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Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study.

ABSTRACT: BACKGROUND:Reducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome. METHODS:We conducted a matched case-control (1:3) study of 98 young infants aged 0-59 days of life presenting to a referral hospital in Bangladesh with suspected sepsis. Plasma levels of Ang-1, Ang-2, sICAM-1, and sVCAM-1 concentrations were measured at admission. The primary outcome was mortality (n?=?18); the secondary outcome was bacteremia (n?=?10). RESULTS:Ang-2 concentrations at presentation were higher among infants who subsequently died of sepsis compared to survivors (aOR 2.50, p =?0.024). Compared to surviving control infants, the Ang-2:Ang-1 ratio was higher among infants who died (aOR 2.29, p =?0.016) and in infants with bacteremia (aOR 5.72, p =?0.041), and there was an increased odds of death across Ang-2:Ang-1 ratio tertiles (aOR 4.82, p =?0.013). CONCLUSIONS:This study provides new evidence linking the Angiopoietin-Tie2 pathway with mortality and bacteremia in young infants with suspected sepsis. If validated in additional studies, markers of the angiopoietin-Tie2 axis may have clinical utility in risk stratification of infants with suspected sepsis.

SUBMITTER: Wright JK

PROVIDER: S-EPMC5866512 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study.

Wright Julie Korol JK Hayford Kyla K Tran Vanessa V Al Kibria Gulam Muhammed GM Baqui Abdullah A Manajjir Ali A Mahmud Arif A Begum Nazma N Siddiquee Mashuk M Kain Kevin C KC Farzin Azadeh A

BMC pediatrics 20180323 1

<h4>Background</h4>Reducing death due to neonatal sepsis is a global health priority, however there are limited tools to facilitate early recognition and treatment. We hypothesized that measuring circulating biomarkers of endothelial function and integrity (i.e. Angiopoietin-Tie2 axis) would identify young infants with sepsis and predict their clinical outcome.<h4>Methods</h4>We conducted a matched case-control (1:3) study of 98 young infants aged 0-59 days of life presenting to a referral hospi ...[more]

PMID: 29571293

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Project description:OBJECTIVES:Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. DESIGN:Cohort study. SETTING:The medical and surgical ICUs at an academic medical center. SUBJECTS:We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. INTERVENTIONS:We assayed nine biomarkers (?-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. MEASUREMENTS AND MAIN RESULTS:Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ? 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). CONCLUSIONS:Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Project description:Esophageal atresia (EA) is a rare anomaly that mandates surgical intervention. Patients with EA often have complicated medical courses due to both esophageal anomalies and related comorbidities. Although several prognostic classification systems have been developed to decrease the mortality rate in EA, most systems focus only on the influence of the major anomaly, and external risk factors that could be influenced by the neonatal caregivers to a certain extent are not included. The aim of this study was to investigate the risk factors for in-hospital mortality in neonates with EA and develop a scoring model to predict mortality.In total, 198 infants with EA who were treated with surgical intervention at the Children's Hospital of Chongqing Medical University between March 2004 and June 2016 were included. The demographic information, clinical manifestations, laboratory testing, and outcomes during hospitalization were analyzed retrospectively. A predictive scoring model was developed according to the regression coefficients of the risk factors.The mortality rate was 18.1% (36/198). In the univariate analysis, higher incidences of prematurity, low birth weight, long gap, anastomotic leak, respiratory failure, postoperative sepsis, respiratory distress syndrome, pneumothorax, and septic shock were found in the nonsurvivor group than in the survivor group (P < .05). In the logistic regression analysis, anastomotic leak (OR: 10.75, 95% CI: 3.113-37.128), respiratory failure (OR: 4.104, 95% CI: 2.292-7.355), postoperative sepsis (OR: 3.564, 95% CI: 1.516-8.375), and low birth weight (OR: 8.379, 95% CI: 3.357-20.917) were associated with a high mortality rate. A scoring model for predicting death was developed with a sensitivity of 0.861, a specificity of 0.827, a positive predictive value of 0.524, and a negative predictive value of 0.963 at a cutoff of 2 points. The area under the receiver-operating characteristic curve of the score was 0.905 (95% CI, 0.863-0.948, P = .000) for death from EA. The mortality rate increased rapidly as the scores increased, and all patients with scores ≥5 died.Anastomotic leak, respiratory failure, postoperative sepsis, and low birth weight are independent risk factors for mortality in EA. Infants with a predictive score of 5 had a high risk of death.

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Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study.

Publications

Biomarkers of endothelial dysfunction predict sepsis mortality in young infants: a matched case-control study.

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