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Najath Abdul Kareem,1 Ayesha Aijaz,1 Marc G Jeschke1– 4 1Sunnybrook Research Institute, Toronto, ON, Canada; 2Department of Surgery, Division of Plastic Surgery, University of Toronto, Toronto, ON, Canada; 3Department of Immunology, University of Toronto, Toronto, ON, Canada; 4Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Toronto, ON, CanadaCorrespondence: Marc G JeschkeRoss Tilley Burn Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Rm D704, Toronto, ON, M4N 3M5, CanadaTel +1 416-480-6703Fax +1 416-480-6763Email marc.jeschke@sunnybrook.caAbstract: Burn injuries affect approximately 11 million people annually, with fatalities amounting up to 180,000. Burn injuries constitute a global health issue associated with high morbidity and mortality. Recent years have seen advancements in regenerative medicine for burn wound healing encompassing stem cells and stem cell-derived products such as exosomes and conditioned media with promising results compared to current treatment approaches. Sources of stem cells used for treatment vary ranging from hair follicle stem cells, embryonic stem cells, umbilical cord stem cells, to mesenchymal stem cells, such as adipose-derived mesenchymal stem cells, bone marrow-derived mesenchymal stem cells, and even stem cells harvested from discarded burn tissue. Stem cells utilize various pathways for wound healing, such as PI3/AKT pathway, WNT-β catenin pathway, TGF-β pathway, Notch and Hedgehog signaling pathway. Due to the paracrine signaling mechanism of stem cells, exosomes and conditioned media derived from stem cells have also been utilized in burn wound therapy. As exosomes and conditioned media are cell-free therapy and contain various biomolecules that facilitate wound healing, they are gaining popularity as an alternative treatment strategy with significant improvement in outcomes. The treatment is provided either as direct injections or embedded in a natural/artificial scaffold. This paper reviews in detail the different sources of stem cells, stem cell-derived products, their efficacy in burn wound repair, associated signaling pathways and modes of delivery for wound healing.Keywords: stem cells, burn injury, exosomes, conditioned media, wound healing

Alan D Rogers, Marc G Jeschke Ross Tilley Burn Centre, Division of Plastic and Reconstructive Surgery, Department of Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada Abstract: Encountered regularly by health care providers across both medical and surgical fields and an increasing socioeconomic burden globally, wound care is severely neglected. Practice is heavily influenced by anecdote rather than evidence-based protocols and industry-biased literature rather than robust randomized controlled trials. Burn units are well placed to address this considerable need, as a result of their infrastructure, their multispecialty staffing, and their need to evolve in light of the declining incidence of major burn injury in developed countries. The aim of this review is to evaluate some of the ideological and practical challenges facing wound practitioners and burn surgeons while managing chronic and complex wounds. It also includes an approach to wound assessment and how to conceptualize and implement dressing strategies and new and existing multimodal therapies. Keywords: negative pressure wound therapy, instillation, antiseptic solutions, dressings, multidisciplinary wound care, stem cells, surgery, autograft, allograft, reconstructive ladder

BACKGROUND: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue [alpha]-tocopherol concentrations are generally accepted to reflect long-term vitamin E status. OBJECTIVE: To test the hypothesis that thermal injury depletes body stores of vitamin E, [alpha]-tocopherol concentrations were measured in adipose tissue samples. DESIGN: Pediatric patients (n = 8) were followed up to 1 y after burn injury. Surgically obtained samples were collected at various intervals and stored at -80°C in a biorepository. [alpha]- and [gamma]-Tocopherols, cholesterol, and triglycerides were measured in the same tissue aliquot. RESULTS: During the first week after injury, adipose tissue [alpha]-tocopherol concentrations were within the expected normal range of 199 ± 40 nmol/g adipose tissue but were substantially lower at weeks 2 and 3 (133 ± 13 and 109 ± 8 nmol/g adipose tissue, respectively). Individual rates of decrease, estimated by linear regression, showed that adipose tissue [alpha]-tocopherol decreased by an average of 6.1 ± 0.6 nmol/g daily. During the first month after injury, adipose tissue triglyceride concentrations also decreased, whereas no changes in cholesterol concentrations occurred. CONCLUSIONS: These data emphasize that the burn injury experienced by these pediatric patients altered their metabolism such that vitamin E status diminished during the month after injury. Further studies are needed to evaluate the mechanism and consequences of the observed vitamin E depletion. This trial was registered at clinicaltrials.gov as NCT00675714. © 2010 American Society for Nutrition [ABSTRACT FROM AUTHOR]

Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality.Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity.Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179).Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14).Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309). [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the risk of developing sepsis following transfusion of blood products in severely burned pediatric patients. DESIGN: Retrospective, cohort study. SETTING: Shriners Hospital for Children and University Hospital. PATIENTS: Severely burned pediatric patients with >30% total body surface area (TBSA) burn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-seven pediatric burn patients over a period of 7 yrs (1997-2004) were included in the study, with 25 patients being septic at admission and therefore excluded. Patients were stratified according to TBSA burn and presence or absence of inhalation injury. The amounts of packed red blood cells (RBCs) and fresh frozen plasma (FFP) were recorded during hospital stay before the development of sepsis. Blood product administration was normalized for the number of surgeries and divided into two groups: high (RBCs>20/FFP>5) or low (RBCs<20/FFP<5) amount of blood products. Sepsis was diagnosed based on the criteria set by the Society of Critical Care Medicine in conjunction with positive blood culture or presence of organisms in the organs at autopsy. By stratifying the groups into low and high blood transfusion, we found that patients with >60% TBSA burn with inhalation injury have an 8% risk of developing sepsis in the low RBC group, which increases to 58% in the high RBC group (p<.05). Similar results were found for RBCs per operation, FFP, and FFP per operation (p<.05). There were no differences in age and gender between groups. CONCLUSIONS: Pediatric burn suffering from a 60% TBSA burn with concomitant inhalation injury are more likely to develop sepsis if they are given high amounts of blood products, indicating an immunocompromised state following blood transfusion. [ABSTRACT FROM AUTHOR]

Facial burns are very common and have significant clinical impact. However, the treatment regimen for superficial to deep facial burns is not well defined. The purpose of this study was to investigate the effects of cadaver skin grafting in deep partial thickness facial burns in comparison to standard care. In a prospective open study design severely injured patients with superficial and deep partial thickness burns were randomized into the group receiving open treatment with silversulfadiazine (standard n=5) or into the group receiving early superficial debridement followed by coverage with glycerolized cadaver skin (n=5). The outcome measures were time and quality of wound healing, and incidence of hypertrophic scarring at 3 and 6 months post burn. There were no significant differences in demographics between groups. In the group treated with the allogenic material time to reepithelialization was 10.5 days, while it was 12.4 days in the silversulfadiazine group (p<0.05). Scar quality was found to be significantly improved in the allogenic treatment group. Three and 6 months postburn there were no patients with significant hypertrophic scarring in the allogenic group while there were two patients who developed hypertrophic scars in the silversulfadiazine group (p<0.05). In this study, we demonstrated that glyzerolized cadaver allograft skin represents a superior biological dressing for shallow and deep partial thickness facial burns. This is in concordance with other reports on scalds. It would be worthwhile to perform more clinical studies with a larger number of patients to further evaluate the effect and function of allogenic skin for facial burns. [ABSTRACT FROM AUTHOR]