Dataset Information

Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study.

ABSTRACT:

Introduction

Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients.

Methods

In this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied.

Results

Plasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.

SUBMITTER: Hastbacka J

PROVIDER: S-EPMC4422709 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study.

Hästbacka Johanna J Fredén Filip F Hult Maarit M Bergquist Maria M Wilkman Erika E Vuola Jyrki J Sorsa Timo T Tervahartiala Taina T Huss Fredrik F

PloS one 20150506 5

<h4>Introduction</h4>Matrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients.< ...[more]

PMID: 25945788

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Project description:BackgroundPatient survival after severe burn injury is largely determined by burn size. Modern developments in burn care have greatly improved survival and outcomes. However, no large analysis of outcomes in paediatric burn patients with present treatment regimens exists. This study was designed to identify the burn size associated with significant increases in morbidity and mortality in paediatric patients.MethodsWe undertook a single-centre prospective observational cohort study using clinical data for paediatric patients with burns of at least 30% of their total body surface area (TBSA). Patients were stratified by burn size in 10% increments, ranging from 30% to 100% TBSA, with a secondary assignment made according to the outcome of a receiver operating characteristic (ROC) analysis. Statistical analysis was done with Student's t test, ?(2) test, logistic regression, and ROC analysis, as appropriate, with significance set at p<0·05.Findings952 severely burned paediatric patients were admitted to the centre between 1998 and 2008. All groups were comparable in age (mean 7·3 [SD 5·3] years, ranging from 6·1 [5·1] years in the 30-39% TBSA group to 9·6 [5·4] years in the 90-100% TBSA group) and sex distribution (628 [66%] boys, ranging from 59% [73/123] in the 60-69% TBSA group to 82% [42/51] in the 90-100% TBSA group). 123 (13%) patients died (increasing from 3% [five of 180] in the 30-39% TBSA group to 55% [28/51] in the 90-100% TBSA group; p<0·0001), 154 (16%) developed multiorgan failure (increasing from 6% [ten] in the 30-39% TBSA group to 45% [23] in the 90-100% TBSA group; p<0·0001), and 89 (9%) had sepsis (increasing from 2% [three] in the 30-39% TBSA group to 26% [13] in the 90-100% TBSA group; p<0·0001). Burn size of 62% TBSA was a crucial threshold for mortality (odds ratio 10·07, 95% CI 5·56-18·22, p<0·0001).InterpretationWe established that, in a modern paediatric burn care setting, a burn size of roughly 60% TBSA is a crucial threshold for postburn morbidity and mortality. On the basis of these findings, we recommend that paediatric patients with greater than 60% TBSA burns be immediately transferred to a specialised burn centre. Furthermore, at the burn centre, patients should be treated with increased vigilance and improved therapies, in view of the increased risk of poor outcome associated with this burn size.FundingShriners Hospitals for Children, US National Institutes of Health, US National Institute on Disability and Rehabilitation Research, Institute for Translational Sciences, CFI Leaders Opportunity Fund, Physicians' Services Incorporated Foundation.

Project description:BackgroundMatrix metalloproteinases (MMPs) are involved in remodeling of the extracellular matrix (ECM) during pregnancy and parturition. Aberrant ECM degradation by MMPs or an imbalance between MMPs and their tissue inhibitors (TIMPs) have been implicated in the pathogenesis of preterm labor, however few studies have investigated MMPs or TIMPs in maternal serum. Therefore, the purpose of this study was to determine serum concentrations of MMP-3, MMP-9 and all four TIMPs as well as MMP:TIMP ratios during term and preterm labor.MethodsA case control study with 166 singleton pregnancies, divided into four groups: (1) women with preterm birth, delivering before 34 weeks (PTB); (2) gestational age (GA) matched controls, not in preterm labor; (3) women at term in labor and (4) at term not in labor. MMP and TIMP concentrations were measured using Luminex technology.ResultsMMP-9 and TIMP-4 concentrations were higher in women with PTB vs. GA matched controls (resp. p = 0.01 and p<0.001). An increase in MMP-9:TIMP-1 and MMP-9:TIMP-2 ratio was observed in women with PTB compared to GA matched controls (resp. p = 0.02 and p<0.001) as well as compared to women at term in labor (resp. p = 0.006 and p<0.001). Multiple regression results with groups recoded as three key covariates showed significantly higher MMP-9 concentrations, higher MMP-9:TIMP-1 and MMP-9:TIMP-2 ratios and lower TIMP-1 and -2 concentrations for preterm labor. Significantly higher MMP-9 and TIMP-4 concentrations and MMP-9:TIMP-2 ratios were observed for labor.ConclusionsSerum MMP-9:TIMP-1 and MMP-9:TIMP-2 balances are tilting in favor of gelatinolysis during preterm labor. TIMP-1 and -2 concentrations were lower in preterm gestation, irrespective of labor, while TIMP-4 concentrations were raised in labor. These observations suggest that aberrant serum expression of MMP:TIMP ratios and TIMPs reflect pregnancy and labor status, providing a far less invasive method to determine enzymes essential in ECM remodeling during pregnancy and parturition.

Dataset Information

Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study.

Introduction

Methods

Results

Publications

Matrix metalloproteinases -8 and -9 and tissue inhibitor of metalloproteinase-1 in burn patients. A prospective observational study.

Similar Datasets

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