Early PREdiction of Sepsis using leukocyte surface biomarkers:: The ExPRES-Sepsis cohort study

Manu Shankar-Hari; Deepankar Datta; Julie Wilson; Valentina Assi; Jacqueline Stephen; Christopher J. Weir; Jillian Rennie; Jean Antonelli; Anthony Bateman; Jennifer M. Felton; Noel Warner; Kevin Judge; Jim Keenan; Alice Wang; Tony Burpee; K Alun Brown; Sion M Lewis; Tracey Mare; Alistair I. Roy; John Wright; Gillian Hulme; Ian Dimmick; Alasdair Gray; Adriano G Rossi; A. John Simpson; Andrew Conway-Morris; Tim Walsh

doi:10.1007/s00134-018-5389-0

Early PREdiction of Sepsis using leukocyte surface biomarkers: The ExPRES-Sepsis cohort study

Manu Shankar-Hari, Deepankar Datta, Julie Wilson, Valentina Assi, Jacqueline Stephen, Christopher J. Weir, Jillian Rennie, Jean Antonelli, Anthony Bateman, Jennifer M. Felton, Noel Warner, Kevin Judge, Jim Keenan, Alice Wang, Tony Burpee, K Alun Brown, Sion M Lewis, Tracey Mare, Alistair I. Roy, John WrightGillian Hulme, Ian Dimmick, Alasdair Gray, Adriano G Rossi, A. John Simpson, Andrew Conway-Morris, Tim Walsh

Research output: Contribution to journal › Article › peer-review

Abstract

PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).

METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).

RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.

CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.

CLINICAL TRIAL REGISTRATION: NCT02188992.

Original language	English
Pages (from-to)	1836-1848
Journal	Intensive Care Medicine
Volume	44
Early online date	5 Oct 2018
DOIs	https://doi.org/10.1007/s00134-018-5389-0
Publication status	Published - Nov 2018

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AAM - Early PREdiction of Sepsis using leukocyte surface...
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BIOMARKER BASED CELLULAR ANALYSIS TO PREDICT STAGES OF INFECTION AND SEPSIS
Walsh, T. (Principal Investigator), Conway-Morris, A. (Co-investigator) & Weir, C. (Co-investigator)
UK central government bodies/local authorities, health and hospital authorities
1/10/12 → 30/06/15
Project: Research

Timothy Walsh
- Deanery of Molecular, Genetic and Population Health Sciences - Chair of Critical Care
- Usher Institute
Person: Academic: Research Active

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Shankar-Hari, M., Datta, D., Wilson, J., Assi, V., Stephen, J., Weir, C. J., Rennie, J., Antonelli, J., Bateman, A., Felton, J. M., Warner, N., Judge, K., Keenan, J., Wang, A., Burpee, T., Brown, K. A., Lewis, S. M., Mare, T., Roy, A. I., ... Walsh, T. (2018). Early PREdiction of Sepsis using leukocyte surface biomarkers: The ExPRES-Sepsis cohort study. Intensive Care Medicine, 44, 1836-1848. https://doi.org/10.1007/s00134-018-5389-0

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title = "Early PREdiction of Sepsis using leukocyte surface biomarkers:: The ExPRES-Sepsis cohort study",

abstract = "PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.CLINICAL TRIAL REGISTRATION: NCT02188992.",

author = "Manu Shankar-Hari and Deepankar Datta and Julie Wilson and Valentina Assi and Jacqueline Stephen and Weir, {Christopher J.} and Jillian Rennie and Jean Antonelli and Anthony Bateman and Felton, {Jennifer M.} and Noel Warner and Kevin Judge and Jim Keenan and Alice Wang and Tony Burpee and Brown, {K Alun} and Lewis, {Sion M} and Tracey Mare and Roy, {Alistair I.} and John Wright and Gillian Hulme and Ian Dimmick and Alasdair Gray and Rossi, {Adriano G} and Simpson, {A. John} and Andrew Conway-Morris and Tim Walsh",

year = "2018",

month = nov,

doi = "10.1007/s00134-018-5389-0",

language = "English",

volume = "44",

pages = "1836--1848",

journal = "Intensive Care Medicine",

issn = "0342-4642",

publisher = "Springer",

}

Shankar-Hari, M, Datta, D, Wilson, J, Assi, V, Stephen, J , Weir, CJ, Rennie, J, Antonelli, J, Bateman, A, Felton, JM, Warner, N, Judge, K, Keenan, J, Wang, A, Burpee, T, Brown, KA, Lewis, SM, Mare, T, Roy, AI, Wright, J, Hulme, G, Dimmick, I, Gray, A , Rossi, AG, Simpson, AJ, Conway-Morris, A & Walsh, T 2018, 'Early PREdiction of Sepsis using leukocyte surface biomarkers: The ExPRES-Sepsis cohort study', Intensive Care Medicine, vol. 44, pp. 1836-1848. https://doi.org/10.1007/s00134-018-5389-0

TY - JOUR

T1 - Early PREdiction of Sepsis using leukocyte surface biomarkers:

T2 - The ExPRES-Sepsis cohort study

AU - Shankar-Hari, Manu

AU - Datta, Deepankar

AU - Wilson, Julie

AU - Assi, Valentina

AU - Stephen, Jacqueline

AU - Weir, Christopher J.

AU - Rennie, Jillian

AU - Antonelli, Jean

AU - Bateman, Anthony

AU - Felton, Jennifer M.

AU - Warner, Noel

AU - Judge, Kevin

AU - Keenan, Jim

AU - Wang, Alice

AU - Burpee, Tony

AU - Brown, K Alun

AU - Lewis, Sion M

AU - Mare, Tracey

AU - Roy, Alistair I.

AU - Wright, John

AU - Hulme, Gillian

AU - Dimmick, Ian

AU - Gray, Alasdair

AU - Rossi, Adriano G

AU - Simpson, A. John

AU - Conway-Morris, Andrew

AU - Walsh, Tim

PY - 2018/11

Y1 - 2018/11

N2 - PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.CLINICAL TRIAL REGISTRATION: NCT02188992.

AB - PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation).METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3).RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity.CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.CLINICAL TRIAL REGISTRATION: NCT02188992.

U2 - 10.1007/s00134-018-5389-0

DO - 10.1007/s00134-018-5389-0

M3 - Article

SN - 0342-4642

VL - 44

SP - 1836

EP - 1848

JO - Intensive Care Medicine

JF - Intensive Care Medicine

ER -

Early PREdiction of Sepsis using leukocyte surface biomarkers: The ExPRES-Sepsis cohort study

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BIOMARKER BASED CELLULAR ANALYSIS TO PREDICT STAGES OF INFECTION AND SEPSIS

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Timothy Walsh

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