tbuckley/cabot-search huggingface dataset:
Randomized phase III and extension studies: efficacy and impacts on quality of life of naldemedine in subjects with opioid-induced constipation and cancer
Authors: N. Katakami, T. Harada, T. Murata, K. Shinozaki, M. Tsutsumi, T. Yokota, M. Arai, Y. Tada, M. Narabayashi, N. Boku
Journal: Annals of Oncology (2018)

The efficacy and safety of naldemedine (a peripherally acting µ-opioid receptor antagonist) for opioid-induced constipation (OIC) in subjects with cancer was demonstrated in the primary report of a phase III, double-blind study (COMPOSE-4) and its open-label extension (COMPOSE-5). The primary end point, the proportion of spontaneous bowel movement (SBM) responders, was met. Here, we report results from secondary end points, including quality of life (QOL) assessments from these studies.In COMPOSE-4, eligible adults with OIC and cancer were randomly assigned 1:1 to receive once-daily oral naldemedine 0.2 mg (n = 97) or placebo (n = 96) for 2 weeks, and those who continued on to COMPOSE-5 received naldemedine for 12 weeks (n = 131). Secondary assessments in COMPOSE-4 included the proportion of complete SBM (CSBM) responders, SBM or CSBM responders by week, and subjects with ≥1 SBM or CSBM within 24 h postinitial dose. Changes from baseline in the frequency of SBMs or CSBMs per week were assessed at weeks 1 and 2. Time to the first SBM or CSBM postinitial dose was also evaluated. In both studies, QOL impact was evaluated by Patient Assessment of Constipation-Symptoms (PAC-SYM) and PAC-QOL questionnaires.Naldemedine improved bowel function for all secondary efficacy assessments versus placebo (all P ≤ 0.0002). The timely onset of naldemedine activity versus placebo was evidenced by median time to the first SBM (4.7 h versus 26.6 h) and CSBM (24.0 h versus 218.5 h) postinitial dose (all P < 0.0001). In COMPOSE-4, significant differences between groups were observed with the PAC-SYM stool domain (P = 0.045) and PAC-QOL dissatisfaction domain (P = 0.015). In COMPOSE-5, significant improvements from baseline were observed for overall and individual domain scores of PAC-SYM and PAC-QOL.Naldemedine provided effective and timely symptomatic relief from OIC and improved the QOL of subjects with OIC and cancer. TRIAL REGISTRATION ID: www.ClinicalTrials.jp: JAPIC-CTI-132340 (COMPOSE-4) and JAPIC-CTI-132342 (COMPOSE-5).
Quantifying the impact of achieving the World Health Organization global health sector strategy goals for hepatitis C in the EURO region
Authors: S. Robbins, S. Blach, S. Brandon, C. Estes, I. Gamkrelidze, H. Nde, D. Razavi-Shearer-Spink, J. Schmelzer, H. Razavi
Journal: Journal of Hepatology (2018)
International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia
Authors: Ondrej Hrusak, Valerie de Haas, Jitka Stancikova, Barbora Vakrmanova, Iveta Janotova, Ester Mejstrikova, Vaclav Capek, Jan Trka, Marketa Zaliova, Ales Luks, Kirsten Bleckmann, Anja Möricke, Julie Irving, Benigna Konatkowska, Thomas B. Alexander, Hiroto Inaba, Kjeld Schmiegelow, Simone Stokley, Zuzana Zemanova, Anthony V. Moorman, Jorge Gabriel Rossi, Maria Sara Felice, Luciano Dalla-Pozza, Jessa Morales, Michael Dworzak, Barbara Buldini, Giuseppe Basso, Myriam Campbell, Maria Elena Cabrera, Neda Marinov, Sarah Elitzur, Shai Izraeli, Drorit Luria, Tamar Feuerstein, Alexandra Kolenova, Peter Svec, Olena Kreminska, Karen R. Rabin, Sophia Polychronopoulou, Elaine da Costa, Hanne Vibeke Marquart, Antonis Kattamis, Richard Ratei, Dirk Reinhardt, John K. Choi, Martin Schrappe, Jan Stary
Journal: Blood (2018)
P267Myocardial electrophysiological effects mediated by KATP channels: controversial aspects about their involvement in the protection by chronic exercise
Authors: C Soler, I Del Canto, M Zarzoso, L Such-Miquel, O Arias-Mutis, P Genoves, A Alberola, A Iradi, F J Chorro, L Such
Journal: Cardiovascular Research (2018)
Integrative analysis of NGS data highlight a genetic variant in ATG7 gene as a novel risk factor for nonalcoholic fatty liver disease progression
Authors: G.A. Baselli, A. Pietrelli, S. Pelusi, M. Meroni, A.L. Fracanzani, G. Soardo, E. Bugianesi, R. Romagnoli, S. Petta, L. Miele, S. Fargion, P. Dongiovanni, L. Valenti
Journal: Journal of Hepatology (2018)
How can we better use Twitter to find a person who got lost due to dementia?
Authors: Kelvin K. F. Tsoi, Nicholas B. Chan, Felix C. H. Chan, Lingling Zhang, Annisa C. H. Lee, Helen M. L. Meng
Journal: npj Digital Medicine (2018)

Twitter is a social media platform for online message sharing. The aim of this study is to evaluate the effectiveness of using Twitter to search for people who got lost due to dementia. The online messages on Twitter, i.e., tweets, were collected through an Application Programming Interface. Contents of the tweets were analysed. The personal characteristics, features of tweets and types of Twitter users were collected to investigate their associations with whether a person can be found within a month. Logistic regression was used to identify the features that were useful in finding the missing people. Results showed that the young age of the persons with dementia who got lost, having tweets posted by police departments, and having tweets with photos can increase the chance of being found. Social media is reshaping the human communication pathway, which may lead to future needs on a new patient-care model.
Higher early post-liver transplant mortality in recipients with severe alcoholic hepatitis versus alcoholic cirrhosis
Authors: B. Lee, G. Im, J. Dodge, M. Voigt, J. Rice, M.R. Lucey, D. Foley, L. Platt, A. Gurakar, N. Mehta, G. Therapondos, H. Han, D. Victor, O. Fix, L. Dinges, D. Dronamraju, C. Hsu, M. Rinella, H. Maddur, S. Eswaran, J. Hause, R.M. Ghobrial, Z. Li, N. Terrault
Journal: Journal of Hepatology (2018)
A randomized, double-blind, double-dummy, controlled, multicenter study of entecavir maleate versus entecavir for treatment of Chinese chronic hepatitis B predominantly genotype B or C: results at week 240
Authors: J.-H. Xu, C.-D. Jing, X.-F. Chen, S. Wang, Z. Zeng, C.-W. Si, J. LI, Q. Mao, D.-Z. Zhang, H. Tang, J.-F. Sheng, X.-Y. Chen, Q. Ning, G.-F. Shi, Q. Xie, J. Dai, X.-Q. Zhang, Z.-N. Xu, Y.-Y. Yu
Journal: Journal of Hepatology (2018)
Molecular Detection and Analysis of Exosomes Using Surface-Enhanced Raman Scattering Gold Nanorods and a Miniaturized Device
Authors: Elyahb Allie Kwizera, Ryan O'Connor, Vojtech Vinduska, Melody Williams, Elizabeth R Butch, Scott E Snyder, Xiang Chen, Xiaohua Huang
Journal: Theranostics (2018)

Exosomes are a potential source of cancer biomarkers. Probing tumor-derived exosomes can offer a potential non-invasive way to diagnose cancer, assess cancer progression, and monitor treatment responses. Novel molecular methods would facilitate exosome analysis and accelerate basic and clinical exosome research. Methods: A standard gold-coated glass microscopy slide was used to develop a miniaturized affinity-based device to capture exosomes in a target-specific manner with the assistance of low-cost 3-D printing technology. Gold nanorods coated with QSY21 Raman reporters were used as the label agent to quantitatively detect the target proteins based on surface enhanced Raman scattering spectroscopy. The expressions of several surface protein markers on exosomes from conditioned culture media of breast cancer cells and from HER2-positive breast cancer patients were quantitatively measured. The data was statistically analyzed and compared with healthy controls. Results: A miniaturized 17 × 5 Au array device with 2-mm well size was fabricated to capture exosomes in a target-specific manner and detect the target proteins on exosomes with surface enhanced Raman scattering gold nanorods. This assay can specifically detect exosomes with a limit of detection of 2×106 exosomes/mL and analyze over 80 purified samples on a single device within 2 h. Using the assay, we have showed that exosomes derived from MDA-MB-231, MDA-MB-468, and SKBR3 breast cancer cells give distinct protein profiles compared to exosomes derived from MCF12A normal breast cells. We have also showed that exosomes in the plasma from HER2-positive breast cancer patients exhibit significantly (P ≤ 0.01) higher level of HER2 and EpCAM than those from healthy donors. Conclusion: We have developed a simple, inexpensive, highly efficient, and portable Raman exosome assay for detection and protein profiling of exosomes. Using the assay and model exosomes from breast cancer cells, we have showed that exosomes exhibit diagnostic surface protein markers, reflecting the protein profile of their donor cells. Through proof-of-concept studies, we have identified HER2 and EpCAM biomarkers on exosomes in plasma from HER2-positive breast cancer patients, suggesting the diagnostic potential of these markers for breast cancer diagnostics. This assay would accelerate exosome research and pave a way to the development of novel cancer liquid biopsy for cancer detection and monitoring.
Validation of the EASL 2017 HBV clinical practice guidelines criteria for switching patients long-term treated with Tenofovir difumarate to Entecavir or Tenofovir alafenamide in a real life setting
Authors: A. Loglio, G. Grossi, R. Soffredini, M. Borghi, F. Facchetti, E. Galmozzi, G. Lunghi, P. Lampertico
Journal: Journal of Hepatology (2018)
Highly immunogenic virally vectored T cell vaccine against HCV are able to induce specific CD4+ T cell helper responses
Authors: I. Esposito, F. Hartnell, L. Swadling, C. Phetsouphanh, A. Brown, C.D. Lara, A. Folgori, S. Capone, E. Barnes, P. Klenerman
Journal: Journal of Hepatology (2018)
Leukemia inhibitory factor induces cholangiocyte proliferation and corrects the impaired bile duct proliferation in sortilin-deficient mice following cholestatic injury
Authors: I. Zvibel, E. Hubel, R. Avraham, E. Lavoie, S. Fishman, J. Dranoff, O. Shibolet
Journal: Journal of Hepatology (2018)
P311Epicardial progenitors are source of myofibroblasts that contribute to fibro-fatty infiltration of atrial subepicardium
Authors: N Suffee, T Moore-Morris, G Dilanian, M Berthet, D Trgouet, M Puceat, S Hatem
Journal: Cardiovascular Research (2018)

epicardial adipocytes and left atrial myocytes has revealed important changes in ionic currents in a rabbit model.Based on these experimental data, we adapted 6 ion currents for adipose induced remodelling, namely I_CaL, I_to, I_Kur, the sodium current (I_Na), slow delayed rectifying potassium current (I_Ks) and inward rectifying potassium current (I_K1).In a 2D tissue model containing a circular region of remodelled myocytes, burst pacing protocols are used to induce arrhythmias (Figure).Results: The predicted changes due to tissue remodelling were a higher resting membrane potential (at 1 Hz pacing: -78.05 mV vs. -80.84mV for normal tissue, -79.07 mV vs. -81.04mV for AF remodelled tissue) and longer action potential duration (at 1 Hz pacing: APD_90 equals 470 ms vs. 310 ms for normal tissue, 450 ms vs. 230 ms for AF remodelled tissue).Simulations at tissue level show that in absence of remodelling due to adipose infiltrates no arrhythmias are induced, while in the presence of remodelling we observe the onset of cardiac arrhythmias (first appearance at: 1.7 Hz for normal tissue, 2.5 Hz for AF remodelled tissue).Conclusion(s): Ionic remodelling due to the presence of adipose tissue results in higher arrhythmogenicity, due to heterogeneity of the tissue.
The effect of post-traumatic stress disorder on refugees' parenting and their children's mental health: a cohort study
Authors: Richard A Bryant, Ben Edwards, Mark Creamer, Meaghan O'Donnell, David Forbes, Kim L Felmingham, Derrick Silove, Zachary Steel, Angela Nickerson, Alexander C McFarlane, Miranda Van Hooff, Dusan Hadzi-Pavlovic
Journal: The Lancet Public Health (2018)

BackgroundChildren and adolescents, who account for most of the world's refugees, have an increased prevalence of psychological disorders. The mental health of refugee children is often associated with the severity of post-traumatic stress disorder (PTSD) in their caregivers. Despite the potential for refugee caregivers' PTSD to affect child mental health, little evidence exists concerning the underlying mechanisms of this association. This study tested the effect of refugee caregivers' previous trauma and levels of ongoing stressors on current PTSD, and in turn how this influences parenting behaviour and consequent child psychological health.MethodsThis cohort study recruited participants from the Building a New Life in Australia study, a population-based prospective cohort study of refugees admitted to 11 sites in Australia between October, 2013, and February, 2014. Eligible participants were aged 18 years or older and the principal or secondary applicant (ie, the refugee applicant within a migrating family unit) for a humanitarian visa awarded between May, 2013, and December, 2013. Primary caregiver PTSD and postmigration difficulties were assessed at Wave 1 (in 2013), and caregiver PTSD was reassessed at Wave 2 (in 2014). At Wave 3, between October, 2015, and February, 2016, primary caregivers repeated measures of trauma history, postmigration difficulties, probable PTSD, and harsh and warm parenting style, and completed the Strengths and Difficulties Questionnaire for their child. We used path analysis to investigate temporal patterns in PTSD, trauma history, postmigration stressors, parenting style, and children's psychological difficulties.FindingsThe current data comprised 411 primary caregivers who provided responses in relation to at least one child (660 children). 394 primary caregivers with 639 children had data on independent variables and were included in the final model. Path analyses revealed that caregivers' trauma history and postmigration difficulties were associated with greater subsequent PTSD, which in turn was associated with greater harsh parenting and in turn, higher levels of child conduct problems (β=0·049, p=0·0214), hyperactivity (β=0·044, p=0·0241), emotional symptoms (β=0·041, p=0·0218), and peer problems (β=0·007, p=0·047). There was also a direct path from primary caregiver PTSD to children's emotional problems (β=0·144, p=0·0001).InterpretationPTSD in refugees is associated with harsh parenting styles, leading to adverse effects on their children's mental health. Programmes to enhance refugee children's mental health should account for PTSD in parents and caregivers, and the parenting behaviours that these children are exposed to.FundingNational Health and Medical Research Council.
Annals Story Slam - Life Lessons
Authors: Megan Miner
Journal: Annals of Internal Medicine (2018)

Web Exclusives17 April 2018Annals Story Slam - Life LessonsFREEMegan Miner, MDMegan Miner, MDSIU Medicine, Springfield, Illinois (M.M.)Search for more papers by this authorAuthor, Article and Disclosure Informationhttps://doi.org/10.7326/W18-0008 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Life Lessons "Life Lessons," by Megan Miner (Duration 6:33)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article and Disclosure InformationCorresponding Author: Megan Miner, MD; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 April 2018Volume 168, Issue 8Page: SS1 ePublished: 17 April 2018 Issue Published: 17 April 2018 CopyrightCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Extrahepatic cancers are the leading cause of death in patients achieving hepatitis B virus control or hepatitis C virus eradication
Authors: Manon Allaire, Pierre Nahon, Richard Layese, Valérie Bourcier, Carole Cagnot, Patrick Marcellin, Dominique Guyader, Stanislas Pol, Dominique Larrey, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean‐Pierre Bronowicki, Jean‐Pierre Zarski, Ghassan Riachi, Paul Calès, Jean‐Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Jean‐Frédéric Blanc, Armand Abergel, Lawrence Serfaty, Ariane Mallat, Jean‐Didier Grangé, Pierre Attali, Yannick Bacq, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen‐Khac, Brigitte Bernard‐Chabert, David Zucman, Vincent DI Martino, Angela Sutton, Eric Letouzé, Etienne Audureau, Françoise Roudot‐Thoraval
Journal: Hepatology (2018)

Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy‐proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child‐Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5‐year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time‐dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV–HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow‐up of 59.7 months, 227 PLCs were diagnosed (5‐year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5‐year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04‐1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08‐2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication. Conclusion : Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (H epatology 2018).
Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study
Authors: Manish A. Shah, Alexander Starodub, Sunil Sharma, Jordan Berlin, Manish Patel, Zev A. Wainberg, Jorge Chaves, Michael Gordon, Kevin Windsor, Carrie Baker Brachmann, Xi Huang, Greg Vosganian, Julia D. Maltzman, Victoria Smith, Jeffrey A. Silverman, Heinz-Josef Lenz, Johanna C. Bendell
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Matrix metalloproteinase-9 (MMP9) is implicated in protumorigenic processes. Andecaliximab (GS-5745, a monoclonal antibody targeting MMP9) was evaluated as monotherapy and in combination with mFOLFOX6. Patients and Methods: Three dosages of andecaliximab monotherapy [200, 600, and 1800 mg i.v. every 2 weeks (q2w)] were investigated in patients with advanced solid tumors (n = 13 in a 3+3 design). After determining a recommended dose, patients with advanced HER2-negative gastric/gastroesophageal junction (GEJ) adenocarcinoma (n = 40) received 800 mg andecaliximab + mFOLFOX6 q2w. Pharmacokinetics, pharmacodynamics, safety, and efficacy were assessed. Results: Andecaliximab monotherapy demonstrated no dose-limiting toxicity (DLT) in any cohort, displaying target-mediated drug disposition at the lowest dose (200 mg) and linear pharmacokinetics at higher doses. Based on target engagement, recommended doses for further study are 800 mg q2w or 1,200 mg q3w. Maximal andecaliximab target binding, defined as undetectable andecaliximab-free MMP9 in plasma, was observed in the gastric/GEJ adenocarcinoma cohort. We observed no unusual toxicity, although there were four deaths on study not attributed to andecaliximab treatment. In first-line patients (n = 36), median progression-free survival (PFS) was 9.9 months [95% confidence interval (CI), 5–13.9 months], and the overall response rate (ORR) was 50%. Among all patients (n = 40), median PFS was 7.8 (90% CI, 5.5–13.9) months, and ORR was 48%, with a median duration of response of 8.4 months. Conclusions: Andecaliximab monotherapy achieved target engagement without DLT. Andecaliximab + mFOLFOX6 showed encouraging clinical activity without additional toxicity in patients with HER2-negative gastric/GEJ adenocarcinoma. A phase III study evaluating mFOLFOX6 ± andecaliximab in this setting is ongoing. Clin Cancer Res; 24(16); 3829–37. ©2018 AACR.
Incidental Metastatic Melanoma Identified on 68Ga–Prostate-Specific Membrane Antigen PET/CT for Metastatic Prostate Cancer
Authors: Hayden A. Snow, Michael S. Hofman, Catherine A. Mitchell, David E. Gyorki, Myles J.F. Smith
Journal: Clinical Nuclear Medicine (2018)

A 78-year-old man with a history of surgically treated prostate cancer and melanoma underwent Ga-prostate-specific membrane antigen (PSMA) PET/CT for biochemical recurrence of his prostate cancer. This revealed locoregionally recurrent prostate cancer and a separate PSMA-avid nodule in his left arm. Subsequent F-FDG PET/CT and excision confirmed this to be an in-transit melanoma metastasis. Prostate-specific membrane antigen PET/CT has become a widely used and valuable tool in the assessment of prostate cancer, particularly biochemically recurrent. Uptake of PSMA has been described in a multitude of different benign and malignant conditions, but it has only rarely been documented in melanoma.
β2-adrenergic receptor autoantibodies alleviated myocardial damage induced by β1-adrenergic receptor autoantibodies in heart failure
Authors: Ning Cao, Hao Chen, Yan Bai, Xiaochun Yang, Wenli Xu, Weiwei Hao, Yi Zhou, Jiayin Chai, Ye Wu, Zhaojia Wang, Xiaochen Yin, Li Wang, Wen Wang, Huirong Liu, Michael L X Fu
Journal: Cardiovascular Research (2018)

β1-adrenergic receptor autoantibodies (β1-AAs) and β2-adrenergic receptor autoantibodies (β2-AAs) are present in patients with heart failure (HF); however, their interrelationship with cardiac structure and function remains unknown. This study explored the effects of the imbalance between β1-AAs and β2-AAs on cardiac structure and its underlying mechanisms in HF.Patients with left systolic HF who suffered from coronary heart disease (65.9%) or dilated cardiomyopathy (34.1%) were divided into New York Heart Association Classes I-II (n = 51) and Classes III-IV (n = 37) and compared with healthy volunteers as controls (n = 41). Total immunoglobulin G from HF patient serum comprising β1-AAs and/or β2-AAs were determined and purified for in vitro studies from neonatal rat cardiomyocytes (NRCMs). In addition, HF was induced by doxorubicin in mice. We observed that the increased ratio of β1-AAs/β2-AAs was associated with worsening HF in patients. Moreover, β2-AAs from patients with HF suppressed the hyper-shrinking and apoptosis of NRCMS induced by β1-AAs from some patients. Finally, β2-AAs alleviated both myocardial damage and β1-AAs production induced by doxorubicin in mice.β2-AAs were capable of antagonizing the effects imposed by β1-AAs both in vitro and in vivo. The imbalance of β1-AAs and β2-AAs in patients with HF is a mechanism underlying HF progression, and the increasing ratio of β1-AAs/β2-AAs should be considered a clinical assessment factor for the deterioration of cardiac function in patients with HF.