Daily Ards Research Analysis

Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage by transmembrane serine protease 2 (TMPRSS2). Vasoactive intestinal peptide (VIP) is known for its immune-modulating effects by suppressing the release of pro-inflammatory cytokines and enhancing regulatory T-cells. Furthermore, it has been tested in SARS-CoV-2-related clinical trials. We set out to investigate its role in the setting of SARS-CoV-2 infection in vitro. Epithelial cells (CaCo-2) were stimulated with SARS-CoV-2 spike protein, treated with native VIP and analyzed to investigate the mRNA and surface expression of ACE2 and TMPRSS2, the enzyme activity of TMPRSS2 and the infection rate by a SARS-CoV-2 pseudovirus. VIP downregulated ACE2 and TMPRSS2 mRNA and surface expression. Beyond these direct effects, VIP mediates the shedding of surface-expressed ACE2 and TMPRSS2 via upregulation of a sheddase protease (ADAM10). Functionally, these dual mechanisms of VIP-mediated downregulation of proteins involved in SARS-CoV-2 cell entry resulted in a reduced infection rate by the SARS-CoV-2 pseudovirus. These data imply that VIP hampers viral entry mechanisms based on SARS-CoV-2 and the linkage to ADAM10 may stimulate research in other indications beyond SARS-CoV-2.

OBJECTIVE: Ketamine, as a sedative, has been administered during mechanical ventilation in critically ill patients; however, its impact on survival outcomes in this patient population remains uncertain. METHODS: This retrospective cohort study extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, version 3.0. Patients were categorized into the ketamine group and the control group based on whether ketamine was administered during mechanical ventilation. Propensity score matching was performed to adjust for demographic variables and coexisting conditions. The primary outcome was 28-day mortality. Secondary outcomes included 14-day and 90-day mortality rates, as well as hospital and ICU lengths of stay. RESULTS: The study included a total of 8569 patients, with 330 in the ketamine group and 8239 in the control group. After propensity score matching, significant differences in mechanical ventilation duration and the proportion of patients with acute respiratory distress syndrome remained between groups. No significant differences were observed in 28-day and 90-day mortality rates between the groups. Subgroup analysis indicated that ketamine was associated with lower 14-day mortality rates among younger patients, those with acute respiratory distress syndrome, and norepinephrine users. Ketamine administration was also found to correlate with increased lengths of stay in both the hospital and ICU. CONCLUSIONS: Ketamine was more frequently selected for patients requiring prolonged mechanical ventilation. The administration of ketamine was associated with reduced 14-day but not with 28-day or 90-day mortality rates.

BACKGROUND: The number of malignancy patients with respiratory failure is rising in pediatric intensive care units (PICU). Our study aims to compare the clinical characteristics and prognostic risk factors of acute respiratory distress syndrome (ARDS) with or without malignancies. METHODS: This retrospective study reviewed medical records of 188 ARDS patients admitted to the PICU between January 2018 and December 2022, including 60 with malignancies and 128 without. Clinical data were collected within 48 h post-ARDS diagnosis. Multivariate logistic regression analysis and receiver operating characteristic curve (ROC) analysis were used to investigate the risk factors for PICU mortality in the malignancy and non-malignancy groups. RESULTS: Compared with pediatric patients without malignancy, the ARDS patients with malignancy presented higher mortality (55.0% vs. 31.3%, P = 0.002), a higher incidence of community-acquired fungal infection (36.1% vs. 6.3%, P < 0.001) and multidrug resistance (MDR) bacteria (65.4% vs. 30.5%, P = 0.003). There were substantial differences in levels of lactate [1.5 (0.8-3.7) vs. 1.0 (0.7-2.0) mmol/L, P = 0.008], C-reactive protein (CRP) [150.0 (83.0-168.0) vs. 31.0 (10.0-108.0) mg/L, P = 0.02], procalcitonin (PCT) [10.4 (2.0-27.5) vs. 1.2 (0.3-6.2) mg/L, P < 0.001], counts of platelet [17.0 (8.0-73.0) vs. 232.0 (152.0-330.0) × 10 CONCLUSION: ARDS patients with malignancies exhibited poorer outcomes. VIS is only an independent predictor of mortality in pediatric ARDS patients with malignancies.