tbuckley/cabot-search huggingface dataset:
PWE-014 Development of an Optimum Treatment Regimen for Transcutaneous Posterior Tibial Nerve Stimulation for Faecal Incontinence
Authors: G Thomas, T Dudding, R J Nicholls, C Vaizey
Journal: Gut (2013)

<h3>Introduction</h3> Posterior tibial nerve stimulation (PTNS) is an effective treatment for faecal incontinence (FI). A wide range of PTNS regimens have been reported. The aim of this study was to determine an improved PTNS regimen. <h3>Methods</h3> Patients were randomised to either daily or twice weekly unilateral transcutaneous PTNS for six weeks. The investigator was blinded to group allocation. Once completed, further patients were recruited. They received daily bilateral transcutaneous PTNS for six weeks. The primary outcome measure was the change in frequency of FI episodes per week. PTNS was self-administered by each patient from home. <h3>Results</h3> Thirty patients received either daily or twice weekly PTNS. The daily unilateral PTNS group achieved a reduction in frequency of incontinent episodes of 5(11.3) to 3.5(4.31), p = 0.025. Three achieved complete continence. No change was seen in the twice weekly group. Neither group improved deferral time. A further 20 patients received daily bilateral PTNS. They achieved a reduction in frequency of incontinent episodes of 6 (8.25) to 2 (7.25), p = 0.029. Two achieved complete continence. There was an increase in deferral time, 3 (4) to 5 (8) minutes, p = 0.027. <h3>Conclusion</h3> Daily bilateral transcutaneous PTNS is an effective treatment for FI. It can be easily self-administered from home. <h3>Disclosure of Interest</h3> None Declared.
P378 BENEFICIAL EFFECT OF THE PROBIOTIC VSL-3 ON LIVER INJURY-ASSOCIATED SICKNESS BEHAVIOR DEVELOPMENT BY ALTERING SYSTEMIC IMMUNITY AND INHIBITING ACTIVATED MONOCYTES FROM ENTERING THE BRAIN
Authors: C. D'Mello, M. Surette, W. Macnaughton, T. Le, C. di Simone, M.G. Swain
Journal: Journal of Hepatology (2014)
Abstract 5406: Chemosensitization of melanoma by use of the minimalistic nonviral MIDGE expression system for improved TNF-alpha expression in vitro and in vivo
Authors: Wolfgang Walther, Dennis Kobelt, Jutta Aumann, Iduna Fichtner, Manuel Schmidt, Peter M. Schlag
Journal: Cancer Research (2011)

Abstract Melanomas are often refractory towards chemotherapy. Tumor necrosis factor alpha (TNF-alpha) is known for its strong chemosensitizing potential. However, to exploit this potential, high doses of TNF-alpha are required, which are often associated with severe toxicities limiting the clinical applicability. Alternatively, TNF-alpha can be generated at high level at the tumor site using local application of gene therapy. To achieve this, we employed the nonviral MIDGE vector system for significantly improved TNF-alpha expression. The minimalistic immunologically defined gene expression (MIDGE; Mologen AG, Berlin, Germany) vector system is a linear DNA molecule that is depleted of bacterial backbone, antibiotic resistance sequences and CpG motifs, which significantly reduces its size. In our in vitro experiments using equimolar amounts of luciferase expressing MIDGE vector or plasmid we observed significant up to 13-fold increased MIDGE vector mediated expression in transfected human A375, MeWo and SKMEL-28 melanoma cells. Accordingly the FACScan analysis revealed improved transfection efficiency of MIDGE vectors. We used the MIDGE vector to efficiently express TNF-alpha in human A375 melanoma cells in vitro. The MIDGE vector generated significantly higher TNF-levels in comparison to plasmid-mediated expression. The in vivo transfer of the TNF-expressing MIDGE vector into A375 melanomas by intratumoral nonviral jet-injection resulted in efficient high level cytokine expression, which was time and vector-dose dependent. Importantly, this high level TNF-expression does not lead to TNF-alpha release into the circulation and does not cause increase in body temperature or losses in body weight. The MIDGE-mediated TNF-alpha expression mediates efficient chemosensitization in the melanoma xenotransplant bearing nude mice by improving the in vivo chemotherapy with vindesine. This is reflected by significant tumor growth inhibition. The study demonstrates the superiority of the MIDGE vector system for nonviral local gene therapy approaches that might be translated into clinical applications. 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 5406. doi:10.1158/1538-7445.AM2011-5406
SP0002 Therapy of Rheumatoid Arthritis
Authors: C. Gabay
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The objective of the lecture is to provide up-to-date information on the therapy of rheumatoid arthritis, including the results of clinical trials comparing different treatment strategies, novel data on different biological agents as well as on small molecules targeting intracellular signaling pathways, the results of head to head clinical trials comparing biological agents, and the safety data from patient's registries. <h3>Disclosure of Interest</h3> C. Gabay Grant/research support from: Roche, Abbvie, MSD, Consultant for: Roche, Abbvie, MSD, Pfizer, BMS
EARLY-ONSET MENOPAUSAL VASOMOTOR SYMPTOMS ARE ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION: THE NATIONAL HEART LUNG AND BLOOD INSTITUTE-SPONSORED WOMEN’S ISCHEMIA SYNDROME EVALUATION (WISE) STUDY
Authors: Rebecca Thurston, B. Delia Johnson, Carl Pepine, Chrisandra Shufelt, Steven Reis, Sheryl Kelsey, Vera Bittner, Frank Stanczyk, Glenn Braunstein, Sarah Berga, George Sopko, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2015)
The Natural History of Idiopathic Hypoglycemia of Infancy and Its Relation to Diabetes Mellitus
Authors: Arlan L. Rosenbloom, Lawrence Sherman
Journal: New England Journal of Medicine (1966)

A SPECIFIC etiology has not been determined in the majority of infants and children with symptomatic spontaneous hypoglycemia.1 This idiopathic hypoglycemia typically has its onset before two years of age, presenting as a seizure disorder. Known endocrine or enzymatic abnormalities cannot be demonstrated, and there are no characteristic physical signs. The hypoglycemia may be continuous or intermittent, can vary greatly in severity from time to time and under-goes spontaneous amelioration over a period of months or years.The present study was undertaken to define a 2ssible relation between infantile idiopathic spontaneous hypoglycemia and other familial abnormalities in carbohydrate metabolism. The . . .
FRI0162 IL-9 Over-Expression and Th9 Polarization Immunologically Characterizes the Subclinical Gut Inflammation of Patients with Psoriatic Arthritis
Authors: F. Ciccia, A. Ferrante, A. Rizzo, V. Rodolico, G. Guggino, S. Raimondo, R. Bignone, S. Peralta, R. Alessandro, G. Triolo
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Subclinical gut inflammation has been demonstrated in patients with psoriatic arthritis (PsA) suggesting a role for the gut in the pathogenesis of inflammation in these patients. A key role for the IL-23, IL-17, IL-22 and IL-9 in the pathogenesis of psoriasis and psoriatic arthritis has been suggested, the immunologic abnormalities underlying subclinical gut inflammation in PsA are still undefined however. <h3>Objectives</h3> This study was undertaken to investigate the expression and tissue distribution of IL-23 and of Th17,Th22 and Th9 related molecules in the subclinical gut inflammation of patients with PsA. <h3>Methods</h3> Gut inflammation was assessed accordingly to De Vos et al (1). Quantitative gene expression analysis of Th1, IL-23/Th17, Th22 and Th9 responses was performed in intestinal biopsy samples obtained from 22 patients with PsA (12 with non-radiographic psoriatic axial SpA, 5 of them displaying HLA-27 positivity), 10 patients with HLA-27 positive-ankylosing spondylitis (AS), 10 patients with Crohn9s disease (CD) and 20 healthy controls. IL-23, IL-17, IL-22 and IL-9 tissue distribution was also evaluated by immunohistochemistry. <h3>Results</h3> Chronic ileal inflammation was observed in 15 PsA patients with no difference regarding axial or peripheral disease. The terminal ileum of PsA patients was characterized by a complex immunological signature. IL-23p19 m-RNA was not significantly over-expressed compared to controls but a clear Th17 and Th22 polarized immune response was demonstrable, at levels comparable to those observed in CD. Differently from CD and similarly to AS, Th1 cytokines were not significantly over-expressed in PsA. Conversely, a strong IL-23p19 and IL-22 expression in the absence of Th17 polarization was confirmed in AS gut. Unlike AS and CD, a strong and significant up-regulation of IL-9 immunologically characterized the gut of PsA patients. In particular, IL-9 immune-reactivity was observed among infiltrating mononuclear cells, high endothelial venules and Paneth cells. IL-9 mononuclear cells were demonstrated to be in large part Th9 cells. IL-9 over-expression was accompanied by significant Paneth cells hyperplasia. <h3>Conclusions</h3> The strong IL-9/Th9 polarization seems to be the predominant immunological signature of subclinical gut inflammation in PsA. Our findings indicate however a complex immune-regulation occurring in the gut of PsA patients where Th17 and Th22 polarization seems also to occur. <h3>References</h3> De Vos M, Cuvelier C, Mielants H et al. Ileocolonscopy in seronegative SPondiloarthropathy. Gastroenterology 1989 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5174
A Pilot Study of the Value of 18F-Fluoro-Deoxy-Thymidine PET/CT in Predicting Viable Lymphoma in Residual 18F-FDG Avid Masses After Completion of Therapy
Authors: Esther Mena, Maria Liza Lindenberg, Baris I. Turkbey, Joanna Shih, Jean Logan, Stephen Adler, Karen Wong, Wyndham Wilson, Peter L. Choyke, Karen A. Kurdziel
Journal: Clinical Nuclear Medicine (2014)

Background Despite its success in diagnosing and staging lymphoma, 18F-FDG PET/CT can be falsely positive in areas of posttreatment inflammation. 3′-18F-fluoro-3′-deoxy-l-thymidine (18F-FLT) is a structural analog of the DNA constituent thymidine; its uptake correlates with cellular proliferation. This pilot study evaluates the ability of 18F-FLT PET/CT to distinguish viable lymphoma from posttreatment inflammatory changes in 18F-FDG avid residual masses. Methods Twenty-one patients with lymphoma with at least 1 18F-FDG avid residual mass after therapy underwent 18F-FLT PET/CT imaging. 18F-FDG and 18F-FLT uptake values were compared, including quantitative pharmacokinetic parameters extracted from the 18F-FLT time activity curves generated from dynamic data using graphical and nonlinear compartmental modeling. Results The true nature of the residual mass was confirmed by biopsy in 12 patients (8 positive and 4 negative for viable lymphoma and by follow-up CT and/or repeat 18F-FDG PET/CT imaging over 1 year); among the remaining 9 patients, 7 lesions resolved or decreased and 2 showed growth indicative of lymphoma. 18F-FLT PET SUVest.max was significantly higher in tumors than in benign lesions (5.5 [2.2] vs 1.7 [0.6]; P < 0.0001), whereas the difference in 18F-FDG SUVs was not significant (malignant, 7.8 [3.8] vs benign, 5.4 [2.4]; P = 0.11). All of the benign lesions had an 18F-FLT SUVest.max of less than 3.0. Conclusions 18F-FLT shows improved specificity over 18F-FDG in distinguishing residual lymphoma from posttreatment inflammation and may be useful in the evaluation of patients with residual 18F-FDG–positive masses after completing therapy.
AB0340 Association between tobacco and anti-CCP in an early rheumatoid arthritis cohort. A dose-dependent effect:
Authors: V. Ruiz-Esquide, S. Cabrera-Villalba, J.A. Gόmez-Puerta, M. Hernández, M. Gόmez-Caballero, E. Graell, J.D. Cañete, G. Ercilla, O. Viñas, R. Sanmarti
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Smoking is the most-widely accepted risk factor for rheumatoid arthritis (RA), especially genetically-susceptible subjects (carriers of the shared epitope (SE)). Many studies also show an association between smoking and the presence of autoantibodies (rheumatoid factor (RF) and anti-citrullinated peptide antibodies (anti-CCP)), although there are discrepancies between cohorts and geographic areas. <h3>Objectives</h3> To analyze the relationship between smoking and the number of cigarettes smoked and the presence of the SE and autoantibodies (RF and anti-CCP) in an early RA cohort. <h3>Methods</h3> 204 patients (82.4% female) with early RA according to 1987 ACR criteria (disease duration &lt;2 years) were included. Demographic, genetic (DRB genotype), clinical, laboratory and radiographic variables were obtained at disease diagnosis. Smoking status and packs/year were evaluated at baseline. Radiologic damage was evaluated using the Larsen score. <h3>Results</h3> Of 204 patients, the smoking status was not available in 3, 111 (55%) were non-smokers and 90 (45%) ever-smokers (60 patients were active smokers and 30 ex-smokers). The mean packs/year was 18.66. Active-smokers had earlier disease onset and shorter disease duration at diagnosis than non-smokers. There were no differences in disease activity, disability or joint damage between groups (Table 1). Smokers were more-frequently RF positive than non-smokers. Likewise smoking was significantly associated with the SE. Anti-CCP positivity and titres were similar in both groups, but when heavy smokers (≥20p/y) (n=35) were compared with non-smokers (n=111) a significant association was found between smoking and anti-CCP+ (94% vs 74%, p=0.009, OR:5.83, CI 95%:1.32–25.86) and titres (703.3±616.2 U vs 587.4±633.6 UI/L, difference not significant p=0.350). <h3>Conclusions</h3> In early RA patients, smoking was associated with SE and RF positivity. Smoking was associated with anti-CCP positivity only in heavy smokers. <h3>Disclosure of Interest</h3> None Declared
S163 The 'Obesity Paradox' in chronic obstructive pulmonary disease
Authors: P. F. Collins, R. J. Stratton, R. Kurukulaaratchy, M. Elia
Journal: Thorax (2010)

<h3></h3> Poor nutritional status in chronic obstructive pulmonary disease (COPD) is associated with increased mortality independently of disease-severity (Collins <i>et al</i>).1 Epidemiological studies have suggested a protective role of obesity against mortality in COPD (Vestbo <i>et al</i>)2 which is contrary to data from the general population where obesity is associated with decreased life expectancy. This relationship has been referred to as the 'obesity paradox' and has been demonstrated in a number of chronic wasting conditions (Kalantar-Zadeh <i>et al</i>).3 This study investigated the existence of the obesity paradox in outpatients with COPD by examining the effect of body mass index (BMI) on 1-year healthcare use and clinical outcome in terms of hospital admission rates, length of hospital stay, outpatient appointments and mortality. BMI was assessed in 424 outpatients with COPD, with measurements performed by specialist respiratory nurses during outpatient clinics. 1-year healthcare use was retrospectively collected from the date of BMI measurement. Abstract S163 Table 1 Patients classified as overweight (25.0–29.9 kg/m<sup>2</sup>) or obese (&gt;30 kg/m<sup>2</sup>) experienced significantly fewer emergency hospital admissions, as well as a reduced length of hospital stay, in comparison to normal weight (20.0–24.9 kg/m<sup>2</sup>) or underweight (&lt;20 kg/m<sup>2</sup>) outpatients. There was a significant negative trend between BMI classification and mortality. This study supports the existence of the 'obesity paradox' in COPD, not only in relation to reduced 1 year mortality rates but also in terms of reduced emergency hospital admissions and reduced length of hospital stay.
Abstract 3015: The miR-21:miR-221 ratio as a serum-based diagnostic for non-small cell lung cancer
Authors: Jayaprakash Karkera, Dana S. Gaffney, Puja Londhe, Xiaoying Wu, Hongtao Fan, Mitch Raponi
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNA) are small (21-25 nucleotides) non-coding regulatory RNAs that control protein expression at the transcriptional level through various mechanisms. Previous studies have shown that circulating miRNA can be utilized as a tool to gain a better understanding of both benign and malignant tumor conditions. Their altered expression has been linked with several cancers including lung cancer. Lung cancer is the leading cause of death worldwide with approximately 85% of diagnoses being attributed to non-small cell lung cancer (NSCLC). The goal of this study was to determine if the presence of circulating miRNAs from NSCLC patients can serve as non-invasive diagnostic biomarkers of disease and therapy monitoring. We initially evaluated the expression of 16 NSCLC-specific miRNAs (miR-146b, miR-155, miR-205, miR-21, miR-221, miR-199a-5p, miR-222, miR-320, miR-223, miR-25, miR-16, miR-191, miR-20a, miR-24, miR-145, and miR-152) in 46 NSCLC serum samples ranging from stage I to IV, including 20 adenocarcinoma and 26 squamous cell carcinoma samples. Eighteen healthy controls were used for comparison. RNA was extracted from serum using the single-step Trizol method and real-time PCR (Taqman). Of the 16 miRNAs tested, six miRNAs were significantly upregulated in the NSCLC when compared to the normals (p&amp;lt;0.0001 with AUROCs of 0.80 to 0.93). Top Scoring Pair analyses identified the ratio of miR-21 to miR-221 as the most robust predictor of NSCLC status compared to healthy subjects with an AUROC of 0.95 (95% CI; 0.91-0.99, p &amp;lt; 0.001) and 17% error rate (leave-one-out cross validation). This miRNA pair was then validated in an independent set of 19 NSCLC and 26 normal serum samples with overall accuracy of 80% (89% and 73% for NSCLC and normal, respectively) and AUC of 0.88 (95%CI: 0.78-0.98). These findings demonstrate the potential of using miR-21 and miR-221 in detecting NSCLC from the serum. Furthermore, these miRNAs could lead to the development of non-invasive biomarkers for early diagnosis, prognosis, and therapy monitoring in NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3015.
AB0482 The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α
Authors: N. Ueda, H. Tsukamoto, H. Mitoma, M. Ayano, A. Tanaka, S.-I. Ohta, Y. Inoue, Y. Arinobu, H. Niiro, K. Akashi, T. Horiuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-tumor necrosis factor α (anti-TNFα) agents have been successfully applied for the treatment of rheumatoid arthritis (RA), Crohn’s disease (CD) and other chronic inflammatory diseases. Not only the neutralization of soluble TNFα but also the effect on transmembrane TNFα is important mechanisms of action of anti-TNFα agents. <h3>Objectives</h3> This study investigated the cytotoxic effects of new anti-TNFα agents, certolizumab pegol and golimumab, that are mediated by transmembrane TNFα. <h3>Methods</h3> Transmembrane TNFα-expressing Jurkat T cells that did not express TNF receptors were used. The binding ability of each anti-TNFα agent to transmembrane TNFα, antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and the apoptotic effect were examined. <h3>Results</h3> Certolizumab pegol and golimumab bound to transmembrane TNFα. Golimumab induced ADCC and CDC, which was comparable to infliximab and adalimumab. However, certolizumab pegol did not induce ADCC or CDC. Certolizumab pegol directly induced nonapoptotic cell death in transmembrane TNFα-expressing cells. Golimumab induced a weaker apoptotic effect than infliximab and adalimumab. <h3>Conclusions</h3> The cytotoxic effects of anti-TNFα agents on TNFα-expressing cells are considered to be associated with the clinical effect of these agents on granulomatous diseases. The direct cytotoxic effect of certolizumab pegol on TNFα-producing cells may contribute to its clinical efficacy in CD. Golimumab may be less effective for granulomatous diseases. <h3>Disclosure of Interest</h3> None Declared
FRI0324 Experience with adalimumab in 123 patients with juvenile idiopathic arthritis (JIA):
Authors: T. Schmalbach, G. Horneff
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Adalimumab is a fully human anti-TNF monoclonal antibody approved for the treatment of resistant polyarticular juvenile idiopathic arthritis at a dosage of 24 mg/kg/m<sup>2</sup>. every other week in children below 13 years and 40mg eow. for children older than 13 years. <h3>Objectives</h3> To report the experience of treatment with Adalimumab in a large number of JIA patients enrolled in the German JIA BIKER registry. <h3>Methods</h3> Patients with JIA with at least the baseline and one follow up visit upon adalimumab were included in the analysis. Efficacy was assessed using single activity parameters and the PedACR30/50 and 70 criteria. Tolerability was assessed by adverse event reporting. <h3>Results</h3> Until 2011 December 31, 123 patients with JIA have been recruited, 67% were females. JIA subgroup distribution was as following: systemic onset JIA (soJIA) 4 (3.3%), seronegative polyarthritis 38 (30.9%), seropositive polyarthritis 13 (10.6%), persistent oligoarthritis 12 (9.8%), extended oligoarthritis 31 (25.2%), enthesitis associated arthritis 16 (13%), psoriasisarthritis 8 (6.5%), unclassified arthritis 1 (0.8%). The most frequent accompanying diagnosis was of course uveitis in 20 pts (16%). The mean (median) disease duration before start of treatment with ADA was 6.8 (5.3) years, the age at start of treatment mean (median) was 13.6 (15) years. The initial concomitant treatment consisted of NSAIDs in 63.4%, oral corticosteroids in 48.8%, MTX in 48.8% and other DMARDs in 17%.Improvement was demonstrable by a marked decrease of single disease activity indicators and a high rate of responders according to the PedACR 30/50/70 criteria (table). No new safety signals were observed. There were 42 adverse events in 24 patients, three were serious (diabetes mellitus, anxiety disorder, sensitive palsy). Opportunistic infections or malignancies were not observed in this cohort. <h3>Conclusions</h3> The establishment of biological registries in rheumatic diseases, especially for children has already provided additional data to controlled trials. In this cohort of JIA patients out of the clinical practice treated with adalimumab high responder rates were observed. Moreover, all disease activity indicators showed a marked decrease upon treatment. <h3>Disclosure of Interest</h3> T. Schmalbach: None Declared, G. Horneff Grant/Research support from: Pfizer, Abbott
Envirionment-Environment Interactions Between Bronchiolitis and PM10 Exposure Could Be Modified by the TLR4 Polymorphism in the Development of Asthma
Authors: Young Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ji-Won Kwon, Hyo-Bin Kim, So Yeon Lee, Gwang Cheon Jang, Dae Jin Song, Woo-Kyung Kim, Jung Yeon Shim, Hwan-Cheol Kim, Jong-Han Leem, Hyung Young Kim, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2013)