tbuckley/cabot-search huggingface dataset:
SAT0008 Early RA Patients Fulfilling the New 2010 Acr/Eular Criteria, Display Better Clinical Responses to Dmard Therapy but have Higher Radiographic Damage Progression than Patients with Early RA not Fulfilling the 2010 Acr/Eular Criteria
Authors: R. Mueller, T. Kaegi, S. Haile, A. Finckh, J. von Kempis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> New ACR/EULAR criteria for the classification of rheumatoid arthritis (RA) were recently proposed. <h3>Objectives</h3> The aim of this analysis was to examine the impact of fulfilling the 2010 ACR/EULAR criteria at the initial visit on long-term progression of disease and radiographic progression. <h3>Methods</h3> For this observational cohort study within the Swiss RA registry SCQM, we included patients suffering from early RA or undifferentiated arthritis (UA, disease duration ≤1 year), as defined by the treating rheumatologist, who had not received any previous DMARDs. Baseline diagnosis of RA/UA was reassessed according to the 2010 ACR/EULAR criteria at baseline. Patients were separated into 2 groups depending on whether or not they fulfilled the 2010 ACR/EULAR criteria at baseline (≥ 6 points versus &lt; 6 points). The primary outcome measures were the DAS 28 and erosions as measured by the Ratingen score over time. <h3>Results</h3> A total number 592 patients was analysed. 352 of them fulfilled the 2010 ACR/EULAR at baseline, 240 were not classifiable as RA according to the new criteria at baseline. The score calculated by the new ACR/EULAR criteria correlated with disease activity at disease onset. Treatment was initiated with DMARDs, mostly MTX, in all patients. There were no significant differences in the therapeutic strategies between patients fulfilling the classification criteria or not. The patients fulfilling ACR/EULAR criteria at baseline developed a 39.1%reduction of DAS 28 scores, as compared to a 33.6%reduction in ACR/EULAR-negative patients after 6 months, independent of their respective treatments. After 1 year of follow-up no differences were found comparing the mean DAS28 scores in the 2 groups. Average radiographic progression was higher among ACR/EULAR-positive patients (progression of Ratingen score/year 0.50 vs. 0.32, resp., p=0.03) after 3 years of follow up. <h3>Conclusions</h3> The 2010 ACR/EULAR criteria appeared to select a subset of patients among early RA/UA patients with a favourable clinical response to conventional anti-rheumatic therapy. Despite this therapy, radiographic progression was higher in 2010 ACR/EULAR positive patients. <h3>Disclosure of Interest</h3> None Declared
TRATAMIENTO ENDOSCOPICO DE PATOLOGIA BENIGNA ESOFAGICA MEDIANTE PROTESIS AUTOEXPANDIBLES
Authors: C Pons, JB Gornals, JM Botargues, S Maisterra, H Aranda, M Miro, L Farran, JM Nogueira
Journal: Endoscopy (2011)

Introducción: el uso de las prótesis esofágicas más habitual y extendido es en la paliación de disfagia en pacientes con cáncer de esófago. Su utilización en patología esofágica benigna, estenosis o fístulas, es más reciente y con poca experiencia.
360 DEFINITION OF INACTIVE HEPATITIS B CARRIER BY SERUM HBSAG AND HBV DNA LEVELS – A LONG-TERM FOLLOW-UP STUDY ON HBSAG SEROCLEARANCE
Authors: H.L.-Y. Chan, G.L-H. Wong, C.-H. Tse, H.-Y. Chan, V.W.-S. Wong
Journal: Journal of Hepatology (2011)
Gene Advisory Group Wrestles With Its Mission
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Gene Advisory Group Wrestles With Its Mission Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 13, 5 July 1995, Pages 959–960, https://doi.org/10.1093/jnci/87.13.959 Published: 05 July 1995
S43 The expression of CRACM ion channels in human lung mast cells
Authors: I. Ashmole, S. M. Duffy, M. Leyland, P. Bradding
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> The influx of extracellular Ca<sup>2+</sup> into human lung mast cells (HLMC) is essential for the IgE-dependent release of preformed granule derived mediators and newly synthesised autacoids and cytokines. However the identity of the ion channels underlying the influx of Ca<sup>2+</sup> remains unknown. Members of the recently discovered CRACM (also known as Orai) ion channel family are candidates for this function. The channels carry Ca<sup>2+</sup> selective currents (I<sub>CRAC</sub>) that are activated when endoplasmic reticulum Ca<sup>2+</sup> stores are emptied. Here we investigate whether CRACM channels are expressed in HLMC and their possible contribution to Ca<sup>2+</sup> influx in these cells. <h3>Methods</h3> HLMC were purified from lung tissue by immuno-magnetic affinity selection. Total RNA purified from cells was used in quantitative RT-PCR using TaqMan probes and primers (Applied Biosystems). For electrophysiology the whole cell method of patch clamp was used. <h3>Results</h3> CRACM1, CRACM2 and CRACM3 mRNA transcripts were all readily detectable in HLMC. CRACM1 transcripts (4.50±0.51 copies/10<sup>3</sup> beta-actin transcripts, n=7 HLMC donors) were more abundant than CRACM2 transcripts (1.79±0.67 copies/10<sup>3</sup> beta-actin transcripts, n=5) and CRACM3 transcripts (3.33±0.95 copies/10<sup>3</sup> beta-actin transcripts, n=5). Consistent with the presence of CRACM transcripts, an I<sub>CRAC</sub>-like current was detected in HLMC following IgE-dependent activation and also in cells dialysed with 30 μM inositol triphosphate to empty endoplasmic reticulum Ca<sup>2+</sup> stores. The Ca<sup>2+</sup>-selective current obtained under both conditions was blocked by the addition of 10 μM La<sup>3+</sup>, a known blocker of CRACM channels. Thus following addition of anti-IgE to 11 HLMC, current at −120 mV increased from −12.1±1.1 pA at baseline to −34.2±2.5 pA (p&lt;0.0001) and following addition of 10 mM La<sup>3+</sup> this was reduced to −17.4±2.1 pA. (p=0.0003). When HLMC were dialysed with IP<sub>3</sub> (n=12), current increased from −15.3±1.2 pA to −40.2±3.2 pA (p&lt;0.0001), and decreased to −17.7±1.5 pA (p&lt;0.0001) by La<sup>3+</sup>. <h3>Conclusions</h3> The presence of an I<sub>CRAC</sub>-like current and CRACM1, -2 and -3 mRNA transcripts in HLMC supports a role for CRACM channels in the influx of extracellular Ca<sup>2+</sup> into these cells following activation. Such a role would make CRACM channels a potential therapeutic target in the treatment of asthma.
Abstract P1-07-18: Association between Bone Turnover Markers in patients with breast cancer and bone metastases on treatment with bisphosphonates (ZOMAR study)
Authors: I Tusquets, C De la Piedra, L Manso, C Crespo, P Gómez, L Calvo, M Ruiz, P Martínez, A Perelló, A Antón, M Codes, M Margelí, A Murias, J Salvador, MA Seguí, A De Juán, J Gavilá, M Luque, D Pérez, P Zamora, A Arizcum, JI Chacón, L Heras, A Barnadas
Journal: Cancer Research (2012)

Abstract Background: The presence of bone metastases (BMe) alters the balance of bone remodeling and consequently, levels of bone turnover markers (BTM). Increased levels of these biomarkers are related to the risk of skeletal-related events (SREs), disease progression and death. Treatment with bisphosphonates reduces the probability of SREs through osteoclastic activity inhibition. The aim of this study was to determine the relation between BTM, bone metastasis development and SREs, disease progression and death in patients with breast cancer (BC) and BMe. Patients and methods: Observational, prospective and multicenter study. Patients with BC and BMe; no previous bone treatment in the last 6 months prior to study entry. Urinary aminoterminal telopeptide of collagen I (NTX, Osteomark NTx Urine, Wampole Laboratories, USA); urinary alpha-alpha-isomer of carboxyterminal telopeptide of collagen I (αα-CTX, ALPHA Crosslaps EIA, ids, UK) and serum bone alkaline phosphatase (BALP, OSTASE BAP, ids, UK) were determined at baseline (V0) and every 3 mo along 18 months (V6). Patients were treated with zoledronic acid (ZA) at inclusion and every 3–4 weeks. Results: 234 patients with BC and BMe were analyzed. BTM results were available for 219 patients at basal visit (V0) and every 3 mo of treatment along 18 months (V6). Population basal characteristics (234 patients): mean age: 59.8 years; ER+: 80.3%; PR+: 64.9%; HER 2+: 18.3%. Patients with pathologic baseline levels were: 49.8% NTX, 39.6% αα-CTX and 83.4% BALP. A significant decrease was observed in BTM at V2 vs V0 after 6 months: 13.7%, 8.4% and 58.4% presented pathologic values of NTX, αα-CTX and BALP respectively. Normalized levels remained steady throughout 18 mo follow-up, finding significant decrease for each BMT for each time point except at V6 for αα-CTX. Regarding association between BTM and SREs, progression and exitus, a significant association was observed between pathologic levels of BTM throughout follow-up: with SRE at V3, V4 for NTX; with disease progression at V3, V4, V5, V6 for NTX, at V2 for αα–CTX and at each follow up visit for BALP; and with death at V1,4,5 for NTX, at V5 for αα–CTX and at V1,2,3,4,5 for BALP. Conclusions: Addition of ZA to standard systemic therapy reduced BTM levels during the first 3 months of treatment and normalized levels remained steady throughout 18 months follow up except at Month 18 for αα-CTX. Pathological levels of BTM were significantly associated with SRE, disease progression and death. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-18.
SPECT and 18F-FDG PET/CT Imaging of Multiple Paragangliomas and a Growth Hormone–Producing Pituitary Adenoma as Phenotypes From a Novel Succinate Dehydrogenase Subunit D Mutation
Authors: Evangelia Skoura, Ioannis E. Datseris, Paraskevi Xekouki, Georgios Tolis, Constantine A. Stratakis
Journal: Clinical Nuclear Medicine (2013)

Mutations in the subunits B, C, D, and recently in A of the succinate dehydrogenase have been associated with the development of paragangliomas. We report the case of a 37-year-old man presented with multiple paragangliomas and a growth hormone-producing pituitary adenoma, with a novel succinate dehydrogenase subunit D mutation as the genetic analysis revealed. We present the similarities and the differences of the findings in patient imaging with either methods of SPECT (I-MIBG and In-pentetreotide) or PET/CT with F-FDG. This case revealed that F-FDG PET/CT detected more lesions and was superior compared with the other methods.
SP0055 Microrna in connective tissue disease
Authors: G. Illei
Journal: Annals of the Rheumatic Diseases (2013)

MicroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs of 19–24 nucleotides in length. They regulate gene expression by messenger RNA degradation and disruption of translation and are important in a wide range of physiological and pathological processes. They have been described as master regulators of gene expression, and are instrumental in regulating immune system development, normal immune function and autoimmunity. The two main characteristics of connective tissue diseases (CTD) is an imbalance between pro- and anti inflammatory processes leading to a prolonged inflammatory response and end organ damage. microRNAs play a fundamental role in both of these. Specific microRNA patterns are associated with various pro- or anti-inflammatory effects and abnormalities in some of these microRNAs have been described in CTDs. MicroRNAs have also been implicated in fibrosis and non-immune mediated mechanisms contributing to end organ damage. MicroRNAs are attractive as biomarker candidates since they can be detected in a variety of biologic sources and there are various methods to reliably assess their expressions. Importantly, they are reasonably stable and appear to be resistant to differences in sample handling. Some microRNAs have already been validated as diagnostic or prognostic biomarkers in various malignant diseases, demonstrating their clinical utility. Preliminary studies in CTDs (lupus, Sjogren's syndrome) have shown some encouraging results. Selected microRNAs correlated with disease activity in lupus and salivary gland inflammation in Sjogren's syndrome. In a pilot study global microRNA profiling reliably distinguished minor salivary glands obtained from SS patients with low or high focus scores from each other as well as from control biopsies. Interestingly, inflammation and decreased salivary gland function were associated with different sets of miRNAs which targeted distinct pathologic pathways. Further studies designed to evaluate microRNAs as biomarkers of specific applications (diagnosis, prognosis, and disease activity) are needed to establish their true potential as biomarkers in CTDs. <h3>Disclosure of Interest</h3> None Declared
Reliable data on 5- and 10-year survival in early-stage breast cancer provides accurate estimates of 15-year survival.
Authors: CI Herold, B Djulbegovic, I Hozo, GH Lyman
Journal: Cancer Research (2009)

Abstract Abstract #4076 Background: Evidence-based medicine encourages utilization of empirical evidence from controlled clinical trials in decision making both at the bedside and in health policy. However, the applicability of this approach may be limited by the lack of long-term results from efficacy studies. Decision analytic methods that model outcomes beyond empirically available evidence, typically over the lifetime horizon, have been proposed. There have been few studies of the accuracy of model-based survival projections utilizing reliable but early empiric results for estimating long-term survival. Such results, however, would have direct clinical and health policy implications.&amp;#x2028; Methods: We took advantage of recently published individual-patient data meta-analysis by Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (Lancet 2005;365:1687-1717) which regularly updates their results at 5-year intervals. A Markov model was built to compare empirical results with those modeled beyond the time horizon for which data was available. We first modeled breast cancer mortality rates comparing the effects of 5 years of tamoxifen versus no treatment. We then modeled the 15-year probability of death from breast cancer using the 5- and 10-year mortality data reported in the overview. Finally, we estimated the effect of breast cancer on life expectancy in women ranging in age from 40 to 70 years by decade.&amp;#x2028; Results: Verification of the model produced 5-, 10-, and 15-year survival data that were identical to the empirical data reported in the EBCTCG overview. Modeling 15-year survival based on 5- and 10-year empirical data resulted in an average error estimate in breast cancer mortality of 0.75% [range: -0.83 to 2.19%]. Although modeling of differences in life expectancies ranged from an underestimate of -7.93% to an overestimate of 12.64%, in absolute terms over the span of 15 years this corresponded to a loss of 18 days or a gain of 40 days of life, respectively. Regardless of the assumptions used in the model, the decision remained stable: tamoxifen remained the better choice compared to no therapy.&amp;#x2028; Conclusions: We conclude that reliable data generated at 5 or 10 years may be used to generate models that estimate 15-year survival. Whether 5-year data can be employed over the lifetime horizon remains to be demonstrated. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4076.
Promoter hypermethylation is an early event in breast carcinogenesis.
Authors: M Park, J Yoon, J Lee, M Choi, H Yoon, S Jung, B Lee, M Fackler, S Sukumar
Journal: Cancer Research (2009)

Abstract Abstract #5041 Background. Aberrant methylation of CpG islands in the promoter region of tumor suppressor genes has become established as an important epigenetic mechanism for gene silencing. Promoter hypermethyaltion in precursor lesions at risk for progression to invasive cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. In breast cancer promoter hypermethylation has been described for several genes covering all aspects of cellular function. However, the methylation studies of precursor lesion of the breast are rather sparse and mostly done in a purely qualitative manner.&amp;#x2028; Design. To evaluate the significance of alterations in promoter hypermethylation during multistage carcinogenesis of the breast, quantitative multiplex methylation-specific PCR of six genes (APC1, Cyclin D2, HIN-1, RAR-b, RASSF1A, and Twist) was performed on DNA from 15 normal breast tissues, 21 usual ductal hyperplasia (UDH), 48 ductal carcinoma in situ (DCIS), and 35 stage I invasive ductal carcinoma (IDC), not otherwise specified.&amp;#x2028; Results. We found no to very low levels of promoter methylation in normal samples. In general UDH, DCIS, and IDC samples revealed varying levels of methylation ranging from 0 to 100%. One-way analysis of variance showed that the methylation levels of all six genes increased significantly with the progression of breast neoplasia from normal epithelium, through hyperplasia, to DCIS. However, methylation levels were not significantly different between DCIS and IDC.&amp;#x2028; Conclusion. Our results suggest that promoter hypermethylation is an early event in breast carcinogenesis. Promoter hypermethylation in the precursor lesions of the breast cancer may be used as a target for cancer chemoprevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5041.
Abstract 4820: Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women.
Authors: Katharina Nimptsch, Xuehong Zhang, Edward Giovannucci, Aedin Cassidy, Éilis J. O'Reilly, Tobias Pischon, Eric B. Rimm, Jennifer Lin, Walter C. Willett, Charles S. Fuchs, Kana Wu
Journal: Cancer Research (2013)

Abstract Background: Flavonoids inhibit the growth of colon cancer cells in vitro. In a recent randomized controlled trial, the Polyp Prevention Trial, a higher intake of one sub-class, flavonols, was significantly associated with a 76% reduced risk of recurrent advanced adenoma. Cohort studies that have examined the association between flavonoid intake and risk of colorectal cancer (CRC) have yielded inconsistent results, but most previous studies only evaluated habitual intake of a limited number of subclasses and there is growing evidence for differential effects depending on subtle difference in structure between the sub-classes Objective: To examine whether higher habitual dietary intake of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones and polymers) are associated with lower risk of CRC. Methods: Using data from validated food frequency questionnaires administered every four years and an updated USDA flavonoid food composition database flavonoid intakes were calculated for 73,666 participants from the Nurses’ Health Study I, and for 32,059 participants from the Health Professionals Follow-up Study. Results: During 16 years of follow-up, 1,405 colorectal cancer cases (652 in men, 753 in women) were identified. Intakes of total flavonoids and subclasses were not associated with risk of CRC (hazard ratios (95% confidence interval) multivariable adjusted for age, smoking before age 30, family history of colorectal cancer, history of endoscopy, aspirin use, body mass index, physical activity, postmenopausal hormone use in women, alcohol consumption, intake of total energy, calcium and vitamin D; highest vs. lowest quintile: total flavonoids, men: 0.97 (0.75-1.26), women: 1.00 (0.80-1.26); flavonols, men: 0.98 (0.76-1.26), women: 1.21 (0.96-1.52); flavones, men: 0.86 (0.67-1.11), women: 0.90 (0.72-1.13); flavanones, men: 0.98 (0.75-1.28), women: 1.00 (0.80-1.26); flavan-3-ols, men: 1.00 (0.78-1.29), women: 0.96 (0.76-1.21); anthocyanins, men: 0.89 (0.69-1.15), women: 1.25 (0.98-1.60); polymers, men: 0.92 (0.71-1.18), women: 0.88 (0.69-1.11)). Conclusion: Our findings do not provide support for the hypothesis that a higher intake of flavonoids or any specific sub-class decrease risk of CRC. Citation Format: Katharina Nimptsch, Xuehong Zhang, Edward Giovannucci, Aedin Cassidy, Éilis J. O'Reilly, Tobias Pischon, Eric B. Rimm, Jennifer Lin, Walter C. Willett, Charles S. Fuchs, Kana Wu. Habitual intake of total flavonoids and flavonoid subclasses and risk of colorectal cancer in men and women. [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 4820. doi:10.1158/1538-7445.AM2013-4820
AB0589 Subclinical atherosclerosis found both in psoriatic arthritis and rheumatoid arthritis
Authors: S. A. Bilgen, U. Kalyoncu, L. Kilic, O. Karadag, U. Canpolat, K. Aytemir, S. Kiraz, A. Akdogan, B. Kaya, I. Ertenli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular disease (CVD) is found in almost all chronic musculoskeletal diseases that include Psoriatic arthritis (PsA) and rheumatoid arthritis (RA). <h3>Objectives</h3> To assess subclinical atherosclerosis in patients with PsA and RA. <h3>Methods</h3> Patients with PsA according to classification of psoriatic arthritis (CASPAR) criteria<sup>1</sup> were enrolled in this cross-sectional study between June 2011 and July 2012. Demographic data (sex, age), PsA and psoriasis duration, joint pattern (monoarthritis, oligoarthritis or polyarthritis) and other PsA involvements (nail, enthesis, dactilytis) were noted. Tender joint count, swollen joint count and disease activity score (DAS)-28 were used for joint activity assessment. Erytrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used for acute phase reactants. Last visit fasting glucose level, lipid profile (total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL) and triglyceride), body mass index (kg/m<sup>2</sup>) and blood pressure were also recorded. Conventional cardiovascular risk factors such as history of diabetes mellitus, hypertension, dyslipidemia, and smoking were noted. Sex and age matched RA and healthy controls were selected as the control group for this study. Flow mediated dilatation (FMD) and intima media thickness (IMT) were measured by a experienced cardiologist. <h3>Results</h3> Thirty-two patients with PsA, 25 RA and 37 healthy controls were enrolled in this cross-sectional study. Psoriasis duration of PsA patients was 116±107 months. Among PsA patients, 20 (62%) patients had peripheral joint, 11 (34%) patients had axial, and 1 (3%) patient had both peripheral and axial involvement. Dactilytis 8 (25%), enthesis 10 (31%) and nail 15 (47%) were other clinical involvements. Twenty-two PsA patients (69%) and 5 (20%) of the RA patients used anti-TNF alpha treatment (p&lt;0.001). PsA patients had lower HDL levels than RA patients (51±18 vs 65±11, p=0.006). Obesity was more frequently found in PsA patients than healthy controls [28.4±5.5 vs 24.5±4.3, p=0.002]. There were no differences in all endothelial dysfunction parameters for PsA and RA patients. However, FMD % was lower in PsA patients than healthy controls [9.4±4.8 vs 11.6±3.2, p=0.032]. Carotis IMT was more obvious in PsA patients than healthy controls [0.67±0.20 vs 0.56±0.12, p=0.01]. Endothelial dysfunction parameters were similar in patients with and without active joint lesion. <h3>Conclusions</h3> Both PsA and RA patients have subclinical endothelial dysfunction. PsA patients had both traditional risk factors such as obesity and dyslipidemia and chronic inflammation for the develeopment of endothelial dysfunction. <h3>References</h3> <h3>Disclosure of Interest</h3> None Declared