tbuckley/cabot-search huggingface dataset:
SP0165 The complex interplay between systemic lupus erythematosus and antiphospholipid syndrome
Authors: E. Svenungsson
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> The antiphospholipid syndrome (APS) was first described in the 1980's. It is diagnosed when antiphospholipid antibodies (aPL) i.e. anti-cardiolipin (aCL), anti-β<sub>2</sub>Glycoprotein-I (aβ<sub>2</sub>GPI) or positivity in the functional lupus anticoagulant test (LA) occur together with any type of thrombosis (e.g. myocardial infarction(MI), stroke, venous or microvascular thromboses) or obstetric complications(.<sup><sup>5</sup></sup> aPL recognise protein co-factors, most importantly the scavenger protein β<sub>2</sub>GlycoproteinI (β<sub>2</sub>GPI), that bind to membrane phospholipids. It is not fully understood how complexes of β<sub>2</sub>GPI and anti-β<sub>2</sub>GP1 antibodies initiate a pro-thrombotic state, but activation of platelets, endothelial cells and the complement cascade are associated features. Approximately 80% of APS patients are women, many are young and severely ill. There is a considerable overlap between APS and SLE. Approximately 30%–40% of SLE patients are aPL positive but only about half of them develop clinical symptoms fulfilling the APS classification criteria. Several prospective studies have demonstrated that aPL are predictive of vascular events in patients with SLE. Though conflicting results exist, we have not noted positive associations between aPL and accelerated atherosclerosis in SLE, rather we believe that it is the pro-thrombotic state, which is the major cause of vascular events in the aPL positive SLE subgroup. Microvascular disease is an often unrecognised and difficult to diagnose feature in the aPL positive SLE subgroup. We have noted that up to 15% of patients diagnosed with nephritis have microvascular pathology in accordance with APS nephropathy in renal biopsies. The aPL positive SLE subgroup has also been demonstrated to have a more rapid accrual of damage, where in addition to vascular damage neuropsychiatric damage makes a notable contribution. When investigating primary APS patients, we and others have noted traits that are normally seen and attributed to SLE, such as low platelets, complement consumption, a low grade of systemic inflammation and even low titers of anti-DNA antibodies. Thus, the distinction between these two groups, APS secondary to SLE and primary APS, is not always clear. <h3>Disclosure of Interest</h3> None declared
Mobile health tools for the management of chronic respiratory diseases
Authors: Kristien Sleurs, Sven F. Seys, Jean Bousquet, Wytske J. Fokkens, Senne Gorris, Benoit Pugin, Peter W. Hellings
Journal: Allergy (2019)

Abstract Background The market of mobile health ( mH ealth) technology is rapidly evolving, making new mobile technologies potentially available for healthcare systems. Patient empowerment through self‐monitoring of symptoms, shared decision making with the physician, and easily accessible education are important features extending the reach of mH ealth technology beyond traditional care. Methods Two digital distribution platforms (Apple App Store and Google Play Store) were searched for currently available mobile applications (apps) for patients with chronic respiratory diseases ( CRD s). A new index (score ranging from 0 to 10) was developed to assess the potential of apps as a tool to empower patients through mobile technology (based on self‐monitoring, personalized feedback, and patient education app features). Results One hundred and twelve apps were retained for analysis and could be classified in 5 categories: Asthma (n = 71), COPD (n = 15), Asthma and COPD (n = 15), Rhinitis and Asthma (n = 5), and Rhinosinusitis (n = 6). Eighty percent were developed by medical technology companies compared to 18% by medical doctors and 2% by pharmaceutical companies. Two‐thirds of apps allow disease self‐monitoring, whereas over half of apps provide patient feedback through graphs. Sixty percent of apps contain easily accessible patient education material. Only three percent of apps reach a score of ≥7 on the newly designed patient empowerment index. Conclusions A variety of apps are available for patients with CRD s of which only few were developed by or jointly with medical doctors. The majority of these apps include self‐monitoring tools, but only few also provide personalized feedback, which is needed to adopt these apps into daily care.
Risk Prediction Tools to Improve Patient Selection for Carotid Endarterectomy Among Patients With Asymptomatic Carotid Stenosis
Authors: Salomeh Keyhani, Erin Madden, Eric M. Cheng, Dawn M. Bravata, Ethan Halm, Peter C. Austin, Mehrnaz Ghasemiesfe, Ann S. Abraham, Alysandra J. Zhang, Jason M. Johanning
Journal: JAMA Surgery (2019)

Randomized clinical trials have demonstrated that patients with asymptomatic carotid stenosis are eligible for carotid endarterectomy (CEA) if the 30-day surgical complication rate is less than 3% and the patient's life expectancy is at least 5 years.To develop a risk prediction tool to improve patient selection for CEA among patients with asymptomatic carotid stenosis.In this cohort study, veterans 65 years and older who received both carotid imaging and CEA in the Veterans Administration between January 1, 2005, and December 31, 2009 (n = 2325) were followed up for 5 years. Data were analyzed from January 2005 to December 2015. A risk prediction tool (the Carotid Mortality Index [CMI]) based on 23 candidate variables identified in the literature was developed using Veterans Administration and Medicare data. A simpler model based on the number of 4 key comorbidities that were prevalent and strongly associated with 5-year mortality was also developed (any cancer in the past 5 years, chronic obstructive pulmonary disease, congestive heart failure, and chronic kidney disease [the 4C model]). Model performance was assessed using measures of discrimination (eg, area under the curve [AUC]) and calibration. Internal validation was performed by correcting for optimism using 500 bootstrapped samples.Five-year mortality.Among 2325 veterans, the mean (SD) age was 73.74 (5.92) years. The cohort was predominantly male (98.8%) and of white race/ethnicity (94.4%). Overall, 29.5% (n = 687) of patients died within 5 years of CEA. On the basis of a backward selection algorithm, 9 patient characteristics were selected (age, chronic kidney disease, diabetes, chronic obstructive pulmonary disease, any cancer diagnosis in the past 5 years, congestive heart failure, atrial fibrillation, remote stroke or transient ischemic attack, and body mass index) for the final logistic model, which yielded an optimism-corrected AUC of 0.687 for the CMI. The 4C model had slightly worse discrimination (AUC, 0.657) compared with the CMI model; however, the calibration curve was similar to the full model in most of the range of predicted probabilities.According to results of this study, use of the CMI or the simpler 4C model may improve patient selection for CEA among patients with asymptomatic carotid stenosis.
Abstract 18581: Machine Learning Algorithms and Coronary Calcium Score for Risk Stratification in Asymptomatic Healthy Population
Authors: Kranthi K Kolli, Donghee Han, Heidi Gransar, Ji Hyun Lee, Su-Yeon Choi, Eun Ju Chun, Jidong Sung, Hae-Won Han, Sung-Hak Park, Hae Ok Jung, James K Min, Hyuk-Jae Chang
Journal: Circulation (2017)

Introduction: Primary prevention of heart disease is most appropriate in patients with high risk of coronary heart disease (CHD) events. Coronary artery calcium score (CACS) is known to be an indep...
Multivariate genome-wide analyses of the well-being spectrum
Authors: Bart M. L. Baselmans, Rick Jansen, Hill F. Ip, Jenny van Dongen, Abdel Abdellaoui, Margot P. van de Weijer, Yanchun Bao, Melissa Smart, Meena Kumari, Gonneke Willemsen, Jouke-Jan Hottenga, Dorret I. Boomsma, Eco J. C. de Geus, Michel G. Nivard, Meike Bartels
Journal: Nature Genetics (2019)
Sex Differences in Coronary Artery and Thoracic Aorta Calcification and Their Association With Cardiovascular Mortality in Heavy Smokers
Authors: Nikolas Lessmann, Pim A. de Jong, Csilla Celeng, Richard A.P. Takx, Max A. Viergever, Bram van Ginneken, Ivana Išgum
Journal: JACC. Cardiovascular imaging (2019)
Integrated Molecular Analysis of Undifferentiated Uterine Sarcomas Reveals Clinically Relevant Molecular Subtypes
Authors: Amrei Binzer-Panchal, Elin Hardell, Björn Viklund, Mehran Ghaderi, Tjalling Bosse, Marisa R. Nucci, Cheng-Han Lee, Nina Hollfelder, Pádraic Corcoran, Jordi Gonzalez-Molina, Lidia Moyano-Galceran, Debra A. Bell, John K. Schoolmeester, Anna Måsbäck, Gunnar B. Kristensen, Ben Davidson, Kaisa Lehti, Anders Isaksson, Joseph W. Carlson
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Undifferentiated uterine sarcomas (UUS) are rare, extremely deadly, sarcomas with no effective treatment. The goal of this study was to identify novel intrinsic molecular UUS subtypes using integrated clinical, histopathologic, and molecular evaluation of a large, fully annotated, patient cohort. Experimental Design: Fifty cases of UUS with full clinicopathologic annotation were analyzed for gene expression (n = 50), copy-number variation (CNV, n = 40), cell morphometry (n = 39), and protein expression (n = 22). Gene ontology and network enrichment analysis were used to relate over- and underexpressed genes to pathways and further to clinicopathologic and phenotypic findings. Results: Gene expression identified four distinct groups of tumors, which varied in their clinicopathologic parameters. Gene ontology analysis revealed differential activation of pathways related to genital tract development, extracellular matrix (ECM), muscle function, and proliferation. A multivariable, adjusted Cox proportional hazard model demonstrated that RNA group, mitotic index, and hormone receptor expression influence patient overall survival (OS). CNV arrays revealed characteristic chromosomal changes for each group. Morphometry demonstrated that the ECM group, the most aggressive, exhibited a decreased cell density and increased nuclear area. A cell density cutoff of 4,300 tumor cells per mm2 could separate ECM tumors from the remaining cases with a sensitivity of 83% and a specificity of 94%. IHC staining of MMP-14, Collagens 1 and 6, and Fibronectin proteins revealed differential expression of these ECM-related proteins, identifying potential new biomarkers for this aggressive sarcoma subgroup. Conclusions: Molecular evaluation of UUS provides novel insights into the biology, prognosis, phenotype, and possible treatment of these tumors.
AB1483-PARE Development and adaptation of rheumabuddy for young people with jia, their families and people with ra residing in the uk
Authors: A Gilbert
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The number of children and young people (CYP) with JIA needing support is on the increase as available allied services continue to face cuts and are under more pressure than ever. A valuable life skill for any CYP with a long-term condition is self-management, the ability to control emotions, learn resilience, communicate, work toward goals and ultimately improve their physical and emotional wellbeing. <h3>Methods</h3> Rheumabuddy is a Danish app developed for children (aged over 12) adults in Denmark with RA. We were approached by the developers, Daman, in June 2016 and meetings and discussions followed regarding NRAS launching and distributing this innovative app in the UK. For a JIA audience, our main concerns were online child safety issues and whether the app could be used by younger children with JIA with their parents as well as by adults with RA. A survey of parents and young people with JIA and RA followed and after discussions with pilot users some adaptations were made, and child safety protection protocols were put in place between NRAS and Daman. <h3>Results</h3> Daman appointed NRAS as its UK partner and NRAS undertook a soft launch of Rheumabuddy in November 2017. <h3>Conclusions</h3> Since its launch, to date we have 2000 active users who are a mixture of children with JIA and their parents, adults with JIA and adults with RA. Here are some quotes from users: "Rheumabuddy has been so helpful and I am now able to track my progress which I can show my consultant. I would often forget how I felt 3 or 4 months ago" "The Rheumabuddy app was a way for my daughter to let me know how she felt each day, normally she doesn't like discussing it" We know that CYP are growing up in a challenging and fast changing world. The ability to use self-management strategies effectively is a skill that becomes very important for success as children grow into adulthood yet is hard to acquire through the NHS alone. Rheumabuddy encourages the self-monitoring and regular recording of key patient reported outcomes. Changes in symptoms over time can be displayed in graph format and can be shared with HCP's, family, and school. The collation of cumulative data around mood, pain and fatigue can, for example, lead to empowerment of the individual or family resulting in ability to effect positive lifestyle change in the person with JIA or RA. <h3>Acknowledgements</h3> <i>Anne Gilbert, Phil Baker, Ailsa Bosworth, Clare Jacklin, The National Rheumatoid Arthritis Society, Maidenhead and Daman Denmark</i> <h3>Disclosure of Interest</h3> None declared
OP0249 The contribution of structural mri lesions to detection of sacroiliitis in patients in the assessments in spondyloarthritis international society (ASAS) classification cohort
Authors: W.P. Maksymowych, M. Østergaard, R.G. Lambert, U. Weber, S.J. Pedersen, J. Sieper, D. Poddubnyy, S. Wichuk, P. Machado, X. Baraliakos
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Active lesions typical of axial spondyloarthritis (axSpA) in the sacroiliac joint (SIJ) were reported by local site readers in about 40% of patients in the ASAS classification cohort (ASAS-CC) when this study was conducted over 10 years ago<sup>1</sup>. There has been no data reported on the occurrence of structural lesions in this cohort. Since this study was conducted, there has been considerable progress in our understanding of SIJ lesions observed on MRI, which raises the possibility that MRI scans of patients in the ASAS-CC could now be interpreted substantially differently. <h3>Objectives</h3> To determine the added contribution of structural lesions in the SIJ to the evaluation of sacroiliitis in an inception cohort of patients with axSpA. <h3>Methods</h3> Recently updated MRI lesion definitions for axSpA (ASAS_MRI_def<sup>n)</sup> were recorded in an eCRF that comprises global assessment (lesion present/absent) and detailed scoring (SPARCC SIJ inflammation, SPARCC SIJ structural). MRI scans were available in a variety of formats (DICOM (n=175), JPEG(n=71), DICOM film(n=32)) and sequences, axial and semicoronal orientations, from 278 of the 495 cases who had MRI performed in the ASAS-CC. Image quality was considered sufficient to record global data by 6 central readers in all cases. An additional reader assessed only images in DICOM format (n=175). Comparison of active and structural lesion frequencies typical of axSpA was assessed descriptively according to individual and majority of central readers data. <h3>Results</h3> Active lesions typical of axSpA were recorded in about 30% of cases in the cohort. Active or structural lesions typical of axSpA were recorded in about 40% of patients (table 1). Similar data was observed when active sacroiliitis was defined using the ASAS definition of a positive MRI. Structural lesions alone, without any active lesions typical of axSpA, were recorded in 6.6% of cases. Active lesions alone, without any structural lesions typical of axSpA, were recorded in 7.8% of cases. Both active and structural lesions typical of axSpA were recorded in 23.1% of cases. The frequencies of these categories were only slightly lower when majority reader data was analysed. <h3>Conclusions</h3> Structural lesions typical of axSpA may be observed without any active lesions typical of axSpA in 5%–10% of cases presenting with undiagnosed back pain in the ASAS-CC. This is the same proportion of the cohort for which active lesions typical of axSpA are seen without any structural lesions typical of axSpA. In view of the concomitant presence of both lesions, contextual interpretation seems optimal. <h3>Reference</h3> [1] Rudwaleit, et al. Ann Rheum Dis2009;68:777–831. <h3>Disclosure of Interest</h3> None declared
THU0557 Therapeutic drug monitoring of biologicals in children with juvenile idiopathic arthritis(JIA): an overview of current practice in anti-tnf therapy
Authors: A. Nassar-Sheikh Rashid, D. Schonenberg-Meinema, A. de Vries, T. Rispens, T.W. Kuijpers, G. Wolbink, J.M. van den Berg
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) is the most prevalent paediatric rheumatic disease.<sup>1</sup> Long term complications include physical disability and a decreased quality of life.<sup>2,3</sup> Since the introduction of anti-TNF drugs for JIA, its prognosis has improved significantly.<sup>1</sup> Personalised medicine is the next step to improve treatment in JIA. Anti-TNF trough levels and demonstration of the presence of anti-drug antibodies (ADA) could help individualise treatment decisions in JIA patients, but evidence supporting this is missing. <h3>Objectives</h3> To describe cross-sectional data of anti-TNF trough levels and ADA, combined with decision effects, in children with JIA. <h3>Methods</h3> Patients' records in children with JIA using etanercept, adalimumab or infliximab were retrospectively checked for measurements of anti-TNF trough levels and ADA. Anti-TNF trough concentrations and ADA were measured using an enzyme-linked immunosorbent assay (ELISA) and antigen-binding test. Data on age, sex, JIA subtype, reason for testing and the decision effect of trough level or presence of ADA on the current therapy were collected. <h3>Results</h3> Eighty-one anti-TNF trough levels were measured in 45 children with JIA. A wide variety of anti-TNF trough levels was found. Therapeutic drug concentrations, according to adult ranges in RA and IBD,<sup>4,5,6</sup> were found in 11 (58%) patients on etanercept (n=19), 2 (14%) on adalimumab (n=14) and 8 (17%) on infliximab (n=48). Four patients on adalimumab and one patient on infliximab showed ADA. All of these five patients had non-detectable drug trough levels. Reasons for testing trough level and/or presence of ADA were loss of response (20%), partial or no response (40%), measurement after dosage increase (2%), remission (17%), uveitis flare (9%) and allergic reaction (11%). Treatment decisions were influenced by trough levels in 70/81 (86.4%) of measurements and in 5/5 (100%) of patients with ADA. <h3>Conclusions</h3> Measuring anti-TNF trough levels and ADA was a valuable tool in making personalised treatment decisions in JIA. Treatment changes included dose/frequency increase, or stopping and switching treatment in the presence of ADA combined with undetectable drug levels. More data are needed to access optimal therapeutic drug levels in anti-TNF treatment in JIA and to implement this strategy more widely. <h3>References</h3> [1] Blazina S, et al. Paediatr Drugs2016;18(6):397–412. [2] Tambralli A, et al. J Rheumatol2013;40(10):1749–55. [3] Haverman L, et al. Rheumatology (Oxford)2012;51(2):368–74. [4] Kneepkens EL, et al. Ann Rheum Dis2015;74(10):1825–9. [5] Pouw MF, et al. Ann Rheum Dis2015;74(3):513–8. [6] Singh N, Dubinsky DC. Gastroenterol Hepatol (NY)2015;11(1): 48–55. <h3>Disclosure of Interest</h3> None declared
THU0348 Time on dialysis adversely affects renal transplant outcome in lupus nephritis
Authors: E. Ntatsaki, V. Vassiliou, A. Velo Garcia, A.D. Salama, D.A. Isenberg
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Lupus nephritis (LN) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) often leading to end stage renal failure (ESRF) and necessitating renal transplantation. However, the optimal timing of transplantation in SLE patients with ESRF is uncertain and could potentially affect survival. <h3>Objectives</h3> We investigated time spent on dialysis before renal transplantation and survival following the transplantation in a cohort of SLE patients. <h3>Methods</h3> Retrospective analysis of all adult SLE patients undergoing renal transplantation over a 40 year period (1975–2015) in two tertiary UK centres followed up until 2017. Cox proportional hazard regression and receiver operator curves (ROC) were used to determine the risk associated with time on dialysis before the transplantation and other potential predictors. <h3>Results</h3> Forty patients (age 35±11 years, 34 female, 15 Caucasian, 15 Afro Caribbean and 10 South Asian underwent transplantation. During a median follow up of 104 months (IQR 80,145), 8 (20%) patients died and the five year survival was 95%. Univariate analysis identified time on dialysis prior to transplantation as the only potentially modifiable risk predictor of survival with a Hazard Ratio of 1.013 for each additional month spent on dialysis (95% CI=1.001–1.026, p=0.03). ROC curve demonstrated that &gt;24 months on dialysis had an adverse effect with sensitivity of 0.875 and specificity 0.500 for death. No other modifiable predictors were significantly associated with mortality, indicating that time on dialysis had an independent effect. <h3>Conclusions</h3> Increased time on dialysis pre-transplantation is an independent modifiable risk factor of mortality in this cohort of patients with lupus nephritis and should be one of the factors considered for patient selection to transplantation. <h3>Disclosure of Interest</h3> None declared
SP0093 Resetting the immune system in autoimmunity
Authors: F. Van Wijk
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Autologous hematopoietic stem cell transplantation (HSCT) is a last resort treatment for refractory autoimmune patients and the only therapy so far that can induce long-term drug-free remission in these patients. Understanding the mechanisms responsible for this regained immune tolerance may help to develop other, less aggressive immune-mediated interventions with a similar outcome. Although the underlying mechanisms are incompletely understood, extensive immune ablation followed by autologous s<b>t</b>em cell infusion seems to be able to rewire a faulty immune system. It is so far unknown which cells need to be removed prior to autologous transplantation and which cells are important in controlling disease after transplantation. We have previously shown that transplantation restores immune tolerance by renewal and modulation of both the CD4 effector T cell (Teff) and FOXP3 Treg compartment in a proteoglycan induced arthritis (PGIA) mouse model. In the human setting we further looked into T cell renewal by TCR CDR3 b chain repertoire sequencing prior to and post HSCT of juvenile idiopathic arthritis and dermatomyositis patients. We found that TCR beta chain diversity of Treg was highly restricted prior to transplantation and that the TCR b chain diversity of Treg increased post-transplantation. The TCR beta chain diversity of the CD4 non-Treg compartment also expanded after aSCT, although not as strikingly as the Treg compartment, indicating that the Treg compartment is more affected. Interestingly, in patients these highly dominant T(reg) cell clones persist over time and (locally) expand with every relapse of disease. The question is now how HSCT or related therapies can efficiently target and stimulate T cell renewal in chronic autoimmune inflammation, with limited toxicity. <h3>Disclosure of Interest</h3> None declared