title: Early PREdiction of Severe Sepsis (ExPRES-Sepsis) study: protocol for an observational derivation study to discover potential leucocyte cell surface biomarkers.
abstract: Sepsis is an acute illness resulting from infection and the host immune response. Early identification of individuals at risk of developing life-threatening severe sepsis could enable early triage and treatment, and improve outcomes. Currently available biomarkers have poor predictive value for predicting subsequent clinical course in patients with suspected infection. Circulating leucocytes provide readily accessible tissues that reflect many aspects of the complex immune responses described in sepsis. We hypothesise that measuring cellular markers of immune responses by flow cytometry will enable early identification of infected patients at risk of adverse outcomes. We aim to characterise leucocyte surface markers (biomarkers) and their abnormalities in a population of patients presenting to the hospital emergency department with suspected sepsis, and explore their ability to predict subsequent clinical course.
  
  
  
  We will conduct a prospective, multicentre, clinical, exploratory, cohort observational study. To answer our study question, 3 patient populations will be studied. First, patients with suspected sepsis from the emergency department (n=300). To assess performance characteristics of potential tests, critically ill patients with established sepsis, and age and gender matched patients without suspicion of infection requiring hospital admission (both n=100) will be recruited as comparator populations. In all 3 groups, we plan to assess circulating biomarker profiles using flow cytometry. We will select candidate biomarkers by cross-cohort comparison, and then explore their predictive value for clinical outcomes within the cohort with suspected sepsis.
  
  
  
  The study will be carried out based on the principles in the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice. Ethics approval has been granted from the Scotland A Research Ethics Committee (REC) and Oxford C REC. On conclusion of this study, the results will be disseminated via peer-reviewed journals.
  
  
  
  NCT02188992; Pre-results.
authors.affiliation: Edinburgh Critical Care Research Group, Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh School of Clinical Sciences, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Deepankar
authors.identifier: 0000-0001-9971-9434
authors.initials: D
authors.lastname: Datta
authors.affiliation: Division of Anaesthesia, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Andrew
authors.identifier: 0000-0002-3211-3216
authors.initials: A
authors.lastname: Conway Morris
authors.affiliation: Edinburgh Clinical Trials Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: Jean
authors.initials: J
authors.lastname: Antonelli
authors.affiliation: BD Biosciences, San Jose, California, USA.
authors.forename: Noel
authors.initials: N
authors.lastname: Warner
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
authors.forename: Kenneth Alun
authors.initials: KA
authors.lastname: Brown
authors.affiliation: Emergency Department, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.affiliation: Institute of Cellular Medicine, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Jillian
authors.initials: J
authors.lastname: Rennie
authors.affiliation: Faculty of Medicine, Flow Cytometry Core Facility Laboratory, Biomedicine West Wing, Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Hulme
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK Edinburgh Health Services Research Unit, Centre for Population Health Sciences, Medical School, Edinburgh, UK.
authors.forename: Sion Marc
authors.initials: SM
authors.lastname: Lewis
authors.affiliation: Vascular Immunology Research Laboratory, Rayne Institute (King's College London), St Thomas' Hospital, London, UK.
authors.forename: Tracey Anne
authors.initials: TA
authors.lastname: Mare
authors.affiliation: Faculty of Medicine, Flow Cytometry Core Facility Laboratory, Biomedicine West Wing, Centre for Life, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Sharon
authors.initials: S
authors.lastname: Cookson
authors.affiliation: Edinburgh Health Services Research Unit, Centre for Population Health Sciences, Medical School, Edinburgh, UK.
authors.forename: Christopher John
authors.initials: CJ
authors.lastname: Weir
authors.affiliation: Flow Cytometry Applications, Instrumentation and Management Consultant, Newcastle upon Tyne, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Dimmick
authors.affiliation: BD Biosciences Europe, Le Pont de Claix, France.
authors.forename: Jim
authors.initials: J
authors.lastname: Keenan
authors.affiliation: MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
authors.forename: Adriano Giorgio
authors.initials: AG
authors.lastname: Rossi
authors.affiliation: Department of Intensive Care Medicine, Guy's and St Thomas' Hospital NHS Foundation Trust, St Thomas' Hospital, London, UK.
authors.forename: Manu
authors.initials: M
authors.lastname: Shankar-Hari
authors.affiliation: Edinburgh Critical Care Research Group, Department of Anaesthesia, Critical Care and Pain Medicine, University of Edinburgh School of Clinical Sciences, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016638:Critical Illness; D004636:Emergency Service, Hospital; D005260:Female; D006760:Hospitalization; D006801:Humans; D007159:Immunologic Tests; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D012606:Scotland; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D014218:Triage; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: ACCIDENT & EMERGENCY MEDICINE; Biomarker; Sepsis