tbuckley/cabot-search huggingface dataset:
AB0615 Favorable response to belimumab seen at three months
Authors: K. Shum, J. Buyon, A. Franks, R. Furie, D. Kamen, S. Manzi, M. Petri, R. Ramsey-Goldman, C.-E. Tseng, D. Wallace, R. van Vollenhoven, A. Askanase
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Belimumab (Benlysta) is a monoclonal antibody that inhibits soluble B-Lymphocyte Stimulator and improves SLE disease activity. <h3>Objectives</h3> This study was initiated to evaluate the use of Belimumab in academic SLE clinical practices. <h3>Methods</h3> An invitation to participate was sent to 16 physicians experienced in SLE Phase III clinical trials. All agreeing to participate completed a one page questionnaire for each patient prescribed Belimumab. The questionnaire contained demographic information on each patient (age, gender, race/ethnicity), SLE data (duration of disease, SELENA-SLEDAI, clinical manifestation(s) targeted, background medications), and Belimumab information (start date, clinical response, side effects). Clinical response was defined as the investigator's impression of a ≥50% improvement in the initial manifestation being treated and no worsening in other organ systems. <h3>Results</h3> Of 16 invitations sent, ten investigators accepted to participate in the study. Questionnaires on 68 treated patients were returned. The mean age was 44.8±11.3 years old, 92.6% were female, 73.5% White, 16.2% Black, 7.4% Asian, and 7.4% Hispanic. The average SLE disease duration was 11.1±8.7 years. All patients were ANA positive. Concomitant medications included: antimalarials in 69.1%, immunosuppressants in 72.0% (Azathioprine 19.1%, Mycophenolate Mofetil 38.2%, Methotrexate 14.7%), and prednisone in 61.8% (average dose of 10.9±11.9 mg, 59.5% on ≥10 mg). Only 2.9% of patients were not on background SLE medications. The dominant clinical manifestation driving treatment was arthritis (77.9%) followed by rash (42.6%) and serositis (19.1%). Other SLE manifestations present included renal (7.4%, 4/5 membranous, 1/5 proliferative) and hematological (8.8%). Approximately half of patients (45.6%) had two or more active manifestations. Twenty-three patients were on Benlysta for at least 3 months. Of those, 17 patients had clinical response observed by 3 months with improvements in arthritis and rash. <h3>Conclusions</h3> These early data support the use of Benlysta across all ethnic groups and efficacy similar to that reported in the Phase III trials. Relevant to physician and patient expectations, improvement was observed within 3 months. <h3>Disclosure of Interest</h3> None Declared
THE COST OF COLONOSCOPY – A WORLDWIDE VIEW
Authors: R Haslam, S El-Khassawneh, U Sucher
Journal: Gut (2013)

<h3>Introduction</h3> Allianz Worldwide Care is a private medical insurer, specialising in providing international (expatriate) health insurance for employees, individuals and their dependants, wherever they are in the world. Allianz Worldwide Care insure over 250,000 people in more than 150 countries. As an international insurer, we see a wide price variation in different regions of the world, for the same procedure. <h3>Aims/Background</h3> To assess the price differences for a colonoscopy +/− biopsies between different countries in the world. We aim also to highlight the differences in length of stay for this procedure around the world. <h3>Method</h3> We assessed all pre-authorisation Guarantees for full colonoscopy from 1st November 2011 to 1st November 2012. Each procedure was assessed for costs, Country of treatment and length of stay. The costs included hospital and doctor fees. Colonoscopies with any intervention other than simple biopsy were excluded. Colonoscopies done in conjunction with any surgery, or that involved admission for complications, were excluded. <h3>Results</h3> Overall, we assessed 260 colonoscopies in 49 different countries. 246 met the study criteria. China, The United Arab Emirates, Brazil and the USA had the highest volumes of colonoscopies in the year. The most expensive countries were The United States and Switzerland, with the average colonoscopy there costing €4,742 and €4,728 respectively. The most expensive colonoscopy was performed in the USA and cost €9,743. The least expensive countries for colonoscopy were Croatia and India with an average cost of €101, and €105 per procedure respectively. <h3>Conclusion</h3> There is a vast difference in costs for the same procedure, depending on the region of the world that the procedure is performed. The most expensive region being nearly 47 times as expensive as the cheapest region. We must ask ourselves what the difference in these costs relates to. What is it that Gastroenterologists in America and Switzerland are doing that equally qualified gastroenterologists in India are not?
Abstract 2141: Analysis of DNA copy number changes in ovarian cancer data reveals differences in progressive vs. complete response samples
Authors: Shams Soheil, Craig Parman, Jeffrey Gregg
Journal: Cancer Research (2010)

Abstract Data from The Cancer Genome Atlas (TCGA) project, related to Ovarian Cancer was obtained from the TCGA web site. The data comprised a total of 489 samples hybridized on 2-color oligo-arrays with 244K probes per array. Raw log-ratio data representing DNA copy number values relative to a DNA pool of normal samples were used in the analysis. The raw data was processed using Nexus Copy Number version 5 software (BioDiscovery, El Segundo CA) and regions of copy number change were identified using the built-in FASST algorithm with significance threshold of 5.0 E-6. After applying a QC filter to remove hybridizations with excessive noise, 463 samples remained for further analysis. Of these, there were 214 solid tumors and 242 normal samples (either surrounding tissue or blood from same patient). In our analysis we compared copy number differences from samples with Progressive disease (n=29) and those with Complete response to therapy (n=245). Using a Fisher's Exact test and a maximum p-value of 0.05 we identified significant regions of copy number change covering a genome area composed of a total of 1049 genes. Included were regions of significant increase in the number of DNA copy number gains in the for the Complete response samples as compared to Progressive cases. The most significant of these were in the 6p21.1 − 6p12.1 and 5p14.1 − 5p13.3 regions. Other regions include a number of well-know genes related to apoptosis, such as TNF (on 6p21.33) and RHOB (on 2p24.1) that were also significantly gained in Complete response but showed DNA loss in Progressive samples. 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 2141.
SAT0407 Double-Blind Randomized Controlled Prospective Trial Assessing the Effectiveness of Oral Corticoids in the Treatment of Lumbar-Canal Stenosis in Symptomatic Patients
Authors: L.C.L. Rodrigues, J. NATOUR
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Study design: Double blind, randomized, controlled prospective trial Summary: no studies were found assessing the effectiveness of oral corticoids in the treatment of symptomatic lumbar stenosis. <h3>Objectives</h3> Assess the effectiveness of decreasing oral corticoids in the treatment of the narrow lumbar canal syndrome. <h3>Methods</h3> 61 patients were electronically randomized. Thirty-one used the oral corticoid in the dosage of 1mg per kilo with the reduction of one third of the dose per week for a 3-week period, and another group with 30 patients used a placebo for the same period. The patients were assessed in four different moments, initially and at 3, 6 and 12 weeks, through the SF 36, Roland Morris, 6-minute walk test, the visual analog scale and a Likert scale. To be included, the patients had to be between 50 and 75 years of age and have neurogenic claudication symptoms associated with a canal area smaller than 100 mm<sup>2</sup>, detected through MRI exams in at least one of the levels studied. <h3>Results</h3> The data found in all instruments used showed very similar outcomes, when comparing those that used the corticoid with those from the placebo group, not presenting statistically significant differences in the different instruments in all moments assessed. As additional data, it was found that obese patients have a worse clinical presentation, which despite not having a statistical correlation, the stenosis in the L4/L5 level was more symptomatic than in other levels. <h3>Conclusions</h3> The use of oral corticoids in the dosage of 1mg per kg, used in a decreasing dose, is not effective in the treatment of the narrow lumbar canal syndrome when compared to the placebo <h3>Disclosure of Interest</h3> None Declared
Soundings: Out of Africa
Authors: Imre Loefler
Journal: BMJ (2005)

Flying across eastern Africa most Mondays for almost 30 years, the surgeon-pilot observed how population growth and environmental destruction went hand in hand, and how the increase in energy use—local and global—changed geography.

He monitored how the glaciers on Mount Kenya and the Ruwenzoris were receding and how the snows of Kilimanjaro were melting. He saw the forests disappearing, the wetlands vanishing, and the rivers either drying up or in raging flood, carrying the fertile red soil out into the sea, and he noticed the steady advance of the desert.

He saw huts, houses, villages everywhere, tracks, roads, and highways, and he flew over huge tracts of land assigned to monoculture: tea, coffee, sugar, wheat, maize, pineapples, and flowers, most destined for export. He flew over struggling subsistence farms, getting increasingly smaller.

Landing at the hospital early in the morning he would be confronted with multitudes of sick people lining up for surgery. He had to decide whether to treat the sickest or the ones with the best prognosis—usually the utilitarian argument won.

Over the years the epidemiology presenting to him changed. There were the old diseases, mostly infectious; then came the trauma epidemic, first road crashes and then violence; next were the cosmopolitan cancers; and recently, with Western lifestyles, and sugar, sodas, salt, refined fats, and the lack of exercise, the degenerative diseases.

The population pyramid also changed. More children, children everywhere, wonderful, bright, joyous children, but, in ecological terms, acting like locusts nevertheless...Eventually AIDS began to nibble at the pyramid: the children would be attended by the grandparents. But the surgeon-pilot was not there to philosophise, he was there to give advice, to teach, to mend...to radiate hope.

On his way home in the evening, when the cumulus clouds in the west became golden and then purple, the lakes silver, and the silhouettes of the mountains cast variegated shadows over the land, the surgeon-pilot's heart was filled with elation, while his mind was preoccupied with the state of Africa, the continent overwhelmed by rapid technological change and heading for unimaginable stresses caused by environmental dislocation.
Inactivation of the DNA-Repair Gene<i>MGMT</i>and the Clinical Response of Gliomas to Alkylating Agents
Authors: Manel Esteller, Jesus Garcia-Foncillas, Esther Andion, Steven N. Goodman, Oscar F. Hidalgo, Vicente Vanaclocha, Stephen B. Baylin, James G. Herman
Journal: New England Journal of Medicine (2000)

The DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) inhibits the killing of tumor cells by alkylating agents. MGMT activity is controlled by a promoter; methylation of the promoter silences the gene in cancer, and the cells no longer produce MGMT. We examined gliomas to determine whether methylation of the MGMT promoter is related to the responsiveness of the tumor to alkylating agents.We analyzed the MGMT promoter in tumor DNA by a methylation-specific polymerase-chain-reaction assay. The gliomas were obtained from patients who had been treated with carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, or BCNU). The molecular data were correlated with the clinical outcome.The MGMT promoter was methylated in gliomas from 19 of 47 patients (40 percent). This finding was associated with regression of the tumor and prolonged overall and disease-free survival. It was an independent and stronger prognostic factor than age, stage, tumor grade, or performance status.Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of the tumors to alkylating agents.
SP0174 Eular points to consider when conducting long term extension studies of trials?
Authors: M. Boers
Journal: Annals of the Rheumatic Diseases (2013)

Randomized controlled trials (RCT) provide data on clinically measurable outcomes (safety and efficacy) in the short-term. The need for longer-term data requires extended follow-up. The biologic era particularly has witnessed an increasing number of reports on post-RCT extension clinical data; their reporting however is fraught with challenges with no guidelines on optimal reporting. At this meeting a scientific abstract is presented on the recommendations recently formulated by a EULAR task force (Buch M et al). My presentation focuses on the above design and reporting challenges. Advantages of long-term extension studies (LTE) include the well-described study groups and information on the retention of therapy beyond the trial. Under the right circumstances, more evidence on efficacy and safety can accrue. And finally, LTE can enable ongoing access to an effective therapy that would otherwise be unavailable to subjects that participated in the prior RCT. Disadvantages include the increased potential for bias mainly through selection of patients to include, method of analysis (e.g. the choice of the denominator to calculate rates), and lack of transparency in reporting. There are also ethical issues such as the assumption that the experimental agent is effective and treatment should be continued where proof is not yet fully available. The key recommendations of the Task Force are: –All patients from the original trial should be accounted for; –Requirement of a minimum set of data, including time of last observation; reason for: TES exclusion if drug discontinued, cessation of follow-up and cessation for other reasons; progress at each stage from RCT start to TES completion; duration of active treatment; –Requirement of a flow chart (see figure example for a placebo/background MTX trial); –Report consistent with existing guidelines (CONSORT, STROBE), ACR/EULAR recommendations; –Minimum set of outcomes, including sustainability and new achievement of high hurdle outcomes (remission/LDA); drop-outs detailed; –Efficacy &amp; safety of a TES reported together. We hope that adoptions of these recommendations will lead to better and more informative LTE reports. <h3>Disclosure of Interest</h3> None Declared
SP0198 Vaccination YES or No, When Having A Rheumatic Disease?
Authors: J.H.E. Voorneveld-Nieuwenhuis
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> This lecture is about issues patients with Rheumatic diseases face when travelling to vaccination requiring destinations. We will discuss how patients can prepare for vaccinations as well as which vaccinations are alive and might inflict their treatments. We will access the alternatives, risks and benefits. During the lecture we will use the EULAR recommendations for vaccination in adult and in paediatric patients with autoimmune inflammatory rheumatic diseases. We will try to give attention to local guidelines and review tests for tuberculosis screening. <h3>Key message</h3> The fact that someone has a rheumatic disease may influence the choice for a holiday destination. Some vaccinations might be necessary or infection risks are higher. We should consider the pros and cons of travelling. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6129
Abstract 998: KLF4 interacts with β-catenin/TCF4 and blocks p300/CBP recruitment by β-catenin
Authors: Xi Chen, Paul M. Evans, Wen Zhang, Chunming Liu
Journal: Cancer Research (2010)

Abstract Wnt signaling is crucial in the organization and maintenance of the human intestinal epithelium, and somatic mutations that result in deregulated Wnt signaling are an early event in the development of colorectal cancer. The Wnt ligand ultimately results in the stabilization of cytoplasmic β-catenin, which is then free to enter the nucleus and activate transcription through its interaction with the transcription factor TCF4. Our laboratory recently found that KLF4, a transcription factor highly expressed in the adult intestine and critical for intestinal differentiation, interacts with β-catenin and inhibits Wnt signaling. In this study, we characterize the molecular mechanisms of KLF4-mediated inhibition of Wnt/β-catenin signaling. We find that the KLF4 directly interacts with the C-terminal transactivation domain of β-catenin and inhibits p300/CBP recruitment by β-catenin. KLF4 inhibits p300/CBP-mediated β-catenin acetylation as well as histone acetylation on Wnt target genes. In addition, we observe that KLF4 directly interacts with TCF4 independently of β-catenin, and that KLF4 and TCF4 are expressed in similar patterns within the large intestine, with greatest staining near the epithelial surface. These results provide a deeper understanding of the regulation of β-catenin in the intestine, and will have important implications in cancer and stem cell research. 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 998.
Successful endoscopic treatment of a 12-cm small-bowel Crohn stricture with a custom-made biodegradable stent
Authors: John Karstensen, Peter Vilmann, Jacob Hendel
Journal: Endoscopy (2014)

A 52-year-old man originally diagnosed with ulcerative colitis presented with an inflamed small-bowel stricture in the ascending limb of an ileoanal J-pouch and was subsequently diagnosed with Crohn disease. The stricture did not respond to medical treatment with either methotrexate or adalimumab, and repeated endoscopic balloon dilation relieved the patient's obstructive symptoms only briefly. As surgical revision was deemed impossible, removal of the J-pouch was advised, but the patient refused an ileostomy. MRI and fluoroscopy during endoscopy revealed a stenosis that was 12 cm in length ([Fig. 1]). A custom-made biodegradable polydioxanone monofilament 15-cm stent was manufactured with a body diameter of 15 mm and a throat diameter of 18 mm (SX-ELLA BD biodegradable stent; ELLA-CS, Hradec Králové, Czech Republic) ([Fig. 2]). The delivery system was designed as a pull system with distal release. The endoscopic procedure with stent deployment was performed under radiological guidance, and with the patient under general anesthesia. The delivery of the stent was uncomplicated and no adverse events were registered ([Fig. 3 a]). The patient described instant relief of his obstructive symptoms. At endoscopic follow-up at 3 weeks the patient felt well and the stent was open ([Fig. 3 b]). After 8 weeks the stent was still in situ, but had started to degrade ([Fig. 3 c]). Nevertheless, at present (3-month follow-up) the patient remains without obstructive symptoms.
Abstract 211: TIS21/BTG2/PC3 triggers cancer cell death, instead of cellular senescence, by enhancing proapoptotic gene expression at the downstream of p53
Authors: Preethi Devanand, Ok Ran Choi, Tae Jun Park, In Kyoung Lim
Journal: Cancer Research (2011)

Abstract It has been known that cytoplasmic p53 regulates cell cycle arrest, apoptosis, autophage, and metabolism of human and animal cells in a transactivation-dependent manner. Wild type p53 induces senescence of EJ human bladder cancer cells, which carries oncogenic H-ras and mutant p53. Tumor supporessor, TIS21/BTG2/PC3, is one of the target genes regulated by wild type p53. Employing adenoviral vectors carrying p53(Ad-p53) and TIS21(Ad-TIS21) genes, we investigated effect of TIS21 on cancer cell senescence induced by p53 supplementation; Infection of EJ cells with p53 rapidly induced senescence phenotypes, such as cellular enlargement, inhibition of its growth, expressions of SA-[[Unsupported Character – Symbol Font ]]-galactosidase and SA-pErk1/2, and generation of reactive oxygen species, in addition to down-regulation of PARP and pRb expressions. A mechanism of the senescence was likely to be upregulations of H-ras and paxillin expressions by p53, evidenced by employing si-p53 RNA construct. On the contrary, the combined effect of p53 plus TIS21 significantly induced apoptosis of EJ cells rather than senescence, when evaluated by Annexin V expression, Calcein-AM and EhtD-1 double staining, increased expressions of proapoptotic genes and caspase 3 activity, whereas TIS21 alone failed to induce any changes, as compared with those of the control. p53 plus TIS21 significantly increased Bax and Apaf-1 expressions, whereas paxillin expression was clearly reduced as compared with those of p53 alone. When its mechanism was investigated, acetylation of p53 on K120 and K373 residues were found to be increased in addition to the significant translocation of p53 after coexpression of TIS21. We strongly suggest here that TIS21 is an endogenous cell death promoting gene at the downstream of p53 even in the expressions of oncogenic H-Ras and mutant p53. 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 211. doi:10.1158/1538-7445.AM2011-211
Abstract ES4-1: Statistical Challenges in Predictive and Prognostic Biomarker Studies: How To Avoid Wasting Your Time and Specimens
Authors: LM McShane
Journal: Cancer Research (2010)

Abstract A better understanding of tumor biology through identification of specific biological characteristics of tumor and host that predict tumor behavior and responsiveness to therapy will be essential for the discovery of new therapies and for optimization of cancer care for individual patients. Progress in identifying promising biomarkers in correlative studies and moving them to the clinic has been slow. Many correlative studies are conducted without clearly specified hypotheses, have poor statistical designs, use assays that are not standardized or lack reproducibility, and often employ inappropriate or misleading statistical analysis approaches. Common statistical problems include underpowered studies or overly optimistic reporting of effect sizes and significance levels due to multiple testing, subset analyses, cutpoint optimization, and model overfitting. For studies aiming to a assess a biomarker's ability to guide treatment decisions, the importance of appropriate control groups and the potential for confounding of prognostic and predictive effects have been underappreciated. Compounding these problems, many correlative studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of the results. Suggestions are provided for how to avoid some of the common statistical pitfalls, how to identify problematic studies, and how to report correlative studies to maximize the interpretability and usefulness of the results. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr ES4-1.