tbuckley/cabot-search huggingface dataset:
FRI0672 Assessment of the nail bed in psoriatic arthritis (PSA) by ultrasound (US) and MRI
Authors: S Paramalingam, A Taylor, H Keen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> PsA can be difficult to distinguish from osteoarthritis (OA) and the treatments vary greatly. Nail involvement can occur in about 15–50% patients with psoriasis<sup>1</sup>, which may aid differentiation from OA. If US can reliably detect nail bed changes in early disease then it might be helpful in differentiating PsA from OA <h3>Objectives</h3> This study aims to investigate the nail bed changes seen in patients with PsA and OA using US and MRI, and to determine the impact of nail bed changes on quality of life (QOL). <h3>Methods</h3> Patients who fulfilled the CASPAR PsA or 1990 ACR OA classification criteria were recruited. At baseline, clinical assessment included patient and physician9s visual analogue scale (VAS), tender and swollen joints, patient9s Leeds Enthesitis Index and quality of life specific to nail psoriasis (NPQ10). Nail abnormalities on the dominant hand such as onycholysis, pitting, nail bed hyperkeratosis and nail bed crumbling were documented. Using US, each nail (1–5) was scored dichotomously for pitting/irregularity, loss of normal trilaminar appearance of the nail. Each nail was scored semi quantitatively for power doppler (PD) signal (0–3) in the nail bed, nail matrix and dermis, and assigned a total PD score. All patients had an MRI of the dominant 2nd to 5th finger. <h3>Results</h3> 14 patients were recruited; demographics, clinical and US detected nail changes are documented in Table 1. Clinical nail changes were not seen in the OA group, but were relatively common in the PsA group. In the PsA group, 54% of nails had US detected structural abnormalities; 12% pitting and 52% loss of trilaminar layer. Only 20% of OA nails had US detected abnormalities. There was a strong relationship between the presence of clinical nail change and US structural changes (chi square 10.769 df 1 p=0.001) but not PD signal score. There was no relationship between clinical or US detected nail scores and NPQ10, patient or physician VAS, swollen joint count or Leeds Enthesitis Index. MRI analysis is pending. <h3>Conclusions</h3> In this small prospective study, structural abnormalities detected by US appear to correlate well against clinical structural findings, but PD signal does not. No relationship was found between US findings and other clinical parameters. US structural abnormalities may be a better differentiator of PsA and OA than PD signal. MRI validation of these results is pending. <h3>References</h3> Gisondi P, Idolazzi L, Girolomoni G. Ultrasonography reveals nail thickening in patients with chronic plaque psoriasis. Arch Dermatol Res 304:727–732,2012. <h3>Acknowledgements</h3> This study was funded by a grant from UCB Australia Pty Ltd. <h3>Disclosure of Interest</h3> None declared
THU0655 Do visual decision aids help patients correctly differentiate between a 2% and a 0.2% risk?
Authors: R Cozmuta, L Fraenkel, E Wilhelms, V Reyna, J Nolte
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Studies have found that patients ignore probabilities when making treatment decisions. <h3>Objectives</h3> The objective of this study was to examine whether addition of an icon array (IA), a series of three consecutive balance-beam (BB) illustrations depicting how medications regulate the immune system, or both resulted in patients being able to better differentiate between an uncommon (2%) and rare (0.2%) adverse event (AE). <h3>Methods</h3> Patients currently being treated for a chronic inflammatory rheumatic disease were mailed a survey in which they were asked to imagine that their symptoms had recently worsened and that their physician was recommending a new medication. The medication was described using eight scenarios (manipulated using a 2x4 design). We varied the probability of a serious AE (pneumonia requiring hospitalization): 2% vs 0.2% and the risk presentation format: numbers only, numbers + IA, numbers + BB, and numbers + IA + BB. Route of administration, benefit, and cost were held constant. Each subject responded to a single, randomly-assigned scenario. Dependent variables included perceived riskiness, worry, global gist related to the acceptability of the AE, and willingness to take the medication (all measured on 5-point ordinal scales). We hypothesized that the IA and BB formats would result in 1) lower perceived riskiness and worry, and 2) greater acceptability of the AE and willingness to take the medication in the 0.2% vs 2% scenarios. Socioeconomic status (SES) was defined based on difficulty paying for medication and education level. <h3>Results</h3> We mailed 1453 surveys. 465 patients completed and mailed the survey back (32% response rate). Overall, the mean age of responders was 58.99 (SD=14.85); 79.7% of were female; 83.2% White and 39.1% had a low SES. There were no statistical differences in demographic or clinical characteristics across the four risk presentation formats. Mean (SD) perceived riskiness, worry, global gist, and willingness to take the medication for 2% versus 0.2% chance of the AE, by SES level, are presented in the Image. Perceived riskiness was lower for a 0.2% versus 2% risk of the AE in the numbers + IA condition in higher SES subjects. Lower SES subjects who viewed both IA and BB were more worried about the AE and found the AE to be less acceptable in the 0.2% versus 2% condition. <h3>Conclusions</h3> With the exception of the IA9s impact on perceived riskiness among subjects with higher SES, the risk formats used did not enable subjects to correctly differentiate between a 0.2% and a 2% risk of a serious AE. These results highlight the lack of impact of quantitative risk information on patients9 risk perceptions. <h3>Disclosure of Interest</h3> None declared
THU0566 Clinical and genetic phenotypes of chinese patients with adult autoinflammatory diseases: report from an adult reference center
Authors: M Shen, D Wu, X Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Autoinflammatory diseases (AUID) is a group of disorders characterized by dysfunction of innate immunity which caused by gene mutations leading to coded proteins changes, finally causing uncontrolled systemic inflammation. AUID are usually diagnosed during pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described. Moreover, AUID have been hardly reported in the Chinese population. <h3>Objectives</h3> We aimed to characterize the clinical and genetic phenotypes of Chinese adult patients with AUID. <h3>Methods</h3> We prospectively evaluated clinical and genetic features of adult patients (≥16 years) suspected monogenic AUID in the period April 2015 to May 2016, at the adult AUID center, Department of Rheumatology, Peking Union Medical College Hospital. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. <h3>Results</h3> During the study period, a total of 37 adult patients with clinical phenotypes suspicious of monogenic AUID requested for a genetic study. A final diagnosis of monogenic AUID was achieved in 16 patients (43.2% of patients tested). Two additional patients were diagnosed with periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Finally, a total of 18 patients with AUID were diagnosed and follow-up in our center, including 7 (38.9%) familial Mediterranean fever (FMF), 2 (11.1%) tumor necrosis factor-receptor associated periodic syndrome (TRAPS), 3 (16.7%) cryopyrin-associated periodic syndrome (CAPS), 3 (16.7%) NLRP12-autoinflammtory disease (NLRP12-AD), 1 (5.6%) Blau syndrome (BS), and 2 (11.1%) PFAPA. Disease onset during adulthood was observed in 15 (83.3%) patients, and the final diagnosis was delayed with a mean time of 10 years. Adult AUID patients usually carried low-penetrance mutations and gene variants were presented as heterozygosis or compound heterozygosis. <h3>Conclusions</h3> Adult AUID is not uncommon. FMF, CAPS, and NLRP12-AD are relatively common monogenic AUID in Chinese adult patients. Adult-onset AUID may be related to the presence of low-penetrance mutations, being characterized by nonspecific, incomplete or atypical disease patterns, leading to a delay of diagnosis. The interpretation of gene analysis in adult suspected AUID should be performed with caution, and if possible, should be referred to expert physicians in the field in adult AUID center. <h3>References</h3> Muscari I, et al. The diagnostic evaluation of patients with potential adult-onset autoinflammatory disorders: our experience and review of the literature. Autoimmun Rev 2012,12:10–13. Hernández-Rodríguez J, et al. Clinical and genetic characterization of the autoinflammatory diseases diagnosed in an adult reference center. Autoimmun Rev 2016,15:9–15. <h3>Disclosure of Interest</h3> None declared
AB0478 Comparative study between patients with normal and overweight in a cohort of systemic lupus eritemathosus from argentina
Authors: AM Beron, S Sapag Duran, M Garcia Carrasco, AM Sapag Duran, G Medina, G Nasswetter, D Dubinsky
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematous (SLE) have an increase cardiovascular risk, worsened by overweight and obesity. Increased BMI is associated with other severe complications and comorbidities as lupus nephritis, hypertension, insulin resistance and dyslipemia. Body weight is a modifiable risk factor. <h3>Objectives</h3> To determine the frequency of overweight and obesity in patients with SLE and their impact on this disease <h3>Methods</h3> Descriptive, cross-sectional study. We reviewed the medical records of outpatients with SLE (ACR 1997) who were seen since 2014 to 2016 in the Clinical Hospital of Buenos Aires, Argentina. We evaluated sex, age, disease duration, obstetric history, use and doses of oral corticosteroids, BMI, 25 OH vitamin D and educational level. Disease activity was scored by SLEDAI. Scores ≥4 were classified as active. The patients were classified into 2 groups, according to BMI: normal weight (NW) (19–25), overweight and obesity (≥25). <h3>Results</h3> One hundred and sixty two of 230 were evaluated. Sixty-eight patients were excluded due to lack of data. 157 (97%) were women. Mean age for both sexes was 40.6±14.3 years (p 0.70). Means of: SLEDAI 4.3±4.47 (54.9% had SLEDAI ≥4), IMC: 27.04±5.22 (56% had a BMI ≥25) and 25-hidroxivitamin D was 25.15±9.0. <i>Relation between 2 groups, according to BMI:</i> 84.5% whom were in NW group have received steroids at some point vs 95.6% in BMI≥25 group (p 0.02). Mean steroids doses: BMI ≥25: 9.53±10.98 vs 5.0±7.2 in NW group (p 0.04). Multivariate analysis showed that BMI ≥25 continued significantly associated with SLE duration, independently of the steroids use and other variables. 25 OH vitamin D tended to be lower in BMI ≥25 vs NW, but no significant differences (24.53±9.91 vs 25.50±9.85) (p=0.071) <h3>Conclusions</h3> Over a half of our cohort had BMI ≥25 and was characterized by older age, more frequent menopause, longer course of the disease, increased steroid use and lower educational level. Depression and hypertension were the statistically more frequent comorbidities found. Obesity was associated with more activity and accrual damage including chronic renal disease. <h3>Disclosure of Interest</h3> None declared
Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage
Authors: Péter István Kulcsár, András Tálas, Krisztina Huszár, Zoltán Ligeti, Eszter Tóth, Nóra Weinhardt, Elfrieda Fodor, Ervin Welker
Journal: Genome biology (2017)

The propensity for off-target activity of Streptococcus pyogenes Cas9 (SpCas9) has been considerably decreased by rationally engineered variants with increased fidelity (eSpCas9; SpCas9-HF1). However, a subset of targets still generate considerable off-target effects. To deal specifically with these targets, we generated new "Highly enhanced Fidelity" nuclease variants (HeFSpCas9s) containing mutations from both eSpCas9 and SpCas9-HF1 and examined these improved nuclease variants side by side to decipher the factors that affect their specificities and to determine the optimal nuclease for applications sensitive to off-target effects.These three increased-fidelity nucleases can routinely be used only with perfectly matching 20-nucleotide-long spacers, a matching 5' G extension being more detrimental to their activities than a mismatching one. HeFSpCas9 exhibit substantially improved specificity for those targets for which eSpCas9 and SpCas9-HF1 have higher off-target propensity. The targets can also be ranked by their cleavability and off-target effects manifested by the increased fidelity nucleases. Furthermore, we show that the mutations in these variants may diminish the cleavage, but not the DNA-binding, of SpCas9s.No single nuclease variant shows generally superior fidelity; instead, for highest specificity cleavage, each target needs to be matched with an appropriate high-fidelity nuclease. We provide here a framework for generating new nuclease variants for targets that currently have no matching optimal nuclease, and offer a simple means for identifying the optimal nuclease for targets in the absence of accurate target-ranking prediction tools.
AB0661 Assessment of damage and prognosis in patients with adult iga vasculitis: retrospective multicentered cohort study
Authors: F. Alibaz-Oner, A. Omma, A. Sarı, Ü. Gazel, D. Üsküdar Cansu, A. Yazıcı, A. Cefle, C. Bes, Ö. Karadağ, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> IgA Vasculitis is a leukocytoclastic vasculitis involving small vessels with depositions of immune complexes containing IgA. IgA Vasculitis is a predominantly paediatric vasculitis. There is limited data for the prognosis of adult IgA Vasculitis, with also no damage assessment. In this study, we aimed to evaluate the clinical characteristics, treatment, outcome and damage of patients with adult IgA Vasculitis. <h3>Methods</h3> We assembled a retrospective cohort of patients with adult IgA Vasculitis from tertiary Rheumatology Centres in Turkey. The demographics, clinical characteristics, treatment and outcomes of patients were abstracted from medical records. Birmingham Vasculitis Activity Score (BVAS), prognostic Five Factor Score (FFS) and vasculitis damage index (VDI) were calculated. <h3>Results</h3> The study included 103 (male/female: 67/36) patients with adult IgA Vasculitis. The mean age was 42.6±17 years. Infection history within 6 weeks before presentation was present in 40 (38.8%) patients (32 upper respiratory tract, 3 urinary tract, 2 gastrointestinal, 3 others). Cutaneous manifestations and arthritis/arthralgia were the most common clinical manifestations (table 1). 92 (89.3%) patients were treated with oral glucocorticoids (GC). Pulse GC treatment was also given to 29 (28.1%) patients. As additional immunosuppressive agents, azathioprine was given to 36 (34.9%) and pulse cyclophosphamide to 13 (12.6%) patients. Fifty-nine patients (58.2%) had follow-up of mean 35.6 months. Eleven (18.6%) patients relapsed during follow-up. While 5 relapses were major, six of them were minor relapses. At the last visit, disease status was evaluated as active or treatment failure by the treating physician in 7 (11.8%) patients. The rate of chronic renal failure was 8.3%(n=5). Mortality was 1.6% (n=1) during follow-up, due to pneumonia. The mean VDI score was 0.3 in the last visit. Twelve (20.3%) patients had at least one damage item at the end of follow-up period. <h3>Conclusions</h3> Our results showed that approximately one fifth of patients with adult IgA Vasculitis had relapses during follow-up and had at least one damage item at the end of follow-up. Although, 31% of patients had FFS≥1, the mortality rate was observed to be very low in the present study. <h3>Disclosure of Interest</h3> None declared
SAT0582 Chagas' disease in patients with autoimmune diseases receiving immunosuppressive therapy. analysis of 48 cases
Authors: S Retamozo, MJ Haye Salinas, A Alvarellos, V Saurit, F Caeiro, JP Caeiro, V Carballo, M Medeot, O Salomone, R Albertini, F Merschon, F Bonisconti, A Sanchez, T Alvarellos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To analyze the main features at diagnosis and Chagas9 Disease (CD) reactivation in patients with autoimmune diseases (AD) receiving immunosuppressive therapy (IT). <h3>Methods</h3> 13 patients with AD diagnosed with CD admitted to our Units between January to December 2016. In addition, we performed a systematic analysis of cases reported to date through a MEDLINE search. Inclusion criteria 1) adults with AD treat with iT (glucocorticoids [GC], disease-modifying anti rheumatic drugs [DMARDs] and biological drugs [BD]); 2) had confirmed or were positive for 2 serological test for CD. Reviews, experimental studies, duplicate publications, and abstracts were excluded. <h3>Results</h3> A total of 48 patients (13 from our Units and 35 from the literature search) fulfilled the inclusion criteria. There were 41 (85.4%) women, mean age of 43.8 years (range: 17–80). The main underlying disease was SLE in 22 (45.8%). Previous/current treatment at time CD diagnosis included GC &gt;40mg/day in 27/48 (56.3%), DMARDs in 32/48 (66.7%) and 7 patients had previously received DB. CD was reactivated in 36 (75%) cases (mean 40.9 months [range: 0–252]) with the following patterns: high <i>T. cruzi</i> load by quantitative real-time polymerase chain reaction (qRTPCR) in 23 (63.8%) from which 20 (86.9%) had no clinical manifestation and 3 (13%) had panniculitis, the remaining 11 patients (30.5%) had positive XD with one of them had myositis, only one patient (2.7%) had fever. After a mean follow-up of 47 (range: 1–120) months, 4 patients with SLE died (8.3%), all had received GC&gt;40mg/day, 3 had CD reactivation and all died due to SLE flare. No statistical differences were found with respect to CD diagnosis, use of GC, DMARDs, BD; in contrast, patients who had CD reactivation on therapy with GC &gt;40mg/day showed higher cardiac involvement (83.3% vs 43.5%, p=0.03 OR 6.50 CI95% 1.15–36.57) where the time of immunosuppression in this group was lower in those who died median 0.53 (IQR 0.46–0.53) vs 3.00 (IQR 1.26–78.00) months, p=0.04. Patients with SLE and CD reactivation showed a higher risk of death (18.8% vs 0.0%, p=0.04, OR: 1.23, CI95% 0.97–1.57). Survival rate of the entire cohort was 91.5%. The poorest survival rates were observed in who had CD reactivation (log rank p=0.037). <h3>Conclusions</h3> Reactivation was presented mainly as high <i>T. cruzi</i> load by qRTPCR without clinical manifestation of CD. Use GC&gt;40mg/day showed a higher risk of CD reactivation with cardiac involvement. Considering this data it9s reasonable to screen serologic and molecular tests before to start treatment with immunosuppressive drugs. <h3>Disclosure of Interest</h3> None declared
FRI0392 Opportunistic infections in patients with myositis. a retrospective cohort study
Authors: A Redondo-Benito, A Curran-Fàbregas, A Villar-Gomez, E Trallero-Araguás, A Fernandez-Codina, I Pinal-Fernandez, A Selva-O'Callaghan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Idiopathic inflammatory myopathies, also known as myositis, are a heterogeneous group of acquired diseases of probable autoimmune origin, characterized by the presence of inflammatory muscle infiltrates.Infectious complications are not uncommon in myositis, and some predisposing factors, such as upper esophageal involvement, calcinosis cutis, ventilatory insufficiency due to diaphragm involvement, and immunosuppressive drug therapies, seem to be implicated. <h3>Objectives</h3> To describe the prevalence, clinical characteristics, and risk factors for opportunistic infection (OI) in a cohort of patients with inflammatory myopathies, and compare mortality rates between those with and without OIs. <h3>Methods</h3> In total, 204 patients from our myositis cohort were reviewed to identify patients who had experienced an OI during the period 1986–2014. The patients9 clinical characteristics, treatment received, and outcome were systematically recorded. Disease activity at the OI diagnosis and cumulative doses of immunosuppressive drugs were analyzed, as well as the specific pathogens involved and affected organs. <h3>Results</h3> The prevalence of OI in the total cohort, was 6.4%: viruses, 44.4% (varicella-zoster virus, cytomegalovirus); bacteria, 22.2% (<i>Salmonella sp.</i>, <i>Mycobacterium tuberculosis</i>, <i>M. chelonae);</i> fungi, 16.7% (<i>Candida albicans</i>, <i>Pneumocystis jirovecii);</i> and parasites, 16.7% (<i>Toxoplamosis gondii</i>, <i>Leishmania spp.</i>) were the pathogens detected. Lung and skin/soft tissues were the organs most commonly affected (27.8%). Overall, 55.6% of OIs developed during the first year after the myositis diagnosis and were significantly associated with administration of high-dose glucocorticoids (p=0.0148). Fever at onset of myositis (p=0.0317), biological therapy (p&lt;0.001) and sequential administration of 4 or more immunosuppressive agents during myositis evolution (p=0.0032) were significantly associated with OI. All-cause mortality in the OI group was 3.69 deaths per 100 patients/year versus 3.40 in the remainder of the cohort (p=0.996). <h3>Conclusions</h3> The prevalence of OI was 6.4% in our myositis cohort. High-dose glucocorticoids at disease onset and severe immunosuppression are implicated in the development of these complications. Mortality did not differ from the remainder of the cohort. <h3>Disclosure of Interest</h3> None declared
SP0087 How antigen presenting cells can be turned into tolerogenic cells
Authors: JD Isaacs
Journal: Annals of the Rheumatic Diseases (2017)

Antigen presenting cells (APCs) lay at the heart of all immune responses. Whereas we generally consider APCs as cells that stimulate immune reactivity, they are also critically important for avoiding autoreactivity. Thus in health our tissues are patrolled by cells such as immature dendritic cells, which downregulate responses to self-antigens. Corruption of this process is a central factor in autoimmunity. A number of groups have developed methods to generate "tolerogenic" antigen presenting cells, that mimic the cells which regulate self-tolerance in health. It is hypothesised that administration of such cells, loaded with autoantigens, to patients with autoimmune disease should be able to overcome autoreactivity and re-establish immune regulation. Our own group has developed a therapeutic approach based upon autologous tolerogenic dendritic cells, which we derive from circulating peripheral blood monocytes. Unlike conventional mature DC, which produce IL-12p70 and other pro-inflammatory cytokines, tolDC produce no IL-12p70 but high levels of IL-10. They deviate naïve T-cells towards an IL-10-producing, anti-inflammatory phenotype and induce hyporesponsiveness in memory T-cells. In mixed cultures they dominate mature, pro-inflammatory DC and down-regulate T-cell activation. Their phenotype is stable in the presence of pro-inflammatory stimuli. Equivalent murine tolDC switch off collagen-induced arthritis, with immune deviation from IL-17 to IL-10 production by CD4+ T cells and a reduction in type II collagen-specific T cell responses. In a phase 1 trial (AuToDeCRA), we demonstrated that these cells are safe when administered into a recently inflamed target knee joint of patients with inflammatory arthritis. However, in that safety study we were unable to demonstrate a tolerogenic effect in vivo. Furthermore, we have reason to believe that administered cells may remain in the target joint, whereas a disease-modifying effect is likely to require migration to secondary lymphoid tissues. Moving forwards we are designing a study that will address the optimal administration route for tolDC, based on a technique to track the cells in vivo and to measure their effect on autoreactivity. <h3>Disclosure of Interest</h3> None declared