tbuckley/cabot-search huggingface dataset:
Deterioration of Limb Muscle Function during Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Raolat M. Abdulai, Tina Jellesmark Jensen, Naimish R. Patel, Michael I. Polkey, Paul Jansson, Bartolomé R. Celli, Stephen I. Rennard
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Section:ChooseTop of pageAbstract <<Chronic Muscle Dysfunctio...Acute Dysfunction in Exac...Therapies for Muscle Dysf...Emerging TherapiesConsiderations for Drug D...ConclusionsReferencesCITING ARTICLES
Association of <i>VHL</i> Genotype With Pancreatic Neuroendocrine Tumor Phenotype in Patients With von Hippel–Lindau Disease
Authors: Amit Tirosh, Samira M. Sadowski, W. Marston Linehan, Steven K. Libutti, Dhaval Patel, Naris Nilubol, Electron Kebebew
Journal: JAMA Oncology (2017)

This study evaluates the natural history of von Hippel–Lindau disease–associated pancreatic lesions to determine the factors associated with pancreatic neuroendocrine tumor phenotype and prognosis.
Actionable gene-based classification toward precision medicine in gastric cancer
Authors: Hiroshi Ichikawa, Masayuki Nagahashi, Yoshifumi Shimada, Takaaki Hanyu, Takashi Ishikawa, Hitoshi Kameyama, Takashi Kobayashi, Jun Sakata, Hiroshi Yabusaki, Satoru Nakagawa, Nobuaki Sato, Yuki Hirata, Yuko Kitagawa, Toshiyuki Tanahashi, Kazuhiro Yoshida, Ryota Nakanishi, Eiji Oki, Dana Vuzman, Stephen Lyle, Kazuaki Takabe, Yiwei Ling, Shujiro Okuda, Kohei Akazawa, Toshifumi Wakai
Journal: Genome Medicine (2017)

Intertumoral heterogeneity represents a significant hurdle to identifying optimized targeted therapies in gastric cancer (GC). To realize precision medicine for GC patients, an actionable gene alteration-based molecular classification that directly associates GCs with targeted therapies is needed.A total of 207 Japanese patients with GC were included in this study. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues were obtained from surgical or biopsy specimens and were subjected to DNA extraction. We generated comprehensive genomic profiling data using a 435-gene panel including 69 actionable genes paired with US Food and Drug Administration-approved targeted therapies, and the evaluation of Epstein-Barr virus (EBV) infection and microsatellite instability (MSI) status.Comprehensive genomic sequencing detected at least one alteration of 435 cancer-related genes in 194 GCs (93.7%) and of 69 actionable genes in 141 GCs (68.1%). We classified the 207 GCs into four The Cancer Genome Atlas (TCGA) subtypes using the genomic profiling data; EBV (N = 9), MSI (N = 17), chromosomal instability (N = 119), and genomically stable subtype (N = 62). Actionable gene alterations were not specific and were widely observed throughout all TCGA subtypes. To discover a novel classification which more precisely selects candidates for targeted therapies, 207 GCs were classified using hypermutated phenotype and the mutation profile of 69 actionable genes. We identified a hypermutated group (N = 32), while the others (N = 175) were sub-divided into six clusters including five with actionable gene alterations: ERBB2 (N = 25), CDKN2A, and CDKN2B (N = 10), KRAS (N = 10), BRCA2 (N = 9), and ATM cluster (N = 12). The clinical utility of this classification was demonstrated by a case of unresectable GC with a remarkable response to anti-HER2 therapy in the ERBB2 cluster.This actionable gene-based classification creates a framework for further studies for realizing precision medicine in GC.
P3.04-009: Evaluation of RT-PCR Methodology for ALK Assessment in Patients with NSCLC in Europe: Results from the ETOP Lungscape Project
Authors: I. Letovanec, S. Peters, Z. Tsourti, SP Finn, A. Soltermann, L. Bubendorf, Ejm Speel, A. Marchetti, D. Nonaka, H. Hager, M. Martorell, K. Monkhorst, A. Sejda, R. Chenev, I. Sansano, EK Verbeken, V. Tischler, S. Savic, A. Di Lorito, MC Calabuig, E. Felip, A. Adjei, A. Warth, P. Baas, P. Meldgaard, F. Blackhall, AM Dingemans, H. Dienemann, R. Dziadziusko, J. Vansteenkiste, R. Kammler, U. Dafni, K. Kerr, E. Thunissen, R. Stahel
Journal: Journal of Thoracic Oncology (2015)
TCT-557 Predictors of advanced conduction disturbances requiring a late (≥48 hours) permanent pacemaker following transcatheter aortic valve implantation
Authors: Antonio Mangieri, Giuseppe Lanzillo, Letizia Bertoldi, Richard Jabbour, Damiano Regazzoli, Marco Ancona, Akihito Tanaka, Satoru Mitomo, Claudio Montalto, Matteo Pagnesi, Francesco Giannini, Matteo Montorfano, Alaide Chieffo, Josep Rodés-Cabau, Ottavio Alfieri, Antonio Colombo, Azeem Latib
Journal: Journal of the American College of Cardiology (2017)
TCT-694 Device-Related Thrombus after Left Atrial Appendage Closure: A 4-year retrospective analysis from a real-world setting
Authors: Jiangtao Yu, Yuan Bai, Manuela Muenzel, Adam Fasakas, Xin Xue, Thorsten Keil, Erich Duenninger
Journal: Journal of the American College of Cardiology (2017)
TCT-564 Monocenter registry of 1248 consecutive patients with a coronary chronic total occlusion: predictor factors of cardiac death
Authors: Victoria Martin Yuste, Ignacio Ferreira Gonzalez, Eduardo Flores, Marco Hernandez, Sara Vazquez, Carlos Robles, Alberto Pernigotti, Xavier Freixa, Ander Regueiro, Salvatore Brugaletta, Manel Sabate
Journal: Journal of the American College of Cardiology (2017)
Low-Dose Exposure to Ionizing Radiation Deregulates the Brain-Specific MicroRNA-134 in Interventional Cardiologists
Authors: Andrea Borghini, Cecilia Vecoli, Antonella Mercuri, Clara Carpeggiani, Emanuela Piccaluga, Giulio Guagliumi, Eugenio Picano, Maria Grazia Andreassi
Journal: Circulation (2017)
Evaluation of a Trainee-Led Project to Reduce Inappropriate Proton Pump Inhibitor Infusion in Patients With Upper Gastrointestinal Bleeding
Authors: Emmanuel Coronel, Nikhil Bassi, Sarah Donahue-Rolfe, Ellen Byrne, Sarah Sokol, Gautham Reddy, Vineet M. Arora
Journal: JAMA Internal Medicine (2017)

This trainee-led quality improvement study evaluates the use of the Culture, Oversight, Systems Change, Training framework to reduce inappropriate proton pump inhibitor infusions in patients with upper gastrointestinal bleeding.
Evolución de la resistencia a antibióticos de salmonellas no tifoideas en Grecia durante el período comprendido entre 1990 y 1997
Authors: E N Velonakis, A Markogiannakis, L Kondili, E Varjioti, Z Mahera, N Vakalis, E Dedouli, A Karaitianou, K Bethimouti
Journal: Eurosurveillance (2001)

La sensibilidad de 1.548 cepas de salmonellas no tifoideas a 15 antibioticos ha sido analizada en Grecia de 1990 a 1997. La prevalencia global de resistencias, tanto de Salmonella enterica serotipo Enteritidis, como de Salmonella enterica serotipo Typhimurium, aumento durante los primeros anos del estudio. A partir de 1996, se observo una disminucion, especialmente en el caso de S. Enteritidis, que habia presentado las tasas de resistencias mas altas. S. Typhimurium fue el serotipo con multirresistencia a antibioticos mas elevada. En el resto de los serotipos, la prevalencia de resistencias fue muy baja comparada con S. Enteritidis y S. Typhimurium.
Epigenetic profiling of Chronic Lymphocytic Leukemia defines CD38 expression status
Authors: Farahnaz Rahmatpanah, Stephanie Carstens, Huidong Shi, Ozy Sjahputera, Rebecca Chitma Matsiga, Mihail Popescu, Sam Hooshmand, Charles W. Caldwell
Journal: Cancer Research (2006)

38   B cell chronic lymphocytic leukemia (B-CLL/SLL) is a clonal malignancy of mature B cells characterized by low proliferation rate and disrupted programmed cell death. This type of malignancy is the most common type of adult leukemia in the United States. B-CLL/SLL is diverse across different groups of patients and is comprised of at least two subtypes; one group possesses mutated immunoglobulin heavy chain variable region ( IgV H  ) genes and a survival rate of decades, whereas the other group possesses an unmutated  IgV H   gene and has a poor prognosis with a survival rate of months. In addition to the hypermutation status of  IgV H   gene, a number of biologic features such as mutation of p53, ZAP 70 and CD38 expression appear to have prognostic implications in the clinical management of the B-CLL/SLL. Identifying new genetic and epigenetic biomarkers that can help explain the biology of these two groups of B-CLL/SLL patients may improve the treatment options for patients with poor prognosis. DNA methylation within the CpG island (CGI) in promoter regions plays an important role in tumorgenesis. A previous study conducted in our laboratory revealed that the patterns of DNA methylation in B-CLL/SLL patient samples may not be homogenous. Toward this goal we used an array based technique called differential methylation hybridization to study two groups of B-CLL/SLL patient samples with different CD38 expression status. A total of 38 genomic microarray (19 CD38 positive and 19 CD 38 negative) experiments were performed to study the epigenetic differences between these two groups of patients. Statistical analysis of data from the CGI microarray (12K chip) identified approximately 145 named genes, variably methylated genes, within B-CLL/SLL subsets and recognized genes that are important to many intracellular process. In order to independently confirm the DNA methylation status of selected genes from microarray studies,  (NRP2, POU3F3, LHX2, PRKCE, and SALL4) , MSP primers were designed and used to test a series of B-CLL/SLL patients. In addition, we used a t-test with p=0.00001 to find the pathways that are differentially hypermethylated between the two types of B-CLL/SLL. One of major interest involves calcium signaling pathway.
Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation
Authors: Shivani Kapoor, Karthika Natarajan, Patrick R. Baldwin, Kshama A. Doshi, Rena G. Lapidus, Trevor J. Mathias, Mario Scarpa, Rossana Trotta, Eduardo Davila, Manfred Kraus, Dennis Huszar, Adriana E. Tron, Danilo Perrotti, Maria R. Baer
Journal: Clinical Cancer Research (2017)

Abstract Purpose: fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML), and these patients have short disease-free survival. FLT3 inhibitors have limited and transient clinical activity, and concurrent treatment with inhibitors of parallel or downstream signaling may improve responses. The oncogenic serine/threonine kinase Pim-1 is upregulated downstream of FLT3-ITD and also promotes its signaling in a positive feedback loop, suggesting benefit of combined Pim and FLT3 inhibition. Experimental Design: Combinations of clinically active Pim and FLT3 inhibitors were studied in vitro and in vivo. Results: Concurrent treatment with the pan-Pim inhibitor AZD1208 and FLT3 inhibitors at clinically applicable concentrations abrogated in vitro growth of FLT3-ITD, but not wild-type FLT3 (FLT3-WT), cell lines. AZD1208 cotreatment increased FLT3 inhibitor–induced apoptosis of FLT3-ITD, but not FLT3-WT, cells measured by sub-G1 fraction, annexin V labeling, mitochondrial membrane potential, and PARP and caspase-3 cleavage. Concurrent treatment with AZD1208 and the FLT3 inhibitor quizartinib decreased growth of MV4-11 cells, with FLT3-ITD, in mouse xenografts, and prolonged survival, enhanced apoptosis of FLT3-ITD primary AML blasts, but not FLT3-WT blasts or remission marrow cells, and decreased FLT3-ITD AML blast colony formation. Mechanistically, AZD1208 and quizartinib cotreatment decreased expression of the antiapoptotic protein Mcl-1. Decrease in Mcl-1 protein expression was abrogated by treatment with the proteasome inhibitor MG132, and was preceded by downregulation of the Mcl-1 deubiquitinase USP9X, a novel mechanism of Mcl-1 regulation in AML. Conclusions: The data support clinical testing of Pim and FLT3 inhibitor combination therapy for FLT3-ITD AML. Clin Cancer Res; 24(1); 234–47. ©2017 AACR.
An Investigation of the Single and Combined Phthalate Metabolite Effects on Human Chorionic Gonadotropin Expression in Placental Cells
Authors: Jennifer J. Adibi, Yaqi Zhao, Lei V. Zhan, Mirhan Kapidzic, Nicholas Larocque, Hannu Koistinen, Ilpo T. Huhtaniemi, Ulf-Håkan Stenman
Journal: Environmental Health Perspectives (2017)
Risk assessment based on the Risk Index for Serious Adverse Events (SAEs) in Phase I trials
Authors: Sigehiro Koganemaru, Yasutoshi Kuboki, Kohei Shitara, Shogo Nomura, Hideaki Takahashi, Yoichi Naito, Takahiro Sakai, Yukie Kimura, Kiyotaka Yoh, Toshihiko Doi
Journal: Annals of Oncology (2017)
TCT-860 Comparison Between Cardiac Computed Tomography and Three-Dimensional Echocardiography for the Evaluation of Patients with Severe Tricuspid Regurgitation
Authors: Fabien Praz, Omar Khalique, Jennifer Jantz, Remi Kouz, Pablo Codner, Amisha Patel, Cheng-Han Chen, Torsten Vahl, Isaac George, Tamim Nazif, Susheel Kodali, Martin Leon, Rebecca Hahn
Journal: Journal of the American College of Cardiology (2017)
TCT-466 Impact of a Comprehensive STEMI System on Outcomes of STEMI Patients with Non-System Delays
Authors: Chetan Huded, Kathleen Kravitz, Stephen Ellis, Travis Gullett, Scott Hantz, Venu Menon, Seth Podolsky, Damon Kralovic, Steve Meldon, Deborah Brosovich, Elizabeth Smith, Samir Kapadia, Umesh Khot
Journal: Journal of the American College of Cardiology (2017)
La surveillance des résultats de traitements antituberculeux – faut-il mettre à jour les recommandations européennes ?
Authors: D Falzon, J Scholten, A Infuso
Journal: Eurosurveillance (2006)

La surveillance des resultats des traitements antituberculeux ainsi que l’adoption, par les pays de la region Europe de l’Organisation Mondiale de la Sante (OMS), des modifications introduites en 2001 pour ameliorer la comparabilite entre pays ont fait l’objet de discussions. 
L’issue des cas de tuberculose pulmonaire confirme a ete compare pour les cas declares en 2001 et 2002. La notification etait consideree comme etant complete si l’issue de la maladie etait notee pour 98% ou plus des cas declares a l’origine. Pour les deux annees, la periode maximale d’observation etait de 12 mois a partir du debut du traitement. En 2000, les issues rapportees par les pays etaient classes sous : ‘gueri’, ‘traitement termine’, ‘decede’, ‘echec therapeutique’, ‘traitement non suivi’, ‘transfere’, et ‘autres, non evalues’ pour les cohortes de nouveaux cas ou de cas ayant deja ete traites anterieurement. En 2001, suite a des changements, il a ete demande aux pays de surveiller egalement les cas sans historique de traitement et deux autres categories d’issues ont ete ajoutees : ‘encore sous traitement’ et ‘inconnu’. 
Sur les 42 pays qui ont notifie les issues de la maladie en 2001, 74% (31/42) disposaient de donnees nationales exhaustives, contre 50% (19/38) en 2000. Douze des 21 pays ayant declare des donnees sur la periode d’observation ont suivi les recommandations. Les categories ‘traitement non suivi’ et ‘transfere’ ont ete utilisees indifferemment a la place de ‘inconnu’. Parmi les nouveaux cas, la categorie ‘encore sous traitement’ a ete utilisee par 15 des 31 pays (de 1% a 15%). ‘Echec therapeutique’ est une issue rarement rapportee dans les pays d’Europe occidentale (l1%).
La surveillance europeenne des resultats de traitements antituberculeux devrait inclure tous les cas pulmonaires confirmes, en appliquant la periode d’observation standard et les categories revises, et la declaration devrait, de preference, utiliser des donnees individuelles.
Abstract 19005: Efficacy of Bupivacaine/Lidocaine Combination in Reducing Opioid Usage Following Pacemaker/Defibrillator Implantation: A Double-Blind Randomized Controlled Trial
Authors: Udaya Padakandla, Giovanni Filardo, Danielle Sass, Ben Pollock, Teresa Phan, Manish Assar, Alan Donsky, Cara East, Jay Franklin, Robert Kowal, Peter Wells, Kevin Wheelan
Journal: Circulation (2016)

Introduction:  Bupivacaine (Bupi) and Lidocaine (Lido) are local anesthetics used in pacemaker/defibrillator implantation. Choice is primarily driven by time to take effect (and duration):    Hypothesis:  Opioid use (morphine equivalent in grams) within 24 hours of awakening from general anesthesia after pacemaker/defibrillator implantation will be lower in patients randomized to Lido (6 cc 1%)/Bupi (4 cc 0.25% solution) than Lido (10 cc 1% solution) alone.   Methods:  We randomized (1:1) 350 consented patients ≥18 years undergoing first isolated pacemaker/defibrillator (ICD, pacemaker) implantation for arrhythmia correction at one hospital (11/03/2008-08/30/2012), stratified by surgeon, device type, and gender. Local anesthetic was administered once according to randomization at time of surgery. Surgeons were blinded to randomization. Data on all opioids given ≤24 hours post-awakening from anesthesia were collected.   Results:  In the Lido/Bupi group, 61.6% of patients received opioids, vs 59.5% in the Lido group (adjusted odds ratio=1.00; 95%CI: 0.65, 1.53; p=0.98). The mean total amount received was lower but not significant in the Bupi/Lido group (6.5 mg morphine equivalent) than the Lido group (7.6 mg; adjusted difference = -1.82; 95%CI: -4.33, 0.68; p= 0.15) (see Table).   Conclusions:  We observed a lower morphine equivalent average in patients receiving Lido/Bupi vs Lido alone, but the difference was not significant. We cannot rule out the possibility that clinician and patient expectations regarding pain management impacted opioid use, masking the intervention effect. A larger study is needed to confirm our results.
Brain surgery improves seizure control in children with drug resistant epilepsy, shows study
Authors: Susan Mayor
Journal: BMJ (2017)

Children and adolescents with drug resistant epilepsy who undergo surgery are significantly more likely to become free from seizures than those who continue medical therapy alone, a randomised trial has found.1

Young people with epilepsy that does not respond to drug treatment have a higher risk of poor long term intellectual and psychosocial outcomes. They are often treated with surgery that aims to reduce or stop seizures, but previous …
Effects of Co-occurring Genomic Alterations on Outcomes in Patients with<i>KRAS</i>-Mutant Non–Small Cell Lung Cancer
Authors: Kathryn C. Arbour, Emmett Jordan, Hyunjae Ryan Kim, Jordan Dienstag, Helena A. Yu, Francisco Sanchez-Vega, Piro Lito, Michael Berger, David B. Solit, Matthew Hellmann, Mark G. Kris, Charles M. Rudin, Ai Ni, Maria Arcila, Marc Ladanyi, Gregory J. Riely
Journal: Clinical Cancer Research (2017)

Abstract Purpose: KRAS mutations occur in approximately 25% of patients with non–small cell lung cancer (NSCLC). Despite the uniform presence of KRAS mutations, patients with KRAS-mutant NSCLC can have a heterogeneous clinical course. As the pattern of co-occurring mutations may describe different biological subsets of patients with KRAS-mutant lung adenocarcinoma, we explored the effects of co-occurring mutations on patient outcomes and response to therapy. Experimental Design: We identified patients with advanced KRAS-mutant NSCLC and evaluated the most common co-occurring genomic alterations. Multivariate analyses were performed incorporating the most frequent co-mutations and clinical characteristics to evaluate association with overall survival as well as response to platinum–pemetrexed chemotherapy and immune checkpoint inhibitors. Results: Among 330 patients with advanced KRAS-mutant lung cancers, the most frequent co-mutations were found in TP53 (42%), STK11 (29%), and KEAP1/NFE2L2 (27%). In a multivariate analysis, there was a significantly shorter survival in patients with co-mutations in KEAP1/NFE2L2 [HR, 1.96; 95% confidence interval (CI), 1.33–2.92; P ≤ 0.001]. STK11 (HR, 1.3; P = 0.22) and TP53 (HR 1.11, P = 0.58) co-mutation statuses were not associated with survival. Co-mutation in KEAP1/NFE2L2 was also associated with shorter duration of initial chemotherapy (HR, 1.64; 95% CI, 1.04–2.59; P = 0.03) and shorter overall survival from initiation of immune therapy (HR, 3.54; 95% CI, 1.55–8.11; P = 0.003). Conclusions: Among people with KRAS-mutant advanced NSCLC, TP53, STK11, and KEAP1/NFE2L2 are the most commonly co-occurring somatic genomic alterations. Co-mutation of KRAS and KEAP1/ NFE2L2 is an independent prognostic factor, predicting shorter survival, duration of response to initial platinum-based chemotherapy, and survival from the start of immune therapy. Clin Cancer Res; 24(2); 334–40. ©2017 AACR.
Long-lived tissue resident HIV-1 specific memory CD8+ T cells are generated by skin immunization with live virus vectored microneedle arrays
Authors: Marija Zaric, Pablo Daniel Becker, Catherine Hervouet, Petya Kalcheva, Barbara Ibarzo Yus, Clement Cocita, Lauren Alexandra O'Neill, Sung-Yun Kwon, Linda Sylvia Klavinskis
Journal: Journal of Controlled Release (2017)

The generation of tissue resident memory (TRM) cells at the body surfaces to provide a front line defence against invading pathogens represents an important goal in vaccine development for a wide variety of pathogens. It has been widely assumed that local vaccine delivery to the mucosae is necessary to achieve that aim. Here we characterise a novel micro-needle array (MA) delivery system fabricated to deliver a live recombinant human adenovirus type 5 vaccine vector (AdHu5) encoding HIV-1 gag. We demonstrate rapid dissolution kinetics of the microneedles in skin. Moreover, a consequence of MA vaccine cargo release was the generation of long-lived antigen-specific CD8+ T cells that accumulate in mucosal tissues, including the female genital and respiratory tract. The memory CD8+ T cell population maintained in the peripheral mucosal tissues was attributable to a MA delivered AdHu5 vaccine instructing CD8+ T cell expression of CXCR3+, CD103+, CD49a+, CD69+, CD127+ homing, retention and survival markers. Furthermore, memory CD8+ T cells generated by MA immunization significantly expanded upon locally administered antigenic challenge and showed a predominant poly-functional profile producing high levels of IFNγ and Granzyme B. These data demonstrate that skin vaccine delivery using microneedle technology induces mobilization of long lived, poly-functional CD8+ T cells to peripheral tissues, phenotypically displaying hallmarks of residency and yields new insights into how to design and deliver effective vaccine candidates with properties to exert local immunosurveillance at the mucosal surfaces.