Further, the samples were collected, shipped, and processed for analysis using identical procedures to minimize any potential artifactual effects on serum levels of the biomarkers measured. Even after adjustments for multiple potentially confounding variables within each dataset according to Dabrafenib different stringencies, there are several biomarkers whose baseline levels appear to be highly correlated with a worsened disease course according to the definitions of disease progression predefined for each study. Several could have been singled out in this context. However, the seven markers that were significantly correlated with disease progression in both studies were IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10, a somewhat disparate set spanning all four functional groupings. While cross-sectional comparisons between studies must always be interpreted with caution, for six of these seven markers, the exception being MCP-1, the absolute levels of each at study entry also appeared to correlate with disease severity at time of enrollment, as reflected principally by their higher geometric mean values in hospitalized patients versus outpatients. As a biomarker with known involvement in the Sorafenib pro-inflammatory cascade associated with many different types of infections, as well as one that has featured prominently in earlier other published analyses of the potential role of biomarkers in predicting influenza disease outcomes, we also chose to validate the strong predictive potential of IL-6 in these two studies. For both outpatients and those requiring hospitalization, serum IL-6 was a strong predictor of disease progression. For the hospitalized patients in FLU 003, those with an IL-6 level in the upper two tertiles were also at an increased of mortality. This is similar to prior observations a decade earlier in a small number of fatal cases of H5N1 infection. A causal explanation for this is not fully elucidated, although animal data do support an association of elevated levels of IL-6 production with enhanced lethality of the infecting virus. Although the strong statistical associations found in these two studies between select individual biomarkers and a worsened disease outcome are compelling, nonetheless these results present an obvious difficulty with extrapolation to the clinical arena at the present time. Most of the biomarkers described here are part of a multiplex testing array generally performed in a research setting and are not a routine part of the diagnostic work-up performed for a typical patient presenting with signs and symptoms of acute influenza. Hence, at present they may be of more value in providing insight into potential mechanisms of viral pathogenesis and host defense rather than in offering direct clinical benefit. There are some potential exceptions to this. D-dimer and CRP assays, for example, are generally available today in most acute care facilities as indicators of recent thrombotic events and abnormal systemic inflammation, respectively, and the test results are generally available in real time. It is fair to say that, at present, there does not appear to be a single discrete biomarker readily available to the physician at the time of presentation that one can conclude adds unequivocably to the ability of the standard diagnostic assessment to predict the likelihood of disease progression in all patients.