The aim of this study was to identify immune cells and inflammatory mediators associated with delayed wound healing in paediatric burn patients. Peripheral blood mononuclear cells (PBMCs) were isolated from 30 paediatric participants: 10 healthy age- and sex-matched controls, 10 burn patients whose wounds healed within 21 days (normal healing), and 10 patients with healing times exceeding 21 days (delayed healing). Flow cytometry was used to quantify immune cell subsets and intracellular cytokine expression, and plasma cytokines were measured via multiplex immunoassay. There were no significant differences in the proportions of major immune cell subsets-including CD4⁺ T-helper cells, CD8⁺ cytotoxic T cells, monocytes, and macrophages-between the groups. However, delayed healing patients exhibited significantly higher frequencies of CCR6⁺ cells and elevated expression of pro-inflammatory cytokines IL-17 and IL-23 in γδ T cells, NKT-like cells, and regulatory T cells (Tregs). Plasma concentrations of IL-33, IL-23, TNF-α, and MCP-1 were also significantly increased in the delayed healing group (p < 0.05). In contrast, patients with normal healing displayed higher proportions of Tregs expressing the anti-inflammatory cytokine TGF-β. These findings suggest that delayed healing in paediatric burn patients may be associated with a persistent systemic pro-inflammatory immune profile, marked by elevated CCR6 expression and IL-17/IL-23 axis activation. This unresolved inflammation could contribute to chronic immune dysregulation and may underlie the long-term comorbidities observed in this population. Targeting these inflammatory pathways may offer novel therapeutic strategies to improve wound healing outcomes in paediatric burns.

OBJECTIVES:To characterise long-term immune dysregulation and persistent inflammatory signalling in paediatric burn survivors with hypertrophic scarring. METHODS:Peripheral blood mononuclear cells and plasma were analysed from 20 paediatric participants: 10 burn survivors with hypertrophic scarring (median 4.1 years post-injury) and 10 age- and sex-matched healthy controls. Multiparameter flow cytometry, multiplex cytokine analysis, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to assess immune cell phenotypes, inflammatory mediators, and inflammatory gene expression. RESULTS:Overall proportions of major immune cell subsets were comparable between groups. However, burn survivors with hypertrophic scarring demonstrated increased CD4⁺TNFα⁺ cells, Th17 cells, CCR6⁺ natural killer T-like cells, IL-23⁺ natural killer cells, and IL-23-expressing macrophage populations (all P < 0.05). Regulatory T cells (Tregs) and CCR4⁺CCR6⁺ double-positive Tregs were also increased (P < 0.05). Plasma concentrations of IL-1β, tumour necrosis factor-α, IL-12p70, IL-17A, and IL-23 were significantly elevated in the scar group (all P < 0.05). Gene expression analysis identified persistent upregulation of nuclear factor kappa B1 (NFκB1; 2.21-fold) and IL-17 (3.38-fold). CONCLUSION:Paediatric burn survivors with hypertrophic scarring demonstrate persistent systemic immune dysregulation several years after injury. However, the cross-sectional design and absence of a normotrophic burn control group limit conclusions regarding whether these immune alterations are specific to pathological scarring or reflect broader long-term post-burn immune dysregulation.

Introduction Dissemination of evidence-based burn first-aid is critical for improving clinical outcomes for patients with acute burn injuries. The overarching goal of this research is the successful and sustainable translation of 20 min of cool running water (20CRW), administered within 3 hours of a burn, as a first-aid treatment for acute thermal injuries within emergency departments (EDs) and emergency medical services (EMSs). Despite the well-established benefits of 20CRW, this treatment is not included in relevant USA burn first-aid guidelines and has not been adopted in clinical settings as a standard first-aid treatment.Methods and analysis This protocol outlines an investigation using an effectiveness-implementation hybrid type III design to evaluate the effectiveness of 20CRW implementation into ED and EMS settings in Sacramento, California. The principal aim of this research is to implement 20CRW as a first-aid treatment for acute thermal burn injuries within participating ED and EMS settings. We will assess adherence to 20CRW guidelines and provision following implementation into routine clinical practice. In addition, we will evaluate the clinical effectiveness of 20CRW in improving patient outcomes, and the acceptability of 20CRW as a burn first-aid treatment, considering both clinician and burn survivor perspectives. This research will generate critical evidence on the implementation and clinical impact of 20CRW in US emergency care settings. It will also evaluate whether the co-designed implementation strategies effectively support adoption of 20CRW within the US ED and EMS settings.Ethics and dissemination Institutional Review Board (IRB) approval has been awarded for this research (IRB ID: 18834-5) from the University of California Davis Office of Research Ethics Committee. Results of this investigation will be disseminated across participating hospital and EMS organisations, presented at national and international conferences and published in open access peer-reviewed journals.

First aid recommendations for chemical burns include copious water irrigation for 30 minutes to 2 h after removal of the substance from skin. The aim of this retrospective analysis was to assess the efficacy of water irrigation on short-term outcomes for chemical burn injuries. Data from the Australian and New Zealand Burn registry (2009-2020) were analyzed to categorize the application of running water for first aid for presence, timing of application postinjury, and duration. The timing of first aid application was classified into whether the application was pre-hospital or in-hospital. Multivariate regression analyses then evaluated how water irrigation affected hospital stay, Intensive Care Unit admission, and the necessity for acute surgery for wound closure. Among 1549 chemical burn patients, for those who received in-hospital first aid their stay was reduced by about 18% compared to those who did not. Patients receiving pre-hospital or in-hospital first aid had 37% and 31% lower odds, respectively, of needing acute care surgery for wound closure compared to those who did not. There was no evidence that first aid provision influenced the need for intensive care admission. Water irrigation is associated with shorter hospital stays and reduced acute care surgery for wound closure following chemical burns without impacting intensive care admission rates.

STUDY OBJECTIVE:The application of 20 minutes of cool running water within 3 hours of a burn injury significantly improves patient burn-related outcomes. To facilitate the integration of 20 minutes of cool running water into clinical practice in the United States, this investigation aimed to determine barriers and facilitators to implementing 20 minutes of cool running water in out-of-hospital emergency medical services (EMS) and in-hospital emergency departments (EDs) and to codesign tailored strategies for its routine use in acute burn first aid. METHODS:Using a sequential mixed-methods design, we identified barriers and facilitators to 20 minutes of cool running water implementation and codesigned strategies to enhance its implementation. EMS and ED clinicians completed an online questionnaire assessing perceived barriers and facilitators, with responses coded using the Consolidated Framework for Implementation Research. Semistructured interviews with a convenience sample of participants further examined determinants and codesigned implementation strategies. RESULTS:A total of 371 (210 EMS, 161 ED) clinicians participated in the questionnaire, and 22 (14 EMS, 8 ED) participated in interviews. Twelve key determinants were identified across 4 Consolidated Framework for Implementation Research domains. Implementation barriers included a lack of resources, challenges adapting 20 minutes of cool running water to local clinical settings, and the absence of external policies incorporating burn first aid cooling, whereas facilitators included high clinician motivation, strong professional networks, and a supportive clinical culture. Codesigned strategies to enhance 20 minutes of cool running water uptake included portable irrigation equipment, nursing-driven protocols, and policy updates. CONCLUSION:Although clinicians appear motivated to implement 20 minutes of cool running water, infrastructure, workflow, and policy challenges hinder widespread adoption. Addressing these barriers through targeted codesigned 20 minutes of cool running water implementation strategies will facilitate integration into EMS and ED settings, improving burn care outcomes.

Pregnancy and live birth rates are commonly used metrics to define fertility in humans and animals. The impact of aberrant microRNA (miRNA) expression on fertility-related genes represents a significant knowledge gap in understanding post-transcriptional regulatory mechanisms associated with reproductive dysfunction. Identifying subfertility markers is therefore critical to the success of fertility intervention strategies, particularly in agriculture, where sustainable farming practices are linked to overall economic performance. Here, we explore the expression patterns and association of blood plasma small extracellular vesicles (sEV)-derived miRNA with Holstein-Friesian dairy cow (Bos taurus) subfertility. Small RNA-seq identified 14 differentially expressed plasma sEV-derived miRNAs (FDR < 0.05 and -logFC > 2) between divergent low fertile (LF) and high fertile (HF) primiparous dairy cows (n = 10/group) with known reproductive outcomes. qRT-PCR miRNA assay validation of these plasma sEV miRNA candidates isolated from a different sample population of young heifers (10 month old) (LF and HF; n = 8/group) confirmed that the abundance of miR-181b-2-3p was significantly higher in LF sEVs compared to HF sEVs [p value = 0.0093, relative expression ratio = 2.665 (2-ΔΔCT; LF = 19.6095, HF = 7.35636)]. Our results suggest that circulating sEV miRNA may contribute, in part, to fertility traits in dairy cows. The association of miR-181b-2-3p with the subfertility phenotype suggests that this miRNA may serve as a putative early indicator of LF status.

Saliva is a child appropriate biofluid, but it has not previously been used to evaluate the systemic response to burn injury in children. The aim of this study was to investigate the salivary proteome of children with small area thermal skin burns relative to different burn characteristics (mechanism, time to re-epithelialization and risk of emotional distress). SWATH Mass Spectrometry was used to quantify the abundance of 742 proteins in the saliva of children with burns (n = 22) and healthy controls (n = 37). Eight proteins were differentially abundant in the saliva of children with burns compared to healthy children, and these were associated with immune processes, epidermal cell differentiation and transferrin receptor binding. Eleven proteins were differentially abundant in patients with burns of different mechanisms. Scald burns had an over-representation of immune/inflammatory response processes, and contact burns had an over-representation of cornification, intermediate filament assembly and cell death cellular processes. Four proteins were elevated in patients who were at high risk for emotional distress and 15 proteins were correlated with time to wound re-epithelialization. This pilot study proves that saliva can be used for paediatric biomarker discovery and can be used as a diagnostic and prognostic sample to investigate systemic changes in a paediatric burn cohort.

AbstractObjectivesThe aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post‐burn.MethodsFlow 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.ResultsWhile 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 NFκβ 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.ConclusionOverall, 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.

The most recognised role of vitamin D in the body is for calcium absorption, and sufficiency is defined as a vitamin D blood serum level greater than 20 ng/mL (50 nmol/L). In growing children, hypovitaminosis D is associated with bone and muscle weakness, fractures, and osteoporosis. Burns patients are at a greater risk of low vitamin D levels due to lack of ultraviolet rays reaching the skin during prolonged hospital admission and sun avoidance post-burn injury. This study aimed to identify any individual, seasonal or burn injury characteristics in paediatric patients that were associated with low total vitamin D levels. Three different vitamin D metabolites were analysed to identify if, and where, in the synthesis pathway any insufficiencies may be occurring. Liquid Chromatography Mass Spectrometry (LCMS) was used to concurrently assess vitamin D3 (25OHD3 or Calcifediol), its epimer (3epi-25(OH)D3), and its precursor Pre Vitamin D3 (Cholecalciferol), in the plasma from 193 Australian paediatric burn patients, compared to 46 healthy controls. The results indicated that 61 % of healthy controls and up to 76 % of all burn patients had below normal clinical ranges of Total 25OHD3 (25(OH)D3 + 3epi-25(OH)D3). However, there were no significant differences between patient groups (control, acute, scarring, and reconstructive). The season of sample collection contributed significantly to total vitamin D levels but patients who were undergoing reconstructive surgery 1–17 years post-burn had consistently low vitamin D levels across all seasons. Routine screening, dietary monitoring, and potential supplementation of vitamin D in the burns population is recommended as it may impact recovery, growth and development of the child post-burn.

Abstract Introduction Burns patients are susceptible to infection, and some studies suggest patients exhibit post-burn immunosuppression. However, the trajectory of immune cells after a burn injury are unknown. Furthermore, the immune cells associated with poor healing outcomes are also unknown. Aim 1 of this study characterised the immune profile of paediatric burn patients for over 18 months post-burn. Aim 2 identified the immune cells and inflammatory markers related to delayed burn wound healing. Methods Flow cytometry was used to measure 26 cell lineage markers, chemokines and cytokines from both pro-inflammatory and anti-inflammatory immune profiles. In aim 1, Peripheral Blood Mononuclear Cells from 6 paediatric burn patients who had returned for burn and scar treatments over 4+ timepoints within 12 months post-burn were compared to 4 healthy controls. Aim 2 recruited 10 burn patients who re-epithelialized in < 21 days, 10 patients who re-epithelialized in >21 days, and 10 healthy control patient cells. All participants were children under 10 years age, with partial or full thickness scald or contact burns, 1-34% TBSA. Healthy controls were age and gender-matched. Results While the level of basic immune cells such as CD4 and CD8 T cells remained relatively constant, over time T cells differentiated into proinflammatory cell phenotypes including Th17 and γδ-T cells. There was a 3-fold increase of IL-17 production from γδ-T cells in the first 3 weeks post-burn(p< 0.01). CCR4+CCR6+ T-regulatory cells positive were elevated at 9-18 months post-burn (p< 0.05). Alternatively activated (M2) macrophages displayed a 3.5-fold increase compared with controls (p< 0.01). Aim 2 preliminary results showed children with burns who re-epithelialized in under 21 days had variable abundance of T regulatory cells. Further, children with burns had a higher abundance of double positive CCR4+CCR6+ Tregs than healthy controls. Conclusions Our results indicate immune cells do not increase or decrease over time post-burn, but they become highly specialised, inflammatory, and skin homing. These changes persist for 18 months post-burn, and this post-burn “immune distraction” may limit the ability of immune cells to prioritise responses to other threats, such as infections. Additionally, therapies which target the immune cells associated with delayed wound healing may enhance healing outcomes for paediatric burn patients. Applicability of Research to Practice This project identifies targets in the immune/inflammatory response which if mediated, could improve burn wound healing outcomes.

BACKGROUND:Acute application of adjunctive negative pressure wound therapy (NPWT) significantly improves time to re-epithelialization in pediatric burn patients. This adjunctive treatment has not yet been broadly or routinely adopted as a standard primary burns dressing strategy. The Implementation of Negative PRessurE for acute Pediatric burns (INPREP) trial will implement and evaluate the impact of adjunctive NPWT in parallel with co-designed implementation strategies and resources across four major pediatric hospitals. METHODS:We will conduct a multi-center, prospective, stepped-wedge cluster randomized controlled trial to implement adjunctive NPWT for acute pediatric burns. Participants will include pediatric burn patients presenting to one of four Australian tertiary pediatric hospitals for burn treatment. The intervention is adjunctive NPWT in parallel with co-designed and tailored implementation strategies and a suite of NPWT implementation resources, which form the INPREP toolkit. Using a hybrid type III design, this trial aims to evaluate the effectiveness of NPWT implementation in parallel with the INPREP toolkit using (i) implementation outcomes (e.g., adoption, appropriateness, acceptability, feasibility, and sustainability) and (ii) clinical outcomes (e.g., days to re-epithelialization, scar management requirements, skin grafting requirements). The primary outcome of this trial is treatment adoption-the proportion of eligible patients who receive NPWT. DISCUSSION:This manuscript outlines a protocol for a hybrid type III stepped-wedge cluster randomized controlled trial of adjunctive NPWT implementation in acute pediatric burn care. We anticipate that NPWT implementation in parallel with the INPREP toolkit will be generalizable to emergency departments and burn services across Australia, and evidence generated will inform pediatric burn care internationally. TRIAL REGISTRATION:Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

PurposePediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies.MethodsA sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes.ResultsSixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning.ConclusionMultiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability.Trial registrationAustralian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

Abstract Introduction Pediatric burn injuries pose a major clinical problem worldwide and result in significant morbidity. Early application of adjunctive negative pressure wound therapy (NPWT) has been shown to significantly improve time to re-epithelialization in pediatric burn patients, however this treatment has not yet been reliably or consistently adopted. Methods This investigation used a sequential mixed methods design to identify and explore barriers to the implementation of adjunctive NPWT in acute pediatric burn care. An online questionnaire was developed and disseminated to healthcare professionals within four major pediatric hospitals, each with a dedicated burns service. Specific barrier data were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews were then conducted with senior clinicians across the four participating hospitals to adapt and tailor implementation strategies to local contexts. A stakeholder consensus meeting was then conducted to consolidate implementation strategies and local processes. Results A total of 63 healthcare professionals participated in the online questionnaire, and semi-structured interviews were conducted with nine senior burn clinicians. Two interviews were also conducted with parents and caregivers of pediatric burn patients who had received NPWT as part of their acute burn treatment within the last 12-months. This investigation identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address these identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies and incentives, intervention complexity, and planning. Conclusions There are multiple and inter-related contextual characteristics that influence the uptake of adjunctive NPWT into acute pediatric burn settings. In order to implement NPWT into clinical practice for the acute treatment of pediatric burn injuries, additional resources, education, training, and updates to policies and guidelines are required. It is anticipated that NPWT, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. Applicability of Research to Practice The time lag in evidence-to-practice implementation is a well-recognized issue in clinical and healthcare research. This investigation is one of the first to define barriers and enablers of implementation in acute pediatric burns. Findings from this research can help inform and guide other acute burn related implementation studies in the future, the implementation of other technologies, devices, or treatment pathways for pediatric patients in a healthcare setting.

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. (c) 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Abstract Fertility is determined to a significant extent by its underlying genetics and success of pregnancy is considered as a tool to define fertility. A substantial knowledge gap exists however, regarding epigenetic abnormalities resulting in infertility. The accuracy of information concerning fertility is critical to the success of an infertility treatment plan. Here, the authors explore the use and the value of blood plasma small extracellular vesicle (sEV) derived micro-RNA (miRNA) as biomarkers of fertility. Next-generation miRNA sequencing identified 14 differentially expressed (DE) miRNAs expressed with a substantial confidence between low fertile (LF) sEV and high fertile (HF) sEV (FDR < 0.05 and -logFC > 2), isolated from plasma of dairy cows (n = 10 per each HF and LF group). Interestingly, the majority of DE miRNAs were uniquely packaged into sEV and not found in circulating plasma. Validation using qRT-PCR miRNA assays indicated similar expression patterns of miR-17-5p, miR-2285dd, miR-2335, miR-12054 and miR-2285aw, and confirmed that miR-181b-5p was significantly upregulated in LF sEV (P value = 0.0093, Fold change = 2.665). The results from this study suggest that circulating sEV miRNA reflect the overall fertility status including the physiological status of the endometrium. Moreover, miR-181b-5p was validated as a prognostic sEV miRNA biomarker of fertility.

MicroRNAs are small, non-coding RNAs that regulate gene expression, and consequently protein synthesis. Downregulation and upregulation of miRNAs and their corresponding genes can alter cell apoptosis, proliferation, migration and fibroproliferative responses following a thermal injury. This review summarises the evidence for altered human miRNA expression post-burn, and during wound healing and scarring. In addition, the most relevant miRNA targets and their roles in potential pathways are described. Previous studies using molecular techniques have identified 197 miRNAs associated with human wound healing, burn wound healing and scarring. Five miRNAs alter the expression of fibroproliferative markers, proliferation and migration of fibroblasts and keratinocytes post-burn: hsa-miR-21 and hsa-miR-31 are increased after wounding, and hsa-miR-23b, hsa-miR-200b and hsa-let-7c are decreased. Four of these five miRNAs are associated with the TGF-β pathway. In the future, large scale, in vivo, longitudinal human studies utilising a range of cell types, ethnicity and clinical healing outcomes are fundamental to identify burn wound healing and scarring specific markers. A comprehensive understanding of the underlying pathways will facilitate the development of clinical diagnostic or prognostic tools for better scar management and the identification of novel treatment targets for improved healing outcomes in burn patients.

Chemical burns can cause deep injury and subsequently significant scarring to the skin. The mechanism and pathophysiology of chemical burns is distinct to thermal burns, and recommended first aid approaches are consequently different. Twenty minutes of cool running water is an effective first aid measure to improve outcomes after thermal burn. For chemical burns to the skin, the recommendations are immediate water lavage for 60 min, removal of contaminated clothing if not stuck to the skin and then covering the wound with a sterile dressing. This review assesses the peer-reviewed literature to find the evidence behind the efficacy of cutaneous chemical burn first aid on short term outcomes such as length of hospital stay, depth of burn and longer-term outcomes such as scarring; in particular, the effect of immediate or early water lavage, and the effect of the duration of water lavage. Ocular chemical burns were not included in this review. The review suggests some evidence to support that the early application of cool water irrigation may reduce length of hospital stay and the extent of scarring. Community education should emphasize that water irrigation is recommended and that the earlier this happens, the better.

Paediatric burn injuries are common, especially in children younger than 5 years, and can lead to poor physical and psychosocial outcomes in the long term. In this Review, we aim to summarise the key factors and interventions before hospital admission and following discharge that can improve the long-term outcomes of paediatric burns. Care can be optimised through first aid treatment, correct initial assessment of burn severity, and appropriate patient referral to a burns centre. Scar prevention or treatment and patient follow-up after discharge are also essential. As most burn injuries in children are comparatively small and readily survivable, this Review does not cover the perioperative management associated with severe burns that require fluid resuscitation, or inhalational injury. Burns disproportionately affect children from low socioeconomic backgrounds and those living in low-income and middle-income countries, with ample evidence to suggest that there remains scope for low-cost interventions to improve care for those patients with the greatest burden of burn injury. Current knowledge gaps and future research directions are discussed.

Serum can be used to investigate changes in cytokine concentration following burn injury in children; however, for children receiving treatment in an outpatient setting, blood is not routinely collected and therefore cannot be used for monitoring. The aim of this study was to investigate the use of saliva as a noninvasive tool for predicting burn outcomes by measuring the concentration of salivary cytokines in children with small area burns. A multiplex cytokine assay was used to measure 17 cytokines in the saliva of pediatric patients with burns (n = 20) and healthy controls (n = 20). After the removal of cytokines that had >30% of samples below the assay lower detection limit, six cytokines including IL-1β, IL-4, IL-7, IL-8, MCP-1, and TNFα were analyzed for association with burns. IL-1β and IL-4 were found to be significantly elevated in the pediatric burn patients compared to healthy controls. Interestingly, IL-1β was also significantly elevated in scald burns, compared to contact burns. In addition, biologically meaningful differences in cytokine concentration were identified in patients with different burn characteristics, which warrant further investigation. This exploratory study provides evidence that cytokines can be detected in the saliva of children and that salivary cytokine profiles differ between healthy controls and children with burns. Overall, this study demonstrates the value of saliva for the investigation of cytokines and its potential application in pediatric diagnostics, specifically in situations where blood collection is not appropriate.