tbuckley/cabot-search huggingface dataset:
SP0017 Shared mechanisms in cancer and autoimmunity
Authors: A Rosen
Journal: Annals of the Rheumatic Diseases (2017)

Some rheumatic disease autoantibodies are powerful markers of subgroups of patients who have distinct disease phenotypes and trajectories. Of particular interest are markers of several disease subgroups in whom cancer and rheumatic disease onset are clustered together in time. For example, a subgroup of scleroderma patients have coincident onset of cancer and scleroderma. This is observed in scleroderma patients with autoantibodies against the RNA polymerase-3 (POLR3), and more recently with autoantibodies recognizing the minor spliceosome. In autoimmune myopathies, temporal clustering of diagnosis of cancer and myositis is associated with autoantibodies to NXP2 and components of the TIF1 complex. Interestingly, although the incidence of cancer is higher in patients with these autoantibodies, most patients with these autoantibodies manifest cancer, even with extended periods of follow-up. These observations provide an important opportunity to investigate the potential mechanisms which operate at the cancer-immune interface during development of rheumatic diseases. We have investigated such mechanisms in scleroderma patients with autoantibodies to POLR3 who also had a cancer diagnosed an average of -2.6 years from scleroderma onset. In cancers from these patients, we found genetic alterations of the POLR3A locus in six of eight patients with antibodies to POLR3 but not in eight patients without these antibodies. 3 antibody-positive patients had somatic mutations in POLR3A; 5 patients had loss of heterozygosity at the POLR3A locus. Analyses of peripheral blood lymphocytes and serum suggested that POLR3A mutations sparked cellular immunity and cross-reactive humoral immune responses. These results offer insight into the pathogenesis of scleroderma, and potentially other autoimmune syndromes. They suggest that somatic mutations in autoantigens in different cancers might initiate an immune response to the mutated autoantigen, which spreads to include the wild type version. Tissues (e.g. blood vessels, regenerating muscle) in which specific autoantigens are expressed at high levels, or potentially play critical functional roles, may be particularly susceptible to immune-mediated dysfunction. The results also provide support for the idea that acquired immunity helps to control naturally occurring cancers in patients with autoimmune rheumatic diseases; it is possible that this immune response may sometimes be fully effective, preventing the emergence of cancer. <h3>Disclosure of Interest</h3> None declared
SAT0717-HPR Pregnancy and delivery in patients with rheumatoid arthritis and spondyloarthritis
Authors: A Zbinden, S van den Brandt, PM Villiger, M Østensen, F Förger
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Inflammatory rheumatic disease do have an influence on pregnancy course and outcome. There is little knowledge about the comparison between two rheumatic diseases. <h3>Objectives</h3> To analyze pregnancy complications, pregnancy outcome and delivery mode in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). <h3>Methods</h3> Patients with RA and SpA were compared with those of matched healthy controls (HC) with respect to pregnancy complications, pregnancy outcome and delivery mode. Patients and controls were prospectively followed at the University of Bern. <h3>Results</h3> We analyzed 244 pregnancies, of which 96 pregnancies occurred in 86 RA patients, 78 in 70 SpA patients and 70 in 70 healthy women. Pregnancy complications (gestational diabetes, preeclampsia, infection, premature rupture of membranes) were more frequent in RA patients (11.5%) and in SpA patients (17.9%) than in HC (1.4%). Pregnancy outcome of 174 pregnancies in RA and SpA patients resulted in 178 live born infants, 6 sets of twins, one stillbirth and one induced fetal demise. The induced fetal demise was performed in a twin pregnancy on a fetus with a congenital anomaly. Congenital anomalies occurred in 6 infants (3 in RA and 3 in SpA patients). All HC had live births. Median birth weight was lower in patients compared with HC (RA: 3100g, SpA: 3245g, HC: 3455g). RA and SpA patients had more often small for gestational age infants (birth weight &lt;10th percentile; RA: 16.2%, SpA: 11.4%, HC: 1.4%) and preterm deliveries (RA: 18.8%, SpA: 11.5%, HC: 1.4%). With regard to delivery mode, most women had vaginal deliveries (RA: 51.0%, SpA: 57.7%, HC: 72.9%). Birth by caesarean section (elective and emergency), was more frequent in RA and SpA patients than in the healthy controls (RA: 44.8%, SpA: 39.7%, HC: 27.2%). Emergency caesarean sections were indicated in 22.9% of pregnancies among RA patients, in 21.8% of SpA patients and in 14.3% of healthy women. <h3>Conclusions</h3> Pregnancy complications, caesarean section, and adverse child outcomes were more frequent in patients with RA and SpA compared to healthy women. However, no significant differences in pregnancy outcomes were observed between RA and SpA patients indicating comparable risks induced by the autoimmune inflammatory process. <h3>Disclosure of Interest</h3> None declared
OP0258-HPR Intensive physical exercise for elderly persons with rheumatoid arthritis improves physical capacity
Authors: E Lange, D Kucharski, K Svensson, S Svedlund, I Gjertsson, K Mannerkorpi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Today, more than 50% of persons with Rheumatoid Arthritis (RA) are over 65 years of age (1). Little is known about the effects of physical exercise in this age group (&gt;65 years). <h3>Objectives</h3> The aim of this randomized controlled study is to investigate the effects of a person-centred progressive aerobic and resistance exercise program, led by a physiotherapist. <h3>Methods</h3> Seventy-four with persons with RA (24% men), mean age 70 years (SD 2.5), were recruited and randomized to an exercise interventions group or an active control group. The intervention consisted of a 20-week individual person-centered exercise program, performed three times a week with guidance from a physiotherapist. Both aerobic and resistance exercise was performed on a high intensity level. The control group followed a home exercise program twice a week. Muscle strength and endurance were assessed by the Chair Stands test, the Timed up and Go and a Bicycle endurance test. Maximal aerobic capacity (VO<sub>2</sub> max) was assessed with ergo spirometry. Activity limitations were assessed by SF36 Physical subscale and the Health Assessment Questionnaire (HAQ). <h3>Results</h3> All participants in the intervention group completed the intervention. The participants had a low disease activity with a mean Clinical Disease Activity Index of 5.4 (SD 3.9). Significant improvements were found for VO<sub>2</sub> max, the Chair Stands test, the Timed up and Go, the Bicycle endurance test on bicycle (p&lt;0,001) and the SF36 physical (p=0.018) in the intervention group, when compared to the controls. No significant differences between groups were seen on HAQ. <h3>Conclusions</h3> Intensive progressive aerobic and resistance exercise is a feasible intervention for elderly persons with RA. Despite old age and RA the participants gained significant improvements in physical capacity. <h3>References</h3> Eriksson JK, Neovius M, Ernestam S, Lindblad S, Simard JF, Askling J. Incidence of rheumatoid arthritis in Sweden: a nationwide population-based assessment of incidence, its determinants, and treatment penetration. Arthritis Care Res (Hoboken). 2013;65(6):870–8. <h3>Disclosure of Interest</h3> None declared
SAT0244 A long-term follow-up study of allogeneic mesenchymal stem cells transplantation in patients with drug-resistant systemic lupus erythematosus
Authors: D Wang, L Sun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Allogeneic mesenchymal stem cells (MSC) transplantation showed therapeutic effect in active and refractory systemic lupus erythematosus (SLE). <h3>Objectives</h3> To determine the long-term safety and efficacy of allogeneic MSC transplantation (allo-MSCT) in severe SLE patients refractory to previous therapies. <h3>Methods</h3> All consecutive SLE patients who received at least one allo-MSCT were analyzed. SLEDAI score of more than or equal to 8 or with at least one BILAG grade A or at least two BILAG grade B manifestations. All the patients were refractory to corticosteroid and/or immunosuppressive drugs treatment. Allogeneic bone marrow and/or umbilical cord derived MSCs were infused intravenously, with one million cells per kilogram of bodyweight for each infusion. The primary end point was 5-year overall survival. Secondary end points included complete clinical remission, partial clinical remission and relapse. <h3>Results</h3> Eighty-one patients were enrolled and underwent allo-MSCT. Thirteen patients died within 5 years post-MSCT and the 5-year overall survival rate was 84% (68/81). At 5-year follow-up, 22 patients (22/68, 32%) were in complete clinical remission and another 6 patients (6/68, 9%) were in partial clinical remission, and the 5-year disease remission was 41% (28/68). In total, 37 patients had achieved clinical remission (27 in complete remission and 10 in partial remission) at the 5 years visit and then 9 patients subsequently relapsed. The 5-year overall rate of relapse was 24% (9/37). SLEDAI scores, levels of serum albumin and complement C3, peripheral white blood cell and platelet numbers, as well as proteinuria levels continued to improve during the follow-up. <h3>Conclusions</h3> Allogeneic MSCT is safe and resulted in long-term clinical remission in severe and drug-resistant SLE patients. <h3>Disclosure of Interest</h3> None declared
THU0439 More obesity and higher serum uric acid in early-onset gout patients in south china
Authors: Q-H Li, L-X Chen, Y-H Li, D-H Zheng, Y-Q Mo, L Dai, J-J Liang, X-N Wei
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Gout incidence increases in a linear fashion with age until 70 years. It was reported that there was a trend of earlier gout onset. Few studies about clinical features of early-onset gout in China are reported. <h3>Objectives</h3> To investigate the characteristics of early-onset gout in south China. <h3>Methods</h3> Patients with primary gout were recruited between June 2012 and December 2016. Face to face interview was carried out to collect demographic information, clinical characteristics of gout and comorbid diseases. The patients with gout onset before age 30 were defined as early-onset group. The other gout patients were enrolled as control group. <h3>Results</h3> (1) Five hundred and one gout patients were recruited, including 99 (19.8%) in the early-onset group and 402 (80.2%) in the control group. The onset age of the early-onset group was 24.2±5.8 (range 14–30) and the control group was 51.7±13.9 (range 31–84). There was no significant difference of gout duration between early-onset group and control group (P&lt;0.05, Table 1). (2) Compared with the control group, the early-onset group presented lower frequency of flare in last year, higher serum uric acid and higher proportion of sUA&gt;10mg/dl (P&lt;0.05, Table 1). Body mass index (BMI) and prevalence of obesity were higher in the early-onset group (P&lt;0.05, Table 1). The early-onset group exhibited lower prevalence of hypertension, diabetic mellitus, urolithiasis and chronic kidney disease (CKD) (P&lt;0.05, Table 1). (3) There were 20 patients (20.2%) with tophi in the early-onset group. Compared with the 79 early-onset gout patients without tophi, the patients with tophi presented higher age (39.6±8.9 VS 29.1±6.2, P&lt;0.001), duration of gout (12.6±4.8 VS 4.5±4.8, P&lt;0.001), number of involved joints (12.5±9.3 VS 4.3±3.7, P&lt;0.001) and prevalence of CKD (30.0% VS 10.1%, P=0.034), and lower BMI (23.7±3.7 VS 26.6±4.1 kg/m<sup>2</sup>, P=0.004). Logistic regression demonstrated that higher disease duration [OR 1.30, 95% CI (1.15, 1.46), P&lt;0.001] and lower BMI [OR 0.80, 95% CI (0.67, 0.96), P=0.015] were associated with tophi in the early-onset gout patients. <h3>Conclusions</h3> Early-onset gout exhibited higher sUA and was associated with obesity but not with hypertension, diabetic mellitus and renal insufficiency. Longer disease duration and lower BMI were associated with tophi in the early-onset gout patients. <h3>Acknowledgements</h3> The present study was supported by Guangdong Natural Science Foundation, China (Grant no. 2014A030310086) to Qian-Hua Li. <h3>Disclosure of Interest</h3> None declared
SP0179 What is disease activity in finger oa?
Authors: R Wittoek
Journal: Annals of the Rheumatic Diseases (2017)

Osteoarthritis of the interphalangeal finger joints constitutes one of the most prevalent musculoskeletal diseases with variable clinical impact ranging from nearly asymptomatic to severe inflammatory pain in and around affected joints, presence of soft tissue and bony swelling, stiffness and gradual loss of function. Current therapeutic options are limited to analgesic treatment but research on targeted therapies is increasing. In order to improve the current treatments, a critical appraisal of the needs for improvement in finger OA is needed and how disease activity is best defined. Assessing disease activity or joint activity in finger OA is challenging: disease activity can comprise pain, inflammatory activity and structural damage. In clinical practice, a combination of patient-reported (e.g. visual analogue scale or Likert scale pain), more objective and performance-based measures (e.g. grip strength) are used to assess and follow disease activity. In clinical research, pharmacological trials and epidemiological studies, a standardized approach to assess the disease activity is necessary to estimate the burden of disease and to evaluate the efficacy of potential new treatments. The instruments being used, depend mostly on the aim of the study or research question. In case structural disease progression is being studied, imaging-based outcome measures are mostly used. Structural changes can be assessed on joint level or on patient level, both by conventional radiographs, ultrasound and magnetic resonance imaging. Several imaging based outcome measures and scoring systems are being suggested but true consensus about the instruments of preference is still lacking. Therefore, further validation of these instruments is warranted. This lecture will give an overview of the current instruments to measure activity in finger OA in several domains and discuss its strengths and limitations. <h3>Disclosure of Interest</h3> None declared
AB0515 Skin manifestations as independent predictors and the initial risk faktors for systemic antiphospholipid events
Authors: L Stojanovich, A Djokovic, N Stanisavljevic, M Zdravkovic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome (APS) patients express skin manifestations with the presence of various levels of antiphospholipid antibodies (aPL).Several studies have shown the frequency of dermatological manifestations with APS<sup>1,2,3</sup>, including livedo reticularis, cutaneous ulcers, acrocyanosis, and other. <h3>Objectives</h3> Dermatological manifestations can be the initial clue in the diagnosis of this disease. <h3>Methods</h3> Our study includes a total of 508 APS patients; 360 were PAPS patients (283 female and 77 male, mean age 44.0±12.9 years),148 had APS associated with SLE/SAPS (133 female and 15 male,mean age 47.7±14.8 years).aPL analysis included:LA, aCL (IgG/IgM), β<sub>2</sub>GPI (IgG/IgM).In all patients, we collected data considering frequently occured skin lesions. <h3>Results</h3> Our results showed prevalence of skin manifestations in SAPS group of patinenst regading to PAPS (Table 1). Patients with skin manifestations overall had higher prevalence of thrombosis (Table 2). <h3>Conclusions</h3> Dermatological manifestations can be very often the initial symptoms of severe manifestations of APS.Our study showed that patients with secondary APS had higher prevalence of skin lesions, and that some aPL types were risk factors for thrombotic manifestations in APS patients <h3>References</h3> Toubi E, Krause I, Fraser A, Lev S, Stojanovich L, Rovensky J, et al. Livedo reticularis is a marker for predicting multi-system thrombosis in antiphospholipid syndrome. Clin Exp Rheumatol 2005;23:499–504. Weinstein S, Piette W. Cutaneous manifestations of antiphospholipid antibody syndrome. Hematol Oncol Clin North Am 2008;22:67–77. Asherson RA, Cervera R, Klumb E, Stojanovich L. et all.: Amputation of Digits or Limbs in Patients with Antiphospholipid Syndrome. 21 January 2008. Seminars in Arthritis and Rheumatism. 2008; 38: 124–31. Stojanovich L, Markovic O, Marisavljevic D et all. Influence of antiphospholipid antibody levels and type on thrombotic manifestations: results from the Serbian National cohort study. Lupus 2011;0: 1–8. Stojanovich L, Kontic M, Djokovic Aet all. Association between Systemic Non-criteria APS Manifestations and Antibody Type and Level: Results from the Serbian National Cohort Study. Clinical and Experimental Rheumatology, 2013,31(5):756–60. <h3>Acknowledgements</h3> This work was supported by research grant number 175041 for 2011 - 2017, issued by the Ministry of Science of the Republic of Serbia. <h3>Disclosure of Interest</h3> None declared
Blinatumomab-induced lineage switch of B-ALL with t(4:11)(q21;q23) KMT2A/AFF1 into an aggressive AML: pre- and post-switch phenotypic, cytogenetic and molecular analysis
Authors: C L Haddox, A A Mangaonkar, D Chen, M Shi, R He, J L Oliveira, M R Litzow, A Al-Kali, W J Hogan, M A Elliott
Journal: Blood Cancer Journal (2017)

Blinatumomab-induced lineage switch of B-ALL with t(4:11)(q21;q23) KMT2A/AFF1 into an aggressive AML: pre- and post-switch phenotypic, cytogenetic and molecular analysis
Changes in dynamic lung mechanics after lung volume reduction coil treatment of severe emphysema
Authors: Demosthenes Makris, Sylvie Leroy, Johana Pradelli, Jonathan Benzaquen, Hervé Guenard, Jeanne-Marie Perotin, Spyros Zakynthinos, Epaminondas Zakynthinos, Gaëtan Deslee, Charles Hugo Marquette
Journal: Thorax (2017)

We assessed the relationships between changes in lung compliance, lung volumes and dynamic hyperinflation in patients with emphysema who underwent bronchoscopic treatment with nitinol coils (coil treatment) (n=11) or received usual care (UC) (n=11). Compared with UC, coil treatment resulted in decreased dynamic lung compliance (C Ldyn ) (p=0.03) and increased endurance time (p=0.010). The change in C Ldyn was associated with significant improvement in FEV 1 and FVC, with reduction in residual volume and intrinsic positive end-expiratory pressure, and with increased inspiratory capacity at rest/and at exercise. The increase in end-expiratory lung volume (EELV) during exercise (EELV dyn-ch =EELV isotime EELV rest ) demonstrated significant attenuation after coil treatment (p=0.02).
AB0370 Development of patient preference phenotypes for rheumatoid arthritis
Authors: WB Nowell, C Wiedmeyer, G Herath, G Michel, L Fraenkel
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Many important treatment decisions for patients with rheumatoid arthritis (RA) are conditional on patient preferences and, according to the U.S. National Academy of Medicine, mandate a shared decision making approach (SDM). Furthermore, SDM is being increasingly recognized as an important quality measure. One of the most common preference sensitive decisions in RA is how to escalate care when response to methotrexate monotherapy is inadequate. However, the number of RA medications currently approved makes it challenging for patients to weigh the pros and cons related to each of the treatment options in order to develop a preference. <h3>Objectives</h3> The objective of this study was to develop representative patient preference phenotypes to enable patient-physician dyads to effectively incorporate patient preferences at the point-of-care. <h3>Methods</h3> People living with RA were invited to complete a Choice-Based Conjoint analysis survey including seven attributes (route of administration, time to onset of action, bothersome adverse events (AEs), serious AEs, extremely rare AEs, duration of time on the market and affordability) developed iteratively based on patient feedback. Each attribute was described across three or four levels using plain language. Preference phenotypes were identified by applying latent class analysis to the conjoint data. Class solutions were replicated five times from random starting seeds. A five-group solution was chosen based on Akaike9s information criterion. We calculated the percentage of importance assigned to each attribute and performed simulations to estimate preferences for triple therapy, SC and IV biologics, or tofacitinib. <h3>Results</h3> 1100 U.S. subjects recruited via the CreakyJoints online patient community completed the survey. Of these, 49 were eliminated because they completed the survey in less than 10 minutes and an additional 45 people were excluded because they did not respond correctly to a dominant choice task. The mean age was 51.7 (11.2). The majority were female; (92%) and Caucasian (93%). Preferences (assuming low cost across options), and the reasons underlying each respondent9s preference, clustered into five groups (Figure 1). There were no differences in the distribution of demographic or clinical characteristics across the five groups. Phenotypes were created based on the stated preference data. <h3>Conclusions</h3> RA patients9 preferences vary and can be classified into distinct phenotypes. Ongoing research is evaluating whether enabling patients to identify with a preference phenotype facilitates SDM at the point-of-care. <h3>Acknowledgements</h3> This research was supported by a grant from the Rheumatology Research Foundation. <h3>Disclosure of Interest</h3> None declared
Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes
Authors: Satish K. Garg, Robert R. Henry, Phillip Banks, John B. Buse, Melanie J. Davies, Gregory R. Fulcher, Paolo Pozzilli, Diane Gesty-Palmer, Pablo Lapuerta, Rafael Simó, Thomas Danne, Darren K. McGuire, Jake A. Kushner, Anne Peters, Paul Strumph
Journal: New England Journal of Medicine (2017)

In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium–glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes.