tbuckley/cabot-search huggingface dataset:
OP0114 Inefficacy of Hydroxychoroquine in Primary Sjögren’s Syndrome: Results at 12 Months of the Randomized Placebo-Controlled Trial of Plaquenil in Primary Sjögren’s Syndrome
Authors: J. E. Gottenberg, P. Ravaud, X. Puechal, V. Le Guern, J. Sibilia, V. Goeb, C. Larroche, J. J. Dubost, S. Rist, A. Saraux, V. Devauchelle, J. Morel, G. Hayem, E. Hachulla, A. Perdriger, D. Sene, C. Zarnitsky, E. Perrodeau, D. Batouche, V. Furlan, J. Benessiano, R. Seror, X. Mariette
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Hydroxychloroquine (HQ, Plaquenil) is often prescribed in patients with primary Sjögren's syndrome (pSS). However, except a crossover trial, no controlled trial has ever evaluated HQ versus placebo. <h3>Objectives</h3> <h3>Methods</h3> 120 patients with pSS were randomly assigned to receive HQ (400 mg/j) or placebo for 24 weeks (controlled phase) and were all prescribed HQ between week 24 and week 48 (open extension). All patients fulfilled the AECG criteria. A favorable overall response (primary outcome criteria) was defined as the patient having &gt;or= 30% improvement between weeks 0 and 24 in the values on 2 of the 3 patient's VAS evaluating dryness, pain and fatigue. Secondary end points were the evolution of the ESSDAI, the ESSPRI, Schirmer's test and unstimulated salivary flow, serum gammaglobulin levels, and of SF-36, HAD, PROFAD, and SSI. Serum interferon-regulated chemokines (CXCL10, CCL2 and CCL19) were assessed at baseline and W24 in the 45 patients with available serum. <h3>Results</h3> Baseline characteristics of the 120 patients were as following: mean age 55.9 years, 91.7% of women, median disease duration: 5 years, anti-SSA positivity : 55.1%, patients with systemic involvement at enrollment: 30%. At 6 months, 19.2% of patients receiving placebo and 19.6% of patients treated with HQ had a favorable overall response (p = 0.9). At 12 months, 18.8% of patients treated for 6 months with placebo, then 6 months with HQ and 32.1% patients treated with 12 months with HQ were responders (p= 0.1). No significant difference was observed in any of the secondary outcome criteria. No significant difference was observed in patients with anti-SSA autoantibodies, high IgG levels, or systemic involvement. In patients treated with HQ, a trend towards a decrease of serum IgG was observed, as well as a significant decrease of IgM. In patients with HQ, a decrease in serum CXCL10 (from 50.5 to 35.8 pg/ml vs from 27.7 to 38.7 pg/ml under placebo, p=0.001) and CCL19 (from 241.6 to 160.9 pg/ml vs from 142.3 to 131.1 pg/ml, p=0.3), but not CCL2, was observed. In the HQ arm, all except 1 had detectable blood levels of HQ at 6 months. Baseline levels of HQ or of IFN-regulated chemokines were not associated with a favorable overall response. Tolerance of HQ was comparable to placebo. <h3>Conclusions</h3> The results of this controlled trial did not show any evidence of short term efficacy of HQ in pSS. HQ induced a decrease in serum level of CXCL10 and CCL19, 2 IFN-induced chemokines but no association with response to HQ could be identified in any subgroup of patients. <h3>Disclosure of Interest</h3> None Declared
The Trials of Prevention Trials
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article The Trials of Prevention Trials Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 15, 2 August 1989, Pages 1123–1126, https://doi.org/10.1093/jnci/81.15.1123 Published: 02 August 1989
Surgical Treatment of Ascites
Authors: Roy C. Crosby, Edward A. Cooney
Journal: New England Journal of Medicine (1946)

ASCITES is a problem frequently encountered and often unsatisfactorily treated. An adjunct in the therapy of ascites has been tried in a limited number of cases and has seemed sufficiently helpful to warrant reporting.Attempts to obtain more lasting relief from ascites have been many and varied. In 1896 Drummond and Morison1 reported the first surgical treatment of ascites. Talma,2 in 1898, is usually credited with the original suggestion for the surgical relief of ascites, and the operation — omentopexy — has come to be known as the Talma-Morison operation. Morison's patient lived two years after the operation. Monprofit3 reported . . .
Group Isolation and Atherosclerosis in Cholesterol-Fed Cockerels
Authors: RUTH PICK, LOUIS N. KATZ, DOLORES CENTURY, Philip J. Johnson
Journal: Circulation Research (1963)

Group isolation, a highly unnatural environmental situation in cockerels, increases atherogenesis and decreases regression of previously induced atherosclerosis. This alteration occurs despite the absence of change in the hypercholesterolemic response to the diet in the induction experiments. It is accompanied by a reduction in weight gain despite food intake similar to the controls. Disturbing the social order by altering the pecking order in flocks of cockerels on a cholesterol-oil containing diet does not alter hypercholesterolemia and atherogenesis. However, it leads to increase in sex characteristics. Physical activity, with or without alterations in pecking order, causes a reduced weight gain even when food intakes are not altered. It is concluded that environmental factors can and do influence atherosclerosis. The types of environmental change which can produce this effect and the exact mechanisms involved require further study.
THU0217 The Aftereffect of the Use of the Inhibitor of Interleukin-1 in Complex Therapy of Secondary Osteoarthritis of the Knee in Patients with Rheumatoid Arthritis
Authors: I. Starodubtseva, L. Vasilieva, A. Nikitin, N. Barsukova
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Numerous studies have proved the advantageous aftereffect of the use of inhibitor of interleukin-1 in the therapy of patients with OA. <h3>Objectives</h3> The aim of the study was to estimate the aftereffect of inhibitor of interleukin-1 in therapy of patients with secondary osteoarthritis of the knee in rheumatoid arthritis. <h3>Methods</h3> The trial embraced 80 patients with secondary OA of the knee in RA. Their average age was 55,2±11,4, disease lasted from 5 to 15 years. Patients of group 1 (n=40) underwent a 6-month therapy of inhibitor of interleukin-1 (50 mg twice per day) on the basis of methotrexate (10-15 mg per week). 40 patients from group 2 took only methotrexate. RA was diagnosed on the basis of the EULAR/ACR criteria. 12 months later we analyzed the dynamic of clinical parameters: pain on VAS, indexes WOMAC, Lequesne and HAQ. The activity of the underlying disease (RA) was determined traditionally, on the basis of DAS 28. During the period of observation all the patients were getting basic therapy. <h3>Results</h3> The activity of RA on DAS 28 statistically significant reduced to 2,56±0,98 (p&lt;0,01) vs 3,47±1,1 before the treatment in group 1, and to 3,23±0,96 (p&lt;0,05) vs 3,9±1,2 in group 2. The level of indexes pain on VAS, WOMAC and Lequesne in group 1 statistically significant decreased to 41±1,51 (p&lt;0,001), 89,9±1,49 (p&lt;0,001) and 9,75±0,28 (p&lt;0,001). Index HAQ in group 1 achieved the average of 0,78±0,31 (p&lt;0,05). Group 1 statistically significant showed better results in comparison with the results in group 2 regarding clinical parameters (pain on VAS, indexes Lequesne, WOMAC) (p&lt;0,05). Despite the advantages in the dynamic of DAS 28 and HAQ in group 1, the comparison of the results in two groups was not statistically significant. <h3>Conclusions</h3> As a result the six-month course of complex therapy of secondary osteoarthritis of the knee in patients with rheumatoid arthritis with the use of interleukin-1 inhibitor has its aftereffect. The aftereffect after the new therapeutical approach with the use of the inhibitor of interleukin-1 has shown more advantages if compared to the traditional basis therapy. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3816
EUS-guided pseudocyst drainage as a one-step procedure using a novel multiple wire insertion technique
Authors: M. Khashab, A. Lennon, V. Singh, E. Shin, M. Canto, A. Kalloo, P. Okolo, S. Giday
Journal: Endoscopy (2010)

The aim of this report is to describe the technique of endoscopic ultrasound (EUS)-guided pseudocyst drainage as a one-step procedure using a novel multiple wire insertion technique facilitated by the double-lumen biliary cytology brush catheter (Cook Medical, Winston-Salem, North Carolina, USA).
SAT0125 Comparing the long-term clinical outcome of etanercept and adalimumab treatment with respect to immunogenicity
Authors: C. Krieckaert, A. Jamnitski, M. Nurmohamed, P. Kostense, M. Boers, G. Wolbink
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To compare rates of sustained low and minimal disease activity and ACR/EULAR remission during 3-year follow-up in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care. <h3>Methods</h3> 407 RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n=203) or adalimumab (n=204) and assessed at 3- and later 6 month intervals. Clinical parameters and anti-adalimumab antibodies (AAA) were measured at each time point. Clinical response was defined as sustained (at least 12 consecutive months) low disease activity (sLDA; DAS28 &lt;3.2), minimal disease activity (sMDA; DAS28 &lt;2.6) or ACR/EULAR remission (sSDAI). Non-overlapping response rates were calculated. <h3>Results</h3> In the adalimumab group, 13% reached sLDA but not sMDA, 15% reached sMDA but not sSDAI and 16% reached sSDAI remission. In the etanercept group corresponding rates were 16%, 11% and 12%, respectively (overall test for linear trend: p=0.42). Adalimumab-treated patients without antibodies (AAA–; n=150, 74%) had best outcomes and AAA+ patients the worst, with etanercept-treated patients in between (p&lt;0.0001). Differences were most apparent in the sSDAI and sMDA categories. For example, 40% of AAA–, 23% of etanercept and 4% of AAA+ patients achieved at least sMDA (Fig. 1). <h3>Conclusions</h3> Overall, etanercept and adalimumab treatment appeared similar in inducing a good long-term clinical outcome. The occurrence of AAA hampered the long-term clinical efficacy of adalimumab. Treatment response rates to adalimumab might be increased by strategies that counteract the development of AAA. <h3>Disclosure of Interest</h3> C. Krieckaert: None Declared, A. Jamnitski: None Declared, M. Nurmohamed Grant/Research support from: Abbott, Roche, Pfizer, Consultant for: Abbott, Roche, Phizer, MSD, UCB, SOBI and BMS, Speakers Bureau: Abbott, Roche, Pfizer, P. Kostense: None Declared, M. Boers Consultant for: Roche, GSK, Novartis, Speakers Bureau: UCB, Abbott, G. Wolbink Grant/Research support from: Pfizer, Speakers Bureau: Pfizer, Amgen
THU0145 A multi-biomarker disease activity (MBDA) score measures rheumatoid arthritis disease activity in patients treated with the JAK inhibitor tofacitinib
Authors: K. Yamaoka, S. Kubo, K. Sonomoto, S. Hirata, A. Voinov, M. Rowe, G. Cavet, K. Saito, Y. Tanaka
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Quantitative assessment of disease activity is important for effective care of rheumatoid arthritis (RA). Treating to target levels of disease activity can improve patient outcomes, but composite indices are subject to inter-assessor variability and not universally adopted. In order to overcome this issue, a multi-biomarker disease activity (MBDA) blood test has been developed for RA disease activity that could complement clinical assessment and provide information about underlying disease processes. Recently, JAK inhibition has gathered attention as a novel therapeutic strategy for rheumatoid arthritis. <h3>Objectives</h3> To evaluate the MBDA test score as a measure of disease activity in patients treated with the JAK inhibitor tofacitinib. <h3>Methods</h3> MBDA was evaluated at baseline, 2 weeks, 3 months, 6 months and 1 year in 47 patients treated with a range of doses of tofacitinib. MBDA combines 12 serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, Leptin, Resistin, CRP, SAA) in a pre-specified algorithm resulting in a score between 1 and 100. Association with clinical disease activity measures and change in these measures was assessed by Spearman correlation. 1. Primary endpoint: correlation of MBDA score with disease activity. 2. Secondary endpoint: correlation of MBDA score changes (ΔMBDA) with ΔDAS28 (ESR), ΔSDAI and ΔCDAI. <h3>Results</h3> Mean baseline characteristics were: age 55 years, duration 6.9 years, MBDA 60, DAS28 (ESR) 6.3, SDAI 37 and CDAI 34. MBDA scores were correlated with DAS28 (ESR), SDAI and CDAI (p&lt;0.01). Median MBDA score dropped significantly to 2 weeks (p&lt;0.001) and continued to decline through 1 year, as did clinical disease activity measures. At 1 year, mean disease activity levels were: MBDA 28, DAS28 (ESR) 3.0, SDAI 7.3 and CDAI 6.9. The decrease in MBDA score was correlated to decreases in DAS28 (ESR), SDAI and CDAI (p&lt;0.01 in all cases). <h3>Conclusions</h3> The MBDA score indicates both current disease activity and change in disease activity in patients treated with tofacitinib. Tofacitinib drives large decreases in the levels of disease activity biomarkers. Biomarker-based assessment of disease activity may complement tools such as CDAI, which include subjective assessments. These results suggest that MBDA may be a useful tool for objective disease activity assessment, requiring just a small amount of patient serum. <h3>Disclosure of Interest</h3> K. Yamaoka: None Declared, S. Kubo: None Declared, K. Sonomoto: None Declared, S. Hirata: None Declared, A. Voinov: None Declared, M. Rowe: None Declared, G. Cavet: None Declared, K. Saito: None Declared, Y. Tanaka Consultant for: Mitsubishi-Tanabe Pharma, Pfizer Inc., Speakers Bureau: Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Abbott, Eisai Pharma, Chugai Pharm
Staphylococcal Scalded-Skin Syndrome in an Adult
Authors: Gerald Levine, Carl W. Norden
Journal: New England Journal of Medicine (1972)

THE term "staphylococcal scalded-skin syndrome" has been proposed to cover a spectrum of clinical lesions including toxic epidermal necrolysis, bullous impetigo, and generalized scarlatiniform eruption.1 This syndrome may be reproduced in newborn mice by the injection of either live staphylococci2 of phage Group II or exfoliative toxin.2 , 3 In that model, exfoliation occurred only in animals under six days of age. The case presented below is unusual in that this syndrome occurred in a 19-year-old man from whom staphylococci of phage Group II, capable of producing exfoliative toxin, were isolated.Case ReportA 19-year-old man had chronic membranoproliferative glomerulonephritis diagnosed 4 . . .
Abstract 2338: EGFR-mediated TGM2 overexpression couples acquired TRAIL-resistance and migration involving c-FLIP and MMP9 in NSCLC cells
Authors: Zi Li, Lang Bai, Wenshu Chen, Xiuling Xu, Yong Lin
Journal: Cancer Research (2011)

Abstract Acquired chemoresistance not only blunts cancer chemotherapy, but may also promote cancer cell migration and metastasis. Our previous studies have revealed that acquired tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in non-small cell lung cancer (NSCLC) cells was associated with Akt-mediated stabilization of cellular FLICE-like inhibitory protein (c-FLIP) and myeloid cell leukemia 1 (Mcl-1). The cells with acquired TRAIL-resistance have significantly increased migration and invasion potential. Gene expression array assay was used to explore the mechanism underlying TRAIL-resistance associated migration, and tissue transglutaminase 2 (TGM2) was identified as one of the genes with the highest expressing increase in TRAIL-resistant cells. Suppressing TGM2 activity or expression dramatically alleviated TRAIL-resistance and cell migration, suggesting TGM2 contributes to the both phenotypes in the TRAIL-resistant cells. TGM2 suppression significantly reduced c-FLIPL but not Mcl-1L expression, suggesting that TGM2 mediates TRAIL-resistance through c-FLIP. The expression of MMP9, a matrix metalloproteinase involved in cancer cell migration, was suppressed when TGM2 was inhibited, suggesting that TGM2 potentiates cell migration through upregulating MMP-9 expression. Furthermore, we found that EGFR was highly upregulated and activated and suppression of which dramatically reduced the expression level of TGM2 in the TRAIL-resistant cells. With chemical inhibitors, we further determined MAPKs (JNK and ERK), but not Akt and NF-κB, are responsible for EGFR-mediated TGM2 expression. Conversely, suppression of TGM2 had no effect on ERK, JNK and Akt activity. These results identify a novel pathway that involves EGFR, MAPK and TGM2 for acquired TRAIL-resistance and cell migration in NSCLC cells. Because TGM2 converges acquired TRAIL-resistance and cell migration, it could be a molecular target for circumventing acquired chemoresistance and metastasis in lung cancer. 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 2338. doi:10.1158/1538-7445.AM2011-2338
MR-04 * DICER REGULATES GLIOMA STEM CELL STATE
Authors: S. Singh, K. Burrell, A. Alamhabspour, S. Agnihotri, A. Vartanian, S. Jalali, J. Gumin, E. Sulman, F. Lang, G. Zadeh
Journal: Neuro-Oncology (2014)

The role of cancer stem cells in tumor formation and tumor heterogeneity is currently one of the most researched topics in cancer biology, and microRNAs likely have functional relevance in regulation of critical genes and parameters implicated in glioma stem cell (GSC) behavior and differentiation. To address this, we investigated global role of microRNA in GSCs, focusing on DICER, which regulates double-stranded RNA processing for microRNA biogenesis. Analysis of data from the Cancer Genome Atlas (TCGA) database suggests that high Dicer expression level is correlated with better prognosis of GBM patients. Gene signatures correlated with DICER expression levels suggest DICER/miRNA mediated mechanisms potentially regulate a multitude of cellular pathways in GBMs. Immunohistochemistry analysis of GBM tissue microarray reveals that of 54 tumor samples, 26 (48%) of GBM patients have low or undetectable levels of DICER1 protein, indicating frequent inactivation in high grade glioma. To characterize this functionally, we utilized various in vitro approaches, including exposure to hypoxia, to characterize the GSC properties after knockdown of DICER (GSCs did not have significant variation in endogenous DICER levels). Using three different GSC lines, we found in all cases with Dicer knockdown resulted in increased proliferation of three independent GSC lines with concomitant decrease in levels of stem cell markers (Sox2, Bmi1 etc.), a phenotype observed even upon exposure to hypoxia, a state that is known to preserve and promote the stem-like cell phenotype. Results from self-renewal assays as well as expression profiling show that GSCs with depleted levels of Dicer lose stem cell characteristics and acquire a progenitor-cell like state. Our results highlight the role of DICER as potential regulators of GSC stem-like versus progenitor-like state.
Brain metastases (BM) in patients presenting with HER-2 amplified advanced breast cancer (ABC).
Authors: C Sweldens, P Huget, R Weytjens, A Prove, P Vermeulen, P Van Dam, L Dirix
Journal: Cancer Research (2009)

Abstract Abstract #1060 Background : The HER-2 amplified breast cancer phenotype is suggested to have an increased propensity for CNS metastasis. The introduction of trastuzumab might be related to this association. In order to elucidate this relationship we analyzed our prospectively collected database of all patients presenting with metastatic HER-2 amplified breast cancer in the time frame between Jan 2002 until Dec 2004.&amp;#x2028; Material and Methods : The AZ-Augustinus Breast Cancer Tissue Bank was initiated in 1999. It ensures the prospective entry of all clinical and pathological features of patients presenting in our Breast Clinic clinical database. The data entry is performed by dedicated Datamanagers and is linked to the Biological Repository Collection (tissue, serum, plasma, bone marrow). Patients presenting with primary metastatic, HER-2 amplified ( FISH +) between 2002 and 2004 were analyzed for this study. Since Jan 2002, all patients presenting with metastatic disease underwent a routine CT-scan of the brain as initial staging procedure.&amp;#x2028; Results : A total of 33 patients presented with HER-2 +, unpretreated metastatic breast cancer. Mean age: 53 years (range 30-69). Sites of metastases at diagnosis ( % of patients) : liver: 71 %, lung: 36 %, bone: 86 %, brain (BM): 15 % (5), lymph nodes and others: 20%. In total 5/33 (15%)&amp;#x2028; presented with brain only metastasis. During the follow-up period 17 more patients developed BM, amounting to 22/33 (67%). The median time between diagnosis of BM after diagnosis of ABC was 22 months (0 – 98). Mean time to developing BM was 18 months. In total 62 lesions in the CNS were counted on MRI in these 22 patients. 23 lesions (38%) had a cerebellar localisation.&amp;#x2028; Conclusions: Assuming that the presentation with metastasis is a reflection of the unperturbed biology of disease, our data suggest that the CNS is not an exceptionally preferred site for metastasis in untreated HER-2 + advanced breast cancer. A preference for a cerebellar localisation is suggested. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1060.