Showing papers by "Charles University in Prague published in 2021"
••
TL;DR: In this paper, the authors evaluated plasma heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc) and characterized its association with SSc-related features.
Abstract: Our previous study demonstrated increased expression of Heat shock protein (Hsp) 90 in the skin of patients with systemic sclerosis (SSc). We aimed to evaluate plasma Hsp90 in SSc and characterize its association with SSc-related features. Ninety-two SSc patients and 92 age-/sex-matched healthy controls were recruited for the cross-sectional analysis. The longitudinal analysis comprised 30 patients with SSc associated interstitial lung disease (ILD) routinely treated with cyclophosphamide. Hsp90 was increased in SSc compared to healthy controls. Hsp90 correlated positively with C-reactive protein and negatively with pulmonary function tests: forced vital capacity and diffusing capacity for carbon monoxide (DLCO). In patients with diffuse cutaneous (dc) SSc, Hsp90 positively correlated with the modified Rodnan skin score. In SSc-ILD patients treated with cyclophosphamide, no differences in Hsp90 were found between baseline and after 1, 6, or 12 months of therapy. However, baseline Hsp90 predicts the 12-month change in DLCO. This study shows that Hsp90 plasma levels are increased in SSc patients compared to age-/sex-matched healthy controls. Elevated Hsp90 in SSc is associated with increased inflammatory activity, worse lung functions, and in dcSSc, with the extent of skin involvement. Baseline plasma Hsp90 predicts the 12-month change in DLCO in SSc-ILD patients treated with cyclophosphamide.
2,948 citations
••
Daniel J. Klionsky1, Amal Kamal Abdel-Aziz2, Sara Abdelfatah3, Mahmoud Abdellatif4 +2980 more•Institutions (777)
TL;DR: In this article, the authors present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes.
Abstract: In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
1,129 citations
••
TL;DR: The European Association of Urology (EAU) has released an updated version of the guidelines on non-muscle-invasive bladder cancer (NMIBC).
316 citations
••
Icahn School of Medicine at Mount Sinai1, Radboud University Nijmegen2, Technische Universität München3, Niigata University4, National and Kapodistrian University of Athens5, Université Paris-Saclay6, Medical University of Vienna7, University of Texas Southwestern Medical Center8, Charles University in Prague9, I.M. Sechenov First Moscow State Medical University10, Samsung Medical Center11, Fudan University12, Aarhus University Hospital13, Guy's and St Thomas' NHS Foundation Trust14, Rambam Health Care Campus15, University of North Carolina at Chapel Hill16, Bristol-Myers Squibb17
TL;DR: In this article, the role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery was not clear, and a phase 3, multicenter, double-blind, randomized, controlled trial was conducted.
Abstract: Background The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. Methods In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. Results A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P Conclusions In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).
289 citations
••
Imperial College London1, Amgen2, Memorial Hospital of South Bend3, Medical University of Łódź4, University of Zielona Góra5, University of Amsterdam6, Opole University7, Leiden University Medical Center8, University of Copenhagen9, Trinity College, Dublin10, Cliniques Universitaires Saint-Luc11, Slovak Medical University12, Sahlgrenska University Hospital13, Magna Græcia University14, University of Gothenburg15, National and Kapodistrian University of Athens16, Charles University in Prague17
TL;DR: In this article, the authors provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement.
Abstract: Aims To provide contemporary data on the implementation of European guideline recommendations for lipid-lowering therapies (LLTs) across different settings and populations and how this impacts low-density lipoprotein cholesterol (LDL-C) goal achievement. Methods and results An 18 country, cross-sectional, observational study of patients prescribed LLT for primary or secondary prevention in primary or secondary care across Europe. Between June 2017 and November 2018, data were collected at a single visit, including LLT in the preceding 12 months and most recent LDL-C. Primary outcome was the achievement of risk-based 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) LDL-C goal while receiving stabilized LLT; 2019 goal achievement was also assessed. Overall, 5888 patients (3000 primary and 2888 secondary prevention patients) were enrolled; 54% [95% confidence interval (CI) 52-56] achieved their risk-based 2016 goal and 33% (95% CI 32-35) achieved their risk-based 2019 goal. High-intensity statin monotherapy was used in 20% and 38% of very high-risk primary and secondary prevention patients, respectively. Corresponding 2016 goal attainment was 22% and 45% (17% and 22% for 2019 goals) for very high-risk primary and secondary prevention patients, respectively. Use of moderate-high-intensity statins in combination with ezetimibe (9%), or any LLT with PCSK9 inhibitors (1%), was low; corresponding 2016 and 2019 goal attainment was 53% and 20% (ezetimibe combination), and 67% and 58% (PCSK9i combination). Conclusion Gaps between clinical guidelines and clinical practice for lipid management across Europe persist, which will be exacerbated by the 2019 guidelines. Even with optimized statins, greater utilization of non-statin LLT is likely needed to reduce these gaps for patients at highest risk.
277 citations
••
TL;DR: These European Resuscitation Council (ERC) Cardiac Arrest in Special Circumstances guidelines are based on the 2020 International Consensus on Cardiopulmonary Resusitation Science with Treatment Recommendations as mentioned in this paper.
250 citations
••
University of Fribourg1, Zoological Society of London2, Stellenbosch University3, University College London4, University of Lisbon5, Durham University6, University of Vienna7, International Union for Conservation of Nature and Natural Resources8, Lincoln University (New Zealand)9, Taizhou University10, University of Konstanz11, Helmholtz Centre for Environmental Research - UFZ12, Martin Luther University of Halle-Wittenberg13, Free University of Berlin14, Leibniz Association15, United States Forest Service16, Czech University of Life Sciences Prague17, Newcastle University18, Academy of Sciences of the Czech Republic19, Charles University in Prague20
TL;DR: These projections are the first quantitative projections of future trajectories of alien species numbers for seven major taxonomic groups in eight continents, accounting for variation in sampling intensity and uncertainty in projections.
Abstract: Biological invasions have steadily increased over recent centuries. However, we still lack a clear expectation about future trends in alien species numbers. In particular, we do not know whether alien species will continue to accumulate in regional floras and faunas, or whether the pace of accumulation will decrease due to the depletion of native source pools. Here, we apply a new model to simulate future numbers of alien species based on estimated sizes of source pools and dynamics of historical invasions, assuming a continuation of processes in the future as observed in the past (a business-as-usual scenario). We first validated performance of different model versions by conducting a back-casting approach, therefore fitting the model to alien species numbers until 1950 and validating predictions on trends from 1950 to 2005. In a second step, we selected the best performing model that provided the most robust predictions to project trajectories of alien species numbers until 2050. Altogether, this resulted in 3,790 stochastic simulation runs for 38 taxon-continent combinations. We provide the first quantitative projections of future trajectories of alien species numbers for seven major taxonomic groups in eight continents, accounting for variation in sampling intensity and uncertainty in projections. Overall, established alien species numbers per continent were predicted to increase from 2005 to 2050 by 36%. Particularly, strong increases were projected for Europe in absolute (+2,543 ± 237 alien species) and relative terms, followed by Temperate Asia (+1,597 ± 197), Northern America (1,484 ± 74) and Southern America (1,391 ± 258). Among individual taxonomic groups, especially strong increases were projected for invertebrates globally. Declining (but still positive) rates were projected only for Australasia. Our projections provide a first baseline for the assessment of future developments of biological invasions, which will help to inform policies to contain the spread of alien species.
250 citations
••
Ohio State University1, Los Angeles Biomedical Research Institute2, University of Leicester3, French Institute of Health and Medical Research4, Salem Hospital5, University of Hong Kong6, Imperial College London7, Mayo Clinic8, University of North Carolina at Chapel Hill9, University of California, Los Angeles10, University of Cambridge11, The George Institute for Global Health12, Mount Elizabeth Novena Hospital13, Nanjing University14, University of Iowa15, Columbia University Medical Center16, University of Toronto17, University of Groningen18, Juntendo University19, Charles University in Prague20, Radboud University Nijmegen21, McMaster University22, Flinders University23, University of Sydney24, University of Calgary25, RWTH Aachen University26
TL;DR: The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline.
180 citations
••
TL;DR: Polarons are quasiparticles that easily form in polarizable materials due to the coupling of excess electrons or holes with ionic vibrations, and have a profound impact on materials properties and functionalities as discussed by the authors.
Abstract: Polarons are quasiparticles that easily form in polarizable materials due to the coupling of excess electrons or holes with ionic vibrations. These quasiparticles manifest themselves in many different ways and have a profound impact on materials properties and functionalities. Polarons have been the testing ground for the development of numerous theories, and their manifestations have been studied by many different experimental probes. This Review provides a map of the enormous amount of data and knowledge accumulated on polaron effects in materials, ranging from early studies and standard treatments to emerging experimental techniques and novel theoretical and computational approaches. Polarons — quasiparticles arising from the interaction of electrons with lattice vibrations — strongly influence materials properties. This Review provides a map of the theoretical models and experimental techniques used to study polarons in materials, presenting paradigmatic examples of different types of polarons and polaron-driven phenomena.
178 citations
••
TL;DR: The aim of the present paper was to provide an up‐to‐date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction.
Abstract: Aims The aim of the present paper was to provide an up-to-date view on epidemiology and risk factors of heart failure (HF) development after myocardial infarction. Methods and results Based on literature review, several clinical risk factors and biochemical, genetic, and imaging biomarkers were identified to predict the risk of HF development after myocardial infarction. Conclusions Heart failure is still a frequent complication of myocardial infarction. Timely identification of subjects at risk for HF development using a multimodality approach, and early initiation of guideline-directed HF therapy in these patients, can decrease the HF burden.
165 citations
••
European Association of Urology1, Autonomous University of Barcelona2, University of Turin3, Charles University in Prague4, Radboud University Nijmegen5, University of Regensburg6, University Health Network7, Medical University of Graz8, Netherlands Cancer Institute9, VU University Amsterdam10, Vienna General Hospital11, University of Paris12, Royal Free London NHS Foundation Trust13
TL;DR: In this paper, the European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT).
••
TL;DR: In this paper, a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3 is presented, which contains at least 92% of stars of stellar type M9 within 100pc of the sun.
Abstract: Aims. We produce a clean and well-characterised catalogue of objects within 100 pc of the Sun from the Gaia Early Data Release 3. We characterise the catalogue through comparisons to the full data release, external catalogues, and simulations. We carry out a first analysis of the science that is possible with this sample to demonstrate its potential and best practices for its use.Methods. Theselection of objects within 100 pc from the full catalogue used selected training sets, machine-learning procedures, astrometric quantities, and solution quality indicators to determine a probability that the astrometric solution is reliable. The training set construction exploited the astrometric data, quality flags, and external photometry. For all candidates we calculated distance posterior probability densities using Bayesian procedures and mock catalogues to define priors. Any object with reliable astrometry and a non-zero probability of being within 100 pc is included in the catalogue.Results. We have produced a catalogue of 331 312 objects that we estimate contains at least 92% of stars of stellar type M9 within 100 pc of the Sun. We estimate that 9% of the stars in this catalogue probably lie outside 100 pc, but when the distance probability function is used, a correct treatment of this contamination is possible. We produced luminosity functions with a high signal-to-noise ratio for the main-sequence stars, giants, and white dwarfs. We examined in detail the Hyades cluster, the white dwarf population, and wide-binary systems and produced candidate lists for all three samples. We detected local manifestations of several streams, superclusters, and halo objects, in which we identified 12 members of Gaia Enceladus. We present the first direct parallaxes of five objects in multiple systems within 10 pc of the Sun.Conclusions. We provide the community with a large, well-characterised catalogue of objects in the solar neighbourhood. This is a primary benchmark for measuring and understanding fundamental parameters and descriptive functions in astronomy.
••
TL;DR: In this article, the authors evaluated event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant.
Abstract: Importance Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Objective To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Design, setting, and participants In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, Intervention Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. Main outcomes and measures The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. Results A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P Conclusions and relevance Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. Trial registration ClinicalTrials.gov Identifier: NCT02393859.
••
National and Kapodistrian University of Athens1, City of Hope National Medical Center2, University College Hospital3, University of Ostrava4, Charles University in Prague5, Murdoch University6, Samsung Medical Center7, University of São Paulo8, French Institute of Health and Medical Research9, Seoul National University Hospital10, University of California, San Francisco11
TL;DR: In this article, the authors compared the efficacy of isatuximab plus carfilzomib-dexamethasone versus CARF-DEXAMETHASONE in patients with relapsed or refractory multiple myeloma.
••
TL;DR: In this article, the ATLAS particle-flow reconstruction method is used to reconstruct the topo-clusters of the proton-proton collision data with a center-of-mass energy of 13$ TeV collected by the LHC.
Abstract: Jet energy scale and resolution measurements with their associated uncertainties are reported for jets using 36-81 fb$^{-1}$ of proton-proton collision data with a centre-of-mass energy of $\sqrt{s}=13$ TeV collected by the ATLAS detector at the LHC. Jets are reconstructed using two different input types: topo-clusters formed from energy deposits in calorimeter cells, as well as an algorithmic combination of charged-particle tracks with those topo-clusters, referred to as the ATLAS particle-flow reconstruction method. The anti-$k_t$ jet algorithm with radius parameter $R=0.4$ is the primary jet definition used for both jet types. Jets are initially calibrated using a sequence of simulation-based corrections. Next, several $\textit{in situ}$ techniques are employed to correct for differences between data and simulation and to measure the resolution of jets. The systematic uncertainties in the jet energy scale for central jets ($|\eta| 2.5$ TeV). The relative jet energy resolution is measured and ranges from ($24 \pm 1.5$)% at 20 GeV to ($6 \pm 0.5$)% at 300 GeV.
••
Katherine S. Ruth1, Felix R. Day2, Jazib Hussain3, Ana Martínez-Marchal4 +307 more•Institutions (91)
TL;DR: In this paper, the authors identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry.
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.
••
TL;DR: The context-dependent impact of CALR on malignant transformation, tumor progression and response to cancer therapy is discussed.
Abstract: Calreticulin (CALR) is an endoplasmic reticulum (ER)-resident protein involved in a spectrum of cellular processes. In healthy cells, CALR operates as a chaperone and Ca2+ buffer to assist correct protein folding within the ER. Besides favoring the maintenance of cellular proteostasis, these cell-intrinsic CALR functions support Ca2+-dependent processes, such as adhesion and integrin signaling, and ensure normal antigen presentation on MHC Class I molecules. Moreover, cancer cells succumbing to immunogenic cell death (ICD) expose CALR on their surface, which promotes the uptake of cell corpses by professional phagocytes and ultimately supports the initiation of anticancer immunity. Thus, loss-of-function CALR mutations promote oncogenesis not only as they impair cellular homeostasis in healthy cells, but also as they compromise natural and therapy-driven immunosurveillance. However, the prognostic impact of total or membrane-exposed CALR levels appears to vary considerably with cancer type. For instance, while genetic CALR defects promote pre-neoplastic myeloproliferation, patients with myeloproliferative neoplasms bearing CALR mutations often experience improved overall survival as compared to patients bearing wild-type CALR. Here, we discuss the context-dependent impact of CALR on malignant transformation, tumor progression and response to cancer therapy.
••
TL;DR: In this paper, the performance of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC is presented, based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$.
Abstract: The performance is presented of the reconstruction and identification algorithms for electrons and photons with the CMS experiment at the LHC. The reported results are based on proton-proton collision data collected at a center-of-mass energy of 13 TeV and recorded in 2016-2018, corresponding to an integrated luminosity of 136 fb$^{-1}$. Results obtained from lead-lead collision data collected at $\sqrt{s_\mathrm{NN}}=$ 5.02 TeV are also presented. Innovative techniques are used to reconstruct the electron and photon signals in the detector and to optimize the energy resolution. Events with electrons and photons in the final state are used to measure the energy resolution and energy scale uncertainty in the recorded events. The measured energy resolution for electrons produced in Z boson decays in proton-proton collision data ranges from 2 to 5%, depending on electron pseudorapidity and energy loss through bremsstrahlung in the detector material. The energy scale in the same range of energies is measured with an uncertainty smaller than 0.1 (0.3)% in the barrel (endcap) region in proton-proton collisions and better than 1 (3)% in the barrel (endcap) region in heavy ion collisions. The timing resolution for electrons from Z boson decays with the full 2016-2018 proton-proton collision data set is measured to be 200 ps.
••
Semmelweis University1, Utrecht University2, University of Debrecen3, Salisbury University4, Charles University in Prague5, Cardiff University6, University of Paris7, Charité8, Medical University of Vienna9, Radboud University Nijmegen Medical Centre10, Paris Descartes University11, University of Salford12, King's College London13, Catholic University of the Sacred Heart14, University of Erlangen-Nuremberg15, University of Giessen16, University of Glasgow17, Leiden University Medical Center18
TL;DR: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.
Abstract: Background Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic These patients can be considered to have ‘difficult-to-treat RA’ However, uniform terminology and an appropriate definition are lacking Objective The Task Force in charge of the “Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis” aims to create recommendations for this underserved patient group Herein, we present the definition of difficult-to-treat RA, as the first step Methods The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting) Results The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient Conclusions The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research
••
Maastricht University Medical Centre1, Monash University2, The Catholic University of America3, University of Michigan4, ISMETT5, Hospital of the University of Pennsylvania6, Charles University in Prague7, Capital Medical University8, University of Düsseldorf9, University of Twente10, University Medical Center Utrecht11, Columbia University12, Northwestern University13, National Taiwan University14, Johns Hopkins University15
••
University of Calgary1, Charles University in Prague2, Cleveland Clinic3, Yale University4, University of Erlangen-Nuremberg5, University of British Columbia6, University of Tennessee7, Johns Hopkins University8, Memorial Sloan Kettering Cancer Center9, Indiana University10, Mayo Clinic11, University of Paris12, Vanderbilt University Medical Center13, Peking University14, Brigham and Women's Hospital15, University of Texas Southwestern Medical Center16, Wakayama Medical University17, Macquarie University18, University of Alabama at Birmingham19, University of Michigan20, Homi Bhabha National Institute21, University of Texas MD Anderson Cancer Center22, Nanjing University23, University of Toronto24, Virginia Commonwealth University25, University of Washington26, University of North Carolina at Chapel Hill27, Tufts Medical Center28, Royal North Shore Hospital29, University of Sydney30, Kolling Institute of Medical Research31
TL;DR: The authors in this article reviewed recent advances in renal neoplasia, particularly post-2016 World Health Organization (WHO) classification, to provide an update on existing entities, including diagnostic criteria, molecular correlates, and updated nomenclature.
••
Brigham and Women's Hospital1, University of Rome Tor Vergata2, Charité3, University of Queensland4, Boston Children's Hospital5, Utrecht University6, Charles University in Prague7, Necker-Enfants Malades Hospital8, Vrije Universiteit Brussel9, Warsaw University of Technology10, University of Amsterdam11, Katholieke Universiteit Leuven12, Medical University of Warsaw13
TL;DR: The EPISTOP clinical trial was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.
Abstract: OBJECTIVE Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants. METHODS In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open-label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure. RESULTS In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty-seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment [RCT: 364 days (95% confidence interval [CI] = 223-535) vs 124 days (95% CI = 33-149); OLT: 426 days (95% CI = 258-628) vs 106 days (95% CI = 11-149)]. At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio [OR] = 0.21, p = 0.032), drug-resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted. INTERPRETATION Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304-314.
••
••
University of Calgary1, Cleveland Clinic2, University of Sydney3, Yale University4, University of Erlangen-Nuremberg5, University of British Columbia6, University of Tennessee Health Science Center7, Johns Hopkins University8, Memorial Sloan Kettering Cancer Center9, Indiana University10, Mayo Clinic11, Pierre-and-Marie-Curie University12, Vanderbilt University13, Peking University14, Harvard University15, University of Texas Southwestern Medical Center16, Wakayama Medical University17, Macquarie University18, University of Alabama at Birmingham19, University of Michigan20, Tata Memorial Hospital21, University of Texas Health Science Center at Houston22, Nanjing University23, University of Toronto24, Virginia Commonwealth University25, University of Washington26, University of Paris27, University of North Carolina at Chapel Hill28, Tufts University29, Charles University in Prague30
TL;DR: In this paper, a review of the recent advances in renal neoplasia, particularly focusing on the newly accumulated evidence post-2016 World Health Organization (WHO) classification is presented.
••
Radboud University Nijmegen1, University of London2, Charles University in Prague3, Vita-Salute San Raffaele University4, University of Cambridge5, Newcastle University6, University of Amsterdam7, National and Kapodistrian University of Athens8, Chelsea and Westminster Hospital NHS Foundation Trust9, Imperial College London10, National Institutes of Health11
TL;DR: In this article, the authors provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women and provide practice points for clinical use according to the latest standards from various related disciplines.
Abstract: Women undergo important changes in sex hormones throughout their lifetime that can impact cardiovascular disease risk. Whereas the traditional cardiovascular risk factors dominate in older age, there are several female-specific risk factors and inflammatory risk variables that influence a woman's risk at younger and middle age. Hypertensive pregnancy disorders and gestational diabetes are associated with a higher risk in younger women. Menopause transition has an additional adverse effect to ageing that may demand specific attention to ensure optimal cardiovascular risk profile and quality of life. In this position paper, we provide an update of gynaecological and obstetric conditions that interact with cardiovascular risk in women. Practice points for clinical use are given according to the latest standards from various related disciplines (Figure 1).
••
Itziar de Rojas1, Itziar de Rojas2, Sonia Moreno-Grau1, Sonia Moreno-Grau2 +356 more•Institutions (96)
TL;DR: In this article, a large genetic association study was performed by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190).
Abstract: Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease.
••
TL;DR: In this paper, the activated B-cell-like (ABC) subtype of diffuse large b-cell lymphoma (DLBCL) showed inferior survival with standard rituximab plus cyclophosphamide, doxorubici...
Abstract: PURPOSEPatients with the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) historically showed inferior survival with standard rituximab plus cyclophosphamide, doxorubici...
••
RWTH Aachen University1, University of Bern2, University of Wrocław3, University of Paris4, Dresden University of Technology5, University of Milan6, Charles University in Prague7, University of Novi Sad8, University of Bremen9, University of Szeged10, Romanian Academy11, Leibniz Association12, University of Bayreuth13
TL;DR: In this paper, a map of the distribution of aeolian sediments (mainly loess) and major potential source areas for Europe is presented, combining geodata of different mapping approaches.
••
TL;DR: In this article, the authors compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients.
Abstract: The immunogenicity of the novel mRNA COVID-19 vaccine in immunocompromised lung transplant recipients is still unknown. We compared the antibody response after the first and second doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) with the response after natural SARS-CoV-2 infection in lung transplant recipients. None of the vaccinees tested after two doses of the mRNA BNT162b2 vaccine developed anti-SARS-CoV-2 IgG, while 85% patients presented an antibody response after SARS-CoV-2 infection. The absence of antibody response to vaccination led us to investigate the cellular response in a subset of patients. We detected SARS-CoV-2 specific T-cells in 4 out of 12 tested patients. Some patients therefore might have clinical benefit from the vaccine despite an absent antibody response. These results contrast with the excellent antibody response in immunocompetent individuals observed in mRNA BNT162b2 trials and indicate an urgent need to identify the best vaccine type and scheme for immunocompromised transplanted patients.
••
Wageningen University and Research Centre1, Utrecht University2, Carleton University3, University of Maryland, College Park4, University of Costa Rica5, Hosei University6, Stellenbosch University7, Chinese Academy of Sciences8, Oregon State University9, University of Toronto10, University of California, Berkeley11, University of Pretoria12, Technical University of Denmark13, Suez Canal University14, University of Kurdistan15, University of Cambridge16, Imperial College London17, University of Kharkiv18, Cape Peninsula University of Technology19, University of Florida20, National Taiwan University21, Norwegian University of Science and Technology22, University of Oslo23, Universidade Federal de Goiás24, Universidade Federal Rural de Pernambuco25, University of the Republic26, University of Perugia27, University of Los Andes28, New York State Department of Health29, University of Neuchâtel30, American Museum of Natural History31, Université catholique de Louvain32, Babcock University33, Beijing Forestry University34, University of Buenos Aires35, Royal Botanic Gardens36, Austral University of Chile37, Spanish National Research Council38, University of Graz39, Scotland's Rural College40, University of Turin41, Sewanee: The University of the South42, Ghent University43, Swedish Museum of Natural History44, Charles University in Prague45, Mae Fah Luang University46, Cornell University47, University of Mauritius48, Landcare Research49, Yeditepe University50, University of Veterinary Medicine Vienna51, University of California, Davis52, Chonnam National University53, Laboratory of Molecular Biology54, Sukachev Institute of Forest55, University of Electronic Science and Technology of China56, University of Queensland57, University of Florence58, Mie University59, University of Gothenburg60, University of Batna61, National Scientific and Technical Research Council62, University of Lisbon63, University of Catania64, Agharkar Research Institute65, Federal University of São Paulo66, Agricultural Research Service67, Federal University of Pernambuco68, University of Southern Queensland69, Northwest A&F University70, University of the Free State71, Royal Botanic Garden Edinburgh72, University of Melbourne73, Shandong Agricultural University74, Leibniz Association75, Uppsala University76, Goethe University Frankfurt77
TL;DR: Fusarioid-ID as discussed by the authors is an online monograph of the genus Fusarium, which is used to identify fusarioids in the Nectriaceae family.