tbuckley/cabot-search huggingface dataset:
OP0190 Smoking is Not Primarily Associated with ACPA, but with the Presence of Multiple Autoantibodies in RA
Authors: A. Muhammad, T. van Wesemael, Y. Kochi, M. Mjaavatten, K. Wevers-de Boer, C. Allaart, L. Trouw, A. Suzuki, K. Yamamoto, T. Huizinga, R. Toes, D. van der Woude
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Smoking is associated with the presence of autoantibodies in various diseases, such as chronic obstructive pulmonary disease (COPD)<sup>1</sup>, systemic lupus erythematosus (SLE)<sup>2</sup> and polymyositis<sup>3</sup>. In rheumatoid arthritis (RA), smoking is assumed to be specifically associated with the presence of anti-citrullinated protein antibodies (ACPA), with smoking putatively leading to increased pulmonary citrullination. <sup>4</sup> <h3>Objectives</h3> To investigate whether the association of smoking with RA is limited to ACPA-positive disease, or whether smoking is associated with autoantibody-positive RA in general. <h3>Methods</h3> A meta-analysis based partly on published data (2 cohorts)<sup>4,5</sup>, and partly on new data (4 cohorts) was performed using 6 cohorts of RA patients from 5 countries: United Kingdom, Sweden, Norway, Japan, and the Netherlands. Complete data on rheumatoid factor (RF)-, ACPA-status and tobacco exposure were available for 7055 RA patients. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the presence of RF, ACPA or both were calculated by logistic regression comparing previous and current smokers with non-smokers, and using the ACPA-negative RF-negative RA patients as the reference category, since not all cohorts had matched controls. <h3>Results</h3> There was no significant association between tobacco exposure and seropositive RA in patients who were positive for only one antibody, being either RF (n = 644, OR 1.04, 95% CI 0.75 – 1.44) or ACPA (n = 770, OR 1.00, 95% CI 0.83 – 1.22). However, smoking was significantly associated with double-positive (ACPA-positive and RF-positive) RA (n = 3598, OR 1.61, 95% CI 1.31 – 2.00). When double-positive patients were compared to single-positive patients, the effect of the additional presence of RF or ACPA was comparable; OR for RF: 1.42 (1.20 – 1.67), OR for ACPA: 1.49 (1.25 – 1.87). <h3>Conclusions</h3> Smoking is not associated with ACPA-positive RA as such, but rather with the concurrent presence of multiple autoantibodies (RF and ACPA) in RA patients. In light of the association between smoking and autoantibodies in other diseases such as SLE and COPD, these data indicate that smoking predisposes to the development of auto-antibodies in general, and not to the development of ACPA per se. <h3>References</h3> Feghali-Bostwick C. A. et al. 2008 Am J Respir Crit Care Med. 177(2):156-63 Freemer M. M. et al. 2006 Ann Rheum Dis. 65(5): 581-4 Chinoy H. et al. 2012 2012 Ann Rheum Dis. 71(6): 961-5 Klareskog L. et al. 2006 Arthritis Rheum. 54(1): 38-46. Morgan A. W. et al. 2009 Arthritis Rheum. 60(9): 2565-76 <h3>Disclosure of Interest</h3> None Declared
NONINVASIVE ASSESSMENT THE HEMODYNAMIC SIGNIFICANCE OF CORONARY STENOSIS USING FUSION OF CARDIAC COMPUTED TOMOGRAPHY AND 3D ECHOCARDIOGRAPHY
Authors: Victor Mor-Avi, Francesco Maffessanti, Mita Patel, James J. Walter, Anuj Mediratta, Diego Medvedofsky, Waseem Cossor, Roberto Lang, Amit Patel
Journal: Journal of the American College of Cardiology (2016)
ADRENERGIC RECEPTOR POLYMORPHISMS INTERACT WITH BETA-BLOCKER DOSE EFFECT ON HEART FAILURE OUTCOMES ESPECIALLY IN BLACK RACE: RESULTS FROM HF-ACTION DNA SUBSTUDY
Authors: Kishan S. Parikh, Mona Fiuzat, Megan Neely, Tariq Ahmad, G. Michael Felker, Ileana Pina, Kirkwood Adams, Mark Donahue, William Kraus, David Whellan, Christopher O’Connor
Journal: Journal of the American College of Cardiology (2015)
SP0170 Clinical Manifestations of Raynaud's Phenomenon during Different Ages
Authors: A. Herrick
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Raynaud9s phenomenon (RP) is an exaggeration of the normal physiological response to cold. Typically the fingers turn white (ischaemia), then blue (deoxygenation) and then red (reperfusion). The toes (and nose and ears) may also be affected. RP can present at any age. Primary (idiopathic) RP typically presents in the teens or twenties. However, children also may present with RP and in 12 to 15 year olds the prevalence of RP has been estimated to be 15%. When RP presents in older age groups, it is especially important to look for an underlying cause. Secondary causes of RP include not only connective tissue diseases but also hand-arm-vibration syndrome, atherosclerotic disease, haematological disorders, and certain drugs and chemicals. The pathogenesis of RP is complex and includes abnormalities of the vasculature, of neural control elements, and intravascular factors. It is important to separate primary from secondary RP. In patients with primary RP, abnormalities in the digital vasculature are thought to be purely functional: structural vascular disease (as seen in systemic sclerosis) does not occur. As a result, patients with primary RP do not progress to irreversible tissue injury, whereas patients with secondary RP, for example systemic sclerosis-related RP, may develop digital ulcers, pitting scars, or gangrene. Early recognition of systemic sclerosis is possible through careful and early evaluation of the patient presenting with RP: this evaluation includes checking for antinuclear antibody (and if there is concern also for systemic sclerosis-specific autoantibodies) and examining the nailfold capillaries by capillaroscopy. For this reason, RP is the main clinical indication for nailfold capillaroscopy. In primary (idiopathic) RP the nailfold capillaries should be normal whereas abnormal capillaroscopy raises suspicion of an underlying systemic sclerosis-spectrum disorder. Raynaud9s phenomenon and abnormal nailfold capillaries are two of the criteria in the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria for SSc. Treatment of RP depends on its severity and on whether or not there is an underlying cause which may be amenable to intervention. Treatment options include general measures, drug treatment and (in patients who have progressed to ulceration or gangene) surgery. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6338
Abstract 834: IGF-II promoter specific methylation patterns are associated with its expression and disease progression in epithelial ovarian cancer
Authors: Lingeng Lu, Dionyssios Katsaros, Biyun Qian, Mario Preti, Guido Menato, Alicia Beeghly, Herbert Yu
Journal: Cancer Research (2010)

Abstract Purpose: High insulin-like growth factor-II (IGF-II) expression in epithelial ovarian cancer is associated with aggressive disease and poor prognosis. IGF-II expression is regulated by promoter methylation; aberrant methylation is common in cancer. The effect of promoter methylation on IGF-II expression and the role of methylation in ovarian cancer are investigated in a clinical study. Patients and Methods: The study enrolled 211 epithelial ovarian cancer patients who were followed after surgery for disease outcomes. Fresh tumor samples were collected from the patients and were analyzed for IGF-II promoter methylation using methylation-specific PCR, as well as for IGF-II mRNA expression with qRT-PCR. IGF-II peptide concentrations were measured with an ELISA kit in tumor tissues. Results: The study found different levels of methylation in 3 IGF-II promoters (P2-P4) which are located in a large CpG island, high methylation in P2 (64.2%) and P3 (52.1%) and low in P4 (9.8%). Promoter-specific mRNA expression was lower in methylated than in unmethylated tumors. P3 methylation and expression appeared to play a major role for IGF-II in ovarian cancer. While methylation in individual promoter was not related to the disease, a methylation pattern between P2 and P3 was significantly associated with clinical and pathological features of ovarian cancer, including tumor grade, debulking results, residual tumor size and treatment response. The methylation pattern was also linked to disease progression, but not overall survival. Conclusions: Our findings suggest that IGF-II expression affects tumor progression and the expression is regulated by methylation which may have clinical implications in disease management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 834.
THE HIGH PREVALENCE AND CLINICAL IMPLICATION OF MYOCARDIAL BRIDGING IN PATIENTS WITH EARLY REPOLARIZATION PATTERN
Authors: Jiwon Seo, Junbeom Park, Jae-Sun Uhm, Kim jong-youn, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Journal of the American College of Cardiology (2015)
SYSTOLIC AND DIASTOLIC FUNCTION IN ACUTE PULMONARY EDEMA: A PROSPECTIVE CONSECUTIVE SERIES
Authors: Gregg W. Stone, Brian Griffin, David Brown, Robert Siegel, Gerald Maurer, Stephen Cook, Prediman K. Shah, Daniel S. Berman
Journal: Clinical Nuclear Medicine (1987)

Stone, Gregg W.; Griffin, Brian; Brown, David; Siegel, Robert; Maurer, Gerald; Cook, Stephen; Shah, Prediman K.; Berman, Daniel S. Author Information
Acute-on-chronic liver failure: a new syndrome in cirrhosis
Authors: Richard Moreau
Journal: Clinical and Molecular Hepatology (2016)

Patients with cirrhosis who are hospitalized for an acute decompensation (AD) and also have organ failure(s) are at high risk of short-term death. These patients have a syndrome called Acute-on-Chronic Liver Failure (ACLF). ACLF is now considered as a new syndrome that it is distinct from "mere" AD not only because of the presence of organ failure(s) and high short-term mortality but also because of younger age, higher prevalence of alcoholic etiology of cirrhosis, higher prevalence of some precipitants (such as bacterial infections, active alcoholism), and more intense systemic inflammatory response. ACLF is a new syndrome also because severe sepsis or severe alcoholic hepatitis do not account for 100% of the observed cases; in fact, almost 50% of the cases are of "unknown" origin. In other words, severe sepsis, severe alcoholic hepatitis and ACLF of "unknown origin" are subcategories of the syndrome. Keywords: Cirrhosis; Inflammation; Organ failures
AB0996 Ultrasonographic Measurement of Femoral Cartilage Thickness in Acromegalic Patients
Authors: M. Karkucak, I. Batmaz, N. Civan, F. Kılınç, E. Capkın, M.A. Sarıyıldız, M. Garipoğlu, M. Önder, L. Ozcakar
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The aim of the study was to evaluate the femoral cartilage thicknesses of acromegalic patients using ultrasound (US). <h3>Methods</h3> Sixty-two patients diagnosed with acromegaly (30 F, 32 M) were included. Patients9 demographic and clinical characteristics were recorded. The thickness of the femoral articular cartilage was measured using a a 6-18 MHz linear probe. Measurements were performed bilaterally from three points (medial condyle, intercondylar area and lateral condyle). <h3>Results</h3> 14 (22.5%) patients had pain in the knee joints. A significant increase in thickness of femoral articular cartilage was determined in the patients compared with the controls (all parameters, p&lt;0.001). While measurements performed with US were correlated among themselves, the same correlation was not obtained with GH and IGF-I. Analysis of acromegaly patients as active (n=37) or inactive (n=25) revealed no significance in the thickness of the femoral cartilage. <h3>Conclusions</h3> Acromegalic patients seem to have thicker femoral articular cartilages. The femoral cartilage was not thicker in active patients, however. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2114
A6.3 Patients with bronchiectasis, with or without rheumatoid arthritis, have an elevated anti-citrullinated peptide antibodies (ACPA) response.
Authors: Anne-Marie Quirke, Elizabeth Perry, Clive Kelly, Anthony de-Soyza, Paul Eggleton, David Hutchinson, Patrick Venables
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> ACPA, particularly antibodies to citrullinated enolase and vimentin, are associated with smoking in patients with rheumatoid arthritis (RA). There is increasing evidence that these links are due to expression of citrullinated proteins in the lungs of smokers. Whether this is a direct effect of smoking or inflammation is presently poorly understood. Bronchiectasis, a strong risk factor for RA, tends to occur in non-smokers, and can therefore be used to examine the role of inflammation in generating an ACPA response independent of smoking. <h3>Materials and Methods</h3> This multi-centre study included 53 patients with HRCT proven bronchiectasis and RA, 50 patients with RA without lung disease, 124 bronchiectasis without RA and 87 asthma patients as controls. Serum samples were analysed for ACPAs using anti-CCP (2<sup>nd</sup> generation assay) and in-house ELISA's were used to measure fine specificities to citrullinated α-enolase (CEP-1), citrullinated vimentin (cVim) and fibrinogen (cFib) together with their arginine-containing control peptides. Smoking history was detailed for all patients. <h3>Results</h3> Comparing the RA/bronchiectasis and the RA patients without lung disease, anti-CCP antibodies were more frequently positive (87% vs 48%) and titre significantly greater (p&lt;0.0001) in the RA/bronchiectasis group, despite a lower frequency of smoking (42% vs 58%). The frequency and titre were also increased in the RA/bronchiectasis group for anti CEP-1 (60% vs 24%; p &lt; 0.001), cVim (34% vs 11%; p &lt; 0.001) and anti-cFib (38% vs 18%; p = 012). Comparing the bronchiectasis with asthma groups, none of who had RA, 5% vs 2% had anti-CCP, 9% vs 2% had anti CEP-1 and none were anti-cVim or anti-cFib positive. However, the increased ACPA response in bronchiectasis vs asthma was significant for anti-CEP-1 (p &lt; 0.001). Testing with REP-1, the arginine-containing control peptide for enolase, showed that the response in the bronchiectasis patients was not citrulline-specific. <h3>Conclusions</h3> We have demonstrated that despite a low prevalence of smokers, RA/bronchiectasis patients have increased anti-CCP antibodies and an ACPA fine specificity profile similar to that previously shown in RA and smoking (anti-CEP-1 and anti-cVIM). Additionally we identified significantly elevated levels of anti-CEP-1 in the bronchiectatis patients, though unlike in the RA patients, the response was not citrulline-specific, similar to that previously reported for periodontitis. This indicates that the lung may be an initiating site for immunity to RA autoantigens due to inflammation independent of smoking.
FRI0248 Effects of bosentan in a homogeneous population of SSC subjects with a predefined restriction of blood flow in the hands (home): Preliminary results
Authors: H. Knaapen, A.E. Voskuyl, P.L. van Daele, J.P.J. Bloemsaat-Minekus, M.C. Vonk, A.J.M. Schuerwegh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Bosentan (Tracleer®) reduces the number of new digital ulcers (DU) in subjects with systemic sclerosis (SSc) and ongoing digital ulcer disease (Korn at all 2004, Matucci et al. 2011). Bosentan also improves skin perfusion of hands in SSc patients with pulmonary arterial hypertension (Rosato et al 2010). Whether SSc patients without PAH have the same benefit remains to be established. <h3>Objectives</h3> The objective of the HOME study was to evaluate the effect of 12 weeks of bosentan treatment on the blood flow in the hands of SSc patients with a clinically relevant reduction of blood flow in the hands, compared to healthy controls, as measured by laser Doppler imaging. <h3>Methods</h3> HOME was a national, multicenter, phase 4, randomized clinical trial. The blood flow in both hands was measured with the PeriScan PIM 3a laser Doppler (Perimed, Sweden) in 52 healthy controls and in 56 bosentan naive SSc patients, suffering from DU in the previous 2 years. The hand was divided into 3 separate regions: ROI1, distal to the PIP joint of the 3 middle fingers; ROI2, distal to the metacarpal joints and proximal to the PIP joint and ROI 3, the hand proximal to the metacarpal joints. Patients with a 50% reduced blood flow in ROI1 compared to mean blood flow in healthy controls were included in the study and were treated with bosentan twice daily for 12 consecutive weeks. The data was evaluated on an intention-to-treat basis. MEC approval was obtained for all sites. The trial was registered in clinicaltrials.gov (NCT01395732). <h3>Results</h3> 18 patients had more than 50% blood flow reduction in ROI1. Two patients refused treatment, so 16 patients were treated with bosentan (4 males, age 49±11 (mean ±stdev)). Three patients stopped the treatment after 5, 8 and 11 weeks (one adverse event and two reasons unrelated to bosentan treatment). In 1 patient with increased ALAT/ASAT, after up-titration, the dose was reduced to 62.5mg. The blood flow in the hand significantly increased from 34.2±10.1 (mean±stdev) before treatment to 42.4±15.4 and 46.5±19.8 at 4 and 12 weeks respectively (p=0.064 and p=0.027, paired sampled t-test). This increase was most profound in ROI1 and absent in ROI3. <h3>Conclusions</h3> Bosentan significantly increases the blood flow in the hands of SSc patients with a history of DU in the 2 previous years and a more than 50% reduction of blood flow in the hands compared to healthy controls. <h3>References</h3> Rosato et al. J. Rheumatol 2010; 37(12): 2531-9 Korn JH et all. Arthritis Rheum 2004; 50: 3985-93. Matucci et al. Annals Rheum Dis 2011;70:32-8. <h3>Disclosure of Interest</h3> H. Knaapen: None Declared, A. Voskuyl: None Declared, P. van Daele: None Declared, J. Bloemsaat-Minekus Employee of: Actelion PharmaceuticalsNederland B.V., M. Vonk: None Declared, A. Schuerwegh: None Declared
Abstract 1787: Dual targeting of PI3K and mTOR results in synergistic growth inhibition in NSCLC cells
Authors: Herta H. Chao, Christopher Zito, Lucia Jilaveanu, Valsamo Anagnostou, David Rimm, Gerold Bepler, Robert Camp, Harriet M. Kluger
Journal: Cancer Research (2010)

Abstract Background: Alterations of components in the PI3K/mTOR pathway can result in malignant transformation and are found in a multitude of human cancers including non-small cell lung cancer (NSCLC). Our purpose was to characterize expression of p85 and p110α PI3K subunits in NSCLC specimens and assess the association with mTOR expression, and to study the effects of co-inhibiting PI3K and mTOR in NSCLC cell lines. Methods: Using Automated Quantitative Analysis (AQUA), a novel method of in situ protein measurement, we quantified expression of PI3K subunits in two cohorts of 251 and 192 resected NSCLC specimens. AQUA scores were correlated with clinical and pathological variables and previously published AQUA scores for mTOR. We studied changes in viability of 6 NSCLC cell lines exposed to two PI3K inhibitors, LY294002 and NVP-BKM-120, alone and in combination with rapamycin, and assessed the activity of a dual PI3K/mTOR inhibitor, NVP-BEZ-235, which is in clinical development. Results: p85 and p110α tend to be co-expressed (p&amp;lt;0.001), and higher expression of p85 was seen in adenocarcinomas than squamous cell carcinomas (SCC). High expression of p85 correlated with poor survival (p&amp;lt; 0.0075). Expression of p110α correlated with mTOR (ρ=0.30). In 6 NSCLC cell lines (3 adenocarcinomas, 3 SCC) the addition of rapamycin to LY294002 or NVP-BKM-120 was highly synergistic. Of note, even small concentrations of rapamycin (1ηM) resulted in sensitization to the PI3K inhibitors, and similar reduction in viability was seen with the addition of 1ηM, 100ηM and 1000ηM of rapamycin. NVP-BEZ-235 was highly active in NSCLC cell lines with IC50s in the ηM range and resultant down-regulation of pAkt and pP70S6K. Conclusions: PI3K is associated with decreased survival in NSCLC, suggesting that it is a good drug target for this disease. Concurrent inhibition of PI3K and mTOR is synergistic in NSCLC cell lines. Dual inhibition of PI3K and mTOR by NVP-BEZ-235 is promising and should be further evaluated in clinical trials for patients with NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1787.
Abstract 35: Phase I study of dasatinib in combination with bevacizumab in advanced solid tumors (NCT01445509).
Authors: Jung-Min Lee, Christina Annunziata, Anne M. Noonan, John L. Hays, Lori Minasian, Jo Anne Zujewski, Helen Chen, John Wright, Nicole Houston, Elise C. Kohn
Journal: Cancer Research (2013)

Abstract Background: Inhibition of the MAPK pathway with sorafenib and neutralization of VEGF with bevacizumab (B) resulted in clinical benefit with interactive toxicity. Dasatinib (D) is a broad spectrum tyrosine kinase inhibitor with high affinity for SRC family kinases. We hypothesized that using this upstream inhibitor of the MAPK pathway with B would maintain activity with less interactive toxicity. Methods: A 3+3 dose escalation design incorporated with B 5mg/kg q2wk plus daily D 50, 70 and 100 mg in dose levels [DL] 1/2/3, then B 10mg/kg q 2wk plus D 100mg in DL4. DLT was defined during the first 6 weeks of treatment. Safety was assessed each 28d cycle and disease was reassessed every 2 cycles. Results: 19 pts were treated in the dose escalation portion on 4 DLs. Pts (17F/2M) had a median age of 64 yrs (25-79), ECOG PS 0-1, and normal end-organ function. Most (14/19) pts had metastatic gynecologic cancers (6 endometrial/5 ovarian-peritoneal/2 cervix/1 rectovaginal GIST). Other cancers included breast (2), pancreatic neuroendocrine (1), medullary thyroid (1) and melanoma (1). Median number of prior treatments was 4 (1-11). The highest planned dose combination was examined without exceeding the MTD. No DLT was observed. Grade (g) 3 events included hypertension (2), pleural effusion (2), dyspnea (1) and pulmonary hypertension (1). D-mediated marrow suppression was observed in 12 pts: anemia (g1/2 [12 pts]), lymphopenia (g1/2 [9pts]; g3 [1pt]), thrombocytopenia (g1/2 [5pts]), and neutropenia (g1/2 [4pts]). Confirmed PR was seen in 1/17 evaluable pts, a pt with HER2+ breast cancer (5 mo). Stabilization &amp;gt;/= 4 mo occurred in 9 pts (median 9 mo [4-18+mo]), yielding clinical benefit in 59%. Conclusions: D 100 mg daily with B 10mg/kg q2wk appears to be active and is well-tolerated in pts with advanced solid tumors. G 3 adverse events were uncommon and g 4 events or severe marrow toxicities were not observed at the doses planned and examined. An expansion cohort is now accruing with functional imaging, tumor biopsies, and blood sampling for measurement of biochemical changes in SRC and VEGF signaling pathways. Citation Format: Jung-Min Lee, Christina Annunziata, Anne M. Noonan, John L. Hays, Lori Minasian, Jo Anne Zujewski, Helen Chen, John Wright, Nicole Houston, Elise C. Kohn. Phase I study of dasatinib in combination with bevacizumab in advanced solid tumors (NCT01445509). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 35. doi:10.1158/1538-7445.AM2013-35
Intense FDG Activity in Focal Hepatic Steatosis
Authors: Yali Le, Yue Chen, Zhanwen Huang, Liang Cai, Li Zhang
Journal: Clinical Nuclear Medicine (2014)

A 38-year-old woman underwent PET/CT to evaluate possible hepatic malignancy. The images revealed intense FDG activity in several hypodense regions in the liver, most prominent in the lateral segment of the left lobe. The pathological examination showed that the patient had focal hepatic steatosis.