tbuckley/cabot-search huggingface dataset:
THU0160 Excellent Outcomes Sustained Even in Long-Term When Targeted Treatment with A Combination of Traditional DMARDs Is Used in Early Rheumatoid Arthritis. The 10-Year Follow-Up Results of A Randomized Clinical Trial, The NEO-RACO Trial
Authors: V. Rantalaiho, T. Sandström, J. Koski, H. Kautiainen, M. Leirisalo-Repo
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The short term outcomes of remission-targeted treatments of rheumatoid arthritis (RA) are well established, but the long-term success of such strategies is less clear, as is the role of initial add on biologics. <h3>Objectives</h3> To assess the evolution of clinical and radiograpich outcomes over 10 years in patients with early RA treated with initial remission-targeted combination-DMARD therapy and additional infliximab or placebo infusions for the first six months <h3>Methods</h3> Ninety-nine patients with early, DMARD-naïve RA were treated with a triple combination of DMARDs, starting with methotrexate (max 25mg/week), sulfasalazine (max 2g/day), hydroxychloroquine (35mg/kg/week), and with prednisolone (7.5mg/day), and randomized to double-blindly receive either infliximab (3mg/kg; FIN-RACo+INFL) or placebo (FIN-RACo+PLA) infusions during the first 6 months. After 2 years the treatment strategies became unrestricted, but the treatment goal was strict ACR remission. At 10 years the clinical and radiographic outcomes were assessed using the intention-to-treat principal. <h3>Results</h3> Ninety patients (91%) were followed after 2 years, 43 in the FIN-RACo+INFL and 47 in the FIN-RACo+PLA group. At 10 years, the respective proportions of patients in strict ACR and in DAS28 remissions in the FIN-RACo+INFL and FIN-RACo+PLA groups were 48% and 38% [p=0.37 (NNT=10)], and 82% and 72% [p=0.30 (NNT=11)] (Figure 1). The radiographic progression remained slow in most of the patients up till 10 years, the mean (SD) total Sharp van der Hejde score (TSS) was 9.8 (14.8) in the FIN-RACo+INFL and 7.3 (8.1) in the FIN-RACo+PLA group (p=0.34). Only 15% of the patients had TSS&gt;20, and 22% had TSS 0. By ten years, 26% of the FIN-RACo+INFL group patients and 30% of the FIN-RACo+PLA group patients were using biologics (p=0.74). After 5 years, 56% of the patients were at least sporadically using prednisolone, the mean (SD) daily dose was 1.8 (1.6) mg in the FIN-RACo+INFL group and PLA 1.6 (1.4) mg in the FIN-RACo+PLA group. <h3>Conclusions</h3> In early RA, excellent results can be maintained up till 10 years in most patients treated with initial combination DMARDs and targeted treatment strategy. Adding initial infliximab for 6 months does not improve these outcomes. <h3>Acknowledgement</h3> The NEO-RACo Trial Group. <h3>Disclosure of Interest</h3> V. Rantalaiho Grant/research support from: Orion-Farmos Research Foundation, Competitive Research Funding of Tampere University Hospital, T. Sandström: None declared, J. Koski: None declared, H. Kautiainen: None declared, M. Leirisalo-Repo Grant/research support from: Helsinki University Central Hospital Research Funds, Finska Läkaresällskapet, Liv och Hälsa
PTH-119 A Comparison of Colonoscopists Performance in Recording and Labelling Images Taken During Endoscopy Using The Recorded Image Quality Index (RIQI) Tool
Authors: D Samuel, JB Berrill, J Hurley, B Lee, E Hawkes, S Yosief, N Hawkes
Journal: Gut (2016)

<h3>Introduction</h3> Recording images on the endoscopic reporting tool and report writing are key skills for a colonoscopist. Together they represent the data set on which other clinicians have to base decisions. The performance level of colonoscopists in this area of endoscopy is not commonly measured. We therefore aimed to examine the variation in image recording amongst a cohort of colonoscopists performing regular colonoscopy using the validated Recorded Image Quality Index (RIQI) tool. <h3>Methods</h3> We searched the HICCS Endoscopic Reporting System for all colonoscopists performing regular colonoscopy (n = 11). All procedures performed between July and December 2015 were identified (screening cases were excluded). All images and the endoscopy report for the first 10 cases with pathological findings for each colonoscopist were obtained, ordered into folders and data anonymised. The 110 image sets were scored by 3 independent assessors using the validated RIQI score. This measures 4 domains representation, labelling, caecal landmarks and image quality high scores indicate high utility of the images as a base for decision-making. Kruskal-Wallis non-parametric test was used to compared differences in rank sums between groups. <h3>Results</h3> 110 data sets were reviewed by 3 assessors generating 330 RIQI scores. These observations were pooled for each colonoscopist yielding a median RIQI score from 30 observations. Inter-observer rating scores for the 3 assessors were in the moderate to good range. Median values for colonoscopists ranged from 2 (scores less than 4 indicate a &lt; 2% utility value as a base for decision-making) to 10 (scores 9–10 have a 96.5% utility rate). Upper quartile performers on RIQI score were significantly better than the lower quartile of colonoscopists (Kruskal-Wallis, H = 1132 (1, n = 180, p &lt; 0.00001). 4/11 (37%) colonoscopists met acceptable standards (median 9–10), 5/11 (45%) were rated as needing improvement (median 6–8) and 2/11 (18%) demonstrated poor performance (median ≤5). <h3>Conclusion</h3> The RIQI tool demonstrates widely varying performance in capture of quality images during endoscopy. High quality image capture and reporting is an important aspect of endoscopic practice. RIQI provides a performance indicator that can be used as an audit and training tool to improve performance in this area of practice. <h3>Disclosure of Interest</h3> None Declared
Development of a Human Anti-CD27 Antibody with Efficacy in Lymphoma and Leukemia Models by Two Distinct Mechanisms
Authors: Li-Zhen He, Larry Thomas, Jeffery Weidlick, Laura Vitale, Tom O'Neill, Naseem Prostak, Karuna Sundarapandiyan, Henry Marsh, Michael Yellin, Thomas A. Davis, Tibor Keler
Journal: Blood (2011)
The origin and evolution of cell types
Authors: Detlev Arendt, Jacob M. Musser, Clare V. H. Baker, Aviv Bergman, Connie Cepko, Douglas H. Erwin, Mihaela Pavlicev, Gerhard Schlosser, Stefanie Widder, Manfred D. Laubichler, Günter P. Wagner
Journal: Nature Reviews Genetics (2016)
Surveillance Mammography in Older Patients With Breast Cancer—Can We Ever Stop?
Authors: Rachel A. Freedman, Nancy L. Keating, Ann H. Partridge, Hyman B. Muss, Arti Hurria, Eric P. Winer
Journal: JAMA Oncology (2016)

Approximately 4% to 5% of breast cancer survivors will develop a new ipsilateral or contralateral cancer (in-breast event) over the 5 years following diagnosis, and annual surveillance mammography is recommended for those with residual breast tissue. The risk for such in-breast events persists over time, though increasing age at cancer diagnosis and treatment with hormonal therapy are associated with lower risk, and most older survivors of breast cancer will ultimately die from nonbreast cancer-related causes. Specific guidelines for surveillance strategies in older patients are limited. Prospective data on the benefits and harms of surveillance mammography in this population are lacking, and most of the evidence is derived from observational, retrospective data, often in the general population.
Immunosuppressive Therapy with Antithymocyte Globulin and Cyclosporine for Fulminant Aplastic Anemia.
Authors: Hiroshi Yagasaki, Ken-ichiro Watanabe, Kazuko Kudo, Masahiro Tsuchida, Hiroyuki Shichino, Akira Morimoto, Ryoji Kobayashi, Hiromasa Yabe, Akira Kikuchi, Shouichi Ohga, Etsuro Ito, Akira Ohara, Tatsutoshi Nakahata, Seiji Kojima
Journal: Blood (2012)
Posttransplant Lymphoproliferative Disorders in Pediatric Solid Organ Recipients: A Multicenter Retrospective Analysis of Patients from 1990 to 2003.
Authors: B. Maecker, T. Jack, H. Abdul-Khaliq, M. Burdelski, J. Ehrich, A. Fuchs, M. Holder, B. Hoppe, P. Hoyer, A. Karow, S. Koepf, U. Kraemer, T. Lang, G.F. Laube, A. Lehnhardt, E. Maass, D. Mueller-Wiefel, H. Netz, M. Pohl, B. Toenshoff, M. Wallot, M. Zimmering, K. Welte, A. Reiter, M. Melter, G. Offner, C. Klein
Journal: Blood (2005)
SAT0621 Effect of An Exercise Therapy on Systemic Biomarkers for Cartilage Metabolism
Authors: M. Azukizawa, H. Ito, T. Yasuda, M. Furu, Y. Hamamoto, T. Fujii, Y. Morita, A. Okahata, K. Masamoto, S. Matsuda
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The number of osteoarthritis (OA) patients is increasing year by year because of the aging society. Especially, knee OA is reported to reduce the health life expectancy. The majority of patients are at the early stage of knee OA and are adapted to conservative treatments such as exercise therapy. A lot of biomarkers for cartilage metabolism were previously reported. However, there are few reports that exercise therapy has an effect on the biomarkers related for cartilage metabolism. <h3>Objectives</h3> To investigate the effect of an exercise therapy on cartilage metabolism using biomarkers. <h3>Methods</h3> Thirty-eight females (mean age: 59 years) participated in this study. All participants started a weekly exercise and continued it for twelve weeks. Before and after the exercise program, we measured their physical activities; Timed Up and Go test (TUG) and Three Minutes Walking test (3MW). Since the program started, we have collected serum and urine samples from the participants at the start of the program (0 week), at the end of it (12 weeks) and 12 weeks after it (24 weeks). For the collected samples, we measured the following two anabolic and one catabolic biomarkers; serum cartilage type II procollagen carboxy propeptide (sPIICP), serum cartilage oligomeric matrix protein (sCOMP), urine C-terminal telopeptide of collagen type II (uCTX-II). These biomarkers were measured with the enzyme-linked immunosorbent assay method. <h3>Results</h3> After the twelve weeks exercise program, both TUG and 3MW were significantly improved (<i>P</i> &lt;0.01 each, respectively) (Fig. A, B). sCOMP concentrations at 12 weeks were relatively greater than those at 0 week. However, sCOMP concentrations at 24 weeks were significantly greater than those at 12 weeks (<i>P</i> &lt;0.01) (Fig. C). In contrast, uCTX-II concentrations at 24 weeks were significantly less than those at 0 week (<i>P</i> &lt;0.01) (Fig. D). There was no significant difference between pre- and post-excise sPIICP concentrations. <h3>Conclusions</h3> These results suggest that an exercise therapy will improve physical activities and that this therapy could influence both cartilage anabolic and catabolic biomarkers. <h3>Disclosure of Interest</h3> None declared
Intrachromosomal Amplification of Chromosome 21(iAMP21): Cytogenetic Characterisation and Outcome in Childhood B-Cell Precursor Acute Lymphoblastic Leukaemia (BCP-ALL). A Study On Behalf of the Ponte Di Legno International Childhood ALL Workshop
Authors: Christine J Harrison, Anthony V. Moorman, Claire Schwab, Nyla A. Heerema, Andrew J. Carroll, Oskar A. Haas
Journal: Blood (2012)
Genome Wide Promoter Methylation Patterns Predict AML Subtype Outcomes and Identify Novel Pathways Characterizing Diagnostic and Relapsed Disease in Children
Authors: Michael Ochs, Jason Farrar, Michael Considine, Rhonda E. Ries, Lisa R. Trevino, Todd A. Alonzo, Jaime Guidry-Auvil, Tanja M. Davidsen, Patee Gesuwan, Donna M. Muzny, Alan S. Gamis, David A. Wheeler, Heather L. Helton, Malcolm A. Smith, Daniela S. Gerhard, Soheil Meshinchi, Robert J. Arceci
Journal: Blood (2012)
Molecular History of Richter Syndrome: Origin From a Common Ancestor Cell Already Present at Chronic Lymphocytic Leukemia Diagnosis
Authors: Davide Rossi, Valeria Spina, Daniela Capello, Francesco Forconi, Maurizio Martini, Silvia Rasi, Marco Fangazio, Valter Gattei, Luigi M. Larocca, Francesco Bertoni, Gianluca Gaidano
Journal: Blood (2010)
THU0026 microRNA-365 Regulates Expression of Catabolic Factors via Modulating IL-1β-Induced EPAS-1 Expression in SW1353 Cells and Human Primary Chondrocytes
Authors: G.H. Park, C.M. Lee, S.Y. Lee, K.M. Son, H.S. Lee, H.S. Hwang, M.H. Lee, H.A. Kim
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> Endothelial PAS domain protein-1 (EPAS-1/HIF-2α), encoded by <i>EPAS1</i> gene, is a catabolic transcription factor to regulate osteoarthritis (OA) cartilage destruction. In this study we examined whether microRNA-365 (miR-365) can regulate interleukin (IL)-1β-induced expression of catabolic factors in SW1353 cells and human articular chondrocytes via regulation of EPAS-1. <h3>Methods</h3> Total RNA was isolated from normal and OA cartilage tissues, human chondrocytes, and SW1353 cells. The level of miR-365 was quantified by TaqMan assay. The effects of miR-365 on expression of EPAS-1 and EPAS-1-modulated genes were measured by quantitative real-time polymerase chain reaction (qRT PCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA). To examine the direct interaction of miR-365 with 39 untranslated region (UTR) of EPAS-1 mRNA, luciferase reporter assay was performed. <h3>Results</h3> The level of miR-365 in human OA cartilage was significantly decreased compared to normal cartilage. The overexpression of miR-365 significantly suppressed IL-1β-induced expression of EPAS-1 in both SW1353 cells and human articular chondrocytes. QRT PCR analysis using pharmacological inhibitors revealed that mitogen activated protein kinase and nuclear factor-κB signaling pathway was involved in IL-1β-induced miR-365 decrease and subsequent increase of EPAS-1 expression. Luciferase reporter assay using DNA construct containing binding site of miR-365 within 39UTR of human EPAS-1 mRNA demonstrated that the overexpression of miR-365 significantly suppressed IL-1β-induced up-regulation of EPAS-1. Furthermore, miR-365 overexpression significantly suppressed IL-1β-induced expression of catabolic factors, including cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinase-1, -3 and -13, in SW1353 cells and human chondrocytes. <h3>Conclusions</h3> MiR-365 regulates IL-1β-stimulated catabolic effects in SW1353 cells and human chondrocytes via modulating the expression of EPAS-1. <h3>Disclosure of Interest</h3> None declared
Results from phase 2 registration trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Lead-in completed, expansion stage ongoing.
Authors: Naveen Pemmaraju, Andrew A. Lane, Kendra Lynn Sweet, Anthony Selwyn Stein, Sumithira Vasu, William G. Blum, David Rizzieri, Eunice S. Wang, Madeleine Duvic, Janice Chen, Shay Shemesh, Peter McDonald, Christopher Brooks, Hagop M. Kantarjian, Marina Konopleva
Journal: Journal of Clinical Oncology (2016)

7006 Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on BPDCN and other hematologic cancers. BPDCN is a rare, aggressive hematologic malignancy of unmet medical need. Results from multicenter Phase 2 completed lead-in and ongoing expansion stage are reported. Methods: This Phase 2 trial includes a lead-in (stage 1) and expansion (stage 2). In stage 1, BPDCN and relapsed/refractory (r/r) AML pts received SL-401 as a daily IV infusion at 7, 9, 12, or 16 ug/kg for up to 5 doses repeated every 21 days. In stage 2, pts received SL-401 at the optimal stage 1 dose. Results: As of 1/20/16, 18 BPDCN pts (9+9 in stages 1&2; including 2 pts not yet evaluable) received SL-401 (7 ug/kg, n=3 [stage 1]; 12 ug/kg, n=15 [6+9 in stages 1&2]), median 70 yrs (45-82, and 15 yr compassionate use pt); 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. In stage 1, 12 ug/kg was the maximum tested/recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. Most common treatment-related AEs, all grades, are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 ug/kg) and gr 4 (12 ug/kg). Safety precautions were successfully implemented to minimize risk of severe CLS which has not occurred at doses up to 12 ug/kg since adoption. 87% (13/15) ORR was seen in evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node, and viscera. ORR was 100% (10/10) in first-line and 60% (3/5) in r/r settings. All 8 first-line patients treated at 12 ug/kg had CR (n=5) or clinical CR (CRc) (n=3). Six of these 8 pts remain on SL-401 in remission (n=4; duration data ongoing at 3+ to 8+ cycles) or were successfully bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles). Conclusions: SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented. Clinical trial information: NCT02113982.
Role for Runt-related Transcription Factor 2 in Proliferative and Calcified Vascular Lesions in Pulmonary Arterial Hypertension
Authors: Grégoire Ruffenach, Sophie Chabot, Virginie F. Tanguay, Audrey Courboulin, Olivier Boucherat, Francois Potus, Jolyane Meloche, Aude Pflieger, Sandra Breuils-Bonnet, Valérie Nadeau, Renée Paradis, Eve Tremblay, Barbara Girerd, Aurélie Hautefort, David Montani, Elie Fadel, Peter Dorfmuller, Marc Humbert, Frédéric Perros, Roxane Paulin, Steeve Provencher, Sébastien Bonnet
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). This is sustained in time by the down-regulation of microRNA (miR)-204. In systemic vascular diseases, reduced miR-204 expression promotes vascular biomineralization by augmenting the expression of the transcription factor Runt-related transcription factor 2 (RUNX2). Implication of RUNX2 in PAH-related vascular remodeling and presence of calcified lesions in PAH remain unexplored.Objectives: We hypothesized that RUNX2 is up-regulated in lungs of patients with PAH, contributing to vascular remodeling and calcium-related biomineralization.Methods: We harvested human lung tissues in which we assessed calcification lesions and RUNX2 expression. We also isolated PASMCs from these tissues for in vitro analyses. Using a bidirectional approach, we investigated the role for RUNX2 in cell proliferation, apoptosis, and calcification capacity. Ectopic delivery of small interfering RNA against RUNX2 was used in an animal model of PAH to evaluate the therapeutic potential of RUNX2 inhibition in this disease.Measurements and Main Results: Patients with PAH display features of calcified lesions within the distal pulmonary arteries (PAs). We show that RUNX2 is up-regulated in lungs, distal PAs, and primary cultured human PASMCs isolated from PAH and compared with patients without PAH. RUNX2 expression histologically correlates with vascular remodeling and calcification. Using in vitro gain- and loss-of-function approaches, we mechanistically demonstrate that miR-204 diminution promotes RUNX2 up-regulation and that sustained RUNX2 expression activates hypoxia-inducible factor-1α, leading to aberrant proliferation, resistance to apoptosis, and subsequent transdifferentiation of PAH-PASMCs into osteoblast-like cells. In the PAH Sugen/hypoxia rat model, molecular RUNX2 inhibition reduces PA remodeling and prevents calcification, thus improving pulmonary hemodynamic parameters and right ventricular function.Conclusions: RUNX2 plays a pivotal role in the pathogenesis of PAH, contributing to the development of proliferative and calcified PA lesions. Inhibition of RUNX2 may therefore represent an attractive therapeutic strategy for PAH.
PWE-126 The ‘Virtual Clinic’ Experience of A Regional Liver Unit
Authors: A Mcneice, I Cadden, J Cash, N McDougall, RB McCorry
Journal: Gut (2016)

<h3>Introduction</h3> ‘Virtual clinics’ are a relatively recent concept that can be used to assess, and deliver advice about, specific patients without the requirement to review them face-to-face in an outpatient clinic. The consultant running the clinic reviews the referral, blood results and imaging to make an assessment before corresponding with the referrer. This audit was completed to assess the impact of the introduction of a regional hepatology virtual clinic. <h3>Methods</h3> All referrals to hepatology outpatients between 1 Dec 2014 and 30 Nov 2015 were triaged by 4 consultants and those that were deemed suitable for virtual clinic assessment were passed on to a single consultant. All referrals dealt with by the virtual clinic were analysed retrospectively. Virtual clinic letters stored on an online system were used to collect data on the source of and reason for referral, the diagnosis and any advice given. <h3>Results</h3> 148 referrals were dealt with by the virtual clinic out of a total of 1420 referrals to the hepatology service. Of those, 87% were sent by General Practitioners (GPs), with the remainder being referred from various hospital specialities. The most common indications for virtual clinic management included misinterpretation of iron profile/HFE genotyping results (28%), Gilbert’s Syndrome (14%), isolated GGT elevation (10%), benign liver lesions on imaging (10%), non-alcoholic fatty liver disease (NAFLD) (8%), misinterpretation of Hepatitis B/C serology (6%) and transient elevations in LFTs associated with acute illness (4%). Only 4 (3%) referrals dealt with by the virtual clinic ultimately required formal review in a hepatology clinic and these were due to deteriorating LFTs post-referral. <h3>Conclusion</h3> A virtual hepatology clinic can safely deal with 10% of referrals and reduce the number of face to face clinic appointments required. This will in turn reduce clinic waiting lists, to the benefit of those patients in need of a clinic appointment. Lastly this audit identifies topics that could be incorporated into education sessions for GPs to help modify referral practise. <h3>Disclosure of Interest</h3> None Declared
VEGF Autocrine System Is Demonstrated in Some of Acute Promyelocytic Leukemia Cases: Relationship to WBC Count at the Disease Onset.
Authors: Toshihiko Sugao, Yoko Oka, Haruko Tashiro, Ryosuke Shirasaki, Nobu Akiyama, Kazuo Kawasugi, Naoki Shirafuji
Journal: Blood (2009)
U2AF1 mutations In Primary Myelofibrosis Cluster With Normal Karyotype and JAK2V617F and Are Strongly Associated With Anemia and Thrombocytopenia
Authors: Ayalew Tefferi, Christy Finke, Terra L Lasho, Emnet A Wassie, Ryan A Knudson, Rhett P Ketterling, Curtis A Hanson, Animesh Pardanani
Journal: Blood (2013)
Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015
Authors: Alison Smith-Palmer, Ken Oates, Diana Webster, Sarah Taylor, Kevin J Scott, Gemma Smith, Benjamin Parcell, Ann Lindstrand, Anders Wallensten, Hans Fredlund, Micael Widerström, Jim McMenamin
Journal: Eurosurveillance (2016)

The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner.