Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Burn Injuries in People Who Used Drug, 2009-2017: A Case-Control Study in Shiraz, Southern Iran

Background Burn injury is a critical health issue, which is associated with several morbidities and mortalities. Substance abuse, which is an important public health problem in Iran, can affect burn injury outcomes and etiologies in victims. This study was aimed to evaluate different aspects of burn injuries in people who used drug (PWUD) in two referral centers in the south of Iran. Methods This Case-Control Study was conducted on burn victims referred to Amir-al Momenin Hospital and Ghotb-al-din Hospital from 2009 to 2017. Patients with a history of drug consumption were selected from the database and compared to randomly selected burn victims with no history of drug use. Demographics, burn etiology, underlying disease, total body surface area, hospitalization duration, and also the outcomes were collected and recorded in both groups. Data analysis was done by SPSS software. Results A total of 5,912 inpatients were included in this study, which 2,397 of them (40.54%) were female. The mean age of the patients was 26.12 ± 19.18. Drug history was positive in 659 patients (11.15%). Familial issues and mental disorders were significantly higher in the PWUD group compared to the control group (P<0.001). Explosion etiology was significantly higher in the PWUD group (P<0.001). Psychiatric disorders (P<0.001), total body surface area (P=0.023), and hospital stay (P<0.001) were significantly higher in PWUD; however, the mortality rate had no statistically significant differences between the groups (P=0.583). Conclusion Substance abuse is a risk factor in burn victims, which can affect burn etiology and burn-related morbidities.

Impairment of μ-calpain activation by rhTNFR:Fc reduces severe burn-induced membrane disruption in the heart

Stress cardiomyopathy is a major clinical complication after severe burn. Multiple upstream initiators have been identified; however, the downstream targets are not fully understood. This study assessed the role of the plasma membrane in this process and its relationship with the protease μ-calpain and tumor necrosis factor-alpha (TNF-α). Here, third-degree burn injury of approximately 40% of the total body surface area was established in rats. Plasma levels of LDH and cTnI and cardiac cell apoptosis increased at 0.5 h post burn, reached a peak at 6 h, and gradually declined at 24 h. This effect correlated well with not only the disruption of cytoskeletal proteins, including dystrophin and ankyrin-B, but also with the activation of μ-calpain, as indicated by the cleaved fragments of α-spectrin and membrane recruitment of the catalytic subunit CAPN1. More importantly, these alterations were diminished by blocking calpain activity with MDL28170. Burn injury markedly increased the cellular uptake of Evans blue, indicating membrane integrity disruption, and this effect was also reversed by MDL28170. Compared with those in the control group, cardiac cells in the burn plasma-treated group were more prone to damage, as indicated by a marked decrease in cell viability and increases in LDH release and apoptosis. Of note, these alterations were mitigated by CAPN1 siRNA. Moreover, after neutralizing TNF-α with rhTNFR:Fc, calpain activity was blocked, and heart function was improved. In conclusion, we identified μ-calpain as a trigger for severe burn-induced membrane disruption in the heart and provided evidence for the application of rhTNFR:Fc to inhibit calpain for cardioprotection.

Age and injury size influence the magnitude of fecal dysbiosis in adult burn patients

Clinical studies have demonstrated that age ≥ 50 years old is an independent risk factor associated with poor prognosis after burn injury, the second leading cause of traumatic injuries in the aged population. While mechanisms driving age-dependent post-burn mortality are perplexing, changes in the intestinal microbiome however may contribute to the heightened, dysregulated systemic response seen in aging burn patients. The fecal microbiome from 22 patients admitted to a verified burn center from July 2018 to February 2019 were stratified based on age of 50 years and total burn surface area (TBSA) size of ≥10%. Significant differences (P = 0.014) in overall microbiota community composition (i.e., beta diversity) were measured across the four patient groups, young <10% TBSA, young ≥10% TBSA, older <10% TBSA, and older ≥10% TBSA. Differences in beta diversity were driven by %TBSA (P = 0.013) and trended with age (P = 0.087). Alpha diversity components, richness, evenness, and Shannon diversity were measured. We observed significant differences in bacterial species evenness (P = 0.0023) and Shannon diversity (P = 0.0033) between the groups. There were significant correlations between individual bacterial species and levels of SCFA. Specifically, levels of fecal butyrate correlated with the presence of Enterobacteriaceae, an opportunistic gut pathogen, when elevated in burn patients lead to worsen outcomes. Overall, our findings reveal that age-specific changes in the fecal microbiome following burn injuries may contribute to immune system dysregulation in patients with varying TBSA burns and potentially lead to worsen clinical outcomes with heightened morbidity and mortality.

Assessing Potential Safety Zone Suitability Using a New Online Mapping Tool

Safety zones (SZs) are critical tools that can be used by wildland firefighters to avoid injury or fatality when engaging a fire. Effective SZs provide safe separation distance (SSD) from surrounding flames, ensuring that a fire’s heat cannot cause burn injury to firefighters within the SZ. Evaluating SSD on the ground can be challenging, and underestimating SSD can be fatal. We introduce a new online tool for mapping SSD based on vegetation height, terrain slope, wind speed, and burning condition: the Safe Separation Distance Evaluator (SSDE). It allows users to draw a potential SZ polygon and estimate SSD and the extent to which that SZ polygon may be suitable, given the local landscape, weather, and fire conditions. We begin by describing the algorithm that underlies SSDE. Given the importance of vegetation height for assessing SSD, we then describe an analysis that compares LANDFIRE Existing Vegetation Height and a recent Global Ecosystem Dynamics Investigation (GEDI) and Landsat 8 Operational Land Imager (OLI) satellite image-driven forest height dataset to vegetation heights derived from airborne lidar data in three areas of the Western US. This analysis revealed that both LANDFIRE and GEDI/Landsat tended to underestimate vegetation heights, which translates into an underestimation of SSD. To rectify this underestimation, we performed a bias-correction procedure that adjusted vegetation heights to more closely resemble those of the lidar data. SSDE is a tool that can provide valuable safety information to wildland fire personnel who are charged with the critical responsibility of protecting the public and landscapes from increasingly intense and frequent fires in a changing climate. However, as it is based on data that possess inherent uncertainty, it is essential that all SZ polygons evaluated using SSDE are validated on the ground prior to use.

Trajectory Curves for Purposes of Benchmarking and Predicting Clinical Outcomes: A Scoping Review

Trajectory curves are valuable tools to benchmark patient health status and predict future outcomes. A longitudinal study is underway to examine social participation after burn injury using the Life Impact Burn Recovery Evaluation (LIBRE) Profile with the goal of developing trajectory curves for specific domains that focus on social re-integration. We conducted a scoping review to inform and understand trajectory curves applied in clinical settings to compare outcomes for an individual to a matched cohort of comparable patients or predicted expected outcomes over time. This scoping review utilized a PubMed search from January 2014 to August 2019 for the following terms: “trajectory curves” or “trajectory models” and “clinic” or “clinical.” Only articles that specifically referenced longitudinal and clinical research designs were included in the scoping review. Articles were assessed using standard scoping review methods and categorized based on clinical application of trajectory curves for either benchmarking or prediction. The initial literature review identified 141 manuscripts and 34 met initial inclusion criteria. The reviewed articles support the clinical use of trajectory curves. Findings provide insight into several key determinants involved with the successful development and implementation of trajectory curves in clinical settings. These findings will inform efforts to use the LIBRE Profile to model social participation recovery and assist in developing effective strategies using trajectory curves to promote social reintegration after burn injury.

Identification and Verification of Five Potential Biomarkers Related to Skin and Thermal Injury Using Weighted Gene Co-Expression Network Analysis

Background: Burn injury is a life-threatening disease that does not have ideal biomarkers. Therefore, this study first applied weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) screening methods to identify pivotal genes and diagnostic biomarkers associated with the skin burn process.Methods: After obtaining transcriptomic datasets of burn patient skin and normal skin from Gene Expression Omnibus (GEO) and performing differential analysis and functional enrichment, WGCNA was used to identify hub gene modules associated with burn skin processes in the burn patient peripheral blood sample dataset and determine the correlation between modules and clinical features. Enrichment analysis was performed to identify the functions and pathways of key module genes. Differential analysis, WGCNA, protein-protein interaction analysis, and enrichment analysis were utilized to screen for hub genes. Hub genes were validated in two other GEO datasets, tested by immunohistochemistry for hub gene expression in burn patients, and receiver operating characteristic curve analysis was performed. Finally, we constructed the specific drug activity, transcription factors, and microRNA regulatory network of the five hub genes.Results: A total of 1,373 DEGs in GSE8056 were obtained, and the top 5 upregulated genes were S100A12, CXCL8, CXCL5, MMP3, and MMP1, whereas the top 5 downregulated genes were SCGB1D2, SCGB2A2, DCD, TSPAN8, and KRT25. DEGs were significantly enriched in the immunity, epidermal development, and skin development processes. In WGCNA, the yellow module was identified as the most closely associated module with tissue damage during the burn process, and the five hub genes (ANXA3, MCEMP1, MMP9, S100A12, and TCN1) were identified as the key genes for burn injury status, which consistently showed high expression in burn patient blood samples in the GSE37069 and GSE13902 datasets. Furthermore, we verified using immunohistochemistry that these five novel hub genes were also significantly elevated in burn patient skin. In addition, MCEMP1, MMP9, and S100A12 showed perfect diagnostic performance in the receiver operating characteristic analysis.Conclusion: In conclusion, we analyzed the changes in genetic processes in the skin during burns and used them to identify five potential novel diagnostic markers in blood samples from burn patients, which are important for burn patient diagnosis. In particular, MCEMP1, MMP9, and S100A12 are three key blood biomarkers that can be used to identify skin damage in burn patients.

Utilising Virtual Reality in Pain Management: A Systematic Review

Virtual reality (VR) offers patient with a drug free supplement, an alternative or complementary therapy to traditional pain management. VR technology allowing its use in a wide variety of settings in the medicine world. So, we would like to evaluate the current existing evidence supporting VR in pain management. We conducted a systematic review of interventional and observational studies that examined VR applications in pain management between 2010 and 2019. We used Scopus databases, PubMed, Web of Science, Ovid MEDLINE and EBSCOhost to identify the studies using keywords “patient”, “virtual reality”, “medicine” and “pain management”. Data was obtained by two investigators and agreement was reached with the involvement of a third and fourth investigator. Narrative synthesis for all research was done. A total of 451 citations were identified, among which 12 studies met the criteria for inclusion. Studies involve various countries with participant age ranging from 6 to 75 years old. Studies were small, employed different design, instrument and measure for outcome. Studies addressed experimental, acute and chronic pain with four categories of condition which are burn injury, orthopedic diseases and chronic headache. VR was effective during the procedure in experimental and acute pain management. Majority of studies involving VR in painful physical rehabilitation therapy found VR reduced chronic pain and some provide evidence of lasting analgesia effect of VR after therapy. The usage of VR in chronic pain in term of psychological and cognitive behavioral therapy (CBT) showed improvement of positive mood, emotional and motivation that could lead to improvement of quality of life. VR also useful to elicit findings during painful cervical kinematics assessment in chronic neck pain. VR is a promising technology to be applied in managing chronic and acute pain. Some research showed that VR usage is able to provide lasting effect of analgesia even after VR session. However, there is a need for long term, larger sample sizes and well controlled studies to show clinical and cost-effectiveness for this technology to be used in clinical settings.