tbuckley/cabot-search huggingface dataset:
Potential Causality and Emerging Medical Therapies for Lipoprotein(a) and Its Associated Oxidized Phospholipids in Calcific Aortic Valve Stenosis
Authors: Sotirios Tsimikas
Journal: Circulation Research (2019)

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.
Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and the Stromal Microenvironment in Bone Marrow Hematopoiesis
Authors: Takayuki Katagiri, Takashi Ushiki, Asami Kawasaki, Shun Uemura, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Hirohito Sone, Michihiro Igarashi, Masayoshi Masuko
Journal: Blood (2018)
Annals Graphic Medicine - #ThisIsOurLane
Authors: Christopher L. Bennett
Journal: Annals of Internal Medicine (2019)

Web Exclusives19 February 2019Annals Graphic Medicine - #ThisIsOurLaneFREEChristopher L. Bennett, MD, MAChristopher L. Bennett, MD, MAMassachusetts General Hospital, Boston, Massachusetts (C.L.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G18-0034 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Massachusetts General Hospital, Boston, Massachusetts (C.L.B.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G18-0034.Author/Illustrator Information: Christopher L. Bennett, MD, MA, is a resident physician in the Harvard Affiliated Emergency Medicine Residency at Massachusetts General Hospital and Brigham and Women's Hospital in Boston, Massachusetts (e-mail, christopher.lee.[email protected]com).This article was published at Annals.org on 12 February 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoFirearm Injury Prevention: AFFIRMing That Doctors Are in Our Lane Darren Taichman , Sue S. Bornstein , and Christine Laine Metrics 19 February 2019Volume 170, Issue 4Page: W78-W79KeywordsConflicts of interestDisclosureEmergency medicineHealth careHospital medicineResidency ePublished: 12 February 2019 Issue Published: 19 February 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
ASSOCIATION OF ALBUMINURIA WITH ADVERSE CARDIAC MECHANICS: FINDINGS FROM THE HYPERGEN STUDY
Authors: Daniel H. Katz, Senthil Selvaraj, Frank Aguilar, Eva Martinez, Lauren Beussink Kwang-Youn Kim, Jie Peng, Jin Sha, Ryan Irvin, Barry Freedman, John Eckfeldt, Donna Arnett, Sanjiv Shah
Journal: Journal of the American College of Cardiology (2013)
Open ADAMTS13 Conformation in Immune-Mediated Thrombotic Thrombocytopenic Purpura Is Induced By Anti-ADAMTS13 Autoantibodies and Corresponds with an Ongoing ADAMTS13 Pathology
Authors: Elien Roose, An-Sofie Schelpe, Edwige Tellier, György Sinkovits, Gilles Kaplanski, Maelle Le Besnerais, Ilaria Mancini, Nele Vandeputte, Aline Vandenbulcke, Inge Pareyn, J. J. Voorberg, Andreas Greinacher, Ygal Benhamou, Hans Deckmyn, Rob FIjnheer, Zoltan Prohászka, Flora Peyvandi, Paul Coppo, Simon F De Meyer, Agnès Veyradier, Karen Vanhoorelbeke
Journal: Blood (2018)
Abstract 20096: Progression of Subclinical Atherosclerosis in Subjects With Rheumatoid Arthritis and Metabolic Syndrome
Authors: Benjamin Burggraaf, Deborah F Van Breukelen-van der Stoep, Marijke A de Vries, Boudewijn Klop, Jende van Zeben, Gert-Jan M van de Geijn, Noelle van der Meulen, Lenneke Prinzen, Manuel Castro Cabezas
Journal: Circulation (2017)

Introduction: Both Rheumatoid Arthritis (RA) and the Metabolic Syndrome (MetS) have been associated with an increased risk of atherosclerosis. We aimed to assess the progression of carotid intima m...
Urine eosinophil-derived neurotoxin declines following mepolizumab treatment in subjects with Eosinophilic Granulomatosis with Polyangiitis
Authors: Paneez Khoury, Michelle Makiya, Anne-Marie Dyer, Praveen Akuthota, Bruce S. Bochner, Vernon M. Chinchilli, Gerald J. Gleich, Nicolas Kovacs, Carol A. Langford, Peter A. Merkel, Benjamin A. Raby, Ulrich Specks, Peter F. Weller, Michael E. Wechsler, Amy D. Klion
Journal: Journal of Allergy and Clinical Immunology (2019)
Patterns of Care of Diffuse Large B Cell Lymphoma Patients 80 Years and Older: Worse Outcomes after Treatment without Increased Relapse
Authors: Madison Keenan, Kirsten Marie Boughan, Brenda Cooper, Molly M Gallogly, Stanton L. Gerson, Hillard M Lazarus, Ehsan Malek, Leland Metheny, Folashade Otegbeye, Benjamin K. Tomlinson, Erika Moore, Kwadwo Asare Oduro, Rose Beck, Howard Meyerson, Marcos de Lima, Paolo F Caimi
Journal: Blood (2018)
Specific Disruption of Abca1 Targeting Largely Mimics the Effects of miR-33 Knockout on Macrophage Cholesterol Efflux and Atherosclerotic Plaque Development
Authors: Nathan L. Price, Noemi Rotllan, Xinbo Zhang, Alberto Canfrán-Duque, Timothy Nottoli, Yajaira Suarez, Carlos Fernández-Hernando
Journal: Circulation Research (2019)

Rationale: Inhibition of miR-33 reduces atherosclerotic plaque burden, but miR-33 deficient mice are predisposed to the development of obesity and metabolic dysfunction. The proatherogenic effects of miR-33 are thought to be in large part because of its repression of macrophage cholesterol efflux, through targeting of Abca1 (ATP-binding cassette subfamily A member 1). However, targeting of other factors may also be required for the beneficial effects of miR-33, and currently available approaches have not allowed researchers to determine the specific impact of individual miRNA target interactions in vivo. Objective: In this work, we sought to determine how specific disruption of Abca1 targeting by miR-33 impacts macrophage cholesterol efflux and atherosclerotic plaque formation in vivo. Methods and Results: We have generated a novel mouse model with specific point mutations in the miR-33 binding sites of the Abca1 3’untranslated region, which prevents targeting by miR-33. Abca1 binding s ite mutant ( Abca1 BSM ) mice had increased hepatic ABCA1 expression but did not show any differences in body weight or metabolic function after high fat diet feeding. Macrophages from Abca1 BSM mice also had increased ABCA1 expression, as well as enhanced cholesterol efflux and reduced foam cell formation. Moreover, LDLR (low-density lipoprotein receptor) deficient animals transplanted with bone marrow from Abca1 BSM mice had reduced atherosclerotic plaque formation, similar to mice transplanted with bone marrow from miR-33 knockout mice. Conclusion: Although the more pronounced phenotype of miR-33 deficient animals suggests that other targets may also play an important role, our data clearly demonstrate that repression of ABCA1 is primarily responsible for the proatherogenic effects of miR-33. This work shows for the first time that disruption of a single miRNA/target interaction can be sufficient to mimic the effects of miRNA deficiency on complex physiological phenotypes in vivo and provides an approach by which to assess the impact of individual miRNA targets.
A Study of Tbo-Filgrastim (Granix) to Disrupt the Bone Marrow Microenvironment in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation
Authors: Meagan Jacoby, Reetom Bera, Theresa Fletcher, Mark A. Fiala, Kathryn Trinkaus, John F. DiPersio, Keith E. Stockerl-Goldstein, Mark A. Schroeder, Daniel C. Link, Ravi Vij
Journal: Blood (2018)
Lipoprotein(a) Levels and the Risk of Myocardial Infarction Among 7 Ethnic Groups
Authors: Guillaume Paré, Artuela Çaku, Matthew McQueen, Sonia S. Anand, Enas Enas, Robert Clarke, Michael B. Boffa, Marlys Koschinsky, Xingyu Wang, Salim Yusuf
Journal: Circulation (2019)

Lipoprotein(a) [Lp(a)] levels predict the risk of myocardial infarction (MI) in populations of European ancestry; however, few data are available for other ethnic groups. Furthermore, differences in isoform size distribution and the associated Lp(a) concentrations have not fully been characterized between ethnic groups.We studied 6086 cases of first MI and 6857 controls from the INTERHEART study that were stratified by ethnicity and adjusted for age and sex. A total of 775 Africans, 4443 Chinese, 1352 Arabs, 1856 Europeans, 1469 Latin Americans, 1829 South Asians, and 1221 Southeast Asians were included in the study. Lp(a) concentration was measured in each participant using an assay that was insensitive to isoform size, with isoform size being assessed by Western blot in a subset of 4219 participants.Variations in Lp(a) concentrations and isoform size distributions were observed between populations, with Africans having the highest Lp(a) concentration (median=27.2 mg/dL) and smallest isoform size (median=24 kringle IV repeats). Chinese samples had the lowest concentration (median=7.8 mg/dL) and largest isoform sizes (median=28). Overall, high Lp(a) concentrations (>50 mg/dL) were associated with an increased risk of MI (odds ratio, 1.48; 95% CI, 1.32-1.67; P<0.001). The association was independent of established MI risk factors, including diabetes mellitus, smoking, high blood pressure, and apolipoprotein B and A ratio. An inverse association was observed between isoform size and Lp(a) concentration, which was consistent across ethnic groups. Larger isoforms tended to be associated with a lower risk of MI, but this relationship was not present after adjustment for concentration. Consistent with variations in Lp(a) concentration across populations, the population-attributable risk of high Lp(a) for MI varied from 0% in Africans to 9.5% in South Asians.Lp(a) concentration and isoform size varied markedly between ethnic groups. Higher Lp(a) concentrations were associated with an increased risk of MI and carried an especially high population burden in South Asians and Latin Americans. Isoform size was inversely associated with Lp(a) concentration, but did not significantly contribute to risk.
A Laboratory Based Scoring System Predicts Early Treatment in Rai 0/Binet a CLL
Authors: Jared A Cohen, Francesca Maria Rossi, Riccardo Bomben, Lodovico Terzi-di-Bergamo, Pietro Bulian, Massimo Degan, Antonella Zucchetto, Giovanni Francesco D'Arena, Enrico Santinelli, Francesco Zaja, Gabriele Pozzato, Davide Rossi, Annalisa Chiarenza, Francesco Di Raimondo, Luca Laurenti, Idanna Innocenti, Giovanni Del Poeta, Christopher Fegan, Chris Pepper, Kari G. Chaffee, Sameer A. Parikh, Neil E. Kay, Valter Gattei
Journal: Blood (2018)
The parametric estimation procedure to predict long-term efficacy on survival from publication data of clinical trials for metastatic colorectal cancer (mCRC).
Authors: Kyongsun Pak, Yu Sunakawa, Masahiro Takeuchi, Wataru Ichikawa, Masashi Fujii
Journal: Journal of Clinical Oncology (2019)

541 Background: In comparative clinical trials with time-to-event outcomes, the long-term treatment effect profile is clinically crucial. The conventional non-parametric measures, i.e., the median survival times and the t-year survival rates are informative but sometimes cannot be observed due to the limited study follow-up. For example, in the PEAK trial (Schwartzberg LS et al. J Clin Oncol 2014), the group contrast over 3 years could not be adequately confirmed due to the short follow-up. To predict the subsequent survival prognosis with the limited outcome data, one may estimate the survival curve using a parametric model. Here, we illustrate the parametric estimation procedure to predict long-term efficacy using the results of two randomized controlled trials for the patients with wild-type KRAS mCRC, i.e., PRIME (Douillard JY et al. J Clin Oncol 2010, Douillard JY et al. Ann Oncol 2014) and PEAK trials. Methods: We considered both the primary and updated results for the PRIME to assess the validity of the procedure, and then estimated the long-term efficacy in the two trials. We used the reconstructed overall survival (OS) data obtained by scanning the Kaplan-Meier curves in the literature. Fitting the data to the Weibull distribution, we estimated the parametric group contrast measures including the difference in the 3- and 5-years restricted mean survival times and mean survival times. Results: The extrapolated parametric OS curves from the primary PRIME results fitted well with the observed Kaplan-Meier curves for OS in the updated results. The parametric estimations demonstrated that, in the PRIME trial, panitumumab plus FOLFOX arm increased 2.0 (95% CI: 0.1-4.0), 4.0 (0.5-7.5), and 5.4 (0.3-10.5) months in survival on average over 3-, 5-years and the entire time, respectively, compared to FOLFOX arm. In PEAK trial, compared to bevacizumab plus FOLFOX arm, panitumumab plus FOLFOX arm increased 3.6 (0.7-6.5), 7.9 (2.1-13.7), and 12.8 (0.5-25.1) months in survival on average, respectively. Conclusions: The estimators for parametric survival curve would provide the informative summaries for long-term survival profile to the clinicians and patients.
Effect of time between diagnosis and surgery in colorectal cancer patients on mortality.
Authors: Benjamin D Fangman, Muhammad Shaalan Beg, Aravind Sanjeevaiah, Farshid Araghizadeh, Shannon Scielzo, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2019)

708 Background: Colorectal cancer is the fourth most common cancer diagnosed in the United States and accounts for &gt; 50,000 deaths nationwide annually. With data showing that oncologic treatment at National Cancer Institute (NCI) designated comprehensive cancer centers improves outcomes in a variety of malignancies, understanding the drivers behind this is vital to help bring the world-class care being administered at comprehensive cancer centers to underserved populations across the U.S. One component of colorectal cancer care that has a paucity of data afforded to it is the effect of increased time from diagnosis to surgery on survival. Methods: Patients diagnosed with AJCC stage II or stage III colorectal cancer between 4/2011 and 11/2015 and either underwent surgery or adjuvant chemotherapy within the University of Texas Southwestern system were selected. Several pertinent data points were abstracted via the EMR including date of diagnosis, surgery, adjuvant chemotherapy, progression, and death. A retrospective analysis was performed on the abstracted data to determine if the number of days between diagnosis and surgery was correlated with increased survival. Spearman coefficients were calculated to determine correlations between the data. All tests were two-sided. Results: Out of 203 patients identified, 113 patients had complete data available and were included in the study. The average age at diagnosis was 62.6 and average follow-up time was 41.4 months. Median time to surgery was 21 days (25th percentile-75th percentile: 4 – 53 days). There was a significant negative correlation between days from diagnosis to surgery and mortality (Spearman’s r = -.392, p &lt; .001). Survivors had a mean of 42.7 days from diagnosis to surgery (SD = 56.4) and nonsurvivors had a mean of 61.7 days (SD = 46.9). Conclusions: There was a significant negative correlation seen in days between diagnosis and surgery and survival during the study period, which indicates that early surgical intervention may be an underappreciated indicator of quality colorectal cancer care. Further research should be conducted to better understand the relationship between early surgical intervention and prognosis in limited-stage colorectal cancer.
Comparison of Clinical Care and In-Hospital Outcomes of Asian American and White Patients With Acute Ischemic Stroke
Authors: Sarah Song, Li Liang, Gregg C. Fonarow, Eric E. Smith, Deepak L. Bhatt, Roland A. Matsouaka, Ying Xian, Lee H. Schwamm, Jeffrey L. Saver
Journal: JAMA Neurology (2019)

Although overall stroke incidence and mortality in the United States is improving, little is known about the characteristics and clinical outcomes of acute ischemic stroke in Asian American individuals.To compare the characteristics, care, and outcomes of Asian American and white patients with acute ischemic stroke.Retrospective analysis of Asian American and white patients admitted with a primary diagnosis of acute ischemic stroke to hospitals participating in the Get With The Guidelines-Stroke (GWTG-Stroke) program between April 1, 2004, and July 31, 2016. The GWTG-Stroke database is a prospectively collected stroke quality improvement registry sponsored by the American Heart Association/American Stroke Association.Multivariable logistic regression models assessed the association of Asian American race/ethnicity, clinical outcomes, and quality measures.The study population of 1 772 299 patients (mean [SD] age, 72.4 [14.2] years; 51.3% female) consisted of 64 337 Asian American patients (3.6%) and 1 707 962 white patients (96.4%) admitted to 2171 GWTG-Stroke hospitals with acute ischemic stroke. After adjustment for patient and hospital variables, Asian American patients were seen with greater stroke severity compared with white patients (National Institutes of Health Stroke Scale [NIHSS] score ≥16) (odds ratio [OR], 1.35; 95% CI, 1.30-1.40; P < .001), manifested higher in-hospital mortality (OR, 1.14; 95% CI, 1.09-1.19; P < .001), had longer length of stay (OR, 1.17; 95% CI, 1.14-1.20; P < .001), and were less likely to ambulate independently at discharge (OR, 0.84; 95% CI, 0.79-0.90; P < .001). Although Asian American patients had fewer intravenous tissue plasminogen activator (IV tPA) administrations than white patients (OR, 0.95; 95% CI, 0.91-0.98; P = .003), they had more symptomatic hemorrhage after tPA (OR, 1.36; 95% CI, 1.20-1.55; P < .001) and overall post-tPA complications (OR, 1.31; 95% CI, 1.18-1.46; P < .001). Asian American patients had better quality measure adherence overall than white patients, including rehabilitation (OR, 1.27; 95% CI, 1.18-1.36; P < .001), door to tPA within 60 minutes (OR, 1.14; 95% CI, 1.06-1.22; P < .001), and intensive statin therapy (OR, 1.14; 95% CI, 1.10-1.18; P < .001). After adjustment for stroke severity, Asian American patients had lower in-hospital mortality than white patients (OR, 0.95; 95% CI, 0.91-0.99; P = .008).Asian American patients manifested more severe ischemic strokes, were less likely to receive IV tPA, and had worse functional outcomes than white patients. These findings warrant additional research toward improving clinical outcomes for Asian American patients with acute ischemic stroke.
Abstract 12057: Improving Hypertension Control and Patient Engagement Using Digital Tools
Authors: Richard V Milani, Carl J Lavie, Robert M Bober, Alexander R Milani, Hector O Ventura
Journal: Circulation (2016)

Introduction: Hypertension (HTN) is present in 30% of the adult US population and is a major contributor to heart and vascular disease. The current office-based approach yields only 50% control rates and low levels of patient activation. Current home technology now provides accurate, reliable data that can be transmitted to the electronic medical record (EMR). Purpose: To evaluate the feasibility and impact of a home blood pressure (BP) monitoring program on BP control and patient activation in patients with uncontrolled HTN (unHTN). Methods: We enrolled 125 patients with unHTN (last 3 readings &gt; 140/90) into a home-based digital monitoring program (digital) and compared them to 400 patients (matched to age, gender, BMI and BP) with unHTN in a usual care (UC) group after 6 months. Digital patients completed questionnaires on-line, were asked to submit ≥1 BP reading/week, and received medication management and lifestyle recommendations via a clinical pharmacist and a health coach. BP units were commercially available, that transmitted data to the EMR (Epic). Results: There were no significant differences at baseline between Digital and UC patients. Digital patients averaged 4.2 BP readings per week. At 6-months 67% of Digital patients versus 32% of UC patients had achieved BP control. Mean drop in systolic/diastolic BP was 15/6 mmHg in Digital versus 7/3 mmHg in UC. Excess sodium consumption decreased from 54% to 41% in the Digital group. Mean patient activation increased from 42.3 to 44.0 (p&lt;0.05) and the percentage of patients with low patient activation decreased from 15.8% to 10.7% (p&lt;0.05). Limitations • Non-randomized trial • Single site Conclusions: A digital HTN program is feasible and associated with significant improvement in BP control rates and lifestyle change. Utilization of a virtual health intervention using connected devices improves patient activation and is well accepted by patients.
Molecular underpinnings of clinical disparity patterns in African American vs. Caucasian American multiple myeloma patients
Authors: Dickran Kazandjian, Elizabeth Hill, Malin Hultcrantz, Evan H. Rustad, Venkata Yellapantula, Theresia Akhlaghi, Neha Korde, Sham Mailankody, Alex Dew, Elli Papaemmanuil, Irina Maric, Mary Kwok, Ola Landgren
Journal: Blood Cancer Journal (2019)

Caucasian Americans (CA) compared with African Americans (AA) have a twofold increased incidence of multiple myeloma (MM) and have an earlier age of diagnosis. However, there is sparse information regarding underlying biological differences across racial/ethnic groups. We characterized genetic alterations using a targeted next-generation sequencing assay called myTYPE, developed at MSKCC, allowing capture of somatic mutations, IgH translocations, gains/losses, and hyperdiploidy. Samples were obtained from the NIH Plasma Cell Dyscrasia Racial Disparity Cohort. In total, 68 patient samples were successfully sequenced and manually curated based on well-established databases. Of the 68 patient samples (47 CA, 21 AA), 84% had at least one type of genomic alteration. Importantly, the IgH translocation, t(11;14), was observed more frequently in the AA group (0 vs. 29%, p = 0.001). Known oncogenic somatic non-synonymous mutations were found in 18 genes and indels in 2 genes. KRAS mutations were the most common mutation found in 16% of patients followed by NRAS and BRAF mutations. TP53 somatic mutations appeared to be more common in CA but lacked significance. This proof-of-principle study indicates the presence of varying underlying tumor biology between racial groups and supports the need of future prospective trials to capture these molecular characteristics.