tbuckley/cabot-search huggingface dataset:
THU0102 Higher Disease Activity Leads to More Damage in the Early Phases of Ankylosing Spondylitis: 12-Year Data from the OASIS Cohort: Table 1.
Authors: S. Ramiro, A. van Tubergen, D. van der Heijde, C. Stolwijk, M. Dougados, F. van den Bosch, R. Landewé
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> For years, it was unclear if inflammation and radiographic progression were related in AS, but studies were only of short follow-up and not analysed optimally. <h3>Objectives</h3> To analyse the long-term relationship between disease activity and radiographic damage. <h3>Methods</h3> Patients from the Outcome in AS International Study (OASIS) were followed-up for 12 years, with biannual clinical and radiographic assessments. Two readers independently scored the x-rays according to the mSASSS. The relationship between disease activity measures (BASDAI, ASDAS-CRP, CRP, patient9s global assessment and spinal pain) and radiographic damage was investigated using generalized estimating equations. Auto-regressive models with 2-year time-lags were used and analyses were adjusted for potential confounders. Different models were constructed: model 1- ASDAS (continuous); model 2– ASDAS disease activity states; model 3– BASDAI continuous and CRP; model 4– BASDAI categories and CRP; model 5– patient global and CRP; model 6– spinal pain and CRP. Model fit was compared using the quasi-likelihood information criterion (QIC). <h3>Results</h3> A total of 184 patients were included (70% males, mean (SD) age: 43 (12) years, mean symptom duration: 20 (12) years and 83% HLA-B27 positive). All disease activity measures were significantly longitudinally associated with radiographic progression. Neither medication, nor the presence of extra-articular manifestations confounded this relationship. The models with ASDAS had the best fit (i.e. lowest QIC): An increase in one ASDAS-unit led to an increase in 0.72 mSASSS-units and a "very high disease activity state" (i.e. ASDAS&gt;3.5) compared to inactive disease (i.e. ASDAS&lt;1.3) represented an additional progression of 2.31 mSASSS-units per 2 years (Table). Results were consistent across disease activity measures. The effect of ASDAS on mSASSS was higher in males vs females (β 0.98 vs -0.06) and in patients with shorter vs longer (&lt;18 vs ≥18 years) disease duration (0.84 vs 0.16). <h3>Conclusions</h3> In AS disease activity is unequivocally longitudinally associated with radiographic progression. ASDAS is the best measure to reflect this relationship. The effect of disease activity on radiographic damage is more pronounced in men and in the earlier phases of the disease. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1709
CORONARY 18F-FLUORIDE HYBRID POSITRON EMISSION TOMOGRAPHY MAGNETIC RESONANCE IMAGING: INITIAL EXPERIENCE
Authors: Philip Robson, Marc Dweck, Maria Giovanna Trivieri, Nicolas Karakatsanis, Ronan Abgral, Johanna Contreras, Umesh Gidwani, Jagat Narula, Valentin Fuster, Jason Kovacic, Zahi Fayad
Journal: Journal of the American College of Cardiology (2016)
P100 An investigation of mutator Pseudomonas aeruginosa in chronically infected cystic fibrosis (CF) patients treated for pulmonary exacerbation
Authors: T. Gouliouris, C. R. Laughton, D. M. Pearce, V. Athithan, J. E. Foweraker
Journal: Thorax (2010)

<h3>Background</h3> <i>Pseudomonas aeruginosa</i> with increased mutation rates due to defective DNA repair are reported in 24–73% of chronically infected patients with bronchiectasis, with or without cystic fibrosis (CF). Mutators may enhance <i>P aeruginosa</i> persistence in the lung by accumulating adaptive mutations including antibiotic resistance, and have been associated with worse lung function. In chronic infection the sputum can contain a heterogeneous population of <i>P aeruginosa</i> with different phenotypes, including variations in colony morphology (morphotype) and antibiotic susceptibility. Most studies on mutator prevalence however only tested one or two isolates per sputum. Investigation of the clinical relevance of mutator strains relies on accurately assessing the prevalence of hypermutators. We therefore performed a detailed investigation of mutators in sputum before and after antibiotic treatment for acute exacerbation. <h3>Methods</h3> Six patients with CF, chronically infected with <i>P aeruginosa,</i> were tested before and after 2 weeks antibiotic treatment for exacerbation. Culture, antibiotic susceptibility testing and pulsed-field gel electrophoresis (PFGE) typing were performed using published methods.1 Mutation rates were measured for up to four colonies of each morphotype. As the original phenotypic method for detecting mutators is very laborious,2 we developed a method to screen pooled cultures using spiral plater quantitation. <h3>Results</h3> 168 <i>P aeruginosa</i> isolates were tested (average 14 per sputum). Three patients had no mutators before or after antibiotics and three cultured mutators before and after antibiotics. One to four PFGE pulsotypes and two to six morphotypes were found in each sputum. Both mutators and non-mutators were present in a single sample with no association with morphotype or genotype. Mutators were more likely to be antibiotic resistant, but there was no obvious selection of mutators after 14 days antibiotics. <h3>Conclusions</h3> With extensive testing, mutators were found in three of six patients with chronic <i>P aeruginosa</i> infection. The phenotypic and genotypic diversity observed means that multiple colonies of each morphotype should be tested to reliably detect mutators. Our method variation allows more extensive testing and may assist future clinical studies.
Reduced Risk of Large-Bowel Adenomas Among Aspirin Users
Authors: E. R. Greenberg, J. A. Baron, F. D. H., J. S. Mandel, R. Haile
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Reduced Risk of Large-Bowel Adenomas Among Aspirin Users Get access E. R. Greenberg, E. R. Greenberg Department of Community and Family Medicine and Department of Medicine, Dartmouth Medical SchoolHanover, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. A. Baron, J. A. Baron Department of Community and Family Medicine and Department of Medicine, Dartmouth Medical SchoolHanover, N.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar Freeman D. H., Jr., Freeman D. H., Jr. Department of Community and Family Medicine and Department of Medicine, Dartmouth Medical SchoolHanover, N.H. Present address: D. H. Freeman, University of Texas Medical Branch, Galveston. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. S. Mandel, J. S. Mandel School of Public Health, University of MinnesotaMinneapolis Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Haile R. Haile R. Haile, School of Public Health, University of CaliforniaLos Angeles Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 11, 2 June 1993, Pages 912–915, https://doi.org/10.1093/jnci/85.11.912 Published: 02 June 1993 Article history Received: 07 December 1992 Revision received: 02 March 1993 Accepted: 11 March 1993 Published: 02 June 1993
THU0043 A Polymorphism in the FOXO3A Promoter is Associated with Protection from Organ Damage in SLE – A Pilot Study
Authors: A.L. Yeo, S. White, S. Raghunath, K. Franklyn, L. Criswell, A. Hoi, E. Morand
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Disease expression and outcome vary greatly in SLE. As well as affecting susceptibility, noncoding gene polymorphisms have been reported to influence disease expression, for example indices of severity. FOXO3A is a transcription factor which induces the anti-inflammatory proteins TGF-beta and GILZ. A gain-of-function <i>FOXO3A</i> promoter single-nucleotide polymorphism (SNP), rs12212067, is associated with anti-inflammatory effects <i>in vitro</i>, and improved outcomes in colitis and RA (Lee et al, Cell, 2013). <h3>Objectives</h3> The association of FOXOoxo3a polymorphisms with disease expression in SLE is unknown. We sought to determine the clinical associations of this SNP in SLE. <h3>Methods</h3> SLE patients (ACR criteria) attending a single centre were recruited for a pilot study. Patients seen between 2007-2012 had disease activity (SLEDAI-2k) recorded at each visit. SLICC-SDI criteria (recorded annually) were used to define end-organ damage. Genomic DNA was isolated from whole blood and genotyped with the Immunochip (Illumina) (SNP) microarray. <h3>Results</h3> 137 SLE patients (84% female, median age 42 years, disease duration 5 years) were studied. Organ damage (SDI) was highly correlated with disease duration (P&lt;0.0001), and with time-adjusted mean SLEDAI (AMS) (P&lt;0.0001) and glucocorticoid exposure (P&lt;0.0001). The distribution of rs12212067 genotypes observed was TT (78.8%) TG (17.5%) and GG (3.7%). The major finding was that rs12212067-G homozygosity was protective against organ damage in the SLICC-SDI domains of renal disease (P=0.001), vascular events (P=0.0002), and glucocorticoid-related damage (P&lt;0.001), compared to rs12212067-T/T and G/T genotypes. rs12212067-G/T heterozygotes were also protected against vascular events. There was no difference between rs12212067 genotypes in total SLICC-SDI, glucocorticoid exposure, AMS, or other demographic, clinical or serological variables. <h3>Conclusions</h3> These data suggest that a gain-of-function <i>FOXO3A</i> promoter SNP exerts a protective effect against end-organ damage in SLE. Confirmation of these findings in a larger study is required, along with investigation of the molecular mechanisms of this effect, for example via regulation of GILZ. <h3>References</h3> Lee, J. C., Espéli, M., Anderson, C. A., Linterman, M. A., Pocock, J. M., Williams, N. J., et al. (2013). Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway. Cell, 155(1), 57–69. <h3>Acknowledgements</h3> LAC funded by NIH grant number P60 AR053308 <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3993
Effect of High Specific-Activity Sulfur Colloid Preparations on Sentinel Node Count Rates
Authors: BORYS R. KRYNYCKYI, ZHUANG-YU ZHANG, CHUN K. KIM, HELENA LIPSZYC, KARINA MOSCI, JOSEF MACHAC
Journal: Clinical Nuclear Medicine (2002)

Purpose: Preliminary results by other investigators suggest that increasing the specific activity of Tc-99m nanocolloid preparations increases the measured counts in sentinel nodes compared with lower specific-activity (SA) preparations using the same initial injected dose. The authors set out to determine whether a similar result could be perceived with Tc-99m sulfur colloid (SC) preparations. Methods: Twenty-three consecutive patients (low SA group) with successful visualization of sentinel nodes by lymphoscintigraphy before our standard protocol was changed to a higher SA preparation were compared with 28 patients (high SA group) just after the switch. Injection techniques were similar in both groups: peritumoral injections at two to four points of a mixture of half-filtered (0.22 μm filter) and unfiltered Tc-99m sulfur colloid in 6 ml followed immediately by intradermal injections of filtered sulfur colloid above the tumor. Activity levels for both types of injections ranged from 3.7 to 11.1 mBq (100 to 300 μCi). Preparation of the higher SA mixture of sulfur colloid was achieved by using only one eighth of the sulfur colloid vial contents when the same activity (125 mCi) of Tc-99 was added. Regions of interest were drawn around the images of sentinel nodes and the initial injection site in the anterior and lateral projections. Ratios of sentinel node to initial injection site count were calculated for both groups. Results: The mean ratio of sentinel node to injection site count in the high SA group was 2.9 times greater than that in the low SA group. The median ratio value was 2.7 times greater in the high SA group. Conclusion: These preliminary results suggest higher counts in the sentinel node are possible with a higher SA preparation.
Abstract 1838: Efficacy of ribonuclease QBI-139 in combination with standard of care therapies
Authors: Laura E. Strong, John A. Kink, Daniel Pensinger, Baigen Mei, Mark Shahan, Ronald T. Raines
Journal: Cancer Research (2012)

Abstract RNA has been recognized as a drug target for cancer therapy, as evidenced by the ongoing clinical trials of RNAi and antisense therapies. An alternative approach that circumvents the delivery and stability issues of those drugs is to harness the activity of naturally occurring RNA degradation enzymes. Human ribonuclease (RNase) variants have been generated with diminished binding to their natural inhibitor inside cells, which allows the new proteins to kill cancer cells. One of these RNase variants, referred to as QBI-139, demonstrated efficacy against multiple tumor types in xenograft models of human cancer and was selected for an ongoing first in human Phase I clinical trial. Non-small cell lung and ovarian cancer are two of the indications where QBI-139 has shown significant efficacy as a single agent in xenograft models. In planning for the next stage of clinical trials, the impact of combinations of QBI-139 plus standard of care agents in these diseases was determined both in vitro and in vivo. QBI-139 showed additive and synergistic activity in combination with cisplatin and docetaxel, which are standard of care for non-small cell lung and ovarian cancer, respectively. Fixed ratios of QBI-139 and the combination drug based on their EC50 values were tested. The Combination Index (CI) was determined using median effect analysis. Synergy was demonstrated with QBI-139 in combination with cisplatin against non-small cell lung cancer (A549 and H1975). An additive effect of QBI-139 and cisplatin was seen in ovarian (Ovcar-3) cancer. In ovarian cancer (SK-OV-3), a combination of docetaxel and QBI-139 was synergistic with QBI-139. The benefit of the combinations were repeated in xenograft models of both cancers and were signifcat relative to each agent alone. Non-small cell lung and ovarian cancer represent critical unmet needs and new, differentiated treatment approaches such as QBI-139 combination therapy are critical. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1838. doi:1538-7445.AM2012-1838
AB0889 Low percentage of MRI changes in clinically suspected axial spondyloarthritis
Authors: I. van der Horst-Bruinsma, M. van der Weijden, S. Bruijnen, S. Weismann, P. Bet, C. van Kuijk, J. Twisk, B. Dijkmans, C. van der Laken, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The prevalence of Ankylosing Spondylitis (AS) reaches about 0.9%, starts at a relatively young age and the burden of the disease is considerable. A diagnostic algorithm was developed in order to detect the disease at an early stage, the so called non-radiographic Axial Spondyloarthritis (SpA) (ref). MRI techniques play an important role in this diagnosis in the absence of radiographic sacroiliitis and was propagated as a diagnostic tool. <h3>Objectives</h3> to study the prevalence of inflammatory changes on MRI of pelvis and spine in patients who are clinically suspected to have of non-radiographic axial SpA. <h3>Methods</h3> Patients above 18 years of age with inflammatory back pain, during at least 3 months with onset below the age of 45 years, were included in case of presence of at least 2 Spondylarhropathy features or at least one Spa feature and either presence of HLA-B27 antigen or at least two family members with definite AS. MRI of the pelvis and spine (T1, T2 and STIR) was performed and repeated after 16 weeks if no signs of inflammation were present the first time. Patients who fulfilled the modified New York criteria for AS were excluded. <h3>Results</h3> 55 candidates were screened, of whom 9 were excluded because they fulfilled the New York criteria of AS already. The MRI results of the remaining 46 patients are: 13 showed signs of inflammation (28%), 12 had a negative MRI once (26%) and 21 had a negative MRI at two time periods (46%). Five out of the 12 patients who had a negative MRI refused to have another MRI because of several reasons, mostly because they were afraid to enter the narrow tunnel again despite premedication. Therefore, out of 46 eligible patients, 33 (71%) showed a negative MRI at least once despite the fact that they fulfilled the clinical algorithm of axial SpA. <h3>Conclusions</h3> In patients who were clinically suspected to have non-radiographic axial Spondyloarthritis, only 29% showed signs of inflammation at the MRI of the sacroiliac joints and or spine at one time point. Therefore, the sensitivity for MRI as a useful tool to establish the diagnosis non radiographic axial SpA seems to be limited. <h3>References</h3> Rudwaleit M, van der HD, Khan MA, Braun J, Sieper J. How to diagnose axial spondyloarthritis early. Ann Rheum Dis 2004; 63(5):535-543. <h3>Disclosure of Interest</h3> I. Van Der Horst-Bruinsma Grant/Research support from: Pfizer, M. van der Weijden: None Declared, S. Bruijnen: None Declared, S. Weismann: None Declared, P. Bet: None Declared, C. van Kuijk: None Declared, J. Twisk: None Declared, B. Dijkmans: None Declared, C. van der Laken: None Declared, M. Nurmohamed: None Declared
The Route of Early Nutrition in Critical Illness
Authors: Deborah Cook, Yaseen Arabi
Journal: New England Journal of Medicine (2014)

Randomized trials may be broadly categorized as explanatory or pragmatic. Explanatory trials address the question, ``Can this intervention work under ideal conditions?" Pragmatic trials ask, ``Does this intervention work under usual conditions?'' Usual conditions, of course, are context-dependent. In the United Kingdom, the CALORIES trial by Harvey et al.,1 reported in the Journal, addresses the clinical effectiveness of early enteral nutrition, as compared with early parenteral nutrition, in critically ill patients without contraindications to either route of delivery. This trial, commissioned and sponsored by the Health Technology Assessment Program of the National Institute for Health Research, was pragmatic in design . . .
Lactose and Milk Intolerance: Clinical Implications
Authors: Theodore M. Bayless, Benjamin Rothfeld, Carol Massa, Ladymarie Wise, David Paige, Marshall S. Bedine
Journal: New England Journal of Medicine (1975)

We studied 166 hospitalized male patients to determine the clinical importance of tolerance-test-determined "lactose intolerance," assumed to affect most of the world's adults. Abnormal lactose tolerance tests were found in 81% of 98 blacks, 12% of 59 whites of Scandinavian or Northwestern European extraction, and three of nine non-European whites. Seventy-two per cent of the "lactose-intolerant" subjects had previously realized that milk drinking could induce abdominal and bowel symptoms. Two hundred and forty milliliters of low-fat milk produced gaseousness or cramps in 59% of 44 "lactose-intolerant" men, and 68% were symptomatic with the equivalent amount of lactose. None of 18 "lactose-tolerant" men noted symptoms with milk or lactose. Refusal to drink 240 ml of low-fat milk served with meals correlated significantly with "lactose-intolerance": 31.4% versus 12.9% among "lactose-tolerant" patients. "Lactose intolerance" is common in adults and is a clinically relevant problem.
Isolated Interventricular Septal Defect Due to Nonpenetrating Trauma
Authors: Amnon Rosenthal, Lucy F. Parisi, Alexander S. Nadas
Journal: New England Journal of Medicine (1970)

A large ventricular septal defect acquired by blunt trauma to the chest spontaneously diminished in size and closed almost completely, as documented by serial cardiac catheterizations. The pulmonary-systemic flow ratio decreased from 3.6:1.0 to 1.2:1.0. The patient was asymptomatic eight years after the septal perforation.
Bevacizumab 15mg/kg plus cisplatin-pemetrexed (CP) triplet versus CP doublet in Malignant Pleural Mesothelioma (MPM): Results of the IFCT-GFPC-0701 MAPS randomized phase 3 trial.
Authors: Gerard Zalcman, Julien Mazières, Jacques Margery, Laurent Greillier, Clarisse Audigier-Valette, Denis Moro-Sibilot, Oliver Molinier, Romain Corre, Isabelle Monnet, Valérie Gounant, Henri Janicot, Radj Gervais, Chrystele Locher, Bernard Milleron, Quan Tran, Marie Paule Lebitasy, Franck Morin, Christian Creveuil, Jean-Jacques Parienti, Arnaud Scherpereel
Journal: Journal of Clinical Oncology (2015)

7500 Background: MPM median overall survival (OS) did not exceed 13 months with pemetrexed-platinum doublet, with virtually no surviving patients at 5 years. Vascular endothelial growth factor is a potent mitogen for MPM cells. Methods: In this French multicenter randomized phase 3 trial, eligible patients had unresectable, histologically proved MPM, age < 76, no prior chemo, PS 0-2, no thrombosis, nor bleeding. Randomized patients (1:1) received pem 500 mg/m2, CDDP 75 mg/m2 at D1, with (arm B) or without bevacizumab (arm A), 15 mg/kg Q21D, for 6 cycles. Arm B non-progressive patients received bevacizumab maintenance therapy until progression or toxicity. Primary endpoint was OS. 445 patients were to be randomized, and 385 events observed, to show a significant OS improvement, with 80% statistical power, 5% a-risk. Results: From Feb. 2008 to Jan. 2014, 448 patients were included in 73 centers. Males: 75.4%, median age: 65.7 years (range 34.7-75.9), PS 0-1: 96.7%. The IDMC recommended a second interim analysis after 85% of events. On 01-Jan-2015, the duration since last news was < 30 days in 105 out of 106 still living patients. Overall survival was significantly longer in the experimental arm (median: 18.8 months, 95%CI[15.9-22.6] vs. 16.1 months, 95%CI[14.0-17.9] for the reference arm, (adj.HR = 0.76, 95%CI[0.61; 0.94], p = 0.012). With only 46/448 non-progressive patients at the date of analysis, median PFS was 9.6 months, 95%CI[8.5-10.6] in bevacizumab arm vs. 7.5 months, 95%CI[6.8-8.1] (adj.HR = 0.62, 95%CI[0.50-0.75], p < 0.0001). G3-4 hematological toxicities did not significantly differ in the two arms (49.5% vs. 47.3%). Significantly more G3 proteinuria (0.0 vs. 3.1%), G3 hypertension (0.0 vs. 23%), G3-4 arterial thrombotic events (0.0 vs. 2.7%) were observed in bevacizumab arm. QOL and exploratory biomarkers studies will be also presented at time of the meeting. Conclusions: Bevacizumab addition to pemetrexed/cis-platin provides a significantly longer survival in pts with MPM, with acceptable toxicity, making this triplet a new treatment paradigm. Clinical trial information: NCT00651456.