tbuckley/cabot-search huggingface dataset:
Abstract 13468: The Interaction Between the Prognostic Value of Chronotropic Incompetence and Cardiorespiratory Fitness: The Henry Ford Exercise Testing (FIT) Project
Authors: Waqas T Qureshi, Wesley T O'Neal, Clinton A Brawner, Jonathan K Ehrman, Steven J Keteyian, Michael J Blaha, Mouaz H Al-Mallah
Journal: Circulation (2015)

Background: Cardiorespiratory fitness (CRF) and chronotropic incompetence (CI) have both been associated with increased all - cause mortality. We tested the hypothesis that the association of CI with all - cause mortality is modified by a CRF level above and below 10 metabolic equivalents of task (METs). Methods: We included 43,402 patients who completed a clinical exercise stress test between 1991 and 2009. Patients on AV nodal blocking agents, antiarrhythmics and with known coronary artery disease/heart failure were excluded. Patients were followed-up for a mean duration of 11.5±5.2 years for all-cause mortality ascertained by a search of the social security death index in April 2013. CRF was estimated in metabolic equivalents of task (METs). Cox proportional hazards regression models were used to assess the risk of all - cause mortality associated with CI with adjustments for confounders. Results: Compared to no CI, patients with CI were older (51±12 vs. 54±13 years), less often white (68% vs. 58%), dyslipidemic (41% vs. 37%) and more likely to be hypertensive (46% vs. 60%), diabetic (15% vs. 22%), and smoke (40% vs. 51%). On average, patients with CI had lower CRF (9.8±2.8 vs. 7.4±3.0, p &lt;.001). In adjusted Cox regression model, CI was associated with higher risk of mortality [Hazard ratio (HR), 2.12; 95% confidence interval (2.00 -2.27); p&lt;.001)]. The association of CI and mortality was attenuated when METs was included as a covariate in the regression model [HR, 1.49; 95% confidence interval (1.39-1.61); p&lt;.001]. There was a significant interaction of CRF ≥ 10 METs with the association of CI and mortality (p interaction 0.004) which is shown in Figure 1. This was a subaditive and multiplicative interaction of CRF with CI. Conclusions: This study demonstrates that CRF attenuates the mortality risk associated with CI. In addition, patients with CI in the presence of CRF ≥ 10 METs have a much lower risk than patients with CI and lower CRF.
Analysis of mutations in formalin-fixed paraffin-embedded (FFPE) tumor samples from two phase II clinical trials using a Sequenom-based approach.
Authors: Maria Orr, James Sherwood, Gael McWalter, Emma Donald
Journal: Journal of Clinical Oncology (2012)

1548 Background: Analysis of tumour samples for biomarker discovery, personalised health care and disease stratification is becoming increasingly important. Methods to detect somatic mutations are often limited by the requirement for a significant amount of input DNA, low sensitivity or low sample throughput. The aim of this work was to obtain a comprehensive mutation profile of tumour samples taken from patients enrolled on two Phase II clinical trials. A Sequenom based approach was used to determine mutation profiles for the samples so that these could be correlated with response at some future date. Methods: After successfully piloting the Sequenom MassArray 4 platform on formalin fixed paraffin embedded (FFPE) tumour samples and tumour cell line admixes, we ran an exploratory analysis of 177 melanoma and 230 non small cell lung cancer (NSCLC) FFPE samples collected from two phase II clinical trials. DNA was extracted from the FFPE samples using the QIAmp DNA FFPE Tissue Kit (Qiagen). We designed a panel of 86 assays in 14 genes covering approximately 160+ mutations. Mutations were chosen based on mutation frequency and biological significance in these tumour types. Results: Using this approach we were able to detect concomitant mutation profiles in a significant percentage of samples using only approximately 20uL of FFPE DNA (500 copies/µL average). Mutation status concordance was over 97% in BRAF and KRAS when compared to data generated via other approaches (sequencing, ARMS). Conclusions: Using Sequenom to screen tumour material, collected during clinical trials, is a feasible, rapid and comprehensive approach. Such an approach can be used to identify mutation profiles which correlate with patient response, potentially identify further patient stratification and help generate new hypotheses for further exploration.
Final results of the phase I study in healthy volunteers of AB928, a dual antagonist of the A2aR and A2bR adenosine receptors being studied as an activator of anti-tumor immune response
Authors: L.C. Seitz, D. Ashok, M. Leleti, J. Powers, B. Rosen, D. Miles, E. Sharif, L. Jin, A. Park, S. Young, A. Rieger, U. Schindler, J. Karakunnel, M. Walters
Journal: Annals of Oncology (2018)
Dynamic change of immune-related gene expression status during chemoradiotherapy in locally advanced esophageal cancer
Authors: T. Mizukami, Y. Sunakawa, H. Arai, M. Chosokabe, A. Doi, Y. Horie, M. Hirakawa, O. Saji, S. Naruki, N. Izawa, T. Ogura, T. Tsuda, T. Enomoto, S. Mikami, T. Fujino, T. Otsubo, T.E. Nakajima
Journal: Annals of Oncology (2018)
Increased FDG Uptake and Chronic Lung Changes in a Case of Persistent Lipoid Pneumonia
Authors: Kianoush Ansari-Gilani, Navid Faraji, Robert C. Gilkeson
Journal: Clinical Nuclear Medicine (2018)

Lipoid pneumonia is uncommon disease caused by presence of macroscopic fat in the lung parenchyma commonly originating from exogenous source secondary to aspiration or inhalation of animal fats or mineral or vegetable oils. Alternatively, it can be due to endogenous fat accumulated in the alveoli in the setting of chronic bronchial obstruction or inflammation. The imaging findings include ground-glass opacities, consolidation, nodules, and masses. Presence of macroscopic fat on CT is helpful; however it might not always be present. Increased FDG uptake can be present secondary to ongoing inflammation mimicking malignancy. Tissue diagnosis might be needed in some cases.
P3.13-21 Apatinib Plus Icotinib as First-Line Therapy For EGFR Co-Mutations NSCLC in Chinese Patients: An Exploratory Study
Authors: Y. Shang, X. Li, R. Huo, M. Ji, Z. Song, B. Liu, Y. Jia, Y. Li, J. Jiao, J. Shi, Y. Zhang, X. Chen, M. Yao, X. Zhang, A. Zang
Journal: Journal of Thoracic Oncology (2018)
Director of troubled Karolinska hospital resigns
Authors: Marta Paterlini
Journal: BMJ (2018)

Melvin Samsom, the director of a new hospital model in Stockholm, Sweden, resigned unexpectedly at the end of September, saying that the time was right to move on now that the system he introduced was up and running.

Samsom was recruited four years ago from the Netherlands to lead the implementation of so-called value based healthcare at the New Karolinska Hospital (Nya Karolinska Sjukhuset, NKS) and to manage the move to new premises.1

The plan was to establish one of the most advanced …
P3.17-09 Retrospective Analysis of the Efficacy and Safety of Multimodal Treatment for Locally-Advanced NSCLC in Elderly Patients
Authors: F. Mazzoni, S. Bongiolatti, G. Di Pierro, L. Paglialunga, V. Scotti, K. Ferrari, B. Fantechi, L. Voltolini
Journal: Journal of Thoracic Oncology (2018)
Impact of bisphosphonate and anti-myeloma therapy on bone turnover markers in multiple myeloma
Authors: A. Jandial, S. HJ, K. Mishra, S. Bhadada, A. Sood, M. Prakash, A. Meshram, R. Sandal, D. Lad, R. Aggarwal, G. Prakash, S. Vikas, A.R. Khadwal, S. Kumari, N. Varma, S.C. Varma, P. Malhotra
Journal: Annals of Oncology (2018)
Acupuncture for peripheral neuropathy in cancer patients: TCM diagnosis as a predictor of treatment response
Authors: W. Liu, A. Qdaisat, G. Lopez, S. Underwood, M. Spano, A.R. Akhila Reddy, Y. Guo, S.-C. Yeung, E. Bruera, M.K. Garcia, L. Cohen
Journal: Annals of Oncology (2018)
Establishment of the South Korean national antimicrobial resistance surveillance system, Kor-GLASS, in 2016
Authors: Hyukmin Lee, Eun-Jeong Yoon, Dokyun Kim, Seok Hoon Jeong, Jong Hee Shin, Jeong Hwan Shin, Kyeong Seob Shin, Young Ah Kim, Young Uh, Chan Park, Kwang Jun Lee
Journal: Eurosurveillance (2018)

Surveillance plays a pivotal role in overcoming antimicrobial resistance (AMR) in bacterial pathogens, and a variety of surveillance systems have been set up and employed in many countries. In 2015, the World Health Organization launched the Global Antimicrobial Resistance Surveillance System (GLASS) as a part of the global action plan to enhance national and global surveillance and research. The aims of GLASS are to foster development of national surveillance systems and to enable collection, analysis and sharing of standardised, comparable and validated data on AMR between different countries. The South Korean AMR surveillance system, Kor-GLASS, is compatible with the GLASS platform and was established in 2016 and based on the principles of representativeness, specialisation, harmonisation and localisation. In this report, we summarise principles and processes in order to share our experiences with other countries planning to establish a national AMR surveillance system. The pilot operation of Kor-GLASS allowed us to understand the national burden of specific infectious diseases and the status of bacterial AMR. Issues pertaining to high costs and labour-intensive operation were raised during the pilot, and improvements are being made.
Trabectedin and radiotherapy in advanced sarcoma: Experience of a reference center
Authors: I.C. Carrasco Garcia, N. Hindi, J. Peinado, I. Rincon, M. Cordeiro, F.J. Jimenez, A. Falcon Gonzalez, R. Lasso de la Vega, M. Noguer Mediavilla, P. Sancho Marquez, J. Martin-Broto
Journal: Annals of Oncology (2018)
Validity of a Novel Point-of-Care Troponin Assay for Single-Test Rule-Out of Acute Myocardial Infarction
Authors: John W. Pickering, Joanna M. Young, Peter M. George, Antony S. Watson, Sally J. Aldous, Richard W. Troughton, Christopher J. Pemberton, A. Mark Richards, Louise A. Cullen, Martin P. Than
Journal: JAMA Cardiology (2018)

Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI.To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time.This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics).The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity.Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%).A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.
Shrinking Poor White Life Spans: Class, Race, and Health Justice
Authors: Erika Blacksher
Journal: The American Journal of Bioethics (2018)

An absolute decline in US life expectancy in low education whites has alarmed policy makers and attracted media attention. Depending on which studies are correct, low education white women have lost between 3 and 5 years of lifespan; men, between 6 months and 3 years. Although absolute declines in life expectancy are relatively rare, some commentators see the public alarm as reflecting a racist concern for white lives over black ones. How ought we ethically to evaluate this lifespan contraction in low education whites? Should we care, or is it racist to care? Does it constitute an injustice or reflect justice being done? I argue that the lifespan contraction in low education whites violates key normative criteria used to make determinations of health justice, and that these judgments do not vitiate concerns about racism. I conclude with reflections on US population health policy and building an inclusive health equity movement.
Blood and tumor inflammation markers in non-small cell lung cancer (NSCLC): Blood leukocytosis as an independent risk factor in early stage.
Authors: Andreas Carus, Morten Ladekarl, Henrik Hager, Hans Pilegaard, Patricia Switten Nielsen, Frede Donskov
Journal: Journal of Clinical Oncology (2012)

e21110 Background: Cancer inflammation is associated with impaired survival in a range of cancers. We reviewed blood and intratumoral inflammatory markers in NSCLC. Methods: At the Departmentof Thoracic Surgery, Skejby Hospital, Aarhus, Denmark, consecutive patients with resected NSCLC from 2000 to 2008 were reviewed, and 906 patients with complete clinical data were identified. A subset of 341 consecutive patients, resected between 2003 and 2006, also had intratumoral CD66b + neutrophils and CD163 + macrophages measured by immunohistochemistry and evaluated by stereological assessment. Results: A total of 526, 197, and 183 patients had stage I, II, and III, respectively. Multivariate analysis stratified for tumor stage revealed elevated blood leukocytes above upper limit of normal as a significant prognostic factor for recurrence-free survival (RFS)(hazard ratio [HR] 1.9; 95% CI 1.4-2.6; p&lt;0.0001), cancer specific survival (CSS)(HR 1.9; 95% CI 1.4-2.7; p&lt;0.0001), and overall survival (OS)(HR 1.5; 95% CI 1.1-1.9; p&lt;0.006) in stage I NSCLC, but not in stage II and III. No prognostic impact of intratumoral neutrophils or macrophages was seen on CSS, RFS, or OS, neither in the entire cohort, nor limited to stage I patients with elevated blood leukocytes or with normal counts. Controlling intratumoral neutrophils and macrophages for localization restricted to tumor tissue, stromal tissue, or blood vessels, respectively, were also with no statistically significant difference. Conclusions: Blood leukocytosis is an independent prognostic factor for short recurrence free survival, cancer specific survival, and overall survival in stage I NSCLC, but not in stage II and III. However, intratumoral neutrophils or macrophages did not impact prognosis. Further studies are needed to elucidate the role of cancer inflammation in NSCLC.
The Impact of Early-Phase Trial Design in the Drug Development Process
Authors: Mark R. Conaway, Gina R. Petroni
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Many of the therapeutic agents that are being used currently were developed using the 3+3 decision rule for dose finding. Over the past 30 years, several dose-finding designs have been proposed and evaluated, including the “continual reassessment method” (CRM) and the “Bayesian optimal interval design” (BOIN). This research investigates the role of the choice of an early-phase design on the likelihood that drugs entering the drug development pipeline will have 2 successful phase III trials. Experimental Design: Using simulation, each agent in a population of hypothetical agents was tracked through the drug development process, from initial dose finding to 2 confirmatory phase III trials. Varying the designs of the phase I, II, and III trials allows for an assessment of the effect of the choice of designs on the proportion of agents with successful phase III trials. Results: The results indicate that using the CRM or BOIN, rather than the 3+3, substantially enhances the proportion of effective agents that have successful phase III trials, with the CRM having a greater effect than BOIN. A larger phase II trial magnifies the effect of the phase I design. Conclusions: The results underscore the importance of the choice of the early-phase designs. Use of the 3+3 results in fewer agents with successful phase III trials compared with the CRM or BOIN. The difference is more pronounced among highly effective agents. In addition, the results show the importance of a sufficiently powered phase II trial.
Abstract 17585: Long-term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome in Mice
Authors: Masato Tsutsui, Mika Kina-Tanada, Mayuko Sakanashi, Toshihiro Matsuzaki, Katsuhiko Noguchi, Masayoshi Ishida, Junko Nakasone, Hiroaki Shimokawa, Yusuke Ohya, Akira Arasaki
Journal: Circulation (2016)

Background: Nitric oxide (NO) is formed not only from L-arginine by a family of NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate (NOx). Green leafy vegetables are rich ...
Experience in treatment of newly diagnosed multiple myeloma patients with renal failure required dialysis
Authors: S. Semochkin, E. Zhelnova, E. Misyurina, T. Tolstykh, N. Arkhipova, E. Baryakh, E. Grishina, E. Karimova, O. Kochneva, E. Mavrina, Y. Polyakov, E. Yaskova
Journal: Annals of Oncology (2018)
Neo-adjuvant ipilimumab and nivolumab in high risk resectable bladder urothelial cancer (NABUCCO)
Authors: N. van Dijk, C.U. Blank, P. Kvistborg, T.N. Schumacher, E. Hooijberg, K. Sikorska, B.V. Rhijn, M.S. van der Heijden
Journal: Annals of Oncology (2018)
Abstract 14227: A Pitx2-microRNA Pathway Functions in Inhibiting Susceptibility to Atrial Fibrillation
Authors: Jun Wang, Yan Bai, Na Li, Stephanie B Greene, Min Zhang, Ye Tao, Xander H Wehrens, James F Martin
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) is the most common adult arrhythmia, but the molecular mechanisms underlying AF remain poorly understood. Genome wide association studies uncovered a major AF susceptibility locus on human chromosome 4q25 in close proximity to the Pitx2 homeobox gene. Pitx2, a target of the left-sided Nodal signaling pathway that initiates early in cardiac development, represses the sinoatrial node (SAN) program and pacemaker activity on the left side. To address the mechanisms underlying this repressive activity, we hypothesize that Pitx2 regulates microRNAs (miRs) to repress the SAN genetic program. microRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally. Methods and Results: Using miR-microarray and chromatin immuno-precipitation (ChIP) sequencing, we discovered that Pitx2 positively regulates miR-17-92 and miR-106b-25. Intra-cardiac electrical stimulation reveals that loss of miR-17-92 and miR-106b-25 increases susceptibility to AF, exhibitin...
Abstract 11162: Total Arterial Off-pump Coronary Artery Bypass Grafting Can Improve Clinical Outcome for Diabetes Mellitus Patients
Authors: tomoaki suzuki, tohru asai, takeshi kinoshita
Journal: Circulation (2014)

Introduction: Diabetes mellitus is a strong risk factor that worsens the outcome of CABG. Following the development of the OPCAB technique, the current trend in revascularization strategy is toward in-situ all-arterial grafting. Hypothesis: We were interested in whether OPCAB with total arterial conduit using the skeletonization technique could improve outcome for diabetes patients. Methods: From January 2002 to December 2013, a total of 1,064 patients underwent isolated OPCAB at our institution, with total arterial reconstruction carried out in 775 (72.8%) cases. Of these 775 patients, 436 had diabetes (DM) and 319 did not (nDM). We compared the clinical results between the two groups using the propensity score matching technique. Results: 301 cases from each group were successfully matched in a 1:1 manner. All procedures were performed via the off-pump technique without conversion to on-pump. Four patients in the DM group (4/301; 1.3%) and one in the nDM group (1/301; 0.3%) died in hospital after surger...
Landscape of germline mutations in hereditary breast and ovarian cancer (HBOC) patients in Russia revealed by target panel sequencing
Authors: E. Shagimardanova, L.H. Shigapova, R.F. Enikeev, M. Druzhkov, A. Nikitin, O. Gusev, M. Gordiev
Journal: Annals of Oncology (2018)
Sunitinib tolerance following an initial exposure period: Results of longitudinal PRO data from S-TRAC study
Authors: D.J. George, R. Figlin, R.J. Motzer, J. Paty, M.J. Lechuga Frean, G. Zanotti, H. Bhattacharyya, K. Ramaswamy, L. Deannuntis, A. Ravaud
Journal: Annals of Oncology (2018)
Hsa-mir-144-3p expression is increased in umbilical cord serum of infants with atopic dermatitis
Authors: Eishika Dissanayake, Yuzaburo Inoue, Shingo Ochiai, Akifumi Eguchi, Taiji Nakano, Fumiya Yamaide, Satomi Hasegawa, Hiroyuki Kojima, Hiroko Suzuki, Chisato Mori, Yoichi Kohno, Masaru Taniguchi, Naoki Shimojo
Journal: Journal of Allergy and Clinical Immunology (2018)
Hepatic hepcidin/intestinal HIF-2α axis maintains iron absorption during iron deficiency and overload
Authors: Andrew J. Schwartz, Nupur K. Das, Sadeesh K. Ramakrishnan, Chesta Jain, Mladen T. Jurkovic, Jun Wu, Elizabeta Nemeth, Samira Lakhal-Littleton, Justin A. Colacino, Yatrik M. Shah
Journal: Journal of Clinical Investigation (2018)

Iron-related disorders are among the most prevalent diseases worldwide. Systemic iron homeostasis requires hepcidin, a liver-derived hormone that controls iron mobilization through its molecular target ferroportin (FPN), the only known mammalian iron exporter. This pathway is perturbed in diseases that cause iron overload. Additionally, intestinal HIF-2α is essential for the local absorptive response to systemic iron deficiency and iron overload. Our data demonstrate a hetero-tissue crosstalk mechanism, whereby hepatic hepcidin regulated intestinal HIF-2α in iron deficiency, anemia, and iron overload. We show that FPN controlled cell-autonomous iron efflux to stabilize and activate HIF-2α by regulating the activity of iron-dependent intestinal prolyl hydroxylase domain enzymes. Pharmacological blockade of HIF-2α using a clinically relevant and highly specific inhibitor successfully treated iron overload in a mouse model. These findings demonstrate a molecular link between hepatic hepcidin and intestinal HIF-2α that controls physiological iron uptake and drives iron hyperabsorption during iron overload.
GW29-e1204 Tracking of Blood Pressure over a 20-year Period in the Chinese Multi-Provincial Cohort Study—Beijing Project, 1992-2012
Authors: Shuai Liu, Dong Zhao, Wei Wang, Yue Qi, Miao Wang, Jiayi Sun, Jun Liu, Yan Li, Jing Liu
Journal: Journal of the American College of Cardiology (2018)