Imperial College London
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DrDavidAntcliffe

Faculty of Medicine, Department of Surgery & Cancer

Clinical Senior Lecturer in Critical Medicine
 
 
 
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Contact

 

d.antcliffe

 
 
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Location

 

Intensive Care UnitCharing Cross HospitalCharing Cross Campus

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Summary

 

Publications

Citation

BibTex format

@article{Antcliffe:2019:10.1164/rccm.201807-1419OC,
author = {Antcliffe, D and Burnham, K and Al-Beidh, F and Santhakumaran, S and Brett, S and Hinds, C and Ashby, D and Knight, J and Gordon, AC},
doi = {10.1164/rccm.201807-1419OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {980--986},
title = {Transcriptomic signatures in sepsis and a differential response to steroids: from the VANISH randomized trial},
url = {http://dx.doi.org/10.1164/rccm.201807-1419OC},
volume = {199},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Rationale: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration but conflicting survival effects. Two transcriptomic sepsis response signatures (SRS) have been identified. SRS1 is relatively immunosuppressed whilst SRS2 is relatively immunocompetent. Objectives: We aimed to categorized patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock. Methods: A post-hoc analysis was performed of a double-blind randomized clinical trial in septic shock (VANISH). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined using a previously established model using seven discriminant genes. Measurements and Main Results: Samples were available from 176 patients, 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (p=0·50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (p=0·02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (OR 7·9, 95%CI 1·6-39·9). Conclusions: Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immuno-competent SRS2 endotype had significantly higher mortality when given corticosteroids compared to placebo. Clinical trial registration available at www.isrctn.com, ID ISRCTN20769191.
AU  - Antcliffe,D
AU  - Burnham,K
AU  - Al-Beidh,F
AU  - Santhakumaran,S
AU  - Brett,S
AU  - Hinds,C
AU  - Ashby,D
AU  - Knight,J
AU  - Gordon,AC
DO  - 10.1164/rccm.201807-1419OC
EP  - 986
PY  - 2019///
SN  - 1073-449X
SP  - 980
TI  - Transcriptomic signatures in sepsis and a differential response to steroids: from the VANISH randomized trial
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.201807-1419OC
UR  - http://hdl.handle.net/10044/1/65779
VL  - 199
ER  -
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