tbuckley/cabot-search huggingface dataset:
SAT0076 Beneficial Effects of Atorvastatin Treatment in Smoking Patients with Rheumatoid Arthritis and Hypercholesterolaemia
Authors: R. Rupinski, Z. Lewandowski, E. Walewska, P. Gluszko
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cigarette smoking significantly increases the risk of cardiovascular diseases (CVD) and predisposes to rheumatoid arthritis (RA) development. <h3>Objectives</h3> Investigate the impact of smoking on serum pro-atherogenic chemokines (CX3CL1 – fractalkine, CCL2 – monocyte chemotactic protein-1, CCL5 – RANTES) and endothelial derivatives (ICAM-1 – intercellular adhesion molecule-1, VEGF – vascular endothelial growth factor) levels in RA patients with hypercholesterolaemia treated with atorvastatin (ATS). <h3>Methods</h3> The study included 36, mainly female (91.7%), RA patients (age – 60.1±7.6 years, anti-CCP positive – 75.0%, total cholesterol – 259±26 mg/dl). All patients received a 16 week ATS treatment, 10 mg daily, according to ATP III guidelines. The Systematic Coronary Risk Evaluation (SCORE) was assessed and serum CX3CL1, CCL2, CCL5, ICAM-1 and VEGF levels were measured using ELISA (R&amp;D Systems) before and after the ATS treatment. Cigarette smoking was determined as being an ever-smoker (63.9%) or a never smoker (non-smoker). A statistical analysis was performed using Mann-Whitney and Wilcoxon tests (Statistica v. 10). <h3>Results</h3> No statistically significant differences were found between smokers and non-smokers at the beginning of the observations, except for SCORE (7.13 vs. 3.92, p=0.031) and the disease duration (6.4 vs. 15.9 years, p=0.002). SCORE values, total cholesterol and ICAM-1 serum concentrations decreased during the study in both groups; in smokers: 7.13 vs. 4.44 (p=0.001), 258 vs. 197 mg/dl (p&lt;0.001), 130 vs. 113 pg/ml (p=0.005), respectively, and in non-smokers: 3.29 vs. 3.00 (p=0.069), 261 vs. 213 mg/dl (p=0.012), 132 vs. 108 pg/ml (p=0.018), respectively. After the ATS treatment, CX3CL1 and CCL5 levels dropped significantly only in ever-smoking patients: 1779 vs. 1446 pg/ml (p=0.031) and 1348 vs. 1020 pg/ml (p=0.001), respectively. The ATS treatment had no effect on serum CCL2 and VEGF throughout the observation period. <h3>Conclusions</h3> By lowering serum cholesterol, the atorvastatin treatment reduces the risk of CVD (SCORE) in smoking and non-smoking RA patients. Ever-smoking RA patients may benefit additionally from a routine statin use, as atorvastatin simultaneously normalizes serum levels of some pro-atherogenic chemokines and endothelial derivatives. <h3>Disclosure of Interest</h3> None Declared
OC-060 Does IGA Tissue Transglutaminase Antibody Levels Correlate with Histological findings of Coeliac Disease (CD)?: Abstract OC-060 Table 1
Authors: M Kurien, A J Johnston, A Avgerinos, D S Sanders
Journal: Gut (2013)

<h3>Introduction</h3> The current gold standard diagnostic test for CD is oesophogastroduodenoscopy (OGD) and duodenal biopsies, aiming to demonstrate the presence of villous atrophy. Given the low sensitivity of endoscopic markers and the patchy distribution of CD within the small bowel, a duodenal bulb biopsy is currently recommended. However, recent studies have raised questions about the need for biopsies in CD, particularly within the paedatric literature, with high anti-tissue transglutaminase antibody (TTG) levels believed to be sufficient. The hypothesis being that high TTG levels correlate closely with definitive CD histology (Marsh 3a-c) giving a high positive predicative value (PPV). This study evaluates TTG levels and histology (inclusive of a bulb biopsy) in adult patients suspected of having CD, with the aim of defining a cut off value for TTG when biopsy may be unnecessary. <h3>Methods</h3> Recruitment occurred between Nov 2008 and July 2012, 523 adult patients (&gt;16 years). All patients had a minimum of 5 duodenal biopsies taken whilst on a gluten containing diet. Furthermore, all patients were tested for IgA TTG, Endomysial Antibody (EMA) and total IgA immunoglobulin at the time of their endoscopy. This study retrospectively reviews the correlation between TTG levels (Aesku Diagnostics, Wendelsheim, Germany) and histological outcomes in these patients, with CD being defined as villous atrophy (Marsh 3a-3c) and a clinical and serological response to a gluten free diet. <h3>Results</h3> Of the 523 adult patients (median age 51 years, range 16–91) recruited, 212 (41%) had positive TTG serology (&gt;15 U/ml). EMA positivity was identified in 31% of the cohort (163/523) with CD diagnosed in 32% (169/523). The sensitivity, specificity, PPV and NPV for TTG was 93.3%, 83.3%, 71.7%, 96.4% respectively and for EMA 93.8%, 98.9%, 97.4% 97.2%. Table 1 shows the PPV for diagnosing CD at differing TTG levels. No cut off level was associated with a PPV of 100%, with the highest PPV value of 97.1% seen when the TTG level was set at 300U/ml (20 × upper normal limit). <h3>Conclusion</h3> Contrary to ESPHGAN guidelines our findings would not support a biopsy avoidance strategy in those with high TTG levels, with patient potentially being wrongly diagnosed. We advocate that duodenal biopsies including a bulb biopsy remain the gold standard diagnostic test in those with suspected CD. <h3>Disclosure of Interest</h3> None Declared
Abstract 5114: Mass spectrometric immunoassays for quantitative determination of protein biomarker variants
Authors: Dobrin Nedelkov, Olgica Trenchevska, Aleksandra Pupinoska, David Phillips, Elena Kamcheva, Slobodanka Romevska, Urban A. Kiernan
Journal: Cancer Research (2011)

Abstract Post-translational modifications and genetic variations give rise to protein variants that significantly increase human proteome complexity. Modified proteins also play an important role in biological processes. Mass spectrometry, coupled to immunoaffinity separations, provides an efficient mean for simultaneous detection and quantification of protein variants. In Mass Spectrometric Immunoassays, affinity interactions are utilized to selectively retrieve specific proteins from complex biological fluids, and are followed by mass spectrometric analysis of the targeted proteins. These assays are similar to traditional enzyme immunoassays in that they use antibodies as reagents for affinity retrieval of specific proteins, but instead of enzymatic reaction for indirect protein detection, mass spectrometric analysis is used for direct identification of the proteins and their modifications. Described here are mass spectrometric immunoassays for targeted quantitative proteomics analysis of specific protein modifications. Assays for several protein biomarkers exhibiting posttranslational modifications were developed, including beta-2-microglobulin, cystatin C, retinol binding protein, and transthyretin. The following assay performance characteristics were examined (and determined): LOQs (sufficient for quantification of normal/healthy levels of the proteins from human serum or plasma); intra- and inter-assay precision (CVs of &amp;lt;10%), linearity and spiking recovery (90-110% range); specificity (&amp;lt;5% cross reactivity with other proteins), and correlation with ELISA-generated results (acceptable Passing &amp; Bablok fits and Cusum linearity p-values of &amp;gt;0.1). The new assays were then utilized to determine the individual concentration of the specific protein variants across larger cohorts of samples (n=500), demonstrating the ability to fully quantify individual forms of post-translationally modified proteins. The mass spectrometric immunoassays are ideally suited for detection and quantification of novel protein variants, not known a priori. These MS-based assays can find use in quantifying specific protein modifications, either as a part of a specific protein biomarker discovery/rediscovery effort to delineate the role of these variants in the onset of the disease, progression, and response to therapy, or in a more systematic study to delineate and understand human protein diversity. 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 5114. doi:10.1158/1538-7445.AM2011-5114
Abstract 5252: CC-223, a selective and potent mTOR kinase inhibitor, synergizes with 5-Aza and Erlotinib in eight NSCLC lines in vitro.
Authors: Tam Tran, Kristen Hege, Deborah Mortensen, Heather Raymon, Shuichan Xu
Journal: Cancer Research (2013)

Abstract CC-223 is a potent and selective mTOR kinase inhibitor currently undergoing Phase 1 clinical evaluation. We evaluated combinatorial effect of CC-223 with 5-Aza and erlotinib at three different ratios of the two combining agents in three different orders of addition in eight NSCLC lines. Combinational indices (CIs) were calculated based upon published method (Chou and Talalay, 1984). CC-223 synergized with azacitidine (CI&amp;lt;0.7) in most of the lines at all ratios of combination when azacitidine was added first to the cells (SeqM2). Synergism (CI&amp;lt;0.7) and moderate synergism (0.7&amp;lt;CI&amp;lt;0.85) was also observed in some cell lines when CC-223 was added first (SeqM1) or simultaneously (Sim) with azacitidine; however, SeqM2 seems to generate better synergistic effect across all lines than SeqM1 and Sim. In SeqM2 addition, no significant difference was observed among different ratios of the two agents. CC-223 synergized with erlotinib (CI&amp;lt;0.7) in most of the cell lines at a ratio of 1:30 (CC-223:erlotinib). Synergism and moderate synergism (0.7&amp;lt;CI&amp;lt;0.85) were also observed at other ratios. Order of addition had no impact on the combinatorial effect for CC-223+erlotinib. Overall, the data demonstrated that CC-223 synergizes with azacitidine and erlotinib in multiple NSCLC cell lines in vitro. Order of addition has an impact for CC-223 combination with 5-Aza but not with Erlotinib. On the other hand, ratio of the two combinatorial agents is important for CC-223+erlotinib combination in vitro. Citation Format: Tam Tran, Kristen Hege, Deborah Mortensen, Heather Raymon, Shuichan Xu. CC-223, a selective and potent mTOR kinase inhibitor, synergizes with 5-Aza and Erlotinib in eight NSCLC lines in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5252. doi:10.1158/1538-7445.AM2013-5252
An alternative method for mucosal flap closure during peroral endoscopic myotomy using an over-the-scope clipping device
Authors: P. Saxena, Y. Chavez, A. Kord Valeshabad, A. Kalloo, M. Khashab
Journal: Endoscopy (2013)

Maintaining the integrity of the mucosal flap and the reliable closure of mucosal entry during peroral endoscopic myotomy (POEM) is paramount in preventing leakage of esophageal contents into the mediastinal space. We describe our experience with POEM, the problems encountered with closure of mucosal flaps, and successful closure with over-the-scope clips (OTSC). Two patients with achalasia underwent successful endoscopic myotomy during POEM. During both procedures, the proximal end of the longitudinal mucosal incision was noted to be gaping and completion of the closure with standard clips was unsuccessful. The sides of the flap were approximated using a Twin Grasper followed by placement of OTSC. Closure of the mucosal entry appeared to be complete at the end of the procedures. Esophagram the following day revealed no leaks in either patient. There were no other complications and patients were discharged home after 1 - 2 days of hospital observation. Patients reported complete resolution of achalasia symptoms during follow-up. We propose closure of mucosal incisions during POEM using one to two OTSC as an alternative to described techniques. The use of OTSC may simplify the procedure and result in a more durable (i. e. full-thickness) closure.
Double-Blind Comparison of the Nephrotoxicity and Auditory Toxicity of Gentamicin and Tobramycin
Authors: Craig R. Smith, James J. Lipsky, Oscar L. Laskin, David B. Hellmann, E. David Mellits, James Longstreth, Paul S. Lietman
Journal: New England Journal of Medicine (1980)

Two hundred fifty-eight patients with suspected sepsis were treated with tobramycin or gentamicin in a prospective, randomized, double-blind trial. One hundred forty-six patients received nine or more doses, had serial determinations of serum creatinine, and were evaluated for nephrotoxicity; 91 were able to cooperate with audiometry and were evaluated for auditory toxicity. Auditory toxicity developed in five of 47 (10 per cent) given gentamicin and five of 44 (11 per cent) given tobramycin. Nephrotoxicity developed in 19 of 72 (26 per cent) given gentamicin and nine of 74 (12 per cent) given tobramycin (P less than 0.025). The severity of the nephrotoxicity was not different; the mean increase in creatinine was 1.3 mg per 100 ml (114.9 mumol per liter) in both groups. Both the tobramycin and gentamicin groups had a similar mean age, initial serum creatinine level, total dose, serum aminoglycoside level, and duration of therapy. We conclude that tobramycin causes nephrotoxicity less frequently than does gentamicin.
INFLUENCE OF CLINICAL TRIAL SITE ENROLLMENT ON PATIENT CHARACTERISTICS, PROTOCOL COMPLETION, AND ENDPOINTS: INSIGHTS FROM THE ASCEND-HF TRIAL
Authors: Stephen Greene, Adrian Hernandez, Jie-Lena Sun, Marco Metra, Javed Butler, Andrew Ambrosy, Justin Ezekowitz, Randall Starling, John Teerlink, Adriaan Voors, Paul Armstrong, Christopher O’Connor, Robert Mentz
Journal: Journal of the American College of Cardiology (2016)
Abstract 9788: Exosomes Released From GATA-4 Overexpressed Mesenchymal Stem Cells Enrich Anti-apoptotic microRNAs and Mediate Cardioprotection
Authors: Bin Yu, Min Gong, Jingcai Wang, Yigang Wang, Ronald W. Millard, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2013)

Increased evidences indicate that exosomes play an important role in cell to cell communication and exert regulatory function by shuttling bioactive molecules. We have previously reported that overexpression of GATA-4 in mesenchymal stem cells (MSC) (MSC GATA-4 ) increased cardioprotection. In this study, we investigated if this action was associated with microRNAs (miRs) carried by exosomes. Our studies indicated: 1) Exosomes isolated from MSC increased cultured neonatal cardiomyocyte (CM) survival under hypoxic environment for 48 hours in a concentration-dependent manner (Fig. A). The cardioprotection was partially attenuated by treating MSC with GW4869 (10μM), an exosome release inhibitor and enhanced in the exosomes obtained from MSC GATA-4 (Exo GATA-4 ) (Fig. B). 2) Exo GATA-4 well maintained mitochondria membrane potential of CM assessed by JC-1 staining and expressed as a ratio of aggregate to monomer fluorescence (Fig. C). 3) The expression of pro-apoptotic miR-15b, miR-34c in CM was up-regulated, and anti-apoptotic miR-19a, miR-451 was down-regulated following exposure to hypoxia (Fig. D). 4) The expression of miR-19a and miR-451 was higher in MSC GATA-4 (Fig. E) and Exo GATA-4 (Fig. F). 5) Treatment CM with Exo GATA-4 dramatically reversed the alteration of these miRs in CM which was induced by exposure to hypoxia and resulted in an increase of expression of miR-19a and miR-451 (Fig. G). It is concluded that GATA-4 enhanced MSC mediated cardioproteciton, which was associated with a transfer of exosomes enriched anti-apoptotic miRs from MSC to CM.
AB0316 Changes of adipokine serum levels after il-6 receptor blockade with tocilizumab in patients with rheumatoid arthritis
Authors: K. Fragiadaki, K. Makrilakis, J. Smith, P. P. Sfikakis, G. D. Kitas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Immune dysregulation and systemic inflammation are integral to the development of accelerated atheromatosis in rheumatoid arthritis (RA), mediated by various cytokines. Imbalance of haemostasis, as evidenced by increased levels of the fibrinolysis inhibitor plasminogen activator inhibitor-1 (PAI-1) contributes to future risk of cardiovascular diseases. IL-6 is implicated in the pathogenesis of RA, and tocilizumab (TCZ), a humanized monoclonal anti-IL-6 receptor antibody is being used for the treatment of RA. Its metabolic effects on serum adipokine levels, fibrinolysis and insulin sensitivity have not been investigated in detail so far. <h3>Objectives</h3> To investigate the metabolic effects of 6-months TCZ treatment of RA patients on serum adipokines and insulin sensitivity. <h3>Methods</h3> A total of 19 consecutive patients with RA (18 females, 1 male), aged 48.6±10.9 years (mean±SD, range 25-62), disease duration 10.5±9.3 years (range 2-23) who received 6 infusions of TCZ (8 mg/kg each) monthly for moderate or severe RA (DAS28-ESR&gt;3.2) participated in this study. All medications used before enrolment remained unchanged. Serum levels of IL-6, IL-1b, TNF-α, adiponectin, leptin, resistin, visfatin, and PAI-1, as well as glucose, insulin and cortisone were measured at baseline and 1, 3 and 6 months after treatment. Insulin resistance and sensitivity were assessed by calculation of HOMA-IR and QUICKI index, respectively. <h3>Results</h3> As expected, CRP (mean±SD, 17.6±20.3 vs. 2.6±1.5 mg/L) and ESR (50.4±25.4 vs. 11.8±2.2) levels, as well as disease activity index (DAS28-ESR 5.5±1.2 vs. 2.5±1.0) decreased after 6 months of TCZ treatment. Insulin resistance and insulin sensitivity index did not change, despite the fact that body mass index (27.3±7.8 vs. 28.4±8.2 kg/m<sup>2</sup>) and waist circumference (95.0±17.9 vs. 98.1±18.3 cm) increased significantly. PAI-1 levels significantly decreased from baseline to 6 months (72.5±27.3 vs. 51.0±27.7 pg/ml, p&lt;0.001). There was no difference in PAI-1 decrease between complete responders (DAS28&lt;2.6 at 6 months [n=10 patients]) and the remaining patients. Baseline individual PAI-1 levels were correlated with baseline CRP levels (r=0.6, p=0.08), CRP decline at 6 months (r=0.58, p=0.012) and IL-6 change at 6 months (r=0.48, p=0.04). The other adipokines measured did not demonstrate sustained or statistically significant changes during TCZ treatment. <h3>Conclusions</h3> TCZ treatment in patients with RA does not adversely affect insulin sensitivity despite increasing adiposity, but favorably alters PAI-1 levels, thus possibly decreasing cardiovascular risk in these patients. <h3>Disclosure of Interest</h3> None Declared
ET-55 * THE LONG TERM RISK OF TUMOR PROGRESSION HAS NOT CHANGED OVER TIME FOR SUPRATENTORIAL GRADE II GLIOMAS AND IS NOT INFLUENCED BY THE MODE OF SURGICAL TREATMENT
Authors: O. Schnell, F. Oehlschlaegel, J.-C. Tonn, F.-W. Kreth
Journal: Neuro-Oncology (2014)

BACKGROUND: To determine the risk pattern of tumor progression over time in supratentorial WHO grade II gliomas, we compared long term outcome either after stereotactic iodine brachytherapy (SBT) or open tumor resection (OTR). The stereotactic group has been treated predominantly in the CT-era, whereas the resection group exclusively referred to the MR-era. PATIENTS AND METHODS: The SBT (OTR) group consisted of 239 (123) adult patients with histologically proven supratentorial WHO grade II (oligo-)astrocytomas undergoing first treatment between 1979-1992 (1991-1998). Adjuvant treatment was always withhold until tumor progression occurred. Primary endpoints were time to tumor progression (PFS) according to the Macdonalds criteria and time to malignant transformation (MTT). Secondary endpoint was survival (OS). Endpoints were estimated with the Kaplan Meier method, prognostic factors were obtained from proportional hazards models. RESULTS: The SBT and OTR group did not differ in terms of age and Karnofsky scores; tumors were smaller (p < 0.001), more often deep seated (p < 0.001) and left sided (p < 0.01) in the SBT group. Median follow up for survivors after SBT (OTR) was 10.5 years (14 years). 5- and 10-years PFS rates were 50% and 25% in the OTR group and 42% and 23% in the SBT group (p = 0.2). 5- and 10-years MTT rates were 32% and 60% in the OTR group and 32% and 54% in the SBT group (p = 0.7). There was no leveling-off of the curves in any of the analyzed groups. OS was longer in the OTR group; but in multivariate models, OTR was not superior to SBT regarding PFS and MTT. CONCLUSION: Risk patterns of tumor progression in supratentorial grade II (oligo-) astrocytomas are still dominated by the natural course of the disease. Longer survival after resection might indicate improvement of salvage treatment concepts over time after tumor progression.
P178 The effect of BAL induced inflammation on nasal innate defence - reduction in experimental human pneumococcal carriage
Authors: A. D. Wright, J. F. Gritzfeld, S. El Batrawy, L. Roche, A. Collins, S. B. Gordon
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> BAL causes pulmonary inflammation post procedure. It is not known if the inflammation affects the upper respiratory tract and nasal mucosa. We have developed an experimental human pneumococcal carriage (EHPC) platform. We wished to establish if prior bronchoscopy was associated with altered carriage rates in EHPC. <h3>Methods</h3> Participants were screened for natural carriage of pneumococcus by nasal wash. <b>Group A</b> then proceeded to <b>inoculation</b> 7 days after initial screening whereas <b>Group B</b> underwent <b>bronchoscopy</b> with BAL prior to inoculation. Bronchoscopy with BAL was performed using fibre optic bronchoscope and instillation of 200 ml 0.9% saline in 50 ml aliquots followed by immediate manual aspiration via the working port of the bronchoscope. Participants were inoculated with 6B or 23F <i>S pneumoniae</i> (15 000–60 000 CFU/ml) within 14 days of bronchoscopy. Carriage was determined by the presence of pneumococci in nasal wash samples at 48 hr and/or 7 days post inoculation. <h3>Results</h3> Thirty-seven participants were recruited, of which 19 proceeded to BAL prior to inoculation; 22 were inoculated with 6B and 15 with 23F. Baseline characteristics were not significantly different between Group A and B. Neither group had any symptoms at the time of inoculation. Both Group A and B were subdivided into 23F or those that received 6B. The inoculum dose was not significantly different between the BAL groups for either 23F or 6B. The mean length of time between bronchoscopy and inoculation was 10 days (±1). Carriage rates between Group A 6B and Group B 6B were significantly different (p=0.008); this difference was not seen between Group A 23F and Group B 23F. In adults challenged with SPN, carriage rates differ by type. In an experiment with high carriage rates, there was a significant decrease in carriage rates in subjects with preceding BAL. <h3>Conclusions</h3> This study suggests that the inflammatory process caused by bronchoscopy with BAL, as highlighted in previous research, may influence innate mucosal defence. The inflammatory effect of bronchoscopy with BAL should be accounted for in future research allowing adequate time before performing interventions which may be affected.
Surgery for hyperparathyroidism is associated with reduced fracture risk
Authors: Jacqui Wise
Journal: BMJ (2016)

Surgery to remove the parathyroid is associated with a reduced risk of fractures in patients with primary hyperparathyroidism, an observational study in Annals of Internal Medicine has found.1 The researchers also found that treatment with bisphosphonate was associated with increased bone mineral density but not fewer fractures.

Untreated primary hyperparathyroidism is a common endocrine disorder that leads to loss of bone mineral density over time, raising a concern about the development …