tbuckley/cabot-search huggingface dataset:
P258 Change in Sleep Study and CPAP Provision Following the NIHCE CPAP TA
Authors: G Hill, JR Stradling
Journal: Thorax (2012)

<h3>Introduction</h3> We have assessed whether Primary Care Trusts’ (PCTs) commissioning of sleep services has improved following the NIHCE 2008 technology appraisal on CPAP. <h3>Methods</h3> We wrote to all PCTs in England, (under the Freedom of Information Act, 2000) for information on sleep studies commissioned, and CPAP prescriptions issued, for the years ending 31 March, 2008, 09, and 10. The PCTs were also asked who provided sleep studies or CPAP on their behalf (NHS hospital, GP, private, or other provider). Some PCTs did not reply, or claimed not to hold data, so we contacted appropriate NHS hospitals to obtain further information. Sleep study data was only obtained from approximately 75% of PCTs or associated hospitals. An alternative set of data, on the Department of Health (DH) website, was also used. Limited sales data from CPAP companies was also available for comparison. <h3>Results</h3> In almost all PCTs, sleep studies and CPAP provision were from NHS hospitals. The incomplete data from PCTs showed that sleep studies rose from about 30,000 in 2007/8 to 48,000 in 2009/10, a 3-year increase of about 60%. Data on sleep studies published by DH rose from over 61,000 in 2007/8 to over 86,000 in 2009/10, a 3-year increase of 41%. For CPAP prescriptions issued, only 66% of PCTs submitted data for 2007/8, rising to a 75% response by 2009/10. On the basis of this incomplete information and with some assumptions, annual CPAP prescriptions rose from less than 17,000 in 2007/8 to over 37,800 by 2009/10, a three year increase of 126%. There may be some under-reporting in the earlier years, and the industry sources suggested a 3-year lower increase of nearer 80%. In addition there are likely to be errors of coding. However, there was wide variation between PCTs suggesting patchy performance. <h3>Conclusions</h3> We believe that the results show a clear improvement in the number of sleep studies and CPAP prescriptions over this period. Thus, following the NIHCE TA there has been an improvement in patient access to the diagnosis and treatment of sleep apnoea, though we are concerned that the wide variation suggests there is a substantial element of post-code lottery.
P657 IN VIVO MUTAGENIC EFFECT OF RIBAVIRIN ON SUBTYPE 3F HEV QUASISPECIES ISOLATED FROM A PATIENT INFECTED FROM PORK MEAT
Authors: R. Casillas, F. Rodríguez-Frias, B. Mínguez, M. Riveiro, J. Gregori, D. Garcia-Cehic, D. Tabernero, M. Homs, M. Blasi, A. Caballero, L. Nieto, A. Hundesa, R. Girones, M. Buti, J. Quer
Journal: Journal of Hepatology (2014)
PWE-119 Decreased Frequency Of Peripheral And Intestinal Nkg2a-positive T Cells In Ulcerative Colitis Patients
Authors: W Kobayashi, T Katsurada, U Tomaru, N Sakamoto, M Kasahara
Journal: Gut (2014)

<h3>Introduction</h3> The intestinal tract is home to a numerous immune cellular components that continuously encounter abundant exogenous stimuli, where remain in a state of controlled inflammation normally. Inflammatory bowel disease (IBD) is characterised by chronic and refractory intestinal inflammation complising ulcerative colitis (UC) and Crohn’s disease (CD) in main. Inhibitory natural killer receptors (iNKRs) are expressed on NK cells, involved in NK-cell tolerance to self. There is increasing evidence that iNKRs like NKG2A expressed on T cells are importantly involved in the regulation of immune responses though no studies have addressed the potential role in the pathogenesis of IBD. We analysed the expression of NKG2A on T cells in dextran sulfate sodium (DSS)-induced colitis model mouse and IBD patients. <h3>Methods</h3> Male BALB/c mice were administrated 5% DSS in distilled water for 7 days ad libitum for induction of experimental colitis. For controls, age-matched BALB/c mice were given distilled water. NKG2A+ T cells in peripheral blood mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) were analysed by flow cytometry. For histological analysis of DSS-induced colitis mice, hematoxylin and eosin (HandE) staining and immunohistochemistry were performed. For blocking experiments using antibody (Ab), mice were intraperitoneally injected with 300 µg of anti-NKG2A monoclonal Ab or control IgG after oral administration of 5% DSS. PBMCs samples from 23 healthy controls, 20 UC and 16 CD patients were analysed by flow cytometry. Tissue sections from 7 controls, 6 UC and 5 CD patients were subjected to histological analysis. Data were evaluated using the Student’s <i>t</i>-test or the Mann-Whitney U-test. <h3>Results</h3> In the active phase of DSS-induced colitis mouse, the frequency of NKG2A+ T cells was significantly decreased in the peripheral blood and increased in the intestine, suggesting the mobilisation of this T cell subset to the sites of inflammation. Administration of anti-NKG2A Ab increased the number of inflammatory foci in DSS-induced colitis, suggesting the involvement of NKG2A+ T cells in this colitis model. In UC patients, the frequency of NKG2A+ T cells in PBMCs was significantly decreased, compared with CD patients and healthy controls, regardless of clinical conditions. Notably, in sharp contrast to the DSS-induced colitis mouse, the frequency of NKG2A+ cells in LPMCs was also decreased in UC patients. <h3>Conclusion</h3> These results suggest that inadequate local infiltration of NKG2A+ T cells may be involved in the pathogenesis of UC. Our study demonstrates the frequency of NKG2A+ T cells is decreased in both PBMCs and LPMCs in UC patients, implicating this T cell subset as a potential therapeutic target for UC. <h3>Disclosure of Interest</h3> None Declared.
MB-16 * BOOST VOLUME EFFECTS ON INCIDENTAL HIPPOCAMPAL DOSE IN PEDIATRIC MEDULLOBLASTOMA
Authors: P. Kundu, I. Gibbs
Journal: Neuro-Oncology (2015)

INTRODUCTION: Radiation treatment for medulloblastoma, which involves craniospinal radiation with posterior fossa boost, has been associated with neurocognitive sequelae, possibly due to impaired hippocampal neurogenesis. The posterior fossa has recently been shown to be radiation tolerant with respect to neurocognitive outcomes, though previous studies highlight effects of tumor bed vs. whole posterior fossa boost volumes. The incidental dose to the hippocampus may account for the boost volume effects, and despite traditional boost volume categories, the relative volume of posterior fossa treated may vary significantly. This study analyzes the association of hippocampal dose and boost volume as a continuous variable. METHODS: Bilateral hippocampi and posterior fossa were contoured on T1 axial images for 25 medulloblastoma patients. Minimum dose received by 100% of each hippocampus (D100) and percent volume of posterior fossa receiving 100% of boost dose (V100) were extracted from dose-volume histograms. Analysis of covariance was used to investigate the effect of V100 as a continuous variable while controlling for total craniospinal dose categorically (Low Dose 18-23.4Gy, High Dose 36Gy). RESULTS: Patient characteristics were as follows: age 3-21Y; 5 female, 20 male; 15 average risk (7 18Gy, 8 23.4Gy), 10 high risk (36Gy). Right and left total incidental hippocampal biologically effective doses were both greater for the high dose group by 13.9Gy (p < 0.0004) and 14.0Gy (p < 0.0001) respectively. Right and left D100 significantly varied with V100 by 0.18Gy (p < 0.0218) and 0.15Gy (p < .0322) per percent volume respectively. CONCLUSION: Incidental hippocampal doses are positively associated with boost volumes and may account for neurocognitive decline in medulloblastoma patients. An estimated 11-13% boost volume increase may further impair neurogenesis for a 2Gy threshold. Posterior fossa V100 can be a useful metric to more accurately describe boost volumes, and new hippocampal sparing techniques may allow for greater posterior fossa coverage.
PTU-265 Improving education quality and attendance of a regionally delivered gastroenterology education programme
Authors: A J Brooks, M Kurien, G James, P Basumani, D S Sanders, K Kapur
Journal: Gut (2012)

<h3>Introduction</h3> The 2010 competency based speciality-training curriculum for gastroenterology requires trainee9s to obtain multiple learning objectives. To ensure these are met training programme directors and postgraduate deaneries need to implement changes in delivery of local education programmes. The aim of this study was to determine factors in the delivery of a locally organised and delivered gastroenterology teaching programme that have the greatest impact on improving educational quality and attendance. <h3>Methods</h3> All consultants and gastroenterology trainees within a deanery received a questionnaire evaluating the 2009–2010 competency based training programme. Responses were compared with data obtained evaluating a previous training programme between 2003 and 2009 designed around the 2003 gastroenterology curriculum involving 6-weekly, half day events at local hospitals organised by individual consultants. Significant interventions made to the new programme included a predetermined programme guide, whole day events, single venue, keynote speakers, continual professional development points, a local training website and increased trainee involvement in programme development. <h3>Results</h3> The majority (15/19) of respondents regarding the competency based training programme attended ≥50% or more of events, compared to only 7/24 in the 2003 curriculum based programme (p=0.001). Of the 11 trainee9s in the region, a response rate of 73% was obtained with a significantly greater proportion (89%) stating that the competency based training programme met their training needs, compared to 42% surveyed on the 2003 curriculum based programme (p=0.001). Reasons for lack of attendance included insufficient time to cancel clinical commitments and poor educational value of the 2003 curriculum based programme. Consultant attendance at training meetings increased significantly following redesign of the programme, with 64% attending &gt;50% of meetings compared 12% prior to instituting a competency based training programme (p=0.004). The three most important factors to increase attendance were full day meetings, a consistent venue and keynote speakers from outside of the region. <h3>Conclusion</h3> This longitudinal study is the first study to evaluate attendance and educational value of a competency based regional gastroenterology teaching programme. Despite increasing demand to provide service provision and restrictions on study leave allowance, implementation of simple measures as identified in this study may increase consultant attendance and educational quality of regionally organised teaching programmes. <h3>Competing interests</h3> None declared.
AB0700 The reliability, validity and responsiveness of the thai version of systemic lupus erythematosus quality of life (SLEQOL-TH) instrument
Authors: N. Kasitanon, S. Wangkaew, S. Puntana, W. Sukitawut, K.P. Leong, W. Louthrenoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) is a validated disease-specific quality of life instrument. According to the domains of health related quality of life (HRQoL) affected by systemic lupus erythematosus (SLE) that may vary in a different socio-cultural context, we therefore selected to translate the SLEQOL into a Thai version. <h3>Objectives</h3> to determine the validity of the SLEQOL-TH in assessing the HRQoL of Thai patients with SLE. <h3>Methods</h3> Two independent translators translated the SLEQOL into Thai. The back translation of this version was performed by another two independent translators. The final version, SLEQOL-TH, was completed after resolving the discrepancies revealed by the back translation. One hundred and nine patients with SLE were enrolled to test the reliability, construct validity, floor and ceiling effects, and sensitivity to the changes of the SLEQOL-TH at six months. The differential item functioning (DIF) between the Thai and English versions was analyzed using the partial gamma. <h3>Results</h3> The internal consistency of the SLEQOL-TH was satisfactory with the overall Cronbach alpha of 0.86. The test-retest reliability of the SLEQOL-TH was acceptable with the intra-class correlation coefficient of 0.86. Low correlations between the SLEQOL-TH and SLEDAI were observed. The total score of the SLEQOL-TH was moderately responsive to the changes, with a standardized response mean of 0.50. Comparing the SLEQOL-TH from Thai SLE patients with the original SLEQOL version obtained from Singapore SLE patients, 11 out of 40 items showed a moderate to large DIF. <h3>Conclusions</h3> The SLEQOL-TH is psychometrically sound and shows construct validity. In comparison with the English version of SLEQOL, there are some items which showed DIF. The applicability of the SLEQOL-TH in real life clinical practice and clinical trials needs to be determined. <h3>Disclosure of Interest</h3> None Declared
Tracking the Peer-Review Process
Authors: Edward W. Campion, Gregory D. Curfman, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2000)

Each week more than 60 manuscripts arrive at our editorial offices for consideration for publication in the Journal. Our job is to determine which of them are most likely to influence clinical practice or biomedical research. It is a challenging task. Here is how we do it. When a manuscript arrives, a staff member checks to make sure that all materials required for submission are included (see “Information for Authors,” which is posted on our Web site and appears in most issues of the Journal ). If everything is present, the article is logged into our computerized manuscript-tracking system. The . . .
AB0010 Polymorphisms of Genes in the Development of Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis
Authors: N.A. Bashlakova, M. Shapturenko, S. Vakula, M. Sinyavskaya, T. Tyabut, O. Davydenko, L. Maslinskaya
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The risk of cardiovascular disease (CVD) due to early and pronounced atherosclerosis in patients with rheumatoid arthritis (RA) is 2-5-fold higher than in population. However, the early development of atherosclerosis is complicated by the combined influence of traditional risk factors and the chronic inflammatory process. According to previous data, the polymorphism of apolipoprotein E (ApoE), matrix metalloproteinase-3 (MMP3), interleukin- 6 (IL-6) -174 genes can be considered as one of the factors predisposing to the development of CVD in RA. <h3>Objectives</h3> The aim of our study was to determine polymorphic variants of ApoE, MMP3, IL-6 - 174 genes involved in the development of early atherosclerosis in patients with RA. <h3>Methods</h3> We examined 83 patients with RA, mean age 51,0 (38,0; 55,0) years old, disease duration 7,0 (3,0;15,0) years, disease activity 4,91 (4,52; 5,81) points. One hundred three healthy subjects at the mean age 42,0 (36,00; 51,00) years old were a control group. Different allelic variants of ApoE (ɛ3/ɛ3, ɛ3/ɛ4, ɛ2/ɛ3, ɛ2/ɛ4, ɛ4/ɛ4), MMP3 (5A/5A, 5A/6A, 6A/6A), and IL-6 - 174 (C/C, G/C, G/G) genes were revealed with the help of PCR-RFLP. The presence of atherosclerotic alterations of the common carotid artery (CCA) was revealed ultrasonographically according to standard procedures. <h3>Results</h3> Subclinical atherosclerosis, manifested by the atherosclerotic plaques of CCA, were 1,6 –fold more often in patients with RA than in controls, and were found in 31,33% and 19,42% cases, respectively. Homozygous alleles of ApoE ɛ3/ɛ3, heterozygous alleles of MMP3 5A/6A were detected more common in patients with RA and subclinical atherosclerosis. The frequency of these genes was 61,54% and 57,69%, respectively. Only homozygous alleles ApoE ɛ3/ɛ3 were more inherent in the control group (70,00%). Rare homozygous alleles ApoE ɛ4/ɛ4 were found only in patients with RA and was 7,69%. The combination of genotypes MMP3 5A/6A and Apo ɛ3/ɛ3 has been found in patients with RA and carotid atherosclerosis and was 53,33%. The combination of IL-6 - 174 C/C and Apo ɛ3/ɛ3 genotypes was detected commonly in the control group. <h3>Conclusions</h3> Thus, we have shown ApoE, MMP3, IL-6 - 174 gene polymorphisms in patients with RA and subclinical atherosclerosis. The presence of carotid atherosclerosis in patients with RA was associated with Apo ɛ3/ɛ3 and MMP3 5A/6A alleles and their combination. The atherosclerotic alterations in the control group were associated with the homozygous alleles Apo ɛ3/ɛ3 and its combination with IL-6 - 174 C/C genotype. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5740
ONE YEAR CLINICAL RESULTS OF THE ECHO GUIDED TRANSAPICAL MITRAL VALVE REPAIR WITH NEOCHORD IMPLANTATION
Authors: Andrea Colli, Eleonora Bizzotto, Laura Besola, Erica Manzan, Fabio Zucchetta, Roberto Bellu, Cristiano Sarais, Lorenzo Bagozzi, Matteo Montagner, Demetrio Pittarello, Dario Gregori, Gino Gerosa
Journal: Journal of the American College of Cardiology (2016)
Abstract 801: Uptake of exogenous neutrophil elastase by breast cancer cells: A novel link between innate immunity, inflammation and breast cancer immunity
Authors: Elizabeth A. Mittendorf, Gheath Alatrash, Na Qiao, Haile Xiao, Pariya Sukhumalchandra, Kathryn Quintanilla, Karen Clise-Dwyer, Jeffrey Molldrem
Journal: Cancer Research (2011)

Abstract Introduction: High level of neutrophil elastase (NE) in tumor tissue from breast cancer (BrCa) patients is associated with poor metastasis-free survival. Modest endogenous expression of NE in some BrCa cell lines has also been observed. However, because the major source of NE is from azurophil granules of activated neutrophils, we hypothesized that breast cancer cells may take up soluble NE released by abundant inflammatory cells in the tumor microenvironment. Methods: Endogenous NE expression was evaluated in MCF7, HER18, MDA-MB-231 (231) and MDA-MB-453 BrCa cell lines by western blot analysis and RT-PCR. Uptake of soluble NE was quantified by flow cytometry by intracellular staining of NE-pulsed BrCa and compared to non-specific uptake of OVA. Dose and time course experiments were performed. Confocal immunoflourescence microscopy was used to confirm uptake and demonstrate subcellular localization of NE. BrCa cells were also co-incubated with activated neutrophils to determine if they were able to take up cell-associated NE. Results: Western blot analysis of BrCa cell lysates showed no NE protein expression in all 4 cell lines. Furthermore, RT-PCR with NE-specific primers demonstrated no NE mRNA expression in the 4 BrCa cell lines. However, BrCa cells pulsed with 5 to 25 μg/ml of soluble NE took up NE in a time and dose dependent manner, consistent with a receptor-mediated mechanism. Maximal intracellular uptake of NE by 231 cells occurred by 24 hours when NE accumulated at comparable levels to that of HL60 leukemia cells that express high levels of NE (987 vs 1300 MFI, p=ns). Uptake was enzyme-independent because it was not affected by alpha-1-antitrypsin, a protease inhibitor. Confocal microscopy demonstrated that NE accumulates in membrane bound compartments by 20 minutes after uptake, whereas there was no significant uptake of OVA by BrCa cells. Similarly, after co-incubation of 231 cells with activated neutrophils, significant uptake of NE was detected (p&amp;lt;.001). Conclusions: These data show that BrCa cells do not express NE but the cells take up extracellular NE by a receptor-mediated enzyme-independent mechanism. This establishes a novel link between NE, a naturally secreted mediator of inflammation and cell growth, and BrCa. Because neutrophils are the major source of NE and chronic inflammation by tumor-infiltrating neutrophils is associated with positive tumor growth, this suggests NE could mediate growth control of BrCa. 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 801. doi:10.1158/1538-7445.AM2011-801
Abstract 4035: MicroRNA-221 levels correlate with aggressive and clinically recurrent prostate cancers
Authors: Aida Gordanpour, Aleksandra Stanimirovic, Robert Nam, Carlos Moreno, Brian Leyland-Jones, Linda Sugar, Arun Seth
Journal: Cancer Research (2010)

Abstract One of the most important challenges in prostate cancer research is to identify biomarkers that are predictive of cancer aggressiveness and future tumor recurrence following radical prostatectomy. Recent studies have shown that altered expression of microRNAs (miRs) is involved in the development of prostate cancer, and among the differentially expressed miRNAs, miR-221 may be critical in metastatic induction/regulation. While the precise role of this miRNA in facilitating malignant progression remains unclear, expression of miR-221 in prostate cancer may correlate with disease state/status and serve as a surrogate biomarker for tumor recurrence and/or aggressiveness. In the present study, we sought to investigate whether miR-221 is differentially regulated in patients with aggressive and non-aggressive tumors relative to control normal prostate cell line RWPE-1 and, more specifically, whether this miRNA can be used as biomarker for disease recurrence. To address this question, we initially chose to assess the relative expression of miR-221 in a series of aggressive (n=69) and non-aggressive (n=45) primary carcinoma tissues derived from clinically resected prostates by quantitative real-time PCR. Aggressive tumors were categorized based on clinicopathological parameters such as Gleason score of 8 or higher, high PSA levels, presence of metastasis, invasion to the seminal vesicles, and recurrence after radical prostatectomy. Relative expression of mature miR-221 in tumors was quantified in comparison to control prostate epithelial cell line, RWPE-1, which was set to be 1x. Levels of miR-221 expression were found to be variable. Among all aggressive and non-aggressive cancer patients, expression of miR-221 transcript levels was differentially expressed relative to control sample. However, when we divided this group of patients on the basis of miR-221 expression levels, 72% of the patients with aggressive tumors had miR-221 less than 5-fold the RWPE-1 levels and only 28% of the patients had miR-221 expression equal to or more than 5-fold RWPE-1 levels. On the other hand, 53% of the patients with non-aggressive tumors had miR-221 less than 5-fold the RWPE-1 levels compared to 47% of the patients with miR-221 equal to or more than 5-fold RWPE-1 levels. Our results show that miR-221 is lower in majority of aggressive prostate cancer and differential expression may have utility as a biomarker for disease recurrence. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4035.