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.

Understanding acute burn injury as a chronic disease

While treatment for burn injury has improved significantly over the past few decades,reducing mortality and improving patient outcomes,recent evidence has revealed that burn injury is associated with a number of secondary pathologies,many of which arise long after the initial injury has healed.Population studies have linked burn injury with increased risk of cancer,cardiovascular disease,nervous system disorders,diabetes,musculoskeletal disorders,gastrointestinal disease,infections,anxiety and depression.The wide range of secondary pathologies indicates that burn can cause sustained disruption of homeostasis,presenting new challenges for post-burn care.Understanding burn injury as a chronic disease will improve patient care,providing evidence for better long-term support and monitoring of patients.Through focused research into the mechanisms underpinning long-term dysfunction,a better understanding of burn injury pathology may help with the development of preventative treatments to improve long-term health outcomes.The review will outline evidence of long-term health effects,possible mechanisms linking burn injury to long-term health and current research into burns as a chronic disease.

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.

An objective measure for the assessment and management of fluid shifts in acute major burns

Background: Major burns are life threatening. Fluid resuscitation is required for survival to maintain intravascular volumes and prevent hypovolemic shock. Bioimpedance spectroscopy (BIS) has been recognised as a potential method of monitoring fluid shifts after burn and in other disease states. The aims of this study were to examine the reliability of BIS across different dressing conditions and electrode positions, establish the influence of Acticoat?on BIS variable measures and determine the validity of whole-body BIS to assess net fluid shift in the presence of moderate to major burns. Methods: An observational longitudinal cohort study was conducted from December 2014 to February 2016. Patients with over 15% total body surface area (TBSA) burns and injury less than 48 h were enrolled in the study. BIS triplicate measures were collected in an open wound and with an ActicoatTMdressing (at 5 half hour intervals). Standard and alternate electrode placements were utilised for the reliability analysis and standard placement only for determining the validity of BIS in moderate to major burns. The ImpediMde SFB7 was used to collect whole-body and segmental BIS measures. Stata statistical software, release 14 was utilised to analyse all results. Descriptive analyses were performed and were reported using the means and standard deviations (SD). Results: BIS-repeated measures established BIS raw resistance (R), and predicted volume variables were reliable in any condition (intra-class correlation coefficient (ICC) 0.996-0.999, 95% confidence intervals (CI) 0.996-0.999) without a systematic difference. Acticoat?dressings significantly influenced all BIS-predicted volumes (p≤0.01) as determined by multilevel mixed effects (MLME) linear regression analysis. Validity of BIS was demonstrated by resistance variables significantly decreasing with increasing net ionic fluid shift and increased TBSA (severity of injury) and calculated fluid volumes increasing with increasing net fluid shift and TBSA. BIS resistance also decreased with time as oedema reduced. For clinical use, a calculator was developed to adjust BIS variables when an Acticoat?dressing is in situ, thus facilitating BIS variable change estimates in real time, with dressings intact. Conclusion: BIS may be used clinically to monitor fluid volume change in major acute burns.

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.

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.