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.

Mechanical Ventilation Strategies in the Critically Ill Burn Patient: A Practical Review for Clinicians

Burn patients are a unique population when considering strategies for ventilatory support. Frequent surgical operations, inhalation injury, pneumonia, and long durations of mechanical ventilation add to the challenging physiology of severe burn injury. We aim to provide a practical and evidence-based review of mechanical ventilation strategies for the critically ill burn patient that is tailored to the bedside clinician.

When More is Still Not Enough: A Case of Ceftazidime-Avibactam Resistance in a Burn Patient

Burn patients have numerous risk factors for multidrug resistant organisms (MDROs) and altered pharmacokinetics, which both independently increase the risk of treatment failure. Data on appropriate antimicrobial dosing are limited in this population and therapeutic drug monitoring (TDM) for beta-lactams is impractical at most facilities. 1-3 Technology is available that can detect genetic markers of resistance, but they are not all encompassing, and often require specialized facilities that can detect less common genetic markers. 4-5 Newer antimicrobials can help combat MDROs, but additional resistance patterns may evolve during treatment. Considering drug shortages and antimicrobial formularies, clinicians must remain vigilant when treating infections. This case report describes the development of resistance to ceftazidime-avibactam in a burn patient. The patient was a 54- year-old burn victim with a 58% total body surface area (TBSA) thermal burn who underwent multiple courses of antibiotics for various Pseudomonal infections. The initial Pseudomonal wound infection was sensitive to cefepime, aminoglycosides, and meropenem. A subsequent resistant pseudomonal pneumonia was treated with ceftazidime-avibactam 2.5 grams every 6 hours due to the elevated MIC to cefepime (16mcg/mL) and meropenem (>8mcg/mL). Although, the patient improved over 7 days, the patient again spiked fevers and had increased white blood counts (WBC). Repeat blood cultures demonstrated a multidrug resistant (MDR) Pseudomonas with a minimum inhibitory concentration (MIC) to ceftazidime-avibactam of 16mcg/mL, which is above the Clinical and Laboratory Standards Institute (CLSI) breakpoint of 8mcg/mL. At first, resistance was thought to have occurred due to inadequate dosing, but genetic work demonstrated multiple genes encoding beta-lactamases.

BACTERIOLOGICAL PROFILE OF INFECTIONS IN BURNS UNIT - PLASTIC AND RECONSTRUCTIVE SURGERY DEPARTMENT - MOHAMMED VI CHU MARRAKECH

The nosocomial bacterial infection being one of the main causes of morbidity and mortality in burn patients, our work aimed on describing the nosocomial bacterial infections in order to establish the bacteriological profile to adapt the antibiotic therapy to our service. This is a retrospective study of 502 bacteriological samples taken from 65 patients hospitalized in the Resuscitation of burns of the plastic surgery department of the CHU Mohamed VI of Marrakech, over a period of 3 years, from January 1, 2016 to December 31, 2018. For this which is characteristic of bacterial infections, the infected sites were mainly the skin (50.1%) and blood (37.7%). The main germs were: Coagulase Negative Staphylococcus (32.1%), AcinetobacterBamannii (13.8%) Staphylococcus Aures (8.45%) AND Pseudomonas Aeruginosa (8.2%). Staphylococci were metabolic-resistant in 16.6% of cases Pseudomonas and Acinetobacter were multidrug resistant (60%). Establishing the bacterial ecology of the service, allowed us to set the right rules for prescribing antibiotic therapy, which was a function of the infected site, the type of germ, its sensitivity, the molecule used and the particular pharmacokinetics in the burn patient.