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Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

Sepsis is the primary cause of burn-related mortality and morbidity. Traditional indicators of sepsis exhibit poor performance when used in this unique population due to their underlying hypermetabolic and inflammatory response following burn injury. To address this challenge, we developed the Machine Intelligence Learning Optimizer (MILO), an automated machine learning (ML) platform, to automatically produce ML models for predicting burn sepsis. We conducted a retrospective analysis of 211 adult patients (age ≥ 18 years) with severe burn injury (≥ 20% total body surface area) to generate training and test datasets for ML applications. The MILO approach was compared against an exhaustive “non-automated” ML approach as well as standard statistical methods. For this study, traditional multivariate logistic regression (LR) identified seven predictors of burn sepsis when controlled for age and burn size (OR 2.8, 95% CI 1.99–4.04, P = 0.032). The area under the ROC (ROC-AUC) when using these seven predictors was 0.88. Next, the non-automated ML approach produced an optimal model based on LR using 16 out of the 23 features from the study dataset. Model accuracy was 86% with ROC-AUC of 0.96. In contrast, MILO identified a k -nearest neighbor-based model using only five features to be the best performer with an accuracy of 90% and a ROC-AUC of 0.96. Machine learning augments burn sepsis prediction. MILO identified models more quickly, with less required features, and found to be analytically superior to traditional ML approaches. Future studies are needed to clinically validate the performance of MILO-derived ML models for sepsis prediction.

To investigate if donor and recipient site morbidity (healing time and cosmesis) could be reduced by a novel, modified split-thickness skin grafting (STSG) technique using a dermal component in the STSG procedure (DG). The STSG technique has been used for 150 years in surgery with limited improvements. Its drawbacks are well known and relate to donor site morbidity and recipient site cosmetic shortcomings (especially mesh patterns, wound contracture, and scarring). The Dermal graft technique (DG) has emerged as an interesting alternative, which reduces donor site morbidity, increases graft yield, and has the potential to avoid the mesh procedure in the STSG procedure due to its elastic properties. A prospective, dual-centre, intra-individual controlled comparison study. Twenty-one patients received both an unmeshed dermis graft and a regular 1:1.5 meshed STSG. Aesthetic and scar assessments were done using The Patient and Observer Scar Assessment Scale (POSAS) and a Cutometer Dual MPA 580 on both donor and recipient sites. These were also examined histologically for remodelling and scar formation. Dermal graft donor sites and the STSG donor sites healed in 8 and 14 days, respectively ( p  < 0.005). Patient-reported POSAS showed better values for colour for all three measurements, i.e., 3, 6, and 12 months, and the observers rated both vascularity and pigmentation better on these occasions ( p  < 0.01). At the recipient site, (n = 21) the mesh patterns were avoided as the DG covered the donor site due to its elastic properties and rendered the meshing procedure unnecessary. Scar formation was seen at the dermal donor and recipient sites after 6 months as in the standard scar healing process. The dermis graft technique, besides potentially rendering a larger graft yield, reduced donor site morbidity, as it healed faster than the standard STSG. Due to its elastic properties, the DG procedure eliminated the meshing requirement (when compared to a 1:1.5 meshed STSG). This promising outcome presented for the DG technique needs to be further explored, especially regarding the elasticity of the dermal graft and its ability to reduce mesh patterns. Trial registration : ClinicalTrials.gov Identifier (NCT05189743) 12/01/2022.

Background Platelet‐rich plasma (PRP) shows promise in burn management, yet optimal platelet concentrations, timing, and standardized protocols remain unclear, leading to inconsistent clinical outcomes. Aims To compare the therapeutic efficacy of PRP at different platelet concentrations in deep second‐degree burns and to explore associated molecular mechanisms. Patients/Methods Twenty‐eight patients with small‐area deep second‐degree burns were randomly assigned to four groups: Group A (PRP 600–1000 × 109/L), Group B (normal saline control), Group C (PRP 1000–1400 × 109/L), and Group D (PRP 1400–1800 × 109/L). Outcomes included wound healing time, wound coverage rates at 2 and 3 weeks, bacterial culture positivity, and 3‐month scar scores. Full‐thickness biopsies were collected on days 5, 9, and 16 for histopathology, immunohistochemistry, and growth factor quantification. Results All PRP groups showed faster healing and lower infection rates compared with controls. Group C achieved the shortest healing time (p < 0.05). Growth factor concentrations rose with increasing platelet levels, but M2 macrophage polarization was highest in Group C. Elevated transforming growth factor‐β (TGF‐β) in Group D appeared to trigger negative feedback, limiting M2 accumulation and diminishing added benefit. Scar scores did not differ significantly among PRP groups. Conclusions PRP accelerates wound healing and reduces infection risk in deep second‐degree burns. A platelet concentration of 1000–1400 × 109/L provides the best therapeutic balance. Excessively high concentrations may impair repair through TGF‐β–mediated inhibitory effects. Future research should explore controlled‐release strategies to optimize PRP‐derived growth factor activity.

Background Burn wounds are commonly encountered in clinical settings and the management aims at the prevention of mortality and morbidity due to disability. The platelet-rich plasma (PRP) is blood-derived biomaterial that is enriched with growth factors and cytokines that facilitate wound healing. The PRP has proven its efficacy in various other wounds, but its role in post-burn raw areas and graft take has not been validated. This proposed multicentre randomized controlled trial aims to evaluate the efficacy and safety of platelet-rich plasma as an adjunct therapy to split-thickness skin graft in burn patients with granulating raw wounds. Method/design This trial is an investigator-initiated, double-blind multicentre, randomized controlled parallel arm trial alongside trial cost-effectiveness analysis. Granulating deep second-degree and third-degree burns affecting 3–20% of total body surface area (TBSA) at 10–14th post-burn day will be included in the study. A total of 550 patients (275 in each group) will be randomized to receive either standard skin graft or allogenic PRP with skin graft treatment. The primary endpoint will be the mean percentage of graft-take on the 14th postoperative day. The result will be analyzed by two independent assessors who are blinded to the study. Secondary endpoints include (a) time taken for complete wound healing; (b) frequency of adverse events; (c) follow-up with scar index at 3 months, 6 months, and 1 year using the Patient and Observer Scar Assessment Scale (POSAS) score; (d) cost-effectiveness analysis of the intervention compared to the comparator; and (e) to estimate in a subset of participants the association between growth factor levels (PDGF BB and TGF ß-1) of activated PRP and clinical response. Discussion The proposed trial will be expected to verify the efficacy and safety of PRP for split-thickness skin graft (STSG) in deep second-degree or third-degree granulating wounds of burn patients based on the outcome of the study.

Standard treatment for large burns is transplantation with meshed split skin autografts (SSGs). A disadvantage of this treatment is that healing is accompanied by scar formation. Application of autologous epidermal cells (keratinocytes and melanocytes) may be a suitable therapeutic alternative, since this may enhance wound closure and improve scar quality. A prospective, multicenter randomized clinical trial was performed in 40 adult patients with acute full thickness burns. On two comparable wound areas, conventional treatment with SSGs was compared to an experimental treatment consisting of SSGs in combination with cultured autologous epidermal cells (ECs) seeded in a collagen carrier. The primary outcome measure was wound closure after 5–7 days. Secondary outcomes were safety aspects and scar quality measured by graft take, scar score (POSAS), skin colorimeter (DermaSpectrometer®) and elasticity (Cutometer®). Wound epithelialization after 5–7 days was significantly better for the experimental treatment (71%) compared to the standard treatment (67%) (p = 0.034, Wilcoxon), whereas the take rates of the grafts were similar. No related adverse events were recorded. Scar quality was evaluated at 3 (n = 33) and 12 (n = 28) months. The POSAS of the observer after 3 and 12 months and of the patient after 12 months were significantly better for the experimental area. Improvements between 12% and 23% (p ≤ 0.010, Wilcoxon) were detected for redness, pigmentation, thickness, relief, and pliability. Melanin index at 3 and 12 months and erythema index at 12 months were closer to normal skin for the experimental treatment than for conventional treatment (p ≤ 0.025 paired samples t-test). Skin elasticity showed significantly higher elasticity (p = 0.030) in the experimental area at 3 months follow-up. We showed a safe application and significant improvements of wound healing and scar quality in burn patients after treatment with ECs versus SSGs only. The relevance of cultured autologous cells in treatment of extensive burns is supported by our current findings.

AimTo compare the predictive outcome of ocular burns using two different prognostic classification systems, that is, Dua and Roper Hall classification.Patients and methodsIn a prospective, randomised, controlled clinical trial, the extent of acute ocular burns in 100 patients was graded by Roper Hall and Dua classifications. Patients were randomised in two groups of 50 each to receive conventional medical therapy alone or additional amniotic membrane transplantation (AMT). Moderate burns were graded similarly (grade II and III) under both systems, while severe burns were classified differently and compared further. Baseline parameters (size of epithelial defect, corneal haze, limbal ischaemia, conjunctival involvement and visual acuity) and outcome variables (healing of epithelial defect, corneal clarity, corneal vascularisation, visual outcome and symblepharon) after 1 year were noted and compared.ResultsThere was no difference in terms of time taken and rate of healing of epithelial defect, but there was a significant difference in extent of corneal vascularisation between grades IV, V and VI (p<0.05). In patients who received AMT in addition to medical therapy, the degree of corneal clarity achieved was significantly better in patients with grade IV burns than either grade V (p=0.045) or grade VI (p=0.024) burns, and final visual acuity was significantly better in these patients (p=0.043). On comparison of patients with grade IV burns (with and without AMT), the outcome in terms of extent of corneal vascularisation was significantly better (p=0.0124) in patients who received AMT.ConclusionsDua classification by providing further subclassification of grade IV ocular burns by Roper Hall into three separate grades has a superior prognostic predictive value in severe ocular burns.

Corneal alkali burns are severe ocular injuries characterized by extensive tissue damage, inflammation, oxidative stress, and neovascularization, which often lead to long-term visual impairment and corneal fibrosis. This review comprehensively examines the mechanisms underlying alkali burn injuries, including the roles of inflammatory mediators, oxidative stress, and cellular responses, while highlighting current and emerging therapeutic approaches. Traditional treatments, such as corticosteroids and surgical interventions, often have limited efficacy and significant side effects. Recent advances in innovative therapies, including stem cell-derived exosomes, hydrogel-based drug delivery systems, and herbal components, demonstrate significant potential for improving corneal healing and reducing complications. These novel approaches aim to mitigate inflammation, enhance epithelial repair, and prevent neovascularization, offering promising pathways for scar-free healing and the restoration of corneal transparency. Future research should focus on integrating these therapies into multifunctional treatment strategies to optimize clinical outcomes and improve quality of life for patients suffering from corneal alkali burns.

Alkaline burns to the cornea lead to loss of corneal transparency, which is essential for normal vision. We used a rat corneal alkaline burn model to investigate the effect of ophthalmic trimebutine solution on healing wounds caused by alkaline burns. Trimebutine, an inhibitor of the high-mobility group box 1-receptor for advanced glycation end products, when topically applied to the burned cornea, suppressed macrophage infiltration in the early phase and neutrophil infiltration in the late phase at the wound site. It also inhibited neovascularization and myofibroblast development in the late phase. Furthermore, trimebutine effectively inhibited interleukin-1β expression in the injured cornea. It reduced scar formation by decreasing the expression of type III collagen. These findings suggest that trimebutine may represent a novel therapeutic strategy for corneal wounds, not only through its anti-inflammatory effects but also by preventing neovascularization.

Corneal alkali burns can cause persistent inflammation and corneal neovascularization. In this study, we divided corneal alkali burned rabbits into the untreated group, the blank lens group, the radiation-treated umbilical cord mesenchymal stem cells (UCMSC) lens group, and the UCMSC I.V. group, and then measured corneal inflammation, neovascularization and corneal injury repair via slit lamp microscopy, captured anterior segment optical coherence tomography (AS-OCT), and performed hematoxylin-eosin staining. Compared with those in the other experimental groups, radiation-treated UCMSC lenses significantly decreased inflammatory index (IF) scores, areas of corneal blood vessels and corneal epithelial injury. The expression of interleukin (IL)-17 in corneas treated with radiation-treated UCMSC lenses was lower than that in corneas treated with blank lenses, and radiation-treated UCMSC lenses exhibited greater expression of IL-4 and signal transducer and activator of transcription 1 (STAT1), while the expression of cluster of differentiation-3G (CD3G), a linker for the activation of T cells (LAT), IL-6, IL-1B, CC chemokine receptor 6 (CCR6) and IL-23 exhibited the opposite effects (all P  < 0.05). Our findings demonstrated that irradiated UCMSC-coated high oxygen-permeable hydrogel lenses on the ocular surface inhibited corneal angiogenesis and inflammation after corneal alkaline burns. The downregulation of Th17 cell differentiation might be responsible for these effects.