tbuckley/cabot-search huggingface dataset:
FRI0095 Rheumatoid arthritis patients have worse outcomes after total hip replacements compared with osteoarthritis patients
Authors: S. M. Goodman, D. Ramsden-Stein, W.-T. Huang, M. P. Figgie, M. Alexiades, L. A. Mandl
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Historically, total hip arthroplasty (THR) outcomes have been poorer for patients with rheumatoid arthritis (RA) compared with osteoarthritis (OA). Whether this is true in a contemporary cohort of RA THR is unknown. <h3>Objectives</h3> To compare outcomes of primary and revision THR in RA vs. OA. <h3>Methods</h3> All THR and revision THR (RTHR) enrolled in a single institution arthroplasty registry between 5/1/2007 and 7/1/2010 with pre-operative data and who were alive at two years were eligible for this analysis. Patients with two eligible procedures only contributed data from the second. RA cases were identified by self report or ICD-9 code 714.0 and were validated by chart review. Patients with any other systemic rheumatic disease or fractures were excluded. Baseline and 2 year data were compared between RA and OA cases. Satisfaction at 2 years was measured on a Likert scale. Differences between groups were compared using unpaired Student’s t test, Chi-Square or Fisher’s exact test as appropriate. <h3>Results</h3> From 6,515 cases, we identified 6012 eligible primary THR (202 RA) and 503 RTHR (58 RA). 95% had 2 year follow-up. (Table 1) RA were more likely to be female and had significantly more comorbidities. Compared with OA, RA THR had no significant difference in age or BMI, while RA RTHR were younger with lower BMI. RA THR had significantly worse baseline and 2 year WOMAC pain and function, though only 2-year function showed a clinically meaningful difference, (WOMAC difference &gt;10). In addition, RA THR had 4x increased prevalence of poor pain and poor function at 2 years compared with OA. RA RTHR had significantly worse function and 2x increased prevalence of poor function at 2 years. RA THR were as satisfied as OA with pain relief but significantly less likely satisfied overall. RTHR showed no difference in satisfaction. <h3>Conclusions</h3> Contemporary RA THR patients have similar absolute improvements in pain and function compared with OA but significantly worse 2-year pain and function. This is important information to convey to RA patients to ensure appropriate expectations. Further study of timing of THR in RA patients may help optimize outcomes. <h3>Disclosure of Interest</h3> None Declared
Abstract 3764: SC-1, a sorafenib derivative, induces apoptosis in epidermal growth factor receptor wild type non-small cell lung cancer through the inhibition of signal transducers and activators of transcription 3
Authors: Cheng-Yi Wang, Ting-Ting Chao, Chung-Wai Shiau, Ang Yuan, Chong-Jen Yu, Kuen-Feng Chen
Journal: Cancer Research (2012)

Abstract Background: Lung cancer is the leading cause of cancer-related death worldwide, but currently there are no available target therapies for EGFR wild type NSCLC patients. Sorafenib, a multiple kinase inhibitors, shows therapeutic effects in renal carcinoma (RCC) and hepatocellular carcinoma (HCC). Our data shows that the inhibition of signal transducers and activators of transcription 3 (STAT3), a transcription factor involving in cell proliferation and survival, represents a major mechanism whereby sorafenib induces apoptosis in HCC cells (Clin Cancer Res 2010). Therefore, we design and synthesize a sorafenib derivative, SC-1, which is devoid of kinase activity (J Hepatol 2011). SC-1 shows higher potency in inducing apoptosis than sorafenib. Here, we tested efficacy of SC-1 to EGFR wild type NSCLC and examined the drug mechanism. Methods: EGFR wild type NSCLC cell lines, A549 H292 H322 and H460, were used for in vitro studies. Apoptosis was examined by both flow cytometry and western blot. Signal transduction pathways in cells were assessed by western blot. Results: SC-1 induced apoptosis in association with reducing the phosphorylation of STAT3 (p-STAT3) in a dose- and time-dependent manner in four NSCLC cells lines (A549 H292 H322 and H460). SC-1 demonstrates dose-dependent anti-proliferation effects on cell viability in NSCLC cell lines on MTT assay. Increased amount of SC-1 represented improvement cell apoptosis by FACS in NSCLC cells. Western blot analysis showed SC-1 exhibit dose-dependent and time-dependent effect on cell apoptosis through inhibition of STAT3 with reducing p-STAT3 and the STAT3-regulating protein, Mcl-1, survivin and cyclinD1. Conclusions: SC-1 provides a proof of concept that targeting STAT3 signaling pathway is a novel approach for the treatment of EGFR wild type NSCLC. 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 3764. doi:1538-7445.AM2012-3764
Recent advances: Diabetes
Authors: T. Mandrup-Poulsen
Journal: BMJ (1998)

Diabetes mellitus is one of the most common endocrine diseases in all populations and all age groups.It is a syndrome of disturbed intermediary metabolism caused by inadequate insulin secretion or impaired insulin action, or both.Diabetes is crudely grouped into the two types-insulin dependent diabetes mellitus and non-insulin dependent diabetes mellitus.Both types are associated with excessive morbidity and mortality.Relative mortality in people with insulin dependent diabetes is between 10 and 30 (equal to a 5-10 year reduction in life expectancy), depending on the age at diagnosis, current age, the duration of the disease, and the year of diagnosis. 1Although cohorts of patients with insulin dependent diabetes diagnosed after 1955 may have a better prognosis, 1 2 this trend seems to be levelling off. 3 Non-insulin dependent diabetes is associated with an overall age adjusted mortality that is about twice that of non-diabetic populations; life expectancy is reduced by 5 to 10 years in middle aged patients with this type of diabetes. 4There are no signs of a reduction in mortality from non-insulin dependent diabetes.Diabetes has a serious economic impact.In 1992, the estimated cost of diabetes in the United States was between $85bn and $92bn, two thirds of which resulted from lost productivity because of admission to hospital and death. 5The worldwide prevalence of diabetes is expected to more than double between 1994 and 2010, to 239 million people (fig 1). 6Tight metabolic control, drug treatment of hypertension and hyperlipidaemia, and efforts directed at changes in lifestyle will therefore pose heavy financial burdens on global healthcare systems.Urgent political and organisational decisions need to be made now. MethodsThe references in this review were selected from reports on the epidemiology, aetiology, pathogenesis, and treatment of diabetes.Most were published in the past five years.The overall aim was to underline the increasing severity of diabetes worldwide.Being a clinical specialist in diabetes and a diabetes immunologist, I apologise for any selection bias resulting from this approach.
ASSESSMENT OF PARAVALVULAR AORTIC REGURGITATION AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION USING CARDIAC MAGNETIC RESONANCE IMAGING: A COMPARATIVE STUDY WITH ECHOCARDIOGRAPHY AND ANGIOGRAPHY
Authors: Najime Bouhzam, Jerome Caudron, Carlos Rodriguez, Eric Durand, Christophe Tron, Matthieu Godin, Fabrice Bauer, G. Alain Cribier, Jean-Nicolas Dacher, Helene Eltchaninoff
Journal: Journal of the American College of Cardiology (2015)
A6.26 Analysis of circulating mirnas in patients with axial sponyloarthritis with different spinal involvement
Authors: K Prajzlerová, M Fojtíková, S Forejtová, K Pavelka, J Vencovský, L Šenolt, M Filková
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> The altered expression of miRNAs and dysregulation of their target genes has been shown to contribute to pathophysiology of many autoimmune diseases. In addition, circulating miRNAs may serve as diagnostic and/or prognostic biomarkers. Our aim was to identify circulating miRNAs in patients with axial spondyloarthritis (AxSpA) and to investigate their relationship with spinal involvement and disease activity. <h3>Material and methods</h3> Total RNA was isolated using phenol-chloroform extraction from plasma of 20 patients with non-radiographic AxSpA (nr-AxSpA), 48 patients with radiographic AxSpA (with and without spinal involvement, including 6 patients with a bamboo spine), and 29 healthy controls (HC). A comprehensive analysis of miRNAs was performed using TaqMan<sup>®</sup> Low Density Array (TLDA) in 5 samples from each group. Expression of miRNAs was further confirmed by single assays in the remaining samples and the levels were normalised to C. elegans spike-in controls. Disease activity was assessed based on C-reactive protein (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were analysed using one-way ANOVA, unpaired t-test with Welch’s correction and Pearson correlation. <h3>Results</h3> Out of 760 miRNAs analysed by TLDA, 21 miRNAs were selected for further analysis, according to differences in the expression and role in the inflammation and bone metabolism. Fourteen miRNAs were significantly lower (p &lt; 0.05) in all patients with AxSpA compared to HC. In all patients with radiographic AxSpA (r-AxSpA), 20 miRNAs were significantly lower in comparison with the group of nr-AxSpA patients and HC, in particular miR-24, miR-27a, miR-106a or miR-223 (p &lt; 0.0001). Levels of these miRNAs were significantly lower (p &lt; 0.05) in a subgroup of patients with bamboo spine compared with other patients with AxSpA. We found, that e.g. miR-625* and miR-885–5p significantly correlated with BASDAI in all patients with r-AxSpA (r = 0.330; p = 0.043 and r = 0.433; p = 0.007 respectively) and were more pronounced in patients with spinal involvement (r = 0.570; p = 0.011 and r = 0.587; p = 0.008). Furthermore, miR-29a significantly correlated with BASDAI (r = 0.474; p = 0.040) and CRP (r = 0.625; p = 0.004) in patients with spinal involvement. <h3>Conclusions</h3> Our analysis revealed different expression of several circulating miRNAs associated with the degree of spinal involvement and disease activity. Our data suggest role of these miRNA in the pathogenesis of AxSpA and potential use of circulating miRNAs as biomarkers of disease progression. <h3>Acknowledgements</h3> IGA project no. NT 14498, project of MHCR for conceptual development of research organisation 023728 and SVV 260 031.
Evaluation of a New Bipyridine Inotropic Agent — Milrinone — in Patients with Severe Congestive Heart Failure
Authors: Donald S. Baim, Arthur V. McDowell, Joseph Cherniles, Ernest S. Monrad, J. Anthony Parker, Jerome Edelson, Eugene Braunwald, William Grossman
Journal: New England Journal of Medicine (1983)

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.
P141 Differential expression of conventional and inhibitory VEGFA isoforms in normal and fibrotic fibroblasts–a potential role in IPF pathogenesis?
Authors: SL Barratt, T Blythe, C Jarrett, K Ourradi, T Maher, GI Welsh, DO Bates, AB Millar
Journal: Thorax (2013)

<h3>Introduction</h3> Vascular endothelial growth factor (VEGFA) has been implicated in the pathogenesis of Idiopathic Pulmonary Fibrosis (IPF). Two families of endogenous isoforms exist formed by alternative splicing of mRNA transcripts: the conventional potent angiogenic and mitogenic isoforms (VEGF<sub>xxx</sub>a family) and the VEGF<sub>xxx</sub>b family that is thought to have contrasting inhibitory functions. <h3>Hypothesis</h3> We hypothesise that differential expression of VEGF<sub>xxx</sub>a and VEGF<sub>xxx</sub>b isoforms by fibroblasts may influence the development of IPF. <h3>Methods</h3> Normal (NF) and fibrotic fibroblasts (FF) (from patients with proven UIP) were extracted from lung samples using the explant method. The expression of VEGF<sub>xxx</sub>a and VEGF<sub>xxx</sub>b by NF and FF was analysed at the mRNA level by RT-PCR and quantified by qPCR. Protein expression was determined by western blotting (WB) and ELISA. We sought to establish a potential functional effect of recombinant VEGF<sub>165</sub>a and VEGF<sub>165</sub>b proteins on fibroblasts by assessing the expression of a) the extracellular matrix (ECM) protein fibronectin and b) α-SMA, a marker of myofibroblast differentiation. <h3>Results</h3> Both NF and FF expressed VEGF<sub>xxx</sub>a and VEGF<sub>xxx</sub>b isoforms at the mRNA level as determined by RT-PCR with confirmation by direct sequencing. There was no statistical difference in total VEGF mRNA expression between the two cell types by qPCR (p = 0.9307, NF n = 5, FF n = 6), but FF expressed significantly more VEGF<sub>165</sub>b mRNA than NF (p = 0.05, NF n = 5, FF n = 6). Total VEGF protein expression was significantly increased in FF (mean expression NF = 180.5pg/ml vs FF 332.0pg/ml, p = 0.0012) by ELISA and confirmed by WB. Furthermore, increased VEGF<sub>165</sub>b protein expression was also observed in FF by WB. Recombinant VEGF<sub>165</sub>b had no effect on fibronectin or α-SMA expression in NF, but VEGF<sub>165</sub>a (10ng/µl) significantly increased expression of fibronectin (p &lt; 0.05). Interestingly, co-administration of VEGF<sub>165</sub>a with VEGF<sub>165</sub>b inhibited both α-SMA and fibronectin expression in these cells (Figure 1). <h3>Conclusion</h3> Differential expression of VEGF isoforms between NF and FF suggests a potential role in the development of IPF. Furthermore, results suggest that factors altering the balance of splice variants may influence the surrounding fibrotic milieu.
<i>Bartonella quintana</i>Endocarditis in a Child
Authors: Klara Pósfay Barbe, Edgar Jaeggi, Béatrice Ninet, Nadia Liassine, Cosima Donatiello, Alain Gervaix, Susanne Suter
Journal: New England Journal of Medicine (2000)

To the Editor: Blood-culture–negative endocarditis has been described in about 12 percent of children with endocarditis.1 Because of recent diagnostic advances, some of the pathogens responsible for these cases have been identified. A 13-year-old girl from Senegal was referred to our center for surgical treatment of rheumatic heart disease, which had been diagnosed when she was 8 years of age. She lived in a large city in a stable environment, did not abuse drugs, and had no close contact with cats. At admission, she was in good general condition and had no signs of intercurrent infection, fever, or lymphadenopathy. The . . .
PWE-202 Feasibility, safety and outcomes of an endoscopic submucosal dissection service in a UK setting: Abstract PWE-202 Table 1
Authors: S Tholoor, P Basford, R Bhattacharyya, P Bhandari
Journal: Gut (2012)

<h3>Introduction</h3> Endoscopic Submucosal Dissection (ESD) is an established treatment of early gastrointestinal neoplasia in Japan. It carries a greater risk of complications than conventional EMR. Use and experience of ESD in the west is limited with most centres having only performed small numbers of cases. We aim to evaluate the outcomes of ESD service in our centre. <h3>Methods</h3> Upper and Lower Gastrointestinal Endoscopic Resections database was evaluated to identify patients who underwent ESD and their demographics, histology, techniques, complications and outcomes were analysed. <h3>Results</h3> <b>Upper Gastrointestinal</b>: 25 ESD were performed in 23 patients between 2006 and 2011 (11 males). Mean age was 61.5 years. 14/25 involved en bloc ESD (where a circumferential incision is made to remove the whole lesion) and 11/25 involved a hybrid technique (where a circumferential incision is made followed by resection using a snare). 2/25 perforations occurred, both managed with endoscopic clips requiring no surgical intervention. 22/25 procedures were completed successfully. In 2/25, lesions were unable to be fully resected and 1/25 was abandoned due to perforation. Due to advanced histology, four proceeded to radical or palliative treatment. <b>Colonic</b>: 66 patients underwent ESD between 2006 and 2011 (21 males). Mean age was 68.5 years. 43/66 had enbloc ESD and 13/66 a hybrid procedure. 14/66 was in the right colon and 52/66 in the left colon. 24 lesions were LST-G, 8 were LST-NG and six were unspecified LST. Bleeding occurred in four cases (three delayed) all treated endosopically. Perforation occurred in four cases, only one required surgery and the rest ere managed with endoscopic clips. 4/66 had incomplete primary resection (one had perforation requiring surgery). 4/66 had recurrence requiring further sessions. 2/66 patients required curative surgery due to advanced histology. <h3>Conclusion</h3> (1) ESD service is feasible, safe and effective in a UK setting. (2) Our data demonstrates that ESD can be used to treat a wide variety of lesions through out the gut. (3) Perforation remains a significant risk but effective clipping technique can avoid the need for surgery. (4) ESD should be centralised to high volume expert centres to achieve good outcomes and establish training programmes. <h3>Competing interests</h3> None declared.
Abstract 2918: Estrogen receptor coactivator MED1 in mammary progenitor/stem cell determination and tamoxifen resistance of breast cancer
Authors: Xiaoting Zhang
Journal: Cancer Research (2012)

Abstract Mediator has recently emerged as the central player to directly transduce signals from transcription factors to the transcription machinery. MED1 (also named TRAP220, DRIP205 and MED220) subunit of the Mediator complex has been shown to directly interact and mediate the transcription of nuclear receptors, in a ligand-dependent fashion, through two classical LxxLL motifs. We have recently generated MED1 LxxLL motifs mutant knockin mice and interestingly, found these mutations do not affect the overall survival and the development of most tissues. However, we did observe severe defects in pubertal mammary gland development of MED1-mutant mice. Consistent with this phenotype, expression of a number of known ERα-regulated genes was downregulated in MED1-mutant mammary epithelial cells and these genes could no longer respond to estrogen stimulation. Interestingly, along with the restricted expression of MED1 in luminal but not basal mammary epithelial cells, we observed a very significant increase in the luminal stem/progenitor cell population in the mammary glands of MED1 mutant mice. We have further crossed this MED1 mutant knockin mice with a MMTV-PyVT mouse model that produce mainly luminal type of mammary tumors. Our date indicate that, although MED1 mutations did not affect the time and number of tumors formed, it significantly impacted the tumor progression and cancer stem cell formation in this model. To further study the role of MED1 in human breast cancer, we examined MED1 protein expression by using human breast cancer tissue microarrays. Consistent with previously reports that MED1 coamplifies with HER2, we found MED1 protein expression level is correlated most strongly with HER2 status. Further study supports HER2 as a major upstream regulator responsible for MED1 phosphorylation at sites known to be critical for MED1 activation. Interestingly, we found an increased recruitment of phosphorylated MED1 but not corepressors SMRT or NcoR to endogenous ER target genes’ promoter by tamoxifen in HER2-overexpressing cells. Importantly, knockdown of MED1 significantly sensitized the otherwise resistant HER2 overexpressing cells to the tamoxifen treatment. These results support MED1 as a key convergence point between ER and HER2 signaling pathways in mediating endocrine resistance. In summary, our studies revealed new roles of MED1 in mediating ER functions in both mammary stem/progenitor cell determination and tamoxifen resistance of breast cancer, and support potential use of MED1 as a tissue-specific therapeutic target for the treatment of human breast cancer. 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 2918. doi:1538-7445.AM2012-2918
P4 Impact of the national lung cancer campaign of 2012 on the diagnosis, management and survival rate of lung cancer in East Kent
Authors: SP Cho, A Creamer, N Goldsack
Journal: Thorax (2013)

<h3>Introduction</h3> Lung cancer is the second most common cancer in the United Kingdom<sub>1</sub>. A national campaign to increase public awareness of lung cancer was launched in May 2012 by the Department of Health. It aimed to increase early diagnosis of lung cancer, thus survival rate. This study assessed the effectiveness of the campaign in increasing early diagnosis, curative treatment rate and survival rate of lung cancer in East Kent Hospital Trust. <h3>Method</h3> This was a retrospective cohort study, which compared data from patients who were diagnosed with lung cancer over a 3-month period at 2 weeks following the launch of the campaign to those over the same period in 2011. The data was obtained from the data which were submitted to the National Lung Cancer Audit and the trust wide electronic patient record system. <h3>Results</h3> There was a 30% increase in the number of lung cancer diagnosed in the 2012 cohort with the proportion of female patients increased by 4% in 2012 (<i>Figure 1)</i>. There was a 9% increase in the number of cases which were curative by staging at the time of diagnosis following the campaign, though this was statistically insignificant (<i>Figure 1)</i>. This said increase however did not yield an increase in the curative treatment rate and survival rate (<i>Figure 1</i>). This was due to a lack of a corresponding improvement in performance status at the time of diagnosis. <h3>Conclusion</h3> The results showed that the campaign successfully increased the number of lung cancer diagnosed. There was also a non-statistically significant increase in the number of cases which were curative by staging at the time of diagnosis. This however did not yield any significant change in the curative treatment rate or survival rate due to smoking-induced patient co-morbidities. The cough campaign is successful but further work on smoking cessation programmes is necessary. <h3>Reference</h3> Office for National Statistics (2013) <i>Cancer Registration Statistics, England 2011</i>. London:Office for National Statistics, p. 1–3