tbuckley/cabot-search huggingface dataset:
SAT0232 B-cell subpopulation dynamics in sle patients following rituximab therapy
Authors: AA Mesnyankina, EN Aleksandrova, SK Soloviev, EV Suponitskaya, AP Aleksankin, AA Novikov, EA Aseeva, EL Nasonov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To study B-cell subpopulation dynamics in SLE patients following Rituximab (RTX) therapy. <h3>Methods</h3> The study included 31 SLE pts (3m/28f) with high (SLEDAI2K≥10–28 pts.) and moderate (SLEDAI2K&lt;10–3 pts.) disease activity; out of them 12 pts with SLE nephritis, 5 pts with neurolupus and 8 with vasculitis. RTX was administered to pts who failed to respond to glucocorticoids (GCs) and cytostatics (CTs). B-cells subpopulations were assessed before RTX administration (Mo0), and at Mo3 and Mo6 of RTX therapy. RTX was administered at 500 to 2000 mg doses depending on disease activity. The absolute counts of CD19+ B-cells, the total population of memory B-cells (CD19+CD27+), "preswitch" (CD19+IgD+CD27+) and "postswitch" (CD19+IgD-CD27+) memory B-cells, "naive" (CD19+IgD+CD27-), plasma cells (CD19+CD38+) and double negative B-cells (CD19+CD27-IgD) were measured. All B cell subsets were analyzed with multicolor flow cytometry using a panel of monoclonal antibodies to B-lymphocytes9 surface membrane markers. <h3>Results</h3> Following initiation of RTX SLE clinical and lab activity indices have decreased in all 31 pts by Mo3 and Mo6 of follow up (SLEDAI-2K Mo0–Me 15 [12;18], Mo3-Me 6 [4;10], Mo6–Me 4 [2;8]), as well as absolute count CD19+ B-cell population (Mo0–Me 0,119x10<sup>9</sup>/l [0,05;0,26], Mo3–Me 0x10<sup>9</sup>/l [0;0,003], Mo6-Me 0,004x10<sup>9</sup>/l [0;0,02]). B-cell repopulation by Mo6 in 15 out of 31 pts without signs of relapse and 4 pts with earlier relapse SLE was dependent on "naïve" B-cells (Me 0,0015x10<sup>9</sup>/l [0,0002;0,01] vs Me 0,006x10<sup>9</sup>/l [0,0033;0,008]), double negative (Me 0,001x10<sup>9</sup>/l [0,0002;0,002] vs Me 0,0035x10<sup>9</sup>/l [0,0018;0,005]) "postswitch" (Me 0,0005x10<sup>9</sup>/l [0,00008;0,003] vs Me 0,0012x10<sup>9</sup>/l [0,0003;0,0035]) and "preswitch" memory B-cells (Me 0,0006x10<sup>9</sup>/l [0,00007;0,001] vs Me 0,0023x10<sup>9</sup>/l [0,0005;0,005]). <h3>Conclusions</h3> Decrease in clinical and lab SLE activity was documented in all 31 pts by Mo3 after one course of RTX therapy. In 4 pts with earlier relapse SLE at Mo6 B-cell was found repopulation and significant increase "naïve" B-cells, double negative, "postswitch" and "preswitch" memory B-cells compared with the group without relapse. <h3>Disclosure of Interest</h3> None declared
Efficacy and tolerability of second-line <i>nab</i>-paclitaxel and gemcitabine (NG) after failing first-line FOLFIRINOX in patients (pts) with advanced pancreatic cancer (APC): A single-institution experience.
Authors: Hanbo Zhang, Curtis Kellett, Pascal J Lambert, Christina Kim
Journal: Journal of Clinical Oncology (2017)

e15723 Background: APC is incurable and has a poor prognosis. First line chemotherapy options include 5-fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) or NG. However, the optimal second-line regimen is unclear. In pts who progress on FOLFIRINOX and maintain a good performance status, NG may be a reasonable second line option. As such, we sought to: 1) describe the clinical and pathologic features of pts who received second line NG compared to pts who received second line gemcitabine (GEM) or best supportive care (BSC); 2) Evaluate the toxicity profile of NG in the second line setting; 3) determine whether a survival benefit exists with second line NG. Methods: Pts ≥18 diagnosed with APC from 2012-2016 and treated with palliative chemotherapy at CancerCare Manitoba (CCMB) were identified from the Manitoba Cancer Registry. CCMB pharmacy records identified pts who received FOLFIRINOX followed by second line NG, GEM or BSC. A retrospective analysis was performed to identify pts and treatment characteristics, toxicity, dose reductions, dose delays and survival. Results: 146 pts received first line FOLFIRINOX. Of those who progressed and were offered second line therapy, 30 (50%) received NG, 8 (16%) received GEM and 22 (37%) chose BSC. Median age at diagnosis was 61 (35-84), 47% were female, 73% had metastatic disease and 63% had primaries in the head of pancreas. Grade 3 and 4 neutropenia was more common with NG compared to GEM (27% vs. 6.7%). There were more dose reductions and dose delays with NG compared to GEM (76.7% vs. 25% and 63.3% vs. 12.5% respectively). The median progression free survival was 3.61 months in the NG group, compared with 2.51 months in the GEM group (hazard ratio 2.48; 95% CI 1.08-5.65; P = 0.03). The median OS was 5.69 months in the NG group compared to 3.82 months the GEM group (hazard ratio 2.611; 95% CI, 1.11-6.38). Conclusions: In a select group of pts with APC who progress after first line FOLFIRINOX, there is a role for second line NG. Although many pts required dose reductions and delays, second line NG was associated with a survival benefit compared to GEM, with manageable toxicity.
THU0660 Polymyalgia rheumatica treatment serum biomarkers versus rheumatoid arthritis
Authors: MK Meyer, M Andersen, TV Stausbo, KJ Elbæk, GN Andersen, A Stensballe
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Polymyalgia rheumatica (PMR) is a systemic inflammatory disorder with unknown etiology and overlapping symptoms with giant cell arthritis and late-onset rheumatoid arthritis (RA). To date, no proteomics studies have been performed on PMR patients, and the number of biomarker studies remain limited. <h3>Objectives</h3> The primary aim of this study was to thoroughly investigate the corticosteroid treatment serum proteome of PMR with a focus on acute-phase reactions, complement system, and cytokines. <h3>Methods</h3> Filter-aided sample preparation for mass spectrometry, cell free DNA (cfDNA) assay, and 10plex cytokine assay were applied to PMR serum samples from the same patients before and after treatment, DMARD-naïve RA patients, and healthy controls. <h3>Results</h3> The core serum proteomes of the four groups were remarkably similar, and consisted of &gt;200 proteins, which included acute-phase reactants, coagulation and complement proteins (figure), immunoglobulins, and apolipoproteins, and several more. Acute Phase Serum Amyloid A (SAA1) was differentially less abundant after PMR treatment, and CRP (after adjusting for two patients with low baseline CRP). cfDNA were more abundant in both groups of PMR compared to healthy controls. Complement factors were narrowly distributed and not affected by PMR treatment. The individual serum proteome of each PMR patient provided more than 100 differentially abundant proteins, and highlights the heterogeneity of patients. <h3>Conclusions</h3> We have established the core serum proteome of PMR in response to treatment, and compared it with RA and healthy controls. The results suggest a functional role of SSA1, and increased cfDNA in the pathogenesis of PMR indicates the activation of NETs. <h3>Disclosure of Interest</h3> None declared
SAT0401 Prevalence of ultrasonographic lower and upper enthesitis in patients with inflammatory bowel disease
Authors: G Cuomo, M Zappia, M Verde, D Sgambato, M Romano
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Spondyloarthritis (SpA) occurs in up to 20% of patients with inflammatory bowel disease (IBD) [1]. Symptomatic enthesitis is a characteristic feature of SpA and represents an early sign of SpA [2]. The prevalence of enthesitis in patients with IBD is not known. <h3>Objectives</h3> This study was designed to evaluate whether patients with IBD showed an increased prevalence of entheseal involvement, even in the absence of clinical symptoms. <h3>Methods</h3> Thirty-five IBD patients (25 M and 10 F, median age 41 yrs), 25 with Crohn9s disease (CD) and 10 with ulcerative colitis (UC), all with moderate intestinal activity, and 22 (13 M and 12 F, median age 44 yrs) control subjects with irritable bowel syndrome underwent a thorough clinical evaluation followed by entheses ultrasonography of upper limb (brachial triceps) and lower limb (quadriceps, proximal and distal rotuleus, Achilles tendon and plantar fascia). The Madrid sonographic entheses index (MASEI) was used to score entheses abnormalities [thickness, enthesophytosis, bursitis, erosions with and without power doppler (PD)]. Correlation between IBD features (type, duration and activity), age, sex and MASEI score was assessed with nonlinear Spearman9s rho. Significance of differences was assessed by chi-square test. The level of statistical significance of differences was set at p <h3>Results</h3> All of 35 patients with IBD presented at least one entheses alteration with a mean MASEI of 5.43 (thickness 57.1%, enthesophytosis 42.8%, bursitis 0%, erosions 0%, PD abnormalities 14.2%) vs 3 patients of control group (enthesophytosis 14%) (p <h3>Conclusions</h3> 1) IBD patients showed a significantly higher prevalence of early entheses involvement, even in the absence of clinical symptoms; 2) the entity of entheses alteration as assessed by MASEI did not correlate with type, duration and activity of IBD; 3) age was the only variable which significantly correlated with ultrasonographic entheses involvement.; 4) we speculate that IBD patients should undergo ultrasonography evaluation of entheses and, if any alteration, be followed up for early detection of SpA. <h3>References</h3> Harbord M et al. J Crohns Colitis. 2016. Sakellariou G et Clin Exp Rheumatol. 2014. <h3>Disclosure of Interest</h3> None declared
SAT0421 Fat mass negatively affects the response to tnf alpha blockers in ankylosing spondylitis patients
Authors: SE Ibáñez Vodnizza, MT Nurmohamed, IM Visman, JC van Denderen, WF Lems, IE der Horst-Bruinsma van
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Women with Ankylosing Spondylitis (AS) seem to be less responsive to TNF-α blockers and have a shorter drug survival. This might be explained by differences in body composition (BC), as women have higher total body fat (BF). <h3>Objectives</h3> Assess the relationship between gender, BC and response to TNF-α blocker treatment in a cohort of TNF-α blocker naïve AS patients. <h3>Methods</h3> AS patients (Modified New York criteria), ≥18 years old, who had a Dual-Energy X-ray Absorptiometry BC analysis before the start of TNF-α treatment and at least 6 months thereafter were included. Demographic information and the disease activity measures ASDAS CRP and BASDAI were reported. Fat Mass (FM) was reported as BF% (FM/Total body mass), and Fat Mass Index (FMI= FM kg/height m<sup>2</sup>). Fat Free Mass (lean mass + bone mineral content) was reported as its index (FFMI kg/m<sup>2</sup>). BF%, FMI, and FFMI percentiles, according to the reference population tables, stratified by age and gender, were also reported. <h3>Results</h3> Forty-one patients were included, 61% were men. Demographic characteristics were similar in men and women. The FFMI percentile was remarkably low in men, probably reflecting muscle wasting (figure 1). The percentiles increased in men and decreased in women after treatment. The clinically important improvement (CII) of ASDAS CRP was achieved by 52% of men and only 37.5% of women. The minimum CII for BASDAI was achieved by 64.7% of men, and only 35.7% of women that had a BASDAI ≥4 at baseline. After multivariate analysis we found a significant relationship between higher BF%, FMI or FMI percentile at baseline and a lower chance of achieving at least a CII of ASDAS CRP; the same relationship was found between FMI percentile at baseline and the minimum CII for BASDAI (table 1). <h3>Conclusions</h3> Higher body fat content at baseline is independently associated with a worse response to treatment with TNF-α blockers, measured by ASDAS-CRP and BASDAI change, and might contribute to the lower response to treatment rates in female patients. Also, there is a trend toward muscle mass recovery in male patients after treatment with TNF-α blockers. <h3>Acknowledgements</h3> This study was endorsed by an ASAS (Assessment of SpondyloArthritis international Society) Fellowship. <h3>Disclosure of Interest</h3> None declared
The Incidence and Prevalence of Systemic Lupus Erythematosus in San Francisco County, California: The California Lupus Surveillance Project
Authors: Maria Dall'Era, Miriam G. Cisternas, Kurt Snipes, Lisa J. Herrinton, Caroline Gordon, Charles G. Helmick
Journal: Arthritis & Rheumatology (2017)

Objective Estimates of the incidence and prevalence of systemic lupus erythematosus (SLE) in the US have varied widely. The purpose of this study was to conduct the California Lupus Surveillance Project (CLSP) to determine credible estimates of SLE incidence and prevalence, with a special focus on Hispanics and Asians. Methods The CLSP, which is funded by the Centers for Disease Control and Prevention, is a population‐based registry of individuals with SLE residing in San Francisco County, CA, from January 1, 2007 through December 31, 2009. Data sources included hospitals, rheumatologists, nephrologists, commercial laboratories, and a state hospital discharge database. We abstracted medical records to ascertain SLE cases, which we defined as patients who met ≥4 of the 11 American College of Rheumatology classification criteria for SLE. We estimated crude and age‐standardized incidence and prevalence, which were stratified by sex and race/ethnicity. Results The overall age‐standardized annual incidence rate was 4.6 per 100,000 person‐years. The average annual period prevalence was 84.8 per 100,000 persons. The age‐standardized incidence rate in women and men was 8.6 and 0.7 per 100,000 person‐years, respectively. This rate was highest among black women (30.5), followed by Hispanic women (8.9), Asian women (7.2), and white women (5.3). The age‐standardized prevalence in women per 100,000 persons was 458.1 in blacks, 177.9 in Hispanics, 149.7 in Asians, and 109.8 in whites. Capture–recapture modeling estimated 33 additional incident cases and 147 additional prevalent cases. Conclusion Comprehensive methods that include intensive case‐finding provide more credible estimates of SLE in Hispanics and Asians, and confirm racial and ethnic disparities in SLE. The disease burden of SLE is highest in black women, followed by Hispanic women, Asian women, and white women.
Health-related quality of life as a marker of treatment benefit with nivolumab in platinum-refractory patients with metastatic or unresectable urothelial carcinoma from CheckMate 275.
Authors: Andrea Necchi, Marc-Oliver Grimm, Margitta Retz, Jose Angel Arranz Arija, Sergio Bracarda, Jens Bedke, Ari David Baron, Padmanee Sharma, Matt D. Galsky, Daniel A. Vaena, Ewa Kalinka-Warzocha, Magdalena Cwikiel, Sumanta K. Pal, Rafael Morales, Fiona Taylor, Kyna McCullough Gooden, Elizabeth R. Plimack
Journal: Journal of Clinical Oncology (2017)

4526 Background: CheckMate 275 (NCT02387996), a phase II, single-arm study of nivolumab (3 mg/kg every 2 weeks) treatment in platinum-refractory patients (pts) with metastatic urothelial carcinoma, showed an objective response rate of 19.6% (95% CI, 15.0%–24.9%) with manageable toxicity. The objective of this analysis was to examine the impact of nivolumab on health-related quality of life (HRQoL) in the study. Methods: HRQoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and three-level EQ-5D (EQ-5D-3L) and visual analog scale (VAS). Questionnaires were completed at baseline and every 8 weeks thereafter for the first 48 weeks. The analysis cohort included pts with scores recorded at baseline and ≥1 postbaseline assessments while on treatment. Data were analyzed using mixed models, adjusting for baseline score. Results: Of the 270 patients treated with nivolumab, 168 (62%) had an assessment at baseline and ≥1 postbaseline assessment and were included in HRQoL analyses. Completion rates at baseline were 97% for both questionnaires. Statistically significant ( P&lt; 0.05) improvements in mean scores for the EORTC QLQ-C30 subscales measuring role, emotional, and social functioning; global health status/quality of life; nausea/vomiting; pain; dyspnea; insomnia; appetite loss; constipation; and diarrhea were observed at ≥1 time points. With the exception of cognitive functioning, no significant worsening in subscale scores was observed in the EORTC QLQ-C30. Statistically significant and clinically meaningful improvement (based on a minimally important difference of 7) in EQ-5D VAS was noted between weeks 17 and 41. EQ-5D-3L utility index scores based on the UK tariff remained stable during treatment. Conclusions: Results of CheckMate 275 indicate that pts with metastatic or unresectable urothelial carcinoma whose disease progressed or recurred after treatment with a platinum agent exhibited stable, or in some cases statistically significantly improved, HRQoL while being treated with nivolumab, as measured by EORTC QLQ-C30 and EQ-5D-3L. Clinical trial information: NCT02387996.
Spinal cord injury-induced immunodeficiency is mediated by a sympathetic-neuroendocrine adrenal reflex
Authors: Harald Prüss, Andrea Tedeschi, Aude Thiriot, Lydia Lynch, Scott M Loughhead, Susanne Stutte, Irina B Mazo, Marcel A Kopp, Benedikt Brommer, Christian Blex, Laura-Christin Geurtz, Thomas Liebscher, Andreas Niedeggen, Ulrich Dirnagl, Frank Bradke, Magdalena S Volz, Michael J DeVivo, Yuying Chen, Ulrich H von Andrian, Jan M Schwab
Journal: Nature Neuroscience (2017)
OP0134 Long term outcome and prognosis factors of complications in takayasu's arteritis: multicenter study of 318 patients
Authors: C Comarmond, L Biard, M Lambert, A Mekinian, Y Ferfar, J-E Kahn, Y Benhamou, L Chiche, F Koskas, P Cluzel, E Hachulla, E Messas, M Resche-Rigon, T Mirault, P Cacoub, D Saadoun
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To assess long term outcome and to elaborate a prognostic score for vascular complications in patients with Takayasu arteritis (TA). <h3>Methods</h3> Retrospective multicenter study of characteristics and outcome of 318 TA patients [86% of females; median age 36 [25–47] years; median follow-up of 6.1 years] fulfilling ACR and/or Ishikawa criteria. Factors associated with the event free survival (EFS), relapse free survival (RFS) and incidence of vascular complications were assessed. A prognostic score for vascular complications was elaborated based on a multivariate model. <h3>Results</h3> The 5- and 10-years event free survival (EFS), relapse free survival (RFS) and complication free survival were 48.2% (42.2;54.9) and 36.4% (30.3;43.9), 58.6% (52.7;65.1) and 47.7% (41.2;55.1), and 69.9% (64.3;76) and 53.7% (46.8;61.7), respectively. Progressive disease course (p=0.018) and carotidodynia (p=0.036) were independently associated with EFS. Male gender (p=0.048), elevated C reactive protein level (p=0.013), and carotidodynia (p=0.003) were associated with RFS. Progressive disease course (p=0.017), thoracic aorta involvement (p=0.009), and retinopathy (p=0.002) were associated with complication free survival. We define high risk patients for vascular complications according to the presence of two of the following factors (i.e a progressive clinical course, thoracic aorta involvement and/or retinopathy). The probability of complication free survival at five years was 78.4% (69.4;88.6) and 51.5% (38.3;69.2) in the low risk and high risk group, respectively. <h3>Conclusions</h3> This nationwide study shows that 50% of TA patients will relapse and experience a vascular complication at 10 years. We could define high risk TA patients for vascular complications. <h3>Disclosure of Interest</h3> None declared
From Programs to Policy and Back Again: The Push and Pull of Realizing Type 2 Diabetes Prevention on a National Scale
Authors: Ronald T. Ackermann
Journal: Diabetes Care (2017)

The U.S. Centers for Disease Control and Prevention (CDC) estimates that about 1.9 million Americans develop diabetes yearly; most of them have type 2 diabetes, and almost one-third remain undiagnosed for several years (1). The Diabetes Prevention Program (DPP) provided strong evidence that lifestyle behavioral counseling interventions can prevent or delay about half of these new cases (2). Unfortunately, 15 years after the DPP, most people at high risk for developing diabetes have not been offered such an intervention (3). This gap separates millions of high-risk Americans from the most evidence-based solution currently known to prevent type 2 diabetes.

In 2010, Congress authorized the CDC to launch the National Diabetes Prevention Program (National DPP), which supports organizational and workforce development, quality monitoring, and evaluation of efforts to scale up delivery of DPP-like lifestyle intervention programs nationally (4). As of April 2017, the National DPP registry listed 1,379 organizations offering DPP-like interventions across all 50 states, including 47 online-only programs and 1,332 organizations delivering face-to-face interventions (4). These numbers underscore the incredible growth in our nation’s capacity to provide DPP-like interventions.

In this issue of Diabetes Care , Ely et al. (5) report findings of an evaluation of the first 14,747 adults who completed ≥1 National DPP visits through one of 220 registered organizations between February 2012 and January 2015. Strengths of this evaluation include the large sample size and inclusion of data for all National DPP participants; limitations include lack of a control group and no information about weight changes or other outcomes for participants who stopped attending the program. Still, this evaluation offers an important first glimpse of the success of National DPP’s scale-up since 2010.

Over a 12-month period after their first visit, National DPP participants completed a median of 14 of 22 possible lessons and about half …