The Short- and Long-Term Outcome Priorities of a Western Australian Adult Burn Population

To optimize patient recovery, understanding which outcomes are most important to burn patients is key. However, research to determine what outcomes are patient priorities is limited. Therefore, we assessed what outcomes are most important to Western Australian burn patients, separately in the short-term (&lt;6 months) and long-term (6-24 months) after injury. Adult patients who had a burn injury 3-36 months ago completed a survey, rating the importance of 36 short- and long-term outcomes. The survey items were ranked according to the number of patients reporting the outcome as "very important."Results were compared between subgroups based on age, gender, burn size, and number of surgeries. Ninety-three patients were included. In the short-term, "not having a wound infection"(87.1%), "good wound healing"(83.9%), and "walking or moving around"(74.7%) were the most important outcomes. "Lifting or moving something"(67.6%), "walking or moving around"(66.2%), and "being independent"(66.2%) were reported as most important in the long-term. Scar-related outcomes were more important to females and to patients with multiple surgeries; mental health outcomes were priorities for females and patients with major burns; walking and moving around to males and older patients; and social and financial outcomes were rated highly by patients with major burns and multiple surgeries. In conclusion, the most important outcomes were consistent across time periods, indicating the importance of core outcomes in longitudinal follow-up. The wide range of priority outcomes and differences between subgroups underlines the need for multidisciplinary care and a patient-centered approach to support patients.</p

Genetic influence on scar height and pliability after burn injury in individuals of European ancestry: A prospective cohort study

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings

Topical Application of an Irreversible Small Molecule Inhibitor of Lysyl Oxidases Ameliorates Skin Scarring and Fibrosis

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance. Here we describe the development and characterisation of an irreversible lysyl oxidase inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily penetrating the skin when applied as a cream and abolishing lysyl oxidase activity. In murine models of injury and fibrosis, topical application reduces collagen deposition and cross-linking. Topical application of PXS-6302 after injury also significantly improves scar appearance without reducing tissue strength in porcine injury models. PXS-6302 therefore represents a promising therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases

Burn injury leads to increased long-term susceptibility to respiratory infection in both mouse models and population studies

Background: Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about longterm consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses. Methods: Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a). Results and conclusions: The burn injured cohort contained 14893 adult patients from 1980-2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27-2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85-2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09-2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response

Cardiometabolic disease risk markers are increased following burn injury in children

IntroductionBurn injury in children causes prolonged systemic effects on physiology and metabolism leading to increased morbidity and mortality, yet much remains undefined regarding the metabolic trajectory towards specific health outcomes.MethodsA multi-platform strategy was implemented to evaluate the long-term immuno-metabolic consequences of burn injury combining metabolite, lipoprotein, and cytokine panels. Plasma samples from 36 children aged 4–8 years were collected 3 years after a burn injury together with 21 samples from non-injured age and sex matched controls. Three different 1H Nuclear Magnetic Resonance spectroscopic experiments were applied to capture information on plasma low molecular weight metabolites, lipoproteins, and α-1-acid glycoprotein.ResultsBurn injury was characterized by underlying signatures of hyperglycaemia, hypermetabolism and inflammation, suggesting disruption of multiple pathways relating to glycolysis, tricarboxylic acid cycle, amino acid metabolism and the urea cycle. In addition, very low-density lipoprotein sub-components were significantly reduced in participants with burn injury whereas small-dense low density lipoprotein particles were significantly elevated in the burn injured patient plasma compared to uninjured controls, potentially indicative of modified cardiometabolic risk after a burn. Weighted-node Metabolite Correlation Network Analysis was restricted to the significantly differential features (q &lt;0.05) between the children with and without burn injury and demonstrated a striking disparity in the number of statistical correlations between cytokines, lipoproteins, and small molecular metabolites in the injured groups, with increased correlations between these groups.DiscussionThese findings suggest a ‘metabolic memory’ of burn defined by a signature of interlinked and perturbed immune and metabolic function. Burn injury is associated with a series of adverse metabolic changes that persist chronically and are independent of burn severity and this study demonstrates increased risk of cardiovascular disease in the long-term. These findings highlight a crucial need for improved longer term monitoring of cardiometabolic health in a vulnerable population of children that have undergone burn injury

The benefits and limitations of using ultrasonography to supplement anatomical understanding

Anatomical understanding is critical to medical education. With reduced teaching time and limited cadaver availability, it is important to investigate how best to utilize in vivo imaging to supplement anatomical understanding and better prepare medical graduates for the proliferation of point-of-care imaging in the future. To investigate whether using short sessions of in vivo imaging using ultrasonography could benefit students\u27 anatomical knowledge and clinical application, we conducted a 2-hour session on abdominal anatomy using ultrasonography in small groups of five to six students, for both first- and second-year student cohorts. Individual feedback was collected to assess student perceptions. To measure retention and understanding, a short examination containing ultrasound images and questions and performance of a clinical skill (gastrointestinal\u27 tract examination) were assessed. Ultrasonography sessions were highly valued by the students, with 90% of the students reporting their understanding was improved, and over 70% reporting increased confidence in their anatomical knowledge. However, the assessments showed no appreciable impact on skills or understanding related to abdominal anatomy and examination. We conclude that the risk associated with limited exposure increasing confidence without increasing skills remains real and that in vivo imaging is not effective when used as a short adjunct teaching tool. The widespread use of ultrasonography means finding the best way to incorporate ultrasound into medical education remains important. To this end, we are currently implementing an extended program including echocardiography and multiple anatomical sessions that will determine if frequency and repetition of use can positively impact on student performance and understanding

Burn Injury Leads to Increased Long-Term Susceptibility to Respiratory Infection in both Mouse Models and Population Studies.

Burn injury initiates an acute inflammatory response that subsequently drives wound repair. However, acute disruption to the immune response is also common, leading to susceptibility to sepsis and increased morbidity and mortality. Despite increased understanding of the impact of burn injury on the immune system in the acute phase, little is known about long-term consequences of burn injury on immune function. This study was established to determine whether burn injury has long-term clinical impacts on patients' immune responses.Using a population-based retrospective longitudinal study and linked hospital morbidity and death data from Western Australia, comparative rates of hospitalisation for respiratory infections in burn patients and a non-injured comparator cohort were assessed. In addition, a mouse model of non-severe burn injury was also used in which viral respiratory infection was induced at 4 weeks post-injury using a mouse modified version of the Influenza A virus (H3NN; A/mem/71-a).The burn injured cohort contained 14893 adult patients from 1980-2012 after removal of those patients with evidence of smoke inhalation or injury to the respiratory tract. During the study follow-up study a total of 2,884 and 2,625 respiratory infection hospital admissions for the burn and uninjured cohorts, respectively, were identified. After adjusting for covariates, the burn cohort experienced significantly elevated admission rates for influenza and viral pneumonia (IRR, 95%CI: 1.73, 1.27-2.36), bacterial pneumonia (IRR, 95%CI: 2.05, 1.85-2.27) and for other types of upper and lower respiratory infections (IRR, 95% CI: 2.38, 2.09-2.71). In the mouse study an increased viral titre was observed after burn injury, accompanied by a reduced CD8 response and increased NK and NKT cells in the draining lymph nodes. This data suggests burn patients are at long-term increased risk of infection due to sustained modulation of the immune response

The use of a non-cultured autologous cell suspension and Integra® dermal regeneration template to repair full-thickness skin wounds in a porcine model: A one-step process

Integra® is a skin substitute used for dermal reconstruction. Current clinical practice consists of two procedures, first applying Integra® to the wound and then replacing the silicone pseudo-epidermis with an epidermal autograft 3 weeks later. This two-step repair limits the clinical use of the product. An effective one-step procedure could reduce the time taken to repair and decrease the number of procedures for use of Integra®. This study examined the effects of simultaneous application of a non-cultured autologous suspension of cells, isolated using the ReCell® autologous cell harvesting device, in combination with Integra®, to achieve a one-step skin repair. In two female Yorkshire swine, 10 full-thickness wounds were created. Wounds were treated with Integra® seeded with cell suspension and compared to controls of Integra® alone and cell suspension alone. Weekly macroscopic and histological assessment demonstrated that the wounds treated simultaneously with Integra® and non-cultured autologous cells had enhanced epithelialization at an early time-point compared to controls. Wounds treated simultaneously with Integra® and cell suspension demonstrate that cells remain viable, migrate through the Integra® template and self-organize into differentiated epidermis. The results indicate that combining Integra® with autologous cells facilitates one-step skin reconstruction of a full-thickness skin wound

The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing

The timely resolution of wound healing is critical for restoring the skin as a protective barrier. The switch from a proinflammatory to a reparative microenvironment must be tightly regulated. Interleukin (IL)-6 is a key modulator of the inflammatory and reparative process: it is involved in the differentiation, activation, and proliferation of leukocytes, endothelial cells, keratinocytes, and fibroblasts. This review examines the role of IL-6 in the healing of cutaneous wounds, and how dysregulation of IL-6 signaling can lead to either fibrosis or a failure to heal. The role of an IL-6/TGF-&beta; feedback loop is discussed in the context of fibrogenesis, while IL-6 expression and responses in advanced age, diabetes, and obesity is outlined regarding the development of chronic wounds. Current research on therapies that modulate IL-6 is explored. Here, we consider IL-6&prime;s diverse impact on cutaneous wound healing