Daily Respiratory Research Analysis

OBJECTIVE: To determine whether high flow nasal cannula (HFNC) oxygenation can reduce the incidence of hypoxia during sedated gastrointestinal endoscopy in patients with obesity. DESIGN: Multicentre, randomised, parallel group trial. SETTING: Three tertiary hospitals in Shanghai, China. PARTICIPANTS: 1000 adult patients with obesity (body mass index ≥28) who were scheduled for gastrointestinal endoscopy. INTERVENTIONS: Participants were randomly allocated to receive regular nasal cannula oxygenation or HFNC oxygenation during a sedated procedure with propofol and low dose sufentanil. MAIN OUTCOME MEASURES: The primary outcome was the incidence of hypoxia (75%≤SpO RESULTS: From 6 May 2021 to 26 May 2023, 984 patients (mean age 49.2 years; 36.9% (n=363) female) completed the study and were analysed. Compared with regular nasal cannula oxygenation, HFNC oxygenation reduced the incidence of hypoxia from 21.2% (103/487) to 2.0% (10/497) (difference -19.14, 95% confidence interval -23.09 to -15.36; P<0.001), subclinical respiratory depression from 36.3% (177/487) to 5.6% (28/497) (difference -30.71, -35.40 to -25.92; P<0.001), and severe hypoxia from 4.1% (20/487) to 0% (0/497) (difference -4.11%, -6.26 to -2.48; P<0.001). Other sedation related adverse events did not differ between the two groups. CONCLUSIONS: In patients with obesity, oxygenation via HFNC during sedated gastrointestinal endoscopy significantly reduced the incidences of hypoxia, subclinical respiratory depression, and severe hypoxia without increasing other adverse events. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500392.

Innate immune responses triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play pivotal roles in the pathogenesis of COVID-19, while host factors including proinflammatory cytokines are critical for viral containment. By utilizing quantitative and qualitative models, we discovered that soluble factors secreted by human monocytes potently inhibit SARS-CoV-2-induced cell-cell fusion in viral-infected cells. Through cytokine screening, we identified that interleukin-1β (IL-1β), a key mediator of inflammation, inhibits syncytia formation mediated by various SARS-CoV-2 strains. Mechanistically, IL-1β activates RhoA/ROCK signaling through a non-canonical IL-1 receptor-dependent pathway, which drives the enrichment of actin bundles at the cell-cell junctions, thus prevents syncytia formation. Notably, in vivo infection experiments in mice confirmed that IL-1β significantly restricted SARS-CoV-2 spread in the lung epithelium. Together, by revealing the function and underlying mechanism of IL-1β on SARS-CoV-2-induced cell-cell fusion, our study highlights an unprecedented antiviral function for cytokines during viral infection. SARS-CoV-2, the agent responsible for COVID-19, has claimed millions of lives across the globe. To better manage this disease and develop new treatments, it is fundamental to understand how the immune system responds to this virus – and, in particular, how it can be thwarted. Like all viruses, SARS-CoV-2 replicates within host cells and bursts out when it has made more of itself and is ready to infect more tissues. It can also cause neighbouring cells to merge, allowing the virus to replicate and spread without stepping outside. This strategy makes it harder for the immune system to access and deactivate the threat. A group of molecules called proinflammatory cytokines (such as IL-1β and IL-1α) are released upon SARS-CoV-2 infection. People receiving immunosuppressive therapies, which can reduce proinflammatory cytokine levels to harness inflammatory damage, find it harder to tackle the virus. However, the full role of these molecules in clearing SARS-CoV-2 remains unknown. To investigate this question, Zheng, Yu, Zhou and Yu et al. developed different experimental models that could examine how proinflammatory cytokines might protect cells from SARS-CoV-2 challenge. The results showed that IL-1β and IL-1α stop the virus from being able to fuse cells together. Further cell studies revealed the underlying mechanism: IL-1β triggers cells to increase the levels of essential components, known as actin bundles, which form the structures that prevent cells from fusing with each other. Experiments in live mice showed that IL-1β treatment significantly prevented SARS-CoV-2 from spreading within the lining of the lungs. Taken together, these findings reveal new insights into how the immune system protects hosts against SARS-CoV-2 infection; further investigation may help identify new treatments for COVID-19.

OBJECTIVES: Managing severe pneumonia remains a challenge. Rapid diagnostic tests, such as multiplex polymerase chain reaction (mPCR), facilitate quick microorganism identification and may enable timely and appropriate antimicrobial therapy. However, studies from low-income countries are scarce. This study aimed to evaluate the diagnostic characteristics of mPCR and its impact on antibiotic therapy and outcomes in critically ill patients with pneumonia. DESIGN: Multicenter observational study. SETTING: Twelve ICUs across Morocco. PATIENTS: Adult patients with pneumonia requiring invasive mechanical ventilation, including community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Respiratory samples were analyzed using both mPCR and conventional microbiological methods. The diagnostic performance of mPCR was evaluated, including its sensitivity and specificity. Additionally, the appropriateness of mPCR-induced modifications in empiric antibiotic therapy and their impact on patient outcomes were assessed. A total of 210 patients were included, with a median age of 50 years (range, 33-67 yr), of whom 66.2% were male. Pneumonia types were distributed as 30% CAP, 58% VAP, and 12% HAP. mPCR demonstrated a sensitivity of 96.9% (95% CI, 92.3-99.2%) and a specificity of 92% (95% CI, 91-93%). Following mPCR, antibiotic therapy modifications were observed in 58% of patients (n = 122), including de-escalation or cessation in 11% (n = 23), escalation in 26.5% (n = 56), adequacy adjustments in 7.5% (n = 16), and initiation of antibiotics in 13% (n = 27). The appropriateness of antibiotic therapy increased significantly from 38.7% (n = 83) to 67% (n = 141; difference, 27.5%; 95% CI, 18.3-36.7; p < 0.0001). Generalized mixed model analysis revealed that appropriate post-mPCR antibiotic therapy was associated with reduced mortality (adjusted odds ratio, 0.37; 95% CI, 0.15-0.93; p = 0.038). CONCLUSIONS: Our findings suggest that the use of mPCR is associated with a significant improvement in the appropriateness of empiric antibiotic therapy and is also associated with a positive impact on the outcome of patients with pneumonia.