tbuckley/cabot-search huggingface dataset:
Effect of preoperative concurrent chemoradiotherapy on survival of patients with resectable esophageal or esophagogastric junction cancer: Results from a multicenter randomized phase III study.
Authors: A. V. Gaast, P. van Hagen, M. Hulshof, D. Richel, M. I. van Berge Henegouwen, G. A. Nieuwenhuijzen, J. T. Plukker, J. J. Bonenkamp, E. W. Steyerberg, H. W. Tilanus
Journal: Journal of Clinical Oncology (2010)

4004 Background: Based on encouraging results of a phase II study we initiated a phase III study comparing preoperative chemoradiotherapy (CRT) followed by surgery versus surgery alone in patients (pts) with esophageal or esophagogastric junction cancer. Methods: Pts with resectable (T2-3N0-1M0) tumors received preoperative CRT consisting of weekly administrations of paclitaxel 50 mg/m2 and carboplatin AUC = 2 for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery versus surgery alone. Stratification parameters included performance status, histology, lymph node status. Results: Between end 2004 and 2008 363 pts were enrolled: male/female 284/79, median age 60 years (36-79), median WHO performance status 0 (0-1), adeno/squamous/other carcinoma 273/86/4. Major toxicities (grade ≥ 3) in the CRT arm: hematologic - leukopenia 7%, nonhematological toxicities were all below 5%. In 162 of the 188 pts (86%) randomized for surgery alone a resection could be performed versus 158 of the 175 pts (90%) who received CRT. The reported R0 resection rate was 92.3% in the CRT arm versus 64.9% in the surgery alone arm. In 132 revised specimens the pCR rate was 32.6%. In-hospital mortality was 3.7% in the surgery alone arm versus 3.8% in the CRT arm. With a median follow-up of 32 months 70 and 97 pts had died in the CRT group versus surgery alone group, respectively. The overall survival was significantly better (p = 0.011) in the group of pts treated with CRT (HR 0.67 [95% CI 0.50-0.92]). Median survival was 49 months in the CRT arm versus 26 months in the surgery alone arm. One, 2 and 3 years survival rates are 82%, 67% and 59% in the CRT arm and 70%, 52% and 48% in the surgery alone arm. Conclusions: Weekly administrations of carboplatin and paclitaxel with concurrent radiotherapy improves overall survival compared to surgery alone. Since toxicity was also acceptable, this regimen can be considered the standard of care for patients with resectable esophageal or esophagogastric junction cancer. No significant financial relationships to disclose.
THE YIELD AND PROGNOSTIC VALUE OF SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY (SPECT) MYOCARDIAL PERFUSION IMAGING (MPI) IN PATIENTS WITH END-STAGE LIVER DISEASE (ESLD) IN THE PRE-OPERATIVE SETTING: ABNORMAL TESTS DO NOT PREDICT SHORT OR MEDIUM-TERM MORTALITY
Authors: Rony Lahoud, Michael Johnson, Rami Kafa, Maan Fares, Venu Menon, Wael Jaber
Journal: Journal of the American College of Cardiology (2015)
P2-01-17: L1-CAM Promotes Adhesion of Breast Cancer Cells to the Endothelium.
Authors: K Milde-Langosch, V Dippel, C Schröder, D Wicklein, S Hein, F Jänicke, V Müller, U Schumacher
Journal: Cancer Research (2011)

Abstract Background: Overexpression of the adhesion molecule L1 -CAM (L1) in breast cancer is correlated with nodal involvement, high grading, and a shorter recurrence-free and overall survival, but the mechanism leading to this effect is poorly understood. L1 is also expressed in endothelial cells promoting the interaction between lymphatic cells and endothelia via homophilic L1-L1 interaction. This mechanism might also mediate adhesion of breast cancer cells to endothelia and thus promote metastasis. To examine this likely role of L1, the impact of L1 expression in breast cancer cells on their adherence to human pulmonary microvascular endothelial cells (HPMEC) was investigated and potential L1 ligands on these cells were identified. Methods: MDA-MB231-Fra2 breast cancer cells expressing high levels of L1 were stably transfected with shRNA vectors to generate two clones with strong L1 downregulation (L1low clones). Adherence of these clones to endothelial cells was studied in dynamic cell-flow adhesion assays in channels seeded with HPMEC simulating in vivo-conditions. Rolling or adherent cells per minute were counted using CapImage software. For the cell-flow assay HPMEC were activated with TNFα. In order to identify the L1 ligand, endothelial cells were partly pre-incubated with blocking antibodies directed to the potential binding partners L1, ALCAM, ICAM-1 and E-selectin before interaction with tumor cells. In additional experiments, flow chambers were coated with recombinant L1-CAM, ICAM1, ALCAM or E-selectin, and the adherence of MDA-MB231 cells with high or low L1 expression to these proteins was investigated. Results: Adhesion of MDA-MB231 cells to activated HPMEC was significantly higher in L1high cells compared to L1low clones, where the number of adherent cells was only 40–50% of the L1high control (p=0.025; p=0.035). Blocking experiments showed that the adherence of L1high cells could be reduced by antibodies directed to ALCAM (p=0.0007), but not to ICAM1. Anti-L1 antibodies had a significant effect only in passages of endothelial cells which showed L1 expression, whereas E-selectin blocking strongly diminished adherence of breast cancer cells irrespective of their L1 expression. In addition, L1low clones showed significantly lower adhesion to recombinant L1, ALCAM and E-selectin proteins compared to the parental cells. Conclusion: Our experiments indicate that L1 expression in breast cancer cells leads to an increased adherence to activated endothelial cells via homophilic (L1-L1) or heterophilic (L1-ALCAM) interactions. This mechanism is a possible explanation for the increased metastatic potential and poor prognosis in L1-positive carcinomas observed in vivo. Our results suggest that this adhesion molecule might be a suitable target for therapeutic interventions. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-17.
PTH-199 Prevalence of Organic Disorders in Consecutive New Patients Meeting Criteria for IBS in a Gastroenterology Clinic
Authors: U Shivaji, D Gracie, A Sainsbury, A C Ford
Journal: Gut (2013)

<h3>Introduction</h3> A positive diagnosis of irritable bowel syndrome (IBS), without the need for recourse to investigation, is encouraged. Patients meeting symptom-based diagnostic criteria for IBS are often given reassurance that there is no serious underlying pathology, and treated symptomatically. However, some studies have suggested that an organic diagnosis, such as coeliac disease or pancreatic insufficiency, may be missed if this approach is adopted. We aimed to examine the yield of investigation in patients meeting criteria for IBS in real-life clinical practise. <h3>Methods</h3> Review of consecutive unselected new patient referrals to a single Gastroenterologist’s outpatient clinic during a 2-year period, from January 2010 to December 2011. All clinic letters were reviewed retrospectively, and symptoms reported by the patient at the initial consultation were recorded. Those who described lower abdominal pain associated with a change in bowel habit, in the absence of alarm features such as rectal bleeding or weight loss, were classified as meeting criteria for IBS at presentation. IBS subtype was classified as diarrhoea-predominant (IBS-D), constipation-predominant (IBS-C), or mixed (IBS-M), according to stool pattern. Radiology, endoscopy, chemical pathology, and histopathology databases were then cross-examined in order to ascertain the final diagnosis following full investigation, to the level deemed appropriate by the consulting physician. <h3>Results</h3> There were 397 consecutive unselected new patient referrals to a single Gastroenterologist between January 2010 and December 2011. Of these, 38 (9.6%) (mean age 40.6 years, 23 (60.5%) female) reported symptoms compatible with IBS in the absence of alarm features, of whom 23 (60.5%) met criteria for IBS-D, 9 (23.7%) IBS-C, and 6 (15.8%) IBS-M. In total, 7 (18.4%) patients were found to have an organic explanation for their symptoms after investigation. The commonest organic diagnosis among patients meeting criteria for IBS was bile acid malabsorption, occurring in 4 (10.5%). Other organic diagnoses detected included inflammatory bowel disease-unclassified (1 patient), pancreatic insufficiency (1 patient), and coeliac disease (1 patient). Organic diagnoses were commoner among those meeting criteria for IBS-D, occurring in 6 (26.1%) patients. <h3>Conclusion</h3> Our data suggest that organic diagnoses may occur in up to one in five patients meeting criteria for IBS without alarm features. Bile acid malabsorption occurred in more than 10%. The yield of investigations in IBS-C was low, suggesting these individuals can be labelled confidently as having IBS without the need for further investigation. <h3>Disclosure of Interest</h3> None Declared.
AB0279 Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: Systematic review and meta-analysis of observational studies
Authors: E. Salgado, J.R. Maneiro, L. Carmona, J.J. Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To explore whether baseline titer or positivity of rheumatoid factor (RF) are predictors of the response of rheumatoid arhtitis (RA) patients to tumor necrosis (TNF) antagonists. <h3>Methods</h3> A systematic review and meta-analysis of observational studies were conducted. Pubmed, EMBASE, Cochrane and abstracts form ACR and EULAR were searched (up to June 2011). The search was limited to longitudinal studies. All studies on association between baseline RF (titer and/or status) and response to any TNF antagonists, or with enough data to estimate this association were included. Qualitative analysis and meta-analysis using random-effects approach by type of outcome response and RF test was performed. Risk of publication bias was also evaluated. Heterogeneity was tested using I<sup>2</sup>, with I<sup>2</sup> value &gt;40% defined as high levels <h3>Results</h3> The systematic review included 18 studies of 4163 identified articles, involving 5703 patients with homogeneous baseline characteristics. The most common outcome measure to assess response was EULAR criteria, usually merging good and moderate categories as responder group. The weighted mean difference (WMD) of baseline IgM RF titer in meta-analysis was higher in the non-responders group [- 101.58 (95% CI -156.58,-46.59) I<sup>2</sup> =0.0]. Combined odds ratios (ORs) of positive IgM RF, positive IgA RF, and positive IgG RF to achieve good/moderate response were 1.08 (0.80, 1.47), I<sup>2</sup> =40.9%; 0.83 (0.39, 1.73), I<sup>2</sup> =39.8%, and 1.30 (0.48, 3.51), I<sup>2</sup> =62.9%, respectively. We did not find and association between positive IgM RF and EULAR good response or remission. <h3>Conclusions</h3> This meta-analysis does not consistently support baseline IgM RF titer as a predictor of response to TNF antagonists in RA. <h3>Disclosure of Interest</h3> E. Salgado: None Declared, J. R. Maneiro: None Declared, L. Carmona Speakers Bureau: LC has received lecture fees from Abbott and Pfizer, J. J. Gomez-Reino Grant/Research support from: JJ G-R has received research grants from Roche and Schering-Plough, Consultant for: JJ.G_R is on the Advisory Boards of BMS, Pfizer, Roche, Schering-Plough and UCB SA., Speakers Bureau: JJ G-R has received lecture fees from BMS, Roche, Schering-Plough and Wyeth
A STUDY OF PRE- AND POSTSYNAPTIC ACTIONS OF THE DOPAMINERGIC SYSTEM WITH PET.
Authors: Randall A. Hawkins, Jorge R. Barrio, Michael E. Phelps, Sung-cheng Huang, Mark Bahn, Nagichettiar Satyamurthy, Andre Luxen, Randy Keen, Charna Nissenson, John M. Hoffman, C. John
Journal: Clinical Nuclear Medicine (1986)

Hawkins, Randall A.; Barrio, Jorge R.; Phelps, Michael E.; Huang, Sung-cheng; Bahn, Mark; Satyamurthy, Nagichettiar; Luxen, Andre; Keen, Randy; Nissenson, Charna; Hoffman, John M.; John, C. Author Information
The Welfare Show
Authors: Colin Martin
Journal: BMJ (2006)

V isiting The Welfare Show is a thought provoking, somewhat surreal experience, in which not everything is quite as it seems. One needs to examine the installations closely, to differentiate elements created by Danish artist Michael Elmgreen and Norwegian artist Ingar Dragset from the existing interior architecture of the gallery, which was their blank canvas. They altered its layout and lead visitors through a succession of corridors that simulate a variety of institutional environments and public spaces, including a hospital corridor, a waiting room, and an airport baggage hall. Their aim is to alert us to the ways in which the social policies of the welfare state govern …
Magnitude of Left Ventricular Hypertrophy and Risk of Sudden Death in Hypertrophic Cardiomyopathy
Authors: P Spirito, P Bellone, K M Harris, P Bernabo, P Bruzzi, B J Maron
Journal: New England Journal of Medicine (2000)

Sudden death is known to be a possible consequence of hypertrophic cardiomyopathy. Quantification of the risk of sudden death, however, remains imprecise for most patients with this disease.We assessed the relation between the magnitude of left ventricular hypertrophy and mortality in 480 consecutive patients with hypertrophic cardiomyopathy. The patients were categorized into five subgroups according to maximal wall thickness: 15 mm or less, 16 to 19 mm, 20 to 24 mm, 25 to 29 mm, and 30 mm or more. Their ages ranged from 1 to 89 years (median, 47).Over a mean follow-up period of 6.5 years, 65 of the 480 patients (14 percent) died: 23 suddenly, 15 of heart failure, and 27 of noncardiac causes or stroke. The risk of sudden death increased progressively and in direct relation to wall thickness (P=0.001), ranging from 0 per 1000 person-years (95 percent confidence interval, 0 to 14.4) for a wall thickness of 15 mm or less to 18.2 per 1000 person-years (95 percent confidence interval, 7.3 to 37.6) for a wall thickness of 30 mm or more and almost doubling from each wall-thickness subgroup to the next. The cumulative risk 20 years after the initial evaluation was close to zero for patients with a wall thickness of 19 mm or less but almost 40 percent for wall thicknesses of 30 mm or more. As compared with the other subgroups, patients with extreme hypertrophy were the youngest (mean age, 31 years), and most (41 of 43) had mild symptoms or no symptoms; of the 12 patients who were less than 18 years old at the initial evaluation, 5 died suddenly.In hypertrophic cardiomyopathy, the magnitude of hypertrophy is directly related to the risk of sudden death and is a strong and independent predictor of prognosis. Young patients with extreme hypertrophy, even those with few or no symptoms, appear to be at substantial long-term risk and deserve consideration for interventions to prevent sudden death. The majority of patients with mild hypertrophy are at low risk and can be reassured regarding their prognosis.
Effects of Menopause on Bone Mineral Density in Women with Endemic Fluorosis
Authors: Mustafa Yildiz, Baha Oral
Journal: Clinical Nuclear Medicine (2003)

Purpose The effects of menopause on bone mineral density (BMD) in women with endemic fluorosis were investigated. Materials and Methods Eighty healthy Turkish women who lived in and around the city of Isparta were selected randomly and enrolled in this study. They were separated into four groups: group 1, 20 premenopausal women with regular menstrual cycles and endemic fluorosis; group 2, 20 postmenopausal women with endemic fluorosis; group 3, 20 premenopausal normal women constituting one control group; and group 4, 20 postmenopausal normal women constituting the other control group. Bone mineral density was measured in the lumbar spine and proximal femur using dual-energy x-ray absorptiometry. Results In the premenopausal group, BMD values of vertebrae L2-L4 and Ward’s triangle in women with endemic fluorosis were significantly greater than the respective values in women without endemic fluorosis (P = 0.024, P = 0.036). There were no differences between the groups in BMD values of the femoral neck (P = 0.156) and intertrochanteric area (P = 0.076). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward’s triangle in the postmenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women without endemic fluorosis (P < 0.001, P = 0.015, P = 0.002, and P < 0.001, respectively). The BMD values of vertebrae L2-L4, the femoral neck, intertrochanteric area, and Ward’s triangle in the premenopausal women with endemic fluorosis were significantly greater than those of postmenopausal women with endemic fluorosis (P = 0.010, P = 0.002, P = 0.004, and P = 0.010, respectively). The BMD values of the sites noted for the premenopausal controls were significantly greater than those of postmenopausal controls (P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). Conclusions Postmenopausal BMD values in both endemic fluorosis and controls were significantly less than premenopausal BMD values. Although the differences were less prominent in women with endemic fluorosis, menopause is still the major determinant of BMD in the spine and femur.
AB0135 Immunomodulatory and Antiinflammatory Properties of Antigen B, A Protein Secreted by Echinococcus Granulosus Larval Stage, in Experimental Arthritis
Authors: M. Farinon, P.G. Oliveira, V.S. Clarimundo, K.M. Monteiro, A. Zaha, H.B. Ferreira, R.M. Xavier
Journal: Annals of the Rheumatic Diseases (2014)

We have evaluated whether i.p. murine ovarian tumors could be treated with an IL-2 plasmid DNA complexed with the cationic lipid, (±)-<i>N</i>-(2-hydroxyethyl)-<i>N</i>,<i>N</i>-dimethyl-2,3-bis(tetradecyloxy)-1-propanaminium bromide/dioleoylphosphatidylethanolamine (DMRIE/DOPE). Reporter gene studies were initially conducted in which mice bearing i.p. murine ovarian teratocarcinoma (MOT) were injected i.p. with reporter gene plasmid DNA (pDNA):DMRIE/DOPE. Histochemical analyses revealed that transfection occurred primarily in the tumor cells of the ascites, with only a minority of other ascitic cells or surrounding tissues transfected. IL-2 levels in the MOT ascites were determined after i.p. injection of either IL-2 pDNA:DMRIE/DOPE or recombinant IL-2 protein. IL-2 was detected in tumor ascites for up to 10 days after a single i.p. injection of IL-2 pDNA:DMRIE/DOPE, but was undetectable 24 h after a single i.p. injection of IL-2 protein. In an antitumor efficacy study, MOT tumor-bearing mice injected i.p. with IL-2 pDNA:DMRIE/DOPE on days 5, 8, and 11 after tumor cell implant had a significant inhibition of tumor ascites (<i>p</i> = 0.001) as well as a significant increase in survival (<i>p</i> = 0.008). A cytokine profile of the MOT tumor ascites revealed that mice treated with IL-2 pDNA:DMRIE/DOPE had an IL-2-specific increase in the levels of IFN-γ and GM-CSF. Taken together, these findings indicate that i.p. treatment of ovarian tumors with IL-2 pDNA:DMRIE/DOPE can lead to an increase in local IL-2 levels, a change in the cytokine profile of the tumor ascites, and a significant antitumor effect.
P753A comprehensive technical assessment of the Athlete's Heart: "The Morganroth Hypothesis" re-visited
Authors: V S Utomi, D Oxborough, G Whyte, J Somauroo, K George
Journal: Cardiovascular Research (2014)

Purpose: The current study evaluated; A) global left ventricular (LV) adaption to endurance vs. resistance training in highly trained male athletes; B) the additional insight into the athlete's heart phenotype provided by modern imaging technologies, and C) the impact of scaling for body size on LV structural data. Methods: A prospective cross-sectional design was employed to comprehensively assess the athlete's heart in 18 elite endurance-trained (ET), 19 elite resistance-trained (RT) and 17 sedentary control (CT) participants. M-mode, 2D, tissue-Doppler imaging (TDI) and speckle tracking echocardiography (STE) were employed to assess LV structure as well as global and regional LV function including myocardial strain. The indexing of LV structural parameters to body surface area (BSA) was undertaken using simple linear ratio scaling as well as a nonlinear allometric model. Results: Absolute, ratio and allometrically scaled LV mass was significantly higher in ET [200±34 g; 98±15mm/m2, 42±7mm/m2.7] than both RT [187±31g; 78±15mm/m2 and 36±6 mm/m2.7] and CT [165±32g; 74±11 mm/m2 and 33±6 mm/m2.7] (p<0.05). The predominant LV geometry in the ET was normal (65%) and eccentric hypertrophy (30%). There was no significant difference in LV mass between the RT and CT groups. Apart from a higher stroke volume in ET, compared to RT and CT, there were no significant group differences in global function during systole or diastole. Whilst regional TDI data were not different between groups, longitudinal, basal circumferential and mid radial strain was reduced in RT compared to ET. Conclusion: In this comprehensive, technical evaluation of the athlete's heart, a larger LV was present in ET even after appropriate body size scaling. Evidence for hypertrophy was lacking in RT. Differences in body size and discrimination of AH from disease pathology can be enhanced by appropriate scaling of data. Further work should evaluate cardiac strain and strain rate in RT athletes.
Endoscopic ultrasound-guided lymph node ablation with a novel radiofrequency ablation probe: feasibility study in an acute porcine model
Authors: Amrita Sethi, Mark Ellrichmann, Shantiswaroop Dhar, Klaus-Gerd Hadeler, Erich Kahle, Frauke Seehusen, Wolfram Klapper, Nagy Habib, Annette Fritscher-Ravens
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Radiofrequency ablation (RFA) is an accepted method of tissue destruction for solid organ tumors. Endoscopic ultrasound (EUS)-guided RFA has been used for lesions in the pancreas and liver, but there is limited experience of lymph node ablation using EUS-guided RFA. The aim of this study was to determine feasibility and safety of prototype EUS-guided RFA of mediastinal lymph nodes. <b>Methods:</b> This was an endoscopic experimental feasibility study in a porcine model. After EUS-guided puncture of targeted lymph nodes, the stylet of a 19-G needle was replaced by a prototype RFA probe. RFA was performed by ERBE generator (bipolar settings: 10 watts, effect 2, 2 minutes). The animals were euthanized, and the targeted lymph nodes were identified and removed for histology and measurement of the effect achieved. <b>Results:</b> A total of 18 mediastinal lymph nodes were ablated (mean size 20.8 ± 6.6 mm in the long axis). The average length of exposed probe was 10.0 ± 3.0 mm. The mean length and diameter of necrosis was 9.8 ± 3.6 mm and 5.5 ± 1.6 mm, respectively. Linear regression comparing needle length with necrosis diameter revealed a coefficient gradient of r = 0.92 (<i>P</i> = 0.0001). With EUS-RFA a mean of 17.6 ± 10.3 % (range 8.0 % – 53.2 %) of the respective lymph node area was ablated. No complications (i. e. hemodynamic instability, local bleeding, tissue damage) occurred during the procedure. Technical problems included stripping of the probe by the EUS needle and bending of the tip of the probe. <b>Conclusions:</b> EUS-RFA of lymph nodes was performed safely and successfully using a prototype EUS-compatible probe. This method may have the potential for future use in patient care.