Wei Cheng Mm1, Yun Long1, Hao Wang1, Wen Han Mm1, Jiahui Zhang1, Na Cui2. 1. Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China. 2. Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China. Electronic address: pumchcn@163.com.
Abstract
BACKGROUND: Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication of sepsis. Mammalian target of rapamycin (mTOR) signalling pathway is significantly associated with SIMD in an animal model; however, there have been no clinical studies of the association in humans. METHODS: We enrolled 88 patients with sepsis who were admitted to the intensive care unit (ICU) between April 2017, and April 2018. Biochemical indexes, hemodynamic parameters, and bedside echocardiographic parameters were recorded. Serum levels of mTOR, phosphorylated ribosome S6 protein kinase (PS6K), microtubule-associated protein light chain 3 type II (LC3B), Bcl-2-interacting mediator of cell death (BIM), interleukin 6, interleukin 10, and interferon-γ were examined. RESULTS: Compared with non-SIMD patients, patients with SIMD had higher ICU and 28-day mortality, PS6K and BIM levels, but lower LC3B levels. Serum PS6K levels in patients with SIMD were significantly negatively and positively correlated with LC3B and BIM, respectively. Multivariate regression analysis revealed that PS6K concentration at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that a PS6K concentration cutoff of 42.43 pg/mL at ICU admission could predict the incidence of SIMD with a sensitivity and specificity of 91.7% and 96.2%, whereas a cutoff concentration of 41.17 pg/mL PS6K could predict 28-day mortality with a sensitivity and specificity of 83.3% and 54.3%, respectively. CONCLUSIONS: Patients with sepsis and SIMD had higher ICU and 28-day mortality. Higher serum PS6K concentrations were significantly associated with SIMD incidence and 28-day mortality, suggesting that activation of the mTOR pathway may play a major role in SIMD.
BACKGROUND:Sepsis-induced myocardial dysfunction (SIMD) is a life-threatening complication of sepsis. Mammalian target of rapamycin (mTOR) signalling pathway is significantly associated with SIMD in an animal model; however, there have been no clinical studies of the association in humans. METHODS: We enrolled 88 patients with sepsis who were admitted to the intensive care unit (ICU) between April 2017, and April 2018. Biochemical indexes, hemodynamic parameters, and bedside echocardiographic parameters were recorded. Serum levels of mTOR, phosphorylated ribosome S6 protein kinase (PS6K), microtubule-associated protein light chain 3 type II (LC3B), Bcl-2-interacting mediator of cell death (BIM), interleukin 6, interleukin 10, and interferon-γ were examined. RESULTS: Compared with non-SIMD patients, patients with SIMD had higher ICU and 28-day mortality, PS6K and BIM levels, but lower LC3B levels. Serum PS6K levels in patients with SIMD were significantly negatively and positively correlated with LC3B and BIM, respectively. Multivariate regression analysis revealed that PS6K concentration at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that a PS6K concentration cutoff of 42.43 pg/mL at ICU admission could predict the incidence of SIMD with a sensitivity and specificity of 91.7% and 96.2%, whereas a cutoff concentration of 41.17 pg/mL PS6K could predict 28-day mortality with a sensitivity and specificity of 83.3% and 54.3%, respectively. CONCLUSIONS:Patients with sepsis and SIMD had higher ICU and 28-day mortality. Higher serum PS6K concentrations were significantly associated with SIMD incidence and 28-day mortality, suggesting that activation of the mTOR pathway may play a major role in SIMD.
Authors: Edy Y Kim; Hadas Ner-Gaon; Jack Varon; Aidan M Cullen; Jingyu Guo; Jiyoung Choi; Diana Barragan-Bradford; Angelica Higuera; Mayra Pinilla-Vera; Samuel Ap Short; Antonio Arciniegas-Rubio; Tomoyoshi Tamura; David E Leaf; Rebecca M Baron; Tal Shay; Michael B Brenner Journal: J Clin Invest Date: 2020-06-01 Impact factor: 14.808
Authors: Bruna A C Rattis; Ana C Freitas; Jordana F Oliveira; João L A Calandrini-Lima; Maria J Figueiredo; Danilo F Soave; Simone G Ramos; Mara R N Celes Journal: Oxid Med Cell Longev Date: 2021-04-08 Impact factor: 6.543