tbuckley/cabot-search huggingface dataset:
PTU-023 Sedation In The Endoscopy Department – Do We Need More Training?
Authors: A Mohanaruban, K Bryce, A Radhakrishnan, J Gallaher, P Trembling, G Johnson
Journal: Gut (2014)

<h3>Introduction</h3> The 2004 report of the National Confidential Enquiry into Patient Outcome and Death (NCEPOD) highlighted that only 35% of endoscopists surveyed were known to have attended courses on safe sedation. The report recommended that all those responsible for the administration of sedation in the endoscopy department should receive formal training and clear protocols for the administration of sedation should be made available and implemented. <h3>Methods</h3> We undertook a paper survey of 40 gastroenterology trainees across 5 UK Deaneries during December 2013 to determine current practices of sedation and training in endoscopy as well as level of knowledge of the sedation agents. <h3>Results</h3> All 40 of the trainees surveyed responded. 21 (53%) had received formal training in sedation for endoscopy with the most common setting for training being at local trust induction. 35 (88%) would value an introductory course in sedation as part of local trust induction. Only 14 (35%) were aware of a sedation protocol in their department. 27 (68%) reported Fentanyl as the commonest first-line opioid used, although it was rarely administered in upper GI endoscopy. 28 (70%) trainees performed the majority of their upper GI endoscopies ‘unsedated’ with throat-spray only. These findings were similar in both sedation-trained and non-trained cohorts. For colonoscopy, 18 (90%) of those who had received formal training in sedation would administer an opioid first, before Midazolam, whereas 13 (72%) trainees without sedation training would use this sequence. 28 (70%) trainees stated correctly the maximum doses for Midazolam and Fentanyl as recommended by BSG guidelines, and were appropriately cautious about the initial dose of Midazolam administered to an elderly patient. 14(74%) of the trained cohort correctly said that Fentanyl takes 1–2 min to act, compared to 7 (39%) in the untrained cohort. All trainees surveyed knew the reversal agents for Midazolam and Fentanyl. <h3>Conclusion</h3> 47% of trainees did not receive structured training in safe sedation, despite national guidelines advising this to be an essential part of the training program. The majority of trainees would value sedation training. We also identified some gaps in trainees’ knowledge of the action of sedation agents. We propose that a formal training session in sedation or an e-learning module could be incorporated as part of a deanery or trust induction for gastroenterology and regularly reviewed thereafter. <h3>References</h3> NCEPOD 2004: Scoping our practice BSG 2003: Guidelines on safety and sedation during endoscopic procedures <h3>Disclosure of Interest</h3> None Declared.
AB0223 Atherosclerotic plaques may be correlating with the duration of rheumatoid arthritis
Authors: E. Stumbra Stumberga, H. Mikazane
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> BACKGROUND AND AIMS: It is widely accepted that patients with rheumatoid arthritis (RA) have increased mortality and morbidity from premature cardiovascular disease. Up to 50% of this excess mortality is secondary to ischaemic heart disease closely followed by cerebrovascular disease. The aim of this study was to investigate changes in arterial wall elastic properties, intima-media thickness (IMT) and plaque formation with relation to age, disease duration and inflammation markers in patients with RA in order to detect and estimate cerebrovascular risk factors. <h3>Methods</h3> METHODS. 20 patients with confirmed RA and 27 sex and age matched healthy controls (aged 27-70) were recruited. Carotid arteries haemodynamic parameters, elastic properties, IMT and plaques were measured using high resolution B-mode, M-mode and Doppler–mode ultrasound to calculate arterial wall distensibility and stiffness indices, blood flow velocities and resistance indices, maximal IMT, size of atherosclerotic plaques. Subjects with arterial hypertension and smoking had been excluded from trial. C-reactive protein was used to measure systemic inflammation. The correlations between brachial arterial blood pressure, carotid haemodynamic, wall elastic indices and patients age, stage of disease, inflammation markers were calculated separately and in comparison with controls. <h3>Results</h3> RESULTS. Statistically, patients with RA had mean values of IMT higher than healthy subjects (+-SD 1,02+-0,21 vs 0,85+-0,22, t=2,45, p=0,19; sin 1,01+-0,28 vs. 0,82+-0,19, t=2,47, p=0,18). This difference was more pronounced in a group of thirty-year. No statistically proved correlations between carotid stiffness parameters, IMT and duration of disease was found. The presence of carotid plaque correlated with the period of rheumatoid arthritis and markers of RA seropositivity - RF and anti CCP, although the changes in IMT and carotid elastic indices did not differ significantly according to seropositivity. These preliminary observations can indicate the need of further investigation with the recruitment of larger number of patients with RA to prove the role of systemic inflammation in the atherosclerotic process. <h3>Conclusions</h3> The presence of carotid plaque correlated with the period of rheumatoid arthritis and markers of RA seropositivity - RF and anti CCP, although the changes in IMT and carotid elastic indices did not differ significantly according to seropositivity <h3>Disclosure of Interest</h3> None Declared
Usefulness of endoscopic retrograde biliary biopsy using large-capacity forceps for extrahepatic biliary strictures: a prospective randomized study
Authors: M. Ikeda, I. Maetani, K. Terada, T. Ukita, T. Tada, H. Shigoka, S. Omuta, K. Takahashi
Journal: Endoscopy (2010)

See also: Commentaire de travail de M. Ikeda et al., pp. 837Endoscopy 2010; 42(10): 883-883DOI: 10.1055/s-0032-1306700
THU0044 Different type of carotid arterial wall remodeling in rheumatoid arthritis as compared to healthy subjects
Authors: A.M. van Sijl, K. van den Hurk, M.J. Peters, V.P. van Halm, G. Nijpels, C.D. Stehouwer, Y.M. Smulders, A.E. Voskuyl, J.M. Dekker, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, but mechanisms explaining this increased risk have not been fully elucidated. Arteries react on hemodynamic changes by arterial remodeling. <h3>Objectives</h3> We investigated whether arterial remodeling is different in RA as compared to control subjects. <h3>Methods</h3> 96 RA-patients and 274 healthy subjects were investigated cross-sectionally in two cohorts. B-mode carotid ultrasonography was used to investigate arterial wall parameters, including carotid intima-media thickness (cIMT), inter-adventitial diameter (IAD) and lumen diameter (LD), calculated as IAD – (2 × cIMT). Using linear regression, the association between presence of RA and arterial wall parameters was assessed. <h3>Results</h3> RA was associated with a 0.57 mm (9.3%) greater LD. IAD was 0.61 mm (7.8%) higher in RA. cIMT did not differ between RA patients and healthy subjects, resulting in a 4.4% greater wall-to-lumen ratio (ratio of IAD to cIMT, an indicator of outward remodeling) in RA. Associations remained similar after exclusion of patients with prior CV disease and after adjustment for demographic factors and CV risk factors. In RA, disability index and current use of prednisone were significantly associated with a greater wall-to-lumen ratio. <h3>Conclusions</h3> RA is associated with outward arterial remodelling, which is relevant because this is associated with plaque instability and rupture. <h3>Disclosure of Interest</h3> None Declared
HLA-DR4 is associated with a diminished risk of the development of chronic myeloid leukemia (CML)
Authors: EFM Posthuma, JHF Falkenburg, JF Apperley, A Gratwohl, B Hertenstein, RF Schipper, M Oudshoorn, JH v Biezen, J Hermans, R Willemze, E Roosnek, D Niederwieser
Journal: Leukemia (2000)
P07.05 * THE ROLE OF SURGERY IN PALLIATIVE TREATMENT OF METASTASES INVOLVING THE CERVICAL SPINE. OUR EXPERIENCE AND REVIEW OF THE LITERATURE
Authors: F. Romeo, S. Toscano, M. Blagia, M. Fina, P. Proto, M. Casiello, P. Colella, G. Cozza, A. D'Agostino
Journal: Neuro-Oncology (2014)

INTRODUCTION: Spinal column is the most common site of skeletal metastases. Cervical spine involvement may occur in 10% of cases. In cervical spine metastases the surgery may have an important role in multidisciplinary palliative treatment. Pain control, neurological improvement, the restoration of cervical spine stability and the very soon mobilization were effective in improving quality of life of these patients with minimally invasive surgical technique. CASE REPORTS: CASE 1) A 68 year-old man with an history of prostate cancer was admitted to our observation with intractable cervical pain. Cervical CT scan and MRI revealed a lesion involving C2. Surgical treatment: biopsy and vertebroplasty of C2 (transoral approach). The post-operative course was uneventful; neck pain relief was reported. Pathological examination was: metastases from prostate cancer. CASE 2) A 51 year-old man with an history of lung cancer was admitted to our observation with radicular pain of the right arm. Cervical CT scan and MRI revealed a vertebral body destruction of C4. Surgical treatment: complete C4 anterior corpectomy and fusion (Ulrich ADD-plus). Uneventful procedure; pain relief was reported. Pathological examination was: metastases from lung cancer. CASE 3) A 49 year-old woman with an history of breast cancer was admitted to our observation with cervical radiculopathy. Cervical CT scan and MRI revealed a vertebral body destruction of C7. Surgical treatment: complete C7 anterior corpectomy and fusion (Ulrich ADD-plus). Uneventful procedure; pain relief was reported. Pathological examination was: metastases from breast cancer. CONCLUSIONS: Minimally invasive surgery may be considered in multidisciplinary palliative treatment. In our cases the surgery has really improved the quality of life of the patients (relief of pain, stabilization of cervical spine). A review of the literature confirmed that in selected cases surgical treatment of cervical metastases is feasible and associated to low rate of morbility.
A6.12 Physiological evidence for diversification of IFNα- and IFNβ-mediated response programs in different autoimmune diseases
Authors: TD de Jong, S Vosslamber, E Mantel, S de Ridder, JG Wesseling, TCTM van der Pouw Kraan, C Leurs, H Hegen, F Deisenhammer, J Killestein, IE Lundberg, J Vencovsky, MT Nurmohamed, D van Schaardenburg, IEM Bultink, AE Voskuyl, DM Pegtel, CJ van der Laken, JW Bijlsma, CL Verweij
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Upregulation of type I IFN response genes is described for several autoimmune diseases, including systemic lupus erythematosus (SLE), multiple sclerosis (MS), myositis (IIM) and rheumatoid arthritis (RA). While IFNα contributes to SLE pathology, IFNβ therapy is beneficial in MS, implying different immunoregulatory roles for these IFNs. This study aimed to investigate potential diversification of IFNα-and IFNβ-mediated response programs in autoimmune diseases. <h3>Materials and methods</h3> Peripheral blood gene expression of 23 prototypical type I IFN response genes (IRGs) was determined in healthy controls (HCs, n = 54), SLE (n = 47), IFNβ-treated MS (n = 71), untreated MS (n = 160), IIM (n = 78) and RA patients (n = 76). An IFN score was calculated and patients with a type I IFN signature (IFN score &gt;mean+2SD in HC) were selected for analysis. <h3>Results</h3> We identified IFNα- and IFNβ-specific response programs by comparing IRG expression in SLE (IFNα-mediated) and IFNβ-treated MS patients. Statistical testing revealed increased expression of 5 IRGs in SLE (Gene cluster (GC-)A, p ≤ 0.006) and 13 IRGs in IFNβ-treated MS (Gene cluster (GC-)B, p ≤ 0.044). Concordantly, the GC-A/GC-B log-ratio was positive for all SLE patients and negative for virtually all IFNβ-treated MS patients. Applying this information to other autoimmune diseases, IIM patients displayed positive GC-A/GC-B log-ratios, indicating predominant IFNα activity. The GC-A/GC-B log-ratios in RA were lower and approached zero in part of the patients, implying relative importance of both clusters. Remarkably, GC-A/GC-B log-ratios appeared most heterogeneous in IFNβ-naive MS; half of the patients displayed GC-A dominance, whereas others showed GC-B dominance or log-ratios near zero. We confirmed these results for SLE, RA and MS using two public microarray datasets containing 22 SLE patients, 112 RA patients, 58 IFNβ-treated MS patients and 62 untreated MS patients. Exploring functional differences between GC-A and GC-B genes revealed enrichment of the ISGF3-binding response element ISRE and IRF8 binding sites only in GC-B, suggesting that IFNβ is more potent in activating these transcription factors than IFNα. <h3>Conclusions</h3> Conclusively, we demonstrated that type I IFN signatures in autoimmune diseases appear less uniform than generally assumed. The diversification of the type I IFN response in &nbsp;autoimmune diseases suggests different pathogenic roles of the type I IFNs.
Abstract 1628: Tumor suppressor gene demethylation and reactivation in human colon cancer cells by black raspberry anthocyanins
Authors: Chieh-Ti Kuo, Claire Seguin, Kristen Stoner, Seung-Ju Cho, Yui Weng, Jay Tichelaar, Yi-Wen Huang, Tim Huang, Gary Stoner, Li-Shu Wang
Journal: Cancer Research (2012)

Abstract Our laboratory has shown that the anthocyanins (ACs) in black raspberries (BRBs) are responsible for much of their chemopreventive effects in the rat esophagus. The present study was undertaken to determine the effects of BRB ACs on human colon cancer cells in vitro. Three days of AC treatment at 5 and 25 μg/ml medium significantly decreased cell proliferation and increased apoptosis in HCT116, Caco2, and SW480 human colon cancer cell lines. The ACs also reduced the activities and protein expression levels of DNA methyltransferases 1 and 3 (DNMT1, DNMT3) in all three cell lines. Promoter methylation of p16 (CDKN2A) and the Wnt pathway inhibitors, Sfrp2, Sfrp5 and Wif1, was decreased by AC treatment resulting in increased mRNA expression levels of all three Wnt inhibitors. ACs did not alter global methylation LINE-1. DNMT1 and DNMT3B knockout (KO) HCT116 cells were generated using siRNA to determine the role of these methyltransferases in AC-induced demethylation. In DNMT1 KO cells, the promoter methylation of Sfrp5 was reduced when compared with wild type HCT116 cells. AC treatment further reduced promoter methylation of Sfrp5 in DNMT1 KO cells suggesting that the ACs targeted protein(s) other than DNMT1 to regulate methylation. Promoter methylation of Sfrp5 was decreased to almost zero by treatment of DNMT3B KO cells with ACs. Interestingly, promoter methylation of p16 was reduced in both DNMT1 and DNMT3B KO cells, and AC treatment further reduced p16 methylation in both lines. In conclusion, these results suggest that ACs demethylated and reactivated tumor suppressor genes through regulation of DNMT1 and DNMT3B. This research was supported by NCI grant CA148818. 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 1628. doi:1538-7445.AM2012-1628
A8.9 Rheumatoid arthritis synovial IL-21 + CD4+ t cells specifically induce matrix metalloproteinase production by fibroblast-like synoviocytes
Authors: M Cristina Lebre, Pedro L Vieira, Saida Aarrass, Thomas Newsom-Davis, Paul P Tak, Gavin R Screaton
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background/Purpose</h3> IL-21 is a cytokine produced by activated CD4+ T cells and T follicular helper cells (TFh) that has been implicated in several autoimmune diseases including rheumatoid arthritis (RA). IL-21 regulates antibody production by B cells and induces osteoclastogenesis, mechanisms that contribute to rheumatoid arthritis (RA) pathology. Importantly, IL-21R blockade ameliorates arthritis in mice. Here we investigated the functional characteristics of synovial CD4+ IL-21 + T cells in RA. <h3>Methods</h3> Matched peripheral blood (PB) and synovial fluid (SF) from 13 RA and 6 psoriatic arthritis (PsA) patients, and PB of 17 healthy control (HC) subjects were stimulated with PMA/Ionomycin/brefeldin A and intracellular cytokine production assessed by FACS. STAT3-dependent IL-21 production by SF CD4+ T cells was investigated by using a STAT3 specific inhibitor (WP1066). The effects of IL-21 were evaluated on cytokine and matrix metalloproteinase (MMP) release by RA synovial biopsies. In addition, the capacity of sorted RA SF IL-21 + or IL-21-CD4+ T cells in mediator release by fibroblast-like synoviocytes (FLS) was evaluated in co-cultures. IL-21, IL-6 and MMP-1 and MMP-3 concentrations were assessed by ELISA. <h3>Results</h3> The frequency of both SF IL-21 + CD4+ or IL-21 + TNF-a + CD4+ T cells in RA was significantly higher compared to PsA (p = 0.0140 and p = 0.0038, respectively). STAT3-specific inhibitor blocked significantly the production of IL-21 by SF CD4+ T cells. Synovial IL-21 + CD4+ T cells did not phenotypically fit the TFh cell paradigm in that they did not co-express CXCR5 and ICOS. The levels of SF IL-21 were associated with CRP, MMP-1 and MMP-3. Related to this, IL-21 selectively induced MMP-1 and MMP-3 secretion by RA synovial biopsies. Sorted SF IL-21 + CD4+ T cells induced specifically the release of MMP-1 and MMP-3 by FLS compared to medium (both p &lt; 0.0001) while IL-21-CD4+ T cells were not able to induce these MMPs. In addition, the capacity of IL-21 + and IL-21- CD4+ T cells to induce IL-6 production by FLS was similar. <h3>Conclusion</h3> The results of this study support the notion that RA IL-21-producing CD4 T cells are involved in promoting joint destruction by inducing MMP release. Therefore IL-21 might be a therapeutic target in RA.
Evaluation of immune-related response criteria (irRC) in patients (pts) with advanced melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475.
Authors: F. Stephen Hodi, Antoni Ribas, Adil Daud, Omid Hamid, Caroline Robert, Richard Kefford, Wen-Jen Hwu, Tara C. Gangadhar, Anthony M. Joshua, Peter Hersey, Jeffrey S. Weber, Roxana Stefania Dronca, Andrea Marie Perrone, Linda Gammage, Darcy Hille, Dahai Xue, Soonmo Peter Kang, Patrick Chun, Scot Ebbinghaus, Jedd D. Wolchok
Journal: Journal of Clinical Oncology (2014)

3006^ Background: Unique response patterns have been observed with immunotherapies, and both objective response and prolonged disease stabilization can occur after an initial increase in tumor size. irRC were developed to better characterize response to immunotherapy, but it is unclear how irRC perform in pts treated with PD-1 blockade. Here, we describe unique patterns of response to MK-3475 in MEL pts and evaluate irRC as an alternative criterion for comprehensive response assessment. Methods: Source population was pts from 3 MEL cohorts treated with MK-3475 2 mg/kg every 3 wk (Q3W), 10 mg/kg Q3W, or 10 mg/kg Q2W in a phase I trial. Tumor imaging was performed every 12 wk. Response was assessed by irRC and RECIST 1.1 by central review; irRC was used for pt management. Tumor flare and atypical delayed response were identified by using centrally assessed irRC data among pts on MK-3475 for ≥28 wk. Tumor flare was defined as unconfirmed PD at assessment 1 (ie, wk 12) and non-PD at assessment 2. Atypical delayed response was defined as PD at any time point followed by non-PD and then response. Survival data were analyzed in pts who had PD by RECIST but CR/PR/SD by irRC. Results: Among the 411 pts enrolled across the 3 MEL cohorts, 192 were on MK-3475 for ≥28 wk as of the analysis cut-off of 10/18/2013. Tumor flare was seen in 7 (3.6%) pts. In these pts, best overall response per irRC was CR (n = 1), PR (n = 4), and SD (n = 2). Atypical delayed response was seen in 6 (3.1%) pts. The 51 pts with PD by RECIST but CR/PR/SD by irRC had favorable OS compared with the 145 pts with PD by both criteria (Table). Conclusions: MEL pts treated with MK-3475 may experience unique patterns of response and should be managed accordingly. Similar to what has been observed with ipilimumab, conventional criteria such as RECIST may underestimate the benefit of MK-3475 in approximately 10% of treated pts. An updated version of response criteria that incorporate new data on PD-1 inhibitors may be appropriate for future consideration. Clinical trial information: NCT01295827. OS Rate 3 mo 6 mo 12 mo Pts with CR/PR/SD by RECIST and irRC (n = 215) 100% 98% 92% Pts with PD by RECIST but CR/PR/SD by irRC (n = 51) 100% 94% 67% Pts with PD by RECIST and irRC (n = 145) 79% 53% 34%
Abstract 1286: Elucidating the role of E2F2 in mediating human breast cancer metastasis
Authors: Inez Yuwanita, Danielle Barnes, Eran Andrechek
Journal: Cancer Research (2012)

Abstract In human breast cancer it is not the primary tumor that is the cause of mortality but tumor metastasis to distant sites. Therefore, it is important to elucidate the biological mechanisms that underlie the metastatic processes. To address this, we utilized bioinformatic methods in combination with biochemical assays and genetic studies. Specifically, we crossed MMTV-Myc transgenic mice with various activator E2Fs mutants. We found that the tumor incidence decreased in MMTV-Myc mice interbred with E2F2 and E2F3 mutant backgrounds. Surprisingly, we also found that the loss of E2F2 sharply increased the percentage of lung metastasis in MMTV-Myc mice. Here, we test whether these observations in mice translate to human breast cancer and identify the genes under the control of E2F2 transcription factor that are responsible for mediating breast cancer metastasis. To achieve these aims, we examined the probability of activation of the E2F2 transcription factors in human breast cancer. We calculated the probability of E2F2 activation and used this data to stratify the human breast cancer samples and their associated metastatic clinical data. Examining this data we found that a low probability of E2F2 pathway activation led to decreased time to distant metastasis. To account for this discrepancy, we performed hierarchical clustering of human and mouse gene expression datasets. We found two clusters of human breast tumors in which E2F2 played distinctly different roles in mediating metastasis. One particular cluster clustered with our mouse gene expression data and exhibited the same role for E2F2 where it increased time to distant metastasis. In addition, we examined the ontology of the genes in this cluster and found that the majority of these genes had putative E2F binding sites. To further identify genes that are involved in metastasis, we stratified human breast cancer metastasis clinical annotation using gene expression values from these genes. We found that there were seven genes that are uniquely differentially regulated in this cluster. Interestingly, we observed that this group of seven genes included genes that were implicated in the metastatic process such as MMP16. Taken together, our results showed that there is an important role for E2F2 in mediating breast cancer metastasis and using our bioinformatic methods, we have begun to elucidate this role of E2F2 in mediating breast cancer metastasis. Our future directions include further validation of these target genes in vitro and in vivo to establish the mechanism by which E2F2 mediates breast cancer metastasis. 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 1286. doi:1538-7445.AM2012-1286