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Importance: Given the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative., Objectives: To determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies., Design, Settings, and Participants: The ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis-114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023., Interventions: Patients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days., Main Outcomes and Measures: A hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death)., Results: Among the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, -14.7 [95% CI -6.2 to -23.2] and -14.7 [95% CI -6.2 to -23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, -13.5; 95% CI -2.6 to -24.3)., Conclusions and Relevance: This randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis., Trial Registration: ClinicalTrials.gov Identifier: NCT04808882.

Rationale: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with pulmonary endothelial dysfunction. There are limited data available on the outcomes of coronavirus disease (COVID-19) in patients with pulmonary hypertension (PH), a disease characterized by pulmonary endothelial dysfunction. Objectives: To describe characteristics and outcomes of patients with precapillary PH and COVID-19. Methods: We prospectively collected characteristics, management, and outcomes of adult patients with precapillary PH in the French PH network who had COVID-19 between February 1, 2020, and April 30, 2021. Clinical, functional, and hemodynamic characteristics of PH before COVID-19 were collected from the French PH registry. Measurements and Main Results: A total of 211 patients with PH (including 123 with pulmonary arterial hypertension, 47 with chronic thromboembolic PH, and 41 with other types of PH) experienced COVID-19, and 40.3% of them were outpatients, 32.2% were hospitalized in a conventional ward, and 27.5% were in an ICU. Among hospitalized patients ( n  = 126), 54.0% received corticosteroids, 37.3% high-flow oxygen, and 11.1% invasive ventilation. Right ventricular and acute renal failure occurred in 30.2% and 19.8% of patients, respectively. Fifty-two patients (all hospitalized) died from COVID-19. Overall mortality was 24.6% (95% CI [confidence interval], 18.8-30.5) and in-hospital mortality 41.3% (95% CI, 32.7-49.9). Nonsurvivors were significantly older, more frequently male and suffering comorbidities (diabetes, chronic respiratory diseases, systemic hypertension, chronic cardiac diseases, and/or chronic renal failure), and had more severe PH at their most recent evaluation preceding COVID-19 diagnosis (in terms of functional class and 6-minute-walk distance; all P  < 0.05). Use of pulmonary arterial hypertension therapy was similar between survivors and nonsurvivors. Conclusions: COVID-19 in patients with precapillary PH was associated with a high in-hospital mortality. The typical risk factors for severe COVID-19 and severity of PH were associated with mortality in this population.

Background: Approval of biologics has recently revolutionized T2 severe asthma management. However, predictive biomarkers remain highly needed to improve patient's selection., Objective: This study aims to determine whether serum immunoglobulins (Igs) levels might be predictive biomarkers of response to anti-interleukin-5 (IL5)/IL5Rα therapies., Methods: Severe asthma patients eligible for mepolizumab or benralizumab were included herein. Serum immunoglobulin quantification was performed at baseline before mepolizumab or benralizumab initiation. After a 6-month treatment of mepolizumab or benralizumab, patients presented a second serum immunoglobulin quantification. The treatment response was evaluated by the GETE (Global Evaluation of Treatment Effectiveness) score at 6 months., Results: A total of 50 patients were included. Median age was 56 [IQR 48.8-65.3] and 50% were females. Compared to baseline, a significant increase in IgG was observed at 6 months (9.2 [7.8-10.2] g/l vs 10.1 [8.8-11.1] g/l, p = 0.04). The area under the ROC curve was 0.58 [95%IC 0.40-0.77] for blood eosinophil count (p = 0.37), 0.75 [95%IC: 0.58-0.92] for serum IgG concentration (p = 0.009) for predicting the treatment response. According to the Youden index, serum IgG concentration ≥ 9.2 g/l predicts the response to anti-IL5 therapies with a sensitivity of 76.9% and a specificity of 75.7%., Conclusion: Baseline serum IgG concentrations may be a useful tool to predict the response to anti-IL5/IL5Rα therapies but should be confirmed in larger clinical trials. Interestingly, anti-IL5/IL5Rα therapies are associated with a significant increase in serum IgG concentrations at 6 months., Competing Interests: Disclosure of interest LG has been an investigator in clinical trials for AstraZeneca, MSD and Novartis, reports grants or fees for consulting from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron, and fees for consulting from Bayer, Chiesi, MSD, not related to the submitted work DB has been an investigator in clinical trials for AstraZeneca, GSK, MSD and Novartis SL, ENS, GP, NG, LR declare no disclosure of interest AD has been an investigator in clinical trials for AstraZeneca, GSK and Novartis, reports grants or fees for consulting from AstraZeneca, GlaxoSmithKline, Novartis and Sanofi-Regeneron, and fees for consulting from Bayer, Chiesi, MSD, outside the submitted work, (Copyright © 2021. Published by Elsevier Masson SAS.)

Introduction: COVID-19 induces venous, arterial and microvascular thrombosis, involving several pathophysiological processes. In patients with severe COVID-19 without macrovascular thrombosis, escalating into high-dose prophylactic anticoagulation (HD-PA) or therapeutic anticoagulation (TA) could be beneficial in limiting the extension of microvascular thrombosis and forestalling the evolution of lung and multiorgan microcirculatory dysfunction. In the absence of data from randomised trials, clinical practice varies widely., Methods and Analysis: This is a French multicentre, parallel-group, open-label, randomised controlled superiority trial to compare the efficacy and safety of three anticoagulation strategies in patients with COVID-19. Patients with oxygen-treated COVID-19 showing no pulmonary artery thrombosis on computed tomography with pulmonary angiogram will be randomised to receive either low-dose PA, HD-PA or TA for 14 days. Patients attaining the extremes of weight and those with severe renal failure will not be included. We will recruit 353 patients. Patients will be randomised on a 1:1:1 basis, and stratified by centre, use of invasive mechanical ventilation, D-dimer levels and body mass index. The primary endpoint is a hierarchical criterion at day 28 including all-cause mortality, followed by the time to clinical improvement defined as the time from randomisation to an improvement of at least two points on the ordinal clinical scale. Secondary outcomes include thrombotic and major bleeding events at day 28, individual components of the primary endpoint, number of oxygen-free, ventilator-free and vasopressor-free days at day 28, D-dimer and sepsis-induced coagulopathy score at day 7, intensive care unit and hospital stay at day 28 and day 90, and all-cause death and quality of life at day 90., Ethics and Dissemination: The study has been approved by an ethical committee (Ethics Committee, Ile de France VII, Paris, France; reference 2020-A03531-38). Patients will be included after obtaining their signed informed consent. The results will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04808882., Competing Interests: Competing interests: AMD reports lectures for Leo Pharma. EA reports personal fees from GBT, personal fees from Hemanext, both unrelated to the present study. GV received research grant from Bio-Mérieux, SOS Oxygène, Janssen, all unrelated to the present study; and advisory board fees from BioMérieux that are unrelated to the present study. VL receives advisory board fees from Amomed, unrelated to the present study., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The authors report their findings regarding lung ultrasound profiles in a population of transplant recipients. Twenty-two patients were studied once each in multiple different ultrasound windows focusing on pleural, lung, and diaphragmatic signatures. All studies were performed in presumably otherwise healthy recipients at an outpatient follow-up visit at least 3 months after transplantation. Those with recent pulmonary infections or decline in lung function were excluded from enrollment. The majority of scans revealed otherwise normal lungs with lung sliding, but there were more abnormalities than one would expect in a healthy control group. Lung ultrasonography will likely never replace other cross-sectional imaging given its inherent visual limitations but adds another modality to interrogate the lung/pleural interface and diaphragmatic function., (© 2018 by the American Institute of Ultrasound in Medicine.)

Background: Cardiac output (CO) is a prognostic factor in pulmonary hypertension (PH). Right heart catheterisation using the direct Fick method or thermodilution (TD) is the reference technique for CO measurement. Impedance cardiography (IPc) is a known non-invasive method of measuring CO., Objectives: In our study, we assume that the measurement of CO by IPc using the PHYSIOFLOW® system is as accurate as TD or using the direct Fick method in patients with PH in group 1 or group 4., Methods: A total of 75 patients were enrolled in a prospective study carried out at the hypertension reference centre of Toulouse University Hospital. Right heart catheterisation was performed for the diagnosis or follow-up of the disease. CO was measured using the Fick method, TD, and IPc simultaneously. A Bland-Altman analysis was plotted., Results: CO was 5.7 ± 1.9 L/min as measured by the Fick method, 5.4 ± 1.5 L/min by TD, and 5.5 ± 1.7 L/min by IPc. The bias between CO measurements by IPc and the direct Fick method was 0.149 L/min (95% CI, -0.298 to 0.596). The bias between CO measurements by IPc and the TD method was -0.153 L/min (95% CI, -0.450 to 0.153). The correlation decreased with the more extreme CO values (< 3 L/min or > 7 L/min). A few factors changed the agreement between measurements (BMI or membership in group 4)., Conclusion: To conclude, this study shows that the measurement of CO by IPc in PH patients is reliable compared to the direct Fick method and TD obtained by right heart catheterisation. This accuracy decreases for extreme CO values., (© 2018 S. Karger AG, Basel.)

Introduction: After 6months, little is known about the optimal anticoagulant strategy for an acute episode of VTE in cancer patients., Aims, Objectives and Methods: The objective was to determine the risk of recurrent VTE and anticoagulant-related bleeding at 6months of follow-up and after 6months, in cancer patients who received tinzaparin during at least 3months for an acute episode of VTE. We conducted a multicenter retrospective cohort study from January 2004 to March 2011., Results: Two hundred fifty patients were included. Stopping anticoagulation before 6months in patients considered at low risk by physicians (i.e.; patients who had prior cancer surgery) and for another reason than bleeding or death was the only factor associated with a significant increased risk of recurrent VTE (OR 7.2 95%CI, 2.0-25.7; p=0.002). The type of anticoagulation did not influence the risk of recurrent VTE. We found a trend towards an increased risk of recurrent VTE when anticoagulation was stopped because of major bleeding while on anticoagulant therapy and patients with metastatic cancer (OR 2.3, 95%CI, 0.9-5.4; p=0.07; and OR 1.8 95%CI, 1.0-3.3; p=0.07; respectively). No factors were found to increase the risk of major bleeding at 6months and after. The overall mortality was 42.8%., Conclusions: The risk of recurrent VTE was mainly related to early discontinuation of anticoagulation in patients considered at low risk of recurrence (after surgery). When the anticoagulation was stopped before the sixth month, the risk was eight fold higher. After 6month, the risks of recurrent VTE, major bleeding and death were similar in patients with either VKA or tinzaparin when patients were treated according to the guidelines., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study evaluated the impact of body mass index (BMI) on venous thromboembolism (VTE) site and assessed a possible interaction between BMI and prothrombotic risk factors in patients included in the EDITH (Etude des Déterminants et Interactions de le THrombose veineuse) study. A cross-sectional study was used to compare the site of unprovoked VTE according to BMI categories in 1077 patients and a matched case-control study (732 pairs) assessed the joint effect of BMI and prothrombotic mutations on VTE risk. The cross sectional analysis showed that the proportion of patients with pulmonary embolism was higher in overweight (63%) and obese (63·5%) patients than among patients with a BMI<25kg/m(2) (55%), P=0·02 and P=0·05 respectively. No interaction was found between F5 G1691A (factor V Leiden) and BMI for VTE risk (P=0·90). There was a significant interaction between F2 G20210A and BMI (P=0·02). The risk of VTE associated with BMI was 1·7 [95% confidence interval (CI): 0·8-3·7], 4·36 (95%CI: 1·49-12·78) and 12·03 (95%CI: 1·53-94·29) in patients with BMI<25kg/m(2) , 25≤BMI<30 and ≥30kg/m(2) respectively after adjustment for age and oestrogen use. This study showed that BMI may play a role in determining the site of VTE and may interact with F2 G20210A but not with F5 G1691A for the risk of VTE., (© 2011 Blackwell Publishing Ltd.)