Inpatient mortality kinase inhibitor Dovitinib is high in children admitted with pneumonia and bacterial meningitis in Malawi; therefore, it is important to determine the utility of these angiogenic factors as biomarkers for the identification of patients at risk of a poor outcome.Our data are in keeping with current evidence that suggests that the growth factors together with Ang-1 may be involved in limiting the deleterious effects of sepsis-induced endothelial dysfunction. Consistent with previous work, growth-factor concentrations were significantly higher in cases compared with controls. In contrast to previous studies, which demonstrated highest levels of growth factors in patients with septic shock [24,25,27,29], we showed that levels were lower in those with the most severe disease, defined as having a fatal outcome.

Very few of our patients demonstrated septic shock or required aggressive fluid resuscitation. Our data are consistent with those of Brueckmann et al. [26], who demonstrated that adults with PDGF levels <200 pg/ml were 7 times more likely to die than were those with higher levels.Karlsson et al. [28] demonstrated that VEGF concentrations in adult patients with sepsis were lower in nonsurvivors than in survivors, but did not adequately predict mortality. The differences in growth factors between gram-positive and gram-negative infections are difficult to explain. Our study was not designed to explain this differential response. We speculate that differences in the way bacterial cell components stimulate the inflammatory cascade might be responsible.

We identified high plasma Ang-1 concentrations and male gender as being independently associated with survival. Our study also supports the concept of intracerebral production of growth factors in bacterial meningitis.The major limitation of our study was that we studied growth-factor and angiopoietin concentrations only at admission and did not follow their course over time. Admission values are potentially more useful as prognostic markers, if they can be made available to the clinician at the time the patient is first seen, as they could help to identify a group of patients requiring aggressive treatment or characterize those eligible for entry to a randomized clinical trial of adjunctive therapies.Interventions that target the inhibition of inflammatory mediators and coagulation pathways have been unsuccessful.

Recently, microcirculatory dysfunction has been shown to be a critical element of the pathogenesis of severe sepsis [36]. The investigation of host mediators that directly influence endothelial function might therefore be a valuable approach to improve our understanding of the pathophysiology Dacomitinib of sepsis.A recent study demonstrated that activated protein C (APC) uses the angiopoietin/Tie-2 axis to promote endothelial barrier function [37].