Daily Ards Research Analysis

STUDY AIM: Acute respiratory distress syndrome (ARDS) is a critical disease of high mortality. Recent studies have confirmed that metabolic alterations and mitochondrial dysfunction is in involved in the progression of various pulmonary diseases. Moreover, significantly altered metabolite abundances are important in determining the severity of ARDS. Therefore, this study aims to illuminate the pulmonary metabolic profile, investigate the mitochondrial features of ARDS METHODS: Metabolomic data from ARDS patients were downloaded and reanalyzed. Then Mice were randomly allocated into one of three groups as follows: the sham group; the LPS-2 day group (L2); and the LPS-4 day group (L4). All the mice in LPS group were anesthetized and received an intratracheal instillation of LPS. The sham group mice received only sterile saline. Pulmonary metabolic profiles were measured by integrating metabolomic analyses with transcriptomic analyses, and mitochondrial features in the mouse lungs were investigated RESULTS: Inflamed lungs induce global metabolic perturbations that limit fatty acid oxidation, facilitate glucose consumption, accelerate amino acid metabolism and anaplerotic flux in the TCA cycle. In addition, impaired energetics followed by mitochondrial morphology alteration and mitochondrial dynamics imbalance are also validated in lung of ARDS. CONCLUSIONS: Global metabolic imbalance and substantial mitochondrial ultrastructural remodeling, characterized by a reduction in cristae density with significant activation of mitochondrial fission processes, have been verified to be pathogenic mechanisms in the lungs of ARDS patients.

BACKGROUND: Sepsis-induced acute respiratory distress syndrome (ARDS) is a common and costly syndrome with high mortality and poor prognosis without targeted therapies. Recently, pyroptosis has been demonstrated to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes (PRGs) in sepsis-induced ARDS and their correlation with prognosis remain unclear. METHODS: In this study, 760 sepsis samples from public datasets were analyzed. We first conducted a comprehensive analysis of single-cell RNA-sequencing data of sepsis from the Gene Expression Omnibus database and identified 8 cell types and 38 hub genes. Subsequently, we used univariate Cox hazard analysis to narrow down the candidate genes and developed a prognostic model using the disease cohorts, which stratified patients into high- and low-risk groups. Four genes associated with the prognosis of patients with sepsis admitted to the intensive care unit for ≥ 28 days were identified. RESULTS: High-risk patients have lower proportions of activated CD8 CONCLUSION: PRGs play a significant role in sepsis immunity. The above four key genes (CCL5, CD3G, IL7R, and GIMAP4) are expected to serve as clinical diagnostic targets, providing a basis for clinical prognosis stratification in patients with sepsis-induced ARDS and guiding the formulation of individualized treatment strategies.

BACKGROUND: Local anesthetic systemic toxicity is a rare but potentially life-threatening complication of local anesthetic use. This study aimed to describe the characteristics of patients with local anesthetic systemic toxicity and to identify initial clinical prognostic factors. METHODS: A retrospective cohort study of patients diagnosed with local anesthetic systemic toxicity from January 2013 to December 2022 was conducted using data from the Ramathibodi Poison Center Toxic Exposure Surveillance System, Thailand. RESULTS: One hundred and forty-three patients were included, with a median age of 41.5 years (IQR: 27.0-56.0 years). Lidocaine was the most commonly implicated local anesthetic (89.5%). The most frequent routes of administration were local infiltration (59.4%) and intravenous (15.4%). Neurological symptoms (perioral numbness, seizures, or coma) were the most common initial presentations (78.3%), followed by cardiovascular symptoms (43.4%), including chest pain, palpitations, hypotension, and cardiac arrest; cardiac arrest occurred in 10.5% of cases. Intravenous lipid emulsion therapy was administered in 12.6% of patients, and the median time from symptom onset to administration was 63 min (IQR: 48-90 min). Adverse effects of intravenous lipid emulsion (acute respiratory distress syndrome and fat overload syndrome) occurred in two of 18 (11.1% [95% CI:3.4-26%]) recipients. A multivariate analysis identified intravenous administration of local anesthetic (OR: 5.59; 95% CI: 1.53-20.33), the initial presence of coma (OR: 12.0; 95% CI: 2.96-48.60), hypotension (OR: 5.23; 95% CI: 1.34-20.29), and cardiac arrest (OR: 210; 95% CI: 22-1,919) as independent predictors of mortality. DISCUSSION: Seizures were the most frequent initial neurological presentation in our study, followed by cardiovascular features, particularly hypotension and palpitations, which is consistent with previous reports of local anesthetic systemic toxicity. CONCLUSIONS: In our study, the presence of hypotension, coma, and cardiac arrest at presentation and intravenous administration of local anesthetic was strongly associated with severe outcomes and increased mortality. Although intravenous lipid emulsion therapy has shown clinical efficacy, delayed access to this treatment remains a considerable barrier, particularly in rural or resource-limited settings.