tbuckley/cabot-search huggingface dataset:
Rapid spread of the novel respiratory syncytial virus A ON1 genotype, central Italy, 2011 to 2013
Authors: A Pierangeli, D Trotta, C Scagnolari, M L Ferreri, A Nicolai, F Midulla, K Marinelli, G Antonelli, P Bagnarelli
Journal: Eurosurveillance (2014)

Respiratory infections positive for human respiratory syncytial virus (RSV) subtype A were characterised in children admitted to hospitals in Rome and Ancona (Italy) over the last three epidemic seasons. Different strains of the novel RSV-A genotype ON1, first identified in Ontario (Canada) in December 2010, were detected for the first time in Italy in the following 2011/12 epidemic season. They bear an insertion of 24 amino acids in the G glycoprotein as well as amino acid changes likely to change antigenicity. By early 2013, ON1 strains had spread so efficiently that they had nearly replaced other RSV-A strains. Notably, the RSV peak in the 2012/13 epidemic season occurred earlier and, compared with the previous two seasons, influenza-like illnesses diagnoses were more frequent in younger children; bronchiolitis cases had a less severe clinical course. Nonetheless, the ON1-associated intensive care unit admission rate was similar, if not greater, than that attributable to other RSV-A strains. Improving RSV surveillance would allow timely understanding of the epidemiological and clinicopathological features of the novel RSV-A genotype.
SAT0541 Analysis of Health Care Costs Associated with Ankylosing Spondylitis in Turkey
Authors: O. Baser, A. Burkan, E. Baser, R. Koselerli, E. Ertugay, A. Altinbas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The economic burden of ankylosing spondylitis (AS) has been analyzed in other countries, yet it is not well documented in Turkey. Therefore, Turkey has invested in MEDULA, a nationwide integrated system between health insurance and healthcare providers. <h3>Objectives</h3> To explore healthcare costs associated with AS in Turkey using nationwide real-world data. <h3>Methods</h3> Using International Classification of Disease Tenth Revision Clinical Modification (ICD-10-CM) codes, adult prevalent and incident AS patients (age 18-99) with two AS-related visits at least 60 days apart, identified between 06/01/2010 and 12/31/2010, with 1 year of continuous health plan enrollment for the baseline and follow-up years were included in the study. Pharmacy, outpatient and inpatient claims were compiled over the study period. Generalized linear models were used to estimate expected annual costs, controlling for baseline demographic and clinical characteristics. <h3>Results</h3> Total 2,986 patients were identified (603 incident, 2,383 prevalent cases). Most subjects were age 18-39 years (58% incident, 51% prevalent) and 44% of incident and 38% of prevalent cases were female. Prevalent patients had higher comorbidity index scores (6.04 vs. 2.24, p&lt;0.001). Risk-adjusted total annual medical costs were €2,253 for incident and €4,233 for prevalent patients. Pharmacy costs accounted for most of the total costs (89% prevalent; 77% incident). <h3>Image/graph</h3> <h3>Conclusions</h3> Findings suggest that AS health care costs in Turkey resemble those in Europe. Costs are driven by comorbidities and treatment choices. Current data provides a baseline to evaluate economic effect of AS-related treatment and policy. <h3>Disclosure of Interest</h3> None Declared
OP0218 Elevated Serum BAFF is Associated with an Increased Risk of Developing A New Systemic Complication: Data from the Prospective ASSESS Cohort
Authors: J.E. Gottenberg, R. Seror, C. Miceli-Richard, J. Benessiano, V. Devauchelle-Pensec, P. Dieude, J.-J. Dubost, A.-L. Fauchais, V. Goeb, E. Hachulla, P.Y. Hatron, C. Larroche, V. Le Guern, J. Morel, A. Perdriger, X. Puéchal, S. Rist, A. Saraux, D. Séné, J. Sibilia, O. Vittecoq, G. Nocturne, P. Ravaud, X. Mariette
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The validation of the EULAR Sjögren9s syndrome Disease Activity Index (ESSDAI, composed of 12 domains) now allows to analyze the natural history of systemic disease activity in pSS. Serum levels of markers of B-cell activation were reported to be associated with the ESSDAI assessed on the same day and serum BAFF to be associated with history of lymphoma. However, their interest to predict new systemic complications has not been evaluated. <h3>Objectives</h3> To determine the evolution of systemic disease activity in pSS and the interest of serum markers of B-cell activation as predictors of new systemic complications. <h3>Methods</h3> The ASSESS cohort is a 5-year prospective cohort of 395 patients. Changes in systemic disease activity were analyzed by the occurence of a new domain of the ESSDAI, taking or not into account its level of activity and the biological domain. Baseline serum levels of markers of B-cell activation and BAFF were centrally assessed. Elevated BAFF was defined by a value ≥ mean+2 SD (1459.3 pg/ml) of 80 age and sex-matched controls. <h3>Results</h3> At enrollment, after 1, 2 and 3 years of follow-up, the ESSDAI scores are already available in 383, 339, 231 and 178 patients. Between enrollment and the 1st year of follow-up, the 1st and the 2nd year,the 2nd and the 3rd year, a <i>new domain</i> of the ESSDAI was observed in 29.1, 33.2, and 31.7% of the patients, respectively (46.7% between enrollment and 3rd year). A <i>new domain with moderate or high activity</i> occurred in 9.4, 12.6 and 6.9% of the patients, respectively. A new moderate/high domain, <i>except the biological domain</i>, was observed in 4.8, 6.7 and 3.5% of the patients, respectively (8.9% between enrollment and 3rd year). Kappa and lambda free light chains of immunoglobulins and beta2-microglobulin were not associated with changes in systemic disease activity. An elevated serum BAFF level was significantly more frequently associated with the occurrence of a <i>new moderate/high domain</i> at 1 and 3 years (20.0% vs 7.7%, P=0.038 and 36.0% vs 15.9%, P=0.041, respectively), and of a <i>new moderate/high domain except the biological domain</i> at 3 years (24.0% vs 7.1%, P=0.031). <h3>Conclusions</h3> Approximately half of the patients have changes in systemic activity and ∼10% develop a new relevant clinical complication after 3 years of follow-up. Baseline serum BAFF was associated with a higher risk of new systemic complications and could be used as a biomarker in clinical trials of new treatments of systemic complications of pSS. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4266
AB0324 Comparison of DAS28-CRP with 3 and 4 variables in rheumatoid arthritis patients treated with biological agents in the daily clinic
Authors: O.R. Madsen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> DAS28 based on CRP (DAS28-CRP) may be calculated using three or four variables. DAS28-CRP(4) is computed using four variables: swollen and tender joint count, CRP and patient global assessment. DAS28-CRP(3) only includes swollen and tender joint count and CRP as patient global assessment has been excluded. The thresholds for low and high disease activity and for improvements are the same for the two scores [1]. <h3>Objectives</h3> The aim of the study was, for the first time, to compare the two DAS scores regarding sensitivity to change and to assess the agreement between the scores and their changes on group and subject level after initiation of biological treatment in an observational clinical setting. <h3>Methods</h3> Baseline and 4 months disease activity data from 239 rheumatoid arthritis patients treated with a biological agent were extracted from the Danish registry for biological treatment (DANBIO). Effect sizes (ES) [mean DAS change/SD baseline] as well as disease activity and improvement levels according to the DAS thresholds were assessed for each of the two DAS versions. The Bland-Altman method was used to examine the agreement between the scores on subject level. Limits of agreement (LOA) were estimated as the mean difference between duplicate measurements (the bias) ±1.96SD, where SD is the standard deviation of all the differences. This means that 95% of the differences will lie between these limits. <h3>Results</h3> DAS28-CRP(4) at baseline was 4.8±1.2 versus 4.6±1.1 for DAS28-CRP(3) (p&lt;0.0001). The bias of DAS28-CRP(3) at baseline was -0.28±0.32 (p&lt;0.0001) with LOA of -0.92 and 0.36. After 4 months of biological treatment, the scores for DAS28-CRP(4) and DAS28-CRP(3) had improved by –1.39±1.34 (p&lt;0.0001) and –1.18±1.22 (p&lt;0.0001), respectively.The bias for DAS28-CRP(3) at this time point was -0.07±0.31 (p&lt;0.0001) with LOA of -0.69 and 0.55. The bias for the change in DAS28-CRP(3) was 0.21±0.35 (p&lt;0.0001) with LOA of -0.49 and 0.91.The two DAS-scores were highly correlated at both baseline (r =0.96, p&lt;0.0001) and at 4 months (r =0.97, p&lt;0.0001). The changes in the DAS-scores were also highly correlated (r =0.97, p&lt;0.0001). ES for DAS28-CRP(4) was 1.2±1.1 vs. 1.1±1.1 for DAS28-CRP(3) (p&lt;0.0001). Compared to DAS28-CRP(4), DAS28-CRP(3) categorized 33% fewer patients as having a high level of disease activity both at baseline and at 4 months, categorized 8% fewer patients as good responders and 12% more patients as non-responders. <h3>Conclusions</h3> DAS28-CRP (3) and DAS28-CRP(4) agree well on group level but may differ widely in individual patients. DAS28-CRP(3) yielded lower scores, categorized less patients as having high disease activity level and was less sensitive to change than DAS28-CRP(4). <h3>References</h3> http://www.das-score.nl <h3>Disclosure of Interest</h3> None Declared
SELF-EXPANDING TAVR IN PATIENTS WITH LOW-GRADIENT AORTIC STENOSIS: 30-DAY RESULTS FROM THE COREVALVE US EXPANDED USE STUDY
Authors: Stanley J. Chetcuti, G. Michael Deeb, Kimberly Skelding, Alfred Casale, Ron Waksman, Ammar Bafi, Steven Yakubov, Michael Reardon, David Adams, Jeffrey Popma
Journal: Journal of the American College of Cardiology (2015)
Treating Mild Asthma -- When Are Inhaled Steroids Indicated?
Authors: Jeffrey M. Drazen, Elliot Israel
Journal: New England Journal of Medicine (1994)

Asthma affects nearly 1 in 15 people in the United States and Europe. Although the cause or causes of asthma remain unknown, its pathophysiology has been well enough characterized to allow the development of two major classes of drugs for treatment -- bronchodilators and antiinflammatory agents. In regard to the latter class, we know that corticosteroids, which have an unspecified antiinflammatory action, provide effective treatment. This appreciation has led, somewhat tautologically, to the concept that controlling airway inflammation, which is present even in patients with mild asthma,13 is an important therapeutic goal4. Indeed, guidelines for the treatment of . . .
Abstract 3151: Navitoclax enhances the activity of chemo-therapeutic and targeted agents across a large panel of epithelial cancer cell lines
Authors: Maureen Wong, Nguyen Tan, Robert Kassees, Megan Berry, Michelle Nannini, Deepak Sampath, Lisa Belmont
Journal: Cancer Research (2011)

Abstract Navitoclax (formerly ABT-263), a potent inhibitor of Bcl-2, Bcl-xL, and Bcl-w, has shown promising activity in CLL, a disease in which Bcl-2 is highly expressed. In this study, we wished to explore its potential as a Bcl-xL inhibitor. Bcl-xL is thought to contribute to resistance to cancer therapy in epithelial cancers. Navitoclax and the related molecule, ABT-737, potentiate the activity of chemotherapy and targeted agents in cell lines and mouse models. In order to identify predictive biomarkers of synergy and identify combinations most likely to translate to the clinical setting, we performed combination studies on a panel of 100 cell lines derived from breast, lung, ovarian and pancreatic cancer. We evaluated the combination of navitoclax with gemcitabine, paclitaxel, as well as targeted agents that inhibit EGFR, phosphatidylinositol-3-kinase and MAP kinase pathways. These studies demonstrate that navitoclax is broadly synergistic with these agents as evaluated by a Bliss independence model. The majority of cell lines and combinations exhibited Bliss scores that exceeded the values predicted for two independent agents. Correlative marker analysis revealed that levels of proteins within the Bcl-2 family correlated with synergy scores for chemotherapy combinations, while activation of the EGFR/Ras/Raf pathway was a better predictor for the combinations of navitoclax with targeted agents. Combination studies in xenograft models demonstrate that navitoclax can enhance the activity of chemotherapy and targeted agents in vivo. Furthermore, biomarker expression correlated with response in vivo. These studies suggest distinct strategies for patient selection that are dependent upon the combination agent. 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 3151. doi:10.1158/1538-7445.AM2011-3151
Tc-99m MDP Thyroid Uptake in a Patient with a Large Nontoxic Goiter
Authors: GERARD RIEDY, LEE ADLER
Journal: Clinical Nuclear Medicine (2000)

A 68-year-old woman underwent a whole-body bone scan with Tc-99m MDP for evaluation of renal cell metastasis from a large right renal cell mass. This study revealed nonvisualization of the right kidney secondary to the mass and a large area of increased uptake in the right lower neck. Additional history and physical examination revealed a long-standing, 14 × 10 cm, well-circumscribed mass consistent with a goiter. The most common causes for increased lower neck uptake on bone scans are cartilage calcification, osteoarthritic changes, free Tc-99m pertechnetate, and metastatic lesions. Calcific degenerated nontoxic goiter and amyloid are more rare causes. Plain films showed a large right lower neck mass without significant amounts of calcification. The patient’s thyroid function tests were within normal limits. The patient refused further examinations.
Abstract 3049: Overexpression of miR-17 family miRNAs in prostate cancer biopsies: Evidence for a stem-cell-like miRNA profile in high grade/high stage tumors
Authors: Sandra M. Gaston, Andrew L. Guerra, Rangarajan C. Nadadur, Julie Meadows, Michael C. Kearney, Lynn Sorbara, Sudhir Srivastava, Stephen J. Meltzer, Paul Pinsky, Gary P. Kearney
Journal: Cancer Research (2010)

Abstract Complex changes in microRNA (miRNA) expression patterns have been observed in many different types of cancer, including prostate cancer. Although the consequences of deregulation of miRNA expression in human cancer are still largely unknown, the use of miRNAs for cancer classification and prognosis has emerged as an important new area of biomarker research. We compared the tissue expression of miRNAs in prostate biopsies from patients with high grade/high stage tumors with biopsies from patients with no evidence of malignancy. Snap frozen prostate biopsy samples were prospectively collected using tissue printing techniques and total RNA was isolated for miRNA analysis using Agilent miRNA microarrays (Version 1, containing 470 human tissue miRNAs). The prostate cancer cases included in the microarray profiling study had at least 5 of 12 cores positive for cancer and significant areas of Gleason 7 or more. The no-cancer controls showed no prostate cancer, HGPIN or suspicious histology in any of the 12 biopsy cores. In our analysis of miRNA expression patterns, “significant change in expression” was defined as at least 2 fold change and F test (p&amp;lt;0.05). Three different internal reference normalization methods were used in the data analysis; here we classify miRNAs as “overexpressed” or “underexpressed” only when all three methods agree. In high grade/high stage biopsy cancer, 64 of the 470 human tissue miRNAs on the microarray (13.6%) were found to be significantly overexpressed when compared with miRNA expression in biopsies from no-cancer controls. This set of overexpressed miRNAs includes 4 of the 5 miR-200 family miRNAs that have been implicated in the regulation of the epithelial-to-mesenchymal transition (EMT). The cancer-overexpressed miRs also include 6 of the 8 miR-17 family genes; this miRNA family has been implicated in the control of stem-cell differentiation during embryogenesis. Interestingly, the 6 miR-17 family miRs that are overexpressed in high grade/high stage prostate cancer include 2 from each of the 3 polycistronic clusters that encode this highly conserved miR family, an expression pattern similar to the coordinated expression observed in early embryonic development. This robust stem-cell-like miRNA profile offers an interesting new candidate biomarker that may be particularly sensitive to an aggressive prostate cancer phenotype. 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 3049.
THU0397 Efficacy of pamidronate in children with osteogenesis imperfecta: An open prospective study
Authors: M. El Rakaawi, N. Hammoumraoui, S. Mellal, F. Sadouki, S. Lehtihet, W. Kerri, H. Djoudi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteogenesis imperfecta (O.I) is a disorder characterized by osteopenia, frequent fractures, progressive deformity, and chronic bone pain. Its severity depends mainly on the severity of the bone lesions. Treatment with pamidronate has changed the pejorative natural evolution of this disease by reducing the fracture incidence. <h3>Objectives</h3> to assess the effects of treatment with pamidronate in children with moderate to severe (OI). <h3>Methods</h3> This is an uncontrolled open-label study in which were included 69 children who were 2 to 16 years old with moderate to severe OI and in whom at least two fractures occurred in the previous year. We administrated pamidronate intraveinously 1 mg of body weight per day for 3 days cyclically every 4 months, All patients received daily supplementation of calcium and vitamine D and physical rehabilitation. Efficiency is measured by the reduction of fracture after one year of treatment. In addition we measured the change in bone density and functional status, before and after treatment. SPSS 13.0 was used for the statistical analysis. <h3>Results</h3> The average age of the 69 children who completed one year of treatment was 6.26 (SD 3.80). The average annual number of radiologic confirmed fractures decrease by 3.59 [95% CI: 2.8 to 4.3]. Before treatment it was 4.71 (3.36) and was reduced to 1.11 (1.4). The average gain in BMD (available in 55 children) was 58.58 mg/cm<sup>2</sup> [42.7 to 72.4], the percentage gain is 20% comparatively to baseline. The mean Bleck functional score increased in mean by 2 stages. Mobility and ambulation was improved according to Bleck score in 43 children who gained at less one stage The mean decrease of chronic bone pain assessed by VAS was 67%. We also assessed 39 children who completed two years of treatment, the fracture rate reduction in this sub-group was 79%. No adverse effect on growth or on fracture healing were observed. Post-infusion transient acute phase reaction and asymptomatic hypocalcaemia were observed. <h3>Conclusions</h3> cyclic administration of intravenous pamidronate In children with moderate and severe osteogenesis imperfecta decreased fracture rate, chronic bone pain, increased bone mineral density and improved clinical outcome. <h3>References</h3> Glorieux FH, Pettifor JM, Jüpner H, editors. Pediatric Bone: Biology and Diseases. SanDiego: Academic Press; 2003. p.401-63. Forin V, Arabi A, Guigonis V, Filipe G, Bensman A, Roux C. Benefits of pamidronate in children with osteogenesis imperfecta: an open prospective study. Joint Bone Spine. 2005; 72: 313-8 <h3>Disclosure of Interest</h3> None Declared
Design of a Computer System to Assist in Differential Preoperative Diagnosis for Pelvic Surgery
Authors: Peter W. Neurath, Kurt Enslein, George W. Mitchell
Journal: New England Journal of Medicine (1969)

To help in making nine common differential diagnoses for pelvic surgery, a computer system has been designed in three parts: a data-collection procedure, based on a checklist of symptoms obtained on admission, each with a weight between 1 and 9; a statistical diagnostic algorithm, for which medical records of over 500 patients were used to calculate the necessary coefficients; and a computer-based information output, which, using the first two parts, gives the physician a condensed history and the most probable diagnoses, before surgery. The system has been shown to be 66 per cent accurate —equal to results in major teaching hospitals. It is designed for further improvements by making very complete data collection and retrieval easy. It was developed for easy implementation at minimal cost.
Abstract 1584: Targeting the mitotic checkpoint with inhibition of MPS1 kinase enhances radiosensitivity of glioblastoma cancer cells.
Authors: Anita T. Tandle, Ryan Hanson, Uday B. Maachani, Tamalee Meushaw, Shuping Zhao, Uma Shankavaram, Philip Tofilon, Natasha J. Caplen, Kevin Camphausen
Journal: Cancer Research (2013)

Abstract During the cell cycle, genomic stability requires accurate chromosome segregation. Errors in this process can cause aneuploidy and lead to tumorigenesis. To ensure faithful chromosome segregation, cells develop a mechanism called the spindle assembly checkpoint (SAC). Cancer cells are addicted to the components of SAC machinery for a faithful entry of the cell into anaphase. Thus, targeting the molecular mechanisms required for the growth of aneuploid cells may be a more cancer cell specific therapeutic approach applicable to broader tumor histologies. Previously, using a siRNA based RNAi screen we identified MPS1 kinase, (also known as TTK) as an important kinase for GBM cell survival. MPS1 is an essential SAC enzyme aberrantly overexpressed in a wide range of tumors and necessary for tumor cell proliferation. We observed inhibition of GBM cell growth when MPS1 was downregulated by number of MPS1 specific siRNAs. This was further validated using a selective and orally bioavailable MPS1 inhibitor NMS-P715 in various in-vitro cell assays. The inhibition of cell death was induced partly by apoptosis; however, the major mechanism was mitotic catastrophe. Cells treated with NMS-P715 showed an increase in cells in G2-M phase of cell cycle compared to control cells followed by mitotic catastrophe. Moreover, inhibition of MPS1 resulted in radiosensitization of GBM cells. We observed decrease in DNA damage repair and significant retention of γH2AX foci after combination of radiation (RT) with NMS-P715 compared to individual treatments. Next, radiation in combination with NMS-P715 inhibited cell survival ability of GBM cells in a colony formation assay. Further, NMS-P715 could inhibit GBM tumor growth in an orthotopic brain tumor model. Finally, in order to determine MPS1 associated molecular pathways, we compared gene expression profile in MPS1 knockdown cells compared to the control by microarray analysis. Ingenuity pathway and Gene Set Enrichment Analysis were used to investigate the biological relevance of the MPS1 modulated genes. We identified genes important in cell assembly, cell organization, DNA repair and cell death pathways. Thus, inhibiting MPS1 kinase in combination with radiation could represent a promising new approach to GBM therapy. Citation Format: Anita T. Tandle, Ryan Hanson, Uday B. Maachani, Tamalee Meushaw, Shuping Zhao, Uma Shankavaram, Philip Tofilon, Natasha J. Caplen, Kevin Camphausen. Targeting the mitotic checkpoint with inhibition of MPS1 kinase enhances radiosensitivity of glioblastoma cancer cells. [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 1584. doi:10.1158/1538-7445.AM2013-1584