Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, the mechanisms of which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated the role of NETs and the underlying mechanism involved in acute lung injury (ALI). We found a higher expression of NETs and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in the airways, which was reduced by Deoxyribonuclease I (DNase I) in ALI. The administration of the STING inhibitor H-151 also significantly relieved inflammatory lung injury, but failed to affect the high expression of NETs in ALI. We isolated murine neutrophils from bone marrow and acquired human neutrophils by inducing HL-60 to differentiate. After the PMA interventions, exogenous NETs were obtained from such extracted neutrophils. Exogenous NETs intervention in vitro and in vivo resulted in airway injury, and such inflammatory lung injury was reversed upon degrading NETs with or inhibiting cGAS-STING with H-151 as well as siRNA STING. In conclusion, cGAS-STING participates in regulating NETs-mediated inflammatory pulmonary injury, which is expected to be a new therapeutic target for ARDS/ALI.
Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies and were inconsistent.Purpose: To determine the microbiology and outcomes of SAP in the lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV).Methods: In this observational study, included patients were divided into SAP and non-SAP based on a comprehensive analysis of symptom, imaging, and laboratory results. Baseline characteristics, clinical characteristics, microbiology, and outcomes were recorded and evaluated.Results: Of 200 patients, 42.5% developed SAP after the onset of stroke, and they had a lower proportion of non-smokers (p = 0.002), lower GCS score (p < 0.001), higher serum CRP (p < 0.001) at ICU admission, and a higher proportion of males (p < 0.001) and hypertension (p = 0.039) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78.8%), followed by Gram-positive aerobic cocci (29.4%). The main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogenes, Serratia marcescens, and Burkholderia cepacia. SAP prolonged length of MV (p < 0.001), duration of ICU stay (p < 0.001) and hospital stay (p = 0.027), shortened MV-free days by 28 (p < 0.001), and caused elevated vasopressor application (p = 0.001) and 60-day mortality (p = 0.001). Logistic regression analysis suggested that patients with coma (p < 0.001) have a higher risk of developing SAP.Conclusion: The microbiology of SAP is similar to early phase of HAP and VAP. SAP prolongs the duration of MV and length of ICU and hospital stays, but also markedly increases 60-day mortality.
Background: The attributable mortality and microbial etiology of stroke-associated pneumonia (SAP) vary among different studies. We intednd to determine the microbiology and outcomes of SAP in lower respiratory tract (LRT) for patients with invasive mechanical ventilation (MV).Methods: In this prospective observational study, included patients were divided into SAP and non-SAP based on comprehensive analysis of symptom, imaging and laboratory results. Baseline characteristic, clinical characteristic, microbiology and outcomes were recorded and evaluated.Results: Of 185 patients, 41.6% developed SAP after onset of stroke, and they had lower proportion of non-smoker (p=0.016), lower GCS score (p<0.001), higher serum CRP score (p<0.001) at ICU admission, and higher proportion of males (p<0.001) and hypertension (p=0.018) than patients with non-SAP. Gram-negative aerobic bacilli were the predominant organisms isolated (78%), followed by Gram-positive aerobic cocci (29.9%). Out of 19 isolated pathogens, main pathogens included K. pneumoniae, S. aureus, H. influenzae, A. baumannii, P. aeruginosa, E. aerogens, Serratia marcescens, and Burkholderia cepacia. SAP significantly prolonged length of MV (p<0.001) and duration of ICU stays (p<0.001), shorten MV-free days by 28 (p<0.001), caused elevated vasopressor application (p=0.002) and 60-day mortality (p=0.001).Conclusion: Microbiology of SAP is similar to early-phase HAP and VAP. SAP significantly prolongs duration of MV and lengths of ICU stays, but also markedly increase 60-day mortality.Trial registration: ChiCTR2000028849; http://www.chictr.org.cn/index.aspx, Registered 05 January 2020.
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