Spencer A. Brown

In search of improved fat transfer viability: A quantitative analysis of the role of centrifugation and harvest site

Fat grafting is an unpredictable procedure that continues to challenge the field of plastic surgery due to irregular resorption. Applications for this procedure are broad in both reconstructive and cosmetic plastic surgery. Fat grafts are carefully obtained and manipulated to obtain better graft takes and results, yet there is no universal agreement on what constitutes an ideal methodology. The present study examines adipocyte viability from four commonly used donor sites in five subjects. No statistical differences in adipocyte viability were demonstrated among abdominal fat, thigh fat, flank fat, or knee fat donor sites that were immediately removed and untreated (p < 0.225). In addition, no differences were observed in representative tissue samples that were removed and centrifuged (thigh, p = 0.508; knee, p = 0.302; flank, p = 0.088; abdomen, p = 0.533). On the basis of these quantitative data, neither harvest location nor centrifugation demonstrated any advantage in terms of lipocyte viability. Fat tissue transfers from these common sites may be considered equal, and centrifugation does not appear to enhance immediate fat tissue viability before implantation.

Autologous Human Fat Grafting: Effect of Harvesting and Preparation Techniques on Adipocyte Graft Survival

Background: Autogenous fat transfer with lipoinjection for soft-tissue augmentation is a commonly used technique without a universally accepted approach. The high percentage and variable amount of fat resorption reduce the clinical efficacy of this procedure and often result in the need for further grafting. The purposes of this study were to evaluate the effect of different harvesting and preparation techniques on human fat tissue viability and to determine fat tissue viability rates among the different fat preparations transplanted into a severe combined immune deficiency mouse model at 3 months. Methods: Using standard liposuction and syringe aspiration, fat was removed from patients (n = 3) undergoing elective body contouring. Tissue was prepared by six different combinations of centrifugation and/or washing the cells with lactated Ringers solution or normal saline. Metabolic activities of fat cell viability were monitored to assess overall cell viability. To analyze viability over 3 months, freshly harvested tissue specimens (minimum n = 5) were prepared by a combination of various procedures (wash, centrifugation, and different solutions) and subsequently injected under the dorsal flank skin of severe combined immune deficiency mice in two experiments. Mice were monitored for 12 weeks and the fat xenografts were removed for mass and histological evaluations. Results: Metabolic analyses showed improved cell viability in tissue specimens undergoing minimal manipulation. No significant differences in fat cell viability, as assessed by graft weight maintenance or histologic evaluations, were observed with regard to harvesting or preparation techniques. Conclusions: Improved viability of freshly harvested but untreated fat specimens may be expected as compared with grafts that have undergone additional manipulations. No unique combination of preparation or harvesting techniques appeared to be more advantageous on transplanted fat grafts at 3 months. This study also demonstrated a reliable animal model for future investigation into examining novel applications for augmenting fat graft survival.

An Acellular Biologic Scaffold Promotes Skeletal Muscle Formation in Mice and Humans with Volumetric Muscle Loss

Scaffolds composed of cell-free extracellular matrix promote de novo formation of functional skeletal muscle tissue in sites of volumetric muscle loss. Cell-Free Matrix Refills Muscle In traumatic accidents, or even in surgery, large amounts of skeletal muscle can be lost, resulting in pain and loss of function. Although muscle has the ability to regenerate naturally, it cannot refill massive defects, such as those seen in volumetric muscle loss (VML). In response, Sicari and colleagues devised a biomaterial scaffold that can be surgically implanted at the site of VML, encouraging local muscle regeneration and improving function in both mice and humans. The biomaterial used in this study was made up of bladder tissue that had been stripped of cells, leaving behind only the protein scaffold called the extracellular matrix (ECM). Sicari et al. first tested it in a mouse model of VML. In mice treated with ECM, they saw signs of new skeletal muscle formation, characterized by muscle markers desmin and myosin heavy chain, as well as striated (striped) tissue organization. The new muscle also appeared to be innervated, which is necessary for function. The authors translated this preclinical work into a clinical study of five patients with VML and saw outcomes similar to the mice. Six months after ECM implantation at the site of muscle loss, all patients showed signs of new muscle and blood vessels. Three of the five patients showed 20% or greater improvement in limb strength during physical therapy. The two patients without functional changes did report improvements in nonfunctional tasks, such as balance, as well as an improvement in quality of life. Because of the widespread availability and known safety of cell-free ECM-based materials, the approach described by Sicari et al. may translate to regeneration of other human tissues in addition to muscle. Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) can provide a microenvironmental niche that alters the default healing response toward a constructive and functional outcome. The present study showed similarities in the remodeling characteristics of xenogeneic ECM scaffolds when used as a surgical treatment for volumetric muscle loss in both a preclinical rodent model and five male patients. Porcine urinary bladder ECM scaffold implantation was associated with perivascular stem cell mobilization and accumulation within the site of injury, and de novo formation of skeletal muscle cells. The ECM-mediated constructive remodeling was associated with stimulus-responsive skeletal muscle in rodents and functional improvement in three of the five human patients.

Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study.

The distributions of plasma lipids, lipoproteins, and apoproteins of 14,524 female and male black and white participants 45 to 64 years old in the Atherosclerosis Risk in Communities (ARIC) Study are presented. All specimens were analyzed at a central laboratory. Mean total cholesterol levels increased with increasing age across all ages from 204 to 229 mg/dL (12%) in women and from 208 to 213 mg/dL (2%) in men. Triglyceride levels increased with age in women, remained stable in men, and were higher in whites than blacks. High-density lipoprotein (HDL) cholesterol levels were higher in black and white women (range, 57 to 59 mg/dL) compared with black men (49 to 52 mg/dL) or white men (42 to 43 mg/dL). Cholesterol associated with HDL was distributed in a relatively constant proportion between HDL3 (70% to 76%) and HDL2 (24% to 30%) for all race/sex groups. Low-density lipoprotein (LDL) cholesterol levels increased with age in black (14.7%) and white (17.1%) women and in black (4.4%) and white (3.7%) men; more than 50% of all participants had LDL cholesterol levels > 130 mg/dL. Apoprotein A-I and B levels followed the same trends as HDL cholesterol and LDL cholesterol levels, respectively. Lipoprotein(a) [Lp(a)] levels were twice as high in blacks as in whites, and womens Lp(a) levels were higher than mens Lp(a) levels for each race. Menopause was associated with elevated total cholesterol, LDL cholesterol, apoprotein B, and Lp(a) levels, and hormone replacement medication use in postmenopausal subjects was associated with higher HDL cholesterol, triglyceride, and apoprotein A-I levels and lower LDL cholesterol, apoprotein B, and Lp(a) levels.

Fat grafting: evidence-based review on autologous fat harvesting, processing, reinjection, and storage.

Background: Over the past 20 years, there has been a dramatic increase in the use of autologous fat grafting to treat volume and contour defects in aesthetic and reconstructive surgery. It is generally accepted that fat grafting is safe, with good patient satisfaction. However, there are many procedural variations, and in terms of objective clinical effectiveness, the major disadvantage of this technique remains the unpredictable fat resorption rates and subsequent adverse events. Because of the rapidly evolving nature of this procedure, this review article provides an update on previous reviews by looking at the current evidence base regarding fat graft techniques and their effect on clinical outcome. Methods: A systematic review of the scientific literature listed on PubMed was performed using 20 search terms focused on harvesting, processing, reinjection, and conservation of fat grafting. An evidence-based system was used to determine eligibility for clinical and preclinical studies. Results: Thirty-seven articles were selected based on inclusion and exclusion criteria: five articles were clinical trials and 32 were experimental comparative studies examining human fat grafting. Conclusions: This systematic review revealed a lack of high-quality data despite the increase in fat grafting over the past 20 years. At present, there is no evidence that supports specific procedural standardization. Evidence-based studies that incorporate randomized controlled, prospective, multicenter trials are required to understand which factors influence positive fat grafting clinical outcomes.

Thromboembolic Risk Assessment and the Efficacy of Enoxaparin Prophylaxis in Excisional Body Contouring Surgery

Background: There is a paucity of evidence within the plastic surgery literature concerning risk stratification and management of patients with respect to thromboembolic disease. A retrospective chart review was conducted to examine whether the Davison-Caprini risk-assessment model could stratify patients undergoing excisional body contouring surgery, allowing prophylaxis to be managed in an evidence-based manner. Methods: Three hundred sixty excisional body contouring patients at the University of Texas Southwestern Medical Center in Dallas, Texas, under the senior authors’ (J.M.K. and R.J.R.) care were reviewed. Patients were stratified into groups according to the risk-assessment model and into groups based on procedure. Patient characteristics were investigated for their effects on thromboembolic risk. Complications of enoxaparin administration were analyzed. The data were analyzed using appropriate statistical procedures. Results: The highest risk patients had a significantly increased rate of venous thromboembolism when compared with lower risk patients. Body mass index greater than 30 and hormone therapy use were associated with a significantly increased venous thromboembolism rate. Enoxaparin administration was associated with a statistically significant decrease in deep venous thrombosis in circumferential abdominoplasty patients. Enoxaparin administration was associated with higher bleeding rates. Conclusions: Low-molecular-weight heparin may affect the incidence of postoperative thrombotic complications in some surgical populations. In this study, patients who scored greater than four risk factors were at significant risk for venous thromboembolism. Enoxaparin significantly decreased deep venous thrombosis risk in patients undergoing circumferential abdominoplasty. This demonstrates the need for a multicenter, prospective, randomized study to examine various thromboembolic therapies and associated possible complications in these patients.

Human adipose stem cells: current clinical applications.

Summary: Adipose-derived stem cells are multipotent cells that can easily be extracted from adipose tissue, are capable of expansion in vitro, and have the capacity to differentiate into multiple cell lineages, which have the potential for use in regenerative medicine. However, several issues need to be studied to determine safe human use. For example, there are questions related to isolation and purification of adipose-derived stem cells, their effect on tumor growth, and the enforcement of U.S. Food and Drug Administration regulations. Numerous studies have been published, with the interest in the potential for regenerative medicine continually growing. Several clinical trials using human adipose stem cell therapy are currently being performed around the world, and there has been a rapid evolution and expansion of their number. The purpose of this article was to review the current published basic science evidence and ongoing clinical trials involving the use of adipose-derived stem cells in plastic surgery and in regenerative medicine in general. The results of the studies and clinical trials using adipose-derived stem cells reported in this review seem to be promising not only in plastic surgery but also in a wide variety of other specialties. Nevertheless, those reported showed disparity in the way adipose-derived stem cells were used. Further basic science experimental studies with standardized protocols and larger randomized trials need to be performed to ensure safety and efficacy of adipose-derived stem cells use in accordance with U.S. Food and Drug Administration guidelines.

Arterial and venous anatomies of the deep inferior epigastric perforator and superficial inferior epigastric artery flaps.

Background: This study uses three- and four-dimensional computed tomographic angiography and venography to evaluate the microvascular anatomy and perfusion of the deep inferior epigastric artery perforator (DIEP) and superficial inferior epigastric artery (SIEA) flaps. Methods: Ten DIEP flaps harvested from fresh cadavers and two abdominoplasty specimens were used. Studies of the largest single perforators from the medial and lateral rows were performed. Injections of the vena comitans of the perforators and of the superficial inferior epigastric veins were performed to evaluate venous drainage. Results: Zone IV was not perfused following injection of a lateral row perforator, whereas injection of a medial row perforator consistently resulted in perfusion of zone IV. Image analysis revealed the presence of large-diameter linking vessels at the level of the subdermal plexus between the perforators of the medial row, whereas lateral row perforators predominantly perfused the lateral aspect of the flap and perfused the medial row perforators by means of recurrent flow through the subdermal plexus. Medial row perforators perfused the flap in a central elliptical pattern, whereas lateral row perforators predominantly perfused the ipsilateral portion of the flap. The SIEA vessel branches were seen to course to the subdermal plexus and then to perfuse ipsilateral perforators through the subdermal plexus. Venous drainage occurred by means of the superficial inferior epigastric veins and the venae comitantes of the perforators. Conclusions: This study demonstrates that flow through medial and lateral row perforators occurs in physiologically stereotyped patterns. A medial row perforator should be selected if zone IV perfusion is required. The SIEA was consistently seen to only perfuse a hemiflap.

Studies of a targeted risk reduction intervention through defined exercise (STRRIDE).

PURPOSE The Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE) trial is a randomized controlled clinical trial designed to study the effects of exercise training regimens differing in dose (kcal.wk-1) and/or intensity (relative to peak VO2) on established cardiovascular risk factors and to investigate the peripheral biologic mechanisms through which chronic physical activity alters carbohydrate and lipid metabolism to result in improvements in these parameters of cardiovascular risk in humans. METHODS We will recruit 384 subjects and randomly assign them to one of three exercise training regimens or to a sedentary control group. The recruiting goal is to attain a subject population that is 50% female and 30% ethnic minority. The overall strategy is to use graded exercise training regimens in moderately overweight subjects with impairments in insulin action and mild to moderate lipid abnormalities to investigate whether there are dose or intensity effects and whether adaptations in skeletal muscle (fiber type, metabolic capacity, and/or capillary surface area) account for improvements in insulin action and parameters of lipoprotein metabolism. We will study these variables before and after exercise training, and over the course of a 2-wk detraining period. The study sample size is chosen to power the study to examine differences in responses between subjects of different gender and ethnicity to exercise training with respect to the least sensitive parameter-skeletal muscle capillary density. RESULTS The driving hypothesis is that improvements in cardiovascular risk parameters derived from habitual exercise are primarily mediated through adaptations occurring in skeletal muscle. CONCLUSION Identification that amount and intensity of exercise matter for achieving general and specific health benefits and a better understanding of the peripheral mechanisms mediating the responses in carbohydrate and lipid metabolism to chronic physical activity will lead to better informed recommendations for those undertaking an exercise program to improve cardiovascular risk.

Racial Differences in Risk Factors for Atherosclerosis The ARIC Study

This paper describes black/white differences in risk factors for atherosclerosis in the large multicenter Atherosclerosis Risk in Communities (ARIC) Project sponsored by the National Heart, Lung, and Blood Institute. It is based on data collected at baseline in ARICs four geographically distinct clinical centers. Participants were randomly selected (4264 black and 11,479 white men and women, ages forty-five to sixty-four years at entry). There were striking differences in obesity between black and white women, higher fasting glucose and greater prevalence of diabetes in blacks, and lower high-density lipoprotein values in white men. Not unexpectedly, blood pressure in black participants exceeded that in whites. Clustering of multiple risk factors was more common in the black population. Conversely, prevalence of no risk factors was greatest among whites. In conclusion, while African-Americans and Caucasians share much the same group of risk factors for atherosclerosis, there are clinically important racial differences in emphasis.