tbuckley/cabot-search huggingface dataset:
PTU-125 Laboratory Investigations for Patients Meeting Diagnostic Criteria for Irritable Bowel Syndrome: Are We Meeting the Standards?
Authors: J Kennedy, L Materacki, K Wright, S Waterman, R Makins, A Di Mambro
Journal: Gut (2016)

<h3>Introduction</h3> Alongside a thorough clinical assessment NICE clinical guideline 61 recommends that patients meeting diagnostic criteria for irritable bowel syndrome (IBS), as defined by the Rome III criteria, should undergo laboratory testing for inflammation (C-reactive peptide (CRP) and plasma viscosity (PV) or erythrocyte sedimentation rate (ESR)), full blood count (FBC) and antibody testing for coeliac disease to exclude non-organic pathology.<sup>1</sup> Faecal calprotectin is a reliable and cost effective adjuvant test to help differentiate between functional and inflammatory bowel disease (IBD).<sup>2,3</sup> Our aim was to assess local adherence to NICE guidelines on investigating patients who meet diagnostic criteria for IBS. <h3>Methods</h3> As part of a wider study into the use of faecal calprotectin as a diagnostic tool within Gloucestershire Hospitals NHS Foundation Trust, we interrogated clinic letters, endoscopy reports and pathology results for patients in whom a negative (&lt;50 mg/g faeces) or intermediate (50–150 mg/g faeces) faecal calprotectin level had been measured between September 2014 and September 2015. In patients diagnosed with IBS, we identified which of CRP, PV/ESR, FBC and antibody testing for coeliac disease had been done prior to or concurrent with faecal calprotectin measurement. <h3>Results</h3> Of the 148 patients (age range: 16–81, median age: 35; 72% female) who satisfied inclusion criteria, 63.5% (n = 94) had not undergone at least one of the recommended laboratory tests around the time of faecal calprotectin measurement. PV/ESR had not been checked in a majority (54.1%). Notably, 7.4% of patients had never had coeliac serology checked, 72.7% of whom presented with a change in bowel habit. <h3>Conclusion</h3> Although clear guidance exists for the investigation of patients meeting diagnostic criteria for IBS and use of faecal calprotectin as a diagnostic tool, insufficient essential accessory investigations are being completed. This risks conditions such as IBD, gastrointestinal cancer and coeliac disease being misdiagnosed as IBS with significant implications for delays in management and ongoing avoidable morbidity. We are reviewing measures to improve local adherence to NICE guidance, and call on other Trusts nationally to reflect on their own practice. <h3>References</h3> 1 Irritable bowel syndrome in adults: diagnosis and management. NICE guidelines [CG61]. Published: February 2008. 2 Konikoff MR, Denson LA. Role of faecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. <i>Inflammatory Bowel Diseases</i> 2006;<b>12</b>(6):524–34. 3 Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel. NICE diagnostics guidance [DG11]. Published: October 2013. <h3>Disclosure of Interest</h3> None Declared
Leukemogenic FLT3 Mutations Confer Enhanced Proliferation and Survival Properties to Multipotent Progenitor Cells in a Murine Model of Chronic Myelomonocytic Leukemia.
Authors: Benjamin H. Lee, Zuzana Tothova, Ross L. Levine, Kristina Anderson, Natalija Buza-Vidas, Dana E. Cullen, Elizabeth P. McDowell, Jennifer Adelsperger, Stefan Frohling, Brian J.P. Huntly, Miloslav Beran, Sten Eirik Jacobsen, D. Gary Gilliland
Journal: Blood (2007)
Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach
Authors: Christopher B. Fox, Mark T. Orr, Neal Van Hoeven, Sarah C. Parker, Traci J.T. Mikasa, Tony Phan, Elyse A. Beebe, Ghislain I. Nana, Sharvari W Joshi, Mark A. Tomai, James Elvecrog, Timothy R. Fouts, Steven G. Reed
Journal: Journal of Controlled Release (2016)

For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.
AB0978 The Association of Power Doppler Signal Grades with The Serum Inflammatory Marker Level
Authors: J.-E. Park, H.-S. Lee, H.-D. Cho, T. Kang
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Power Doppler can show the degree of hyperemia in inflamed synovium. Serum inflammatory markers also reflect the arthritic activity in various rheumatic disease including rheumatoid arthritis. However, no report has been published regarding an association between them. <h3>Objectives</h3> We investigated an association between power Doppler semiquantitative signal grade and all the 5 serum inflammatory markers of white blood cell (WBC), hemoglobin (Hb) and platelet (PLT) count which possibly can be used in the practical field as well as commonly used ESR and CRP. <h3>Methods</h3> Rheumatic disease patients initially presenting with objective joint tenderness or swelling were evaluated with ultrasound and blood test was done to determine serum inflammatory marker level. A total of 827 ultrasound examined joints (112 metacarpophalangeal, 85 metatarsophalangeal, 82 proximal interphalangeal, 13 knee, 46 tendons, 136 ankle, 53 elbow, 15 hip, 255 wrist, 29 shoulder) from 2009 to 2014 were analyzed in this study. According to rheumatic disease classification, rheumatoid arthritis was most common and undifferentiated arthritis, ankylosing spondylitis and gout followed. ANOVA, two sample T-test, Spearman correlation test, multiple linear regression and logistic regression analysis were performed for statistics using SAS 9.2 version. p&lt;0.05 were considered as significant. <h3>Results</h3> The presence of positive Doppler signal itself was associated with elevated ESR, CRP and PLT number but not Hb level at the time of ultrasound examination (ESR, CRP: p&lt;0.0001, WBC: p=0.0116, platelet: p=0.0246). Spearman correlation coefficients showed positive linear association between power Doppler grade and serum levels inflammatory markers (ESR: r=0.21, CRP: r=0.30, WBC: r =0.13, platelet: 0.11, p-value &lt;0.05) except Hb level. However, multiple linear regression test after adjusting confounding variables showed that only the CRP level among the 5 variables showed a positive relationship with power Doppler grade (p=0.0022). Furthermore, logistic regression test showed one step increase of Doppler grade resulted in 1.3 mg/dL increase of serum CRP level. Post hoc (Scheffe) analysis showed rheumatoid arthritis was the most correlated disease among the rheumatic diseases we included. <h3>Conclusions</h3> In a patient with presenting objective joint tenderness or swelling, if there is a positive power Doppler signal, it is associated with elevated serum markers of inflammation. Especially, the CRP is the only marker that have positive correlation with the Doppler signal semi-quantitative grade. One grade up of Power Doppler signal is expected to elevate CRP as amount of 1.3 mg/dL. Rheumatoid arthritis is the most associated disease that can be applied this result. <h3>Disclosure of Interest</h3> None declared
Abstract 15541: Effect of Stress Perfusion and Wall Motion Response on Outcome of Obese versus Non-Obese Subjects Without Known Coronary Artery Disease
Authors: Gaibazzi Nicola, Valentina Lorenzoni, Claudio Reverberi, Juefei Wu, Feng Xie, Thomas R Porter
Journal: Circulation (2014)

Background: Although several studies have demonstrated a protective effect of obesity in coronary artery disease (CAD), it is unclear whether this protective effect is evident in patients referred for stress imaging. Real time contrast echocardiography (RTCE) permits the simultaneous analysis of perfusion and wall motion during different forms of stress echocardiography.The objective of this study was to determine whether a protective effect of obesity is evident in subjects referred for pharmacologic stress RTCE. Methods and Results: Wall motion (WM) and myocardial perfusion (MP) with RTCE (using SonoVue and Definity ultrasound contrast) were assessed in 2106 consecutive patients without known CAD referred for either dobutamine (n=1209) or dipyridamole (n=897) stress echocardiography. Of these, 481 (23%) were obese (body mass index&gt;30 kg/m2). Outcome (death/non-fatal infarction) was determined over a median follow-up of 1022 days. Multivariate Cox Models were created from significant univariate variables to assess hazard ratios (HR) and 95% confidence intervals (CI). Abnormal MP and/ or WM were seen in 246 dobutamine and 169 dipyridamole studies (equally distributed between obese and non-obese). Although event free survival (EFS) was significantly better for obese versus non-obese subjects with normal tests (p=0.01) and in obese patients with abnormal dobutamine stress perfusion/wall motion responses (p=0.009), obesity was not an independent clinical predictor of outcome, while age (HR 1.04 (95% CI 1.03-1.06) and male gender (HR 2.26;(95% CI 1.59-3.21) did independently predict outcome (both p&lt;0.001). Furthermore, abnormal responses to stress (either dobutamine or dipyridamole) were associated with significantly worse prognosis, independent of age, gender, or obesity (HR 2.67;95% CI 1.91-3.77). Conclusions: Although obese subjects with both normal and abnormal responses to pharmacologic stress have improved EFS when compared to non-obese with the same test result, this trait is not independently associated with outcome. Perfusion and wall motion responses determined with RTCE add significant predictive value in this setting irrespective of age, gender, or obesity status.
AB0099 Overexpression of uPAR in Fibroblast-like Synoviocytes Promotes Angiogenesis in Patients with Rheumatoid Arthritis
Authors: L. Yan, P.Y. Feng, W.Y. Ting, L. Meng
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Urokinase-type plasminogen activator receptor (uPAR), is a multi-functional receptor on cell surface, widely present in endothelial cells, fibroblasts, and a variety of malignant cells. Our previous studies have suggested that expression of uPAR is higher in patients with rheumatoid arthritis (RA) compared to osteoarthritis (OA) and the traumatic patients. <h3>Objectives</h3> Our objective was to investigate the promoting-angiogenesis effects of uPAR in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLSs). <h3>Methods</h3> Chemically synthesized small interference RNA (siRNA) specifically targeting the uPAR gene was transfected into RA-FLSs by cationic liposome and the cell supernatants from uPAR gene-silenced RA-FLSs were extracted to cultivate the EA.hy926 (a human endothelial cell line). Transwell and tubule formation assays were used to explore the influence of RA-FLSs uPAR on EA.hy926 angiogenesis. <h3>Results</h3> EA.hy926 cells treated with conditioned medium of uPAR-siRNA RA-FLSs had a worse migrating ability and tubule formation effects, for they had only about 38% transmembrane cells and the average number of complete tubular structures decreased to 38.2%,relative to the transfection reagent control group (*P&lt;0.05). <h3>Conclusions</h3> uPAR in RA-FLSs affects neoangiogenesis of synovial tissues in patients with RA, which imply that targeting uPAR and its downstream signal pathway may provide beneficial therapeutic effects on RA. <h3>References</h3> Noh H, Hong S, Huang S. Role of urokinase receptor in tumor progression and development. Theranostics. 2013;3(7):487–95. Ferraris GM, Sidenius N. Urokinase plasminogen activator receptor: a functional integrator of extracellular proteolysis, cell adhesion, and signal transduction. Seminars in thrombosis and hemostasis. 2013;39(4):347–55. Yoo SA, Kwok SK, Kim WU. Proinflammatory role of vascular endothelial growth factor inthe pathogenesis of rheumatoid arthritis: prospects for therapeutic intervention. Mediators of inflammation. 2008;2008:129873. <h3>Disclosure of Interest</h3> None declared
An older man with thoracic back pain
Authors: Joseph Dalby Sinnott, David C Howlett
Journal: BMJ (2016)

A 76 year old man with a history of prostate cancer presented to his general practitioner with increasing mid thoracic back pain. Radiographs of the thoracic spine were obtained (fig 1⇓).What do these show?



Fig 1  Radiographs of the thoracic spine



The plain film radiographs show a …
FRI0458 Assessment of Comorbidity in Psoriatic Disease: How Often Should Be Performed?: Table 1
Authors: L. Carmona, J.C. Torre-Alonso, M. Moreno, E. Galíndez, J. Babío, P. Zarco, L.F. Linares, E. Collantes, M. Fernández-Barrial, J.C. Hermosa, P. Coto, C. Suárez, R. Almodόvar, J. Luelmo, V. Cárcaba, S. Castañeda, T. Otόn, R. Curbelo, J. Gratacόs
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Psoriatic disease (PsD) is associated with multiple comorbidities. When establishing management protocols, the periodicity for detection and evaluation of such comorbid conditions needs to be specified. <h3>Objectives</h3> To establish guidelines for the follow-up of selected comorbidities in patients with PsD. <h3>Methods</h3> An expert panel with specialists in Rheumatology, Internal Medicine, Dermatology and General Practitioners defined the comorbidities with higher impact on PsD based on the existing literature and their experience. The periodicity for detection and monitoring of comorbidities in the Rheumatology setting was established by consensus after iterations and systematic review. <h3>Results</h3> The expert panel agreed to evaluate comorbidities as part of routine clinical practice at the time of diagnosis, upon changes in systemic treatment and at follow-up visits (evidence level 5, level of agreement 8.8). In any case, monitoring must be customized depending on the risk profile, morbidity, comorbidities and patient preferences. The following table shows the proposed periodicity for detection, assessment, and monitoring of the most important comorbidities in PsD. <h3>Conclusions</h3> This proposal for a periodic assessment of comorbidities in patients with PD allows systematic clinical monitoring of the patient by the Rheumatologist and Dermatologist, and can contribute to the early detection and management of these comorbidities <h3>Acknowledgement</h3> The GECOAP project was funded by Merck Sharp &amp; Dohme of Spain <h3>Disclosure of Interest</h3> None declared
SP0038 How Can The Proliferation of Biosimilars Impact on R&amp;D and Quality?
Authors: R. Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2016)

Almost twenty years ago, the advent of biological therapies changed the world of rheumatology in three ways: clinical results became dramatically better; treating patients became more complicated but also much more rewarding; and the price of antirheumatic therapy skyrocketed. The advent of biosimilars that has started recently is viewed by many as an important correction of the third aspect; it will also add a little to the complexity of treating patients; but by definition, it will not make clinical results any better at the individual patient level: “bio-<i>similar</i>”. Certainly, making antirheumatic therapy sustainable at the societal level is a laudable goal, if not for the individual physician, then at least for the health care system as a whole. But are there any downsides to the introduction in practice of biosimilars? Part of the answer to that question can be understood if one asks another question: <i>why</i> are biosimilars less expensive than the originator products? An important part of the answer to that question is that the manufacturer of biosimilars can avoid the very large investments in research and development (R&amp;D) that are needed for developing originator products. But this is then also the answer to the first question: the savings generated by biosimilars are to a significant extent taken from the R&amp;D budgets in pharmaceutical industry. For those who are concerned about the long-term perspectives of health care from the societal point of view this should be a sobering thought. A second concern is generated by the increasing number of biological products on the market, including both originator and biosimilar products. These medications are by their nature complex mixtures of proteins, the quality control of which is an extremely demanding task. The agencies charged with overseeing these processes will have to adjust to a reality where, for the treatment of RA alone, nine approved originator products will co-exist with easily as many biosimilar products, some of which are manufactured in several different places around the globe and transported across continents under varying physical conditions. To maintain the highest possible level of quality under these circumstances will be a daunting task for these agencies. Biosimilars are now a fact of rheumatological life. Neither of the two concerns described here should be a reason not to use biosimilars when it would be medically appropriate to do so. But for those who are charged with setting health-care priorities, enthusiasm over the shorter-term financial gains with biosimilars should be balanced with prudence in view of the longer-term perspectives for future generations of patients. <h3>Disclosure of Interest</h3> R. Van Vollenhoven Grant/research support from: AbbVie, Amgen, BMS, GSK, Pfizer, Roche, UCB, Consultant for: AbbVie, Biotest, BMS, Celgene, Crescendo, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Vertex
Impact of KIR and HLA Genotypes on Outcome in Nonmyeloablative Hematopoietic Cell Transplantation (HCT) Using HLA Matched Related Donors.
Authors: Ramaprasad Srinivasan, Mary Carrington, Dante Suffredini, Aleah Smith, Maureen Martin, Maria Berg, A. John Barrett, Shivani Srivastava, Andreas Lundqvist, Hisayuki Yokoyoma, Bipin N. Savani, Richard W. Childs
Journal: Blood (2006)
Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome
Authors: Ping-yuan Wang, Jie Li, Farzana L. Walcott, Ju-Gyeong Kang, Matthew F. Starost, S. Lalith Talagala, Jie Zhuang, Ji-Hoon Park, Rebecca D. Huffstutler, Christina M. Bryla, Phuong L. Mai, Michael Pollak, Christina M. Annunziata, Sharon A. Savage, Antonio Tito Fojo, Paul M. Hwang
Journal: Journal of Clinical Investigation (2016)

Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism in patients. However, the implications of altered mitochondrial function for tumorigenesis in LFS are unclear. Here, we have reported that genetic or pharmacologic disruption of mitochondrial respiration improves cancer-free survival in a mouse model of LFS that expresses mutant p53. Mechanistically, inhibition of mitochondrial function increased autophagy and decreased the aberrant proliferation signaling caused by mutant p53. In a pilot study, LFS patients treated with metformin exhibited decreases in mitochondrial activity concomitant with activation of antiproliferation signaling, thus reproducing the effects of disrupting mitochondrial function observed in LFS mice. These observations indicate that a commonly prescribed diabetic medicine can restrain mitochondrial metabolism and tumorigenesis in an LFS model, supporting its further consideration for cancer prevention in LFS patients.
The Effect of the Interaction between Proton Pump Inhibitors (PPI) and Tyrosine Kinase Inhibitors (Imatinib, Nilotinib and Dasatinib).
Authors: Piera La Cava, Annalisa Chiarenza, Daniele Tibullo, Cesarina Giallongo, Alessandra Romano, Fabio Stagno, Giuseppe A. Palumbo, Francesco Di Raimondo
Journal: Blood (2007)
SP0103 Apoptotic Cell Engulfment Machinery and Rheumatoid Arthritis
Authors: S. Arandjelovic
Journal: Annals of the Rheumatic Diseases (2016)

Specific recognition and removal of apoptotic cells is a process that occurs throughout life in all tissues, as part of homeostasis and during pathological conditions. In active rheumatoid arthritis, apoptotic cells are seen in the synovial fluid of human patients and in mice with experimental arthritis, but their contribution to disease severity is not well understood. Recently, many components of apoptotic cell clearance machinery have been identified. Using global and conditional knockout mouse strains and primary cell cultures, we have addressed specific components of the engulfment machinery for their role in rheumatoid arthritis. We observe that molecules linked to apoptotic cell clearance can affect both the extent of inflammation and bone erosion seen during arthritis in mouse models. These data suggest that targeting the components of the engulfment machinery might be a viable therapeutic approach. <h3>Disclosure of Interest</h3> None declared
The Role of Stem Cell Mobilization Regimen on Lymphocyte Collection Yield and Survival after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma.
Authors: Luis F. Porrata, Suzanne R. Hayman, Morie A. Gertz, Martha Q. Lacy, Angela Dispenzieri, Shaji K. Kumar, Mark R. Litzow, David J. Inwards, Stephen M. Ansell, Ivnna N. Micallef, Patrick B. Johnston, Dennis A. Gastineau, Ayalew Tefferi, Michelle Elliot, William J. Hogan, Svetomir N. Markovic
Journal: Blood (2005)
Meta-analysis of the performance of ultrathin vs. standard colonoscopes
Authors: Aijaz Sofi, Ali Nawras, Muhammad Khan, Colin Howden, Wade Lee
Journal: Endoscopy (2016)

Background and study aims Colonoscopy should reliably intubate the cecum with minimal patient discomfort and without complications. Use of thinner endoscopes to overcome pain during the procedure has shown promise. However, the use of thinner scopes could lead to excess looping and difficulty with therapeutic procedures. The aim of this meta-analysis was to analyze the performance of ultrathin colonoscopes (UTC) and standard colonoscopes for routine colonoscopy. Patients and methods We searched several electronic databases for all randomized controlled trials and nonrandomized (prospective) studies that compared the efficacies of UTC (diameter ≤ 9.8 mm) and standard colonoscopes. We used fixed effect or random effects models to compare cecal intubation rate, cecal intubation time, pain score, and polyp and adenoma detection rates using standard mean differences (SMD) or odds ratios (OR) with 95 % confidence intervals (CI). Results Seven studies (2191 patients) met the inclusion criteria. There was no significant heterogeneity among studies except for pain scores. The cecal intubation rate was higher with UTC (OR 2.30; 95 %CI 1.31 to 4.03). There was no difference in the cecal intubation time between UTC and standard colonoscopes. Pain scores were significantly lower with UTC than with standard colonoscopes (SMD - 0.59, 95 %CI - 0.93 to - 0.25). Polyp and adenoma detection rates were similar for both types of colonoscope. Conclusion Use of UTC appears to improve the cecal intubation rate and reduce abdominal pain but does not affect polyp detection. Future trials are needed to evaluate the therapeutic performance of UTC vs. standard colonoscopes.
Hydroxyurea-Mediated Reactivation of Fetal Genes in Primary Erythroid Cell Cultures from Beta-Thalassemia Patients.
Authors: Roberta Calzolari, Aurelio Maggio, Alice Pecoraro, Vito Borruso, Antonio Troia, Santina Acuto, Danilo D’Apolito, Leda Ferro, Rosalba Di Marzo
Journal: Blood (2006)