Background Coronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function.Methods The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death.The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). FindingsFrom March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0•22 [95% CI 0•11-0•41; p<0•0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0•22 [95% CI 0•10-0•49]; p=0•0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group.Interpretation Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require con trolled trials.

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Introduction Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Previous studies reported pulmonary embolism (PE) in severe COVID-19 patients. Aim of the study was to estimate the prevalence of symptomatic PE in COVID-19 patients and to identify the clinical, radiological or biological characteristics associated with PE. Patients/methods We conducted a retrospective nested case-control study in 2 French hospitals. Controls were matched in a 1:2 ratio on the basis of age, sex and center. PE patients with COVID-19 were compared to patients in whom PE was ruled out (CTPA controls) and in whom PE has not been investigated (CT controls). Results PE was suspected in 269 patients among 1042 COVID-19 patients, and confirmed in 59 patients (5.6%). Half of PE was diagnosed at COVID-19 diagnosis. PE patients did not differ from CT and CTPA controls for thrombosis risk factors. PE patients more often required invasive ventilation compared to CTPA controls (odds ratio (OR) 2.79; 95% confidence interval (CI) 1.33–5.84) and to CT controls (OR 8.07; 95% CI 2.70–23.82). PE patients exhibited more extensive parenchymal lesions (>50%) than CT controls (OR 3.90; 95% CI 1.54–9.94). D-dimer levels were 5.1 (95% CI 1.90–13.76) times higher in PE patients than CTPA controls. Conclusions Our results suggest a PE prevalence in COVID-19 patients close to 5% in the whole population and to 20% of the clinically suspected population. PE seems to be associated with more extensive lung damage and to require more frequently invasive ventilation.

PurposeThis study aimed to evaluate the accuracy and diagnostic test performance of the U-net-based segmentation method in neuromelanin magnetic resonance imaging (NM-MRI) compared to the established manual segmentation method for Parkinson’s disease (PD) diagnosis.MethodsNM-MRI datasets from two different 3T-scanners were used: a “principal dataset” with 122 participants and an “external validation dataset” with 24 participants, including 62 and 12 PD patients, respectively. Two radiologists performed SNpc manual segmentation. Inter-reader precision was determined using Dice coefficients. The U-net was trained with manual segmentation as ground truth and Dice coefficients used to measure accuracy. Training and validation steps were performed on the principal dataset using a 4-fold cross-validation method. We tested the U-net on the external validation dataset. SNpc hyperintense areas were estimated from U-net and manual segmentation masks, replicating a previously validated thresholding method, and their diagnostic test performances for PD determined.ResultsFor SNpc segmentation, U-net accuracy was comparable to inter-reader precision in the principal dataset (Dice coefficient: U-net, 0.83 ± 0.04; inter-reader, 0.83 ± 0.04), but lower in external validation dataset (Dice coefficient: U-net, 079 ± 0.04; inter-reader, 0.85 ± 0.03). Diagnostic test performances for PD were comparable between U-net and manual segmentation methods in both principal (area under the receiver operating characteristic curve: U-net, 0.950; manual, 0.948) and external (U-net, 0.944; manual, 0.931) datasets.ConclusionU-net segmentation provided relatively high accuracy in the evaluation of the SNpc in NM-MRI and yielded diagnostic performance comparable to that of the established manual method.Electronic supplementary materialThe online version of this article (10.1007/s00234-019-02279-w) contains supplementary material, which is available to authorized users.

Evaluation of myelin by magnetic resonance imaging (MRI) is a difficult challenge, but holds promise in demyelinating diseases, such as multiple sclerosis (MS). Although multiple techniques have been developed, no gold standard has been established. This study aims to evaluate the correlation between synthetic MRI myelin volume fraction (SyMRIMVF) and myelin fraction estimated by other techniques, i.e., magnetization transfer saturation (MTsat), T1-weighted images divided by T2-weighted images (T1w/T2w), and radial diffusivity (RD) in patients with MS. We also compared the sensitivities of these techniques for detecting MS-related myelin damage. SyMRIMVF, MTsat, T1w/T2w, and RD were averaged on plaque, periplaque white matter, and normal-appearing white matter (NAWM). Pairwise correlation was calculated using Spearman’s correlation analysis. For all segmented regions, strong correlations were found between SyMRIMVF and T1w/T2w (Rho = 0.89), MTsat (Rho = 0.82), or RD (Rho = −0.75). For each technique, the average estimated myelin differed significantly among regions, but the percentage change of NAWM from both periplaque white matter and plaque were highest in SyMRIMVF. SyMRIMVF might be suitable for myelin evaluation in MS patients, with relevant results as compared to other well-studied techniques. Moreover, it presented better sensitivity for the detection of the difference between plaque or periplaque white matter and NAWM.

Points• Early in the pandemic, numbers of patients undergoing non-COVID-19 emergent CTs dropped sharply but diagnostic yield did not increase, suggesting potentially undiagnosed emergencies in patients not seen in healthcare institutions.

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Objective:To determine whether the association between increasing number of clot retrieval attempts (CRA) and unfavorable outcome is due to an increase in emboli to new territory (ENT) and greater infarct growth (IG) in successfully recanalized patients with acute ischemic stroke due to large vessel occlusion (AIS LVO).Methods:Data were extracted from two pooled multicentric prospective registries of consecutive anterior AIS-LVO patients treated with mechanical thrombectomy (MT) between January 2016-2019. Patients with pretreatment and 24 hours post-treatment diffusion-weighted imaging (DWI) achieving successful recanalization, defined as expanded Thrombolysis in Cerebral Infarction Scale (eTICI) scores 2b, 2C or 3 were included. ENT were assessed and IG measured by voxel-based segmentation after DWI co-registration. Associations between number of CRA, ENT, IG and 3-month outcome were analyzed.Results:Four hundred nineteen patients achieving successful recanalization were included. ENT occurrence was strongly correlated with increasing CRA (ρ=0.73, p=10-4). In multivariable linear analysis, IG was independently associated with CRA (β=1.6 per retrieval attempt, 95% CI = [0.97–9.74], p=0.03) and ENT (β=2.7, [1.21-4.1], p=0.03). Unfavorable functional outcome (3-month modified Rankin Score >2) increased with each additional CRA. IG was an independent predictor of unfavorable outcome (OR=1.05 [1.02-1.07] per 1 mL IG increase, p=10-4) in binary logistic regression analysis.Conclusion:Increasing number of CRA in acute stroke is correlated with an increased ENT rate and increased IG volume, affecting functional outcome even when successful recanalization is achieved.Classification of evidence:This study provides Class II evidence that, for patients with acute stroke undergoing successful recanalization, an increasing number of clot retrieval attempts is associated with poorer functional outcome.