Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome.

Purpose: Immunoparalysis defined by prolonged monocyte human leukocyte antigen DR depression is associated with adverse outcomes in adult severe sepsis and can be reversed with granulocyte macrophage colony-stimulating factor (GM-CSF). We hypothesized that immunoparalysis defined by whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNFα) response <200 pg/mL beyond day 3 of multiple organ dysfunction syndrome (MODS) is similarly associated with nosocomial infection in children and can be reversed with GM-CSF.

Methods: In study period 1, we performed a multicenter cohort trial of transplant and nontransplant multiple organ dysfunction syndrome (MODS) patients (≥2 organ failure).

Timing of correct parenteral antibiotic initiation and outcomes from severe bacterial community-acquired pneumonia in children.

Background: The impact of timing of appropriate antibiotic initiation for critically ill children with severe bacterial community-acquired pneumonia (CAP) is unknown. We hypothesized that longer time to initiation of correct parenteral antibiotic would be associated with longer durations of mechanical ventilation, intensive care unit length of stay, and hospital length of stay.

Methods: We retrospectively reviewed medical records of children admitted to Nationwide Children's Hospital between January 2004 and December 2006 with bacterial CAP treated with mechanical ventilation, excluding those with documented viral infection.

Failure to recover somatotropic axis function is associated with mortality from pediatric sepsis-induced multiple organ dysfunction syndrome.

Objectives: To describe the associations between mediators of the somatotropic axis and mortality from sepsis-induced multiple organ dysfunction syndrome in children; and to examine the relationship between immune function and the somatotropic axis in this setting.

Design: Retrospective study using banked plasma.

Setting: Single mixed surgical/medical intensive care unit at a quaternary level children's hospital.

Inflammasome mRNA expression in human monocytes during early septic shock.

Rationale: Monocytes are central to the initiation of the inflammatory response in sepsis, with caspase-1 activation playing a key role. Monocyte deactivation during sepsis has been linked to poor outcomes.

Objectives: Given the importance of caspase-1 in the immune response, we investigated whether monocytes from patients early in septic shock demonstrate alterations in mRNAs for caspase-1-related molecules.

Monocyte mRNA phenotype and adverse outcomes from pediatric multiple organ dysfunction syndrome.

Impairment of the ability to mount an inflammatory response is associated with death from adult critical illness. This phenomenon, characterized by reduced monocyte production of proinflammatory mediators such as tumor necrosis factor alpha (TNF-alpha), is poorly understood in children. We hypothesized that differential expression of inflammation-related genes would be seen in monocytes from children with adverse outcomes from multiple organ dysfunction syndrome (MODS).

Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release.

Macrophage responses to Francisella infection have been characterized previously by subdued proinflammatory responses; however, these studies have generally focused on macrophage cell lines or monocyte-derived macrophages. Therefore, we studied the ability of fresh human blood monocytes to engulf and respond to Francisella by using the live vaccine strain variant and Francisella novicida. Because Francisella organisms have been reported to escape from the phagolysosome into the cytosol, we hypothesized that this escape may trigger the activation of caspase-1.