tbuckley/cabot-search huggingface dataset:
SAT0055 18-Month Cardiovascular Risk Assessment in Rheumatoid Arthritis (RA) Patients Treated by Biologic Response Modifiers
Authors: M. Khraishi, R. Aslanov, K. Doyle
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The pathogenic mechanisms involved in increased CV complications in RA patients are multifactorial due to RA-related inflammation as well as the traditional risk factors affecting the general population. <h3>Objectives</h3> To assess 10-year CV event risk in patients with RA at the baseline, 12 and 18 months after the initiation of treatment with Biologic DMARDs (BDMARDs). <h3>Methods</h3> 215 patients with RA receiving biologic therapy (Etanercept, Adalimumab, Rituximab, Tocilizumab and Abatacept) were included in this study. The FRS was used for the assessment of the 10-year CV risk. The presence of CV risk factors was ascertained by a medical records review throughout the study. Paired t-test and Regression analyses before and after treatment with biologics were performed. The mean age was 55.6 (12) years. The mean age at RA diagnosis was 41.6 (13.2) years with mean duration of RA 14.6 (8.6) years. 7 patients had MI and 5 TIA/Stroke prior to the study. 41 patients smoked at the baseline. 61 patients were on Lipid-lowering treatment, of them 31 (45%) started it after the initiation of the treatment with biologics. TJC and SJC were significantly reduced after 12 and 18 months of treatment. The mean TC not significantly increased from the baseline measures. HDL significantly increased at 12-month and not significantly at 18-month period. The AI was significantly reduced during the two follow-up periods. CRP, ESR and DAS28 were also significantly reduced from the baseline levels. Patients were grouped by their 10-year CVD risk level: 5.2% of men and 3.8% of women in an 18-month period lowered their risk from the high to the moderate/low. The overall risk of CVD was slightly reduced at 12-month but significantly at 18-month (from 11.5±9.4 to 10.7±8.9, p=0.011; 95%CI 0.18-1.36). 10-year CV event risk was significantly improved at 18-month in Tocilizumab (14.2±10.0 vs. 12.7±9.1; p=0.026; 95%CI 0.20-2.85) and Abatacept (12.7±10.3 vs. 10.6±9.8; p=0.011; 95%CI 0.53-3.64) cohorts. <h3>Conclusions</h3> Our findings showed a trend in reducing a 10-year CV event risk over 18-month period. No CV event was observed during the study period. The results demonstrated a favorable effect of BDMARDs on the levels of atheroprotective HDL-C. Good control of the chronic inflammation by biologic DMARDs effectively decreased the intermittent disease activity and possibly played a pivotal role in reducing the risk for CV event in patients with RA. <h3>Disclosure of Interest</h3> M. Khraishi Grant/research support from: Dr. Khraishi received non restricted educational grants from Hoffman-La Roche Canada, Amgen and Pfizer Canada, and Abbott Canada, R. Aslanov: None Declared
Abstract 2351: Evaluation of KRAS and BRAF mutation analysis in primary metastatic colorectal cancers versus matched syn- and metachronous metastases
Authors: Wolfgang Dietmaier, Alexander Kiesl, Corinna Lang-Schwarz, Petra Ruemmele, Benedikt Groeschl, Ferdinand Hofstaedter
Journal: Cancer Research (2010)

Abstract Background: The KRAS mutation status was shown in recent studies to be a predictive biomarker for anti-EGFR monoclonal antibody (mAB) therapy in metastatic colorectal cancer (mCRC). Patients without KRAS mutations (wild type KRAS) did benefit from anti-EGFR-mAB therapy whereas patients with tumors bearing a KRAS mutation did not benefit from this targeted therapy. KRAS mutation analysis is thus required before anti-EGFR-mAB treatment in all mCRCs. As published in the clinical studies, primary tumors are commonly used as the standard tissue. However, KRAS mutation analysis is often complicated because primary tumors are being discarded by many institutes of pathology years after diagnosis. Instead recent metastases are available and are used for KRAS mutation analysis. However the question is raised if primary tumors and metastases are equally informative regarding the KRAS and BRAF mutation status especially when considering the multiple steps during tumor cell dissemination and metastatic processes. So far only little and heterogeneous data are available about this issue. Patients and methods: To address this question we performed a KRAS mutation analysis (codons 12, 13, 61) in 111 colorectal cancers and 171 matched metastases in lymph nodes, liver, lung, ovary, peritoneum, brain, urinary bladder and bone. Additionally, BRAF mutation analysis was done in all KRAS wild type tumors. In addition, multiple (&amp;gt;=2) matched synchronous or metachronous metastases and corresponding primary tumors were analysed in 44 cases. KRAS and BRAF mutation analysis was done using pyrosequencing technology. Tumor cells were gained either by microscopically controlled manual microdissection or by laser assisted microdissection. Results: Primary tumors and matched metastases with initially discrepantly appearing KRAS mutation status were re-analysed using laser-microdissection. By means of laser microdissection we finally did not find any discrepancies in the KRAS and BRAF mutation status in primary tumors versus matched syn- or metachronous metastases. Conclusion: KRAS and BRAF mutation analysis in metastases appears to be as valid as in primary tumors and should serve as reliable specimens in cases where primary tumors are not available to predict response to therapies with anti-EGFR targeted monoclonal antibodies in metastatic colorectal cancer. 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 2351.
Daring to Practice Low-Cost Medicine in a High-Tech Era
Authors: Sean Palfrey
Journal: New England Journal of Medicine (2011)

A child with chest pain or tics, a toddler who is limping, a 12-year-old girl with abdominal pain or headaches, an infant whose fever does not respond to antibiotics — these are age-old challenges that pediatricians face. I have been teaching pediatrics to residents and medical students for more than three decades, but over the past few years, as I've watched trainees at work, sitting at their computers, and ordering and monitoring tests, I've grown worried that the practice of medicine has tipped out of balance.Recent advances in scientific knowledge and technology have resulted in the development of a . . .
The Use of Medicare Home Health Care Services
Authors: H. Gilbert Welch, David E. Wennberg, W. Pete Welch
Journal: New England Journal of Medicine (1996)

Medicare's home health care program, consisting primarily of home visits by nurses and health aides, was conceived as a means to facilitate hospital discharge. Because home health care is now one of the fastest-growing categories of Medicare expenditures, we analyzed Medicare claims data to determine current patterns of use.
Assessing the Risk of Breast Cancer
Authors: Katrina Armstrong, Andrea Eisen, Barbara Weber
Journal: New England Journal of Medicine (2000)

Each year in the United States, breast cancer is diagnosed in more than 170,000 women.1 Despite this substantial burden of disease, however, assessment of breast-cancer risk has received very little attention outside the oncology clinic.2,3 In primary care, the main result of the recognition of individual variation in breast-cancer risk is the use of age to determine recommendations regarding mammography (older age is a strong risk factor for breast cancer).4 Recent developments in the ability to predict and alter breast-cancer risk warrant a new look at the role of assessment of this risk in primary care. Physicians must become . . .
Chemotherapy Compared with Autologous or Allogeneic Bone Marrow Transplantation in the Management of Acute Myeloid Leukemia in First Remission
Authors: Peter A. Cassileth, David P. Harrington, Frederick R. Appelbaum, Hillard M. Lazarus, Jacob M. Rowe, Elisabeth Paietta, Cheryl Willman, David D. Hurd, John M. Bennett, Karl G. Blume, David R. Head, Peter H. Wiernik
Journal: New England Journal of Medicine (1998)

In young adults with acute myeloid leukemia, intensive chemotherapy during the initial remission improves the long-term outcome, but the role of bone marrow transplantation is uncertain. We compared high-dose cytarabine with autologous or allogeneic marrow transplantation during the first remission of acute myeloid leukemia.
ARRHYTHMIAS AND ASSOCIATED OUTCOMES IN ADULTS WITH CONGENITAL HEART DISEASE IN THE UNITED STATES
Authors: Dhaval Kolte, Sahil Khera, Prakash Harikrishnan, Chandrasekar Palaniswamy, Marjan Mujib, Wilbert Aronow, Diwakar Jain, Sachin Sule, Ali Ahmed, William Frishman, Howard Cooper, Jason Jacobson, Sei Iwai, Gregg Fonarow, Julio Panza
Journal: Journal of the American College of Cardiology (2015)
A2.3 AnTI-Apoptotic IgG Antibodies from Patients with Primary Sjögren’s Syndrome and Systemic Lupus Erythematosus Inhibit the Phagocytosis of Apoptotic Cells
Authors: Aigli G Vakrakou, George E Fragoulis, Menelaos N Manoussakis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> Recent studies in our laboratory have revealed that a significant portion of SS patients manifests significantly impaired phagocytosis of apoptotic cells (ApoCell-phagocytosis), in a manner similar to SLE, a fact which probably leads to the inflammatory and autoimmune responses that characterise these two disorders. Furthermore, our data indicate that approximately 80% of sera from patients with SS and SLE, but not those with RA and healthy individuals, inhibit the clearance of early apoptotic cells from healthy monocytes. In the present study, we sought to investigate the role of IgG immunoglobulins from patients with SLE and SS in the phagocytosis of apoptotic cells. <h3>Materials and Methods</h3> Total IgG immunoglobulin was isolated from the serum of patients with SS (n = 24), SLE (n = 12) and RA (n = 8) and healthy donors (n = 11) using Melon Gel Resin columns. Apoptotic Jurkat cells (induction of apoptosis by UV-radiation) were incubated with purified IgG (50 µg/ml) in PBS/BSA 1%. The binding of IgG on the surface of apoptotic cells was assessed by flow cytometry and analysed with the binding index (% positive cells × mean fluorescence intensity). ApoCell-phagocytosis was assessed by flow cytometry using monocyte-derived macrophages (MDM) from healthy individuals (n = 3) that were incubated (90 min) with CFSE-labelled early apoptotic Jurkat cells which had been opsonised with IgG from patients or healthy individuals or with PBS (control). <h3>Results</h3> IgG from patients with SS and SLE exhibited high binding levels in apoptotic cells compared to healthy donors and patients with RA (all for p &lt; 0.0001). Pre-incubation of apoptotic cells with IgG from patients with both SS and SLE had a significant inhibitory effect on the phagocytosis process (comparative ApoCell-phagocytosis: after pre-incubation with PBS [x = 100%], with IgG from healthy individuals [n = 11, x = 100%], with IgG from RA patients [n = 4, x = 100%], with IgG from SS patients [n = 17, x = 75%, p &lt; 0.0001], with IgG from SLE patients [n = 10, x = 71%, p = 0.0002]). Finally, negative correlation was found between the apoptotic cell binding levels of IgG from patients and healthy individuals and the results of ApoCell-phagocytosis assays using apoptotic cells pre-incubated with the corresponding IgG (n = 42, p &lt; 0.0001). <h3>Conclusions</h3> Our results indicate that the impaired phagocytosis of apoptotic cells observed in patients with SS and SLE is primarily due to the presence of antibodies reactive with the surface of apoptotic cells. Further studies need to focus on the mechanism by which immunoglobulins exert such blocking effect, as well as its immunological consequences.
Abstract 3324: The discovery and optimisation of small-molecule inhibitors of human 5’-tyrosyl DNA phosphodiesterase (Tdp2).
Authors: Allan M. Jordan, Paul Depledge, Nicola Hamilton, James Hitchin, Gemma Hopkins, Laura Maguire, Alison McGonagle, Daniel Mould, Ali Raoof, Mathew Rushbrooke, James Smith, Kate Smilth, Graeme Thomson, Fabrice Turlais, Ian Waddell, Mandy Watson, Donald Ogilvie
Journal: Cancer Research (2013)

Abstract Topoisomerases (topo) regulate DNA topology by the transient cleavage and re-ligation of DNA during transcription and replication. Topo II poisons such as etoposide can induce abortive DNA strand breaks in which topo II remains covalently bound to a 5’ DNA strand terminus via a phosphotyrosyl linker. Tyrosyl DNA phosphodiesterase 2 (Tdp2, TTRAP, EAPII) is a recently discovered human 5’-tyrosyl DNA phosphodiesterase which repairs this topo-mediated DNA damage, therefore playing a central role in maintaining normal DNA topology in cells. Cellular depletion of Tdp2 has been shown to result in an increased susceptibility and sensitivity to topo II-induced DNA double strand breaks. It has therefore been proposed that selective pharmacological inhibition of Tdp2 may be a novel approach to overcome intrinsic or acquired resistance to topo II targeted drug therapy. To date, no known drug-like inhibitors of Tdp2 have been identified. We have recently reported a robust ‘mix and read’ HTS compatible assay and this was used to screen a diverse chemical library of approximately 92,000 compounds. From this endeavour, 2 distinct hit series have been identified. Following further chemical exploration of the original hit compounds, small molecule inhibitors of Tdp2 with sub-100nM potencies have been identified. This poster will describe our biological and chemical progress in this area, detailing SAR and some lessons learnt during investigation of this target. Citation Format: Allan M. Jordan, Paul Depledge, Nicola Hamilton, James Hitchin, Gemma Hopkins, Laura Maguire, Alison McGonagle, Daniel Mould, Ali Raoof, Mathew Rushbrooke, James Smith, Kate Smilth, Graeme Thomson, Fabrice Turlais, Ian Waddell, Mandy Watson, Donald Ogilvie. The discovery and optimisation of small-molecule inhibitors of human 5’-tyrosyl DNA phosphodiesterase (Tdp2). [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 3324. doi:10.1158/1538-7445.AM2013-3324
Abstract 1494: Intrinsic and extrinsic TME factors modulate breast cancer progression
Authors: Andrea L. George, Shilpi Rajoria, Robert Suriano, Abraham Mittelman, Raj K. Tiwari
Journal: Cancer Research (2012)

Abstract The tumor microenvironment (TME) of breast cancer is a heterogeneous population of tumor cells, infiltrating endothelial cells, immunomodulatory cells, and underlying stroma. This cellular cross-talk is key to tumor progression; however the signaling pathways involved remain unclear. Rapid expansion of breast cancer cells requires sufficient supply of oxygenated blood supported by tumor induced neovasculature. Our previous studies demonstrated that estrogen mediates neovascularization via recruitment of bone marrow derived endothelial progenitor cells (BM-EPCs). However, hypoxia, a major cellular characteristic of cancer cell growth, mimics estrogen induced vascularization as evidenced by HIF-1α translocation and secretion of vascular endothelial growth factor (VEGF). These studies were carried out in the TG1-1 murine mammary cancer cell line and used as a model. Conditioned media from TG1-1 cells enhanced endothelial cell migration and tube formation in vitro. Treatment of tumor cells with the anti-estrogen Fulvestrant as well as the HIF-1 inhibitor YC-1 abrogated the effects of estrogen. Further, use of the PI3K inhibitor wortmannin as well as the protein inhibitor cyclohexamide, elucidated the necessity of a functional AKT signaling pathway in this estrogen induced neovasculogenesis. While the cell-cell interaction studies demonstrate a considerable modulation of the tumor microenvironment, the co-culture experiments using immunomodulatory cells and epithelial cells induced epithelial to mesenchymal transition (EMT) in TG1-1 cells. We demonstrated that the murine macrophage cell line RAW264.7 secretes factors that modulate tumor cell EMT via upregulation of TWIST and Slug and an increase in tumor cell migration and invasion. To elucidate the modulatory secreted factors, we performed western blot analysis of the TGF-β signaling pathway and observed differences in SMAD levels. However, neutralizing antibody studies indicate that TGF-β is not the sole modulator of RAW264.7 induced EMT in Tg1-1 cells. Taken together, cytokines as extrinisic factors and tumor hypoxic conditions generating intrinsic factors, act in concert to alter breast cancer progression. Our data demonstrate a need to target multiple TME interacting pathways as a future breast cancer treatment strategy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1494. doi:1538-7445.AM2012-1494
SAT0150 Prevalence of Forefoot Deformities in Patients with Rheumatoid Arthritis – A Cross-Sectional Study from Kurama Cohort-
Authors: H. Ito, Y. Hamamoto, M. Furu, M. Hashimoto, T. Fujii, M. Ishikawa, N. Yamakawa, C. Terao, T. Mimori, S. Matsuda
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Forefoot deformity is one of the most dominant deformities in patients with rheumatoid arthritis (RA). However, the prevalence, degree, contributing factors and influence on daily activity are not well understood. We conducted a cross-sectional study on this subject using a comprehensive RA cohort (KURAMA cohort). <h3>Objectives</h3> To investigate the prevalence, contributing factors and the influence of daily activity of forefoot deformities from a RA cohort. <h3>Methods</h3> Surveillance was performed on 740 feet of 370 patients with RA in KURAMA cohort. The average age was 62.9 years old, and the female ratio was 87.6%. The statistical analyses were conducted using demographic data such as age, gender, the duration of disease, disease activity, and functional activity, and radiological measurements such as hallux valgus angle, metatarsal deformities (M1M2 angle), Larsen grade of metatarsophalangeal joints (MTP joints) and dislocation of the MTP joints. <h3>Results</h3> Hallux valgus deformity was found in 47%, and severe deformity (40°&lt;HV angle) was in 13% of patients. Severe spread foot was found in 10%. Joint destruction evaluated by Larsen grade was found in 34%, 26%, 24%, 24%, and 30% of the first to the fifth MTP joint, respectively. Joint dislocation was found 13%, 8%, 8%, 5%, and 10% of the first to the fifth MTP joint, respectively. The presence of forefoot deformities was significantly associated with the duration of the disease (p=0.003), but not with age, gender, medication and disease activity at the time of surveillance. Moreover, the presence of forefoot deformities was significantly associated with functional activity (HAQ) (p=0.005). Found was 30% of patients with two or more MTP joint destruction despite of no or slight deformity of both wrist joints. <h3>Conclusions</h3> We found a high prevalence of forefoot deformities in patients with RA. The dominance of forefoot deformities compared with the wrist joint was found 30% of patients, and the deformities was associated with functional activities. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1599
AB0815-PC Patients with osteoartrhritis in an area with ageing population
Authors: J. Lopez, S. fernandez, A. B. Vega, A. Rodriguez, Y. Ureña, M. López
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The osteoarthritis is one of the most frequent consultations in primary medical care. The prevalence is between 6, 2 % and 26, 1 %. This is more frequent in women than in men. The results are similar to those of Europe, where people older than 75, the prevalence in women is double than in men. <h3>Objectives</h3> To know the prevalence of osteoarthritis in the different locations in our patients, the different treatment that this patient’s use, how much pain they refer and the health education they have. <h3>Methods</h3> Design This is a transversal descriptive study in a basic urban area of health (19.658 persons &gt; 14 years, 16.2% &gt; 75 years. Population Randomization 450 osteoarthritis patients from 2514 patients with this diagnostic. Review the clinic histories and after that we interview the patients in the consultation or by telephone (patients or patients’ family) Variables Age, sex, localization, overweight, drug treatment (analgesic, AINEs, Sysadoas, capsaicin, IBP/antagonists H2), slim if overweight, Physical exercise (walking &gt; 30 minutes 3 days/week). Physical measures, prosthesis, orthoses, rehabilitation, balneareoteraphy, alternative therapy, health education, how much pain (pain descriptive verbal scale). <h3>Results</h3> We interview 406 patients (80,5%) 243 in the consulting room. Middle age 71 yeras (15,2), woman 73,6%. They describe the pain like moderate 30,4% and much several pain 26%. 81.9% the patient’s used≥1 drug, and 2 drugs 42%. The 60.9% have drug when they have pain, the 18.1% have drugs all time (&gt;3 month). Overweight 42,8%. Only 8,7% have normalized the weight. The 65% said that they know their illness and the 73% said that their the doctors has given their recommendation about doing exercise and losing weight <h3>Conclusions</h3> The localization more frequent is the knees, the most patients needs drugs. Only 25% are in the ideal weight but a few patients are slimming. <h3>References</h3> Carmona L, Ballina J, Gabriel R, Laffon A, EPISER Study Group. The burden of musculoskeletal diseases in the general population of Spain: results from a national survey. Ann Rheum Dis. 2001; 60:1040-5. Medline Hunsche E, Chancellor JV, Bruce N. The burden of arthritis and nonsteroidal anti-inflammatory treatment. A European literature review. Pharmacoeconomics. 2001; 19(Suppl 1):1-15. Medline <h3>Disclosure of Interest</h3> None Declared
AB0159 The Investigation of Blood Micro-Rna Levels in Ankylosing Spondylitis and the Relationship between Disease Activity and Functional Capacity
Authors: K. Çoğul, A. Biçer, S. Balcı, S. Akbayır, L. Tamer
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing Spondylitis (AS) is a chronic inflammatory disease which affects axiel and peripheral joints. The relationship between AS and microRNAs (miRNAs) has not been well documented in the literature. <h3>Objectives</h3> The objective of this study is to investigate some of the blood miRNA levels in patients with AS, and their correlations between disease activity and functional capacity. <h3>Methods</h3> Fifty patients with AS and 42 healty volunteers, total of 92 subjects have been enrolled in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, the The Bath Ankylosing Spondylitis Functional Index (BASFI) and The Bath Ankylosing Spondylitis Metrology (BASMI) scores have been calculated. miRNA analysis were carried out by using high capacity real-time Polymerase Chain Reaction (PCR) method. <h3>Results</h3> No significant relationship has been found between patients and healty subjects in terms of miRNA expressions. Expressions of miRNA-16-5p, miRNA-451a, miRNA-320a, miRNA-126-3p, miRNA-17-5p, miRNA 146a-5p and miRNA-223-3p were found to be in low levels in patients with AS. Positive correlations between BASDAI and BASFI scores with the expression of miRNA-205-5p have been found in patients with AS. <h3>Conclusions</h3> The results of our study have revealed that there was no any relationship between AS and the blood expression of miRNA levels. However, the blood expression of miRNA-205-5p may play a role in terms of disease activity and functional capacity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3529