Investigation of the hyporesponsive endotype to inform a precision medicine approach to sepsis

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What is being done? This research aims to improve the care of patients with sepsis by providing new insights into the nature and drivers of the individual patient sepsis response. Our long-term goal is to help to develop a precision medicine approach to sepsis that allows the right patients to be getting the right treatment at the right time.Why is this needed? Sepsis occurs when the body's response to infection is dysregulated and inappropriate. This results in organ failure and sometimes death. Why this happens in some people is unclear and we have no current treatments that target this. Sepsis is the most common reason for admission to medical intensive care units in the UK and has a high mortality of 25-30%. This is a major current problem for the NHS and sepsis is recognised by the WHO as a global health priority. How will this be done? In this research we will use our finding that levels of gene activity in blood cells can predict your type of sepsis response. We will study sepsis patients with a hyporesponsive state as these patients have the worse outcomes and may benefit from specific immunomodulatory therapies. Our first objective is to work out how doctors can identify such patients with confidence by measuring biomarkers in the blood. Our second objective is to determine how this response may change over time during the sepsis illness. Our third objective is to understand genetic predisposing factors. Our fourth objective is to understand the nature of white blood cell dysfunction in the hyporesponsive sepsis state. Our fifth objective is to work with doctors undertaking clinical trials to use knowledge of the hyporesponsive state to help develop new treatments for sepsis. We will do this through the UK Genomic Advances in Sepsis study, applying big data (-omics) and clinical experimental medicine approaches.Where will the work be done? The work will be undertaken at the University of Oxford, Sanger Institute and Imperial College.When will the work be carried out? The work will be undertaken from 2020 to 2024.