39 Biomarkers in sepsis Introduction Sepsis is characterized by a complex pathophysiology and heterogeneous phenotypes of affected patients regarding their symptoms, response to treatment and outcome. Currently there is no gold standard to diagnose sepsis, no tool to select, evaluate and de-escalate treatment and no reliable way to assign risk profiles or predict outcome [1]. Biomarkers can be the key to personalized medicine in sepsis where patients receive tailored treatment based on their unique characteristics [2, 3]. Biomarkers are naturally occurring molecules, genes or other characteristics by which particular physiological or pathological processes can be identified. In the clinical setting a biomarker is useful once it can aid decision-making. The ideal biomarker has fast kinetics, a high sensitivity and specificity, can be identified by fully automated technology, has a short turnaround time and is available as a point-ofcare-test with low production costs [1]. In other words, a biomarker needs to quickly assist the physician confronted with an ill patient in his or her decision on the best possible treatment. Current clinical biomarkers can be roughly divided into two types: diagnostic and prognostic markers (Figure 1). Biomarkers that can discriminate sepsis from non-infectious critical illness or can differentiate between causative organisms in sepsis can be regarded as diagnostic biomarkers. A diagnostic biomarker can diminish improper use of antibiotics and could be used for antibiotic stewardship. While pathogen detection remains the gold standard in establishing the etiology of infection, blood cultures are only positive in 30-40% of the sepsis cases and in one third of (clinically defined) sepsis cases all cultures are sterile [4, 5]. In addition, the presence of a pathogen does not prove the presence of disease and infections can be caused by multiple pathogens, further illustrating the need for biomarkers that indicate infection. Prognostic biomarkers can help predict outcome in patients with sepsis by assigning risk profiles. In addition, biomarkers can aid in stratifying patients in subgroups based on specific pathophysiological features, thereby paving the way to personalized therapy with biomarker-guided follow-up of response to treatment [6]. The approach to use biomarker tests to select and evaluate specific therapies is known as theranostics and is seen as a main tool in the future management of many diseases [7]. Such biomarker tests should be applicable on easily obtained samples such as urine or blood. Rapid testing should identify subgroups of patients that would benefit from certain targeted therapies. The biomarker test could further be of use by evaluating the effect of the therapy on its target. 3
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