Browsing by Subject "ARDS"

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  • Bellingan, Geoff; Brealey, David; Mancebo, Jordi; Mercat, Alain; Patroniti, Nicolo; Pettilä, Ville; Quintel, Michael; Vincent, Jean-Louis; Maksimow, Mikael; Jalkanen, Markku; Piippo, Ilse; Ranieri, V. Marco (2017)
    Background: Acute respiratory distress syndrome (ARDS) results in vascular leakage, inflammation and respiratory failure. There are currently no approved pharmacological treatments for ARDS and standard of care involves treatment of the underlying cause, and supportive care. The vascular leakage may be related to reduced concentrations of local adenosine, which is involved in maintaining endothelial barrier function. Interferon (IFN) beta-1a up-regulates the cell surface ecto-5'-nucleotidase cluster of differentiation 73 (CD73), which increases adenosine levels, and IFN beta-1 may, therefore, be a potential treatment for ARDS. In a phase I/II, open-label study in 37 patients with acute lung injury (ALI)/ARDS, recombinant human IFN beta-1a was well tolerated and mortality rates were significantly lower in treated than in control patients. Methods/design: In this phase III, double-blind, randomized, parallel-group trial, the efficacy and safety of recombinant human IFN beta-1a (FP-1201-lyo) will be compared with placebo in adult patients with ARDS. Patients will be randomly assigned to receive 10 mu g FP-1201-lyo or placebo administered intravenously once daily for 6 days and will be monitored for 28 days or until discharged from the intensive care unit. Follow-up visits will then take place at days 90, 180 and 360. The primary endpoint is a composite endpoint including any cause of death at 28 days and days free of mechanical ventilation within 28 days among survivors. Secondary endpoints include: all-cause mortality at 28, 90, 180 and 360 days; organ failure-free days; length of hospital stay; pharmacodynamic assessment including measurement of myxovirus resistance protein A concentrations; and measures of quality of life, respiratory and neurological function at 180 and 360 days. The estimated sample size to demonstrate a reduction in the primary outcome between groups from 30% to 15% is 300 patients, and the study will be conducted in 70-80 centers in nine countries across Europe. Discussion: There are no effective specific treatments for patients with ARDS and mortality rates remain high. The results from this study will provide evidence regarding the efficacy of a potential new therapeutic agent, FP-1201-lyo, in improving the clinical course and outcome for patients with moderate/severe ARDS.
  • Linko, Rita Teresa; Hedger, Mark P.; Pettila, Ville; Ruokonen, Esko; Ala-Kokko, Tero; Ludlow, Helen; de Kretser, David M. (2014)
  • Biancari, Fausto; Mariscalco, Giovanni; Dalen, Magnus; Settembre, Nicla; Welp, Henryk; Perrotti, Andrea; Wiebe, Karsten; Leo, Enrico; Loforte, Antonio; Chocron, Sidney; Pacini, Davide; Juvonen, Tatu; Broman, L. Mikael; Di Perna, Dario; Yusuff, Hakeem; Harvey, Chris; Mongardon, Nicolas; Maureira, Juan P.; Levy, Bruno; Falk, Lars; Ruggieri, Vito G.; Zipfel, Svante; Folliguet, Thierry; Fiore, Antonio (2021)
    Objectives: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). Design: Multicenter retrospective, observational study. Setting: Ten tertiary referral university and community hospitals. Participants: Patients with confirmed severe COVID-19-related ARDS. Interventions: Venovenous or venoarterial ECMO. Measurements and Main Results: One hundred thirty-two patients (mean age 51.1 +/- 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 +/- 4.4, mean pH was 7.23 +/- 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 +/- 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 +/- 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. Conclusions: The present findings suggested that about half of adult patients with severe COVID-19 -related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. (C) 2021 The Authors. Published by Elsevier Inc.
  • Scaramuzzo, Gaetano; Broche, Ludovic; Pellegrini, Mariangela; Porra, Liisa; Derosa, Savino; Tannoia, Angela Principia; Marzullo, Andrea; Borges, Joao Batista; Bayat, Sam; Bravin, Alberto; Larsson, Anders; Perchiazzi, Gaetano (2019)
    Modern ventilatory strategies are based on the assumption that lung terminal airspaces act as isotropic balloons that progressively accommodate gas. Phase contrast synchrotron radiation computed tomography (PCSRCT) has recently challenged this concept, showing that in healthy lungs, deflation mechanisms are based on the sequential de-recruitment of airspaces. Using PCSRCT scans in an animal model of acute respiratory distress syndrome (ARDS), this study examined whether the numerosity (ASnum) and dimension (ASdim) of lung airspaces change during a deflation maneuver at decreasing levels of positive end-expiratory pressure (PEEP) at 12, 9, 6, 3, and 0 cmH(2)O. Deflation was associated with significant reduction of ASdim both in the whole lung section (passing from from 13.1 +/- 2.0 at PEEP 12 to 7.6 +/- 4.2 voxels at PEEP 0) and in single concentric regions of interest (ROIs). However, the regression between applied PEEP and ASnum was significant in the whole slice (ranging from 188 +/- 52 at PEEP 12 to 146.4 +/- 96.7 at PEEP 0) but not in the single ROIs. This mechanism of deflation in which reduction of ASdim is predominant, differs from the one observed in healthy conditions, suggesting that the peculiar alveolar micromechanics of ARDS might play a role in the deflation process.