• Michiel van der Flier, Ewout M Baerveldt, Annemieke Miedema, Nico G Hartwig, Jan A Hazelzet, Marieke Emonts, Ronald de Groot, Errol P Prens, Adrianus J van Vught, and Nicolaas J Jansen.
• 1Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands. 2The Nijmegen Institute for Infection, Inflammation, and Immunity, Radboud University Medical Centre, Nijmegen, The Netherlands. 3Department of Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands. 4Department of Dermatology, Erasmus Medical Centre, Rotterdam, The Netherlands. 5Pediatric Intensive Care Unit, University Medical Centre Utrecht, Utrecht, The Netherlands. 6Department of Pediatric Infectious Diseases and Immunology, Erasmus Medical Centre, Rotterdam, The Netherlands. 7Pediatric Intensive Care Unit, Erasmus Medical Centre, Rotterdam, The Netherlands.
• Pediatr Crit Care Me. 2013 Sep 1;14(7):682-5.

ObjectivesTo determine the skin microvessel expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels in children with meningococcal sepsis.DesignObservational study.SettingTwo tertiary academic children hospital PICUs.PatientsChildren with meningococcal sepsis.InterventionSkin biopsy and blood sample collection.Measurements And Main ResultsDetermination of skin microvessel vascular endothelial growth factor receptor 2 expression in skin biopsies by immunohistochemistry and measurement of serum-soluble vascular endothelial growth factor receptor 2 by enzyme-linked immunosorbent assay. Percentage of vascular endothelial growth factor receptor 2-positive skin microvessels and the staining intensity were significantly lower in children with meningococcal sepsis (n = 10) compared to controls (7.6% ± 8.8% vs 44.6% ± 39.2%; p = 0.009 and 0.7% ± 0.7% vs 1.7% ± 1.1%; p = 0.033, respectively). In addition, circulating serum levels of soluble vascular endothelial growth factor receptor 2 were decreased in sepsis (8,148 ± 1,140 pg/mL vs 13,414 ± 2,692 pg/mL; p < 0.001). Serum-soluble vascular endothelial growth factor receptor 2 levels (n = 28) were inversely correlated with Pediatric Risk of Mortality III score (r = -0.43; p = 0.023) and more decreased in nonsurvivors compared to survivors (5,640 ± 1,940 pg/mL vs 7,378 ± 2,336 pg/mL; p = 0.037).ConclusionsMicrovascular expression of vascular endothelial growth factor receptor 2 and serum-soluble vascular endothelial growth factor receptor 2 levels are decreased in children with sepsis. Serum-soluble vascular endothelial growth factor receptor 2 levels are inversely correlated with disease severity indicated by Pediatric Risk of Mortality III score and survival. Decreased vascular endothelial growth factor receptor 2 expression may hinder natural recovery from sepsis-associated microvascular injury and the effectiveness of therapeutic strategies targeting vascular endothelial growth factor-vascular endothelial growth factor receptor 2 signaling in sepsis patients.

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