tbuckley/cabot-search huggingface dataset:
Abstract 17358: Preliminary Results from AATAC: Ablation vs Amiodarone for the Treatment of Persistent and Long Standing Persistent Atrial Fibrillation in Patients With Congestive Heart Failure.
Authors: Luigi Di Biase, Prasant Mohanty, Antonio Raviele, Pierre Jais, Sakis Themistoclakis, Pasquale Santangeli, Sanghamitra Mohanty, Antonio Dello Russo, Michela Casella, Gemma Pelargonio, Pietro Santarelli, William R. Lewis, Robert A. Schweikert, Raimondo Massaro, Raffaele Fanelli, Domenico Potenza, Javier Sanchez, Rodney Horton, Dhanunjay Lakkireddy, Jason Zagrodzky, Claude Elayi, Amin Al-Ahamad, Giovanni Forleo, Claudio Tondo, J. David Burkhardt, Michelle Haissaguerre, Andrea Natale
Journal: Circulation (2010)

Introduction: Catheter ablation is being increasingly used for the treatment of patients with congestive heart failure and atrial fibrillation (AF). Whether catheter ablation is superior to Amiodarone for the treatment of AF in this subset of patients is unknown. The aim of this study was to randomize the two different treatments and to look at freedom from AF at follow-up. Methods: 105 consecutive patients with symptomatic, persistent or long-standing persistent atrial fibrillation, with EF ≤ 35% and NYHA II-III were randomized into 2 groups: pts undergoing treatment of AF with Amiodarone (n=52) and patients undergoing catheter ablation of atrial fibrillation off Amiodarone (n=53). In patients undergoing ablation, pulmonary vein isolation (PVI) was guided by circular mapping. The electrical isolation of the pulmonary veins was extended to the entire posterior wall. In addition linear lesions and ablation of complex fractionated atrial electrograms (CFAEs) in the right and left atrium and in the coronary ...
AB0445 Therapeutic maintenance of abatacept in rheumatoid arthritis: results of the ric-aba study (517 PATIENTS)
Authors: J.H. Salmon, J.G. Letarouilly, P. Coquerelle, V. Goeb, M.H. Guyot, E. Houvenagel, N. Lecuyer, L. Le Dantec, L. Marguerie, G. Morel, G. Baudens, E. Solau, R.-M. Flipo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Objectives</h3> Study the therapeutic maintenance, associated factor with maintenance at 12 months and reasons for abatacept (ABA) stop in daily practice. <h3>Methods</h3> Retrospective multicentric study, from the RIC Nord de France network, of patients treated for rheumatoid arthritis who received at least one ABA treatment between January 2008 and July 2016. We studied the therapeutic maintenance at 12 months, according to the number of previous bDMARDs and according to the date of initiation (group 1: from 2008 until 31/07/2010 (ABA authorised in anti-TNFfailure) and group 2 from 01/08/2010 (ABA authorised in the first line)). Therapeutic maintenance was evaluated using the Kaplan-Meier method. <h3>Results</h3> Of the 517 patients (74% women) who were included, the mean age was 61.4±13.3 years. There were 76% positive anti-CCP. ABA was used as monotherapy in 176 patients (34%) and 22% of patients were naïve to bDMARDs. The mean DAS 28-VS at initiation of ABA was 4.7±1.3. Therapeutic maintenance at 12 months was 68%. Among the 166 patients (32%) stopped ABA, the reason for discontinuation was primary ineffectiveness (n=54, 32.5%), loss of efficacy (n=40, 24%), adverse events (n=43, 26%) and other (n=29, 17.5%). On multivariate analysis CRP &lt;10 mg/L was associated with better maintenance at 12 months. No significant difference in therapeutic maintenance was found at 12 months according to the date of initiation and according to the number of previous bDMARDs. <h3>Conclusions</h3> Therapeutic maintenance at 12 months was 68%, this rate is similar to Pan-European Registry. The rate of CRP at initiation seems to have an impact on the maintenance of ABA at 12 months. <h3>Reference</h3> [1] Gottenberg JE, Courvoisier DS, Hernandez MV, Iannone F, Lie E, Canhão H, et al. Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis. Arthritis Rheumatol2016Jun;68(6):1346–52. doi:10.1002/art.39595 <h3>Disclosure of Interest</h3> None declared
Abstract 16229: The Performance of Dispatcher Assisted Cardiopulmonary Resuscitation Among Elderly Laypersons is Inferior Compared to Young Laypersons: A Simulation Study
Authors: Mette A Nebsbjerg, Stinne E Rasmussen, Katrine Bjørnshave, Lise Q Krogh, Kristian Krogh, Jonas A Povlsen, Ingunn S Riddervold, Thorbjørn Grøfte, Hans Kirkegaard, Bo Løfgren
Journal: Circulation (2015)

Introduction: Standardized instructions in dispatcher assisted CPR (DA-CPR) increase the rate and quality of bystander CPR. Most cardiac arrests occur in private homes and the most likely bystander to initiate CPR is an elderly layperson. Studies on elderly performing DA-CPR are sparse. The aim of this study was to compare the performance of DA-CPR between elderly and young laypersons. Hypothesis: DA-CPR performance is inferior among elderly laypersons compared to young laypersons. Methods: The study was performed in two substudies. Substudy 1 compared the performance of DA-CPR between elderly (&gt;65 years) and young (18 - 40 years) laypersons. Substudy 2 evaluated the attainable level of CPR skills after attending a standardized CPR course. CPR was performed in a mock cardiac arrest scenario in both substudies. CPR quality data was obtained from the manikin and video recordings. CPR performance was evaluated by two assessors. The primary endpoint was chest compression depth during DA-CPR. Secondary endpoints included chest compression rate, time to first compression and hands-off time. Results: In total, 120 laypersons were included. Substudy 1 (DA-CPR): Elderly laypersons performed significantly shallower (mean (SD): 39 (19) mm vs. 56 (14) mm, p&lt;0.001) and slower (median (IQR): 84 (74 - 107) min-1 vs. 107 (97 - 112) min-1, p&lt;0.001) chest compressions compared to young laypersons. Elderly laypersons had significantly longer time to first compression (mean (SD): 104 (38) sec vs. 71 (11) sec, p&lt;0.001) and significantly more hands-off time pr. minute (median (IQR): 5 (2 - 10) sec vs. 0 (0 - 1) sec, p&lt;0.001) than young laypersons. Substudy 2 (End-of-course assessment): Elderly laypersons performed significantly shallower (mean (SD): 50 (14) mm vs. 64 (8) mm, p&lt;0.001) and slower (mean (SD): 93 (18) min-1 vs. 111 (11) min-1, p&lt;0.001) chest compressions compared to young laypersons. Conclusions: Performance of DA-CPR is inferior among elderly laypersons compared to young laypersons. The study found an acceptable quality of CPR skills among both elderly and young laypersons after CPR-training.
Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass smoke-related COPD
Authors: Baishakhi Ghosh, Akshay H. Gaike, Kanchan Pyasi, Bill Brashier, Vandana V. Das, Jyoti D. Londhe, Sanjay Juvekar, Yogesh S. Shouche, Louise E. Donnelly, Sundeep S. Salvi, Peter J. Barnes
Journal: European Respiratory Journal (2018)

Lower airway colonisation with species of potentially pathogenic bacteria (PPB) is associated with defective bacterial phagocytosis, in monocyte-derived macrophages (MDMs) and alveolar macrophages, from tobacco smoke-associated chronic obstructive pulmonary disease (S-COPD) subjects. In the developing world, COPD among nonsmokers is largely due to biomass smoke (BMS) exposure; however, little is known about PPB colonisation and its association with impaired innate immunity in these subjects.We investigated the PPB load (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa) in BMS-exposed COPD (BMS-COPD) subjects compared with S-COPD and spirometrically normal subjects. We also examined the association between PPB load and phagocytic activity of MDMs and lung function. Induced sputum and peripheral venous blood samples were collected from 18 healthy nonsmokers, 15 smokers without COPD, 16 BMS-exposed healthy subjects, 19 S-COPD subjects and 23 BMS-COPD subjects. PPB load in induced sputum and MDM phagocytic activity were determined using quantitative PCR and fluorimetry, respectively.Higher bacterial loads of S. pneumoniae, H. influenzae and P. aeruginosa were observed in BMS-COPD subjects. Increased PPB load in BMS-exposed subjects was significantly negatively associated with defective phagocytosis in MDMs and spirometric lung function indices (p<0.05).Increased PPB load in airways of BMS-COPD subjects is inversely associated with defective bacterial phagocytosis and lung function.
Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity
Authors: Hannelie Korf, Johannie du Plessis, Jos van Pelt, Sofie De Groote, David Cassiman, Len Verbeke, Bart Ghesquière, Sarah-Maria Fendt, Matthew J Bird, Ali Talebi, Matthias Van Haele, Rita Feio-Azevedo, Lore Meelberghs, Tania Roskams, Rajeshwar P Mookerjee, Gautam Mehta, Rajiv Jalan, Thierry Gustot, Wim Laleman, Frederik Nevens, Schalk Willem van der Merwe
Journal: Gut (2018)

Acute-on-chronic liver failure (ACLF) is associated with dysfunctional circulating monocytes whereby patients become highly susceptible to bacterial infections. Here, we identify the pathways underlying monocyte dysfunction in ACLF and we investigate whether metabolic rewiring reinstates their phagocytic and inflammatory capacity.Following phenotypic characterisation, we performed RNA sequencing on CD14+CD16- monocytes from patients with ACLF and decompensated alcoholic cirrhosis. Additionally, an in vitro model mimicking ACLF patient-derived features was implemented to investigate the efficacy of metabolic regulators on monocyte function.Monocytes from patients with ACLF featured elevated frequencies of interleukin (IL)-10-producing cells, reduced human leucocyte antigen DR isotype (HLA-DR) expression and impaired phagocytic and oxidative burst capacity. Transcriptional profiling of isolated CD14+CD16- monocytes in ACLF revealed upregulation of an array of immunosuppressive parameters and compromised antibacterial and antigen presentation machinery. In contrast, monocytes in decompensated cirrhosis showed intact capacity to respond to inflammatory triggers. Culturing healthy monocytes in ACLF plasma mimicked the immunosuppressive characteristics observed in patients, inducing a blunted phagocytic response and metabolic program associated with a tolerant state. Metabolic rewiring of the cells using a pharmacological inhibitor of glutamine synthetase, partially restored the phagocytic and inflammatory capacity of in vitro generated- as well as ACLF patient-derived monocytes. Highlighting its biological relevance, the glutamine synthetase/glutaminase ratio of ACLF patient-derived monocytes positively correlated with disease severity scores.In ACLF, monocytes feature a distinct transcriptional profile, polarised towards an immunotolerant state and altered metabolism. We demonstrated that metabolic rewiring of ACLF monocytes partially revives their function, opening up new options for therapeutic targeting in these patients.
A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma
Authors: Wan-Hong Zhao, Jie Liu, Bai-Yan Wang, Yin-Xia Chen, Xing-Mei Cao, Yun Yang, Yi-Lin Zhang, Fang-Xia Wang, Peng-Yu Zhang, Bo Lei, Liu-Fang Gu, Jian-Li Wang, Nan Yang, Ru Zhang, Hui Zhang, Ying Shen, Ju Bai, Yan Xu, Xu-Geng Wang, Rui-Li Zhang, Li-Li Wei, Zong-Fang Li, Zhen-Zhen Li, Yan Geng, Qian He, Qiu-Chuan Zhuang, Xiao-Hu Fan, Ai-Li He, Wang-Gang Zhang
Journal: Journal of Hematology & Oncology (2018)

Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM). This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group. At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached. LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered
Acute stressor alters inter-species microbial competition for resistant starch-supplemented medium
Authors: Ida Gisela Pantoja-Feliciano, Jason W. Soares, Laurel A. Doherty, J. Philip Karl, Holly L. McClung, Nicholes J. Armstrong, Tobyn A. Branck, Steven Arcidiacono
Journal: Gut Microbes (2018)

Gut microbiome community dynamics are maintained by complex microbe-microbe and microbe-host interactions, which can be disturbed by stress. In vivo studies on the dynamics and manipulation of those interactions are costly and slow, but can be accelerated using in vitro fermentation. Herein, in vitro fermentation was used to determine how an acute stressor, a sudden change in diet, impacts inter-bacterial species competition for resistant starch-supplemented medium (RSM). Fermentation vessels were seeded with fecal samples collected from 10 individuals consuming a habitual diet or U.S. military rations for 21 days. Lactobacillus spp. growth in response to RSM was attenuated following ration consumption, whereas growth of Ruminococcus bromii was enhanced. These differences were not evident in the pre-fermentation samples. Findings demonstrate how incorporating in vitro fermentation into clinical studies can increase understanding of stress-induced changes in nutrient-microbiome dynamics, and suggest that sudden changes in diet may impact inter-species competition for substrates.
Abstract P003: Application of a Lifestyle-based Score to Predict Cardiovascular Health in the Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Holly C Gooding, Hongyan Ning, Matthew W Gillman, Christina M Shay, Norrina Allen, David C Goff, Jamal S Rana, Stephanie Chiuve, Donald Lloyd-Jones
Journal: Circulation (2017)

Introduction: The Healthy Heart Score (HHS) is a lifestyle-based risk prediction tool developed to predict cardiovascular disease (CVD) events in young and middle-aged adults. We evaluated the performance of the HHS to predict cardiovascular health (CVH). Methods: We applied the HHS to 3288 white and black adults ages 18-30 years at the CARDIA study baseline exam in 1985-6. The HHS includes age, smoking status, body mass index, alcohol intake (g/d), exercise (hours/week) and a diet score composed of self-reported daily intake of cereal fiber, fruits/vegetables, nuts, sugar-sweetened beverages, and red/processed meats. We tested the utility of the HHS to predict having all ideal CVH factors at the year 25 exam when participants were ages 43-55 years, defined as the simultaneous presence of unmedicated blood pressure &lt;120/80 mmHg, total cholesterol&lt;200 mg/dl, fasting glucose&lt;100 mg/dl and absence of diabetes or CVD. We assessed the HHS in the total population, in race and sex-specific groups, and in those with and without clinical CVD risk factors (RFs) at baseline. We first applied original HHS coefficients, then cohort specific coefficients. We assessed model discrimination in comparison to age-only models with Harrell’s C-statistic and model calibration with Hosmer-Lemeshow’s chi-square. Results: Mean (SD) age at baseline was 25.1 (3.6) years; 57% were female, 46% black, and 8% had at least one clinical CVD RF at baseline. Only 593 participants (18%) had all ideal CVH factors in middle age; the prevalence was lower in men compared to women, blacks compared to whites, and in those with vs. without clinical CVD RFs in young adulthood (Table). The HHS showed moderate discrimination for CVH prediction (Table). The HHS was adequately calibrated overall and within each sub-group. Conclusions: The HHS performs moderately well predicting CVH 25 years later when applied to young adults. Its reliance on self-reported, modifiable lifestyle factors makes it an attractive tool for the promotion of CVH across the lifespan.
Scientists on the Spot: the Guide to Immunopharmacology as a new resource for the cardiovascular community
Authors: Pasquale Maffia, Alberto Mantovani, Michael Spedding
Journal: Cardiovascular Research (2018)

In this Onlife interview, the Guide to Immunopharmacology is introduced: a free database containing immunopharmacological targets and associated cell types. Professors Mantovani and Spedding speak about the usefulness of this resource for the cardiovascular community and more.
One stone with two birds: Phytic acid-capped platinum nanoparticles for targeted combination therapy of bone tumors
Authors: Zhengjie Zhou, Tianqi Fan, Yang Yan, Song Zhang, Yi Zhou, Hanbin Deng, Xiaopan Cai, Jianru Xiao, Dianwen Song, Qiang Zhang, Yiyun Cheng
Journal: Biomaterials (2018)
The impact of diabetes mellitus on early cervical cancer in Αsia: A population-based cohort study.
Authors: Hung-Yang Kuo, Zhong-Zhe Lin, Raymond Nienchen Kuo, Wen-Yi Shau, Chiu-Lin Lai, Yen-Yun Yang, Yu Yun Shao, Chiun Hsu, Wen-Fang Cheng, Ann-Lii Cheng, James Chih-Hsin Yang, Mei-Shu Lai
Journal: Journal of Clinical Oncology (2014)

e16501 Background: Diabetes mellitus (DM) has been associated with increased incidence and poor prognosis of several cancers such as colon, liver, and breast cancer. However, the impact of DM on survival outcomes of patients with early cervical cancer (CCa) remained undetermined. Methods: Patients (pts) who had been newly diagnosed with FIGO stage I-IIA CCa between 2004 and 2008 were identified from the Taiwan Cancer Registry (TCR).DM status was determined using National Health Insurance claim database. Eligible pts should receive definitive treatments (definitive radiotherapy, chemoradiation, or surgery) with curative intent. Survival outcomes were compared using the Kaplan Meier Curves. Multivariate analysis was performed using Cox Proportional regression models. Results: After screening of 21,352 newly diagnosed CCa pts from TCR, total 2,946 pts were eligible for the final analysis. Of them, 284 (9.6%) had DM. No significant difference in tumor size and stage was found between DM and non-DM groups. The overall survival (OS) rates for pts with and without DM were 73.9% and 87.9% at 5 years, respectively. The 5-yr cancer-specific survival rates (CSS) for pts with and without DM were 85.4% and 91.5%, respectively. In multivariate analysis, DM is an independent predictor of a lower CSS probability (adjusted hazard ratio [HR], 1.46; 95% CI, 1.03 –2.08; p = 0.032) and OS probability (adjusted HR, 1.55; 95% CI, 1.21-2.00; p = 0.0007) after adjusting for age, tumor size and stage, nodal stage, histology, modalities of curative treatment, and comorbidities. Conclusions: DMincreases the risks of both OS and CSS for pts with stage I-IIA CCa after curative treatments.
Macrophage entrapped silica coated superparamagnetic iron oxide particles for controlled drug release in a 3D cancer model
Authors: Sami Ullah, Katja Seidel, Sibel Türkkan, Dawid Peter Warwas, Tatyana Dubich, Manfred Rohde, Hansjörg Hauser, Peter Behrens, Andreas Kirschning, Mario Köster, Dagmar Wirth
Journal: Journal of Controlled Release (2018)
Abstract P207: An Interpretation-Friendly Approach for Model Comparison of Risk Scores for Adult Obesity in the International Childhood Cardiovascular Cohort (I3c) Consortium
Authors: Tian Hu, Alan Sinaiko, Jessica Woo, Trudy Burns, Julia Steinberger, Lydia Bazzano, Elaine Urbina, Nanhua Zhang, Costan Magnussen, Alison Venn, Markus Juonala, Olli Raitakari, Stephen Daniels, Terence Dwyer, David Jacobs
Journal: Circulation (2018)

Introduction: Continuous Net Reclassification Improvement (NRI) compares risk prediction between 2 models, but the NRI scale is hard to interpret as a difference of differences of correct vs. incorrect reclassification. We developed Discrimination Improvement Analysis (DIA), a mathematically-related alternative. We illustrate DIA in i3C comparing P(adult obese) estimated from childhood either using body mass index (BMI; base model) or BMI percentile (CDC Chart 2000; alternative model). Methods: In both DIA and NRI (described in the Table), reclassification is based on the regression discriminant to assess reclassification up when predicted risk is increased under the alternative model (&gt;0), and down when the opposite is true (≤0). The DIA metric is the “added spread”: observed P(adult obese) in those reclassified up minus in those reclassified down. Using Bayes rule, continuous NRI is a weighted average of the P(adult obese) in those reclassified up vs down. We used first childhood BMI (age 3-19 y) and last adult BMI (age 30-50 y) in i3C. Logistic regression estimated P(adult obese) in the base model and the alternative model. Results: Of 8864 participants (47% men, 89% white, mean child BMI age 11 y (SD 4), mean adult age 38 y (SD 6)), 2436 were obese adults (last adult BMI≥30 kg/m 2 ). Both absolute BMI and BMI percentile were independent predictors (Table). Average P(adult obese) in the base model was 24.1%. The alternative model significantly added spread of 11.2%: observed P(adult obese) 30.2% in those reclassified up vs 19.0% in those reclassified down, P&lt;0.001). Using the continuous NRI yields a result qualitatively similar to DIA: 0.28 (95% CI: 0.25, 0.31). Conclusions: The DIA and NRI agreed that prediction of P(adult obese) was improved using BMI percentile over using absolute BMI, although DIA and NRI may disagree due to different weighting. The DIA method of quantifying added spread in prediction has the advantage of being on the natural scale. The DIA principle may also be applied to a continuous dependent variable.