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      Biomarkers of sepsis: time for a reappraisal

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          Abstract

          Introduction

          Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers.

          Methods

          Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms “Biomarker” AND “Sepsis.” There were no restrictions by age or language, and all studies, clinical and experimental, were included.

          Results

          We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis.

          Conclusions

          The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

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          Most cited references136

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          Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection

          The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.
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            The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study

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              Comparison of procalcitonin and C-reactive protein as markers of sepsis.

              To compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in the detection of infection and sepsis and in the assessment of severity of sepsis. Prospective study. Medicosurgical intensive care unit. Seventy consecutive adult patients who were admitted to the intensive care unit for an expected stay >24 hrs. None. PCT and CRP plasma concentrations were measured daily during the intensive care unit stay. Each patient was examined daily for signs and symptoms of infection and was classified daily in one of the following four categories according to the American College of Chest Physicians/Society of Critical Care Medicine criteria: negative, systemic inflammatory response syndrome, localized infection, and sepsis group (sepsis, severe sepsis, or septic shock). The severity of sepsis-related organ failure was assessed by the sepsis-related organ failure assessment score. A total of 800 patient days were classified into the four categories. The median plasma PCT concentrations in noninfected (systemic inflammatory response syndrome) and localized-infection patient days were 0.4 and 1.4 ng/mL (p <.0001), respectively; the median CRP plasma concentrations were 79.9 and 85.3 mg/L (p =.08), respectively. The area under the receiver operating characteristic curve was 0.756 for PCT (95% confidence interval [CI], 0.675-0.836), compared with 0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median plasma PCT concentrations in nonseptic (systemic inflammatory response syndrome) and septic (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p <.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001), respectively. The area under the receiver operating characteristic curve was 0.925 for PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622-0.733) (p <.0001). The linear correlation between PCT plasma concentrations and the four categories was much stronger than in the case of CRP (Spearman's rho, 0.73 vs. 0.41; p <.05). A rise in sepsis-related organ failure assessment score was related to a higher median value of PCT but not CRP. PCT is a better marker of sepsis than CRP. The course of PCT shows a closer correlation than that of CRP with the severity of infection and organ dysfunction.
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                Author and article information

                Contributors
                jlvincent@intensive.org
                Journal
                Crit Care
                Critical Care
                BioMed Central (London )
                1364-8535
                1466-609X
                5 June 2020
                5 June 2020
                2020
                : 24
                : 287
                Affiliations
                [1 ]GRID grid.4989.c, ISNI 0000 0001 2348 0746, Intensive Care Department, Brugmann University Hospital, , Université Libre de Bruxelles, ; Brussels, Belgium
                [2 ]GRID grid.412458.e, Internal Medicine Department, , University Hospital of Patras, ; Patras, Greece
                [3 ]GRID grid.4989.c, ISNI 0000 0001 2348 0746, Department of Intensive Care, Erasme Hospital, , Université Libre de Bruxelles, ; Route de Lennik 808, 1070 Brussels, Belgium
                [4 ]GRID grid.415502.7, Surgery/Critical Care Medicine, , St. Michael’s Hospital, ; Toronto, Ontario Canada
                Author information
                http://orcid.org/0000-0001-6011-6951
                Article
                2993
                10.1186/s13054-020-02993-5
                7273821
                32503670
                3c38092f-4319-444f-b19b-c843e9512d8e
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 February 2020
                : 14 May 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Emergency medicine & Trauma
                procalcitonin,c-reactive protein,diagnosis,prognosis,infection,validation
                Emergency medicine & Trauma
                procalcitonin, c-reactive protein, diagnosis, prognosis, infection, validation

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