tbuckley/cabot-search huggingface dataset:
Retrospective Analysis of Seasonal Respiratory Viral Infections (SRVI) in Hematology, Lymphoma and Oncology Patients
Authors: Samar Kulkarni, Stephanie Michail, Charlotte Smith, Joanna Tomlins, John Murray, Michael Dennis, Jim Cavet, Tim Somervaille, Daniel Wiseman, Anna Z Castleton, Adrian Bloor
Journal: Blood (2016)
FRI0572 Identifying women and men at high fracture risk by leveraging the electronic medical records to estimate frax treatment thresholds
Authors: S Amin, E Atkinson, S Khosla
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In the busy clinic, identifying individuals at high fracture (fx) risk who warrant intervention can be a challenge. There are several medical conditions that increase the risk for bone loss and falls which are recorded in the electronic medical record (EMR). <h3>Objectives</h3> We explored whether we could exploit data available in the EMR to estimate FRAX treatment thresholds to help passively identify patients who would benefit from further bone mineral density screening and management. <h3>Methods</h3> We studied 912 women and men, previously recruited for our bone health studies, in whom FRAX scores (with and without BMD) had been determined and comprehensive medical diagnoses were available through the medical linkage system of the Rochester Epidemiology Project. All diagnoses were categorized by the Clinical Classification Software (CCS) system whereby over 14,000 ICD-9-CM diagnoses are reduced to 568 clinically meaningful categories. If a subject had at least two diagnoses in a CCS category that were at least 30 days apart and within 5 years of their FRAX assessment, the subject was treated as having that CCS code. We used Gradient Boosting Machine (GBM) to create models that would predict the treatment thresholds for the FRAX 10-year risk for major osteoporotic (OP) fx (&gt;20%) and hip fx (&gt;3%), based on available diagnoses. Models were fit using age, sex and CCS category from 80% of the data, retaining 20% for validation. <h3>Results</h3> Of the 564 (62%) women and 348 (38%) men, the mean ± SD age was 61±16 yrs. There were no significant differences in subject characteristics used for FRAX calculation or FRAX scores between the training and validation sets. The c-statistic for GBM models predicting treatment thresholds for FRAX, calculated with BMD, for major OP fx and hip fx were 0.95 and 0.96, respectively, for the training set, and 0.88 and 0.94 for the validation set. Similar results were observed for FRAX scores without BMD. <h3>Conclusions</h3> FRAX treatment thresholds may be reasonably estimated from data available in the EMR to help identify to the clinician those at highest risk for fracture who would warrant further evaluation. Further work to implement and validate these findings in the EMR system would be necessary. <h3>Disclosure of Interest</h3> None declared
SAT0136 Association of genotypes for BCL1 polymorphism in the glucocorticoid receptor gene with ischemic heart disease in patients with rheumatoid arthritis
Authors: VSSU Kmyta, O Savchenko, L Prystupa
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The objective is to study association of genotypes for Bcl1 polymorphism in the glucocorticoid receptor (GR) gene with ischemic heart disease (IHD) in patients with rheumatoid arthritis (RA). <h3>Methods</h3> 161 subjects with rheumatoid arthritis aged 40 years and older were examined by means of instrumental, clinical and laboratory examinations. Rheumatoid arthritis was diagnosed according to ACR/EULAR Classification Criteria (2010). The IHD diagnosis was verified by means of AHA/ACC guidelines (2012). BCL1 polymorphism in exon 2 was identified using polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism by Fleury I. et al. (venous blood was used as the material for the study). Statistical analysis was performed using SPSS–17 program. <h3>Results</h3> It was revealed that 76 (47.2%) patients had isolated RA (group I), while 85 (52.8%) individuals had RA with concomitant IHD (group II). In group I, there were 29 (38.2%) patients with C/C genotype, 39 (51.3%) – with C/G genotype, and 8 (10.5%) – with G/G genotype. The distribution in group I was as following: 16 were homozygous for the C allele (18.8%), 40 were heterozygous (47.1%) and 29 were homozygous for the G allele (34.1%) (χ<sup>2</sup>=15.23; p=0.02). It was established that the risk of ischemic heart disease was 6.57 times higher in homozygotes for the G allele (OR=6.57; 95% CI=2.44−17.73; p=0.001) as compared with homozygotes for the C allele. <h3>Conclusions</h3> It was established that G/G genotype prevailed in RA patients with ischemic heart disease, while C/C genotype prevailed in patients with isolated RA. The risk of IHD development in patients with RA was associated with G/G genotype for Bcl1 polymorphism in the GR gene. <h3>Disclosure of Interest</h3> None declared
THU0177 ABT-494 pharmacokinetics following administration of the once-daily extended-release tablet formulation being utilized in the ongoing rheumatoid arthritis phase 3 trials
Authors: M-EF Mohamed, J Zeng, I-H Song, AA Othman
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> ABT-494 is a selective Janus Kinase 1 inhibitor. In two Phase 2b studies in subjects with rheumatoid arthritis, 6 mg and 12 mg twice-daily (BID) doses of ABT-494 immediate-release formulation achieved optimal benefit-risk profiles. To enhance patients9 compliance, an extended-release formulation was developed targeting to achieve comparable exposures with the 6 mg and 12 mg BID of the immediate-release formulation with once-daily (QD) administration. <h3>Objectives</h3> The objective of this work was to characterize the pharmacokinetics of ABT-494 with the extended-release formulation that is currently being utilized in Phase 3. <h3>Methods</h3> Comparison of ABT-494 pharmacokinetics from the immediate-release and extended-release formulations was conducted following multiple-dose administration in healthy subjects. Two cohorts of subjects were evaluated. In the first cohort, healthy subjects (N=12) received multiple 15 mg QD doses of the extended-release tablet formulation and multiple 6 mg BID doses of the immediate-release capsule formulation for 7 days. In the second cohort, healthy subjects (N=12) received multiple 30 mg QD doses of the extended-release tablet formulation and multiple 12 mg BID doses of the immediate-release capsule formulation for 7 days. Both evaluations were conducted following an open-label, randomized, 2-period, 2-sequence, crossover design under fasting conditions. ABT-494 plasma concentrations were measured and pharmacokinetic parameters were calculated using non-compartmental analyses. <h3>Results</h3> At steady-state, ABT-494 AUC0–24 ratio [and 90% confidence interval] was 0.94 [0.84 – 1.05], C<sub>max</sub> ratio was 0.91 [0.74 – 1.12] and C<sub>min</sub> ratio was 1.09 [0.85 – 1.40] for the 15 mg QD regimen of the extended-release formulation relative to the 6 mg BID regimen of the immediate-release formulation. Similarly, ABT-494 mean AUC<sub>0–24</sub> ratio was 0.97 [0.87 – 1.09], C<sub>max</sub> ratio was 0.90 [0.73 – 1.11] and C<sub>min</sub> ratio was 0.87 [0.75 – 1.02] for the 30 mg QD regimen of the extended-release formulation relative to the 12 mg BID regimen. All evaluated regimens were well-tolerated by healthy subjects. <h3>Conclusions</h3> ABT-494 regimens of 15 mg QD and 30 mg QD of the extended-release formulation, currently being utilized in Phase 3 RA studies, provide similar exposures to 6 mg BID and 12 mg BID, respectively of the immediate-release capsule formulation previously shown to provide optimal benefit-risk profiles in RA Phase 2 trials. <h3>Disclosure of Interest</h3> M.-E. Mohamed Shareholder of: AbbVie, Employee of: AbbVie, J. Zeng Shareholder of: AbbVie, Employee of: AbbVie, I.-H. Song Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie
A Pink Nodule on a Boy's Left Cheek
Authors: Wei Liu, Jia-Wei Liu, Dong-Lai Ma
Journal: JAMA (2017)

A 4-year-old boy had a 1-cm well-circumscribed, symmetrical, pinkish, dome-shaped nodule with central erosions on the left cheek. Hair, nails, and mucosae were of normal appearance, and the remainder of the examination was unremarkable. What would you do next?
FRI0671 Ultra-high field mri and biomechanical investigation of vertebral bone microarchitecture
Authors: S Guis, D Guenoun, A Fouré, M Pithioux, T Le Corroller, JP Mattei, V Pauly, M Bernard, P Chabrand, P Champsaur, D Bendahan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Fracture risk prediction in patient relies chiefly on bone mineral density (BMD) measurement. However, the decreased bone strength characteristic of osteoporosis is dependent not only on BMD, but also on other factors, most notably bone microarchitecture. <h3>Objectives</h3> The purpose of this study was to investigate bone microarchitecture variables of cadaveric vertebrae using ultra-high field MRI (7 Tesla). <h3>Methods</h3> Twenty four vertebrae (L2, L3, L4) from eight cadavers were studied using 7 Tesla MRI. Their Bone Mineral Density (BMD) were investigated using dual energy X Ray absorptiometry. Then, all specimens underwent mechanical compression tests to failure and the failure load (in Newton) and constraint (in Mpa) were measured. Bone Volume Fraction (BV/TV), Trabecular Thickness (Tb.Th), and Trabecular Spacing (Tb.Sp) were measured in MR images using a Digital topological analysis (Bone J). Measurements were performed by two observators in order to characterize the inter-rater reliability. Statistical analyses were performed using SPSS. Correlations between variables were analyzed using Spearman correlations and Stepwise regression. A p value of 0.05 was considered as significant. <h3>Results</h3> The inter-rater reliability for bone microarchitecture parameters quantification was good. Tb.Th and Tb.Sp measured using high-field MRI were 0.52±0.18 and 0.48±0.10 respectively while the BV/TV fraction was 0.52±0.13. The mean BMD was 0.86±0.20 g/cm<sup>2</sup>. The failure load and the constraint measured during the compression tests were 2600±1267N and 1.57±0.81 Mpa respectively. Interestingly, the variables measured during the mechanical tests were significantly The failure load and constraint measured during the compression tests were significantly correlated with the BMD. Regarding the bone indices quantified using high-field MRI, a significant linear relationship was observed between the trabecular spacing and the BMD (<i>R</i><sup>2</sup>=0.23, <i>p</i>=0.01 and the constraint values to failure (<i>R</i><sup>2</sup>=0.18, <i>p</i>=0.04). A stepwise regression with backward elimination demonstrated that combining BV/TV and BMD improved the relationship with the constraints from an adjusted <i>R</i><sup>2</sup>=0.384 for BMD alone to an adjusted <i>R<sup>2</sup></i>=0.41 for BMD + BV/TV. <h3>Conclusions</h3> In the present study, we demonstrated for the first time that the variables characterizing the vertebral bone microarchitecture quantified using ultra-high field MRI were significantly correlated with biomechanical parameters. In addition, we illustrated that the vertebral bone strength was better described by a variable combining BMD and trabecular bone spacing. <h3>Disclosure of Interest</h3> None declared
THU0531 Use of rituximab in paediatric rheumatology - experiences from a single tertiary centre
Authors: S Deepak, R Obrien, K Warrier, E Mcdermott, S Rangaraj
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rituximab is an anti-CD20 monoclonal antibody therapy used widely in the management of paediatric rheumatological conditions. Studies suggest that Rituximab is safe and effective in rheumatic autoimmune diseases, but data on paediatric use remains limited. Although Rituximab spares plasma cells, hypogammaglobulinaemia can still develop, leading to recurrent infections. Frequency of hypogammaglobulinaemia in children receiving Rituximab for rheumatological conditions is unknown. <h3>Objectives</h3> To analyse the use of Rituximab in a tertiary Paediatric Rheumatology centre over the last 15 years (2001–2015). The primary aims were to identify the number of patients who received Rituximab, the underlying diagnoses and the response to treatment. Our secondary aims were to identify the incidence of hypogammaglobulinemia associated with Rituximab use and the frequency and severity of infections. Frequency of monitoring of immunoglobulin levels, lymphocyte subsets and functional antibodies to pneumococcus were noted. <h3>Methods</h3> Retrospective analysis of case notes, electronic records and laboratory data of patients who received Rituximab in the paediatric rheumatology department from 2001–2015. <h3>Results</h3> A total of 22 patients received Rituximab (total of 1500mg/m<sup>2</sup> per cycle over 2 – 4 divided doses) during the study period. 3 were excluded due to insufficient data. Median time of commencement of Rituximab from diagnosis was 2 years 8 months. Of these, 12 patients achieved remission within 6 to 12 months. Rituximab was discontinued in the non-responders at 12 months. 8 patients (42%) were noted to have hypogammaglobulinaemia at some point. The role of cyclophosphamide contributing to hypogammaglobulinaemia could not be excluded in 2 and a further patient is currently being investigated for an underlying primary immune deficiency. In the remaining 5 (26%) patients, we believe the low IgG levels are secondary to Rituximab, of which two needed long term Ig replacement. Overall 12 patients reported recurrent/severe infections of which 6 had low immunoglobulin levels. <h3>Conclusions</h3> RF+ JIA patients appear to have responded the best to Rituximab and RF- JIA patients the least (0/4), with good results in JDM and SLE subgroups (80–83%). The incidence of hypogammaglobulinaemia secondary to Rituximab in our cohort was 26%, which can be prolonged and worsen with increased number of cycles. Prior treatment with cyclophosphamide may be contributory. We suggest regular monitoring of immunoglobulin levels and lymphocyte markers on all patients prior to commencement of Rituximab and regular intervals subsequently, including further cycles. <h3>Disclosure of Interest</h3> None declared
FRI0412 The positive effect of rituximab in pulmonary fibrosis of systemic sclerosis
Authors: P Kiryttopoulos, T Michailidis, E Papchianou, M Charalampidis, P Dimitriadis, A Agorastos
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Pulmonary fibrosis is one of the gravest manifestations of Systemic Sclerosis (SSc) and conventional DMARDs therapy has not shown any particular positive effect. <h3>Objectives</h3> Our goal was to see whether the elimination pf B - lymphocytes through use of anti – CD20 Mab, Rituximab (RTX) would offer to the improvement of the pulmonary function of SSc patients. <h3>Methods</h3> We studied 23 SSc patients with pulmonary fibrosis, who received treatment with RTX (n=12) or DMARDs treatment (n=11) for 1 to 3 years (1,9 years). Conventional therapy included azathioprine (n=4), mycophenalate (n=6) and methotrexate (n=2). RTX – treated patients were recorded with FVC improvement in the first year of treatment (FVC 81,3 +/- 12,6 vs FVC 87,4 +/- 11,3 out on the onset of the study and at the first year respectively, p=0,02) when on the other hand DMARDs treated patients didn9t show any FVC improvement at all. <h3>Results</h3> All RTX – treated patients did not present any lung HRCT deterioration imaging, in contrast to DMARDs – treated patients who were also submitted to lung HRCT each year of the study, all showing signs of CT imaging deterioration. Similar findings, as far as FVC was concerned, were recorded at the 3rd year of the study (RTX patients, n=6 and DMARDs patients, n=11). 3rd year RTX FVC was 92,6 +/-13,2 vs 80,7 +/-11,8 at the onset of the study, p=0,04 when DMARDs treated patients were all presented with worst 3rd year FVC compared to their primary FVC, p&lt;0,01. <h3>Conclusions</h3> Our small cohort of SSc patients with pulmonary fibrosis shows that it is possible that rituximab may be proven helpful to at least prevent the deterioration of the interstitial pulmonary fibrosis of Systemic Sclerosis. The pathophysiology of this particular fibrosis and the possible molecular role of B-lymphocytes in the inversion of this procedure need yet to be furtherly explored. <h3>Disclosure of Interest</h3> None declared
People at high risk of diabetes should undergo intensive lifestyle change, says NICE
Authors: Anne Gulland
Journal: BMJ (2017)

All people in England at high risk of developing type 2 diabetes should be offered a place on an intensive lifestyle change programme, says updated guidance from the UK National Institute for Health and Care Excellence (NICE).1

The guidance now states that anyone with a fasting glucose concentration between 5.5 and 6.9 mmol/L should be offered a place on such a programme but that priority should be given to anyone with a reading between 6.5 and 6.9 mmol/L, because of their increased risk of developing diabetes.

The guidance …
Astarabine, a Novel Leukemia-Targeted Cytarabine Composition Allows, for the First Time, the Delivery of High Cytarabine Doses for Older or Unfit Patients with Acute Leukemia. Results of an Ongoing Phase I/IIa Study
Authors: Tsila Zuckerman, Stela Gengrinovitch, Ruth Ben-Yakar, Ron Hoffman, Israel Henig, Noa Lavi, Luiza Akria, Yishai Ofran, Netanel A Horowitz, Olga Nudelman, Maya Koren-Michowitz, Shay Yeganeh, Martin S. Tallman, Jacob M. Rowe
Journal: Blood (2016)
THU0316 Epidemiology of takayasu arteritis in northern italy
Authors: G Restuccia, L Boiardi, P Macchioni, M Catanoso, P Mancuso, C Salvarani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Takayasu arteritis (TAK) is a large vessel vasculitis of unknown etiology, predominantly affecting the aorta and/or its major branches and occurring before the age of 40 years.TAK has been described worldwide with an annual incidence in Europe ranging from 0.4 to 1.3 /1.000.000. TAK is more common in female. In the largest study from Japan, the female to male ratio was eight to one. In a recent Swedish epidemiologic study no male were identified. There are no epidemiological studies regarding Takayasu arteritis in Italian population. <h3>Objectives</h3> To investigate the epidemiology of Takayasu arteritis in a Northern Italy area. <h3>Methods</h3> All patients with incident TAK diagnosed between 1997 and 2015 living in the Reggio Emilia area were identified by capture and re-capture checking at computerized discharge diagnosis codes (ICD10) and at outpatients databases from rheumatology, internal medicine, surgery, pathology, imaging departments of Reggio Emilia Hospital and by examining the Reggio Emilia district database for rare diseases.The Reggio Emilia population is predominantly of Caucasian origin (92.5%) with a yearly increase in general population of 0.5% (from 438.588 inhabitants in 1997 to 533.827 in 2015). <h3>Results</h3> There were 5 women satisfyng ACR 1990 criteria for TAK diagnosis during the 18 years study period. The overall age and sex-adjusted 18 years incidence per 100.000 persons aged &lt;40 years was 2.2. (95% CI:0.71 to 5.09). The overall age-and sex-adjusted 20 years incidence per 100,000 women aged &lt;40 years was 4.5. (95% CI:1.46 to 10.48). Median age at disease onset was 36y and at diagnosis was 39 years. The prevalence of TAK in the general population on December 31 2015 was 0.9 (95% CI: 0.31 to 2.19) while in female population aged &lt;40 years was 4.4 (95% CI 1.47 to 10.54). All patients are still alive on December 31 2015. <h3>Conclusions</h3> As observed in other epidemiological studies, TAK is a rare disease also in Northern Italy with a large prevalence of female. <h3>Disclosure of Interest</h3> None declared
AB0810 Correlation between knee extensor muscle strength and gait endurance after total knee arthroplasty
Authors: MJ Suh, BR Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> This study was undertaken to identify the relationship of objective physical performance and gait endurance after 1 month after total knee arthroplasty. <h3>Methods</h3> One-hundred ninety-five patients (32 males and 163 females; average age 72.6±6.1 years) who underwent a primary total knee arthroplasty (TKA). Patients completed 6-minute walk test (6MWT) to assess gait endurance. Additional physical performance test including timed up and go (TUG) test, timed Stair Climbing Test (SCT), instrumental gait analysis for spatio-temporal parameters, and isometric knee flexor and extensor strength of the surgical and nonsurgical knees 1 month after TKA were measured. To evaluate self-reported physical function, self-reported disease-specific physical function measured by using the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and self-reported quality of life measured by using EuroQOL five dimensions (EQ-5D) questionnaire. Visual analog scale (VAS) of post-operative knee pain was recorded each patient. <h3>Results</h3> In the bivariate analyses, the postoperative gait endurance had a significant positive correlation with the postoperative gait speed (r=0.48, p&lt;0.001), cadence (r=0.40, p&lt;0.001), stride length (r=0.58, p&lt;0.001), postoperative peak torque (PT) extensor of surgical knee (r=0.36, p&lt;0.001), postoperative peak torque (PT) flexor of surgical knee (r=0.25, p&lt;0.001), postoperative peak torque (PT) extensor of non-surgical knee (r=0.49, p&lt;0.001), postoperative peak torque (PT) flexor of non-surgical knee (r=0.34, p&lt;0.001), EQ5D (r=0.33, p&lt;0.001) and a significant negative correlation with TUG (r=-0.46, p&lt;0.001), SCT-ascent (r=-0.63, p&lt;0.001), SCT-descent (r=-0.68, p&lt;0.001), WOMAC pain score (r=-0.29, p&lt;0.001), WOMAC stiffness score (r=-0.35, p&lt;0.001), WOMAC function score (r=-0.43, p&lt;0.001). In the linear regression analyses, the postoperative Visual analog scale (VAS) (β=-6.91, p=0.03), peak torque (PT) extensor of surgical knee (β=0.56, p=0.04) and peak torque (PT) extensor of non-surgical knee (β=0.77, p&lt;0.001) were a factors predictive of the postoperative 6MWT. <h3>Conclusions</h3> This study demonstrated that quadriceps muscle strength significantly influenced on gait endurance 1 month after TKA. Using variables measured after surgery, it may be possible to predict with good accuracy for postoperative gait speed. In addition, these results could be of importance in determining effective rehabilitation strategies focusing on resistance training for improvement of gait speed early after TKA. <h3>Disclosure of Interest</h3> None declared
Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor Development
Authors: Swapna Thomas-Jinu, Patricia M. Gordon, Triona Fielding, Richard Taylor, Bradley N. Smith, Victoria Snowden, Eric Blanc, Caroline Vance, Simon Topp, Chun-Hao Wong, Holger Bielen, Kelly L. Williams, Emily P. McCann, Garth A. Nicholson, Alejandro Pan-Vazquez, Archa H. Fox, Charles S. Bond, William S. Talbot, Ian P. Blair, Christopher E. Shaw, Corinne Houart
Journal: Neuron (2017)

(Neuron 94, 322–336; April 19, 2017) As a result of an author oversight in the originally published version of this article, the first name of author Kelly L. Williams was written as “Katherine.” This error has now been corrected in the article online. The authors apologize for the error. Non-nuclear Pool of Splicing Factor SFPQ Regulates Axonal Transcripts Required for Normal Motor DevelopmentThomas-Jinu et al.NeuronApril 6, 2017In BriefThomas-Jinu et al. demonstrate that a non-nuclear pool of the splicing factor SFPQ is necessary for normal motor development, through local mRNA maintenance or processing. SFPQ’s coiled-coil domain is required for axonal localization. Their findings may have an important impact in understanding human motor neuron disorders. Full-Text PDF Open Access