Identifying molecular subtypes of critical illness to inform better treatments using a precision medicine framework

危重症是一种急性疾病，病因多样，导致器官功能障碍，需要器官支持才能生存。在类似的危重疾病中，临床和生物学的异质性是常态。更重要的是，不同的重症在生物学上有共性。目前危重疾病的范例是诸如败血症、胰腺炎、多发创伤和呼吸窘迫综合征（ARDS）等综合征。最近，在一篇概念论文中，强调有必要淡化危重疾病中使用的基于综合征的框架，以便为危重成人提供精准医疗（Maslove et al., 2022）。主要主管领导一个精确医学项目，在危重疾病中实现可治疗的特征方法- TRAITS项目。这项全球独特的研究计划包括在成人危重患者专利中嵌入生物学特性的数据支持适应性随机对照试验（rct）。随机对照试验的适应可能包括选择新的治疗方法或鉴定性状中的目标亚群。在TRAITS项目中，可治疗的特征被定义为可测量和可治疗的生物状态，具有与患者预后相关的独特生物特征。淋巴细胞减少伴呼吸衰竭是一种可治疗的特征。该规划的基本假设得到数据的支持，即可治疗的特征与导致严重疾病综合征的煽动性侮辱无关，这是实现时间紧迫的精准医疗的有效方法。使用临床数据和来自TRAITS试验的生物样本，目的是得出并验证淋巴细胞减少-呼吸衰竭特征的分子特征-多变量生物标志物谱，这些谱可以高度预测对一种治疗方法（Baricitinib或皮质类固醇）的治疗反应，或具有淋巴细胞减少-呼吸衰竭特征的危重患者的临床结果。Maslove， D.M.等人（2022）“重新定义危重疾病”，《自然医学》28(6)，第1141-1148页。可在：https://doi.org/10.1038/s41591-022-01843-x。

Critical illness is an acute illness, from diverse aetiology, resulting in organ dysfunction, necessitating organ support to survive. Clinical, and biological heterogeneity within similar critical illnesses is the norm. More importantly, there are biological commonalities across different critical illnesses. The current paradigm in critical illness is syndromes such as sepsis, pancreatitis, polytrauma and respiratory distress syndrome (ARDS). Recently, in a concept paper, the need to de-emphasise this syndrome based framework used in critical illness to enable precision medicine for critically ill adults was stressed (Maslove et al., 2022).The primary supervisor leads a precision medicine programme to enable a treatable trait approach within critical illness - TRAITS programme. This globally unique research programme consists of data enabled adaptive randomized controlled rials (RCTs) with embedded biological characterization in adult critically ill patents. The RCT adaptation may include selection of new treatments or identification of target sub-groups within traits. In the TRAITS programme, treatable traits are conceptualised as measurable and treatable biological states with distinct biological signatures that are associated with patient outcomes. Lymphopenia with respiratory failure is an example of treatable trait. The underpinning hypothesis of this programme, supported by data, is that treatable traits agnostic of the inciting insult that led to critical illness syndromes occur and that this is a valid approach to enable time-critical precision medicine.Using clinical data, and biological samples from the TRAITS Trial, the aims are to derive, and validate the- Molecular signatures for lymphopenia-respiratory failure trait- Multivariable biomarker profiles that are either highly predictive of treatment responses to one of the treatments tested (Baricitinib or corticosteroids), or of clinical outcomes for critically ill patients with lymphopenia-respiratory failure trait.Maslove, D.M. et al. (2022) 'Redefining critical illness', Nature Medicine, 28(6), pp. 1141-1148. Available at: https://doi.org/10.1038/s41591-022-01843-x.