tbuckley/cabot-search huggingface dataset:
PWE-237 Ciclosporin in acute severe ulcerative colitis: a meta-analysis
Authors: R Krishnamoorthy, K R Abrams, N Guthrie, S Samuel, T Thomas
Journal: Gut (2012)

<h3>Introduction</h3> The efficacy of intravenous Ciclosporin in the treatment of acute severe steroid refractory ulcerative colitis is variable in several small studies.<sup>1 2</sup> The benefit of immunosuppression in initial responders for preventing delayed colectomy is unclear and large randomised trials are not forthcoming. The primary aim of the meta-analysis was to evaluate the efficacy of intravenous Ciclosporin in steroid refractory acute colitis. Primary end points were immediate and delayed colectomy rates. Secondary end points were delayed colectomy rates in responders on immunosuppression vs no immunosuppression. <h3>Methods</h3> MEDLINE (1966–2011), EMBASE and PubMed databases searched using keywords, “colitis” “acute colitis,” “ciclosporin,” “cyclosporin,” “ulcerative colitis” and “fulminant colitis” from January 1965 to December 2011. Articles were selected/reviewed based on a pre-defined inclusion criteria and independently reviewed by three authors (RK, NG and TT) and data collected. Meta-analysis using random effects model was done. <h3>Results</h3> 31 studies involving 1295 patients were included in the final analysis (692 males, average age 37.4 years, range 27–58.8 years). The average duration of colitis prior to admission (25 studies, 1062 patients) was 54 months and 660 patients (26 studies, 1148 patients) had pancolitis. The immediate colectomy rate was 23.6%, (95% CI 20% to &gt;27.5%) and delayed colectomy 37.8% (95% CI 32.8% to 43.1%) at an average follow-up of 28.8 months. On meta-regression analysis the duration of colitis was the only confounding factor for delayed colectomy (p=0.05). On sub-group analysis, immunosuppression (Aza/6MP) in initial responders significantly reduced delayed colectomy rates by 20% (OR 0.36, 95% CI 0.61 to 0.81, p=0.014). The number need to treat to prevent one delayed colectomy was 5. There was a 13% increase in colectomy rates in the sub-group of patients (5 studies, 113 patients) who were on immunosupression (failed immunospression) prior to iv ciclosporin although this was not statistically significant (p=0.22). <h3>Conclusion</h3> Intravenous Ciclosporin prevents immediate and delayed colectomy in 76.4% and 62% respectively. There is a non-significant increase in colectomy rates (13%) in patients who failed immunosuppression prior to Ciclosporin. Immunosuppression in initial responders significantly reduces delayed colectomy rates and should be considered unless contraindicated. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Cheifetz AS</b>, <i>et al.</i> Ciclosporin is safe and effective in patients with severe Ulcerative Colitis. <i>J Clin Gastroenterol</i> 2011;<b>45</b>:107–12. 2. <b>Lichtiger S</b>, <i>et al.</i> Cyclosporin in severe Ulcerative Colitis refractory to steroid therapy. <i>N Engl J Med</i> 1994;<b>330</b>:1841–5.
SAT0359 Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does not Prevent Vertebral Fractures
Authors: M. Van Der Weijden, C.J. van Denderen, W.W. Lems, M.M. Nurmohamed, B.B. Dijkmans, I.I. van der Horst-Bruinsma
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing spondylitis (AS) is characterized by chronic inflammation often leading to ankylosis of the spine, but also by a decrease of bone mineral density (BMD) and high prevalence of vertebral fractures (VF). Treatment with TNF blocking agents decreases inflammation and has shown to be effective in increasing BMD, but its effect on bone quality is not fully elucidated. <h3>Objectives</h3> To study the effects of etanercept (TNF-blocker) on BMD and vertebral fractures in AS patients after two years of treatment. Additionally, changes in markers of bone turnover (CTXI, CTXII, RANKL, OPG, Osteocalcin) and radiological progression, including the thoracic spine, were studied during treatment with etanercept. <h3>Methods</h3> Consecutive patients with active AS, treated with etanercept for two years, were included. BMD lumbar spine and hips was measured at baseline and after two years, as well as the radiological damage (mSASSS, including thoracic spine), vertebral fractures (Genant method) and change in bone-markers. <h3>Results</h3> Forty-nine AS patients were included (Table). After two years of etanercept, hip BMD raised with 2.2% (p=0.014) and lumbar spine BMD with 7.0% (p&lt;0.001). The BASDAI decreased significantly (p&lt;0.001) as well as CRP and ESR (p&lt;0.001). Despite etanercept therapy, the number of patients with vertebral fractures more than doubled (from 6 to 15 patients, p=0.004) as well as the severity. Also the radiological damage mSASSS+ThSpine increased significantly over time (from 12.1 to 18.5, p&lt;0.001). No significant change in bone-markers was found during treatment. <h3>Conclusions</h3> This prospective longitudinal observational cohort study in AS patients showed that after two years etanercept treatment, BMD of the hip and spine increased significantly. However, the number and severity of vertebral fractures increased, as well as the radiological progression, including the thoracic spine. Thus, the favourable effect of etanercept on BMD in AS is accompanied by unfavourable outcomes on vertebral fractures and radiological damage. <h3>Acknowledgements</h3> This is an investigator initiated cohort study financed with an unrestricted Grant of Pfizer <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2147
P1014 FACTORS CONTRIBUTING TO VARIANCE BETWEEN ARFI ELASTOGRAPHY AND LIVER HISTOLOGY: RESULTS OF A LARGE UNSELECTED CONSECUTIVE SERIES WITH SIMULTANEOUS BIOPSY OF ARFI MEASUREMENT SITE
Authors: D.I. Sherman, M. Jagtiani, P. Bassett, D. Abeles, O. Kemp, P. Shorvon
Journal: Journal of Hepatology (2014)
UTILIDAD DE UN NUEVO SISTEMA DE REGISTRO DE LA IMAGEN PARA LA NAVEGACIÓN EN EL MEDIASTINO: ESTUDIO COMPARATIVO EN UN MODELO PORCINO
Authors: H Córdova, R San José Estépar, A Rodríguez-D'Jesús, G Martínez-Pallí, A Arguis, C Rodríguez de Miguel, JM Perdomo, J Llach, KG Vosburgh, G Fernández-Esparrach
Journal: Endoscopy (2012)

Introducción: El mediastino es un potencial órgano de interés para los procedimientos endoscópicos mínimamente invasivos. La mediastinoscopia transesofágica ha demostrado ser posible en modelos animales. Sin embargo, las complicaciones son frecuentes cuando se utiliza un acceso a ciegas. Objetivo: evaluar la utilidad y seguridad de un sistema de registro de la imagen (SRI) para identificar las estructuras mediastínicas. Métodos: Se realizó mediastinoscopia de 30 minutos en 30 cerdos: 15 utilizando el SRI (MED-SRI) y 15 a ciegas (MED). El acceso al mediastino se realizó en ambos grupos a través de un túnel submucoso de 10cm de longitud en la pared del esófago. Se realizó una exploración sistemática con identificación de 8órganos (carina, arteria pulmonar derecha, aurícula derecha, vena cava, bronquio del cerdo, tronco braquiocefálico, nervio vago derecho y pulmón. La necropsia se realizó inmediatamente después del procedimiento. Resultados: La mediastinoscopia fue posible en todos los animales del grupo MED-SRI pero no en 2 animales del grupo MED. El número total de órganos identificados fue igual en ambos grupos (MED-SRI: 6,13±1,3; MED: 4,7±2,3; p=0,066). Sin embargo, la aurícula derecha y la vena cava fueron identificados en más casos en MED-SRI (13 y 15 vs. 3 y 11; p=0.000 y 0.03, respectivamente). Las complicaciones fueron iguales en ambos grupos (MED-SRI: 3, 23%; MED: 4, 27%; p=ns), siendo el neumotórax la complicación más frecuente (2 y 3, respectivamente).
Abstract 4939: MicroRNA-375 regulates tumor invasion and metastasis phenotypes and is associated with poor outcome in head and neck squamous cell carcinoma.
Authors: Lizandra Jimenez, Thomas Harris, Nicole Kawachi, Thomas Belbin, Nicolas Schlecht, Jihyeon Lim, Ruth Angeletti, Michael B. Prystowsky, Geoffrey Childs, Jeffrey Segall
Journal: Cancer Research (2013)

Abstract Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group identified miR-375 as the most consistently down-regulated miRNA in tumor samples when compared to paired normal samples. Patients in the lowest quartile of miR-375 expression had significantly decreased disease-specific survival, increase incidence of loco-regional recurrence and distant metastasis. The highly significant association of lower miR-375 expression in patients with poor prognosis and distant metastasis led us to investigate the mechanism by which miR-375 expression causes alterations to the invasive properties of HNSCC. Stable transductant cell lines with increased expression of miR-375 have been generated from two oral cavity cell lines, UMSCC1 and UMSCC47, utilizing lentiviral constructs driving expression of the miR-375 precursor. We have not seen a significant change in proliferation rate for either of the miR-375 expressing lines compared to the empty vector control expressing lines. We have observed diminished invasion properties in vitro correlates with increased miR-375 expression. We have also identified that miR-375 expression in HNSCC result in impaired chemotactic migration properties and suppressed matrix degradation properties. To identify proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC) to identify candidate miRNA target proteins to identify differentially expressed proteins in control and miR-375 over-expressing lines. Candidate target proteins will be validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, miR-375 represents a potential prognostic marker of poor outcome and metastasis in HNSCC and may function by suppressing the expression of genes and proteins which are involved in the invasive properties of HNSCC. Citation Format: Lizandra Jimenez, Thomas Harris, Nicole Kawachi, Thomas Belbin, Nicolas Schlecht, Jihyeon Lim, Ruth Angeletti, Michael B. Prystowsky, Geoffrey Childs, Jeffrey Segall. MicroRNA-375 regulates tumor invasion and metastasis phenotypes and is associated with poor outcome in head and neck squamous cell carcinoma. [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 4939. doi:10.1158/1538-7445.AM2013-4939
PTH-076 Dried Blood Spot Testing For Hepatitis B And C In The Chinese Community Living In Northern Ireland
Authors: AA Mccurley, N McDougall
Journal: Gut (2014)

<h3>Introduction</h3> The epidemiology of hepatitis B and C in Europe is changing, with migration causing significant increases in prevalence rates. Northern Ireland still has a very low prevalence of viral hepatitis, with an average of 80–100 HBV and 100–120 HCV cases being diagnosed every year. Certain groups however are at higher risk of infection including those born in high or intermediate endemic areas. <h3>Aim</h3> The aim was to set up a single viral hepatitis community screening event to offer testing to members of the Chinese community in Belfast and determine the prevalence of HBV and HCV in those tested. <h3>Methods</h3> Members of the Belfast Chinese Community were invited to attend a Hepatitis BandC awareness and testing session held in the Chinese Welfare Centre. All those attending for testing were educated regarding the advantages and disadvantages of screening through a presentation (translated) and literature. Dry blood spot (DBS) testing was used as an alternative to venous sampling to try and encourage participation. All patients (and their GPs) were informed of results by letter. Those with positive HBsAg or positive HCV antibody individuals were contacted by letter and also by telephone with the assistance of an interpreter and asked to attend a hospital clinic. Those who tested HBsAg negative and HBcAb positive were advised to attend their GP surgery for follow up HBV serology and HBV DNA. HIV testing was offered to all those with a positive result. <h3>Results</h3> 97 individuals expressed an interest in coming forward testing but 29 (30%) could not be screened as they were not registered with a GP in Northern Ireland. Of those that attended the event 55 individuals were tested (62% female, mean age 47, range 22 -67). 13 (24%) individuals tested. HBsAg negative and HBcAb positive, - suggesting previous infection. Five patients (9%) individuals tested positive for chronic viral hepatitis – 4 were HBsAg positive and 1 was HCV PCR positive. All 5 subsequently attended a hepatology clinic for follow-up. 49 (89%) of those presenting for testing reported they had never been vaccinated against HBV. <h3>Conclusion</h3> DBS testing of a sample of the Chinese community living in a low prevalence area of the UK can detect chronic viral hepatitis in 9%. In addition, one third of those requesting screening were not registered with a GP and therefore could not be detected by current NHS services. This suggests that the NHS need to consider setting up screening services for ethnic communities even in low prevalence areas of the UK. Project Funding: Funding for the dried blood spot testing kits and the analysis of these were paid for by Roche Pharmaceuticals. <h3>References</h3> <b>Disclosure of Interest</b> A. Mccurley Grant/research support from: Roche, N. McDougall Grant/research support from: Roche.
Recurrent Lymphoma Detected on F-18 FDG Coincidence Imaging with Negative Findings on Ga-67 Citrate Scintigraphy
Authors: Buddhiwardhan Ojha, Luvenia W Bender, Robert Francisco, Johnny W Scott
Journal: Clinical Nuclear Medicine (2002)

Ga-67 citrate scintigraphy and computer tomography have been used in tumor staging, to determine disease extent, and for the pre- and post-therapeutic management of Hodgkin’s and non-Hodgkin’s lymphoma. Today, localization of hypermetabolic tissue using F-18 FDG is beginning to play a role in the staging and restaging of lymphoma. The authors report a case of recurrent Hodgkin’s lymphoma in a 31-year-old man detected by F-18 FDG. Findings of the Ga-67 citrate scintigram were negative. Palpable right axillary adenopathy was found on routine physical examination follow-up. Comparison with previous negative findings obtained with Ga-67 citrate was unchanged. However, computed tomography revealed new right axilla lymphadenopathy, prompting further investigation with F-18 FDG SPECT, which showed hypermetabolic activity corresponding to the region of the right axilla involvement. Pathologic examination showed changes indicative of interfollicular recurrence of Hodgkin’s lymphoma.
Failure of Rubella Herd Immunity during an Epidemic
Authors: Lawrence E. Klock, Gary S. Rachelefsky
Journal: New England Journal of Medicine (1973)

Between January 8 and May 20, 1971, over one thousand cases of rubella occurred in Casper, Wyoming. Eighty-four per cent of these cases were in persons 12 to 18 years old; 27 cases occurred in women, seven of whom were pregnant. Nine months before the epidemic, a rubella vaccination program had been conducted in this community in which 83 per cent of elementary-school children and 52 per cent of preschool children were vaccinated. During the epidemic the attack rate for all preschool and elementary-school children was 1 per cent; for those in grades eight through 12, the attack rate was approximately 15 per cent. The concept that a highly immune group of prepubertal children will prevent the spread of rubella in the rest of the community was shown by this epidemic not always to be valid.
Significance of Abnormally Low Blood Urea Levels
Authors: J. C. Gallagher, David Seligson
Journal: New England Journal of Medicine (1962)

LITTLE attention in the past has been paid to an understanding of the significance of an abnormally low level of urea in the blood. The major portion of the published literature discussing levels of urea is concerned with abnormal elevations. Factors causing an elevation have been subjected to much study. In contrast, little mention of the clinical conditions causing a lowering of the blood urea can be found. It is the impression of many clinicians, on the basis of textbook statements,1 , 2 that low blood urea levels are rare and that very low values, when they do occur, are seen almost . . .
AB0075 Calgizzarin (S100A11) is Up-Regulated in Rheumatoid Arthritis
Authors: L. Andres Cerezo, K. Prajzlerová, D. Veigl, K. Pavelka, J. Vencovský, L. Šenolt
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Calgizzarin (S100A11) is a member of the S100 protein family that acts in many different tumors via regulating variety of biologic functions such as cell proliferation and inflammation. <h3>Objectives</h3> To compare the expression of calgizzarin in synovial tissue, synovial fluid and serum between patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to investigate its association with disease activity. <h3>Methods</h3> Calgizzarin expression was analysed in synovial tissues from six patients with RA and six patients with OA by immunohistochemistry. Serum and synovial fluid calgizzarin levels were measured by ELISA in 43 patients with RA and 40 subjects with OA. Disease activity score based on 28 joints (DAS28-CRP) was used to assess disease activity. For in vitro experiments, peripheral blood mononuclear cells (PBMCs) were isolated from blood of patients with RA (n=3-9). <h3>Results</h3> The expression of calgizzarin was significantly up-regulated in synovial lining as well as sublining layers in samples from patients with RA compared to those with OA. In agreement, serum (18.23±2.83 vs. 11.43±0.86 ng/ml; p=0.009) and particularly synovial fluid (280.35±38.84 vs. 55.50±10.92 ng/ml; p&lt;0.0001) calgizzarin levels were significantly higher in patients with RA compared to OA. In addition, PBMCs from patients with RA spontaneously secreted higher levels of calgizzarin in comparison with OA (p=0.011) after 24 hours, and this secretion was enhanced by other S100 proteins, including S100A4 (p&lt;0.001), S100A8 (p&lt;0.01) and S100A9 (p&lt;0.0001), but not by S100A12 (p=0.08). In patients with RA, synovial fluid calgizzarin levels correlated significantly with DAS28 (r=0.359, p=0.018), CRP (r=0.478, p=0.001), synovial fluid leucocyte count (r=0.662, p&lt;0.0001) and serum anti-CCP levels (r=0.484, p=0.001), but not with IgM-RF levels (r=0.139, p=0.375). No such associations were observed for serum calgizzarin. <h3>Conclusions</h3> Our data provide the first evidence of up-regulation of calgizzarin and its association with inflammation and disease activity in patients with RA. <h3>Acknowledgements</h3> This study was supported by MHCR Research Project No. 00023728, Research Project SVV: 262512 and by IGA Research Project No. NT 13698-4 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2463
TEMPORAL TREND IN THE INCIDENCE OF STENT THROMBOSIS: IMPACT OF IMPROVED ANTIPLATELET REGIMEN AND EVOLVING CORONARY STENT TECHNOLOGY
Authors: Pranav Kansara, Wasif Qureshi, Usman Choudhry, James Hopkins, Claudine Jurkovitz, James Laughery, Ehsanur Rahman, Sandra Weiss, William S. Weintraub
Journal: Journal of the American College of Cardiology (2015)
P1-01-04: Immunological Effects of Bisphosphonates on gdT Cells in Breast Cancer.
Authors: T Sugie, Y Tanaka, M Toi, N Minato
Journal: Cancer Research (2011)

Abstract Background: Human γδT cells play an important role in the first-line of defence. Accumulating data demonstrate that γδ T cells recognize nonpeptide antigens such as IPP and HMBPP and activated γδT cells have potent cytotoxic activity against tumor cells. Nitrogen-containing bisphosphonates like zoledronic acid inhibit farnesyl diphosphate synthetase, resulting in the accumulation of upstream metabolites such as IPP. Previous studies on the adoptive transfer of ex-vivo amplified γδ T cells demonstrated the safety and feasibility of γδT cell-based immunotherapy for metastatic cancer. According to ABCSG-12 clinical trial, zoldedoric acid improved DFS of patients with early-stage breast cancer under adjuvant endocrine therapy. Whereas a precise mechanism remained unclear, it is likely that γδT cells are involved in this anti-tumor effect in breast cancer. Materials and Methods: Peripheral blood mononuclear cells derived from 63 (54 untreated non-metastatic and 9 metastatic) patients with breast cancer were examined for the baseline population of γδT cells and their proliferative responses to zoledronic acid in vitro. Tumor-infiltrating lymphocytes were isolated from 20 tumor biopsies and 2 pleural effusions. Peripheral blood γδT cells were stimulated with 5 μM zoledronic acid and cultured in the presence of 100 IU/ml IL-2 for 10 days. Amplified γδ T cells were analyzed for cytokine production and cytotoxic activity. Results: The proportion of γδ (TCRVδ2 -bearing) T cells among peripheral blood CD3+ cells was 4.2 ± 5.0%. Although it was equivalent to the previously reported value of 4.3 ± 2.2% in healthy volunteers, 14% (9/63) of patients exhibited an increase in the number of peripheral blood γδT cells at baseline. The level of TCRVδ2 T cells with potent anti-tumor activity was significantly higher than that of TCRVδ1 T cells (4.2± 5.0% vs. 1.5 ± 1.8%, p&amp;lt;0.001), whereas they were present in tumor-infiltrating cells at essentially the same levels (4.4± 9.6% vs. 3.7 ± 9.7%, p=0.434). Percentage of TCR Vδ2+ CD3+ cells among amplified γδ T cells in vitro and cytokine (IFN-γ and TNF-α) production by them were significantly proportional to the initial level of TCRVδ2+/CD3+ ratio in peripheral blood. Upon treatment with zoledronic acid, breast cancer cell lines became susceptible to γδ T cells. Conclusions: γδ (TCR Vδ2-bearing) T cells increased in some patients with breast cancer and the TCRVδ2+/CD3+ ratio at baseline was correlated with the efficiency of proliferation and cytotoxic activity when treated with zoledronic acid. Zoledronic acid efficiently sensitized breast tumor cells to be lyzed by γδ T cells. The present results suggest that γδ T cells stimulated with zoledronic acid can be utilized for immunotherapy against breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-04.