tbuckley/cabot-search huggingface dataset:
PWE-144 Frax Score in the Assessment of Bone Mineral Density Changes in Tenofovir Treated Chronic Hepatitis B Patients
Authors: U S Gill, A Zissimopoulos, S Al-shamma, K Burke, M McPhail, D Barr, V Ross, Y Kallis, P Kooner, R Marley, G R Foster, P T Kennedy
Journal: Gut (2013)

<h3>Introduction</h3> Tenofovir Disoproxil Fumarate (TDF) is an established oral antiviral (OAV) in the treatment of Chronic Hepatitis B (CHB). Bone Mineral Density (BMD) loss has been described in TDF treated HIV patients, but limited data exist in CHB. We have used DEXA scanning to determine BMD changes in TDF treated patients and have reported the possibility of BMD loss. DEXA scanning, however, is costly and requires longitudinal follow-up. We assessed the value of the FRAX® score and of bone biochemistry to evaluate their utility in TDF treated patients. <h3>Methods</h3> The FRAX score is a WHO web-based tool, used to calculate 10-year fracture risk and the need for lifestyle modification, DEXA scanning or preventative treatment. CHB patients treated with TDF for a minimum of 12-months and a control group not exposed to TDF were studied. 122 TDF exposed patients (male = 89), median age 45 (range = 26–64) and 48 patients (male = 31), median age 36 (range = 20–62) not exposed to TDF were DEXA scanned and included in the study. We calculated FRAX scores and recorded bone biochemical markers, comprising serum Alkaline Phosphatase (sALP), Calcium (sCa) and Phosphate (sPO). <h3>Results</h3> TDF treated patients had lower hip T-scores compared to controls (p = 0.02). On univariate analysis factors associated with a hip T-score &lt; 1 included older age, lower BMI, smoking and TDF exposure (p = &lt; 0.05). On multivariate analysis the same factors were associated with a hip T-score &lt; 1, but TDF lost significance. For the development of a major osteoporotic fracture the pre-DEXA FRAX score was 4.77% compared to 4.33% (post-DEXA FRAX) (p = 0.9) and for a hip fracture this was 0.54% (pre-DEXA FRAX) and 0.77% (post-DEXA FRAX) (p = 0.5). The pre-DEXA FRAX score was a significant predictor of the post-DEXA FRAX treatment recommendation (p = &lt; 0.001). TDF therapy was associated with increased sALP after 12-months, but this was not significant. No change was observed in pre-treatment sCa and sPO levels compared to those after 12-months exposure (p = 0.5 &amp; 0.09 respectively). <h3>Conclusion</h3> Our results demonstrate the FRAX score alone can accurately predict the risk of developing an osteoporotic fracture in TDF treated CHB patients. This potentially obviates the need for DEXA scanning and the associated costs. The relationship between sALP and TDF is noteworthy, but bone parameters are of limited use in predicting BMD changes. Although BMD loss in TDF treated CHB patients remains unproven, we demonstrate the use of the FRAX score may determine those at risk of osteoporotic fractures in CHB. <h3>Disclosure of Interest</h3> None Declared.
Targeting Factor 12 (F12) with a Novel RNAi Delivery Platform As a Prophylactic Treatment for Hereditary Angioedema (HAE)
Authors: Stacey Melquist, Darren Wakefield, Holly Hamilton, Qili Chu, Aaron Almeida, Lauren Almeida, Megan Walters, Jessica Montez, Julia Hegge, Jason Klein, Christine Hazlett, Tracie Milarch, Stephanie Bertin, Aaron Andersen, Edie Doss, Rachael Schmidt, Linda Goth, Sheryl Ferger, David Rozema, James Hamilton, David Lewis, Steven Kanner
Journal: Journal of Allergy and Clinical Immunology (2016)
Creating clinical trial designs that incorporate clinical outcome assessments
Authors: Mark R. Gilbert, Lawrence Rubinstein, Glenn Lesser
Journal: Neuro-Oncology (2016)

Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints.
Case 28-2000
Authors: Elizabeth M. Breen, Joeseph Misdraji
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 34-year-old man was admitted to the hospital because of ulcerative colitis with perirectal pain, swelling, and discharge.The ulcerative colitis had initially been diagnosed 10 years earlier, in Puerto Rico. Thereafter, the patient often failed to take his medications as directed. Eight years before the current admission, after he had been well for an uncertain interval, he had bloody diarrhea and was admitted to this hospital for one week. Treatment with prednisone and sulfasalazine resulted in improvement in his symptoms. Two years before the current admission, he spent four weeks in this hospital because of severe . . .
Surveillance of human immunodeficiency virus suggests that younger men who have sex with men are at higher risk of infection, European Union, 2003 to 2012
Authors: J Janiec, K Haar, G Spiteri, G Likatavicius, M Van de Laar, A J Amato-Gauci
Journal: Eurosurveillance (2013)

In 2012, newly reported human immunodeficiency virus diagnoses in the European Union /European Economic Area remained stable at around 30,000 cases. Since 2003, cases in men who have sex with men (MSM) aged 20 to 29 years-old doubled, while the proportion of late presenters in this group remained stable. Persistent declines occurred among older MSM age groups, particularly that between 30 and 39 years-old. Interventions targeting younger MSM are needed to prevent a resurgence of the epidemic in Europe.
THU0592-HPR Precipitating, Predisposing and Maintenance Factors Associated with Sexual Disorders in Patients with Rheumatoid Arthritis
Authors: A. Palomino, V. Giraldo, G. Saavedra-Martinez, L. Villarreal, D. Gomez, J. Bello-Gualtero, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sexuality is an important dimension of personality and human body, therefore any involvement in this area should be considered as important. Sexual disturbances in rheumatoid arthritis (RA) patients are poorly described in literature. On the other hand, there are predisposing, precipitating and maintenance factors for sexual disturbances in patients with RA. <h3>Objectives</h3> The aim of this study using CIE-10 was to describe different type of factors that may influence the prevalence and worsening of sexual disturbances in patients with RA. <h3>Methods</h3> A descriptive cross-sectional study was performed in a specialized clinic dedicated to Ra patients care. Patients seen by the area of psychology, information was collected through semi-structured interviews and non-probability sampling. Descriptive epidemiology was done, using averages and percentages for categorical and qualitative variables; and Pearson9s statistics for bi-variated analysis. <h3>Results</h3> The total sample of patients was 349, 279 (79.9%) were women and 70 (20.0%) were men, average DAS28-2.46. Average age is 58.1 years. 146 (52.3%) of women reported no sexual activity, while 133 (47.6%) report sexual activity. 18 (25.7%) of men reported no sexual activity, while 54 (70.2%) report sexual activity. <i>Precipitating factors</i> in women: 26 (9.3%) infidelity, 17 (6.0%) anxiety about sexual performance, 36 (12.9%) loss of attraction, 35 (12.5%) alteration of self-image. while in men: 19 (27.1%) insecurity in sexual male role, 12 (30.7%) loss of attraction, 4 (5.7%) infidelity, 4 (5.7%) alteration of self-image. <i>Predisposing factors</i> in women: 73 (26.1%) biological causes, 36 (12.9%) infidelity, 19 (6.8%) poor or inadequate information, 13 (4.6%) insecurity about sexual performance, while in men 13 (18.5%) biological causes, 5 (7.1%) infidelity, 5 (7.1%) poor or inadequate information, 11 (15.7%) insecurity about sexual performance. <i>Maintenance factors</i> in women: 61 (21.8%) biological causes, 42 (15.0%) general alteration of couple relationship, 19 (6.8%) depression and anxiety, 18 (6.4%) infidelity, 2 (0.7%) partner9s sexual dysfunction, while in men: 16 (22.8%) general alteration of couple relationship, 14 (20%) biological causes, 12 (17.1%) anxiety about sexual performance. It was not established a correlation between precipitating, predisposing or maintenance factors and RA disease activity. <h3>Conclusions</h3> According to these findings sexual disorders are present in a half of patients with RA both men and women. There are many factors that may influence the prevalence and worsening of sexual disturbances. However sexual disturbances do not affect disease activity, but quality of life probably is very affected. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5404
P206 HEPATITIS C VIRUS COMPARTMENTALISATION: UNRAVELLING GENETIC COMPLEXITY WITHIN THE LIVER
Authors: D.L. Hedegaard, D.C. Tully, G.M. Reynolds, I. Rowe, S.G. Hübscher, K. Power, A.W. Tarr, J. Ball, T. Allen, J.A. McKeating, P. Balfe
Journal: Journal of Hepatology (2014)
Magnitude Of Changes In Patient Symptom and Medication Scores In Grass Allergy Immunotherapy Trials: Dependency On Levels Of Pollen Exposure
Authors: Hendrik Nolte, Stephen R. Durham, Harold S. Nelson, David I. Bernstein, Peter S. Creticos, Ziliang Li, Jens Andersen
Journal: Journal of Allergy and Clinical Immunology (2014)

While symptomatic therapy trials for seasonal allergic rhinitis with or without conjunctivitis (AR/C) begin while subjects have symptoms, pollen immunotherapy trials generally begin treatment preseasonally and assess efficacy during seasonal exposure. We investigated the impact of pollen exposure variability on magnitude of recorded immunotherapy treatment effect. Data from 7 North American and European randomized placebo-controlled trials of standardized Timothy grass sublingual immunotherapy tablet (SLIT-T), MK-7243 (Merck/ALK; 2800 BAU of Phleum pratense) were included (omitting 1 trial, as lack of pollen-count/symptom relationship suggested etiology other than grass pollen exposure). Predefined preseasonal treatment ranged from 8-16 weeks. Boundaries of 3 consecutive days with pollen count ≥10 grains/m3 defined grass pollen season (GPS). We assessed correlation of between-treatment difference in total combined score (TCS; combined symptom/medication scores) per trial or trial year to first-20-days-of-GPS cumulative grass pollen count and entire-GPS average pollen count. Data included 1798/1765 MK-7243/placebo subjects. TCS for both groups increased with grass pollen counts. Treatment effect in TCS in each trial (or trial year) was correlated to cumulative grass pollen count during first 20 days of GPS (R2=0.803). Correlation was also seen between TCS and average pollen count over entire GPS (R2=0.464). Post hoc analysis of 7 MK-7243 trials demonstrates that treatment effect magnitude was highly correlated to pollen exposure. Difference in pollen-exposure levels should be considered when comparing results among pollen immunotherapy trials and should also be considered with other methodological differences when comparing to symptomatic medication trials. The early-season–exposure/efficacy correlation does not confirm prevailing theories regarding priming.
Recombinant Human Hyaluronidase (rHuPH20) Facilitates Subcutaneous Infusion of Immunoglobulin, Increases Local Fluid Dispersion, and Reduces Induration in a Porcine Model
Authors: D.W. Kang, L.M. Jadin, T.A. Nekoroski, M.L. Zepeda
Journal: Journal of Allergy and Clinical Immunology (2012)
IMPACT OF CHRONIC KIDNEY DISEASE ON OUTCOMES IN PATIENTS UNDERGOING TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT WITH BIVALIRUDIN OR UNFRACTIONATED HEPARIN: FROM THE EFFECT OF BIVALIRUDIN ON AORTIC VALVE INTERVENTION OUTCOMES (BRAVO) TRIAL
Authors: Christian Hengstenberg, Gennaro Giustino, Thierry Lefevre, Christian Kupatt, Didier Tchetche, Ulrich Schaefer, Antonio Colombo, Peter Boekstegers, Roxana Mehran, Axel Linke, Oliver Husser, Eberhard Grube, Efthymios Deliargyris, Debra Bernstein, Prodromos Anthopoulos, George Dangas
Journal: Journal of the American College of Cardiology (2016)
Abstract 5011: Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia
Authors: Agnes Lendvai, Frank Johannes, Christina Grimm, Jasper JH Eijsink, Rene Wardenaar, Haukeline H. Volders, Harry G. Klip, Harry Hollema, Ritsert C. Jansen, Ed Schuuring, Ate GJ van der Zee, G. Bea A. Wisman
Journal: Cancer Research (2012)

Abstract Introduction: Cervical cancer is the second most common cancer in women worldwide and development of cervical cancer goes through different well-defined premalignant stages. Epigenetic modifications, such as aberrant DNA promoter methylation is frequently observed in cervical cancer. Identification of hypermethylated regions that allow discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia or worse (CIN2+) by DNA methylation state may improve current population-based screening programs for cervical cancer. In this study, the DNA methylome of CIN3 lesions were characterized using genome-wide methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methods and results: Methyl-DNA ImmunoPrecipitation (MeDIP) assay combined with DNA microarray hybridization was used to compare DNA methylation patterns of epithelial cells derived from CIN3 lesions with normal cervical epithelium. In total, 80 hypermethylated differentially methylated regions (DMRs) were identified that significantly distinguished CIN3 lesions from normal cervice. Selected DMRs (n=9) were evaluated by methylation-specific PCR (MSP) on additional tissue specimens including normal cervix, CIN2/3 and cervical cancer samples and showed hypermethylation in up to 94.7% in CIN2/3 and 100% in cervical cancers. Quantitative MSP (QMSP) for two candidate biomarkers was applied to explore the test performance in a large series of cervical scrapings. Frequency and relative level of DNA methylation were significantly different between normal and cancer samples (p&amp;lt;0.05). In cervical scrapings from patients referred with an abnormal Pap smear, frequency and relative level of DNA methylation were also related with increasing severity of the underlying CIN lesion (p&amp;lt;0.01) In addition, ROC analysis showed that the methylation level was discriminative between low-grade CIN lesions and CIN2+ (p&amp;lt;0.05). Conclusion: Our study demonstrates specific DNA methylation patterns in high-grade CIN lesions through the newly identified discriminative hypermethylated DMRs and represents candidate biomarkers for early detection of high-grade CIN. This study was supported by the Dutch Cancer Society (NKB) (project-number RUG 2004-3161) and by OncoMethylome Sciences S.A., Liège, Belgium. CG was funded by the German Ministry of Education and Research (BMBF) within the NGFN-PLUS project PKT-01GS08111. 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 5011. doi:1538-7445.AM2012-5011
A8.16 The cholinergic anti-inflammatory pathway does not influence sialadenitis or diabetes in the non-obese diabetic mouse model of SjÖgren’s syndrome
Authors: FA Koopman, N Roescher, JL Vosters, N Broekstra, PP Tak, MJ Vervoordeldonk
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> Activation of the cholinergic anti-inflammatory (CAP) reduces inflammation in different animal models, while abrogation of the pathway has been shown to increase inflammation. Sjögren's syndrome (SjS) is a chronic autoimmune disease of the salivary glands, which can currently only be treated symptomatically. The pathogenesis of SjS can be studied in the non-obese diabetic (NOD) mouse model; these mice spontaneously develop immune cell infiltration in the salivary glands (SG) in addition to type I diabetes due to pancreatic immune cell infiltration (insulitis). <h3>Methods</h3> The CAP was activated in the NOD mouse model for 4 weeks (10–14 weeks of age) with two agonists of the α7 subunit of nicotinic acetylcholine receptor (α7nAChR), AR-R17779 and nicotine. In the next study the pathway was abrogated by unilateral cervical vagotomy performed at 12 weeks of age; animals were monitored until 20 weeks of age. Alpha-7nAChR expression and focus score (FS) were evaluated in the SG in addition to the insulitis score in the pancreas. Salivary function was evaluated by measuring stimulated salivary flow. Cytokines levels were measured in serum and SG. <h3>Results</h3> Alpha-7nAChR was expressed on myoepithelial cells in the SG surrounding the ducts. There were no changes in cytokine production in the serum, but in the SG monocyte chemotactic protein (MCP)-1 was reduced after AR-R17779 treatment (p = 0.023) and tumour necrosis factor (TNF) production was increased in the vagotomy group (p = 0.042). This however did not change the FS or stimulated salivary flow in the two CAP intervention studies. The NOD mice developed diabetes more rapidly in the vagotomy group, but at completion of the study the same number of animals had developed diabetes and there were no significant differences in insulitis scores. <h3>Conclusion</h3> The cholinergic anti-inflammatory pathway does not influence the inflammatory processes in the NOD mouse model of SjS and type I diabetes.
Tips for Leaders Part IV
Authors: Jay Harolds
Journal: Clinical Nuclear Medicine (2011)

It is important that a leader assesses his strengths and weaknesses and evaluates where and how he does well. It is also important that a leader is aware of his emotions and is able to use that to better manage himself. Finally, a leader should be aware of the emotions of others, feel and show empathy, and use that understanding to exhibit better leadership within groups of people. This is referred to as emotional intelligence. This article examines these principles.
Deliberative democracy and epistemic humility
Authors: Kevin Chien-Chang Wu
Journal: Behavioral and Brain Sciences (2011)

Abstract Deliberative democracy is one of the best designs that could facilitate good public policy decision making and bring about epistemic good based on Mercier and Sperber's (M&amp;S's) theory of reasoning. However, three conditions are necessary: (1) an ethic of individual epistemic humility, (2) a pragmatic deflationist definition of truth, and (3) a microscopic framing power analysis during group reasoning.
FRI0438 Toxic Hepatitis in Patients with Systemic Lupus Erythematosus:
Authors: N. Park, M. Her, D. Kim, S.-K. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although subclinical liver disease is common in SLE, strikingly high levels of liver enzymes are rare. Liver enzyme abnormalities in lupus are multifactorial and can be drug induced or caused by disease activity. <h3>Objectives</h3> Our aim was to determine the cause of high levels of liver enzymes in lupus patients, particularly in patients diagnosed with toxic hepatitis. <h3>Methods</h3> We performed a retrospective chart review of SLE patients treated at the Inje University Hospital between 2001 and 2013. We defined liver enzyme abnormality as a ≥2 fold increase in 2 or more of the 4 components: bilirubin, AST, ALT and LDH or ALP. Toxic hepatitis was diagnosed by a score 5 in the Roussel Uclaf Causality Assessment Method (RUCAM) and classified according to their pattern of liver enzyme: cholestatic, hepatocellular and mixed. <h3>Results</h3> Clinical and laboratory findings of liver disease was reviewed in 301 SLE patients who met ≥4 ACR criteria. Of 301 SLE patients, 74 (24.6%) met strict criteria for the liver enzyme abnormality and had the following diagnoses: toxic hepatitis (<i>n</i>=20), viral hepatitis (<i>n</i>=3), autoimmune hepatitis (<i>n</i>=5), liver enzyme elevation associated with infection (<i>n</i>=4) and an indeterminate clinical diagnosis, presumably associated with lupus activity (n=42). In total, 20 patients (6.6%) had presumed toxic hepatitis associated with either herbal medicines (<i>n</i>=8), anti-tuberculosis (Tb) drug (<i>n</i>=4), antibiotics (<i>n</i>=5), NSAIDS (<i>n</i>=1), or anticonvulsant drug (<i>n</i>=2). There were striking abnormalities in patients with toxic hepatitis (mean peak values: AST 610±551 U/L, ALT 369±352 U/L, ALP 598±387 U/L, LDH1,128±761 U/L). 5 had a cholestatic pattern, 9 had a hepatocellular pattern, 3 had a mixed pattern and 3 were undeterminated. Among the 20 patients with toxic hepatitis, 17 were found to have active lupus (SLEDAI≥4). After cessation of the suspected causative medication and subsequent steroids treatment, liver enzymes were improved. <h3>Conclusions</h3> In our study, herbal medicines was the most common cause of toxic hepatitis in Korean lupus patients. Antibiotics and anti-Tb drugs also could lead to toxic hepatitis in lupus patients. Since most herbal medicines contain a mixture of various products, we could not ascertain what specific ingredient lead to increase in liver enzyme levels. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2193
Abstract 3032: Role of ruffles and filopodia in adhesion gradient sensing
Authors: Carol A. Heckman, Surya P. Amarachintha
Journal: Cancer Research (2012)

Abstract Filopodia play a sensory role in directing motility during embryonic development and axon pathfinding. They also show a low prevalence in cancer cells. Here, we determine whether cells from a rat tracheal epithelial line in vitro use filopodia to sense adhesive gradients. Cells exhibit haptotaxis (movement toward a more adhesive surface) when placed on a metal-glass gradient. Tantalum (Ta) and platinum (Pt) gradients were created on glass slides and high (H), middle (M), and low (L) positions defined along the gradient. Cell counts in randomly selected fields confirmed that the cells recognized the gradient. To determine whether the prevalence of protrusions differed at the H, M, and L locations, we measured the values of latent factors 4 (filopodia), 5, and 7. Factor 4 values were high at H and significantly lower at M and L (p&amp;lt;0.05). Cells’ ability to form large protrusions, represented by factors 5 (lamellar distribution) and 7 (nascent neurites), was uniform across the Ta gradient. To detect the cells’ ability to interpret directional cues, we distinguished the cell's top (T) side, i.e. the side oriented toward H location, from the bottom (B) side. Factor 4 values at H-T exceed those at M-B and L-T (Table 1). Trend analysis confirmed a decrease in factor 4 over the gradient with significance of p&amp;lt;0.001 (Ta) and p&amp;lt;0.023 (Pt). On Pt only, factor 5 increased (p=0.000) as the metal content of the substrate declined. Ruffling activity is generally inverse to filopodia but positively related to factor 5 (Heckman et al., doi:10.1016/j.cellsig.2011.08.023). On haptotactic substrates, the former relationship was observed by correlation analysis but was restricted to the L location on the gradient. This suggests that poor adhesion may help to convert mechanisms of filopodia formation to ruffle formation. The above results suggest that sensing depends on net filopodia stabilization at the more adhesive H location. We conclude that filopodia respond to the gradient and that regulation of the sensing and signaling mechanisms can now be evaluated. 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 3032. doi:1538-7445.AM2012-3032