tbuckley/cabot-search huggingface dataset:
FRI0329 The net-effect of combining rituximab with belimumab in severe systemic lupus erythematosus
Authors: O. Teng, T. Kraaij, S. Kamerling, E. de Rooy, P. van Daele, O. Bredewold, J. Bakker, I. Bajema, H. Scherer, R. Toes, T. Huizinga, T. Rabelink, C. van Kooten
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In systemic lupus erythematosus (SLE) patients, excessive formation of neutrophil extracellular traps (NETs) is observed while their degradation is impaired. <i>In vitro</i>, immune complexes (ICx) trigger NET formation while NET-derived DNA is a postulated autoantigen for anti-nuclear autoantibodies (ANAs), found in SLE. Based on these self-perpetuating mechanisms in SLE, we hypothesised that interfering with ICx formation should regress NET formation and potentially ameliorate disease. Objectives: Investigate the effect of Rituximab+Belimumab therapy on pathogenic autoantibodies in relation to NET formation in severe refractory SLE <h3>Methods</h3> A phase 2A, open-label, single arm proof-of-concept study was performed wherein 16 SLE patients with severe, refractory disease were treated with a combination of CD20-mediated B-cell depletion with rituximab and sustained inhibition of B-cell activating factor with belimumab. Besides safety, the study's endpoints were chosen to address the concept of autoantibodies in relation to excessive NET formation. <h3>Results</h3> We demonstrated that SLE-derived immobilised IgG, but not soluble IgG, induced excessive NET formation, confirming <i>ex vivo</i> that ICx mediate excessive NET formation in SLE. We showed that therapeutic intervention with RTX+BLM led to specific reductions in ANAs and regression of excessive NET formation. RTX+BLM appeared to be safe and achieved clinically significant responses: low lupus disease activity state was achieved in 10 patients, renal responses in 11 patients and concomitant immunosuppressive medication was tapered in 14 out of the 16 patients. <h3>Conclusions</h3> This study provides novel insights into clinical beneficence of reducing excessive NET formation in SLE by therapeutic targeting ANA production with RTX+BLM. Altogether putting forward a new treatment concept that specifically ameliorates underlying SLE pathophysiology. <h3>Acknowledgements</h3> We thank professor C. Pusey (Imperial College London, UK) for kindly providing the Syk inhibitor R406 for our experiments. <h3>Disclosure of Interest</h3> O. Teng Grant/research support from: GlaxoSmithKline, Consultant for: Aurinia Pharmaceuticals, GlaxoSmithKline, T. Kraaij: None declared, S. Kamerling: None declared, E. de Rooy: None declared, P. van Daele: None declared, O. Bredewold: None declared, J. Bakker: None declared, I. Bajema: None declared, H. Scherer: None declared, R. Toes: None declared, T. Huizinga: None declared, T. Rabelink: None declared, C. van Kooten: None declared
Raising awareness of non-technical skills in operating theatres
Authors: Simon Paterson-Brown, George Youngson, Craig McIlhenny, Nikki Maran, Rhona Flin, Steve Yule
Journal: BMJ (2019)

The effects of surgical egos and poor behaviour on teamwork, clinical performance, and patient outcomes have been recognised for some time but are often poorly understood and very poorly managed.1 Although action must be taken to educate and if possible rescue poor performers, they may sometimes need to be removed from the clinical frontline—often a …
High-Throughput T Cell Receptor (TR) Repertoire Analysis of Virus-Specific T Cells: Implications for T Cell Immunotherapy and Viral Infection Risk Stratification
Authors: Chrysi Galigalidou, Anastasia Papadopoulou, Evangelia Stalika, Andreas Agathangelidis, Elisavet Vlachonikola, Katerina Gemenetzi, Kiriakos Koukoulias, Kostas Pasentsis, Achilles Anagnostopoulos, Kostas Stamatopoulos, Evangelia Yannaki, Anastasia Hadzidimitriou
Journal: Blood (2018)
Phase 3 Study of Lenalidomide (LEN) Vs Placebo in Non-Transfusion Dependent (TD) Low Risk Del(5q) MDS Patients with Del(5q) — Preliminary Blinded Analysis of the European Sintra-REV Trial
Authors: Félix López Cadenas, Eva Lumbreras, Blanca Xicoy, Joaquin Sanchez-Garcia, Pierre Fenaux, Rosa Coll, Borhane Slama, Jose Angel Hernandez-Rivas, Sylvain Thepot, Teresa Bernal, Beatriz Arrizabalaga, Agnès Guerci, Guillermo Sanz, Joan Bargay, Maria Luz Amigo, Raquel de Paz, Aristoteles Giagounidis, Uwe Platzbecker, Benet Nomdedeu, Eric Jourdan, Katharina S. Götze, Ali Arar, Jesús María Hernández-Rivas, Consuelo Del Cañizo, María Díez-Campelo
Journal: Blood (2018)
Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG
Authors: Yan Gu, Yanfang Liu, Li Fu, Lili Zhai, Jie Zhu, Yanmei Han, Yingming Jiang, Yi Zhang, Peng Zhang, Zhengping Jiang, Xiang Zhang, Xuetao Cao
Journal: Nature Medicine (2019)
SAT0440 Phenotypic features and predictors of the clinical severity of keratoconjunctivitis sicca and salivary gland dysfunction in patients with sjÖgren’s syndrome: a longitudinal analysis of the kiss cohort
Authors: J.H. Koh, Y.S. Suh, J. Lee, S.-K. Kwok, S.-H. Park
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hyposecretion of tears and saliva is the main phenotype of primary Sjögren's syndrome (PSS). However, the prevalence and degree of ocular and oral involvement in PSS is highly variable. <h3>Objectives</h3> The aims of this study were 1) to investigate oral and ocular signs and changes in primary SS patients, and 2) to explore possible predisposing factors for moderate to severe oral or ocular signs in primary SS. <h3>Methods</h3> We analysed 140 participants from the Korean Initiative of PSS cohort who completed a two-year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined by the Schirmer I test (Moderate-to-severe [MS],≤5 mm/5 min; mild [Mi],&gt;5 mm/5 min). Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary flow rate (UWS) (MS, UWS &lt;0.1 ml/min; Mi≥0.1 ml/min). Subgroups were divided into three groups according to the severity of KCS and SGD: MS-KCS/MS-SGD, MS-KCS/Mi-SGD, and Mi-KCS/MS-SGD group. We analysed the severity of changes in KCS and SGD during the follow-up period. <h3>Results</h3> Among the 140 participants enrolled in this study, 108 (61%) were placed in the MS-KCS/MS-SGD group, 17 (24%) were in the MS-KCS/Mi-SGD, 15 (16%) were in the Mi-KCS/MS-SGD at the two-year follow-up. The MS-KCS/Mi-SGD group was younger than the other two groups, had a lower xerostomia inventory, and lower level of β2 microglobulin. Participants in the Mi-KCS/MS-SGD group had less hyperimmunoglobulinemia, rheumatoid factor (RF), antinuclear antibodies, anti-Ro, and anti-La antibodies. Older patients and those with positive RF, anti-Ro, or anti-La antibodies at baseline were more likely to have moderate to severe KCS at the two-year follow-up. <h3>Conclusions</h3> Patients with PSS and positive RF, anti-Ro, or anti-La antibodies at baseline may benefit from regular ophthalmology exams, even if they do not have KCS at baseline or dry eye symptoms. <h3>References</h3> [1] Le Gall M, Cornec D, Pers J-O, Saraux A, Jousse-Joulin S, Cochener B, et al. A prospective evaluation of dental and periodontal status in patients with suspected Sjögren's syndrome. Joint Bone Spine. doi:http://dx.doi.org/10.1016/j.jbspin.2015.02.015. [2] Lim SA, Nam S, Kwok SK, Park SH, Chung SH. Serologic Markers Are Associated With Ocular Staining Score in Primary Sjogren Syndrome. Cornea2015;34:1466–70. [3] Shiboski CH, Baer AN, Shiboski SC, Lam M, Challacombe S, Lanfranchi HE, et al. Natural History and Predictors of Progression to Sjogren's Syndrome Among Participants of the Sjogren's International Collaborative Clinical Alliance Registry. Arthritis Care Res (Hoboken)2017. doi:10.1002/acr.23264. <h3>Acknowledgements</h3> We wish to thank So Young Kim, the research nurse for the KISS cohort, for her excellent support. <h3>Disclosure of Interest</h3> None declared
THU0154 A program for screening and treatment of cardiovascular risk factors in patients with chronic arthritis: 2-year results
Authors: G. Albert-Espi, N. Martinez-Alberola, R. Martin-Domenech, C. Fernandez-Carballido, T. Pedraz-Penalva, F. Sivera
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Assess the efficacy of a program for the screening and management of cardiovascular risk factors (CVRF) in patients with chronic arthritis at 2 year follow-up. <h3>Methods</h3> Longitudinal and prospective study of patients included in a program aimed at the screening and improvement of the management of CVRF. Patients diagnosed with rheumatoid arthritis (RA), spondyloarthritis (SpA) and psoriatic arthritis (PsA) were included in the program. In the baseline and follow-up visits, CVRF were recorded, as was their treatment and whether treatment targets were achieved. SCORE index was calculated and modified according to <sup>EULAR 2010</sup> recommendations. Tailored education was performed by the nurse and (if needed) referral to the rheumatologist or GP was performed for CVRF drug treatment. For this analysis, we selected patients who completed baseline assessment and the 2 year follow-up. Prevalence and degree of control of CVRF were compared at both time points. <h3>Results</h3> Out of a total of 416 patients included in the program, 123 have completed both the baseline visit and the 2 year follow-up: 79 (64%) women with a mean age of 59.3±10 years. Patients with RA (n=85), SpA (n=14) and PsA (n=24) were included. The mean modified SCORE index was 4.6±4 at baseline and 4.6±4 at follow-up. Risk stratification (according to European guidelines) was 73 patients with intermediate risk, 20 with high risk and 20 with very high risk. Meanwhile, at 2 year follow-up, 74 patients showed an intermediate risk, 25 a high risk and 19 a very high risk. <h3>Conclusions</h3> A specific program aimed at detecting CVRF increases the proportion of patients with a CVRF diagnosis. However, it is also associated with an increase rate of well-controlled hypercholesterolemic patients, with a trend observed in hypertensive patients and smokers. In case the improvement in CVRF control is confirmed, programs such as this could improve the CV prognosis of patients with chronic arthritis. <h3>Disclosure of Interest</h3> None declared
AB0145 Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis
Authors: S. Jo, J. Han, Y.L. Lee, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Ankylosing spondylitis (AS) is characterized by excessive spinal ankylosis and bone formation. Alkaline phosphatase (ALP) activity is reported to be high in AS, but little is known about the molecular relationship between ALP and AS. <h3>Objectives</h3> The aims of this study were to investigate the relevance of ALP to AS and the role of ALP in the regulation of osteoblast differentiation in AS. <h3>Methods</h3> The high-throughput data were downloaded from Gene Expression Omnibus with accession numbers GSE73754 and GSE41038. We retrospectively collected the ALP levels of male patients with AS, to compare with those of gender and age-matched healthy controls (HC) and rheumatoid arthritis (RA) patients. Total ALP and ALP activity in patient's sera were measured in AS and RA groups. ALP gene expression and intracellular ALP activity were analyzed in microarray data of primary bone-derived cells (BdCs) and in In Vitro experiments. Furthermore, the effect of ALP knockdown and inhibitor were performed in primary BdCs and human osteoblasts cells, respectively. <h3>Results</h3> ALP level was increased in AS compared with RA and HC. Increased ALP level in AS was associated with radiograph progression. ALP expression was also enriched in bone tissue of AS patients. Furthermore, AS BdCs exhibited elevated ALP activity, leading to accelerating osteoblastic activity and differentiation. Intriguingly, suppression of ALP expression and activity inhibited expression of osteoblastic genes, which are critical for osteogenic differentiation. <h3>Conclusions</h3> A multifaceted analysis showed ALP was highly expressed in AS patients. ALP may be involved in the ankylosis of AS and a therapeutic target for preventing ankylosis. <h3>Disclosure of Interest</h3> None declared
Abstract 16738: International Variation in Management and Clinical Outcome of Patients With Type 2 Diabetes and Heart Failure: Insights From TECOS
Authors: Ankeet S Bhatt, Nancy Luo, Nicole Solomon, Neha J Pagidipati, Giuseppe Ambrosio, Jennifer B Green, Darren K McGuire, Eberhard Standl, Jan H Cornel, Sigrun Halvorsen, Renato D Lopes, Harvey White, Rury R Holman, Eric D Peterson, Robert J Mentz
Journal: Circulation (2017)

Introduction: We evaluated international variations in management and clinical outcome for patients with type 2 diabetes and heart failure (HF) by region in the Trial Evaluating Cardiovascular Outc...
<i>Frizzled-7</i> Is Required for Wnt Signaling in Gastric Tumors with and Without <i>Apc</i> Mutations
Authors: Dustin J. Flanagan, Nick Barker, Natasha S. Di Costanzo, Elizabeth A. Mason, Austin Gurney, Valerie S. Meniel, Sarah Koushyar, Chloe R. Austin, Matthias Ernst, Helen B. Pearson, Alex Boussioutas, Hans Clevers, Toby J. Phesse, Elizabeth Vincan
Journal: Cancer Research (2019)

Abstract A subset of patients with gastric cancer have mutations in genes that participate in or regulate Wnt signaling at the level of ligand (Wnt) receptor (Fzd) binding. Moreover, increased Fzd expression is associated with poor clinical outcome. Despite these findings, there are no in vivo studies investigating the potential of targeting Wnt receptors for treating gastric cancer, and the specific Wnt receptor transmitting oncogenic Wnt signaling in gastric cancer is unknown. Here, we use inhibitors of Wnt/Fzd (OMP-18R5/vantictumab) and conditional gene deletion to test the therapeutic potential of targeting Wnt signaling in preclinical models of intestinal-type gastric cancer and ex vivo organoid cultures. Pharmacologic targeting of Fzd inhibited the growth of gastric adenomas in vivo. We identified Fzd7 to be the predominant Wnt receptor responsible for transmitting Wnt signaling in human gastric cancer cells and mouse models of gastric cancer, whereby Fzd7-deficient cells were retained in gastric adenomas but were unable to respond to Wnt signals and consequently failed to proliferate. Genetic deletion of Fzd7 or treatment with vantictumab was sufficient to inhibit the growth of gastric adenomas with or without mutations to Apc. Vantictumab is currently in phase Ib clinical trials for advanced pancreatic, lung, and breast cancer. Our data extend the scope of patients that may benefit from this therapeutic approach as we demonstrate that this drug will be effective in treating patients with gastric cancer regardless of APC mutation status. Significance: The Wnt receptor Fzd7 plays an essential role in gastric tumorigenesis irrespective of Apc mutation status, therefore targeting Wnt/Fzd7 may be of therapeutic benefit to patients with gastric cancer.
SP0053 Memory plasma cells in chronic inflammatory diseases – a roadblock to tolerance induction
Authors: A. Radbruch
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Regeneration of tolerance is the Holy Grail of treating inflammatory rheumatic diseases. Obviously neither physiological nor therapeutic immunosuppression does achive this for most patients. What are the roadblocks for therapies inducing therapy-free remission? We have identified memory plasma cells secreting pathogenic (auto)antibodies as one such roadblock. Such cells are often generated already before disease becomes clinically apparent. They persist over time in inflamed tissues and in the bone marrow, in niches which protect them from environmental stress, including conventional therapies. By constitutive secretion of pathogenic antibodies they fuel relapse and refraction. Any therapy aiming at induction of therapy-free remission will have to remove this roadblock. Recently we and others have developed therapeutic concepts to ablate memory plasma cells, based on a molecular understanding of their lifestyle. Such therapies, however, have two major inherent problems:<sup><sup>1</sup></sup> they also ablate protective humoral immunity, increasing risk of infection, and<sup><sup>2</sup></sup> the pathogenic memory plasma cells can be regenerated, if tolerance is not regenerated. To address the latter point, ablation of plasma cells has to be combined with tolerance-inducing therapeutic options, and until then, patients have to be protected passively by IV-Ig. For selective targeting of pathogenic memory plasma cells, differences in the lifestyle between protective and pathogenic plasma cells could be exploited, but few have been identified so far. We have now developed a novel technology to target plasma cells according to the specificity of the antibodies they secrete. Plasma cells are labelled <i>in vivo</i> with a given antigen, and those plasma cells secreting specific antibodies are selectively killed by their own antibodies. We have now demonstrated feasibility and efficacy of this therapeutic approach in a preclinical model. Apart from the therapeutic perspective, this technology also offers a unique option to identify pathogenic plasma cell specificities in experimental and clinical rheumatology. <h3>Disclosure of Interest</h3> None declared
Differential Roles of GRK2 and GRK5 in Cardiac Aldosterone Signaling Suggest GRK5-Mediated Cardio-protection Against Mineralocorticoids
Authors: Anastasios Lymperopoulos, Katie Anne McCrink, Ava Brill, Jennifer Maning, Victoria Desimine, Beatrix Aukszi
Journal: Circulation (2019)

Introduction: Aldosterone (Aldo) contributes significantly to the morbidity & mortality of heart failure (HF). In the heart, Aldo binds the mineralocorticoid receptor (MR) to exert damaging effects...
SAT0695 Hospitalisation rates among patients with primary sjÖgren’s syndrome: a population-based study, 1995–2016
Authors: G. Maciel, L. Servioli, C. Nannini, A. Berti, C. Crowson, S. Achenbach, E. Matteson, D. Cornec
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> To determine rates and primary discharge diagnoses of hospitalisation in a cohort of patients with incident primary Sjögren's syndrome (pSS) compared to the general population. <h3>Methods</h3> This was a retrospective population-based cohort study focused on Olmsted County, Minnesota. The pSS cohort consisted of patients with incident pSS in the 1976–2015 period and was compared with a cohort of individuals without pSS matched 3:1 for age, sex and calendar year, randomly selected from the same population. Hospitalizations in 1995–2016 were examined. Discharge diagnoses were categorised using the Clinical Classifications Software for ICD-9-CM. <h3>Results</h3> A total of 385 hospitalizations occurred in the 160 patients with pSS during 1592 person-years of follow-up. Among 466 comparators, there were 899 hospitalizations during 4660 person-years of follow-up, resulting in a significantly higher rate of hospitalizations in patients with pSS (rate ratio [RR]:1.25, 95% CI:1.11–1.41). Rates of hospitalisation were increased among patients with pSS for endocrine, nutritional and metabolic diseases and immunity disorders (RR:1.82, 95% CI:1.08–2.98), diseases of the musculoskeletal system and connective tissue (RR:1.49, 95% CI:1.05–2.05), and for injuries and poisoning (RR:1.46, 95% CI:1.01–2.06). While not significantly increased overall, hospitalizations for diseases of the circulatory system were significantly increased in patients with pSS aged ≥75 years (RR:1.54, 95% CI: 1.11–2.11). <h3>Conclusions</h3> Patients with pSS experienced higher rates of hospitalisation than the general population. Hospitalizations for endocrine/metabolic disorders, diseases of the circulatory system, diseases of the musculoskeletal system and connective tissue disorders, and injuries were more common among patients with pSS than comparators. <h3>Disclosure of Interest</h3> None declared
Abstract 19277: Incidence and Prognosis of Heart Failure in Persons With Type 2 Diabetes Compared With Nondiabetic Individuals - A Nation-wide Study From Finland During the Years 1996-2012
Authors: Klas Winell, Arto Pietilä, Veikko Salomaa
Journal: Circulation (2017)

Introduction and Aims: Heart failure (HF) is a serious disease with a major burden to health care. Diabetes increases the risk for HF. The aims of the present study were (1) to quantify the inciden...
CAR‐T cells beyond CD19, UnCAR‐Ted territory
Authors: Mark B. Leick, Marcela V. Maus
Journal: American Journal of Hematology (2019)

CAR‐T cells have made dramatic inroads in targeting CD19‐positive B‐cell malignancies. This review focuses on application of CAR‐T cells in hematologic malignancies beyond targeting CD19, with specific attention to Hodgkin's lymphoma and acute myeloid leukemia.
The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Diffuse Large B-Cell Lymphoma: A Study from the Latin American Group of Lymphomas (GELL)
Authors: Brady E. Beltrán, Victoria Otero, Marialejandra Torres Viera, Camila Peña, Myriam Lucía Rodriguez, Gabriel Borelli, Teodoro Chisesi, Fabiola Valvert Gamboa, Abel Berrios, Gregorio Ignacio, Carlos Sérgio Chiattone, Sally Paredes, Denisse A. Castro, Maria Elena Cabrera, Raul Gabus, Eduardo Sotomayor, Jorge J. Castillo
Journal: Blood (2018)
Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL): The Lymphoma Study Association (LYSA) Registry Data
Authors: Fabien Le Bras, Philippe Gaulard, Marc Andre, Corinne Haioun, Romain Bosc, Camille Laurent, Lionel Tortelano, Thua-Ha Dao, Emmanuel Itti, Caroline Malhaire, Schiano de Colella Jean Marc, Marie Bannier, Emmanuel Bachy, Borhane Slama, Luc Mathieu Fornecker, Lucie Oberic, Alexandra Traverse-Glehen, Manon Croix, Julie Bonnefoy, Patrick Fogarty, Feriel Bouabbas, Nadia Amara, Virginie Fataccioli, Romain Ricci, Tania Cassubie-Mercier, Youlia Kirova, Fabien Reyal, Herve Tilly, Emmanuelle Nicolas-Virelizier, Luc Xerri, Christophe Bonnet
Journal: Blood (2019)
3D Electrophysiological Measurements on Cells Embedded within Fiber‐Reinforced Matrigel
Authors: Natascha Schaefer, Dieter Janzen, Ezgi Bakirci, Andrei Hrynevich, Paul D. Dalton, Carmen Villmann
Journal: Advanced Healthcare Materials (2019)

Abstract 2D electrophysiology is often used to determine the electrical properties of neurons. In the brain however, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. In this study, 3D electrophysiology is established within a fiber‐reinforced matrix to enable fast readouts from transfected cells, which are often used as model systems for 2D electrophysiology. Using melt electrowriting (MEW) of scaffolds to reinforce Matrigel, 3D electrophysiology is performed on a glycine receptor‐transfected Ltk‐11 mouse fibroblast cell line. The glycine receptor is an inhibitory ion channel associated when mutated with impaired neuromotor behavior. The average thickness of the MEW scaffold is 141.4 ± 5.7 µm, using 9.7 ± 0.2 µm diameter fibers, and square pore spacings of 100, 200, and 400 µm. For the first time, the electrophysiological characterization of glycine receptor‐transfected cells is demonstrated with respect to agonist efficacy and potency in a 3D matrix. With the MEW scaffold reinforcement not interfering with the electrophysiological measurement, this approach can now be further adapted and developed for different kinds of neuronal cultures to study and understand pathological mechanisms under disease conditions.