tbuckley/cabot-search huggingface dataset:
THU0256 Development and validation of a score to predict the risk of severe infection in sle
Authors: B Tejera Segura, I Rúa-Figueroa, J Pego-Reigosa, V Campo Pérez del, D Isenberg, A Rahman
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Infection is a major cause of morbidity and mortality in SLE patients. It would be helpful to have a tool to predict the risk that an individual patient with SLE will develop serious infection. <h3>Objectives</h3> To develop a predictive risk calculator algorithm (SCORE) that assesses the probability of serious infection (i.e. leading to hospitalization) in SLE patients and to test it in an independent cohort. <h3>Methods</h3> The SCORE was developed using data from the RELESSER (Spanish Society of Rheumatology Lupus Registry) cohort of 3658 SLE patients. A Cox regression model for repeated events (Andersen-Gill) was applied to assess which demographic and clinical factors were independently associated with increased risk of developing serious infection (Table 1). The SCORE was then validated using retrospective data from the UCLH (University College London Hospital) cohort including 699 SLE patients. Median SCORE values were compared between sub-groups of patients using the U-Mann-Whitney test. <h3>Results</h3> Among 699 SLE UCLH patients, 98 (14%) developed serious infection. We compared these patients with 111 SLE controls who have never suffered serious infection. The characteristics of both groups are summarized in table 2. The infection group were more likely to have suffered previous infection (P=0.001) and/or hospitalized for SLE (P&lt;0.001) and had renal and joint disease (P=0.005). Over a quarter of the infection group died from their infection. Median (Md) SCORE at diagnosis in SLE patients with infection was 4.27 (IQR 3.18) which was significantly higher than in the control group (Md 2.55, IQR 3.79) (z=3.341; P=0.0008). Md SCORE before infection in patients was 5.3 (IQR 3.68) which was significantly higher than SCORE at diagnosis (z=-5.733; P≤0.001) in those patients. By ROC analysis, we defined three possible cut-offs to distinguish patients with and without infection. The area under the ROC curve was 0.66 (CI 95% 0.56 to 0.71). A cut-off for SCORE at diagnosis &gt;3.18 identified patients who would develop serious infection with sensitivity (S)76.5% and specificity (SPC) 50.5%. For SCORE &gt;3.79, S was 64.3% and SPC 57.7%. For SCORE &gt;4.24, S was 64.3% and SPC 60.4%. <h3>Conclusions</h3> We have developed a SCORE for predicting risk of serious infection in SLE and validated it in an independent cohort. Given the potential mortality from such infections, this SCORE could be clinically useful though the moderate sensitivity and specificity necessitate caution and further prospective studies. <h3>Disclosure of Interest</h3> None declared
EMC10 (Endoplasmic Reticulum Membrane Protein Complex Subunit 10) Is a Bone Marrow–Derived Angiogenic Growth Factor Promoting Tissue Repair After Myocardial Infarction
Authors: Marc R. Reboll, Mortimer Korf-Klingebiel, Stefanie Klede, Felix Polten, Eva Brinkmann, Ines Reimann, Hans-Joachim Schönfeld, Maria Bobadilla, Jan Faix, George Kensah, Ina Gruh, Michael Klintschar, Matthias Gaestel, Hans W. Niessen, Andreas Pich, Johann Bauersachs, Joseph A. Gogos, Yong Wang, Kai C. Wollert
Journal: Circulation (2017)

Background: Clinical trials of bone marrow cell–based therapies after acute myocardial infarction (MI) have produced mostly neutral results. Treatment with specific bone marrow cell–derived secreted proteins may provide an alternative biological approach to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in bone marrow cells from patients with acute MI and discovered a poorly characterized secreted protein, EMC10 (endoplasmic reticulum membrane protein complex subunit 10), showing activity in an angiogenic screen. Methods: We investigated the angiogenic potential of EMC10 and its mouse homolog (Emc10) in cultured endothelial cells and infarcted heart explants. We defined the cellular sources and function of Emc10 after MI using wild-type, Emc10 -deficient, and Emc10 bone marrow–chimeric mice subjected to transient coronary artery ligation. Furthermore, we explored the therapeutic potential of recombinant Emc10 delivered by osmotic minipumps after MI in heart failure–prone FVB/N mice. Results: Emc10 signaled through small GTPases, p21-activated kinase, and the p38 mitogen-activated protein kinase (MAPK)–MAPK-activated protein kinase 2 (MK2) pathway to promote actin polymerization and endothelial cell migration. Confirming the importance of these signaling events in the context of acute MI, Emc10 stimulated endothelial cell outgrowth from infarcted mouse heart explants via p38 MAPK-MK2. Emc10 protein abundance was increased in the infarcted region of the left ventricle and in the circulation of wild-type mice after MI. Emc10 expression was also increased in left ventricular tissue samples from patients with acute MI. Bone marrow–derived monocytes and macrophages were the predominant sources of Emc10 in the infarcted murine heart. Emc10 KO mice showed no cardiovascular phenotype at baseline. After MI, however, capillarization of the infarct border zone was impaired in KO mice, and the animals developed larger infarct scars and more pronounced left ventricular remodeling compared with wild-type mice. Transplanting KO mice with wild-type bone marrow cells rescued the angiogenic defect and ameliorated left ventricular remodeling. Treating FVB/N mice with recombinant Emc10 enhanced infarct border-zone capillarization and exerted a sustained beneficial effect on left ventricular remodeling. Conclusions: We have identified Emc10 as a previously unknown angiogenic growth factor that is produced by bone marrow–derived monocytes and macrophages as part of an endogenous adaptive response that can be enhanced therapeutically to repair the heart after MI.
AB0875 Do we control gout in primary care following eular recommendations?
Authors: F Leon Vazquez, C Sanz Rodrigo, C Muñoz Martínez de Salinas, M Ferruelo Magán, M Metola Gόmez, A Del Caño Garrido, C González Fernández
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Inadequate control of hyperuricaemia in gout patients can lead to more arthritis, activity limitations and higher gout-related treatment costs. General Practitioners can use well tolerated urate-lowering drugs, but some patients are inadequately controlled. European League against Rheumatism (EULAR) has published new guidelines<sup>1</sup> in 2016 with similar serum Uric Acid (sUA) goals. <h3>Objectives</h3> To evaluate sUA control in patients diagnosed with gout who were attended in primary care and to compare them to EULAR 2016 guidelines<sup>1</sup>. <h3>Methods</h3> Retrospective analysis, carried out in 2 primary care health centres (8 family doctors) in Spain. We selected patients that have consulted in the last year diagnosed with gout at any time. Demographic variables, gout-related drugs and last sUA level were collected. Adequate control was defined as sUA level &lt;6 mg/dL. Limitations: We used only one isolated sUA value. No drug doses were analyzed. We did not distinguish severe from mild gout. Ethical-legal aspects: We did not identify the patients. There was no intervention. <h3>Results</h3> We analyzed 231 patients diagnosed with gout, mean 70.1 years-old (Confidence Interval CI<sub>95%</sub> 68.3–72.0), 189 (81.8%) were men. The mean sUA was 6.55 mg/dL (CI<sub>95%</sub> 6.31–6.79 mg/dL). 39% were adequately controlled according to EULAR (sUA &lt;6 mg/dL), 25.5% were close to the objective (6–7mg/dL) and clearly inadequate (&gt;7mg/dL) in 35.5%. 10% had really bad control (sUA &gt;9 mg/dL). There was no difference between control in male 6.58 mg/dL (IC<sub>95%</sub> 6.33–6.83) and female 6.40 mg/dL (CI<sub>95%</sub> 5.73–7.07). Control improves in elder people: &lt;60 years 7.01 mg/dL (CI<sub>95%</sub> 6.60–7.42) vs.&gt;70 years 6.30 mg/dL (CI<sub>95%</sub> 6.00–6.60) The only 14 patients receiving febuxostat achieved similar control using allopurinol (6.5 versus 6.7 mg/dL). <h3>Conclusions</h3> The degree of control of sUA in primary care patients in our area is mostly between optimal and acceptable, but it can be optimized in more than half of the cases. In a few patients the control is lousy. The worst-controlled patients were the youngest. <h3>References</h3> Richette P, Doherty M, Pascual E, Barskova V, Becce F, Castañeda-Sanabria J, Coyfish M, Guillo S, Jansen TL, Janssens H, Lioté F, Mallen C, Nuki G, Perez-Ruiz F, Pimentao J, Punzi L, Pywell T, So A, Tausche AK, Uhlig T, Zavada J, Zhang W, Tubach F, Bardin T. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2017 Jan;76(1):29–42. http://ard.bmj.com/content/76/1/29.abstract. <h3>Disclosure of Interest</h3> None declared
SP0122 Autoimmune phenomena associated with biological agents
Authors: P Quartier
Journal: Annals of the Rheumatic Diseases (2017)

Biologic agents are being increasingly used in pediatric rheumatology, particularly TNF antagonists but also abatacept, tocilizumab, interleukin (IL)-1 antagonists and some other drugs. In Juvenile Idiopathic Arthritis (JIA) and some autoinflammatory diseases, data from phase 3 and extension trials or from cohorts such as Pharmachild allow to prospectively collect information on adverse events “of special interest”, including autoimmune complications. A few patients develop autoimmune/dysimmune features while on biologics, as seen in adults, including central nervous system lesions, inflammatory bowel disease or psoriasis. In addition, in patients with systemic-onset JIA, anti- IL-1 treatment is usually associated with the appearance of a type 1 interferon signature (gene expression analyses) which might in some cases favour lupus-like autoimmune features. On the other hand, among patients with early-onset arthritis, vasculitis, recurrent fever or other inflammatory manifestations, an increased number of children are diagnosed with complex monogenic diseases resulting in auto-inflammation, immune deficiency and autoimmunity. In such cases, biologics might not be responsible for the occurrence of autoimmune features that may sometimes be diagnosed on treatment. This distinction is important as biologics are useful treatments also in some of these patients, as was shown in patients with a diagnosis of Systemic-onset JIA and ANCA-associated glomerulonephritis in whom anti-IL-1 treatment was beneficial. It was also more recently shown in patients with <i>lipopolysaccharide-responsive beige-like anchor</i> (<i>LRBA)</i> mutations associated with autoimmunity and inflammation, including polyarthritis: as LRBA is a partner of cytotoxic-T lymphocyte antigen-4 (CTLA4),. abatacept has been used as a targeted treatment and shown efficacy. We hence aim to discuss the way to explore patients who develop autoimmune features while on biologics in order to take the right decisions regarding treatment maintenance, withdrawal or modification and regarding patients follow-up. <h3>Disclosure of Interest</h3> P. Quartier Grant/research support from: Abbvie, Novartis, Pfizer, Roche, Consultant for: Abbvie, Novartis, Sanofi, SOBI, Speakers bureau: Abbvie, BMS, Novartis, PfiZer, Roche, SOBI
AB0554 Relationship between disease activity and neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and mean platelet volume in behÇet's disease
Authors: IE Okatan, M Torgutalp, A Ateş, E Uslu Yurteri, ME Yayla, AB Dinçer Keleşoğlu, TM Turgay, G Kınıklı
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> Behcet9s syndrome (BS) is an autoimmune disease characterized by chronic inflammation and endothelial dysfunction. There are only a few studies examining the relationship between neutrophil-lymphocyte ratio (NLR), mean platelet volume (MPV), platelet-lymphocyte ratio (PLR) and BS. The aim of this study was to determine NLR, PLR and MPV levels and their association with disease activation in BS patients with mucocutaneous, ocular and vascular involvement. <h3>Methods</h3> The study included 259 patients with BS and 41 healthy individuals. Age, sex, total white blood counts, neutrophil, platelet, mean platelet volume and lymphocyte counts of the patients were recorded. Patients with inflammatory bowel, hematological, infectious, cardiovascular diseases, hyperlipidemia, chronic liver, chronic kidney disease, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, malignancy and corticosteroid use were excluded from the study. Of 259 patients, 163 had active disease (75 active mucocutaneous (MC), 40 active ocular, 48 active vascular involvement) and 96 had inactive disease. MPV, NLR and PLR values of the patients were compared between the groups. P value &lt;0.05 was considered significant. <h3>Results</h3> Age and sex were similar between the groups. We compared the MPV, NLR and PLR values of patients with active and inactive disease. NLR and PLR were significantly higher while MPV was lower in the active group than the inactive and control groups (Table 1). Statistically significant higher PLR and NLR were found in the active MC and vascular groups, significantly lower MPV was seen only in vascular active group. This significance was not seen in active ocular group (Table 2). We also evaluated the same patient9s active and inactive periods of the disease, lower MPV, higher NLR and PLR values were seen MC and vascular groups (for all groups p&lt;0,05). When the active 3 groups were compared within themselves, the MPV value was significantly lower and NLR and PLR values were significantly higher in vascular group than active ocular and active mucocutaneous groups (p=0.033, &lt;0.001, 0.001, respectively). <h3>Conclusions</h3> The low MPV and the high NLR and PLR are found in the active disease, which is especially significant in vascular and mucocutaneous groups. In the light of our findings, NLR and PLR were associated with the activity of BS especially with vascular involvement. The low MPV and the high NLR and PLR. The low MPV and the high NLR and PLR may be useful disease activity markers in behcet9s disease. <h3>Disclosure of Interest</h3> None declared
THU0464 A genome-wide association study of gout in people of european ancestry
Authors: TR Merriman, M Cadzow, M Merriman, A Phipps-Green, R Topless, A Abhishek, M Andres, L Bradbury, R Buchanan, K Cremin, E de Guzman, J de Zoysa, M Doherty, C Hill, T Huizinga, T Jansen, M Janssen, L Joosten, F Kurreeman, S Lester, F Liote, D Macartney-Coxson, H Matsuo, G McCarthy, S McCormick, R Murphy, K Pavelka, F Perez-Ruiz, J Puig, T Radstake, P Riches, M Rischmueller, E Roddy, M Smith, E Stahl, B Stiburkova, R Stubbs, A-K Tausche, R Torres, R Walker, K Yamamoto, M Brown, H Choi, N Dalbeth, A So, L Stamp, T Flynn
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout progresses through three stages: hyperuricemia, deposition of monosodium urate (MSU) crystals, and innate immune system response to MSU crystals. Genome wide association studies (GWAS) have provided insight into the molecular control of progression to hyperuricemia. However, less is known about the progression from hyperuricemia to gout. <h3>Objectives</h3> To conduct a GWAS for gout (where an immune response to MSU crystals has occurred) using 5,835 cases - the largest GWAS of gout to date. <h3>Methods</h3> The GWAS comprised 3 data sets: NZ/Eurogout (2,365 clinically-ascertained cases; 1,485 controls), the Health Professionals Follow-Up (HPFS) and Nurses9 Health Studies (NHS) (1,038 cases, self-ascertained using ACR criteria; 1,095 controls), and UK Biobank (2,432 cases, ascertained by self-report of gout, hospital records, and/or use of urate-lowering therapy; 102,989 controls). The NZ/Eurogout samples were genotyped using the Illumina CoreExome v24 bead chip array (547,644 markers), the HPFS/NHS samples using the Illumina OmniExpress v12 bead chip array (730,525 markers), and the UK Biobank samples using an Affymetrix Axiom array (820,967 markers). UK Biobank genotypes had been imputed to ∼73.3M SNPs. Neither the NZ/Eurogout nor NHS/HPFS genotype sets were imputed. Markers common to all three data sets (279,939) were associated with gout (adjusted for sex, age) within each data set separately using PLINK 1.9. An inverse-variance weighted meta-analysis was done with meta v4.4 in R. <h3>Results</h3> There were seven loci with genome-wide significant (<i>P</i>&lt;5x10<sup>-8</sup>) evidence for association with gout: <i>SLC2A9</i> (OR=1.67), <i>ABCG2</i>(OR=1.72), <i>GCKR</i> (OR=1.24), <i>SLC17A1-A4</i> (OR=1.20), <i>SLC22A12</i> (OR=1.21), <i>PDZK1</i> (OR=1.14), <i>TRIM46</i> (OR=1.18). <h3>Conclusions</h3> All seven loci have been previously associated with serum urate levels in GWAS. Our data emphasise the relative importance of genetic control of serum urate, compared to the genetic control of MSU crystal formation or the innate immune response, in determining gout. <h3>Disclosure of Interest</h3> None declared
ALK and NRG1 Fusions Coexist in a Patient with Signet Ring Cell Lung Adenocarcinoma
Authors: Lucia Anna Muscarella, Domenico Trombetta, Federico Pio Fabrizio, Aldo Scarpa, Vito Michele Fazio, Evaristo Maiello, Antonio Rossi, Paolo Graziano
Journal: Journal of Thoracic Oncology (2017)
Abstract 18420: Does Maximum 10-hour Daily Activity From Objective Activity Monitoring Correlate With Self-reported or Performance-based Function in Older Adults With Severe Aortic Stenosis?
Authors: Yufei Tang, Mathew Maurer, Rosa Lazarte, Jonathan Rubin, Ming Y Hung, Melissa Garcia, Susheel Kodali, Tamara Harris, Philip Green
Journal: Circulation (2015)

Objectives: In older adults with aortic stenosis, we evaluated whether accelerometer-measured physical activity provides distinct clinical information apart from self-reported surveys or performance-based function tests (PBFT). Background: Wearable accelerometers can objectively quantify and monitor activity counts over an extended period of time, making them an ideal tool for measuring physical activity in older adults with cardiovascular disease; however, the relationship between accelerometer-measured activity and self-reported surveys or PBFT is unknown. Methods: We employed wrist-mounted accelerometry in 54 subjects with severe aortic stenosis prior to TAVR. Daily daytime activity was estimated using the maximum 10 hours of daily accelerometer-measured activity (M10) reported in activity counts. Subjects completed baseline surveys (NYHA, SF12, KCCQ, EQ-5D, LOT-R, Life Space, Detailed Activity Form) and PBFT (short physical performance battery, 6 minute walk test, grip strength) to estimate functional status. Simple and multiple linear regression models were used to evaluate the relationship between accelerometer-measured activity and survey data and PBFT. Results: The mean age was 87 years, 61% were female. Median ejection fraction was 63% (IQR 12). Most were NYHA Class III (65%), none were Class IV. There was a weak negative association between M10 and SF-12 Mental Composite Score (R2=0.1970, P=0.04) and between M10 and grip strength (R2=0.1568, P=0.004). However, neither multiple linear regression of overall survey data (R2=0.6159, P=0.23) nor PBFT (R2=0.1743, P=0.10) predicted M10. Conclusions: Self-reported surveys and performance-based function tests did not correlate well with maximal 10 hours of daily accelerometer-measured activity in older adults with aortic stenosis. Further studies will evaluate the distinct utility of accelerometer-measured activity in older adults with aortic stenosis predicting outcomes of TAVR.
Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection
Authors: Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato
Journal: Nature Immunology (2017)
AB0334 Knee function after total knee arthroplasty is influenced by disease activity in patients with rheumatoid arthritis
Authors: K Harigane, K Kumagai, Y Mochida, K Ishii, Y Miyamae, H Choe, A Nagaoka, Y Inaba, N Mitsugi, T Saito
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several studies reported that development of phaemacological treatment for rheumatoid arthritis (RA) contributed to decreased number of orthopaedic surgery. [1–3] Surgical treatment is, however, still required in many cases, and the impact of orthopaedic surgery on disease activity remain unclear. <h3>Objectives</h3> The aims of current study was to evaluate the effect of total knee arthroplasty (TKA) with capsulosynovectomy on changes of disease activity and knee function after TKA in patients with RA. <h3>Methods</h3> Seventy-seven serial patients with RA (61 female and 16 male) who underwent primary TKA with more than one year of follow-up were retrospectively reviewed to assess postoperative disease activity and knee function. The mean age at the time of surgery was 68.3 years old. The disease activity of RA was measured using Disease Activity Score in 28 Joints (DAS28). Clinical outcome was measured by treatment score for RA knee of the Japanese Orthopaedic Association (JOA) score. To evaluate the effects of disease activity on knee function, outcomes at before and one year after surgery were separately investigated following two groups; patients who had remission or low disease activity in DAS28-CRP (good controlled group), and patients who had moderate or high disease activity (poor controlled group) one year after surgery. <h3>Results</h3> The disease activity of RA was significantly decreased in DAS28-CRP one year after surgery. (3.9 vs. 2.7, p&lt;0.01) Postoperative knee function was significantly improved in JOA scores one year after surgery. (48.9 vs. 86.0, p&lt;0.01) As for differences of knee function between good and poor controlled group, the mean JOA score in good controlled group was significantly better than in poor controlled group. (90.4 vs. 82.1, p&lt;0.01) Postoperative knee function was negatively correlated with RA disease activity. (R<sup>2</sup>=0.21, p&lt;0.01) <h3>Conclusions</h3> TKA with capsulosynovectomy improves both knee function and disease activity in patients with RA. Based on the results, knee function after TKA is influenced with disease activity. <h3>References</h3> Dusad A et al. Impact of Total Knee Arthroplasty as Assessed Using Patient-Reported Pain and Health-Related Quality of Life Indices: Rheumatoid Arthritis Versus Osteoarthritis. Arthritis Rheumatol. 2015; 67: 2503–11. Yano K et al. Effect of total knee arthroplasty on disease activity in patients with established rheumatoid arthritis: 3-year follow-up results of combined medical therapy and surgical intervention. Mod Rheumatol. 2010; 20: 452–7. Oh K et al. Effects of surgical intervention on disease activity of rheumatoid arthritis: cases of surgery for rheumatoid arthritis of the lower limbs treated with biologics. Mod Rheumatol. 2014; 24: 606–11. <h3>Disclosure of Interest</h3> None declared