40 Chapter 3 Useof biomarker Bedside test in simply obtainable sample (e.g., blood or urine) that affects clinical decision Clinician Types of biomarkers Diagnostic Prognostic Theranostic Examples of use • Distinquish infectious versus non-infectious • Causative organism and antibiotic stewardship • Assigningrisk profiles • Predict outcome • Stratify based on pathophysiology • Select and evaluate specific therapies; key to personalized medicine Figure 1: What is a biomarker? Biomarkers are host characteristics such as molecules or genes by which particular physiological or pathological processes can be identified. When developing and validating novel biomarkers their potential clinical use is of upmost importance. Biomarkers can be used to distinguish sepsis from non-infectious critical illness or to determine causative pathogens to initiate the best possible treatment, thereby contributing to antibiotic stewardship. Furthermore, biomarkers can help stratify patients based on risk profiles, predict outcome or identify pathophysiological pathways that can be the target for personalized therapy. Biomarker tests that select and monitor specific therapies are known as theranostics and are seen as a future aid for a targeted personalized approach in patients with sepsis. Biomarkers have been implemented in clinical practice in various fields of medicine, including cardiology (e.g., troponin T in myocardial infarction), vascular medicine (e.g., D-dimer in patients suspected of pulmonary embolism) and in particular oncology (numerous examples). In contrast, in sepsis management the use of biomarkers is still at its very beginning. In a comprehensive systematic review, conducted nearly a decade ago, 178 biomarkers were evaluated in the context of sepsis [8]. A crude search in the PubMed database shows that biomarkers in sepsis is a trending topic (Figure 2). In the last ten years almost five thousand papers on biomarkers in sepsis have been published, whilst before 2007 the total number of published papers was less than three thousand. Roughly one hundred clinical trials are currently enrolling patients to study biomarkers in sepsis [9]. Even though numerous biomarkers for sepsis have been identified [8, 10], the recently updated guidelines of the Surviving Sepsis Campaign only see a minor role for one in clinical practice, i.e. procalcitonin (PCT)[11]. This underlines the current status of biomarkers in sepsis. So far, no biomarker has been found reliable enough to diagnose sepsis or predict prognosis; only PCT is used in some medical centers to guide antibiotic treatment in critically ill patients [12]. This is largely attributed to the complex pathophysiology of sepsis and it seems unlikely that a single biomarker can provide accurate information about the main driver(s) of the disturbed host response in an individual patient with sepsis. A panel of biomarkers may deliver unique sepsis-signatures that are informative for specific pathophysiological derailments and/or prognosis, which is very much desired for the development of targeted therapies [3, 13-15]. New developments such as omics technologies and the human genome project are promising aids in the search for new useful biomarkers in sepsis. This article reviews current and novel biomarkers in sepsis and their potential use at the bedside to guide clinical decision making.
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