tbuckley/cabot-search huggingface dataset:
PTU-091 UK Multicentre Audit of Management and Outcome of Autoimmune Hepatitis: Meeting The Standards: Abstract PTU-091 Table 1
Authors: VM Gordon
Journal: Gut (2016)

<h3>Introduction</h3> Early diagnosis of liver disease is a current UK health priority. (Williams et al., 2015) Autoimmune Hepatitis (AIH), affects 8000–15000 people in the UK and despite effective treatment, still results in excess mortality. At present there are no data reporting current standards of care regarding how AIH is diagnosed and managed in the UK as a whole. We assessed adherence to pre-defined standards of care via the UK AIH audit and present results from 1267 patients diagnosed and managed with AIH in 28 UK centres (of varying size) between 2000–2015. <h3>Methods</h3> We collected all prevalent (still-attending) cases diagnosed since 2000 and all incident cases diagnosed since 2007 by searching electronic patient letters, histology databases and hospital coding. Validation was by 1999 IAIHG diagnostic criteria. Information on diagnosis, initial severity, treatment and outcome was entered into a web-based data collection system. There were 1267 patients followed up for 4 (0–14) years. Results are shown in the table: <h3>Results</h3> <h3>Conclusion</h3> Standards pertaining to diagnosis were achieved but there was a notable delay in diagnosis. Fewer patients than expected received steroid treatment for at least one year. Only 38% achieved histological remission on follow-up biopsy. Fewer patients than expected died or required transplantation, perhaps because of the duration of follow-up. <h3>Reference</h3> 1 Williams R, <i>et al</i>. Implementation of the Lancet standing commission on liver disease in the UK. <i>The Lancet</i> 2015;<b>386</b>(10008):2098–2111. <h3>Disclosure of Interest</h3> None Declared
Defects in the RAS/RTK Signaling Pathways Predominate the Mutational Spectrum of EVI1/GATA2 Rearranged Myeloid Malignancies with Inv(3)/t(3;3)
Authors: Mathijs A. Sanders, Stefan Gröschel, Remco M. Hoogenboezem, Annelieke Zeilemaker, Marije Havermans, Claudia Erpelinck, Eric M. J. Bindels, Berna Beverloo, Hartmut Döhner, Bob Löwenberg, Konstanze Döhner, Ruud Delwel, Peter J.M. Valk
Journal: Blood (2014)
An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015
Authors: Jay Lucidarme, Kevin J Scott, Roisin Ure, Andrew Smith, Diane Lindsay, Bianca Stenmark, Susanne Jacobsson, Hans Fredlund, J Claire Cameron, Alison Smith-Palmer, Jim McMenamin, Steve J Gray, Helen Campbell, Shamez Ladhani, Jamie Findlow, Paula Mölling, Ray Borrow
Journal: Eurosurveillance (2016)

The 23rd World Scout Jamboree in 2015 took place in Japan and included over 33,000 scouts from 162 countries. Within nine days of the meeting ending, six cases of laboratory-confirmed invasive serogroup W meningococcal disease occurred among scouts and their close contacts in Scotland and Sweden. The isolates responsible were identical to one-another by routine typing and, where known (4 isolates), belonged to the ST-11 clonal complex (cc11) which is associated with large outbreaks and high case fatality rates. Recent studies have demonstrated the need for high-resolution genomic typing schemes to assign serogroup W cc11 isolates to several distinct strains circulating globally over the past two decades. Here we used such schemes to confirm that the Jamboree-associated cases constituted a genuine outbreak and that this was due to a novel and rapidly expanding strain descended from the strain that has recently expanded in South America and the United Kingdom. We also identify the genetic differences that define the novel strain including four point mutations and three putative recombination events involving the horizontal exchange of 17, six and two genes, respectively. Noteworthy outcomes of these changes were antigenic shifts and the disruption of a transcriptional regulator.
First detection and complete genome sequence of a phylogenetically distinct human polyomavirus 6 highly prevalent in human bile samples
Authors: Jasper F.W. Chan, Kah-Meng Tee, Garnet K.Y. Choi, Zheng Zhu, Rosana W.S. Poon, Kevin T.P. Ng, Kwok-Hung Chan, Ivan F.N. Hung, Kwan Man, Kwok-Yung Yuen
Journal: Journal of Infection (2016)
AB0677 Comparative Characteristics of Radiographic and Non-Radiographic Axial Spondyloarthritis (NR-AXSPA) Based on Data from 12 Month Follow Up of Corsar Cohort: Table 1
Authors: T. Dubinina, D. Rumyantseva, O. Rumyantseva, A. Demina, E. Gubar, S. Erdes
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Clinical similarity of nr-axSpA and ankylosing spondylitis (AS) has been well established, but whether nr-axSpA is an initial stage of AS, or these two subtypes are nosologically self-determined entities is still being debated. <h3>Objectives</h3> To study the evolution of early axial spondyloarthritis (axSpA) in the Moscow axSpA cohort of patients (pts) - CoRSaR (Russian acronym from CohoRt of early axSpA pts). <h3>Methods</h3> Currently the CoRSaR cohort includes 94 axSpA pts with &lt;5 years of inflammatory back pain duration (ASAS 2009y.criteria). 54 out of them with at least 12 months (mo) follow up pts (FUP) were included into preliminary analysis of axSpA evolution study. Evaluation of all pts at inclusion (Mo0) and FUP (Mo12) visits was similar and included: medical case history, clinical examination, X-ray of pelvis (and other segments of the back bone and joints, when necessary) - following ASAS guidelines, MRI of sacroiliac joints. Pts9 mean age at Mo0 visit was 27,1±5,5 y., average disease duration - 22,4±15,1 mo, 49 (90,7%) pts were HLA-B27 positive. <h3>Results</h3> Pts were grouped into 2 arms to analyze axSpA evolution: Group 1 – nr-axSpA, Group 2 – AS. The table shows pts9 baseline and FUP Mo12 visit characteristics. No significant difference has been found between the two groups – radiographic AS and nr-axSpA - in terms of prevalence of arthritis, enthesitis, BASDAI, ASDAS CRP, and BASFI scores. Radiographic sacroiliitis, i.e., AS, has developed in 9 (39%) out of 23 nr-axSpA pts during 12 Mo FUP. <h3>Conclusions</h3> No clinical differences between radiologically confirmed axSpA (i.e., AS) and nr-axSpA were established. AS has developed in 9 (39%) out of 23 nr-axSpA pts during 12 Mo. <h3>Disclosure of Interest</h3> None declared
Loss of CIITA and MHC Class II Expression in Diffuse Large B-Cell Lymphoma Is Not Explained by Methylation of CIITA Promoters III and IV.
Authors: Sarah T Wilkinson, Diane R Fernandez, Shawn P Murphy, Wing C. Chan, Randy D. Gascoyne, Elias Campo, Elaine S. Jaffe, Louis M. Staudt, Jan Delabie, Andreas Rosenwald, Lisa M Rimsza
Journal: Blood (2008)
Relation between the TRIB3 Gln84Arg genetic variation and vascular complications in type 2 diabetes: an analysis of a 2 × 2 factorial randomised controlled trial
Authors: Fazhong He, Mouze Liu, Xingyu Wang, Xin Liu, Honghao Zhou, Xiaoping Chen, Wei Zhang
Journal: The Lancet Diabetes & Endocrinology (2016)
PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1
Authors: Alexandra Lacey, Aline Rodrigues-Hoffman, Stephen Safe
Journal: Cancer Research (2016)

Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric disease driven by expression of the oncogenic fusion gene PAX3-FOXO1A. In this study, we report overexpression of the nuclear receptor NR4A1 in rhabdomyosarcomas that is sufficient to drive high expression of PAX3-FOXO1A there. RNAi-mediated silencing of NR4A1 decreased expression of PAX3-FOXO1A and its downstream effector genes. Similarly, cell treatment with the NR4A1 small-molecule antagonists 1,1-bis(3-indolyl)-1-(p-hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A. Mechanistic investigations revealed a requirement for the NR4A1/Sp4 complex to bind GC-rich promoter regions to elevate transcription of the PAX3-FOXO1A gene. In parallel, NR4A1 also regulated expression of β1-integrin, which with PAX3-FOXO1A, contributed to tumor cell migration that was blocked by C-DIM/NR4A1 antagonists. Taken together, our results provide a preclinical rationale for the use of NR4A1 small-molecule antagonists to treat ARMS and other rhabdomyosarcomas driven by PAX3-FOXO1A. Cancer Res; 77(3); 732-41. ©2016 AACR.
PWE-089 Prognostic Implications of Synchronous and Metachronous Adenomas in Patients with Colorectal Cancer
Authors: A Patel, E Spector, R Ranat, O Ali, N Williams, R Arasaradnam
Journal: Gut (2016)

<h3>Introduction</h3> The prognostic significance of adenoma detection in colorectal cancer (CRC) survivors is poorly characterised. This study aimed to determine if patients with synchronous adenomas (SAs) are more likely to develop metachronous adenomas (MAs) and its impact on locoregional recurrence and survival. <h3>Methods</h3> Patients with stage I-III CRC undergoing curative surgery at our institution, between 2006 and 2012, were included. The SA group included patients with adenomas at pre-operative colonoscopy or in the resection specimen. SPSS version 21 was used for univariate analysis (chi-squared test) and multivariate analysis (logistic regression/Cox regression modelling). <h3>Results</h3> In total, 562 patients (M:F 323:239, median age 69 years (62–77)) were included; 197 had SAs. Male gender and older age were significantly associated with SAs (p &lt; 0.001 and p = 0.020 respectively). By 60 months, 70/366 (19%) patients undergoing colonoscopic examination developed MA. On univariate analysis, SA patients were more likely to develop MA than non-SA patients (26% versus 16% respectively, Odds ratio 1.91, p = 0.014). On multivariate analysis, the only independent predictor of MA by 24 months was SA at presentation. However, by 60 months, male gender and right sided tumours were independent predictors of risk of developing MA. SA patients had a significantly lowerl local recurrence rate compared to non-SA patients (2/188 (1%) versus 18/314 (5%), p = 0.008). After correction for age, sex and pathological T stage, no difference in overall (OS) or disease free survival (DFS) between SA patients and non-SA patients was observed (Hazards Ratio (HR) 0.926, p = 0.687 and HR 2.367, p = 0.460, respectively). Similarly, MA patients had similar OS compared to those that did not have MAs (OS 99 months versus 102 months, p = 0.504). <h3>Conclusion</h3> At 5 years, proximal tumours and male gender were predictors of risk of developing metachronous adenomas. However, there was no difference in overall or disease free survival amongst patients presenting with SAs or MAs compared to patients without such adenomatous lesions. Detection of adenomas in CRC survivors does not indicate adverse prognosis. <h3>Disclosure of Interest</h3> None Declared
Single Cell Network Profiling (SCNP) Identifies Altered Signaling Between Patient Risk Groups in B-Cell Chronic Lymphocytic Leukemia (B-CLL).
Authors: Jason Ptacek, Erik Evensen, Greg Friedland, James Cordeiro, Jodi R. Ware, Charles C. Chu, Rajendra N Damle, Lu Zhang, Nicholas Chiorazzi, Alessandra Cesano, Rachael E. Hawtin
Journal: Blood (2012)
Treatment with the Heat Shock Protein (hsp) 90 Inhibitor17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (DMAG) Abrogates the Levels and Activity of the Receptor Tyrosine Kinase TrkA in Acute Leukemia Cells.
Authors: Sandhya Kumaraswamy, Que T. Lambert, Kathy Rocha, Purva Bali, Warren Fiskus, Maria Balasis, Michael Pranpat, Sandhya Boyapalle, Alison Hannah, Gary W. Reuther, Kapil Bhalla
Journal: Blood (2005)
Closer to closing the loop on inpatient glycaemia
Authors: Gerry Rayman
Journal: The Lancet Diabetes & Endocrinology (2016)

Automated systems that deliver safer patient care are becoming increasingly important in health care and particularly in disorders such as diabetes, where therapy needs to be dynamically matched to physiological and metabolic measures. An area of particular interest is diabetes in inpatients, in whom establishing and maintaining good metabolic control is challenging yet important, because there is increasing evidence for the benefits of good glycaemic control on length of hospital stay, patient outcomes, and cost savings.
Analysis of the Coding Genome of Follicular Lymphoma Identifies Multiple Novel Recurrently Mutated Genes
Authors: Sami Malek, Yifeng Li, Hongxiu Li, Peter Ouillette, Sian Jones, Heather Fox, Kathryn Jacobi, Kamlai saiya-Cork, Dale Bixby, Daniel Lebovic, Kerby Shedden, Michael Sabel, Lawrence Marentette, Vincent Cimmino, Alfred Chang, Mark S. Kaminski
Journal: Blood (2012)
OP0072 Inhibition of Notch1 Promotes Hedgehog Signaling in A HES1-Dependent Manner and Exacerbates Experimental Osteoarthritis
Authors: N.Y. Lin, A. Distler, C. Beyer, A. Philipi-Schöbinger, M. Stock, A. Niemeier, F. Dell'Accio, G. Schett, J.H. Distler
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The Notch pathway is one of the so-called morphogen pathways, which are evolutionary conserved key-regulators of embryonic development. Notch signaling has recently been implicated in the pathogenesis of osteoarthritis (OA). However, cell-type and context dependent differences in outcome have been reported and the underlying molecular mechanisms are incompletely understood. <h3>Objectives</h3> OA is characterized by degeneration of articular cartilage, limited intraarticular inflammation with synovitis, changes in periarticular and subchondral bone and osteophyte formation by endochondral ossification. Several studies have identified Notch- and Hedgehog-signaling as essential pathways involved in cartilage development and bone remodeling. <h3>Methods</h3> Notch and hedgehog signaling were analyzed by real-time PCR and immunohistochemistry. Mice overexpressing a Notch-1 antisense construct (Notch-1 AS) were employed as a model of impaired Notch signaling. Experimental OA was induced by destabilization of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analyzed by safranin-O staining with subsequent assessment of the OARSI and Mankin scores and μCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of Hes-1 was investigated with knockdown and overexpression experiments. <h3>Results</h3> Notch signaling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain (NICD1) and increased transcription of Hes-1. Notch1 AS mice showed exacerbated osteoarthritis with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signaling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signaling on Gli-expression were mimicked by Hes-1. <h3>Conclusions</h3> Inhibition of Notch signaling activates hedgehog signaling, enhances chondrocyte hypertrophy and exacerbates experimental osteoarthritis including osteophyte formation. These data suggest that the activation of the Notch pathway may serve to limit aberrant hedgehog signaling in OA. <h3>Disclosure of Interest</h3> None declared
OC-012 The Effect of Mental Workload Experienced During Colonoscopy on Endoscopists Performance
Authors: I Rahman, P Boger, P Patel
Journal: Gut (2016)

<h3>Introduction</h3> Studies have shown that there are a multitude of factors that affect the quality of colonoscopy. However, the effect of the endoscopist mental workload on their performance has been neglected. It is shown that health professionals exposed to excessive workloads and fatigue show degraded performance. The aim of this study was to measure the effect of mental workload as represented by the National Aeronautics and Space Administration-Task Load Index (NASA-TLX), on colonoscopic performance relative to the experience of the endoscopist and colonoscopy scheduling. <h3>Methods</h3> Procedures were observed prospectively in one institution for 3 groups; trainees, consultants and bowel cancer specialist programme (BCSP) endoscopists. On reaching the caecum the endoscopist marked on a validated pro-forma their corresponding workload on six subscales; mental demand, physical demand, temporal demand, effort, frustration and own performance, to generate a NASA-TLX score. Data on performance which included caecal intubation times (CIT), patient comfort and polyp detection rate (PDR) were noted. In addition, withdrawal times, time of day (am or pm) and queue order for procedures were recorded. <h3>Results</h3> A total of 202 procedures were undertaken between 6 endoscopists with a mean CIT of 9.2 minutes and PDR of 42%. Increasing mental workload was associated with increasing CIT (r = 0.61, p = 0.07) and inversely associated with withdrawal time (r = 0.72, p = 0.03). The mean mental workload during colonoscopy was lower in BCSP endoscopist v consultants v trainees (188 v 254 v 352 p &lt;0.01). On multivariate analysis, absence of polyp detection was associated with a procedure that was undertaken in pm with an above mean mental workload (OR 1.62, 95% CI 1.38–2.07) and withdrawal time of &lt;5 minutes (OR 1.53, 95% CI 1.32–1.91). Increased patient discomfort was associated with increased frustration on the subscale of the NASA-TLX score (OR 1.59, 95% 1.37–1.93) and being a trainee (OR 1.11, 95% 1.03–1.22). The use of ScopeGuide reduced the mental workload of consultants (227 v 282 p&lt;0.01), but not trainees or experts. Queue position had no impact on any of the markers of performance. <h3>Conclusion</h3> This study shows that high mental workload experienced during colonoscopy has a significant detrimental effect on the performance of endoscopists. Drop in PDR in pm procedures when only associated with high mental workload may explain some of the conflicting results of daily variations of PDR in other studies. Further studies are now required to look into measures that may reduce excessive mental workload. <h3>Disclosure of Interest</h3> None Declared
Genomic Alterations of Histone Modification Genes Are Significantly Less Common in Non-Hodgkin Lymphomas of Adolescents and Young Adults Compared to Older Patients
Authors: Kai Wang, Deborah Morosini, Roman Yelensky, Norma Palma, Adrienne Johnson, Doron Lipson, Juliann Chmielecki, Siraj Ali, Jeffrey S Ross, Philip J. Stephens, Vincent Miller
Journal: Blood (2014)
Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE.
Authors: Santina Bruzzone, Floriana Fruscione, Sara Morando, Alessandro Poggi, Anna Garuti, Martina Selmo, Tiziana Ferrando, Federica Benvenuto, Michele Cea, Debora Soncini, Eva Moran, Ilaria Rocco, Gabriella Cirmena, Gabriele Zoppoli, Alberto Ballestrero, Bernard Sordat, Franco Patrone, Antonio Uccelli, Alessio Nencioni
Journal: Blood (2009)
Low<i>TLR7</i>gene expression in atherosclerotic plaques is associated with major adverse cardio- and cerebrovascular events
Authors: Glykeria Karadimou, Lasse Folkersen, Martin Berg, Ljubica Perisic, Andrea Discacciati, Joy Roy, Göran K. Hansson, Jonas Persson, Gabrielle Paulsson-Berne
Journal: Cardiovascular Research (2016)

Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis.Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n = 123). Increased levels of TLR7 transcript in the plaques were associated with better outcome in a follow-up study over a maximum of 8 years. Patients with higher TLR7 transcript levels had a lower risk of experiencing major cardiovascular and cerebrovascular events (MACCE) during the follow-up period after CEA (hazard ratio: 2.38, P = 0.012, 95% CI 1.21-4.67). TLR7 was expressed in all plaques by T cells, macrophages and endothelial cells in capillaries, as shown by immunohistochemistry. In short-term tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod elicited dose-dependent secretion of IL-10, TNF-α, GM-CSF, and IL-12/IL-23p40. This secretion was blocked with a TLR7 inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r = 0.4031, P < 0.0001) and GM-CSF receptor A (r = 0.4354, P < 0.0001) transcripts.These findings demonstrate that TLR7 is abundantly expressed in human atherosclerotic plaques. TLR7 ligation elicits the secretion of pro-inflammatory and anti-inflammatory cytokines, and high TLR7 expression in plaques is associated with better patient outcome, suggesting that TLR7 is a potential therapeutic target for prevention of complications of atherosclerosis.
Monitoring Minimal Residual Disease by Quantitative PCR in Chronic Myeloid Leukemia Patients in Complete Cytogenetic Remission
Authors: Carolina Pavlovsky, Isabel Giere, Virginia Lombardi, Pedro Negri, Beatriz Moiraghi, Juan García, Miguel Arturo Pavlovsky, Maria Fernanda Garcia Reinoso, Raquel Bengio, Reinaldo Campestri, Jorge Milone, Rosario Uriarte, Alicia Magariños, Lem Martinez, Nora Mur, Valentin Labanca, Gabriel Via, Claudia Corrado, Isolda Fernandez, Santiago Pavlovsky
Journal: Blood (2008)
Immunogenicity of a BCR-ABL e1a2 p190 Translocation in a Balb/c Mouse Model.
Authors: Marta Gomez-Nunez, Javier Pinilla-Ibarz, Tao Dao, Victoriya Zakhaleva, Tatyana Korontsvit, Rena J. May, David A. Scheinberg
Journal: Blood (2005)
A Phase I/II Multicenter Study of Single-Agent Foretinib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma
Authors: Thomas C.C. Yau, Riccardo Lencioni, Wattana Sukeepaisarnjaroen, Yee Chao, Chia-Jui Yen, Wirote Lausoontornsiri, Pei-Jer Chen, Theeranun Sanpajit, Aaron Camp, Donna S. Cox, Robert C. Gagnon, Yuan Liu, Kristen E. Raffensperger, Diptee A. Kulkarni, Howard Kallender, Lone Harild Ottesen, Ronnie T.P. Poon, Donald P. Bottaro
Journal: Clinical Cancer Research (2016)

Abstract Purpose: This phase I/II single-arm study evaluated the safety, pharmacokinetics, pharmacodynamics, and activity of foretinib, an oral multikinase inhibitor of MET, ROS, RON, AXL, TIE-2, and VEGFR2, in the first-line setting in advanced hepatocellular carcinoma patients. Experimental Design: In the phase I part, advanced hepatocellular carcinoma patients were dose escalated on foretinib (30–60 mg) every day using the standard 3+3 design. Once the maximum tolerated dose (MTD) was determined, an additional 32 patients were dosed at the MTD in the phase II expansion cohort for assessment of efficacy and safety. Exploratory analyses were conducted to assess potential biomarkers that might correlate with clinical efficacy and survival. Results: The MTD of foretinib was established as 30 mg every day. The most frequent adverse events were hypertension, decreased appetite, ascites, and pyrexia. When dosed at 30 mg every day in the first-line setting, foretinib demonstrated promising antitumor activity. According to the modified mRECIST, the objective response rate was 22.9%, the disease stabilization rate 82.9%, and the median duration of response 7.6 months. The median time to progression was 4.2 months and the median overall survival (OS) was 15.7 months. Fifteen candidate biomarkers whose levels in the circulation were significantly altered in response to foretinib treatment were elucidated. Multivariate analyses identified IL6 and IL8 as independent predictors of OS. Conclusions: Foretinib demonstrated promising antitumor activity and good tolerability in the first-line setting in Asian advanced hepatocellular carcinoma patients. Baseline plasma levels of IL6 or IL8 might predict the response to foretinib. Clin Cancer Res; 23(10); 2405–13. ©2016 AACR.