tbuckley/cabot-search huggingface dataset:
THU-192-All-oral, 12-week ravidasvir plus ritonavir-boosted danoprevir and ribavirin delivers 100% svr12 in treatment-naive noncirrhotic hcv genotype 1 patients with resistance-associated substitutions of a phase 2/3 clinical trial in china
Authors: Lai Wei, xiaoyuan Xu, yujuan Guan, sujun Zheng, Ji-Fang Sheng, xingxiang Yang, yuanji Ma, Yan Huang, Yi Kang, Xiaofeng Wen, Jun Li, Youwen Tan, Qing He, Qing Xie, Maorong Wang, Ping An, Guozhong Gong, Huimin Liu, Qin Ning, Rui Hua, Bo Ning, Wen Xie, Jiming Zhang, Wenxiang Huang, Yongfeng Yang, Minghua Lin, Yingren Zhao, Yanhong Yu, Ji-Dong Jia, Dongliang Yang, Liang Chen, Yinong Ye, Yuemin Nan, Zuojong Gong, Quan Zhang, Peng Hu, Fu-Sheng Wang, Yongguo Li, Dongliang Li, Zhansheng Jia, Jinlin Hou, Chengwei Chen, Jinzi Wu
Journal: Journal of Hepatology (2019)
THU-204-Analysis of interleukin 28B rs12979860 polymorphism relationship with spontaneous clearance of hepatitis D virus infection in Mongolian population
Authors: Zaya Batsuuri, Purevjargal Bat-Ulzii, Anir Enkhbat, Naranbaatar Dashdorj, Ganzorig Chimed, Enkhbaatar Perenlei, Odgerel Oidovsambuu
Journal: Journal of Hepatology (2019)
Paclitaxel/ carboplatin/ bevacizumab in non-small cell lung cancer patients induces peripheral effector CD8 T cell proliferation that could be prone for treatment with checkpoint inhibitors
Authors: D. Dumoulin, P. de Goeje, M. Poncin, K. Bezemer, H.J.M. Groen, E.F. Smit, A.-M.C. Dingemans, A. Kunert, R. Hendriks, J.G. Aerts
Journal: Annals of Oncology (2019)

Background: Checkpoint inhibitors targeting programmed death receptor (PD)-1 or PD-ligand 1 (PD-L1) became the cornerstone in the treatment of advanced NSCLC. Several phase III trials showed a better overall survival by treating with combination chemotherapy and checkpoint inhibition, suggesting that addition of chemotherapy increased the response to checkpoint inhibitors. Recently, peripheral blood biomarkers such as Ki67+PD-1+CD8 cells were found to be predictive for clinical outcome with PD-1 treatment. Knowing more about immune modulatory capacities of chemotherapy can help us to design better treatment strategies. We investigated the immune-modulatory effects of paclitaxel/carboplatin/bevacizumab (PCB), focusing on known immune populations associated with response to checkpoint inhibitors in peripheral blood. Methods: In the NVALT 12 study, 223 patients with advanced NSCLC were enrolled to receive PCB, with or without nitroglycerin patch. At baseline and after the first and second treatment cycle, peripheral blood was drawn. By flow cytometry, the proportions of T cells and several subsets and co-inhibitory receptors of these, B cells and monocytes were determined. Results: 6 weeks after starting treatment with PCB, the proportions of T cells were significantly increased compared to baseline values. Within the T cells subsets, proliferation of CD4 T cells remained stable whereas proliferation of CD8 T cells (Ki67+) were significantly increased. The proliferating Ki67+ CD8 T cells expresses more PD-1 compared to non-proliferating CD8 T cells. However, patients with >2 fold increased proliferation of T cells did not show a better outcome. Conclusions: Paclitaxel/ carboplatin/ bevacizumab induces proliferation of CD8 T cells which expresses more co-inhibitory checkpoint molecules. Progression free and overall survival was unchanged by this increase on its own, showing the rationale to combine PCB with checkpoint inhibition in lung cancer, as used in Impower 150. Clinical trial identification: NCT01171170. Legal entity responsible for the study: The authors. Funding: NVALT. Disclosure: D. Dumoulin: Speakers fee: BMS, Roche, Pfizer, Novartis. A-M.C. Dingemans: Advisory boards, lectures: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, Amgen, Novartis, MSD, Takeda (honoraria to institution). J.G. Aerts: Advisory boards: BMS, Boehringer Ingelheim, MSD, AstraZeneca, Eli Lilly, Takeda, Amphera; Stock owner: Amphera B.V. All other authors have declared no conflicts of interest.
Advisory Group recommendations on priorities for the IARC Monographs
Authors: M Matilde Marques, Amy Berrington de Gonzalez, Frederick A. Beland, Patience Browne, Paul A Demers, Dirk W Lachenmeier, Tina Bahadori, Dinesh K. Barupal, Fiorella Belpoggi, Pietro Comba, Min Dai, Robert D Daniels, Catterina Ferreccio, Oleg A Grigoriev, Yun-Chul Hong, Robert N. Hoover, Jun Kanno, Manolis Kogevinas, Gérard Lasfargues, Reza Malekzadeh, Scott Masten, Robert Newton, Teresa Norat, Jane J Pappas, Camila Queiroz Moreira, Teresa Rodríguez, Julietta Rodríguez-Guzmán, Vikash Sewram, Lauren Zeise, Lamia Benbrahim-Tallaa, Véronique Bouvard, Ian A Cree, Fatiha El Ghissassi, Jennifer Girschik, Yann Grosse, Amy L Hall, Michelle C Turner, Kurt Straif, Michael Korenjak, Valerie McCormack, Karen Müller, Joachim Schüz, Jiri Zavadil, Mary K Schubauer-Berigan, Kathryn Z Guyton
Journal: The Lancet Oncology (2019)
BRAF inhibition as conversion therapy for malignant melanoma may provide durable disease control.
Authors: John WT Walker, David Olson, Aiden Zalasky, Michael Smylie
Journal: Journal of Clinical Oncology (2015)

e20120 Background: Inhibitors of the V600 mutant form of the MAPK BRAF protein induce rapid and deep responses. Unfortunately, the benefit seen with targeted therapy may be finite, with mean progression-free intervals of < 1 year. Conversion therapy, where unresectable disease is made amenable to curative-intent resection is a standard component of oncologic care, with breast cancer the best recognized example. The response pattern typical of BRAF inhibitors makes them suitable for consideration for conversion therapy. Methods: This project was undertaken as a retrospective quality control analysis. Patients rendered free of disease by resection following treatment with a BRAF inhibitor were identified. Approval from the local Research and Ethics Board was in place prior to the review. Results: Three patients treated between 2012 and the present were identified, 2 harbouring V600E mutations, 1 with a V600R mutation. One patient received Dabrafenib, 2 received Vemurafenib. Systemic therapy was abandoned in favour of surgery due to treatment-related toxicity, expressed patient preference and recognition of the opportunity for complete resection. All patients underwent R0 surgical resections. With a median follow-up of 27 weeks, 2 patients are alive and free of disease, while the third succumbed to an intracranial recurrence. The median duration of targeted therapy was 7 weeks. Dose intensity was maintained at 100% for 2 patients, while the third received 78% of full-dose therapy. Significant toxicities included fatigue (grade 2, n = 2; grade 3, n = 1), arthralgia (grade 2, n = 1; grade 3, n = 1) and dermatitis (grade 3, n = 1). Conclusions: The identification of successful therapies for melanoma has lead to a situation where treatment algorithms must be developed. Conversion therapy with targeted agents may be a successful approach to patients initially presenting with unresectable/oligometastatic disease. Clinical trials are investigating the neoadjuvant application of targeted therapy, but may not fully address conversion therapy. While we await the data from these studies, careful selection of patients for targeted therapy before an attempt at surgical resection may offer the prospect of durable disease control.
THU-198-Efficacy and safety of glecaprevir/pibrentasvir treatment for 8 weeks in treatment-naive patients with chronic hepatitis C virus infection without cirrhosis or with compensated cirrhosis: Analysis of data pooled from phase 2 and 3 studies
Authors: Eli Zuckerman, Julio Gutierrez, Andrew Ustianowski, Susanna Naggie, Florin Alexandru Caruntu, Natarajan Ravendhran, Samuel Sigal, Lisa Barrett, Stanley Cohen, Eric Crown, Doug Dylla, Linda Fredrick, Stanley Wang, Ariel Porcalla, Federico Mensa, Savino Bruno
Journal: Journal of Hepatology (2019)
Immune escape correlates with an inflamed phenotype in malignant mesothelioma.
Authors: Arun Khattri, Zhixiang Zuo, Aliya Noor Husain, Hedy Lee Kindler, Tanguy Y. Seiwert
Journal: Journal of Clinical Oncology (2015)

7566 Background: Malignant mesothelioma (MM) is commonly associated with an inflammatory reaction, although the specific patterns of immune escape remain incompletely understood. We used emerging, high-fidelity gene expression data from the TCGA Mesothelioma cohort to interrogate subgroups based on expression of immune related genes, and determined associated immune escape mechanisms. Methods: RNA-seq data from 76 MM from TCGA were analyzed using genes representative of 1. T-cells, 2. NK-cells, 3. neutrophils, 4. dendritic cells/macrophages, as well as genes associated with immune escape (immune checkpoints and cellular immune escape). Using this gene set, unsupervised, hierarchical clustering was performed to identify intrinsic immune subgroups. Groups were correlated with T-cell inflammation (Kindler ASCO 2014), based on the 12-gene inflammation signature (Harlin/Gajewski Cancer Res 2009). Results: MM tumors readily clustered into two large groups with 35% of tumors showing high levels of inflammation (group 1), presence of all four immune cell components, and 80% of tumors showing a TCIP-high phenotype. Non-inflamed tumors (group 2) showed low immune cell related gene expression and were 85% non-T-cell inflamed. Prominent immune escape was present in all group 1 tumors, including expression of PD-1/PD-L1, CTLA4, LAG3, and FOXP3 (however not B7H3). Inflammation strongly correlated with presence of immune escape (functional immune response) in group 1, while group 2 tumors exhibited neither infiltration with immune cells, nor immune escape (immunological ignorance). Conclusions: MM can be classified into inflamed/group 1 and non-inflamed/group 2 tumors. Group 1 tumors show simultaneous infiltration with multiple immune cell components, and prominent immune escape. Inflamed and non-inflamed MM may require differential treatment strategies for immunotherapy.
Comparison of a Potential Hospital Quality Metric With Existing Metrics for Surgical Quality–Associated Readmission
Authors: Laura A. Graham, Hillary J. Mull, Todd H. Wagner, Melanie S. Morris, Amy K. Rosen, Joshua S. Richman, Jeffery Whittle, Edith Burns, Laurel A. Copeland, Kamal M. F. Itani, Mary T. Hawn
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The existing readmission quality metric does not meaningfully distinguish readmissions associated with surgical quality from those that are not associated with surgical quality and thus may not reflect the quality of surgical care. <h3>Objective</h3> To compare a quality metric that classifies readmissions associated with surgical quality with the existing metric of any unplanned readmission in a surgical population. <h3>Design, Setting, and Participants</h3> Cohort study using US nationwide administrative data collected on 4 high-volume surgical procedures performed at 103 Veterans Affairs hospitals from October 1, 2007, through September 30, 2014. Data analysis was conducted from October 1, 2017, to January 24, 2019. <h3>Main Outcomes and Measures</h3> Hospital-level rates of unplanned readmission (existing metric) and surgical readmissions associated with surgical quality (new metric) in the 30 days following hospital discharge for an inpatient surgical procedure. <h3>Results</h3> The study population included 109 258 patients who underwent surgery at 103 hospitals. Patients were majority male (94.1%) and white (78.2%) with a mean (SD) age of 64.0 (10.0) years at the time of surgery. After case-mix adjustment, 30-day surgical readmissions ranged from 4.6% (95% CI, 4.5%-4.8%) among knee arthroplasties to 11.1% (95% CI, 10.9%-11.3%) among colorectal resections. The new surgical readmission metric was significantly correlated with facility-level postdischarge complications for all procedures, with ρ coefficients ranging from 0.33 (95% CI, 0.13-0.51) for cholecystectomy to 0.52 (95% CI, 0.38-0.68) for colorectal resection. Correlations between postdischarge complications and the new surgical readmission metric were higher than correlations between complications and the existing readmission metric for all procedures examined (knee arthroplasty: 0.50 vs 0.48; hip replacement: 0.44 vs 0.18; colorectal resection: 0.52 vs 0.42; and cholecystectomy: 0.33 vs 0.10). When compared with using the existing readmission metric, using the new surgical readmission metric could change hip replacement–associated payment penalty determinations in 28.4% of hospitals and knee arthroplasty–associated penalties in 26.0% of hospitals. <h3>Conclusions and Relevance</h3> In this study, surgical quality–associated readmissions were more correlated with postdischarge complications at a higher rate than were unplanned readmissions. Thus, a metric based on such readmissions may be a better measure of surgical care quality. This work provides an important step in the development of future value-based payments and promotes evidence-based quality metrics targeting the quality of surgical care.
SAT-329-Ethyl glucuronide inhair uncovers a high rate of harmful alcohol consumption in patients with presumed NAFLD
Authors: Katharina Staufer, Georg Strebinger, Ursula Huber-Schönauer, Silke Süße, Manuela Teufelhart, Gerhard Prager, Bernhard Paulweber, Peter Ferenci, Thomas Stimpfl, Michel Yegles, Christian Datz, Michael Trauner
Journal: Journal of Hepatology (2019)
A Mendelian randomization study of the effects of Crohn’s disease on lung cancer
Authors: J. Liu, H. Zhou, Y. Zhang, W. Fang, Y. Yang, S. Hong, G. Chen, S. Zhao, J. Shen, W. Xian, Y. Huang, H. Zhao, L. Zhang
Journal: Annals of Oncology (2019)

Background: Crohn's disease is associated with increased lung cancer risk in observational studies, but the causality of this association is uncertain. Here we conducted a two-sample Mendelian randomisation (MR) study to examine whether Crohn's disease is causally related to lung cancer. Methods: We used the summary data of the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC, 5,956 cases and 14,927 controls; European ancestry) and International Lung Cancer Consortium (ILCCO, 11348 lung cancer cases and 15861 controls; European ancestry). 52 single nucleotide polymorphisms (SNPs) associated with Crohn's disease were used as instrumental variables in the MR analysis. We utilized various MR methods (inverse-variance weighting (IVW), MR Egger, weighted median regression) to explore the causality. To investigate whether the effect of Crohn's disease is associated with the histology of lung cancer, we also performed similar analyses on two different histologic subtypes of lung cancer (adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Results: Crohn's disease was not significantly associated with risk of lung cancer (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.97-1.04; p = 0.76, IVW method). Weighted median (OR, 1.03; 95% CI, 0.98-1.07; p = 0.26) and MR Egger analysis (OR, 1.03; 95% CI, 0.95-1.11; p = 0.49) showed similar effect estimates of Crohn's disease on lung cancer. The MR-Egger regression analysis showed that there was no evidence for the presence of horizontal pleiotropy (intercept β=-0.005, p = 0.532). Our leave-one-out analysis revealed that no single SNP strongly drove the overall effect of Crohn's disease on lung cancer. The similar causal trend was observed in both LUAD and LUSC (LUAD, OR 0.99, 95% CI 0.94-1.04, p = 0.67, IVW method; LUSC, OR 0.98, 95% CI 0.94-1.03, p = 0.47, IVW method). Conclusions: Our findings indicated that Crohn's disease might not be causally associated with lung cancer, although patients with Crohn's disease were at increased lung cancer risk in observational studies. Our study suggested there might be other risk factors associated with lung cancer in patients Crohn's disease, which needs to be confirmed in the further study. Legal entity responsible for the study: The authors. Funding: National Key R&D Program of China (2016YFC0905500). Disclosure: All authors have declared no conflicts of interest.
PS-046-Suppression of complex protumorigenic phenotypes in chronic injury-associated hepatocarcinogenesis is dependent on IL-6/STAT3 signaling
Authors: Anat Shriki, tali lanton, Amir Sonnenblick, Orr Levkovitch, Rinat Abramovitch, Lina Mizrahi, Devorah Olam, Orit Pappo, Sharona Elgavish, Amnon Peled, Stefan Rose-John, Eithan Galun, Jonathan Axelrod
Journal: Journal of Hepatology (2019)
Myeloid-derived suppressor cells endow stem-like qualities to multiple myeloma cells by inducing piRNA-823 expression and DNMT3B activation
Authors: Lisha Ai, Shidai Mu, Chunyan Sun, Fengjuan Fan, Han Yan, You Qin, Guohui Cui, Yadan Wang, Tao Guo, Heng Mei, Huafang Wang, Yu Hu
Journal: Molecular Cancer (2019)

Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood.The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells.Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo.Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.
Comparison of Proteasome Inhibition Activity between Carfilzomib and Bortezomib in the Phase 3 Endeavor Study
Authors: Heinz Ludwig, Andrew Spencer, Tibor Kovacsovics, Nashat Y. Gabrail, Leonard Minuk, Amy S. Kimball, Robert J. Pelham, Ying C. Ou, Robert Z. Orlowski
Journal: Blood (2017)
A Psoriasiform Drug Eruption Secondary to Nivolumab for Hepatocellular Carcinoma: A Case Report
Authors: Matthew J. Stotts, Opaku Adjapong, David E. Kaplan
Journal: Hepatology (2019)

1Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 2Corporal Michael J Crescenz VA Medical CenterPhiladelphiaPA *Address Correspondence and Reprint Requests to: Matthew J. Stotts, M.D. Perelman School of Medicine, University of Pennsylvania 3400 Civic Center Boulevard Philadelphia, PA 19104 E‐mail: [email protected] Tel.: +1‐215‐662‐4000
Abstract 12664: Persistence on Warfarin Therapy in Patients with Venous Thromboembolism: A Large US Insurance Database Analysis
Authors: Xianchen Liu, Lin Xie, Hemant Phatak, Jack Mardekian, Wilson Tan, Onur Baser, Eduardo Ramacciotti
Journal: Circulation (2013)

Introduction: Adherence to antithrombotic therapy is crucial to prevent recurrence of venous thromboembolism (VTE). This study examined persistence on warfarin therapy among VTE patients in the US ...
Association Between Pharmacy Closures and Adherence to Cardiovascular Medications Among Older US Adults
Authors: Dima M. Qato, G. Caleb Alexander, Apurba Chakraborty, Jenny S. Guadamuz, John W. Jackson
Journal: JAMA Network Open (2019)

<h3>Importance</h3> It is unknown whether and how pharmacy closures alter medication adherence. <h3>Objective</h3> To examine the association between pharmacy closures and adherence to statins, β-blockers, and oral anticoagulants among adults 50 years or older in the United States. <h3>Design, Setting, and Participants</h3> In this retrospective cohort study, comparative interrupted time series analyses were performed using a nationally representative 5% random sample of anonymized, longitudinal, individual-level pharmacy claims from IQVIA LRx LifeLink. Analyses included all prescription claims for individuals followed up between January 1, 2011, and December 31, 2016. Separate cohorts were derived for users of statins, β-blockers, and oral anticoagulants. The differential association of pharmacy closure was examined as a function of baseline adherence, pharmacy, and individual characteristics. <h3>Main Outcomes and Measures</h3> Difference in monthly adherence, measured as proportion of days covered, during 12-month baseline and follow-up periods among patients using a pharmacy that subsequently closed (closure cohort) compared with their counterparts (control cohort). <h3>Results</h3> Among 3 089 803 individuals filling at least 1 statin prescription between January 1, 2011, and December 31, 2016 (mean [SD] age, 66.3 [9.3] years; 52.0% female), 3.0% (n = 92 287) filled at a pharmacy that subsequently closed. Before closure, monthly adherence was similar in the closure and control cohorts (mean [SD], 70.5% [26.7%] vs 70.7% [26.5%]). In multivariable models, individuals filling at pharmacies that closed experienced an immediate and significant decline (on average, an absolute change of −5.90%; 95% CI, −6.12% to −5.69%) in statin adherence during the first 3 months after closure compared with their counterparts. This difference persisted over 12 months of follow-up. A similar decline in adherence was observed when examining cohorts using β-blockers (−5.71%; 95% CI, −5.96% to −5.46%) or oral anticoagulants (−5.63%; 95% CI, −6.24% to −5.01%). The mean association of pharmacy closure with adherence was greater among individuals using independent pharmacies (−7.89%; 95% CI, −8.32% to −7.47%) or living in neighborhoods with fewer pharmacies (−7.98%; 95% CI, −8.50% to −7.47%) compared with their counterparts. <h3>Conclusions and Relevance</h3> Pharmacy closures are associated with persistent, clinically significant declines in adherence to cardiovascular medications among older adults in the United States. Efforts to reduce nonadherence to prescription medications should consider the role of pharmacy closures, especially among patients at highest risk.