Purpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed... Show morePurpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (.EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. Results 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in.EVLWi between the groups (0.19 ml/kg, 95% CI - 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (- 1.17 ml/kg, 95% CI - 1.87 to - 0.44). Conclusions IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Show less
Different aspects of respiratory tract infection have been studied. Automatic syndromic surveillance for early detection of infections is feasible. Peak in ILI in hospitals is most flu seasons... Show moreDifferent aspects of respiratory tract infection have been studied. Automatic syndromic surveillance for early detection of infections is feasible. Peak in ILI in hospitals is most flu seasons before rise in cases in primary care. Influenza vaccination can safely be given to oncology patients who use checkpoint inhibitors. we were unable to demonstrate an attenuation of immune response in patients treated with non-lytic rifampicin for pneumococcal pneumonia. Cardiac surgery during influenza season is a risk factor for postoperative ARDS. Show less
Background Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality... Show moreBackground Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS. Methods The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO2/FiO(2). Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany. Discussion The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS. Show less
Aim: Biomarkers of acute respiratory distress syndrome (ARDS) after cardiac-surgery may help risk-stratification and management. Preoperative single-value proADM increases predictive capacity of... Show moreAim: Biomarkers of acute respiratory distress syndrome (ARDS) after cardiac-surgery may help risk-stratification and management. Preoperative single-value proADM increases predictive capacity of scoring-system EuroSCORE. To include the impact of surgery, we aim to assess the predictive value of the perioperative proADM-change on development of ARDS in 40 cardiac-surgery patients. Materials & methods: ProADM was measured in nine sequential blood samples. The Berlin definition of ARDS was used. For data-analyses, a multivariate model of EuroSCORE and perioperative proADM-change, linear mixed models and logistic regression were used. Results: Perioperative proADM-change was associated with ARDS after cardiac-surgery, and it was superior to EuroSCORE. A perioperative proADM-change >1.5 nmol/l could predict ARDS. Conclusion: Predicting post-surgery ARDS with perioperative proADM-change enables clinicians to intensify lung-protective interventions and individualized fluid therapy to minimize secondary injury. Show less
