It is indisputable from the biological and clinical perspectives that not all cases of sepsis are the same. On the contrary, most have great many differences, that is, different portals of entry, clinical manifestations, immunologic responses, and survival outcomes. Therefore, why is there a single definition for something as complex and diverse as sepsis? This is the antithesis of precision medicine. We propose that all encompassing definitions such as Sepsis-1, Sepsis-2, and Sepsis-3 should no longer be used to guide the clinical management or to dictate trial designs for sepsis.

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