Endothelial Dysfunction and Selenium Status in Children With Acute Systemic Inflammatory Response
Condition: Endothelial Dysfunction; Regulation of Acute Inflammatory Response; Selenium Deficiency
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        children admitted to an intensive care unit (ICU) with systemic inflammatory response.
      
Biospecimen description: 
      blood