tbuckley/cabot-search huggingface dataset:
Abstract 11653: The Dynamic Norwood Mortality Estimator: Characterizing Instantaneous, Personalized Risk Trajectories for Infants After the Norwood Operation
Authors: James M Meza, Eugene H Blackstone, Lucy Thuita, Ashley Lowry, Jeevanantham Rajeswaran, Kristina Kovach, Christopher A Caldarone, James K Kirklin, Anusha Jegatheesawaran, William M DeCampli, Kamal Pourmoghadam, Peter J Gruber, William G Williams, Brian W McCrindle
Journal: Circulation (2017)

Background: Post-Norwood, mortality is high and unpredictable. Adverse events and re-interventions are also common. Current risk scores only incorporate baseline data. We sought to create a novel s...
Abstract 13355: Risk Factors and Prognostic Role of Left Atrial Enlargement in Patients With Light-chain Cardiac Amyloidosis
Authors: Lei Zhao, Zhuang Tian, Quan Fang
Journal: Circulation (2015)

Introduction: Cardiac AL amyloidosis carries a poor prognosis so early diagnosis is essential for effective disease-modifying therapy. Echocardiography is a non-invasive modality used for evaluating cardiac diastolic dysfunction, which appears to be a convenient examination. Left atrium (LA), a characteristic of diastolic feature, plays a role in modulating cardiovascular performance. As part of routine clinical examination, we adopted LA diameter indexed to body surface area (LADi) as the parameter to evaluating LA size. Therefore, we aimed to assess risk factors and prognostic values of LA size measured by a simple echocardiographic index in cardiac AL amyloidosis. Methods: A retrospective analysis of patients with biopsy-proven cardiac AL amyloidosis was conducted. LA enlargement was defined as LADi greater than 23mm/m 2 . Results: A total of 104 cardiac AL amyloidosis patients were included in the final analysis, 61(58.7%) of which showed a presentation of LA enlargement. 64.4% were males, mean age was 55 ± 12 y and 57.7% were accompanied with severe heart failure (HF) (NYHA III to IV). Age, NYHA, ejection fraction (EF) and early/late mitral velocity ratio (E/A ratio) were independently associated with LA enlargement in the univariate analysis. But after fitting a multivariate logistic model, NYHA and EF did not remain in the final analysis. During a mean follow-up period of 39 months, the overall survival was significantly shorter in the group with a larger LA (median 5 months vs 22 months, p&lt;0.001). LA enlargement was related with all-cause mortality with a hazard ratio of 1.94 (95%CI: 1.14-3.29, p=0.015) and was also a risk factor of severe HF (hazard ratio 2.18, 95%CI: 1.12-4.23, p=0.022). Conclusion: In cardiac AL amyloidosis, age and E/A ratio were main independent risk factors regarding LA enlargement. LA enlargement, evaluated by LADi, seemed to be related to prevalence and incidence of severe HF and was also a significant predictor of mortality.
Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
Authors: Anna Bill-Axelson, Lars Holmberg, Hans Garmo, Jennifer R. Rider, Kimmo Taari, Christer Busch, Stig Nordling, Michael Häggman, Swen-Olof Andersson, Anders Spångberg, Ove Andrén, Juni Palmgren, Gunnar Steineck, Hans-Olov Adami, Jan-Erik Johansson
Journal: New England Journal of Medicine (2014)

Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.).
Virus, Vessel, Victory: A Novel Approach to Tumor Killing
Authors: Yonina Bykov, Dmitriy Zamarin
Journal: Clinical Cancer Research (2018)

Abstract Ovarian cancer is intimately dependent on aberrant tumor vasculature. A unique therapeutic approach combining a systemic oncolytic virus with a novel vascular-normalizing agent in ovarian cancer demonstrates the potential to enhance antitumor efficacy through improved delivery of the virus and enhanced infiltration of immune cells into the tumors. See related article by Matuszewska et al., p. 1624
Association of Cardiac Injury and Malignant Left Ventricular Hypertrophy With Risk of Heart Failure in African Americans
Authors: Ambarish Pandey, Neil Keshvani, Colby Ayers, Adolfo Correa, Mark H. Drazner, Alana Lewis, Carlos J. Rodriguez, Michael E. Hall, Ervin R. Fox, Robert J. Mentz, Christopher deFilippi, Stephen L. Seliger, Christie M. Ballantyne, Ian J. Neeland, James A. de Lemos, Jarett D. Berry
Journal: JAMA Cardiology (2018)

African Americans have a higher burden of heart failure (HF) risk factors and clinical HF than other racial/ethnic groups. However, the factors underlying the transition from at-risk to clinical HF in African Americans are not well understood.To evaluate the contributions of left ventricular hypertrophy (LVH) and subclinical myocardial injury as determined by abnormal high-sensitivity cardiac troponin-I (hs-cTnI) measurements toward HF risk among African Americans.This prospective, community-based cohort study was conducted between July 2016 and September 2018 and included African American participants from Jackson, Mississippi enrolled in the Jackson Heart Study without prevalent HF who had hs-cTnI measurements and an echocardiographic examination at baseline. Participants were stratified into categories based on the presence or absence of LVH and subclinical myocardial injury (category 1: hs-cTnI <4 ng/L in women and <6 ng/L in men; category 2: 4-10 ng/L in women and 6-12 ng/L in men; category 3: >10 ng/L in women and >12 ng/L in men).Adjusted associations between LVH, subclinical myocardial injury, and the risk of incident HF hospitalization were assessed using Cox proportional hazards models.The study included 3987 participants (2552 women [64%]; 240 (6.0%) with LVH; 1003 (25.1%) with myocardial injury) with 285 incident HF events over a median follow-up of 9.8 years (interquartile range, 8.9-10.6 years). In adjusted analyses, higher LV mass and subclinical myocardial injury were independently associated with the risk of HF with a significant interaction between the 2 (Pint < 0.001). The highest risk of HF was noted among individuals with both LVH and myocardial injury (absolute incidence, 35%; adjusted hazard ratio [aHR; vs no LVH and no myocardial injury], 5.35; 95% CI, 3.66-7.83). A significant interaction by sex was also observed. Men with LVH and subclinical myocardial injury had an almost 15-fold higher risk of HF (aHR, 14.62; 95% CI, 7.61-28.10) vs those with neither LVH nor injuries. By contrast, women with this phenotype had a nearly 4-fold higher risk of HF (aHR, 3.81; 95% CI, 2.40-6.85).The combination of LVH and subclinical myocardial injury identifies a malignant, preclinical HF phenotype in African Americans with a very high risk of HF, particularly among men. This finding could have implications for future screening strategies that are designed to prevent HF in the population.
Indirect Comparison Using Individual Patient Level Data Comparing Efficacy and Safety of a Daratumumab Monotherapy Vs. EU Approved Comparator Therapies in Patients with Multiple Myeloma
Authors: Irina Demmer, Susanne Huschens, Dietrich Potthoff, Jörg Tomeczkowski, Christian Englisch, Pushpike Thilakarathne, Joris Diels, Shaji K. Kumar, Brian GM Durie, Lewin Eisele
Journal: Blood (2018)
Abstract 18410: Prescriptions for and Use of β-Blocker Following Heart Failure Hospitalization: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Emily B Levitan, Melissa K Van Dyke, Ligong Chen, Raegan W Durant, Todd M Brown, J D Rhodes, Olusola Olubowale, Oluwole A Muyiwa, Meredith L Kilgore, Justin Blackburn, Karen C Albright, Monika M Safford
Journal: Circulation (2015)

Introduction: In heart failure (HF) with reduced ejection fraction (HFrEF), there is evidence that the β-blockers metoprolol succinate, bisoprolol and carvedilol improve prognosis. Objective: To examine β-blocker prescriptions and fills after HF hospitalization. Methods: In 2006-2011, we identified 344 HF hospitalizations (147 HFrEF, 152 with preserved ejection fraction, 45 unknown) with linked Medicare claims among 201 participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a cohort of 30,239 black and white adults. Comorbidities and prescriptions were abstracted from medical records. Claims were used to assess prescription fills. Risk ratios (RR) and confidence intervals (CI) for β-blocker prescriptions and fills were calculated using generalized estimating equations adjusted for age, race and sex. Results: Women accounted for 59% of HF hospitalizations and blacks 54%; 90% had prior HF. β-blockers were prescribed for 78% (87% with HFrEF); 58% (74% with HFrEF) of β-blocker prescriptions were metoprolol succinate, bisoprolol or carvedilol. Prescriptions were filled within 30 days of discharge for 46%. There was evidence of β-blocker up-titration for 9% (21% with HFrEF). HFrEF was more strongly associated with prescriptions and fills of metoprolol succinate, bisoprolol or carvedilol (RR 1.82 [95% CI 1.32, 2.53] and 1.73 [95% CI 1.12, 2.68], respectively) than any β-blocker (RR 1.12 [95% CI 0.99, 1.27] and 1.06 [95% CI 0.82, 1.36], respectively). After HFrEF hospitalization, black race and β-blockers at admission were positively associated with β-blocker prescriptions, female sex was positively associated with fills and chronic obstructive pulmonary disease was inversely, but not significantly, associated with prescriptions and fills ( Table ). Conclusions: β-blockers were prescribed at discharge for most HF hospitalizations, but many prescriptions do not appear to have been filled and up-titration was rare.
Abstract 055: Adherence to a DASH (Dietary Approaches to Stop Hypertension) Dietary Pattern and Risk of Abdominal Aortic Aneurysm
Authors: Bernhard Haring, Elizabeth Selvin, Xintong He, Josef Coresh, Lyn M Steffen, Aaron R Folsom, Weihong Tang, Casey M Rebholz
Journal: Circulation (2018)

Background: Abdominal aortic aneurysms (AAAs) develop in up to 8% of men and 6% of women over a lifetime. Although they typically remain asymptomatic, rupture of an AAA carries high mortality. Smoking and hypertension have been identified as modifiable risk factors for developing an AAA. The role of diet, however, is yet unclear. Objective: To evaluate the relationship between adherence to a DASH-style dietary pattern and the risk of incident AAA in a large, community-based cohort of middle-aged adults. Methods: Dietary intake was assessed via a 66-item FFQ at two visits in 14,322 participants enrolled in the ARIC study (Atherosclerosis Risk in Communities) without clinical AAA, incomplete dietary/covariate information or extreme energy intake at baseline. Adherence to a DASH-style dietary pattern was assessed using a previously developed dietary scoring index. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). Results: During a median follow-up of 23 years, there were 539 incident AAA cases. Participants with a DASH diet score in the highest quintile had a 39% lower risk to develop AAAs than those in the lowest score quintile (HRQ5 vs. Q1: 0.61; 95% CI 0.45, 0.84; ptrend =0.004) after adjusting for sociodemographics, total caloric intake, smoking, physical activity, BMI, abdominal obesity, diabetes, hypertension, hypercholesterolemia and cardiovascular disease. Higher intake of fruits, vegetables, whole grains, low-fat dairy, and nuts and legumes was related to a decreased risk for AAA. Conclusions: Greater adherence to a DASH-style dietary pattern was found to be associated with lower incidence of AAA. Higher consumption of fruits, vegetables, whole grains, low-fat dairy as well as nuts and legumes may help to decrease the burden of AAA in U.S. adults.
MLL-Menin Inhibition Reverses Pre-Leukemic Progenitor Self-Renewal Induced By NPM1 Mutations and Prevents AML Development
Authors: Hannah J. Uckelmann, Stephanie M. Kim, Noa J. C. Antonissen, Andrei V. Krivtsov, Charles Hatton, Gerard M. McGeehan, Ross L. Levine, George S. Vassiliou, Scott A. Armstrong
Journal: Blood (2018)
Normothermic Machine Perfusion (NMP) Inhibits Proinflammatory Responses in the Liver and Promotes Regeneration
Authors: Wayel Jassem, Emmanuel Xystrakis, Yasmeen G. Ghnewa, Muhammed Yuksel, Oltin Pop, Marc Martinez‐Llordella, Yamen Jabri, Xiaohong Huang, Juan J. Lozano, Alberto Quaglia, Alberto Sanchez‐Fueyo, Constantin C. Coussios, Mohamed Rela, Peter Friend, Nigel Heaton, Yun Ma
Journal: Hepatology (2018)

Liver transplantation (LT) is a successful treatment for patients with liver failure. However, organ shortage results in over 11% of patients losing their chance of a transplant attributed to liver decompensation (LD) and death. Ischemia/reperfusion injury (IRI) following conventional cold storage (CS) is a major cause of injury leading to graft loss after LT. Normothermic machine perfusion (NMP), a method of organ preservation, provides oxygen and nutrition during preservation and allows aerobic metabolism. NMP has recently been shown to enable improved organ utilization and posttransplant outcomes following a phase I and a phase III randomized trial. The aim of the present study is to assess the impact of NMP on reducing IRI and to define the underlying mechanisms. We transplanted and compared 12 NMP with 27 CS‐preserved livers by performing gene microarray, immunoprofiling of hepatic lymphocytes, and immunochemistry staining of liver tissues for assessing necrosis, platelet deposition, and neutrophil infiltration, and the status of steatosis after NMP or CS prereperfusion and postreperfusion. Recipients receiving NMP grafts showed significantly lower peak aspartate aminotransferase (AST) levels than those receiving CS grafts. NMP altered gene‐expression profiles of liver tissue from proinflammation to prohealing and regeneration. NMP also reduced the number of interferon gamma (IFN‐γ) and interleukin (IL)‐17–producing T cells and enlarged the CD4 pos CD25 high CD127 neg FOXP3 pos regulatory T cell (Treg) pool. NMP liver tissues showed less necrosis and apoptosis in the parenchyma and fewer neutrophil infiltration compared to CS liver tissues. Conclusion: Reduced IRI in NMP recipients was the consequence of the combination of inhibiting inflammation and promoting graft regeneration.
Abstract 15539: Anticoagulant Treatment Patterns for Cancer-Associated Thrombosis in a Commercial Insurance Population
Authors: Alok A Khorana, Keith McCrae, Dejan Milentijevic, Nora McCormick, François Laliberté, Concetta Crivera, Patrick Lefebvre, Dominique Lejeune, Heather Rozjabek, Jeff Schein, Michael Streiff
Journal: Circulation (2017)

Introduction: Recent evidence among Medicare cancer patients with venous thromboembolism (VTE) showed LMWH is associated with lower persistence than rivaroxaban or warfarin (WAR). This study analyz...
Inhaled corticosteroids in COPD: the final verdict is…
Authors: Janice M. Leung, Don D. Sin
Journal: European Respiratory Journal (2018)

Inhaled corticosteroids (ICS) were first discovered 50 years ago [1] and are now the most widely used controller medication in the world for chronic obstructive pulmonary disease (COPD). Over the past two decades, >40 000 patients with COPD have participated in large-scale ICS therapeutic trials. What have we learned from these studies? History (and features) of asthma, along with peripheral blood eosinophil counts, can guide provision of inhaled corticosteroids in COPD management <http://ow.ly/uApH30mgEh4>
The Long Noncoding RNA TTTY15, Which Is Located on the Y Chromosome, Promotes Prostate Cancer Progression by Sponging let-7
Authors: Guang’an Xiao, Jingjing Yao, Depei Kong, Chen Ye, Rui Chen, Li Li, Tao Zeng, Liujun Wang, Wei Zhang, Xiaolei Shi, Tie Zhou, Jing Li, Yue Wang, Chuan Liang Xu, Junfeng Jiang, Yinghao Sun
Journal: European Urology (2018)
Abstract P042: Coffee Intake and the Risk of Subclinical Myocardial Damage, Cardiovascular Events and All-cause Mortality
Authors: Roberta Florido, Chiadi E Ndumele, Natalie Daya, Yuan Chen, Roger S Blumenthal, Christie M Ballantyne, Casey M Rebholz, Erin D Michos, Michael J Klag, John W McEvoy, Elizabeth Selvin
Journal: Circulation (2017)

Introduction: Whether coffee intake is protective against cardiovascular disease (CVD) risk and mortality is controversial and putative mechanisms are incompletely understood, but prior studies may be confounded by a “healthy user” effect. Hypothesis: Habitual coffee consumption would not be associated with subclinical myocardial damage assessed using high-sensitivity cardiac troponin T (hs-cTnT), CVD events (coronary heart disease, heart failure or stroke) and all-cause mortality, after adjustment for rigorously measured confounders. Methods: We evaluated 11,281 ARIC participants free of CVD at baseline (Visit 2, 1990-1992). Coffee consumption was assessed via a modified food frequency questionnaire at Visit 2 and categorized according to number of cups/day. We used logistic regression models adjusted for demographic characteristics, smoking status and traditional CVD risk factors to test the cross-sectional associations with hs-cTnT, and adjusted Cox models for incident CVD events and mortality. Results: Mean age of participants was 57 years, 58% were women and 24% black. In cross-sectional analyses, compared to individuals reporting “almost never” having consumed coffee, no significant association was found between higher levels of coffee consumption and elevated hs-cTnT (OR for ≥6 cups/day vs. almost never 0.69; 95% CI 0.39, 1.21; Table). In prospective analyses, the association between coffee and incident CVD was not significant (HR for ≥6 cups/day vs. almost never: 1.15; 95% CI 0.99, 1.34; Table). Compared to almost never consuming coffee, 2-3 cups/day was associated with reduced risk of all-cause mortality and ≥6 cups/day with elevated risk of all-cause mortality (Table). Conclusion: In this bi-racial cohort of middle-aged adults, coffee intake was not associated with subclinical myocardial damage or CVD. However, moderate coffee consumption may be associated with a modestly reduced risk of all-cause mortality and very high coffee consumption with a mild increase in all-cause mortality.
Abstract 20871: Frequency and Characteristics of Exercise Induced Second Degree AV Block in Patients Undergoing Stress Testing
Authors: Amanda R Bonikowske, Suraj Kapa, Danova A Lopez Fajerstein, Thomas G Allison
Journal: Circulation (2017)

Background: Spontaneous second degree AV block induced by exercise (Ex2AVB) is reportedly rare (N=14 for largest published case series) but can cause profound exercise intolerance. Hypothesis: We s...
The role of VEGF receptor signaling in gastrointestinal carcinoma cell migration
Authors: Maria Pia Morelli, Todd Pitts, Amy Meyer, Fortunato Ciardiello, Anderson Ryan, S. Gail Eckhardt
Journal: Cancer Research (2008)

275  Background: The VEGF signaling axis is a key mediator of endothelial cell proliferation, migration and survival, and both normal and pathological angiogenesis. In addition, it has been suggested that autocrine signaling through the VEGF receptors (VEGFR) may play a role in tumor cell survival (Lee et al, PLoS Med. 2007 Jun;4(6):e186), invasion and migration (Fan et al, Oncogene 2005:24:2647-53)The purpose of the present study was to determine the expression of VEGFR family members (VEGFR-1, -2 and -3) and VEGFR ligands (VEGF-A, -C and -D) in a panel of gastrointestinal (GI) carcinoma cells, and to evaluate the effects of potential autocrine signaling on tumor cell migration and proliferation utilizing cediranib (AZD2171), a highly potent inhibitor of all three VEGF receptors  Methods and Results: Eight GI carcinoma cell lines (including colorectal, pancreatic and hepatocellular carcinoma lines) were screened for VEGF receptor and ligand expression by RT-PCR, Western blotting, FACS and ELISA. All cell lines expressed VEGFR-3 and VEGF-A, whereas VEGFR-2 was not detected. Expression of VEGFR-1 and VEGF-C was more variable and cell-line dependent. For example, VEGF-C secretion was detected only in SK-Hep1 cells. Tumor cell proliferation and migration was assessed under different growth conditions: 10% FBS, VEGF-A (10 ng/ml), VEGF-B (50 ng/ml), and VEGF-C (50 ng/ml). The effect of cediranib (1-100nM) on tumor cell proliferation and migration was determined. Of the cell lines investigated, only SW480 and SK-Hep1 cells showed migratory activity in all experimental conditions. Tumor cell migration was inhibited by cediranib at doses