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Critical Care

, 14:R91

First Online: 21 May 2010Received: 02 January 2010Revised: 26 February 2010Accepted: 21 May 2010


IntroductionSevere sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors vascular endothelial growth factor VEGF, platelet-derived growth factor PDGF, fibroblast growth factor FGF, and angiopoietin-1 Ang-1 and -2 Ang-2 are mortality indicators in Malawian children with severe bacterial infection.

MethodsIn 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model.

ResultsThe median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis 72% and 82 28% with pneumonia, and 154 53% children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis P = 0.007. Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors 6,000 versus 3,900 pg-ml, P = 0.03; and 7,700 versus 11,900 pg-ml, P = 0.02, respectively. With a logistic regression model and controlling for confounding factors, only female sex OR, 3.95; 95% CI, 1.33 to 11.76 and low Ang-1 OR, 0.23; 95% CI, 0.08 to 0.69 were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors P = 0.02 and 0.001, respectively.

ConclusionsLower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome.



FGFfibroblast growth factor

IPDinvasive pneumococcal disease

NBIno detectable bacterial infection

PDGFplatelet-derived growth factor

SBIserious bacterial infection

VEGFvascular endothelial growth factor.

Electronic supplementary materialThe online version of this article doi:10.1186-cc9025 contains supplementary material, which is available to authorized users.

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Autor: Limangeni A Mankhambo - Daniel L Banda - The IPD Study Group - Graham Jeffers - Sarah A White - Paul Balmer - Standwell N


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