Identifying changes in immune cells and constructing prognostic models using immune-related genes in post-burn immunosuppression

Background Burn patients are prone to infection as well as immunosuppression, which is a significant cause of death. Currently, there is a lack of prognostic biomarkers for immunosuppression in burn patients. This study was conducted to identify immune-related genes that are prognosis biomarkers in post-burn immunosuppression and potential targets for immunotherapy. Methods We downloaded the gene expression profiles and clinical data of 213 burn patients and 79 healthy samples from the Gene Expression Omnibus (GEO) database. Immune infiltration analysis was used to identify the proportion of circulating immune cells. Functional enrichment analyses were carried out to identify immune-related genes that were used to build miRNA-mRNA networks to screen key genes. Next, we carried out correlation analysis between immune cells and key genes that were then used to construct logistic regression models in GSE77791 and were validated in GSE19743. Finally, we determined the expression of key genes in burn patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results A total of 745 differently expressed genes were screened out: 299 were up-regulated and 446 were down-regulated. The number of Th-cells (CD4+) decreased while neutrophils increased in burn patients. The enrichment analysis showed that down-regulated genes were enriched in the T-cell activation pathway, while up-regulated genes were enriched in neutrophil activation response in burn patients. We screened out key genes (NFATC2, RORA, and CAMK4) that could be regulated by miRNA. The expression of key genes was related to the proportion of Th-cells (CD4+) and survival, and was an excellent predictor of prognosis in burns with an area under the curve (AUC) value of 0.945. Finally, we determined that NFATC2, RORA, and CAMK4 were down-regulated in burn patients. Conclusion We found that NFATC2, RORA, and CAMK4 were likely prognostic biomarkers in post-burn immunosuppression and potential immunotherapeutic targets to convert Th-cell dysfunction.

The Interplay between Host Defense, Infection, and Clinical Status in Septic Patients: A Narrative Review

Sepsis is a life-threatening condition that arises when the body’s response to an infection injures its own tissues and organs. Despite significant morbidity and mortality throughout the world, its pathogenesis and mechanisms are not clearly understood. In this narrative review, we aimed to summarize the recent developments in our understanding of the hallmarks of sepsis pathogenesis (immune and adaptive immune response, the complement system, the endothelial disfunction, and autophagy) and highlight novel laboratory diagnostic approaches. Clinical management is also discussed with pivotal consideration for antimicrobic therapy management in particular settings, such as intensive care unit, altered renal function, obesity, and burn patients.

Limb Salvage through Intermediary Wound Coverage with Acellular Dermal Matrix Template after Persistent Pseudomonas Aeruginosa Infection in a Burn Patient

Secondary infections of skin grafts pose a continuous problem in burn patients, very often leading to loss of transplanted skin grafts and making multiple surgical revisions necessary. We present a case report about persisting Pseudomonas aeruginosa infection in burn patients with known diabetes. The burn wounds in lower extremities required repeated debridements, multiple skin grafting attempts and finally an application of the dermal scaffold NovoSorb BTM. With these measures, we managed to undertake a successful reconstruction of infected burn defects and pre-vent an amputation. We concluded that the NovoSorb BTM could be seen as an additional promising tool in a burn surgery armamentarium. In cases where radical surgical wound decontamination is not possible without risking the loss of the limb, the application of NovoSorb BTM over a contaminated field can win extra time for topical infection treatment and additionally provide an excellent skin grafting ground.

The Frequency of Class1 and 2 and 3 Integrons in Vancomycin-resistant and Aminoglycoside Resistance Enterococcus Strains Isolated From Burn Patients in Southwest Iran

The full text of this preprint has been withdrawn by the authors due to author disagreement with the posting of the preprint. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.

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.

A 3-Years Pneumonia Incidence in Burn Cases with Inhalation Injury at the Burn Center of Dr. Soetomo General Hospital Surabaya in 2015-2018

Introduction: Inhalation injury is one of burns impact. Airway burns due to inhalation injury is a non-specific term which refer to all respiratory tract injuries occurred due to irritative chemicals, including heat and smoke during inspiration. Inhalation injury increases the risk of death in burns. Pneumonia is one of burns-related inhalation injury complications.Methods: This was a descriptive retrospective study aiming to determine the incidence of pneumonia in burn patients with inhalation injury using secondary data at Burn Center Dr. Soetomo General Hospital Surabaya in the period of January 2015 - December 2018.Results: There were 5 cases of pneumonia in 14 burn cases with inhalation injury (35.71%). Respectively, 2 and 3 cases were found in 2017 and 2018. There were 2 female (40%) and 3 male (60%) patients, with age varied within 28-73 years old. The burn area of burn patients with inhalation injury and pneumonia were found by 15%, 20%, 24%, 32% and 71%, or within the classification of 11-20% burn area, and most complication found was hypoalbuminemia, as much as 3 cases (60%).\Conclusion: Most pneumonia in burn cases with inhalation injury was occurred in 2018, dominated by male patients. The age of the patient were ranging from early adulthood to elderly. Most burns were in the range of 11-20% burn area with the most complication found was hypoalbuminemia.

5 -Year Retrospective Analysis of a Vented Mobility Algorithm in the Burn ICU

Early mobilization with mechanically ventilated patients has received significant attention within recent literature, however limited research has focused specifically on the burn population. The purpose of this single center, retrospective analysis was to review the use of a burn critical care mobility algorithm, to determine safety and feasibility of a burn vented mobility program, share limitations preventing mobility progression at our facility, and discuss unique challenges to vented mobility with intubated burn patients. A retrospective review was completed for all intubated burn center admissions between January 2015 to December 2019. Burn Therapy notes were then reviewed for data collection, during the intubation period, using stages of the mobility algorithm. In 5 years following initial implementation, the vented mobility algorithm was utilized on 127 patients with an average total body surface area of 22.8%. No adverse events occurred. Stage 1 (Range of motion) was completed with 100% of patients (n=127). Chair mode of bed, stage 2a, was utilized in 39.4%(n=50) of patients, while 15.8% (n=20) of patients were dependently transferred to the cardiac chair in stage 2b. Stage 3 (sitting on the edge-of-bed) was completed with 25% (n=32) of patients, with 11% (n=14) progressing to stage 5 (standing), and 3.9% (n=5) actively transferring to a chair. In 5 years, only 4.7% (n=6) reached stage 6 (ambulation). The most common treatment limitations were medical complications (33%) and line placement (21%). Early mobilization during mechanical ventilation is safe and feasible within the burn population, despite challenges including airway stability, sedation, and line limitations.

Assessment of urinary interleukin-18 in the early post-burn period to predict acute kidney injury of various degrees of burn patients

Background: Early detection of acute kidney injury (AKI) in burn-injured patients can help modify the treatment to prevent progression of acute renal failure and reduce the need for renal replacement therapy. The aim of the study was to evaluate urinary interleukin-18 in the early post-burn period to predict the AKI for the various degrees of burn patients.Methods: This prospective observational study was conducted in the department of nephrology, Dhaka medical college in collaboration with burn and plastic surgery unit of the same medical college hospital, from July 2017 to June 2018 for a period of one year. The 48 burn patients (Age>18 years) who attended in the burn unit of Dhaka medical college, Dhaka of both sexes were enrolled in this study. Data were analyzed by using SPSS 22.0. A value of p<0.05 was considered statistically significant for all tests.Results: In this study, mean age of the burn patients was 32.41±10.59 years. Male female ratio was 3.36:1. Urinary IL-18 in diagnosis of AKI showed accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 93.8%, 91.7%, 94.4%, 84.6% and 97.1% respectively. AUC for urinary IL-18 at admission was 0.968 (CI, 0.921-1.000) and AUC for serum creatinine at admission was 0.937 (CI, 0.871-1.000). Conclusions: According to Kappa value, AUC and sensitivity and specificity urinary IL-18 is a good biomarker in predicting of early AKI in burn patients.

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.