Gut mucosal cell damage in meningococcal sepsis in children:Relation with clinical outcome

Objective: The pathophysiological sequelae of meningococcal sepsis are mainly caused by deregulated microvasculature function, leading to impaired tissue blood flow. Because mature enterocytes are known to be susceptible to altered perfusion, we aimed to investigate: (1) the development of enterocyte damage; and (2) the relation between enterocyte damage and severity of disease and outcome in children with meningococcal sepsis. Design: Retrospective human study. Setting: Pediatric intensive care unit at a university hospital. Patients: Nineteen consecutive children with meningococcal sepsis were studied during their pediatric intensive care unit stay. Interventions: None. Measurement and Main Results: Circulating levels of intestinal fatty acid binding protein, a small cytosolic protein constitutively present in mature enterocytes and released on cell injury, were assessed. Severity of disease was represented by meningococcal-specific Rotterdam Score, generic Pediatric Risk of Mortality II score, and circulating interleukin-6. Clinical outcome was measured by length of pediatric intensive care unit stay and number of ventilator days. Highest plasma intestinal fatty acid binding protein values were measured on pediatric intensive care unit stay admission. At the time of admission, eight of 19 patients had higher intestinal fatty acid binding protein plasma levels than the upper reference limit of 30 healthy volunteers. In all survivors, intestinal fatty acid binding protein levels declined to normal values within 12 hrs after starting intensive treatment, whereas the three nonsurvivors maintained elevated intestinal fatty acid binding protein plasma levels. A significant correlation was found among intestinal fatty acid binding protein and Rotterdam Score, Pediatric Risk of Mortality II, interleukin-6 at admission (Spearman's r(2) = 0.402, p =.006; r(2) = 0.243, p = .045; r(2) = 0.687, p <.001, respectively). Next, a significant correlation was found between intestinal fatty acid binding protein and clinical outcome. Conclusions: Elevated plasma intestinal fatty acid binding protein is found in eight of 19 children with severe pediatric intensive care unit stay at the time of clinical presentation, suggesting the presence of enterocyte damage. Furthermore, prolonged enterocyte damage is found in nonsurvivors. Further studies are needed to clarify the potential role for assessment of plasma intestinal fatty acid binding protein in monitoring treatment of pediatric intensive care unit stay. (Crit Care Med 2010; 38:133-137

Lower pre-treatment T cell activation in early- and late-onset tuberculosis-associated immune reconstitution inflammatory syndrome

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART.Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies.CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028).Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype