tbuckley/cabot-search huggingface dataset:
NHS can use gagging clauses as long as employees know they don't apply to safety issues, guidance says
Authors: C. Dyer
Journal: BMJ (2013)

Confidentiality or “gagging” clauses can still be used in agreements to settle disputes between NHS trusts and departing employees as long as they make it clear that former employees are free to speak out on patient safety and other public interest issues, NHS Employers says in new guidance.1

Agreements may still bar former employees from revealing the fact that an agreement existed, negotiations over it, and its terms. NHS organisations may also bar former employees from revealing confidential information acquired as a result of their employment, …
Abstract SY11-02: Microenvironment matters: TGFβ regulates the response to DNA damage
Authors: Mary Helen Barcellos-Hoff
Journal: Cancer Research (2012)

Abstract Transforming growth factor β1 (TGFβ) is a central regulator of the microenvironment in both normal tissues and tumors. TGFβ resides in the extracellular matrix as a latent complex that requires activation prior to binding to ubiquitous cell surface receptors to initiate a signaling cascade culminating in nuclear Smad activation of transcription. Most cancer cells are no longer responsive to TGFβ growth suppression, yet maintain a partially intact signaling pathway. Why? Surprisingly, we found that either Tgfb1 genetic deletion in mouse cells or TGFβ inhibition in human cells compromises the execution of the molecular cascade in response to DNA damage. Irradiated epithelial cells exhibit decreased ATM kinase activity and autophosphorylation, reduced phosphorylation of critical DNA damage transducers, and abrogation of cell cycle blockade and apoptosis, which together result in increased radiosensitivity. The ability of exogenous TGFβ to restore these responses indicates that the effect is both cell intrinsic and distal to TGFβ signaling. Recent studies suggest that TGFβ regulates multiple components of the DNA damage response, supporting the conclusion that extrinsic TGFβ is necessary for efficient execution of the intrinsic DNA damage response. TGFβ may thus provide a survival advantage in tumors, which are a source of exuberant TGFβ activity, provides an unexpected avenue for in cancer treatment. Both ionizing radiation and chemotherapy actually elicit TGFβ activity via redox- and integrin-mediated activation. We tested the translational potential of the requirement for TGFβ in the genotoxic stress program during radiotherapy using TGFβ neutralizing antibodies and small molecule inhibitors of the TGFβ type I receptor kinase in experimental models of breast, lung and brain cancer in vivo and in vitro. TGFβ inhibition prior to radiation increased the radiosensitivity of 10 of 12 human cancer cell lines as measured by clonogenic assay and decreased γH2AX phosphorylation. Notably, glioma stem cells were preferentially protected from DNA damage by high levels of TGFβ, which also promoted self-renewal, both of which were compromised by TGFβ inhibition. Administration of TGFβ neutralizing antibody in vivo increased tumor growth delay following single or multiple radiation fractions and also reduced metastasis. We anticipate that use of TGFβ inhibitors in the context of radiotherapy will increase radiosensitivity and impair the protective tumor microenvironment, providing both local and systemic benefit. 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 SY11-02. doi:1538-7445.AM2012-SY11-02
OP0050 Evolution of the alternative classification of HLA-DRB1 alleles in rheumatoid arthritis: Impact on the production of the anti-citrullinated protein antibodies and structural progression, data from the ESPOIR cohort
Authors: A. Ruyssen-Witrand, P.-A. Gourraud, D. Nigon, C. Lukas, C. Miceli-Richard, B. Jamard, A. Cantagrel, A. Cambon-Thomsen, P. Dieudé, A. Constantin
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> <i>HLA-DR shared epitope</i> alleles have been previously reclassified in an alternative classification (1) relevant in terms of rheumatoid arthritis (RA) susceptibility, ACPA production and severity. However, subclassification of S2 alleles according to the amino acid at position 70 has never been assessed. <h3>Objectives</h3> The aim of this work was to validate a modified version of this alternative classification in terms of association with ACPAs production and radiographic progression in a cohort of early RA. We proposed to devise S2 groups into 2 groups (S2D and S2P) according to the amino acid at position 70 and to pool the different alleles in 3 risk groups. <h3>Methods</h3> 612 patients included in the ESPOIR cohort, fulfilling ACR/EULAR 2009 criteria for RA were genotyped for <i>HLA-DRB1</i> alleles. Radiographs were centrally read and scored using the Total Sharp/van der Heijde Score (mTSS). The different alleles were classified according to a modified version of the alternative classification (X, S1, S2D, S2P, S3D, S3P) and were pooled according to ACPA production risk: the "L group" for low risk (S1 and X), the "N group" for neutral risk (S2D and S3D), "H group" for high risk (S3P and S2P). The association between the different genotypes and 1) the ACPA positivity was assessed by a Chi square test, 2) the radiographic progression at 12 months by Wilcoxon's rank sum test. Finally, a logistic regression was used to assess the risk of progression (≥1 mTSS unit). <h3>Results</h3> The LH, NH and HH genotypes were significantly associated with ACPA positivity (respectively OR[95%CI]=1.92 [1.34-2.75], p=0.0002, OR[95%CI]=1.84 [1.02-3.37], p=0.03, OR[95%CI]=4.83 [2.66-9.20], p&lt;0.0001), whereas LL genotype had a protective effect (OR[95%CI]=0.18 [0.11-0.28], p&lt;0.0001). LH and HH genotypes were associated with structural progression (respectively p=0.0067 and p&lt;0.0001) whereas LL and LN genotypes seemed to have a protective effect on progression (respectively p&lt;0.0001 and p=0.0151). H allele carriage was significantly associated with progression in the multivariate model independently of ACPA status (OR [95%CI]=1.90 [1.08-3.35], p=0.026). <h3>Conclusions</h3> Pooling alleles in 3 risk groups simplify the alternative classification of <i>HLA-DRB1</i> alleles and is relevant in terms of association with ACPA production and radiographic progression. <h3>References</h3> du Montcel ST, Michou L, Petit-Teixeira E, Osorio J, Lemaire I, Lasbleiz S, Pierlot C, Quillet P, Bardin T, Prum B, et al: New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility. Arthritis Rheum 2005, 52:1063-1068. <h3>Disclosure of Interest</h3> None Declared
P11 Induction of hyperammonaemia from the small and large intestine in patients with cirrhosis with magnetic resonance quantification of brain water and metabolites
Authors: H. Mardini, F. Smith, A. Blamirel, C. Record
Journal: Gut (2011)

<h3>Introduction</h3> Induction of hyperammonaemia from glutaminase action in the small intestine1 or systemic catabolism of oral amino acids23 is well recognised but, although suggested in 1959 by Walser and Bodenlos,4 ureolysis resulting in hyperammonaemia has not been demonstrated from urea delivered to the colon. Hepatic encephalopathy (HE) is now thought to be caused by cerebral oedema. <h3>Aim</h3> We hypothesised that if hyperammonia is a key factor in hepatic encephalopathy, induced hyperammonaemia from oral amino acid or urea challenge would lead to transient changes in brain water distribution and metabolite concentration. <h3>Method</h3> Amino acid (mixture of equal parts of glycine, serine and threonine) or urea challenges were undertaken in 18 patients with stable cirrhosis 5 of whom gave a history of hepatic encephalopathy. Sequentail blood ammonia concentration was determined with the ammonia checker and brain water and metabolites with magnetic resonance diffusion tensor imaging and spectroscopy. <h3>Results</h3> Oral urea and amino acids (delivered to the colon by coating) resulted in peak increments in blood ammonia of 146±SD 164 and 55±51 μmol/l while for uncoated amino acids the mean increment was 58 (±41) μmol/l. The latter was accompanied by a significant increase in ADC of 9% (p=0.004). Increased ADC was significantly correlated with blood ammonia (r=0.58, p=0.04). The change in ammonia levels also correlated with the increase in glutamine levels (r=0.78, p=0.002). <i>Myo</i>-inositol concentration decreased significantly by 0.7 (±0.7) mMol/l between scans and this correlated with the mean difference in ADC (r=0.59, p&lt;0.04). <h3>Conclusion</h3> These results show that hyperammonia can be derived from nitrogenous substrates in the colon and can <i>directly</i> drive changes in brain water distribution as a mechanism for cerebral oedema development. Since cerebral astrocytes contain glutamine synthetase, our MRS data suggests intracerebral formation of glutamine from ammonia. Developments in therapy for hepatic encephalopathy need to focus on amelioration of colonic ammonia formation.
AB0525 Local open-label multicenter study to evaluate the quality of life in patients with moderate to severe active rheumatoid arthritis and an inadequate response to DMARDS when adding tocilizumab
Authors: E. Nasonov, E. Panasyuk, E. Shikina, T. Plaksina, A. Dmitrieva, L. Troegubova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid Arthtritis (RA) is systemic autoimmune disease affecting 1% of the population. The disease process is characterized by persistent synovitis and progressive joint destruction leading to disability. In spite of some biological therapies most of RA patients don’t reach good quality of life. <h3>Objectives</h3> <i>Primary objective:</i> to assess the change in rheumatoid arthritis (RA) quality of life with adding of tocilizumab (TCZ) to traditional DMARDs (tDMARDs) therapy <i>Secondary objective:</i> to assess the efficacy of TCZ in combination with tDMARDs in terms of the change in DAS28, ACR 20/50/70 responses and EULAR response at Week 24 and safety based on the reports on adverse events, serious adverse events, laboratory data and vital signs <h3>Methods</h3> A multicentre open-label phase IV study was performed from August 2009 till February 2011. A total 202 adult patients with active RA (DAS&gt;3,2) who had not been treated previously with any biological agents were enrolled in the study. Patients remained on stable doses of tDMARDs and recieved TCZ 8 mg/kg every 4 weeks for 24 weeks (total 6 infusions). Mean age of the patients was 49±12 years. And their mean disease duration was 7,5±6,5 years. <h3>Results</h3> Average disease activity score (DAS) 28 of all 202 patients significantly decreased from 6,75±0,85 (baseline) to 2,6±1,18 (week 24). DAS28 remission (DAS28&lt;2,6) rate at week 24 being achieved by 51,3%, SDAI remission – 21,4%. ACR 20/50/70 responses were achieved by 88,6/70,3/44,1% patients at week 24. Response was seen early - 50% patients had ACR20 improvement at week 4. 38,3% was established by ACR70 at week 24. C-reactive protein levels was reduced from 33,5±34,84 (baseline) to 4,78±12,94 (week 24). 88% patients had a clinically meaningful improvement in physical function measured by Health Questionnaire Disease Index (HAQ-DI). The safety profile of TCZ was comparable to that previously observed in the phase III trial programme. There were registered 100 AEs in 51 (25,2%) patients. Most of AE were mild or moderate. Which were mostly high level transaminases (29%) and respiratory infections (17%). 73% of AEs resolved by the time of reporting. There were 14 serious AEs. <h3>Conclusions</h3> Tocilizumab in combination with traditional DMARDs is highly effective in the treatment of moderate to severe RA with a rapid and sustained improvement in signs and symptoms. Rapid and sustained improvement was also noted in quality of life. A manageable safety profile was seen over the 24-week study period. <h3>Disclosure of Interest</h3> None Declared
TCTAP A-010 A Prospective, Observational, Multicenter Study Comparing Tenecteplase Facilitated PCI Versus Primary PCI in Indian Patients with STEMI (STEPP – AMI)
Authors: Suma Malini Victor, Vijayakumar Subban, Thomas Alexander, Bahuleyan C. Gopalan, Arun Srinivas, Selvamani Sethuraman, Ajit S. Mullasari
Journal: Journal of the American College of Cardiology (2014)
Synchronous lymph node metastasis in apparently low-risk T1 colon cancer
Authors: Masao Yoshida, Kenichiro Imai, Kinichi Hotta, Hiroyuki Ono
Journal: Endoscopy (2014)

The risk for lymph node metastasis is low in T1 colorectal cancer when none of the following pathologic findings is present: invasion to a depth of 1000 μm or more, positive horizontal or vertical margin, lymphovascular permeation, severe tumor budding, and either a poorly differentiated or a mucinous component [1] [2] [3]. To the best of our knowledge, no case of such a low-risk T1 tumor associated with lymph node metastasis has been reported.
FRI0081 Radiographing one hand, one foot or both hands and feet in rheumatoid arthritis, does it make a difference?
Authors: K.Y. Kwok, R. Knevel, D.P. de Rooy, M.D. Posthumus, T.W. Huizinga, E. Brouwer, A.H. van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Radiological damage is an important outcome measure in rheumatoid arthritis (RA), both for research and clinical purposes. Depending on the setting, both hands and feet are radiographed, or only a part of these. It is unknown whether radiographing part of the four extremities gives comparable information to radiographing both hands and feet. The results of recent MRI studies increased our interest in this issue. <h3>Objectives</h3> To compare the radiological information obtained both when evaluating single time-point radiographs and progression over time, in early and advanced RA. <h3>Methods</h3> 6,261 sets of hands and feet X-rays of 2,193 RA-patients from Leiden, Groningen (both from Netherlands) and North America were studied. Correlations between joint damage at different regions were compared (unilateral versus bilateral and hands versus feet). Analyses were done at single time-points (cross-sectional) and for progression over time (longitudinal), both for continuous severity measures (Sharp-van der Heijde score, SHS) and binomial measures of erosiveness. <h3>Results</h3> When studying single time-points, the severity of joint damage (SHS) is highly correlated between left and right with correlation coefficient more than 0.7, but weakly correlated between hands and feet. Correlation coefficients were higher in advanced than early RA. These findings were comparable in the three datasets. When evaluating erosiveness using only unilateral X-rays or hands without feet, 19.3% and 24.0-40.4% is incorrectly classified as non-erosiveness. Similarly, when evaluating disease progression by imaging only unilateral X-rays or only hands X-rays, progression would have been missed in 11.6-16.2% and 21.2-31.0% of the patients. <h3>Conclusions</h3> Evaluations on the presence/absence of erosive disease are preferably done by radiographing both hands and both feet because of the risk of false-negative classification. The severity of joint damage is highly correlated between left and right but not between hands and feet. <h3>References</h3> Ostergaard M, Dohn UM, Jensen AD et al. Patterns of magnetic resonance imaging bone erosion in rheumatoid arthritis – Which bones are most frequently involved and show the most change? J Rheumatol 2011; 38:2014-2017. <h3>Disclosure of Interest</h3> None Declared
HIGH-DOSE STATIN THERAPY IS EFFECTIVE AT PREVENTING THE DEVELOPMENT OF CONTRAST-INDUCED NEPHROPATHY IN PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE CORONARY SYNDROMES: A META-ANALYSIS
Authors: Theodoros A. Zografos, Evangelos Oikonomou, Gerasimos Siasos, Konstantinos Mourouzis, Efstathios Dimitropoulos, Alexis Antonopoulos, Manolis Vavuranakis, Sotirios Tsalamandris, Aimilios Kalampogias, Vasiliki Tsigkou, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
Abstract 3734: Paclitaxel disrupts polarized entry of membrane permeable C6 ceramide into ovarian cancer cells resulting in synchronous induction of cell death
Authors: Charles Best, David Calianese, Kevin Szulak, Gabriella Brum, Katelyn Higgins, Thomas Carbone, Michael McCauley, Wen Di, Harold Wanebo, Yinsheng Wan
Journal: Cancer Research (2012)

Abstract Exogenous cell permeable C6 ceramide is demonstrated to act synergistically with chemotherapeutic drugs: paclitaxel, cisplatin, doxorubicin and histone deacetylase inhibitor trichostatin A (TSA) to induce cell death in a variety of cancer cells. We previously showed that C6 ceramide and paclitaxel act synergistically to induce ovarian cancer cell death via modulation of PI3/AKT cell survival pathway. This current study is focused on the process of C6 ceramide into the cell and its behavior during apoptosis. We investigated the entry pattern of C6 ceramide into ovarian cancer cells using fluorescent short chain C6-NBD sphingomyelin (or C6-NBD). As imaged with confocal microscopy, we observed that C6-NBD enters cells in a polarized pattern, characterized by strong signals at one cellular end, a probable mitosis initiation site. Pretreatment of the cells with filipin, an inhibitor of the raft/caveolae endocytosis pathway, decreases C6-NBD entry into cells. Pretreatment of water channel inhibitor CuSO4 also reduces entry of C6-NBD. Interestingly, pretreatment of cells with paclitaxel disrupts the polarized entry of C6-NBD into the cells, resulting in even distribution of C6-NBD in the cytoplasm. Further studies show that pretreatment of the cells with paclitaxel destabilizes cytoskeletal proteins, releasing increased number of short fragments of tubulins. The data suggests that C6 ceramide enters the cells preferably through a predetermined initial site of mitosis. In addition to diffusion, short chain C6 ceramide enters cells also via water channels and caveolae-mediated endocytosis. Paclitaxel disrupts cytoskeletons and induces an even distribution of C6 ceramide in the cytoplasm resulting in synergistic ovarian cancer cell death. 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 3734. doi:1538-7445.AM2012-3734
New rules are proposed for benefits that must be covered under health reform
Authors: J. H. Tanne
Journal: BMJ (2012)

The Obama administration’s proposed rules for health insurance prohibit discrimination by health insurance companies, require coverage of 10 essential health benefits, and emphasize wellness programs to prevent disease and lower health costs.

The public, consumer groups, and health insurance companies have until December 26 to comment on two of the proposed rules and until January 25 to comment on the third rule, which deals with employee wellness programs. When finalized, the rules will go into effect for health insurance policies after 1 January 2014.

Kathleen Sebelius, the Health and Human Services secretary, said, “The Affordable Care Act is building a health …
A population-based, retrospective, cohort study of esophageal cancer missed at endoscopy
Authors: Georgina Chadwick, Oliver Groene, Jonathan Hoare, Richard Hardwick, Stuart Riley, Tom Crosby, George Hanna, David Cromwell
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Several studies have suggested that a significant minority of esophageal cancers are missed at endoscopy The aim of this study was to estimate the proportion of esophageal cancers missed at endoscopy on a national level, and to investigate the relationship between miss rates and patient and tumor characteristics. <b>Patients and methods:</b> This retrospective, population-based, cohort study identified patients diagnosed with esophageal cancer between April 2011 and March 2012 in England, using two linked databases (National Oesophago-Gastric Cancer Audit and Hospital Episode Statistics). The main outcome was the rate of previous endoscopy within 3 – 36 months of cancer diagnosis. This was calculated for the overall cohort and by patient characteristics, including tumor site and disease stage. <b>Results:</b> A total of 6943 new cases of esophageal cancer were identified, of which 7.8 % (95 % confidence interval 7.1 – 8.4) had undergone endoscopy in the 3 – 36 months preceding diagnosis. Of patients with stage 0/1 cancers, 34.0 % had undergone endoscopy in the 3 – 36 months before diagnosis compared with 10.0 % of stage 2 cancers and 4.5 % of stage 3/4 cancers. Of patients with stage 0/1 cancers, 22.1 % were diagnosed after ≥ 3 endoscopies in the previous 3 years. Patients diagnosed with an upper esophageal lesion were more likely to have had an endoscopy in the previous 3 – 12 months (<i>P</i> = 0.040). The most common diagnosis at previous endoscopy was an esophageal ulcer (48.2 % of investigations). <b>Conclusion:</b> Esophageal cancer may be missed at endoscopy in up to 7.8 % of patients who are subsequently diagnosed with cancer. Endoscopists should make a detailed examination of the whole esophageal mucosa to avoid missing subtle early cancers and lesions in the proximal esophagus. Patients with an esophageal cancer may be misdiagnosed as having a benign esophageal ulcer.
EFFECT OF PURIFIED OMEGA-3 FATTY ACIDS ON REDUCING LEFT VENTRICULAR REMODELING AFTER ACUTE MYOCARDIAL INFARCTION (OMEGA-REMODEL STUDY: A DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL)
Authors: Bobby Heydari, Siddique Abbasi, Ravi Shah, Shuaib Abdullah, William Harris, Joseph McConnell, Jiazuo Feng, Udo Hoffmann, Evan Appelbaum, Ron Blankstein, Michael Steigner, Michael Jerosch-Herold, Raymond Kwong
Journal: Journal of the American College of Cardiology (2015)