tbuckley/cabot-search huggingface dataset:
THU0685 Cardiovascular risk estimation in sle patients: a comparison of three algorithms
Authors: D. Chimera, C. Tani, C. Stagnaro, E. Elefante, R. Vagelli, L. Carli, M. Mosca
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cardiovascular (CV) disease is a major cause of mortality and morbidity in SLE patients; several instruments have been developed to estimate the 10 years risk of major CV events in the general population according to the presence of traditional CV risk factors. However, it is well known that traditional CV risk factors cannot fully explain the increased CV disease in SLE. Recently, a new version of the Qrisk algorithm was released (QRISK3) incorporating new variables associated with increased risk of CV disease, including SLE diagnosis and the GC use. <h3>Objectives</h3> To assess the 10 years CV risk in a cohort of SLE patients by comparing three different algorithms. <h3>Methods</h3> Consecutive patients with a diagnosis of SLE according to the ACR criteria were recruited from the inpatients and outpatients clinics of our Unit. Previous major CV events (myocardial infarction and stroke) were considered exclusion criteria. Traditional CV risk factors, disease activity and damage as well as therapies and comorbidities were evaluated. Disease activity was assessed with the SLEDAI score, organ damage with the SLICC/DI. Three algorithms to estimate the 10 years risk of major events were applied: the Framingham score, the ACC/AHA score and the QRISK3. This latter incorporates new variables associated with increased risk of cardiovascular disease, including SLE and GC use. <h3>Results</h3> 115 SLE patients (90.5%) without previous major CV events were included in this analysis. They were predominantly females (93%), Caucasian (96.5%) with a mean age at enrollment of 42.8±12.5 and a mean disease duration of 13.4±9.2 years. The prevalence of organ involvement and traditional risk factors are reported in table 1. Disease activity at enrollment was low (median SLEDAI 2, IQR 0–4) while 39.1% was presenting at least one organ damage. The median Framingham risk score resulted 4.5% (IQR 2.4–8.6), the ACC/AHA resulted 1.2% (0.5–3.2), the QRISK3 resulted 5.4% (2.4–9.6). According to the three methods, there was a significant difference in the risk stratification: 10% of patients at medium-high CV risk according to the Framingham score, 5% with the ACC/AHA score and 21% with the QRISK3. The median “healthy heart age” of our cohort (the age at which a healthy subject has the same CV risk) provided by the QRISK3 resulted 62 years.<sup>52–68</sup> <h3>Conclusions</h3> These data show that by applying the QRISK3 algorithm a significant percentage of patients would be reclassified at high risk of CV events with respect to the traditional CV risk scores. Longitudinal data are necessary to validate the QRISK3 accuracy against the traditional scores in the identification of SLE patients at higher risk of CV events. <h3>Disclosure of Interest</h3> None declared
Colorectal cancer: the APC-lncRNA link
Authors: Pat J. Morin
Journal: Journal of Clinical Investigation (2019)

The adenomatous polyposis coli (APC) gene plays, among other things, a crucial role in the regulation of cell proliferation and survival through its ability to regulate canonical Wnt signaling. In this issue of the JCI, Wang et al. provide an intriguing new mechanism for APC function involving the regulation of a novel long noncoding RNA (lncRNA), leading to changes in exosome production. APC signaling via this novel pathway can regulate cell proliferation and invasion as well as angiogenesis. In addition to enhancing our understanding of APC function, this new mechanism is of particular clinical significance, as it may provide additional targets for the treatment of APC-mutated cancers.
SP0139 The role of phagocytes at the inflammatory site
Authors: S. Uderhardt
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Inflammation is a highly conserved, multicellular response to infection or injury ensuring host defense and tissue integrity. Immune cell activation, however, can cause substantial collateral damage, often further amplifying the inflammatory response and significantly contributing to disease pathology (e.g. influenza, myocardial infarction). Hence, mechanisms are required not only to promote and resolve inflammation, but also to regulate the primary events that initiate this process in order to avoid unwanted and potentially harmful immune responses. Using state-of-the-art intravital and static multi-parameter imaging techniques in mice, our lab seeks to understand the complex interactions and functions of different immune cells types in the execution and regulation of the inflammatory responses to sterile damages in peripheral tissues. With primary focus on the innate immune system, we’re particularly interested in the dynamic interplay of embryonically-derived tissue macrophages and recruited neutrophils, which can prevent unwanted immune cell activation and thereby fine-tune the threshold for the onset of damaging inflammation. This presentation will provide novel insights into the multi-layered regulation of the very initial steps in an inflammatory response to tissue damage, and will further discuss the differential roles of different populations of phagocytes at sites of inflammation. This research was supported by the Intramural Research Program of the NIAID. <h3>Disclosure of Interest</h3> None declared
Cost-Effectiveness Analysis of Lenalidomide for Maintenance Therapy after Autologous Stem Cell Transplant (ASCT) in Newly Diagnosed Multiple Myeloma (NDMM) Patients: A United States Payer Perspective
Authors: Zheng-Yi Zhou, Kejal Parikh, Xinglei Chai, Ariel Rokito, Chuka Udeze, Jipan Xie, Amit Agarwal
Journal: Blood (2018)
FRI0147 Analysis of radiographic joint destruction in the patients with rheumatoid arthritis who have withdrawn, spaced and continued biologics after achieving sustained remission from local biologics registry
Authors: Y. Takakubo, J. Nagai, H. Oki, Y. Naganuma, S. Yang, J. Ito, Y. Suzuki, K. Sasaki, M. Takagi
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Increasing of remission reached by biologics agents in early and established RA patients<sup>1, 2</sup>. Data on withdrawn, spacing or reducing of biologics (BIO) medication after sustained remission are limited<sup>3,4</sup>. After withdrawn, spacing or reducing, it is less known to be influenced the radiographic destruction of the joints. <h3>Objectives</h3> To retrospectively analyse the joint destruction using modified Total Sharp Score (mTSS) in RA patients in sustained remission, either withdrawing, spacing and continuing BIO. <h3>Methods</h3> Local prefectural (ZAO) registry which is open-labelled BIO cohort study has registered 356 RA patients. RA Patients were enrolled into this study if they maintained in DAS remission (DAS28-ESR&lt;2.6) more than one year after starting BIO. ΔmTSS1 was estimated between starting BIO and withdrawn or spacing or reaching remission in each group, ΔmTSS2 between the beginning of withdrawn or spacing, or reaching remission in continuing group and latest follow-up or flare-up. <h3>Results</h3> 40 RA patients (32 female) using BIO was fulfilled in the criteria of this study in ZAO registry. Of 40 RA Patients, 10 has withdrawn BIO, 15 has spaced and 15 has continued it after maintain DAS remission more than one year. Mean age was 43, 55, 54 year-old, mean RA affiliation 4.6, 15.3, 9.1 years before BIO and mean duration of remission 6.2, 7.6, 7 years, mean dosage of MTX and PSL was 7.7, 6, 5 mg/week and 1.1, 3, 4 mg/day, respectively. ΔmTSS1 and ΔmTSS2 was +2.4 and+4.5 in withdrawn group,+3.6 and+0.9 in spacing group,+0.2 and −1.4 in continuing group, respectively (figure 1, p<i>&lt;0.05</i>). Five cases in withdrawing group had resumed BIO because of flare-up of their disease activity. <h3>Conclusions</h3> Several studies reported the potential of BIO withdrawing, spacing or reducing in the patients with RA who reached remission<sup>3), 5)</sup>. All cases in spacing and withdrawing group have shown DAS28–4ESR&lt;2.6 in this study, however, 50% (5/10 cases) in withdrawing group have re-flare and shown the radiological joint destruction. Spacing or reducing of BIO may have potential to maintain the remission of RA and prevent the joint destruction. Withdrawing of BIO after even sustained deeper remission may be difficult to keep real remission. <h3>References</h3> [1] O'Dell JR. Arthritis Rheum2002;46:283–85. [2] Smolen JS, et al. Ann Rheum Dis2017;76:960–77. [3] Tanaka Y, et al: Ann Rheum Dis2015;74:389–95. [4] Takeuchi T, et al: Ann Rheum Dis2014;73:536–43. [5] Fautrel B, et al. Ann Rheum Dis2016;75:59–67. <h3>Acknowledgements</h3> <h3>Disclosure of Interest</h3> None declared
SAT0146 At diagnosis of rheumatoid arthritis, at-risk patients followed in ccp+ clinic showed milder disease activity than conventionally referred patients.
Authors: L. Duquenne, P. Pentony, K. Mankia, J. Nam, L. Hunt, A. L. Tan, L. Garcia-Montoya, P. Emery
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Early treatment of rheumatoid arthritis (RA) improves clinical and radiological outcomes<sup>1</sup>. Risk stratification models can identify patients at high risk of developing RA,<sup>2–5</sup> which may lead to an extension of the window of opportunity. Whether identifying and following at-risk individuals improves outcomes after the development of RA however is yet to be determined. <h3>Objectives:</h3> The hypothesis is that patients followed in a specific at-risk clinic will have less severe disease at diagnosis than those referred via the conventional route if/when they develop RA. <h3>Methods:</h3> In two single-centre prospective observational cohorts, patients fulfilling the 2010 EULAR classification criteria for RA were compared on a demographic and clinical approach. The first group was composed of 59 patients positive for anti-cyclic citrullinated protein antibodies (CCP) with non-specific musculoskeletal symptoms, considered to be "at-risk of RA", who were followed until RA diagnosis. The second group was composed of 92 CCP positive RA patients referred to a standard 'Early Arthritis' rheumatology clinic. <h3>Results:</h3> Demographic data at RA development were consistent between both groups including smoking history and BMI. Immunological features were also similar. CCP titre: at risk median 193U/ml (IQR 41,300), standard care 300U/ml (IQR 81,300, p=0.176)). Rheumatoid factor (RF) titre: at risk median 84iU/mL (IQR 15,223), standard care 87iU/mL (IQR18,161, p=0.850). RF positivity: at risk 75%, standard care 70% (p=0.544). High-titre CCP blood levels: at risk 95%, standard care 97% (p=0.566). As shown in table 1, DAS28CRP score were significantly lower in the at risk group than in standard care, this was due to a difference in the general health Visual Analogue Scale score and the CRP levels. Patients in the at risk group also had fewer swollen large joints and reported significantly shorter time between onset of subjective joint swelling and diagnosis. There was no difference between the presence of erosions on ultrasound scans (at risk: 39%, standard care 38%, p=0.921). <h3>Conclusions:</h3> Patients who were diagnosed with RA while being followed in an at-risk cohort had milder disease activity and less pain than those diagnosed through standard referral despite equivalent demographics and serology. This reflects an earlier diagnosis and hence shorter exposure to inflammation. Follow-up will be required to see if these differences convert to long-term benefits. <h3>References</h3> [1]van der Heide. Ann Intern Med1996;124(8). [2]Rakieh. Ann Rheum Dis2015;74(9). [3]Van de Stadt. Ann Rheum Dis2013;72(12). [4]Van Steenbergen. Ann Rheum Dis2016;75(10). [5]Nam JL. Ann Rheum Dis2016;75(12). <h3>Disclosure of Interest:</h3> None declared
SP0022 How to assess bone erosions – indications, pitfalls and new techniques + demo
Authors: M. Szkudlarek
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> Detection of bone erosions is essential for the early diagnosis, the prediction of future bone damage, and the monitoring of therapeutic outcomes in patients with rheumatoid arthritis (RA). Yet, bone erosions are not pathognomonic for RA. They occur in many other disease entities. Presence of bone erosions is characteristic for mixed connective tissue disease, juvenile idiopathic arthritis, gout, hemochromatosis, pigmented villonodular synovitis, among others. It is not uncommon in osteoarthritis. Bone erosions can be detected at entheses in spondyloarthropathy and in the joints of patients with psoriatic arthritis. Erosive changes can also be seen in bone neoplastic disease. Conventional radiography is still considered the basic imaging method of detection of bone erosions, as well as a monitoring tool. However, more modern imaging techniques are becoming more widely used. They include ultrasonography, magnetic resonance imaging and computed tomography. Apart from higher sensitivity for detection of bone erosions, the new techniques offer simultaneous visualisation of soft tissues. Their role in follow-up of patients with erosive disease as well as erosive progression is still a subject of research. In the short time allowed, the presentation will also address localization, pitfalls and characteristic appearance of bone erosions in main rheumatological diseases. <h3>Disclosure of Interest</h3> None declared
Human neutrophils express low levels of FcγRIIIA, which plays a role in PMN activation
Authors: Josée Golay, Rut Valgardsdottir, Gerta Musaraj, Damiano Giupponi, Orietta Spinelli, Martino Introna
Journal: Blood (2019)

We have identified a rare healthy FcγRIIIB (CD16B)-null donor completely lacking FCGR3B RNA and protein expression and dissected the role of the different neutrophil Fcγ receptors in the response to therapeutic anti-CD20 monoclonal antibodies. We observed that polymorphonuclear neutrophils (PMNs) from FcγRIIIB wild-type (WT) individuals or the null donor were more effectively activated by chronic lymphocytic leukemia (CLL) B-cell targets opsonized with glycoengineered anti-CD20 antibodies compared with fully core-fucosylated anti-CD20 antibodies, suggesting the presence and role of FcγRIIIA (CD16A) on PMNs. Indeed, we demonstrated by reverse-transcription polymerase chain reaction, flow cytometry, and western blot analysis that PMNs from FcγRIIIB WT donors and the null individual express low levels of FcγRIIIA on their surfaces. FcγRIIIA is a functional and activating molecule on these cells, because anti-CD16 F(ab')2 antibodies alone were able to activate highly purified PMNs from the FcγRIIIB-null donor. Use of blocking anti-CD16 and anti-CD32 antibodies showed that FcγRIIIA is also a major mediator of phagocytosis of CD20-opsonized beads by FcγRIIIB WT and null PMNs. In contrast, trogocytosis of antibody-opsonized CLL B cells by PMNs was mediated primarily by FcγRIIIB in WT PMNs and by FcγRIIA in null PMNs. We conclude that FcγRIIIA is an important player in PMN functions, whereas FcγRIIIB is dispensable for activation and phagocytosis. We discuss the clinical implications of these findings.
AB0573 Influence of smoking and obesity on the risk of developing primary sjÖgren’s syndrome: a population-based cohort study
Authors: G. Maciel, L. Servioli, C. Nannini, C. Crowson, E. Matteson, D. Cornec, A. Berti
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Cigarette smoking and obesity have been identified as risk factors for developing several autoimmune diseases, and may be protective for others. This study explored the role of these risk factors in primary Sjögren's syndrome (pSS). <h3>Methods</h3> A cohort of Olmsted County, Minnesota residents diagnosed with pSS between January 1, 2000 and December 31, 2015 was identified based on individual medical record review. Each of the cases was matched to 3 age- and sex-matched comparators without pSS randomly selected from Olmsted County residents, indexed to the date of pSS diagnosis. Smoking status was divided into three categories of current smoker, ex-smoker and never smoker. The body weight and height closest to date of diagnosis/index date (±1 year) were used. Obesity was defined as a body mass index (BMI) ≥30/kg/m<sup>2</sup>. <h3>Results</h3> 106 incident cases of pSS and 318 controls were identified. The odds ratio (OR) of pSS comparing current smokers with never smokers was 0.34 (95% confidence interval (CI): 0.14, 0.85; p&lt;0.05), while the OR for former smokers compared to never smokers was 1.27 (95% CI, 0.80, 2.03). Smoking status was not associated with antinuclear antibody, anti-SSA, anti-SSB or rheumatoid factor positivity (p&gt;0.05). The OR of pSS comparing obese subjects with non-obese subjects was 0.79 (95% CI, 0.48, 1.30), while the OR of pSS for BMI analysed as a continuous variable was 0.97 (95% CI, 0.94, 1.01). <h3>Conclusions</h3> In this population-based study, current smokers have a lower risk of developing pSS while BMI does not affect this risk. <h3>Disclosure of Interest</h3> None declared
SAT0144 Effect of aging on bone mass and skeletal muscle mass in elderly patients with rheumatoid arthritis: tomorrow study
Authors: K. Inui, T. Koike, Y. Sugioka, T. Okano, K. Mamoto, Y. Yamada, K. Mandai, M. Tada, H. Nagata, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Both osteoporosis and sarcopenia are common in patients with chronic inflammatory conditions such as rheumatoid arthritis (RA). Fragility fractures occur on osteoporotic bone on falling. Unstable gait caused by sarcopenia increases the frequency of such falls. <h3>Objectives:</h3> To evaluate the relationship between bone mineral density (BMD) and appendicular skeletal muscle index (ASMI) in patients with RA and healthy controls. <h3>Methods:</h3> We used data collected over a 7-year period from 2010 to 2016 as part of a prospective cohort study (TOMORROW Study: UMIN000003876) that included RA patients and age- and sex-matched volunteers recruited through mass media as controls. BMD of the lower leg and ASMI were determined using whole-body dual-energy X-ray absorptiometry. These were collected for all participants together with baseline characteristics including anthropometric data and blood test data related to lipid and sugar metabolism. Each parameter for the RA patients was compared with that for the healthy controls. Multiple regression analysis was carried out in the RA population only. In RA patients, treatment regimen and disease activity score 28 were recorded. <h3>Results:</h3> Among 413 participants of the TOMORROW Study (208 RA patients; 349 women; mean age 58 years), 137 participants age 65 years or older (77 RA; 117 women) were enrolled in the present study. BMD and ASMI decreased significantly over the 7-year study period in RA patients and healthy controls from baseline. BMD and ASMI were lower in RA patients than in healthy controls at every time point through the 7-year study period. There was no interaction between time and RA (p=0.194, 0.089; repeated measure ANOVA). The change of BMD at year 7 from baseline (ΔBMD) and change of ASMI at year 7 from baseline (ΔASMI) did not correlate in health controls, however, in RA patients, ΔBMD correlated positively with ΔASMI (r=0.331, p=0.023) (Fig). Multiple regression analysis with ΔBMD as the outcome variable and anti-citrullinated peptide antibody, Rheumatoid factor, ASMI, body mass index, disease activity score 28, homeostatic model assessment (HOMA)-R, Matrix metalloprotease (MMP)-3 and sex as independent variables revealed that male sex (p=0.0036) and ASMI (p=0.0020) were independently related with ΔBMD. <h3>Conclusions:</h3> Decrease of BMD and ASMI were correlated with each other in elderly patients with RA. <h3>Disclosure of Interest:</h3> None declared
SAT0473 Clinical and echocardiographic associates of all-cause mortality and cardiovascular outcomes in patients with systemic sclerosis
Authors: S.E. van Wijngaarden, M. Boonstra, B. Bloem, D. Cassani, F.C. Tanner, S. Jordan, O. Distler, V. Delgado, J.J. Bax, J.K. de Vries-Bouwstra, N. Ajmone Marsan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Cardiac events are an important cause of mortality in Systemic Sclerosis (SSc), but its diagnosis remains challenging. Left ventricular global longitudinal strain is a novel parameter derived from speckle tracking echocardiographic analysis which has been proposed to identify patient at higher risk of cardiac events. <h3>Objectives</h3> We aimed to identify clinical and echocardiographic (including GLS) parameters associated with all-cause mortality and cardiovascular events in SSc patients. <h3>Methods</h3> 408 SSc patients (344 females, age 54±14 years.) were prospectively evaluated at baseline and follow-up (FU time 3.3 years. [IQR 1.8 to 5.5]). Cardiovascular events included: heart failure, cardiac infarction, coronary interventions, device implantation, arrhythmias, cerebral infarction, peripheral ischaemic vascular disease. <h3>Results</h3> All-cause mortality (n=37) or cardiovascular events (n=57) occurred in 84 patients. At baseline, these patients were older (59±14 vs. 53±14 years., p&lt;0.001), more often male (24 vs. 13%, p=0.018), more often had skin pigment changes (21 vs. 5%, p=0.011), coronary artery disease (11 vs. 3%, p=0.001), holter abnormalities (45 vs. 24%, p≤0.001), increased ESR (24 [IQR 14 to 46] vs. 11 [IQR 6 to 25], p&lt;0.001), worse NT-proBNP (151 [IQR 60 to 644] vs. 82 [IQR 51 to 145] ng/L, p&lt;0.001), worse lung function test results (FVC 92±19 vs. 104%±21%, p&lt;0.001; DLCO 55±17 vs. 70%±19%, p&lt;0.001), worse left ventricular diastolic function (E/E-prime ratio 9.9 [IQR 6.7 to 10.2] vs. 7.8 [IQR 6.4 to 9.7], p&lt;0.001), higher systolic pulmonary artery pressure (31±12 vs. 25±7 mmHg, p&lt;0.001) and lower GLS (−18.8 [IQR −20.3 to −19.5] vs. −21.1 [IQR −22.1 to −20.0]%, p&lt;0.001). In a multivariate cox-regression analyses, age (HR 1.029, 95% CI 1.006 to 1.052), female sex (HR 0.527, 95% CI 0.302 to 0.922), NT-proBNP (HR 1.000, 95% CI 1.000–1.001), DLCO (HR 0.973, 95% CI 0.961–0.986) and GLS (HR 1.281, 95% CI 1.172–1.399) were independently associated with outcome. After dividing patients into groups according to median GLS (−20.9%) and elevated NT-proBNP (&gt;200 ng/L), survival rates were lower and cardiovascular events increased when GLS was impaired and worsened when NT-proBNP was elevated (Log-rank p&lt;0.001). <h3>Conclusions</h3> In SSc patients, next to age, DLCO and NT-proBNP, GLS strongly associates with all-cause mortality and cardiovascular events, indicating that these parameters reflect relevant cardiac involvement in SSc, and as such can contribute to risk stratification and patient management. <h3>Disclosure of Interest</h3> None declared
The HLA-B −21 dimorphism impacts on NK cell education and clinical outcome of immunotherapy in acute myeloid leukemia
Authors: Alexander Hallner, Elin Bernson, Brwa Ali Hussein, Frida Ewald Sander, Mats Brune, Johan Aurelius, Anna Martner, Kristoffer Hellstrand, Fredrik B. Thorén
Journal: Blood (2019)