The modulation of the burn wound environment by negative pressure wound therapy: Insights from the proteome.

Negative pressure wound therapy has been used to promote wound healing in a variety of settings, including as an adjunct to silver-impregnated dressings in the acute management of paediatric burns. Fluid aspirated by the negative pressure wound therapy system represents a potentially insightful research matrix for understanding the burn wound microenvironment and the intervention's biochemical mechanisms of action. The aim of this study was to characterize the proteome of wound fluid collected using negative pressure wound therapy from children with small-area thermal burns. Samples were obtained as part of a randomized controlled trial investigating the clinical efficacy of adjunctive negative pressure wound therapy. They were compared with blister fluid specimens from paediatric burn patients matched according to demographic and injury characteristics. Protein identification and quantification were performed via liquid chromatography tandem mass spectrometry and sequential window acquisition of all theoretical mass spectra data-independent acquisition. Proteins and biological pathways that were unique to or enriched in negative pressure wound therapy fluid samples were evaluated using principal components, partial least squares-discriminant, and gene ontology enrichment analyses. Eight viable samples of negative pressure wound therapy fluid were collected and analyzed with eight matched blister fluid samples. A total of 502 proteins were quantitatively profiled in the negative pressure wound therapy fluid, of which 444 (88.4%) were shared with blister fluid. Several proteins exhibited significant abundance differences between fluid types, with negative pressure wound therapy fluid showing a higher abundance of matrix metalloproteinase-9, arginase-1, low affinity immunoglobulin gamma Fc region receptor III-A, filamin-A, alpha-2-macroglobulin, and hemoglobin subunit alpha. The results lend support to the hypothesis that negative pressure wound therapy augments wound healing through the modulation of factors involved in the inflammatory response, granulation tissue synthesis, and extracellular matrix maintenance. Data are available via ProteomeXchange with identifier PXD023168.

Cool Running Water First Aid Decreases Skin Grafting Requirements in Pediatric Burns: A Cohort Study of Two Thousand Four Hundred Ninety-five Children.

STUDY OBJECTIVE: First-aid guidelines recommend the administration of cool running water in the early management of thermal injury. Our objective is to analyze the associations between first aid and skin-grafting requirements in children with burns. METHODS: This cohort study used a prospectively collected registry of patients managed at a tertiary children's hospital. Multivariate logistic regression models were used to evaluate the relationship between first aid and the requirement for skin grafting. Secondary outcomes included time to re-epithelialization, wound depth, hospital admission and length of stay, and operating room interventions. Adequate first aid was defined as 20 minutes of cool running water within 3 hours of injury. RESULTS: In our cohort of 2,495 children, 2,259 (90.6%) received first aid involving running water, but only 1,780 (71.3%) were given the adequate duration. A total of 236 children (9.5%) required grafting. The odds of grafting were decreased in the adequate first aid group (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.4 to 0.8). The provision of adequate running water was further associated with reductions in full-thickness depth (OR 0.4; 95% CI 0.2 to 0.6), hospital admission (OR 0.7; 95% CI 0.3 to 0.9), and operating room interventions (OR 0.7; 95% CI 0.5 to 0.9), but not hospital length of stay (hazard ratio=0.9; 95% CI 0.7 to 1.2; P=.48). CONCLUSION: Burn severity and clinical outcomes improved with the administration of cool running water. Adequate first aid must be prioritized by out-of-hospital and emergency medical services in the preliminary management of pediatric burns.

Barriers to adequate first aid for paediatric burns at the scene of the injury.

ISSUE ADDRESSED: The recommended first aid for burns, consisting of 20 minutes of cool running water (CRW) delivered within three hours of the injury, offers a simple yet effective means of improving health outcomes. The aim of this study was to determine patient and injury characteristics associated with inadequate CRW therapy among children with thermal burns, with the goal of identifying populations at greatest risk of undertreatment. METHODS: A cross-sectional study was performed on children treated at a large tertiary paediatric burns centre. First aid was evaluated as either "adequate" or "inadequate", and then descriptive analyses were conducted to examine differences between the groups in age, ethnicity, location and socioeconomic status, among others. RESULTS: From 2013 to 2016, the families of 2522 patients were interviewed. Overall, 31.3% of children received adequate CRW at the scene of the injury. Provision of adequate CRW did not significantly differ with sex, ethnicity or nationality. Factors that were associated with inadequate first aid included very young age and early adolescence (P < 0.001), rural or remote location (P = 0.045), low socioeconomic status (P = 0.030), radiant heat and flame burns (P < 0.001), as well as burns occurring at recreational sites, on farm/trade/industrial properties and in the street (P = 0.001). CONCLUSIONS: Although most burns occurred in close proximity to sources of CRW, first aid was poor across all demographics. The highest levels of undertreatment were found in children aged 0-2, adolescents aged 15-16, those living rurally or remotely, and the socioeconomically disadvantaged. SO WHAT?: The study highlights the need for improved public education of first aid for burn injuries.

Delirium in hospitalised adults with acute burns - A systematic review.

INTRODUCTION: Delirium is a potentially modifiable, acutely altered mental state, commonly characterised as a hospital-acquired complication. Studies of adult inpatients with acute burns with and without delirium identify causative risks related to the injury or treatment and outcomes related to the patient and healthcare system. We compare patients with and without delirium, providing a high-level quantitative synthesis of delirium risks and outcomes to inform guidelines and future research. METHODS: A systematic review, meta-analysis and GRADE evaluation of risks and outcomes associated with delirium in adults with acute burns was conducted using PRISMA guidelines and PROSPERO protocol CRD42021283055. The Newcastle-Ottawa Scale was used to assess quality. RESULTS: Investigators reviewed ten studies. ASA score ≥ 3, Total Body Surface Area Percentage (TBSA)> 10%, surgery done, ICU admission, hospital and also Intensive Care Unit (ICU) lengths of stay all had statistically significant associations with delirium, with low-very low certainty on GRADE evaluation. Limitations were heterogeneous studies, review methodology and study bias. CONCLUSION: Delirium represents a significant risk to comorbid patients with burns that are hospitalised, receive ICU care, and surgery. Further research is indicated to precisely categorise delirium along the clinical journey to identify modifiable factors, prevention, and proactive therapy.

Adequacy of cool running water first aid by healthcare professionals in the treatment of paediatric burns: A cross-sectional study of 4537 children.

OBJECTIVE: To determine the adequacy of cool running water first aid provided by healthcare professionals in the early management of children with thermal burn injuries. METHODS: A cross-sectional study was undertaken using a prospectively collected registry of children who presented with a thermal burn to the only major paediatric burns centre in Queensland, Australia, from January 2013 to December 2018. Main outcome measures included the type and duration of first aid administered by paramedics, general practitioners and emergency providers at local general hospitals and a children's hospital. In accordance with current Australian guidelines, adequate cooling was defined as 20 min of cool running water within 3 h of the injury. RESULTS: Of the 4537 children who presented to the paediatric burns centre, 3261 (71.9%) received adequate first aid, including 1502 (33.1%) at the scene of injury. Paramedics and general practitioners administered adequate cooling to 184 (25.0%) and 52 (24.2%) of their patients, respectively. ED clinicians adhered to guidelines in the treatment of 1019 (56.3%) children at general hospitals and 411 (76.0%) at the children's hospital. Among ED patients who presented with incomplete prior first aid, the risk of inadequate cooling was significantly greater for those transported via ambulance (P < 0.001). CONCLUSION: Deficiencies remain in the cooling of paediatric burns patients at all levels of initial management. There is a need in the healthcare community for improved education regarding the parameters and clinical benefits of cool running water first aid.

Cost-effectiveness of adjunctive negative pressure wound therapy in paediatric burn care: evidence from the SONATA in C randomised controlled trial.

Negative pressure wound therapy (NPWT) has been shown to improve clinical outcomes for children with burns by accelerating wound re-epithelialisation. Its effects on healthcare costs, however, remain poorly understood. The aim of this study was to evaluate the cost-effectiveness of NPWT from a healthcare provider perspective using evidence from the SONATA in C randomised controlled trial, in which 101 children with small-area burns were allocated to either standard care (silver-impregnated dressings) or standard care in combination with adjunctive NPWT. The primary outcome, time to re-epithelialisation, was assessed through a blinded photographic review. Resource usage and costs were prospectively recorded for each participant for up to 6 months. Incremental cost-effectiveness ratios and dominance probabilities were estimated and uncertainty quantified using bootstrap resampling. Mean costs per participant-including dressings, labour, medication, scar management, and theatre operations-were lower in the NPWT group (AUD $903.69) relative to the control group (AUD $1669.01). There was an 89% probability that NPWT was dominant, yielding both faster re-epithelialisation and lower overall costs. Findings remained robust to sensitivity analyses employing alternative theatre costs and time-to-re-epithelialisation estimates for grafted patients. In conclusion, adjunctive NPWT is likely to be a cost-effective and dominant treatment for small-area paediatric burns (ANZCTR.org.au:ACTRN12618000256279).

Study of negative pressure wound therapy as an adjunct treatment for acute burns in children (SONATA in C): protocol for a randomised controlled trial.

BACKGROUND: Although negative pressure wound therapy (NPWT) is widely used in the management of several wound types, its efficacy as a primary therapy for acute burns has not yet been adequately investigated, with research in the paediatric population particularly lacking. There is limited evidence, however, that NPWT might benefit children with burns, amongst whom scar formation, wound progression and pain continue to present major management challenges. The purpose of this trial is to determine whether NPWT in conjunction with standard therapy accelerates healing, reduces wound progression and decreases pain more effectively than standard treatment alone. METHODS/DESIGN: A total of 104 children will be recruited for this trial. To be eligible, candidates must be under 17 years of age and present to the participating children's hospital within 7 days of their injury with a thermal burn covering <5% of their total body surface area. Facial and trivial burns will be excluded. Following a randomised controlled parallel design, participants will be allocated to either an active control or intervention group. The former will receive standard therapy consisting of Acticoat™ and Mepitel™. The intervention arm will be treated with silver-impregnated dressings in addition to NPWT via the RENASYS TOUCH™ vacuum pump. Participants' dressings will be changed every 3 to 5 days until their wounds are fully re-epithelialised. Time to re-epithelialisation will be studied as the primary outcome. Secondary outcomes will include pain, pruritus, wound progression, health-care-resource use (and costs), ease of management, treatment satisfaction and adverse events. Wound fluid collected during NPWT will also be analysed to generate a proteomic profile of the burn microenvironment. DISCUSSION: The study will be the first randomised controlled trial to explore the clinical effects of NPWT on paediatric burns, with the aim of determining whether the therapy warrants implementation as an adjunct to standard burns management. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12618000256279 . Registered on 16 February 2018.

Maturational characteristics of HIV-specific antibodies in viremic individuals.

Despite the rare appearance of potent HIV-neutralizing mAbs in infected individuals requiring prolonged affinity maturation, little is known regarding this process in the majority of viremic individuals. HIV-infected individuals with chronic HIV viremia have elevated numbers of nonconventional tissue-like memory (TLM) B cells that predominate in blood over conventional resting memory (RM) B cells. Accordingly, we investigated affinity maturation in these 2 memory B cell populations. Analysis of IgG-expressing TLM B cells revealed a higher number of cell divisions compared with RM B cells; however, TLM B cells paradoxically displayed significantly lower frequencies of somatic hypermutation (SHM). To assess Ab reactivity in TLM and RM B cells, single-cell cloning was performed on HIV envelope CD4-binding site-sorted (CD4bs-sorted) B cells from 3 individuals with chronic HIV viremia. Several clonal families were present among the 127 cloned recombinant mAbs, with evidence of crosstalk between TLM and RM B cell populations that was largely restricted to non-VH4 families. Despite evidence of common origins, SHM frequencies were significantly decreased in TLM-derived mAbs compared with SHM frequencies in RM-derived mAbs. However, both cell populations had lower frequencies of SHMs than did broadly neutralizing CD4bs-specific mAbs. There was a significant correlation between SHM frequencies and the HIV-neutralizing capacities of the mAbs. Furthermore, HIV neutralization was significantly higher in the RM-derived mAbs compared with that seen in the TLM-derived mAbs, and both SHM frequencies and neutralizing capacity were lowest in TLM-derived mAbs with high polyreactivity. Thus, deficiencies in memory B cells that arise during chronic HIV viremia provide insight into the inadequacy of the Ab response in viremic individuals.