A Randomized Controlled Clinical Trial Investigating the Weaning Process From Mechanical Ventilation in Elderly Patients With Dementia.

BACKGROUND: Limited data is available regarding the weaning techniques employed for mechanical ventilation (MV) in elderly patients with dementia in China. OBJECTIVE: The primary objective of this study is to investigate diverse weaning methods in relation to the prognostic outcomes of elderly patients with dementia undergoing MV in the intensive care unit (ICU). Specifically, we seek to compare the prognosis, likelihood of successful withdrawal from MV, and the length of stay (LOS) in the ICU. METHODS: The study was conducted as a randomized controlled trial, encompassing a group of 169 elderly patients aged ≥ 65 years with dementia who underwent MV. Three distinct weaning methods were used for MV cessation, namely, the tapering parameter, spontaneous breathing trial (SBT), and SmartCare (Dräger, Germany). RESULTS: In the tapering parameter group, the LOS in the ICU was notably prolonged compared to both the SBT and SmartCare groups. However, no statistically significant differences were observed among the groups with respect to demographic characteristics, such as age and sex, as well as factors including the rationale for ICU admission, cause of MV, MV mode, oxygenation index, hemoglobin levels, albumin levels, ejection fraction, sedation and analgesia practices, tracheotomy, duration of MV, successful extubation, successful weaning, incidences of ventilator-associated pneumonia, and overall prognosis. CONCLUSIONS: Both the SBT and SmartCare withdrawal methods demonstrated a reduction in the duration of MV and LOS in the ICU when compared to the tapering parameter method. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900028449.

Glycyrrhetinic acid triggers a protective autophagy by inhibiting the JAK2/STAT3 pathway in cerebral ischemia/reperfusion injury.

Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.