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The overall hypotheses of this project is that severe sepsis is associated with endothelial dysfunction in pediatric patients and that selenium deficiency is associated with changes in biological markers of endothelial dysfunction and that these changes, in turn, are associated with worse clinical prognosis.
Background: Oxidative stress occurs during shock as a result of granulocytes and endothelial cell activation. Higher intensity of endothelial activation is associated with unfavorable outcomes. Selenium is an essential trace element that plays a key role in the antioxidant defenses and whose plasma concentrations have been low in critically ill patients. There are no clinical studies, especially in pediatric patients that consider the roles of selenium and nutritional status in the modulation of endothelial adaptive response during the inflammatory response secondary to shock. The investigators hypothesize that selenium deficiency is associated with changes in biological markers of endothelial dysfunction and that these changes, in turn, are associated with worse clinical prognosis. Objectives: 1) to investigate the association between selenium (Se) status and the endothelial activation in children during acute systemic inflammatory response and 2) to investigate whether the intensity of endothelial activation can predict the clinical outcome in children with systemic inflammatory response.
Methodology: prospective, observational study in children admitted to an intensive care unit (ICU) with systemic inflammatory response. The primary outcome will be 'intensity endothelial activation' which will be defined based on biological markers (SE-selectin, soluble intercellular molecule 1 of Vascular Cell adhesion Molecule and soluble adhesion-1). The association between the state of Se (anthropometric measurements, blood levels of selenium and erythrocyte glutathione peroxidase, selenoprotein P activity) and this outcome will be investigated in a multiple logistic model considering age, gender, primary diagnosis, prognostic scores and clinical characteristics. The secondary outcome will be 'clinical prognosis' which will be defined based on 'organ dysfunction' (creatinine level, platelets level and arterial hypotension), infectious complications during the staying in ICU and death up to 28 days. In this step the explanatory variables will be the same used in the first analyse plus to 'intensity of endothelial activation'. Participants will be followed for the duration of ICU/Hospital stay, an expected average of 28 days. Particularly, biological markers of endothelial activation will be evaluated in three different times: at baseline and on days 3 and 5 ICU. Expected results: if the study hypotheses are correct, they may justify the analysis of biomarkers of endothelial activation in medical practice and in future studies assessing the benefits of selenium supplementation in critical illness.
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| Measure | Description | Time Frame |
|---|---|---|
| association between selenium status and the endothelial activation | To investigate the association between selenium status and the endothelial activation in children during acute systemic inflammatory response. | 30/06/2016 (up to 2 years) |
| Measure | Description | Time Frame |
|---|---|---|
| Endothelial activation and clinical outcome in children with SIRS | To investigate whether the intensity of endothelial activation can predict the clinical outcome in children with systemic inflammatory response | 30/06/2016 (up to 2 years) |
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Inclusion Criteria:
Exclusion Criteria:
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children admitted to an intensive care unit (ICU) with systemic inflammatory response.
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| Name | Affiliation | Role |
|---|---|---|
| Heitor Pons Leite, professor | Federal University of São Paulo | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emílio Lopes Junior | São Paulo | São Paulo | 05579-000 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23353941 | Background | Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af. | |
| 15636651 |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Nov 21, 2016 | |
| Reset | Jan 17, 2017 | |
| Release | Jul 7, 2017 | |
| Reset | Jan 26, 2018 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Nov 21, 2016 | Jan 17, 2017 | |||
| Jul 7, 2017 |
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blood
| Background |
| Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8. doi: 10.1097/01.PCC.0000149131.72248.E6. |
| Jan 26, 2018 |