Mesenchymal stem cell dysfunction in diabetes.

Diabetes mellitus (DM) is a chronic disease that results in a variety of systemic complications. Recently, stem cell-based therapies have been proposed as potential modalities to manage DM related complications. Mesenchymal stem cell (MSC) based therapies are often considered as an ideal stem cell-based treatment for DM management due to their immunosuppressive characteristics, anti-inflammatory properties and differentiation potential. While MSCs show tremendous promise, the underlying functional deficits of MSCs in DM patients is not well understood. Using the MEDLINE database to define these functional deficits, our search yielded 1826 articles of which 33 met our inclusion criteria. This allowed us to review the topic and illuminate four major molecular categories by which MSCs are compromised in both Type 1 DM and Type II DM models which include: (1) changes in angiogenesis/vasculogenesis, (2) altered pro-inflammatory cytokine secretion, (3) increased oxidative stress markers and (4) impaired cellular differentiation and decreased proliferation. Knowledge of the deficits in MSC function will allow us to more clearly assess the efficacy of potential biologic therapies for reversing these dysfunctions when treating the complications of diabetic disease.

Age and Number of Surgeries Increase Risk for Complications in Polytrauma Patients with Operative Maxillofacial Fractures.

BACKGROUND: Poly-trauma patients often sustain complex head/neck injuries requiring prolonged hospitalizations and multiple operations. Few studies have evaluated the associated injury patterns and risk factors for poor clinical outcomes. METHODS: Consecutive poly-trauma patients with operative maxillofacial fractures treated at a level 1 trauma medical center between 1995 and 2013 were evaluated. Concomitant head/neck injuries to identify potential injury patterns were numerated. Lastly, a multivariate analysis was performed to determine independent risk factors for complications during the acute hospitalization period. RESULTS: Totally, 232 poly-trauma patients presented with operative maxillofacial fractures, while 38.8% of patients had a secondary maxillofacial fracture, 16.4% had intracranial hemorrhage, 23.7% had skull fractures, and 12.1% had spinal fractures. The rate of complication during admission was 28.3%. Multivariate analysis revealed advanced patient age and increased number of operations to predict the rate of complication. Patients requiring more than one operation had a 1.8-fold increase in complication rate (p<0.01) and older patients had a 4.5% increase in complication rate (p<0.05) for every year of increased age. CONCLUSION: Poly-trauma patients have a high incidence of secondary maxillofacial fractures, concomitant head/neck injury, and inpatient complication rate. Knowledge of associated injury patterns can help increased awareness and can guide physician decision-making to avoid missed/delayed injuries.

Prepectoral Breast Reconstruction with Fenestrated Acellular Dermal Matrix: A Novel Design.

Fenestrated acellular dermal matrix (ADM) has improved patient outcomes in both direct-to-implant and 2-stage tissue expander/implant breast reconstruction. This technical alteration utilizes optimal fenestration overlap to enhance the breast reconstruction experience. We present a novel, surgeon-designed shaped fenestrated ADM, placed in the recently repopularized prepectoral pocket for anterior coverage of implants in direct-to-implant and 2-stage breast reconstruction. A retrospective review of 10 patients (18 breasts) who underwent direct-to-implant or 2-stage breast reconstruction utilizing fenestrated shaped ADM in the prepectoral plane at a major academic institution in 2016 was conducted. Sixteen breasts (88.9%) underwent direct-to-implant reconstruction, and 2 breasts (11.1%) received tissue expanders. All reconstructions were performed using FlexHD Pliable ADM with surgeon-designed shape and fenestrations. The average implant size was 544.4 cc (±137.2 cc). The average intraoperative tissue expander fill volume measured 450 cc (90% of tissue expander size). The single expander case utilized 1 office fill (day 21) for full expansion. Major complications requiring reoperation within 90 days postoperatively were observed in 22.2% (4 breasts) of reconstructions. Three breasts (16.7%) due to partial mastectomy flap necrosis, 1 breast (5.5%) explantation due to infection. There was no seroma or capsular contracture. Prepectoral reconstruction with shaped fenestrated ADM is safe with high intraoperative fill volumes and facilitates more direct-to-implant reconstructions. Patients undergo fewer postoperative expansions, experience less time to full expansion, and subjectively report less pain. Patients benefit from improved cosmetic outcomes with better shape and no functional loss or animation deformity.

Trends in Rhinoplasty Research: A 20-Year Bibliometric Analysis.

BACKGROUND: Rhinoplasty is a popular aesthetic and reconstructive surgical procedure. It is one of the top five surgical cosmetic procedures performed worldwide. OBJECTIVES: To evaluate global trends in rhinoplasty research spanning 20 years between 1994 and 2013. METHODS: The top 15 plastic surgery and otolaryngology journals containing rhinoplasty research were determined using impact factors (IF). A database of rhinoplasty articles from 1994 to 2013 was created to include the following classifications: IF, authors' geographic location, study design, level of evidence (LOE), and pertinence to aesthetic or reconstructive rhinoplasty. Productivity index and productivity share were calculated for each region. RESULTS: A total of 1244 rhinoplasty articles were included in the database. The mean IF among the 15 journals increased from 0.75 in 1994 to 1.90 in 2013 (p < 0.001). The majority of rhinoplasty publications were clinical in study design (91.0%) and were predominantly of weaker LOE (level IV: 42.4%; level V: 33.2%). The USA led in proportion of total rhinoplasty publications by volume and productivity index (37.9%, 41.2%), followed by Asia (29.1%, 28.2%) and Western Europe (18.8%, 18.2%). The majority of articles published were classified as aesthetic (60.4%), whereas 30.6% were reconstructive; there was a significant increase in the proportion of aesthetic rhinoplasty articles published per year (p = 0.009). CONCLUSIONS: The USA has consistently been the most productive country in rhinoplasty research. However, its lead has diminished over the last 20 years. The trend in rhinoplasty research appears to be toward aesthetic rather than reconstructive topics. Attention should be given to producing stronger LOE studies. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Readability of Online Materials for Rhinoplasty.

BACKGROUND: Rhinoplasty is a popular aesthetic and reconstructive surgical procedure. However, little is known about the content and readability of online materials for patient education. The recommended grade level for educational materials is 7th to 8th grade according to the National Institutes of Health (NIH). This study aims to assess the readability of online patient resources for rhinoplasty. METHODS: The largest public search engine, Google, was queried using the term "rhinoplasty" on February 26, 2016. Location filters were disabled and sponsored results excluded to avoid any inadvertent search bias. The 10 most popular websites were identified and all relevant, patient-directed information within one click from the original site was downloaded and saved as plain text. Readability was analyzed using five established analyses (Readability-score.com, Added Bytes, Ltd., Sussex, UK). RESULTS: Analysis of ten websites demonstrates an average grade level of at least 12th grade. No material was at the recommended 7th to 8th grade reading level (Flesch-Kincaid, 11.1; Gunning-Fog, 14.1; Coleman-Liau, 14.5; SMOG 10.4; Automated Readability, 10.7; Average Grade Level, 12.2). Overall Flesch-Kincaid Reading Ease Index was 43.5, which is rated as "difficult." CONCLUSION: Online materials available for rhinoplasty exceed NIH-recommended reading levels, which may prevent appropriate decision-making in patients considering these types of surgery. Outcomes of this study identify that Plastic Surgeons should be cognizant of available online patient materials and make efforts to develop and provide more appropriate materials. Readability results can also contribute to marketing strategy and attracting a more widespread interest in the procedure.

Adipose-Derived Tissue in the Treatment of Dermal Fibrosis: Antifibrotic Effects of Adipose-Derived Stem Cells.

Treatment of hypertrophic scars and other fibrotic skin conditions with autologous fat injections shows promising clinical results; however, the underlying mechanisms of its antifibrotic action have not been comprehensively studied. Adipose-derived stem cells, or stromal cell-derived factors, inherent components of the transplanted fat tissue, seem to be responsible for its therapeutic effects on difficult scars. The mechanisms by which this therapeutic effect takes place are diverse and are mostly mediated by paracrine signaling, which switches on various antifibrotic molecular pathways, modulates the activity of the central profibrotic transforming growth factor ß/Smad pathway, and normalizes functioning of fibroblasts and keratinocytes in the recipient site. Direct cell-to-cell communications and differentiation of cell types may also play a positive role in scar treatment, even though they have not been extensively studied in this context. A more thorough understanding of the fat tissue antifibrotic mechanisms of action will turn this treatment from an anecdotal remedy to a more controlled, timely administered technology.

Deconstructing negative pressure wound therapy.

Since its introduction 20 years ago for the treatment of chronic wounds, negative pressure wound therapy use has expanded to a variety of other wound types. Various mechanisms of action for its efficacy in wound healing have been postulated, but no unifying theory exists. Proposed mechanisms include induction of perfusion changes, microdeformation, macrodeformation, exudate control and decreasing the bacterial load in the wound. We surmise that these different mechanisms have varying levels of dominance in each wound type. Specifically, negative pressure wound therapy is beneficial to acute open wounds because it induces perfusion changes and formation of granulation tissue. Post-surgical incisional wounds are positively affected by perfusion changes and exudate control. In the context of chronic wounds, negative pressure wound therapy removes harmful and corrosive substances within the wounds to affect healing. When skin grafts and dermal substitutes are used to close a wound, negative pressure wound therapy is effective in promoting granulation tissue formation, controlling exudate and decreasing the bacterial load in the wound. In this review, we elucidate some of the mechanisms behind the positive wound healing effects of negative pressure wound therapy, providing possible explanations for these effects in different wound types.

Venous Thromboembolism: A Comparison of Chronic Spinal Cord Injury and General Surgery Patients in a Metropolitan Veterans Affairs Hospital.

BACKGROUND: Venous thromboembolic events result in significant morbidity, mortality, and costly therapeutic interventions. As medical resource allocation strategies are becoming more pervasive, appropriate risk stratification and prophylactic regimens are essential. Previous studies have shown a decreased incidence of perioperative venous thromboembolism in the chronic spinal cord injury population. The question remains of whether chronic spinal cord injury is protective against venous thromboembolism. METHODS: A retrospective review of all cases involving chronic spinal cord injury patients who underwent plastic and reconstructive surgery operations (n = 424) and general surgery patients (n = 777) with a primary outcome of deep venous thrombosis or pulmonary embolism within 90 days of surgery was performed. RESULTS: The incidence of postoperative deep venous thrombosis in the control and spinal cord injury groups was 1.7 percent and 0.2 percent, respectively (p = 0.027). However, such significance was not observed with regard to postoperative pulmonary embolism incidence (p = 0.070). Collectively, the incidence of postoperative venous thromboembolism-specifically, deep venous thrombosis or pulmonary embolism-was significantly greater in the general surgery population (p = 0.014). A nearly 10-fold increased risk of venous thromboembolism was seen among the control group (1.9 percent versus 0.2 percent) despite administration of optimal prophylaxis. CONCLUSIONS: This study demonstrates a profoundly low incidence of venous thromboembolism among chronic spinal cord injury patients compared with general surgery patients. Future efforts to elucidate how chronic spinal cord injury confers a protective mechanism may potentially influence the evolution of venous thromboembolism prevention guidelines, and spark the development of alternative prophylactic agents or customized application of prevention efforts.

Plastic Surgery and Acellular Dermal Matrix: Highlighting Trends from 1999 to 2013.

The last decade has ushered in a rapidly expanding global discussion regarding acellular dermal matrix (ADM) applications, economic analyses, technical considerations, benefits, and risks, with recent emphasis on ADM use in breast surgery. This study aims to evaluate global trends in ADM research using bibliometric analysis. The top nine Plastic Surgery journals were determined by impact factor (IF). Each issue of the nine journals between 1999 and 2013 was accessed to compile a database of articles discussing ADM. Publications were further classified by IF, authors' geographic location, study design, and level of evidence (LOE, I-V). Productivity index and productivity share were calculated for each region. In total, 256 ADM articles were accessed. The annual global publication volume increased significantly by 4.2 (0.87) articles per year (p<0.001), with a mean productivity index of 36.3 (59.0). The mean impact factor of the nine journals increased significantly from 0.61 (0.11) to 2.47 (0.99) from 1993 to 2013 (p<0.001). Despite this increase in the global ADM literature, the majority of research was of weaker LOE (level I: 2.29% and level II: 9.17%). USA contributed the most research (87%), followed by Asia (4.76%) and Western Europe (4.71%). USA contributed the greatest volume of research. Regarding clinical application of ADM, the majority of publications focused on ADM use in breast surgery, specifically breast reconstruction (154 articles, 60.2%). The majority of research was of lower LOE; thus, efforts should be made to strengthen the body of literature, particularly with regard to cost analysis.

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

BACKGROUND: Optimization of fat grafting continues to gain increasing attention in the field of regenerative medicine. "Nanofat grafting" implements mechanical emulsification and injection of standard lipoaspirate for the correction of superficial rhytides and skin discoloration; however, little is known about the cellular constituents of the graft. Based on recent evidence that various stressors can induce progenitor activity, the authors hypothesized that the shear forces used in common fat grafting techniques may impact their regenerative capacities. METHODS: Lipoaspirates were obtained from 10 patients undergoing elective procedures. Half of each sample was subjected to nanofat processing; the other half was left unchallenged. The viscosity of each sample was measured for computational analysis. The stromal vascular fraction of each sample was isolated, quantified, and analyzed by means of flow cytometry with two multicolor fluorescence antibody panels. RESULTS: Standard lipoaspirate is ideally suited for mechanical stress induction. The mechanical emulsification involved in nanofat processing did not affect cell number; however, viability was greatly reduced when compared with the stromal vascular fraction of standard lipoaspirate. Interestingly, nanofat processing resulted in stress-induced stromal vascular fraction with a higher proportion of endothelial progenitor cells, mesenchymal stem cells, and multilineage differentiating stress-enduring cells. Single-parameter analysis also revealed significant increases in CD34, CD13, CD73, and CD146 of the stress-induced stromal vascular fraction, markers associated with mesenchymal stem cell activity. CONCLUSIONS: Mechanical processing used in techniques such as nanofat grafting induces the up-regulation of progenitor phenotypes consistent with multipotency and pluripotency. These data provide a first step in characterizing the potential regenerative benefits realized through stress induction in fat grafting. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Current concepts related to hypertrophic scarring in burn injuries.

Scarring following burn injury and its accompanying aesthetic and functional sequelae still pose major challenges. Hypertrophic scarring (HTS) can greatly impact patients' quality of life related to appearance, pain, pruritus and even loss of function of the injured body region. The identification of molecular events occurring in the evolution of the burn scar has increased our knowledge; however, this information has not yet translated into effective treatment modalities. Although many of the pathophysiologic pathways that bring about exaggerated scarring have been identified, certain nuances in burn scar formation are starting to be recognized. These include the effects of neurogenic inflammation, mechanotransduction, and the unique interactions of burn wound fluid with fat tissue in the deeper dermal layers, all of which may influence scarring outcome. Tension on the healing scar, pruritus, and pain all induce signaling pathways that ultimately result in increased collagen formation and myofibroblast phenotypic changes. Exposure of the fat domes in the deep dermis is associated with increased HTS, possibly on the basis of altered interaction of adipose-derived stem cells and the deep burn exudate. These pathophysiologic patterns related to stem cell-cytokine interactions, mechanotransduction, and neurogenic inflammation can provide new avenues of exploration for possible therapeutic interventions.

The Effects of Perioperative Tamoxifen Therapy on Microvascular Flap Complications in Transverse Rectus Abdominis Myocutaneous/Deep Inferior Epigastric Perforator Flap Breast Reconstruction.

BACKGROUND: Tamoxifen is an important adjunct therapy in breast cancer treatment; however, it has been implicated in increasing microvascular flap complications. Current recommendations on stopping tamoxifen are conflicting and do not address tamoxifen therapy that is continued perioperatively. The purpose of this study is to determine whether tamoxifen taken at the time of free transverse rectus abdominis myocutaneous (TRAM) and deep inferior epigastric perforator (DIEP) flap breast reconstruction affects thrombotic complication rates. METHODS: A retrospective review of microvascular breast reconstruction with TRAM/DIEP flaps over the last 20 years was carried out at a single institution. Patients were divided into 2 cohorts: those receiving tamoxifen at the time of reconstruction (tamoxifen cohort) and those not taking tamoxifen (control). Demographic information, procedural characteristics, and rates of microvascular flap complications were compared. RESULTS: Forty-three patients (56 flaps) received tamoxifen at the time of microvascular breast reconstruction, and 185 patients (267 flaps) did not. Patients in the tamoxifen cohort had a lower mean age of 48.9 years (P = 0.013). A greater percentage of patients in the tamoxifen cohort had preoperative radiation (P < 0.0001) and chemotherapy (P = 0.018) and underwent delayed reconstruction (P < 0.0001). There were no significant differences between the 2 cohorts with regard to flap complications including both arterial and venous thrombosis, flap failure, and other local flap complications. CONCLUSIONS: Patients receiving tamoxifen during TRAM/DIEP flap breast reconstruction did not have increased rates of flap thrombosis or failure; therefore, stopping tamoxifen prior to these procedures may not be necessary.

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.

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.

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

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/m, 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.

Frequency and risk factors of blood transfusion in abdominoplasty in post-bariatric surgery patients: data from the nationwide inpatient sample.

BACKGROUND: There are limited data regarding blood transfusion following abdominoplasty, especially in post-bariatric surgery patients. The purpose of this study was to evaluate (1) the frequency and outcomes of blood transfusion in post-bariatric surgery patients undergoing abdominoplasty and (2) the predictive risk factors of blood transfusion in this patient population. METHODS: Using the Nationwide Inpatient Sample database, the authors examined the clinical data of patients with a history of bariatric surgery who underwent abdominoplasty from 2007 to 2011 in the United States. RESULTS: A total of 20,130 post-bariatric surgery patients underwent abdominoplasty during this period. Overall, 1871 patients (9.3 percent) received blood transfusion. Chronic anemia patients had the highest rate of blood transfusion (25.6 percent). Post-bariatric surgery patients who received blood transfusion experienced a significantly higher complication rate (10.1 percent versus 4.8 percent; p < 0.01), longer mean hospital stay (4.0 days versus 2.4 days; p < 0.01), and higher mean total hospital charges ($49,116 versus $33,927; p < 0.01). Multivariate regression analysis showed that deficiency anemia (adjusted OR, 3.8), congestive heart failure (adjusted OR, 2.4), concurrent breast reduction (adjusted OR, 1.5), diabetes mellitus (adjusted OR, 1.4), coronary artery disease (adjusted OR, 1.4), African American race (adjusted OR, 1.4), Hispanic race (adjusted OR, 1.4), and female sex (adjusted OR, 1.3) were all independent risk factors for blood transfusion. CONCLUSIONS: The blood transfusion rate in post-bariatric surgery abdominoplasty patients is not insignificant. Chronic anemia and congestive heart failure are the two major predictors of transfusion. Modifying risk factors such as anemia before abdominoplasty might significantly decrease the possibility of blood transfusion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Single-lumen and multi-lumen poly(ethylene glycol) nerve conduits fabricated by stereolithography for peripheral nerve regeneration in vivo.

BACKGROUND: The use of nerve conduits to facilitate nerve regrowth after peripheral nerve injury is limited to defects less than 3 cm. The purpose of this study is to determine the capability of novel single and multi-lumen poly(ethylene glycol) (PEG) conduits manufactured by stereolithography to promote peripheral nerve regeneration. MATERIALS AND METHODS: Eight Sprague Dawley rats with sharp transection injuries of the sciatic nerve were randomly assigned to receive single-lumen or multi-lumen PEG conduits to bridge a 10-mm gap. Sciatic nerve and conduit samples were harvested after 5 weeks, and axon number, myelin thickness, fiber diameter, and g-ratio were analyzed. The contralateral intact nerve was also harvested for comparison. RESULTS: Partial nerve regeneration was observed in three out of four single-lumen conduits and one out of four multi-lumen conduits. Axon number in the single-lumen regenerated nerve approached that of the contralateral intact nerve at 4,492 ± 2,810.0 and 6,080 ± 627.9 fibers/mm(2), respectively. The percentage of small fibers was greater in the single-lumen conduit compared with the intact nerve, whereas myelin thickness and g-ratio were consistently greater in the autologous nerve. Axon regrowth through the multi-lumen conduits was severely limited. CONCLUSION: Single-lumen stereolithography-manufactured PEG nerve conduits promote nerve regeneration, with regenerating axon numbers approaching that of normal nerve. Multi-lumen conduits demonstrated significantly less nerve regeneration, possibly due to physical properties of the conduit inhibiting growth. Further studies are necessary to compare the efficacy of the two conduits for functional recovery and to elucidate the reasons underlying their differences in nerve regeneration potential.