Critical care wardCritical care involves the care of the sickest patients in the hospital. Critically ill patients have usually been through a significant insult to their body (such as trauma, infection, burn) and have developed organ failure and require life-support. Critical Care is the largest theme bringing together clinicians and scientists from diverse backgrounds and includes collaborative research from hospitals throughout north-west London. Investigations range from evaluating biological mechanisms of organ failure through to the development of innovative technologies which allow the short-term and long-term support and recovery of organs. 

Many people are exposed to the environment of an Intensive care unit (ICU) either personally or through a family member. It is often a life-changing event and our work aims to reduce this impact facilitating post-ICU recovery.

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Citation

BibTex format

@article{Davenport:2016:10.1016/S2213-2600(16)00046-1,
author = {Davenport, EE and Burnham, KL and Radhakrishnan, J and Humburg, P and Hutton, P and Mills, TC and Rautanen, A and Gordon, AC and Garrard, C and Hill, AVS and Hinds, CJ and Knight, JC},
doi = {10.1016/S2213-2600(16)00046-1},
journal = {Lancet Respiratory Medicine},
pages = {259--271},
title = {Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study},
url = {http://dx.doi.org/10.1016/S2213-2600(16)00046-1},
volume = {4},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundEffective targeted therapy for sepsis requires an understanding of the heterogeneity in the individual host response to infection. We investigated this heterogeneity by defining interindividual variation in the transcriptome of patients with sepsis and related this to outcome and genetic diversity.MethodsWe assayed peripheral blood leucocyte global gene expression for a prospective discovery cohort of 265 adult patients admitted to UK intensive care units with sepsis due to community-acquired pneumonia and evidence of organ dysfunction. We then validated our findings in a replication cohort consisting of a further 106 patients. We mapped genomic determinants of variation in gene transcription between patients as expression quantitative trait loci (eQTL).FindingsWe discovered that following admission to intensive care, transcriptomic analysis of peripheral blood leucocytes defines two distinct sepsis response signatures (SRS1 and SRS2). The presence of SRS1 (detected in 108 [41%] patients in discovery cohort) identifies individuals with an immunosuppressed phenotype that included features of endotoxin tolerance, T-cell exhaustion, and downregulation of human leucocyte antigen (HLA) class II. SRS1 was associated with higher 14 day mortality than was SRS2 (discovery cohort hazard ratio (HR) 2·4, 95% CI 1·3–4·5, p=0·005; validation cohort HR 2·8, 95% CI 1·5–5·1, p=0·0007). We found that a predictive set of seven genes enabled the classification of patients as SRS1 or SRS2. We identified cis-acting and trans-acting eQTL for key immune and metabolic response genes and sepsis response networks. Sepsis eQTL were enriched in endotoxin-induced epigenetic marks and modulated the individual host response to sepsis, including effects specific to SRS group. We identified regulatory genetic variants involving key mediators of gene networks implicated in the hypoxic response and the switch to glycolysis t
AU  - Davenport,EE
AU  - Burnham,KL
AU  - Radhakrishnan,J
AU  - Humburg,P
AU  - Hutton,P
AU  - Mills,TC
AU  - Rautanen,A
AU  - Gordon,AC
AU  - Garrard,C
AU  - Hill,AVS
AU  - Hinds,CJ
AU  - Knight,JC
DO  - 10.1016/S2213-2600(16)00046-1
EP  - 271
PY  - 2016///
SN  - 2213-2619
SP  - 259
TI  - Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study
T2  - Lancet Respiratory Medicine
UR  - http://dx.doi.org/10.1016/S2213-2600(16)00046-1
UR  - http://hdl.handle.net/10044/1/29791
VL  - 4
ER  -
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