tbuckley/cabot-search huggingface dataset:
Abstract 17966: Circadian Variation of Intracoronary Thrombus Aspiration Efficacy in Patients With St-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Stephane Fournier, Sarah Hugelshofer, Sophie Degrauwe, Pedro P. Marques-Vidal, Dragana Radovanovic, Paul Erne, Eric Eeckhout, Olivier Muller, Juan-F. Iglesias
Journal: Circulation (2015)

Introduction: The clinical benefit of intracoronary thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) in patients with STEMI remains controversial. Different studies have suggested a circadian variation of myocardial infarction size (IS) among patients with STEMI depending on the time of the day at symptom onset. Hypothesis: Clinical efficacy of manual TA varies according to circadian rhythms. Methods: We analyzed data from a large, nationwide, prospective, multicenter registry of patients admitted with ACS in Switzerland (AMIS). Patients undergoing primary PCI for STEMI with (TA+) or without (TA-) manual TA within 12 hours of symptom onset were included. We divided 24 hours into 4 time groups based on the time of symptom onset: group 1 (00:00-05:59), group 2 (06:00-11:59), group 3 (12:00-17:59) and group 4 (18:00-23:59). The primary endpoint was in-hospital all-cause mortality. Results: Between 2008 and 2014, a total of 3,648 patients (TA+, n=1,800; TA-, n=1,848) were included. In-hospital death of any cause occurred in 3.8% of the patients in the TA+ group, as compared with 3.7% in the TA- group (p=0.44). In-hospital mortality was not statistically different between the 4 time groups in TA+ and TA- patients (2.1%, 4.6%, 2.9% and 5.1% respectively in TA+ group, p=0.082 and 3.1%, 3.0%, 5.6% and 2.9% respectively in TA- group, p=0.098). We observed a circadian variation of myocardial IS in patients undergoing TA with larger myocardial IS occurring during the night period (group 1: 2,833±2,304 U/l; group 2: 2,449±2,336 U/l; group 3: 2,542±2,114 U/l; group 4: 2,995±2,424 U/l, p=0.001). Of note, there was a statistically significant net benefit of manual TA in terms of myocardial salvage in patients with symptom onset between 06:00 and 18:00 (groups 1 vs. 2: p&lt;0.001; groups 1 vs. 3: p&lt;0.05; groups 4 vs. 2: p&lt;0.001; groups 4 vs. 3: p &lt;0.05). Conclusion: In a real-world registry of patients with STEMI, intracoronary TA during primary PCI was not associated with improved in-hospital all-cause mortality, independently of the time of symptom onset. However, our results suggest a circadian variation of the efficacy of manual TA with a significant reduction of myocardial IS in patients with symptom onset between 06:00 and 18:00.
Intensified Dosing of Gemtuzumab Ozogamicin Can be Safely Combined with Induction Chemotherapy in Children with Acute Myeloid Leukaemia (AML) and High Risk Myelodysplasia (MDS)
Authors: Brenda Gibson, Aimee E Houlton, Andre Baruchel, Guy Leverger, Owen P Smith, Anna Lawson, Keith Wheatley, Pamela R. Kearns
Journal: Blood (2018)
Obstructive sleep apnoea and venous thromboembolism: pathophysiological links and clinical implications
Authors: Alberto García-Ortega, Eva Mañas, Raquel López-Reyes, María José Selma, Aldara García-Sánchez, Grace Oscullo, David Jiménez, Miguel Ángel Martínez-García
Journal: European Respiratory Journal (2018)

Obstructive sleep apnoea (OSA) and pulmonary embolism (PE) remain major health issues worldwide. Data from pathophysiological studies suggest that both intermittent hypoxia and sleep fragmentation are associated with increased blood coagulability, endothelial dysfunction and venous stasis. There is growing evidence that OSA is potentially prevalent in and a risk factor for PE. Conversely, patients with acute PE have two to four times greater risk of moderate-to-severe OSA. The role of continuous positive airway pressure (CPAP) treatment in improving clinically meaningful outcomes in PE patients remains unclear, although some authors have suggested that CPAP could improve the hypercoagulability state and normalise circadian alterations in some of the coagulation molecules, as observed in patients with OSA. Emerging research highlights the complex interdependent relationships between OSA and PE, emphasising the need for rigorous, well-powered trials that address the impact of OSA and its treatment on the prevention and management of PE. Undoubtedly, these will require closer collaboration between the sleep medicine and clinical/venous thromboembolism communities.
New Hope for Therapeutic Cancer Vaccines in the Era of Immune Checkpoint Modulation
Authors: Michael A. Curran, Bonnie S. Glisson
Journal: Annual Review of Medicine (2018)

The driver and passenger mutations accumulated in the process of malignant transformation offer an adequate spectrum of immune visible alterations to the cellular proteome and resulting peptidome to render these cancers targetable-and, in theory, rejectable-by the host T cell immune response. In addition, cancers often overexpress tissue-specific and developmental antigens to which immune tolerance is incomplete. Sometimes, virally transferred oncogenes drive malignant transformation and remain expressed throughout the cancer. Despite this state of antigenic sufficiency, cancer grows progressively and overcomes all efforts of the host immune system to contain it. While therapeutic cancer vaccination can mobilize high frequencies of tumor-specific T cells, these responses remain subject to intratumoral attenuation. Antibody modulation of T cell function through checkpoint blockade or costimulatory activation can restore survival, proliferation, and effector function to these tumor-infiltrating T cells and convert otherwise subtherapeutic vaccines into potentially curative cancer immunotherapeutics.
Genetic loci determining total immunoglobulin E levels from birth through adulthood
Authors: Tsung‐Chieh Yao, Ren‐Hua Chung, Chung‐Yen Lin, Pei‐Chien Tsai, Wei‐Chiao Chang, Kuo‐Wei Yeh, Ming‐Han Tsai, Sui‐Ling Liao, Man‐Chin Hua, Shen‐Hao Lai, Li‐Chen Chen, Su‐Wei Chang, Ya‐Wen Yu, Jing‐Ya Hsu, Su‐Ching Chang, Wen‐Chih Cheng, Donglei Hu, Xiumei Hong, Esteban G. Burchard, Xiaobin Wang, Jung‐Ying Tzeng, Hui‐Ju Tsai, Jing‐Long Huang
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Circulating Levels of Soluble Dipeptidyl Peptidase-4 Are Dissociated from Inflammation and Induced by Enzymatic DPP4 Inhibition
Authors: Elodie M. Varin, Erin E. Mulvihill, Jacqueline L. Beaudry, Gemma Pujadas, Shai Fuchs, Jean-François Tanti, Sofia Fazio, Kirandeep Kaur, Xiemin Cao, Laurie L. Baggio, Dianne Matthews, Jonathan E. Campbell, Daniel J. Drucker
Journal: Cell Metabolism (2018)
Abstract 17882: Differential Responses of Local Coagulation after Implantation of Second-Generation Drug-Eluting Stent Compared with First-Generation Drug-Eluting Stents
Authors: Hiromu Yamazaki, Testuszo Wakatsuki, Koji Yamaguchi, Kumiko Imada, Kazuhisa Matsumoto, Yuriko Takagawa, Eri Takagi, Yoshihito Saijo, Tomoya Hara, Yuko Saito, Mika Bando, Akira Takashima, Sachiko Bando, Tomomi Matsuura, Takayuki Ise, Junko Hotchi, Takeshi Tobiume, Shusuke Yagi, Takashi Iwase, Hirotsugu Yamada, Takeshi Soeki, Masataka Sata
Journal: Circulation (2014)

Purpose: We have previously demonstrated local persistent hypercoagulation after sirolimus-eluting stent(SES) implantation by measuring plasma prothrombin fragment F1+2(frF1+2) levels. The aim of t...
Smoking and Hepatitis B Virus–Related Hepatocellular Carcinoma Risk: The Mediating Roles of Viral Load and Alanine Aminotransferase
Authors: Ya‐Hui Wang, Ya‐Hui Chuang, Chih‐Feng Wu, Meng‐Chin Jan, Wan‐Jung Wu, Chih‐Lin Lin, Chun‐Jen Liu, Ya‐Chien Yang, Pei‐Jer Chen, Shi‐Ming Lin, Mong‐Hsun Tsai, Yi‐Wen Huang, Ming‐Whei Yu
Journal: Hepatology (2018)

Smoking interacts with hepatitis B virus (HBV) to increase the risk of hepatocellular carcinoma (HCC), which might be explained by its role in antiviral immunity. We evaluated the potential mediating role of viral load and/or alanine aminotransferase (ALT) in the relation of smoking with HBV‐associated HCC risk. Using multiple mediation analyses to analyze data from 209 HCC cases and 1,256 controls nested within a cohort of 4,841 male HBV carriers, we found that the effect of smoking on the risk of subsequent HCC was substantially mediated through viral load (percent mediated, 31.7%; P = 0.0054), and a significant mediation effect by both viral load and ALT was also evidenced. Among the 1,143 subjects with repeated measures of viral load and ALT over periods of up to 16 years, we further observed that a higher number of pack‐years of smoking was associated with higher viral load, maintenance of a high viral load (&gt;4.39 log copies/mL), more severe hepatotoxicity grade, and increased likelihood of ALT ≥80 U/L (odds ratio, 3.14; 95% confidence interval, 1.03‐9.64; odds ratio, 6.06; 95% confidence interval, 1.10‐33.25, respectively, for 10‐19 and ≥20 pack‐years versus nonsmokers) during follow‐up. Furthermore, plasma interferon‐γ levels were reduced in smokers compared with nonsmokers (interferon‐γ‐positive rate, 14.9% versus 28.7%; P &lt; 0.0001) at baseline. Smoking was also associated with a reduced natural killer (NK) cell frequency in peripheral blood, characterized by reduced NK function through a systems immunology approach, after long‐term follow‐up in a subsample (n = 171). The combination of smoking and reduced NK cell frequency further increased viral load and the likelihood of ALT ≥80 U/L. Conclusion : The data highlight a role of smoking in HBV viral load, underlining the importance of smoking prevention and cessation in hepatitis B management.
Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity
Authors: Zhiqin Cao, Shaoyang Li, Jianming Lv, Hao Gao, Guodong Chen, Takayoshi Awakawa, Ikuro Abe, Xinsheng Yao, Dan Hu
Journal: Acta Pharmaceutica Sinica B (2018)

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid (fus cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except fusC1 and fusB1. Introduction of the two genes into the Aspergillus oryzae NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of fusC1 and fusB1 revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes fusC1 and fusC2 in the fus cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.
Inflammation and vascular permeability correlate with growth in sporadic vestibular schwannoma
Authors: Daniel Lewis, Federico Roncaroli, Erjon Agushi, Dominic Mosses, Ricky Williams, Ka-loh Li, Xiaoping Zhu, Rainer Hinz, Ross Atkinson, Andrea Wadeson, Sharon Hulme, Helen Mayers, Emma Stapleton, Simon K L Lloyd, Simon R Freeman, Scott A Rutherford, Charlotte Hammerbeck-Ward, D Gareth Evans, Omar Pathmanaban, Alan Jackson, Andrew T King, David J Coope
Journal: Neuro-Oncology (2018)

Inflammation is hypothesized to be a key event in the growth of sporadic vestibular schwannoma (VS). In this study we sought to investigate the relationship between inflammation and tumor growth in vivo using the PET tracer 11C-(R)-PK11195 and dynamic contrast enhanced (DCE) MRI derived vascular biomarkers. Nineteen patients with sporadic VS (8 static, 7 growing, and 4 shrinking tumors) underwent prospective imaging with dynamic 11C-(R)-PK11195 PET and a comprehensive MR protocol, including high temporal resolution DCE-MRI in 15 patients. An intertumor comparison of 11C-(R)-PK11195 binding potential (BPND) and DCE-MRI derived vascular biomarkers (Ktrans, vp, ve) across the 3 different tumor growth cohorts was undertaken. Tissue of 8 tumors was examined with immunohistochemistry markers for inflammation (Iba1), neoplastic cells (S-100 protein), vessels (CD31), the PK11195 target translocator protein (TSPO), fibrinogen for vascular permeability, and proliferation (Ki-67). Results were correlated with PET and DCE-MRI data. Compared with static tumors, growing VS displayed significantly higher mean 11C-(R)-PK11195 BPND (−0.07 vs 0.47, P = 0.020), and higher mean tumor Ktrans (0.06 vs 0.14, P = 0.004). Immunohistochemistry confirmed the imaging findings and demonstrated that TSPO is predominantly expressed in macrophages. Within growing VS, macrophages rather than tumor cells accounted for the majority of proliferating cells. We present the first in vivo imaging evidence of increased inflammation within growing sporadic VS. Our results demonstrate that 11C-(R)-PK11195 specific binding and DCE-MRI derived parameters can be used as imaging biomarkers of inflammation and vascular permeability in this tumor group.
HCV genotype 1-6 NS3 residue 80 substitutions impact protease inhibitor activity and promote viral escape
Authors: Long V. Pham, Sanne Brun Jensen, Ulrik Fahnøe, Martin Schou Pedersen, Qi Tang, Lubna Ghanem, Santseharay Ramirez, Daryl Humes, Stéphanie B.N. Serre, Kristian Schønning, Jens Bukh, Judith M. Gottwein
Journal: Journal of Hepatology (2018)
Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial
Authors: Michinori Ogura, Juan Manuel Sancho, Seok-Goo Cho, Hideyuki Nakazawa, Junji Suzumiya, Gayane Tumyan, Jin Seok Kim, Anne Lennard, José Mariz, Nikolai Ilyin, Wojciech Jurczak, Aurelio Lopez Martinez, Olga Samoilova, Edvard Zhavrid, Eduardo Yañez Ruiz, Marek Trneny, Leslie Popplewell, Bertrand Coiffier, Christian Buske, Won-Seog Kim, Sang Joon Lee, Sung Young Lee, Yun Ju Bae, Larry W Kwak
Journal: The Lancet Haematology (2018)
AB1312 Effects of vitamin d on disease activity, functional disability and serum interleukin-6 in rheumatoid arthritis
Authors: K. Gopal, M. Thevarajah, C.M. Ng, J. Raja
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vitamin D may have a potential role in rheumatoid arthritis (RA) pathogenesis by inhibiting the expression of pro-inflammatory cytokines including interleukin-6 (IL-6)<sup>1–2</sup>. <h3>Objectives</h3> The aim of this study is to determine the clinical factors of vitamin D deficiency in a multi-ethnic Malaysian RA patients and its association with disease activity, functional disability and serum IL-6 level. <h3>Methods</h3> One-hundred RA patients and 50 healthy controls, age- and sex-matched were recruited. DAS28 and HAQ score were assessed. Baseline serum vitamin D and IL-6 were measured in all subjects. RA patients who were vitamin D deficient were given loading dose of vitamin D3 and repeated assessments were done. <h3>Results</h3> Vitamin D deficiency (&lt;50 nmol/L) was found in 63% of RA patients and 76% of healthy controls. Chinese RA patients and healthy controls had significantly more sufficient vitamin D levels compared to Malays and Indians (p=0.002) and (p=0.006), respectively. Only BMI was significantly associated with vitamin D deficiency in RA patients (p=0.012) after adjustment for potential confounding variables. 21 patients received and were compliant to 8 weeks of loading dose 50,000 IU/week vitamin D. Serum vitamin D levels improved from 24.10±7.78 to 91.57±23.70 nmol/L (p&lt;0.001) during this period, whereas no improvement was seen in serum IL-6 levels (16.33±24.58 to 16.38±22.56 pg/ml). No significant association was seen between vitamin D level and disease activity or serum IL-6 level in both pre- and post-treatment groups. A negative association was observed between vitamin D levels and functional disability, including a 33% improvement post-treatment (mean ±SD 0.30±0.46 to 0.20±0.18). The table below shows the independent factors association with serum vitamin D level in RA patients (n=100). <h3>Conclusions</h3> Vitamin D deficiency is prevalent in Malaysian RA patients. This study suggests that vitamin D does not have a role in disease activity or serum IL-6 but it may have a role in functional disability in RA patients. <h3>References</h3> [1] van Hamburg JP, et al.TNF blockade requires 1,25(OH)2D3 to control human Th17-mediated synovial inflammation. Ann Rheum Dis,2012.71(4):606–12 [2] Wen H, et al. 1,25 (OH) 2-Vitamin-D3 attenuates Th17-related cytokines expression in peripheral blood mononuclear cells in patients with early-diagnosed rheumatoid arthritis. Zhonghua nei ke za zhi,2015.54(4):317–21 <h3>Acknowledgements</h3> We thank Arthritis Foundation Malaysia for the financial support of this study. <h3>Disclosure of Interest</h3> None declared
Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr−/− mice
Authors: Yoshimasa Takafuji, Mika Hori, Toshihide Mizuno, Mariko Harada-Shiba
Journal: Cardiovascular Research (2018)

Atherosclerosis is a chronic inflammatory disease of the vasculature. Mesenchymal stem cells (MSCs) exert immunomodulatory and immunosuppressive effects by secreting humoral factors; however, the intravascular MSC administration presents a risk of vascular occlusion. Here, we investigated both the effect of conditioned medium from cultured MSCs (MSC-CM) on atherosclerosis and the underlying mechanism.Low-density lipoprotein receptor-deficient (Ldlr-/-) mice were fed a high-fat diet and received intravenous injections of either MSC-CM from adipose tissue-derived MSCs or control medium 2×/week for 13 weeks. MSC-CM treatment decreased the atherosclerotic plaque area in the aorta and aortic root of Ldlr-/- mice by 41% and 30%, respectively, with no change in serum lipoprotein levels. Histopathologically, the MSC-CM treatment decreased the expression of cell adhesion molecules (CAMs) and the accumulation of macrophages on the vascular walls. Extracellular vesicles (EVs) and supernatant (MSC-CM supernatant) were separated from the MSC-CM by ultracentrifugation. In tumour necrosis factor-α stimulated human aortic endothelial cells (HAOECs), both the MSC EVs and MSC-CM supernatant decreased CAM expression by inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NFκB) pathways. In macrophages, the MSC-CM supernatant decreased the lipopolysaccharide-induced increases in M1 marker expression by inhibiting both the MAPK and NFκB pathways and increased the expression of M2 markers by activating the signal transducer and activator of transcription 3 pathway. In co-culture, inflamed HAOECs pretreated with MSC-CM supernatant and MSC EVs exhibited decreased monocyte adhesion to HAOECs. In addition, the neutralization of hepatocyte growth factor (HGF) in MSC-CM or MSC-CM supernatant attenuated their abilities to suppress monocyte adhesion to HAOECs in co-culture.MSC-CM ameliorated atherosclerosis in Ldlr-/- mice and suppressed CAM expression and macrophage accumulation in the vascular walls. Humoral factors, including HGF and EVs from MSCs, hold promise as therapeutic agents to reduce the residual risk of coronary artery diseases.
Abstract 17397: Exosomes Isolated From Human Inducible Pluripotent Stem Cell-Derived Cardiomyocytes Enhance Angiogenesis in-vitro; a New Potential Therapy for the Post-Ischemic Heart
Authors: Julie Dougherty, Muhamad Mergaye, Chen Chun-An, Mark G Angelos, Mahmood Khan
Journal: Circulation (2017)

Introduction: Due to the relative poor regenerative properties of cardiac tissue, acute ischemic events can lead to progressive terminal heart failure over time unless cardiac regeneration can be a...
18F-FDG PET/CT Revealing Constrictive Pericarditis as the Only Manifestation of Malignant Mesothelioma
Authors: Jan Pieter Edel, Hans Balink
Journal: Clinical Nuclear Medicine (2018)

A 57-year-old man presented with shortness of breath and ankle edema. Constrictive pericarditis with an unexplained mass surrounding the heart was diagnosed by ultrasound. Accordingly, F-FDG PET/CT was performed. Multiple PET-positive noduli and irregular tissue were located in the pericardium, with pleural fluid present, but without additional pulmonic or pleural pathology. A pericardiectomy was successfully performed. Histopathology and immunohistochemical staining revealed epithelioid mesothelioma.
On-Demand Sildenafil as a Treatment for Raynaud Phenomenon
Authors: Matthieu Roustit, Joris Giai, Olivier Gaget, Charles Khouri, Myriam Mouhib, Adrien Lotito, Sophie Blaise, Christophe Seinturier, Fabien Subtil, Adeline Paris, Claire Cracowski, Bernard Imbert, Patrick Carpentier, Sunita Vohra, Jean-Luc Cracowski
Journal: Annals of Internal Medicine (2018)

Background: Treatment of Raynaud phenomenon (RP) with phosphodiesterase-5 inhibitors has shown moderate efficacy. Adverse effects decrease the risk–benefit profile of these drugs, and patients may not be willing to receive long-term treatment. On-demand single doses before or during exposure to cold may be a good alternative. Objective: To assess the efficacy and safety of on-demand sildenafil in RP. Design: Series of randomized, double-blind, n-of-1 trials. (ClinicalTrials.gov: NCT02050360) Setting: Outpatients at a French university hospital. Participants: Patients with primary or secondary RP. Intervention: Each trial consisted of a multiple crossover study in a single patient. Repeated blocks of 3 periods of on-demand treatment were evaluated: 1 week of placebo, 1 week of sildenafil at 40 mg per dose, and 1 week of sildenafil at 80 mg per dose, with a maximum of 2 doses daily. Measurements: Raynaud Condition Score (RCS) and frequency and daily duration of attacks. Skin blood flow in response to cooling also was assessed with laser speckle contrast imaging. Mixed-effects models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated efficacy. Results: 38 patients completed 2 to 5 treatment blocks. On the basis of aggregated data, the probability that sildenafil at 40 mg or 80 mg was more effective than placebo was greater than 90% for all outcomes (except for RCS with sildenafil, 80 mg). However, the aggregated effect size was not clinically relevant. Yet, substantial heterogeneity in sildenafil's efficacy was observed among participants, with clinically relevant efficacy in some patients. Limitation: The response to sildenafil was substantially heterogeneous among patients. Conclusion: Despite a high probability that sildenafil is superior to placebo, substantial heterogeneity was observed in patient response and aggregated results did not show that on-demand sildenafil has clinically relevant efficacy. In this context, the use of n-of-1 trials may be an original and relevant approach in RP. Primary Funding Source: GIRCI (Groupement Interrégional de Recherche Clinique et d'Innovation) Auvergne Rhône-Alpes (academic funding) and Pfizer.