Daily Ards Research Analysis

BACKGROUND: Sugammadex, a novel cyclodextrin reversal agent, reduces the incidence of residual neuromuscular block compared with neostigmine and was associated with fewer postoperative pulmonary complications in a systematic review of small randomised trials. However, evidence from a large RCT is required. METHODS: We designed an international, multicentre RCT (the SNaPP study). A total of 3500 patients, aged ≥40 yr and undergoing abdominal or thoracic surgery, will be enrolled and randomly allocated in a 1:1 ratio to receive sugammadex or neostigmine for reversal of neuromuscular block, stratified by centre. The primary outcome is a composite of postoperative pulmonary complications (atelectasis, pneumonia, acute respiratory distress syndrome, aspiration pneumonitis, or a combination of these) or death until hospital discharge (or postoperative day 7 if still in hospital). Secondary outcomes are components of the primary outcome, postoperative nausea and vomiting, unplanned ICU/high-dependency unit admission, days alive and at home at 30 days, and health-related quality of life at 3 months. The trial aims to determine whether sugammadex compared with neostigmine reduces the incidence of postoperative pulmonary complications or death. Data will be analysed on an intention-to-treat basis. ETHICS AND DISSEMINATION: The SNaPP study is approved by the ethics committees at participating sites in Australia, Aotearoa New Zealand, and Hong Kong and is endorsed by the Australian and New Zealand College of Anaesthetists Clinical Trials Network. Participant recruitment began on 20 July 2023 and was completed on 3 July 2025. Publication of the SNaPP study results is anticipated in 2026. CLINICAL TRIAL REGISTRATION: ACTRN 12623000394640.

Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates, and macrophage polarization is critical for its pathogenesis. Exosomes are crucial inflammation mediators; however, their role and mechanism in LPS-induced ARDS remain unclear. We investigated whether airway epithelial cell-derived exosomes on lipopolysaccharide (LPS)-induced ARDS model regulate macrophage polarization via the GATA1 pathway. Exosomes isolated from PBS- or LPS-treated airway epithelial cells (BEAS-2B) were injected into C57BL/6 wild-type mice intratracheally; macrophage polarization, cytokine secretion, and cell apoptosis were examined. In an in vitro co-culture system, human macrophage precursor (THP-1) was co-cultured with these exosomes to further confirm the results of the in vivo animal study. Bioinformatic analysis and miRNA mimic/inhibitor were used to explore the potential mechanisms involved. LPS-induced exosomes promoted M1 macrophage polarization, cytokine secretion, and cell apoptosis in vivo and in vitro co-culture models. Bioinformatic analysis indicated that miR-301a-3p-mediated LPS-exosomes (LPS-Exo) functioned via targeting the GATA1 downstream pathway in macrophages. Administering miR-301a-3p mimic significantly aggravated LPS-Exo-induced M1 macrophage polarization, cytokine secretion, and cell apoptosis, which were partially reversed by the miR-301a-3p inhibitor. The miR-301a-3p mediated LPS-Exo function via upregulating the GATA1/NF‑κB and downregulating GATA1/Akt pathways in macrophages. Exosomal miR-301a-3p derived from airway epithelial cells aggravates ARDS development via promoting M1 macrophage polarization, inflammatory response, and lung injury via regulating the GATA1 pathway.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome with high morbidity and mortality. Despite advances in understanding its pathophysiology, definitive biomarkers for ARDS disease stratification and management remain lacking. This study evaluated the utility of circulating PRDX1 in predicting 28-day mortality in ARDS patients. METHODS: A retrospective cohort study was conducted at Third Xiangya Hospital, enrolling 90 ARDS patients. Serum PRDX1 levels and clinical data were collected and compared with those from healthy volunteers and non-ARDS pneumonia patients to examine its alterations in ARDS patients; multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were then employed to assess the prognostic value of circulating PRDX1 for 28-day mortality. An independent validation cohort of 20 ARDS patients was recruited from Xiangya Hospital intensive care units. Additionally, serum Prdx1 dynamics were assessed in LPS-induced acute lung injury (ALI) and sepsis-associated ALI murine models. RESULTS: Serum PRDX1 levels were significantly elevated in a cohort of 90 ARDS patients, particularly among those with multiorgan injury. Multivariate analysis identified PRDX1 and age as independent risk factors for 28-day mortality. ROC curves revealed PRDX1's prognostic utility (area under the curve, AUC=0.776, p<0.0001), which was comparable to the APACHE II score (AUC=0.778, p<0.0001). These findings were validated in the 20-patient cohort. Animal experiments confirmed that serum PRDX1 positively correlated with lung injury severity and exhibited earlier elevation and higher abundance in multiorgan injury contexts. CONCLUSIONS: Serum PRDX1 was significantly elevated in ARDS patients, particularly in those with multiorgan injury, and demonstrated potential as a prognostic biomarker, showing correlation with 28-day mortality. Its integration into the ARDS management framework holds significant potential for improving clinical outcomes.