Weaning-induced pulmonary oedema (WiPO) is a well-recognised cause of failure of weaning from mechanical ventilation, but its incidence and risk factors have not been reliably described. We wanted to determine the incidence and risk factors in a population of critically ill patients. In addition, we wanted to describe the effects of diuretics when they are administered in this context. We monitored 283 consecutive spontaneous breathing trials (SBT; T-piece trial) performed in 81 patients. In cases with cardiac output monitoring (n = 85, 29 patients), a passive leg raising (PLR) test was performed before SBT. Three experts established the diagnosis of WiPO based on various patient characteristics. SBT failed in 128 cases (45 % of all SBT). WiPO occurred in 59 % of these failing cases. Compared to patients without WiPO (n = 52), patients with at least one WiPO (n = 29) had a higher prevalence of chronic obstructive pulmonary disease (COPD) (38 % vs. 12 %, respectively; p < 0.01), previous “structural” cardiopathy (dilated and/or hypertrophic and/or hypokinetic cardiopathy and/or significant valvular disease, 9 % vs. 25 %, respectively; p < 0.01), obesity (45 % vs. 17 %, respectively; p < 0.01), and low left ventricular ejection fraction (55 % vs. 21 %, respectively; p = 0.01). At logistic regression, COPD (odds ratio (OR) 8.7, 95 % confidence interval (CI) 2.0–37.3), previous structural cardiopathy (OR 4.5, 95 % CI 1.4–14.1), and obesity (OR 3.6, 95 % CI 1.2–12.6) were independent risk factors for experiencing at least one episode of WiPO. In 16 cases with WiPO and a negative PLR at baseline, treatment including diuretics was started. In 9 of these cases, the PLR remained negative before the following SBT. A new episode of WiPO occurred in 7 of these instances, while the two other were extubated. In 7 other cases, the PLR became positive before the following SBT. WiPO did not occur anymore in 6 of these 7 patients who were extubated, while the remaining one was not. In our population of critically ill patients, WiPO was responsible for 59 % of weaning failures. COPD, previous “structural” cardiopathy, and, to a lesser extent, obesity were the main risk factors. When a treatment including fluid removal had changed preload-independence to preload-dependence, the following SBT was very likely to succeed.

The growing population of elderly neurocritically ill patients highlights the need for effective prognosis prediction tools. This study aims to develop and validate machine learning (ML) models for predicting 28-day mortality in intensive care units (ICUs). Data were extracted from the Medical Information Mart for Intensive Care IV(MIMIC-IV) database, focusing on elderly neurocritical ill patients with ICU stays ≥ 24 h. The cohort was split into 70 % for training and 30 % for internal validation. We analyzed 58 variables, including demographics, vital signs, medications, lab results, comorbidities, and medical scores, using Lasso regression to identify predictors of 28-day mortality. Seven ML algorithms were evaluated, and the best model was validated with data from Guizhou Medical University Affiliated Hospital. A log-rank test was used to assess survival differences in Kaplan-Meier curves. Shapley Additive Explanations (SHAP) were used to interpret the best model, while subgroup analysis identified variations in model performance across different populations. The study included 1,773 elderly neurocritically ill patients, with a 28-day mortality rate of 28.6 %. The Light Gradient Boosting Machine (LightGBM) outperformed other models, achieving an area under the curve (AUC) of 0.896 in internal validation and 0.812 in external validation. Kaplan-Meier analysis showed that higher LightGBM prediction scores correlated with lower survival probabilities. Key predictors identified through SHAP analysis included partial pressure of arterial carbon dioxide (PaCO₂), Acute physiology and chronic health evaluation II (APACHE II), white blood cell count, age, and lactate. The LightGBM model demonstrated consistent performance across various subgroups. The LightGBM model effectively predicts 28-day mortality risk in elderly neurocritically ill patients, aiding clinicians in management and resource allocation. Its reliable performance across diverse subgroups underscores its clinical utility.

Purpose/aim: Activated coagulation and reduced fibrinolysis in alveolar compartment are an important characteristics in acute respiratory distress syndrome (ARDS). Alveolar epithelial cell type II (AECII) participates in regulating the intra-alveolar abnormalities of coagulation and fibrinolysis mainly through adjusting the productions of tissue factor (TF), plasminogen activator inhibitor (PAI)-1 and activated protein C (APC) in ARDS. NF-κB signal pathway may be involved in coagulation regulation in sepsis-induced ALI. The purpose of this study was to testify the hypothesis that NF-κB p65 (p65) knock-down would improve the abnormalities of coagulation and fibrinolysis mediated by lipopolysaccharide (LPS) stimulation in AECII. Materials and Methods: p65 gene knock-down in AECII was achieved by small interfering RNA (siRNA) transfection. Rat AECII (RLE-6TN) with or without p65 gene knock-down were stimulated by LPS for 24 hours. And then cytolysate was used for TF, PAI-1 expression examination, and supernatant was collected for TF, PAI-1 and PC concentrations determination. Activation of NF-κB canonical pathway was simultaneously checked by western-blotting, RT-PCR and immunofluorescence respectively. Results: TF, PAI-1 expressions in normal cells obviously increased under LPS stimulation with NF-κB canonical pathway activation represented by high levels of p65, p-p65, p-IκB with increased nuclear translocation of p-p65. Cells with NF-κB p65 knock-down, however, showed significant decreases in TF, PAI-1, p65, p-p65, p-IκB expressions following LPS stimulation with significant reduction in p-p65 nuclear translocation as compared to normal and siRNA control cells. The high concentrations of TF, PAI-1 and low level of APC in supernatant induced by LPS in normal cells were significantly reversed through p65 knock-down. Conclusions: The experimental findings demonstrate that NF-kB signaling pathway is involved in regulating the expressions of coagulation and fibrinolysis factors in LPS-stimulated AECII, which suggest that NF-kB signaling pathway may be a new target to correct intra-alveolar coagulation and fibrinolytic abnormalities in ARDS.

Background: It has been confirmed that NF-κB p65 signaling pathway is involved in the regulation of alveolar hypercoagulation and fibrinolysis inhibition in acute respiratory distress syndrome (ARDS). Whether SN50, a NF-κB cell permeable inhibitor, could attenuate alveolar hypercoagulation and fibrinolysis inhibition in ARDS remains to be elucidated. Purpose: We explored the efficacy and potential mechanism of SN50 on alveolar hypercoagulation and fibrinolysis inhibition in ARDS in mice. Materials and methods: Mouse ARDS was made by 50 μl of lipopolysaccharide (LPS) (4 mg/ml) inhalation. Male BALB/c mice were intraperitoneally injected with different does of SN50 1 h before LPS inhalation. Lung tissues were collected for hematoxylin-eosin (HE) staining, wet/dry ratio. Pulmonary expressions of tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), collagen III, as well as phosphorylated p65 (p-p65), p65 in nucleus (p’-p65), IκBα and IKKα/β were measured. Bronchoalveolar lavage fluid (BALF) was gathered to test the concentrations of TF, PAI-1, activated protein C (APC) and thrombinantithrombin complex (TAT). DNA binding activity of NF-κB p65 was also determined. Results: After LPS stimulation, pulmonary edema and exudation and alveolar collapse occured. LPS also stimulated higher expressions of TF and PAI-1 in lung tissues, and higher secretions of TF, PAI-1, TAT and low level of APC in BALF. Pulmonary collagen III expression was obviously enhanced after LPS inhalation. At same time, NF-κB signaling pathway was activated with LPS injury, shown by higher expressions of p-p65, p’-p65, p-IKKα/β, p-Iκα in pulmonary tissue and higher level p65 DNA binding activity. SN50 dose-dependently inhibited TF, PAI-1 and collagen IIIexpressions, and decreased TF, PAI-1, TAT but increased APC in BALF. SN50 treatment attenuated pulmonary edema, exudation and reduced lung tissue damage as well. SN50 application significantly reduced p’-p65 expression and weakened p65 DNA binding activity, but expressions of p-p65, p-IKKα/β, p-Iκα in cytoplasm of pulmonary tissue were not affected. Conclusions: SN 50 attenuates alveolar hypercoagulation and fibrinolysis inhibition in ARDS via inhibition of NF-κB p65 translocation. Our data demonstrates that NF-κB p65 pathway is a viable new therapeutic target for ARDS treatment.

Pulmonary inflammation strongly promotes alveolar hypercoagulation and fibrinolytic inhibition. NF‑κB signaling regulates the expression of molecules associated with coagulation and fibrinolytic inhibition in type‑II alveolar epithelial cells (AECII) stimulated by lipopolysaccharide. However, whether TNF‑α‑induced alveolar hypercoagulation and fibrinolysis inhibition is also associated with the NF‑κB pathway remains to be determined. The aim of the present study was to determine whether BAY11‑7082, an inhibitor of the NF‑κB pathway, inhibits the expressions of tissue factor (TF) and plasminogen activator inhibitor‑1 (PAI‑1) in AECⅡ in response to TNF‑α. Rat AECII were treated with BAY11‑7082 for 24 h and stimulated with TNF‑α for 1 h. The expression of TF and PAI‑1 were determined using western blotting and reverse transcription‑quantitative PCR. The concentrations of TF and PAI‑1 in culture supernatant were also measured by ELISA. Moreover, levels of NF‑κB p65 (p65), phosphorylated (p)‑p65 (p‑p65), inhibitor of NF‑κB α (IκBα) and p‑IκBα were also evaluated. Immunofluorescence was used to detect p65 levels in cell nuclei. TNF‑α significantly promoted TF and PAI‑1 expression either at the mRNA or protein level in AECII cells. Concentrations of TF and PAI‑1 in supernatant also significantly increased upon TNF‑α stimulation. Furthermore, TNF‑α upregulated the levels of p‑IκBα, p65, and p‑p65 in the cytoplasm. Immunofluorescence analysis indicated that TNF‑α increased p65 translocation from the cytoplasm to the nucleus. However, AECII pre‑treated with BAY11‑7082 expressed lower levels of TF and PAI‑1 following TNF‑α treatment. Levels of p‑IκBα, p65 and p‑p65 in the cytoplasm also decreased, and translocation of p65 from cytoplasm into the nucleus was inhibited by BAY11‑7082 pretreatment. These findings suggest that BAY11‑7082 improves the hypercoagulation and fibrinolytic inhibition induced by TNF‑α in alveolar epithelial cells via the NF‑κB signaling pathway. BAY11‑7082 might represent a therapeutic option for alveolar hypercoagulation and fibrinolytic inhibition in acute respiratory distress syndrome.

Alveolar hypercoagulation and pulmonary inflammation are important characteristics and they regulate each other in acute respiratory distress syndrome (ARDS). NF-κB pathway has been confirmed to be involved in regulation of this crosstalk. Emodin, a traditional Chinese herb, shows potent inhibitory effect on NF-κB pathway, but whether it is effective in alveolar hypercoagulation and pulmonary inflammation in ARDS remains to be elucidated. The aim of this experiment was to evaluate the efficacy of emodin on LPS-provoked alveolar hypercoagulation and excessive pulmonary inflammation in ARDS, and its potential mechanism. Mice ARDS was set up through LPS (40 μl, 4 mg/ml) inhalation. Male mice were randomly received with BPS, LPS only, LPS+ emodin (5 mg/kg, 10 mg/kg, 20 mg/kg, respectively) and BAY65-1942, an inhibitor of IKKβ. After 48 h of LPS stimulation, pulmonary pathological injury, expressions of Tissue factor (TF), plasminogen activator inhibitor (PAI)-1, activated protein C (APC), collagen Ⅰ, collagen III, interleukin (IL) 8, IL-1β and tumor necrosis factor (TNF)-α in lung tissues, as well as concentrations of antithrombin III (AT III), procollagen peptide type III (PIIIP), soluble thrombomodulin (sTM), thrombin antithrombin complex (TAT), myeloperoxidase (MPO) and the percentage of inflammatory cells in bronchoalveolar lavage fluid (BALF) were all determined. NF-κB pathway activation as well as NF-κB DNA binding activity in pulmonary tissue were simultaneously checked. LPS stimulation resulted in obvious lung injury, excessive inflammatory cells infiltration, which all were dose-dependently ameliorated by emodin. Expressions of TF, PAI-1, collagen Ⅰ and collagen III as well as IL-8, IL-1β and TNF-α in pulmonary tissue were all elevated while APC decreased under LPS provocation, which were all reversed by emodin treatment in dose-dependent manner. LPS promoted the secretions of PIIIP, sTM, TAT and inhibited AT III production in BALF, and resulted in high levels of MPO and the percentage of inflammatory cells in BALF, all of which were significantly and dose-dependently attenuated while AT III production was increased by emodin. Meanwhile, emodin effectively inhibited NF-κB pathway activation and attenuated p65 DNA binding activity induced by LPS inhalation. Emodin and BAY-65-1942 had similar impacts in this experiment. Emodin improves alveolar hypercoagulation and fibrinolytic inhibition and depresses excessive pulmonary inflammation in ARDS mice in dose-dependent manner via NF-κB inactivation. Our data demonstrate that emodin is expected to be an effective drug in alveolar hypercoagulation and pulmonary inflammation in ARDS.