tbuckley/cabot-search huggingface dataset:
SAT0532 Sleep quality in patients with knee osteoarthritis
Authors: M Sezgin, E Yeşildal, S Sevim, H Ankaralı, G Sahin
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The aim of this study was to investigate sleep quality in patients with knee osteoarthritis (OA). <h3>Methods</h3> One hundred patients with knee OA and age and gender-matched 75 healthy controls were enrolled into the study. Demographic characteristics of the participants were recorded. All patients was examined by a single physician, the findings were recorded. Knee radiographs of the patients were staged according to the Kellgren-Lawrence grading. In addition, to evaluate the clinical status and quality of life of patients was performed Western Ontario ve McMaster Universities Osteoarthritis Index (WOMAC) and Nottingham Health Profile (NHP). The sleep quality of two groups with MOS sleep scale and polysomnography (PSG) were subjectively and objectively evaluated. <h3>Results</h3> All scores of MOS sleep scale were significantly lower in patients with knee OA than controls (p&lt;0.001). When PSG outcomes of the patients compared with the controls,waketime during sleep period (WTSP) (37.2±35.9, 13.1±19.4 p=0.012 respectively) and number of awakeness (NOAW) (9.2±18.2, 2.6±3.5, p=0.05 respectively) were significantly higher, sleep efficiency (SE) (84.2±21.1, 96.7±4.6 p=0.009 respectively) was significantly lower in patients with knee OA. There were significantly positive correlations between MOS sleep scale and PSG (sleep period, sleep onset, REM duration and REM latans) outcomes of the patients (r:0.44–0.59 p=0.04–0.006). In addition, MOS sleep scale scores of patients were negatively related with both NHP (pain, emotional reaction, sleep and social isolation subgroup scores) and WOMAC (total and functional) scores (r:-0.20–0.47, p=0.04–0.0001). <h3>Conclusions</h3> The sleep quality of patients with knee OA was worse compared to healthy controls. The poor sleep and sleep quality in knee OA had adversely affected the clinical status and quality of life. <h3>References</h3> Hays RD, Martin SA, Sesti AM, Spritzer KL. Psychometric properties of the Medical Outcomes Study Sleep measure. Sleep Med 2005; 6:41–44. Wilcox S, Brenes GA, Levine D, et al. Factors related to sleep disturbance in older adults experiencing knee pain or knee pain with radiographic evidence of knee osteoarthritis. J Am Geriatr Soc 2000; 48:1241. Leigh TJ, Hindmarch I, Bird HA, Wright V. Comparison of sleep in osteoarthritic patients with age and sex matched healthy controls. Ann Rheum Dis 1988;47:40–2. Vivien CA, Priscilla SA, Christian G. Sleep and rheumatologic disorders. Sleep medicine reviews 2008;12: 211–228.97. Stewart AL, Sherbourn C, Hays RD, et al. Summary and discussion of MOS measures. Measuring functioning and well-being: The Medical Outcomes Study approach. Durham: Duke University Press, 1992:345–371. <h3>Disclosure of Interest</h3> None declared
SAT0617 Salivary gland ultrasound can differentiate primary sjÖgren's syndrome from systemic diseases with salivary gland involvement
Authors: K Delli, JF Van Nimwegen, S Arends, AJ Stel, M Van den Berge, WF Bierman, H Bootsma, FKL Spijkervet, A Vissink
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ultrasound of the major salivary glands (SGUS) has shown high diagnostic accuracy for primary Sjögren9s syndrome (pSS) [1,2]. None of the existing studies, however, included a control group of patients with sarcoidosis, amyloidosis, human immunodeficiency virus (HIV) or hepatitis C (HCV) infection [2]. These diseases are known to frequently affect the major salivary glands, cause dry mouth or may have histopathology similar to pSS. <h3>Objectives</h3> To assess the diagnostic accuracy of SGUS to differentiate pSS from systemic diseases with salivary gland involvement. <h3>Methods</h3> Twenty consecutive patients fulfilling the AECG criteria for pSS and 20 consecutive patients with well-established systemic diseases, i.e., 5 patients with sarcoidosis, 5 patients with amyloidosis, 5 patients with HIV infection and 5 patients with HCV infection, were included. Echogenicity, parenchymal homogeneity, presence of hypoechogenic areas and clearness of posterior glandular border of both parotid and submandibular salivary glands were scored independently by two blinded observers and rated according to the Hocevar et al scoring system (ultrasound total score (UTS), range: 0–48) [3]. The optimal cut-off point was determined by using ROC curve. The agreement between SGUS positivity and classification as pSS was assessed. <h3>Results</h3> The median age of patients with pSS and systemic diseases was 50 and 53 years, respectively. Daily complaints of dry mouth longer than 3 months, need of liquid to swallow food and recurrent or persistent swelling of the major salivary glands were reported by 95%, 85% and 70% of patients with pSS compared to 45%, 30% and 20% of patients with systemic diseases. The accuracy of SGUS to discriminate pSS was excellent, with an area under ROC of 0.91 and optimal cut off point of 15. The agreement between SGUS and diagnosis for pSS was good (κ=0.75, percentage of absolute agreement 87.5) with a sensitivity of 90%, specificity of 85%, positive predictive value of 86%, negative predictive value of 89% and diagnostic odds ratio of 51. UTS was positive in 2 patients with HIV infection and one patient with sarcoidosis. Patients with pSS had significantly higher UTS than patients with systemic diseases (median UTS 27 vs. 10, p&lt;0.001) and patients of the various subgroups (p&lt;0.05; Fig). <h3>Conclusions</h3> This pilot study indicates that SGUS has a high diagnostic accuracy to discriminate pSS from associated systemic diseases with salivary gland involvement. A minority of HIV and sarcoidosis patients, however, may show SGUS findings mimicking pSS. <h3>References</h3> Jousse-Joulin et al. Rheumatology (Oxford) 2016;55:789–800. Delli et al. Oral Dis 2015;21:792–800. Hocevar et al. Rheumatology (Oxford) 2005;44:768–72. <h3>Disclosure of Interest</h3> None declared
Erratum: Interrogating open issues in cancer medicine with patient-derived xenografts
Authors: Annette T. Byrne, Denis G. Alférez, Frédéric Amant, Daniela Annibali, Joaquín Arribas, Andrew V. Biankin, Alejandra Bruna, Eva Budinská, Carlos Caldas, David K. Chang, Robert B. Clarke, Hans Clevers, George Coukos, Virginie Dangles-Marie, S. Gail Eckhardt, Eva Gonzalez-Suarez, Els Hermans, Manuel Hidalgo, Monika A. Jarzabek, Steven de Jong, Jos Jonkers, Kristel Kemper, Luisa Lanfrancone, Gunhild Mari Mælandsmo, Elisabetta Marangoni, Jean-Christophe Marine, Enzo Medico, Jens Henrik Norum, Héctor G. Palmer, Daniel S. Peeper, Pier Giuseppe Pelicci, Alejandro Piris-Gimenez, Sergio Roman-Roman, Oscar M. Rueda, Joan Seoane, Violeta Serra, Laura Soucek, Dominique Vanhecke, Alberto Villanueva, Emilie Vinolo, Andrea Bertotti, Livio Trusolino
Journal: Nature reviews. Cancer (2017)
Abstract P300: A Novel Highly Selective Adenosine A1Receptor Agonist (VCP28) Reduces Ischemia/Reperfusion Injury at Concentrations that Do Not Affect Heart Rate
Authors: Paul J White, Vijay Urmaliya, Colin W Pouton, Shane Devine, Peter Scammells
Journal: Circulation Research (2011)

Whilst adenosine A1 receptor agonists have repeatedly been shown to protect the ischaemic myocardium, the clinical use of these agents is limited by strong cardiodepressant effects. The cardioprotective effects of a novel adenosine A1 receptor agonist N6-(2,2,5,5-tetramethylpyrrolidin-1-yloxyl-3-ylmethyl) adenosine (VCP28) were compared with the selective adenosine A1receptor agonist N6-cyclopentyladenosine (CPA) in a H9c2(2–1) cardiac cell line-simulated ischemia (SI) model (12 hours) and a global ischemia (30 minutes) and reperfusion (60 minutes) model in isolated rat heart model. H9c2(2–1) cells were treated with CPA and VCP28 at the start of ischemia for entire ischemic duration, whereas isolated rat hearts were treated at the onset of reperfusion for 15 minutes. In a H9c2(2–1) cell SI model, CPA and VCP28 (100 nM) significantly (P , 0.05, n = 5–6) reduced the proportion of nonviable cells (30.88% 6 2.49% and 16.17% 6 3.77% of SI group, respectively) and lactate dehydrogenase efflux. In isolated rat hearts, CPA and VCP28 significantly (n = 6–8, P , 0.05) improved postischemic contractility (dP/dtmax, 81.69% 6 10.96%, 91.07% 6 19.87% of baseline, respectively), left ventricular developed pressure, and end diastolic pressure and reduced infarct size. The adenosine A1 receptor antagonist DPCPX abolished the cardioprotective effects of CPA and VCP28 in both models. At the concentrations used in the ischaemia models, VCP28 had no effect on heart rate, unlike CPA. In conclusion, the adenosine A1 receptor agonist VCP28 has cardioprotective equal effects to the prototype A1 agonist CPA at concentrations that have no effect on heart rate.
Trilaciclib (G1T28): A cyclin dependent kinase 4/6 inhibitor, in combination with etoposide and carboplatin (EP) for extensive stage small cell lung cancer (ES-SCLC)—Phase 1b results.
Authors: Caio Max S. Rocha Lima, Patrick J. Roberts, Victor M. Priego, Stephen G. Divers, Melanie B. Thomas, Ralph V. Boccia, Katie Stabler, Elizabeth Andrews, Rajesh K. Malik, Raid Aljumaily, John Turner Hamm, Vi Kien Chiu, Donald A. Richards, Petros Nikolinakos, Maen A. Hussein, Steven Robert Schuster, Robert John Hoyer, Geoffrey Shapiro, Konstantin H. Dragnev, Taofeek Kunle Owonikoko
Journal: Journal of Clinical Oncology (2017)

8568 Background: Chemotherapy (chemo) has significant clinical utility, however consequent damage to hematopoietic stem and progenitor cells (HSPCs) and the immune system may limit activity. If chemo-mediated anti-tumor activity was maximized, while minimizing myelosuppression and immunosuppression, patient outcomes would be improved. Trilaciclib (T) is an intravenous CDK4/6 inhibitor in development to reduce myelosuppression and preserve immune system function during chemo. HSPCs are dependent on CDK4/6 for proliferation. Preclinical data demonstrated that transient T-induced G1 cell cycle arrest renders HSPCs resistant to chemo cytotoxicity, allowing faster hematopoietic recovery, preservation of long-term function, and enhancement of anti-tumor immunity and activity. Methods: Objectives of this ongoing multicenter Phase 1b/2a study are to assess dose limiting toxicities (DLTs), safety, tolerability, hematological profile, PK, and anti-tumor activity of T administered prior to EP. Phase 1b was open-label, dose-finding, and the ongoing Phase 2a is randomized (1:1), double-blind. Eligible pts had confirmed diagnosis of ES-SCLC, adequate organ function, ECOG PS 0-2, no prior chemo, and no symptomatic brain metastases. Results: 19 pts were enrolled in the Phase 1b: 10 pts received T 200 mg/m 2 + EP and 9 pts received T 240 mg/m 2 + EP. T + EP was well tolerated. 2 pts at T 200 mg/m 2 and 1 pt at T 240 mg/m 2 experienced asymptomatic DLTs in cycle 1. 2 pts (1 at each dose) had an ANC &lt; 1500 on cycle 2 day 1, delaying the start of cycle 2, and 1 pt at the T 200 mg/m 2 dose had grade 4 thrombocytopenia. There were no cases of febrile neutropenia or bleeding. PK analysis showed no drug interactions between T and EP. 17/19 pts were evaluable: 1 pt had CR, 14 had PR (confirmed ORR = 88%); 1 pt had SD (clinical benefit rate = 94%). Conclusions: In the Phase 1b part of the study, T + EP was well tolerated. Early activity results are promising with a confirmed objective response rate of 88%. This novel approach allowing the administration of chemotherapy while preserving HSPC and immune system function could potentially improve treatment outcomes for SCLC pts. Clinical trial information: NCT02499770.
AB1143 The impact of anti-cyclic citrullinated peptide seropositivity on erosion prevalence among patients with rheumatoid arthritis of varying disease duration
Authors: L Harrold, K Price, H Litman, S Connolly, E Alemao, S Rebello, W Hua, J Kremer
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Little is known regarding the prevalence of erosive disease in a contemporary cohort of patients with RA and whether erosive disease prevalence differs by disease duration and seropositivity to anti-citrullinated protein antibodies (ACPA). <h3>Objectives</h3> To characterize the proportion of patients with RA with erosive disease by disease duration category and stratified by positive and negative serological status (anti-cyclic citrullinated peptide [anti-CCP], a surrogate for ACPA). <h3>Methods</h3> We identified patients with RA aged ≥18 years who were enrolled in the Corrona registry (October 2001–June 2016), with available disease duration, radiographic/MRI/ultrasound studies and serological status based on anti-CCP. Patients were grouped based on RA disease duration (0–2, 3–5, 6–10 and &gt;10 years from diagnosis). Unadjusted prevalence erosion rates were calculated based on the proportion of patients with reports of erosions present on joint radiographs/MRIs/ultrasounds. Seropositivity was based on laboratory results (anti-CCP ≥20 U/mL) at enrolment in the Corrona registry. Chi-squared tests were used to assess differences in prevalence rates. <h3>Results</h3> There were 9759 patients who met inclusion criteria. Most were women (76%), middle-aged (mean [SD] 57 years [14]), with moderate disease activity (mean [SD] CDAI 14.7 [13.4]). Prior use of at least one biologic or targeted synthetic DMARD had occurred in 41% of patients. Overall, the prevalence of erosive disease was 28.6%, with higher prevalence among CCP+ (35.4%) vs CCP– (20.1%) patients (p&lt;0.001, chi-squared test). The prevalence of erosions increased with increasing disease duration (p&lt;0.001; Table). For each disease duration group, the prevalence of erosions was higher in patients who were CCP+ compared with those who were CCP−. <h3>Conclusions</h3> Erosions were common in this cohort of patients, and prevalence of erosions increased with longer disease duration. Patients who were CCP+ had higher rates of prevalent erosions than those who were CCP– with similar disease duration. <h3>Disclosure of Interest</h3> L. Harrold Shareholder of: Corrona LLC, Grant/research support from: Pfizer, AstraZeneca, Consultant for: Roche, Med IQ, K. Price Employee of: Bristol-Myers Squibb, H. Litman Employee of: Corrona LLC, S. Connolly Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Rebello Employee of: Corrona LLC, W. Hua Employee of: Corrona LLC, J. Kremer Shareholder of: Corrona LLC, Grant/research support from: AbbVie, Bristol-Myers Squibb, Genentech, Lilly, Novartis, Pfizer, Employee of: Corrona LLC, Speakers bureau: Genentech
THU0338 Clinical presentation and outcomes of eosinophilic granulomatosis with polyangiitis: anca-negative versus anca-positive
Authors: E Zagvozdkina, P Novikov, S Moiseev
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> The aim of the prospective study was to compare clinical presentation at diagnosis and long-term outcomes of eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA) patients according to antineutrophil cytoplasmic antibody (ANCA) status. <h3>Methods</h3> EGPA was classified according to the Revised CHCC Nomenclature and ACR1990 criteria. Activity of vasculitis was evaluated using BVAS. A minor relapse was defined as an increase in at least one new or worse minor item and no major BVAS items. A major relapse was an increase in at least one major BVAS item. <h3>Results</h3> We followed 93 patients with EGPA for a mean±SD of 6.3±6.5 years. Their mean±SD age was 46.6±13.8 years, and 96.8% patients had a history of asthma. The most common EGPA manifestations at diagnosis included ENT manifestations (88.2%), fever (78.5%), peripheral neuropathy (73.1%), lung involvement (59.1%) and skin lesions (49.5%). Thirty seven of 93 patients (39.8%) were ANCA-positive. These patients had significantly more frequent myalgia and mononeuritis multiplex, than the ANCA-negative patients. The difference in occurrence of kidney disease between the two groups did not reach statistical significance. However, all three patients with rapidly progressive kidney failure were ANCA-positive. BVAS at diagnosis and VDI at the end of the follow-up were significantly higher for ANCA-positive patients. The follow up duration was 587.7 patient-years. The incidence of all vasculitis relapses was 14 per 100 patient-years, including major and minor vasculitis relapses (5.3 and 8.7 per 100 patient-years, respectively). The 3- and 5-year relapse-free survival rate was 65.4% (95% CI 54.6–76.2) and 43.1% (95% CI 30.4–55.7), respectively. The frequency of vasculitis relapses was 21.0 per 100 patient-years in the ANCA-positive group versus 19.6 per 100 patient-years in the ANCA-negative group (P=0.4). <h3>Conclusions</h3> The characteristics of EGPA patients differ according to their ANCA status, although long-term outcomes were similar in both groups. EGPA is characterized by relapsing course of disease. The minor vasculitis relapses predominated in the structure of relapses. <h3>Disclosure of Interest</h3> None declared
FRI0064 Chemokine receptor 6 modulates arthritis in a t cell dependent manner
Authors: M Bonelli, A Puchner, L Goeschl, S Hayer, B Niederreiter, JS Smolen, C Scheinecker, S Blueml
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, characterized by synovial infiltration of various cells. Chemokines are involved in the recruitment of different cell types into the synovial membrane. Accumulation of CCR6 expressing mononuclear cells can be found in joints of RA patients. CCR6 expression has also been reported on CD4<sup>+</sup> T cells, in particular regulatory as well as Th17 cells. In addition, a subset of regulatory T cells, namely CD25<sup>-</sup>Foxp3<sup>+</sup> T cells, can upregulate CCR6 and RANKL and thereby can promote osteoclastogenesis. <h3>Objectives</h3> In this study, we investigated the role of CCR6 in the pathogenesis of arthritis using different arthritis models. <h3>Methods</h3> Clinical as well as histological signs of arthritis were investigated in the collagen-induced arthritis (CIA), K/BxN serum transfer arthritis and in the human tumor necrosis factor (hTNFtg) arthritis model, comparing <i>wt</i> and <i>CCR6-/-</i> mice. We analyzed the phenotype of lymph node cells by flow cytometry and cytokine concentrations in serum. Anti-collagen antibodies and cytokines were measured by enzyme-linked immunosorbent assay. <h3>Results</h3> The K/BxN serum transfer arthritis and hTNFtg arthritis model are known to be T cell independent. Since CCR6 is an important component of the innate immune system we compared the development of arthritis in both models. We did not detect any significant differences in clinical signs of inflammation or histological severity of arthritis between <i>wt</i> and <i>CCR6-/-</i> mice. In addition, bone volume was similar between <i>wt</i> and <i>CCR6-/-</i> mice. To investigate the role of CCR6 as part of the adaptive immune system in the development of arthritis we induced CIA in <i>wt</i> and <i>CCR6-/-</i> mice, which is known to be T cell dependent. <i>CCR6-/-</i> mice were almost completely protected from CIA. Indeed, analyses of T cell subsets by flow cytometry revealed a significant reduction of CD25<sup>-</sup>Foxp3<sup>+</sup> T cells. <h3>Conclusions</h3> CCR6 is necessary for the generation of pathogenic CD25<sup>-</sup>Foxp3<sup>+</sup> T cells in CIA, suggesting an important function of CCR6 on T cells in the development of autoimmune arthritis. <h3>Disclosure of Interest</h3> None declared
THU0505 Low literacy but not parental smoking or breast feeding worsens outcome in juvenile idiopathic arthritis in a low income population
Authors: FAC Rocha, JI Vasques, LN Rocha, MG Aguiar, JPE Accioly, CN Lechiu, LHA Costa, MFCD Silva, ARX Feitosa, HAL Rocha, CN Rabelo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> JIA data from underdeveloped regions are scant. We evaluated JIA patients living in low latitude (3<sup>o</sup>439S), highly exposed to sunlight. We have shown their mean serum vitamin D levels as the higher ever reported, being not associated to disease status. Here are data on monthly income, breastfeeding, parental smoking, and literacy in this JIA cohort. <h3>Methods</h3> Clinical and demographic data [n (%)] from 165 JIA patients followed between May 2015 - Dec 2016 in two reference outpatient centers in Fortaleza-CE Brazil were consecutively collected. Family income (more or less than 300 US$/month), breast feeding (more or less than 3 months), literacy [more or less than 8 school-years (SY)], and parental smoking (present/absent) were compared using Juvenile Arthritis Disease Activity Score (JADAS27), Childhood Health Assessment Questionnaire (CHAQ) and presence of deformities as prognostic outcomes. <h3>Results</h3> Mean age was 14±4.9 years with 94 (56.9); 63 (38), 40 (24), 37 (22.4), 19 (11.5), 5 (3), and 1 (0.6) of the polyarticular, enthesitis-related, oligoarticular, systemic, undifferentiated, and psoriatic categories, respectively. Mean total CHAQ was 0.4±0.58 with a trend to be higher in polyarticular (0.55±0.69) than oligoarticular (0.3±0.4) category as well as higher JADAS 27 and more deformities in the former. Among 97 respondents, all but one patient was ever breastfed with 71 (73) for more than 3 months; 15 (17) out of 86 mothers were smokers and 28 (33.7) out of 83 smoked among family respondents; 49 (56.3) out of 87 parents had less than 8 SY and only 3 had superior level; 32 (37.6) out of 85 respondents earned less than 300US$. Lower literacy was associated to worse CHAQ (p=0.021). Neither maternal/family smoking nor breastfeeding time was associated to outcome. Lower income <i>per se</i> did not affect outcome. <h3>Conclusions</h3> This is the largest JIA database coming from an equatorial region reporting social and environmental aspects. Low literacy predominates, meaning more than half with less than elementary school, affecting prognosis. There is a low income profile and most family constituents do not smoke. Different from other countries, polyarticular category prevails despite low mean CHAQ <i>vis-à-vis</i> data from wealthy regions. Breast feeding for more than 1 month is almost universal and having breastfed for more than 3 months did not appear to influence prognosis <h3>Acknowledgements</h3> Conselho Nacional de Desenvolvimento Científico e Tecnolόgico - CNPq - Grant 459334/2014–0 <h3>Disclosure of Interest</h3> None declared