tbuckley/cabot-search huggingface dataset:
THU-464-NASH-related liver carcinogenesis is critically affected by hypoxia-inducible factor 2 alpha
Authors: Beatrice Foglia, Salvatore Sutti, Stefania Cannito, Erica Novo, Marina Maggiora, Claudia Bocca, Elisabetta Morello, Stefania Bruzzì, Naresh Naik Ramavath, Chiara Rosso, Ramy Younes, Elisabetta Bugianesi, Emanuele Albano, Maurizio Parola
Journal: Journal of Hepatology (2019)
SAT-240-Metabolic liver function improves 12 weeks after successful sofosbuvir-based direct-acting antiviral therapy in patients with chronic hepatitis C and advanced liver disease
Authors: Tea Lund Laursen, Cecilie Brøckner Siggard, Konstantin Kazankov, Thomas Damgaard Sandahl, Holger Jon Møller, Lena Hagelskjær Kristensen, Britta Tarp, Alex Laursen, Henning Grønbæk
Journal: Journal of Hepatology (2019)
Molecular Genetic Anatomy and Risk Profile of Hirschsprung’s Disease
Authors: Joseph M. Tilghman, Albee Y. Ling, Tychele N. Turner, Maria X. Sosa, Niklas Krumm, Sumantra Chatterjee, Ashish Kapoor, Bradley P. Coe, Khanh-Dung H. Nguyen, Namrata Gupta, Stacey Gabriel, Evan E. Eichler, Courtney Berrios, Aravinda Chakravarti
Journal: New England Journal of Medicine (2019)

Hirschsprung's disease, or congenital aganglionosis, is a developmental disorder of the enteric nervous system and is the most common cause of intestinal obstruction in neonates and infants. The disease has more than 80% heritability, including significant associations with rare and common sequence variants in genes related to the enteric nervous system, as well as with monogenic and chromosomal syndromes.
Survival post relapse of soft tissue limb sarcomas: A 10-year retrospective review.
Authors: Shailendra Verma, Sharon McGee, Tamir Streiner, Lisa Simmonds, Lise Paquet
Journal: Journal of Clinical Oncology (2015)

e21522 Background: Adult limb soft tissue sarcomas (STS’s) are rare, solid tumours accounting for less than 1% of all cancers. Such cases are best managed at institutions which provide expert multidisciplinary management including surgery, radiation and chemotherapy. Outcome of non-metastatic limb STS management have been reported by large groups or institutions. We undertook a 10-year review of our experience with a focus on post relapse survival. Methods: Records were reviewed from 2004 to 2014 of patients with limb STS. A database describing individual patient and tumour characteristics and treatments was generated. Statistical analyses (chi-square, t-test and one way ANOVA ) were undertaken to investigate the impact of tumour characteristics and treatment modalities on outcomes including time to relapse and survival. Survival of relapsers and non-relapsers was evaluated. Results: A total of 134 patients with limb STS’s were treated at the center between 2004 to 2014. The median age was 64 years with 58% males and high-grade (2-3) tumours (67%).Upper extremity was involved in 30% , lower extermity in 70% with proximal involement in 60% and 78% respectively. The median size was 9.1 cm. The three most common histologies were pleomorphic (25%), malignant fibrous histiocytoma (17%) and liposarcomas (16%). Management include surgery in 92%, any radiation (preop/postop) in 60% and any chemotherapy (neoadjuvant or adjuvant) in 24%. At the time of this analysis, 34% patients have relapsed, with median time to relapse of 13 months (range 1-63 months). The probability of relapse was significantly increased in patient with high grade tumours (p = .026), lower extremity tumours (p = .07) and in those who received any chemotherapy (p = .010). Histological subtypes had no meaningful impact. . Of interest, at the time of this analysis, 54% of relapsers were alive with a median survival (MS) post relapse of 35 months. Of those who died (43%) the median time to death was 9 months. MS of those with distant relapse first was 21 months compared to those with local relapse first , 29 months. Post relapse therapies will be discussed. Conclusions: Durable survival of relapsed patients with limb STS is possible with appropriate multidisciplinary management.
PS-108-NGM, a novel activator of beta-Klotho/FGFR1c: A single dose significantly reduces steatosis (liver fat by MRI-PDFF), inflammation (ALT, AST) and fibrogenic activity (Pro-C3) in NAFLD subjects
Authors: Alex DePaoli, Mustafa Bashir, Van Phung, Andrew Yan, Lei Ling, Bryan Baxter, Hui Tian
Journal: Journal of Hepatology (2019)
FRI-029-Non-alcoholic fatty liver disease and steatohepatitis in autoimmune hepatitis: important player or innocent bystander?
Authors: Kalliopi Zachou, Kalliopi Azariadi, Ellina Lytvyak, Nikolaos Gatselis, Atsushi Takahashi, Mercedes Robles, Raul J. Andrade, Christoph Schramm, Ansgar W. Lohse, Atsushi Tanaka, Aldo J Montano-Loza, George N. Dalekos
Journal: Journal of Hepatology (2019)
The Critical Role of Statistical Analyses in Maximizing Power Gains From Covariate-Adaptive Trial Designs
Authors: Michael Rosenblum, Bingkai Wang
Journal: JAMA Network Open (2019)

Helen C. Stankiewicz Karita, MD; Kirsten Hauge, MPH; Amalia Magaret, PhD; Constance Mao, MD; Jeffrey Schouten, MD, JD; Verena Grieco, MD; Long Fu Xi, PhD; Denise A. Galloway, PhD; Margaret M. Madeleine, PhD; Anna Wald, MD, MPH
Nutritional Strategies for Prevention and Management of Diabetes: Consensus and Uncertainties
Authors: Judith Wylie-Rosett, Frank B. Hu
Journal: Diabetes Care (2019)

The nutrition Consensus Report (1) and four featured papers (2–5) in the special section on nutrition in this issue of Diabetes Care focus on nutrition therapy and medical nutrition therapy (MNT) in the management and prevention of diabetes. The Consensus Report, which is intended to update and replace the 2014 American Diabetes Association (ADA) nutrition position statement (6), examines “studies published in English between 1 January 2014 and 28 February 2018” to “provide clinical professionals with evidence-based guidance” (1) related to the 42 questions listed in Table 1. The ADA has indicated, “A consensus report is not an ADA position and represents expert opinion only” and does not include the ADA evidence-grading system (7). We examine the Consensus Report and nutrition articles featured in this issue considering epidemiological trends, population health versus professional intervention approaches, implications of feeding studies and interventional trials, and potential for personalization/individualization of nutritional approach based on genetic, metabolomic, and microbiomic variation or personal/cultural preferences.

View this table:

Table 1 
Questions addressed by the nutrition Consensus Report expert panel



The 2014 statement (6) focused on nutrition therapy for “adults with diabetes” whereas the 2019 Consensus Report has a broader scope and addresses nutrition therapy for “adults with diabetes or prediabetes” (1). Inclusion of adults with prediabetes expands the population base for nutrition therapy to 43.3% of U.S. adults based on the Centers for Disease Control and Prevention prevalence estimates that 9.4% of U.S. adults have diabetes and 33.9% of U.S. adults have prediabetes (8).

A recent systematic review and meta-analysis published in Diabetes Care (9) synthesized the global evidence on the impact of lifestyle modifications on reducing the incidence of diabetes in a parsimonious model to inform resource allocation. Although evidence from clinical trials shows that type 2 diabetes is largely preventable clinically, population-level reductions in the …
PS-186-Functional liver imaging score derived from gadoxetic acid-enhanced MRI predicts outcomes in patients with advanced chronic liver disease
Authors: Mattias Mandorfer, Nina Bastati, Lucian Beer, Sarah Poetter-Lang, Dietmar Tamandl, Yesim Bican, Michael C. Elmer, Henrik Einspieler, Georg Semmler, Benedikt Simbrunner, Jacqueline C. Hodge, Federica Vernuccio, Claude Sirlin, Ahmed Ba-Ssalamah, Thomas Reiberger
Journal: Journal of Hepatology (2019)
Breast implant-associated anaplastic large cell lymphoma: Proposal for optimal management.
Authors: Mark Warren Clemens, Charles E Butler, Kelly Hunt, Michelle A. Fanale, Steven M. Horwitz, Hui Liu, Colleen McCarthy, Loretta J. Nastoupil, Jun Liu, L Jeffrey Medeiros, Roberto N. Miranda
Journal: Journal of Clinical Oncology (2015)

8550 Background: Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a newly identified lymphoma arising around breast implants placed for cosmetic or reconstructive indications. Patterns of disease progression and optimal treatment strategies have not been described. Methods: The literature was reviewed for all published cases of BI-ALCL from 1997 to November 2014, contacted corresponding authors to update clinical follow up, management, and combined data with institutional cases. A novel clinic-pathologic TNM staging system is proposed and was compared to traditional Ann Arbor staging to determine prognostic value for overall survival (OS) and progression free survival (PFS). A Prentice, Williams and Peterson (PWP) model was used to assess treatment effect on progression events. Results: We identified 128 unique cases of BI-ALCL, including 91 previously reported and 37 unreported cases.Pathologic slides were available in 56 patients for pathologic staging.Average follow up was 45 months (30-217 months). The median OS was 13 years, OS rate 93% at 3-years and 89% at 5-years. 18 progression events were noted and median PFS was 13 months, with 3-year and 5-year PFS at 79.4%. Total capsulectomy with implant removal (TCIR) prolonged OS (p = 0.022) and improved PFS (p = 0.014), and the effect of definitive surgery was statistically significant for PFS benefit (HR = 0.14, 95%, CI = 0.05-0.46, p = 0.001). After definitive surgery, patients had 4% of risk of having events by the end of the first year while the rates were 18%, 24% and 60% when patient had radiation, chemotherapy or limited surgery. The PFS was significantly different by Ann Arbor staging (p = 0.013) and by the newly proposed clinical staging (p = 0.030). Conclusions: Advanced stage, presence of mass, incomplete resection, and delay in definitive surgical treatment were associated with poor OS and PFS in patients with BI-ALCL. Surgical management with definitive excision and oncologic surveillance is adequate for most patients with BI-ALCL. The role for chemotherapy, targeted immunotherapy, and/or radiation for advanced disease requires further research in larger series.
Integrative analysis on expression of estrogen, environmental tobacco smoke and EGFR mutations from a prospective cohort study for never-smokers with non-small cell lung cancer.
Authors: Naoki Yoshimoto, Tomoya Kawaguchi, Akihiro Tamiya, Shun-ichi Isa, Shigeki Shimizu, Kazuhisa Asai, Shinzoh Kudoh, Kazuto Hirata
Journal: Journal of Clinical Oncology (2015)

e18517 Background: Non-small cell lung cancer (NSCLC) in never smokers constitutes higher proportions of females and East Asian, which implies that sex hormones contribute to the carcinogenesis there. Because environmental tobacco smoke (ETS) is commonly exposed to females in East Asia, we examine the expression of estrogen receptor(ER) and its association with the amount of ETS and EGFR mutations in the Japanese never-smokers. Methods: A total of 92 never-smokers with NSCLC were included in this study. Expression of ERα, ERβ and progesterone (PRG) were examined with immunohistochemical staining (IHC). Detailed ETS information was obtained through a standardized questionnaire including exposure period, place and duration. Cumulative dose of ETS (CETS) was evaluated as a sum of the number of the exposure year at home and/or work place. The EGFR mutation was examined using real time polymerase chain reaction amplification. Results: Positive nuclear expression was observed in the 14 cases for ERβ and the 3 cases for progesterone (PRG) but no cases for ERα. A total of 90 patients (97.9%) had ETS exposure and the median CETS was 47.5 years (range 0 - 103). There was no significant correlation between ETS exposure and the expression of sex hormone (ERβ; p = 0.1010, PRG; p = 0.3224). Twelve cases (85.7%) had EGFR mutations in the 14 tumors expressing ERβ, and there was a tendency in the association between expression of ERβ and EGFR mutations (p = 0.067). Conclusions: Nuclear expression of ERβ was observed in NSCLC in never-smokers. ERβ tended to correlate with EGFR mutations, but not ETS exposure.
Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study
Authors: T.K. Owonikoko, H.R. Kim, R. Govindan, N. Ready, M. Reck, S. Peters, S.R. Dakhil, A. Navarro, J. Rodriguez-Cid, M. Schenker, J.S. Lee, V. Gutierrez, I. Percent, D. Morgensztern, J. Fairchild, C. Baudelet, K. Park
Journal: Annals of Oncology (2019)
Local immunity of patients with various molecular subtypes of breast cancer.
Authors: Elena Yurievna Zlatnik, Yuliana Sergeyevna Shatova, Inna Arnoldovna Novikova, Andrey Vladimirovich Bakhtin
Journal: Journal of Clinical Oncology (2015)

e12080 Background: The purpose of the study was to assess some parameters of local cellular immunity in luminal A and B, triple negative (TN) and HER2+/neu breast cancer. Methods: Samples of tumor and peritumoral area of 95 patients with luminal A (n = 26, 27.4%), luminal B (n = 33, 34.7%), HER2+/neu (n = 15, 15.8%) and TN (n = 21, 22.1%) breast cancer were studied. Populations and subpopulations of lymphocytes of peripheral blood, tumor tissue and peritumoral area (PA) were determined in tissue homogenates using flow cytometer FACSCantoII (BD). The proportion of lymphocytes expressing CD3, CD4, CD8, CD19 and CD16/56 markers was calculated as a percentage from the total number of CD45+ lymphocytes. Results: Tumor tissue was characterized by a higher content of T-lymphocytes in comparison with blood (85.9±2.36 and 60.1±4.5%, respectively), mainly due to CD3+CD8+ cells (34.0±1.9 and 20.3±5.36%, respectively); percentage of B- and NK-cells in tumor tissue was lower. Higher content of CD3+ and CD3+CD8+ cells and lower content of CD19+ lymphocytes were observed in PA in comparison with blood; percentage of CD3+CD4+ lymphocytes was lower and that of CD3+CD16/56+ higher than in tumor. Some differences in local immunity parameters were found in various subtypes of breast cancer: maximum content of CD3+ cells (92.2±1.4%) in TN tumor and maximum level of NK-cells in tumor in luminal A breast cancer (10.6±1.73%), which was significantly higher than in luminal B (4.34±1.27%) and TN (4.13±1.63%) cancer (Р < 0.05). HER2+/neu subtype showed a high content of NK-lymphocytes in PA but not in tumor. Conclusions: A marked predominance of T-lymphocytes, especially СD8+, was observed in tumor tissue; besides, maximum level of NK-lymphocytes was detected in the most clinically favorable (luminal A) subtype of breast cancer.
Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk
Authors: Michelle L. O’Donoghue, Sergio Fazio, Robert P. Giugliano, Erik S.G. Stroes, Estella Kanevsky, Ioanna Gouni-Berthold, KyungAh Im, Armando Lira Pineda, Scott M. Wasserman, Richard Češka, Marat V. Ezhov, J. Wouter Jukema, Henrik K. Jensen, S. Lale Tokgözoğlu, François Mach, Kurt Huber, Peter S. Sever, Anthony C. Keech, Terje R. Pedersen, Marc S. Sabatine
Journal: Circulation (2019)

Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined.Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration.The median (interquartile range) baseline Lp(a) concentration was 37 (13-165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01-1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%-46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated ( r=0.37; 95% CI, 0.36-0.39; P<0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67-0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80-1.08; P interaction=0.07) in those ≤median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively.Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition.URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.
Correlation of genomic analysis by MyAML with chemotherapy drug sensitivity.
Authors: Pamela S. Becker, Michael W. Schmitt, Lawrence A. Loeb, Weiyi Gu, Qi Wei, Zhiyi Xie, Andrew R. Carson, Timothy Martins, Carl Anthony Blau, Vivian Oehler, Ka Yee Yeung
Journal: Journal of Clinical Oncology (2015)

7080 Background: Whole genome sequencing has demonstrated tremendous heterogeneity in the mutations and chromosomal translocations associated with acute myeloid leukemia (AML), yet we remain quite limited in our ability to predict outcomes of treatment. Most patients with AML cannot be cured with chemotherapy, and the overall survival remains poor. Thus, new approaches are needed to better tailor treatment for individual patients. Methods: MyAML uses next generation sequencing to analyze the coding regions and gene fusion genomic breakpoints of 194 genes associated with AML. Fragmented genomic DNA is captured with a customized probe design, and sequenced with 300bp paired end reads on an Illumina MiSeq instrument to an average depth of coverage > 1000x. Using a custom bioinformatics pipeline, MyInformatics, single nucleotide variants (SNVs), indels, inversions and translocations are identified and annotated. High throughput drug sensitivity testing was performed against a panel of 160 drugs, of which 56 are FDA approved. De-identified samples from 12 patients with de novo AML and 12 patients with relapsed AML were analyzed. For 2 patient samples, Duplex Sequencing was also performed to detect sub-clonal mutations below the detection limit of conventional next-generation sequencing. Pearson’s correlation was used to examine all possible pairs of missense mutations and the in vitro cytotoxicity response across the sample set. Results: From the 24 patient samples analyzed to date, an average of 129 missense mutations were identified in each sample with an allelic frequency > 5%. These samples also contained an average of over 12 coding indels (~5 frameshift and 7 inframe indels) per sample. In addition, MyAML identified 3 samples with inv(16) and 6 samples with translocations, including the cryptic NUP98-NSD1t(5;11) that were not detected by karyotyping. For 2 of the samples, Duplex Sequencing was performed at a depth of > 6000x. The FLT3 D835 tyrosine kinase domain (TKD) was identified in 2 patients not previously known to have this mutation. Conclusions: Data from disease focused genomics and in vitro chemotherapy sensitivity testing of individual patient samples will likely lead to innovations in treatment and improved outcomes in AML.
FRI-465-The INCRNA H19 is an oncogenic driver of HCC in chronic inflammation-mediated mouse model
Authors: Lika Gemaev, Lina Mizrahi, Orit Pappo, Devorah Olam, Luisa Dandolo, Stefano Caruso, Jessica Zucman-Rossi, Daniel S Goldenberg, Eithan Galun
Journal: Journal of Hepatology (2019)
THU-167-Prevalence, linkage to care and treatment of hepatitis C virus in person who inject drugs under opioid substitution therapy in a Spanish area
Authors: Ylenia Pérez Castaño, Alexandra Gomez Garcia, Jose Manuel Chouza Pérez, Vanesa Sanz Largo, Sandra Arranz Diaz, Itxaso Urtasun Lugea, Francisco Javier Esandi Gonzalez, Agustin Castiella Eguskiza, Edurne Almandoz Cortajarena, Maria Jose Sanchez Iturri, Juan Arenas Ruiz Ruiz
Journal: Journal of Hepatology (2019)
Abstract 11448: Deficiency of Mouse Mast Cell Protease 4 Mitigates Cardiac Dysfunctions in Mice After Myocardium Infarction
Authors: Yunzhe Wang, Cong-lin Liu, Xian Zhang, Wenqiang Fang, Jinying Zhang, Guo-ping Shi
Journal: Circulation (2018)

Introduction: Mouse mast cell protease-4 (mMCP4) is a chymase that has been implicated in cardiovascular diseases, including myocardial infarction (MI). Here we tested a direct role of mMCP4 in mou...