Daily Ards Research Analysis

The benefits of non-invasive respiratory support strategies (NIRS), such as high-flow nasal oxygen therapy, in delaying intubation remain uncertain. We used an emulated target trial approach to evaluate outcomes associated with late intubation in patients with severe acute respiratory failure due to COVID-19. We conducted a retrospective multicentre cohort study using the French prospective OUTCOMEREA database. Adult patients admitted to intensive care units (ICUs) for severe SARS-CoV-2 pneumonia with an ICU length of stay of at least seven days were included in the study. Descriptive analyses were used to compare patients who were intubated after day 6 with those who remained under NIRS. In the emulated target trial, patients who were eligible between ICU days 7 and 12 were assigned to undergo late intubation or to remain under NIRS. Weighted Cox proportional hazards models were used. The primary outcome was 60-day mortality. Of the 1206 ICU patients with SARS-CoV-2 pneumonia, 288 were still in the ICU on day 7. Of these, 65 (22.6%) subsequently underwent late intubation and had a 60-day mortality rate of 78.5%. In the emulated target trial, which included 234 patients at risk of intubation, 57 underwent late intubation. Late intubation was associated with a higher risk of death (adjusted hazard ratio: 2.89; 95% confidence interval: 1.50-3.92). The estimated absolute difference in 60-day survival was - 0.34 (95% CI - 0.62 to 0.30). The restricted mean survival time was 17.8 days shorter in the late intubation group (95% CI - 30.6 to 10.8). In this multicentre cohort, patients requiring late intubation had a very high mortality rate. In the emulated target trial analysis, late intubation was associated with poorer survival compared to continued NIRS, suggesting a subgroup of patients with progressive respiratory failure rather than a direct effect of intubation timing.

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are severe respiratory diseases with a high mortality rate, characterized by pathological lung damage induced by excessive inflammation. Current therapeutic strategies for ALI are limited; conventional treatments are associated with severe side effects and lack targeted efficacy. Hesperetin(Hes)is a natural flavanone abundant in citrus fruits that exhibits promising anti-inflammatory potential, yet its further clinical application is hindered by poor solubility and low bioavailability. Small intracellular vesicles (sIVs) derived from mesenchymal stem cells have been demonstrated to possess the advantages of high yield, rapid cellular uptake and excellent stability. In view of this, the present study constructed a Hes-loaded sIVs-liposome nanodelivery system (sIVs-LPs@Hes) for the treatment of ALI via nebulized inhalation. Our findings revealed that sIVs-LPs@Hes could be efficiently absorbed and persistently retained in the lung, and it exerted a superior protective effect by inhibiting glycolysis through the MCU-mCa

BACKGROUND: Survivors of the early exudative phase of acute respiratory distress syndrome (ARDS) may develop a fibroproliferative repair response and persistent microstructural remodeling associated with adverse outcomes. Conventional imaging, including chest computed tomography (CT), has limited biological specificity for early microscopic remodeling. Confocal laser endomicroscopy (CLE) enables real-time bronchoscopic imaging of the alveolar compartment with near-histologic resolution. We evaluated the feasibility and safety of bedside bronchoscopic CLE in invasively ventilated ICU patients with acute respiratory failure and explored whether in vivo CLE provides microscopic alveolar information complementary to chest CT. METHODS: In this single-center observational pilot study, mechanically ventilated adult ICU patients with a clinical indication for bronchoalveolar lavage (BAL) underwent additional bedside bronchoscopic CLE. Primary endpoints were feasibility (≥ 1 interpretable alveolar video with visible septal architecture per procedure) and safety (CLE-related adverse events within 24 h). Secondary exploratory endpoints were dominant in vivo CLE patterns of alveolar filling (air, fluid, cells) and architecture (thin elastin fibers with hexagonal architecture; increased elastin with preserved architecture; increased elastin with distortion) and qualitative comparison with CT abnormalities in the imaged segments. As an exploratory additional analysis, ex vivo CLE was performed in a single autopsy case and compared with histopathology. RESULTS: A total of 33 patients were included (median age 64 years; 61% male); 31/33 met Berlin ARDS criteria. Forty-one CLE procedures were performed, all yielding high-resolution alveolar imaging (procedural feasibility 100%). A total of 150 videos were acquired (mean acquisition time 46 s per video), with a mean of three bronchial segments imaged per procedure. No CLE-related adverse events occurred. Patterns that were recognized by CLE were: alveolar filling with air (n = 94, 63%), fluid (n = 18, 12%), cells (n = 38, 25%); alveolar architecture was described as thin elastin fibers with hexagonal architecture (n = 37; 25%), increased elastin fibers with preserved architecture (n = 80; 53%) or distorted architecture (n = 29; 19%). Architecture was undeterminable in 4 (3%) videos. CLE detected abnormalities in 6/7 CT-normal appearing segments and demonstrated architectural changes in 60/78 segments with ground-glass opacities. In the autopsy case, ex vivo CLE was concordant with histopathology: regions with increased and distorted CLE signal corresponded to thickened alveolar septa and fibrotic remodeling. CONCLUSION: Bedside bronchoscopic CLE is feasible and safe in mechanically ventilated ICU patients with ARDS. CLE provides complementary microscopic information on alveolar filling and architecture beyond chest CT, including features compatible with early structural remodeling.