tbuckley/cabot-search huggingface dataset:
PWE-055 Bowel Cleansing Agents Enhance Reader Confidence Levels When Excluding Significant Findings At Capsule Endoscopy
Authors: R Rameshshanker, A O’Rourke, J Butcher, C Fraser
Journal: Gut (2014)

<h3>Introduction</h3> Capsule endoscopy (CE) is the first line of investigation for examining the small bowel (SB) mucosa. While standard preparation (SP) is more convenient for patients, mucosal visibility may deteriorate within the distal SB. Recent meta-analyses suggest that bowel-cleansing agents (BCA) can improve small bowel image quality (IQ). The influence of BCA compared to SP on reader confidence levels (RCL) when excluding clinically significant findings (CSF) has not been examined. <h3>Methods</h3> <h3>Aim</h3> To compare RCL when excluding CSF and assessing IQ during reading following SP or BCA prior to CE. <h3>Methodology</h3> We performed a retrospective analysis of SB capsule images of 100 consecutive patients who underwent a complete CE examination at our institution from Oct 2012 - Mar 2013. Patients had SP (intake of clear liquids for 18 h and 12 h fasting prior to the procedure without BCA) or BCA (2l of polyethylene glycol (PEG) or magnesium citrate (MC) in addition to SP). The participants’ demographic and clinical data were collected and SB transit time (SBTT) calculated. A four point scale was used to assess IQ (grade 1 = &lt;80% of mucosa visible ± excessive debris ± severely reduced brightness to grade 4 = ≥ 90% of mucosa visible ± mild debris± mildly reduced brightness). The SBTT was divided into quartiles (Q1-Q4) by time and the IQ score, RCL and number of CSF for each quartile were determined by a gastroenterologist experienced in CE, blinded to the preparation. Procedures were examined in randomised order. <h3>Results</h3> 49 (49%) patients had SP (group A) while 51 (51%) had one of the BCA (39% had PEG and 61% had MC, group B). There was no significant difference in age (p = 0.87), sex (p = 0.57), indication (p = 0.25) and SBTT (group A: 264 ± 112 mins vs. group B: 233 ± 100 mins, p = 0.14) between groups. For each quartile, IQ scores were significantly higher for group B than A except in Q1 (Q1: 3.7 ± 0.7 vs. 3.5 ± 0.6, p = 0.06; Q2: 3.6 ± 0.5 vs. 3.1 ± 0.6, p &lt; 0.0001; Q3: 3.2 ± 0.6 vs. 2.3 ± 0.7, p &lt; 0.0001; Q4: 2.8 ± 0.5 vs. 1.9 ± 0.8, p &lt; 0.0001). There was no difference in detection of CSF between group A and B (41% vs. 51%, p = 0.33, respectively). For each quartile, RCL for excluding significant findings were significantly higher for group B than A except in Q1 (Q1: 100% vs. 96%, p = 0.06; Q2: 96% vs. 73%, p &lt; 0.0001; Q3: 88% vs. 33%, p &lt; 0.0001; Q4: 77% vs. 20%, p &lt; 0.0001). There was no significant difference in IQ or RCL between PEG or MC. 3 procedures (all SP) were considered unsatisfactory for IQ with recommendation to repeat these after BCA. <h3>Conclusion</h3> BCA pre-capsule endoscopy significantly improve small bowel IQ and RCL when excluding CSF. Bowel cleansing appears to be an important parameter for optimising the qualitive aspects of CE reading. <h3>Disclosure of Interest</h3> None Declared.
Fatal central nervous system air embolism during elective esophagogastroduodenoscopy
Authors: K. Niehaus, E. Zamora, M. Harkins
Journal: Endoscopy (2013)

A 64-year-old woman with gastric adenocarcinoma and esophageal stricture underwent esophagogastroduodenscopy (EGD) and dilation. During the procedure no bleeding or mucosal tears were observed. She later appeared sedated but was unresponsive to naloxone. Physical examination revealed spontaneous eye opening with leftward gaze, autonomic instability, decerebrate posturing, myoclonus, absent gag reflex, and a positive Babinski sign.
Abstract 2381: Preclinical molecular targeting therapy of pancreatic cancer using a genetically engineered mouse model
Authors: Koji Miyabayashi, Hideaki Ijichi, Dai Mohri, Motohisa Tada, Yoshinari Asaoka, Tsuneo Ikenoue, Masao Omata, Harold L. Moses, Kazuhiko Koike
Journal: Cancer Research (2011)

Abstract Patients with pancreatic ductal adenocarcinoma have a poor prognosis. New therapeutic approaches to improve the prognosis are expected. We generated pancreas-specific Tgfbr2 knockout mice in the context of Kras activation, which recapitulated clinical and histopathological manifestations of human pancreatic cancer. Using this model we investigated the anti-tumor effects of gemcitabine and molecular targeted drugs. We treated the mice with EGFR inhibitor elrotinib or VEGFR inhibitor axitinib in combination with gemcitabine. Median survival times were 45, 60, 77, and 74 days for control, gemcitabine alone, gemcitabine + axitinib, and gemcitabine + erlotinib, respectively. In vitro assays, elrotinib inhibited phosphorylation of EGFR and both drugs also inhibited proliferation of human pancreatic cancer cell lines in vitro.This mouse model also recapitulated chemosensitivity of human pancreatic cancer and suggested erlotinib and axitinib in combination with gemcitabine can be superior to gemcitabine alone. This mouse model helps us to investigate the mechanism of the action of drugs and chemoresistance. 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 2381. doi:10.1158/1538-7445.AM2011-2381
Abstract LB-382: Inhibition of CD95 signalling by APG-101 enhances efficacy of radiotherapy (RT) and reduces RT-induced tumor satellite formation
Authors: Philipp N. Pfenning, Markus Weiler, Christian Merz, Manfred Jugold, Christian Gieffers, Michael Platten, Harald Fricke, Wolfgang Wick
Journal: Cancer Research (2011)

Abstract CD95 is a prototype death receptor that regulates the induction of apoptosis, upon binding of its ligand CD95L. Therefore, activation of the CD95L/CD95 system has been regarded an excellent target for treatment of various malignancies. In contrast to the aim of promoting CD95 activation, there is compelling evidence that CD95 is able to promote tumor growth through intracellular non-apoptotic signalling mechanisms. This mechanism has recently been described for glioblastoma, in which activation of CD95 by CD95L leads to invasive growth and glioma cell migration. This is signalled through increased activity of pivotal glioblastoma invasion-related proteases, that is matrix metalloproteinases (MMP). With this shift of paradigms, blocking of the CD95L mediated invasion of tumor cells and subsequent tumor progression may therefore be a promising approach in anti-glioma therapy. APG101 is a fusion protein, consisting of the extracellular domain of human CD95 and the Fc-region of human immunoglobulin G. Hence, it acts as a soluble CD95 receptor trapping the CD95 ligand. The presented project aims at analyzing the clinical relevance of blocking CD95 signalling, given the fact that glioma patients with upregulated CD95 expression have worse survival rates than those with intermediate expression levels. In proof-of principle experiments APG101 inhibits CD95L-mediated invasion of glioma cells. More importantly, APG101-treatment (100 mg/kg body weight) resulted in significantly prolonged survival of SMA560-tumor bearing Vm/Dk mice, less glioma cell satellites in the surrounding tissue and reduced activity of MMP. APG101 in combination with focal irradiation at 6 Gy demonstrated a remarkable reduction of tumor growth with a significantly prolonged survival compared with irradiation treatment alone and inhibition of the proinvasive properties of radiotherapy as demonstrated by magnetic resonance imaging and histology. Surprisingly, APG-101 added to the vascular endothelial growth factor receptor (VEGFR) inhibitor cediranib (AZD2171) did not increase the survival of SMA-560-tumor bearing mice as compared to cediranib alone nor did it impair the proinvasive consequences of cediranib. Our data strongly support the potential use and clinical evaluation of APG101 in combination with radiotherapy in the treatment of malignant glioma. 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 LB-382. doi:10.1158/1538-7445.AM2011-LB-382
AB1188 Long-term safety of anti TNF therapy in children: Experience from a single center:
Authors: R. Campanilho-Marques, F. Ramos, A.F. Mourão, H. Canhão, J.E. Fonseca, J.A. Pereira da Silva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-tumor necrosis factor (TNF) therapies have been shown to be highly effective in the treatment of pediatric rheumatic patients. The experience from long term follow up of adult patients treated with anti TNF drugs have identified the occurrence of infections and immune mediated reactions possibly related with the use of these therapies. <h3>Objectives</h3> This study was undertaken to evaluate the long-term safety of anti-TNF agents in pediatric rheumatic patients, followed up in a single center. <h3>Methods</h3> Patients were followed up using Reuma.pt, an electronic medical chart coupled with a database developed by the Portuguese Society of Rheumatology. This evaluation was based on all pediatric rheumatic patients followed up in the Rheumatology Department of Hospital de Santa Maria, Lisbon, who started an anti TNF drug before the age of 18 years. <h3>Results</h3> Twenty-four patients treated with anti-TNF agents were analyzed. Fifteen were female (62.5%) and 9 were male (37.5%). Mean age was 16.3±5.7 years old, mean disease duration was 9.6±6.0 years, the mean duration of biological therapy was 42.7±34.6 months. In a total of 24 patients, 14 were under treatment with etanercept (ETN), 8 with infliximab (IFX) and 2 with adalimumab (ADA). Seventy-one percent of the patients were under treatment for more than 2 years. From the 24 patients, 22 had Juvenile Idiopathic Arthritis, 1 Polyarteritis nodosa and 1 Idiopathic uveitis. Twenty-eight possibly related adverse events (AE) were registered, of which 2 were severe (bronchospasm and tuberculosis) and led to the switch to another TNF antagonist in one case and to stopping definitely biological therapy in another case. Twenty four AE were registered in patients treated with IFX, (82,1%) mild-moderate and 1 (3,6%) severe AE. Three (10,7%) mild-moderate and none severe AE in patients treated with ETN and 1 (3,6%) severe and none mild-moderate in patients on ADA. Fifty six percent of the mild-moderate AE were due to infections (urinary and upper respiratory systems), 13% due to elevated liver enzymes, 13% due to cytopenia and the remaining 18% due to diverse causes (cough, tachycardia, and hypotension).No malignancies, lymphomas, demyelinating disorders or deaths were reported. <h3>Conclusions</h3> These data confirms an acceptable safety profile for the use of anti-TNF agents in pediatric rheumatic patients. <h3>Disclosure of Interest</h3> None Declared
176 PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PILOT STUDY EVALUATING EFFICACY AND SAFETY OF INTRAVENOUS SILIBININ IN PATIENTS WITH HCV RECURRENCE ON THE GRAFT AFTER LIVER TRANSPLANTATION
Authors: M. Rendina, M. D'Amato, A. Castellaneta, N.M. Castellaneta, N. Brambilla, G. Giacovelli, L. Rovati, S.F. Rizzi, M. Zappimbulso, R. Bringiotti, A. Di Leo
Journal: Journal of Hepatology (2013)
A Controlled Trial of a Two-Component Acellular, a Five-Component Acellular, and a Whole-Cell Pertussis Vaccine
Authors: Lennart Gustafsson, Hans O. Hallander, Patrick Olin, Elisabet Reizenstein, Jann Storsaeter
Journal: New England Journal of Medicine (1996)

Because of concern about safety and efficacy, no pertussis vaccine has been included in the vaccination program in Sweden since 1979. To provide data that might permit the reintroduction of a pertussis vaccine, we conducted a placebo-controlled trial of two acellular and one whole-cell pertussis vaccines.
Pancreaticoduodenectomy without Preoperative Radiological and Histological Diagnosis Diagnostic strategy/management
Authors: N Van der Gaag, Y Nio, M Van Berge Henegouwen, T Van Gulik, M Bruno, O Busch, E Rauws, P Fockens, D Gouma
Journal: Endoscopy (2006)

Introduction: Controversy exits about the diagnostic strategy/management of patients with clinical suspicion of a periampullary tumour but without a 'visible mass' noticed on US/CT/MRCP. In these patients EUS/brush/biopsy might be helpful in deciding whether surgery is indicated. Objective: The present study evaluated the additional value of EUS/brush/biopsy in the diagnostic workup of patients with inconclusive radiological imaging. Pathology after resection was correlated with preoperative diagnostics. Methods: A consecutive cohort of 303 patients, suspected to have a periampullary malignancy, underwent pancreaticoduodenectomy from Jan 2000-Oct 2005. Patients were classified by results of preoperative diagnostic workup: (A) visible mass on US/CT/MRCP, (B) no visible mass, conclusive additional EUS/brush/biopsy, (C) no mass, inconclusive results of additional diagnostic workup. Pathological findings after resection were correlated with preoperative diagnostic results. Results: A visible mass was found in 231 patients (group A: 76%). Of the 72 patients without a visible mass in 62 (86%) EUS/brush/biopsy had led to a preoperative diagnosis (group B: 21%). Remaining 10 patients had inconclusive results of additional diagnostic workup or no further diagnostics performed (group C: 3%). Pathological findings after resection were, overall & each group separately (A/B/C): (pre)malignancy 85% (85/87/60), benign cystic 5% (7/0/0), focal pancreatitis 10% (8/11/30), no tumour 1% (-/2/10). Conclusions: In patients clinically suspected to have a periampullary tumour, 76% has a visible mass of which 85% had a (pre)malignancy at pathology. Additional diagnostic workup (EUS/brush/biopsy) leads in 86% of the cases of the remaining group to a preoperative diagnosis. In the small subgroup without conclusive preoperative diagnostics, 60% has a (pre)malignancy after resection.
Mucin-1 Increases Renal TRPV5 Activity In Vitro, and Urinary Level Associates with Calcium Nephrolithiasis in Patients
Authors: Mingzhu Nie, Manjot S. Bal, Zhufeng Yang, Jie Liu, Carolina Rivera, Andrea Wenzel, Bodo B. Beck, Khashayar Sakhaee, Denise K. Marciano, Matthias T.F. Wolf
Journal: Journal of the American Society of Nephrology (2016)

Hypercalciuria is a major risk factor for nephrolithiasis. We previously reported that Uromodulin (UMOD) protects against nephrolithiasis by upregulating the renal calcium channel TRPV5. This channel is crucial for calcium reabsorption in the distal convoluted tubule (DCT). Recently, mutations in the gene encoding Mucin-1 ( MUC1 ) were found to cause autosomal dominant tubulointerstitial kidney disease, the same disease caused by UMOD mutations. Because of the similarities between UMOD and MUC1 regarding associated disease phenotype, protein structure, and function as a cellular barrier, we examined whether urinary MUC1 also enhances TRPV5 channel activity and protects against nephrolithiasis. We established a semiquantitative assay for detecting MUC1 in human urine and found that, compared with controls ( n =12), patients ( n =12) with hypercalciuric nephrolithiasis had significantly decreased levels of urinary MUC1. Immunofluorescence showed MUC1 in the thick ascending limb, DCT, and collecting duct. Applying whole–cell patch-clamp recording of HEK cells, we found that wild-type but not disease mutant MUC1 increased TRPV5 activity by impairing dynamin-2– and caveolin-1–mediated endocytosis of TRPV5. Coimmunoprecipitation confirmed a physical interaction between TRPV5 and MUC1. However, MUC1 did not increase the activity of N -glycan–deficient TRPV5. MUC1 is characterized by variable number tandem repeats (VNTRs) that bind the lectin galectin-3; galectin-3 siRNA but not galectin-1 siRNA prevented MUC1-induced upregulation of TRPV5 activity. Additionally, MUC1 lacking VNTRs did not increase TRPV5 activity. Our results suggest that MUC1 forms a lattice with the N -glycan of TRPV5 via galectin-3, which impairs TRPV5 endocytosis and increases urinary calcium reabsorption.
Abstract 715: TGF-beta blockade improves the distribution and efficacy of chemotherapeutic agents in breast carcinoma
Authors: Jieqiong Liu, Shan Liao, Benjamin Diop, Wei Chen, Shom Goel, Yuhui Huang, Yves Boucher, Rakesh K. Jain, Lei Xu
Journal: Cancer Research (2011)

Abstract Although the role of TGF-β has been studied extensively, its impact upon drug delivery within tumors remains poorly understood. In this study, we blocked the TGF-β pathway in mouse models of breast cancer and studied the effect on delivery and efficacy of chemotherapeutics. We used both genetic (overexpression of sTβRII, a soluble TGF-β type II receptor) and pharmaceutical (1D11, a TGF-β antibody) approaches to block the TGF-β signaling in two orthotopic breast cancer models (human MDA-MB-231 cells and murine 4T1 cells). TGF-β blockade significantly decreased the growth and metastasis of orthotopic human breast carcinoma xenografts. In addition, TGF-β blockade increased the recruitment and incorporation of myofibroblasts into tumor blood vessels and restored vascular perfusion. Moreover, TGF-β blockade normalized the tumor extracellular matrix (ECM) by decreasing collagen I content. As a result of this vessel and ECM normalization, TGF-β blockade improved the transvascular and interstitial transport of both small and large molecular weight chemotherapeutic agents, and consequently enhanced their efficacy. In conclusion, our study shows that TGF-β blockade might represent a new approach to improve delivery of both low molecular weight conventional drugs as well as nanomedicines in order to maximize therapeutic outcomes. 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 715. doi:10.1158/1538-7445.AM2011-715
SAT0557 Osteoblast-Specific Expression of the Nuclear Receptor Ppar-Delta Controls Bone and Glucose Homeostasis
Authors: C. Scholtysek, N. Ipseiz, F. Djouad, G. Schett, G. Krönke
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> As members of the nuclear receptor superfamily, peroxisome proliferator-activated receptors (PPARs) do not only act as central metabolic regulators but simultaneously orchestrate the inflammatory response and bone homeostasis. However, underlying mechanisms are incompletely understood. <h3>Objectives</h3> Here we aimed to study the role of the nuclear receptor PPARdelta in bone biology and during the regulation of energy homeostasis by the skeleton. <h3>Methods</h3> We analysed the involvement of PPARdelta in the differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Furthermore, we generated mice with a conditional deletion of PPARdelta in osteoblasts by crossing animals carrying floxed alleles of PPARdelta with mice expressing a Cre recombinase under the Runx2 promoter. <h3>Results</h3> We observed a robust induction of the expression of PPARdelta during the differentiation of MSCs into osteoblasts, whereas PPARgamma was downregulated. Notably, deletion of PPARdelta in MSCs resulted in an impaired differentiation of osteoblasts. Mice carrying a conditional deletion of PPARdelta in pre-osteoblasts showed reduced numbers of osteocytes, osteopenia and developed insulin resistence. <h3>Conclusions</h3> Our data demonstrates a crucial role of PPARdelta in the differentiation of osteoblasts and identifies this nuclear receptor as an important factor mediating the crosstalk between systemic energy homeostasis and the skeleton. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4341
Abstract 2422: Early features of EMT in <i>Abcb4−/</i> <i>−</i>-cholangiocytes: A novel cellular model for testing antimetastatic drugs
Authors: Amaia Arbizu, Carmen Gil-Puig, Juan Cabello, Jon Lecanda
Journal: Cancer Research (2012)

Abstract Discovering novel drugs for epithelial tumors remains a challenge since cellular events underlying the onset of carcinoma progression are largely unknown. We previously reported the therapeutic effects of oral 5′-methylthioadenosine in the Abcb4−/− mouse (Latasa et al, PLoS ONE 2010: e15690), a clinically relevant model of chronic liver disease leading to carcinoma development. Aiming to gain insight into malignant cellular traits, we then generated primary cultures of intrahepatic bile duct cells from this Abcb4−/− mouse model. We found that Abcb4−/−-cholangiocytes exhibit a fibroblastoid-like appearance which is accompanied by diminished expression of epithelial hallmarks (CK19), and a concomitant up-regulation of mesenchymal markers such as Snail1. The trans-epithelial-electrical-resistance analyses indicated that whereas confluent monolayers of normal cholangiocytes retained the epithelial polarity, Abcb4−/−-cholangiocytes fail to repolarize. Abcb4−/−-cholangiocytes proliferated at reduced growth rates (p&amp;lt;0.05), formed a higher number of colonies in soft agar (p&amp;lt;0.01) and were less sensitive to antiproliferative effect of TGFβ1 (p&amp;lt;0.05). Consistent with EMT characteristics, Abcb4−/−-cholangiocytes induced TGFβ isoforms and were more sensitive to TGFβ1-signaling. Collectively, this data suggests that Abcb4−/− cholangiocytes acquire EMT features that may be largely regulated in vivo by TGFβ1. This original bile ductular cell line of Abcb4−/−-cholangiocytes will be useful for testing compounds that may interfere with metastatic malignancy of EMT. 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 2422. doi:1538-7445.AM2012-2422
THU0108 Global molecular effects of tocilizumab therapy in synovial biopsies of early RA patients
Authors: J. Ducreux, A. Nzeusseu Toukap, F.A. Houssiau, P. Durez, B. Lauwerys
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab is an approved humanized anti-IL-6 Receptor antibody with proven therapeutic benefits in the treatment of patients with RA. <h3>Objectives</h3> This study aimed to investigate the global molecular effects of Tocilizumab versus Methotrexate therapy in synovial biopsy samples obtained from early RA patients harvested prospectively before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. <h3>Methods</h3> Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. Total RNA was extracted, labeled according to standard Affymetrix procedures, and hybridized on GeneChip HGU133 Plus 2.0 slides. Quantitative real-time reverse transcriptase-polymerase chain reaction (qPCR) experiments were performed to confirm the differential expression of selected transcripts. <h3>Results</h3> We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines (IL-6, IL-7, IL-22, ...) &amp; chemokines (CCL8, CCL11, CCL13, CCL19, CCL20, CXCL5, CXCL13, ...), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared with the effects of Methotrexate, Rituximab, and Adalimumab therapies. Real-time qPCR experiments, performed until now, confirm the down-regulation of CXCL13 and up-regulation of BMPR1A expression following Tocilizumab treatment. <h3>Conclusions</h3> Tocilizumab displays distinct molecular effects on synovial biopsies of RA patients. These results open perspectives for the individualization of therapeutic decisions, based on the molecular profiles of the patients. <h3>Disclosure of Interest</h3> None Declared