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  • Journal article
    The REMAP-CAP, ACTIV-4a, and ATTACC Investigators, 2021,

    Therapeutic anticoagulation with heparin in critically Ill patients with Covid-19

    , New England Journal of Medicine, Vol: 385, Pages: 777-789, ISSN: 0028-4793

    BACKGROUNDThrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.METHODSIn an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.RESULTSThe trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.CONCLUSIONSIn critically ill patients with Covid-19, an initial strategy of therapeu

  • Journal article
    The ATTACC, ACTIV-4a, and REMAP-CAP Investigators, 2021,

    Therapeutic anticoagulation with heparin in noncritically Ill patients with Covid-19

    , New England Journal of Medicine, Vol: 385, Pages: 790-802, ISSN: 0028-4793

    BACKGROUNDThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODSIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTSThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic

  • Journal article
    Arabi Y, Gordon A, Derde L, Nichol A, Murthy S, Al-Beidh F, Annane D, Al Swaidan L, Beane A, Beasley R, Berry L, Bhimani Z, Bonten M, Bradbury C, Brunkhorst F, Buxton M, Buzgau A, Cheng A, De Jong M, Detry M, Duffy E, Estcourt L, Fitzgerald M, Fowler R, Girard T, Goligher E, Goossens H, Haniffa R, Higgins A, Hills T, Horvat C, Huang D, King A, Lamontagne F, Lawler P, Lewis R, Linstrum K, Litton E, Lorenzi E, Malakouti S, McAuley D, McGlothlin A, Mcguinness S, McVerry B, Montgomery S, Morpeth S, Mouncey P, Orr K, Parke R, Parker J, Patanwala A, Rowan K, Santos M, Saunders C, Seymour C, Shankar-Hari M, Tong S, Turgeon A, Turner A, Van de Veerdonk FL, Zarychanski R, Green C, Berry S, Marshall J, McArthur C, Angus D, Webb Set al., 2021,

    Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized control trial

    , Intensive Care Medicine, Vol: 47, Pages: 867-886, ISSN: 0342-4642

    Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19) Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir, and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ-support free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR >1 is favorable. Results: We randomized 694 patients to receive lopinavir-ritonavir (n=255), hydroxychloroquine (n=50), combination therapy (n=27) or control (n=362). The median (IQR) organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (–1 to 15), 0 (–1 to 9) and –1 (–1 to 7), respectively, compared to 6 (–1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥99.0%), and high probabilities of harm (98.0%, 99.9% and >99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). Conclusion: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.Trial registration identifier: NCT02735707

  • Journal article
    Medjeral-Thomas NR, Pusey CD, 2021,

    New Insights into Epidemiology and Outcome of Bacterial Infection?Related Glomerulonephritis

  • Journal article
    Vallant N, Wolfhagen N, Sandhu B, Hamaoui K, Cook T, Pusey C, Papalois Vet al., 2021,

    A Comparison of Pulsatile Hypothermic and Normothermic Ex Vivo Machine Perfusion in a Porcine Kidney Model

    , TRANSPLANTATION, Vol: 105, Pages: 1760-1770, ISSN: 0041-1337
  • Journal article
    Liu T, Gao Y, Wang H, Zhou Z, Wang R, Chang S, Liu Y, Sun Y, Rui H, Yang G, Firmin D, Dong J, Xu Let al., 2021,

    Association between right ventricular strain and outcomes in patients with dilated cardiomyopathy

    , Heart, Vol: 107, Pages: 1233-1239, ISSN: 1355-6037

    Objective To explore the association between three-dimensional (3D) cardiac magnetic resonance (CMR) feature tracking (FT) right ventricular peak global longitudinal strain (RVpGLS) and major adverse cardiovascular events (MACEs) in patients with stage C or D heart failure (HF) with non-ischaemic dilated cardiomyopathy (NIDCM) but without atrial fibrillation (AF).Methods Patients with dilated cardiomyopathy were enrolled in this prospective cohort study. Comprehensive clinical and biochemical analysis and CMR imaging were performed. All patients were followed up for MACEs.Results A total of 192 patients (age 53±14 years) were eligible for this study. A combination of cardiovascular death and cardiac transplantation occurred in 18 subjects during the median follow-up of 567 (311, 920) days. Brain natriuretic peptide, creatinine, left ventricular (LV) end-diastolic volume, LV end-systolic volume, right ventricular (RV) end-diastolic volume and RVpGLS from CMR were associated with the outcomes. The multivariate Cox regression model adjusting for traditional risk factors and CMR variables detected a significant association between RVpGLS and MACEs in patients with stage C or D HF with NIDCM without AF. Kaplan-Meier analysis based on RVpGLS cut-off value revealed that patients with RVpGLS <−8.5% showed more favourable clinical outcomes than those with RVpGLS ≥−8.5% (p=0.0037). Subanalysis found that this association remained unchanged.Conclusions RVpGLS-derived from 3D CMR FT is associated with a significant prognostic impact in patients with NIDCM with stage C or D HF and without AF.

  • Journal article
    Domingo P, Mur I, Mateo GM, Gutierrez MDM, Pomar V, de Benito N, Corbacho N, Herrera S, Millan L, Muñoz J, Malouf J, Molas ME, Asensi V, Horcajada JP, Estrada V, Gutierrez F, Torres F, Perez-Molina JA, Fortun J, Villar LM, Hohenthal U, Marttila H, Vuorinen T, Nordberg M, Valtonen M, Frigault MJ, Mansour MK, Patel NJ, Fernandes A, Harvey L, Foulkes AS, Healy BC, Shah R, Bensaci AM, Woolley AE, Nikiforow S, Lin N, Sagar M, Shrager H, Huckins DS, Axelrod M, Pincus MD, Fleisher J, Lampa J, Nowak P, Vesterbacka JC, Rasmuson J, Skorup P, Janols H, Niward KF, Chatzidionysiou K, Asgeirsson H, Parke Å, Blennow O, Svensson A-K, Aleman S, Sönnerborg A, Henter J-I, Horne AC, Al-Beidh F, Angus D, Annane D, Arabi Y, Beane A, Berry S, Bhimani Z, Bonten M, Bradbury C, Brunkhorst F, Buxton M, Cheng A, Cove M, De Jong M, Derde L, Estcourt L, Goossens H, Gordon A, Green C, Haniffa R, Ichihara N, Lamontagne F, Lawler P, Litton E, Marshall J, McArthur C, McAuley D, McGuinness S, McVerry B, Montgommery S, Mouncey P, Murthy S, Nichol A, Parke R, Parker J, Reyes F, Rowan K, Saito H, Santos M, Seymour C, Shankar-Hari M, Turgeon A, Turner A, van Bentum-Puijk W, van de Veerdonk F, Webb S, Zarychanski R, Baillie JK, Beasley R, Cooper N, Fowler R, Galea J, Hills T, King A, Morpeth S, Netea M, Ogungbenro K, Pettila V, Tong S, Uyeki T, Youngstein T, Higgins A, Lorenzi E, Berry L, Salama C, Rosas IO, Ruiz-Antorán B, Muñez Rubio E, Ramos Martínez A, Campos Esteban J, Avendaño Solá C, Pizov R, Sanz Sanz J, Abad-Santos F, Bautista-Hernández A, García-Fraile L, Barrios A, Gutiérrez Liarte Á, Alonso Pérez T, Rodríguez-García SC, Mejía-Abril G, Prieto JC, Leon R, VEIGA VC, SCHEINBERG P, FARIAS DLC, PRATS JG, CAVALCANTI AB, MACHADO FR, ROSA RG, BERWANGER O, AZEVEDO LCP, LOPES RD, DOURADO LK, CASTRO CG, ZAMPIERI FG, AVEZUM A, LISBOA TC, ROJAS SSO, COELHO JC, LEITE RT, CARVALHO JC, ANDRADE LEC, SANDES AR, PINTÃO MCT, SANTOS SV, ALMEIDA TML, COSTA AN, GEBARA OCE, FREITAS FGR, PACHECO ES, MACHADO DJB, MARTINet al., 2021,

    Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19

    , JAMA, ISSN: 0098-7484

    Importance Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.Objective To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data Sources Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study Selection Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data Extraction and Synthesis In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main Outcomes and Measures The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.Results A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL

  • Journal article
    Teng YKO, Pusey CD, Vaglio A, Mok CC, van Kooten Cet al., 2021,

    Editorial: Immune Monitoring Responses in Renal Autoimmune Diseases

    , FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224
  • Journal article
    Lv J, Zhu J, Yang G, 2021,

    Which GAN? A comparative study of generative adversarial network (GAN) based fast MRI reconstruction

    , Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol: 379, Pages: 1-17, ISSN: 1364-503X

    Fast magnetic resonance imaging (MRI) is crucial for clinical applications that can alleviate motion artefacts and increase patient throughput. K-space undersampling is an obvious approach to accelerate MR acquisition. However, undersampling of k-space data can result in blurring and aliasing artefacts for the reconstructed images. Recently, several studies have been proposed to use deep learning based data-driven models for MRI reconstruction and have obtained promising results. However, the comparison of these methods remains limited because the models have not been trained on the same datasets and the validation strategies may bedifferent. The purpose of this work is to conduct a comparative study to investigate the generative adversarial network (GAN) based models for MRI reconstruction. We reimplemented and benchmarked four widely used GAN based architectures including DAGAN, ReconGAN, RefineGAN and KIGAN. These four frameworks were trained and tested on brain, knee and liver MRI images using 2, 4 and 6- fold accelerations with a random undersampling mask. Both quantitative evaluations and qualitative visualisation have shown that the RefineGAN method has achieved superior performance in reconstruction with better accuracy and perceptual quality compared to other GAN based methods.

  • Journal article
    Gulati K, Roufosse C, McAdoo SP, 2021,

    Diffuse crescentic glomerulonephritis presenting with preserved renal function

    , RHEUMATOLOGY, Vol: 60, Pages: 18-20, ISSN: 1462-0324

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