tbuckley/cabot-search huggingface dataset:
PTH-143 Cytosponge instead of Endoscopy in Symptomatic Patients: a Feasibility Study
Authors: H Saravanapavan, J M Hoare
Journal: Gut (2013)

<h3>Introduction</h3> The estimated annual incidence for oesophageal adenocarcinoma in individuals with Barrett’s oesophagus is 0.2–0.5%<sup>1</sup>. However, endoscopic screening of individuals with risk factors for Barrett’s oesophagus including chronic heartburn and reflux<sup>2</sup> are not part of current clinical recommendations. The cytosponge, a non-endoscopic immunocytological screening kit is undergoing a multicentre study and promises to alter our current practice<sup>3</sup>. The cytosponge is less invasive than gastroscopy and would reduce the burden on endoscopy units if screening is to be introduced. It has also been shown to detect other benign diseases such as helicobacter, oesophagitis and candidiasis<sup>4</sup> and therefore may be able to replace routine gastroscopy in symptomatic patients. The aim of this study was to examine the percentage of endoscopy referrals to St Marys hospital that could be alternatively investigated with a non-endoscopic sampling method such as the cytosponge to detect Barrett’s oesophagus and/or exclude more serious pathology. <h3>Methods</h3> All pending endoscopy requests were audited on a randomly selected day. Of these, gastroscopy referrals from GP practises and outpatient department were analysed. Patients who were suitable for the cytosponge were identified using the following criteria. Inclusion - Age 45 years and above, symptoms of dyspepsia and reflux; Exclusion - Previous diagnosis of Barrett’s oesophagus, previous endoscopy in the last year, portal hypertension, patients on clopidogrel or warfarin, clotting disorders. <h3>Results</h3> A total of 161 gastroscopy referral forms were analysed; 73% from outpatients and 27% from GP surgeries. 22% of referrals were for dyspepsia and 8% for reflux. 16% of referrals were suitable for cytosponge as defined by the inclusion and exclusion criteria. <h3>Conclusion</h3> One in six referrals from GP surgeries and outpatients could be offered cytosponge instead of endoscopy for detection of Barrett’s oesophagus. Cytosponge would reduce cost, enable rapid bedside testing and provide a non-invasive method for individuals reluctant to have an endoscopic procedure. It could also be extended to detect benign oesophageal pathology and therefore avoid secondary care referrals and waiting list pressures. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> Yousef F<i> et al.</i> The incidence of esophageal cancer and high-grade dysplasia in Barrett’s oesophagus: a systematic review and meta-analysis. Am J Epidemiol. 2008: 168:237–49 Guidelines for the diagnosis and management of Barrett’s columnar-lined oesophagus. BSG. 2005 Kadri SR <i>et al.</i> Acceptability and accuracy of a non-endoscopic screening test for Barrett’s oesophagus in primary care: cohort study. BMJ. 2010: Sep 10: 341:c4372 O’Donovan M, Lao-Sirieix P and Fitzgerald RC, Non-endoscopic diagnostic tests for esophageal diseases and H.pylori using the Cytosponge, Gastroenterology. 2012: Vol. 142, Issue 5, Supplement 1, Page S-421
REASONABLE REVASCULARIZATION AFTER PERCUTANEOUS CORONARY INTERVENTION: VALIDATION OF THE SYNTAX REVASCULARIZATION INDEX FROM THE SYNTAX TRIAL
Authors: Philippe Genereux, Carlos Campos, Vasim Farooq, Christos Bourantas, Friedrich Mohr, Antonio Colombo, Marie-angèle Morel, Ted Feldman, David Holmes, Michael Mack, Marie Morice, Keith Dawkins, A. Kappetein, Tullio Palmerini, Gregg Stone, Patrick Serruys
Journal: Journal of the American College of Cardiology (2015)
The Effect of Parity on the Later Development of Non-Insulin-Dependent Diabetes Mellitus or Impaired Glucose Tolerance
Authors: Donna Kritz-Silverstein, Elizabeth Barrett-Connor, Deborah L. Wingard
Journal: New England Journal of Medicine (1989)

To determine the effect of parity on the later development of non-insulin-dependent diabetes mellitus or impaired glucose tolerance, we studied a population-based sample of 1186 women at least 40 years of age; those who had been given a diagnosis of diabetes mellitus before the age of 40 or who had insulin-dependent diabetes mellitus were excluded from the study. On the basis of the World Health Organization's criteria, 714 had normal glucose tolerance, 326 had impaired glucose tolerance, and 146 had non-insulin-dependent diabetes mellitus (NIDDM). After adjustment for age, obesity, and family history of diabetes, increased parity was associated with a significantly increased risk of both NIDDM (odds ratio, 1.16 [95 percent confidence interval, 1.04 to 1.29] per pregnancy) and impaired glucose tolerance (odds ratio 1.10 [95 percent confidence interval, 1.01 to 1.19] per pregnancy). Obesity, whether estimated by means of the body-mass index or the waist–hip ratio, was significantly associated with an increased risk of both NIDDM and impaired glucose tolerance, but this factor did not explain the association between parity and diabetes or impaired glucose tolerance; neither the maximal lifetime body-mass index nor the waist–hip ratio was significantly associated with parity in this cohort. We conclude that there is a slight increase in the risk of NIDDM or impaired glucose tolerance with increasing parity many years after childbearing and that this association is not explained by obesity. (N Engl J Med 1989; 321: 1214–9.)
P104 ROLE OF TUMOR NECROSIS FACTOR-a DURING THE DUCTULAR REACTION IN MOUSE MODELS OF LIVER INJURY
Authors: J. Best, S. Verhulst, N. Van Hul, W.-K. Syn, F. Heindryckx, H. Van Vlierberghe, H. Reynaert, I.A. Leclercq, L.A. van Grunsven, L. Dollé
Journal: Journal of Hepatology (2014)
Abstract SY03-02: Tumor metabolic phenotyping and treatment stratification by positron emission tomography
Authors: Caius Radu, Jason T. Lee, Dean O. Campbell, Johannes Czernin
Journal: Cancer Research (2011)

Abstract The ability to noninvasively measure key metabolic pathways in living subjects may assist the development of new, more efficacious therapies against cancer. Here we show that two new positron emission tomography (PET) probes, 1-(2′-deoxy-2′-18F-fluoro-β-D-arabinofuranosyl)cytosine (18F-FAC) and 1-(2′-deoxy-2′-18F-fluoro-β-L-arabinofuranosyl)-5-methylcytosine (L-18F-FMAC), detect distinct phenotypic signatures of tumor nucleoside metabolism. 18F-FAC and L-18F-FMAC accumulation in tumors measured in vivo by PET is indicative of the activities of deoxycytidine kinase (dCK) and cytidine deaminase (CDA), two key enzymes in nucleic acid metabolism. Metabolic subtypes detected by 18F-FAC and L-18F-FMAC were shown to correspond to the differential utilization by cancer cells of the nucleoside salvage pathway to generate and maintain deoxyribonucleotide pools required to sustain tumor growth. We also show that the metabolic subtypes defined by 18F-FAC and L-18F-FMAC PET measurements correlate with markedly distinct sensitivities to therapeutic interventions. These findings support the utility of PET-based phenotyping of tumor nucleoside metabolism for treatment stratification in cancer. 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 SY03-02. doi:10.1158/1538-7445.AM2011-SY03-02
P79 Plasma succinylacetone is raised after liver transplantation for tyrosinaemia type 1 and is associated with reduced porphobilinogen synthase activity suggesting it is functional
Authors: D. C. Bartlett, M. A. Preece, E. Holme, C. Lloyd, P. N. Newsome, P. J. McKiernan
Journal: Gut (2011)

<h3>Introduction</h3> Tyrosinaemia type 1 (TT1) is a rare disorder of tyrosine metabolism leading to accumulation of toxic metabolites such as succinylacetone (SA) and a high risk of hepatocellular carcinoma. Children with TT1 traditionally required liver transplantation (OLT) and while the need for this has reduced since the introduction of nitisinone some still go on to require OLT. Circulating SA inhibits the enzyme porphobilinogen (PBG) synthase and its activity can be used as a marker of functional circulating SA. Elevated urinary SA post OLT thought to be due to local production has been reported. <h3>Aim</h3> This study describes a novel finding of elevated plasma SA following OLT for TT1. <h3>Method</h3> A retrospective analysis was performed of patients treated for TT1 at our institution from 1989 to 2010. <h3>Results</h3> In patients who received nitisinone prior to OLT mean urinary SA was elevated at presentation (159.6 mmol/mol creatinine, ref. range &lt;1) as was plasma SA (17.58 mol/l, ref. range &lt;0.01) but both became undetectable on nitisinone prior to OLT (p&lt;0.05). This was associated with increased mean PBG synthase activity from 0.032 to 0.99 nkat/g Hb (ref. range 0.58 1.25). In patients who did not receive nitisinone, mean urinary SA was 274.6 mmol/mol creatinine immediately prior to transplant. Plasma SA levels/PBG synthase activity prior to OLT were not available in this group. Following OLT in patients treated with nitisinone, mean urinary SA levels quickly rose and remained elevated for the duration of follow-up. Plasma SA levels also rose with a progressive decrease in mean PBG synthase activity to low-normal levels. In patients who had not received nitisinone, mean urinary SA fell quickly by 1 year post OLT but remained above normal at levels similar to those seen in the nitisinone treated group. No data were available for plasma SA/PBG synthase activity in this group until 13 years post OLT. However, from this point onwards mean plasma SA remained elevated with a low-normal PBG synthase activity similar to that seen in nitisinone treated patients. There was no apparent correlation between SA levels and renal function. Despite reduced PBG synthase levels, no patients developed porphyria-like symptoms. <h3>Conclusion</h3> Urinary and plasma SA levels are elevated following OLT for TT1. Low-normal PBG synthase activity suggests the circulating SA may be functional. The clinical significance of this is unclear.
Normal breast tissue cells from breast cancer patients express epidermal growth factor receptor HER1-4 protein concentrations characteristic for cancer cells.
Authors: DA Olsen, B Oestergaard, S Bokmand, EH Jakobsen, I Brandslund
Journal: Cancer Research (2009)

Abstract Abstract #3052 Background: The epidermal growth factor receptor HER2 is expressed to higher than normal concentrations in 25%-30% of human breast cancers and in approximately 90% of these cases the overexpression is a result of gene amplification. The mechanism behind HER2 amplification is unknown but may be caused by continuous stimulation and activation of the HER1 system. Consequently we have mapped the concentrations of all four epidermal growth factor receptors HER1-4 in breast cancer tissue, in autologous non-cancer breast tissue and normal breast tissue from healthy women.&amp;#x2028; Material and Methods: Tissue samples of malignant and adjacent normal breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. In addition 26 samples of normal breast tissue from healthy women were collected. The tissue samples weighing between 10 and 40 mg were homogenized and the proteins were extracted. The total protein amount in the samples were measured and the protein concentrations of HER1-4 were determined quantitatively using ELISA expressed as pg/mg total protein.&amp;#x2028; Results: HER1 demonstrated lower than normal concentrations both in autologous non-cancer tissue and cancer tissue. HER2 showed 4 times higher than normal concentrations in autologous reference tissue and 24 times higher in cancer tissue, while the corresponding figures for HER3 was factor 8 and 13 and for HER4 factor 10 and 8. These differences were significant at p&amp;lt;10-4. Further it was observed that correlations between the receptors were maintained from normal breast tissue to autologous reference breast tissue but were lost in cancer tissue. Adjusting the concentrations of receptors by differences in cell number content did not change differently in the cancer patients.&amp;#x2028; Discussion: We propose these findings to indicate that breast cancer is a systemic disease where also non-cancer tissue cells in the cancer patients are continuously activated thus favouring the subsequent development of cancer. This may explain the observation that occurrence of new cancers are increased in patients previously treated for cancer. Measurement of decreased HER1 and increased HER2-4 in breast cells from healthy women may in the future be used as an indicator of increased risk for cancer development. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3052.
AB0006 CNStream2: a powerful tool for the study of the genetic basis of rheumatic diseases
Authors: A. Alonso, A. Julià, R. Tortosa, S. Marsal
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the last years, high throughput genotyping techniques have widely used for the characterization of new genetic variants associated with rheumatic diseases. Amongst these, Illumina Beadchip microarrays have been widely used, being able to scan from 100,000 to &gt;2,000,000 genome markers in one single assay. Although this technology was principally designed for Single Nucleotide Polymorphism genotyping, several methods have been developed for the parallel estimation of Copy Number Variants (CNVs), although with limited accuracy. <h3>Objectives</h3> To improve the genotyping of SNPs and CNVs from GWAS studies using the Illumina platform, we have developed CNStream2 software. <h3>Methods</h3> Several improvements have been included to the original version of CNstream software<sup>1</sup>. For CNV analysis, CNstream2 starts by combining the information of multiple samples to assign a probability relative to the number of copies. The accuracy of the call is then increased by combing the information of nearby probes. In this new version, several key aspects of the analysis algorithms have been optimized to increase the sensitivity, accuracy and computational speed of the method. We have used publicly available HapMap data on Illumina microarrays to benchmark our method in comparison to other established methods. <h3>Results</h3> The changes introduced in the new software version have substantially increased the accuracy and sensitivity of CNV calls. Importantly, it shows a superior call rate compared to the most commonly used SNP genotyping programs like GeneStudio, thereby, increasing the power to detect significant associations. CNStream 2 has now an improved computational performance and is now able to compute SNP and CNV genotypes in 10x less time (i.e. genotyping of 600,000 markers in 5,000 individuals isestimated in ∼10 hours compared to &gt;100 hours in the previous version). Our results with Hapmap samples confirm the increase in sensitivity and accuracy in SNP and CNV call in any of the Illumina genotyping microarray versions compared to other established methods. <h3>Conclusions</h3> CNStream2 is a powerful tool for those biomedical researchers conducting GWAS with the Illumina platform that want to increase the statistical power of their studies. <h3>References</h3> Alonso A, Julia A, Tortosa R, Canaleta, C., Canete, J. D., Ballina, J. Balsa, A., Tornero, J. Marsal, S et al. CNstream: A method for the identification and genotyping of copy number polymorphisms using Illumina microarrays. BMC Bioinformatics 2010;11:264. <h3>Disclosure of Interest</h3> None Declared
OFF-PUMP VERSUS ON-PUMP CORONARY ARTERY BYPASS SURGERY: AN UPDATED META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS ON ACUTE KIDNEY INJURY AND MORTALITY OUTCOMES
Authors: Ittikorn Spanuchart, Wisit Cheungpasitporn, Charat Thongprayoon, Supawat Ratanapo, Narat Srivali
Journal: Journal of the American College of Cardiology (2015)
Abstract 3880: Application of tyramide signal amplification technology to high content analysis of cellular kinase translocation assays
Authors: Stephen Hurt, Michael Campisano, Stefan Letzsch
Journal: Cancer Research (2012)

Abstract Deregulation of cellular kinase signaling pathways plays a key role in the ability of cancer cells to sustain uncontrolled proliferation, resist apoptosis, and undergo metastasis. The activation of kinase transduction pathways commonly involves the translocation of various molecular components of the pathway from one subcellular compartment to another. For example, growth factor stimulation of cells activates signaling pathways that are regulated by the level of phosphorylation of protein kinases such as protein kinase C (PKC) and protein kinase B (PKB/Akt); PKC and Akt are first recruited from the cytosol to the cell membrane where the phosphorylation event occurs. High Content Analysis (HCA) assays have become important tools in screening for potential new drugs to modulate aberrant signaling pathways. Confocal imaging provides the highest degree of spatial resolution, and can also yield lower background signals than wide-field imaging. The downside of confocal imaging is that it requires longer signal acquisition times, and it may be difficult to detect targets present in low abundance. The longer acquisition time can also result in decreased throughput when HCA is used as the detection mode for high throughput screening. Tyramide signal amplification (TSA) is an enzyme-based technology that has previous been used to enhance signal sensitivity in immunochemical staining procedures. We have applied TSA technology to the HCA of cellular kinase translocation assays using the Operetta High Content Imaging System in confocal fluorescence mode. HeLa cells were treated with compounds that induced kinase cytosol to plasma membrane translocation. Kinase localization was measured using a texture-based image analysis algorithm. We compared the signal intensity with and without TSA amplification. We will present data showing that TSA enhanced the signal intensity by at least an order of magnitude without a loss of resolution. As a result, the detection antibody can be reduced 5-fold, and the exposure time reduced 10-fold. In conclusion, TSA amplification of HCA kinase translocation assays can significantly increase sample throughput when screening compound libraries. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3880. doi:1538-7445.AM2012-3880
Abstract P1-12-06: Outcome of Frail Elderly Patients Treated with Letrozole Alone
Authors: JMJ Dixon, L Renshaw, J Keys, AD Leeper, L Williams, DB. Evans
Journal: Cancer Research (2010)

Abstract Background There are no data on the rate of progression of infirm or elderly postmenopausal patients unfit for surgery who have been treated with aromatase inhibiors alone. The aim was to determine the rate of disease control in a series of patients treated in the Edinburgh Breast Unit. Patients 79 patients with a median age of 81 years (range 57 to 98) with ER rich breast cancers (Allred score 6-8) have been treated with letrozole alone. The median follow up is 2.06 years, range 0.34 to 7.64. Of 71 patients with HER2 results, 59 (83%) were negative and 12 (17%) were positive. Results At two years, 65% were progression-free. By five years, this was 43%. The median time to first progression was 3.1 years (95% CI 1.7 to 4.5). By the Log Rank test, there was evidence of a significant difference between HER2+ve and-ve cancers (p=0.014). Median time to first progression for HER2-ve patients was 3.1 years (95% CI 1.9 to 4.2) and for HER2+ve patients was 1.8 years (95% CI 0.7 to 2.8). By two years, 67% of HER2-ve patients were progression-free, while 34% of the HER2+ve patients remained progression-free. At five years, 32% of the HER2-ve patients were progression free, however HER2+ve patients had insufficient follow up to estimate the 5 year progression-free rate. At two years, 77% of patients were still alive. By five years, that number was 33%. The median survival time was only 3.2 years (95% CI 2.4 to 4.1). There was no evidence to suggest a difference in mortality rates between HER2+ve and HER2-ve patients (p=0.79). Median survival time for HER2- ve patients was 2.6 years (95% CI 1.6 to 3.7) and for HER2+ve patients it was 3.0 years (95% CI 2.5 to 3.5). Conclusions In an elderly unfit population with ER rich breast cancer two thirds of these women will have their cancer controlled at 2 years by letrozole alone. HER2+ve cancers have a significantly shorter progression free survival than HER2-ve cancers. For older or infirm women unfit for surgegy with ER rich breast cancers, letrozole will control their cancer in the majority to the time of their death which was from other causes in all patients in this series. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-06.
Abstract 5245: C-Kit isoforms predict melanoma drug sensitivity.
Authors: Bengt Phung, Eiríkur Steingrímsson, Lars Rönnstrand
Journal: Cancer Research (2013)

Abstract The receptor tyrosine kinase c-Kit is an essential regulator of melanocyte and melanoma development. Alternative splicing of c-Kit produces one long variant, c-Kit(+), with a tetrapeptide GNNK located in the extracellular juxtamembrane domain, and one short variant, c-Kit(-), which lacks this sequence. In this study we characterize for the first time the function of the GNNK tetrapeptide sequence in melanoma. Our results show that step by step elimination of the GNNK tetrapeptide gradually increases receptor tyrosine phosphorylation, ubiquitination and downstream MAP kinase ERK activation. Successively increasing insert length, progressively leads to reduced melanoma cell survival during dacarbazine or rapamycin drug treatment. Our results indicate that the ratio between c-Kit isoforms might be useful as a prognostic marker for melanoma drug response. Citation Format: Bengt Phung, Eiríkur Steingrímsson, Lars Rönnstrand. C-Kit isoforms predict melanoma drug sensitivity. [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 5245. doi:10.1158/1538-7445.AM2013-5245
Routine coagulation screening is an unnecessary step in patients without evidence of biochemical jaundice prior to ERCP
Authors: Jonathan Nicholls, Richard Egan, Michael Stechman
Journal: International Journal of Surgery (2013)

s / International Journal of Surgery 11 (2013) 589e685 643 ABSTRACTS was also a prognostic indicator for the OS (HR1⁄42.48, p1⁄40.035) in HCC after resection. Conclusions: Liver function prior to surgery and poor tumour differentiation are prognostic factors for OS and PFS after resection. 0871: LAPAROSCOPIC SUBTOTAL CHOLECYSTECTOMY WITHOUT CYSTIC DUCT LIGATION e AN ALTERNATIVE TO OPEN CONVERSION. A PROSPECTIVE STUDY Pavan Padaki , Himanshu Wadhawan , Sanjay Pandanaboyana , Afshin Alijani . NHS Tayside, Dundee, UK; Royal Infirmary of Edinburgh,