tbuckley/cabot-search huggingface dataset:
SP0120 How to Treat Interstitial Lung Disease in Rheumatic Diseases – Lessons Beyond Cyclophosphamide
Authors: B. M. Lynch
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Parenchymal lung disease is an important complication of autoimmune rheumatic disease. There are a variety of patterns recognised; non-specific interstitial pneumonia (NSIP) and organising pneumonia (OP) being most prevalent but other processes include usual interstitial pneumonia (UIP), diffuse alveolar damage (DAD), reactive pulmonary lymphoid hyperplasia, desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RBILD). Pulmonary involvement is the leading cause of morbidity and mortality in Systemic Sclerosis. A variety of immunosuppressive agents have been evaluated as potential disease-modifying therapies in systemic sclerosis related interstitial lung disease (SSc-ILD). Two double-blind randomised controlled trials examined the efficacy of cyclophosphamide in SSc-ILD; the Scleroderma lung study (SLS) and the Fibrosing Alveolitis in Scleroderma Trial (FAST). Although each trial compared cyclophosphamide to placebo, there were important differences in the route of administration and the types of concurrent treatment in the active therapy arm. There are emerging data supporting mycophenolate mofetil (MMF) in SSc-ILD, which is both safe and well tolerated. A number of case reports have highlighted a potential role for rituximab in SSc-ILD. Cases will be presented that reflect the diversity of interstitial lung disease seen in the rheumatology clinic and current approaches to therapy reviewed including treatments of gastro-oesophageal reflux disease (GORD), potential of antioxidant therapies and the place for second line immunosuppression. Finally consideration of future approaches such as autologous stem cell transplantation and targeted anti-fibrotic agents such as pirfenidone or selective signalling inhibitors such as nintedanib will be discussed. <h3>Disclosure of Interest</h3> None Declared
AB1281 Making a diagnosis and predicting prognosis of bone structure by low field compact magnetic resonance imaging machine in patients with rheumatoid arthritis
Authors: M. Sugihara, Y. Okamoto, T. Hirota, T. Suzuki, M. Horikoshi, C. Hagiya, H. Miki, M. Yokosawa, S. Hagiwara, Y. Takano, N. Umeda, Y. Kondo, H. Tsuboi, H. Ogishima, T. Hayashi, Y. Chino, D. Goto, I. Matsumoto, T. Sumida
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Magnetic resonance imaging (MRI) is able to detect synovitis, bone marrow edema and bone erosion, which X-ray radiograph is not. This modality of imaging would be helpful in clinical practice in rheumatic diseases. <h3>Objectives</h3> To assess the usefulness of low field MRI to make a diagnosis of rheumatoid arthritis (RA), and to predict future bone destruction. <h3>Methods</h3> We developed 0.3 tesla low field compact MRI (cMRI). All the patients who underwent examination by cMRI were included. T1 weighted image and short tau inversion recovery image of both hands were taken. We scored every site for 0-3 points by compact MRI score [1] as degree of affection; 23 sites for bone erosion, 23 sites for bone marrow edema and 11 sites for synovitis. Of all RA patients, those who had 2 sequential examinations with 6 to 12 months interval were analyzed to find the poor prognosis factor of bone destruction. <h3>Results</h3> Five hundreds and sixty four hands of 283 patients were included and divided into 4 groups; 168 hands of 84 patients were RA treated with biologic agents (infliximab 37 patients, etenercept 23, tocilizumab 13, adalimumab 6 and abatacept 5) (Group 1), 209 hands of 105 patients were RA treated without biologic agent (Group 2), 54 hands of 27 patients had arthralgia or synovitis caused by other connective tissue diseases (Group 3) and 133 hands of 67 patients were undifferentiated arthritis (Group 4). Erosion score, bone marrow edema score and synovitis score in group 1, 2 and 3 were significantly higher than that of Group 4 (erosion score; 19.13±14.37, 11.40±11.32, 6.98±11.67 and 1.94±2.42 for group 1 to 4 respectively, bone marrow edema score; 2.55±6.62, 1.18±4.47, 0.66±6.00 and 0.25±1.92, synovitis score; 5.16±6.43, 3.57±3.89, 1.91±3.04 and 0.64±1.35, p&lt;0.05 for each pair with group 4). One hundred and three hands of 53 RA patients had two sequential examinations. In those patients, synovitis score at the first evaluation was significantly correlated with progression of erosion score 6 to 12 months later (r<sup>2</sup>=0.29, p=0.0031). One synovitis score at the first examination would predict 0.33 point progression in erosion score at the second examination. <h3>Conclusions</h3> cMRI examination would be of use to make diagnosis of RA from undifferentiated arthritis. Synovitis observed by cMRI would be a poor prognosis factor of bone destruction. <h3>References</h3> Suzuki, et al. Mod Rheumatol 2009, 19, 358 <h3>Disclosure of Interest</h3> None Declared
Vitamin D — Baseline Status and Effective Dose
Authors: Robert P. Heaney
Journal: New England Journal of Medicine (2012)

There has been more ink spilled over the efficacy of vitamin D than over that of most nutrients, with the possible exception of sodium. Why is this? Dozens of randomized, controlled trials have been conducted — some large, and many small. Unfortunately, their results have been inconsistent — some positive, some null, and the odd one or two actually negative. Even the many available meta-analyses on the topic have yielded inconsistent results. If vitamin D is actually efficacious, why is there this inconsistency?In this issue of the Journal, in yet another meta-analysis, Bischoff-Ferrari et al.1 suggest several explanations, including . . .
Effect of a clean stove intervention on inflammatory biomarkers in pregnant women in Ibadan, Nigeria: a randomised controlled study
Authors: Elizabeth Frank, E Bartlett, D Alexander, A Dutta, D Adu, T Ibigbami, F Edem, G Arinola, T Karrison, CO Olopade
Journal: The Lancet Global Health (2016)

Background 3 billion people cook, heat, and light their homes using polluting fuels such as biomass and kerosene. Household air pollution is a known risk factor for acute lower respiratory tract infections and non-communicable diseases including stroke, chronic obstructive pulmonary disease, and lung cancer. Exposure to household air pollution has been linked to increased presence of systemic inflammatory biomarkers. Here we aimed to assess whether a change from a traditional wood or kerosene biomass stove to use of a bioethanol-burning stove could reduce the presence of inflammatory biomarkers in pregnant women in Nigeria.
P17.39 * TURN OLD INTO NEW: METFORMIN AS ANTINEOPLASTIC AGENT IN GLIOBLASTOMA
Authors: C. Seliger, K. Renner, M. Kreutz, A. Meyer, B. Jachnik, U. Bogdahn, A. Vollmann-Zwerenz, P. Hau
Journal: Neuro-Oncology (2014)

Metformin is one of the most widely prescribed oral antidiabetic drugs. In addition to its known hypoglycemic effects there is current evidence, that metformin may also reduce the risk and mortality of cancer in diabetic patients. The antineoplastic role of metformin has been extensively studied in breast-, prostate-, pancreatic-, lung- and colon cancer, however, the effect of metformin on glioblastomas, one of the most devastating forms of human tumors, has not been thoroughly investigated. We examined the effects of metformin on a variety of brain tumor initiating cells (BTIC) from fresh tumor resections of primary glioblastomas using proliferation assays (cell count, BRDU-assay) and migration assays (scratch and spheroid migration assay), and investigated differentiation of cells by means of immunocytochemistry. Tumor cell metabolism was investigated by measuring extracellular lactate levels, mitochondrial respiration by high resolution respirometry and determination of cellular oxygen consumption under cell culture conditions using the PreSens-assay. Important signalling molecules, such as AMPK, Akt and mTOR were investigated by means of Western Blot analysis. Functional assays were compared in BTIC and differentiated tumor cells from the same patients. In BTIC, we observed a markedly impaired proliferation and migration of cells after treatment with metformin and inhibition of complex I of the respiratory chain. In addition, we observed increased extracellular lactate levels and activation of the AMPK/mTOR signalling cascade. Metformin-treated BTIC showed reduced expression of stem cell markers. Differentiated tumor cells were distinctly less responsive to treatment with metformin. We hypothesize that differential sensitivity of brain tumor initiating cells and differentiated tumor cells to metformin is due to different use of and dependence on oxidative energy production and impaired glycolytic and glutaminolytic rescue pathways in BTIC. Further investigation of metformin as a possible antineoplastic agent in glioblastoma is warranted, especially in the light of a multitude of promising ongoing clinical studies on metformin and other tumor types.
OP0054 Ultrasound Synovitis Reflects Synovial Inflammation at A Histopathological Level: Table 1.
Authors: N. Ng, S. Kelly, F. Humby, M. DiCicco, V. Rocher, R. Hands, M. Bombardieri, C. Pitzalis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ultrasound (US) is widely used by rheumatologists to assess inflammatory burden on patients with inflammatory arthritis. Some studies have shown that US measures of inflammation reflects aspects of histological synovitis in a heterogeneous groups of patients with rheumatoid arthritis (RA)<sup>1</sup>. Little work has been done to describe this relationship in an early arthritis population. <h3>Objectives</h3> Our aim of this study is to investigate, at a single joint level, the correlation of US synovitis with histological synovial inflammation before and after treatment initiation in a homogenous cohort of patients with early RA. <h3>Methods</h3> Data was collected from 54 patients with early RA (fulfills 1987 ACR classification, symptom onset &lt;12 months). Patients were naïve to both disease modifying anti-rheumatic drugs (DMARD) and to steroids. All patients underwent a core data set assessment including clinical, biochemical, imaging and an US guided minimally invasive synovial biopsy of the most inflamed joint. Patients were then initiated on DMARD according to standardised protocol. A repeat assessment and US guided biopsy was performed at 6 months follow up. US images of the joint are scored using a semi quantitative score (0-3). Sections of paraffin embedded synovial tissue were stained by immunohistochemistry for CD3, CD20, CD68, CD68sl and CD138 and these parameters were graded in a semiquantitative fashion (0-4). Spearman9s rho was used to correlate scores at each time point. <h3>Results</h3> At baseline, US power doppler (PD) was significantly correlated with histological markers of inflammation - CD3, CD20, CD68, CD68sl, CD138 as well as with inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) (see Table 1). After 6 months of therapy, most of these correlations were still present, most notably with CD68sl (r=0.36, p&lt;0.05). Interestingly, we also found that a fall in US PD in response to treatment at 6 months is associated with a fall in CD68sl (r=0.50, p&lt;0.005) and a fall in DAS28 (r=0.40, p&lt;0.05). <h3>Conclusions</h3> US PD has long been recognised as an accurate reflection of disease activity in inflammatory arthritis. Our results have shown that US PD also reflects synovial inflammation at a histopathological level. The association of US PD, CD68sl and DAS28 supports the current opinion that Power Doppler US is a biomarker for treatment response and reflects both clinical and histological markers of disease activity in patients with RA. <h3>References</h3> Andersen M, Ellegaard K, Hebsgaard JB, et al. Ultrasound colour Doppler is associated with synovial pathology in biopsies from hand joints in rheumatoid arthritis patients: a cross-sectional study. Ann Rheum Dis. 2013 Mar 8 Epub. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3411
Asthmatics Infected with Rhinovirus (RV) Demonstrate Up-regulation of IL-15
Authors: J.L. Kennedy, J.W. Steinke, D. Murphy, H. Carper, A.P. Stallings, T.A.E. Platts-Mills, L. Borish, P.W. Heymann
Journal: Journal of Allergy and Clinical Immunology (2012)
NON-ALCOHOLIC FATTY LIVER DISEASE IS INDEPENDENTLY ASSOCIATED WITH NEW ONSET ATRIAL FIBRILLATION: A NATIONWIDE COHORT STUDY IN KOREA
Authors: Seng Chan You, Pil-Sung Yang, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung
Journal: Journal of the American College of Cardiology (2016)
RANKL plays a role in migration and invasion of the bone-seeking cell line MDA-MB-231-BO2 through human type I collagen by up-regulating MMP1.
Authors: S Casimiro, I Alho, A Fernandes, A Lipton, T Guise, L Costa
Journal: Cancer Research (2009)

Abstract Abstract #2052 Background: Cancer-induced bone destruction is associated with increased osteoclastogenic activity induced by tumor cells, and an unbalanced bone remodelling cycle that favours bone osteolysis. In this proccess the RANK-RANKL signaling is crucial for both osteoclastogenesis and osteoclastic activity. Furthermore, breast cancer cells have been shown to also express the RANK receptor and to increase migration towards RANKL stimuli, however it is not known if RANK - RANKL interaction stimulates breast cancer cell to invade and degrade bone collagen. Objective: To determine if RANKL increases the ability of breast cancer cells to invade a type I collagen matrix and degrade bone collagen. Material and Methods: The influence of sRANKL on MDA-MB-231-BO2 cell migration or cell invasion (type I collagen) were assessed by Boyden-chamber chemotaxis assay. Binding of RANKL to BO2 cells, levels of RANK expression and levels of matrix metalloproteinases secreted during invasion were determined by RT-PCR and WB analysis. The activation of AKT signaling pathway was determined by WB against the phosphorylated form pAKT1/2/3(Ser473). Results: sRANKL influences the migration and invasion of RANK-expressing BO2 cells in a dose-dependent manner (dose range 0.75-2.5 ug/mL), while the neutralization of sRANKL with a specific antibody abrogated this effect. sRANKL stimuli activates AKT pathway downstream of RANK, while the pre-treatment of cells with 100 nM of wortmannin (a PI(3)K inhibitor) blocked this effect and impaired invasion. During invasion of type I collagen the levels MMP1 expression and of secreted MMP1 increase and are positively correlated with the increase in sRANKL concentration. Conclusions: Our data suggest that RANKL can trigger an increase in expression of MMP1 by breast cancer cells expressing RANK, contributing to invasion via degradation of matrix proteins directly by the cancer cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2052.
FRI0189 Assessment of Exercise Status in Routine Care Using Mdhaq: Evidence That Initiating Exercise is Associated with Substantially Better Outcomes than NO Exercise: Table 1.
Authors: I. Castrejόn, S. Celik, T. Pincus, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Extensive evidence indicates major benefits of exercise in rheumatoid arthritis<sup>1</sup> and many rheumatic diseases,<sup>2</sup> not only for cardiovascular and general fitness, but also for better rheumatologic clinical status. Most reported exercise data are derived from structured research studies rather than from usual care. A multidimensional health assessment questionnaire (MDHAQ) designed for usual care includes a query concerning exercise status for the rheumatologist to analyze possible associations with clinical outcomes. <h3>Objectives</h3> To compare baseline demographic and clinical data, and changes in status over 1 year, in patients classified into 4 categories: a) exercise at both baseline and 1 year later (YES/YES); b) no exercise at baseline and exercise 1 year later (NO/YES); c) exercise at baseline and not 1 year later (YES/NO); d) no exercise at either time point (NO/NO). <h3>Methods</h3> Each patient seen at an academic rheumatology setting completes an MDHAQ at each visit while waiting to see the rheumatologist. The MDHAQ includes scores for physical function, pain, patient global estimate (PATGL), and RAPID3 (Routine Assessment of Patient Index Data), an index of these 3 measures, each scored 0-10; total=0-30. Patients were classified into 4 groups according to exercise 3 times a week at baseline and 1 year: YES/YES, NO/YES, YES/NO, NO/NO. Mean baseline data and percentage change from baseline to 1 year were analyzed and compared by analysis of variance (ANOVA), with multivariate adjustment for age, disease duration, education, sex and baseline physical function (MANOVA). <h3>Results</h3> YES/YES patients were younger with a higher level of education than the NO/NO exercise group (data not shown). YES/YES patients had best baseline status, which was progressively worse in the NO/YES, YES/NO, and NO/NO groups. Patients in the NO/YES group had substantially greater improvement in scores 1 year later than those in all other groups, including the YES/YES group, while the YES/NO group was the only patient group with poorer status 1 year later. <h3>Conclusions</h3> Exercise 3 times a week is associated with better clinical status. Patients who report no exercise at baseline and performing exercise 1 year later have considerably better status, while patients who reported performing exercise at baseline and not 1 year later have poorer status, although it is not known how frequently changes in outcomes resulted from changes in exercise status. Clinically relevant information concerning exercise status is available on MDHAQ in usual care settings. <h3>References</h3> Sokka T, Hakkinen A. Clin Exp Rheumatol. 2008; 26(5 Suppl 51):S14-20 Perandini LA, de Sa-Pinto AL, Roschel H, et al. Autoimmunity Rev 2012;12:218-24 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3451
Abstract 1711: Bax delta2: A gain-of-function Bax mutant for selective chemotherapy.
Authors: Honghong Zhang, Bonnie Haferkamp, Jialing Xiang
Journal: Cancer Research (2013)

Abstract The pro-death Bcl-2 family protein and tumor suppressor Bax is frequently mutated in tumors with microsatellite instability (MSI). Recently, we identified a novel Bax homolog, BaxΔ2, which is generated by a unique combination of mutation and alternative splicing in MSI tumors. BaxΔ2 is a potent cell death inducer. Unlike the parental Baxα, BaxΔ2 does not directly target to mitochondria, rather activates the caspase 8-mediated mitochondrial pathway. BaxΔ2-positive cancer cells are less invasive and more sensitive to a sub-set of chemotherapeutic agents. Thus, our data provide evidence that gain-of-function BaxΔ2 mutant resulted from mutation and aberrant splicing may be detrimental to tumor and thereby could be beneficial for treatment of cancer. Citation Format: Honghong Zhang, Bonnie Haferkamp, Jialing Xiang. Bax delta2: A gain-of-function Bax mutant for selective chemotherapy. [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 1711. doi:10.1158/1538-7445.AM2013-1711 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
BRCA1 as a predictive marker of survival in sporadic ovarian cancer
Authors: C. R. James, J. E. Quinn, P. B. Mullan, P. G. Johnston, D. P. Harkin
Journal: Journal of Clinical Oncology (2007)

5512 Background: First line treatment of ovarian cancer (OC) involves both Platinum and Taxane based chemotherapy and reduced BRCA1 mRNA and protein expression levels are observed in up to 70% of sporadic ovarian tumours. We, therefore, investigated whether BRCA1 may represent a biomarker of response to chemotherapy in sporadic ovarian cancer. Methods: As in vitro models of sporadic ovarian cancer, we used both antisense and siRNA to abrogate BRCA1 expression in BG-1 and OVCAR5 ovarian cancer cells, respectively. Apoptotic responses to DNA damaging agents and antimicrotubule agents were measured using dose inhibition assays and Annexin V flow cytometry. Quantitiative real time PCR analysis (qRTPCR) was employed to measure BRCA1 mRNA expression in 54 surgically resected ovarian tumours. Univariate analysis provided an evaluation of the effect of BRCA1 mRNA expression and response to platinum or platinum/Taxane containing chemotherapy. Results: We provide in vitro evidence that BRCA1 differentially modulates chemosensitivity in sporadic ovarian cancer. Specifically, we demonstrate that antisense and siRNA inhibition of BRCA1 expression in both BG1 and OVCAR5 ovarian cancer cells, respectively, results in increased sensitivity to both cisplatin and carboplatin and decreased apoptotic response to both paclitaxel and docetaxel. Subsequently, by retrospective clinical analysis of 54 fresh frozen sporadic ovarian tumours we demonstrate that patients with low levels of BRCA1 have a significantly improved overall survival when treated with a platinum based chemotherapy regimen in comparison to patients with high levels of BRCA1 (30.4 months vs 21 months, p=0.047, HR 0.5). In addition, overall median survival for high BRCA1 expressing patients was found to double upon the addition of a taxane containing regimen (46.82 months vs 21 months, p=0.068, HR 0.44). Conclusions: We demonstrate both in vitro and in vivo evidence to support a role for BRCA1 as a predictive marker of response to chemotherapy in sporadic ovarian cancer. We believe that this study is significant given the high incidence of reduced BRCA1 mRNA and protein levels observed in sporadic ovarian cancer and may therefore have implications for the future management of this disease. No significant financial relationships to disclose.