tbuckley/cabot-search huggingface dataset:
Abstract 17415: Dobutamine Stress Echocardiography Does Not Predict Outcomes in Patients with Low Transvalvular Gradient Undergoing Transcatheter Aortic Valve Replacement
Authors: Salim Hayek, Vasilis Babaliaros, Vinod Thourani, Emir Veledar, Stamatios Lerakis
Journal: Circulation (2012)

Introduction: Patients with severe aortic stenosis and low mean transvalvular gradient have poor outcomes with an estimated 30 day post-surgical Aortic Valve Replacement (AVR) mortality of 21%. Low...
Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry
Authors: Chotima Böttcher, Stephan Schlickeiser, Marjolein A. M. Sneeboer, Desiree Kunkel, Anniki Knop, Evdokia Paza, Pawel Fidzinski, Larissa Kraus, Gijsje J. L. Snijders, René S Kahn, Axel R Schulz, Henrik E Mei, Elly M. Hol, Britta Siegmund, Rainer Glauben, Eike J Spruth, Lot D de Witte, Josef Priller
Journal: Nature Neuroscience (2018)
Assessment of Risk Factors and Biomarkers Associated With Risk of Cardiovascular Disease Among Women Consuming a Mediterranean Diet
Authors: Shafqat Ahmad, M. Vinayaga Moorthy, Olga V. Demler, Frank B. Hu, Paul M Ridker, Daniel I. Chasman, Samia Mora
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Higher Mediterranean diet (MED) intake has been associated with lower risk of cardiovascular disease (CVD), but limited data are available about the underlying molecular mechanisms of this inverse disease association in human populations. <h3>Objective</h3> To better characterize the relative contribution of traditional and novel factors to the MED-related risk reduction in CVD events in a US population. <h3>Design, Setting, and Participants</h3> Using a prospective cohort design, baseline MED intake was assessed in 25 994 initially healthy US women in the Women's Health Study who were followed up to 12 years. Potential mediating effects of a panel of 40 biomarkers were evaluated, including lipids, lipoproteins, apolipoproteins, inflammation, glucose metabolism and insulin resistance, branched-chain amino acids, small-molecule metabolites, and clinical factors. Baseline study information and samples were collected between April 30, 1993, and January 24, 1996. Analyses were conducted between August 1, 2017, and October 30, 2018. <h3>Exposures</h3> Intake of MED is a 9-category measure of adherence to a Mediterranean dietary pattern. Participants were categorized into 3 levels based on their adherence to the MED. <h3>Main Outcomes and Measures</h3> Incident CVD confirmed through medical records and the proportion of CVD risk reduction explained by mediators. <h3>Results</h3> Among 25 994 women (mean [SD] age, 54.7 [7.1] years), those with low, middle, and upper MED intakes composed 39.0%, 36.2%, and 24.8% of the study population and experienced 428 (4.2%), 356 (3.8%), and 246 (3.8%) incident CVD events, respectively. Compared with the reference group who had low MED intake, CVD risk reductions were observed for the middle and upper groups, with respective HRs of 0.77 (95% CI, 0.67-0.90) and 0.72 (95% CI, 0.61-0.86) (<i>P </i>for trend &lt; .001). The largest mediators of the CVD risk reduction of MED intake were biomarkers of inflammation (accounting for 29.2% of the MED-CVD association), glucose metabolism and insulin resistance (27.9%), and body mass index (27.3%), followed by blood pressure (26.6%), traditional lipids (26.0%), high-density lipoprotein measures (24.0%) or very low-density lipoprotein measures (20.8%), with lesser contributions from low-density lipoproteins (13.0%), branched-chain amino acids (13.6%), apolipoproteins (6.5%), or other small-molecule metabolites (5.8%). <h3>Conclusions and Relevance</h3> In this study, higher MED intake was associated with approximately one-fourth relative risk reduction in CVD events, which could be explained in part by known risk factors, both traditional and novel.
Coronary CTA reduced risk for coronary events at 5 years in patients with stable chest pain
Authors: Michael P. Hudson
Journal: Annals of Internal Medicine (2018)

ACP Journal Club18 December 2018Coronary CTA reduced risk for coronary events at 5 years in patients with stable chest painMichael P. Hudson, MDMichael P. Hudson, MDHenry Ford Hospital, Detroit, Michigan, USA (M.P.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2018-169-12-070 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationSCOT-HEART Investigators; Newby DE, Adamson PD, Berry C, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018;379:924-33. https://pubmed.ncbi.nlm.nih.gov/30145934Clinical Impact RatingsCardiology: References1 Bittencourt MS, Hulten EA, Veeranna V, Blankstein R. Coronary computed tomography angiography in the evaluation of chest pain of suspected cardiac origin. Circulation. 2016;133:1963-8. [PMID: 27185023] Google Scholar2 Foy AJ, Dhruva SS, Peterson B, et al. Coronary computed tomography angiography vs functional stress testing for patients with suspected coronary artery disease: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:1623-31. [PMID: 28973101] Google Scholar Author, Article, and Disclosure InformationAffiliations: Henry Ford Hospital, Detroit, Michigan, USA (M.P.H.)This article was published at Annals.org on 4 December 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 December 2018Volume 169, Issue 12Page: JC70KeywordsAngiographyCongenital heart diseaseCoronary computed tomographic angiographyCoronary heart diseaseCoronary revascularizationIschemiaMyocardial infarctionRevascularizationStable coronary artery diseaseStroke ePublished: 18 December 2018 Issue Published: 18 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract B53: Sonic Hedgehog inhibition in glioblastoma potentializes temozolomide effect?
Authors: Jessica Honorato, Giselle Pinto de Faria Lopes, Gabriela Basile, Vivaldo Moura-Neto, Tania Spohr
Journal: Clinical Cancer Research (2018)

Abstract Gliomas are malignant intracranial tumors and may occur in any region of central nervous system (CNS). Among them, glioblastoma (GBM) is the most aggressive and frequent brain tumors. In GBM treatment, the alkylating agent temozolomide (TMZ) is the first-line chemotherapy used; however, the patients' prognosis remains limited. During tumorigenesis, several signaling pathways vital for embryonic development are activated or inhibited, such as transforming growth factor beta (TGFbeta), Wingless (Wnt), and Sonic hedgehog (Shh). Currently, it is known that Shh pathway is involved in the chemoresistance of GBMs, and most of them have this pathway constitutive activated, which is one of the factors responsible to resistance to TMZ treatment. The limitation of using TMZ treatment can be solved by the identification of cell type with stem cell-like properties, the cancer stem cells (CSCs). To overcome this problem, some selective inhibitory drugs of Shh pathway have been developed, such as GANT-61. In this work, we investigated if Shh inhibition potentiates the effects of TMZ and verified the mechanisms involved in this process. To achieve our goals, GBM11 and T98G cell lines were treated with TMZ (100, 200, and 400 μM) and GANT-61 (20 μM) at different times of incubation. Our results suggest that both cell lines are resistant to TMZ, and the combination of GANT-61 with TMZ during 72 h reduced the cell viability of T98G lineage by MTT assay. Also, our results suggest that among the mechanisms involved in the cell viability reduction observed by combination of TMZ+GANT, cell death occurs due to DNA fragmentation and loss of membrane integrity, as well as formation of acidic vesicles that are indicative of autophagy and reactive oxygen species (ROS) production. In short, our results suggest that selective inhibition of the Shh pathway by GANT-61 is potentiating the effect of TMZ, being a promising strategy for GBMs treatment. Citation Format: Jessica Honorato, Giselle Pinto de Faria Lopes, Gabriela Basile, Vivaldo Moura-Neto, Tania Spohr. Sonic Hedgehog inhibition in glioblastoma potentializes temozolomide effect? [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B53.
Metabolic Phenotype of Wild-Type and <i>As3mt</i> -Knockout C57BL/6J Mice Exposed to Inorganic Arsenic: The Role of Dietary Fat and Folate Intake
Authors: Madelyn C. Huang, Christelle Douillet, Ellen N. Dover, Chongben Zhang, Rowan Beck, Ahmad Tejan-Sie, Sergey A. Krupenko, Miroslav Stýblo
Journal: Environmental Health Perspectives (2018)

Inorganic arsenic (iAs) is a diabetogen. Interindividual differences in iAs metabolism have been linked to susceptibility to diabetes in iAs-exposed populations. Dietary folate intake has been shown to influence iAs metabolism, but to our knowledge its role in iAs-associated diabetes has not been studied.The goal of this study was to assess how folate intake, combined with low-fat (LFD) and high-fat diets (HFD), affects the metabolism and diabetogenic effects of iAs in wild-type (WT) mice and in As3mt-knockout (KO) mice that have limited capacity for iAs detoxification.Male and female WT and KO mice were exposed to 0 or [Formula: see text] iAs in drinking water. Mice were fed the LFD containing [Formula: see text] or [Formula: see text] folate for 24 weeks, followed by the HFD with the same folate levels for 13 weeks. Metabolic phenotype and iAs metabolism were examined before and after switching to the HFD.iAs exposure had little effect on the phenotype of mice fed LFD regardless of folate intake. High folate intake stimulated iAs metabolism, but only in WT females. KO mice accumulated more fat than WT mice and were insulin resistant, with males more insulin resistant than females despite similar %fat mass. Feeding the HFD increased adiposity and insulin resistance in all mice. However, iAs-exposed male and female WT mice with low folate intake were more insulin resistant than unexposed controls. High folate intake alleviated insulin resistance in both sexes, but stimulated iAs metabolism only in female mice.Exposure to [Formula: see text] iAs in drinking water resulted in insulin resistance in WT mice only when combined with a HFD and low folate intake. The protective effect of high folate intake may be independent of iAs metabolism, at least in male mice. KO mice were more prone to developing insulin resistance, possibly due to the accumulation of iAs in tissues. https://doi.org/10.1289/EHP3951.
Disease progression of Takayasu arteritis in two patients treated with tocilizumab
Authors: Catalina Sanchez-Alvarez, Matthew Koster, Ali Duarte-García, Kenneth J Warrington
Journal: Annals of the Rheumatic Diseases (2018)

In recent years there has been growing interest in the use of tocilizumab for the treatment of large vessel vasculitis, particularly giant cell arteritis.1 Nakaoka et al recently suggested that tocilizumab may be of therapeutic benefit in patients with relapsing Takayasu arteritis (TAK).2 In this journal, a case of aortic ulceration in a patient with TAK while on tocilizumab was described.3 We report two additional patients who had disease progression despite tocilizumab therapy.

### Case 1

A 44-year-old woman with a 20-year history of seropositive rheumatoid arthritis in clinical remission on adalimumab presented with new-onset right upper extremity claudication. A diagnosis of TAK was made after angiography demonstrated arterial thickening of the aorta and arch branches with multifocal narrowing of the subclavian and common carotid arteries. …
FDA Approval Summary: (Daunorubicin and Cytarabine) Liposome for Injection for the Treatment of Adults with High-Risk Acute Myeloid Leukemia
Authors: Aviva C. Krauss, Xin Gao, Liang Li, Michael L. Manning, Paresma Patel, Wentao Fu, Kumar G. Janoria, Gerlie Gieser, David A. Bateman, Donna Przepiorka, Yuan Li Shen, Stacy S. Shord, Christopher M. Sheth, Anamitro Banerjee, Jiang Liu, Kirsten B. Goldberg, Ann T. Farrell, Gideon M. Blumenthal, Richard Pazdur
Journal: Clinical Cancer Research (2018)

On August 3, 2017, the FDA granted regular approval to Vyxeos (also known as CPX-351; Jazz Pharmaceuticals), a liposomal formulation of daunorubicin and cytarabine in a fixed combination, for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia (t-AML) or acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC). Approval was based on data from Study CLTR0310-301, a randomized, multicenter, open-label, active-controlled trial comparing Vyxeos with a standard combination of daunorubicin and cytarabine ("7+3") in 309 patients 60-75 years of age with newly diagnosed t-AML or AML-MRC. Because of elemental copper concerns with the Vyxeos formulation, patients with Wilson disease were excluded from the study. Vyxeos demonstrated an improvement in overall survival (HR 0.69; 95% confidence interval, 0.52-0.90; P = 0.005) with an estimated median overall survival of 9.6 months compared with 5.9 months for the "7+3" control arm. The toxicity profile of Vyxeos was similar to that seen with standard "7+3" with the exception of more prolonged neutropenia and thrombocytopenia on the Vyxeos arm. Because the pharmacology of Vyxeos differs from that of other formulations of daunorubicin and cytarabine, labeling includes a warning against interchanging formulations during treatment. This is the first FDA-approved treatment specifically for patients with t-AML or AML-MRC.
Targeting early changes in the synovial microenvironment: a new class of immunomodulatory therapy?
Authors: Susan R Aungier, Alison J Cartwright, Anja Schwenzer, Jennifer L Marshall, Michael R Dyson, Peter Slavny, Kothai Parthiban, Aneesh Karatt-Vellatt, Ilfita Sahbudin, Eric Culbert, Patrick Hextall, Felix IL Clanchy, Richard Williams, Brian D Marsden, Karim Raza, Andrew Filer, Christopher Dominic Buckley, John McCafferty, Kim S Midwood
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Controlled immune responses rely on integrated crosstalk between cells and their microenvironment. We investigated whether targeting proinflammatory signals from the extracellular matrix that persist during pathological inflammation provides a viable strategy to treat rheumatoid arthritis (RA). Methods Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. Clones that neutralised FBG activation of toll-like receptor 4 (TLR4), without impacting pathogenic TLR4 activation, were epitope mapped by crystallography. Antibodies stained synovial biopsies of patients at different stages of RA development. Antibody efficacy in preventing RA synovial cell cytokine release, and in modulating collagen-induced arthritis in rats, was assessed. Results Tenascin-C is expressed early in the development of RA, even before disease diagnosis, with higher levels in the joints of people with synovitis who eventually developed RA than in people whose synovitis spontaneously resolved. Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. Conclusions Early changes in the synovial microenvironment contribute to RA progression; blocking proinflammatory signals from the matrix can ameliorate experimental arthritis. These data highlight a new drug class that could offer early, disease-specific immune modulation in RA, without engendering global immune suppression.
Reducing loss to follow-up during treatment for drug-resistant tuberculosis
Authors: Ibrahim Abubakar, Marc Lipman
Journal: European Respiratory Journal (2019)

The global strategy to end tuberculosis (TB) highlights integrated patient-centred care, bold policies and supportive systems, and intensified research and innovation as major priorities [1]. Central to this is the need to keep people in care and ensure that they are successfully treated using the best evidence-based approaches. This is of particular relevance to people with drug-resistant disease, who will generally need treatment for longer and require a more complicated, potentially toxic regimen. In this issue of the European Respiratory Journal , Law et al. [2] summarise, in their systematic literature review, the evidence for measures that minimise loss to follow-up during treatment of drug-resistant TB in adults. Loss to follow-up during treatment for drug-resistant TB can be reduced by regular and sustained psychosocial support provided by the patient's healthcare workers <http://ow.ly/VzkI30n4sni> M. Lipman is Chief Investigator on the NIHR (National Institute for Health Research, England) Health Technology Assessment-funded study "Intervening with a Manualised Package to AChieve treatment adherence in people with Tuberculosis: the IMPACT study" (16/88/06). The views expressed are those of the authors and not necessarily those of the NHS (National Health Service, UK), the NIHR or the Department of Health and Social Care.
Tissue Engineering for the Temporomandibular Joint
Authors: Timothy M. Acri, Kyungsup Shin, Dongrim Seol, Noah Z. Laird, Ino Song, Sean M. Geary, Jaidev L. Chakka, James A. Martin, Aliasger K. Salem
Journal: Advanced Healthcare Materials (2018)

Tissue engineering potentially offers new treatments for disorders of the temporomandibular joint which frequently afflict patients. Damage or disease in this area adversely affects masticatory function and speaking, reducing patients' quality of life. Effective treatment options for patients suffering from severe temporomandibular joint disorders are in high demand because surgical options are restricted to removal of damaged tissue or complete replacement of the joint with prosthetics. Tissue engineering approaches for the temporomandibular joint are a promising alternative to the limited clinical treatment options. However, tissue engineering is still a developing field and only in its formative years for the temporomandibular joint. This review outlines the anatomical and physiological characteristics of the temporomandibular joint, clinical management of temporomandibular joint disorder, and current perspectives in the tissue engineering approach for the temporomandibular joint disorder. The tissue engineering perspectives have been categorized according to the primary structures of the temporomandibular joint: the disc, the mandibular condyle, and the glenoid fossa. In each section, contemporary approaches in cellularization, growth factor selection, and scaffold fabrication strategies are reviewed in detail along with their achievements and challenges.
Bundle Branch Block Site in a Patient With a Right-Lying Heart and Wide QRS Complex
Authors: Qinghua Chang, Renguang Liu, Zizhen Feng
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome
Authors: Jorge E. Cortes, Florian H. Heidel, Andrzej Hellmann, Walter Fiedler, B. Douglas Smith, Tadeusz Robak, Pau Montesinos, Daniel A. Pollyea, Pierre DesJardins, Oliver Ottmann, Weidong Wendy Ma, M. Naveed Shaik, A. Douglas Laird, Mirjana Zeremski, Ashleigh O’Connell, Geoffrey Chan, Michael Heuser
Journal: Leukemia (2018)

Glasdegib is a Hedgehog pathway inhibitor. This phase II, randomized, open-label, multicenter study (ClinicalTrials.gov, NCT01546038) evaluated the efficacy of glasdegib plus low-dose cytarabine (LDAC) in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome unsuitable for intensive chemotherapy. Glasdegib 100 mg (oral, QD) was administered continuously in 28-day cycles; LDAC 20 mg (subcutaneous, BID) was administered for 10 per 28 days. Patients (stratified by cytogenetic risk) were randomized (2:1) to receive glasdegib/LDAC or LDAC. The primary endpoint was overall survival. Eighty-eight and 44 patients were randomized to glasdegib/LDAC and LDAC, respectively. Median (80% confidence interval [CI]) overall survival was 8.8 (6.9–9.9) months with glasdegib/LDAC and 4.9 (3.5–6.0) months with LDAC (hazard ratio, 0.51; 80% CI, 0.39–0.67, P = 0.0004). Fifteen (17.0%) and 1 (2.3%) patients in the glasdegib/LDAC and LDAC arms, respectively, achieved complete remission (P < 0.05). Nonhematologic grade 3/4 all-causality adverse events included pneumonia (16.7%) and fatigue (14.3%) with glasdegib/LDAC and pneumonia (14.6%) with LDAC. Clinical efficacy was evident across patients with diverse mutational profiles. Glasdegib plus LDAC has a favorable benefit–risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy.
Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency
Authors: Shaoning Wang, Chunxiu Liu, Cunyang Wang, Jia Ma, Hui Xu, Jianbo Guo, Yihui Deng
Journal: Asian Journal of Pharmaceutical Sciences (2018)

In this study, arsenic trioxide (ATO) was encapsulated in liposomes via copper acetate (Cu(OAc)2) gradients and high entrapment efficiency of over 80% was obtained. The average particle size and the zeta-potential of the liposomes were detected to be 115.1 ± 29.1 nm and -21.97 ± 0.6 mV, respectively. The TEM images showed rod-like precipitates in the inner aqueous phase, which was supposed be due to the formation of insoluble ATO-Cu complex. The in vitro drug release of ATO-Cu liposomes exhibited a sustained release over 72 h, and the release rates decreased with the increase of the pH of release media. Pharmacokinetic and tissue distribution studies of ATO liposomes showed significantly reduced plasma clearance rate, increased AUC0-12h and T1/2, and improved tumor distribution of As compared to iv administration of ATO solution. The anti-tumor effect of ATO loaded liposomes to S180 tumor-bearing mice was significantly improved with a tumor inhibition rate of 61.2%, meanwhile the toxicity of encapsulated ATO was greatly decreased. In conclusion, ATO can be effectively encapsulated into liposomes by remote loading method via Cu(OAc)2 gradients; the co-administration of ATO and Cu(II) via liposomal formulation may find wide applications in the treatment of various tumors.
Abstract 17491: Disparities in Death Rates in Patients With Peripartum Cardiomyopathy Among Advanced vs. Emerging Countries: A Meta-Analysis
Authors: Kate Kerpen, Paraskevi Koutrolou-Sotiropoulou, Chencan Zhu, Jie Yang, Fabio V Lima, Kathleen Stergiopoulos
Journal: Circulation (2017)

Introduction: Peripartum cardiomyopathy (PPCM) is a significant cause of maternal morbidity and mortality worldwide. There is limited information reading the differences in maternal death rates in ...