This was addressed to a small extent: one of the independent test datasets we used contained both influenza A- and B-infected individuals. In this dataset, all of the influenza-infected samples exhibited a similar gene-expression signature, as calculated by the SVM integer (Figure (Figure6B).6B). Attempts have been made by others to address this question by including multiple respiratory virus 17-DMAG Phase 2 types [24], and their results point toward a relatively conserved nature of the host response to viral infection. A signature that distinguishes a response to a viral opposed to a bacterial infection would be useful in the clinical management of pneumonia patients. Confounding variables such as effect of therapeutic interventions, including medications, should be addressed in future studies with a larger sample size; however, this is outside the scope of this study.
ConclusionsWe have identified a T-cell-dominant gene-expression signature that is associated with the host response to severe influenza pneumonia. This signature provides an insight into the pathophysiology of influenza and may serve as an alternative diagnostic approach to assist in the management of severe community-acquired pneumonia. The validity of such an approach warrants further study in a large independent patient cohort.Key messages? The whole-blood gene-expression profile of H1N1 influenza A was distinctly different from bacterial pneumonia and systemic inflammatory response syndrome.? Increased expression levels of genes linked to the cell cycle and its regulation were the main determinant of the host response in influenza infection, whereas most immune and inflammatory genes were downregulated.
? Deconvolution of the whole-bloo
Severe sepsis and septic shock are among the leading causes of death worldwide. Their incidence is constantly increasing, and almost 1,500,000 cases of severe sepsis and septic shock occur annually in North America and another 1,500,000 cases in Europe. Despite early intervention with antimicrobials, fluid resuscitation, and management in intensive care units (ICUs), mortality remains high, often exceeding 30%. This can be explained, in part, by the coexistence of chronic health disorders and the increasing rate of antimicrobial resistance that complicates management [1].The mainstay in the proper management of sepsis is early recognition of the patient at high risk for death.
This is traditionally based on the application of severity scores and serum biomarkers. The most widely applied score is that of the Acute Physiology and Chronic Health Evaluation II (APACHE II). However, APACHE II has several limitations that can give a misleading score. For example, in the Drug_discovery case of young patients with severe sepsis but without chronic organ failures, the APACHE II score may be relatively low despite the risk of an unfavorable outcome.
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