tbuckley/cabot-search huggingface dataset:
PROGNOSIS OF GASTRIC DYSPLASIA AFTER COMPLETE RESECTION WITH ENDOSCOPIC PROCEDURES CONSIDERING MUCIN PHENOTYPE
Authors: J Park, JS Lee, JO Kim, SR Jeon, HG Kim, TH Lee, JH Cho
Journal: Endoscopy (2019)

Gastric adenomas are considered premalignant, and some can be interpreted as cancer according to different pathologic guidelines. The dysplastic lesions share histologic characteristics including mucin phenotype that are related prognosis. The prognosis of the lesions has been studied but tends to be researched separately. Moreover, the proposed prognostic factors are mostly derived from the study of surgical specimens, and most of them did not consider the anatomical changes after surgery. Previously researched prognostic factors of gastric dysplasia were evaluated on the recurrence after complete resection with endoscopic procedure.
Enhanced American College of Cardiology/American Heart Association Strategy for Prevention of Sudden Cardiac Death in High-Risk Patients With Hypertrophic Cardiomyopathy
Authors: Martin S. Maron, Ethan J. Rowin, Benjamin S. Wessler, Paula J. Mooney, Amber Fatima, Parth Patel, Benjamin C. Koethe, Mikhail Romashko, Mark S. Link, Barry J. Maron
Journal: JAMA Cardiology (2019)

Strategies for reliable selection of high-risk patients with hypertrophic cardiomyopathy (HCM) for prevention of sudden cardiac death (SCD) with implantable cardioverter/defibrillators (ICDs) are incompletely resolved.To assess the reliability of SCD prediction methods leading to prophylactic ICD recommendations to reduce the number of SCDs occurring in patients with HCM.In this observational longitudinal study, 2094 predominantly adult patients with HCM consecutively evaluated over 17 years in a large HCM clinical center were studied. All patients underwent prospective ICD decision making relying on individual major risk markers derived from the HCM literature and an enhanced American College of Cardiology/American Heart Association (ACC/AHA) guidelines-based risk factor algorithm with complete clinical outcome follow-up. Data were collected from June 2017 to February 2018, and data were analyzed from February to July 2018.Arrhythmic SCD or appropriate ICD intervention for ventricular tachycardia or ventricular fibrillation.Of the 2094 study patients, 1313 (62.7%) were male, and the mean (SD) age was 51 (17) years. Of 527 patients with primary prevention ICDs implanted based on 1 or more major risk markers, 82 (15.6%) experienced device therapy-terminated ventricular tachycardia or ventricular fibrillation episodes, which exceeded the 5 HCM-related SCDs occurring among 1567 patients without ICDs (0.3%), including 2 who declined device therapy, by 49-fold (95% CI, 20-119; P = .001). Cumulative 5-year probability of an appropriate ICD intervention was 10.5% (95% CI, 8.0-13.5). The enhanced ACC/AHA clinical risk factor strategy was highly sensitive for predicting SCD events (range, 87%-95%) but less specific for identifying patients without SCD events (78%). The C statistic calculated for enhanced ACC/AHA guidelines was 0.81 (95% CI, 0.77-0.85), demonstrating good discrimination between patients who did or did not experience an SCD event. Compared with enhanced ACC/AHA risk factors, the European Society of Cardiology risk score retrospectively applied to the study patients was much less sensitive than the ACC/AHA criteria (34% [95% CI, 22-44] vs 95% [95% CI, 89-99]), consistent with recognizing fewer high-risk patients.A systematic enhanced ACC/AHA guideline and practice-based risk factor strategy prospectively predicted SCD events in nearly all at-risk patients with HCM, resulting in prophylactically implanted ICDs that prevented many catastrophic arrhythmic events in this at-risk population.
Quelle classification prédit le mieux le risque de cancer sous-muqueux et intra-muqueux avec des endoscopes HD sans zoom? Etude prospective sur 200 dissections colorectales
Authors: J Jacques, H Lepetit, M Fabritius, R Legros, M Dahan, J Albouys, V Valgueblasse, D Sautereau, J Rivory, T Ponchon, M Pioche
Journal: Endoscopy (2019)

L'analyse précise du polype, selon son aspect morphologique, sa taille, l'étude de sa structure vasculaire et glandulaire de surface avec des chromoendoscopies doit permettre de déterminer sa nature, d'estimer son degré de dégénérescence et surtout d'adapter le choix de la thérapeutique: resection endoscopique monobloc indispensable, résection endoscopique fragmentée possible, résection chirurgicale avec curage ganglionnaire.
THERAPEUTIC IMPACT OF COLON CAPSULE AS A PAN-ENTEROSCOPIC TEST
Authors: C Carretero, C Prieto de Frias, R Angos, M Betes, S De la Riva, M Herraiz, M Muñoz-Navas
Journal: Endoscopy (2019)

Colon capsule is a non-invasive device primarily designed for colonic visualization. However, a slight modification of the ingestion protocol may allow both the visualization of the small bowel and colon with only one prep and one capsule.
Abstract P079: Body Fat Changes Mediate the Effects of Antiretroviral Therapy on Blood Pressure and Blood Glucose Levels in People Living with HIV in a Sub-Saharan African Setting: A Mediation Analysis
Authors: Chidozie U Nduka, Olalekan A Uthman, Peter K Kimani, Abraham O Malu, Saverio Stranges
Journal: Circulation (2016)

Background: Previous studies of HIV-infected patients show significant associations of highly active antiretroviral therapy (HAART) with worsening blood pressure and blood glucose levels; however, the mechanisms involved are less clear. Therefore, we sought to investigate the potential mediating effects of body fat changes on HAART-associated increases in blood pressure and blood glucose levels among people living with HIV. Methods: Four Hundred and Six consenting patients (≥ 18 years) attending a tertiary HIV clinic in semi-urban Nigeria were recruited between August and November 2014 as part of a cross-sectional study. We performed bias-corrected bootstrap tests of mediation using 95% confidence intervals (CI) to determine the mediating effects of body mass index and waist circumference (mediators) on the total effects of HAART exposure (primary predictor) on blood pressure and blood glucose levels (outcomes), while adjusting for potential confounders including age, sex, smoking status, CD4 cell count and duration of HIV infection. Results: Waist circumference remained a significant partial mediator of the total effects of HAART exposure on increasing systolic blood pressure (coefficient: 1.01, 95% CI 0.33 to 2.52, 11% mediated), diastolic blood pressure (coefficient: 0.68, 95% CI 0.26 to 1.89, 9% mediated) and blood glucose levels (coefficient: 0.67, 95% CI 0.14 to 1.67, 25% mediated) after adjusting for all potential confounders; whereas, no significant mediating effect was observed with body mass index or combined body mass index/waist circumference. Conclusion: Our findings suggest that body fat, especially central fat accumulation, may mediate HAART-associated increases in blood pressure and blood glucose levels among HIV-infected patients, independent of the role of traditional risk factors. The use of waist circumference as a complementary measure of body fat to body mass index may improve the clinical prediction of hypertension and diabetes among HIV-infected patients on antiretroviral therapy.
Clinical outcome of early stage breast cancer patients with 1 to 3 positive axillary lymph nodes: A single institution experience
Authors: A. Arjunan, S. Abbas, P.S. George
Journal: Annals of Oncology (2019)

Background: There is no definite consensus on the role of post-operative radiotherapy (RT) in breast cancer patients with 1-3 axillary lymph node positivity. EBCTCG meta-analysis and Danish trials (DBCG 82 b and c) showed improvement in loco regional control and overall survival (OS) with post operative radiotherapy in 1-3 node positive patients, but level I evidence is awaited [SUPREMO trial]. With this background we conducted this retrospective analysis to evaluate clinical outcomes of patients with 1 to 3 axillary node positive breast cancer. Methods: From 1 January 2010 to 31 December 2014, a total of 474 patients with pT1-T2 pN1 breast cancer were identified from Hospital Registry. Clinical outcomes in terms of Disease Free Survival (DFS), Local Recurrence Rate (LRR), OS and patterns of failure were assessed. Results: Of the 474 patients, all of them except 3 were females, with a mean age of 52 years. 89% of the patients had >/=10 axillary lymph nodes dissected and around half of the patients studied had single node positivity. Adjuvant RT was given to 364 patients (76.8%) and 75.5% of them received conventional fractionation schedule. The median follow up was 77.4 months. At the time of analysis, 403 patients were alive without any evidence of disease. Forty-one patients died due to disease sequelae and 8 patients were alive with disease. The 5 year OS and DFS were 93% and 89.4% respectively. Eighteen patients (3.7%) had locoregional relapse. There was a significant difference in outcome in terms of OS and DFS in favor of single node positivity when compared with 2-3 node positivity (5 year DFS 94.4% vs. 83.5 %, p = 0.000017, 5 year OS 96.6% vs. 89.1%, p = 0.00023). There was no difference in OS and DFS between patients who received adjuvant RT and patients who did not. Conclusions: 76% of the patients received adjuvant RT and there was no statistically significant difference in the outcome between those who received adjuvant RT and those who did not. Patients with single node positivity had better DFS and OS when compared with patients with 2-3 node positivity. The ongoing prospective trial (SUPREMO Trail) may give us further insight into the exact role for RT in patients with 1-3 node positivity. Legal entity responsible for the study: Regional Cancer Centre, Trivandrum, India. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 12130: Risk Stratification of Severe Hypercholesterolemia Using EHR and Sequencing for Familial Hypercholesterolemia Genes
Authors: Prashant Patel, Amy Kolinovsky, Jeffrey Ruhl, Caroline deRichemond, Dominik Beer, Sarath B Krishnamurthy, Amy Sturm, H L Kirchner, Raghu P Metpally, David J Carey, David H Ledbetter, Frederick E Dewey, Michael F Murray, Marc S Williams, Vishal C Mehra
Journal: Circulation (2017)

Background: Heterozygous familial hypercholesterolemia (FH) affects 1 in 200 individuals, however severe hypercholesterolemia (untreated low density lipoprotein (LDL) cholesterol ≥ 190mg/dl) affect...
OPTIMAL TIMING OF RESUMPTION OF WARFARIN AND CLINICAL OUTCOMES AFTER GASTROINTESTINAL BLEEDING IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: D Lee, JU Lim, BJ Kim, SJ Kim, JH Kim, TH Kim
Journal: Endoscopy (2019)

According to the 2018 official statement of the Asian Pacific Association of Gastroenterology about management of patients on warfarin, early resumption can be considered, once primary endoscopic hemostasis was done well.
CIP2A as a novel target to combat basal like breast cancer
Authors: S. Nagelli, A. Laine, T. Suomi, L. Elo, J. Westermarck
Journal: Annals of Oncology (2019)

Background: Although both kinases and phosphatases have equally important roles in maintaining cellular homeostasis, the protein phosphatases are understudied and their functional relevance in human malignancies is not fully understood yet. This project aims to better understand the role of a major serine threonine phosphatase called protein phosphatase 2A (PP2A) in cancer particularly basal-like breast cancer (BLBC). BLBC is the most challenging breast cancer subtype as it is very aggressive with no targeted therapies, and the main reason can be attributed to poor understanding of the molecular mechanisms that drive this cancer subtype. Hence, there is a critical clinical need to identify new targets and develop novel therapies for this subtype. Our research group discovered CIP2A (cancerous inhibitor of PP2A) (Cell, 2007) and its role as an oncoprotein in breast cancer and several studies have indicated that high CIP2A expression correlates with more aggressive cancer and poor prognosis in the clinic. This project aims to unravel the molecular mechanisms by which CIP2A drives tumour initiation in BLBC and to establish CIP2A biomarker signature which can serve as a predictive and prognostic tool for better clinical management of BLBC. Methods: The key methods used in the project are CIP2A Knockout mouse models, RNA sequencing of basal like breast cancer cell lines, Immunohistochemistry (IHC) of patient material, DNA Damage Ionization radiation induced foci (IRIF) formation, Colony formation experiments with depletion of CIP2A using siRNA, Flow cytometry, Western blotting, Co-Immunoprecipitation (CO-IP), Immunofluorescence and microscopy. Results: Our results have shown that CIP2A knockout mice were resistant to DMBA induced BLBC tumour formation. Mechanistic studies indicated that it has an important role in DNA Damage Response signaling. Analysis of patient material revealed that CIP2A has a prognostic benefit particularly in basal type TNBC patients. We generated a CIP2A Biomarker signature (269 genes, p = 0.01) by RNA Seq of CIP2A depleted BLBC cell lines and validated it with publicly available TCGA and METABRIC datasets. Conclusions: CIP2A is a promising novel target for BLBC and it has the potential to be used as a predictive and prognostic biomarker for BLBC. Legal entity responsible for the study: Jukka Westermarck (Principal investigator). Funding: Finnish Cancer Foundation, Business Finland, University of Turku Graduate School. Disclosure: All authors have declared no conflicts of interest.
<i>Streptococcus pyogenes</i> evades adaptive immunity through specific IgG glycan hydrolysis
Authors: Andreas Naegeli, Eleni Bratanis, Christofer Karlsson, Oonagh Shannon, Raja Kalluru, Adam Linder, Johan Malmström, Mattias Collin
Journal: The Journal of Experimental Medicine (2019)

Streptococcus pyogenes (Group A streptococcus; GAS) is a human pathogen causing diseases from uncomplicated tonsillitis to life-threatening invasive infections. GAS secretes EndoS, an endoglycosidase that specifically cleaves the conserved N-glycan on IgG antibodies. In vitro, removal of this glycan impairs IgG effector functions, but its relevance to GAS infection in vivo is unclear. Using targeted mass spectrometry, we characterized the effects of EndoS on host IgG glycosylation during the course of infections in humans. Substantial IgG glycan hydrolysis occurred at the site of infection and systemically in the severe cases. We demonstrated decreased resistance to phagocytic killing of GAS lacking EndoS in vitro and decreased virulence in a mouse model of invasive infection. This is the first described example of specific bacterial IgG glycan hydrolysis during infection and thereby verifies the hypothesis that EndoS modifies antibodies in vivo. This mechanisms of immune evasion could have implications for treatment of severe GAS infections and for future efforts at vaccine development.
Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment – Synergistic effect of thrombolysis and antioxidant –
Authors: Ting Mei, Ahram Kim, Long Binh Vong, Aiki Marushima, Sandra Puentes, Yuji Matsumaru, Akira Matsumura, Yukio Nagasaki
Journal: Biomaterials (2019)
Differences in Presentation and Survival Outcomes for African American Patients with Newly Diagnosed Multiple Myeloma
Authors: Nisha Joseph, Vikas A. Gupta, Craig C Hofmeister, Charise Gleason, Leonard Heffner, Lawrence H. Boise, Jonathan L Kaufman, Madhav V Dhodapkar, Sagar Lonial, Ajay K Nooka
Journal: Blood (2018)
Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling
Authors: Yosaku Watatani, Yasuharu Sato, Hiroaki Miyoshi, Kana Sakamoto, Kenji Nishida, Yuka Gion, Yasunobu Nagata, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Lanying Zhao, Yotaro Ochi, Yasuhide Takeuchi, June Takeda, Hiroo Ueno, Yasunori Kogure, Yusuke Shiozawa, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Masahiro M. Nakagawa, Yasuhito Nanya, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Ryota Matsuoka, Masayuki Noguchi, Nobuhiro Hiramoto, Takayuki Ishikawa, Junichi Kitagawa, Nobuhiko Nakamura, Hisashi Tsurumi, Tatsuhiko Miyazaki, Yusuke Kito, Satoru Miyano, Kazuya Shimoda, Kengo Takeuchi, Koichi Ohshima, Tadashi Yoshino, Seishi Ogawa, Keisuke Kataoka
Journal: Leukemia (2019)

Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor samples from 133 cases, we have delineated the entire landscape of somatic alterations, and discovered frequently affected driver pathways in PTCL, NOS, with and without a T-follicular helper (TFH) cell phenotype. In addition to previously reported mutational targets, we identified a number of novel recurrently altered genes, such as KMT2C, SETD1B, YTHDF2, and PDCD1. We integrated these genetic drivers using hierarchical clustering and identified a previously undescribed molecular subtype characterized by TP53 and/or CDKN2A mutations and deletions in non-TFH PTCL, NOS. This subtype exhibited different prognosis and unique genetic features associated with extensive chromosomal instability, which preferentially affected molecules involved in immune escape and transcriptional regulation, such as HLA-A/B and IKZF2. Taken together, our findings provide novel insights into the molecular pathogenesis of PTCL, NOS by highlighting their genetic heterogeneity. These results should help to devise a novel molecular classification of PTCLs and to exploit a new therapeutic strategy for this group of aggressive malignancies.
Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients
Authors: Christian Vogelberg, Stanley J. Szefler, Elianne J.L.E. Vrijlandt, Attilio L. Boner, Michael Engel, Georges El Azzi, Sebastian Dan Vulcu, Petra M. Moroni-Zentgraf, Olaf Eickmeier, Eckard H. Hamelmann
Journal: European Respiratory Journal (2019)

There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance. Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with symptomatic asthma aged 1–17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment. Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), tiotropium 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or sex. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs. This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat add-on therapy in paediatric patients with symptomatic asthma.
THE ROLE OF MULTIDISCIPLINARY APPROACH IN ENDOSCOPIC SLEEVE GASTROPLASTY
Authors: I Boškoski, V Bove, R Landi, L Laterza, F Mangiola, F D'Aversa, G Gibiino, A Tringali, P Familiari, F Attili, V Perri, G Costamagna
Journal: Endoscopy (2019)

Endoscopic sleeve gastroplasty (ESG) is a relatively novel endoscopic procedure that reduces the gastric lumen with proven less complications and less 6 months weight loss compared to laparoscopic sleeve gastroplasty. At present there are no studies investigating the role of multidisciplinary approach in ESG. The aims of the present study were to evaluate the role of multidisciplinary assessment (MA) prior ESG, weight loss outcomes and quality of live improvements.
EUS-GUIDED TRANSMURAL BILIARY DRAINAGE SHOULD BE THE FIRST CHOICE THERAPY IN PATIENTS WITH UNFEASIBLE PAPILLARY CANNULATION
Authors: JJ Vila, G González, L Aburruza, J Costa, J Carvalho, C Prieto, I Fernández-Urién, J Carrascosa, JF Juanmartiñena, M Gómez
Journal: Endoscopy (2019)

To compare the outcomes of EUS-guided rendezvous technique (RVT) versus EUS-guided transmural technique (TMT) for biliary drainage after ERCP failure.
GATA-2–deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in human subjects
Authors: Avanti Desai, Kathryn Sowerwine, Yihui Liu, Monica G. Lawrence, Jack Chovanec, Amy P. Hsu, Michael P. O'Connell, Jiwon Kim, Lisa Boris, Nina Jones, Laura Wisch, Robin R. Eisch, Melody C. Carter, Hirsh D. Komarow, Christa Zerbe, Joshua D. Milner, Irina Maric, Xiaoping Sun, Chyi-Chia R. Lee, Ilker Tunc, Mehdi Pirooznia, Kelly D. Stone, Steven M. Holland, Dean D. Metcalfe, Jonathan J. Lyons
Journal: Journal of Allergy and Clinical Immunology (2019)
Pluronic block copolymers enhance the anti-myeloma activity of proteasome inhibitors
Authors: Hangting Hu, Armen Petrosyan, Natalia A. Osna, Tong Liu, Appolinaire A. Olou, Daria Y. Alakhova, Pankaj K. Singh, Alexander V. Kabanov, Edward A. Faber, Tatiana K. Bronich
Journal: Journal of Controlled Release (2019)
MSKCC and Heng prognostic risk assessment for synchronous metastatic renal cell carcinoma (syncmRCC) and the tumor in place treated in the targeted therapy era.
Authors: Allard Noe, Christian U. Blank, Simon Horenblas, John B. A. G. Haanen, Axel Bex
Journal: Journal of Clinical Oncology (2013)

e15525 Background: SyncmRCC is heterogenous and selection for cytoreductive nephrectomy (CN) and targeted therapy is required. MSKCC and Heng models for overall survival (OS) are validated for targeted therapy. However, they were developed from predominantly metachronous mRCC patients. It is unknown how they perform in syncmRCC and if they can be used to decide about CN. Methods: Retrospective study of pretherapeutic MSKCC and Heng scores and outcome from 146 patients with syncmRCC and the primary tumor in place treated at a single institute with targeted therapy since 2006. CN was performed in patients WHO 0-1 and low metastatic burden. Results: Table: distribution of risk and OS compared to Heng et al., JCO 27:5794, 2009 . Only n=2 were favorable risk. Overall, n=117 were treated by sunitinib, others by temsirolimus or sorafenib. CN was performed in n=94 (64.3%). Among Heng poor risk 46% (n=29) were intermediate risk by MSKCC. Of Heng poor risk n=37 (58.7%) had CN with a median OS of 8.5 months; 2y OS was 18.9% and higher than for MSKCC poor risk. Of Heng intermediate risk n=57 (69.5%) underwent CN (median OS 15.5 months (1-68); 2y OS 36.8%). Conclusions: In syncmRCC MSKCC and Heng intermediate risk patients have shorter OS than previously reported for each model in the targeted therapy era. However, 25-30 % of intermediate risk patients live &gt;2 y and a potential benefit of CN may be apparent in this group. A discrepancy exists between Heng and MSKCC poor risk percentage. We speculate that the primary tumor in place may influence thrombocyte and neutrophile counts resulting in significantly more Heng poor risk among patients with MSKCC intermediate risk. Especially MSKCC poor risk carries a dismal median and 2y OS in syncmRCC. MSKCC risk assessment performs well in identifying poor risk patients unlikely to benefit from CN. [Table: see text]