Colin Song

Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells

Summary Dendritic cell (DC)-mediated cross-presentation of exogenous antigens acquired in the periphery is critical for the initiation of CD8+ T cell responses. Several DC subsets are described in human tissues but migratory cross-presenting DCs have not been isolated, despite their potential importance in immunity to pathogens, vaccines, and tumors and tolerance to self. Here, we identified a CD141hi DC present in human interstitial dermis, liver, and lung that was distinct from the majority of CD1c+ and CD14+ tissue DCs and superior at cross-presenting soluble antigens. Cutaneous CD141hi DCs were closely related to blood CD141+ DCs, and migratory counterparts were found among skin-draining lymph node DCs. Comparative transcriptomic analysis with mouse showed tissue DC subsets to be conserved between species and permitted close alignment of human and mouse DC subsets. These studies inform the rational design of targeted immunotherapies and facilitate translation of mouse functional DC biology to the human setting.

Capsular Contracture in Subglandular Breast Augmentation with Textured versus Smooth Breast Implants: A Systematic Review

Background: There are conflicting recommendations in the literature regarding the use of textured implants to reduce capsular contracture in subglandular breast augmentation. The authors reviewed the literature to evaluate the effectiveness of surface texturization in reducing capsular contracture. Methods: The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials comparing textured with smooth implants for subglandular breast augmentation. Study quality was evaluated, and data were extracted from the relevant studies by two reviewers. Outcome measures were reduction in capsular contracture as defined by Baker grade, applanation tonometry, and patient self-assessment. Overall, the treatment effects were expressed as relative risk for dichotomous data and as weighted mean differences for continuous data. Results: Six randomized controlled trials were identified with a total of 235 patients (470 breasts). Textured implants were associated with less capsular contracture as evaluated by Baker grade at 1 year (relative risk, 4.16; 95% CI, 1.58 to 10.96), 3 years (relative risk, 7.25; 95% CI, 2.42 to 21.69), and 7 years (relative risk, 2.98; 95% CI, 0.86 to 10.37) of follow-up. Applanation tonometry used as an objective measure of firmness, however, was not sensitive enough to detect any significant difference in contractures in the two groups (weighted mean differences, −1.54; 95% CI, −6.83 to −3.75). Interestingly, the self-assessment questionnaire revealed that capsular contracture or firmness is one (albeit a very important factor) of many facets in patient overall satisfaction. Conclusions: This systematic review suggests that implant texturization reduces the incidence of early capsular contracture in subglandular breast augmentation. However, further studies are needed to evaluate the long-term effect of texturization and confirm the long-term benefits noted in this study.

Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro

Keloids are disfiguring, proliferative scars that represent a pathological response to cutaneous injury. The overabundant extracellular matrix formation, largely from collagen deposition, is characteristic of these lesions and has led to investigations into the role of the fibroblast in its pathogenesis. Curiously, the role of the epidermis in extracellular matrix collagen deposition of normal skin has been established, but a similar hypothesis in keloids has not been investigated. The aim of this study was to investigate the influence of keloid epithelial keratinocytes on the growth and proliferation of normal fibroblasts in an in vitro serum-free co-culture system. A permeable membrane separated two chambers; the upper chamber contained a fully differentiated stratified epithelium derived from the skin of excised earlobe keloid specimens, whereas the lower chamber contained a monolayer of normal or keloid fibroblasts. Both cell types were nourished by serum-free medium from the lower chamber. Epithelial keratinocytes from five separate earlobe keloid specimens were investigated. Four sets of quadruplicates were performed for each specimen co-cultured with normal fibroblasts or keloid-derived fibroblasts. Controls consisted of (1) normal keratinocytes co-cultured with normal fibroblasts, and (2) fibroblasts grown in serum-free media in the absence of keratinocytes in the upper chamber. Fibroblasts were indirectly quantified by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay, with results confirmed by DNA content measurement, at days 1 and 5 after the co- culture initiation.Significantly, increased proliferation was seen in fibroblasts co-cultured with keloid keratinocytes, as compared with the normal keratinocyte controls at day 5 (analysis of variance, p < 0.001). These results strongly suggest that the overlying epidermal keratinocytes of the keloid may have an important, previously unappreciated role in keloid pathogenesis using paracrine or epithelial-mesenchymal signaling.

Topical negative pressure wound therapy: a review of its role and guidelines for its use in the management of acute wounds

Over the past two decades, topical negative pressure (TNP) wound therapy has gained wide acceptance as a genuine strategy in the treatment algorithm for a wide variety of acute and chronic wounds. Although extensive experimental and clinical evidence exists to support its use and despite the recent emergence of randomised control trials, its role and indications have yet to be fully determined. This article provides a qualitative overview of the published literature appertaining to the use of TNP therapy in the management of acute wounds by an international panel of experts using standard methods of appraisal. Particular focus is applied to the use of TNP for the open abdomen, sternal wounds, lower limb trauma, burns and tissue coverage with grafts and dermal substitutes. We provide evidence‐based recommendations for indications and techniques in TNP wound therapy and, where studies are insufficient, consensus on best practice.

Synchronous Activation of ERK and Phosphatidylinositol 3-Kinase Pathways Is Required for Collagen and Extracellular Matrix Production in Keloids

Keloid fibroproliferation appears to be influenced by epithelial-mesenchymal interactions between keloid keratinocytes (KKs) and keloid fibroblasts (KFs). Keloid and normal fibroblasts exhibit accelerated proliferation and collagen I and III production in co-culture with KKs compared with single cell culture or co-culture with normal keratinocytes. ERK and phosphatidylinositol 3-kinase (PI3K) pathway activation has been observed in excessively proliferating KFs in co-culture with KKs. We hypothesized that ERK and PI3K pathways might be involved in collagen and extracellular matrix production in KFs. To test our hypothesis, four samples of KFs were co-cultured in defined serum-free medium with KKs for 2–5 days. KF cell lysate was subjected to Western blot analysis. Compared with KF single cell culture, phospho-ERK1/2 and downstream phospho-Elk-1 showed up-regulation in the co-culture groups, as did phospho-PI3K and phospho-Akt-1, indicating ERK and PI3K pathway activation. Western blotting of the conditioned medium demonstrated increased collagen I–III, laminin β2, and fibronectin levels. Addition of the MEK1/2-specific inhibitor U0126 or the PI3K-specific inhibitor LY294002 (but not p38 kinase and JNK inhibitors) completely nullified collagen I–III production and significantly decreased laminin β2 and fibronectin secretion. In the presence of the MEK1/2 or PI3K inhibitor, fibronectin demonstrated changes in molecular mass reflected by faster in-gel migration. These data strongly suggest that synchronous activation of both the ERK and PI3K pathways is essential for collagen I–III and laminin β2 production. These pathways additionally appear to affect the side chain attachments of fibronectin. Modulation of these pathways may suggest a direction for keloid therapy.

Multi-resistant Acinetobacter baumannii on a burns unit—clinical risk factors and prognosis

Burns patients are highly susceptible to infection, and preventing and treating infection are integral to the successful management of severe burns.Multi-resistant Acinetobacter baumannii (MR-AB) strains are becoming increasingly important in nosocomial infections. We conducted a retrospective study of all adult admissions to the Singapore General Hospital (SGH) National Burns Center over an 18-month period. The only independent risk factors for the acquisition of MR-AB were the APACHE II score on admission and the number of intravascular lines placed. The only independent predictor of infection with MR-AB was the number of intravascular lines placed. The only independent predictors of longer length of stay were the total number of operations required and infection with MR-AB. The only independent predictor of mortality was the APACHE II score. This is in contrast to other studies that have suggested that the acquisition of MR-AB is an independent risk factor for mortality.

Nonlinear Finite Element Simulations to Elucidate the Determinants of Perforator Patency in Propeller Flaps

The propeller-type flap design is increasingly used in reconstructive surgery for various regions of the body. To date, determinants of perforator patency when subjected to twisting have not been elucidated. We propose a simulation model to study parameters affecting perforator patency under such conditions. Nonlinear finite element procedure was used to simulate a perforator consisting of an artery and a vein with both ends fixed. A rigid body was attached to the top of the perforator for applying prescribed angular displacement. The effect of the following parameters on the pedicle patency was determined: (1) increasing angle of twist, (2) vessel stiffness, (3) vessel length, (4) diameter, (5) intraluminal pressure, and (6) the presence or absence of blood flow during twisting. Simulation results were reported in effective stress and strain on the twisted pedicle. In the context of perforator patency, effective strain, which is a measure of vessel deformation or collapse, is the more relevant outcome. The vein was more prone to occlusion because of its weaker wall and lower intraluminal pressure. Four factors that affected perforator patency were identified: angle of twist, intraluminal blood pressure, and perforator diameter and length. There was no significant difference whether twisting was performed prior to or after restoration of blood flow (P > 0.05). Therefore, to optimize condition for maintaining perforator patency, the angle of twist should be kept <180 degrees, perioperative blood pressure should be kept stable (avoiding periods of hypotension), and the selected perforator should be approximately 1 mm in diameter and >30 mm in length. We found that the propeller flap is a feasible design. This study defined the determinants of perforator patency and will serve as a useful guide when performing such flaps.

Approach to debridement in necrotizing fasciitis

Aggressive debridement is a cornerstone intervention in necrotizing fasciitis. Our approach consists of 4 steps: (1) confirming the diagnosis and isolate the causative organism; (2) defining the extent of fasciitis; (3) surgical excision; and (4) post-excision wound care. The extent of the infection is defined by probing the wound bluntly. Systematic excision follows. Fascial excision must be complete and uncompromising with the full extent of the involved wound laid open. We classify the infected skin into zones 1, 2, and 3. Zone 1 is necrotic tissue. Zone 2 is infected but potentially salvageable soft tissue, and zone 3 is non-infected skin. Zone 1 is completely excised. Zone 2 is meticulously assessed and cut back as necessary to remove nonviable tissue while maximally preserving salvageable tissue. Zone 3 is left alone. The aim of surgical debridement is to remove all infected tissue in a single operation. This halts the progression of the fasciitis and minimizes unnecessary returns to the operating room.

The gluteus maximus muscle flap for reconstruction of sacral chordoma defects.

Four patients diagnosed with sacral chordoma underwent reconstruction with the gluteus maximus flap using an approach based on available muscle remnants and their residual blood supply. The entire unilateral gluteus maximus muscle was turned over to fill the defect in 2 patients. The flap was based on 1 or 2 gluteal vessels, depending on vessel availability following tumor resection. When all 4 major pedicles had been ligated, bilateral advancement gluteal muscle flaps based on their distal blood supply were used (patient 3). A longitudinally split flap was used for secondary reconstruction of a partially obliterated defect (patient 4). Over a mean follow-up period of 8 months, there was no wound breakdown and all patients were ambulant.

Vacuum Assisted Closure: Recommendations for Use: A Consensus Document

international group of experts (see below) to provide guidance on the successful integration of vacuum assisted closure therapy (V.A.C. Therapy) into clinical practice. The document specifically reviews its potential use in the following selected indications*: diabetic foot ulcers, complex leg ulcers, pressure ulcers, dehisced sternal wounds, open abdominal wounds and traumatic wounds. In addition, it considers quality of life and cost-effectiveness, both of which are gaining importance when evaluating treatment. This document highlights questions for future research and is designed to be practical and adaptable for local use in countries worldwide.