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

正在做什么？本研究旨在通过对个体患者脓毒症反应的性质和驱动因素提供新的见解来改善脓毒症患者的护理。我们的长期目标是帮助开发一种针对败血症的精准医学方法，让正确的患者在正确的时间得到正确的治疗。为什么需要这样做？当身体对感染的反应失调和不适当时，就会发生败血症。这会导致器官衰竭，有时甚至死亡。为什么这种情况会发生在某些人身上尚不清楚，我们目前也没有针对这种情况的治疗方法。脓毒症是英国重症监护病房最常见的入院原因，死亡率高达25-30%。这是NHS目前面临的一个主要问题，世界卫生组织认为败血症是全球卫生重点问题。如何做到这一点？在这项研究中，我们将利用我们的发现，血细胞中的基因活性水平可以预测你的败血症反应类型。我们将研究具有低反应状态的脓毒症患者，因为这些患者预后较差，可能受益于特异性免疫调节治疗。我们的第一个目标是找出医生如何通过测量血液中的生物标志物来确定这类患者。我们的第二个目标是确定在脓毒症期间这种反应如何随时间变化。我们的第三个目标是了解遗传易感因素。我们的第四个目标是了解低反应性败血症状态下白细胞功能障碍的性质。我们的第五个目标是与进行临床试验的医生合作，利用对低反应状态的了解来帮助开发治疗败血症的新方法。我们将通过英国败血症基因组研究进展来实现这一目标，应用大数据（组学）和临床实验医学方法。工作将在哪里进行？这项工作将在牛津大学、桑格研究所和帝国理工学院进行。这项工作什么时候开始？这项工作将于2020年至2024年进行。

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.