283 Towards precision medicine in sepsis Patients may deteriorate further to the end of the spectrum in sepsis and develop a state of extreme over-inflammation termed ‘macrophage activation syndrome’-like, which is recognized by fever, low leukocyte counts, liver function abnormalities and very high ferritin concentrations; this is amenable to treatment with anti-cytokine therapies such as recombinant interleukin 1 (IL-1) receptor antagonist [9]. However, due to fast recognition and improved therapeutic and supportive care, fewer sepsis patients die during the first days after ICU admission, but rather develop a critical illness that in addition to persistent inflammation, is also characterized by immunosuppression. The notion that the course of sepsis is now more protracted lasting for days to weeks instead of acute is important for understanding the pathophysiological mechanisms that impact on patient outcome. In sepsis patients with a prolonged clinical course, the disturbances in the host response involve increased lymphocyte apoptosis and lymphopenia, decreased expression of activation markers such as human leukocyte antigen (HLA)-DR on the surface of monocytes, dysregulated cellular metabolism of immune cells, and impaired cytokine production capacity [5, 10-12]. These disturbances in the homeostasis of host defence mechanisms, often a combination of hyper-inflammation and immunosuppression, are main causes of the unfavourable outcome of sepsis due to either hypotension and shock, organ dysfunction, or secondary infections. A precision medicine approach to establish personalized modulator immunotherapy in sepsis is needed in order to identify the precise mechanisms underlying the dysregulated immune response in septic patients, and apply appropriate therapy in an individualized manner. 11
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