tbuckley/cabot-search huggingface dataset:
The role of patient performance status and its changes before and after completion of multimodal treatment for inoperable stage III NSCLC
Authors: L. Käsmann, J. Taugner, C. Eze, O. Roengvoraphoj, M. Dantes, K. Gennen, M. Karin, A. Tufman, C. Belka, F. Manapov
Journal: Annals of Oncology (2019)

Background: The Eastern Cooperative Oncology Group performance score (ECOG-PS) is used in clinical routine to quantify patients' general condition. We evaluated ECOG-PS before, after and its changes in the course of chemoradiotherapy (CRT) in patients with inoperable stage III NSCLC. Methods: The data of ninety-nine patients with NSCLC UICC stage IIIA/B (TNM 7th edition) were evaluated. ECOG-PS before treatment, at first follow-up and the difference was examined for their impact on overall survival (OS) from initial diagnosis and event-free survival (EFS) from the first day of radiation. Results: Median survival for the entire cohort was 20.8 (range: 15.3-26.2) months. Before the start of multimodal treatment, ECOG-PS was 0 in 48% and 1 in 52% of patients; median OS, 1- and 2-year survival rates were 26.4 months, 85% and 53% for ECOG-PS 0 and 18.9 months, 69% and 37% for ECOG-PS 1 patients (p = 0.1). After completion of CRT 65% of patients had the same or better and 35% worse ECOG-PS: 0 in 34%, 1 in 46%, 2 in 18% and 3 in 2% of patients. Median OS, 1- and 2-year survival rates were 40.3 months, 88% and 64% for ECOG-PS 0; 19.3 months, 82% and 40% for ECOG-PS 1; 11.9 months, 50% and 28% for ECOG-PS 2 and 7.6 months, 0% and 0% for ECOG-PS 3 (p < 0.001). Deterioration of ECOG-PS after multimodal treatment significantly impaired survival in the initial ECOG-PS 0 (p = 0.005, median 19.1 vs 31.4 months) and 1 (p = 0.001, median 22.9 vs 11.1 months) subgroups. Median EFS was 9.6, 9.0, 7.9 and 3.5 months for patients with ECOG-PS 0, 1, 2, 3 after completion of CRT (p = 0.018). EFS was not affected by initial ECOG-PS but was significantly impaired by deterioration of ECOG-PS after completion of multimodal therapy with a median time of 9.4 vs 7.7 months (p = 0.049), respectively. Conclusions: Deterioration of ECOG-PS after completion of primary multimodal treatment is a significant negative prognostic factor. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Li Shen, Pardeep S. Jhund, Kieran F. Docherty, Mark C. Petrie, Inder S. Anand, Peter E. Carson, Akshay S. Desai, Christopher B. Granger, Michel Komajda, Robert S. McKelvie, Marc A. Pfeffer, Scott D. Solomon, Karl Swedberg, Michael R. Zile, John J.V. McMurray
Journal: JACC Heart Failure (2019)
Half of patients prescribed statins fail to hit target reduction in LDL cholesterol
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Half of patients prescribed statins in primary care fail to reach the target cholesterol concentration specified by the National Institute for Health and Care Excellence (NICE) after two years, a new study has found.1

Researchers analysed data for 165 411 patients taking statins, who did not have cardiovascular disease before starting them, and found that 51.2% did not meet the 40% reduction target for low density lipoprotein (LDL) cholesterol.

The study could not account for the effect of non-adherence to statins by patients, a factor which cardiologist Marcio Bittencourt said could explain why the reduction in LDL cholesterol was lower than expected in “most cases.” …
Esophageal diverticulosis associated with Barrett’s esophagus and erosive esophagitis
Authors: Supriya Rao, Ashish Sharma, H. Christian Weber
Journal: Endoscopy (2019)

A 62-year-old man with a history of symptomatic gastroesophageal reflux disease presented to our clinic with longstanding solid food dysphagia. Physical examination and laboratory values were unremarkable.
Tumor infiltrating lymphocyte (TIL) classifications and association with survival in primary melanomas.
Authors: Sarah Ann Weiss, Sung Won Han, Matjaz Vogelsang, Michelle Krogsgaard, Kevin P. Lui, Richard L. Shapiro, Tomas Kirchhoff, Farbod Darvishian, Iman Osman
Journal: Journal of Clinical Oncology (2015)

e20042 Background: TILs in primary melanomas may represent a surrogate of anti-tumor immune response, yet debate exists if TIL grade offers independent prognostication. In a large, prospectively accrued, well-characterized patient (pt) cohort, we examined if quantitative TIL detection contributes to improved outcome predictions and tested if germline variants are associated with TIL grade. Methods: We studied 1,241 pts with primary cutaneous melanoma presenting to NYU from 2002-13 (median f/u 3.9 years). TILs were graded as absent, non-brisk or brisk on H&E as previously defined. Association between TIL grade and primary tumor characteristics was analyzed using the Chi square test. Quantitative CD3 and CD45 immunohistochemistry for TILs was performed on a subset of 200 tumors representing the cohort. We examined 365 single nucleotide variants in genes related to melanoma risk and immunomodulation for association with TIL grade in a subset of 607 pts. Hazard ratios (HR) for recurrence-free survival (RFS) and overall survival (OS) by TIL grade were estimated by Cox models. Logistic regression analyses were used to test the association between germline variants and TIL grade. Results: TILs were classified as absent (n = 388, 31%), non-brisk (n = 330, 27%) and brisk (n = 523, 42%) on H&E. Pts with brisk TILs had significantly longer RFS and OS (p = 0.007, HR 0.56; p = 0.0017, HR 0.54, respectively) compared to non-brisk TILs on univariate and multivariate analysis controlling for thickness (p = 0.036). Interestingly, pts with non-brisk TILs had the worst RFS (p = 0.017) and OS (p = 0.008) among all TIL grades. TIL quantitation for CD3, CD45 and the combination did not improve outcome predictions. Two independent germline variants of the BCL10 gene, involved in apoptotic and NF-kappaB pathways, associated with TIL grade, most significantly rs962409 (OR = 2.98, p = 0.0007). Conclusions: Presence of TILs is a heterogeneous group and caution in prognostic interpretation is warranted. Studies are underway to characterize T-cell effector and suppressor interactions among TIL subtypes. Identification of germline variants associated with TIL grade suggests that inherited genetic factors may contribute at least in part to TIL grade.
The Unique Pharmacological and Pharmacokinetic Profile of Teneligliptin: Implications for Clinical Practice
Authors: Antonio Ceriello, Valeria De Nigris, Hiroaki Iijima, Takahiro Matsui, Maki Gouda
Journal: Drugs (2019)

Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that was approved for the treatment of type 2 diabetes mellitus (T2DM) in Japan and Korea and is being researched in several countries. Teneligliptin is a potent, selective, and long-lasting DPP-4 inhibitor with a t½ of approximately 24 h and unique pharmacokinetic properties: it is metabolized by cytochrome P450 (CYP) 3A4 and flavin-containing monooxygenase 3 (FMO3), or excreted from the kidney in an unchanged form. Because of its multiple elimination pathways, dose adjustment is not needed in patients with hepatic or renal impairment, and it is considered to have a low potential for drug–drug interactions. Clinical studies and postmarketing surveillance show that teneligliptin, administered as monotherapy and/or in combination with antihyperglycemic agents, is effective and well tolerated in T2DM patients, including in elderly patients and those with renal impairment. Furthermore, teneligliptin has antioxidative properties, which induce the antioxidant cascade, as well as ·OH scavenging properties. In addition, it has shown endothelial protective effects in several non-clinical and clinical studies. From its unique profile and clinical data, teneligliptin represents a potential therapeutic option in a wide variety of patients, including elderly diabetic patients and those with renal impairment. The fixed-dose combination (FDC) tablet of teneligliptin and canagliflozin has been approved in Japan; this is the first FDC tablet of a DPP-4 inhibitor and sodium glucose co-transporter 2 inhibitor in Japan, and the third globally. The FDC tablet may also provide additional prescribing and adherence benefits.
ARQ 197 in patients with previously-treated malignant mesothelioma (MM): A phase II trial from the University of Chicago Phase II Consortium.
Authors: Steven Brad Maron, Theodore Karrison, Rajani Kanteti, Krishna A. Rao, David R. Gandara, Marianna Koczywas, Ravi Salgia, Hedy Lee Kindler
Journal: Journal of Clinical Oncology (2015)

7511 Background: The MET receptor tyrosine kinase plays a key role in MM biology. MET and its ligand, hepatocyte growth factor (HGF), are each over-expressed in ~80% of MM; MET is mutated and/or amplified in ~10% of MM. Cancers with MET over-expression or mutation are potentially more sensitive to MET inhibitors, such as ARQ 197 (tivantinib), which inhibits MM growth and proliferation in preclinical models. Methods: We conducted a multicenter phase II trial of ARQ 197 in previously-treated pts with histologically-confirmed pleural (PL) or peritoneal (PER) MM, measurable disease, PS 0-1, and ≤ 2 prior chemotherapies. Primary endpoint: response. ARQ 197 360mg was given orally BID. CT scans were obtained Q8 weeks. A Simon, optimal, 2-stage design required 2 responses in 16 pts to proceed to a 2nd stage. Correlatives: MET mutation, gene amplification, IHC, and serum HGF. Results: 18 pts enrolled at 4 centers between 2/13 and 12/13. Male 61%; median age 66 (range 19-81); PS 0: 50%; epithelial/biphasic/sarcomatoid histology: 89%/5%/5%; PL/PER: 61%/39%; Median # cycles: 3 (range 2-14). There were no objective responses. Stable disease (SD): 50% (33% PL pts, 71% PER pts). 3 PER pts had SD for 9.7, 11, and 15.2 months, respectively. Median PFS: 1.9 mo (95% CI: 1.8-5.4); PL/PER 1.8/3.8 mo (95% CI: 1.8-5.4/1.8-11). Median OS 12.2 mo (95% CI: 7.1-22.2); PL/PER: 8.0/22.2 mo (95% CI: 4.6-12.2/7.1-NR). Grade 3/4 toxicities: leukopenia, lymphopenia, abdominal pain, fatigue, infection 6% each. Correlatives: N = 16. IHC expression (0/1+/2+/3+): c-MET (38%/31%/19%/13%), p-MET (0%/0%/31%/69%,) and p-AKT (0%/13%/31%/56%). One pt had a T110I mutation in the MET juxtamembrane domain. There was no correlation between MET pathway IHC expression or mutation and PFS or OS upon preliminary analysis. Conclusions: The trial did not meet its pre-specified response endpoint. However, 43% of peritoneal pts had SD for > 9 months. Though p-MET expression was high, MET IHC expression or mutation did not correlate with disease control. Alternative biomarkers predictive of the activity of ARQ 197 in PER MM pts should be evaluated. Funded by NCI N01-CM-2011-0071C.
THU-051-Establishment of a new animal model for the acute-on-chronic liver failure
Authors: Katharina Schwarzkopf, Sabrina Rüschenbaum, Marcus Maximilian Muecke, Sina Fuchs, Marie Messmer, Monika Bayer, Edith Hintermann, Stefan Zeuzem, Urs Christen, Christian Lange
Journal: Journal of Hepatology (2019)
A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2)
Authors: Ying Z. Mazzu, Joshua Armenia, Goutam Chakraborty, Yuki Yoshikawa, Si'Ana A. Coggins, Subhiksha Nandakumar, Travis A. Gerke, Mark M. Pomerantz, Xintao Qiu, Huiyong Zhao, Mohammad Atiq, Nabeela Khan, Kazumasa Komura, Gwo-Shu Mary Lee, Samson W. Fine, Connor Bell, Edward O'Connor, Henry W. Long, Matthew L. Freedman, Baek Kim, Philip W. Kantoff
Journal: Clinical Cancer Research (2019)

Defects in genes in the DNA repair pathways significantly contribute to prostate cancer progression. We hypothesize that overexpression of DNA repair genes may also drive poorer outcomes in prostate cancer. The ribonucleotide reductase small subunit M2 (RRM2) is essential for DNA synthesis and DNA repair by producing dNTPs. It is frequently overexpressed in cancers, but very little is known about its function in prostate cancer.
Overall survival and treatment response in patients with myelodysplastic syndrome and acute myeloid leukemia treated with DNA methyl-transferase inhibitors vs. conventional care regimens: A meta-analysis of 5 randomized trials.
Authors: Seongseok Yun, Nicole Vincelette, Jennifer Segar
Journal: Journal of Clinical Oncology (2015)

7037 Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are two of the most common myeloid neoplastic disorders that are characterized by genetic instability and ineffective hematopoiesis. DNA methyl-transferase inhibitors (DMTI) have been widely used for elderly MDS and AML patients who are not qualified for stem cell transplantation (SCT), however the outcomes from previous trials were inconsistent. The purpose of current meta-analysis is to assess the efficacy of DMTI compared to conventional care regimens (CCRs) in patients with high risk MDS or AML. Methods: Relevant articles were searched in PubMed, EMBASE and Cochrane database. Eligible studies were limited to randomized trials comparing DMTI (azacitidine or decitabine) and CCRs (best supportive care, low dose cytarabine or intensive chemotherapy) in adult patients with MDS or AML. Cochrane’s Q statistic was used for the calculation of the statistical heterogeneity. Relative risks and 95% CI were calculated using random effect model and RevMan 5.3 software. Results: Significant OS benefit was associated with DMTI treatment compared to CCR with OS of 33.2% vs. 21.4% (RR 0.83, 95% CI, 0.71 to 0.98, P= 0.03). CR/PR rate was also significantly higher in DMTI group with a response rate of 23.7% vs. 13.4% (RR 0.87, 95% CI, 0.81 to 0.93). In a subgroup analysis, only azacitidine treatment showed OS improvement (RR 0.75, 95% CI, 0.67 to 0.85), but not in decitabine (RR 0.96, 95% CI, 0.92 to 1.01). Additional subgroup analysis according to cytogenetic risk and BM blast counts did not show significant RR difference. Conclusions: In a meta-analysis of randomized trials in patients with MDS or AML, DMTI treatment was associated with treatment response and survival benefit, although the initial treatment response failed to translate into survival benefit in patients treated with decitabine. Collectively, these results suggest that azacitidine may be the best therapeutic option in high risk MDS or AML patients who are not eligible for allogeneic SCT regardless of cytogenetic risk or degree of bone marrow involvement.
FRI-070-Long-term clinical outcomes in patients with autoimmune hepatitis according to treatment response in Asian country
Authors: Sun Yoo, Jonggi Choi, Gwang Hyun Choi, Danbi Lee, Ju Hyun Shim, Young-Suk Lim, Han Chu Lee, Young-Hwa Chung, Yung-Sang Lee, Kang Mo Kim
Journal: Journal of Hepatology (2019)
SAT-079-Respiratory infection in patients with cirrhosis and acute variceal bleeding on antibiotic prophylaxis: A multicenter observational study of 2138 patients
Authors: Javier Martinez, Tellez luis, Virginia Hernandez-Gea, Bogdan Procopet, Alvaro Giraldez-Gallego, Lucio Amitrano, Candid Villanueva, Dominique Thabut, Luis Ibañez, Gilberto Silva-Junior, Joan Genesca, Bureau christophe, Elba Llop, Wim Laleman, Jose María Palazon, José Castellote, Susana G. Rodrigues, Lise Lotte Gluud, Carlos Noronha Ferreira, Rafael Barcelo, Nuria Cañete, Manuel Rodriguez, Prof. Dr. Arnulf Ferlitsch, Jose Luis Mundi, Henning Granbæk, Manuel Hernandez-Guerra, Romanno Sassatelli, Alessandra Dell'Era, Marco Senzolo, Juan Abraldes, Manolo Romero-gómez, Alexander Zipprich, Meritxell Casas, Helena Masnou, Massimo Primignani, Aleksander Krag, Frederik Nevens, José Luis Calleja Panero, Christian Jansen, Marie Angele Robic, Irene Conejo, Maria-Vega Catalina, Marika Rudler, Rafael Bañares, Edilmar Alvarado, Jonel Trebicka, Maria Anna Guardascione, Marcel Tantau, Ferran Torres, Jaime Bosch, Garcia Pagan Juan Carlos, Agustin Albillos
Journal: Journal of Hepatology (2019)
SAT-150-Validation of Korean stroop test in the screening of minimal hepatic encephalopathy
Authors: Eileen Yoon, Dae Won Jun, Jaeyoon Jeong, Tae Yeob Kim, Do Seon Song, Sang Bong Ahn, Hee Yeon Kim, Young Kul Jung, Myeong Jun Song, Sung Eun Kim, Hyoung Su Kim, Soung Won Jeong, sang gyune kim, Tae Hee Lee, Yong Kyun Cho
Journal: Journal of Hepatology (2019)
THU-494-MicroRNA-96 in non-B non-C hepatocellular carcinoma
Authors: Matsui Takeshi, Susumu Tsutsumi, Yutaka Naito, Masanori Nojima, Etsuko Iio, Akihiro Tamori, Shoji Kubo, Tatsuya Ide, Yasuteru Kondo, Yuichiro Eguchi, Atsumasa Komori, Mitsuo Shimada, Tohru Utsunomiya, Koichi Kimura, Yoichi Hiasa, Takahiro Ochiya, Yasuhito Tanaka
Journal: Journal of Hepatology (2019)
THU-152-New in France: Universal access for HCV-treatment as demonstrated by a nationwide real-world cohort
Authors: Dominique Larrey, Stanislas Pol, André-Jean Remy, Jérôme Dumortier, Christophe Hézode, Jean-Pierre Bronowicki, Caroline Jezequel, Jean-Didier Grangé, Dominique Thabut, Victor De Ledinghen, Christophe Renou, Frédéric Heluwaert, Ghassan Riachi, Régine Truchi, Isabelle Rosa, François Bailly, Denise Glorian-Kergavarat, Olivier Libert, Philippe Bonnard, Denis Ouzan
Journal: Journal of Hepatology (2019)
Magnetic ternary nanohybrids for nonviral gene delivery of stem cells and applications on cancer therapy
Authors: Rih-Yang Huang, Yee-Hsien Lin, Ssu-Yu Lin, Yi-Nan Li, Chi-Shiun Chiang, Chien-Wen Chang
Journal: Theranostics (2019)

Cancer toxic agent-expressing mesenchymal stem cells (MSCs), which possess inherent tumor migration and penetration capabilities, have received increasing attention in cancer therapy. To ensure that this approach is successful, safe and efficient gene delivery methods for stem cell engineering must be developed.
Abstract P167: High vs. Standard Protein Diets in Obese Patients with Heart Failure: Effects on Chronic Disease Risks
Authors: Lorraine S Evangelista, Dawn Lombardo, Tamara Horwich, Michele Hamilton, Gregg C Fonarow
Journal: Circulation (2017)

Background: There is controversy over dietary protein’s effect on long-term chronic disease risks in overweight and obese patients with heart failure. The aim of this study was to compare the effects of two calorie-restricted diets differing in protein content on chronic disease risks (e.g., weight, adiposity, glycemic control, lipid profiles, and blood pressure). Methods: A total of 97 overweight and obese (mean body mass index [BMI], 37.0 ± 6.2 kg/m 2 ) patients with heart failure, aged 58.8 ± 9.7 years, 70% males, consumed two diets, each for 12 weeks, in a randomized controlled design. The diets were: (1) a high protein diet (30% protein, 40% carbohydrates, and 30% fat) and (2) a standard protein diet (15% protein, 55% carbohydrates, and 30% fat). Their effects on weight (BMI) visceral fat (i.e. waist circumference), glycemic control (i.e. glycosylated hemoglobin [HgbA1C]), lipid profiles (total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides [TG]), and blood pressure at the beginning and end of each dietary intervention were analyzed. Results: Both diets were equally effective in promoting weight loss and visceral fat loss and in improving TC, but the high protein diet decreased to a greater extent HgbA1C levels ( P &lt; 0.001) when compared with the standard protein diet. The high protein diet improved significantly TG levels ( P &lt; 0.001) and both systolic and diastolic blood pressures when compared with the standard protein diet ( P &lt; 0.001 and P &lt; 0.001, respectively, see figure). No differences were noted in LDL and HDL levels. Conclusion: Energy restricted diets facilitate weight loss and visceral fat loss and lower TC in overweight and obese patients with heart failure. However, the high protein diet promoted better improvements in TG levels, glycemic control, and blood pressure than the standard protein diet, and may be superior in reducing chronic disease risks and potentially slowing the progression of disease in this population.
<i>Synechococcus elongatus</i> PCC7942 secretes extracellular vesicles to accelerate cutaneous wound healing by promoting angiogenesis
Authors: Hao Yin, Chun-Yuan Chen, Yi-Wei Liu, Yi-Juan Tan, Zhi-Li Deng, Fei Yang, Fei-Yu Huang, Cong Wen, Shan-Shan Rao, Ming-Jie Luo, Xiong-Ke Hu, Zheng-Zhao Liu, Zhen-Xing Wang, Jia Cao, Hao-Ming Liu, Jiang-Hua Liu, Tao Yue, Si-Yuan Tang, Hui Xie
Journal: Theranostics (2019)

Poor wound healing affects millions of people worldwide each year and needs better therapeutic strategies.Synechococcus elongatus PCC 7942 is a naturally occurring photoautotrophic cyanobacterium that can be easily obtained and large-scale expanded.Here, we investigated the therapeutic efficacy of this cyanobacterium in a mouse model of acute burn injury and whether the secretion of extracellular vesicles (EVs), important mediators of cell paracrine activity, is a key mechanism of the cyanobacterium-induced regulation of wound healing.Methods: The effects of Synechococcus elongatus PCC 7942 on burn wound healing in mice under light or dark conditions were evaluated by measuring wound closure rates, histological and immunofluorescence analyses.A series of assays in vivo and in vitro were conducted to assess the impact of the cyanobacterium on angiogenesis.GW4869 was used to interfere with the secretion of EVs by the cyanobacterium and the abilities of the GW4869-pretreated and untreated Synechococcus elongatus PCC 7942 to regulate endothelial angiogenesis were compared.The direct effects of the cyanobacterium-derived EVs (S. elongatus-EVs) on angiogenesis, wound healing and expressions of a class of pro-inflammatory factors that have regulatory roles in wound healing were also examined.Results: Synechococcus elongatus PCC 7942 treatment under light and dark conditions both significantly promoted angiogenesis and burn wound repair in mice.In vitro, the cyanobacterium enhanced angiogenic activities of endothelial cells, but the effects were markedly blocked by GW4869 pretreatment.S. elongatus-EVs were capable of augmenting endothelial angiogenesis in vitro, and stimulating new blood vessel formation and burn wound healing in mice.The expression of interleukin 6 (IL-6), which has an essential role in angiogenesis during skin wound repair, was induced in wound tissues and wound healing-related cells by S. elongatus-EVs and Synechococcus elongatus PCC 7942.Conclusion: Synechococcus elongatus PCC 7942 has the potential as a promising strategy for therapeutic angiogenesis and wound healing primarily by the delivery of functional EVs, not by its photosynthetic activity.The promotion of IL-6 expression may be a mechanism of the cyanobacterium and its EVs-induced pro-angiogenic and -wound healing effects.
SAT-292-Effectively reducing screen failure rate in non-alcoholic fatty liver disease clinical trial using the FibroScan-based FAST score combining liver stiffness, controlled attenuation parameter and AST
Authors: Peter Eddowes, Michael Allison, Emmanouil Tsochatzis, Quentin Anstee, David Sheridan, Indra Neil Guha, Jeremy Cobbold, Valérie Paradis, Pierre Bedossa Philip Newsome
Journal: Journal of Hepatology (2019)