Daily Ards Research Analysis

BACKGROUND: Postoperative patients have been underrepresented in randomized controlled trials of acute respiratory distress syndrome (ARDS). Whether postoperative ARDS differs from medical ARDS in its clinical trajectory, outcomes, and prognostic determinants remains unclear. We aimed to compare postoperative and medical ARDS with respect to early trajectory, mortality, and risk factors for mortality. METHODS: We conducted a retrospective analysis of prospectively collected data in a tertiary ICU from 2003 to 2023. All consecutive intubated adults fulfilling the ARDS New Global Definition were included. ARDS cases were labeled as postoperative when onset occurred within 15 days after surgery. The primary outcome was 90-day mortality, assessed with multivariable Cox analysis. Early ARDS trajectories were assessed at day 3. Multivariable Cox analyses were used to identify factors independently associated with mortality. RESULTS: Among 1,077 intubated ARDS patients, 455(42%) had postoperative ARDS. Compared with medical ARDS, postoperative ARDS showed more favorable early trajectories (p = 0.03) and lower 90-day mortality (36% vs. 49%, p < 0.001). Postoperative ARDS remained independently associated with lower 90-day mortality after adjustment (adjusted hazard ratio[aHR] = 0.68, 95%CI:0.56-0.83, p < 0.001). Prognostic determinants differed markedly. In postoperative ARDS, mortality was independently associated with extrapulmonary organ dysfunction (non-respiratory SOFA score: aHR = 1.10, 95%CI:1.05-1.15; bicarbonate: aHR = 0.81 per 5mmol/L, 95%CI:0.69-0.96) and surgical context, (esophageal surgery: aHR = 0.41, 95%CI:0.24-0.70; upper abdominal surgery: aHR = 0.64, 95%CI:0.46-0.91 versus lower abdominal surgery), while no marker of respiratory failure was independently associated with mortality. In medical ARDS, mortality was independently associated with respiratory failure, including PaO CONCLUSION: Postoperative ARDS differs from medical ARDS in its early clinical trajectory, outcomes, and prognostic determinants. These findings support postoperative ARDS as a distinct clinical subtype, mainly driven by extrapulmonary and surgery-related factors rather than by the lung injury itself, supporting a management approach focused on perioperative prevention and early identification of surgery-related complications.

Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung injury. Regulatory T-cells (Tregs) and their extracellular vesicles (Treg-EVs) possess immunomodulatory properties that may be therapeutic in ARDS. However, evidence is scattered across individual studies, hindering the assessment of their safety and efficacy. To address this gap, we applied a systematic review (SR) methodology, a common approach in clinical research that has increasingly been recognized for its value in preclinical evidence synthesis. Specifically, we synthesized studies of Tregs/Treg-EVs in animal models of acute lung injury (ALI) or patients with ARDS. Importantly, we provide explanatory text throughout for readers less familiar with SRs. The primary preclinical and clinical outcomes were histological lung injury and mortality, respectively. Study selection and data extraction were performed in duplicate. Twenty-two preclinical and two clinical studies met the inclusion criteria, all using whole-cell Tregs. Meta-analysis of animal studies demonstrated that, compared to controls, Treg treatment significantly reduced histological lung injury (≤7 days: standardized mean difference (SMD) = -2.06 [95% confidence interval (CI): -2.96, -1.15]; >7 days: SMD = -2.18 [95% CI: -3.28, -1.08]). Tregs also reduced bronchoalveolar lavage fluid pro-inflammatory cytokines, total protein, total cells, and neutrophil counts. Clinically, early-phase study designs precluded meta-analysis; however, safety and tolerability of Tregs for ARDS were supported. Identified mechanisms underlying Treg effects included immunomodulation, cytokine regulation, and epigenetic pathways. Our review demonstrates the utility of formal preclinical evidence synthesis and supports the therapeutic potential of Tregs. Further investigations are justified to refine Tregs as a cellular therapy for ARDS.

BACKGROUND: During the COVID-19 pandemic, Mesenchymal Stromal Cells (MSCs) were rapidly proposed as a therapeutic option for Acute Respiratory Distress Syndrome (ARDS) based on their immunomodulatory properties. We report the results of COVIDMES, a multicenter trial initiated within a public blood and tissue bank infrastructure during unprecedented period of volatility and scientific uncertainty of the first pandemic waves. AIMS: To evaluate the safety, feasibility and exploratory efficacy of Wharton's Jelly-derived MSCs (WJ-MSCs) in hospitalized patients with moderate-to-severe COVID-19 associated ARDS. METHODS: This was a multicenter, prospective, double-blind, randomized, placebo-controlled Phase I/II pilot trial. The primary endpoint was all-cause 28-day mortality. Secondary endpoints included duration of mechanical ventilation, length of intensive care unit (ICU) stay, and longitudinal inflammatory biomarker kinetics. RESULTS: Twenty-six patients were enrolled between July 15th, 2020, and June 30th, 2021, of whom 25 received two intravenous doses of either 1 × 10 CONCLUSIONS: In this exploratory pilot study, WJ-MSCs demonstrated a favorable safety profile and evidence of biochemical immunomodulation but no clinical efficacy in moderate-to-severe COVID-19 associated ARDS. These findings highlight the challenges of evaluating advanced therapy medicinal products within a rapidly evolving standard of care and support the need for biomarker-guided patient stratification and optimized dosing strategies in future MSC trials. The successful execution of this trial also validates the resilience of academic "donor-to-patient" networks in global health emergencies.