tbuckley/cabot-search huggingface dataset:
AB0147 The effect of treatment with hydroxychloroquine on soluble tissue factor levels in patients with antiphospholipid antibodies and antiphospholipid syndrome with and without underlying systemic lupus erythematosus
Authors: K Schreiber, K Breen, K Parmar, BJ Hunt
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Antiphospholipid syndrome (APS) is characterized by venous, microvascular and/or arterial and/or obstetric morbidity (obstetric APS) in patients who are persistently positive for antiphospholipid antibodies (aPL)[1]. The mainstay of treatment is based on anticoagulation therapy; however, increasing interest is currently received by the antimalarial hydroxychloroquine (HCQ). The use of HCQ has been associated with a reduced risk of thrombosis but HCQ9s antithrombotic mechanism of action is unclear particularly in patients with aPL and APS. <h3>Objectives</h3> The aim of our study was to assess soluble tissue factor (TF) levels in HCQ naïve-patients with persistent aPL or APS at baseline and 12 weeks after commencing HCQ. We hypothesise that HCQ lowers levels of soluble TF. <h3>Methods</h3> Twenty- two individuals with APS with or without other associated autoimmune disease (20 females, two males, median age 55 (range 18–70) years) had blood samples taken before and 12 weeks after starting HCQ 200mg. Plasma was stored at -80<sup>o</sup>C and thawed to measure TF using Imubind TF kit (Invitech Ltd, Cambridgeshire, UK). The assay was performed according to the manufacturer9s instructions. Patient characteristics are outlined in table 1. Statistical analysis was performed using SPSS Version 22. For continuous normally distributed data a two-tailed student9s paired t-test was performed. A value of p=0.05 was considered as significant. There are no previous data in this area, so we were unable to do a power calculation to work out study size. Our study is therefore a pilot study. <h3>Results</h3> Soluble TF levels were above our normal range (40–300 pg/ml) prior to the commencement of HCQ and were significantly reduced (pre level mean (SD) 401.8 (152.8) pg/ml versus post 300.9 (108) pg/ml (p=0.010). <h3>Conclusions</h3> There was a significant reduction in soluble TF levels in this patient cohort of patients with apL and APS after commencing HCQ. Our previous work has shown that HCQ has not affected complement turnover, VEGF levels, thromboelastometry findings or CRP levels. Our findings of a reduction of soluble TF levels in aPL positive patients after the commencement of HCQ maybe a key mechanism by which HCQ reduces thrombotic risk. Further studies of a larger patient cohort are required to confirm our observation. <h3>References</h3> Miyakis, S., et al., International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost, 2006. 4(2): p. 295–306. <h3>Disclosure of Interest</h3> K. Schreiber Shareholder of: Novo Nordisk, Grant/research support from: educational support from Daiichi Sankyo, K. Breen: None declared, K. Parmar: None declared, B. Hunt: None declared
AB0402 Rituximab may delay the movement of rheumatoid arthritis patients on cardiorenal continuum: results from a prospective observational single-centre cohort study
Authors: IR Gaisin, LV Ivanova, AA Trukchina, AA Tukmacheva, YA Volkova, AA Tebenkova, NI Maximov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Similarities in risk factors, initial stages, progression and final stage of both atherosclerotic cardiovascular disease (CVD) and chronic kidney disease (CKD) allowed formulating a concept of cardiorenal continuum.<sup>1</sup> CVD and CKD remain the main causes of mortality in rheumatoid arthritis (RA) patients.<sup>2,3</sup> <h3>Objectives</h3> We aimed to evaluate the effects of rituximab biologic therapy on cardiorenal continuum of RA patients. <h3>Methods</h3> Biologics-naïve RA patients (n=50; age 55.1±10.3) were followed up for 72 months after commencing and continuing rituximab therapy (1–10 standard courses) compared with 30 control RA patients (age 53.2±9.8). <h3>Results</h3> At year 6, rituximab patients have fewer incidences of hypertension, anxiety/depression, atherosclerosis and diastolic dysfunction than control patients (Table). There were no significant differences in frequencies of other risk factors, signs of asymptomatic multiorgan damage and cases of established heart, cerebrovascular and renal diseases/complications. <h3>Conclusions</h3> Rituximab may be effective in delay of the movement of RA patients on cardiorenal continuum. The clinical implications of rituximab for cardiorenal correlations in RA patients need to be confirmed in large-scale clinical outcome trials. <h3>References</h3> Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis 2000;35(4, Suppl. 1):117–31. Avina-Zubieta JA, Choi HK, Sadatsafarvi M, et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008;59:1690–7. Gullick NJ, Scott DL. Co-morbidities in established rheumatoid arthritis. Best Pract Res Clin Rheumatol 2011;25:469–83. <h3>Disclosure of Interest</h3> None declared
AB0988 BehÇet's disease in a defined area of northwestern spain
Authors: M Estévez, A Argibay, R Lorenzo, M Freire, J Fernandez-Martín, B Gimena, C Vázquez-Triñanes, A Rivera
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Behçet9s disease (BD) is a multisystemic inflammatory chronic disease. There is a wide variation in the clinical features of BD among geographical groups. <h3>Objectives</h3> To determine the demographic and clinical characteristics of BD in a defined area of northwestern Spain (Vigo). <h3>Methods</h3> Patients with BD (International Criteria BD) and seen in the University Hospital of Vigo in Spain, from 1994 to 2016, were retrospectively enrolled. Demographic, clinical, treatment and evolution data were recorded and analyzed using SPSS 22.0. <h3>Results</h3> Our patients were 26 male and 25 female. The mean age at the onset of the disease was 33±11.95 years (11–62). Oral and genital ulcers were seen in 100% and 84.3% respectively and skin lesions in 88.2%. Ocular involvement occurred in 35.3%, neurological disease in 39.2% and gastrointestinal involvement in 29.4% (the area worst affected was colon and small bowel). Vascular disease was present in 33.3%. See table 1. Pathergy test was performed in 18 patients (35.29%) and 10 (55.5%) were positives. HLA B51 was studied in only 13 patients (25.5%) and 8 (61.5%) were positives. 62.7% of patients had no cardiovascular risk factors (CVRF), 27.4% were smokers, 7.8% were hypertensive and 3.9% were hyperlipidemic and diabetic respectively. CVRF were not related to thrombotic events (p&gt;0.05). In regard to gender influence, only pseudofolliculitis was significantly more frequent in men (p&lt;0.001). There was a trend for increased prevalence of ocular disease and elevated erythrocyte sedimentation rate/serum C-reactive protein in men, and anemia in women, which, however, did not reach statistical significance. Treatment consisted of corticosteroids (92.2%), colchicine (68.6.%) and another immunosuppressive agent (35.3%). During the disease course 78.4% of the patients had an outbreak, 45.1% initiated or changed to immunosuppressive agent and 19.6% used biological drugs. Most of our patients (92.1%) were admitted to hospital and these constitute an evident bias. Two patients died during the followup period, but only one in relation of BD (upper gastrointestinal bleeding and seizures). <h3>Conclusions</h3> Our series has some particular aspects especially the high frequency of gastrointestinal lesions and neurologic involvement. CVRF do not seem to play a role in the development of thrombotic events. Our results confirm the ethnic and geographic variation of BD expression. <h3>Disclosure of Interest</h3> None declared
AB0527 Progranulin and insulin-like growth factor-2 as biomarkers for disease activity and pathological changes in lupus nephritis
Authors: S Goma, M Abdelaziz, E El-Hakeim, M El Zohri, S Sayed
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease (1), characterized by the production of autoantibodies, and formation of immune complexes due to the polyclonal activation of T and B lymphocytes that result in tissue and organ damage (2). During inflammation, neutrophils and macrophages release serine proteases to cleave progranulin (PGRN) into granulin (GRN), which exert their pro-inflammatory effects that counteract the anti-inflammatory effects of intact PGRN (3). Insulin-like growth factor-2 (ILGF-2) binds to insulin-like growth factors (IGFs) with high affinity (4). Although reports suggest that IGFBP-2 is a reliable biomarker of renal deterioration, it is still needed to confirm that it has high sensitivity and specificity in discriminating kidney disease caused by SLE from other origins. <h3>Objectives</h3> The aim of this study was to explore whether PGRN and ILGF-2 can be used as useful markers not only for accurate diagnosis of patients with active lupus nephritis (LN) but also for prediction of the disease activity in these patients. <h3>Methods</h3> Twenty-five patients with systemic lupus erythematosus, twenty-five patients with chronic renal failure and twenty-five age- and sex-matched healthy volunteers were enrolled in the study. Routine laboratory investigations and measurement of serum PRGN and IGFBP-2 levels were done. <h3>Results</h3> Our results showed that the mean age of SLE, CRF and control groups 31.12±12.34, 38.7±9.4 and 32.96±13.66 respectively with no significant difference between the three groups. There was female predominance in the three groups. Disease duration was 4.78±4.26 in SLE patients.The mean of SLEDAI score was 15.04±7.54. All renal biopsy results were class 2, 3, and 5 with a percentage of 32%, 24%, and 44% respectively. <h3>Conclusions</h3> PGRN and ILGF-2 are significantly elevated in SLE than CRF and control and were associated with SLEDAI. Hence they are considered specific to LN. <h3>References</h3> Rahman A, Isenberg DA. (2008) Systemic lupus erythematosus. N Engl J Med 358:929–939. Kotzin BL. (1996) Systemic lupus erythematosus. Cell 85: 303–306. Park B, Buti L, Lee S et al. (2011) Granulin is a soluble cofactor for toll-like receptor 9 signaling. Immunity 34(4):505–513. Firth SM, Baxter RC. (2002) Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev 23(6):824–54. <h3>Disclosure of Interest</h3> None declared
SiFit: inferring tumor trees from single-cell sequencing data under finite-sites models
Authors: Hamim Zafar, Anthony Tzen, Nicholas Navin, Ken Chen, Luay Nakhleh
Journal: Genome biology (2017)

Single-cell sequencing enables the inference of tumor phylogenies that provide insights on intra-tumor heterogeneity and evolutionary trajectories. Recently introduced methods perform this task under the infinite-sites assumption, violations of which, due to chromosomal deletions and loss of heterozygosity, necessitate the development of inference methods that utilize finite-sites models. We propose a statistical inference method for tumor phylogenies from noisy single-cell sequencing data under a finite-sites model. The performance of our method on synthetic and experimental data sets from two colorectal cancer patients to trace evolutionary lineages in primary and metastatic tumors suggests that employing a finite-sites model leads to improved inference of tumor phylogenies.
THU0429 Clinical significance of increased serum levels of FGF23 in fibrous dysplasia
Authors: H Florez, S Mandelikova, X Filella, A Monegal, N Guañabens, P Peris
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fibrous dysplasia of bone (FD) is an uncommon skeletal disorder, caused by missense mutations of the <i>GNAS1</i> gene and is characterized by the development of fibro-osseous lesions that replace normal bone. FD can present with a broad spectrum of clinical manifestations, including the development of hypophosphatemic osteomalacia which is due to the production of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) by the dysplastic bone tissue. Nevertheless, the prevalence of this clinical complication is not well known. <h3>Objectives</h3> To analyse the serum levels of FGF-23 in patients with FD and determine their relationship with the extension and activity of the disease, as well as with serum phosphate levels. <h3>Methods</h3> Twelve patients (7F:5M) with FD with a mean age of 50.67±16.4 years (24–79) were included. The clinical reports of the patients were reviewed, with special attention to the extension and activity of the disease, number and location of the affected bones, clinical complications and treatments received. Serum FGF-23 values were recorded in all subjects (determined by Immunotopics, CA, USA [measuring FGF23 C- terminal], normal value &lt;130 RU/ml), as well as serum phosphate and calcium values, bone turnover markers and their evolution with treatment. <h3>Results</h3> Serum levels of FGF-23 were increased (&gt;130 RU/ml) in 6/12 patients (50%). In patients with and without high FGF-23 levels the number of affected bones (2.2±2 <i>vs</i>. 1.9±1, respectively) and the skeletal locations of FD were similar as was the age in both groups of patients (48.2±14 <i>vs</i>. 53.2±19 years). In addition, FD disease activity and extension were similar in the two groups as were the bone turnover marker values (FAO, PINP and CTx). Strikingly, differences between serum phosphate values were not observed between the two groups (FGF23 &gt;130: 3.9±0.9 mg/dl <i>vs</i>. FGF23 &lt;130: 3.5±0.6 mg/dl). Indeed, none of the patients with high FGF-23 levels had low serum phosphate values. Following bisphosphonate (zoledronate) treatment, there were no significant changes in FGF-23 values. Nevertheless, an increase of 123% was found in one patient receiving denosumab, although hypophosphatemia was not associated. <h3>Conclusions</h3> Patients with FD frequently present elevated FGF-23 values with no effects on serum phosphate levels, thereby suggesting the presence of an alteration in processing this protein in the dysplastic bone tissue in this disease. The role of denosumab treatment in FD and its repercussion on FGF-23 levels need further study. <h3>Disclosure of Interest</h3> None declared
SAT0758-HPR Depression but not core symptoms predict caregiver strain in adults sharing a home with primary sjÖgren's syndrome patients
Authors: K Hackett, D Lendrem, T Rapley, V Deary, K Deane, J Newton, W-F Ng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Patients with primary Sjögren9s syndrome (PSS) experience a range of symptoms including dryness, fatigue, pain and low mood. The impact of these symptoms upon the people with whom they live, is unknown. The caregiver strain index (CSI) is a thirteen item questionnaire which measures strain in caregivers (Robinson 1983). <h3>Objectives</h3> To determine whether adults living in the same household as a person with PSS experience caregiver strain and to examine the relationship between caregiver strain and other factors. <h3>Methods</h3> We collected age, Carer Strain Index (CSI) and quality of life (QOL) (SF-36) scores from 62 adults who shared a home with a PSS patient. We also collected various measures from the PSS patients that they lived with. The patient measures included; age, time since diagnosis, fatigue, dryness, pain, QOL, depression, anxiety, and physical function (Improved HAQ). We conducted Spearman correlations to compare the relationship between the carers9 CSI and SF-36 scores as well as the measures from the patients they lived with. We performed multivariate analyses on factors that significantly correlated with CSI scores. <h3>Results</h3> The caregiver strain scores are shown in the Figure. Although a median CSI score of 1 demonstrates that most AHM participants experienced very little caregiver strain, 14% of AHM participants did experience high levels (indicated with a CSI score ≥7). Age and PSS disease duration negatively correlated with carer strain. Increased pain, fatigue, mental fatigue, physical functioning, anxiety, depression in the patients and SF-36 physical component scores in the household members all significantly correlated with increased carer strain. There was no relationship between dryness scores and age of the PSS patient and CSI scores. Multivariate analysis suggests the main predictor of increased carer strain was depression in the PSS patient and younger age of the household member. <h3>Conclusions</h3> Caregiver strain is evident in a proportion of adults sharing a home with a person with PSS. Caregivers of patients with high depression scores are particularly susceptible and may benefit from additional support. <h3>References</h3> Robinson BC Validation of a Caregiver Strain Index. J Gerontol 1983; 38: 344–48. <h3>Acknowledgements</h3> Arthritis Research UK (grant 20169) and the United Kingdom Occupational Therapy Research Foundation. <h3>Disclosure of Interest</h3> None declared
OP0231 The effect of “triple therapy” with anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulins on the mortality of catastrophic antiphospholipid syndrome (CAPS) patients
Authors: I Rodríguez-Pintό, G Espinosa, D Erkan, Y Shoenfeld, R Cervera
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Triple therapy (anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulins) is empirically prescribed for the management of catastrophic antiphospholipid syndrome (CAPS). However, previous analyses have been inconsistent regarding the beneficial effect of triple therapy on patients9 survival. <h3>Objectives</h3> The objective of this study was to assess the effect that triple therapy has on the mortality risk of CAPS patients. <h3>Methods</h3> In a cohort including 525 episodes of CAPS (CAPS Registry), we evaluated the relationship between triple therapy and mortality. Patients were grouped in three based on their treatments: a) triple therapy (anticoagulation plus corticosteroids plus plasma exchange and/or intravenous immunoglobulins); b) drugs included in the triple therapy but in different combinations; c) none of the treatments included in the triple therapy. The primary endpoint was all-cause mortality. Multivariate logistic regression models were used to compare mortality risk between groups taking into account a set of possible confounding variables. <h3>Results</h3> The “CAPS registry” cohort included 525 episodes of CAPS accounting for 502 patients. After excluding 38 episodes (7.2%), a total of 487 episodes of CAPS accounting for 471 patients (mean age 38 years; 67.9% female; primary APS patients 68.8%) were analyzed. Overall, 177 (36.3%) patients died. Triple therapy was prescribed in 197 episodes (40.5%), other combinations in 278 (57.1%), and none of those treatments in 12 episodes (2.5%). According to these three groups, mortality rate increased up to 27.9%, 40.6%, and 75%, respectively. Triple therapy was positively associated with a higher chance of survival when compared to non-treatment (adjusted odds ratio [OR]: 7.7 95%; confidence interval [95CI] 2.0–29.7) or to treatment with other combinations of drugs included in the triple therapy (adjusted OR 6.8; 95CI 1.7–26.9). Triple therapy accounted for a 64% decrease of the risk of death in patients with CAPS that received this combination of drugs. <h3>Conclusions</h3> Triple therapy is independently associated to a higher survival rate among CAPS. <h3>Acknowledgements</h3> To the CAPS Registry Project Group (European Forum on Antiphospholipid Antibodies). <h3>Disclosure of Interest</h3> None declared
AB0399 Rituximab treatment and immunoglobulin levels monitoring
Authors: G Kasavkar, S Kamath
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis is a well-known inflammatory condition with a prevalence around 1% in females and 0.5% in males in UK (as per NOAR study). In the past decade use of biologic therapy has helped clinicians to treat rheumatoid arthritis more effectively. Rituximab is one of the biologics which is used commonly for treating rheumatoid arthritis. Rituximab is chimeric monoclonal antibody targeting CD20 molecule of B cells. First trial of rituximab in treating rheumatoid arthritis was published in 2004 and since then it has shown promising results in trials. In order to guide clinicians British society of rheumatology proposed recommendations in March 2010. An audit is required to ensure adherence to clinical guidelines at Haywood hospital. <h3>Objectives</h3> To assess whether patients receiving Rituximab are appropriately monitored with pretherapy evaluation of immunoglobulin levels To assess the effects of rituximab on immunoglobulin levels and incidence of infection among patients on rituximab <h3>Methods</h3> Data was collected of all (N=105) patients who received Rituximab between May 2014 until April 2015 at the Haywood Hospital where patients attend for Rituximab injections. Data was collected retrospectively from the Diamond System, Medisec system and Clinical Information System and entered onto an excel spread sheet which included following details Start date of Rituximab IgG levels prior to Rituximab and current IgG levels Total doses of rituximab and frequency of IgG monitoring Intermittent infections and type of infections. <h3>Results</h3> We observed that 82 out of 105 patients were started on rituximab after February 2011 when the BSR guidance was published and 53 out of 105 patients had their immunoglobulin levels checked prior to commencing rituximab 35/76 (46%) patients had 1 or more episodes of infections whilst on Rituximab which required treatment. Of these, 16 (46%) had recurrent infections. 39 patients had dropped their IgG levels after starting rituximab 18 (46%) of these suffered from infections. 17 patients had a drop in IgG ≥20% and 6 of these (36%) had recurrent infections and 1 patient had 1 episode of infection. None of the patients had dropped their IgG levels below 5 <h3>Conclusions</h3> A significant number of patients (35/76 =46%) had 1 or more episodes of infections despite IgG levels being above lower normal limit Among patients who dropped their IgG levels had increased number infections. Also they had more than 1 episodes of infection Patients who dropped IgG levels ≥20% suffered with recurrent infections <h3>References</h3> BSR and BHPR guidelines on the use of rituximab in rheumatoid arthritis doi:10.1093/rheumatology/ker106b. <h3>Disclosure of Interest</h3> None declared