Keyianoosh Z. Paydar

Sustained expression of Hif-1α in the diabetic environment promotes angiogenesis and cutaneous wound repair

Impaired wound healing in diabetic patients is associated with deficiencies in the production of factors involved in cell proliferation and migration, such as vascular endothelial growth factor. However, it remains unclear how the transcriptional regulation of the genes encoding these factors is affected by the diabetic environment. Hypoxia‐inducible factor‐1α (Hif‐1α), the regulatory subunit of the Hif‐1 transcription factor, plays an important role in activating many of these genes. Therefore, we tested whether Hif‐1α function is impaired in the diabetic wound environment and whether restoring Hif‐1 function improves wound healing. Here, we show that Hif‐1α protein levels are dramatically reduced in wounds of leptin receptor‐deficient diabetic mice compared with nondiabetic littermates. Reduction in Hif‐1α levels results in decreased DNA‐binding activity and in decreased expression of several Hif‐1 target genes, including vascular endothelial growth factor, heme oxygenase‐1, and inducible nitric oxide synthase. Furthermore, we demonstrate that sustained expression of Hif‐1α in leptin receptor‐deficient diabetic wounds restores expression of these factors, enhances angiogenesis, and significantly accelerates wound healing. Taken together, these results suggest that Hif‐1α function plays a significant role in wound healing and reduced levels of Hif‐1α may contribute to impaired healing.

Peripheral Nerve Injuries: An International Survey of Current Treatments and Future Perspectives

Peripheral nerve injuries are a serious health concern and leave many patients with lifelong disabilities. There is little information about incidences, current practice, outcomes, and type of research that may help delineate new strategies. A questionnaire was designed to determine characteristics of peripheral nerve injuries and the need for alternative strategies and sent to 889 plastic, hand, trauma, and orthopedic surgeons in 49 countries; 324 completed surveys were collected and analyzed (total response rate of 36.45%). The majority of institutions treat more than 3000 patients annually. Trauma was the leading cause of injury with the majority located on the upper extremity. In most cases, a primary repair was achieved, but 2.52% were unrepairable. The overall outcome was linked to their Sunderland classification (SCL). A grade 1 nerve injury (SCL-1) reached a maximum outcome after 7.15 months. SCL-2, -3, -4, and -5 needed 10.69, 14.08, 17.66, and 19.03 months, respectively. Tissue engineering was considered the most important research field, resulting in a visual analogue scale of 8.6. Despite marked advances in the treatment of peripheral nerve injuries, clinical outcomes still appear unsatisfactory. The importance of research in the field of tissue engineering should be emphasized as a pathway toward improving these outcomes.

Implantable Venous Doppler Monitoring in Head and Neck Free Flap Reconstruction Increases the Salvage Rate

BACKGROUND Free flap success depends on rapid identification and subsequent salvage of failing flaps. Conventional free flap monitoring techniques require an external component, whereas an implantable monitor readily indicates changes in free flap perfusion, especially in buried flaps used in head and neck reconstruction. METHODS This is a retrospective review of 169 consecutive head and neck free flaps reconstructed mostly for oncologic surgical defects in 155 patients from April of 2000 to December of 2006, all of which were monitored by an implantable venous Doppler device. RESULTS There were 25 buried flaps, representing 14.8 percent of 169 flaps. Flap ischemia caused by thrombosis (n = 16), hematoma (n = 2), or tight closure (n = 1) occurred in 11.2 percent of the cases. The Doppler probe detected all of the failing free flaps, and we were able to salvage 18 of 19 ischemic flaps (94.7 percent). All Doppler-detected ischemic nonburied flaps (100 percent) and three of the four buried free flaps were salvaged (75 percent). There were 33 total complications (19.5 percent), with thrombosis occurring in 9.5 percent of the flaps, whereas 12 flaps required reoperation for vascular revision (7.1 percent). The mortality rate was less than 1 percent (0.6 percent). The overall success rate using the implantable Doppler probe was 98.2 percent, which was similar to that of the most recent reported cases of all free flaps in the literature, with significant improvement in the salvage rate for both buried and nonburied head and neck free flaps. CONCLUSION The implantable Doppler probe is a useful monitoring device in buried free flaps and should be considered for use in head and neck reconstruction.

Stromal vascular fraction: A regenerative reality? Part 1: Current concepts and review of the literature

Stromal Vascular Fraction (SVF) is a heterogeneous collection of cells contained within adipose tissue that is traditionally isolated using enzymes such as collagenase. With the removal of adipose cells, connective tissue and blood from lipoaspirate, comes the SVF, a mix including mesenchymal stem cells, endothelial precursor cells, T regulatory cells, macrophages, smooth muscle cells, pericytes and preadipocytes. In part 1 of our 2-part series, we review the literature with regards to the intensifying interest that has shifted toward this mixture of cells, particularly due to its component synergy and translational potential. Trials assessing the regenerative potential of cultured Adipose Derived Stem Cells (ADSCs) and SVF demonstrate that SVF is comparably effective in treating conditions ranging from radiation injuries, burn wounds and diabetes, amongst others. Aside from their use in chronic conditions, SVF enrichment of fat grafts has proven a major advance in maintaining fat graft volume and viability. Many SVF studies are currently in preclinical phases or are moving to human trials. Overall, regenerative cell therapy based on SVF is at an early investigative stage but its potential for clinical application is enormous.

Stromal vascular fraction: A regenerative reality? Part 2: Mechanisms of regenerative action

Adipose tissue is a rich source of cells with emerging promise for tissue engineering and regenerative medicine. The stromal vascular fraction (SVF), in particular, is an eclectic composite of cells with progenitor activity that includes preadipocytes, mesenchymal stem cells, pericytes, endothelial cells, and macrophages. SVF has enormous potential for therapeutic application and is being investigated for multiple clinical indications including lipotransfer, diabetes-related complications, nerve regeneration, burn wounds and numerous others. In Part 2 of our review, we explore the basic science behind the regenerative success of the SVF and discuss significant mechanisms that are at play. The existing literature suggests that angiogenesis, immunomodulation, differentiation, and extracellular matrix secretion are the main avenues through which regeneration and healing is achieved by the stromal vascular fraction.

Predictive risk factors of venous thromboembolism in autologous breast reconstruction surgery.

BackgroundVenous thromboembolism (VTE) can be a significant cause of morbidity and mortality in autologous breast reconstruction surgery. The aim of this study was to evaluate the effect of patient characteristics, comorbidities, payer type, reconstruction type, reconstruction timing, radiation, chemotherapy, and teaching status of hospital on VTE (deep venous thrombosis and/or pulmonary embolism) in autologous breast reconstructive surgery. MethodsUsing the Nationwide Inpatient Sample (NIS) database, we examined the clinical data of patients who underwent autologous breast reconstructive surgery in 2009 to 2010 in the United States. Univariate and multivariate regression analyses were performed to identify factors predictive of in-hospital VTE. ResultsA total of 35,883 patients underwent autologous breast reconstructive surgery during this period. Overall rate of VTE was 0.13%. The highest rate of VTE (0.26%) was observed in pedicled transverse rectus abdominis myocutaneous flap. Patients who experienced VTE had significantly longer mean hospital stay (11.6 vs 3.9 days; P < 0.001) and higher mean total hospital charges (

Capsular Contracture in Implant-Based Breast Reconstruction: Examining the Role of Acellular Dermal Matrix Fenestrations.

146,432 vs

Use of fenestrations in acellular dermal allograft in two-stage tissue expander/implant breast reconstruction.

61,794; P < 0.001) compared with non-VTE patients; however, there was no significant difference observed in mortality rate (VTE, 0.0% vs non-VTE, 0.04%; P = 0.886). Using multivariate regression analysis, immediate reconstruction after mastectomy (adjusted odds ratio [AOR], 5.4), older than 65 years (AOR, 4.2), obesity (AOR, 3.7), history of chemotherapy (AOR, 3.5), and chronic lung disease (AOR, 2.5) were associated with higher risk of VTE. There was no association between race, payer type, diabetes, hypertension, liver disease, congestive heart failure, peripheral vascular disease, chronic kidney disease, smoking, reconstruction type, radiation, or teaching status of hospital on VTE. ConclusionsIn patients undergoing autologous breast reconstruction surgery, immediate reconstruction, older than 65 years, obesity, history of chemotherapy, and chronic lung disease are all independent predictors of higher VTE. Surgeons should consider these factors and use appropriate prophylaxis to minimize the risk of VTE development.

Phenotypic Analysis of Stromal Vascular Fraction after Mechanical Shear Reveals Stress-Induced Progenitor Populations.

Background: Acellular dermal matrices have been proposed to decrease the incidence of capsular contracture in implant-based breast reconstructions. The authors have modified acellular dermal matrices with fenestrations to facilitate greater lower pole expansion and improve contour. The effect of fenestrations on the ability of matrices to suppress capsule formation, however, has not been examined. Methods: A retrospective review of all fenestrated acellular dermal matrix–assisted, implant-based breast reconstructions performed by the two senior authors, with a minimum of 1-year follow-up after permanent implant placement, was completed. Patient demographics, details of extirpative and reconstructive procedures, and complications were examined. Capsular contractures were scored according to the Baker grading scale and compared to those reported in the literature. Results: Thirty patients (50 breasts) underwent fenestrated acellular dermal matrix–assisted reconstruction, with mean follow-up times of 3.3 and 2.6 years after expander placement and implant exchange, respectively. Seven patients (23 percent) had a body mass index greater than 30 kg/m2, three (10 percent) were active smokers, and six breasts (12 percent) were irradiated. Complications included one infection (2 percent), six cases (12 percent) of incisional superficial skin necrosis, and one (2 percent) tissue expander extrusion. Zero breasts had clinically significant Baker grade III/IV capsular contracture. The average Baker grade was 1.1. Conclusions: Fenestrated acellular dermal matrices decrease capsular contracture to rates similar to what is seen with nonfenestrated matrices. Further research is necessary to determine whether this observation is a result of decreased need for inferolateral acellular dermal matrix coverage to achieve these effects or modified physical interaction of acellular dermal matrices with surrounding soft tissues. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Single-Lumen and Multi-Lumen Poly(Ethylene Glycol) Nerve Conduits Fabricated by Stereolithography for Peripheral Nerve Regeneration In Vivo

Summary: The authors present a new technique of alteration of the acellular dermal matrix through strategically placed fenestrations, improving the reconstructive experience and overall cosmetic outcome. The authors present a retrospective chart review following two surgeons’ experience at the University of California, Irvine, Department of Plastic Surgery using surgeon-designed fenestrated acellular dermal matrices in two-stage tissue expander breast reconstruction. The authors found that this leads to improved intraoperative fill volume, decreased number of postoperative expansions, increased expansion rate with subjectively less pain, decreased time to full expansion, and subjectively improved cosmetic outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.