Showing papers by "University of Barcelona published in 2019"
Barbara Burtness1, Kevin J. Harrington2, Richard Greil, Denis Soulières3 +202 more•Institutions (18)
TL;DR: A randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries finds that pembrolizumab alone improved overall survival and progression-free survival and cetuximab with chemotherapy improved Overall survival in the total population.
1,490 citations
Harvard University1, University of Glasgow2, University of Minnesota3, Fudan University4, National University of Cordoba5, Baylor University Medical Center6, University Medical Center Groningen7, Université de Montréal8, Medical University of South Carolina9, University of Lorraine10, University of Barcelona11, Northwestern University12, Charité13, University of Groningen14, Cardiovascular Institute of the South15, University of São Paulo16, Semmelweis University17, Novartis18
TL;DR: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failureand an ejection fraction of 45% or higher, and among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit in patients with lower ejection fractions and in women.
Abstract: Background The angiotensin receptor–neprilysin inhibitor sacubitril–valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients ...
1,306 citations
TL;DR: In this article, the authors review recent advances and challenges in the understanding of electrochemical CO2 reduction and discuss existing models for the initial activation of CO2 on the electrocatalyst and their importance for understanding selectivity.
Abstract: The electrocatalytic reduction of carbon dioxide is a promising approach for storing (excess) renewable electricity as chemical energy in fuels. Here, we review recent advances and challenges in the understanding of electrochemical CO2 reduction. We discuss existing models for the initial activation of CO2 on the electrocatalyst and their importance for understanding selectivity. Carbon–carbon bond formation is also a key mechanistic step in CO2 electroreduction to high-density and high-value fuels. We show that both the initial CO2 activation and C–C bond formation are influenced by an intricate interplay between surface structure (both on the nano- and on the mesoscale), electrolyte effects (pH, buffer strength, ion effects) and mass transport conditions. This complex interplay is currently still far from being completely understood. In addition, we discuss recent progress in in situ spectroscopic techniques and computational techniques for mechanistic work. Finally, we identify some challenges in furthering our understanding of these themes. Electrocatalytic reduction of CO2 to fuels could be used as an approach to store renewable energy in the form of chemical energy. Here, Birdja et al. review current understanding of electrocatalytic systems and reaction pathways for these conversions.
1,141 citations
University of Manchester1, University of Barcelona2, University of Texas Health Science Center at San Antonio3, National Institutes of Health4, McGill University Health Centre5, Brigham and Women's Hospital6, Temple University7, Flinders University8, Royal Devon and Exeter Hospital9, University of Michigan10, University of the Republic11, NewYork–Presbyterian Hospital12, Central University of Venezuela13, University of Ferrara14, Paris Descartes University15, University of British Columbia16, University of Birmingham17, University of Marburg18
TL;DR: Blood eosinophils are recommended as a biomarker to support clinical decisions regarding the use of inhaled corticosteroids in chronic obstructive pulmonary disease patients, based on recent evidence from clinical trials.
Abstract: Precision medicine is a patient-specific approach that integrates all relevant clinical, genetic and biological information in order to optimise the therapeutic benefit relative to the possibility of side-effects for each individual. Recent clinical trials have shown that higher blood eosinophil counts are associated with a greater efficacy of inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD) patients. Blood eosinophil counts are a biomarker with potential to be used in clinical practice, to help target ICS treatment with more precision in COPD patients with a history of exacerbations despite appropriate bronchodilator treatment. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 pharmacological treatment algorithms, based on the ABCD assessment, can be applied relatively easily to treatment-naive individuals at initial presentation. However, their use is more problematic during follow-up in patients who are already on maintenance treatment. There is a need for a different system to guide COPD pharmacological management during follow-up. Recent large randomised controlled trials have provided important new information concerning the therapeutic effects of ICSs and long-acting bronchodilators on exacerbations. The new evidence regarding blood eosinophils and inhaled treatments, and the need to distinguish between initial and follow-up pharmacological management, led to changes in the GOLD pharmacological treatment recommendations. This article explains the evidence and rationale for the GOLD 2019 pharmacological treatment recommendations.
1,122 citations
TL;DR: Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.
Abstract: Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
1,090 citations
Harvard University1, Asan Medical Center2, National Cheng Kung University3, University of California, Los Angeles4, University of Barcelona5, Icahn School of Medicine at Mount Sinai6, Samsung Medical Center7, Memorial Hospital of South Bend8, Gachon University9, Eli Lilly and Company10, Kindai University11
TL;DR: Overall survival, progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, and time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8) were significantly improved in the ramucirumab group compared with the placebo group.
Abstract: Summary Background Patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations have poor prognosis. We aimed to establish the efficacy of ramucirumab in patients with advanced hepatocellular carcinoma and α-fetoprotein concentrations of 400 ng/mL or higher. Methods REACH-2 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 92 hospitals, clinics, and medical centres in 20 countries. Eligible patients were aged 18 years or older and had histologically or cytologically confirmed hepatocellular carcinoma, or diagnosed cirrhosis and hepatocellular carcinoma, Barcelona Clinic Liver Cancer stage B or C disease, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group (ECOG) performance statuses of 0 or 1, α-fetoprotein concentrations of 400 ng/mL or greater, and had previously received first-line sorafenib. Participants were randomly assigned (2:1) via an interactive web response system with a computer-generated random sequence to 8 mg/kg intravenous ramucirumab every 2 weeks or placebo. All patients received best supportive care. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportion of patients achieving an objective response, time to radiographic progression, safety, time to deterioration in scores on the Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index 8 (FHSI-8), and time to deterioration in ECOG performance status. We also pooled individual patient data from REACH-2 with data from REACH (NCT01140347) for patients with α-fetoprotein concentrations of 400 ng/mL or greater. Efficacy analyses were by intention to treat, whereas safety analyses were done in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02435433. Findings Between July 26, 2015, and Aug 30, 2017, 292 patients were randomly assigned, 197 to the ramucirumab group and 95 to the placebo group. At a median follow-up of 7·6 months (IQR 4·0–12·5), median overall survival (8·5 months [95% CI 7·0–10·6] vs 7·3 months [5·4–9·1]; hazard ratio [HR] 0·710 [95% CI 0·531–0·949]; p=0·0199) and progression-free survival (2·8 months [2·8–4·1] vs 1·6 months [1·5–2·7]; 0·452 [0·339–0·603]; p Interpretation REACH-2 met its primary endpoint, showing improved overall survival for ramucirumab compared with placebo in patients with hepatocellular carcinoma and α-fetoprotein concentrations of at least 400 ng/mL who had previously received sorafenib. Ramucirumab was well tolerated, with a manageable safety profile. To our knowledge, REACH-2 is the first positive phase 3 trial done in a biomarker-selected patient population with hepatocellular carcinoma. Funding Eli Lilly.
1,057 citations
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, National and Kapodistrian University of Athens8, Medical University of South Carolina9, University of Cambridge10, University of Barcelona11, The Feinstein Institute for Medical Research12, Toronto Western Hospital13, University of California, Los Angeles14, Humboldt University of Berlin15, Copenhagen University Hospital16, University of Michigan17, University of the Basque Country18, University Health Network19, University of Crete20, University of Zagreb21, University of Paris-Sud22, University of Hong Kong23, University of Calgary24, Hospital for Special Surgery25, University of Pécs26, University of Padua27, Medical University of Graz28, National Institutes of Health29, New York University30, Université Paris-Saclay31, University Hospital Complex Of Vigo32, University of Occupational and Environmental Health Japan33, University of Porto34, Leeds Teaching Hospitals NHS Trust35, Cedars-Sinai Medical Center36, Istanbul Bilim University37, McMaster University38
TL;DR: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism and the American College of Rheumatology (ACR).
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
1,018 citations
Alfred Wegener Institute for Polar and Marine Research1, Geological Survey of Canada2, University of Lisbon3, George Washington University4, University of Alaska Fairbanks5, University of Ottawa6, Laval University7, Humboldt State University8, University of Fribourg9, University of Potsdam10, University of Oslo11, Technical University of Denmark12, Norwegian Meteorological Institute13, Hokkaido University14, Lund University15, Free University of Berlin16, University of Lausanne17, Rhodes University18, University of Barcelona19, University of Alcalá20, Stockholm University21
TL;DR: Climate change strongly impacts regions in high latitudes and altitudes that store high amounts of carbon in yet frozen ground, and the authors show that the consequence of these changes is global warming of permafrost at depths greater than 10 m in the Northern Hemisphere, in mountains, and in Antarctica.
Abstract: Permafrost warming has the potential to amplify global climate change, because when frozen sediments thaw it unlocks soil organic carbon. Yet to date, no globally consistent assessment of permafrost temperature change has been compiled. Here we use a global data set of permafrost temperature time series from the Global Terrestrial Network for Permafrost to evaluate temperature change across permafrost regions for the period since the International Polar Year (2007–2009). During the reference decade between 2007 and 2016, ground temperature near the depth of zero annual amplitude in the continuous permafrost zone increased by 0.39 ± 0.15 °C. Over the same period, discontinuous permafrost warmed by 0.20 ± 0.10 °C. Permafrost in mountains warmed by 0.19 ± 0.05 °C and in Antarctica by 0.37 ± 0.10 °C. Globally, permafrost temperature increased by 0.29 ± 0.12 °C. The observed trend follows the Arctic amplification of air temperature increase in the Northern Hemisphere. In the discontinuous zone, however, ground warming occurred due to increased snow thickness while air temperature remained statistically unchanged.
906 citations
TL;DR: In this paper, a global analysis of the neutrino oscillation data available as of fall 2018 in the framework of three massive mixed neutrinos with the goal at determining the ranges of allowed values for the six relevant parameters.
Abstract: We present the results of a global analysis of the neutrino oscillation data available as of fall 2018 in the framework of three massive mixed neutrinos with the goal at determining the ranges of allowed values for the six relevant parameters. We describe the complementarity and quantify the tensions among the results of the different data samples contributing to the determination of each parameter. We also show how those vary when combining our global likelihood with the χ2 map provided by Super-Kamiokande for their atmospheric neutrino data analysis in the same framework. The best fit of the analysis is for the normal mass ordering with inverted ordering being disfavoured with a Δχ2 = 4.7 (9.3) without (with) SK-atm. We find a preference for the second octant of θ23, disfavouring the first octant with Δχ2 = 4.4 (6.0) without (with) SK-atm. The best fit for the complex phase is δCP = 215° with CP conservation being allowed at Δχ2 = 1.5 (1.8). As a byproduct we quantify the correlated ranges for the laboratory observables sensitive to the absolute neutrino mass scale in beta decay, $$ {m}_{
u_e} $$
, and neutrino-less double beta decay, mee, and the total mass of the neutrinos, Σ, which is most relevant in Cosmology.
860 citations
TL;DR: The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations.
Abstract: Background Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions...
782 citations
University of Rome Tor Vergata1, University of Alberta2, University of Lisbon3, Frederiksberg Hospital4, University of Naples Federico II5, Sheba Medical Center6, Mater Dei Hospital7, Royal London Hospital8, University College London9, The Catholic University of America10, Sapienza University of Rome11, Pennine Acute Hospitals NHS Trust12, Cleveland Clinic13, University of Barcelona14, St James's University Hospital15, University Medical Center Groningen16, Katholieke Universiteit Leuven17, University of Amsterdam18
TL;DR: Christian Maaser, a Andreas Sturm,b Stephan R. Vavricka,c Torsten Kucharzik,d Gionata Fiorino,e Vito Annese,f Emma Calabrese,f Daniel C. Baumgart,h Dominik Bettenworth,i Paula Borralho Nunes,j, Johan Burisch,k, Fabiana Castiglione,l Rami Eliakim,m Pierre Ellul,n Yago Gonz
Abstract: Christian Maaser,a Andreas Sturm,b Stephan R. Vavricka,c Torsten Kucharzik,d Gionata Fiorino,e Vito Annese,f Emma Calabrese,g Daniel C. Baumgart,h Dominik Bettenworth,i Paula Borralho Nunes,j, Johan Burisch,k, Fabiana Castiglione,l Rami Eliakim,m Pierre Ellul,n Yago González-Lama,o Hannah Gordon,p Steve Halligan,q Konstantinos Katsanos,r Uri Kopylov,m Paulo G. Kotze,s Eduards Krustiņš,t Andrea Laghi,u Jimmy K. Limdi,v Florian Rieder,w Jordi Rimola,x Stuart A. Taylor,y Damian Tolan,z Patrick van Rheenen,aa Bram Verstockt,bb, Jaap Stokercc; on behalf of the European Crohn’s and Colitis Organisation [ECCO] and the European Society of Gastrointestinal and Abdominal Radiology [ESGAR]
TL;DR: A Kavli Institute for Theoretical Physics workshop in July 2019 directed attention to the Hubble constant discrepancy and proposed solutions focused on the pre-recombination era as mentioned in this paper.
Abstract: A Kavli Institute for Theoretical Physics workshop in July 2019 directed attention to the Hubble constant discrepancy. New results showed that it does not appear to depend on the use of any one method, team or source. Proposed solutions focused on the pre-recombination era.
University of Paris-Sud1, University of California, Los Angeles2, Sheba Medical Center3, University of Barcelona4, Aix-Marseille University5, university of lille6, University of California, San Francisco7, University of Sydney8, Royal Prince Alfred Hospital9, The Royal Marsden NHS Foundation Trust10, University of Manchester11, Netherlands Cancer Institute12, Sunnybrook Health Sciences Centre13, Merck & Co.14, Royal North Shore Hospital15
TL;DR: Pembrolizumab improved progression-free survival and overall survival versus ipilimumab in patients with advanced melanoma and is now a standard of care in the first-line setting, however, the optimal duration of anti-PD-1 administration is unknown.
Abstract: Summary Background Pembrolizumab improved progression-free survival and overall survival versus ipilimumab in patients with advanced melanoma and is now a standard of care in the first-line setting. However, the optimal duration of anti-PD-1 administration is unknown. We present results from 5 years of follow-up of patients in KEYNOTE-006. Methods KEYNOTE-006 was an open-label, multicentre, randomised, controlled, phase 3 study done at 87 academic institutions, hospitals, and cancer centres in 16 countries. Patients aged at least 18 years with Eastern Cooperative Oncology Group performance status of 0 or 1, ipilimumab-naive histologically confirmed advanced melanoma with known BRAFV600 status and up to one previous systemic therapy were randomly assigned (1:1:1) to intravenous pembrolizumab 10 mg/kg every 2 weeks or every 3 weeks or four doses of intravenous ipilimumab 3 mg/kg every 3 weeks. Treatments were assigned using a centralised, computer-generated allocation schedule with blocked randomisation within strata. Exploratory combination of data from the two pembrolizumab dosing regimen groups was not protocol-specified. Pembrolizumab treatment continued for up to 24 months. Eligible patients who discontinued pembrolizumab with stable disease or better after receiving at least 24 months of pembrolizumab or discontinued with complete response after at least 6 months of pembrolizumab and then progressed could receive an additional 17 cycles of pembrolizumab. Co-primary endpoints were overall survival and progression-free survival. Efficacy was analysed in all randomly assigned patients, and safety was analysed in all randomly assigned patients who received at least one dose of study treatment. Exploratory assessment of efficacy and safety at 5 years' follow-up was not specified in the protocol. Data cutoff for this analysis was Dec 3, 2018. Recruitment is closed; the study is ongoing. This study is registered with ClinicalTrials.gov, number NCT01866319. Findings Between Sept 18, 2013, and March 3, 2014, 834 patients were enrolled and randomly assigned to receive pembrolizumab (every 2 weeks, n=279; every 3 weeks, n=277), or ipilimumab (n=278). After a median follow-up of 57·7 months (IQR 56·7–59·2) in surviving patients, median overall survival was 32·7 months (95% CI 24·5–41·6) in the combined pembrolizumab groups and 15·9 months (13·3–22·0) in the ipilimumab group (hazard ratio [HR] 0·73, 95% CI 0·61–0·88, p=0·00049). Median progression-free survival was 8·4 months (95% CI 6·6–11·3) in the combined pembrolizumab groups versus 3·4 months (2·9–4·2) in the ipilimumab group (HR 0·57, 95% CI 0·48–0·67, p Interpretation Pembrolizumab continued to show superiority over ipilimumab after almost 5 years of follow-up. These results provide further support for use of pembrolizumab in patients with advanced melanoma. Funding Merck Sharp & Dohme.
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Abstract: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
RMIT University1, University of Sydney2, University of Melbourne3, Hull York Medical School4, Carlos III Health Institute5, University of Barcelona6, Catalan Institution for Research and Advanced Studies7, University of Queensland8, University of New South Wales9, University of Adelaide10, University of Glasgow11, Pontifical Catholic University of Chile12, University of Toronto13, Centre for Addiction and Mental Health14, Deakin University15, Hofstra University16, Charité17, South London and Maudsley NHS Foundation Trust18, King's College London19, Manchester Academic Health Science Centre20, University of Salford21, University of Manchester22, University College London23, Dalhousie University24, Seconda Università degli Studi di Napoli25, Universidade Federal de Santa Maria26, Anglia Ruskin University27, University of Padua28, Park Centre for Mental Health29, Beth Israel Deaconess Medical Center30, The George Institute for Global Health31, Katholieke Universiteit Leuven32, National Research Council33
TL;DR: This Commission summarises advances in understanding on the topic of physical health in people with mental illness, and presents clear directions for health promotion, clinical care, and future research.
Karolinska Institutet1, Ghent University2, Eastern Virginia Medical School3, Université de Montréal4, Katholieke Universiteit Leuven5, Regeneron6, University of Pittsburgh7, University of Barcelona8, University of Pennsylvania9, Brigham and Women's Hospital10, Royal Brisbane and Women's Hospital11, St Thomas' Hospital12, Charité13, Humanitas University14, University of Pisa15, University of South Florida16, University of Amsterdam17, University of Fukui18
TL;DR: Dupilumab significantly improved the coprimary endpoints in both studies and was added to standard of care in adults with severe CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both.
TL;DR: An overview of how integrin function is regulated from both a biochemical and a mechanical perspective, affecting integrin cell-surface availability, binding properties, activation or clustering is provided, and how this biomechanical regulation allows integrins to respond to different ECM physicochemical properties and signals.
Abstract: Integrins, and integrin-mediated adhesions, have long been recognized to provide the main molecular link attaching cells to the extracellular matrix (ECM) and to serve as bidirectional hubs transmitting signals between cells and their environment. Recent evidence has shown that their combined biochemical and mechanical properties also allow integrins to sense, respond to and interact with ECM of differing properties with exquisite specificity. Here, we review this work first by providing an overview of how integrin function is regulated from both a biochemical and a mechanical perspective, affecting integrin cell-surface availability, binding properties, activation or clustering. Then, we address how this biomechanical regulation allows integrins to respond to different ECM physicochemical properties and signals, such as rigidity, composition and spatial distribution. Finally, we discuss the importance of this sensing for major cell functions by taking cell migration and cancer as examples.
Dresden University of Technology1, Brigham and Women's Hospital2, University of California, San Francisco3, University of Düsseldorf4, University of Pisa5, Northwestern University6, Medical University of Vienna7, University of Cyprus8, National and Kapodistrian University of Athens9, Medical University of South Carolina10, University of Cambridge11, University of Barcelona12, University Health Network13, The Feinstein Institute for Medical Research14, Toronto Western Hospital15, University of California, Los Angeles16, Humboldt University of Berlin17, Copenhagen University Hospital18, University of Michigan19, Harvard University20, University of the Basque Country21, University of Crete22, University of Kiel23, University Hospital Centre Zagreb24, University of Paris-Sud25, University of Hong Kong26, University of Calgary27, Hospital for Special Surgery28, University of Pécs29, University of Padua30, Medical University of Graz31, National Institutes of Health32, New York University33, Université Paris-Saclay34, University Hospital Complex Of Vigo35, University of Occupational and Environmental Health Japan36, University of Porto37, University of Leeds38, Leeds Teaching Hospitals NHS Trust39, Cedars-Sinai Medical Center40, Istanbul Bilim University41, McMaster University42, University of Toronto43, University of Paris44
TL;DR: These new classification criteria for systemic lupus erythematosus have excellent sensitivity and specificity, and were developed using rigorous methodology with multidisciplinary and international input.
Abstract: Objective To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects. Results The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria. Conclusion These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
National and Kapodistrian University of Athens1, University of Brescia2, Utrecht University3, University of Paris4, University of Barcelona5, Paris Descartes University6, University of Navarra7, Charité8, University of Kent9, Dubai Hospital10, University of Pisa11, University of Padua12, University Hospital of Bern13, Sheba Medical Center14, Karolinska University Hospital15, University of Lorraine16, National Institutes of Health17
TL;DR: Evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults based on evidence from a systematic literature review and expert opinion were formulated and voted.
Abstract: The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
TL;DR: The results suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero, which supports the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.
TL;DR: The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index.
Abstract: Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)8,9 and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
Mental Health Foundation1, King's College London2, South London and Maudsley NHS Foundation Trust3, University of Bath4, University of Cambridge5, University College London6, University of Palermo7, University of Bologna8, French Institute of Health and Medical Research9, Hospital General Universitario Gregorio Marañón10, University of Amsterdam11, University of Barcelona12, University of São Paulo13, Maastricht University Medical Centre14, University of Hong Kong15, University Medical Center Utrecht16
TL;DR: Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites, giving important implications for public health.
TL;DR: Tensions between the early and the late universe were discussed at the Kavli Institute for Theoretical Physics on July 15-17 2019 as mentioned in this paper to evaluate increasing evidence for these discrepancies, primarily in the value of the Hubble constant as well as ideas recently proposed to explain this tension.
Abstract: The standard cosmological model successfully describes many observations from widely different epochs of the Universe, from primordial nucleosynthesis to the accelerating expansion of the present day. However, as the basic cosmological parameters of the model are being determined with increasing and unprecedented precision, it is not guaranteed that the same model will fit more precise observations from widely different cosmic epochs. Discrepancies developing between observations at early and late cosmological time may require an expansion of the standard model, and may lead to the discovery of new physics. The workshop "Tensions between the Early and the Late Universe" was held at the Kavli Institute for Theoretical Physics on July 15-17 2019 (More details of the workshop (including on-line presentations) are given at the website: this https URL) to evaluate increasing evidence for these discrepancies, primarily in the value of the Hubble constant as well as ideas recently proposed to explain this tension. Multiple new observational results for the Hubble constant were presented in the time frame of the workshop using different probes: Cepheids, strong lensing time delays, tip of the red giant branch (TRGB), megamasers, Oxygen-rich Miras and surface brightness fluctuations (SBF) resulting in a set of six new ones in the last several months. Here we present the summary plot of the meeting that shows combining any three independent approaches to measure H$_0$ in the late universe yields tension with the early Universe values between 4.0$\sigma$ and 5.8$\sigma$. This shows that the discrepancy does not appear to be dependent on the use of any one method, team, or source. Theoretical ideas to explain the discrepancy focused on new physics in the decade of expansion preceding recombination as the most plausible. This is a brief summary of the workshop.
TL;DR: This is the most precise measurement of R_{K} to date and is compatible with the standard model at the level of 2.5 standard deviations.
Abstract: A measurement of the ratio of branching fractions of the decays
B
+
→
K
+
μ
+
μ
−
and
B
+
→
K
+
e
+
e
−
is presented. The proton-proton collision data used correspond to an integrated luminosity of
5.0
fb
−
1
recorded with the LHCb experiment at center-of-mass energies of 7, 8, and 13 TeV. For the dilepton mass-squared range
1.1
<
q
2
<
6.0
GeV
2
/
c
4
the ratio of branching fractions is measured to be
R
K
=
0.84
6
+
0.060
−
0.054
+
0.016
−
0.014
, where the first uncertainty is statistical and the second systematic. This is the most precise measurement of
R
K
to date and is compatible with the standard model at the level of 2.5 standard deviations.
TL;DR: Animal models have started to reveal the complexity of the underlying pathogenic mechanisms and will lead to novel treatments beyond immunotherapy, and future studies should aim at identifying prognostic biomarkers and treatments that accelerate recovery.
Abstract: The identification of anti-NMDA receptor (NMDAR) encephalitis about 12 years ago made it possible to recognise that some patients with rapidly progressive psychiatric symptoms or cognitive impairment, seizures, abnormal movements, or coma of unknown cause, had an autoimmune disease. In this disease, autoantibodies serve as a diagnostic marker and alter NMDAR-related synaptic transmission. At symptom onset, distinguishing the disease from a primary psychiatric disorder is challenging. The severity of symptoms often requires intensive care. Other than clinical assessment, no specific prognostic biomarkers exist. The disease is more prevalent in women (with a female to male ratio of around 8:2) and about 37% of patients are younger than 18 years at presentation of the disease. Tumours, usually ovarian teratoma, and herpes simplex encephalitis are known triggers of NMDAR autoimmunity. About 80% of patients improve with immunotherapy and, if needed, tumour removal, but the recovery is slow. Animal models have started to reveal the complexity of the underlying pathogenic mechanisms and will lead to novel treatments beyond immunotherapy. Future studies should aim at identifying prognostic biomarkers and treatments that accelerate recovery.
TL;DR: European trends in CRC incidence and mortality in subjects younger than 50 years, consistent with an age-cohort phenomenon, are analyzed and screening guidelines may need to be reconsidered.
Abstract: Objective The incidence of colorectal cancer (CRC)
declines among subjects aged 50 years and above. An
opposite trend appears among younger adults. In Europe,
data on CRC incidence among younger adults are
lacking. We therefore aimed to analyse European trends
in CRC incidence and mortality in subjects younger than
50 years.
Design Data on age-related CRC incidence and
mortality between 1990 and 2016 were retrieved from
national and regional cancer registries. Trends were
analysed by Joinpoint regression and expressed as
annual percent change.
Results We retrieved data on 143.7million people
aged 20–49 years from 20 European countries. Of
them, 187 918 (0.13%) were diagnosed with CRC. On
average, CRC incidence increased with 7.9% per year
among subjects aged 20–29 years from 2004 to 2016.
The increase in the age group of 30–39 years was 4.9%
per year from 2005 to 2016, the increase in the age
group of 40–49 years was 1.6% per year from 2004
to 2016. This increase started earliest in subjects aged
20–29 years, and 10–20 years later in those aged 30–39
and 40–49 years. This is consistent with an age-cohort
phenomenon. Although in most European countries the
CRC incidence had risen, some heterogeneity was found
between countries. CRC mortality did not significantly
change among the youngest adults, but decreased with
1.1%per year between 1990 and 2016 and 2.4% per
year between 1990 and 2009 among those aged 30–39
years and 40–49 years, respectively.
Conclusion CRC incidence rises among young
adults in Europe. The cause for this trend needs to be
elucidated. Clinicians should be aware of this trend. If
the trend continues, screening guidelines may need to be
reconsidered.
TL;DR: In this paper, a new pentaquark state, P_{c}(4312)+, was discovered with a statistical significance of 7.3σ in a data sample of Λ_{b}^{0}→J/ψpK^{-} decays, which is an order of magnitude larger than that previously analyzed by the LHCb Collaboration.
Abstract: A narrow pentaquark state, P_{c}(4312)^{+}, decaying to J/ψp, is discovered with a statistical significance of 7.3σ in a data sample of Λ_{b}^{0}→J/ψpK^{-} decays, which is an order of magnitude larger than that previously analyzed by the LHCb Collaboration. The P_{c}(4450)^{+} pentaquark structure formerly reported by LHCb is confirmed and observed to consist of two narrow overlapping peaks, P_{c}(4440)^{+} and P_{c}(4457)^{+}, where the statistical significance of this two-peak interpretation is 5.4σ. The proximity of the Σ_{c}^{+}D[over ¯]^{0} and Σ_{c}^{+}D[over ¯]^{*0} thresholds to the observed narrow peaks suggests that they play an important role in the dynamics of these states.
TL;DR: A novel genetically-engineered mouse model of HCC enables interrogating how different genetic alterations affect immune surveillance and response to immunotherapies and shows that β-catenin activation promotes immune escape and resistance to anti-PD-1 and could represent a novel biomarker for HCC patient exclusion.
Abstract: PD-1 immune checkpoint inhibitors have produced encouraging results in hepatocellular carcinoma (HCC) patients. However, what determines resistance to anti-PD-1 therapies is unclear. We created a novel genetically-engineered mouse model of HCC that enables interrogating how different genetic alterations affect immune surveillance and response to immunotherapies. Expression of exogenous antigens in MYC;p53-/- HCCs led to T cell-mediated immune surveillance, which was accompanied by decreased tumor formation and increased survival. Some antigen-expressing MYC;p53-/- HCCs escaped the immune system by upregulating β-catenin (CTNNB1) pathway. Accordingly, expression of exogenous antigens in MYC;CTNNB1 HCCs had no effect, demonstrating that β-catenin promoted immune escape, which involved defective recruitment of dendritic cells and consequently, impaired T cell activity. Expression of chemokine Ccl5 in antigen-expressing MYC;CTNNB1 HCCs restored immune surveillance. Finally, β-catenin-driven tumors were resistant to anti-PD-1. In summary, β-catenin activation promotes immune escape and resistance to anti-PD-1 and could represent a novel biomarker for HCC patient exclusion.
TL;DR: Who, when, if and how to screen for PH will be addressed, as will the current state of knowledge with regard to the role of treatment with pulmonary vasoactive agents.
Abstract: Pulmonary hypertension (PH) frequently complicates the course of patients with various forms of chronic lung disease (CLD). CLD-associated PH (CLD-PH) is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. The aetiology of CLD-PH is complex and multifactorial, with differences in the pathogenic sequelae between the diverse forms of CLD. Haemodynamic evaluation of PH severity should be contextualised within the extent of the underlying lung disease, which is best gauged through a combination of physiological and imaging assessment. Who, when, if and how to screen for PH will be addressed in this article, as will the current state of knowledge with regard to the role of treatment with pulmonary vasoactive agents. Although such therapy cannot be endorsed given the current state of findings, future studies in this area are strongly encouraged.
Imperial College London1, Drugs for Neglected Diseases Initiative2, Kirby Institute3, Harvard University4, Universidade Federal do Rio Grande do Sul5, King's College6, Toronto General Hospital7, University of Washington8, Aga Khan University9, Burnet Institute10, Monash University11, University of Barcelona12, University of Lagos13, Alaska Native Tribal Health Consortium14, University of Cape Town15, Johns Hopkins University School of Medicine16, Centers for Disease Control and Prevention17
TL;DR: Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020.