tbuckley/cabot-search huggingface dataset:
THU0269 Electrocardiographic nonspecific ST-T abnormalities are associated with higher modified framingham risk score in systemic lupus erythematosus patients without clinical cardiovascular disease
Authors: E George, T Perez-Recio, L Geraldino-Pardilla
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cardiovascular disease (CVD) is a leading cause of mortality in systemic lupus erythematosus (SLE). Traditional CVD risk scores underperform in SLE. Interestingly, a high prevalence of nonspecific ST-T changes (NST-T) has been recently reported in lupus patients<sup>1,2</sup>. These electrocardiographic findings are known to increase the risk for myocardial infarction, coronary artery disease, CVD, and all-cause mortality<sup>3</sup> in the general population, but in SLE this association remains unknown. Therefore, we sought to define the association of NST-T with the modified Framingham Risk Score (mFRS) as a surrogate outcome for CVD<sup>4</sup>. <h3>Objectives</h3> To evaluate if NST-T are associated with higher mFRS in SLE patients without clinical cardiovascular disease. <h3>Methods</h3> Adult SLE patients without clinical CVD continuously seen at the Columbia University Lupus Center between April 2016 and January 2017, meeting 1997 American College of Rheumatology classification criteria for SLE were studied. Twelve-lead electrocardiogram (EKG), high sensitivity C-reactive Protein (hsCRP), demographics, disease-specific characteristics, medication use, and CVD risk factors were ascertained. Univariable and multivariable linear regression models were constructed to test the association of NST-T with the mFRS. <h3>Results</h3> Seventy-four lupus patients were studied (baseline characteristics in table 1). In univariable analysis, patients with NST-T had a significantly higher mFRS (0.44, p=0.018). There were no confounders identified in the analysis. However after adjusting for variables associated with the mFRS: smoking, diabetes, hsCRP, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI], aspirin use, this association remained statistically significant (0.38, p=0.05). Image 1 shows the association of mFRS with NST-T vs no NST-T. <h3>Conclusions</h3> Non Specific ST-T changes are independently associated with a higher mFRS in SLE patients without clinical CVD. <h3>References</h3> Bourré-Tessier J, Urowitz MB, Pineau CA. et al. Electrocardiographic findings in systemic lupus erythematosus: data from an international inception cohort.Arthritis Care Res (Hoboken). 2015 Jan;67(1):128–35. Geraldino-Pardilla L,Gartshteyn Y, Piña P, et al.ECG non-specific ST-T and QTc abnormalities in patients with systemic lupus erythematosus compared with rheumatoid arthritis. Lupus Sci Med. 2016 Dec 16;3(1):e000168. Daviglus ML, Liao Y, Stamler J, et al. Association of Nonspecific Minor ST-T Abnormalities With Cardiovascular Mortality The Chicago Western Electric Study. JAMA. 1999;281(6):530–536. Urowitz MB, Ibañez D, Gladman DD,et al. Modified Framingham Risk Factor Score for Systemic Lupus Erythematosus. J Rheumatol. 2016 May;43(5):875–9. <h3>Disclosure of Interest</h3> None declared
First-in-human phase I study: Results of a second-generation non-ansamycin heat shock protein 90 (HSP90) inhibitor AT13387 in refractory solid tumors.
Authors: Daruka Mahadevan, Diane M Rensvold, Sandra E Kurtin, James M. Cleary, Leena Gandhi, John F. Lyons, Victoria Lock, Samantha Lewis, Geoffrey Shapiro
Journal: Journal of Clinical Oncology (2012)

3028 Background: AT13387 is a second-generation potent, novel non-ansamycin HSP90 inhibitor (IC 50 0.71 nM). AT13387 has good tissue distribution, long tumor t 1/2 resulting in extended knockdown of client proteins in cells and animal models of gastric, prostate and melanoma. Methods: AT13387 was administered as a 1-hr IV infusion twice weekly on Days 1, 4, 8, 11, 15 and 18 (Part A) and then subsequently, weekly on Days 1, 8 and 15 (Part B) of a 28-day cycle in a standard 3+3 dose-escalation design. The primary endpoint was to determine the MTD; secondary endpoints included PK, PD, safety and tolerability. Results: As of 1 Dec 2011, 53 patients received 1–12 cycles of AT13387 (median 2). In Part A, AT13387 was evaluated at 5 doses (10, 20, 40, 80, 120 mg/m 2 ). In Part B, 4 additional doses (150, 220, 260 and 310 mg/m 2 ) were explored. Common treatment related toxicities (≥ 10%) included transient and reversible GI disturbance (vomiting, nausea, dry mouth, diarrhea, abdominal pain), fatigue, local infusion site irritation and systemic infusion-related symptoms including chills, rash, itch, cardiovascular (tachycardia, bradycardia, hypertension, hypotension), and visual changes (diplopia, transient flashes, delayed light/dark accommodation, blurred vision). Severity of infusion-related symptoms, GI toxicities, and fatigue at 310 mg/m 2 prevented further dose escalation. A dose of 260 mg/m 2 has been identified as the once weekly MTD and the study is currently accruing at this dose. Biological evidence of HSP90 inhibition, demonstrated by an increase in HSP70 in PBMCs, was detected at all doses and exhibited evidence of dose dependence. PK demonstrated dose proportionality, without significant accumulation. One durable RECIST PR (8 months) in an imatinib relapsed metastatic GIST patient with c-kit mutations in exons 11 and 17 was observed. Three SD ≥ 6 months (follicular cell thyroid carcinoma, metastatic uveal melanoma, GIST) were also observed. Conclusions: The MTD of AT13387, administered as a once weekly IV, is 260 mg/m 2 . All drug-related toxicities were generally reversible. Single-agent activity was observed. Dose expansion at MTD and phase II studies are ongoing.
AB0289 Predictor of the simplified disease activity index 50 (SDAI 50) at month 6 during bdmards treatment in patients with long-established rheumatoid arthritis: a single-center, retrospective study
Authors: Y Miwa, A Nishimi, S Nishimi, T Tokunaga, S Ishii, T Kasama
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The simplified disease activity index (SDAI) 50 has good agreement with the EULAR response measures for early rheumatoid arthritis (RA). Although there are reports on early RA, there have been no reports on long-established RA. <h3>Objectives</h3> In this study, we analyzed the relationships between various baseline factors and SDAI 50 after six months of biological disease-modifying antirheumatic drugs (bDMARDs) treatment to determine the prognostic factors for long-established RA. <h3>Methods</h3> The subjects were 332 RA patients who had been treated with bDMARDs for 6 months. The following characteristics were investigated: age, gender, disease duration, smoking history, body mass index, steroid and methotrexate dosage, previous bDMARDs use, combined csDMARDs use, ESR, CRP, serum matrix metalloproteinase-3 levels, SDAI score, health assessment questionnaire disability index score (for daily living activities) and short form-36 score (for quality of life). As a primary outcome index, SDAI response was defined as a 50% reduction in SDAI score between baseline and 6 months (SDAI 50). <h3>Results</h3> The group of RA patients who achieved SDAI 50 (Group A: 204 patients) had a higher tender joint count (p=0.041), swollen joint count (p=0.001), evaluator9s global assessment (p=0.027) and SDAI (p=0.006) than did those who did not achieve SDAI 50 (Group B: 152 patients). Before the start of the treatment, steroid dosage (p=0.0187, odds ratio: 1.119, 95% CI: 1.029–1.229) and SDAI (p=0.0003, odds ratio: 0.953, 95% CI: 0.928–0.978) were determined based on logistic regression analysis. Comparisons were performed between Groups A and B and between before treatment and after 6 months of SDAI. Group A showed a significant improvement compared to Group B by repeated measure analysis of variance (ANOVA) (Interaction: p=0.000, Group A vs. Group B: p=0.000, before vs. after treatment: p=0.000). <h3>Conclusions</h3> Our study demonstrated that RA patients with a lower steroid dosage and higher SDAI baseline are more likely to achieve SDAI 50 with bDMARD treatment. <h3>Acknowledgements</h3> ASHURA Resistry Groups <h3>Disclosure of Interest</h3> Y. Miwa Grant/research support from: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, AbbVie CK, Pfizer Japan Inc., Chugai Pharmaceutical Co., Ltd., Eizai Co., Ltd, Asahi Kasei Pharm Co., Ltd, YL biologics Ltd., Japan Blood Products Organization,. Ono Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., and Teijin Pharma Ltd., A. Nishimi: None declared, S. Nishimi: None declared, T. Tokunaga: None declared, S. Ishii: None declared, T. Kasama Grant/research support from: Mitsubishi Tanabe Pharma Corporation and AbbVie CK.
Status, quality and specific needs of Zika virus (ZIKV) diagnostic capacity and capability in National Reference Laboratories for arboviruses in 30 EU/EEA countries, May 2016
Authors: Ramona Mögling, Hervé Zeller, Joana Revez, Marion Koopmans, Chantal Reusken
Journal: Eurosurveillance (2017)

With international travel, Zika virus (ZIKV) is introduced to Europe regularly. A country's ability to robustly detect ZIKV introduction and local transmission is important to minimise the risk for a ZIKV outbreak. Therefore, sufficient expertise and diagnostic capacity and capability are required in European laboratories. To assess the capacity, quality, operational specifics (guidelines and algorithms), technical and interpretation issues and other possible difficulties that were related to ZIKV diagnostics in European countries, a questionnaire was conducted among national reference laboratories in 30 countries in the European Union/European Economic Area (EU/EEA) in May 2016. While the coverage and capacity of ZIKV diagnostics in the EU/EEA national reference laboratories were found to be adequate, the assessment of the quality and needs indicated several crucial points of improvement that will need support at national and EU/EEA level to improve ZIKV preparedness, response and EU/EEA ZIKV surveillance activities.
Investigation of the Safety of Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Natural Canine Model of Aging
Authors: Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony Schwab, Elizabeth Head, Kullervo Hynynen
Journal: Theranostics (2017)

Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD).Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory.Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations.Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits.Methods: Aged dogs naturally accumulate plaques and show associated cognitive declines.Low-frequency ultrasound was used to open the BBB unilaterally in aged beagles (9-11yrs, n=10) in accordance with institutionally approved protocols.Animals received either a single treatment or four weekly treatments.Magnetic resonance imaging(MRI) was used to guide the treatments and assess the tissue effects.The animals underwent neurological testing during treatment follow-up, and a follow-up MRI exam 1 week following the final treatment.Results: The permeability of the BBB was successfully increased in all animals (mean enhancement: 19±11% relative to untreated hemisphere).There was a single adverse event in the chronic treatment group that resolved within 24 hrs.Follow-up MRI showed the BBB to be intact with no evidence of tissue damage in all animals.Histological analysis showed comparable levels of microhemorrhage between the treated and control hemispheres in the prefrontal cortex (single/repeat treatment: 1.0±1.4vs 0.4±0.5/5.2±1.8 vs. 4.0±2.0).No significant differences were observed in beta-amyloid load (single/repeat: p=0.31/p=0.98)although 3/5 animals in each group showed lower Aβ loads in the treated hemisphere.Conclusion: Whole-hemisphere opening of the BBB was well tolerated in the aged large animal brain.The treatment volumes and frequencies used are clinically relevant and indicate safety for clinical translation.Further study is warranted to determine if FUS has positive effects on naturally occurring amyloid pathology.
SAT0177 Safety events are similar with abatacept vs placebo treatment in ra: results from integrated data analysis from nine clinical trials
Authors: B Soule, M Hochberg, D Fleming, A Torbeyns, T Simon, S Banerjee, M Boers
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Abatacept is a selective co-stimulation modulator that consists of the extracellular domain of human cytotoxic T lymphocyte-associated antigen-4 linked to the modified Fc portion of human immunoglobulin and was approved initially for the treatment of RA in 2005. The integrated safety database for abatacept in adult RA comprises data from short- and long-term periods of 16 open-label and double-blind RA clinical trials, and combines studies of both IV and SC abatacept involving 7044 total patients. Of these, data from the 9 double-blind, placebo-controlled studies involving 4138 total patients were included in this analysis. The most recent overall safety analysis was performed in 2012 and reported IV and SC results separately. <h3>Objectives</h3> To provide an update of the overall abatacept safety profile based on data analysis from both IV and SC trials. <h3>Methods</h3> This evaluation included all patients with RA enrolled in 9 key double-blind, placebo-controlled clinical trials of IV and/or SC abatacept. The safety analysis includes all serious adverse events (SAEs), as well as AEs of interest including infections, malignancies and autoimmune diseases. <h3>Results</h3> In total, 2653 patients were exposed to abatacept and 1485 received placebo. During the double-blind, controlled period, the mean (SD) duration of exposure was 10.3 (3.5) months for the placebo group and 10.8 (3.3) months for the abatacept group for a total exposure of 2357 and 1254 patient years, respectively (Table 1). The proportion of patients as well as incidence rates for death, SAEs, infections, malignancy and autoimmune diseases were similar between those treated with abatacept and placebo (Table 2). <h3>Conclusions</h3> In a large RA clinical trial database, safety events including deaths, serious infections, opportunistic infections, malignancies and autoimmune diseases occurred at similar frequencies and rates in the abatacept and placebo treatment groups. <h3>Disclosure of Interest</h3> B. Soule Employee of: Bristol-Myers Squibb, M. Hochberg Shareholder of: Theralogix LLC, Grant/research support from: NIH, Consultant for: Bristol-Myers Squibb, EMD Serono Inc., Genentech/Roche, Novartis Pharma AG, Pfizer Inc, UCB Inc., D. Fleming Employee of: Bristol-Myers Squibb, A. Torbeyns Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, T. Simon Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Boers Consultant for: Bristol-Myers Squibb
SAT0687 Adherence of rheumatic patients to inh prophylaxis prescribed before biological treatment: hur-bio single center real life results
Authors: E Şeyhoğlu, OA Uyaroğlu, A Erden, L Kılıç, B Armağan, A Sarı, M Baykal, S Ak, Ö Karadağ, A Akdoğan, S Bilgen Apraş, S Kiraz, I Ertenli, U Kalyoncu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Isoniazid (INH) prophylaxis is strongly recommended for the patients who have latent tuberculosis (TB) and who are going to be under anti-TNF treatment. INH is prescribed for 9 months and patient adherence to INH affects the risk of active TB development. <h3>Objectives</h3> In this study we aimed to assess the levels of patient adherence to INH prophylaxis. <h3>Methods</h3> Patients, who are under biological treatment and who have a quantiferon (QFT) test result, were evaluated with a questionnaire between August 2015-August 2016. Questionnaire included the demographic and clinical characteristics. Besides, patients were asked whether they had been prescribed INH. Patients, who were given INH prophylaxis, were asked to answer those questions: i) Did you take INH daily and regularly for 9 months? ii) If not what was the reason? The reasons are classified into three categories: 1) The patient discontinued INH of his/her own volition before 9 months. 2) Continued INH for 9 months but did not take regularly due to forgetfulness. 3) Treatment stopped by physicisan due to an adverse effect (elevation of liver enzymes, neuropathy, etc.) <h3>Results</h3> 1. 710 patients were recruited. INH was prescribed to 169 (23.8%) of 710. Demographic characteristics of INH-prescribed patients: 88 (52.1%) of 169 were female, mean age was 46.2 (SD:11.4), 82 (48.5%) of 169 at least graduated from a high school. Diagnosis were followed; RA 65 (38.4%), SpA 85 (50.3%), PsA 13 (7.7%), others 6 (3.6%). Totally 34 (20.1%) of 169 took INH irregularly. 19 (11.2%) of 169 patients discontinued INH of his/her own volition before 9 months. During follow-up 5 of 19 were prescribed INH again by the physician and they completed the 9-months duration. 9 (5.3%) of 169 patients did not take INH regularly due to forgetting. INH was stopped by a physician due to liver enzyme elevation in 6 (3.5%) of 169 patients. There was not a statistically difference in demographical and clinical characteristics between regular and irregular INH takers. <h3>Conclusions</h3> There is an inadherence to INH treatment approximately in one of five patients. Only 3.5% of INH-recommended patients had a medical reason of inadherence. Among other patients, causes of inadherence were discontinuance of own volition and forgetfulness or perfunctoriness. Physicians should be aware that reminding of INH is one of the question in every outpatient clinic visits. Other reminding methods such as regular calling should be considered in those of high risk population. Further studies were needed for reminding process. <h3>Disclosure of Interest</h3> None declared
THU0333 Are the demographic and clinical features of polyarteritis nodosa similar between the uk and turkey?
Authors: O Karadag, A Erden, ED Batu, S Gopaluni, A Sari, B Armagan, I Ertenli, S Ozen, D Jayne
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Polyarteritis Nodosa (PAN) is the first described but the least frequent primary systemic vasculitis. Various subgroups of necrotizing vasculitis have separated out from PAN, and are now defined such as HBV-related, cutaneous PAN or monogenic forms of vasculitis. There is a paucity of information on the current phenotypes and, ethnic and geographic differences of PAN. <h3>Objectives</h3> This study compares the demographic and clinical features between two PAN cohorts. <h3>Methods</h3> A retrospective survey of databases from two vasculitis centres between 1990–2016 for PAN patients fulfilling the EMEA Vasculitis Classification algorithm. All paediatric patients met the Ankara 2008 (EULAR/PReS endorsed) criteria for childhood PAN. Patients with typical angiographic and/or histopathologic findings consistent with PAN were included. Demographics, and clinical characteristics, Disease Extent Index (DEI) and Vasculitis Damage Index were recorded. A subgroup analysis based on disease extent between the UK patients with Turkish (TR) patients was performed. <h3>Results</h3> 93 (M/F: 51/42) patients (UK: 47, TR: 46) were recruited into the study. The mean age was 46.7 (20.7) years. Three were HBV-related, 20 (21.5%) had paediatric onset, 16 (16.5%) were cutaneous PAN. Turkish patients had younger disease of onset (28.7 (17.8) vs. 43.0 (18.0), p&lt;0.001). Twelve (26%) of Turkish patients had a monogenic disease (FMF association in 7, DADA2 in 5). Cutaneous PAN was more frequent in the UK group (12 pts vs. 4pts, p=0.031) whereas renal involvement was increased in the TR group (Table). In contrast to systemic involvement, female predominance was seen in cutaneous PAN (40.3% vs. 68.8%, p=0.037). DEI was similar in both systemic involved groups (6.1 (2.4) vs. 6.5 (2.3), p=0.428). No difference was found between paediatric and adult onset patients except for frequency of cutaneous lesions (100% vs. 64.3%, p=0.002). During a median 67.5 (32–126) months follow up, 13 patients deceased. No difference was found between the groups regarding relapse rate, death and vasculitis damage index (Table). <h3>Conclusions</h3> Even though, the Turkish group had a younger disease onset and higher additional monogenic disease; disease extent, relapse rate, death, and damage index were similar in both groups. Among the cutaneous PAN group there was a female predominance. A multi-centre GWAS study could highlight the impact of genetic background on disease presentation and severity. <h3>Disclosure of Interest</h3> None declared
OP0121 Validation of mri structural lesions using computed tomography in patients with axial spondyloarthritis
Authors: WP Maksymowych, D Loeuille, M Raynal, J Melchior, M-A D'Agostino, J Paschke, RG Lambert
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> MRI can detect both inflammatory and structural lesions in the sacroiliac joints (SIJ) of patients with axial SpA. However, standard MRI sequences do not directly depict bone and the appearance of erosion may vary according to the presence/absence of inflammation. Consequently, further validation using an accepted gold standard, namely, computed tomography (CT), is essential. <h3>Objectives</h3> We aimed to assess the detection of structural lesions in the SIJ by MRI using CT as the gold standard. <h3>Methods</h3> CT scans from 44 patients (26 females, mean age 49.4 years, mean symptom duration 9.1 years) were reconstructed in the semicoronal plane parallel to the superior border of the sacrum, as for conventional MRI evaluation of the SIJ, and scoring of lesions by CT was confined to this plane. Structural lesions were scored in consecutive slices in SIJ quadrants (erosion, sclerosis) or SIJ halves (ankylosis) on a dichotomous basis (present/absent) using the same anatomical principles for defining SIJ quadrants as developed for the SPARCC MRI SIJ inflammation and structural scores. T1W MRI scans of the SIJ from the same cases conducted at the same time as CT were assessed independently for structural lesions (erosion, fat, backfill, ankylosis, sclerosis) blinded to CT assessments using the SPARCC method. Agreement between CT and MRI was assessed by kappa statistics. Sensitivity/specificity of MRI for CT lesions was calculated. The primary analysis was based on lesions detected concordantly by both readers at the level of the individual iliac/sacral joint surface (erosion, sclerosis) or the individual joint (ankylosis, backfill). <h3>Results</h3> With CT as gold standard and a lesion defined as being present when recorded in the same location on at least 1 coronal slice by both readers, MRI-defined ankylosis had 56.3% sensitivity and 100% specificity for CT ankylosis (Table). For erosion, sensitivity and specificity of MRI was 81.3% and 96.2%, and for sclerosis, sensitivity and specificity of MRI was 50% and 97%, respectively. Agreement between CT and MRI for erosion increased when the cut-off for presence of a lesion was set at 2 slices but only marginally for sclerosis, even when the cut-off for presence of a lesion was set at 3 slices. Lesions observed on CT corresponding to backfill on MRI were ankylosis, erosion, and sclerosis, in 66.7%, 66.7%, and 80% of backfill lesions, respectively. <h3>Conclusions</h3> Ankylosis and erosion on MRI correspond closely with the same type of lesion observed on CT. Both new bone formation and erosion are frequently evident on CT at locations where backfill is observed on MRI supporting the hypothesis that backfill is an intermediary tissue between erosion and ankylosis. <h3>Disclosure of Interest</h3> None declared