tbuckley/cabot-search huggingface dataset:
IKZF2 Drives Self-Renewal and Blocks Myeloid Differentiation Programs in Myeloid Leukemic Stem Cells
Authors: Sun-Mi Park, Hyunwoo Cho, Angela Thornton, Trevor Stephen Barlowe, Timothy Chou, Sagar Chhangawala, Lauren Fairchild, Arthur Chow, James Taggart, Alexander Schurer, Antoine Gruet, Matthew Witkin, Jun Hyun Kim, Ethan Shevach, Andrei Krivstov, Scott A. Armstrong, Christina Leslie, Michael G. Kharas
Journal: Blood (2018)
Abstract 20154: Rhythm Control by Catheter Ablation Can Ameliorate Functional Mitral Regurgitation Associated With Tachycardia-Induced Heart Failure
Authors: Kazuhiro Nagaoka, Yasushi Mukai, Daisuke Yakabe, Shunsuke Kawai, Susumu Takase, Shujiro Inoue, Akiko Chishaki, Hiroyuki Tsutsui
Journal: Circulation (2017)

Background: Functional mitral regurgitation frequently coexists with heart failure and adversely affects its clinical status. We retrospectively analyzed the effects of rhythm control with catheter ablation (CA) on the degree of mitral regurgitation and tachycardia-induced heart failure. Methods: Among consecutive 622 patients undergoing first CA at our institution for atrial or ventricular tachycardia, we studied 16 patients (6 males, 70±7 y.o.) having at least moderate degree of mitral regurgitation due to tethering of the mitral apparatus or leaflet prolapse before CA. We compared clinical variables, echocardiographic parameters, and the degree of mitral regurgitation (0: none, 1:trivial, 2: mild, 3: moderate, 4: severe), before and after the CAs. Results: Targeted arrhythmia was atrial fibrillation (AF) in 13 (11 persistent AF), and incessant form of ventricular tachycardia (VT) in 2. At the 1-year of follow up, the degree of mitral regurgitation significantly decreased from 2.8±0.4 to 2.1±0.4(p=0.001...
Abstract 197: Coronary Aneurysm and Ectasia In Adults
Authors: Nam Su Kim, Jae-kyoon Hwang
Journal: Circulation (2015)

Background: We investigate the status of coronary aneurysm or ectasia in adults. Methods: We retrospectively reviewed all coronary angiograms and coronary computed tomography angiograms (CT) performed at Hanyang University Hospital between January 2011 and August 2014. Results: Coronary angiography was performed in 4383 patients. Coronary CT was performed in 4099 patients. Coronary aneurysm or ectasia was detected in 28 patients (0.63%) on coronary angiography and in 21 patients (0.51%) on coronary CT angiography. Mean age of patient with coronary aneurysm or ectasia on angiography or coronary CT is 60.5(SD 14.7) or 58.0(SD 11.2). Mean age of patient without coronary aneurysm or ectasia on angiography or coronary CT is 63.2(SD 12.7) or 57.2(SD 12.0). For 28 patients with coronary aneurysm or ectasia on coronary angiography, male and female ratio was 16:12. Age was for 57.6(SD 11.9) for male and 64.5(SD 17.6) for female. For 21 patients with coronary aneurysm or ectasia on CT angiography, male and female ratio was 14:7. Age was for 53.9(SD 8.3) for male and 66.1(SD 13.4) for female. The age gap between male and female was increased for patients with coronary aneurysm or ectasia on both studies. These suggest adult with coronary aneurysm or ectasia might have Kawasaki disease in young age. Conclusions: The mean age of male patients with coronary aneurysm or ectasia was lower than that of female patients without coronary aneurysm or ectasia. This indicates adult with coronary aneurysm or ectasia might have Kawasaki disease in young age.
FRI0320 Antimalarials protective effects in systemic lupus erythematosus in china
Authors: F. Wang, W. Zhang, X. Feng, L. Sun
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hydroxychloroquine (HCQ) and chloroquine (CQ), both known as antimalarial drugs, have become fundamental therapeutic elements in systemic lupus erythematosus (SLE) in these decades. However, their specific benefits on organs or in a large cohort of Chinese SLE patients haven't been elucidated. <h3>Objectives</h3> This retrospective multicenter study sought to examine the potential protective roles of antimalarials in a large retrospect multicenter study of SLE patients in China. <h3>Methods</h3> Data were collected from 1372 patients' first and following hospitalizations during 1999 to 2009. Laboratory variables, medications, disease activity, organ involvements, and survival statuses were analysed according to antimalarial usage. <h3>Results</h3> Antimalarials improved the survival of SLE patients as an independent predictor (HR 0.503, p=0.000). Using antimalarials protected patients with longer disease duration (&gt;2 years), SLEDAI (&gt;15) on admission, high SLEDAI (&gt;10) on discharge, organ involvements (cardiopulmonary, gastrointestinal, renal, hematologic), anti-dsDNA positive, and no application of cyclophosphamide. In second hospitalisation, compared to non-users, SLE patients who had been treating with antimalarial drugs had lower levels of total cholesterol (TC) (4.47 (0.13) mmol/L vs 5.03 (0.21) mmol/L, p=0.027) and less chance of anaemia (46.5% vs 58.2%, p=0.033). <h3>Conclusions</h3> Using antimalarials benefits outcomes of SLE patients through multiple facets in Chinese patients. <h3>Disclosure of Interest</h3> None declared
AB0920 Tumour necrosis factor inhibitors persistence in psoriatic arthritis patients
Authors: E. Vieira-Sousa, M. Eusébio, P. Ávila-Ribeiro, N. Khmelinskii, A.R. Machado, T. Martins Rocha, M. Bernardes, D. Santos-Faria, J. Leite Silva, H. Santos, C. Miguel, P. Carvalho, T. Costa, L. Teixeira, T. Meirinhos, P. Nero, M.J. Santos
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tumour necrosis factor inhibitors (TNFi) lead to a dramatic improvement in the management of psoriatic arthritis (PsA). Nevertheless, a significant proportion of patients still do not respond and/or are intolerant to TNFis, requiring treatment switch for an adequate control of disease activity. <h3>Objectives</h3> To assess TNFis drug retention and the main reasons for TNFi discontinuation in PsA patients. <h3>Methods</h3> This was a non-interventional study of PsA patients registered at the Rheumatic Diseases Portuguese Registry (Reuma.pt), with at least one TNFi prescription. Drug retention for a first, second and third line TNFi was assessed by Kaplan-Meier survival analysis. The reasons for discontinuation were described as frequencies. <h3>Results</h3> 750 PsA patients were included, with a mean age of 47.6 years (±11.6); 50.3% (n=377) female. 200 patients (26.7%) treated with adalimumab, 335 (44.7%) with etanercept, 114 (12.2%) with golimumab and 101 (13.5%) with infliximab, as first line TNFi. The majority (67.6%) were receiving concomitantly conventional synthetic disease modifying anti-rheumatic drugs (62.3% MTX) and 33.9% corticosteroids. The mean duration of TNFi retention was of 48.5±40.1 months, when treated with a 1st TNFi, decreasing to 35.5±33 months for the 2nd TNFi, and to 22.7±22.9 months for the 3rd TNFi (figure 1). After being treated with a 1st TNFi, the majority of discontinuers (35,8% of the total population), withdraw due to lack or loss of effectiveness (53.5%) and due to adverse events (24.4%). The rates of discontinuation for the 2nd and 3rd TNFi were of 39% and 54%, respectively. Lack or loss of effectiveness and adverse events were maintained the two main reasons of withdrawal for the 2nd (62.3%; 21.6%) and 3rd TNFi (63%; 22.2%). <h3>Conclusions</h3> PsA patients registered at Reuma.pt treated with a 1st TNFi had an overall drug retention of 49 months. We observed a decrease in the average retention of TNFi therapy of 13.0 months in PsA patients who switched to a 2nd TNFi or a 3rd TNFi. Lack or loss of response were the main reason for TNFi discontinuation, independently of TNFi position, responsible for more than half of the discontinuations. The observed short survival of TNFis in PsA, and the inability to regain drug expectancy when switching to another TNFi, highlights the limitations from recycling between TNFi when aiming at long-term disease remission. <h3>Acknowledgements</h3> Financial support for statistics and report writing was provided by Novartis, Produtos Farmacêuticos S.A. <h3>Disclosure of Interest</h3> None declared
c-Abl regulates YAPY357 phosphorylation to activate endothelial atherogenic responses to disturbed flow
Authors: Bochuan Li, Jinlong He, Huizhen Lv, Yajin Liu, Xue Lv, Chenghu Zhang, Yi Zhu, Ding Ai
Journal: Journal of Clinical Investigation (2019)

Local flow patterns determine the uneven distribution of atherosclerotic lesions. This research aims to elucidate the mechanism of regulation of nuclear translocation of Yes-associated protein (YAP) under oscillatory shear stress (OSS) in the atheroprone phenotype of endothelial cells (ECs). We report here that OSS led to tyrosine phosphorylation and strong, continuous nuclear translocation of YAP in ECs that is dependent on integrin α5β1 activation. YAP overexpression in ECs blunted the anti-atheroprone effect of an integrin α5β1–blocking peptide (ATN161) in Apoe–/– mice. Activation of integrin α5β1 induced tyrosine, but not serine, phosphorylation of YAP in ECs. Blockage of integrin α5β1 with ATN161 abolished the phosphorylation of YAP at Y357 induced by OSS. Mechanistic studies showed that c-Abl inhibitor attenuated the integrin α5β1–induced YAP tyrosine phosphorylation. Furthermore, the phosphorylation of c-Abl and YAPY357 was significantly increased in ECs in atherosclerotic vessels of mice and in human plaques versus normal vessels. Finally, bosutinib, a tyrosine kinase inhibitor, markedly reduced the level of YAPY357 and the development of atherosclerosis in Apoe–/– mice. The c-Abl/YAPY357 pathway serves as a mechanism for the activation of integrin α5β1 and the atherogenic phenotype of ECs in response to OSS, and provides a potential therapeutic strategy for atherogenesis.
Focus on automating care may lead us astray
Authors: Katie Featherstone, Paula Boddington
Journal: BMJ (2019)

Oliver is concerned by Ara Darzi’s call for full automation of repetitive tasks in health and care services.1 Robotics may be a useful avenue to explore, but to present care as repetitive tasks ripe for automation may be problematic.

Our team’s research programme involves detailed observations of ward staff’s bedside care to people with dementia …
Abstract 14086: Investigation of Inflammatory Markers and Cardiac Events Following Discontinuation of Interleukin-1 Receptor Antagonist in NSTE-ACS Patients
Authors: Alexander M Rothman, Allison Morton, John Greenwood, Julian Gunn, Alex Chase, Bernard Clarke, Alistair Hall, Keith Fox, Claire Foley, Winston Banya, Duolao Wang, Marcus Flather, David C Crossman
Journal: Circulation (2015)

Background: The ILA HEART study demonstrated that administration of IL-1 receptor antagonist (IL-1ra) for 14 days after onset of NSTE-ACS reduced high sensitivity C-reactive protein (hsCRP) at 7 and 14 days, however day 30 hsCRP and 1 year MACE were both increased. Objectives: To analyze the inflammatory effect of withdrawal of IL-1ra following effective suppression of hsCRP in the context of NSTE-ACS. Methods and Results: Mixed-model analysis was performed with log hsCRP as dependent variable, day 1 hsCRP as covariate, treatment, day, and treatment/day interaction as fixed effects, and patient as random effect. Mixed-model analysis (Table 1) demonstrates increased hsCRP in the IL-1ra group at day 30 (vrs day 14 IL-1ra, p&lt;0.0001 and vrs day 30 placebo, p=0.0196). Analysis of achieved hsCRP at day 14 demonstrates suppression of hsCRP with IL-1ra in each tertile (Fig 1A). In contrast to the placebo group, withdrawal of IL-1ra results in loss of hsCRP suppression. Within the IL-1ra group hsCRP was higher in patients suffering MACE events (Fig 1B). Conclusions: Inhibition of IL-1 for 14 days after NSTE-ACS temporarily suppresses CRP. It seems likely that anti-IL-1 therapy will need to be continued for longer after NSTE-ACS.
The Prognostic Impact of t(14;16) in Multiple Myeloma: A Multicenter Retrospective Study of 213 Patients. Is It Time to Revise the Revised ISS?
Authors: Artur Jurczyszyn, Sarah Goldman-Mazur, Jorge J. Castillo, Anna Waszczuk-Gajda, Norbert Grząśko, Jakub Radocha, Max Bittrich, Alessandro Gozzetti, Lidia Usnarska-Zubkiewicz, Iwona Hus, Andrew J Yee, David S Jayabalan, Ruben Niesvizky, Julia Kelman, Daniel Coriu, Laura Rosinol Dachs, Łukasz Szukalski, Julio Dávila, Veronica Gonzalez De La Calle, Krzysztof Jamroziak, Irit Avivi, Yael C Cohen, Anna Suska, Aimee Chappell, Deepu Madduri, Saurabh Chhabra, Ariel Kleman, Parameswaran Hari, Paweł Robak, Massimo Gentile, Izabela Kozłowska, Stuart L. Goldberg, David H Vesole
Journal: Blood (2018)
THU0266 The value of belonging to patients’ association for axial spondyloarthritis: results from the atlas-2017
Authors: M. Garrido-Cumbrera, D. Gálvez-Ruiz, E. Collantes Estevez, C. Blanch Mur, V. Navarro-Compán
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> International guidelines suggest that patients with axial spondyloarthritis (axSpA) become members of patient associations and self-help groups. However, the scientific evidence for this advice is limited and poor. <h3>Objectives</h3> To assess the relationship between membership of axSpA patient associations with regard to physical and psychological outcomes of the disease. <h3>Methods</h3> A sample of 680 axSpA patients was interviewed as part of the Spanish-2017 Atlas, which aimed to promote early referral, improve healthcare, and the use of effective treatments in patients with axSpA. By means of an online survey, the following self-reported data were collected: sociodemographic, smoking habits, degree of functional limitation in 18 daily activities (graded from 0–3 as none, little, some, moderate), spinal stiffness level at cervical, thoracic, and lumbar spine (0–3 none, little, some, moderate), disease activity through BASDAI (0–10), risk of severe psychiatric illness using General Health Questionnaire – GHQ-12 (0–12), and treatment received (NSAIDs and biological therapy). Differences for all these variables between associated-patients and non-associated patients were tested, using Mann-Whitney or Chi-square tests. <h3>Results</h3> Out of 680 patients, 301 (44.3%) were members of patient associations. Compared to non-associated patients, those associated were older, more frequently male, married, and few smoked (table 1). Additionally, despite having longer disease duration and receiving similar treatment, associated patients had lower disease activity (BASDAI 5.1 vs 5.8; p=0.001), less functional limitation (26.5 vs 28.7; p&lt;0.05), and less risk of severe psychiatric illness (GHQ-12 4.9 vs 6.5; p&lt;0.001). <h3>Conclusions</h3> In axSpA, belonging to patient associations is related to better physical and psychological outcomes. Accordingly, rheumatologists should encourage patients to join these groups. However, further data on longitudinal studies is required to confirm these results. <h3>Acknowledgements</h3> The Atlas was promoted by CEADE and funded by Novartis <h3>Disclosure of Interest</h3> M. Garrido-Cumbrera: None declared, D. Gálvez-Ruiz: None declared, E. Collantes Estevez: None declared, C. Blanch Mur Employee of: Novartis, V. Navarro-Compán: None declared
A novel non-peptide and orally active proteasome inhibitor overcomes bortezomib-resistance in multiple myeloma (MM) cells
Authors: Dharminder Chauhan, Laurence Catley, Guilan Li, Martin Sattler, Klaus Podar, Teru Hideshima, Nikhil Munshi, Paul Richardson, Ta-Hsiang Chao, Saskia Neuteboom, Michael Palladino, Kenneth C. Andersn
Journal: Cancer Research (2005)

6153  Bortezomib/PS-341 is a novel proteasome inhibitor for the treatment of relapsed/refractory multiple myeloma (MM) patients; however, some patients have intrinsic and others acquire resistance. Here we demonstrate that a novel non-peptide proteasome inhibitor NPI-0052 triggers apoptosis even in bortezomib-resistant patient MM cells, without altering the viability of normal cells. NPI-0052 overcomes MM cell-resistance to conventional therapies including melphalan (LR5), doxorubicin (Dox-40), and dexamethasone (MM.1R, U266, RPMI-8226) Moreover, NPI-0052 retains its anti-tumor activity in cancer cells overexpressing P-glycoprotein and altered topoisomerase-II activity. Importantly, NPI-0052 blocks MM cell growth triggered by adhesion to bone marrow stromal cells (BMSCs) and related cytokine secretion. Moreover, NPI-0052 induces MM cells apoptosis even in the presence of interleukin-6 or insulin-like growth factor-1, two major survival/anti-apoptotic factors for MM cells. NPI-0052 also overcomes the cytoprotective effects of anti-apoptotic proteins Bcl2 and Hsp27 in MM cells. NPI-0052-triggered MM cell death is associated with these events: loss of mitochondrial membrane potential; superoxide generation; release of mitochondrial proteins cytochrome-c/Smac; and activation of caspase-8/9/3. Conversely, the pan caspase inhibitor Z-VAD-fmk abrogates NPI-0052-induced apoptosis. Initial in vivo studies in animal models using either oral or intravenous administration have established the maximum tolerated dose (MTD) based on the whole blood proteasome activity. NPI-0052 decreased proteasome activity in packed whole blood lysates in a dose dependent fashion, and these data also suggest that NPI-0052 is orally active. Finally, combining NPI-0052 and bortezomib triggers synergistic apoptosis (Combination Index
Outcomes of treatment for hepatitis C in prisoners using a nurse-led, statewide model of care
Authors: Timothy Papaluca, Lucy McDonald, Anne Craigie, Annabelle Gibson, Paul Desmond, Darren Wong, Rebecca Winter, Nick Scott, Jessica Howell, Joseph Doyle, Alisa Pedrana, Andrew Lloyd, Mark Stoove, Margaret Hellard, David Iser, Alexander Thompson
Journal: Journal of Hepatology (2019)
Abstract 15975: Multimorbidity is Associated With Greater Risk of Thromboembolism and Bleeding in Patients With Atrial Fibrillation but a Constant Benefit of Apixaban: Results From ARISTOTLE
Authors: Karen P Alexander, Marc Brouwer, Hillary Mulder, Dragos Vinereanu, Renato D Lopes, Sana M Al-Khatib, Ziad Hijazi, Sigrun Halvorsen, Elaine M Hylek, Freek W Verheugt, John H Alexander, Lars Wallentin, Christopher B Granger
Journal: Circulation (2017)

Background: Multimorbidity (MM), defined as ≥3 chronic conditions, is a marker of frailty, polypharmacy, and adverse events. For patients with atrial fibrillation (AF), anticoagulation may pose increased risks with greater MM burden. We assessed prevalence of MM, its association with clinical outcomes, and the efficacy and safety of apixaban and warfarin in the setting of MM. Methods: ARISTOTLE randomized patients with AF to apixaban or warfarin. Baseline information on 17 different comorbid conditions including endocrine, GI, musculoskeletal, renal, hematologic, pulmonary, cognitive, vascular, and cardiac systems was collected. Enrolled patients age ≥55 years (N=16,800) were divided into groups based on number of conditions; few 0-2 (n=6087, 36.2%), moderate 3-5 (n=8491, 50.6%), and greatest 6+ (n=2222, 13.2%). Median follow-up was 1.8 years. Results: MM was present in 63%. Compared with those with few comorbidities, the greatest comorbidity group was older (74 vs. 69 yrs), took twice as many medications...
Is laser lithotripsy the most successful and the safest advanced lithotripsy technique for retained biliary tract stones?
Authors: Zheng Jin, Jing Yang, Hangbin Jin, Xiaofeng Zhang
Journal: Endoscopy (2018)

We read with interest the recent systematic review by Veld et al. [1] comparing the efficacy and safety of electrohydraulic lithotripsy (EHL), laser lithotripsy, and extracorporeal shock wave lithotripsy in the management of retained biliary tract stones. The authors concluded that laser lithotripsy was currently the most successful and the safest advanced lithotripsy technique for retained biliary tract stones. However, we believe that several issues need to be addressed.
THU0283 Patients with psoriatic arthritis who are not eligible for randomised clinical trialsfor tnf inhibitors have similar treatment response and drug survival. results from the icebio registry
Authors: O. Palsson, B. Guðbjörnsson, G.A. Jóhannsdóttir, A. Gunnarsdóttir, P.S. Gunnarsson, T.J. Love, E. Rúnarsdóttir
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> We have recently reported that a majority of patients with psoriatic arthritis who are being treated with TNF inhibitors in Iceland would not have been eligible for the randomised clinical trials (RCTs) performed leading up to registration of the respective pharmaceutical product.<sup><sup>1</sup></sup> <h3>Objectives</h3> To determine whether patients with psoriatic arthritis who did not fulfil the inclusion criteria (group B) in RCTs receive similar benefits and drug survival from TNF inhibitors as those patients who would have fulfilled the inclusion criteria (group A). <h3>Methods</h3> All patients with rheumatic disorders who are treated with biologic DMARDs in Iceland are registered in ICEBIO. ICEBIO is based on the Danish Registry for biologic therapies in rheumatology<sup><sup>2</sup></sup> and has data about approximately 98% of all patients with psoriatic arthritis treated with biologic DMARDs in Iceland. On February 1st 2016 there was information on 1058 individuals in ICEBIO.231 patients with psoriatic arthritis received their first-line treatment and could be classified according to inclusion criteria of respective pharmaceutical RCT.<sup><sup>1</sup></sup> Information on disease activity at baseline was collected and we estimate the treatment response at 6 and 18 months according to ACR20 and DAS28CRP and drug survival. <h3>Results</h3> The groups were similar at baseline (table 1), although Group A predictably had higher SJC (5,5 vs 3,8) and subsequently higher DAS28CRP (4.6 vs 4.2). Out of 231 patients we have sufficient data to determine ACR20 and DAS28CRP response in 92 and 91 patients respectively. Treatment response is outlined in table 2, with better response in group A in regards to HAQ and SJC. There was similar drug survival between the groups (figure 1). <h3>Conclusions</h3> Patients with psoriatic arthritis that would not have fulfilled the inclusion criteria in RCTs seem to respond to treatment effectively and have similar drug survival. Thus, treatment outcomes for psoriatic arthritis from RCTs may probably be applied to daily clinical practice, whether patients would have fulfilled RCT criterias or not. However, more detailed studies are needed. <h3>References</h3> [1] Runarsdottir EE, Gunnarsdottir AI, Love TJ, Gunnarsson PS, Gudbjornsson B. The majority of patients with psoriatic arthritis are not eligible for randomized clinical trials. [2] DANBIO 2017. https://danbio-online.dk/om-danbio. <h3>Disclosure of Interest</h3> None declared
Number of Mutations and Type of Prior Myeloproliferative Neoplasm Are Prognostic Factors in Acute Myeloid Leukemia Post Myeloproliferative Neoplasms
Authors: Edmond Chiche, Sarah Bonnet, Sarah Bertoli, Andrew T Kuykendall, Lauris Gastaud, Pascal Boulay, Veronique De Mas, Eric Delabesse, Alice Marceau-Renaut, Claude Preudhomme, Anne Murati, David A Sallman, S. Dominique Raynaud, Christian Recher, Norbert Vey, Thomas Cluzeau
Journal: Blood (2018)