The funder had no role in the design and conduct of the study, collection, management, analysis,

Rational To evaluate the respective impact of standard oxygen, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) on oxygenation failure rate and mortality in COVID-19 patients admitted to intensive care units (ICUs). Methods Multicenter, prospective cohort study (COVID-ICU) in 137 hospitals in France, Belgium, and Switzerland. Demographic, clinical, respiratory support, oxygenation failure, and survival data were collected. Oxygenation failure was defined as either intubation or death in the ICU without intubation. Variables independently associated with oxygenation failure and Day-90 mortality were assessed using multivariate logistic regression. Results From February 25 to May 4, 2020, 4754 patients were admitted in ICU. Of these, 1491 patients were not intubated on the day of ICU admission and received standard oxygen therapy (51%), HFNC (38%), or NIV (11%) (P < 0.001). Oxygenation failure occurred in 739 (50%) patients (678 intubation and 61 death). For standard oxygen, HFNC, and NIV, oxygenation failure rate was 49%, 48%, and 60% (P < 0.001). By multivariate analysis, HFNC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.36–0.99, P = 0.013) but not NIV (OR 1.57, 95% CI 0.78–3.21) was associated with a reduction in oxygenation failure). Overall 90-day mortality was 21%. By multivariable analysis, HFNC was not associated with a change in mortality (OR 0.90, 95% CI 0.61–1.33), while NIV was associated with increased mortality (OR 2.75, 95% CI 1.79–4.21, P < 0.001). Conclusion In patients with COVID-19, HFNC was associated with a reduction in oxygenation failure without improvement in 90-day mortality, whereas NIV was associated with a higher mortality in these patients. Randomized controlled trials are needed.

Background Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. Patients and methods We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Results Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05–1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. Conclusion COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.

Background: Although patients with MPN may achieve complete hematological remission (CHR) with cytoreductive therapy (CRT), lifelong treatment represents a major burden for these chronically ill patients. IFN has emerged as a major MPN therapy thought to positively alter the natural history of MPN and appears to be the only drug that can provide long-term CHR after discontinuation in some patients (Hasselbalch HC et al., Seminars in Immunopathology, 2019). In this study, we aimed to identify clinical and molecular factors associated with long-term CHR after IFN treatment discontinuation and to compare clinical outcome of patients who discontinued therapy, to patients who continued IFN treatment despite achieving a CHR. Methods: All MPN patients followed between January 2000 and May 2020 in our institution who received at least 3 months of IFN were included. Logistic regression analysis was performed to identify variables associated with long-term CHR after discontinuation. Cumulative incidence of relapse was calculated from time of IFN discontinuation, considering death without relapse as a competitive event. Overall survival (OS) and thrombotic/hemorrhagic events free survival (EFS) curves were estimated using the Kaplan-Meier method and compared by cause-specific hazard Cox models. Results: 381 patients treated with IFN were included in the study. Median age at MPN diagnosis was 44 years [interquartile range: 33-54]. 171 had polycythemia vera (PV), 169 essential thrombocythemia (ET) and 34 primary myelofibrosis (PMF). JAK2V617F was the most frequent driver mutation (78.8% of patients), while CALR and MPL were mutated in 15.5%, and 2.9% of patients respectively. Median driver variant allele frequency (VAF) at time of IFN therapy initiation was 34% [12; 51]. Reasons to start IFN included age younger than 50 years in 44.9%, intolerance/resistance to previous therapies in 17.8% or pregnancy in 1.8% patients. CHR was achieved with IFN in 77.2% of patients. After a median follow-up of 72.4 months [28.4; 119.7] from IFN initiation, 131 patients were still on IFN treatment, while 250 patients had discontinued therapy. No significant difference was observed between continued and discontinued IFN patients in terms of MPN subtype, initial clinical, biological or molecular characteristics. Reasons for discontinuation were toxicity in 128 (50.4%), prolonged hematological CHR in 76 (29.9%), failure in 16 (6.3%) and other in 30 (11.8%) patients. At time of IFN discontinuation, 170 (66.9%) patients were in CHR and the median driver mutation VAF was 12% [3; 35]. Of note, IFN was re-introduced in 61 patients who lost CHR with a second CHR rate of 83.6%, arguing for the absence of development of IFN resistance in post-discontinuation relapses. In multivariate logistic regression analysis, stopping for prolonged CHR (OR 3.52, 95%CI [1.18; 10.56], p=0.024) was associated with a higher CHR without CRT rate, while VAF ≥ 10% at time of IFN discontinuation (OR 0.26, 95%CI [0.1; 0.65], p=0.004) was associated with lower long-term CHR without CRT. Accordingly, VAF ≥ 10% at time of IFN discontinuation (HR 3.06 [1.59; 5.90], p=0.001) was independently associated with a higher cumulative incidence of relapse after IFN discontinuation (Figure A). Driver VAF at IFN discontinuation time was available for 117 patients. 53 patients (45.3%) had a driver VAF &lt; 10% at IFN discontinuation. Finally, we compared discontinued IFN patients who stopped IFN for CHR (n=76) to patients who obtained CHR and are still on IFN therapy (n=116). Hematological transformation could not be evaluated due to very low incidence of events: 2 patients from each group progressed to myelofibrosis while leukemic progression was only observed in 1 patient. Importantly, OS (HR 0.23, 95%CI [0.5; 1.14], p=0.07) and EFS (HR 0.53, 95%CI [0.19; 1.45], p=0.217) were not significantly different between patients who discontinued and those who continued IFN. Conclusion: Overall, our study demonstrates that IFN discontinuation represents a safe strategy in MPN patients who achieved CHR, and particularly in patients with a driver VAF lower than 10% at time of discontinuation. Importantly, relapsed patients did not develop IFN resistance. Our data contributes to set the frame for future clinical trials evaluating the possibility of IFN treatment holidays in good responding MPN patients. Disclosures Benajiba: Gilead Foundation: Research Funding. Kiladjian:Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees.