Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study

被引：53

作者：

Shankar-Hari, Manu ^{[1
,2
]}

Datta, Deepankar ^{[3
]}

Wilson, Julie ^{[1
,2
]}

Assi, Valentina ^{[4
,5
]}

Stephen, Jacqueline ^{[5
]}

Weir, Christopher J. ^{[4
,5
]}

Rennie, Jillian ^{[3
]}

Antonelli, Jean ^{[4
]}

Bateman, Anthony ^{[6
]}

Felton, Jennifer M. ^{[3
]}

Warner, Noel ^{[7
,8
]}

Judge, Kevin ^{[7
,8
]}

Keenan, Jim ^{[7
,8
]}

Wang, Alice ^{[7
,8
]}

Burpee, Tony ^{[7
,8
]}

Brown, Alun K. ^{[2
]}

Lewis, Sion M. ^{[2
]}

Mare, Tracey ^{[2
]}

Roy, Alistair I. ^{[7
,8
]}

Wright, John ^{[9
]}

Hulme, Gillian ^{[10
]}

Dimmick, Ian ^{[10
]}

Gray, Alasdair ^{[4
,11
]}

Rossi, Adriano G. ^{[3
]}

Simpson, A. John ^{[12
]}

Morris, Andrew Conway ^{[13
]}

Walsh, Timothy S. ^{[3
,4
,5
]}

机构：

[1] Kings Coll London, Sch Immunol & Microbial Sci, London, England

[2] Guys & St Thomas NHS Fdn Trust, London SE1 7EH, England

[3] Univ Edinburgh, MRC Ctr Inflammat Res, 47 Little France Crescent, Edinburgh, Midlothian, Scotland

[4] Univ Edinburgh, Usher Inst, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland

[5] Univ Edinburgh, Edinburgh Clin Trials Unit, Edinburgh, Midlothian, Scotland

[6] Univ Edinburgh, Dept Anaesthesia Crit Care & Pain Med, Edinburgh, Midlothian, Scotland

[7] Becton Dickinson Biosci, Franklin Lakes, NJ USA

[8] Sunderland Royal Hosp, Integrated Crit Care Unit, Sunderland, England

[9] Newcastle Upon Tyne Hosp NHS Fdn Trust, Emergency Dept, Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England

[10] Newcastle Univ, Fac Med Sci, Flow Cytometry Core Facil Lab, Ctr Life, Newcastle Upon Tyne, Tyne & Wear, England

[11] Royal Infirm Edinburgh NHS Trust, Dept Emergency Med, Edinburgh, Midlothian, Scotland

[12] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[13] Addenbrookes Hosp, Univ Div Anesthesia, Dept Med, Hills Rd, Cambridge, England

来源：

INTENSIVE CARE MEDICINE | 2018年 / 44卷 / 11期

基金：

“创新英国”项目;

关键词：

Sepsis; Infection; Mortality; Cohort study; Biomarker; risk prediction; INTERNATIONAL CONSENSUS DEFINITIONS; SEPTIC SHOCK; INDUCED IMMUNOSUPPRESSION; BACTERIAL-INFECTION; DISEASE PROGRESSION; NATURAL-HISTORY; CD64; EXPRESSION; NEUTROPHILS; BLOOD; CYTOMETRY;

D O I：

10.1007/s00134-018-5389-0

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

PurposeReliable 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 score2 at 24h and/or 72h following ED presentation).MethodsIn 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).ResultsBetween 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.ConclusionsFrom a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection.Clinical trial registrationNCT02188992.

引用

页码：1836 / 1848

页数：13

共 49 条

[1] A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria [J].

Angus, Derek C. ;

Seymour, Christopher W. ;

Coopersmith, Craig M. ;

Deutschman, Clifford S. ;

Klompas, Michael ;

Levy, Mitchell M. ;

Martin, Gregory S. ;

Osborn, Tiffany M. ;

Rhee, Chanu ;

Watson, R. Scott .

CRITICAL CARE MEDICINE, 2016, 44 (03) :E113-E121

[2] Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure [J].

Boomer, Jonathan S. ;

To, Kathleen ;

Chang, Kathy C. ;

Takasu, Osamu ;

Osborne, Dale F. ;

Walton, Andrew H. ;

Bricker, Traci L. ;

Jarman, Stephen D., II ;

Kreisel, Daniel ;

Krupnick, Alexander S. ;

Srivastava, Anil ;

Swanson, Paul E. ;

Green, Jonathan M. ;

Hotchkiss, Richard S. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 306 (23) :2594-2605

[3] TLR2, TLR4, CD14, CD11b, and CD11c expressions on monocytes surface and cytokine production in patients with sepsis, severe sepsis, and septic shock [J].

Brunialti, MKC ;

Martins, PS ;

de Carvalho, HB ;

Machado, FR ;

Barbosa, LM ;

Salomao, R .

SHOCK, 2006, 25 (04) :351-357

[4] Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis [J].

Chang, Katherine ;

Svabek, Catherine ;

Vazquez-Guillamet, Cristina ;

Sato, Bryan ;

Rasche, David ;

Wilson, Strother ;

Robbins, Paul ;

Ulbrandt, Nancy ;

Suzich, JoAnn ;

Green, Jonathan ;

Patera, Andriani C. ;

Blair, Wade ;

Krishnan, Subramaniam ;

Hotchkiss, Richard .

CRITICAL CARE, 2014, 18 (01)

[5] Multicentric Standardized Flow Cytometry Routine Assessment of Patients With Sepsis to Predict Clinical Worsening [J].

Daix, Thomas ;

Guerin, Estelle ;

Tavernier, Elsa ;

Mercier, Emmanuelle ;

Gissot, Valerie ;

Herault, Olivier ;

Mira, Jean-Paul ;

Dumas, Florence ;

Chapuis, Nicolas ;

Guitton, Christophe ;

Bene, Marie C. ;

Quenot, Jean-Pierre ;

Tissier, Cindy ;

Guy, Julien ;

Piton, Gael ;

Roggy, Anne ;

Muller, Gregoire ;

Legac, Eric ;

de Prost, Nicolas ;

Khellaf, Mehdi ;

Wagner-Ballon, Orianne ;

Coudroy, Remi ;

Dindinaud, Elodie ;

Uhel, Fabrice ;

Roussel, Mikael ;

Lafon, Thomas ;

Jeannet, Robin ;

Vargas, Frederic ;

Fleureau, Catherine ;

Roux, Mickael ;

Kaoutarallou ;

Vignon, Philippe ;

Feuillard, Jean ;

Francois, Bruno .

CHEST, 2018, 154 (03) :617-627

[6] Early PREdiction of Severe Sepsis (ExPRES-Sepsis) study: protocol for an observational derivation study to discover potential leucocyte cell surface biomarkers [J].

Datta, Deepankar ;

Morris, Andrew Conway ;

Antonelli, Jean ;

Warner, Noel ;

Brown, Kenneth Alun ;

Wright, John ;

Simpson, A. John ;

Rennie, Jillian ;

Hulme, Gillian ;

Lewis, Sion Marc ;

Mare, Tracey Anne ;

Cookson, Sharon ;

Weir, Christopher John ;

Dimmick, Ian ;

Keenan, Jim ;

Rossi, Adriano Giorgio ;

Shankar-Hari, Manu ;

Walsh, Timothy S. .

BMJ OPEN, 2016, 6 (08)

[7] Marked alterations of neutrophil functions during sepsis-induced immunosuppression [J].

Demaret, Julie ;

Venet, Fabienne ;

Friggeri, Arnaud ;

Cazalis, Marie-Angelique ;

Plassais, Jonathan ;

Jallades, Laurent ;

Malcus, Christophe ;

Poitevin-Later, Francoise ;

Textoris, Julien ;

Lepape, Alain ;

Monneret, Guillaume .

JOURNAL OF LEUKOCYTE BIOLOGY, 2015, 98 (06) :1081-1090

[8] Estimation of the Youden index and its associated cutoff point [J].

Fluss, R ;

Faraggi, D ;

Reiser, B .

BIOMETRICAL JOURNAL, 2005, 47 (04) :458-472

[9] Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial [J].

Francois, Bruno ;

Jeannet, Robin ;

Daix, Thomas ;

Walton, Andrew H. ;

Shotwell, Matthew S. ;

Unsinger, Jacqueline ;

Monneret, Guillaume ;

Rimmele, Thomas ;

Blood, Teresa ;

Morre, Michel ;

Gregoire, Anne ;

Mayo, Gail A. ;

Blood, Jane ;

Durum, Scott K. ;

Sherwood, Edward R. ;

Hotchkiss, Richard S. .

JCI INSIGHT, 2018, 3 (05)

[10] Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With Sepsis [J].

Glickman, Seth W. ;

Cairns, Charles B. ;

Otero, Ronny M. ;

Woods, Christopher W. ;

Tsalik, Ephraim L. ;

Langley, Raymond J. ;

van Velkinburgh, Jennifer C. ;

Park, Lawrence P. ;

Glickman, Lawrence T. ;

Fowler, Vance G., Jr. ;

Kingsmore, Stephen F. ;

Rivers, Emanuel P. .

ACADEMIC EMERGENCY MEDICINE, 2010, 17 (04) :383-390

← 1 2 3 4 5 →