tbuckley/cabot-search huggingface dataset:
PWE-033 Promoter Region Variations in The Glutaminase Gene as A Risk Factor for The Development Hepatic Encephalopathy in Patients with Cirrhosis: Abstract PWE-033 Table 1
Authors: ET Goh, MJ Way, SR Atkinson, A McQuillin, MY Morgan
Journal: Gut (2016)

<h3>Introduction</h3> Hepatic encephalopathy (HE) is the commonest complication of cirrhosis but its development is not invariable; thus approximately 20% of individuals remain free of neuropsychiatric complications and patients with minimal HE do not invariably develop overt HE. It is possible that genetic factors, most likely resulting in deregulation of ammonia metabolism, might determine an individual’s susceptibility to develop this complication. In 2010, Romero-Gomez and colleagues,<sup>1</sup> identified a functional microsatellite consisting of GCA repeats near the promoter region of the glutaminase gene, <i>GLS1, </i>and proposed that patients with cirrhosis who were homozygous for the long microsatellite allele were more likely to develop overt HE. The aim of this study was to further investigate the association between <i>GLS1</i> promoter microsatellite variants and HE. <h3>Methods</h3> The study population comprised 110 patients with cirrhosis, of British/Irish ancestry, in whom neuropsychiatic status had remained stable during monitoring for a minimum of 5 years, except in those treated for overt HE. Patients were classified using clinical, neurophysiological and neuropsychometric variables as: unimpaired (51; 46%) or as having minimal (24; 22%) or overt (35; 32%) HE. The control population comprised 325 ancestrally-matched healthy controls. DNA was genotyped using gel electrophoresis and verified by Sanger sequencing. Alleles were stratified as long (≥14 GCA repeats) or short (&lt;14 GCA repeats). Genotype distributions and allele frequencies were compared between groups. <h3>Results</h3> There were no significant differences in allele frequencies or genotype distributions between cases and controls. The proportion of long-short heterozygotes was significantly higher in the unimpaired patients (62.7%) than in those with either minimal HE (37.5%) or overt HE (37.1%) (p = 0.029; Table). <h3>Conclusion</h3> There was no evidence that the long-long genotype is a risk factor for HE in the present study. However, there was evidence of possible heterozygote advantage resulting in significant protection against the development of this syndrome. More studies are needed to confirm or refute these findings. <h3>Reference</h3> 1 Romero-Gomez M, <i>et al</i>. Variations in the promoter region of the glutaminase gene and the development of hepatic encephalopathy in patients with cirrhosis: a cohort study. <i>Ann Intern Med</i> 2010;<b>153</b>:281–8. <h3>Disclosure of Interest</h3> None Declared
PTH-039 The First Randomised Controlled Trial of Endocuff Vision® Assisted Colonoscopy Versus Standard Colonoscopy for Polyp Detection in Bowel Cancer Screening Patients (E-Cap Study): Abstract PTH-039 Table 1
Authors: R Bhattacharyya, F Chedgy, K Kandiah, C Fogg, B Higgins, L Gadeke, F Thursby-Pelham, R Ellis, P Goggin, G Longcroft-Wheaton, P Bhandari
Journal: Gut (2016)

<h3>Introduction</h3> Up to 25% polyps are missed during colonoscopy. The Endocuff Vision® is a cap with soft flexible arms that attaches to the colonoscope tip and improves views during withdrawal. We have performed the first randomised controlled trial to identify the role of Endocuff Vision® in improving polyp detection. We aim to investigate the impact of Endocuff Vision® assisted colonoscopy on polyp detection, as compared to standard colonoscopy, in the UK Bowel Cancer Screening Programme (BCSP). <h3>Methods</h3> Single centre, parallel group, randomised controlled trial. Ethics ref: 14/SC/0207. Adopted on UKCRN portfolio (ID: 16985). Patients attending for BCSP colonoscopy were stratified based on attendance for index screening colonoscopy or for polyp surveillance. Within each stratum participants were randomised to either Standard or Endocuff assisted colonoscopy. All procedures were performed by accredited BSCP endoscopists, who have carried out &gt; 5000 colonoscopies and have caecal intubation rates of &gt;90%. <h3>Results</h3> 534 patients recruited from Sep 2014 to Sep 2015. 3 excluded due to new diagnosis of polyposis syndrome. 531 were included and randomised to the 2 study arms. No significant difference was seen between the 2 groups for the primary endpoint of number of polyps per patient. Secondary endpoints: No significant difference was observed between the 2 groups for adenoma detection rate (ADR) or number of adenomas per patient (Table 1). No significant adverse events were encountered during the study in either arm. The cecal intubation time was not prolonged and patients did not experience any additional discomfort due to the Endocuff Vision. <h3>Conclusion</h3> In the UK, bowel cancer screening is performed by highly experienced endoscopists. Our results suggest that in expert hands, ADR exceeds 60% even without Endocuff. In such settings, Endocuff Vision did not improve polyp detection rates (PDR) or ADR. However, it did not cause any adverse events, prolong procedure duration or cause additional discomfort. These data demonstrate the safety and feasibility of Endocuff. However, no additional gain was demonstrated in expert hands. <h3>Disclosure of Interest</h3> None Declared
NLRP2 controls age-associated maternal fertility
Authors: Anna A. Kuchmiy, Jinke D’Hont, Tino Hochepied, Mohamed Lamkanfi
Journal: The Journal of Experimental Medicine (2016)

Nucleotide-binding domain and leucine-rich repeat (NLR) proteins are well-known for their key roles in the immune system. Ectopically expressed NLRP2 in immortalized cell lines assembles an inflammasome and inhibits activation of the proinflammatory transcription factor NF-κB, but the physiological roles of NLRP2 are unknown. Here, we show that Nlrp2-deficient mice were born with expected Mendelian ratios and that Nlrp2 was dispensable for innate and adaptive immunity. The observation that Nlrp2 was exclusively expressed in oocytes led us to explore the role of Nlrp2 in parthenogenetic activation of oocytes. Remarkably, unlike oocytes of young adult Nlrp2-deficient mice, activated oocytes of mature adult mice developed slower and largely failed to reach the blastocyst stage. In agreement, we noted strikingly declining reproductive rates in vivo with progressing age of female Nlrp2-deficient mice. This work identifies Nlrp2 as a critical regulator of oocyte quality and suggests that NLRP2 variants with reduced activity may contribute to maternal age-associated fertility loss in humans.
Concordance of intrinsic subtyping and risk of recurrence (ROR) scores between matched primary and metastatic tissue from Triple Negative Breast Cancer Trial (TNT).
Authors: Maggie Chon U Cheang, Judith Bliss, Mitch Dowsett, Lucy Kilburn, Anita Grigoriadis, Cheryl Gillett, Sarah Pinder, Patrycja Gazinska, Ben Haynes, Sarah Kernaghan, Holly Tovey, Julie Owen, Mark Harries, Paul Anthony Ellis, Andrew Nicholas James Tutt
Journal: Journal of Clinical Oncology (2015)

1019 Background: The majority of triple negative breast cancers are of basal-like subtype (BLBC). There is uncertainty about concordance of intrinsic subtypes and ROR scores by PAM50 between matched primary and metastasis samples. We sought to examine agreement of intrinsic subtypes and ROR groups using tissue in the TNT trial. Methods: TNT is a phase III, multicentre, randomized trial of carboplatin vs docetaxel in women with ER- PgR- HER2- metastatic/recurrent locally advanced breast cancer. Using Prosigna test on Nanostring nCounter, intrinsic subtyping was performed in a central laboratory on primary tumour (PT) from 216 patients, 66 positive lymph nodes (PLN) and 13 recurrent tissue samples (RC). The ROR-S (ROR based on subtype contents) and ROR-P (ROR based on subtype contents and proliferation index) were calculated using research-based PAM50 classifier (Parker JCO 2009). Agreement on classification was assessed by kappa statistics (k). Results: Of 216 PT, 175 (81%) were BLBC, 23 (11%) HER2enriched (HER2E), 13 (6%) Luminal A (LumA), 5 (2%) Luminal B (LumB). Of 66 PLN, 49 (74%) were BLBC, 12 (18%) HER2E, 2 (3%) LumA, 3 (5%) LumB. Of RC, majority were BLBC (12/13, 92%) with 1 HER2E. There were 63 matched PT and PLN pairs, with substantial agreement between subtype calls (k = 0.74 (95% CI 0.56-0.92), p < 0.0001; Table 1). 1 BLBC PT was classified HER2E in PLN. Of the 8 LumA PT, 5 (63%) were HER2E, 1 (13%) LumB, 2 (25%) LumA in their matched PLN. Comparing ROR risk groups, all high risk cases remained high risk (Table 1), while low/med switched to med/high risk groups. Conclusions: Our study confirms that BLBC and high risk ROR assignments in PT were substantially conserved with matched PLN and RC. None of the PT/non-BLBC was classified as BLBC in matched PLN or RC. LumA appeared to switch to aggressive subtypes or higher ROR-defined risk groups in matched PLN and RC. Gene expression profiles of matched samples will be presented. Comparison of intrinsic subtypes and ROR groups between matched PT/PLN. PLN Total BLBC HER2E LumA LumB PT BLBC 46 1 0 0 47 HER2E 0 6 0 0 6 LumA 0 5 2 1 8 LumB 0 0 0 2 2 ROR-S High Med Low High 46 1 0 47 Med 6 3 0 9 Low 0 5 2 7 ROR-P High Med Low High 48 1 0 49 Med 4 8 0 12 Low 0 1 1 2
Clinical Outcome of Patients with Follicular Lymphoma and Bulky Disease After Rituximab-CHOP Immunochemotherapy with and without Consolidating Radiotherapy.
Authors: Fabienne McClanahan, Thomas Hielscher, Michael Rieger, Manfred Hensel, Kai Neben, Jens Hillengass, Klaus Herfarth, Anthony D. Ho, Mathias Witzens-Harig
Journal: Blood (2009)
OC-034 Identifying Patients with Elevated Circulating Bacterial DNA May Reduce Infection and Death in Alcoholic Hepatitis
Authors: N Vergis, SR Atkinson, JB Maurice, E Forrest, MR Thursz
Journal: Gut (2016)

<h3>Introduction</h3> Prednisolone has been shown to improve 28 day survival in alcoholic hepatitis (AH). However, use of this therapy is associated with increased infection that could explain the loss of survival benefit by 90 days. A large body of data has also emerged implicating bacterial translocation in the pathogenesis of AH. We therefore sought to elucidate the impact of prednisolone in patients with elevated pre-treatment circulating bacterial DNA (bDNA). <h3>Methods</h3> DNA was extracted from the whole blood of patients recruited to the STOPAH study before therapy. In these patients, clinicians confirmed that any prior infection, if present, was controlled. bDNA levels were quantified by quantitative PCR using a Taqman probe that targeted a region within a 380 bp fragment of bacterial 16 S ribosomal DNA. As part of the STOPAH study, patients would then receive therapy with or without prednisolone by random allocation. After unmasking, levels of bacterial DNA were then compared to clinical outcomes such as the development of infection within 7 days, static and dynamic markers of liver function and mortality at 28 and 90 days. <h3>Results</h3> bDNA was quantified in 714 whole blood samples. There was no correlation between bDNA levels and baseline characteristics such as age and gender, nor with static markers of liver function such as MELD. Elevated bDNA levels were associated with development of infection within the first 7 days in patients treated with prednisolone (<i>p</i> = 0.001), and remained independently associated with the subsequent development of infection after multivariate analysis (<i>p</i> = 0.02). Importantly, bDNA levels were not associated with the development of infection in patients treated without prednisolone (<i>p</i> = 0.43). Elevated bDNA levels were associated with death at 90 days (<i>p</i> = 0.05). Mortality in prednisolone treated patients was increased for patients with high bDNA compared to patients with low bDNA (hazard ratio 2; <i>p</i> = 0.02). Accordingly, patients with elevated bDNA were more likely to die if they were randomly allocated prednisolone therapy (OR 2.9, 95% CI 1.2–6.9, <i>p</i> = 0.02). We estimate that if patients with elevated bDNA were instead treated without prednisolone, 90 day mortality in AH could be reduced (odds ratio 0.5, <i>p</i> = 0.03 [one-tailed]). <h3>Conclusion</h3> Infection is more likely to develop within 7 days if patients with elevated bDNA are treated with prednisolone. Measuring pre-treatment bDNA could therefore inform decisions to initiate corticosteroid therapy and has the potential to increase survival at 90 days in AH. <h3>Disclosure of Interest</h3> None Declared
Evaluation of the Safety, Efficacy of Recombinant Factor IX (nonacog alfa) in Japanese Patients with Hemophilia B- Interim Result of Post Marketing Surveillance Study -
Authors: Takashi Suzuki, Katsuyuki Fukutake, Kagehiro Amano, Hideji Hanabusa, Masashi Taki, Tadashi Matsushita, Midori Shima, Michio Sakai, Masahiro Iizuka, Yoshiyuki Shibasaki
Journal: Blood (2012)
PTH-031 Knife Assisted Resection for Dysplasia Associated Lesion or Mass: A Video Abstract
Authors: K Kandiah, S Subramaniam, FJQ Chedgy, S Thayalasekaran, P Bhandari
Journal: Gut (2016)

<h3>Introduction</h3> The risk of colonic neoplasia is increased in inflammatory bowel disease. Dysplasia-associated lesion or mass (DALM) can be difficult to detect and challenging to resect endoscopically. Conventional endoscopic mucosal resection (EMR) has been used but as these lesions are often flat morphologically, the snare slips off. Endoscopic submucosal dissection (ESD) has been shown to be able to resect flat lesions, however, they carry a high perforation rate outside the rectum. Knife assisted snare resection (KAR) is a novel technique that combines the principles of EMR and ESD. We aim to evaluate the safety and efficacy of this technique in resecting DALMS as well as demonstrate the technique in the accompanying video abstract. <h3>Methods</h3> Data of all KARs undertaken by a single endoscopist in our institution from 2012 to 2014 were prospectively compiled in a pre-designed database. 2 independent researchers interrogated the database. Endoscopic follow-up was performed to identify recurrence. <h3>Results</h3> 9 patients underwent KAR during this period. 8 patients had ulcerative colitis and 1 had Crohn’s colitis. The mean polyp size was 29 mm (10–60 mm). Scarring was noted in 89% of resections despite no previous resection attempts. En-bloc resection was achieved in 7 patients (78%). Endoscopic curative resection was achieved in 7 patients and 1 patient is awaiting endoscopic follow-up. 1 patient experienced a delayed perforation, which was managed surgically. Histological assessment of the resected polyps revealed 8 adenomas with low grade dysplasia and 1 cancer. <h3>Conclusion</h3> DALMs are difficult to detect and challenging to resect endoscopically using conventional methods. We have demonstrated that KAR as a novel technique is safe and effective in resecting DALMs. As the learning curve of KAR is not as steep as ESD, we believe that is a viable endoscopic resection technique of DALMs in inflammatory bowel disease. <h3>Disclosure of Interest</h3> None Declared
Allogeneic STEM CELL Transplants for Patients with Myelofibrosis: Changes in the Transplant Platform and Improved the Outcome
Authors: Stefania Bregante, Alida Dominietto, Anna Ghiso, Anna Maria Raiola, Francesca Gualandi, Riccardo Varaldo, Carmen Di Grazia, Teresa Lamparelli, Silvia Luchetti, Simona Geroldi, Lucia Casarino, Sarah Pozzi, Elisabetta Tedone, Maria Teresa van Lint, Federica Galaverna, Gianni Barosi, Andrea Bacigalupo
Journal: Blood (2015)
A Worldwide Observational Registry Collecting Longitudinal Data On the Management of CML Patients (The WORLD CML Registry) - Summary of the First 1001 Patients.
Authors: Ricardo Pasquini, Jorge Cortes-Franco, Hagop M. Kantarjian, David Joske, Zhixiang Shen, Luis Meillon, Lidia Mongay, Dawn F. Eng, Jim Wang, Timothy P. Hughes, Dong-Wook Kim
Journal: Blood (2009)
The continuum of causality in human genetic disorders
Authors: Nicholas Katsanis
Journal: Genome biology (2016)

Studies of human genetic disorders have traditionally followed a reductionist paradigm. Traits are defined as Mendelian or complex based on family pedigree and population data, whereas alleles are deemed rare, common, benign, or deleterious based on their population frequencies. The availability of exome and genome data, as well as gene and allele discovery for various conditions, is beginning to challenge classic definitions of genetic causality. Here, I discuss recent advances in our understanding of the overlap between rare and complex diseases and the context-dependent effect of both rare and common alleles that underscores the need for revising the traditional categorizations of genetic traits.
Prognostic Factors For Outcome In Patients (pts) With Myelofibrosis (MF) Treated With Ruxolitinib (Rux)
Authors: Elias Jabbour, Hagop M. Kantarjian, Jing Ning, Guillermo Garcia-Manero, Tapan M. Kadia, Susan O'Brien, Jorge E. Cortes, Daniela Hoehn, Jeffrey Bryan, Farhad Ravandi, Srdan Verstovsek
Journal: Blood (2013)
SAT0118 Dyslipidemia Is Undertreated in Patients with Rheumatoid Arthritis: Results from A Large Cohort of RA Patients in Daily Clinical Practice
Authors: K. Thomas, A. Lazarini, E. Kaltsonoudis, A. Drosos, P. Katsimbri, D. Boumpas, P. Tsatsani, S. Gazi, E. Grika, P. Vlachoyiannopoulos, P.P. Sfikakis, K. Karagianni, L. Sakkas, L. Pantazi, K. Boki, T. Dimitroulas, G. Evangelatos, A. Iliopoulos, C. Georganas, P. Vounotrypidis, M. Areti, P. Georgiou, K. Mavragani, I. Bournazos, G. Katsifis, G. Kitas, D. Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Existing guidelines advocate aggressive management of dyslipidemia in rheumatoid arthritis (RA) patients according to cardiovascular disease (CVD) risk scores generated for the general population (SCORE). More specific RA scores such as the ERS-RA score have not been extensively studied. <h3>Objectives</h3> To evaluate the use of lipid-lowering agents for CVD prevention (primary/secondary) in RA patients according to different CVD risk scores (SCORE, ERS-RA). <h3>Methods</h3> Prospective, multicenter (12 hospitals, 6 private offices), cross-sectional, epidemiological study in Greece (06/2015–01/2016, RA Study Group). Demographics, disease characteristics, treatment and comorbidities were collected and SCORE/ERS-RA were calculated. <h3>Results</h3> Among 1475 patients, 178 (12%) had CVD (44% coronary artery disease, 44% peripheral vascular disease, 27% stroke) and 43% were not receiving any hypolipidemic therapy. From those on therapy, only 12% achieved an LDL-cholesterol (LDL-C) level &lt;70 mg/dl while 48% had LDL-C&lt;100 mg/dl. 859 patients without CVD, diabetes or hypolipidemic therapy were further analyzed (79% women, mean age 59.5 yrs, mean disease duration 3.4 yrs, mean DAS28-ESR 3.4, mean HAQ 0.45). Complete data for SCORE calculation were available in 225/859 patients (26%). When stratified according to CVD risk, 31.5%, 66%, 2% and 0.5% of patients had a SCORE of &lt;1% (low risk), ≥1 to &lt;5% (moderate), ≥5 to &lt;10% (high) and ≥10% (very high), respectively. In moderate risk (1–5%) patients, 78% had an LDL-C&gt;100 mg/dl while among high or very high risk (≥5%) patients, 100% had an LDL-C&gt;70 mg/dl (target groups for drug therapy). Among 996 patients (40–75 yrs old), without CVD events, there were 99 diabetic patients (10%) and less than half (48%) were on hypolipidemic therapy. For the rest, the ERS-RA score was calculated (619/897, 69% with available data); 50% of them (308/619) had a 10-year risk of ≥7.5% (therapeutic cutoff) but only 40% of patients in this group were being treated. <h3>Conclusions</h3> A substantial proportion of RA patients with established CVD or diabetes do not receive lipid-lowering therapy or they do not achieve therapeutic targets. Among those without CVD or diabetes, more than half belong to moderate to high CVD risk groups and are not receiving appropriate hypolipidemic therapy. <h3>Acknowledgement</h3> Supported by grants from the Hellenic Rheumatology Society and Professional Association of Rheumatologists. <h3>Disclosure of Interest</h3> None declared
PTU-143 Clinical Yield of Using Common Reflux-Symptom Correlation Methods: A Retrospective Study Comparing The Demeester Score, Symptom Index, and Symptoms Association Probability in Predicting Response to Antireflux Treatment in Patients with GORD
Authors: C Premathilaka, M Adesanya, I Miah, T Wong, J Jafari
Journal: Gut (2016)

<h3>Introduction</h3> Oesophageal pH-impedance monitoring is the gold standard for the diagnosis of gastroesophageal reflux disease (GORD). The DeMeester score is a global measure of acid exposure calculated from reflux parameters. Symptom Index (SI) and the Symptoms Association Probability (SAP) scores correlate symptoms to episodes of gastroesophageal reflux (GOR). Currently, it is not clear which of these scoring methods best relate to the patient’s response to treatment. This study investigates the value of these 3 metrics in predicting the clinical outcome of treatment in GORD patients. <h3>Methods</h3> We retrospectively selected patients who had 24 hour pH-impedance monitoring on suspicion of GORD during December 2014 to October 2015. Abnormal DeMeester was defined as ≥14.72, +ve SI as ≥50%, and +ve SAP as ≥95%. The Reflux Disease Questionnaire (RDQ) was completed by each patient before investigation. After reflux monitoring, patients were followed up to calculate their post-treatment RDQ at least 2 months post treatment. Sensitivity, specificity, positive and negative likelihood ratios and predictive values were calculated. <h3>Results</h3> 42 patients (11 male; total mean age 51 [25–79]) were included. 25 (59.52%) of these patients were treated. Of these, 21 patients, had medical treatment and 6 had surgical treatment (2 had both). 10/25 (40%) had a reduced RDQ score post-treatment: 8/10 (80%) having medical treatment, 1/6 (23.33%) having surgical treatment. In patients without treatment, 7/17 (41.18%) had a reduced RDQ. The two-tailed <i>p</i> value between the treated and untreated group was not significant (<i>p</i> = 1.00). Considering individual metrics, abnormal DeMeester score showed highest specificity and SAP showed the highest sensitivity in predicting lowering RDQ score post-treatment. When combining different metrics, having all three parameters positive yielded the highest overall clinical value: sensitivity 60%, specificity 95%, positive likelihood ratio 12, positive predictive value 75%, negative predictive value 90% (table 1). <h3>Conclusion</h3> In patients diagnosed with GORD by pH-impedance monitoring, having all three parameters positive i.e. abnormal DeMeester score, SAP +ve and SI +ve had a high overall value in predicting the response to treatment. Nevertheless, reduction of RDQ was equally seen in untreated GORD group. A study on a larger number of patients might be required to further confirm the findings of this research <h3>Disclosure of Interest</h3> None Declared
Identification of Target Molecules and Anti-Leukemic Effects of Novel Phospha Sugar Derivative, TMPP.
Authors: Satoki Nakamura, Mitsuji Yamashita, Tomonari Takemura, Daisuke Yokota, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Kiyoshi Shibata, Michio Fujie, Shinya Fujisawa, Kaori Shinjo, Kazunori Ohnishi
Journal: Blood (2009)
Administration of an HE2100 Depot Preparation after 60Co Total Body Irradiation (400 cGy) Reduces the Duration of Severe Neutropenia, Thrombocytopenia and Anemia in Rhesus Macaques.
Authors: Charles Dowding, James Frincke, Armando Garsd, Dwight R. Stickney, Christopher L. Reading
Journal: Blood (2004)