tbuckley/cabot-search huggingface dataset:
Efficacy of High-Sensitivity Troponin T in Identifying Very-Low-Risk Patients With Possible Acute Coronary Syndrome
Authors: W. Frank Peacock, Brigette M. Baumann, Deborah Bruton, Thomas E. Davis, Beverly Handy, Christopher W. Jones, Judd E. Hollander, Alexander T. Limkakeng, Abhi Mehrotra, Martin Than, Andre Ziegler, Carina Dinkel
Journal: JAMA Cardiology (2017)

Physicians need information on how to use the first available high-sensitivity troponin (hsTnT) assay in the United States to identify patients at very low risk for 30-day adverse cardiac events (ACE).To determine whether a negative hsTnT assay at 0 and 3 hours following emergency department presentation could identify patients at less than 1% risk of a 30-day ACE.A prospective, observational study at 15 emergency departments in the United States between 2011 and 2015 that included individuals 21 years and older, presenting to the emergency department with suspected acute coronary syndrome. Of 1690 eligible individuals, 15 (no cardiac troponin T measurement) and 320 (missing a 0-hour or 3-hour sample) were excluded from the analyses.Serial hsTnT measurements (fifth-generation Roche Elecsys hsTnT assay).Serial blood samples from each patient were collected after emergency department presentation (once identified as a potential patient with acute coronary syndrome) and 3 hours, 6 to 9 hours, and 12 to 24 hours later. Adverse cardiac events were defined as myocardial infarction, urgent revascularization, or death. The upper reference level for the hsTnT assay, defined as the 99th percentile, was established as 19 ng/L in a separate healthy US cohort. Patients were considered ruled out for acute myocardial infarction if their hsTnT level at 0 hours and 3 hours was less than the upper reference level. Gold standard diagnoses were determined by a clinical end point committee. Evaluation of assay clinical performance for acute myocardial infarction rule-out was prespecified; the hypothesis regarding 30-day ACE was formulated after data collection.In 1301 healthy volunteers (50.4% women; median age, 48 years), the upper reference level was 19 ng/L. In 1600 patients with suspected acute coronary syndrome (48.4% women; median age, 55 years), a single hsTnTlevel less than 6 ng/L at baseline had a negative predictive value for AMI of 99.4%. In 974 patients (77.1%) with both 0-hour and 3-hour hsTnT levels of 19 ng/L or less, the negative predictive value for 30-day ACE was 99.3% (95% CI, 99.1-99.6). Using sex-specific cutpoints, C statistics for women (0.952) and men (0.962) were similar for acute myocardial infarction.A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.
Characteristics associated with maintenance of mean A1C<6.5% in people with dysglycemia in the ORIGIN trial
Authors: Matthew C Riddle, Hertzel C Gerstein, Leanne Dyal, Markolf Hanefeld, Peter Johnston, Jeffrey Probstfield, Ambady Ramachandran, Julio Rosenstock, Lars E Rydén, Giagten A Spinas
Journal: Diabetes Care (2013)

OBJECTIVE: To assess the success and baseline predictors of maintaining glycemic control for up to 5 years of therapy using basal insulin glargine or standard glycemic care in people with dysglycemia treated with zero or one oral glucose-lowering agents.
RESEARCH DESIGN AND METHODS: Data from 12,537 participants in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were examined by baseline glycemic status (with or without type 2 diabetes) and by therapeutic approach (titrated insulin glargine or standard therapy) using an intention-to-treat analysis. Median values for fasting plasma glucose (FPG) and A1C and percentages with A1C<6.5% (48 mmol/mol) during randomized treatment were calculated. Factors independently associated with maintaining updated mean A1C<6.5% were analyzed with linear regression models.
RESULTS: Median A1C in the whole population was 6.4% at baseline; at 5 years, it was 6.2% with glargine treatment and 6.5% with standard care. Of those with diabetes at baseline, 60% using glargine and 45% using standard care had A1C<6.5% at 5 years. Lack of diabetes and lower baseline A1C were independently associated with 5-year mean A1C<6.5%. Maintaining mean A1C<6.5% was more likely with glargine (odds ratio [OR] 2.98 [95% CI 2.67-3.32], P<0.001) than standard care after adjustment for other independent predictors.
CONCLUSIONS: Systematic intervention with basal insulin glargine or standard care early in the natural history of dysglycemia can maintain glycemic control near baseline levels for at least 5 years, whether diabetes is present at baseline or not. Keeping mean A1C<6.5% is more likely in people with lower baseline A1C and with the glargine-based regimen.
Distribution and pathogenicity of nsSNPs in receptor tyrosine kinases (RTKs) in non-small cell lung cancer (NSCLC) patients (pts).
Authors: Ari M. Vanderwalde, Matthew K Stein, Lindsay Kaye Morris, Srishti Sareen, Saradasri Karri, Kruti Patel, Jennifer Sullivan, Lee Steven Schwartzberg, Michael Gary Martin
Journal: Journal of Clinical Oncology (2017)

e20618 Background: Non-synonymous SNPs (nsSNPs) in RTKs can alter kinase activity and are not exclusive to the tyrosine kinase domain (TKD). In NSCLC, EGFR lesions were previously identified using TKD-limited tests; however, next-generation sequencing (NGS) enables the entire protein sequence of many RTKs to be interrogated. Methods: We analyzed all nsSNPs in 28 RTKs in lung cancer pts who received tumor profiling with Caris NGS from 2013-2015. Mutations were classified by location including the TKD, extracellular domain (ECD), transmembrane domain (TM), juxtamembrane domain (JM), and carboxy-terminal (CT) regions. nsSNPs underwent in silico analysis using PolyPhen-2 (Harvard) to predict pathogenicity. Results: 167 pts (156 NSCLC, 11 SC) were identified with a median age 65 (range 26-85); 51% male; 65% white, 31% black; 77% ≥20 pack-years (py), 11% non-smokers; 52% samples tested were metastases. NSCLC pts were 63% adenocarcinoma, 22%, squamous, 8% large-cell; 81% stage IV, 14% III; 17 were EGFR+, 6 BRAF+, 3 HER2+, 3 ROS1 rearranged and 1 MET exon 14. A total 300 nsSNPs (286 NSCLC, 14 SC) were found in 28 RTKs, excluding EGFR. 123/156 NSCLC pts (79%) and 9/11 SC (82%) had ≥1 RTK lesion with median 2 (range 0-8); 143/300 (48%) nsSNPs were predicted-damaging (pnsSNP) by in silico and 89 pts (53%) had ≥1 pnsSNP (median 1; range 0-5). 28/28 RTKs had ≥3 mutations, with median 11 (range 3-23), and 26/28 contained ≥1 pnsSNP (median 5; range 0-14). RTKs in NSCLC with the most frequent nsSNPs were EPHA3 (14/23 variants were pnsSNP), EPHA5 (11/17), EPHB1 (10/11), RET (9/11), ERBB4 (8/12), ALK (7/16), NTRK3 (7/15), ROS1 (6/22) and FLT1 (6/15). 6/14 lesions in SC pts were pnsSNPs in ERBB3, ERBB4, FGFR1, FLT1, RET and ROS1. nsSNPs were found along RTKs: 57% were ECD (72/172 pnsSNP), 26% TKD (47/77), 10% CT (14/29), 6% JM (8/18) and 1% TM (2/4). 6/6 SC pnsSNPs were ECD. 67% BRAF+ and ROS1-rearranged, 59% EGFR+, 33% HER2+ and 0/1 MET exon 14 pts had ≥1 pnsSNP. Conclusions: Nearly 80% NSCLC and SC pts had ≥1 nsSNP in 28 RTKs, excluding EGFR, with 48% pnsSNPs by in silico analysis. As &gt; 70% nsSNPs were extra-TKD lesions, further characterization is needed to identify kinase-effecting variants and their potential clinical significance.
Evans Blue Attachment Enhances Somatostatin Receptor Subtype-2 Imaging and Radiotherapy
Authors: Rui Tian, Orit Jacobson, Gang Niu, Dale O. Kiesewetter, Zhantong Wang, Guizhi Zhu, Ying Ma, Gang Liu, Xiaoyuan Chen
Journal: Theranostics (2017)

Purpose: Radionuclide therapy directed against tumors that express somatostatin receptors (SSTRs) has proven effective for the treatment of advanced, low-to intermediate-grade neuroendocrine tumors in the clinic.In clinical usage, somatostatin peptide-based analogs, labeled with therapeutic radionuclides, provide an overall response rate of about 30%, despite the high cumulative activity injected per patient.We set out to improve the effectiveness of somatostatin radiotherapy by preparing a chemical analog that would clear more slowly through the urinary tract and, concomitantly, have increased blood circulation half-life and higher targeted accumulation in the tumors.Experimental Design: We conjugated a common, clinically-used SST peptide derivative, DOTA-octreotate, to an Evans blue analog (EB), which reversibly binds to circulating serum albumin.The resulting molecule was used to chelate 86 Y and 90 Y, a diagnostic and a therapeutic radionuclide, respectively.The imaging capabilities and the radiotherapeutic efficacy of the resulting radioligand was evaluated in HCT116/SSTR2, HCT116, and AR42J cell lines that express differing levels of SST2 receptors. Results:The synthesized radiopharmaceutical retained affinity and specificity to SSTR2.The new molecule also retained the high internalization rate of DOTA-octreotate, and therefore, showed significantly higher accumulation in SSTR2-positive tumors.Labeling of our novel EB-octreotate derivative with the therapeutic, pure beta emitter, 90 Y, resulted in improved tumor response and survival rates of mice bearing SSTR2 xenografts and had long term efficacy when compared to DOTA-octreotate itself.Conclusions: The coupling of a targeted peptide, a therapeutic radionuclide, and the EB-based albumin binding provides for effective treatment of SSTR2-containing tumors.
Nanomaterial‐Enabled Wearable Sensors for Healthcare
Authors: Shanshan Yao, Puchakayala Swetha, Yong Zhu
Journal: Advanced Healthcare Materials (2017)

Abstract Highly sensitive wearable sensors that can be conformably attached to human skin or integrated with textiles to monitor the physiological parameters of human body or the surrounding environment have garnered tremendous interest. Owing to the large surface area and outstanding material properties, nanomaterials are promising building blocks for wearable sensors. Recent advances in the nanomaterial‐enabled wearable sensors including temperature, electrophysiological, strain, tactile, electrochemical, and environmental sensors are presented in this review. Integration of multiple sensors for multimodal sensing and integration with other components into wearable systems are summarized. Representative applications of nanomaterial‐enabled wearable sensors for healthcare, including continuous health monitoring, daily and sports activity tracking, and multifunctional electronic skin are highlighted. Finally, challenges, opportunities, and future perspectives in the field of nanomaterial‐enabled wearable sensors are discussed.
Abstract 17298: Real-world Evaluation of Healthcare Resource Use and Costs of Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Apixaban vs. Warfarin in the US
Authors: Steve Deitelzweig, Xuemei Luo, Kiran Gupta, Jeffrey Trocio, Jack Mardekian, Melissa Lingohr-Smith, Brandy Menges, Jay Lin
Journal: Circulation (2016)

Introduction:  The impact of apixaban vs. warfarin usage on healthcare resource use (HRU) and associated costs among elderly patients with nonvalvular atrial fibrillation (NVAF) is not well known in the real-world setting.   Hypothesis:  The objectives of this study were to evaluate whether differences exist in HRU and costs among elderly NVAF patients treated with apixaban vs. warfarin in the US.   Methods:  Patients (≥65 years of age) initiating apixaban or warfarin (index event) were identified from the Humana database (1/1/2013-9/30/2015). Patients were required to have an NVAF diagnosis and 12 months of continuous health plan enrollment (baseline period) prior to the index event date. Patient characteristics were evaluated during the baseline period. Propensity score matching (PSM) was conducted. HRU and costs in the follow-up period were compared between patients receiving apixaban vs. warfarin.   Results:  Of the pre-matched population, 7,443 (mean age: 77.8 years) were treated with apixaban and 12,392 (mean age: 78.1 years) treated with warfarin. Mean Charlson Comorbidity Index (CCI, 2.7 vs. 3.0, p 2  score (2.6 vs. 2.7, p 2 -VASc score (4.4 vs. 4.6, p   Conclusions:  In the real-world setting after controlling for differences in patient characteristics, apixaban vs. warfarin usage is generally associated with lower HRU and costs for all causes and bleeding-related services among elderly NVAF patients.
Abstract 18552: Adherence to a Healthy Dietary Pattern and Quality of Life in Two Population-based Cohorts of Older Adults in Spain
Authors: Pilar Guallar-Castillon, Raul F Perez-Tasigchana, Luz M Leon-Muñoz, Esther Lopez-Garcia, Fernando Rodriguez-Artalejo
Journal: Circulation (2014)

Introduction:  Adherence to a healthy dietary pattern (HDP) is associated with lower mortality and reduced risk of chronic diseases. However, the influence of HDP on health-related quality of life (HRQL) is uncertain among the elderly. The aim of this study was to assess the association between the adherence to an HDP and HRQL in 2 cohorts representative of the Spanish older adult population (≥ 60 years).   Methods:  The UAM-cohort (n= 2376) was selected in 2000/2001 and followed prospectively through 2003. Diet was collected with a food frequency questionnaire, which was used to develop an 8-item index of HDP; adherence to this pattern was defined as a score greater than the median (4 points) in this index. HRQL was assessed using the SF-36 questionnaire. The ENRICA-Seniors cohort (n=1911) was recruited in 2008-2010 and followed prospectively through 2012. A validated dietary history was used to collect diet. Two dietary indexes were used to assess the HDP (Mediterranenan diet): the MEDAS and the Trichopoulou index. Adherence to the HDP was defined as a score of ≥ 9 and ≥ 7, respectively, in the MEDAS and in the Trichopulou index. HRQL was assessed using the SF-12v.2 questionnaire. For both cohorts, physical and mental component summaries (PCS and MCS) of HRQL were computed. An increase of ≥ 3 points in either the PCS or MCS during follow-up was considered a clinically relevant improvement in HRQL. Analyses were conducted with logistic regression and adjusted for the main confounders, including HRQL at baseline.   Results:  In the UAM-cohort, adherence to the HDP showed no statistically significant association with improved HRQL during the follow-up. In the ENRICA-Seniors cohort, adherence to the Mediterranenan diet, as assessed by MEDAS, was associated with an improvement in the PCS (Odds Ratio [OR]:1.28; 95% confidence interval [CI]: 1.01-1.70) but not in the MCS (OR: 1.02; 95% CI 0.81-1.30). A higher adherence to the Trichopoulou index did not show an association with either the PCS (OR:0.84; 95% CI: 0.63-1.13), or the MCS (OR:1.00; 95% CI: 0.80-1.30).   Conclusions:  After two years of follow-up, we found no consistent association between an HDP and better HRQL in two cohorts of older adults in Spain. Funding: Grants from the Instituto de Salud Carlos III, PI11/01379 and PI12/1166.
Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air–lung study
Authors: Coralynn Sack, Sverre Vedal, Lianne Sheppard, Ganesh Raghu, R. Graham Barr, Anna Podolanczuk, Brent Doney, Eric A. Hoffman, Amanda Gassett, Karen Hinckley-Stukovsky, Kayleen Williams, Steve Kawut, David J. Lederer, Joel D. Kaufman
Journal: European Respiratory Journal (2017)

We studied whether ambient air pollution is associated with interstitial lung abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and quantitative measurements of subclinical interstitial lung disease (ILD) on computed tomography (CT). We performed analyses of community-based dwellers enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used cohort-specific spatio-temporal models to estimate ambient pollution (fine particulate matter (PM 2.5 ), nitrogen oxides (NO x ), nitrogen dioxide (NO 2 ) and ozone (O 3 )) at each home. A total of 5495 participants underwent serial assessment of HAAs by cardiac CT; 2671 participants were assessed for ILAs using full lung CT at the 10-year follow-up. We used multivariable logistic regression and linear mixed models adjusted for age, sex, ethnicity, education, tobacco use, scanner technology and study site. The odds of ILAs increased 1.77-fold per 40 ppb increment in NO x (95% CI 1.06 to 2.95, p = 0.03). There was an overall trend towards an association between higher exposure to NO x and greater progression of HAAs (0.45% annual increase in HAAs per 40 ppb increment in NO x ; 95% CI −0.02 to 0.92, p = 0.06). Associations of ambient fine particulate matter (PM 2.5 ), NO x and NO 2 concentrations with progression of HAAs varied by race/ethnicity (p = 0.002, 0.007, 0.04, respectively, for interaction) and were strongest among non-Hispanic white people. We conclude that ambient air pollution exposures were associated with subclinical ILD.
Abstract 18522: Importance of Endothelium-dependent Hyperpolarization and Oxidative Activation of PKG1α in Coronary Microcirculation in Mice
Authors: Yosuke Ikumi, Shoko Kajitani, Akiyo Ito, Shuhei Tanaka, Hiroki Saito, Shigeo Godo, Takashi Shiroto, Hiroaki Shimokawa
Journal: Circulation (2017)

Background:  The endothelium plays an important role in modulating vascular tone by synthesizing and releasing several vasodilators, including prostacyclin, nitric oxide (NO), and endothelium-dependent hyperpolarization (EDH) factor(s). We have previously demonstrated that the importance of EDH increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H 2 O 2 ) is one of EDH factors. Endothelium-derived H 2 O 2  oxidizes cyclic GMP-dependent protein kinase-1α (PKG1α) in vascular smooth muscle cells (VSMC) and causes interprotein disulfide bond in PKG1α, leading to activation of PKG1α. Activated PKG1α then opens BKCa channel and causes hyperpolarization and relaxation of VSMC. In this study, we tested our hypothesis that oxidative activation of PKG1α plays an important role in the effects of EDH to maintain homeostasis of the coronary microcirculation.   Methods:  We used wild-type (WT) and redox-dead C42S PKG knock-in (KI) mice. Isolated perfused heart experiment was performed for examination of coronary flow. The isolated heart was mounted onto Langendorff apparatus, perfused at a constant pressure of 80 mmHg with 37 o C Krebs-Henseleit buffer aerated with 95%O 2  and 5%CO 2 , and paced at 400 bpm. Coronary flow was continuously measured and corrected by heart weight. We used bradykinin (10 -6  mol/L) as an endothelium-dependent vasodilator, and indomethacin (10 -5  mol/L) and L-NNA (10 -4  mol/L) for inhibition of PGs and NO, respectively.   Results:  Heart weight/ body weight ratio was comparable between WT and KI mice (WT n=18, KI n=16). In the presence of indomethacin, L-NNA decreased basal flow and increase in flow in response to BK in both WT and KI mice (n=3-7 each). Importantly, in the presence of indomethacin and L-NNA, which is an EDH condition, increase in flow to BK was significantly less in KI mice compared with WT mice (WT n=6, KI n=7).   Conclusions:  These results indicate that both NO and EDH play important roles in coronary microcirculation and that oxidative activation of PKG1α plays an important role in the effects of EDH to maintain homeostasis of the coronary microcirculation.
Effect of exercise and dietary fish consumption on risk of recurrence in colon cancer: A multinational study.
Authors: Mohammed Shaik, Hemasri Tokala, Rama Modali, Terri Lehman, Borys Hrinczenko
Journal: Journal of Clinical Oncology (2014)

1514 Background: Dietary factors and physical activity have been associated with the risk of occurrence of colon cancer(CCa) but their role in the recurrence of colon cancer(rCCa) has not been established. The aim of our study was to examine the association between dietary intake, exercise, and other risk factors with the rCCa. Methods: Data were obtained from the Global Epidemiological Study(GES), a multinational database to assess disease risk factors. Patients(pts) were recruited from Poland, Vietnam, Western Europe and the USA. Pts diagnosed with CCa gave informed consent to provide data including their exercise activity and dietary intake. Chi-square and t-test were used for categorical and continuous variables. The association[adjusted odds ratio(aOR)] between rCCa and risk factors was obtained using logistic regression. Results: A total of 1,515 pts were surveyed, of which 188 pts had rCCa later in life. The average age and the no. of current smokers with rCCa and those without rCCa were, 63 yrs vs. 64 yrs and 21(11.1%) vs.164(12.3%), respectively. There were 54.3% males and 46.7% females. Those with and without rCCa were compared regarding food intake, exercise, tobacco and alcohol use. In LR, food intake besides fish did not influence rCCa, neither did smoking duration or alcohol consumption. Fish intake of less than 2 servs per week had an aOR of 2.58 (1.07-6.29) and exercise less than 60 minutes per week had an aOR of 2.68 (1.02-7.0, Table). Conclusions: Fish consumption of more than 2 servs per week and also 60 minutes of weekly exercise, were each independently associated with a reduced risk of recurrence of colon cancer. Predictors of rCCa. Variables Adjusted OR (CI) p-value Fish (< 2/wk vs. > 2/wk) 2.58 (1.07-6.29) 0.03 Whole grain (<3/day vs. >3/day 1.44 (0.40- 5.17) 0.57 Dairy (< 2/day vs. > 2/day) 1.16 (0.63-2.14) 0.62 Vegetables (< 2/day vs. > 2/day) 0.75 (0.43-1.32) 0.32 Fruits (< 2/day vs. > 2/day) 0.82 (0.47-1.43) 0.49 Meat (< 2/wk vs. > 2/wk) 1.07 (0.68-1.69) 0.74 BMI 1.02 (0.99-1.05) 0.18 Nonsteroidal use (no vs. yes) 0.94 (0.59-1.51) 0.82 Total years of smoking (<25 yrs vs. >25 yrs) 0.90 (0.56-1.43) 0.66 Alcohol (no vs. yes) 1.23 (0.77-1.98) 0.37 Exercise (<60 min/wk vs. > 60 min/wk) 2.68 (1.02-7.0) 0.04
Abstract 15911: Essential Role of MicroRNA-21 in Hydrogen Sulfide-induced Protection against Myocardial Ischemia/Reperfusion Injury
Authors: Ramzi A Ockaili, Vinh Q Chau, Chang Yin, Anindita Das, Rakesh C Kukreja, Fadi N Salloum
Journal: Circulation (2013)

Background:  Hydrogen sulfide (H 2 S) protects against myocardial ischemia/reperfusion (I/R) injury through activation of Akt. Since Ser473/Thr308 phosphorylation of Akt induces microRNA (miR-21) in the heart, we speculated that H 2 S would also induce myocardial miR-21 and protect against I/R injury as well.   Methods and Results:  Adult C57BL wild-type or miR-21 knock-out (KO) mice were treated with vehicle (saline) or the H 2 S donor, Na 2 S, (100 μg/kg, ip) 1 h before 30 min ischemia followed by 24 h reperfusion. To test reperfusion therapy with H 2 S, Na 2 S (100 μg/kg, iv) or vehicle were administered at the onset of reperfusion in another subset of mice. After reperfusion, LV function was monitored by echocardiography and infarct size (IS) was measured by TTC staining. MiR-21 expression was assessed with qPCR 1h after treatment. Na 2 S increased miR-21 in wild-type mice (2.8-Fold, P 2 S when given as a preconditioning mimetic (Fig. A) or as reperfusion therapy (Fig. B) compared to vehicle. The infarct-limiting effect of Na 2 S was abolished in the miR-21 KO mice in both treatment scenarios. Moreover, Na 2 S preserved fractional shortening (FS: 30±2.8%) as compared to the control (17±1.8%, P 2 S was absent in miR-21 KO mice in both cases (FS: 14±2.1% and 17±1%, respectively).   Conclusion:  :  Hydrogen sulfide reduces myocardial infarct size and preserves LV function through miR-21-dependent pathway. We propose that H 2 S might be a novel strategy to up-regulate miR-21 for its therapeutic use against I/R injury and other cardiovascular diseases.