Current understanding of the chronic stress response to burn injury from human studies

There is a marked inflammatory and hypermetabolic response following a burn injury.The inter-linked responses are more pronounced than for other forms of trauma and can persist for≥3 years post-injury in burned patients.After a burn,patients have an increased risk of diseases of ageing including cancer,diabetes and cardiovascular disease,highlighting the need for effective long-term strategies to ameliorate the stress response post-burn.Current therapeutic strategies for post-burn recovery include removal of damaged tissue with surgical excision and wound repair,nutritional supplementation and rehabilitative exercise.These strategies aim to minimize the hypermetabolic and inflammatory responses,as well as reducing the loss of lean body mass.This review briefly summarises the inflammatory and hypermetabolic responses and provides an update on the current therapeutic strategies for burned patients.The review examines the persistent nutritional challenge of ensuring sufficient energy intake of each macronutrient to fuel the hypermetabolic and counteract the catabolic response of burn injury,whilst reducing periods of hyperglycaemia and hypertriglyceridemia.Patients require individualized treatment options tailored to unique systemic responses following a burn,facilitated by a precision medicine approach to improve clinical and physiological outcomes in burned patients.Thus,this review discusses the utility of metabolic flexibility assessment to aid clinical decision making and prescription relating to nutritional supplementation and rehabilitative exercise in the burned patient.

Plasma lipidomics reveal systemic changes persistent throughout early life following a childhood burn injury

Background:Non-severe paediatric burns can result in poor long-term health outcomes.This occurs even in cases with good acute burn-related outcomes,including minimal scarring.The mechanisms that underpin the transition from non-severe burn to sustained negative long-term health impacts are currently unknown.However,sustained metabolic and immune changes have been observed in paediatric burn studies,suggesting these changes may be important.The plasma lipidome consists of a rich pool of bioactive metabolites that play critical roles in systemic processes including molecular signalling and inflammation.We hypothesised that changes in the plasma lipidome may reflect underlying changes in health status and be linked to long-term health after burn trauma.Methods:This study analysed the lipidome in children who had previously experienced a non-severe burn,compared to non-injured controls.Thirty-three participants were recruited between the ages of 5 and 8 years who had experienced a non-severe burn between the ages of 1 and 3 years.Plasma samples were also collected from a non-injured,healthy,age and gender matched control group(n=21).Plasma lipids were measured using reversed-phase liquid chromatographymass spectrometery(LC-MS).Results:In total 838 reproducible lipid species from 19 sub-classes passed quality control procedures and progressed to statistical analysis.Analysis of individual lipid metabolites showed significantly higher concentrations of lysophosphatidylethanolamines and phosphatidylethanolamines,and significantly lower concentrations in myristic,palmitic and palmitoleic acids in the plasma of those who had experienced burn injury compared to controls.Conclusion:Long-term changes in the lipid profile may give insight into the mechanisms underlying poor long-term health subsequent to non-severe burn injury.Further work to investigate the relationship between long-term pathology and lipidomic changes may lead to a better understanding of the causes of secondary morbidity post-burn and to clinical intervention to reduce the long-term health burden of burn trauma.

Non-severe burn injury increases cancer incidence in mice and has long-term impacts on the activation and function of T cells

Background:Recent evidence suggests that burn patients are at increased risk of hospital admission for infection,mental health conditions,cardiovascular disease and cancer for many years after discharge for the burn injury itself.Burn injury has also been shown to induce sustained immune system dysfunction.This change to immune function may contribute to the increased risk of chronic disease observed.However,the mechanisms that disrupt long-term immune function in response to burn trauma,and their link to long-term morbidity,remain unknown.In this study we investigated changes to immune function after burn injury using a murine model of non-severe injury.Methods:An established mouse model of non-severe burn injury(full thickness burn equivalent to 8%total body surface area)was used in combination with an orthotopic model of B16 melanoma to investigate the link between burns and cancer.Considering that CD8^(+)T cells are important drivers of effective tumour suppression in this model,we also investigated potential dysregulation of this immune population using mouse models of burn injury in combination with herpes simplex virus infection.Flow cytometry was used to detect and quantify cell populations of interest and changes in immune function.Results:We demonstrate that 4 weeks after a non-severe burn injury,mice were significantly more susceptible to tumour development than controls using an orthotopic model of B16 melanoma.In addition,our results reveal that CD8^(+)T cell expansion,differentiation and memory potential is significantly impaired at 1 month post-burn.Conclusions:Our data suggests that CD8^(+)T cell-mediated immunity may be dysfunctional for a sustained period after even non-severe burn injury.Further studies in patients to validate these findings may support clinical intervention to restore or protect immunity in patients after burn injury and reduce the increased risk of secondary morbidities observed.

Identification of factors predicting scar outcome after burn injury in children:a prospective case-control study

Background:There is a lack of rigorous research investigating the factors that influence scar outcome in children. Improved clinical decision-making to reduce the health burden due to post-burn scarring in children will be guided by evidence on risk factors and risk stratification. This study aimed to examine the association between selected patient, injury and clinical factors and the development of raised scar after burn injury. Novel patient factors were investigated including selected immunological co-morbidities (asthma, eczema and diabetes type 1 and type 2) and skin pigmentation (Fitzpatrick skin type). Methods:A prospective case-control study was conducted among 186 children who sustained a burn injury in Western Australia. Logistic regression was used to explore the relationship between explanatory variables and a defined outcome measure:scar height measured by a modified Vancouver Scar Scale (mVSS). Results:The overall correct prediction rate of the model was 80.6%;80.9%for children with raised scars (>1 mm) and 80.4%for children without raised scars (≤1 mm). After adjustment for other variables, each 1%increase in%total body surface area (%TBSA) of burn increased the odds of raised scar by 15.8%(95%CI=4.4-28.5%). Raised scar was also predicted by time to healing of longer than 14 days (OR=11.621;95%CI=3.727-36.234) and multiple surgical procedures (OR=11.521;1.994-66.566). Conclusions:Greater burn surface area, time to healing of longer than 14 days, and multiple operations are independently associated with raised scar in children after burn injury. Scar prevention strategies should be targeted to children with these risk factors.

A retrospective cohort study to compare post-injury admissions for infectious diseases in burn patients, non-burn trauma patients and uninjured people

Background: Injury triggers a range of systemic effects including inflammation and immune responses. This study aimed to compare infectious disease admissions after burn and other types of injury using linked hospital admissions data. Methods: A retrospective longitudinal study using linked health data of all patients admitted with burns in Western Australia (n = 30,997), 1980–2012, and age and gender frequency matched cohorts of people with non-burn trauma (n = 28,647) and no injury admissions (n = 123,399). Analyses included direct standardisation, negative binomial regression and Cox proportional hazards regression. Results: Annual age-standardised infectious disease admission rates were highest for the burn cohort, followed by the non-burn trauma and uninjured cohorts. Age-standardised admission rates by decade showed different patterns across major categories of infectious diseases, with the lower respiratory and skin and soft tissue infections the most common for those with burns and other open trauma. Compared with the uninjured, those with burns had twice the admission rate for infectious disease after discharge (incident rate ratio (IRR), 95% confidence interval (CI): 2.04, 1.98–2.11) while non-burn trauma experienced 1.74 times higher rates (95%CI: 1.68–1.81). The burn cohort experienced 10% higher rates of first-time admissions after discharge when compared with the non-burn trauma (hazard ratio (HR), 95%CI: 1.10, 1.05–1.15). Compared with the uninjured cohort, incident admissions were highest during the first 30 days after discharge for burns (HR, 95%CI: 5.18, 4.15–6.48) and non-burn trauma (HR, 95%CI: 5.06, 4.03–6.34). While incident rates remained high over the study period, the magnitude decreased with increasing time from discharge: burn vs uninjured: HR, 95%CI: 30 days to 1 year: 1.69, 1.53–1.87;1 to 10 years: 1.40, 1.33–1.47;10 years to end of study period: 1.16, 1.08–1.24;non-burn trauma vs uninjured: HR, 95%CI: 30 days to 1 year: 1.71, 1.55–1.90;1 to 10 years: 1.30, 1.24–1.37;10 years to end of study period: 1.09, 1.03–1.17). Conclusions: Burns and non-burn trauma patients had higher admission rates for infectious diseases compared with age and gender matched uninjured people. The pattern of annual admission rates for major categories of infectious diseases varied across injury groups. Overal , the burn cohort experienced the highest rates for digestive, lower respiratory and skin and soft tissue infections. These results suggest long-term vulnerability to infectious disease after injury, possibly related to long-term immune dysfunction.

Burn care: The challenges of research

Burn care is an area which has advanced relentlessly over the past decades with improved survival and quality of survival. However, there are many challenges which overshadow the successes. The translation of what we know into clinical practice remains a challenge due to issues on many levels from overcoming personal opinion to resource allocation. We live in a time of exponential increase in knowledge in diverse areas which could be harnessed to improve the lives of those suffering burn injuries. Breaking down silos in education training and research remain challenging and again the allocation of resource is key. Ultimately when the goal is "One World One Standard of Burn Care" the greatest challenge is in education with specific reference to burn injury prevention and first aid.

Demonstration of the test-retest reliability and sensitivity of the Lower Limb Functional Index-10 as a measure of functional recovery post burn injury:a cross-sectional repeated measures study design

Background:Lower limb burns can significantly delay recovery of function.Measuring lower limb functional outcomes is challenging in the unique burn patient population and necessitates the use of reliable and valid tools.The aims of this study were to examine the test-retest reliability,sensitivity,and internal consistency of Sections 1 and 3 of the Lower Limb Functional Index-10(LLFI-10)questionnaire for measuring functional ability in patients with lower limb burns over time.Methods:Twenty-nine adult patients who had sustained a lower limb burn injury in the previous 12 months completed the test-retest procedure of the study.In addition,the minimal detectable change(MDC)was calculated for Section 1 and 3 of the LLFI-10.Section 1 is focused on the activity limitations experienced by patients with a lower limb disorder whereas Section 3 involves patients indicating their current percentage of pre-injury duties.Results:Section 1 of the LLFI-10 demonstrated excellent test-retest reliability(intra-class correlation coefficient(ICC)0.98,95%CI 0.96–0.99)whilst Section 3 demonstrated high test-retest reliability(ICC 0.88,95%CI 0.79–0.94).MDC scores for Sections 1 and 3 were 1.27 points and 30.22%,respectively.Internal consistency was demonstrated with a significant negative association(rs=?0.83)between Sections 1 and 3 of the LLFI-10(p<0.001).Conclusions:This study demonstrates that Section 1 and 3 of the LLFI-10 are reliable for measuring functional ability in patients who have sustained lower limb burns in the previous 12 months,and furthermore,Section 1 is sensitive to changes in patient function over time.

Venous thromboembolism prophylaxis practice and its association with outcomes in Australia and New Zealand burns patients

Background:Patients with burn injuries are considered to have an increased risk of venous thromboembolism(VTE).While untreated VTEs can be fatal,no studies have examined chemoprophylaxis effectiveness.This study aimed to quantify the variation in prevalence of VTE prophylaxis use in patients in Australian and New Zealand burns units and whether prophylaxis use is associated with in-hospital outcomes following burn injury.Methods:Admission data for adult burns patients(aged≥16 years)admitted between 1 July 2016 and 31 December 2018 were extracted from the Burns Registry of Australia and New Zealand.Mixed effects logistic regression modelling investigated whether VTE prophylaxis usewas associated with the primary outcome of in-hospital mortality.Results:There were 5066 admissions over the study period.Of these patients,81%(n=3799)with a valid response to the VTE prophylaxis data field received some form of VTE prophylaxis.Use of VTE prophylaxis ranged from 48.6%to 94.8%of patients between units.In-hospital death was recorded in<1%of patients(n=33).After adjusting for confounders,receiving VTE prophylaxis was associated with a decrease in the adjusted odds of in-hospital mortality(adjusted odds ratio=0.21;95%CI,0.07–0.63;p=0.006).Conclusions:Variation in the use of VTE prophylaxis was observed between the units,and prophylaxis use was associated with a decrease in the odds of mortality.These findings provide an opportunity to engage with units to further explore differences in prophylaxis use and develop future best practice guidelines.

Long-term mental health outcomes after unintentional burns sustained during childhood:a retrospective cohort study

Background:Burns are a devastating injury that can cause physical and psychological issues. Limited data exist on long-term mental health (MH) after unintentional burns sustained during childhood. This study assessed long-term MH admissions after paediatric burns. Methods:This retrospective cohort study included all children (<18 years) hospitalised for a first burn (n=11,967) in Western Australia, 1980–2012, and a frequency matched uninjured comparison cohort (n=46,548). Linked hospital, MH and death data were examined. Multivariable negative binomial regression modelling was used to generate incidence rate ratios (IRR) and 95%confidence intervals (CI). Results:The burn cohort had a significantly higher adjusted rate of post-burn MH admissions compared to the uninjured cohort (IRR, 95%CI:2.55, 2.07–3.15). Post-burn MH admission rates were twice as high for those younger than 5 years at index burn (IRR, 95%CI 2.06, 1.54–2.74), three times higher for those 5–9 years and 15–18 years (IRR, 95%CI:3.21, 1.92–5.37 and 3.37, 2.13–5.33, respectively) and almost five times higher for those aged 10–14 (IRR, 95%CI:4.90, 3.10–7.76), when compared with respective ages of uninjured children. The burn cohort had higher admission rates for mood and anxiety disorders (IRR, 95%CI:2.79, 2.20–3.53), psychotic disorders (IRR, 95%CI:2.82, 1.97–4.03) and mental and behavioural conditions relating to drug and alcohol abuse (IRR, 95%CI:4.25, 3.39–5.32). Conclusions:Ongoing MH support is indicated for paediatric burn patients for a prolonged period after discharge to potentially prevent psychiatric morbidity and associated academic, social and psychological issues.

Sexuality following trauma injury: A literature review

Restoration of the quality of life(QoL)of trauma injury survivors is the aim of trauma rehabilitation.It is generally acknowledged that sexuality is an important component of QoL;however,rehabilitation services frequently fall short of including sexuality as a matter of routine.The literature was reviewed to examine the experiences of trauma survivors from three groups:spinal cord injury(SCI),traumatic brain injury(TBI)and burns.The focus was on the impact of trauma on the QoL to identify future research directions and to advocate for the inclusion of sexuality as an integral part of rehabilitation.Databases searched were Proquest,Ovid,Cinahl,Medline,PsycInfo and Cochrane Central Register of controlled trials.A total of 36 eligible studies were included:SCI(n=25),TBI(n=6),burns(n=5).Four themes were identified across the three trauma groups that were labeled as physiological impact of trauma on sexuality,cognitive-genital dissociation(CGD),sexual disenfranchisement(SD)and sexual rediscovery(SR).Trauma injury has a significant impact on sexuality,which is not routinely addressed within rehabilitation services.Further sexuality research is required among all trauma groups to improve rehabilitation services and in turn QoL outcomes for all trauma survivors.

A population-based comparison study of the mental health of patients with intentional and unintentional burns

Background:A number of studies report high prevalence of mental health conditions among burn patients. However there is a need to understand differences in the temporal relationship between mental health conditions and intentional and unintentional burns to hasten psychological prevention and intervention. This study aims to compare the socio-demographic profile, burn characteristics and pre-and post-burn psychiatric morbidity of burn patients by intent-of-injury. Methods:De-identified linked hospital, death and mental health (MH) case registry data of burn patients hospitalised in Western Australia between 1 January 1980 and 30 June 2012 were analysed. Crude (observed) post-burn rates of mental health admissions were generated by burn intent-of-injury. Descriptive statistics were performed to compare the characteristics of the burn patients. Results:A total of 30,997 individuals were hospitalised for a first burn;360 (1.2%) had self-harm burns and 206 (0.7%) assault burns. Over the study period, admission rates for assault burns increased by 4.8%per year (95%confidence interval (CI) 3.1–6.5%) and self-harm burns increased 6.9%per year (95%CI 4.8–9.1%). Self-harm and assault burns occurred mainly among those aged 15 to 44 years (median age, interquartile range (IQR):self-harm 30 years, 22–40;assault 31 years, 23–38). Those with self-harm burns had a longer index hospital stay (median (IQR):self-harm 15 days (5–35) vs 4 days (1–11) assault vs 4 days (1–10) unintentional) and higher in-hospital mortality (7.2%self-harm vs 1.9%assault burns vs 0.8%unintentional). More than half (55.0%) of self-harm burns had a prior hospitalisation (5-year lookback) for a MH condition vs 10.7%of assault burns and 2.8%of unintentional burns. Crude post-burn rates of MH admissions per 100 person-years (PY) by intent-of-burn subgroups:self-harm 209 per 100 PY, assault burns 11 per 100 PY and unintentional burns 3 per 100 PY. Conclusions:Intentional burn patients experienced significantly higher pre-and post-burn mental health morbidity along with significant adverse outcome in comparison with unintentional burns. Early psychological assessment and intervention could help in improving the MH of these patients.