Daily Ards Research Analysis

RATIONALE: The Early versus Delayed Enteral Nutrition (EDEN) trial found no significant difference in mortality between trophic and full enteral nutrition strategies in acute respiratory distress syndrome (ARDS) patients. Heterogeneity of treatment effect (HTE) has been identified in prior ARDS trials. We previously identified intestine-derived incretin hormones (glucose-dependent insulinotropic peptide [GIP] and glucagon-like peptide [GLP]-1 as potential predictive biomarkers in the response to nutrition. OBJECTIVES: To investigate incretins as biomarkers predictive of HTE in EDEN. METHODS: GIP, GLP-1, and host immune response biomarkers were measured from pre-intervention EDEN plasma samples. We investigated HTE with 60-day mortality as a primary outcome by testing interaction of treatment with circulating incretin levels in analyses adjusted for demographics, severity of illness, diabetes mellitus, and circulating interleukin-6, and assessed mortality by treatment arm across incretin tertiles. We additionally tested for HTE by de novo ARDS subphenotypes and by risk of mortality. MEASUREMENTS & MAIN RESULTS: 889 participants were included (452 randomized to trophic and 437 to full enteral nutrition). GIP predicted HTE to enteral nutrition strategies (adjusted interaction p-value 0.01) with lower mortality from trophic feeds (14.1% vs 27.2% in full) in patients in the highest GIP tertile but similar mortality in other tertiles. GLP-1, ARDS subphenotypes, and baseline risk of mortality did not predict HTE. CONCLUSIONS: GIP was unique among incretins in predicting HTE to enteral nutrition strategies in EDEN. Further studies are needed to validate our findings as GIP might serve as a biomarker to guide level of enteral nutrition for ARDS patients.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a critical life-support intervention for patients with severe respiratory and circulatory failure. Nevertheless, identifying the optimal timing of ECMO initiation and its correlation with survival, mortality, and complication rates continues to pose significant clinical challenges. PURPOSE: This study intends to conduct a systematic review of the existing medical literature to clarify ECMO initiation timing and its association with patient outcomes, aiming to furnish evidence-based recommendations for clinical decision-making. METHODS: We performed systematic searches across PubMed, Embase, Scopus, The Cochrane Library, and Web of Science for eligible cohort and case-control studies. Studies combining ECMO with other extracorporeal life-support modalities were excluded to eliminate survival confounding. Inclusion criteria encompassed adult ECMO recipients with reported initiation timing and at least one outcome measure. Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). RESULTS: From 1583 identified records, 30 studies were finally included, comprising 2 prospective cohorts, 1 case-control, and 27 retrospective cohorts. ECMO initiation timing was heterogeneously defined across multiple time intervals and clinical scenarios. Of the full set of 30 included studies, 23 performed statistical analyses examining the link between ECMO initiation delay and mortality; 18 of these 23 studies (60% of all 30 included studies) reported that prolonged ECMO initiation time was significantly associated with higher in-hospital or long-term mortality. Five of the 23 mortality-analyzing studies detected no statistically significant timing-mortality correlation, while the remaining 7 studies only reported organ complication outcomes and did not conduct any statistical testing of mortality as an endpoint. Quality appraisal demonstrated only one low-quality study, with all others graded as medium to high quality. CONCLUSION: For patients with severe ARDS, cardiogenic shock, drug-induced shock, cardiac arrest, or post-cardiotomy shock, early ECMO initiation-such as within 7 days of mechanical ventilation-can effectively decrease mortality and reduce the incidence of neurological, hepatic, and renal complications. TRIAL REGISTRATION: This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD420250652365).

SARS-CoV-2 has caused a global pandemic, resulting in over two million deaths and creating an urgent need for effective treatments. Severe COVID-19 is frequently complicated by respiratory failure and acute respiratory distress syndrome (ARDS), the primary drivers of mortality. Indole-3-Carbinol (I3C), a natural compound derived from Brassicaceae that acts as an inhibitor of HECT family E3 ubiquitin ligases, exhibits potent anti-SARS-CoV-2 activity and inhibits viral egress. However, its in vivo therapeutic efficacy against SARS-CoV-2-induced lung injury remains unproven. We evaluated the therapeutic efficacy of I3C in reducing the severity of SARS-CoV-2 infection and associated lung lesions using the Syrian golden hamster (Mesocricetus auratus) model, which recapitulates the acute lung injury observed in human COVID-19. Treatment with a non-toxic dose of I3C (2 mg) significantly ameliorated disease across all parameters, reducing weight loss, improving clinical symptom scores and reducing histopathological lung damage observed post-mortem. A significant reduction in pulmonary TNF-α levels accompanied this. These findings indicate that I3C mitigates COVID-19-related morbidity at clinically relevant, non-toxic doses. Given its dual antiviral and anti-inflammatory mechanisms, I3C represents a compelling therapeutic candidate for further clinical investigation.