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

危重病是一种急性疾病，由多种病因引起，导致器官功能障碍，需要器官支持才能生存。相似的危重疾病的临床和生物学异质性是正常的。更重要的是，不同的危重疾病之间存在生物学共性。目前危重病的范例是综合征，如败血症，胰腺炎，多发性创伤和呼吸窘迫综合征（ARDS）。最近，在一篇概念论文中，强调了不强调这种用于危重病的基于综合征的框架的需要，以使危重病成人能够获得精确医学（Maslove et al.，2022).主要主管领导一个精准医学计划，以实现危重疾病中可治疗的特质方法-特质计划。这一全球独特的研究项目包括数据支持的适应性随机对照试验（RCT），其中包含成人重症患者的生物学特征。随机对照试验的适应性调整可能包括选择新的治疗方法或识别性状内的目标亚组。在TRAITS项目中，可治疗的特征被概念化为可测量和可治疗的生物状态，具有与患者结局相关的独特生物特征。淋巴细胞减少症伴呼吸衰竭是可治疗特征的一个例子。该项目的基本假设得到了数据的支持，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，这是一种有效的方法，可以实现时间紧迫的精准医学。使用临床数据和来自TRAITS试验的生物样本，目的是推导出，并验证-淋巴细胞减少-呼吸衰竭性状的分子特征-多变量生物标志物谱，其高度预测对所测试的治疗之一的治疗反应（Baricitinib或皮质类固醇），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。等人（2022）“重新定义危重病”，Nature Medicine，28（6），pp. 1141-1148.可在以下网址获得：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.