tbuckley/cabot-search huggingface dataset:
AB1117 Burden of Disease in Systemic Lupus Erythematosus Patients Treated with Corticosteroids
Authors: V. Strand, J. Johnson, C. Vandeloo, C. Galateanu, S. Lobosco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> Current treatments for systemic lupus erythematosus (SLE) include corticosteroids (CS), immunosuppressants (IM), antimalarials (AM) and biologics. SLE treatments, in particular CS, are associated with adverse effects which impact tolerability and treatment-burden. This study sought to assess the use of CS in SLE, and the burden associated with this treatment class. <h3>Methods</h3> Data were extracted from the Adelphi 2013 Lupus Disease-Specific Programme (a multinational survey of clinical practice). Physicians completed Patient Record Forms (PRFs) and underwent face-to-face interviews; patients self-reported data including the EQ-5D, Work Productivity and Activity Impairment Index for SLE (WPAI-Lupus) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in Patient Self-Completion Records (PSCs). Patient eligibility was determined by physicians; disease activity and severity were based on physician and patient assessment. <h3>Results</h3> Data were collected from rheumatologists in the USA (n=97), France (n=37) and Germany (n=35), including PRFs (550/200/207, respectively) and PSCs (303/109/149, respectively). 57%/84%/89% of patients in USA/France/Germany were receiving CS treatment. CS were perceived to be equal/superior to AM, IM and biologics in the ability to rapidly treat flare and pain but inferior in terms of safety/tolerability and inhibition of disease progression. More than half of patients had concerns regarding CS treatment, mainly due to side-effects and fear of long-term use. Patients receiving CS had greater resource use (increased IM/biologic use, greater physician consultation and hospitalization) and worse Health-Related Quality of Life (HRQoL) and activity impairment vs non-CS patients (EQ-5D=0.78 vs 0.87; FACIT-F=34.41 vs 39.56; WPAI=23.30 vs 13.22), but were also associated with worse clinical status (more moderate-to-severe SLE, more "deteriorating" disease state, more rash/pain/flaring/depression, greater organ system involvement). <h3>Conclusions</h3> Although a major component of SLE standard of care, clear unmet needs are associated with CS use regarding HRQoL and resource use. Long-term safety and tolerability are also major areas of concern for both physicians and patients. <h3>Acknowledgements</h3> The authors acknowledge Costello Medical Consulting for writing and editorial assistance which was funded by UCB Pharma. <h3>Disclosure of Interest</h3> V. Strand Consultant for: UCB Pharma, J. Johnson: None declared, C. Vandeloo Employee of: UCB Pharma, C. Galateanu Employee of: UCB Pharma, S. Lobosco: None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2239
SAT0375 Chronic low back pain in osteoporotic females with rheumatoid arthritis a randomized clinical trial
Authors: R.M. Traistaru, O. Rogoveanu, D. Matei, R. Popescu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Chronic low back pain (LBP) is one of the most common symptom in osteoporosis rheumatoid arthritis patients leading to complex disability (1). Various therapeutic approaches (range-of-motion exercises and exercise programs) have been proposed for chronic low back pain in patients with rheumatoid arthritis and osteoporosis and can delay the loss of joint function and help keep muscles strong (2) <h3>Objectives</h3> The aim of our study is to compare the effects of three therapeutic approaches in these patients in terms of pain, disability (severity of rheumatoid arthritis) and self-control of the complex disorders. We take into consideration the literature data about the evidence-based primary care options for chronic LBP. <h3>Methods</h3> 67 females (mean age 42.8 years) with rheumatoid arthritis (mean disease duration 6.8 years) and osteoporosis (mean disease duration 3,4 years) were randomized to the three groups in accordance to the type of treatment: I (23% of patients) - only medication, II (40% of patients) - medication + physiotherapy (TENS, interferential current, ultrasound), III (37% of patients) medication + aerobic training. The rehabilitation program was represented by 12 physiotherapy sessions and 18 aerobic training sessions (3 sessions/week). Outcome measures were VAS pain, DAS 28, BMD (T-Score), HAQ score and Arthritis Self-Efficacy Scale (ASES). All assessments were performed pre-post intervention and at six month follow-up. <h3>Results</h3> All the groups showed similar decrease in pain on the third assessment and there was no significant difference between the groups. In the first and group the second there was a significant improvement in DAS28 values (p&lt;0,05) as well as HAQ (p&lt;0,05) after treatment. The third group also showed significant improvement in DAS28 value as well as ASES and T Score at six month follow-up (p&lt;0,01). <h3>Conclusions</h3> All of the three therapeutic approaches were found to be effective in diminishing pain and disability in osteoporosis rheumatoid arthritis patients with chronic low back pain, but aerobic training was found to be more effective in improving bone mineral density (T-Score) and psychological status. Our results confirm the literature data - physical activity is an interesting therapy for the prevention and treatment of bone loss and osteoporosis because it has no adverse side effects, it is low cost, and it confers additional benefits such as postural stability and fall prevention. Type and duration of physical training must be individualized to each patient, in accordance with severity of rheumatoid arthritis. <h3>References</h3> Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B. (Aug 2007). Vitamin D in rheumatoid arthritis. Autoimmun Rev 7(1):59–64. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010 Sep 25;376(9746):1094-108. <h3>Disclosure of Interest</h3> None Declared
Abstract SY02-02: Inhibition of methyltransferase EZH2
Authors: Dashyant Dhanak
Journal: Cancer Research (2012)

Abstract Enhance of Zeste Homolog 2 (EZH2) is the biochemical activity of the Polycomb Repressive Complex 2 (PRC2) that transfers a methyl group from the cofactor S-adenosyl methionine (SAM) to histone H3 on lysine 27 (H3K27), resulting in epigenetic silencing of target gene expression. Activity of the multi-component PRC2 complex is crucial for normal development and differentiation. However, dysregulation of H3K27 methylation is implicated in tumorigenesis and occurs through multiple mechanisms. Elevated levels of EZH2 correlate with poor prognosis in a number of solid tumors including prostate, breast, kidney and lung. The increased EZH2 expression observed in many solid tumors has been linked to loss of one or more miRNAs including mir-101, mir-26A, and mir-214; aberrant E2F activity and chromosomal amplification. Inactivating mutations in UTX, an H3K27 demethylase which acts in opposition to EZH2, have been described in several tumor types including transitional cell bladder carcinoma, esophageal squamous cell carcinoma, renal cell carcinoma and multiple myeloma. Recently, somatic activating mutations in EZH2 have been identified in follicular lymphoma (FL) and GCB diffuse large B cell lymphoma (DLBCL). The frequency of the most prevalent mutation, Y641, is reported to be 7-12% in FL and as high as 22% in DLBCL. In view of the above, biochemical inhibitors of EZH2 may have therapeutic utility and herein we report on the identification and characterization of potent and selective small molecule EZH2 inhibitors with in vitro and in vivo antiproliferative activity in cancer cell lines and mouse xenografts. The studies provide a compelling rationale for the clinical evaluation of EZH2 inhibitors in EZH2 driven human cancers. 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 SY02-02. doi:1538-7445.AM2012-SY02-02
Abstract 1704: AC electrokinetic isolation of cell free high molecular weight DNA (CF-HMW DNA) from serum
Authors: Jerry Lu, William Hanna, Lucas S. Kumosa, Megha Bhalla, Veronica W. Cheung, Robert P. Turner, James P. McCanna, Eugene Tu, David J. Charlot, Rajaram Krishnan
Journal: Cancer Research (2012)

Abstract Recent reports of CF-HMW DNA in a variety of diseases has led to interest in its use as a prognostic biomarker, a diagnostic or screening tool for cancer. Apoptotic DNA (&amp;lt;200bp) is present in the circulation of normal healthy individuals. In cancer, unregulated cell growth leads to uncontrolled cell death, or necrosis, which produces HMW DNA (&amp;gt;500bp) that is then trafficked into circulation. Dielectrophoresis, or DEP (movement of particles in a non-uniform AC electric field), based electrokinetic techniques have been used for protein biomarker screening, cell separation, and DNA manipulation. Using specific DEP frequencies, analytes are moved to known locations (high or low field region) based on their inherent dielectric properties. The process allows specific nano-sized particles to be highly concentrated into high field regions, while micron-size cells are held weakly in low field regions. With fluidic washing, cells can be removed while nano-sized particles are held in high field regions. This method can effectively act as a CF-HMW DNA enrichment process for biological fluids. Unfortunately, DEP does not work well in (high conductance) physiological buffers, requiring significant dilution of the sample and, as a result, the target analyte concentration. Here, we describe a novel AC electrokinetic (ACE) technique using a custom microelectrode array and AC parameters to isolate and analyze CF-HMW DNA from high conductance serum. DNA from normal serum samples and the A549 cell line were isolated using Qiagen kits to determine initial DNA quantities. Normal sera were spiked with A549 cell line DNA at concentrations from 0 to 500 ng/ml and subjected to a 20 minute ACE protocol. DNA isolation was visualized in situ using SYBR Green I fluorescence and then eluted for use in secondary analyses. Results showed minimal fluorescence from samples without spike whereas A549 DNA spiked samples showed concentration-dependent fluorescence on the microelectrodes. After elution, levels of DNA were quantitated using ALU-sequence based qPCR and K-ras mutational status was confirmed by ABI CastPCR. Future experiments will compare CF-HMW DNA levels from normal and cancer patients across a variety of solid tumors. The ACE technique enables rapid isolation and detection of CF-HMW DNA directly from biological fluids without prior sample prep and has broad utility for diagnosis and monitoring of cancer and other diseases in which CF-HMW DNA may be used as a marker. 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 1704. doi:1538-7445.AM2012-1704
Heterogeneity of Genomic Signatures in Breast Cancer Core Biopsy
Authors: M. Jarzab, W. Bal, M. Kowalska, M. Kowal, J. Rembak-Szynkiewicz, K. Steinhof-Radwan´ska, E. Stobiecka, E. Chmielik, B. Bobek-Billewicz, R. Tarnawski
Journal: Annals of Oncology (2013)
Abstract 3701: Dimethylbenzanthracene (DMBA) and DMBA dihydrodiol mutagenicity in rat epithelial and fibroblast cell lines, and its inhibition by combinations of nutraceuticals
Authors: Peter G. Sacks, Zhong-Lin Zhao, Wieslawa Kosinska, Zhiming He, P. David Josephy, Joseph B. Guttenplan
Journal: Cancer Research (2011)

Abstract 7,12-Dimethylbenzanthracene (DMBA) is a potent mammary carcinogen in rats. Combinations of non-toxic nutraceutical agents, administered at or near physiological levels, were investigated for their abilities to inhibit the mutagenicity of DMBA or DMBA-dihydrodiol (DMBAD, a primary metabolite and proximate mutagen of DMBA) in vitro, in rat mammary epithelial and fibroblast cells derived from a lacI (BigBlue) Fischer rat (McDiarmid, H.M., Douglas, G.R., Coomber, B.L., and Josephy, P.D. Epithelial and fibroblast cell lines cultured from the transgenic BigBlue rat: an in vitro mutagenesis assay. Mutat. Res., 497: 39-47, 2001). In the epithelial cells, DMBA was not appreciably mutagenic at concentrations up to 4 µM, but DMBAD, was significantly mutagenic at ten-fold lower concentrations. These results indicate that the epithelial cells can bioactivate the intermediate, DMBAD, but cannot effect the complete biotransformation of DMBA to its ultimate mutagenic metabolite, DMBA-dihydrodiolepoxide. In the fibroblast cell line, in contrast, DMBA was mutagenic at concentrations as low as 20 nM and DMBAD was even more potent than DMBA. Several combinations of nutraceuticals (dietary components providing health benefits) were tested for their abilities to inhibit mutagenesis in these cell lines; the concentrations tested were based on reported serum concentrations and these were used to establish 1x concentrations. The agents and their 1x concentrations were: resveratrol (Res), 2.4 μM; sulforaphane (Sul), 0.06 μM; antioxidant mix (α- and γ-tocopherol, 30 μM, plus vitamin C, 68 μM – VCE); α-lipoic acid (LA), 2 μM; epigallocatechin gallate (EGCG), 0.7 μM; and N-acetylcysteine (NAC), 12 μM. None of the agents or their combinations, tested at 1 – 3 x concentrations, showed any cytotoxicity. In both epithelial and fibroblast cells, Sul and Res alone slightly inhibited mutagenesis at 2x concentrations; no other agents had observable effects. All binary combinations of Res, LA, and Sul, at 2x concentrations, inhibited mutagenesis; the Res + Sul combination was particularly effective (ca. 50% inhibition). These results suggest a role for fibroblast cells in the bioactivation of carcinogens, implicating the microenvironment, and indicate that combinations of nutraceuticals can inhibit mutagenesis by polycyclic aromatic hydrocarbons. Supported by the Susan Komen Foundation grant # KG080836 (JBG) and NSERC Canada (PDJ). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3701. doi:10.1158/1538-7445.AM2011-3701
Thyrotoxic Periodic Paralysis in Chinese Patients
Authors: Wen Long, Yansong Lin
Journal: Clinical Nuclear Medicine (2013)

Thyrotoxic periodic paralysis (TPP) is a complication of thyrotoxicosis mainly observed in male Asian patients. It was proposed that patients with TPP tend to have lower thyroid hormone levels. We aimed to prove this observation and to assess whether a lower I dose is feasible for prompt control of TPP.A total of 123 male TPP patients were enrolled in this study in a 7-year period. Baseline characteristics were compared with 70 thyrotoxic patients without periodic paralysis (nTPP). Different I doses were given to 90 TPP patients with a median follow-up of 11 months, and the outcome was evaluated.The serum thyroid hormone levels, including total T3 and T4, and free T3 and T4, in TPP patients were slightly less elevated compared with those in nTPP patients. Patients who received lower radioactivity of I had an unsatisfactory overall remission rate of 28.6%. Longer time to remission (P = 0.004; hazard ratio, 1.846; 95% confidence interval, 1.216-2.798) was also observed in patients with lower dose.The serum thyroid hormone levels of TPP patients are lower than those of nTPP patients. Median/high dose of I is necessary to achieve rapid control of thyrotoxicosis.
AB0132 Presence of Synovial Lymphocyte Aggregates Correlates with A More Severe Clinical Phenotype in Patients with Early Inflammatory Arthritis
Authors: M. Di Cicco, F. Humby, S. Kelly, N. Ng, A. Mahto, R. Hands, V. Rocher, M. Bombardieri, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although many observations have suggested that ectopic lymphoid structures within the inflamed synovium are immunologically functional and can support chronic inflammation, their clinical significance is still controversial. Moreover, most of data comes from patients with long standing disease activity, while data in early arthritis is still scarce. In particular, it is unclear whether the presence of lymphocytic aggregates within the synovium correlates with clinical phenotype and degree of inflammation in early inflammatory arthritis patients. <h3>Objectives</h3> The aim of this study is to evaluate the correlation between synovial lymphocytic aggregates with clinical phenotype in an early inflammatory arthritis cohort. <h3>Methods</h3> 155 disease-modifying antirheumatic drug-naïve patients with early inflammatory arthritis (&lt;12 months duration, at least 1 swollen joints) has been recruited at Barts and The London Hospital. Baseline disease characteristics assessment included erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) and 28 joints-disease activity score (DAS28). Ultrasound-guided synovial biopsy has been obtained for all patients. Sections of paraffin embedded synovial tissue were stained with standard Haematoxylin and Eosin (H&amp;E) and graded as either a diffuse or aggregate synovitis. The degree of lymphoid organisation was further assessed by immnohistochemical staining of sequentially cut sections. The number of lymphocytic aggregates was counted in each section and graded according to a validated, previously published grading system [Manzo, A. et al; European Journal of Immunology2005]. <h3>Results</h3> The presence of lymphocytic aggregates has been found in almost 30% of patients; Lymphocytic aggregates are associated with increased inflammatory markers and DAS28, as well as RF and CCP seropositivity (p&lt;0.05); The number of B cells and plasma cells in the synovium of early rheumatoid arthritis patients is closely associated (p&lt;0.05), suggesting in situ differentiation. <h3>Conclusions</h3> The presence of lymphocytic aggregates within the synovium in early arthritis correlates with a more severe clinical phenotype, including inflammatory markers, disease activity and antibody status. Further studies are needed in order to establish the clinical relevance of this association, and in particular its potential prognostic value. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5836
Low-Molecular-Weight Heparin (Enoxaparin) as Prophylaxis against Venous Thromboembolism after Total Hip Replacement
Authors: David Bergqvist, Göran Benoni, Ola Björgell, Hans Fredin, Urban Hedlundh, Sylvain Nicolas, Paul Nilsson, Göran Nylander
Journal: New England Journal of Medicine (1996)

The risk of venous thromboembolism in patients undergoing total hip replacement is known to be high. However, the optimal duration of prophylaxis with anticoagulant agents after this procedure is unknown. We sought to determine whether one month of anticoagulant therapy with the low-molecular-weight heparin enoxaparin is more effective than enoxaparin therapy given only during the hospitalization for surgery.Two hundred sixty-two patients undergoing total hip replacement received enoxaparin during their hospitalizations (average stay, 10 to 11 days). They were then randomly assigned to receive enoxaparin or placebo (131 patients each). Blinded outpatient therapy (or placebo) was continued long enough that the total treatment period, inpatient plus outpatient, was one month for each patient. Bilateral ascending phlebography was performed 19 to 23 days after discharge, with deep-vein thrombosis as the primary end point. Distal and proximal thrombosis, pulmonary embolism, and hemorrhage were also recorded, as were deaths.Venography was adequate in 116 patients in the placebo group and 117 in the enoxaparin group. We observed 43 episodes of deep-vein thrombosis and 2 episodes of pulmonary embolism in the placebo group, but only 21 episodes of deep-vein thrombosis and no episodes of pulmonary embolism in the enoxaparin group (incidence of thromboembolism, 39 percent and 18 percent, respectively; P<0.001). The difference in the incidence of proximal deep-vein thrombosis was also significant (24 percent and 7 percent in the placebo and enoxaparin groups, respectively; P<0.001). Six enoxaparin groups, respectively; P<0.001). Six patients in the enoxaparin group and one patient in the placebo group had hematomas at their injection sites. No patients died or had major complications.There were significantly fewer venous thromboembolic complications in patients undergoing elective hip replacement when prophylaxis with enoxaparin was given for a total of one month, rather than only during the hospitalization.
Role for Pregnant Women in Clinical Trials Debated
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Role for Pregnant Women in Clinical Trials Debated Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 24, 21 December 1994, Pages 1820–1822, https://doi.org/10.1093/jnci/86.24.1820 Published: 21 December 1994
AB0945 Heparin-Binding Protein (HBP) in Joint Fluid Distinguishes Rheumatoid Arthritis from Osteoarthritis
Authors: A. Gülfe, A. Linder
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Heparin-binding protein (HBP, azurocidin, cationic antimicrobial protein of 37 kDa), a serin protease abundant in neutrophil granulocytes, has shown promise as a plasma marker of severe sepsis, but it has not been studied in joint fluid. It has been demonstrated to be a powerful promoter of vascular permeability, causing plasma leakage. <h3>Objectives</h3> To (i) investigate the feasibility of HBP analysis in joint fluid and to (ii) determine HBP levels in rheumatoid arthritis (RA) and osteoarthritis (OA) joint fluid. <h3>Methods</h3> Knee joint fluid was drawn from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) in need of a local steroid injection and stored at -80° C after centrifugation. HBP concentrations were determined using ELISA (1). A few of the RA patients were on disease-modifying anti-rheumatic drugs but none on biologics. <h3>Results</h3> In RA (n=54), HBP median (interquartile range) concentration was 172 (6.43-448) ng/mL and in OA (n=22) the corresponding values were 5.80 (3.62-15.1) ng/mL. This difference was statistically significant (Mann-Whitney U-test, p&lt;0.0001) (Figure). <h3>Conclusions</h3> In this pilot study, to our knowledge the first investigating HBP in other body fluids than plasma and cerebrospinal fluid, measurement of HBP in joint fluid was shown to be feasible. Significantly higher levels were demonstrated in RA than in OA. <h3>References</h3> Tapper H, Karlsson A, Mörgelin M et al: Blood 2002; 99:1785-1793 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1818