tbuckley/cabot-search huggingface dataset:
AB0258 Decreased Phosphostat5 Contributed To Impairment of CD4+CD25+Foxp3+ Tregs in RA Patients
Authors: Z. Huang, L. Chen, B. Yang, J. Chen, L. Wang
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Our previous research has demonstrated decreased expression of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells (Tregs) enrolled in the pathogenesis of rheumatoid arthritis (RA). Anti-TNF-α mAb therapy could improve Tregs expansion in RA and associate with clinical amelioration of RA patients. STAT5 is reported to have effects on many aspects of immune function, particularly in regulatory T cell development. <h3>Objectives</h3> In this study, we aim to monitor phosphoSTAT5 expression in Tregs and investigate its role in RA disease. <h3>Methods</h3> Flowcytometry was employed to detect the phosphorylation level of STAT5 in CD3<sup>+</sup>CD4<sup>+</sup> T cells, CD4<sup>+</sup>CD25<sup>high</sup> regulatory T cells and the expression of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>Tregs in peripheral blood of 20 patients with RA disease and 20 age and gender-matched normal controls. STAT5 mRNA expression in peripheral blood mononuclear cells (PBMC) were also monitored of these RA patients and normal controls. <h3>Results</h3> Phosphorylation level of STAT5 deceased in RA patients both in CD3<sup>+</sup>CD4<sup>+</sup> T cells and in CD4<sup>+</sup>CD25<sup>high</sup> regulatory T cells, along with reduction of expression of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Tregs. Detection of mRNA also confirmed STAT5 down regulation in Tregs in RA patients. <h3>Conclusions</h3> Compared with normal controls, the expression of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>Tregs decreased in RA patients. PhosphoSTAT5 reduction in CD3<sup>+</sup>CD4<sup>+</sup> T cells, mainly in CD4<sup>+</sup>CD25<sup>high</sup> regulatory T cells contributed to impairment of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> regulatory T cells in RA. <h3>References</h3> Niu Q, Cai B, Huang ZC, Shi YY, Wang LL. Disturbed Th17/Treg balance in patients with rheumatoid arthritis. Rheumatol Int. 2012 Sep;32(9):2731–6. Huang Z, Yang B, Shi Y, Cai B, Li Y, Feng W, Fu Y, Luo L, Wang L. Anti-TNF-α therapy improves Treg and suppresses Teff in patients with rheumatoid arthritis. Cell Immunol. 2012 Sep;279(1):25–9. <h3>Disclosure of Interest</h3> None declared
SP0022 Inflammatory Mediators in Inflammatory Myopathies
Authors: B. De Paepe
Journal: Annals of the Rheumatic Diseases (2016)

Idiopathic inflammatory myopathies (IM) constitute a heterogeneous group of chronic disorders which include dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM) and necrotizing autoimmune myopathy (NAM). These diseases represent distinct pathological entities but, most often, share predominant inflammation in muscle tissue. Many of the immunopathogenic processes behind the IM remain poorly understood until today, however, the role played by various inflammatory mediators becomes more and more clear. Induction of major histocompatibility complexes on the membranes, makes that IM muscle fibers actively participate to the immune processes by becoming antigen presenters. Several myositis-specific autoantibodies have been recognized, typing different subgroups of patients with distinct clinical phenotype. Cytokines, the master regulators of leukocyte activation and migration, have especially been recognized as crucial factors. The IM are characterized by strong expression of subsets of Tumor Necrosis Factors (TNFα, LTβ, BAFF), Interferons (IFNα/β/γ), Interleukins (IL-1/6/12/15/18/23) and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21) in the muscle tissue. The latter are important for attracting distinct subsets of T-cells, B-cells, macrophages and dendritic cells, and for their intra-muscular organization. The complex inflammatory network in IM pinpoints targets for neutralization through a selective therapeutic approach as a necessary alternative for patients that do not respond to conventional immune-suppressants. Results so far are promising, but have also shown the necessity for further subtyping of patients to develop future precision therapies and predict treatment outcome. <h3>Disclosure of Interest</h3> None declared
WHO urges restrictions on e-cigarettes
Authors: Anne Gulland
Journal: BMJ (2016)

The World Health Organization has urged countries to restrict the sale, promotion, and use of electronic cigarettes.

WHO made the call in a paper to be discussed at this week’s meeting of the Framework Convention on Tobacco Control in India.1 The paper said that the aerosol produced by e-cigarettes contained glycols, aldehydes, volatile organic compounds, polycyclic aromatic hydrocarbon, tobacco specific nitrosamines, metals, silicate particles, and other elements. A number …
Ex Vivo Gene Therapy for Haemophilia A: FVIII-Overexpressing Mesenchymal Stromal Cells Fail To Produce Sustained Therapeutic Levels of Circulating FVIII In Vivo.
Authors: Daniel L. Coutu, Moira Francois, Jessica Cuerquis, Hideto Matsui, David Lillicrap, Jacques Galipeau
Journal: Blood (2006)
AB0832 Increased Serum Uric Acid (SUA) Levels Are A Common Finding in Patients with High Blood Pressure, Insulin Resistance, Obesity and Cardiovascular (CV) Disease
Authors: I. Tasic, S. Kostic, V. Skakic, A. Đorđević, D. Djordjevic, J. Radicovic, M. Nikolic, S. Andonov, M. Karadzic, I. Krstic
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To evaluate the connection between SUA and severity of coronary heart disease (CHD) assessed by angiography in patients with CHD. <h3>Methods</h3> 198 patients (75.8% men) undergoing cardiovascular rehabilitation at the Institute "Niska Banja" from October 1, 2014, to January 31, 2015, were evaluated. Mean (SD) patient age (62.1±10.4), prevalence of patients with 3-vessel coronary artery disease with stenosis &gt;70% (31.3%), coronary artery bypass grafting (CABG) (37.4%), percutaneus coronary intervention (PCI) (38.9%), primary PCI (32.8%), mean ejection fraction (50% ±11). Prevalence of hyperuricemia (&gt;386 μmol/l) 33.3%, hypertension 85.9%, hypelipoproteinemia 81.8%, diabetes mellitus 24%, family history of CHD (47%) and mean number risk factors 2.65. Patients were separated into a normal SUA group (n=132, with SUA &lt;386 μmol/L) and a high SUA group (n=66, with SUA ≥386 μmol/L). <h3>Results</h3> Patients with high SUA had significantly higher 3-vessel coronary artery disease with stenosis &gt;70% (40.9% vs. 26.5%; P=0.04), low ejection fraction (EF&lt;34%)(19.7% vs. 8.3%; p=0.021), obesity (27% vs. 14.4; P=0.03), significantly higher triglycerides (2.38±1.7 vs. 1.88±1.44; P=0.028) and serum creatinine (111.5±46 vs. 90±21; p&lt;0.001). <h3>Conclusions</h3> SUA levels were independently associated with EF in patients with CHD. Hyperuricemia is associated with severity of CAD- 3-vessel coronary artery disease with stenosis &gt;70%. <h3>Disclosure of Interest</h3> None declared
AB0985 Clinical Characteristics and Mortality of Our Patients Admitted To ICU
Authors: A. Garcia Vadillo, E. Garcia-Lorenzo, D.A. Rodriguez-Serrano, I. Llorente, L. Merino, J.P. Lopez-Bote, M.I. Lopez-Fernandez, I. Gonzalez-Alvaro
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To determine the characteristics and mortality of patients with inflammatory rheumatic diseases admitted to intensive care unit (ICU). <h3>Methods</h3> We present a retrospective observational study including all patients with inflammatory rheumatic diseases admitted to the ICU of a tertiary hospital in Madrid from January 2004 to December 2014. We excluded all those with stay of less than 24 hours in this unit. Patients who were readmitted to ICU during the same hospital admission were considered as a single entry. We retrospectively collected several characteristics of the diseases, including biological activity, and also treatments received for the three months before admission to the ICU. Statistical analysis was performed using Stata 12.1. <h3>Results</h3> A total population of 56 patients required 62 income in ICU (6 of them required 2 consecutive admissions). The mean age was 58.6 ±14 years. 55% were women. 41% of patients (23) had systemic vasculitis, 7 of them ANCA positive. 28.5% (16) suffered connective tissue disease: 10 spondylitis, 3 rheumatoid arthritis and 4 other different processes. The average from diagnosis until their first ICU admission was 127± 176 months. 67% of patients had previously been treated with glucocorticoids for an average of 13 months at a dose of 7 mg (p50) prednisone/day. 14% of patients had received boluses of glucocorticoids, 20% biologic therapies and 18% cyclophosphamide. 63% showed signs of disease activity at the time of entering the ICU. At ICU admission APACHE II severity index was p50: 20 (p25-p75: 13.5–26) and p50 SAPSII: 34.5 (p25-p75: 24–43). The most common causes were respiratory failure (58% of episodes) and septic shock (14.5%). During their stay in ICU 79% of patients required glucocorticoids, 35% received boluses of glucocorticoids, 20% cyclophosphamide and 11% plasmapheresis. 41 patients (68%) required mechanical ventilation, being invasive in 38. The mean ICU stay was 15.8 ±14 days. 28.5% (16) patients died during their stay in this unit, and 11% (7 patients) died in the hospital after leaving the ICU. Deaths was significantly associated with age (OR: 1.09 annually), elderly (OR: 7.52 for patients &gt;70 compared to those &lt;45) female sex (OR 3.7), APACHE II (OR: 1.15 per unit increased) and iv administration of gamma globulins in ICU (OR: 16.6) in multivariate analysis. <h3>Conclusions</h3> Vasculitis and connective tissue diseases are the main inflammatory rheumatic diseases that require our patients to ICU admission. At the time of these they have high rates of disease gravity. Mortality was associated with advanced age, elderly, female sex, severity measured by APACHE II and also with the need of gamma globulin iv administration. <h3>Disclosure of Interest</h3> None declared
SP0202 Psychoneuroimmunology: from Psyche To Immune Activity and Back
Authors: C. Schubert
Journal: Annals of the Rheumatic Diseases (2016)

Current biomedical thinking is characterized by mind-body dualism and reductionism. Psychoneuroimmunology (PNI) is a modern research area of psychosomatic medicine which tries to overcome such paradigmatic engravings. PNI investigates the interrelationship between psychological factors and stress system activities. In normal individuals, chronic psychosocial stress is associated with increased releases in cortisol (hypercortisolism), lower levels in T helper type 1 (TH1) and higher levels in T helper type 2 (TH2) immune activity. Such stress-induced TH1/TH2 shift promotes diseases in which TH1 is protective (e.g. virus infection) and TH2 is damaging (e.g. allergy). In traumatized patients, stress system functioning is disturbed which is associated with blunted cortisol decreases (hypocortisolism) and inflammation increases under stressful conditions. Inflammation increases, on the other hand, trigger behavioral symptoms related to atypical depression (e.g. fatigue). Investigating bidirectional PNI effects (from psyche to immune, from immune to psyche) is not possible by applying biomedical research approaches (e.g. pre-post design). PNI findings from integrative single-case studies on lupus patients will be presented. <h3>Disclosure of Interest</h3> None declared
Secondary Mutations of JAK3 and SETBP1 in Juvenile Myelomonocytic Leukemia and Their Propagating Capacity; A Report from the AIEOP Study Group
Authors: Silvia Bresolin, Paola De Filippi, Francesca Vendemini, Riccardo Masetti, Franco Locatelli, Geertruy te Kronnie
Journal: Blood (2014)
Suspension of Vitamin K Antagonists Is Not Required for Cataract Surgery: A Prospective Study in a Cohort of 135 Consecutive Patients on Long-Term Anticoagulant Therapy.
Authors: Berardino Pollio, Giuseppe A. Demarie, Patrizia Ocello, Grazia Delios, Marco Tucciarone, Gabriele Aitoro, Rossella Perna, Stefano D’Ardia, Marco Ladetto, Luigi Bauchiero, Mauro Girotto
Journal: Blood (2006)
The Importance of Pharmacovigilance during Ibrutinib Therapy for Chronic Lymphocytic Leukemia (CLL) in Routine Clinical Practice
Authors: Heidi D. Finnes, Kari G. Chaffee, Timothy G. Call, Wei Ding, Deborah A. Bowen, Michael Conte, Kristen B. McCullough, Julianna A. Merten, Gabriel T. Bartoo, Matthew D. Smith, Susan M. Schwager, Susan L. Slager, Neil E. Kay, Tait D. Shanafelt, Sameer A. Parikh
Journal: Blood (2015)
Bortezomib and High Dose Melphalan Followed by Autologous Stem Cell Transplantation (BortHDM/SCT) for the Treatment of AL Amyloidosis: Results of a Feasibility Study.
Authors: Vaishali Sanchorawala, Lisa Yanarella, Karen Quillen, John Mark Sloan, Nancy T. Andrea, Kathleen T. Finn, David C. Seldin
Journal: Blood (2009)
Immune Modulation of Brown(ing) Adipose Tissue in Obesity
Authors: Susan M. van den Berg, Andrea D. van Dam, Patrick C. N. Rensen, Menno P. J. de Winther, Esther Lutgens
Journal: Endocrine Reviews (2016)

Obesity is associated with a variety of medical conditions such as type 2 diabetes and cardiovascular diseases and is therefore responsible for high morbidity and mortality rates. Increasing energy expenditure by brown adipose tissue (BAT) is a current novel strategy to reduce the excessive energy stores in obesity. Brown adipocytes burn energy to generate heat and are mainly activated upon cold exposure. As prolonged cold exposure is not a realistic therapy, researchers worldwide are searching for novel ways to activate BAT and/or induce beiging of white adipose tissue. Recently, the contribution of immune cells in the regulation of brown adipocyte activity and beiging of white adipose tissue has gained increased attention, with a prominent role for eosinophils and alternatively activated macrophages. This review discusses the rediscovery of BAT, presents an overview of modes of activation and differentiation of beige and brown adipocytes, and describes the recently discovered immunological pathways that are key in mediating brown/beige adipocyte development and function. Interventions in immunological pathways harbor the potential to provide novel strategies to increase beige and brown adipose tissue activity as a therapeutic target for obesity.
AB0891 Dynamics of Parameters of Connective Tissue Metabolism in Children with Juvenile Idiopathic Arthritis by The Follow-Up Study
Authors: Y. Zaytseva, I. Lebec
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is a chronic and socially significant disease as it leads to quick disability in childhood. Metabolic processes of connective tissue are important part of pathogenesis of JIA. <h3>Objectives</h3> It was to study dynamics of parameters of connective tissue metabolism in children with JIA against the background of standard therapy with methotrexate by the follow-up study. <h3>Methods</h3> The study involved 65 children within 2–18 years with JIA: oligoarthritis in 39,6%, polyarticular form - 37,7%, systemic form - 20,8%, enthesitis-related arthritis – 1,9%. In serum the total level of glucosaminoglycans (GAG) and chondroitinsulfate (CS), level of chondroitin-6-sulfate as I fraction of GAG, level of chondroitin-4-sulfate as II fraction of GAG, level of heparansulfate as III fraction of GAG, calcium, phosphorus and in urine level of oxyproline, uronic acid, calcium, phosphorus were determined. Parameters were assessed depending on the duration of disease: till 1 years (19 patients), 1–2 years (17 patients), 2–3 years (29 patients). They had being evaluated over the following 3 years. <h3>Results</h3> 77.78% of patients had decreased level of GAG in the serum. Decrease of I fraction of GAG was determined in 11.11% of patients, of II fraction of GAG -92.59% and III fraction of GAG – 96.3% of patients. Increased level of I fraction of GAG was presented in 48.15% of children. Mean general level of GAG was not difference in comparison with persons of control group and did not depend on duration of disease. Mean level of I and II fractions of GAG in patients with JIA was higher in comparison with persons of control group, beginning from 1st year of diseases development and for next 3 years (p&lt;0.001). Mean level of III fraction of GAG was not difference in comparison with persons of control group and did not depend on duration of disease. 51.85% of patients had increased level of CS. Mean level of CS in patients with JIA was higher in comparison with persons of control group, beginning from 1st year of diseases development and for next 3 years (p&lt;0.001). 59.26% of children with JIA had increased urinary excretion of oxyproline. The mean levels of oxyproline, uronic acid, phosphorus in urine in patients with JIA were not different in comparison with children of control group and did not depend on duration of disease. The level of serum calcium in the majority of patients (96.3%) was within the limits of norm, in urine – in 74.07% of patients was increased. The average level of calcium in urine was reliably below, than at group of the control (p &lt;0, 01), irrespective of duration of disease. <h3>Conclusions</h3> Changes in the exchange of connective tissue metabolism are occurred already during the first year of JIA development and presented in subsequent years, despite treatment. <h3>Disclosure of Interest</h3> None declared
A Phase I Dose Escalation Study of the mTOR Inhibitor Sirolimus and MEC Chemotherapy Targeting Signal Transduction in Leukemic Stem Cells for Acute Myeloid Leukemia.
Authors: Selina Luger, Alexander Perl, Allison Kemner, Edward A. Stadtmauer, David Porter, Stephen J. Schuster, Stephen C. Goldstein, Donald E. Tsai, S. Nasta, A. Loren, Jamil K. Dierov, D. Vogl, C. Andreadis, Stephen G. Emerson, Martin Carroll
Journal: Blood (2006)
PTU-150 Simplified Barrett’s Radiofrequency Ablation Technique in The Elderly. Consideration Should Be Given to Balancing The Increased Risks with Benefits
Authors: JA Campbell, AD Hopper
Journal: Gut (2016)

<h3>Introduction</h3> Barrett’s oesophagus (BO) is a major risk factor for the development of oesophageal adenocarcinoma. Radiofrequency ablation (RFA) is an established treatment option in high risk patients with high grade dysplasia (HGD). Recent simplified methods have also been shown to have equivocal treatment success with shorter treatment times. New recommendations to treat patients with low grade dysplasia have been established which will increase numbers of eligible patients. Reduction in procedure duration is attractive to accommodate the increasing referrals, and reduce sedation requirements, especially in the elderly. We aimed to assess the complications and success of simplified RFA technique in consecutive patients undergoing treatment for Barrett’s oesophagus. <h3>Methods</h3> All patients discharged from simplified RFA treatment course for BO over a 2 year period were identified. Circumferential RFA (c-RFA) or Focal Ultra RFA (u-RFA) was performed with a simplified double application of RFA (12 J/cm) - the device was not removed or cleaned. Simplified Focal RFA (f-RFA) with smaller devices was performed with a (3×15 J/cm no clean) regimen. Strict RFA medication protocol and repeat 3 month follow up was performed for each patient. Patient demographics, success of treatment, withdrawal from treatment and complications were noted. Outcomes were compared in age groups under and over 75 (Fisher’s exact test) to assess if there was a difference in complication rate. <h3>Results</h3> 36 patients discharged from simplified RFA treatment were identified (11 female; median age 71: range 46–80). 76 treatments were performed in total (22 c-RFA 11 u-RFA and 43 f-RFA). Complete eradication of Barrett’s mucosa was successful in 83.3% (30/36) patients. Median number of treatments was 2 (range 1–6). 1 patient with an incomplete response after 4 treatments was treated twice with a non simplified RFA method but after no further response the patient was discharged from RFA programme. 4/36 patients (11.1%) reported complications which resulted in discharging from programme. Reasons were: prolonged atrial-fibrillation with haemodynamic compromise (2 nd treatment u-RFA); significant oesophageal stricture (c-FRA); hypotensive fall with 7 day admission (u-RFA); prolonged post procedure pain (f-RFA). All complications lead to withdrawal from the RFA programme. 30.7% of patients aged over 75 experienced complications compared to 0% in patients under 75 (p = 0.0121). <h3>Conclusion</h3> A simplified oesophageal RFA regime is effective to remove BO, however its use in the elderly may be linked with increased complications leading to program withdrawal. <h3>Disclosure of Interest</h3> None Declared
AB1044 Pain and Psychological Health May Be Associated To Risk Factors for Cardiovascular Disease in Patients with Rheumatic Joint Disease: Table 1
Authors: S.A. Provan, I.J. Berg, H. Dagfinrud, N. Østerås, T.K. Kvien, T. Uhlig
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Patients with rheumatological joint diseases (RJD) have an increased risk of cardiovascular disease (CVD). There is a lack of knowledge concerning the impact of health status on CVD risk. Augmentation index (AIx) and reactive hyperemia index (RHI) are two markers of CVD risk. High values of AIx, and low values of RHI signify an increased risk of CVD. <h3>Objectives</h3> To investigate whether pain and self-reported health status are associated with CVD risk in patients with RJD. <h3>Methods</h3> 895 patients with RJD were included. 425 patients with self-reported osteoarthritis (OA), 159 patients with ankylosing spondylitis (AS) and 148 patients with rheumatoid arthritis (RA). Variables of demography, co-morbidities, self-reported pain, health related quality of life (EuroQOL (EQ-5D) (AS and OA)) and health status (Short form 36 (SF-36)) were collected on questionnaires. Clinical examinations were performed by a study nurse and the 28-tender joint count recorded (28-TJC) (RA and OA). AIx (Sphygmocor apparatua (Atcor®)) and RHI (Itamar®) were measured. Cross-sectional linear regression analyses were performed with AIx and RHI as dependent variables in separate models. The associations between pain, health status and CVD risk (AIx and RHI as dependent variables) were examined in cross-sectional models adjusted for type of RJD, age and sex. (AIx was also adjusted for height). Possible confounders were identified from previous literature and plotted in directed acyclic graphs<sup>1</sup>. Relevant variables were entered into multivariate models. <h3>Results</h3> 895 patients with RJD were included, mean age was 61.3 (range 28–85), (64.7%) females. AIx was available in 143 patients with RA, 130 with AS, and 424 with OA. RHI was available in 143 patients with RA and 42 with AS. The results from the linear regression models are presented in the table. The multivariate models were adjusted for body mass index and disease activity (DAS ≥2.6 or ASDAS ≥1.3 = active disease). <h3>Conclusions</h3> Pain and psychological health are related to markers of CVD risk in RJD, after adjustments for disease activity. These novel findings require confirmation in longitudinal studies. <h3>References</h3> Williamson EJ. Respirology 2014. <h3>Disclosure of Interest</h3> None declared