects cell maintenance and differentiation switches in BMSCs.
PMID: 30352880
ISSN: 1939-327x
CID: 3384652

Advanced Age Is a Risk Factor for Complications Following Abdominal Panniculectomy

Cammarata, Michael J; Kantar, Rami S; Rifkin, William J; Greenfield, Jason A; Levine, Jamie P; Ceradini, Daniel J
BACKGROUND:Widespread adoption of bariatric surgery in the treatment of obesity has led to greater numbers of patients seeking panniculectomy, including aged patients, who represent a rapidly growing proportion of the U.S population. Although the quality of life and functional benefits of abdominal panniculectomy have been established, its safety in patients 65 years and older has not been evaluated. METHODS:The American College of Surgeons National Surgical Quality Improvements (ACS-NSQIP) database was used to identify patients undergoing panniculectomy between 2010 and 2015. Age 65 years and older was the risk factor of interest, and primary outcomes included 30-day wound complications, overall complications, reoperation, readmission, and mortality. Multivariate regression was performed to control for confounders. RESULTS:Review of the database identified 7030 patients who underwent abdominal panniculectomy. When stratified by age, 6455 (91.8%) of patients were younger than 65, and 575 (8.2%) were 65 or older. Multivariate regression analysis demonstrated that age over 65 was a significant independent risk factor for wound complications (OR = 1.81; 95% CI 1.35-2.42; p < 0.001) and all complications (OR = 1.46; 95% CI 1.15-1.87; p = 0.002). BMI, smoking, diabetes, and partial or total dependence were also identified as significant independent risk factors for wound and all complications. CONCLUSION/CONCLUSIONS:Our analysis demonstrates that advanced age is an independent risk factor for wound and overall complications following abdominal panniculectomy. These results highlight the importance of preoperative evaluation and optimization of modifiable preoperative risk factors as well as close postoperative follow-up for safe outcomes in patients 65 and older.
PMID: 30238217
ISSN: 1708-0428
CID: 3300872

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

Stranix, John T; Rifkin, William J; Lee, Z-Hye; Anzai, Lavinia; Jacoby, Adam; Ceradini, Daniel J; Thanik, Vishal; Saadeh, Pierre B; Levine, Jamie P
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:-tests. RESULTS: = 0.004). CONCLUSION/CONCLUSIONS: 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.
PMID: 29906811
ISSN: 1098-8947
CID: 3155352

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

Kantar, Rami S; Rifkin, William J; David, Joshua A; Cammarata, Michael J; Diaz-Siso, J Rodrigo; Levine, Jamie P; Golas, Alyssa R; Ceradini, Daniel J
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) (β = .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.
PMID: 29719063
ISSN: 1098-2752
CID: 3056552

In Vivo Imaging of Reactive Oxygen Species in a Murine Wound Model

Rabbani, Piul S; Abdou, Salma A; Sultan, Darren L; Kwong, Jennifer; Duckworth, April; Ceradini, Daniel J
The generation of reactive oxygen species (ROS) is a hallmark of inflammatory processes, but in excess, oxidative stress is widely implicated in various pathologies such as cancer, atherosclerosis and diabetes. We have previously shown that dysfunction of the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/ Kelch-like erythroid cell-derived protein 1 (Keap1) signaling pathway leads to extreme ROS imbalance during cutaneous wound healing in diabetes. Since ROS levels are an important indicator of progression of wound healing, specific and accurate quantification techniques are valuable. Several in vitro assays to measure ROS in cells and tissues have been described; however, they only provide a single cumulative measurement per sample. More recently, the development of protein-based indicators and imaging modalities have allowed for unique spatiotemporal analyses. L-012 (C13H8ClN4NaO2) is a luminol derivative that can be used for both in vivo and in vitro chemiluminescent detection of ROS generated by NAPDH oxidase. L-012 emits a stronger signal than other fluorescent probes and has been shown to be both sensitive and reliable for detecting ROS. The time lapse applicability of L-012-facilitated imaging provides valuable information about inflammatory processes while reducing the need for sacrifice and overall reducing the number of study animals. Here, we describe a protocol utilizing L-012-facilitated in vivo imaging to quantify oxidative stress in a model of excisional wound healing using diabetic mice with locally dysfunctional Nrf2/Keap1.
PMID: 30507922
ISSN: 1940-087x
CID: 3520222

Appraisal of the Free Ulnar Flap Versatility in Craniofacial Soft-tissue Reconstruction

Kantar, Rami S; Rifkin, William J; Cammarata, Michael J; Jacoby, Adam; Farber, Scott J; Diaz-Siso, J Rodrigo; Ceradini, Daniel J; Rodriguez, Eduardo D
The unique anatomical characteristics of the forearm region make it especially popular as a free flap donor site for craniofacial soft-tissue reconstruction. The free ulnar forearm flap is less hirsute and allows for better concealment of donor site scar as compared with its radial counterpart. Despite these factors, the free radial forearm flap remains more popular among reconstructive surgeons. Through the presented case series, we hope to emphasize the versatile nature of the free ulnar forearm flap in addressing various craniofacial soft-tissue defects. Following institutional review board approval, a retrospective review of the senior authors' clinical experience performing microvascular free ulnar forearm flap reconstruction of craniofacial soft-tissue defects was performed. A total of 10 patients were identified through our review. Soft-tissue defect locations included lower eyelid (n = 2), tongue and floor of mouth (n = 2), lower lip (n = 2), palatopharyngeal area (n = 1), nose (n = 1), and palate (n = 1). Trauma was the most common defect etiology (n = 5), followed by malignancy (n = 4), and iatrogenic injury in 1 case. All patients demonstrated good aesthetic and functional outcomes related to vision, speech, and oral intake at follow-up when applicable. The free ulnar forearm flap is a versatile reconstructive option that can be used to address a wide spectrum of craniofacial soft-tissue defects and offers numerous advantages over its radial counterpart.
PMID: 30349774
ISSN: 2169-7574
CID: 3384452

Ex Vivo Major Histocompatibility Complex I Knockdown Prolongs Rejection-free Allograft Survival

Chang, Jessica B; Rifkin, William J; Soares, Marc A; Duckworth, April; Rao, Nakul; Low, Yee Cheng; Massie, Jonathan P; Rabbani, Piul S; Saadeh, Pierre B; Ceradini, Daniel J
Background/UNASSIGNED:Widespread application of vascularized composite allotransplantation (VCA) is currently limited by the required lifelong systemic immunosuppression and its associated morbidity and mortality. This study evaluated the efficacy of ex vivo (after procurement but before transplantation) engineering of allografts using small interfering RNA to knockdown major histocompatibility complex I (MHC-I) and prolong rejection-free survival. Methods/UNASSIGNED:Endothelial cells (ECs) were transfected with small interfering RNA targeted against MHC-I (siMHC-I) for all in vitro experiments. MHC-I surface expression and knockdown duration were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. After stimulating Lewis recipient cytotoxic lymphocytes (CTL) with allogeneic controls or siMHC-I-silenced ECs, lymphocyte proliferation, CTL-mediated and natural killer-mediated EC lysis were measured. Using an established VCA rat model, allografts were perfused ex vivo with siMHC-I before transplantation. Allografts were analyzed for MHC-I expression and clinical/histologic evidence of rejection. Results/UNASSIGNED:< 0.05). Conclusions/UNASSIGNED:Ex vivo siMHC-I engineering can effectively modify allografts and significantly prolong rejection-free allograft survival. This novel approach may help reduce future systemic immunosuppression requirements in VCA recipients.
PMID: 30276052
ISSN: 2169-7574
CID: 3327792