Intensive Care Unit, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
Department of Internal Medicine, Division of Oncology, Medical University of Graz, 8036 Graz, Austria.
Nutrients. 2021 Sep 3;13(9):3106. doi: 10.3390/nu13093106.
Sepsis biomarkers and potential therapeutic targets are urgently needed. With proton nuclear magnetic resonance (H NMR) spectroscopy, several metabolites can be assessed simultaneously. Fifty-three adult medical ICU sepsis patients and 25 ICU controls without sepsis were prospectively enrolled. H NMR differences between groups and associations with 28-day and ICU mortality were investigated. In multivariate metabolomic analyses, we found separate clustering of ICU controls and sepsis patients, as well as septic shock survivors and non-survivors. Lipoproteins were significantly different between sepsis and control patients. Levels of the branched-chain amino acids (BCAA) valine (median 43.3 [29.0-53.7] vs. 64.3 [47.7-72.3] normalized signal intensity units; = 0.005), leucine (57.0 [38.4-71.0] vs. 73.0 [54.3-86.3]; = 0.034) and isoleucine (15.2 [10.9-21.6] vs. 17.9 [16.1-24.4]; = 0.048) were lower in patients with septic shock compared to those without. Similarly, BCAA were lower in ICU non-survivors compared to survivors, and BCAA were good discriminators for ICU and 28-day mortality. In uni- and multivariable logistic regression analyses, higher BCAA levels were associated with decreased ICU- and 28-day mortality. In conclusion, metabolomics using H NMR spectroscopy showed encouraging potential for personalized medicine in sepsis. BCAA was significantly lower in sepsis non-survivors and may be used as early biomarkers for outcome prediction.
脓毒症的生物标志物和潜在治疗靶点亟待研究。质子磁共振波谱（1H NMR）技术可同时评估多种代谢物。前瞻性纳入 53 例成年重症监护病房（ICU）脓毒症患者和 25 例无脓毒症的 ICU 对照者。分析两组间的 1H NMR 差异及其与 28 天和 ICU 死亡率的相关性。多变量代谢组学分析发现，ICU 对照组和脓毒症患者、脓毒性休克存活者和非存活者能够分开聚类。脂蛋白在脓毒症患者和对照组间存在显著差异。与对照组相比，脓毒症患者的支链氨基酸（BCAA）亮氨酸（中位数 43.3 [29.0-53.7] 与 73.0 [54.3-86.3] 归一化信号强度单位； = 0.005）、缬氨酸（43.3 [29.0-53.7] 与 64.3 [47.7-72.3] 归一化信号强度单位； = 0.005）和异亮氨酸（15.2 [10.9-21.6] 与 17.9 [16.1-24.4] 归一化信号强度单位； = 0.048）水平较低，而脓毒性休克患者的 BCAA 水平显著低于非脓毒性休克患者。同样，ICU 非存活者的 BCAA 水平低于存活者，BCAA 可作为 ICU 死亡率和 28 天死亡率的良好预测指标。在单变量和多变量逻辑回归分析中，较高的 BCAA 水平与 ICU 死亡率和 28 天死亡率降低相关。总之，1H NMR 波谱代谢组学显示出在脓毒症个体化治疗方面的巨大潜力。脓毒症非存活者的 BCAA 水平显著降低，可能作为预后预测的早期生物标志物。
