Dataset Information

IL-10 polymorphism associated with decreased risk for mortality after burn injury.

ABSTRACT:

Objective

Evaluation of single nucleotide polymorphisms (SNPs) in the interleukin-10 promoter (-592 and -819) on risk for death after burn injury.

Methods

Association between the IL-10 SNPs and outcome after burn injury was evaluated in a cohort of 265 patients from Parkland Hospital, Dallas, TX with ? 15% TBSA burns without non-burn trauma (ISS ? 16), traumatic or anoxic brain injury or spinal cord injury, who survived >48 h under an IRB-approved protocol. Clinical data were collected prospectively and genotyping was conducted by TaqMan assay. Whole blood from 31 healthy volunteers was stimulated with LPS (100 ng/mL) to determine the level of IL-10 expression for each allele by enzyme-linked immunosorbent assay (ELISA).

Results

After adjustment for percent total body surface area (TBSA) burned, inhalation injury, age, gender, and race/ethnicity, carriage of ?592A and/or ?819T was significantly associated (P = 0.014) with a decreased risk for death (adjusted odds ratio: 0.404; 95% CI: 0.197-0.829). As the candidate SNPs were in complete linkage disequilibrium, it was not possible to distinguish which allele was associated with decreased mortality risk. Age, inhalation injury, and full-thickness burn size were significantly associated with increased risk for death. In the LPS stimulated blood of healthy controls, carriage of the -592A and/or -819T allele demonstrated a trend for decreased levels of IL-10 (P = 0.079).

Conclusion

Carriage of the ?592A and/or ?819T allele in the IL-10 promoter appears to reduce the risk for death after burn injury.

SUBMITTER: Huebinger RM

PROVIDER: S-EPMC2987274 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-10 polymorphism associated with decreased risk for mortality after burn injury.

Huebinger Ryan M RM Rivera-Chavez Fernando F Chang Ling-Yu LY Liu Ming-Mei MM Minei Joseph P JP Purdue Gary F GF Hunt John L JL Arnoldo Brett D BD Barber Robert C RC

The Journal of surgical research 20100806 1

<h4>Objective</h4>Evaluation of single nucleotide polymorphisms (SNPs) in the interleukin-10 promoter (-592 and -819) on risk for death after burn injury.<h4>Methods</h4>Association between the IL-10 SNPs and outcome after burn injury was evaluated in a cohort of 265 patients from Parkland Hospital, Dallas, TX with ≥ 15% TBSA burns without non-burn trauma (ISS ≤ 16), traumatic or anoxic brain injury or spinal cord injury, who survived >48 h under an IRB-approved protocol. Clinical data were coll ...[more]

PMID: 20863526

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Project description:BackgroundNo methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, noninvasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients.MethodsThis prospective observational study enrolled two patient cohorts within a single burn center into an institutionally approved institutional review board study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells. We then performed confirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid quantitative polymerase chain reaction. Findings were validated and modeled associations with clinical outcomes using a regression model.ResultsA total of 149 genes with a significant difference in expression from burn patients compared with controls were identified. Pathway analysis identified pathways related to interleukin (IL)-10 and inducible nitric oxide synthase signaling to have significant z scores. quantitative polymerase chain reaction analysis of IL-10, IL-12, arginase 1 (ARG1), and inducible nitric oxide synthase demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of nitric oxide synthase 2 (NOS2) and IL-12. Burn severity, acute lung injury, development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2, and (ARG1-IL-10)/(NOS2-IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1-IL-10)/(NOS2-IL-12) significantly correlated with burn severity and development of acute lung injury.ConclusionWe present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction.Level of evidencePrognostic/Epidemiological; Level II.

Project description:BackgroundData on severe and extensive burns in China are limited, as is data on the prevalence of a range of related gastrointestinal (GI) disorders [such as stress ulcers, delayed defecation, opioid-related bowel immotility, and abdominal compartment syndrome (ACS)]. We present a multicentre analysis of coincident GI dysfunction and its effect on burn-related mortality.MethodsThis retrospective analysis was conducted on patients with severe [≥ 20% total burn surface area (TBSA)] and extensive (> 50% TBSA or > 25% full-thickness TBSA) burns admitted to three university teaching institutions in China between January 1, 2011 and December 31, 2020. Both 30- and 90-day mortality were assessed by collating demographic data, burn causes, admission TBSA, % full-thickness TBSA, Baux score, Abbreviated Burn Severity Index (ABSI) score, and Sequential Organ Failure Assessment (SOFA) score, shock at admission and the presence of an inhalation injury. GI dysfunction included abdominal distension, nausea/vomiting, diarrhoea/constipation, GI ulcer/haemorrhage, paralytic ileus, feeding intolerance and ACS. Surgeries, length of intensive care unit (ICU) stay, pain control [in morphine milligram equivalents (MME)] and overall length of hospital stay (LOHS) were recorded.ResultsWe analyzed 328 patients [75.6% male, mean age: (41.6 ± 13.6) years] with a median TBSA of 62.0% (41.0-80.0%); 256 (78.0%) patients presented with extensive burns. The 90-day mortality was 23.2% (76/328), with 64 (84.2%) of these deaths occurring within 30 d and 25 (32.9%) occurring within 7 d. GI dysfunction was experienced by 45.4% of patients and had a significant effect on 90-day mortality [odds ratio (OR) = 14.070, 95% confidence interval (CI) 5.886-38.290, P < 0.001]. Multivariate analysis showed that GI dysfunction was associated with admission SOFA score and % full-thickness TBSA. Overall, 88.2% (67/76) of deceased patients had GI dysfunction [hazard ratio (HR) for death of GI dysfunction = 5.951], with a survival advantage for functional disorders (diarrhoea, constipation, or nausea/vomiting) over GI ulcer/haemorrhage (P < 0.001).ConclusionPatients with severe burns have an unfavourable prognosis, as nearly one-fifth died within 90 d. Half of our patients had comorbidities related to GI dysfunction, among which GI ulcers and haemorrhages were independently correlated with 90-day mortality. More attention should be given to severe burn patients with GI dysfunction.

Dataset Information

IL-10 polymorphism associated with decreased risk for mortality after burn injury.

Objective

Methods

Results

Conclusion

Publications

IL-10 polymorphism associated with decreased risk for mortality after burn injury.

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