Unremitting pro-inflammatory T-cell phenotypes, and macrophage activity, following paediatric burn injury.

Objectives: The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn. Methods: Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro-inflammatory and anti-inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for > 4 timepoints within 12 months post-burn were compared to four age-matched healthy controls. Results: While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro-inflammatory mediators throughout the burn recovery, with a 3-6 fold increase of IL-17 at 1-3 weeks, and NFκß 9-18 months post-burn. T-regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin-homing T-regs (CCR4+) and increased inflammatory (CCR6+) at 1-month post-burn, to double-positive cell types (CCR4+CCR6+) elevated in circulation for 18 months post-burn. Furthermore, Tregs were observed to proportionally express less IL-10 but increased TNF-α over 18 months. Conclusion: Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post-burn, instead they become highly specialised, inflammatory and skin-homing. In this patient population, these changes persisted for at least 18 months post-burn, this 'immune distraction' may limit the ability of immune cells to prioritise other threats post-burn, such as respiratory infections.

Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Non-severe thermal burn injuries induce long-lasting downregulation of gene expression in cortical excitatory neurons and microglia.

Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. In the context of the nervous system, burn injury patients commonly develop chronic neurological disorders and have been suggested to have impaired motor cortex function, but the long-lasting impact on neurons and glia in the brain is unknown. Using a mouse model of non-severe burn injury, excitatory and inhibitory neurons in the primary motor cortex were labelled with fluorescent proteins using adeno-associated viruses (AAVs). A total of 5 weeks following the burn injury, virus labelled excitatory and inhibitory neurons were isolated using fluorescence-activated cell sorting (FACS). In addition, microglia and astrocytes from the remaining cortical tissue caudal to the motor cortex were immunolabelled and isolated with FACS. Whole transcriptome RNA-sequencing was used to identify any long-lasting changes to gene expression in the different cell types. RNA-seq analysis showed changes to the expression of a small number of genes with known functions in excitatory neurons and microglia, but not in inhibitory neurons or astrocytes. Specifically, genes related to GABA-A receptors in excitatory neurons and several cellular functions in microglia were found to be downregulated in burn injured mice. These findings suggest that non-severe burn injuries lead to long lasting transcriptomic changes in the brain, but only in specific cell types. Our findings provide a broad overview of the long-lasting impact of burn injuries on the central nervous system which may help identify potential therapeutic targets to prevent neurological dysfunction in burn 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.

Inflammatory proteins and neutrophil extracellular traps increase in burn blister fluid 24h after burn.

Burn wound blister fluid is a valuable matrix for understanding the biological pathways associated with burn injury. In this study, 152 blister fluid samples collected from paediatric burn wounds at three different hospitals were analysed using mass spectrometry proteomic techniques. The protein abundance profile at different days after burn indicated more proteins were associated with cellular damage/repair in the first 24 h, whereas after this point more proteins were associated with antimicrobial defence. The inflammatory proteins persisted at a high level in the blister fluid for more than 7 days. This may indicate that removal of burn blisters prior to two days after burn is optimal to prevent excessive or prolonged inflammation in the wound environment. Additionally, many proteins associated with the neutrophil extracellular trap (NET) pathway were increased after burn, further implicating NETs in the post-burn inflammatory response. NET inhibitors may therefore be a potential treatment to reduce post-burn inflammation and coagulation pathology and enhance burn wound healing outcomes.

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.

Evaluation of the accuracy of diagnostic coding and clinical documentation for traumatic heterotopic ossification diagnoses in Western Australian hospitals.

BACKGROUND: Traumatic heterotopic ossification (tHO) refers to the pathological formation of ectopic bone in soft tissues that can occur following burn, neurological ororthopaedic trauma. As completeness and accuracy of medical diagnostic coding can vary based on coding practices and depend on the institutional culture of clinical documentation, it is important to assess diagnostic coding in that local context. To the authors' knowledge, there is no prior study evaluating the accuracy of medical diagnostic coding or specificity of clinical documentation for tHO diagnoses across Western Australia (WA) trauma centres or across the full range of inciting injury and surgical events. OBJECTIVE: To evaluate and compare the clinical documentation and the diagnostic accuracy of ICD-10-AM coding for tHO in trauma populations across 4 WA hospitals. METHODS: A retrospective data search of the WA trauma database was conducted to identify patients with tHO admitted to WA hospitals following burn, neurological or orthopaedic trauma. Patient demographic and tHO diagnostic characteristics were assessed for all inpatient and outpatient tHO diagnoses. The frequency and distribution of M61 (HO-specific) and broader, musculoskeletal (non-specific) ICD-10-AM codes were evaluated for tHO cases in each trauma population. RESULTS: HO-specific M61 ICD-10-AM codes failed to identify more than a third of true tHO cases, with a high prevalence of non-specific HO codes (19.4 %) and cases identified via manual chart review (25.4 %). The sensitivity of M61 codes for correctly diagnosing tHO after burn injury was 50 %. ROC analysis showed that M61 ICD-10-AM codes as a predictor of a true positive tHO diagnosis were a less than favourable method (AUC=0.731, 95 % CI=0.561-0.902, p = 0.012). Marked variability in clinical documentation for tHO was identified across the hospital network. CONCLUSION: Coding inaccuracies may, in part, be influenced by insufficiencies in clinical documentation for tHO diagnoses, which may have implications for future research and patient care. Clinicians should consistently employ standardised clinical terminology from the point of care to increase the likelihood of accurate medical diagnostic coding for tHO diagnoses.

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.

Non-severe burn injury causes sustained platelet hyperreactivity.

Individuals who present to a hospital for treatment of a burn of any magnitude are more frequently hospitalised for ischemic heart disease, even decades after injury. Blood platelets are key mediators of cardiovascular disease. To investigate platelet involvement in post-burn cardiovascular risk, platelet reactivity was assessed in patients at 2- and 6-weeks after non-severe (TBSA < 20%) burn injury, and in a murine model 30 days after 8% TBSA full-thickness burn injury. Platelets were stimulated with canonical agonists and function reported by GPIIb/IIIa PAC1-binding site, CD62P expression, and formation of monocyte-platelet aggregates. In vivo thrombosis in a modified Folts model of vascular injury was assessed. Burn survivors had elevated frequencies of circulating monocyte-platelet aggregates, and platelets were hyperreactive, primarily to collagen stimulation. Burn plasma did not cause hyper-reactivity when incubated with control platelets. Platelets from burn injured mice also demonstrated increased response to collagen peptides but did not show any change in thrombosis following vascular injury. This study demonstrates the persistence of a small but significant platelet hyperreactivity following burn injury. Although our data does not suggest this heightened platelet sensitivity modulates thrombosis following vascular injury, the contribution of sub-clinical platelet hyperreactivity to accelerating atherogenesis merits further investigation.

Functional Brain Changes Following Burn Injury: A Narrative Review.

BACKGROUND: Burn injuries cause significant motor and sensory dysfunctions that can negatively impact burn survivors' quality of life. The underlying mechanisms of these burn-induced dysfunctions have primarily been associated with damage to the peripheral neural architecture, however, evidence points to a systemic influence of burn injury. Central nervous system (CNS) reorganizations due to inflammation, afferent dysfunction, and pain could contribute to persistent motor and sensory dysfunction in burn survivors. Recent evidence shows that the capacity for neuroplasticity is associated with self-reported functional recovery in burn survivors. OBJECTIVE: This review first outlines motor and sensory dysfunctions following burn injury and critically examines recent literature investigating the mechanisms mediating CNS reorganization following burn injury. The review then provides recommendations for future research and interventions targeting the CNS such as non-invasive brain stimulation to improve functional recovery. CONCLUSIONS: Directing focus to the CNS following burn injury, alongside the development of non-invasive methods to induce functionally beneficial neuroplasticity in the CNS, could advance treatments and transform clinical practice to improve quality of life in burn survivors.

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.

In vivo burn scar assessment with speckle decorrelation and joint spectral and time domain optical coherence tomography.

Significance: Post-burn scars and scar contractures present significant challenges in burn injury management, necessitating accurate evaluation of the wound healing process to prevent or minimize complications. Non-invasive and accurate assessment of burn scar vascularity can offer valuable insights for evaluations of wound healing. Optical coherence tomography (OCT) and OCT angiography (OCTA) are promising imaging techniques that may enhance patient-centered care and satisfaction by providing detailed analyses of the healing process. Aim: Our study investigates the capabilities of OCT and OCTA for acquiring information on blood vessels in burn scars and evaluates the feasibility of utilizing this information to assess burn scars. Approach: Healthy skin and neighboring scar data from nine burn patients were obtained using OCT and processed with speckle decorrelation, Doppler OCT, and an enhanced technique based on joint spectral and time domain OCT. These methods facilitated the assessment of vascular structure and blood flow velocity in both healthy skin and scar tissues. Analyzing these parameters allowed for objective comparisons between normal skin and burn scars. Results: Our study found that blood vessel distribution in burn scars significantly differs from that in healthy skin. Burn scars exhibit increased vascularization, featuring less uniformity and lacking the intricate branching network found in healthy tissue. Specifically, the density of the vessels in burn scars is 67% higher than in healthy tissue, while axial flow velocity in burn scar vessels is 25% faster than in healthy tissue. Conclusions: Our research demonstrates the feasibility of OCT and OCTA as burn scar assessment tools. By implementing these technologies, we can distinguish between scar and healthy tissue based on its vascular structure, providing evidence of their practicality in evaluating burn scar severity and progression.

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.

Carbon dioxide laser treatment of burn-related scarring: Results of the ELIPSE (Early Laser Intervention Promotes Scar Evolution) prospective randomized controlled trial.

AIM: To investigate the impact of ablative fractional carbon dioxide laser (AFCO2L) on patient-reported outcomes measures, subjective scar appearance, dermal architecture, and gene transcription in early burn scars. METHODS: Fifteen adult patients with a burn-related scar were recruited. Inclusion criteria were two non-contiguous scar areas of 1% total body surface area, similar baseline Vancouver scar scale (VSS) score and 3months since the time of injury. All participants acted as their own control. Scars were randomized to treatment or control. Treatment scars received three AFCO2L treatments at 6-week intervals. Outcome measures were recorded at baseline, 3, 6, and 12-months post-treatment. Measures included blinded VSS, Patient Observer Scar Assessment Scale (POSAS), Brisbane Burn Scar Impact Profile (BBSIP), blinded scar photo assessment, histological tissue analysis, and RNA sequencing analysis. RESULTS: No significant difference was found in VSS, scar erythema, or pigmentation. Patient POSAS improved in scar thickness and texture following AFCO2L. All elements of BBSIP improved in control and laser groups. AFCO2L-treated scars were scored better than control scars by blinded raters. RNA sequencing illustrated that AFCO2L induced sustained changes in fibroblast gene expression. CONCLUSIONS: AFCO2L treated scars had significantly altered scar thickness and texture 6 months post-laser and were rated better than controls on blinded photo analysis after 3 treatments. RNASeq results suggest laser treatment alters the transcriptome of treated fibroblasts for at least 3 months after treatment. Expansion of this research to study in more depth fibroblast changes in response to laser, as well as assessing the impact on daily activity and quality of life, will be beneficial.

Cardiometabolic disease risk markers are increased following burn injury in children.

Introduction: Burn 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. Methods: A 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. Results: Burn 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 <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. Discussion: These 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.

Higher operating theatre temperature during burn surgery increases physiological heat strain, subjective workload, and fatigue of surgical staff.

Raising the ambient temperature of the operating theatre is common practice during burn surgeries to maintain the patient's core body temperature; however, the effects of operating in the heat on cognitive performance, manual dexterity, and perceived workload of surgical staff have not been assessed in a real-world context. Therefore, the aim was to assess the real-time impact of heat during burn surgeries on staff's cognitive function, manual dexterity, and perceptual measures (workload, thermal sensation, thermal comfort, perceived exertion, and fatigue) and physiological parameters (core temperature, heart-rate, fluid loss, and dehydration). Ten burn surgery staff members were assessed in CON (24.0±1.1°C, 45±6% relative humidity [RH]) and HOT (30.8±1.6°C, 39±7% RH) burn surgeries (average 150 min duration). Cognitive performance, manual dexterity, and perceptual measures were recorded pre- and post-surgery, while physiological parameters were recorded throughout surgery. HOT conditions did not significantly affect manual dexterity or cognitive function (p > .05), however HOT resulted in heat strain (increased heart-rate, core temperature, and fluid loss: p < .05), and increased subjective workload, discomfort, perceived exertion, and fatigue compared to CON conditions (p < .05). Cognitive function and manual dexterity were maintained in hot conditions, suggesting that operating in approximately 31°C heat is a safe approach for patient treatment. However, job burnout, which is positively correlated with perceived workload, and the impact of cumulative fatigue on the mental health of surgery staff, must be considered in the context of supporting an effective health workforce.

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.

Long-Term Laryngotracheal Complications After Inhalation Injury: A Scoping Review.

Long-term laryngotracheal complications (LTLC) after inhalation injury (II) are an under-recognized condition in patients with burns. The purpose of this study was to systematically review all available evidence on LTLC after II and identify gaps in knowledge to guide the direction of future research. A scoping review was performed to synthesize all available evidence on LTLC after II, as guided by the question, "What are the LTLC after II, in patients with or without a history of translaryngeal intubation and/or tracheostomy?". MEDLINE, Web of Science, Ovid Embase, Cochrane Library, and Google Scholar were searched for publications on this topic. Of the 3567 citations screened, a total of 153 full-text articles were assessed for eligibility and 49 were included in the scoping review. The overall level of evidence was low, with case reports constituting 46.7% of all included human studies. The lesions were most frequently in the trachea (36.9%), followed by the glottis (34.7%) and subglottis (19.0%). LTLC occur in 4.8 to 6.5% of patients after II and these complications are under-recognized in burns patients. The risk factors for LTLC include high-grade II, elevated initial inflammatory responses, prolonged translaryngeal intubation, and a history of tracheostomy. The goal of management is to restore airway patency, preserve voice quality, and restore normal diet and swallow function. There is limited high-level evidence on LTLC, particularly with regards to long-term functional morbidity in voice and swallow. Large, prospective studies are required to address this gap in knowledge.

Quality of life in paediatric burn patients with non-severe burns.

BACKGROUND: Burns are common worldwide, and the vast majority are non-severe burns of less than 20% of the total body surface area (TBSA). In Australia, paediatric burns account for a third of all burn admissions, thus understanding the quality-of-life outcomes after a non-severe burn in children is important. METHODS: This retrospective cohort study describes a paediatric cohort from Western Australia with non-severe burns occurring between 2018 and 2020 and characterises the child's quality-of-life outcomes which is measured using the Paediatric quality of life survey (PedsQL). The PedsQL included a parent-report and child-report assessment, each with a physical function domain and a psychosocial function domain which comprised of an emotional, a social and a school category. RESULTS: Data collected from 249 patients; 50.6% were male, 45.6% were toddlers. The most common cause was scald (48.19%), the majority had burns smaller than 5% TBSA (91.97%), and most included visible areas such as head, neck or hands (77.51%). The parent-report PedsQL scores were significantly different for both physical and psychosocial domains between the different age groups (p = 0.002, p = 0.001, respectively) and for burn cause (p = 0.004, p = 0.005, respectively). For child-reported scores we found evidence of an effect of burn cause across both domains that did not reach a statistical significance (p = 0.076, p = 0.078, respectively). The psychosocial functions in both the parent-report and the self-report were significantly different for the socioeconomic status groups (p = 0.015, p = 0.032, respectively). Quality of life scores were critically low in 16.46% of paediatric burn patients at three months after burn. CONCLUSION: Parent-reported and child-reported psychosocial function was significantly poorer in higher socioeconomic groups, for older children and for those with flame burns. About 16% of patients had scores below the critical cut off. These data provide insight into the quality-of-life outcomes of paediatric patients with non-severe burns, allowing future studies to investigate burn prevention strategies and services to help paediatric burn patients in their recovery.