tbuckley/cabot-search huggingface dataset:
THU0283 Anticoagulation and Long-Term Outcomes in Patients with Renal Artery Stenosis and Antiphospholipid Syndrome:
Authors: A. Casian, S. Sangle (joint first author), S. ManouStathopoulou, N. Jordan, D. D'Cruz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Our previous data [1],[2],[3] showed that renal artery stenosis (RAS) is more prevalent in antiphospholipid syndrome (APS) (26%) compared to the general hypertensive population (8%),and anticoagulation with INR≥3 was associated with initial reduction of chronic kidney disease (CKD) and hypertension. <h3>Objectives</h3> To characterise the long-term outcomes and associations with anticoagulant treatment for patients with renal artery stenosis and antiphospholipid syndrome. <h3>Methods</h3> We identified 37 patients with RAS and APS fulfilling Sapporo criteria [4]: anticardiolipin IgG/IgM titer&gt;40 units or &gt;99th percentile (or +lupus anticoagulant) on ≥2 occasions ≥6 weeks apart AND vascular thrombosis (or pregnancy morbidity). RAS was diagnosed by magnetic resonance angiography (MRA). <h3>Results</h3> 15 patients had APS alone and 22 APS associated with autoimmune conditions (13 lupus, 5 ANCA vasculitis, 4 mixed). Median age at RAS diagnosis was 48 years, 31/37 (83.8%) were female and median follow-up was 10.4 years. 25/37 (67.6%) had previous thrombosis. 7/37 (18.9%) had bilateral RAS, 3 artery occlusion. 6/37 (16.2%) had concurrent coeliac stenosis. Recanalization of RAS occurred after hydroxychloroquine in 3/37 and 9/37 (24.3%) underwent angioplasty +/− stenting. MRA was repeated in 11/37 (29.7%) after 2 years. 23/37 (62.2%) were anticoagulated, with 9/37 (24.3%) on antiplatelet therapy. 13/37 (35.1%) received hydroxychloroquine, 10/22 (45.5%) immunosuppressives and 18/37 (48.6%) antihypertensives. 9/37 (24.3%) died after a median of 10 years since RAS diagnosis. 21/37 (56.8%) developed CKD: 6 endstage renal failure (ESRD) and 15 with median eGFR 39 mls/min. <h3>Conclusions</h3> The majority of patients with RAS and APS were female, developed CKD and did not benefit from renal angioplasty. Anticoagulation was not associated with longterm reduction of ESRD or death, suggesting a non-thrombotic pathogenic process underlying RAS, such as intimal hyperplasia. Treatment of associated vascular risk factors and autoimmune disease is paramount. Anticardiolipin antibodies and renal MRA are useful screening tests for lupus patients with difficult blood pressure control. <h3>References</h3> S R Sangle, D P D9Cruz et al. Ann Rheum Dis 2003;62:999–1002. S R Sangle, D P D9Cruz et al. Rheumatology 2005;44:372–37 Jordan NP, Chaib A, Sangle S, D9Cruz DP. Arthritis Care and Research) 2013 Sipek-Dolnicar A, Hojnik M, Bozic B, Vizjak A. Clin Exp Rheumatol. 2002; 20:335–42. <h3>Disclosure of Interest</h3> None declared
FRI0015 Leucine Rich Alpha-2 Glycoprotein (LRG) Is Involved in Pulmonary Fibrosis by Enhancing TGF-β Signaling in Fibroblasts
Authors: H. Honda, M. Fujimoto, H. Urushima, T. Ohkawara, S. Serada, T. Naka
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Lung diseases related to collagen disorder are often accompanied by fibrosis and TGF-β is one of the essential mediators in tissue fibrosis. Leucine rich alpha-2 glycoprotein (LRG) is a novel serum protein that is increased in patients with inflammatory diseases, such as rheumatoid arthritis. LRG expression is increased in inflamed tissues, suggesting that the molecule is involved in the pathogenesis of the diseases. Since LRG has recently been reported as a modulator of TGF-β signals [1] [2], LRG may play a role in tissue fibrosis. <h3>Objectives</h3> In this study, we aimed to investigate the involvement of LRG in a murine model of lung fibrosis. <h3>Methods</h3> Wild type mice and LRG knockout (KO) mice were intratrachally treated with bleomycin and fibrosis were evaluated 21 days after the treatment. At the time of sacrifice, the lungs were harvested and processed for histological examination using hematoxylin and eosin staining, detection of collagen fibers using azan staining, and immunohistochemistry. Furthermore, the effect of LRG on TGF-β signaling was investigated using L929 mouse fibroblast cell line. <h3>Results</h3> Intratracheal administration of bleomycin increased LRG protein levels in bronchial alveolar lavage fluids (BALF) and lung tissues. When compared to wild type mice, fibrosis was markedly inhibited in LRG knockout (KO) mice, as evalulated by azan staining and by hydroxyproline assay. Although there was no significant difference in BALF TGF-β levels between WT and LRG KO mice, phosphorylation and nuclear translocation of Smad2 protein were attenuated in the lung of LRG KO mice. In vitro experiments using L929 revealed that LRG enhanced TGF-β-induced Smad2 phosphorylation and the expression of downstream genes, such as plasminogen activator inhibitor-1 (PAI-1) and alpha smooth muscle actin (SMA). Furthermore, TGF-β-induced Smad2 phosphorylation was enhanced by exogenous LRG protein in a dose-dependent manner. Although LRG has been reported to interact with endoglin, an accessory receptor of TGF-β, knockdown of endoglin showed no effect on LRG-induced enhancement of Smad2 activation. <h3>Conclusions</h3> These data demonstrate that LRG enhances TGF-β-induced activation of Smad2 cascade in fibroblasts leading to promote fibrosis in murine model of lung fibrosis. <h3>References</h3> Nature 2013 Jul 18; 499 (7458):306–11 Oncotarget 2015 May 10; 6 (13):11009–22 <h3>Acknowledgement</h3> We wish to thank K. Omori and Y. Maeda for their advice and expertise, E. Harada and R. Nishi for their technical assistance and the staff of Animal Bioscience Department of the Nagahama Institute of Bio-Science and Technology for their help in histopathological evaluation. <h3>Disclosure of Interest</h3> None declared
AB0503 Large Vessel Vasculitis in Systemic Lupus Erythematosus - A Case Series from A Single Centre in South india
Authors: R.V.P. Irlapati, A.R. Sabella, L. Rajasekhar
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> In Systemic lupus erythematosus (SLE), vasculitis is seen in 11% to 36% of patients. Small vessel vasculitis is seen in upto 86% and medium vessel vasculitis in the rest, and rarely large vessels are involved. We present a series of 4 such patients which is unique in that aortitis and lupus were diagnosed at the first presentation. <h3>Objectives</h3> To study the clinical profile of SLE patients presenting with Large vessel vasculitis (LVV). <h3>Methods</h3> Patients presenting to Rheumatology department between January 2012 and February 2015 fulfilling ACR criteria for SLE with evidence of large vessel involvement clinically and by Doppler ultrasound, CT angiography or MR angiography were included and followed prospectively. Demographic, clinical, laboratory and imagelogy data were studied. <h3>Results</h3> All patients were females, between 21–37 years of age. All had clinical features suggestive of SLE with a positive serology for ANA and double stranded DNA. Mean age of the patients was 25.25±4 years, with median duration of disease of 34.5 (range 4 -60) months with mean SLEDAI of 22±7. All patients had history of claudication of extremities. Imaging findings are described in table 1. Patients 1, 2 and 4 had subclavian artery and aortic bruit. Patient 3, who presented with cerebrovascular accident had MR angiography showing multiple focal intracranial vessel stenosis along with large vessel involvement. Three patients had nephritis, one had CNS lupus. Three patients had high ESR 68,106,70 mm after one hour. One patient had a positive Anticardiolipin antibodies (1/3). Three had low complements (3/3). Patient 2 underwent renal biopsy, and found to have class V lupus nephritis. Patient 1,2 and 3 received intravenous pulse cyclophosphamide therapy, Patient 4 was treated with azathioprine. Patient 1 underwent PTCA to aorta and subclavian artery in view of persistent claudication. After a mean follow up of 29±22 months all patients are stable. <h3>Conclusions</h3> Large vessel involvement in SLE predominantly involves aorta and subclavian arteries and is associated with high disease activity. <h3>References</h3> Barile-Fabris L, Hernández-Cabrera MF, Barragan-Garfias JA. Vasculitis in systemic lupus erythematosus. Current rheumatology reports. 2014 Sep 1;16(9):1–6. Ramos-Casals M, Nardi N, Lagrutta M, Brito-Zerόn P, Bové A, Delgado G, Cervera R, Ingelmo M, Font J. Vasculitis in systemic lupus erythematosus: prevalence and clinical characteristics in 670 patients. Medicine. 2006 Mar 1;85(2):95–104. <h3>Disclosure of Interest</h3> None declared
Interruption of imatinib (IM) in GIST patients with advanced disease: Updated results of the prospective French Sarcoma Group randomized phase III trial on survival and quality of life
Authors: A. Le Cesne, D. Perol, I. Ray-Coquard, B. Bui, F. Duffaud, M. Rios, J. M. Coindre, J. F. Emile, P. Berthaud, J. Y. Blay
Journal: Journal of Clinical Oncology (2005)

9031 Background: IM (Gleevec/Glivec; Novartis Pharma) the first-line treatment (Tx) for advanced GIST, must be given continuously until disease progression (PD) or intolerance (Blay et al, ASCO 2004). The impact on overall survival (OS) of IM discontinuation in responding patients (pts) and its reintroduction at progression is unknown. Methods: This prospective multicenter BFR14 study was initiated in June 2002. After 1 year of IM 400mg/day, 58 pts free from progression were randomly offered to continue or interrupt Tx until PD. Pts allocated to the interruption (I) arm could restart IM (same dose) in case of PD. Primary endpoint was progression-free survival (PFS); secondary endpoints were OS, quality of life (QoL), secondary response after IM re-introduction, identification of molecular determinants of response. Survival data were compared using the log-rank test. Results: Patient characteristics were well balanced between the two arms. Current median follow-up after randomization is 21 months (range 12–29). 21/32 pts (66%) in arm I versus 4/26 pts (15%) in continuous (C) arm experienced PD. IM interruption was significantly associated with reduced PFS (P<10-4) with a median of 6 months (95% CI, 3–9) for arm I. IM reintroduction allowed tumor control (OR or SD) in 11/14 evaluated pts (79%). One-year OS rates were 89% and 87% for arms I and C, respectively (P = 0.46), with no significant difference in QoL. Conclusions: A statistically significant increase in the rate of PD was observed when IM was interrupted (experimental arm). IM re-introduction was safe and allows further tumor control in the majority of the randomized pts. At the time of the present analysis, no impact of IM discontinuation on OS could be detected. Updated results including mutational analysis will be presented at the meeting. No significant financial relationships to disclose.
Driver mutations’ effect in secondary myelofibrosis: an international multicenter study based on 781 patients
Authors: F Passamonti, B Mora, T Giorgino, P Guglielmelli, M Cazzola, M Maffioli, A Rambaldi, M Caramella, R Komrokji, J Gotlib, J J Kiladjian, F Cervantes, T Devos, F Palandri, V De Stefano, M Ruggeri, R Silver, G Benevolo, F Albano, D Caramazza, E Rumi, M Merli, D Pietra, R Casalone, T Barbui, L Pieri, A M Vannucchi
Journal: Leukemia (2016)
SP0061 The Role of Patient Organisations in Health Technology Assessment
Authors: K. Facey
Journal: Annals of the Rheumatic Diseases (2016)

Health Technology Assessment (HTA) is defined as a multidisciplinary process that summarises information about the medical, social, economic and ethical issues related to use of a health technology (medicines, devices, vaccines, rehabilitation etc) in a systematic, transparent, unbiased, robust manner. Its aim is to inform health policy at local or national level including decisions about reimbursement and access. Principles of good practice for HTA were published in 2008 and these included “stakeholder involvement”, recognising that policy initiatives should include a democratic right for involvement. Patients and their representatives are clearly key stakeholders, but questions arise about how they should be involved in the complex processes of HTA without compromising scientific integrity. The Health Technology Assessment International (HTAi) Interest Group for Patient/Citizen Involvement in HTA believes that patients and their representatives can provide valuable input to HTA by sharing their experiences of living with a condition, use of current health technologies and experiences and expectations of new health technologies. This unique knowledge can add value to every stage of the HTA process, but in many countries there is no involvement of patients and no transparency about how patients can be involved in HTA. So, the HTAi Interest Group works with all stakeholders to develop tools and initiatives to support HTA bodies to involve patients and patient organisations in a meaningful manner and to support patient organisations to get involved in HTA. Any patient group9s approach to HTA must be specific to their own setting, but can draw on the international recommendations made by HTAi – such as their Values and Quality Standards for Patient Involvement in HTA. Furthermore, patient groups can help support capacity building through better collaboration about their experiences in HTA and development of generic information about their condition and its unmet needs that can be shared internationally. Finally they have a crucial role in evaluating HTA processes to ensure that they are fair and transparent. <h3>Disclosure of Interest</h3> K. Facey Consultant for: A range of health technology companies, HTA bodies and patient organsiations
Comparative Antithrombotic and Bleeding Effects of Two U.S. Generic Enoxaparins
Authors: Walter Jeske, Jeanine M. Walenga, Vicki Escalante, Debra Hoppensteadt, Josephine Cunanan, Daniel Kahn, Anwar Akhras, Michelle Paulus, Jawed Fareed, Mamdouh Bakhos
Journal: Blood (2012)
PTH-094 An Analysis of The Relationship Between Ethnicity and Hepatitis B (HBV) Phenotypes Over An 8 Year Period: Abstract PTH-094 Table 1
Authors: BD Warner, H Garnett, J Ria, TD Choudhury, M Farwana, M Chicco, K Ghafoor, K Singh, S Douthwaite, G Tritto, T Wong
Journal: Gut (2016)

<h3>Introduction</h3> Ethnicity is associated with certain HBV phenotypes which in turn affect prognosis. <h3>Methods</h3> We performed a search for patients with HBV DNA measured at GSTT(March 2007 to March 2015). sAg+ve patients were analysed for:Ethnic group,HIV,Hep C and D co-infection,eAg status, ALT and viral load. Phenotypes were assigned to patients at diagnosis and at last f/up.ALT cut offs were &gt;30 U/L for men and &gt;20 U/L for females.The American Association for the Study of Liver Disease guidelines divide HBV phenotype into 4 groups although a recent study defined an “Indeterminant” group for patients who do not fit into any phenotype <h3>Results</h3> 1799 patients were sAg+ve,mean f/up duration was 39.2 months(SD 41.2).45% of the cohort were lost to f/up.47% were male, mean age at diagnosis was 36(No difference between ethnicities).82% were eAg-ve,1.5% Hepatitis D+ve,10% HIV+ve,2% hepatitis C+ve. 49% of the cohort were African/Afro-Caribbean,14% Caucasian,10% Chinese,1.5% South Asian, 2.6% South East Asian(other than Chinese),0.3% Arab,3.4% Mixed,2.3% unknown,6.6% “other”. The table shows HBV phenotype at diagnosis compared to last f/up in all patients and then according to the 3 main ethnic groups.Rates of seroconversion and treatment are also shown. 90.5% of African/Afro-Caribbeans were eAg-ve compared to 71% of Caucasians and 63.9% of Chinese(P &lt; 0.01).There was an association between the risk of cirrhosis and older age at diagnosis,HIV or Hep C co-infection(P &lt; 0.01). Comparing the 3 largest ethnic groups only,in 2007,70% were African/Afro-Caribbean,19% Caucasian,11% Chinese compared to 51%,36% and 13% respectively in 2014. <h3>Conclusion</h3> Ethnicity is significantly associated with HBV phenotypes with a higher percentage of immunotolerants being Chinese and a higher percentage of African/Afro-Caribbeans being inactive. Compared to 2007,a higher percentage of HBV patients in 2014 were Caucasian reflecting changes in immigration.This may affect HBV outcomes and demand on Hepatology services. <h3>Disclosure of Interest</h3> None Declared
A Novel Heat Shock Protein (HSP) 90 Inhibitor KW-2478 shows Activity in B-Cell Malignancies in Vitro and in Vivo.
Authors: Simone Juliger, Takayuki Nakashima, Lenushka Maharaj, Toshihiko Ishii, Hiroshi Nakagawa, Yutaka Kanda, Heather Oakervee, James Cavenagh, Shiro Akinaga, Yukimasa Shiotsu, Simon P Joel
Journal: Blood (2008)
Early Impact Of a Nurse-Based Program To Reduce The Time From First Fever To Antibiotic Infusion In Neutropenic Patients In a Oncohematological and Bone Marrow Transplantation Unit In Brazil
Authors: Tania Michele Barreto Waisbeck, Guilherme Fleury Perini, Patricia do Carmo Della Vechia, Lidiane Soares Sodre Costa, Andrea Coletti, Cristina Vogel, Andreza Alice Feitosa Ribeiro, Nelson Hamerschlak
Journal: Blood (2013)
Dementia‐related adverse events in <scp>PARADIGM‐HF</scp> and other trials in heart failure with reduced ejection fraction
Authors: Jane A. Cannon, Li Shen, Pardeep S. Jhund, Søren L. Kristensen, Lars Køber, Fabian Chen, Jianjian Gong, Martin P. Lefkowitz, Jean L. Rouleau, Victor C. Shi, Karl Swedberg, Michael R. Zile, Scott D. Solomon, Milton Packer, John J.V. McMurray
Journal: European Journal of Heart Failure (2016)

Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials.In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with 'broad' and 'narrow' preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18-96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33-1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75-1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF.We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.
THU0119 Rheumatoid Arthritis and Periodontal Disease: Association between Salivary Citrulline, ACPA Levels and Clinical Presentation
Authors: I. Tar, Έ. Csösz, Έ. Veiszenbacher, E. Végh, K. Bágyi, K. Lundberg, N. Kharlamova, I. Márton, Z. Szekanecz
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Periodontitis and other dental conditions have been associated with the pathogenesis of rheumatoid arthritis (RA). In addition, these dental pathologies are also important comorbidities for RA. <h3>Objectives</h3> We wished to evaluate the periodontal involvement of rheumatoid arthritis (RA) patients, and we correlated with various laboratory biomarkers including lipids, autoantibodies, serum vitamin D levels, markers of bone metabolism in relation with the periodontal condition and cariological indices; and also correlated them with salivary citrulline and anti citrullinated protein autoantibody levels with the above mentioned clinical and blood test findings. <h3>Methods</h3> Twenty-three RA patients were recruited for the study. Saliva samples were taken following whole scale periodontal and cariological examination. Protein concentration, peptidyl-citrulline and anti-cyclic citrullinated protein (anti-CCP) levels were measured from saliva samples. Blood test results were provided by rheumatologists. Citrullinated enolase protein-1 (CEP-1) level from serum was also measured. <h3>Results</h3> Periodontal diagnoses (scores) seem to have a positive dependency on LDL (R=0.722, p=0.008), PTH1 (R=0.586, p=0.022), D<sub>3</sub> vitamin level (R=0.586, 0.022), the sum of D3/D2 (R=0.634, p=0.011) respectively, in these patients. Anti-CEP-1 positive patients had significantly higher periodontal scores (2.71±0.11 vs 2.50±0.09, p&lt;0.05) compared to anti-CEP-1 negative subjects. Interestingly, anti-CEP-1 positive patients had significantly higher triglyceride levels compared to seronegative ones (1.81±0.17 vs 1.42±0.05 mmol/l; p&lt;0.05). Salivary citrulline and salivary anti-CCP, (p=0.007, R: 0.583) level has a correlation with the maximum of clinical probing depth. <h3>Conclusions</h3> Our results may add further pieces to the mosaic of RA-periodontitis connection. The possible role of antimicrobial immunity, as well as the possible role of lipids and bone metabolism have also been delineated. Future therapies should aim the disruption of this framework. <h3>Disclosure of Interest</h3> None declared
Relevant Role of Von Willebrand Factor in Ischemia-Reperfusion Model of Acute Kidney Injury in Mice
Authors: Shiro Ono, Hideto Matsui, Masashi Noda, Shogo Kasuda, Yasunori Matsunari, Noritaka Yada, Kenji Nishio, Mitsuhiko Sugimoto
Journal: Blood (2015)
Similar Background of Graft-Versus-Host Disease (GVHD) Following Allogeneic Blood and Marrow Transplantation (Tx) in Korean and Japanese Populations Allows a Uniform Foundation To Perform Large-Scale Clinical Studies in the Region.
Authors: Sung-Won Kim, Jong-Wook Lee, Hyeoung-Joon Kim, Takahiro Fukuda, Yoshinobu Kanda, Hee-Je Kim, Woo-Sung Min, Shin-ichiro Mori, Ryuji Tanosaki, Je-Hwan Lee, Kyoo-Hyung Lee, Takuya Yamashita, Hisashi Sakamaki, Sang-Kyun Sohn, Yee-Soo Chae, Kumi Ohshima, Tatsuo Ichinohe, Junya Kanda, Masaharu Kasai, Naoki Kobayashi, Kiyoshi Ando, Masahito Onizuka, Shuichi Taniguchi, Sachiko Seo, Deok-Hwan Yang, Yeo-Kyeoung Kim, Ho-Jin Shin, Yoichi Takaue, Chun-Choo Kim
Journal: Blood (2007)