Daily Ards Research Analysis

BACKGROUND: Prolonged prone positioning (PPP) for ≥ 24 h may enhance outcomes in moderate to severe acute respiratory distress syndrome (ARDS), but may also increase risks such as pressure injuries and complications. Despite clinical rationale, high-quality evidence for PPP's safety and efficacy remains scarce. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCT) and observational studies. Trials that compared two distinct treatment groups in adult patients with ARDS were included: prone position < 24 h (standard) and ≥ 24 h (prolonged). Databases searched included MEDLINE, CENTRAL, ClinicalTrials.gov, ISRCTN, ICTRP and the Cochrane Covid-19 Study Register (last search: 3 July 2025). Risk of bias was assessed using ROB-2 for RCTs, and the ROBINS-I V2 tool for non-randomised intervention studies (NRSI). The primary outcome was mortality. Secondary outcomes included improvement of oxygenation and adverse events. Outcomes (Risk ratios and hazard ratios) were calculated using a random-effect model with 95% confidence intervals (CI). The quality of evidence was evaluated using the GRADE assessment. RESULTS: Of 19,986 records, 9 (n = 1,045) were included in the qualitative and quantitative analysis. Four studies, including two small RCTs (n = 112) and two NRSIs (n = 581), had a low to moderate risk of bias. Most studies included patients with COVID-19 ARDS. Meta-analysis showed no significant effect on 90-day mortality (n = 641, HR 0.72; 95% CI 0.41-1.25). No heterogeneity was detected among studies (I² = 0%), but the confidence interval for I² was wide (95% CI: 0-89%), suggesting the possibility that substantial heterogeneity may exist. Similarly, no significant differences were found for secondary outcomes. DISCUSSION: Current evidence does not support the use of PPP outside of clinical studies. Pooled data from small trials and NRSIs reveal no significant effect of PPP on mortality, oxygenation, or safety outcomes. The evidence is of low to very low certainty, limited by inconsistency and imprecision. The wide confidence intervals indicate low statistical power, therefore both harm and benefit remain plausible on the basis of the available evidence. Well-powered RCTs are needed to clarify the potential benefits and risks of PPP in ARDS.

BACKGROUND: We aimed to assess the prognostic performance of different indexes of oxygenation, respiratory mechanics and ventilation intensity in predicting 90-day mortality, and to estimate their independent associations, in a "real world" observational cohort of acute respiratory distress syndrome (ARDS) patients on ICU mortality. METHODS: This is a secondary analysis of the "Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure" (LUNG SAFE), an international prospective cohort study of patients with severe respiratory failure involving 459 Intensive Care Units (ICUs) from 50 countries. We evaluated prognostic performance of oxygenation (PaO RESULTS: Among 2813 early ARDS patients, 516 (18.3%) met inclusion criteria: mean age 60 years (±16), 61% male. Normalized elastance, plateau, DP and 4DP+RR were significantly associated with mortality, with adjusted ORs ranging from 1.02 (95%CI 1.01-1.03) for 4DP+RR to 1.48 (95%CI 1.15-1.95) for normalized elastance. These parameters showed higher predictive accuracy for mortality compared to PaO CONCLUSIONS: Normalized elastance, DP and 4DP+RR-measured at day1 of ARDS-were best predictors of ICU mortality, and outperformed oxygenation and MP. DP showed the best balance between predictive accuracy and clinical simplicity. These results reinforce the importance of focusing on DP and 4DP+RR as key metrics to guide lung-protective strategies and ARDS severity classification.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions characterized by non-cardiogenic pulmonary edema, hypoxic respiratory failure, reduced functional residual capacity, decreased lung compliance, non-hydrostatic bilateral pulmonary infiltrates, and increased vascular permeability due to protein-rich exudates and neutrophil infiltration in the alveolar spaces. ALI/ARDS is associated with high mortality due to poor prognosis, lack of effective therapies, and prolonged hospitalization. Macrophages play a pivotal role in modulating the inflammatory response during ALI/ARDS, with M1 macrophages initiating severe inflammation and lung damage while M2 macrophages regulate tissue repair. Targeting macrophage polarization is a promising therapeutic approach for alleviating tissue damage and promoting resolution in ALI/ARDS. In response to this, we developed novel self-assembling carrier-free nanoparticles, bilirubin (BR) and melatonin (MT), with surface-adsorbed immunoglobulin G (IgG), referred to as IgG@BMNP. These nanoparticles are designed to target M1 macrophages in the lungs of ALI model mice. Under oxidative stress, IgG@BMNP disintegrate, releasing BR and MT, which scavenge excess reactive oxygen species (ROS) in the lungs and inhibit overactivation of the NLRP3 inflammasome, thereby promoting macrophage polarization from the M1 to the M2 phenotype. In ALI model mice, IgG@BMNP effectively alleviate lung injury, demonstrating potential as a therapeutic approach for ALI. This opsonization strategy, which involves M1 macrophages engulfing carrier-free IgG@BMNP to suppress inflammation, shows promising potential for the treatment and management of ALI/ARDS.