Institution
Hospital Universitario La Paz
Healthcare•Madrid, Spain•
About: Hospital Universitario La Paz is a healthcare organization based out in Madrid, Spain. It is known for research contribution in the topics: Population & Medicine. The organization has 8960 authors who have published 11499 publications receiving 191509 citations.
Topics: Population, Medicine, Cancer, Transplantation, Haemophilia
Papers published on a yearly basis
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TL;DR: RASFib production of IL-15 induces the proinflammatory cytokines TNF-α, IFN-γ, and IL-17 in cocultured TLs through a cell contact-dependent mechanism, thereby creating a feedback loop that favors persistent synovial inflammation.
Abstract: To characterize the molecules responsible for synovial fibroblast-T lymphocyte (TL) cross-talk in rheumatoid arthritis (RA), synovial fibroblasts from patients with established RA (RASFibs) were cocultured with TLs from peripheral blood of early RA patients (RAPBTL). TLs from peripheral blood of healthy controls and from synovial fluid of RA served as controls. Adhesion molecules and cytokines were determined by flow cytometry, ELISA, and real-time PCR. RAPBTL (n = 20) induced an up-regulation of ICAM-1, intracellular IL-8, IL-6, IL-15, and surface IL-15 in cocultured RASFibs. In turn, RAPBTL showed an up-regulation of TNF-alpha, IFN-gamma, IL-17, CD25, and CD69 expression. Responses seen with TLs from peripheral blood of healthy controls (n = 20) were significantly lower, whereas responses with TLs from synovial fluid of RA (n = 20) were maximal. Blocking Abs to IL-15 and CD54, but not an isotype-control Ab, down-regulated the increased TL cytokine and activation marker expression. Abs to CD69, CD11a, IL-17, TNF-alpha, and IFN-gamma significantly decreased the up-regulation of RASFib cytokine and CD54 expression. Cocultures using 0.4- micro m inserts did not result in up-regulation of surface molecules or cytokines. Methotrexate significantly inhibited RASFib/TL cross-talk signals and decreased adhesion of TL to RASFibs. In summary, RASFib production of IL-15 induces the proinflammatory cytokines TNF-alpha, IFN-gamma, and IL-17 in cocultured TLs through a cell contact-dependent mechanism. In turn, these cytokines stimulate the expression of IL-15, IL-8, and IL-6 in RASFibs, thereby creating a feedback loop that favors persistent synovial inflammation. Methotrexate seems to disrupt this loop by decreasing cell adhesion.
142 citations
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University of North Carolina at Chapel Hill1, University Health Network2, University of Virginia3, Wrocław Medical University4, Jagiellonian University Medical College5, University of Southern California6, Hospital Universitario La Paz7, Karolinska University Hospital8, Katholieke Universiteit Leuven9, University of South Florida10, Catholic University of the Sacred Heart11, Ohio State University12, University of California, Irvine13, Texas A&M University14, Leiden University Medical Center15
TL;DR: The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantIBodies with efgartigimod may offer an innovative approach to treat MG.
Abstract: Objective To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. Methods A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity. Results Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement. Conclusions Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG. Classification of evidence This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.
142 citations
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Agostino Gemelli University Polyclinic1, Catholic University of the Sacred Heart2, University of Cologne3, University of Milan4, University of California, San Diego5, Medical University of Graz6, University of Cambridge7, University of Insubria8, University of Milano-Bicocca9, Ankara University10, Masaryk University11, Churchill Hospital12, Autonomous University of Barcelona13, University Medical Center Groningen14, Palacký University, Olomouc15, Hamad Medical Corporation16, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico17, King's College London18, University of Rijeka19, Hospital General Universitario Gregorio Marañón20, Gomel State Medical University21, University of Szeged22, Mansoura University23, Marmara University24, Katholieke Universiteit Leuven25, Karolinska University Hospital26, University of Rome Tor Vergata27, Vanderbilt University Medical Center28, Hospital Universitario La Paz29, University of Belgrade30, Sultan Qaboos University31, Spanish National Research Council32, Wrocław Medical University33, University of Hamburg34, University Hospital of Basel35, Innsbruck Medical University36, Paris-Sorbonne University37, University of Montpellier38, Federal University of Rio de Janeiro39, University Hospital Centre Zagreb40, University of Zagreb41
TL;DR: In this paper, the authors studied the risk factors for adverse outcomes in patients with hematological malignancies (HM) who developed COVID-19 and analyzed predictors of mortality.
Abstract: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.
141 citations
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TL;DR: The long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent and the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine.
Abstract: The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.
141 citations
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Charles University in Prague1, University Hospital of Basel2, Vilnius University3, Washington University in St. Louis4, Duke University5, Georgetown University6, The Royal Marsden NHS Foundation Trust7, Vanderbilt University Medical Center8, University of Bern9, University of Pennsylvania10, European Institute of Oncology11, University of Paris12, University of Cyprus13, National and Kapodistrian University of Athens14, University of Vienna15, Charité16, University of Göttingen17, Tel Aviv University18, University of Zurich19, University of Warwick20, Serbian Academy of Sciences and Arts21, University of Ljubljana22, Academy for Urban School Leadership23, Leiden University24, American University of Beirut25, University Hospital of Bern26, Hospital Universitario La Paz27, University Medical Center Groningen28, Imperial College London29
TL;DR: Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio‐oncology biomarker research is discussed.
Abstract: Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.
141 citations
Authors
Showing all 9020 results
Name | H-index | Papers | Citations |
---|---|---|---|
Jaakko Tuomilehto | 115 | 1285 | 210682 |
Vincent Soriano | 87 | 762 | 34084 |
Lina Badimon | 86 | 682 | 35774 |
Francisco J. Blanco | 84 | 789 | 33319 |
Michael A. Gatzoulis | 82 | 478 | 32562 |
Jose Lopez-Sendon | 81 | 460 | 41809 |
Victor Moreno | 80 | 635 | 31511 |
Joaquín Dopazo | 75 | 396 | 24790 |
Fernando Rodríguez-Artalejo | 74 | 512 | 23296 |
José R. Banegas | 74 | 421 | 28249 |
Michael Becker | 72 | 317 | 18189 |
Gianfranco Ferraccioli | 70 | 402 | 26515 |
Maria-Victoria Mateos | 66 | 480 | 24278 |
Manuel Romero-Gómez | 64 | 420 | 19006 |
Eulogio García | 63 | 270 | 15354 |