tbuckley/cabot-search huggingface dataset:
FRI0673 Do patient reported outcome measurement information system (PROMIS) computer adaptive tests correlate with disease activity in juvenile idiopathic arthritis?
Authors: R. Trachtman, E. T. Murray, J. Szymonifka, A. B. Adams, N. Pan, S. F. Taber, K. B. Onel, L. A. Mandl
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> The importance of patient-reported outcomes is increasingly recognized both in clinical care and in research. PROMIS is an NIH-supported collection of patient-reported outcome measures, covering a variety of domains that are designed without disease specificity. While 'short forms' have been studied in juvenile idiopathic arthritis (JIA), PROMIS computer adaptive tests (CATs) have not. <h3>Objectives:</h3> This study evaluates whether PROMIS CATs correlate with disease activity in patients with JIA. <h3>Methods:</h3> A convenience sample of patients with JIA (N=21) were recruited from a single center. Patients aged 10–17 years completed all available pediatric PROMIS CATs, and parents of patients aged 2–9 years completed all available parent proxy PROMIS CATs (fatigue, pain interference, peer relations, anxiety, depressive symptoms, and mobility). Correlation of the CATs t-scores with disease activity, as measured by the Juvenile Disease Activity Score-71 (JADAS-71), (0–101, higher being worse) was evaluated using Spearman correlation coefficients. <h3>Results:</h3> All families approached completed the PROMIS CATs: 13 patients and 8 parents (table 1). Median age was 12.7 years (range 1.3 – 18.6 years), and mean JADAS-71 score was 9.58 (SD 2.07). 69% of patients completed PROMIS CATs remotely via smartphone. Anxiety (r=0.74, p=0.006), depressive symptoms (r=0.84, p&lt;0.001), and pain interference (r=0.64, p=0.018) CATs correlated strongly with JIA disease activity (table 2). Among parent proxy CATs, only anxiety correlated with disease activity (r=0.71); however the association was not statistically significant. <h3>Conclusions:</h3> Our results demonstrate that the PROMIS CATs are feasible to administer in an outpatient pediatric rheumatology setting. Anxiety, depressive symptoms, and pain interference were significantly correlated with disease activity, even though mean disease activity was relatively low. This underscores the negative effect on quality of life of even mild disease. Parent proxy CATs showed poor correlations with disease activity, suggesting parents are inaccurate in assessing important aspects of their child's health. Larger prospective studies are needed to evaluate the sensitivity of PROMIS CATS to change in disease activity over time. <h3>Disclosure of Interest:</h3> None declared
THU0435 Long-term outcome and prognosis factors of complications in thromboangiitis obliterans (BUERGER’S DISEASE): a multicenter study of 224 patients
Authors: A. Le Joncour, S. Soudet, A. Dupont, O. Espitia, F. Koskas, P. Cluzel, P.-Y. Hatron, P. Cacoub, M. Resche-Rigon, M. Lambert, D. Saadoun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Buerger's disease or thromboangiitis obliterans (TAO) is a non-atherosclerotic arteritis of distal extremities. Data regarding long term outcome of patients with Buerger's disease or thromboangiitis obliterans (TAO) are lacking and most series come from Middle-East and Far-East. <h3>Objectives</h3> We aim report clinical presentation and assess long-term outcome and prognosis factors in a large cohort of TAO. <h3>Methods</h3> Retrospective multicenter study of characteristics and outcomes of 224 TAO patients fulfilling Papa's and/or 5 Shinoya's criterias were analysed. Factors associated with vascular event free survival and amputation free survival were identified. <h3>Results</h3> The median age at diagnosis was 38.5<sup>32–46</sup> years, 51 (28.5%) patients were female and 81.5% were Caucasians. All but 3 were smokers with a median of 22 pack-year and 22.8% were also addict to cannabis. At diagnosis, 53% had claudication, 73% trophic disorders and 8.8% an infection. Lower extremities and upper extremities were affected in 54% and 28% respectively. Superficial vein thrombosis, Raynaud's phenomen and arthralgia occurred in 18%, 41% and 8%, respectively. Ethnic group (non-Caucasian) and ischaemic ulcers or necrosis were independent factors of vascular events HR=7.67 [3.1–19.2] p=0.005 and 2.28 [1.3–4] p&lt;0.001. At 15 years, amputation-free survival and major amputation-free survival were 66% and 91%, respectively. Infection was the only independent predictive factor of amputation HR=4.6[1.9–11], p&lt;0001. Age, sex and cannabis addiction were not associated with events or amputation. Patient who stopped their tobacco consumption had lower vascular event (p=0.029) and amputation rate (p=0.001) than those who continued. Three patients died during follow-up. <h3>Conclusions</h3> This nationwide study shows that 34% of TAO patients will experience an amputation within 15 years from diagnosis. We identified specific characteristics that identified those at highest risk for subsequent vascular complications. <h3>Disclosure of Interest</h3> None declared
Genome-wide association analyses of risk tolerance and risky behaviors in over 1 million individuals identify hundreds of loci and shared genetic influences
Authors: Richard Karlsson Linnér, Pietro Biroli, Edward Kong, S. Fleur W. Meddens, Robbee Wedow, Mark Alan Fontana, Maël Lebreton, Stephen P. Tino, Abdel Abdellaoui, Anke R. Hammerschlag, Michel G. Nivard, Aysu Okbay, Cornelius A. Rietveld, Pascal N. Timshel, Maciej Trzaskowski, Ronald de Vlaming, Christian L. Zünd, Yanchun Bao, Laura Buzdugan, Ann H. Caplin, Chia-Yen Chen, Peter Eibich, Pierre Fontanillas, Juan R. Gonzalez, Peter K. Joshi, Ville Karhunen, Aaron Kleinman, Remy Z. Levin, Christina M. Lill, Gerardus A. Meddens, Gerard Muntané, Sandra Sanchez-Roige, Frank J. van Rooij, Erdogan Taskesen, Yang Wu, Futao Zhang, Adam Auton, Jason D. Boardman, David W. Clark, Andrew Conlin, Conor C. Dolan, Urs Fischbacher, Patrick J. F. Groenen, Kathleen Mullan Harris, Gregor Hasler, Albert Hofman, Mohammad A. Ikram, Sonia Jain, Robert Karlsson, Ronald C. Kessler, Maarten Kooyman, James MacKillop, Minna Männikkö, Carlos Morcillo-Suarez, Matthew B. McQueen, Klaus M. Schmidt, Melissa C. Smart, Matthias Sutter, A. Roy Thurik, André G. Uitterlinden, Jon White, Harriet de Wit, Jian Yang, Lars Bertram, Dorret I. Boomsma, Tõnu Esko, Ernst Fehr, David A. Hinds, Magnus Johannesson, Meena Kumari, David Laibson, Patrik K. E. Magnusson, Michelle N. Meyer, Arcadi Navarro, Abraham A. Palmer, Tune H. Pers, Danielle Posthuma, Daniel Schunk, Murray B. Stein, Rauli Svento, Henning Tiemeier, Paul R. H. J. Timmers, Patrick Turley, Robert J. Ursano, Gert G. Wagner, James F. Wilson, Jacob Gratten, James J. Lee, David Cesarini, Daniel J. Benjamin, Philipp D. Koellinger, Jonathan P. Beauchamp
Journal: Nature Genetics (2019)
Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells
Authors: Warren Fiskus, Tianyu Cai, Courtney D. DiNardo, Steven M. Kornblau, Gautam Borthakur, Tapan M. Kadia, Naveen Pemmaraju, Prithviraj Bose, Lucia Masarova, Kimal Rajapakshe, Dimuthu Perera, Cristian Coarfa, Christopher P. Mill, Dyana T. Saenz, David N. Saenz, Baohua Sun, Joseph D. Khoury, Yu Shen, Marina Konopleva, Kapil N. Bhalla
Journal: Blood Cancer Journal (2019)

Abstract First-generation bromodomain extra-terminal protein (BETP) inhibitors (BETi) (e.g., OTX015) that disrupt binding of BETP BRD4 to chromatin transcriptionally attenuate AML-relevant progrowth and prosurvival oncoproteins. BETi treatment induces apoptosis of AML BPCs, reduces in vivo AML burden and induces clinical remissions in a minority of AML patients. Clinical efficacy of more potent BETis, e.g., ABBV-075 (AbbVie, Inc.), is being evaluated. Venetoclax and A-1210477 bind and inhibit the antiapoptotic activity of BCL2 and MCL1, respectively, lowering the threshold for apoptosis. BETi treatment is shown here to perturb accessible chromatin and activity of enhancers/promoters, attenuating MYC, CDK6, MCL1 and BCL2, while inducing BIM, HEXIM1, CDKN1A expressions and apoptosis of AML cells. Treatment with venetoclax increased MCL1 protein levels, but cotreatment with ABBV-075 reduced MCL1 and Bcl-xL levels. ABBV-075 cotreatment synergistically induced apoptosis with venetoclax or A-1210477 in patient-derived, CD34+ AML cells. Compared to treatment with either agent alone, cotreatment with ABBV-075 and venetoclax was significantly more effective in reducing AML cell-burden and improving survival, without inducing toxicity, in AML-engrafted immune-depleted mice. These findings highlight the basis of superior activity and support interrogation of clinical efficacy and safety of cotreatment with BETi and BCL2 or MCL1 inhibitor in AML.
SP0099 A case of painful dyspnea
Authors: M. Gatto
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> A 20-year-old female patient was admitted to ER due to dyspnea and stinging chest and interscapular pain, associated with neck pain worsened by physical exercise. She reported worsening of respiratory symptoms in the past ten days and concomitant onset of acrocyanosis. At physical examination she displayed tachycardia and tachypnea, no abnormalities at lung auscultation, with oxygen saturation 94% at pulse oxymeter. Arterial blood gas tests showed a decreased pO2 and pCO2. Urgent blood examination showed low leucocyte count 2900/mm3 and mild normocytic anaemia Hb 10.8 g/dl. Due to chest pain, dyspnea and concomitant gas findings, a CT scan was prompted in the suspicion of pulmonary embolism, yet no vascular abnormalities were shown, but a small rim of pleural fluid at the right base. The patient was admitted to Internal medicine department where she underwent pulmonary function tests showing a restrictive respiratory pattern with decreased TLCO and but normal KCO. HRCT was performed ruling out interstitial lung disease. Elevation of right emidiaphgram was shown at AP imaging. Upcoming blood and urine analysis showed increased serum creatinine with proteinuria 1 g/day and hematuria. Following interdisciplinary consultation immunologic investigations were performed showing elevated titres of ANA, anti-dsDNA and decreased complement levels. The patient was diagnosed with SLE with shrinking lung and active renal involvement and was referred to Rheumatology Unit where treatment was initiated with prednisone 0.5 mg/kg/day and mycophenolate mofetil 2 g/day. Respiratory symptoms as well as pulmonary function tests improved within some days after initiation of steroid treatment. After 12 months the patient displayed still abnormally restrictive respiratory pattern at pulmonary function tests, despite clinical improvement. She was also displaying proteinuria 0.8 g/day with active urinary sediment and rising anti-dsDNA antibodies. Thus, she underwent Rituximab 1 g 2 weeks apart with subsequent improvement of both renal and respiratory signs and symptoms. Improvement remained stable at 2 years. <h3>Disclosure of Interest</h3> None declared
Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy
Authors: Imran Siddiqui, Karin Schaeuble, Vijaykumar Chennupati, Silvia A. Fuertes Marraco, Sandra Calderon-Copete, Daniela Pais Ferreira, Santiago J. Carmona, Leonardo Scarpellino, David Gfeller, Sylvain Pradervand, Sanjiv A. Luther, Daniel E. Speiser, Werner Held
Journal: Immunity (2019)
FRI0024 Do age and education influence the disease activity score? an explorative analysis in the norwegian cohort study nor-dmard
Authors: M. Van Onna, P. Putrik, E. Lie, T. Kvien, A. Boonen, T. Uhlig
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> While ageing influences auto-immune inflammation and the structure of the joints, knowledge about its influence on appraisal of disease outcomes is more limited. <h3>Objectives</h3> To examine the effect of age and education on the components of the 28-joint Disease Activity Score (DAS28-ESR) in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Baseline data of Disease Modifying Anti-Rheumatic Drug (DMARD)-naive patients with RA from the Norwegian Register of DMARDs (NOR-DMARD) were used. Linear regression models, adjusted for gender and education (low, intermediate and high level), were used to investigate the strength of the association between age (&lt;45, 45–65 and &gt;65 years) and each DAS28-component (Erythrocyte Sedimentation Rate (ESR), 28-tender joint count (28-TJC), 28-swollen joint count (28-SJC), and patient global assessment of disease activity (PGA)). Adjusted scores for components of DAS28 and total DAS28-ESR were computed and relative change across age categories was explored. Interactions between age and gender and age and education were also tested. <h3>Results</h3> Baseline data from 2037 patients (mean (SD) age 55.2 (14.0) years, 68% female) were available. Regression models were stratified for gender (p –interaction &lt;0.05); education was a significant covariate in all regression analyses. Older males (&gt;65 years) with an intermediate level of education would have a 21% higher ESR and 14% higher 28-SJC, as compared to their younger counterparts (&lt;45 years). For females in the intermediate education category, the corresponding differences were 16% and 15%, respectively. Conversely, differences in 28-TJC and the PGA between the highest and lowest age group were negligible in both males and females (table 1). In absolute effects on DAS28, this means that in male patients the adjusted DAS28 for those &gt;65 years was 4.8 compared to 4.3 in patients&lt;45 years (females 5.0 compared to 4.6). For low and high levels of education, the results were comparable in terms of relative contribution to each DAS28-component. <h3>Conclusions</h3> As expected, DAS28 increases with age. However, the components of DAS28 increase at different rates. The age-related increase in ESR and 28-SJC without a simultaneous increase in 28-TJC and PGA might imply that age-related processes (e.g. osteoarthritis and physiological increase in ESR) drive the DAS28 in older patients. The observed patterns were largely comparable between males and females. The age effect on DAS28 is relevant in a treat-to-target strategy and may be considered when identifying a defined target in individual patients. <h3>Disclosure of Interest</h3> None declared
KRAS-enhanced macropinocytosis and reduced FcRn-mediated recycling sensitize pancreatic cancer to albumin-conjugated drugs
Authors: Huiqin Liu, Mengnan Sun, Zhengsheng Liu, Chao Kong, Weijian Kong, Junxiao Ye, Jianan Gong, David C.S. Huang, Feng Qian
Journal: Journal of Controlled Release (2019)
SAT0380 Panlar-accar recommendations on diagnosis and treatment of chikungunya-related inflammatory arthropathies in latin america
Authors: P. Monge, A.M. Sapag, I.Y. Moreno, R.A. Montúfar, V. Khoury, P. Camilo, R.E. Rivera, J.C. Rueda, D. Jaramillo-Arroyave, J. Londoño, M.C. Ruiz, F. Fernández-Castillo, M. Quintero, Y. Fuentes, J.L. Aguilar, C.V. Caballero-Uribe, H. Sandoval, C. Pineda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Although mortality rates related with Chikungunya (CHIK) outbreaks into Latin America’s endemic-dengue rural and new urban regions are low, dealing with symptoms and sequelae can produce both a significant burden of disease and diminish quality of life — from many months to years — after the acute phase of infection, with a significant impact on public and individual health. <h3>Objectives</h3> The aim of this work was to establish a PANLAR-ACCAR consensus on diagnosis and treatment of CHIK-related inflammatory arthropathies transmitted by Ae. Aegypti and Ae. Albopictus in Latin America (LA). <h3>Methods</h3> Based on the Consensus Development Conference format, a panel of ACCAR rheumatologists (n=10) took part in this PANLAR initiative. Experts voted recommendations from a previous content analysis of the medical literature on CHIK, four subsequent topic’s Conferences and a workshop. Consensus represents the majority agreement (≥80%) achieved for each recommendation. <h3>Results</h3> The panel reach four overarching principles: 1) CHIK virus (CHIKV) is a re-emergent virus transmitted by two species of mosquitoes: Ae. Aegypti and Ae. Albopictus; 2) CHIKV caused massive outbreaks in LA; 3) Chronic CHIKV infection produces an inflammatory joint disease that in some cases can last several months to years, and 4) Currently, there are no vaccines or antivirals available for CHIKV infections. <h3>Conclusions</h3> PANLAR-ACCAR achieve 13 recommendations on CHIK categorised in three groups: 1) epidemiology and clinical manifestations; 2) diagnosis, and 3) treatment, representing the consensus agreement from the panel’s members. <h3>References</h3> [1] Pineda C, Munoz-Louis R, Caballero-Uribe CV, Viasus D. Chikungunya in the region of the Americas. A challenge for rheumatologists and health care systems. Clin Rheumatol2016;35(10):2381–5. [2] Fernandez-Salas I, Danis-Lozano R, Casas-Martinez M, Ulloa A, Bond JG, Marina CF, et al. Historical inability to control Aedes aegypti as a main contributor of fast dispersal of chikungunya outbreaks in Latin America. Antiviral Res2015;124:30–42. [3] Khoury VJ, Camilo PR. Chikungunya virus (CHIKV): what can be expected after the acute phase?Reumatol Clin2016;12(1):1–3. [4] JC Rueda, J-I Angarita, AM Santos, E-L Saldarriaga, I Pelaez-Ballestas, MJ Soares-Santeugini, J Londono. SAT0576 [5] Improved clinical scenario for chikungunya diagnosis Annals of the Rheumatic Diseases2017Jun;76(Suppl 2):994. <h3>Disclosure of Interest</h3> None declared
FRI0430 Effect of oral nutritional intervention on nutritional status in patients with systemic sclerosis
Authors: A. Wojteczek, M. Ziętkiewicz, S. Małgorzewicz, Z. Zdrojewski
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with systemic sclerosis (SSc) are at risk of malnutrition, which ranges from 18% to 56% of cases.<sup>1,2</sup> The high impact of nutritional status on clinical outcome has been shown for many diseases. The optimal nutritional treatment can lead to improvement or preservation of the current nutritional status and increases probability of long-term survival.<sup>3</sup> <h3>Objectives</h3> The aim of the study was to determine whether nutritional support has an impact on improvement of nutritional status in SSc patients. <h3>Methods</h3> The study included 61 patients with SSc and 49 healthy adults. Nutritional status was determined with subjective global assessment (SGA), body mass index (BMI), bioelectrical impedance analysis (BIA) and anthropometric measurements. Nutrition-related laboratory tests were measured. Appetite was assessed by simplified nutritional appetite questionnaire (SNAQ). <h3>Results</h3> Impaired nutritional status was confirmed in 16 patients with SSc (26,2%). Those patients had significantly lower SGA, BMI (p=0,0019), hand grip strength (p=0,0019), appetite (p=0,019) and BIA parameters such as lean tissue mass (p=0,013), intracellular water (p=0,0006), adipose tissue mass (p=0,04). In laboratory tests levels of haemoglobin, albumin and HDL cholesterol were significantly lower, while erythrocyte sedimentation rate (ESR) was higher (p=0,0025). Thirteen patients had dietary intervention (high-energy, high-protein, oral, liquid nutritional supplements) for 12 weeks. SGA (p=0,017) and hand grip strength (p=0,006) improved after nutritional treatment. BMI, appetite, BIA parameters, lipid profile and ESR after 12 weeks remained stable. <h3>Conclusions</h3> Assessment of nutritional status in SSc patients should be performed regularly, because inclusion of oral nutritional intervention may improve SGA and hand grip strength. <h3>References</h3> [1] Baron M, et al. Malnutrition is common in systemic sclerosis: results from the Canadian scleroderma research group database. J Rheumatol2009;36:2737–43. [2] Krause L, et al. Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis. Ann Rheum Dis2010;69:1951–1957. [3] Harrison E, et al. Long-term outcome of patients with systemic sclerosis requiring home parenteral nutrition. Clinical Nutrition2015;34:991–996. <h3>Disclosure of Interest</h3> None declared
FRI0094 Does subclinical inflammation explain joint pain in patients with arthralgia suspicious for progression to rheumatoid arthritis? – results of a cross-sectional mri-study
Authors: L.E. Burgers, R.M. ten Brinck, D.M. Boeters, A.H.M. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The development of Rheumatoid Arthritis (RA) is often preceded by a symptomatic phase of arthralgia. The etiology of symptoms in this phase is unclear. <h3>Objectives</h3> Since subclinical joint inflammation is expected to be causally related to pain, we aimed to determine associations between subclinical MRI-detected inflammation and pain in patients with arthralgia suspicious for progression to RA. <h3>Methods</h3> Unilateral MRIs of the wrist, MCP(2–5)- and MTP(1–5)-joints of 325 patients who fulfilled the EULAR definition of arthralgia suspicious for progression to RA were made and scored by two readers on subclinical inflammation (synovitis, bone marrow oedema (BME) and tenosynovitis). Associations between MRI-detected inflammation and overall pain severity at patient level (measured using the visual analogue scale (VAS)), and local tenderness at joint palpation, were studied in all patients, in ACPA-positive and ACPA-negative patients separately, and in the subgroup of patients that progressed to inflammatory arthritis. <h3>Results</h3> At patient level, synovitis (β=0.10, p=0.048) and tenosynovitis (β=0.11, p=0.026) associated with the VAS-pain. Of the 1620 imaged joints, 447 (28%) were tender. Subclinical inflammation was present in 32% of tender joints and in 25% of non-tender joints. MRI-detected synovitis associated independently with joint tenderness (OR 1.74, p&lt;0.001). In ACPA-negative patients synovitis associated independently with joint tenderness (OR 1.96, p&lt;0.001), while BME was independently associated with joint tenderness in ACPA-positive patients (OR 2.39, p=0.005). Sensitivity analyses in patients who developed arthritis during follow-up (n=61) revealed similar associations. <h3>Conclusions</h3> In patients with arthralgia suspicious for progression to RA, joint tenderness and pain are associated with MRI-detected subclinical inflammation. The association is incomplete, indicating that subclinical inflammation is not the sole explanation of the arthralgia. <h3>Disclosure of Interest</h3> None declared
Ibrutinib Treatment Reduces Myeloid Derived Suppressor Cell Numbers and Function in Chronic Lymphocytic Leukemia
Authors: Gerardo Ferrer, Byeongho Jung, Aslam Rukhsana, Pui Yan Chiu, Andrea Nicola Mazzarello, Florenca Palacios, Shih-Shih Chen, Xiao J. Yan, Jacqueline C. Barrientos, Jan A. Burger, Jonathan E. Kolitz, Steven L. Allen, Kanti R Rai, Barbara Sherry, Nicholas Chiorazzi
Journal: Blood (2018)