tbuckley/cabot-search huggingface dataset:
Abstract 18901: Endothelium Based Feeder Improves Capacity of Human Embryonic Stem Cells Derived Cardiomyocytes
Authors: Jennifer Pasquier, Jessica Hoarau-Véchot, Damien Riout, Renuka Gupta, Nadine Abu-Kaoud, Charbel Abi Khalil, Shahin Rafii, Arash Rafii
Journal: Circulation (2015)

Introduction: The regenerative ability of the heart is very low, making patients with myocardial damage potential candidates for cell-based regenerative therapy. Pluripotent human embryonic stem cells (hESC) are a promising source of cardiomyocytes (CMs). While the quantity of CMs obtained is no longer a limitation in current differentiation protocols, their functionality remains to be improved. Indeed contracting areas in cell cultures are still heterogeneous and non-consistent Hypothesis: Endothelial cells (ECs) and CMs are derived from a common precursor. Moreover, endothelial secreted and contact dependent factors play a role at different phases of cardiac development and repair. We hypothesized that creating a mixture of cell types that more closely resembles heart tissue - i.e. containing both ECs and CMs - will lead to improved maturation and functionality Methods: We co-cultured NKX2-5-GFP reporter hESC line and an autonomous Akt-activated ECs and induced differentiation of NKX2-5GFP hESC into CMs We assessed functionality by evaluating beating and coordination between different CMs clusters. Results: Around 94% ± 6 of the NKX2-5GFP+ cells were beating when hESCs embryonic body (EBs) were plated on E4+ECs comparing to 34% ± 12.9 for controls. The spatial organization of beating areas in co-cultures was different. In 7 different experiments clustered in two populations, the average BPM of CMs in co-culture was faster and closer to a physiologic heart rate compare to controls (49.6 ± 13.77; n=13 vs 24.76 ±9.36; n=8 for controls; p&lt;0.05). Our protocol increased and accelerated the differentiation of CMs. More importantly CMs formed under these conditions displayed a higher rate of contractility with synchronized beating relying on an endothelial network. Conclusions: We have been able to build a culture platform in vitro capturing partially complexity of cardiac tissue. Such strategy resulted in the obtaining of more synchronized interconnected CMs nodes displaying faster beating. Our data showed that co-culture of differentiating hESCs with ECs increased functionality of the CMs, suggesting that an endothelial based feeder could promote the in vitro functionalization of clinically relevant cell type.
Trabectedin triggers direct and NK-mediated cytotoxicity in multiple myeloma
Authors: Maria Cucè, Maria Eugenia Gallo Cantafio, Maria Anna Siciliano, Caterina Riillo, Daniele Caracciolo, Francesca Scionti, Nicoletta Staropoli, Valeria Zuccalà, Lorenza Maltese, Anna Di Vito, Katia Grillone, Vito Barbieri, Mariamena Arbitrio, Maria Teresa Di Martino, Marco Rossi, Nicola Amodio, Pierosandro Tagliaferri, Pierfrancesco Tassone, Cirino Botta
Journal: Journal of Hematology & Oncology (2019)

Genomic instability is a feature of multiple myeloma (MM), and impairment in DNA damaging response (DDR) has an established role in disease pathobiology. Indeed, a deregulation of DNA repair pathways may contribute to genomic instability, to the establishment of drug resistance to genotoxic agents, and to the escape from immune surveillance. On these bases, we evaluated the role of different DDR pathways in MM and investigated, for the first time, the direct and immune-mediated anti-MM activity of the nucleotide excision repair (NER)-dependent agent trabectedin. Gene-expression profiling (GEP) was carried out with HTA2.0 Affymetrix array. Evaluation of apoptosis, cell cycle, and changes in cytokine production and release have been performed in 2D and 3D Matrigel-spheroid models through flow cytometry on MM cell lines and patients-derived primary MM cells exposed to increasing nanomolar concentrations of trabectedin. DNA-damage response has been evaluated through Western blot, immunofluorescence, and DNA fragmentation assay. Trabectedin-induced activation of NK has been assessed by CD107a degranulation. miRNAs quantification has been done through RT-PCR. By comparing GEP meta-analysis of normal and MM plasma cells (PCs), we observed an enrichment in DNA NER genes in poor prognosis MM. Trabectedin triggered apoptosis in primary MM cells and MM cell lines in both 2D and 3D in vitro assays. Moreover, trabectedin induced DDR activation, cellular stress with ROS production, and cell cycle arrest. Additionally, a significant reduction of MCP1 cytokine and VEGF-A in U266-monocytes co-cultures was observed, confirming the impairment of MM-promoting milieu. Drug-induced cell stress in MM cells led to upregulation of NK activating receptors ligands (i.e., NKG2D), which translated into increased NK activation and degranulation. Mechanistically, this effect was linked to trabectedin-induced inhibition of NKG2D-ligands negative regulators IRF4 and IKZF1, as well as to miR-17 family downregulation in MM cells. Taken together, our findings indicate a pleiotropic activity of NER-targeting agent trabectedin, which appears a promising candidate for novel anti-MM therapeutic strategies.
Abstract 39: Statin Use is Associated with Elevated Serum Glucose and Incidence of Type 2 Diabetes in US Veterans
Authors: Luc Djousse, Brittany Deane, Brian Charest, Constance Nelson, Kelly Cho, J M Gaziano, David R Gagnon
Journal: Circulation (2017)

Background: While some but not all trial data have suggested a slightly elevated risk of type 2 diabetes (T2D), limited data are available on the relation of statin use with glycemia among US veterans. Objective: To test the hypothesis that treatment with a statin is associated with elevated serum glucose and a higher risk of T2D among US veterans. Methods: We studied 549,143 US veterans with electronic health records from 1998 to 2016. We used the VA Corporate Data Warehouse to obtain information on glucose (fasting and non-fasting). Statin use was captured using the pharmacy database. T2D was defined as having at least one inpatient diagnosis or at least 2 outpatient diagnoses of T2D using ICD 9 codes 250.xx, or the use of hypoglycemic agents. We addressed confounding by indication using propensity score (included 444 variables/interactions) for receiving statin and inverse probability weighting in the Cox regression. Results: The mean age was 60±12.8 y; 94.3% were men; 77.1% were white; and 15.4% were black. In this cohort, simvastatin was the most prescribed statin (84%) followed by lovastatin (7%). During a median follow-up of 4.4 years, 130,819 new cases of T2D occurred. Among 418,847 veterans receiving statin, we observed a 2 mg/dl increase in serum glucose when comparing serum glucose measured at the time of statin initiation and short-term &lt;1 y as well as long-term glucose values (all p &lt;0.01). In crude analysis, statin use was associated with a 53% higher risk of T2D compared with non-users of statin [HR=1.53 (95% CI: 1.51-1.54)]. In a multivariable adjusted model, hazard ratio (95% CI) for T2D was 1.25 (95% CI: 1.24-1.26) after adjustment for propensity score for being on statin. There was a borderline statistically significant interaction between statin and triglycerides on T2D risk (p=0.09): HR=1.15 (95% CI: 1.14-1.16) for people with triglecerides below 150 mg/dl and HR=1.36 (95% CI: 1.35-1.38) for people with triglycerides of at least 150 mg/dl in the adjusted model. We did not have enough data to stratify by type of statin given the predominance of simvastatin in this population. Conclusions: Our data show a positive association between statin use and increase in both serum glucose and incidence of T2D among US veterans. If confirmed by others, this suggests closer monitoring of patients at risk of T2D when statin therapy is initiated.
Therapy for the Malnourished Heart
Authors: Elizabeth Molyneux
Journal: JAMA Network Open (2019)

Bernadette Brent, MD; Nchafatso Obonyo, MB, ChB; Samuel Akech, MD, PhD; Mohammed Shebbe, DiplClinMedChir; Ayub Mpoya, MSc; Neema Mturi, MMed; James A. Berkley, FMedSci, MD; Robert M. R. Tulloh, MA, DM; Kathryn Maitland, FMedSci, PhD
Comparative Overall Comorbidity Burden Among Patients With Hidradenitis Suppurativa
Authors: Sarah Reddy, Andrew Strunk, Amit Garg
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> The overall comorbidity burden among patients with hidradenitis suppurativa (HS) has not been systematically evaluated. <h3>Objectives</h3> To investigate the standardized overall comorbidity burden among patients with HS and to compare it with the comorbidity burden in patients with psoriasis and a control group. <h3>Design, Setting, and Participants</h3> A cross-sectional analysis was conducted of 5306 patients with HS, 14 037 patients with psoriasis, and 1 733 810 controls identified using electronic health records data from October 1, 2013, through October 1, 2018. <h3>Main Outcome and Measure</h3> The primary outcome was the mean Charlson Comorbidity Index (CCI) score. <h3>Results</h3> Each matched cohort had 3818 patients (2789 women and 1029 men; mean [SD] age, 45.7 [15.0]). Before matching, the overall mean (SD) CCI score was highest among the psoriasis cohort (2.33 [3.13]), followed by the HS cohort (1.80 [2.79]) and control cohort (1.26 [2.35]). In matched analyses, the overall mean (SD) CCI score was highest among the HS cohort (1.95 [2.96]), followed by the psoriasis cohort (1.47 [2.43];<i>P</i> &lt; .001) and control cohort (0.95 [1.99];<i>P</i> &lt; .001) patients. A total of 516 patients with HS (13.5%) had an overall mean CCI score of 5 or greater. Mean CCI score was highest for patients with HS across all sex, race, and age groups. The most common comorbidities among patients with HS were chronic pulmonary disease (1540 [40.3%]), diabetes with chronic complications (365 [9.6%]), diabetes without chronic complications (927 [24.3%]), and mild liver disease (455 [11.9%]). Patients with HS with a CCI score of 5 or greater had 4.97 (95% CI, 1.49-16.63) times the adjusted risk of 5-year mortality compared with patients with HS with a CCI score of zero. <h3>Conclusions and Relevance</h3> Patients with HS have a higher overall comorbidity burden compared with patients with psoriasis and a control group. A significant proportion of patients with HS have CCI scores of 5 or greater, which are associated with increased mortality. This degree of comorbidity burden may warrant multidisciplinary implementation of routine screening measures.
THU-391-Impact of early screening and treatment of hepatitis C virus and improvements in risk reduction on HCV transmission among HIV-infected men who have sex with men in France: A modeling approach
Authors: Mathieu Castry, Anthony Cousien, Virginie Supervie, Annie Velter, Jade Ghosn, A. David Paltiel, Yazdan Yazdanpanah, Sylvie Deuffic-Burban
Journal: Journal of Hepatology (2019)
PS-017-Long-term impact of sustained virological response on systemic and pulmonary hemodynamics in HCV-cirrhotic patients with portal hypertension
Authors: Sabela Lens, Edilmar Alvarado, Isabel Blanco, Zoe Mariño, Tanya Orizaga, Luis Ibañez, Jose Ignacio Fortea, Xavier Torras, Anna Baiges, Fanny Turon, Virginia Hernandez-Gea, Rafael Bañares, Angela Puente, Jaume Bosch, Joan Albert Barbera, Candid Villanueva, Xavier Forns, Garcia Pagan Juan Carlos
Journal: Journal of Hepatology (2019)
SAT-251-The association of serum IFN-λ3 levels with liver fibrosis and hepatocarcinogenesis in chronic hepatitis C patients treated with direct-acting antiviral agents
Authors: Miyako Murakawa, Yasuhiro Asahina, Emi Inoue, Mina Nakagawa, Jun Tsuchiya, Ayako Sato, Masato Miyoshi, Tomoyuki Tsunoda, Fukiko Kawai-Kitahata, Sayuri Nitta, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Mamoru Watanabe
Journal: Journal of Hepatology (2019)
FRI-454-Reappraisal of portal vein tumor thrombosis as a prognostic factor for patients with hepatocellular carcinoma
Authors: Young Chang, SuJong Yu, Jun Sik Yoon, Hyo Young Lee, Sun Woong Kim, Sungwon CHUNG, Minseok Albert Kim, Yun Bin Lee, EunJu Cho, Jeong-Hoon Lee, YoonJun Kim, Jung-Hwan Yoon
Journal: Journal of Hepatology (2019)
TCTAP A-069 A Long-term Clinical Follow-up of Sirolimus Coated Balloon in Real World Population: Results from NANOLUTE Study
Authors: Bernardo Cortese, Sameer Dani, Keyur Parikh, Ranjan Shetty, Prathap Kumar Pillai, Jagdish Hiremath, Dinesh Shah
Journal: Journal of the American College of Cardiology (2019)
Testicular sperm extraction and hCG-based hormonal treatment in cancer survivors with postchemotherapy azoospermia.
Authors: Koji Shiraishi, Hideyasu Matsuyama
Journal: Journal of Clinical Oncology (2015)

e20621 Background: To investigate the efficacy of microdissection testicular sperm extraction (micro-TESE) in patients with postchemotherapy azoospermia (PCA), we reviewed our results of micro-TESE combined with intracytoplasmic sperm injection (ICSI), which are the most commonly used fertility treatments. Furthermore, we investigated the efficacy of hCG-based hormonal therapy for men who failed to restore sperms by micro-TESE. Methods: In 4,211 new male infertility patients, 63 cancer survivors were found (1.5%) from 2007 to 2014 and they had never been recommended for sperm cryopreservation from oncology specialists. Among 52 PCA patients, 47 patients with the mean age of 35.3 years (range: 23-42) received micro-TESE and were included in this study. The cancer types included testicular cancer (14 patients), Hodgkin’s lymphoma (11 patients), non-Hodgkin’s lymphoma (9 patients), leukemia (7 patients), neuroblastoma (3 patients), osteosarcoma (2 patients), and malignant pheochromocytoma (1 patients). The mean interval from chemotherapy to micro-TESE was 14.5 years (range: 7-25), and the mean age of the female partners was 34.5 years. Results: Sperms were retrieved in 18 (38%) of the patients. Eight patients who did not obtain successful sperm retrieval underwent hCG-based hormonal therapy, and sperms were retrieved from 3 patients by the second micro-TESE. Using ICSI, 13 (28%) pregnancies and 9 (19%) live birth deliveries were achieved. Patients with PCA after testicular cancer treatment were able to achieve a high rate (75%) of sperm retrieval and those who had been exposed to alkylating agents (e.g., leukemia) resulted in lower sperm retrieval rates. Conclusions: Micro-TESE and ICSI is an effective fertility treatment for patients with PCA. Furthermore, patients who could not achieve successful sperm retrieval by micro-TESE might obtain improved outcomes with hormonal therapy, indicating that these treatments might provide the patients with PCA with the opportunity to retrieve sperms and father a child.
FRI-012-Analysis of clinical and histological factors to differentiate autoimmune hepatitis of drug induced liver injury
Authors: Lidia Cuevas del Campo, Elena Gómez-Domínguez, Yolanda Rodriguez Gil, Maria Luisa Manzano Alonso, Ana Martin Algibez, Gregorio Castellano Tortajada, Inmaculada Fernández Vázquez
Journal: Journal of Hepatology (2019)
Abstract 16546: Difference in Impact of CYP2C19 Polymorphism on Platelet Reactivity and Clinical Outcomes Between Acute Coronary Syndrome (ACS) and Stable Angina
Authors: Seiji Hokimoto, Tomonori Akasaka, Koichi Kaikita, Kazuko Nakagawa, Hisao Ogawa
Journal: Circulation (2013)

Background: As compared with Caucasian, Japanese more often carry the CYP2C19 loss-of-function (LOF) allele with the CYP2C19*3 variant. The difference in influence of the CYP2C19 LOF alleles (*2 and *3) on clopidogrel response and clinical outcomes between ACS and stable angina (SA) has not been reported. The Aim was to examine the difference in impact of the CYP2C19 variants on platelet reactivity and prognosis between ACS and SA after stent implantation. Methods: We enrolled 509 patients following stent implantation, taking dual antiplatelet therapy with 100 mg/day aspirin and 75 mg/day clopidogrel as a maintenance dose after a loading dose of clopidogrel 300 mg, in this prospective study with 12 months follow-up. Patients were divided into ACS (n=217, male 71%, age 69.9 ys) and SA (n=292, male 70%, age 70.3 ys). Adenosine diphosphate induced platelet aggregation using light transmission aggregometer was measured as response to clopidogrel. CYP2C19 polymorphism was examined, and classified into three ph...
Results Update from the DRIVE PK Study: Effects of AG-348, a Pyruvate Kinase Activator, in Patients with Pyruvate Kinase Deficiency
Authors: Rachael F. Grace, D. Mark Layton, Frédéric Galactéros, Christian Rose, Wilma Barcellini, D. Holmes Morton, Eduard J. Van Beers, Hassan M. Yaish, Yaddanapudi Ravindranath, Kevin H.M. Kuo, Sujit Sheth, Janet L. Kwiatkowski, Bruce Silver, Charles Kung, Marvin Cohen, Hua Yang, Penelope A. Kosinski, Lei Hua, Ann Barbier, Bertil Glader
Journal: Blood (2017)
THU-272-A study investigating the effect of extracorporeal cellular therapy with C3A cells on the survival of alcoholic hepatitis designed along the guidelines of the NIAAA
Authors: Nikolaos T. Pyrsopoulos, Tarek Hassanein, Ram Subramanian, Julie Thompson, Stephen Caldwell, Ali Al-Khafaji, David Reich, Cyril Sieberhagen, Jan Stange
Journal: Journal of Hepatology (2019)
Roadmap for a precision-medicine initiative in the Nordic region
Authors: Pål Rasmus Njølstad, Ole Andreas Andreassen, Søren Brunak, Anders D. Børglum, Joakim Dillner, Tõnu Esko, Paul W. Franks, Nelson Freimer, Leif Groop, Hakon Heimer, David M. Hougaard, Eivind Hovig, Kristian Hveem, Anu Jalanko, Jaakko Kaprio, Gun Peggy Knudsen, Mads Melbye, Andres Metspalu, Preben Bo Mortensen, Juni Palmgren, Aarno Palotie, Wenche Reed, Hreinn Stefánsson, Nathan O. Stitziel, Patrick F. Sullivan, Unnur Thorsteinsdóttir, Marc Vaudel, Eero Vuorio, Thomas Werge, Camilla Stoltenberg, Kári Stefánsson
Journal: Nature Genetics (2019)
PS-184-Real-world effectiveness and safety of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus infection: A meta-analysis
Authors: Markus Cornberg, Francesco Negro, Pietro Lampertico, Juan Turnés, Michael Curry, Ashley Brown, Heiner Wedemeyer, José Antonio Carrión, Nicole Wick, Andreas Pangerl, Lois Larsen, Yao Yu, Marcello Persico
Journal: Journal of Hepatology (2019)
THU-079-Study of anti-fibrotic activity of human umbilical-cord tissue-derived mesenchymal stromal cells during fibrogenesis or resolution in murine models of liver fibrosis
Authors: Debashis Haldar, Richard Wilkin, Ditte Hedegaard, Mohammed Alfaifi, Vasanthy Vigneswara, Nguyet Luu, Lisa O'flynn, Steven Elliman, Madhu Gargesha, Debashish Roy, Neil Henderson, Gideon Hirschfield, Philip Newsome
Journal: Journal of Hepatology (2019)
Abstract 19567: Recovery From Prolonged Resuscitation and Multi-Organ System Failure Following Refractory Ventricular Fibrillation Cardiac Arrest
Authors: Jason A Bartos, Kathleen Carlson, Claire Carlson, Ganesh Raveendran, Cindy Martin, Emil Missov, Ranjit John, Tom P Aufderheide, Demetris Yannopoulos
Journal: Circulation (2017)

Introduction: Recovery from refractory out-of-hospital (OOH) ventricular fibrillation/ventricular tachycardia (VF/VT) cardiac arrest requires hemodynamic stabilization and reversal of organ injury. This study sought to describe the prevalence of, and recovery from, multi-organ system failure in patients suffering refractory VF/VT cardiac arrest treated with the Minnesota Resuscitation Consortium advanced perfusion and reperfusion protocol. Methods: Between December 1, 2015 and February 1, 2017, consecutive adult patients with refractory OOH VF/VT cardiac arrest requiring ongoing CPR were transported to the cardiac catheterization laboratory (CCL). ECLS, coronary angiography, and percutaneous coronary intervention were performed as needed. Patients achieving an organized cardiac rhythm were admitted to the cardiac intensive care unit (CICU). Results: Sixty patients received full resuscitation in the CCL, 52/60 (87%) were admitted to the CICU, and 26/60 (43%) survived to hospital discharge neurologically in...
Optimisation of the use of APRI and FIB-4 to rule out cirrhosis in patients with chronic hepatitis B: results from the SONIC-B study
Authors: Milan J Sonneveld, Willem P Brouwer, Henry L-Y Chan, Teerha Piratvisuth, Ji-Dong Jia, Stefan Zeuzem, Yun-Fan Liaw, Bettina E Hansen, Hannah Choi, Cynthia Wat, Vedran Pavlovic, Anuj Gaggar, Qing Xie, Maria Buti, Robert J de Knegt, Harry L A Janssen
Journal: The Lancet. Gastroenterology & hepatology (2019)
FRI-339-Clinical translatability of a diet-induced obese mouse model of non-alcoholic steatohepatitis
Authors: Kristoffer Rigbolt, Sanne Veidal, Malte Suppli, Peter Lykke Eriksen, Michael Feigh, Filip Krag Knop, Henning Grønbæk, Karen Louise Thomsen, Jacob Jelsing, Niels Vrang
Journal: Journal of Hepatology (2019)
Annals Story Slam - The “Difficult” Patient, a Grandmother's Love
Authors: Carolina Consejo y Chapela
Journal: Annals of Internal Medicine (2019)

Web Exclusives7 May 2019Annals Story Slam - The “Difficult” Patient, a Grandmother's LoveFREECarolina Consejo y Chapela, MDCarolina Consejo y Chapela, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W19-0002 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - The "Difficult" Patient, a Grandmother's Love "The 'Difficult' Patient, a Grandmother's Love," by Dr. Carolina Consejo y Chapela (Duration 4:32)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 InformationAffiliations: This article was published at Annals.org on 12 April 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 May 2019Volume 170, Issue 9Page: SS1 ePublished: 12 April 2019 Issue Published: 7 May 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.Loading ...