tbuckley/cabot-search huggingface dataset:
Impact of tamoxifen (TAM) serum concentration on side effects among premenopausal patients (pts) with early breast cancer (BC) in the prospective multicenter CANTO cohort
Authors: A.R. Ferreira, A. Paci, A. Di Meglio, F. André, S. Everhard, A.-L. Martin, L. Fasse, G. Menvielle, I. Vaz-Luis, B. Pistilli
Journal: Annals of Oncology (2019)

Background: TAM causes several side effects that impact the quality of life and adherence to treatment in patients with BC. Due to the complexity of TAM metabolism, serum biomarkers predicting TAM side effects have not been identified. We hypothesized that TAM levels may be associated with side effects, thus identifying pts eligible to tailored supportive interventions. Methods: CANTO cohort (NCT01993498) is a French multicenter prospective longitudinal study including 12000 women with stage I-III BC aimed at characterizing long-term toxicities of BC treatment. CANTO COMPLETE is a pre-defined sub study of adherence to endocrine therapy evaluating TAM serum concentrations in premenopausal pts. Here, we analyzed the association between continuous TAM serum levels and side effects at 1 year of TAM initiation in pts with serum defined adherence to TAM (> 60 ng/mL). TAM level was determined by liquid chromatography tandem mass spectrometry on 200 µL of serum. Selected TAM-related toxicities were assessed by increase in body weight ≥5%, CTCAE v4.0 and patient reported outcomes (EORTC C30 and hospital anxiety and depression scale [HADS]). Univariate and multivariate linear and logistic regressions were fitted to measure the association between TAM levels and selected toxicities. Results: A cohort of 989 pts with serum defined adherence to TAM was identified. Median age at diagnosis was 45 yrs (min.-max. 22 - 57), 43.7% were stage I, 64.6% received (neo)adjuvant chemotherapy, 89.4% had Charlson score 0, 33.8% had BMI≥25 kg/m2, 20.9% were active smokers and 52.4% had education ≥ college. Median serum TAM was 119 ng/ml (P25-P75 96-152). In univariate and multivariate analyses, TAM levels were not associated with worse side effects, in specific: weight gain; gynecological, musculoskeletal or neurologic toxicities (including cognitive); fatigue or insomnia; and anxiety or depression. Conclusions: In premenopausal women adherent to adjuvant TAM, TAM serum levels were not associated with TAM-related side effects at 1 year post treatment initiation. As next steps, we will analyze the association of tamoxifen metabolites and side effects. Clinical trial identification: NCT01993498. Legal entity responsible for the study: INSERM UMR 981. Funding: Institut National du Cancer (to Fabrice André and Barbara Pistilli), Susan G. Komen (to Ines Vaz-Luis) and Fondation ARC (to Ines Vaz-Luis and Gwenn Menvielle). Disclosure: All authors have declared no conflicts of interest.
Medical Therapy for Heart Failure Caused by Ischemic Heart Disease
Authors: Islam Y. Elgendy, Dhruv Mahtta, Carl J. Pepine
Journal: Circulation Research (2019)

Patients with heart failure (HF) syndromes have been categorized as those with reduced ejection fraction (EF) or preserved EF (HFpEF), and ischemia plays a key role in both types. HF remains a major cause of morbidity and mortality worldwide, and with the aging of our population this burden continues to rise, predominantly as a result of hospitalizations for HFpEF. Patients with obstructive coronary artery disease more likely have HF with reduced EF, rather than HFpEF, secondary to acute ischemic injury resulting in myocardial infarction, and large outcomes trials of treatments with neurohumoral inhibition have documented reduced adverse outcomes. In contrast, similar treatments in patients with HFpEF have not proven beneficial. This therapeutic dilemma may be attributed, in part, to heterogeneity in the underlying pathophysiology with different systemic and myocardial signaling pathways, despite similar clinical presentations and findings, in patients with HFpEF. Also, emerging evidence indicates that impaired myocardial perfusion and inflammation secondary to multiple comorbidities are key mechanisms in HFpEF. We will thoroughly review the role of ischemic heart disease in the pathogenesis of HF with reduced EF and HFpEF, and discuss the medical management strategies available for these conditions.
Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma
Authors: Lisa H. Butterfield, Lazar Vujanovic, Patricia M. Santos, Deena M. Maurer, Andrea Gambotto, Joel Lohr, Chunlei Li, Jacob Waldman, Uma Chandran, Yan Lin, Huang Lin, Hussein A. Tawbi, Ahmad A. Tarhini, John M. Kirkwood
Journal: Journal for ImmunoTherapy of Cancer (2019)

Cancer vaccines are designed to promote systemic antitumor immunity and tumor eradication. Cancer vaccination may be more efficacious in combination with additional interventions that may build on or amplify their effects.Based on our previous clinical and in vitro studies, we designed an antigen-engineered DC vaccine trial to promote a polyclonal CD8+ and CD4+ T cell response against three shared melanoma antigens. The 35 vaccine recipients were then randomized to receive one month of high-dose IFNα or observation.The resulting clinical outcomes were 2 partial responses, 8 stable disease and 14 progressive disease among patients with measurable disease using RECIST 1.1, and, of 11 surgically treated patients with no evidence of disease (NED), 4 remain NED at a median follow-up of 3 years. The majority of vaccinated patients showed an increase in vaccine antigen-specific CD8+ and CD4+ T cell responses. The addition of IFNα did not appear to improve immune or clinical responses in this trial. Examination of the DC vaccine profiles showed that IL-12p70 secretion did not correlate with immune or clinical responses. In depth immune biomarker studies support the importance of circulating Treg and MDSC for development of antigen-specific T cell responses, and of circulating CD8+ and CD4+ T cell subsets in clinical responses.DC vaccines are a safe and reliable platform for promoting antitumor immunity. This combination with one month of high dose IFNα did not improve outcomes. Immune biomarker analysis in the blood identified several predictive and prognostic biomarkers for further analysis, including MDSC.NCT01622933 .
Abstract 18306: New Echocardiographic Findings Related With Short And Long-term Prognosis in Acute Pulmonary Embolism
Authors: Juan Martinez-Milla, Angelica María Romero-Daza, Ana Lucía Rivero, Ana Devesa, Miguel Ángel Navas, Marcelino Cortés, Jerónimo Farré
Journal: Circulation (2017)

Introduction: Transthoracic echocardiogram (TTE) is routinely used for the initial assessment of patients with acute pulmonary embolism (APE). But there is little information about TTE findings in ...
Abstract 12209: Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation
Authors: Inmaculada Hernandez, Yuting Zhang, Maria M Brooks, Paul K Chin, Samir Saba
Journal: Circulation (2016)

Introduction: Little is known about the patterns of anticoagulation use and clinical outcomes associated with the resumption of anticoagulation after a major hemorrhage. Hypothesis: We hypothesized that the discontinuation of anticoagulation would be associated with higher thromboembolic risk but lower risk of recurrent bleeding than the post-hemorrhage resumption of anticoagulation with warfarin or dabigatran. Methods: Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until a clinical event of ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the risk of ischemic stroke, all-cause mortality, and recurrent bleeding between treatment groups. Results: CHA2DS2-Vasc and HAS-BLED scores did not affect the odds of post-hemorrhage anticoagulation resumption. The odds of resuming anticoagulation decreased however by 11% (95%CI, 4%-18%) and 24% (95%CI, 9%-37%) for every 5 years increase in age for warfarin and dabigatran users, respectively. Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients who were prescribed warfarin after the bleeding event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation. Conclusions: The benefit/risk ratio of dabigatran among atrial fibrillation patients who have survived a major hemorrhage is superior to that of warfarin and of anticoagulation discontinuation.
UK BOWEL CANCER SCREENING PROGRAM: A LOCAL EXPERIENCE OF POLYPECTOMY FOR POLYPS ≥2CM
Authors: M Ding, F Nawaz, J Aleem, K Hameed, M Ahmed
Journal: Endoscopy (2019)

The English National Health Service (NHS) Bowel Cancer Screening Program (BCSP) was introduced in 2006 to improve CRC mortality by earlier detection of CRC and has been associated with a 15% reduction in mortality. We wanted to study the outcome of large polypectomies under BCSP in our department.
The role of dose-dense (DD) adjuvant chemotherapy (CT) in HER2-positive (HER2+) early breast cancer (BC) patients (pts) before and after the introduction of trastuzumab (T): Exploratory analysis of the GIM2 trial
Authors: M. Lambertini, M. Bruzzone, F. Poggio, B. Conte, E. de Azambuja, G. Bisagni, M. De Laurentiis, S. de Placido, F. Cognetti, L. Del Mastro
Journal: Annals of Oncology (2019)

Background: DD adjuvant CT is standard of care in high-risk early BC pts. However, the role of DD CT in HER2+ BC pts remains uncertain, particularly when T is administered. In this exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015), we investigated the efficacy of DD CT in the subgroup of HER2+ BC pts with or without subsequent exposure to T. Methods: Using a 2x2 factorial design, the GIM2 trial randomized node-positive early BC pts to receive 4 cycles of (fluorouracil)epirubicin/cyclophosphamide (F)EC every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel (P). The same number of cycles (4 (F)EC and 4 P) and doses (FEC 600/90/600 mg/m2, P 175 mg/m2) were used in all treatment arms. After the approval of adjuvant T, protocol was amended in April 2006 to mandate use of T for 1 year after CT completion in all HER2+ pts. The efficacy of DD CT in terms of disease-free survival (DFS) and overall survival (OS) was compared between HER2+ pts with or without subsequent exposure to T and those with HER2-negative /HER2-unknown (HER2-/ukn) status. Results: Out of 2,003 pts randomized to DD or SI CT in the GIM2 study, HER2 status was positive in 452 (22.6%) pts, negative in 1,243 (62.0%) and unknown in 308 (15.4%). Among 452 pts with HER2+ disease, T was administered to 132 (29.2%) pts. Overall median follow-up was 8.1 years (interquartile range: 7.0-9.3). There was no significant interaction between T therapy and the effect of DD CT, (pinteraction=0.603 for DFS and pinteraction=0.776 for OS); however, among pts treated with T, the effect of DD CT appeared to be smaller as shown in the table. Table90O% 7-year DFS SI% 7-year DFS DDHR (95% CI)HER2+ NO trastuzumab67.072.10.84 (0.56-1.24)HER2+ with trastuzumab72.370.40.80 (0.40-1.59)HER2-/ukn73.379.90.72 (0.59-0.88)% 7-year OS SI% 7-year OS DDHER2+ NO trastuzumab78.685.20.67 (0.39-1.16)HER2+ with trastuzumab86.184.91.04 (0.36-3.00)HER2-/ukn85.390.90.64 (0.49-0.84) Open table in a new tab Conclusions: In HER2+ early BC pts, DD adjuvant CT appears to have a role only in pts without subsequent exposure to T. Clinical trial identification: NCT00433420. Legal entity responsible for the study: GIM (Gruppo Italiano Mammella) Study Group. Funding: Bristol-Myers Squibb, Pharmacia, and Dompè Biotec. Disclosure: M. Lambertini: Advisory role: Teva; Speakers' honoraria: Theramex. E. de Azambuja: Honoraria: Roche-Genentech; Research grants: Roche-Genentech (to the institution); Travel grants: Roche-Genentech, GlaxoSmithKline outside the submitted work. L. Del Mastro: Personal fees: Novartis Pharma AG, Roche-Genentech, Ipsen, AstraZeneca, Takeda, Eli Lilly outside the submitted work. All other authors have declared no conflicts of interest.
INSPECTION OF THE COLON IN RETROFLECTION USING A RETROGRADE VIEWING ENDOSCOPE INCREASES ADENOMA DETECTION RATE
Authors: T Rath, F Vitali, E Klenske, J Siebler, M Neurath, S Zopf
Journal: Endoscopy (2019)

Adenoma detection rate (ADR) is inversely related to the incidence of interval colorectal cancers and therefore serves as a benchmark criterion for quality assessment during screening or surveillance colonoscopies Within this study, we evaluated whether additional retrograde inspection of the colon can increase ADR and the number of adenomas per patient.
IMMEDIATE DIRECT ENDOSCOPIC NECROSECTOMY FOLLOWING ONE-STEP EXCHANGE FREE EUS-GUIDED DRAINAGE OF WALLED OFF PANCREATIC NECROSIS
Authors: D Ligresti, E Utzeri, F Cipolletta, M Amata, L Barresi, A Granata, M Traina, I Tarantino
Journal: Endoscopy (2019)

EUS-guided drainage with Lumen Apposing Metal Stents (LAMS) and direct endoscopic necrosectomy (DEN) is an effective mininvasive treatment of infected or symptomatic WOPNs. It revealed a lower complication and mortality rate compared to surgery or percutaneous approach. The aim of our study is to evaluate efficacy and safety of EUS-guided drainage of infected WOPNs with a LAMS and immediate DEN in a consecutive cohort of patients.
COMPARING COLON CAPSULE ENDOSCOPY TO COLONOSCOPY; A PATIENT'S PERSPECTIVE
Authors: G Murphy, MS Ismail, C Msaky, D McNamara
Journal: Endoscopy (2019)

Patients from our centre who had both CCE and colonoscopy within the last 12 months were identified. We performed over-the-phone interviews focused on satisfaction, comfort and overall preference. A 10-point scale was used to assess comfort and satisfaction. Electronic records were also reviewed. Student t-test was used to compare parametric data and a p < 0.05 was significant.
Abstract 18108: Extreme Physical Activity Reverses Beneficial Vascular Effects of Moderate Physical Activity. Study in an Animal Model
Authors: Cira Rubies, Montserrat Batlle, Nadia Castillo, Ana P Dantas, Marta Sitges, Josep Brugada, Lluís Mont, Eduard Guasch
Journal: Circulation (2015)

Introduction: Moderate aerobic exercise reduces atherosclerotic burden. However, recent data show increased cardiovascular disease burden and mortality in the most trained individuals. Aim: To assess vascular remodeling after very high intensity training. Methods: Wistar rats underwent very high (INT, 60min 60cm/s, n=20) or moderate intensity (MOD, 45min 35cm/s, n=20) treadmill training for 16 weeks. Sedentary rats (SED n=20) served as controls. Morphologic analyses were performed in descending thoracic aorta and intramyocardial arteries. Aortic wall oxidative stress was quantified with dihydroethidium (DHE). In vivo functional remodeling was assessed in a hemodynamic study. Ex vivo vascular reactivity to acetilcholine (Ach), phenylephrine (Phe) and KCl was studied in intact- and denuded-endothelium conditions. Results: INT promoted increased aorta wall thickness, elastin fiber disorganization and disruptions in tunica media compared to MOD and SED. Lumen of intramyocardial arteries was narrower and tunica media was thicker in INT rats (Fig A). An in vivo hemodynamic study showed a higher pulse pressure in the INT group (Fig B), suggesting a stiffer aorta. MOD exercise improved ex vivo endothelial function by increasing Ach-mediated vasodilatation and reducing Phe vasoconstriction response; INT exercise did not provide further benefits (Fig C). Conversely, Phe response was increased in endothelium deanuded aorta of the INT group (Fig D); increased response to KCl in the INT group confirmed tunica media hypereactivity. DHE staining was increased in the tunica media of the INT group. Conclusions: While moderate exercise improves vascular function, high intensity exercise blunts it by increasing vascular wall thickness and stiffness, and by inducing tunica media hipereactivity. Oxidative stress likely mediates these effects. Our findings provide important insights into increased atherosclerotic burden in very high trained individuals.
Magnetic Resonance Imaging-targeted Biopsy Versus Systematic Biopsy in the Detection of Prostate Cancer: A Systematic Review and Meta-analysis
Authors: Veeru Kasivisvanathan, Armando Stabile, Joana B. Neves, Francesco Giganti, Massimo Valerio, Yaalini Shanmugabavan, Keiran D. Clement, Debashis Sarkar, Yiannis Philippou, David Thurtle, Jonathan Deeks, Mark Emberton, Yemisi Takwoingi, Caroline M. Moore
Journal: European Urology (2019)
Abstract 4614: Progesterone receptor and ErbB-2 crosstalk in breast cancer
Authors: Wendy Béguelin, María C. Díaz Flaqué, Florencia Cayrol, Cecilia J. Proietti, Martín A. Rivas, Mercedes Tkach, Eduardo H. Charreau, Roxana Schillaci, Patricia V. Elizalde
Journal: Cancer Research (2010)

Abstract Progesterone receptor (PR) and ErbB-2, a member of the ErbBs family of receptor tyrosine kinases, play key roles in breast cancer development. Here, we identified a new mechanism of PR and ErbB-2 interaction in breast cancer cells. Our findings demonstrated that progestin stimulates the rapid activation of ErbB-2, its nuclear translocation, and a striking nuclear colocalization of ErbB-2 with signal transducer and activator of transcription 3 (Stat3) in human T47D breast cancer cells and C4HD cells, from a murine progestin-dependent mammary tumor. By using quantitative chromatin immunoprecipitation (ChIP) and sequential ChIP, we demonstrated that progestin induces the recruitment of Stat3 and ErbB-2 to Stat3 response elements (GAS sites) in the cyclin D1 promoter, which lacks ErbB-2 response elements (HAS sites). Through a series of experimental approaches including transient transfection with cyclin D1 promoter luciferase constructs and RNA interfering-reconstitution strategies employing functional ErbB-2 and Stat3 mutants, we revealed ErbB-2 role as a transcriptional coactivator of Stat3 in progestin-induced cyclin D1 promoter activation. Inhibition of ErbB-2 nuclear migration by transfection of breast cancer cells with the ErbB-2 nuclear localization domain mutant ErbB-2ΔNLS (Mol Cell Biol, 24: 11005-11018, 2005), which we here found that functions as a dominant negative inhibitor of endogenous ErbB-2 nuclear translocation, resulted in complete abrogation of progestin-induced in vitro and in vivo breast cancer growth. Our findings reveal a novel therapeutic intervention in PR- and ErbB-2- positive breast tumors via the specific blockage of ErbB-2 nuclear translocation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4614.
Cellular metabolism and pore lifetime of human skin following microprojection array mediation
Authors: Isha N. Haridass, Jonathan C.J. Wei, Yousuf H. Mohammed, Michael L. Crichton, Christopher D. Anderson, Joakim Henricson, Washington Y. Sanchez, Stefano C. Meliga, Jeffrey E. Grice, Heather A.E. Benson, Mark A.F. Kendall, Michael S. Roberts
Journal: Journal of Controlled Release (2019)
COLON CAPSULE ENDOSCOPY WITH OR WITHOUT BIOMARKERS AS A VIABLE ALTERNATIVE TO COLONOSCOPY IN UNSELECTED PATIENTS WITH LOWER GI SYMPTOMS: RESULTS OF A PILOT STUDY
Authors: MS Ismail, S Semenov, A O'Connor, N Breslin, B Ryan, D McNamara
Journal: Endoscopy (2019)

Lower-gastrointestinal symptoms (LGS) are poor at predicting Clinically-Significant Disease (CSD) despite being the main way of prioritising referrals. This has lead to prolonged wait-times with majority having normal colonoscopies. Alternative diagnostic pathways are needed; biomarkers and/or colon capsule endoscopy (CCE) may be helpful.
ESD OF LST-NG TYPE WITH UNDERLYING SUBMUCOSAL TUMOR
Authors: A Herreros de Tejada, D De Frutos, J Santiago, G Vazquez, I Gonzalez-Partida, B Agudo, M Gonzalez-Haba, A Garrido, P Matallanos, E Blazquez, M Bote, M Sol Delgado, G Pilar, JL Calleja
Journal: Endoscopy (2019)

Colonic lipomas are benign submucosal lesions which exceptionally may associate with colonic neoplasia or adenoma. LST-NG pseudo-depressed type over 2 cm commonly require en-bloc resection with ESD or other alternative techniques.
Résection endoscopique des petits polypes rectocoliques: Quelle est la technique optimale?
Authors: H Jlassi, D Trad, N Bibani, M Sabbah, A Ouakaa Kchaou, H Elloumi, D Gargouri
Journal: Endoscopy (2019)

Plus de 70% des polypes découverts lors des coloscopies sont de petite taille (1 – 10 mm). Leur résection endoscopique peut être dans certains cas incomplète. De ce fait, les modalités optimales de leurs exérèse constituent un sujet de préoccupation des endoscopistes. L'objectif de cette étude était d'analyser les diverses techniques utilisées pour la résection des petits polypes et de suggérer quelle technique serait la plus efficace en comparant les différents taux de résection incomplète.