Their additional value may be in pinpointing areas of this response that may be amenable to dampening or other forms of therapeutic intervention. Thus, at the same time that one is treating the virus in at-risk individuals, it is conceivable that adjunctive therapy directed at abrogating or redirecting an overly exuberant host response could also be introduced to further improve prognosis. Tasocitinib 477600-75-2 Although this leap from the PI-103 research setting to the bedside still remains a challenge for the reasons cited, it is still reasonable to ask whether in the future even stronger prognostic utility or power might be found in analyzing select combinations or subsets of these markers, whether identified through statistical modeling or de novo as biologically plausible groupings. In addition to allowing for more intelligent utilization of available biomarkers, such an approach might further minimize justifiable concerns over potential over-interpretation of statistical associations seen in comparatively large batteries of single assay results not adjusted for multiple comparisons, such as those generated by the multiplex platforms in increasingly common use. In a limited look at this possibility, we found that combinations of multiple biomarkers from even four relatively indiscrete functional groupings did generate odds ratios for disease outcomes that were statistically robust, generalizable across both studies, and comparable to the most potent of the single biomarkers studied. The fact that elevated levels of certain biomarkers were found in each of the four groupings suggests a very broad and diverse immunologic response to acute influenza. But with further dissection of specific categories of markers it may be possible to delineate more precisely what role the disparate portions of the host response play in modulating the course of infection. Whether with 
further exposition such a combination approach might prove to be either more powerful or, ideally, disease-specific than any of the single biomarkers highlighted remains yet to be determined. In any case, these preliminary results are intriguing and provide a rationale for performing more detailed analyses of these particular biomarkers as additional patients are accrued in these studies and additional progression events recorded. It is certainly possible, for example, that combinations of other biomarkers, or even different logical groupings of the same biomarkers into other categories based upon such factors as common cellular origin or relative positioning within the pro-inflammatory cascade, might offer results of equal or superior prognostic value or provide even greater insight into potentially deleterious aspects of the host immune response. The focus of this present analysis has been on the prognostic value of baseline biomarkers in predicting the subsequent course of disease specifically in Apdm09 virus-infected patients. Since both studies are ongoing on a multi-year basis in both the Northern and Southern Hemispheres, have been broadened to include patients presenting with all major subtypes of seasonal virus in circulation at the time, and now collect serial blood specimens for up to 60 days following enrollment, the intention is that these analyses can be expanded in at least two ways. One goal will be to map the kinetics in serum and plasma of each of the major biomarkers, singly and in groupings, from baseline.