Nonsevere Burn Induces a Prolonged Systemic Metabolic Phenotype Indicative of a Persistent Inflammatory Response Postinjury.

Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic comorbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on the impact of nonsevere injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of a nonsevere burn injury, longitudinal plasma was collected from adults (n = 35) who presented at hospital with a nonsevere burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from nonburn control participants (n = 14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoprotein signatures and 852 lipid species from across 20 subclasses. Multivariate data modeling (orthogonal projections to latent structures-discriminate analysis; OPLS-DA) revealed alterations in lipoprotein and lipid metabolism when comparing the baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value < 1.0e-4), low density lipoprotein-2 subfractions (variable importance in projection score; VIP > 6.83e-1) and monoacyglyceride (20:4) (p-value < 1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP > 7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols, and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of a nonsevere burn injury. The phenotype is indicative of an acute inflammatory profile that continues to be sustained postinjury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have an elevated incidence postburn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalize intervention strategies, and improve acute care, reducing the risk of chronic comorbidity.

Comprehensive Lipidomic Workflow for Multicohort Population Phenotyping Using Stable Isotope Dilution Targeted Liquid Chromatography-Mass Spectrometry.

Dysregulated lipid metabolism underpins many chronic diseases including cardiometabolic diseases. Mass spectrometry-based lipidomics is an important tool for understanding mechanisms of lipid dysfunction and is widely applied in epidemiology and clinical studies. With ever-increasing sample numbers, single batch acquisition is often unfeasible, requiring advanced methods that are accurate and robust to batch-to-batch and interday analytical variation. Herein, an optimized comprehensive targeted workflow for plasma and serum lipid quantification is presented, combining stable isotope internal standard dilution, automated sample preparation, and ultrahigh performance liquid chromatography-tandem mass spectrometry with rapid polarity switching to target 1163 lipid species spanning 20 subclasses. The resultant method is robust to common sources of analytical variation including blood collection tubes, hemolysis, freeze-thaw cycles, storage stability, analyte extraction technique, interinstrument variation, and batch-to-batch variation with 820 lipids reporting a relative standard deviation of <30% in 1048 replicate quality control plasma samples acquired across 16 independent batches (total injection count = 6142). However, sample hemolysis of ≥0.4% impacted lipid concentrations, specifically for phosphatidylethanolamines (PEs). Low interinstrument variability across two identical LC-MS systems indicated feasibility for intra/inter-lab parallelization of the assay. In summary, we have optimized a comprehensive lipidomic protocol to support rigorous analysis for large-scale, multibatch applications in precision medicine. The mass spectrometry lipidomics data have been deposited to massIVE: data set identifiers MSV000090952 and 10.25345/C5NP1WQ4S.

Sampling the skin surface chemistry for diagnosis and prognosis.

Skin and wound blotting are non-invasive techniques used to sample the skin and wound surface chemistry, whereby a nitrocellulose membrane is applied to an intact or broken cutaneous surface to detect biomarkers. However, there has been no comprehensive review of the evidence for the techniques used and data obtained to date. The primary aim of this study was to review the utilities of surface blotting for the diagnosis and prognosis of physiological, pre-disease, and pathological states. The secondary aim was to summarise the procedural steps. A systematic literature search was conducted on 9 July 2021 using Medline, Embase, and Google Scholar databases. Investigators used McMaster's Critical Review Form for Quantitative Studies to assess quality, then performed a narrative synthesis reporting according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Twenty-five studies were reviewed. Eighteen studies were of good quality, and seven were of moderate quality. These studies conducted skin and wound blotting on 176 animals and 1546 humans. Studies reported physiological and pathological states for diagnosis and prediction of conditions, including skin tears, wound healing, biofilm detection, and skin barrier function. The four steps for blotting are surface preparation, blot preparation, application and removal of blot, and analysis. This review demonstrates that blotting can determine the skin and wound surface chemistry using a versatile and reproducible technique. However, future research is needed to validate the technique and skin biomarkers identified.

An Experimental Simulation of Heat Effects on Cognition and Workload of Surgical Team Members.

OBJECTIVE: To isolate heat exposure as a cause of cognitive impairment and increased subjective workload in burns surgical teams. SUMMARY OF BACKGROUND DATA: Raising ambient temperature of the operating room can improve burns patient outcomes, but risks increased cognitive impairment and workload of surgical team members. Prior research indicates ambient heat exposure depletes physiological and cognitive resources, but these findings have not been studied in the context of burns surgical teams. METHODS: Seventeen surgical team members completed 2 surgery simulations of similar complexities in a hot and in a normothermic operating room. During each simulation, participants completed multiple cognitive tests to assess cognitive functioning and the SURG-TLX to self-assess workload. Order effects, core body temperature changes due to menstruation, and circadian rhythms were controlled for in the experimental design. Descriptive statistics, correlations, and mixed ANOVAs were performed to assess relationships between ambient heat exposure with cognitive functioning and perceived workload. RESULTS: Heat had a main effect on executive functioning and verbal reasoning. Duration of heat exposure (heat ∗ time) increased response times and negatively impacted executive functioning, spatial planning, and mental rotation. Perceived workload was higher in the hot condition. CONCLUSIONS: We provide causal evidence that over time, heat exposure impairs cognitive speed and accuracy, and increases subjective workload. We recommend building on this study to drive best-practices for acute burns surgery and design work to enable burns teams to maintain their cognitive stamina, lower their workload, and improve outcomes for patients and surgeons.

The epigenetics of keloids.

Keloid scarring is a fibroproliferative disorder of the skin with unknown pathophysiology, characterised by fibrotic tissue that extends beyond the boundaries of the original wound. Therapeutic options are few and commonly ineffective, with keloids very commonly recurring even after surgery and adjunct treatments. Epigenetics, defined as alterations to the DNA not involving the base-pair sequence, is a key regulator of cell functions, and aberrant epigenetic modifications have been found to contribute to many pathologies. Multiple studies have examined many different epigenetic modifications in keloids, including DNA methylation, histone modification, microRNAs and long non-coding RNAs. These studies have established that epigenetic dysregulation exists in keloid scars, and successful future treatment of keloids may involve reverting these aberrant modifications back to those found in normal skin. Here we summarise the clinical and experimental studies available on the epigenetics of keloids, discuss the major open questions and future perspectives on the treatment of this disease.

The psychological impact of paediatric burn injuries: a systematic review.

OBJECTIVE: To review and synthesise qualitative literature regarding the psychological outcomes following paediatric burn injuries, and to determine if children and adolescents who experience a burn injury have elevated risk of psychopathology following the injury. DESIGN: Systematic review of quantitative and qualitative studies. DATA SOURCES: Informit health, Medline, Embase, and PsycINFO were searched from January 2010 to December 2020. DATA EXTRACTION AND SYNTHESIS: Two reviewers screened articles, and one reviewer extracted data (with cross-checking from another reviewer) from the included studies and assessed quality using an established tool. Narrative synthesis was used to synthesise the findings from the quantitative studies, and thematic synthesis was used to synthesise the findings of included qualitative studies. RESULTS: Searches yielded 1240 unique titles, with 130 retained for full-text screening. Forty-five studies from 17 countries were included. The psychological outcomes included in the studies were mental health diagnoses, medication for mental illness, depression, anxiety, stress, fear, post-traumatic stress, post-traumatic growth, emotional issues, self-harm, self-esteem, self-concept, stigmatisation, quality of life, level of disability, resilience, coping, and suicidality. CONCLUSIONS: Our findings highlight paediatric burn patients as a particularly vulnerable population following a burn injury. Studies suggest elevated anxiety and traumatic stress symptoms, and higher rates of psychopathology in the long-term. Further research is recommended to determine the psychological outcomes in the other mental health domains highlighted in this review, as findings were mixed. Clinical care teams responsible for the aftercare of burn patients should involve psychological support for the children and families to improve outcomes.

Poorer first aid after burn is associated with remoteness in Australia: Where to from here?

OBJECTIVE: Early intervention with appropriate first aid following burn injury improves clinical outcomes. Previous evidence suggests geographic remoteness may be a barrier to receiving appropriate burns first aid. This study investigated the prevalence of gold standard first aid in patients managed in Australian burn services and whether geographic remoteness was associated with receiving gold standard first aid. DESIGN: Registry-based cohort study. SETTING: Binational clinical quality registry. PARTICIPANTS: Burn-injured patients admitted to a specialist Australian burn service. MAIN OUTCOME MEASURES: Receiving gold standard first aid following a burn injury. RESULTS: Approximately two-thirds of patients received gold standard first aid. Patients whose burns were sustained in very remote regions had a greater risk of receiving no first aid, compared to gold standard first aid, relative to patients who sustained their burn injuries in major cities. CONCLUSIONS: Nearly two-thirds of patients received gold standard burns first aid following injury. However, patients who were injured in the most remote regions of Australia were at an increased risk of not receiving gold standard first aid treatment within 3 hours of injury. Further examination of factors contributing to poorer first aid standards in remote areas is required.

A review of epigenetic regulation in wound healing: Implications for the future of wound care.

Epigenetic regulatory mechanisms are essential for maintaining skin homeostasis and aid in the processes of wound healing. The nucleus co-ordinates gene expression using epigenetic regulatory mechanisms based on distinct chromatin structural states and their remodeling. These include DNA methylation and hydroxymethylation, post-translational histone modifications, ATP-dependent chromatin remodeling and higher-order chromatin structure and 3D genome organization. Epigenetic pathways play a key role in co-ordinating the behavior and activity of the multitude of cell types seen during skin repair, and research is now focusing on how wound healing can be modulated by altering the activity of certain reparative genes. Herein, we aim to highlight recent advances in understanding epigenetic regulatory mechanisms, with particular reference to those involved in keratinocyte and fibroblast biology. We also propose future directions for exploration of epigenetic mechanisms, and their potential clinical applications in acute wound care.

Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands.

BACKGROUND: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands. METHODS: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD). RESULTS: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup < 5% TBSA burned > 24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0-1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands. CONCLUSIONS: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries.

Optical coherence tomography angiography for longitudinal monitoring of vascular changes in human cutaneous burns.

Assessment of vasculature is an important aspect of monitoring healing of cutaneous burn injuries. Recent advances in optical coherence tomography (OCT) have enabled it to be used to perform high-resolution imaging of the cutaneous vasculature in vivo, with the potential to provide a superior alternative to the conventional assessment of scoring skin color. The goal of this study is to investigate the feasibility of OCT angiography for longitudinal monitoring of vasculature and identification of vascular features in human cutaneous burns. We integrate several OCT imaging protocols and image-processing techniques into a systematic method for longitudinal monitoring and automatic quantification. The demonstration of this method on a partial-thickness burn shows the accurate co-location of longitudinal scans; characteristic vascular features in different healing phases; and eventual decrease of the elevated vasculature area density and vessel diameter to normal levels. Such a method holds promise for longitudinal monitoring of vasculature in burn injures as well as in other cutaneous vascular pathologies and responses to treatment.

The Burns Registry of Australia and New Zealand: progressing the evidence base for burn care.

OBJECTIVE: Analysis of data from the Burns Registry of Australia and New Zealand (BRANZ) to determine the extent of variation between participating units in treatment and in specific outcomes during the first 4 years of its operation. DESIGN: BRANZ, an initiative of the Australian and New Zealand Burn Association, is a clinical quality registry developed in accordance with the Australian Commission on Safety and Quality in Healthcare national operating principles. SETTING: Patients with burn injury who fulfil pre-defined criteria are transferred to and managed in designated burn units. There are 17 adult and paediatric units in Australia and New Zealand that manage almost all patients with significant burn injury. Twelve of these units treat adult patients. PARTICIPANTS: Data on 7184 adult cases were contributed by ten acute adult burn units to the registry between July 2010 and June 2014.Major outcomes: In-hospital mortality, hospital length of stay, skin grafting rates, and rates of admission to intensive care units. RESULTS: Considerable variations in unit profiles (including numbers of patients treated), in treatment and in outcomes were identified. CONCLUSIONS: Despite the highly centralised delivery of care to patients with severe or complex burn injury, and the relatively small number of specialist burn units, we found significant variation between units in clinical management and in outcomes. BRANZ data from its first 4 years of operation support its feasibility and the value of further development of the registry. Based on these results, the focus of ongoing research is to improve understanding of the reasons for variations in practice and of their effect on outcomes for patients, and to develop evidence-informed clinical guidelines for burn management in Australia and New Zealand.

Verapamil is Less Effective than Triamcinolone for Prevention of Keloid Scar Recurrence After Excision in a Randomized Controlled Trial.

A double-blind randomized controlled trial with a paired split-scar design compared verapamil, an L-type Ca2+ channel antagonist, and triamcinolone for prevention of keloid recurrence after excision. Ca2+ channel blocking activity of verapamil in keloid cells was explored. One keloid was excised per subject and each wound half randomized to receive intralesional injections of triamcinolone (10 mg/ml) or verapamil (2.5 mg/ml) at monthly intervals (4 doses). Interim analysis was performed after 14 subjects were completed. Survival analysis demonstrated significantly higher keloid recurrence with verapamil compared to triamcinolone 12 months post-surgery (log-rank test, p = 0.01) and higher overall risk of recurrence with verapamil (hazard ratio 8.44, 95% CI 1.62-44.05). The study was terminated early according to the stopping guideline (p < 0.05). Verapamil is safe but not as effective as triamcinolone in preventing keloid recurrence after excision. Further study is necessary to determine if clinical response to verapamil is linked to modulation of intracellular Ca2+.

Long-term mortality among older adults with burn injury: a population-based study in Australia.

OBJECTIVE: To assess if burn injury in older adults is associated with changes in long-term all-cause mortality and to estimate the increased risk of death attributable to burn injury. METHODS: We conducted a population-based matched longitudinal study - based on administrative data from Western Australia's hospital morbidity data system and death register. A cohort of 6014 individuals who were aged at least 45 years when hospitalized for a first burn injury in 1980-2012 was identified. A non-injury comparison cohort, randomly selected from Western Australia's electoral roll (n = 25 759), was matched to the patients. We used Kaplan-Meier plots and Cox proportional hazards regression to analyse the data and generated mortality rate ratios and attributable risk percentages. FINDINGS: For those hospitalized with burns, 180 (3%) died in hospital and 2498 (42%) died after discharge. Individuals with burn injury had a 1.4-fold greater mortality rate than those with no injury (95% confidence interval, CI: 1.3-1.5). In this cohort, the long-term mortality attributable to burn injury was 29%. Mortality risk was increased by both severe and minor burns, with adjusted mortality rate ratios of 1.3 (95% CI: 1.1-1.9) and 2.1 (95% CI: 1.9-2.3), respectively. CONCLUSION: Burn injury is associated with increased long-term mortality. In our study population, sole reliance on data on in-hospital deaths would lead to an underestimate of the true mortality burden associated with burn injury.

The influence of a single bout of aerobic exercise on short-interval intracortical excitability.

Regular physical activity can have positive effects on brain function and plasticity. Indeed, there is some limited evidence that even a single bout of exercise may promote plasticity within the cortex. However, the mechanisms by which exercise acutely promotes plasticity are not clear. To further explore the effects of acute exercise on cortical function, we examined whether a single bout of exercise was associated with changes in cortical excitability and inhibition. Using standard techniques, cortical stimulus-response curves [90% resting motor threshold (RMT)-150% RMT] were investigated in nine subjects (four females, 31.1 ± 11.7 years) and short-interval intracortical inhibition (SICI) [interstimulus interval 2 ms and 3 ms, conditioning intensities of 80% active motor threshold (AMT) and 90% AMT] in 13 subjects (six females, 28.4 ± 5.1 years) before and at 0 and 15 min following 30 min of ergometer cycling at low-moderate or moderate-high intensity. There were no changes in cortical excitability following exercise but less SICI at both 0 and 15 min post-exercise (F [2, 24] = 7.7, P = 0.003). These findings show that a short period of exercise can transiently reduce SICI. Such a change in inhibition after exercise may contribute to the development of a cortical environment that would be more optimal for plasticity and may partially explain previous findings of enhanced neuroplasticity following low-intensity exercise.

Postoperative hypothermia is associated with reduced length of stay in adult acute burn survivors.

BACKGROUND: The hypermetabolic response after a burn predisposes patients to hypothermia due to dysfunction of thermoregulation. Traditionally, hypothermia is avoided actively in burn care due to reported complications associated with low body temperature. The likelihood of hypothermia with acute burn surgery is compounded by general anesthesia, exposure of wound areas and prolonged operation times. However, we find limited studies exploring the effects of perioperative hypothermia on length of stay in the adult burn population. OBJECTIVE: To determine associations between postoperative hypothermia and hospital length of stay in adult burns patients. METHOD: This retrospective cohort study involved patients admitted to the State Adult Burn Unit in Western Australia between 1st January 2015 to 28th February 2021. All adults who underwent surgery for acute burn, and had postoperative recovery room body temperature recorded, were included in the study. In this study, we defined normothermia as >36.5C and hypothermia as < 36.0 °C with mild, moderate, and severe hypothermia being 35.0-35.9 °C, 34.0-34.9 °C and < 34.0 °C, respectively. Patients with hyperthermia were excluded. Multivariable general linear models explored if hypothermia was independently associated with length of stay. RESULTS: Among 1486 adult patients, 1338 (90%) were normothermic postoperatively, with temperatures >36.0C. We included 148 (10%) patients with hypothermia (temperature <36.0 °C) postoperatively. Most burns in the study population were minor: 96% had burns < 15% TBSA. Data modelling demonstrated that hypothermia was associated with a shorter length of hospital stay (coefficient = -0.129, p = 0.041). CONCLUSION: In adult acute burn patients, postoperative hypothermia was associated with reduced length of stay after surgery. The positive results of this study indicate that a review of the core temperature targets with acute burn surgery, and timing of burn patient cooling practices in general is warranted.

A randomised investigation of film-forming silicone gel in superficial partial thickness face and neck burn patients: Indication of improved early scar pigmentation outcomes.

INTRODUCTION: Burns to the face and neck are a source of considerable distress and a challenge to manage with dressings. Further, these often superficial injuries pose a risk of scarring and altered pigmentation. Silicone gels have emerged as a potential solution to the challenges of conservative management for face and neck burn injuries. The aims of this study were to explore the effect of topical silicone compared to routine treatment of conservatively managed burns to the face and neck. METHODS: This single-blind, randomised, controlled trial compared topical silicone film-forming dressing to standard of care for superficial partial thickness burns to the face and neck. Time to healing was the primary outcome and secondary outcomes included: 1) scar assessments (modified Vancouver Scar Scale, Dermalab Combo and Patient and Observer Scar Assessment Scale) at six weeks and three months; and 2) pain intensity scale at wound review appointments. RESULTS: Of the 55 participants in the face/neck study, 34 were male and 21 were female. Median age was 36 years (range from 25 to 47 years). The median time to healing for the silicone group was 9 days (CI 7.6 -10.4) and the control group was 7 days (CI 5.3- 8.7), p = 0.056. Analysis demonstrated significantly reduced pigmentation at six weeks in mVSS scores for the silicone group (Md = 0, IQR = 0) compared to the control group (Md = 0, IQR = 0 - 3), p = 0.043. We found no evidence of differences in reported pain between the groups (Silicone - Md = 1.15, IQR 0.3 - 4.5 vs control group - Md = 1.5, IQR 0.6 - 3.8, z = -0.63, p = 0.53). No other differences were observed, and no adverse events were associated with the topical silicone in the study whereas an infection and a reaction were experienced in the control group. CONCLUSION: Film-forming silicone gel had comparable effects to standard of care emollient on wound healing of superficial partial thickness burns of the face and neck. Silicone treated wounds were associated with a significant improvement in scar pigmentation outcome at six weeks post-burn.

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 (<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.

Trauma patient heterotopic ossification diagnosis is associated with increased hospital length of stay.

BACKGROUND: Traumatic heterotopic ossification (tHO) refers to the development of extra-skeletal bone in muscle and soft tissues following tissue insult secondary to surgery or trauma. This presents a persistent clinical concern associated with significant patient morbidity and expense to diagnose and treat. Traumatic HO is a substantial barrier to rehabilitation for trauma-injured patients. As such, the development of tHO after burn and other trauma is hypothesised to prolong inpatient length of stay (LOS) and thus increase health care costs. OBJECTIVE: To investigate the association between an inpatient tHO diagnosis and hospital LOS in trauma patients. METHODS: A retrospective audit of trauma patients over a 14-year period was completed using data from four WA hospitals. Burn and neurological trauma patients diagnosed with tHO as an inpatient (tHO+) and control subjects (tHO-), matched (1:3) by age, gender, and injury severity factors, were identified using medical diagnostic codes. Data relating to patient and injury-related determinants of LOS from tHO+ and tHO- subjects were analysed to model the association of tHO on total hospital length of stay. RESULTS: 188 identified patients were hospitalised due to traumatic injury; 47 patients with tHO following burn injury (n = 17), spinal cord injury (n = 13) and traumatic brain injury (n = 17), and 141 control patients. Those who developed tHO during hospitalisation had a significantly higher median LOS than matched trauma patients who did not develop tHO (142 days vs. 61 days). Multivariate regression analyses identified the following independent predictive factors of a prolonged hospital LOS: tHO diagnosis, mechanical ventilation hours, injury to the hip region and thigh area, other ossification disorder, pressure injury, admission to intensive care unit and deep vein thrombosis. Trauma patients diagnosed with tHO during their hospital admission stayed 1.6 times longer than trauma patients matched for injury severity without a tHO diagnosis (IRR 1.56, 95% CI 1.35-1.79, p<0.001). CONCLUSION: Traumatic heterotopic ossification is an independent explanatory factor for increased hospital LOS in patients following burns, spinal cord, and traumatic brain injury. Early diagnosis may assist in reducing the impact of tHO on acute hospital stay after trauma.

The impact of burn injury on the central nervous system.

Burn injuries can be devastating, with life-long impacts including an increased risk of hospitalization for a wide range of secondary morbidities. One area that remains not fully understood is the impact of burn trauma on the central nervous system (CNS). This review will outline the current findings on the physiological impact that burns have on the CNS and how this may contribute to the development of neural comorbidities including mental health conditions. This review highlights the damaging effects caused by burn injuries on the CNS, characterized by changes to metabolism, molecular damage to cells and their organelles, and disturbance to sensory, motor and cognitive functions in the CNS. This damage is likely initiated by the inflammatory response that accompanies burn injury, and it is often long-lasting. Treatments used to relieve the symptoms of damage to the CNS due to burn injury often target inflammatory pathways. However, there are non-invasive treatments for burn patients that target the functional and cognitive damage caused by the burn, including transcranial magnetic stimulation and virtual reality. Future research should focus on understanding the mechanisms that underpin the impact of a burn injury on the CNS, burn severity thresholds required to inflict damage to the CNS, and acute and long-term therapies to ameliorate deleterious CNS changes after a burn.