tbuckley/cabot-search huggingface dataset:
AB0108B PREVALENCE AND RISK FACTORS INFLUENCING THE DEVELOPMENT OF ARTERIAL HYPERTENSION IN PATIENTS WITH A GOUT
Authors: Eugenia Markelova, Diana Novikova, Maxim Eliseev, Tatiana Popkova, Svetlana Glukhova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cardiovascular diseases (CVD) is the leading cause of death for gout. Arterial hypertension (AH) is a proven CVD risk factor (CVD-RF). <h3>Objectives</h3> To assess the factors influencing on development of an AH in patients with a gout. <h3>Methods</h3> 286 male patients fulfilling Wallace proposed criteria for gout were included in the study: age 51.2 [42.8;59.4] years (ys), disease duration – 6.2 [3.8;12.1] ys, number of joints involved during disease course – 7[4;12], subcutaneous tophi – in 35% pts, intraosseous tophi – in 44% pts, nephrolithiasis – in 69% pts, abdominal obesity – in 71%. All pts underwent standard clinical examination, C-reactive protein (CRP), total cholesterol (TC), triglycerides (TG), low and high density lipoproteins (LDL/HDL), serum uric acid, serum creatinine, smoking, family history of AH, body mass index (BMI), diabetes mellitus was performed by standard procedure. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). <h3>Results</h3> There were two groups of patients with AH diagnosed on clinical data: group 1 (with AH) - 244 (85%) pts, group 2 (without AH) - 42 (15%) pts. The 1<sup>st</sup> group pts were older (52.3[44.5; 61.1] vs 41.9[38.3; 50.1] ys), had longer duration of gout (6.7[3.9; 13.7] vs 4.5[3; 7.9]), a higher number of joints involved during disease course (8[4; 12] vs 5[3; 9]). The frequency of family history of AH (68.3% vs 48.8%), abdominal obesity (55.3% vs 33.3%), nephrolithiasis (71% vs 54.7%), intraosseous tophi (48% vs 21%) was higher in group 1 as compared with group 2, p&lt;0,05. BMI and CRP level was higher in group 1 compared with group 2: 30.2[27.4; 33.1] vs 27.9[26.3; 30.5] kg/m2, and 12.7[5.84; 19.2] vs 7.8[3.7;16.4]mg/l, accordingly, p&lt;0.05. We didn't find differences of lipid profile, serum uric acid, and serum creatinine level in 1 and 2 group. We also didn't find differences the frequency of smoking, diabetes mellitus, subcutaneous tophi in both groups (table 1). <h3>Conclusion</h3> Majority (85%) of patients with gout had AH. Abdominal obesity, family history of AH, disease duration more 10 ys, intraosseous tophi were associated with an increased risk of AH in pts with a gout. <h3>Disclosure of Interests</h3> None declared
High-Plex Predictive Marker Discovery for Melanoma Immunotherapy–Treated Patients Using Digital Spatial Profiling
Authors: Maria I. Toki, Christopher R. Merritt, Pok Fai Wong, James W. Smithy, Harriet M. Kluger, Konstantinos N. Syrigos, Giang T. Ong, Sarah E. Warren, Joseph M. Beechem, David L. Rimm
Journal: Clinical Cancer Research (2019)

Protein expression in formalin-fixed, paraffin-embedded tissue is routinely measured by IHC or quantitative fluorescence (QIF) on a handful of markers on a single section. Digital spatial profiling (DSP) allows spatially informed simultaneous assessment of multiple biomarkers. Here we demonstrate the DSP technology using a 44-plex antibody cocktail to find protein expression that could potentially be used to predict response to immune therapy in melanoma.Experimental Design: The NanoString GeoMx DSP technology is compared with automated QIF (AQUA) for immune marker compartment-specific measurement and prognostic value in non-small cell lung cancer (NSCLC). Then we use this tool to search for novel predictive markers in a cohort of 60 patients with immunotherapy-treated melanoma on a tissue microarray using a 44-plex immune marker panel measured in three compartments (macrophage, leukocyte, and melanocyte) generating 132 quantitative variables.The spatially informed variable assessment by DSP validates by both regression and variable prognostication compared with QIF for stromal CD3, CD4, CD8, CD20, and PD-L1 in NSCLC. From the 132 variables, 11 and 15 immune markers were associated with prolonged progression-free survival (PFS) and overall survival (OS). Notably, we find PD-L1 expression in CD68-positive cells (macrophages) and not in tumor cells was a predictive marker for PFS, OS, and response.DSP technology shows high concordance with QIF and validates based on both regression and outcome assessment. Using the high-plex capacity, we found a series of expression patterns associated with outcome, including that the expression of PD-L1 in macrophages is associated with response.
Are guidelines for monitoring chronic disease in primary care evidence based?
Authors: Martha M C Elwenspoek, Rita Patel, Jessica C Watson, Penny Whiting
Journal: BMJ (2019)

### What you need to know Pathology tests have a unique place in management of chronic diseases. They are used to guide disease management; assess risk and compliance; and enable early detection of adverse events, complications, and development of secondary diseases. Primary care clinicians rely on guidelines for common chronic diseases such as type 2 diabetes, chronic kidney disease, and hypertension to inform them which tests they should recommend to their patients and how frequently these should be done. With rates of pathology tests rising—at an estimated annual cost of £1.8bn to primary care in the UK1—and the potential for harm from over-testing, it is important to consider the evidence base for these recommendations. In this article, we review monitoring strategies in current UK guidelines for patients with type 2 diabetes, chronic kidney disease, and hypertension (box 1), highlighting the uncertainties in these guidelines and the need for further research. Box 1 ### Search strategy and guideline selection We searched for published UK guidelines for the management of patients with type 2 diabetes, chronic kidney disease stages 1-3*, or hypertension using the following sources: The following guidelines are included in this review:RETURN TO TEXT
Abstract 20379: Glycemic Load Predicts Cardiovascular Risk Factors in School-Aged Children in Quebec
Authors: Karine Suissa, Andrea Benedetti, Melanie Henderson, Katherine Gray-Donald, Gilles Paradis
Journal: Circulation (2017)

Introduction: There is growing evidence to support that dietary glycemic index (GI), a measure of carbohydrate quality, and glycemic load (GL), a measure of carbohydrate quantity and quality, is as...
SUPPA2: fast, accurate, and uncertainty-aware differential splicing analysis across multiple conditions
Authors: Juan L. Trincado, Juan C. Entizne, Gerald Hysenaj, Babita Singh, Miha Skalic, David J. Elliott, Eduardo Eyras
Journal: Genome biology (2018)

Despite the many approaches to study differential splicing from RNA-seq, many challenges remain unsolved, including computing capacity and sequencing depth requirements. Here we present SUPPA2, a new method that addresses these challenges, and enables streamlined analysis across multiple conditions taking into account biological variability. Using experimental and simulated data, we show that SUPPA2 achieves higher accuracy compared to other methods, especially at low sequencing depth and short read length. We use SUPPA2 to identify novel Transformer2-regulated exons, novel microexons induced during differentiation of bipolar neurons, and novel intron retention events during erythroblast differentiation.
A novel knock-in mouse model of cryopyrin-associated periodic syndromes with development of amyloidosis: Therapeutic efficacy of proton pump inhibitors
Authors: Arinna Bertoni, Sonia Carta, Chiara Baldovini, Federica Penco, Enrica Balza, Silvia Borghini, Marco Di Duca, Emanuela Ognio, Alessio Signori, Paolo Nozza, Francesca Schena, Patrizia Castellani, Claudia Pastorino, Carola Perrone, Laura Obici, Alberto Martini, Isabella Ceccherini, Marco Gattorno, Anna Rubartelli, Sabrina Chiesa
Journal: Journal of Allergy and Clinical Immunology (2019)
SAT0250 MUSCLE INVOLVEMENT REVEALED BY 18F-PET-CT IN POLYMYALGIA REUMATICA
Authors: Daniel Wendling, Maxime Sondag, Nicolas Giraud, Mickaël Chouk, Hatem Boulahdour, Clément Prati, Frank Verhoeven
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Imaging techniques in polymyalgia reumatica (PMR) have revealed mainly bursitis, tenosynovitis, capsulitis and enthesitis. This is also the case for 18F-FDG-PET-CT. This technique, which has shown its interest in the diagnosis of PMR, allows an assessment of the metabolic activity of the entire musculoskeletal system and in particular of muscle structures. <h3>Objectives:</h3> The objective of this work was to evaluate muscle damage using 18F-FDG-PET-CT in PMR. <h3>Methods:</h3> This is a retrospective study including patients with PMR (ACR/EULAR 2012 criteria) seen in our department, who had an 18F-FDG PET-CT examination between September 2012 and November 2018. A control group consisting of subjects without rheumatological manifestations who had such an examination as part of neoplastic research or neoplastic disease control was also evaluated. PET evaluation included 17 sites suggestive of PMR, as previously reported [1], leading to a global PET score ranging from 0 to 51. Muscle hypermetabolism areas were similarly rated according to the same Goerres classification [2](0 = no uptake; 1 = slight uptake, less than liver; 2 = uptake like liver; 3 = uptake higher than liver). Muscle activity sites have been identified. A comparison of PMR patients with and without muscle involvement was performed using the Mann Whitney or Fisher's exact test. <h3>Results:</h3> 134 cases were reviewed, concerning 80 PMR (mean age 67.9) and 54 "controls" (mean age 68.1). Overall, PET muscle damage was observed in 27 cases (34%) in PMR and 6 cases (11%) in controls (p=0.004). The damage is bi or multi-focal in 16/27 cases. The affected sites are: thighs and ischium-leg (n = 10), spinal (11), piriform/buttocks (7), pectoral (5), large serrated (4), subspinatus/subscapular (3), deltoid (1), trapezius (1). Fasciitis was found in 4 cases. As expected, PMR patients exhibited higher TEP scores than controls (p&lt;0.001). In PMR patients, PET muscle involvement was associated with higher ESR values (p&lt;0.05), but not with age, CRP or global PMR PET score. <h3>Conclusion:</h3> Muscle involvement assessed by 18F-Fluorodeoxyglucose PET-CT is frequent in PMR (1/3), located at usual sites of symptoms of the disease, without association with age, CRP levels or global PET score for PMR. Muscle should be carefully evaluated during PET in cases of PMR; these pictures may be a new diagnosis feature of the disease. <h3>References</h3> [1] Sondag.M, et al. Rheumatology 2016;55(8):1452-7. [2] Goerres GW, et al. Clin Nucl Med 2006;31:386-90. <h3>Disclosure of Interests:</h3> None declared
Plasmacytoid dendritic cells develop from Ly6D+ lymphoid progenitors distinct from the myeloid lineage
Authors: Regine J. Dress, Charles-Antoine Dutertre, Amir Giladi, Andreas Schlitzer, Ivy Low, Nurhidaya Binte Shadan, Alicia Tay, Josephine Lum, Muhammad Faris Bin Mohd Kairi, You Yi Hwang, Etienne Becht, Yang Cheng, Marion Chevrier, Anis Larbi, Evan W. Newell, Ido Amit, Jinmiao Chen, Florent Ginhoux
Journal: Nature Immunology (2019)
FRI0108 SHORT-TERM EFFICACY OF BCD-089, NOVEL MONOCLONAL ANTI-IL-6 RECEPTOR ANTIBODY, IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS: 12-WEEK RESULTS OF PHASE 2 AURORA STUDY
Authors: V Mazurov, Evgeniy Zotkin, Elena Ilivanova, Tatyana Kropotina, Tatyana Plaksina, Olga Nesmeyanova, Nikolaj Soroka, Alena Kundzer, Anton Lutskii, Ekaterina Dokukina, Ekaterina Chernyaeva, Roman Ivanov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> In the previous phase 1 study BCD-089 (INN: levilimab) was well-tolerated, had favorable safety profile and low immunogenicity<sup>1</sup>. Here we report 12-week efficacy and safety results of ongoing phase 2 clinical study of BCD-089 in patients with active RA. <h3>Objectives:</h3> This study is aimed to assess efficacy and safety of 2 dosing regimens of BCD-089 in patients with MTX-IR active RA. <h3>Methods:</h3> During this multicenter double-blind placebo-controlled randomized clinical study (NCT03455842) 105 MTX-IR patients with active RA (ACR2010) were assigned (1:1:1) to receive 162 mg of BCD-089 s.c. (QW arm and Q2W arm) or PBO. MTX (10-25 mg/week) was used in all groups. After completion of 12-week blinded period patients from QW/Q2W arms continued the treatment, patients from PBO arm were switched to BCD-089 Q2W until Wk56. The primary efficacy endpoint was the rate of ACR20 at Wk12. Secondary endpoints included ACR50/70 and DAS28-CRP(4). The safety was routinely evaluated. <h3>Results:</h3> The efficacy analysis showed that 95% confidence interval for BCD-089 treatment effect relative to PBO was [38.45 – 81.55] for QW arm and [16.53 – 63.4] for Q2W arm, which confirms the superiority to PBO of either dosing regimens. Summary of efficacy results is presented in table 1. The majority of adverse events (AE) were laboratory abnormalities. The spectrum of AEs is similar to other IL6R inhibitors (Table 2). Three serious AE (SAEs) were reported: community-acquired pneumonia (QW arm, treatment-related), acute cholecystitis (PBO arm, not related, did not lead to treatment discontinuation), and acute heart failure leading to death (Q2W arm, not related). One case of moderate local reaction (erythema) was reported in QW arm. <h3>Conclusion:</h3> BCD-089 in combination with MTX had superior efficacy compared with MTX plus PBO in MTX-IR patients with active RA. BCD-089 showed safety profile consistent with other IL6R inhibitors. Further clinical studies are needed. <h3>Reference:</h3> [1] Khlyabova P, et al. doi: 10.1136/annrheumdis-2018-eular.2410 <h3>Disclosure of Interests:</h3> V Mazurov Grant/research support from: JSC BIOCAD, Evgeniy Zotkin: None declared, Elena Ilivanova Grant/research support from: JSC BIOCAD, Tatyana Kropotina Grant/research support from: JSC BIOCAD, Tatyana Plaksina Grant/research support from: JSC BIOCAD, Olga Nesmeyanova Grant/research support from: JSC BIOCAD, Nikolaj Soroka: None declared, Alena Kundzer: None declared, Anton Lutskii Employee of: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Ekaterina Chernyaeva Employee of: JSC BIOCAD, Roman Ivanov Employee of: JSC BIOCAD
PF730 CHRONIC RENAL FAILURE IN CHILDHOOD CANCER: AN INSIGHT FROM KIDS INPATIENT DATABASE
Authors: E.M. Elsabbagh, M. Almasri
Journal: HemaSphere (2019)

Background: Chronic Renal Failure (CRF) is prevelant in oncology patients. CRF may pre‐exist cancer diagnosis, occur secondry to cancer infiltration, complicate chemotherapy and other toxic drugs or follow hematopoietic stem‐cell transplantation. CRF is associated with prolonged hospital stay, high healthcare cost and increased mortality. Despite the increased prevelance and these associations, the national rate and clinical outcome of CRF among pediatric oncology patients is not well described. Aims: Define CRF incidence and its health outcomes among pediatric oncology patients in the United States (U.S.). Methods: We performed a retrospective cohort analysis of the Health Cost and Utilization Project (HCUP) Kids’ Inpatient 2000–2012 Database (KID) for patient ≤ 20 years of age. Patients with principal diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), lymphomas (Hodgkin and non‐Hodgkin), brain tumor, neuroblastoma, bone tumors (Ewing's Sarcoma and Osteosarcoma) and hepatoblastoma were reviewed. Encounters for chemotherapy were excluded. Patients with medical diagnosis of CRF were identified using ICD‐9‐CM codes. We performed descriptive statistics to characterize the cohort in terms of demographic factors (age, race, sex, insurance type), hospital characteristics and comorbidities. Data weights were applied to sampled patients to provide national estimates. The in‐hospital mortality rate, total charges, and hospital length of stay (LOS) were compared between cancer patients with and without CRF using bivariable analyses. Results: A total of 266,113 admissions were included for analysis. The cohort was comprised of 1,035 patients with CRF, with an overall incidence 4 per 1,000 admissions. The median age was 15 years.51.5% of CKD patients were among the age group above 12‐year‐old. Males (57%), and whites (52.3%) were more commonly affected. South and Midwest regions (59.5%) of the U.S. had higher frequency of CRF. 15% of CRF complicated acute kidney injury (AKI). Lymphoma was the most common diagnosis associated with CRF (1.3%). Patients with CRF had significantly higher mortality rates (5.5% vs. 1.36%, p &lt; 0.0001), longer median LOS (15 days vs. 4 days, p &lt; 0.0001) in CRF patients complicated AKI and higher median total charges per hospitalization ($36,600 vs $18,856) when compared to patients without CRF. Summary/Conclusion: CRF in pediatric oncology patients is significantly associated with increased in‐hospital mortality and higher healthcare cost in pediatric oncology patients. Attention should be directed towards strategies to minimize risk of CRF in those population.
SP0080 STRUCTURAL DAMAGE PROGRESSION IN AXSPA
Authors: Denis Poddubnyy
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Structural damage in axial spondyloarthritis (axSpA) develops usually first in the sacroiliac joints and later in the spine. While development of structural damage in the sacroiliac joints is mostly relevant for diagnosis and classification (non-radiographic versus radiographic axSpA), structural damage in the spine has a relevance for the long-term outcome of the disease. Structural damage in the spine and inflammatory activity are two major determinant of functional status and spinal mobility in axSpA. Structural damage in the spine in axSpA is mostly attributable to the process of new bone formation (development of syndesmophytes resulting in bony ankylosis) occurring in the areas affected by inflammation. Advanced ankylosis of the spine is the worst long-term outcome of this disease, although this occurs less frequently nowadays if compared to former decades. This fact might be related either to the natural course of the disease that becomes milder over time or to a consequent anti-inflammatory treatment initiated earlier in patients with axSpA. Structural damage in the spine in axSpA is usually assessed on plain radiographs of the spine and, therefore, is frequently referred to as radiographic spinal progression. In the presentation, pathophysiology, assessment and ways of prevention and/or retardation of structural damage progression in the spine in patients with axSpA will be discussed. <h3>Disclosure of Interests:</h3> Denis Poddubnyy Grant/research support from: AbbVie, Merck Sharp &amp; Dohme, Novartis, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, UCB Pharma, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, UCB Pharma
Abstract 18649: Vascular Prostanoids Paradoxically Amplify Vasoconstriction During Platelet Activation
Authors: Jane A Mitchell, Joshua Benson, Fisnik Shala, Blerina Ahmetaj-Shala, Nicholas S Kirkby
Journal: Circulation (2017)

Introduction: Platelet activation is associated with release of vasoactive factors which drive vasoconstriction, vasospasm and promote tissue hypoperfusion. These include the monoamine 5-HT and the...
OP0167 B LYMPHOCYTES DIRECTLY CONTRIBUTE TO TISSUE FIBROSIS IN IGG4-RELATED DISEASE
Authors: Emanuel Della Torre, Elena Rigamonti, Cory Perugino, Massimo Falconi, John H. Stone, Angelo Manfredi, Shiv Pillai
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing (1-3). <h3>Objectives</h3> In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in IgG4-RD. <h3>Methods</h3> Total circulating CD19+ B-lymphocytes, naïve B cells, memory B cells, or plasmablasts from IgG4-RD patients were cultivated with human fibroblasts. Pro-fibrotic soluble factors and collagen production in the co-cultures were assessed by ELISA and Luminex assays. RNA-sequencing and quantitative RT-PCR were used to assess fibroblast activation in the presence of B cells, as well as the induction of pro-fibrotic pathways in B cell subsets. Relevant pro-fibrotic and inflammatory molecules were confirmed in vitro by functional experiments and on IgG4-RD tissue sections by multi-color immunofluorescence studies. <h3>Results</h3> B cells from IgG4-RD patients (i) produced the pro-fibrotic molecule PDGF-B and stimulated collagen production by fibroblasts; (ii) expressed enzymes implicated in extracellular matrix remodeling such as LOXL2; (iii) produced the chemotactic factors CCL-4, CCL-5, and CCL-11; and (iv) induced the production of these same chemokines by activated fibroblasts. Plasmablasts expressed sets of genes implicated in fibroblast activation and proliferation, and therefore represent cells with intrinsic pro-fibrotic properties <h3>Conclusion</h3> We have demonstrated that B cells, contribute directly to tissue fibrosis in IgG4-RD. These unanticipated pro-fibrotic properties of B lymphocytes, particularly of plasmablasts, might be relevant for fibrogenesis in other fibro-inflammatory disorders and for wound healing processes in physiological conditions. <h3>References</h3> [1] Della-Torre E, Lanzillotta M, Doglioni C. Immunology of IgG4-related disease. Clin Exp Immunol2015;181:191-206. [2] Carruthers MN, Topazian MD, Khosroshahi A, Witzig TE, Wallace ZS, Hart PA, et al. Rituximab for IgG4-related disease: a prospective, open-label trial. Ann Rheum Dis. 2015;74:1171-7. [3] Della-Torre E, Feeney E, Deshpande V, Mattoo H, Mahajan V, Kulikova M, et al. B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease. Ann Rheum Dis2015;74:2236-43. <h3>Disclosure of Interests</h3> Emanuel Della Torre: None declared, Elena Rigamonti: None declared, Cory Perugino: None declared, Massimo Falconi: None declared, John H. Stone Grant/research support from: F. Hoffmann-La Roche, Genentech, Xencor, Consultant for: Chugain, F. Hoffmann-La Roche, Genentech, Xencor, Angelo Manfredi: None declared, Shiv Pillai: None declared