Wu Junru, Cyr Anthony, Gruen Danielle S, Lovelace Tyler C, Benos Panayiotis V, Chen Tianmeng, Guyette Francis X, Yazer Mark H, Daley Brian J, Miller Richard S, Harbrecht Brian G, Claridge Jeffrey A, Phelan Herb A, Zuckerbraun Brian S, Neal Matthew D, Johansson Pär I, Stensballe Jakob, Namas Rami A, Vodovotz Yoram, Sperry Jason L, Billiar Timothy R
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Pittsburgh Trauma Research Center, Division of Trauma and Acute Care Surgery, Pittsburgh, Pennsylvania, US.
Res Sq. 2021 Jan 8:rs.3.rs-106579. doi: 10.21203/rs.3.rs-106579/v1.
Alterations in lipid metabolism have the potential to be markers as well as drivers of the pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. Early in the clinical course, Fresh Frozen Plasma administration led to improved survival in association with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers. Late over-representation of phosphatidylethanolamines with critical illness led to the validation of a Lipid Reprogramming Score that was prognostic not only in trauma but also severe COVID-19 patients. Our lipidomic findings provide a new paradigm for the lipid response underlying critical illness.
脂质代谢的改变有可能成为急性危重病病理生物学的标志物和驱动因素。在此，我们利用创伤作为危重病常见病因所提供的时间精确性，来确定危重病患者循环脂质组中的动态模式。主要发现包括，所有种类的循环脂质早期减少，随后在注定仍处于危重病状态的患者中出现延迟且选择性的脂肪生成。在临床病程早期，输注新鲜冰冻血浆与脂质水平保持相关，从而改善了生存率，这与凝血和炎症生物标志物的有利变化有关。危重病时磷脂酰乙醇胺的后期过度表达导致脂质重编程评分得到验证，该评分不仅对创伤患者，而且对重症COVID-19患者都具有预后价值。我们的脂质组学发现为危重病背后的脂质反应提供了一个新的范例。
