tbuckley/cabot-search huggingface dataset:
AB0670 Short and long-term treatment with infliximab in retinal vasculitis of behÇet’s disease. multicenter study of 72 patients
Authors: J.L. Martín-Varillas, V. Calvo-Río, R. Demetrio-Pablo, B. Atienza-Mateo, J. Loricera, M.V. Hernández, A. Adán, M. Mesquida, D. Peiteado, E. Pato, D. Díaz, L. Martínez, E. Valls, M.A. Caracuel, A.M. García, J.M. Herreras, M. Cordero, C. Montilla, A. Fonollosa, A. Atanes, F.F. Hernández, I. Torre, O. Maíz, A. Blanco, C. Espartero, N. Ortego, E. Raya, M. Gandía, F.J. López, M. Alcalde, C. Fernández, Ó. Ruiz, F. Jiménez, R. Almodovar, C. Carrasco, L. Linares, F. Romero, S. Insua, S. González, M. Hernández, E. Beltrán, J. Cruz, C. Fernández, E. Aurrecoechea, M.A. González-Gay, R. Blanco
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Retinal vasculitis (RV) is a serious complication of uveitis due to Behçet's disease (BD).<sup><b>1–2</b></sup> <h3>Objectives</h3> We assess the short/long-term efficacy of Infliximab (IFX) in refractory RV of BD. <h3>Methods</h3> Multicenter study of patients with RV of BD refractory to corticosteroids and at least 1 conventional immunosuppressant (IS). We compared efficacy of IFX between baseline, 1st week, 1–6 months and 1–6 years. <h3>Results</h3> 72 patients/129 affected eyes (40♂/32♀) with mean age of 39.6±9.7 years. HLA-B51 was (+) in 63%. Before IFX onset, patients had received: oral/e.v. glucocorticoids (n=98), CyA (n=56), AZA (n=43), MTX (n=34) and other IS (n=22). IFX was used as monotherapy in 17 patients and combined with conventional IS in the remaining 55. IFX dose was as follows: 3 mg/kg/4–8 w (n=5), 4 mg/kg/4 w (n=1), 5–5.5 mg/kg/4–8 w (n=66). Following IFX onset, an improvement in RV was seen, as well as in the other ocular outcomes. This enhancement was maintained (table 1). After a mean follow-up of 26.5±22.1 months, IFX was discontinued in 44: remission (n=15), primary failure (n=16), preference of another route of administration (n=8), pregnancy (n=1) and adverse effects (n=4). <h3>Conclusions</h3> IFX seems an effective short/long-term treatment in RV of BD. <h3>References</h3> [1] Calvo-Río V, Blanco R, Beltrán E, et al. Anti-TNF-alfa therapy in patients with refractory uveitis due to Behçet's disease: a 1-year-follow-up study of 124 patients. Rheumatol. 2014; 53(12):2223–31 [2] Santos-Gómez M, Calvo-Río V, Blanco R, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet's disease: results of a multicentre open-label study. Clin Exp Rheumatol. 2016; 34 (6Suppl 102):S34-S40 <h3>Disclosure of Interest</h3> None declared
Abstract 17415: Generation of Cardiac/Skeletal Myogenic Progenitors From Human Induced Pluripotent Stem Cells Using a Small Molecule
Authors: Ibrahim Elmadbouh, Yaoliang Tang, Muhammad Ashraf
Journal: Circulation (2017)

Background: The aim was to evaluate the conversion of human induced pluripotent stem cells (hiPSCs) into cardiac (CMPs) or skeletal myogenic progenitors (SMPs) with a single small molecule for cell...
Abstract 19603: Chronic Loop Diuretic Treatment Induces Tubular Remodeling via IGF-1R Dependent and IGF-1R Independent Signaling
Authors: Aram J Krauson, Elisabeth M Walczak, Jon M Nizar, Ragwa Elsayed, Sonali M Iyer, Vivek Bhalla
Journal: Circulation (2017)

Introduction: Furosemide, a loop diuretic for management of heart failure, inhibits sodium reabsorption in the thick ascending limb. Chronic use leads to tubular hypertrophy, resistance with higher...
Multiple myeloma-derived exosomes are enriched of amphiregulin (AREG) and activate the epidermal growth factor pathway in the bone microenvironment leading to osteoclastogenesis
Authors: Stefania Raimondo, Laura Saieva, Emanuela Vicario, Marzia Pucci, Denise Toscani, Mauro Manno, Samuele Raccosta, Nicola Giuliani, Riccardo Alessandro
Journal: Journal of Hematology & Oncology (2019)

Multiple myeloma (MM) is a clonal plasma cell malignancy associated with osteolytic bone disease. Recently, the role of MM-derived exosomes in the osteoclastogenesis has been demonstrated although the underlying mechanism is still unknown. Since exosomes-derived epidermal growth factor receptor ligands (EGFR) are involved in tumor-associated osteolysis, we hypothesize that the EGFR ligand amphiregulin (AREG) can be delivered by MM-derived exosomes and participate in MM-induced osteoclastogenesis. Exosomes were isolated from the conditioned medium of MM1.S cell line and from bone marrow (BM) plasma samples of MM patients. The murine cell line RAW264.7 and primary human CD14+ cells were used as osteoclast (OC) sources. We found that AREG was specifically enriched in exosomes from MM samples and that exosomes-derived AREG led to the activation of EGFR in pre-OC, as showed by the increase of mRNA expression of its downstream SNAIL in both RAW264.7 and CD14+ cells. The presence of neutralizing anti-AREG monoclonal antibody (mAb) reverted this effect. Consequently, we showed that the effect of MM-derived exosomes on osteoclast differentiation was inhibited by the pre-treatment of exosomes with anti-AREG mAb. In addition, we demonstrated the ability of MM-derived AREG-enriched exosomes to be internalized into human mesenchymal stromal cells (MSCs) blocking osteoblast (OB) differentiation, increasing MM cell adhesion and the release of the pro-osteoclastogenic cytokine interleukin-8 (IL8). Accordingly, anti-AREG mAb inhibited the release of IL8 by MSCs suggesting that both direct and indirect effects are responsible for AREG-enriched exosomes involvement on MM-induced osteoclastogenesis. In conclusion, our data indicate that AREG is packed into MM-derived exosomes and implicated in OC differentiation through an indirect mechanism mediated by OBs.
Co-Targeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Refractory Mantle Cell Lymphoma with Complex Karyotype Changes
Authors: Pavel Klener, Marek Trněný, Ladislav Andera, Zuzana Nahacka, Magdalena Klanova, Jana Karolova, Michael Svaton, Ondrej Havranek, Jan Soukup, Zuzana Zemanova, Diana Tuskova, Eva Pokorna, Kristina Forsterova, Petra Vockova, Eva Fronkova, Dana Prukova
Journal: Blood (2018)
The Incidence of Post-Thrombotic Syndrome after the Treatment of Upper Extremity Deep Vein Thrombosis with Oral Rivaroxaban
Authors: Kirill Lobastov, Victor Barinov, Iliya Schastlivtsev, Leonid Laberko, Grigory Rodoman, Sergey Zhuravlev, Valeriy Boyarintsev
Journal: Blood (2018)
Immune cell constitution in bone marrow microenvironment predicts outcome in adult ALL
Authors: Helena Hohtari, Oscar Brück, Sami Blom, Riku Turkki, Marjatta Sinisalo, Panu E. Kovanen, Olli Kallioniemi, Teijo Pellinen, Kimmo Porkka, Satu Mustjoki
Journal: Leukemia (2019)

As novel immunological treatments are gaining a foothold in the treatment of acute lymphoblastic leukemia (ALL), it is elemental to examine ALL immunobiology in more detail. We used multiplexed immunohistochemistry (mIHC) to study the immune contexture in adult precursor B cell ALL bone marrow (BM). In addition, we developed a multivariate risk prediction model that stratified a poor survival group based on clinical parameters and mIHC data. We analyzed BM biopsy samples of ALL patients (n = 52) and healthy controls (n = 14) using mIHC with 30 different immunophenotype markers and computerized image analysis. In ALL BM, the proportions of M1-like macrophages, granzyme B+CD57+CD8+ T cells, and CD27+ T cells were decreased, whereas the proportions of myeloid-derived suppressor cells and M2-like macrophages were increased. Also, the expression of checkpoint molecules PD1 and CTLA4 was elevated. In the multivariate model, age, platelet count, and the proportion of PD1+TIM3+ double-positive CD4+ T cells differentiated a poor survival group. These results were validated by flow cytometry in a separate cohort (n = 31). In conclusion, the immune cell contexture in ALL BM differs from healthy controls. CD4+PD1+TIM3+ T cells were independent predictors of poor outcome in our multivariate risk model, suggesting that PD1 might serve as an attractive immuno-oncological target in B-ALL.
Abstract 16126: NOAC Dosing in Patients With Atrial Fibrillation and Kidney Disease: Insights From the Veterans Health Administration TREAT-AF Study
Authors: George Leef, Jun Fan, Mariam Askari, Alexander C Perino, Fahd N Yunus, Andrew Cluckey, Abhishek Deshmukh, Mintu P Turakhia
Journal: Circulation (2017)

Introduction: In chronic kidney disease (CKD), elimination of non-vitamin K antagonist oral anticoagulants (NOACs) is impaired and dose reductions are specified in FDA labeling. Recent studies have...
Discovery of Novel Androgen Receptor Ligands by Structure-Based Virtual Screening and Bioassays
Authors: Wenfang Zhou, Mojie Duan, Weitao Fu, Jinping Pang, Qin Tang, Huiyong Sun, Lei Xu, Shan Chang, Dan Li, Tingjun Hou
Journal: Genomics Proteomics & Bioinformatics (2018)

Abstract Androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling pathway. Therefore, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening (VS) on the basis of the crystal structure of the AR ligand binding domain (LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them (HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC50 values of HBP1-51 and HBP1-58 are 3.96 µM and 4.92 µM, respectively, which are even lower than that of enzalutamide (Enz, IC50 = 13.87 µM), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics (MD) simulations and principal components analysis (PCA) were carried out to reveal the binding principle of the newly-identified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary, the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases.
Extracorporeal Photopheresis for First Line Treatment of Acute Graft Versus Host Disease
Authors: Florent Malard, Simona Sestili, Sandra Eder, Ramdane Belhocine, Annalisa Ruggeri, Giorgia Battipaglia, Eolia Brissot, Clemence Mediavilla, Remy Dulery, Mohamad Mohty
Journal: Blood (2018)
Publisher Correction: The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group
Authors: Nelson Leung, Frank Bridoux, Vecihi Batuman, Aristeidis Chaidos, Paul Cockwell, Vivette D. D’Agati, Angela Dispenzieri, Fernando C. Fervenza, Jean- Paul Fermand, Simon Gibbs, Julian D. Gillmore, Guillermo A. Herrera, Arnaud Jaccard, Dragan Jevremovic, Efstathios Kastritis, Vishal Kukreti, Robert A. Kyle, Helen J. Lachmann, Christopher P. Larsen, Heinz Ludwig, Glen S. Markowitz, Giampaolo Merlini, Peter Mollee, Maria M. Picken, Vincent S. Rajkumar, Virginie Royal, Paul W. Sanders, Sanjeev Sethi, Christopher P. Venner, Peter M. Voorhees, Ashutosh D. Wechalekar, Brendan M. Weiss, Samih H. Nasr
Journal: Nature Reviews Nephrology (2018)
Chronic Kidney Disease, Hypertension and Cardiovascular Sequelae during Long Term Follow up of Adults with Atypical Hemolytic Uremic Syndrome
Authors: Shruti Chaturvedi, Alison R. Moliterno, Samuel A. Merrill, Evan M Braunstein, Xuan Yuan, Christopher John Sperati, Gebran Khneizer, Robert A. Brodsky
Journal: Blood (2018)
Reducing the Expert Halo Effect on Pharmacy and Therapeutics Committees
Authors: Jared P. Austin, Stephanie A. C. Halvorson
Journal: JAMA (2019)

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AB0110 Serum and salivary iga1 and iga2 acpa subclasses in established rheumatoid arthritis and associations to smoking
Authors: A. Svärd, K. Roos Ljungberg, A. Kastbom, T. Skogh, K. Martinsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> A prevailing hypothesis regarding the pathogenesis of rheumatoid arthritis (RA) involves an association between mucosal immunity and the development of RA. A pathogenetic role for antibodies against citrullinated peptides (ACPA) is assumed, and there are indications of mucosal immunisation in the lungs, the oral mucosa and the intestinal mucosa preceding overt RA.<sup>1</sup> IgA antibodies are produced both locally, at mucosal membranes, and systemically. Among the two IgA subtypes, IgA1 dominates in serum IgA2 in mucosal secretions. We have previously reported the presence of ACPA of IgA isotype in both serum and saliva of RA patients,<sup>2</sup> and that IgA ACPA is associated with cigarette smoking.<sup>3</sup> <h3>Objectives</h3> To investigate the presence and levels of mucosal and circulating IgA1 and IgA2 isotypes of ACPA in patients with RA, and to investigate their association to cigarette smoking habits. <h3>Methods</h3> Patients with established RA, mean disease duration of 12.2 years (n=196), and healthy controls (n=101), included in the Secretory Antibodies in Rheumatoid Arthritis (SARA) study were analysed by enzyme immunoassays regarding total IgA ACPA and the subclasses IgA1 and IgA2 ACPA in serum and saliva. The results are presented as delta-values of optical density (OD) between each IgA ACPA subclass and the corresponding arginine peptide. <h3>Results</h3> Serum IgA1 ACPA was detected in 44% of the RA patients and serum IgA2 in 39%. 10% of the RA patients had detectable salivary IgA1 and/or IgA2 ACPA. Both serum and salivary IgA2 levels were higher among smokers than never-smokers, while this association was not seen for IgA1 class antibodies. <h3>Conclusions</h3> In this study of patients with established RA, IgA2 ACPA but not IgA1 ACPA was associated to cigarette smoking. As IgA2 predominate over IgA1 in mucosal secretions, this finding strengthens the hypothesis that smoking via mucosal ACPA production is one pathway to develop RA. <h3>References</h3> [1] Tracy A, Buckley CD, Raza K. Pre-symptomatic autoimmunity in rheumatoid arthritis: when does the disease start?Seminars in immunopathology2017;39(4):423–35. [2] Svärd A, Kastbom A, Sommarin Y, Skogh T. Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis. Immunobiology2013;218(2):232–7. [3] Svärd A, Skogh T, Alfredsson L, Ilar A, Klareskog L, Bengtsson C, et al. Associations with smoking and shared epitope differ between IgA- and IgG-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis. Arthritis Rheumatol2015;67(8):2032–7. <h3>Disclosure of Interest</h3> None declared
Abstract 20797: Sphingosine-1-Phosphate Receptor Agonist Fingolimod After Prolonged Circulatory Arrest Improves Cardiac and Neurological Outcomes in a Rat Model of Extracorporeal Life Support.
Authors: Alessio Rungatscher, Daniele Linardi, Livio San Biagio, Maria Giovanna Berton, Nasser Ahmed, Maddalena Tessari, Giovanni Battista Luciani, Giuseppe Faggian
Journal: Circulation (2016)

Introduction: Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for the treatment of multiple sclerosis and exerts anti-inflammatory and antiapoptotic properties. Hypothesis: We hypot...
Safety and Efficacy of Venetoclax (VEN) in Combination with Bendamustine (B) Plus Rituximab (R) or Obinutuzumab (G) in Patients (pts) with Previously Untreated Chronic Lymphocytic Leukemia (CLL): Results from a Phase Ib Study (GO28440)
Authors: Stephan Stilgenbauer, Franck Morschhauser, Clemens-Martin Wendtner, Guillaume Cartron, Michael Hallek, Barbara Eichhorst, Mark F. Kozloff, Thomas Giever, Gerard Lozanski, Yanwen Jiang, Huang Huang, Daniela Soriano Pignataro, William Schary, Kathryn Humphrey, Mehrdad Mobasher, Gilles Salles
Journal: Blood (2018)
SAT0405 Findings of a cohort of patients with chikungunya in a colombian population
Authors: M.A. López, R. Badillo, E. Rojas, M. Gelvez, Y. Santamaría
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chikungunya virus is a Togaviridae family virus transmitted by mosquitoes, which generates febrile syndrome with joint pain. It has been widely studied for the findings of chronic inflammatory polyarthropathy similar to rheumatoid arthritis. In Colombia, an epidemic occurred between 2014 and 2015, which was studied in several cities. International meta-analyses have shown a prevalence of 32.13% in the follow-up cohorts greater than 18 months. At present, this issue has gained a new opportunity due to the appearance of new outbreaks in Italy and France, after 10 years of the first epidemic. <h3>Objectives</h3> To compare the clinical findings of a cohort of patients with Chikungunya in the subacute phase and the chronic phase. <h3>Methods</h3> Follow-up of 70 patients who attended Chikungunya in a Colombian population who were evaluated in person by a rheumatologist, initially at 40 days after the disease and after two years. <h3>Results</h3> The average age of the study participants was 59.88 years, being more frequent in women with 78.6% of the cases. 40% of the cases were older than 65 years, with the older adult population being a representative part of the cases. The history of osteoarthrosis occurred in 11.7% of cases. There was no history of systemic lupus erythematosus. The most frequent symptoms presented at the first visit (outbreak context) were as follows, in order: Joint pain (71.4%), morning stiffness (48.6%), Metacarpophalangeal compression test (51.2%). The most frequent symptoms in the second visit (two years after the outbreak) were: joint pain (74.2%), morning stiffness (21.4%) and metacarpophalangeal compression test (17.1%). At the time of the second visit, the clinical findings were classified by diseases, according to the rheumatologist’s assessment as follows: Post-Chikungunya polyarthropathy (17.1%), Fibromyalgia (10%), Carpal tunnel syndrome (17.1%), Osteoarthritis of knees (32.8), osteoarthritis of distal interphalangeal (20%), painful shoulder syndrome (17.1%), tenosynovitis (18.6%), gout (1.4%), sequelae of fracture of hip (1.4%), lateral epicondylitis (1.4%). 28.5% of the cases had no diagnosis of rheumatological pathology. Of the total cases, only 24.3% (17 people) had symptoms for more than 6 weeks. <h3>Conclusions</h3> Chikungunya virus infection increases the prevalence of joint and extra-articular rheumatological diseases in the Colombian population evaluated. <h3>References</h3> [1] Rodríguez- Morales A, et al. Prevalence of post-Chikungunya Chronic Inflammatory Rheumatism: A Systematic Review and Meta-Analysis2016. [2] Campion E. Chikungunya Virus and the Global Spread of a Mosquito-Borne Disease. NEJM2015. [3] CDC. Chikungunya in Italy2017. <h3>Acknowledgements</h3> Association Colombian of rheumatology The epidemiological research centre, Industrial University of Santander. <h3>Disclosure of Interest</h3> None declared
Abstract 17020: Increasing Tachycardic Asymmetry in Heart Rate Variability is Associated With Sudden Cardiac Death in a Community Cohort: The Atherosclerotic Risk in Community Study
Authors: Aron Bender, Muammar Kabir, Jason Thomas, Golriz Sedaghat, Srini Mukundan, David German, Nona Sotoodehnia, Wendy S Post, Scott D Solomon, Elsayed Z Soliman, David S Siscovick, Larisa G Tereshchenko
Journal: Circulation (2017)

Introduction: Poincare plot asymmetry has been associated with sustained ventricular tachyarrhythmias, implicating involvement of the autonomic nervous system. Porta’s index provides a quantitative assessment of the degree and direction of temporal asymmetry in heart rate variability (HRV), either toward relative bradycardia or tachycardia. The association between temporal asymmetry of HRV with sudden cardiac death (SCD) in the general population has not been previously studied. Hypothesis: We hypothesized that temporal asymmetry in HRV is associated with SCD. Methods: We analyzed index visit 10-second ECGs in 14,250 participants of the Atherosclerosis Risk in Communities (ARIC) cohort (mean age 54.1±5.87y; 6,380 [45%] men; 10,569 [74%] white, 1,582 [11%] with prevalent cardiovascular disease (CVD)). Participants with atrial fibrillation, premature contractions, or second- or third- degree SA or AV block were excluded. Only normal sinus beats were included in the semi-automated analysis, which was validat...