Improved Short-Term Prognosis of Pediatric Partial-Thickness Burns: Emergency Conservative Debridement Under Topical Anesthesia.

OBJECTIVES: Early wound management for pediatric patients with partial-thickness burns in the emergency department remains debatable. This study aims to evaluate the value of emergency conservative debridement under topical anesthesia in improving short-term prognosis of pediatric partial-thickness burns. METHODS: This retrospective cohort study enrolled children with partial-thickness thermal burns presenting to the emergency department within 6 hours postburn. All the enrolled patients were divided into 2 groups: the debridement group and the dressing group. The associations between emergency conservative debridement and time to reepithelialization was analyzed by using Kaplan-Meier curves with log rank test and multivariate Cox regression analysis. Moreover, the associations between emergency conservative debridement and in-hospital cost and length of stay were also evaluated. RESULTS: All baseline characteristics between groups were comparable (all P > 0.05). Emergency conservative debridement under topical anesthesia significantly decreased the median value of time to reepithelialization (13 vs 14 days, P = 0.02). Cox regression analysis showed that emergency conservative debridement significantly improved wound reepithelialization after adjusting for burn size (odds ratio, 4.07; 95% confidence interval, 1.64-10.11; P < 0.01). The mean length of stay of patients receiving conservative wound debridement was lower than that of patients in the wound dressing group (14.3 ± 7.3 vs 18.8 ± 10.4 days, P < 0.01), but not in terms of mean in-hospital cost per 1% total body surface area (2.8 ± 1.9 vs 3.0 ± 2.1 × 103 RMB per 1% total body surface area, P = 0.58). CONCLUSIONS: Emergency conservative debridement of pediatric partial-thickness burns under topical anesthesia significantly improves the wound healing outcomes without increasing health care burden.

Selenomethionine in gelatin methacryloyl hydrogels: Modulating ferroptosis to attenuate skin aging.

During skin aging, the degeneration of epidermal stem cells (EpiSCs) leads to diminished wound healing capabilities and epidermal disintegration. This study tackles this issue through a comprehensive analysis combining transcriptomics and untargeted metabolomics, revealing age-dependent alterations in the Gpx gene family and arachidonic acid (AA) metabolic networks, resulting in enhanced ferroptosis. Selenomethionine (Se-Met) could enhance GPX4 expression, thereby assisting EpiSCs in countering AA-induced mitochondrial damage and ferroptosis. Additionally, Se-Met demonstrates antioxidative characteristics and extensive ultraviolet absorption. For the sustained and controllable release of Se-Met, it was covalently grafted to UV-responsive GelMA hydrogels via AC-PEG-NHS tethers. The Se-Met@GelMA hydrogel effectively accelerated wound healing in a chronological aging mice model, by inhibiting lipid peroxidation and ferroptosis with augmented GPX4 expression. Moreover, in a photoaging model, this hydrogel significantly mitigated inflammatory responses, extracellular matrix remodeling, and ferroptosis in UV-exposed mice. These characteristics render Se-Met@GelMA hydrogel valuable in practical clinical applications.

A nanoenzyme-modified hydrogel targets macrophage reprogramming-angiogenesis crosstalk to boost diabetic wound repair.

Diabetic wounds has a gradually increasing incidence and morbidity. Excessive inflammation due to immune imbalance leads to delayed wound healing. Here, we reveal the interconnection between activation of the NLRP3 inflammatory pathway in endotheliocyte and polarization of macrophages via the cGAS-STING pathway in the oxidative microenvironment. To enhance the immune-regulation based on repairing mitochondrial oxidative damage, a zeolitic imidazolate framework-8 coated with cerium dioxide that carries Rhoassociated protein kinase inhibition Y-27632 (CeO2-Y@ZIF-8) is developed. It is encapsulated in a photocross-linkable hydrogel (GelMA) with cationic quaternary ammonium salt groups modified to endow the antibacterial properties (CeO2-Y@ZIF-8@Gel). CeO2 with superoxide dismutase and catalase activities can remove excess reactive oxygen species to limit mitochondrial damage and Y-27632 can repair damaged mitochondrial DNA, thus improving the proliferation of endotheliocyte. After endotheliocyte uptakes CeO2-Y@ZIF-8 NPs to degrade peroxides into water and oxygen in cells and mitochondria, NLRP3 inflammatory pathway is inhibited and the leakage of oxidatively damaged mitochondrial DNA (Ox-mtDNA, a damage-associated molecular pattern) through mPTP decreases. Futhermore, as the cGAS-STING pathway activated by Ox-mtDNA down-regulated, the M2 phenotype polarization and anti-inflammatory factors increase. Collectively, CeO2-Y@ZIF-8@Gel, through remodulating the crosstalk between macrophage reprogramming and angiogenesis to alleviate inflammation in the microenvironment and accelerates wound healing.

Development and validation of a nomogram for pneumonia risk in burn patients with inhalation injury: a multicenter retrospective cohort study.

BACKGROUND: Burn patients with inhalation injury are at higher risk of developing pneumonia, and yet there is no reliable tool for the assessment of the risk for such patients at admission. This study aims to establish a predictive model for pneumonia risk for burn patients with inhalation injury based on clinical findings and laboratory tests. METHOD: This retrospective study enrolled 546 burn patients with inhalation injury. They were grouped into a training cohort and a validation cohort. The least absolute shrinkage and selection operator (LASSO) regression analysis and binary logistic regression analysis were utilized to identify risk factors for pneumonia. Based on the factors, a nomogram for predicting pneumonia in burn patients with inhalation injury was constructed. Areas under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in both the training and validation cohorts. RESULTS: The training cohort included 432 patients, and the validation cohort included 114 patients, with a total of 225 (41.2%) patients experiencing pneumonia. Inhalation injury, tracheal intubation/tracheostomy, low serum albumin, and high blood glucose were independent risk factors for pneumonia in burn patients with inhalation injury and they were further used to build the nomogram. The AUC of the nomogram in the training and validation cohorts were 0.938 (95% CI: 0.917-0.960) and 0.966 (95% CI: 0.931-1), respectively. The calibration curve for probability of pneumonia showed optimal agreement between the prediction by nomogram and the actual observation, and the DCA indicated that the constructed nomogram conferred high clinical net benefit. CONCLUSION: This nomogram can accurately predict the risk of developing pneumonia for burn patients with inhalation injury, and help professionals to identify high-risk patients at an early stage as well as to make informed clinical decisions.

A study on the preoperative risk factors for primary healing failure in the reconstruction of deep sternal wound infection with platelet-rich plasma and negative pressure trauma therapy.

Deep sternal wound infection (DSWI) is a relatively complex wound in wound reconstruction surgery. Because plastic surgeons deal with DSWI patients late. The primary healing (healing by first intention) after reconstruction of DSWI is restricted by many preoperative risk factors. The purpose of this study is to explore and analyse the risk factors of primary healing failure in patients with DSWI treated with platelet-rich plasma (PRP) and negative pressure trauma therapy (NPWT). 115 DSWI patients treated with the PRP and NPWT (PRP + NPWT) modality were retrospectively (2013-2021) analysed. They were divided into two groups according to primary healing results after the first PRP + NPWT treatment. Univariate and multivariate analyses were used to compare the data of the two groups to find out the risk factors and their optimal cut-off values were identified by ROC analysis. The primary healing results, debridement history, wound size, sinus, osteomyelitis, renal function, bacterial culture, albumin (ALB), platelet (PLT) between the two groups were significantly different (P < 0.05). Binary logistic regression showed that osteomyelitis, sinus, ALB and PLT were the risk factors affecting primary healing outcomes (P < 0.05). ROC analysis showed that AUC for ALB in the non-primary healing group was 0.743 (95% CI: 0.650-0.836, P < 0.05) and its optimal cutoff value of 31 g/L was associated with primary healing failure with a sensitivity of 96.9% and specificity of 45.1%. AUC for PLT in the non-primary healing group was 0.670 (95% CI: 0.571 ~ 0.770, P < 0.05) its optimal cutoff value of 293 × 109 /L was associated with primary healing failure with a sensitivity of 72.5% and specificity of 56.3%. In the cases included in this study, the success rate of primary healing of DSWI treated with PRP + NPWT was not affected by the most common preoperative risk factors for wound non-union. It is indirectly confirmed that PRP + NPWT is an ideal treatment. However, it should be noted that it will still be adversely affected by sinus osteomyelitis, ALB and PLT. The patients need to be carefully evaluated and corrected before reconstruction.

A Potential Resuscitation Route on Battlefield: Immediate Intraperitoneal Fluid Administration Post-burn Shows Satisfactory Fluid Absorption and Anti-shock Effects.

INTRODUCTION: Timely fluid resuscitation remains the key to the early treatment of severe burns. Intraperitoneal (IP) fluid administration is a simple, rapid resuscitation strategy via a puncture in the abdominal wall. This study aimed to evaluate the fluid absorption and anti-shock effects of IP delivery in the early stage after severe burns. MATERIALS AND METHODS: A 30% total body surface area full-thickness burn model was established using male C57BL/6 mice. A total of 126 mice were randomly assigned into six groups (n = 21): the sham injury group (SHAM), the burn group without fluid resuscitation (NR), and the four IP resuscitation groups (IP-A/B/C/D, each being intraperitoneally administered with 60, 80, 100, and 120 mL/kg of sodium lactate Ringer's solution post-injury). Three-hour post-burn, six mice in each group were randomly selected and sacrificed for blood and tissue sampling to detect the IP fluid absorption rate and evaluate organ damage because of low perfusion. The remaining 15 mice in each group were observed for the vital signs within 48-h post-injury, and their survival rate was calculated. RESULTS: The 48-h survival rate increased in the IP-A (40.0%), IP-B (66.7%), IP-C (60.0%), and IP-D (13.3%) groups, compared with the NR group (0%). The mean arterial pressure, body temperature, and heart rate of mice were significantly stabilized in the IP groups. For the first 3-h post-injury, the absorption rates of groups IP-A (74.3% ± 9.5%) and IP-B (73.3% ± 6.9%) were significantly higher than those of groups IP-C (59.7% ± 7.1%) and IP-D (48.7% ± 5.7%). The levels of arterial blood pH, partial pressure of oxygen, partial pressure of carbon dioxide, lactate, and hematocrit were better maintained in the IP groups. Intraperitoneal resuscitation remarkably reduced the injury scores in burn-induced histopathology of the liver, kidneys, lungs, and intestines, accompanied by decreased alanine transaminase, creatinine, interleukin-1, and tumor necrosis factor-α in plasma, and augmented superoxide dismutase 2 and inhibited malondialdehyde in tissues. Group IP-B has the best performance for these indices. CONCLUSIONS: Intraperitoneal administration of isotonic saline post-burn can be adequately and rapidly absorbed, thereby boosting circulation and perfusion, precluding shock, alleviating organ damage caused by ischemia and hypoxia, and significantly increasing the survival rate. This technique, with a potential to be a supplement to existing resuscitation methods on the battlefield, is worth further investigation.

An innovated elastic compression hemostasis technique for extremity excision in patients with extensive burns: A prospective clinical randomized controlled trial.

OBJECTIVE: To introduce an innovative elastic compression hemostasis technique for extremity excision in extensively burnt patients and investigate its effectiveness. METHODS: Ten patients were included and divided into 2 groups: the control group (4 patients, 12 extremities) receiving the conventional hemostasis technique and the experimental group (6 patients, 14 extremities) receiving the innovative technique. General data of the patients were collected, excision size measured, hemostasis time recorded, average blood loss per 1% total body surface area of the excised wound calculated, incidence of subcutaneous hematoma and take rate determined. RESULTS: The 2 groups had no statistical difference in the baseline data. Average blood loss per 1% total body surface area of the excised wound in the upper and the lower extremities was (62.1 ± 11.5) mL and (35.6 ± 11.0) mL in the experimental group, significantly less than (94.3 ± 6.9) mL and (82.3 ± 6.2) mL in the control group; a reduction of 34.1% and 56.8% respectively. Hemostasis time in the upper and the lower extremities were (5.0 ± 0.7) min/1% total body surface area and (2.6 ± 0.3) min/1% total body surface area, respectively, in the experimental group, significantly less than (7.4 ± 0.6) min/1% total body surface area and (4.0 ± 0.9) min/1% total body surface area in the control group; a reduction of 31.8% and 34.9% respectively. The incidences of subcutaneous hematoma were 7.1% and 8.3%, and the take rate (85.9 ± 6.0)% and (86.5 ± 4.8)% in the experimental and the control group, respectively, with no statistically significant differences. CONCLUSION: The innovative elastic compression hemostasis technique is a reliable new method that significantly reduces blood loss during extremity excision in patients with extensive burns and is worth wider understanding and application.

Role and Mechanism of Endoplasmic Reticulum Stress in Mice Pancreatic Islet Dysfunction After Severe Burns.

This study attempted to investigate the role and mechanism of endoplasmic reticulum (ER) stress in the islet dysfunction in mice after severe burns. C57BL/6 mice were randomly divided into the sham group, burn group, and burn+4-phenylbutyric acid (4-PBA) group. Mice were burned with full thickness of 30% total surface area (TBSA), and 4-PBA solution was intraperitoneally injected into mice in burn+4-PBA group. Glucose-stimulated insulin secretion (GSIS), Fasting blood glucose (FBG) and glucose tolerance were detected 24 hours post severe burns. The ER stress-related pathway markers immunoglobulin binding protein (BIP), X-box binding protein 1 (XBP1), phosphorylation-PKR-like ER kinase (p-PERK), phosphorylation-eukaryotic translation initiation factor 2α (p-eIF2α), CHOP, activating transcription factor 6 (ATF6), apoptosis-related protein Cleaved-Caspase 3, and islet cell apoptosis were measured. Mice were characterized with elevated FBG, decreased glucose tolerance and GSIS levels post severe burns. The expression of BIP, XBP1, p-PERK, p-eIF2α, CHOP, ATF6, Cleaved-Caspase 3, and islet cell apoptosis were increased significantly after severe burns. 4-PBA treatment contributed to decreased FBG, improved glucose tolerance, increased GSIS, inhibited islet ER stress, and reduced pancreatic islet cell apoptosis in mice post severe burns. ER stress occurs in islets of severely burned mice, which leads to increased apoptosis of islet cells, thus resulting in islet dysfunction.

Sirt3-dependent regulation of mitochondrial oxidative stress and apoptosis contributes to the dysfunction of pancreatic islets after severe burns.

BACKGROUND: Severe burns are often complicated with hyperglycemia caused by mitochondrial oxidative stress-related pancreatic islet dysfunction. Silent information regulator of transcription 3 (Sirt3) can regulate mitochondrial oxidative stress. However, the role and mechanism of Sirt3 on islet function after severe burns remain unclear. Therefore, this study aimed to investigate whether Sirt3 played a role in both mitochondrial oxidative stress in islets and mediating islet function post severe burns. METHODS: A mouse model of 30% total body surface area full-thickness burn and an in vitro MIN6 cell hypoxia model were established. Sirt3 KO mice were used to demonstrate further the role of Sirt3 in maintaining redox homeostasis and regulating islet function. Fasting blood glucose and glucose-stimulated insulin secretion (GSIS) were detected to assess the islet function. The levels of mitochondrial ROS and deacetylation, and the activities of Mn-SOD and IDH2 were measured to evaluate oxidative stress. The mitochondrial membrane potential (MMP)was detected and the apoptosis rate measured. RESULTS: In vitro MIN6 cells, the hypoxia treatment significantly reduced Sirt3 expression, resulting in increased deacetylation of Mn-SOD and IDH2, which further led to a higher level of mitochondrial ROS. In addition, hypoxia reduced MMP and increased apoptosis rate, which impaired GSIS eventually. Knockdown of Sirt3 caused similar alterations. The hypoxia-induced high level of mitochondrial ROS and apoptosis and impaired GSIS could be reversed by overexpression of Sirt3. Similarly, after severe burns, the expression of Sirt3 in islets decreased significantly with a high level of deacetylation of Mn-SOD, IDH2, mitochondrial ROS and apoptosis, and islet dysfunction. Oxidative stress and apoptosis also occurred in islets of Sirt3 KO mice, accompanied by islet dysfunction. CONCLUSIONS: Sirt3 and downstream signalling are critical in modulating the islet function post severe burns by regulating mitochondrial oxidative stress and apoptosis.

A novel skin grafting modality: prefabricated large sheet of postage-stamp autografts and allografts to repair extensive burn wounds; a prospective matched-control study.

BACKGROUND: The excessively long operative time has been the greatest barrier to the success of transplanting postage-stamp auto- and allografts directly and piece-by-piece onto extensive burn wounds. To solve this challenge, the authors present a novel grafting modality, that is, the prefabricated-large-sheet grafting that moves the labor-intensive and time-consuming process of grafts-positioning before grafting and thereby markedly shortens the operative time. METHODS: Twenty-one operations using the novel modality were performed on 11 patients with extensive deep burns. The grafting time using the novel modality was recorded and compared with that of the conventional piece-by-piece grafting. Eventually, the take rates of the two modalities were compared. RESULTS: All patients were healed and discharged. The average grafting time per unit area (100 cm2) of prefabricated-large-sheet grafting and piece-by-piece grafting were (0.41±0.09) min and (7.46±1.07) min, respectively, and the difference is statistically significant(P<0.001). The average take rate of the prefabricated sheets was (85.43±6.14)% and that of the piece-by-piece transplanted grafts was (87.29±5.23)% and there is no significant difference(P>0.05). CONCLUSIONS: The prefabricated-large-sheet grafting significantly reduces the intraoperative grafting time while ensures uniformity of the skin grafts and secures good outcomes, thereby making the intermingled transplantation of postage-stamp auto- and allografts, which has been an excellent modality per se but limited to repair small residual wounds, now feasible to repair extensive deep burn wounds. It is worth wider understanding and application in the treatment of extensive deep burns.