tbuckley/cabot-search huggingface dataset:
Statin use is associated with improved survival in multiple myeloma: A Swedish population‐based study of 4315 patients
Authors: Elsa Brånvall, Sara Ekberg, Sandra Eloranta, Tove Wästerlid, Brenda M. Birmann, Karin E. Smedby
Journal: American Journal of Hematology (2020)

Abstract Statin use has been associated with reduced cancer‐specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population‐based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6‐month periods pre‐ and post‐diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure‐related MM‐specific and all‐cause mortality using Cox regression. We assessed statin exposure during the entire follow‐up and risk of MM‐specific mortality in a nested case‐control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow‐up. Statin use was associated with reduced MM‐specific mortality (pre‐diagnosis use multivariate‐adjusted HR, 95% CI: 0.83, 0.71‐0.96; 6 months post‐diagnosis: 0.73, 0.60‐0.89; entire follow‐up: 0.65, 0.52‐0.80) and (more weakly) with all‐cause mortality. Intensity analyses suggested a dose‐response; MM‐specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post‐diagnosis: low [0.76 (0.56‐1.03)], medium [0.73 (0.58‐0.92)], high [0.33 (0.08‐1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre‐diagnosis use. In this large population‐based MM cohort, statin use was associated with improved MM‐specific survival in both sexes. Randomized prospective studies are warranted to evaluate statins as adjuvant treatment in MM.
Minimal PD-1 expression in mouse and human NK cells under diverse conditions
Authors: Sean J. Judge, Cordelia Dunai, Ethan G. Aguilar, Sarah C. Vick, Ian R. Sturgill, Lam T. Khuat, Kevin M. Stoffel, Jonathan Van Dyke, Dan L. Longo, Morgan A. Darrow, Stephen K. Anderson, Bruce R. Blazar, Arta M. Monjazeb, Jonathan S. Serody, Robert J. Canter, William J. Murphy
Journal: Journal of Clinical Investigation (2020)

PD-1 expression is a hallmark of both early antigen-specific T cell activation and later chronic stimulation, suggesting key roles in both naive T cell priming and memory T cell responses. Although significant similarities exist between T cells and NK cells, there are critical differences in their biology and functions reflecting their respective adaptive and innate immune effector functions. Expression of PD-1 on NK cells is controversial despite rapid incorporation into clinical cancer trials. Our objective was to stringently and comprehensively assess expression of PD-1 on both mouse and human NK cells under multiple conditions and using a variety of readouts. We evaluated NK cells from primary human tumor samples, after ex vivo culturing, and from multiple mouse tumor and viral models using flow cytometry, quantitative reverse-transcriptase PCR (qRT-PCR), and RNA-Seq for PD-1 expression. We demonstrate that, under multiple conditions, human and mouse NK cells consistently lack PD-1 expression despite the marked upregulation of other activation/regulatory markers, such as TIGIT. This was in marked contrast to T cells, which were far more prominent within all tumors and expressed PD-1. These data have important implications when attempting to discern NK from T cell effects and to determine whether PD-1 targeting can be expected to have direct effects on NK cell functions.
Abstract 56: Blood Pressure Control in the Real World - Early Evidence From a National Blood Pressure Surveillance System
Authors: Rhonda M Cooper-DeHoff, Valy Fontil, Thomas Carton, Kathryn McAuliffe, Myra Smith, Sujung Choi, Jonathon Todd, Alanna M Chamberlain, Emily O'Brien, Madelaine Faulkner, Carlos Maeztu, LINDA MURAKAMI, Gregory Wozniak, Michael Rakotz, Christina M Shay, Mark J Pletcher
Journal: Circulation (2020)

Background: The Patient-Centered Outcomes Research Institute (PCORI) funded National Blood Pressure Surveillance System (BP Track) is a new national system that generates quarterly metrics of blood pressure (BP) control and BP-related quality metrics for participating healthcare systems from electronic health record (EHR) data. Methods: Queries against standardized EHR data in the national Patient-Centered Clinical Research Network (PCORnet) Common Data Model format produce a set of quality metrics relevant to improving BP control, including Controlling High BP (NQF 0018) and Improvement in BP (CMS65v7), and eight process measures specific to clinical management and treatment practices for improving BP control ( Table ). The metrics, aggregated overall and by health system are reported back to health systems via user-friendly Tableau dashboards, and allow for observation of metric trends. Results: To date, 19 datamarts have contributed EHR data from 1,177,232 patients who met the eligibility criteria for the BP Control measure and 4,454,729 encounters that included a BP measurement during the measurement period. Average age was 62 years; 10% were young adults (&lt;45 years), 17% were African American, 52% female, 28% had diabetes, 15% had coronary heart disease, and 14% had depression. Results demonstrate substantial opportunity for improvement in overall BP control (60% with BP&lt;140/&lt;90 mmHg, range: 42-72%), and many healthcare processes, including medication intensification (12%, 0.6-22%) and use of fixed dose combination medications (24%, 0-88%, Table ). Conclusion: Major opportunities exist for improving BP control, especially in improving the frequency and quality of BP medication prescribing for patients with high BP. The BP Track National BP Surveillance System will track these metrics, by demographic subgroup and over time, and will generate data that can guide and focus quality improvement initiatives aimed at effective BP management.
Systemic potency of fluticasone in asthma
Authors: Brian Lipworth, Chris RuiWen Kuo, Rory Chan
Journal: European Respiratory Journal (2020)

We read with interest the data from Maijers et al. [1], suggesting that in a post hoc analysis of trials in oral corticosteroid (OC)-dependent asthma, the majority of the OC-sparing effects of high-dose inhaled corticosteroids are due to their systemic effects. The meta-regression estimates showed a prednisone (Pred) decrease of 4.9 mg per 1.0 mg increase in fluticasone propionate (FP) dose. This was based on the premise from an analysis of two studies where 1.0 mg FP was equivalent to 5.0 mg Pred for cortisol suppression, although this was only calculated in reference to a 10 mg dose of Pred. A ratio of 1.02 was then inferred for the proportion of the OC-sparing effect due to systemic absorption of FP. Use of high dose fluticasone propionate requires similar considerations as starting maintenance low dose prednisone <http://bit.ly/3aLXcjO>
Defining trained immunity and its role in health and disease
Authors: Mihai G. Netea, Jorge Domínguez-Andrés, Luis B. Barreiro, Triantafyllos Chavakis, Maziar Divangahi, Elaine Fuchs, Leo A. B. Joosten, Jos W. M. van der Meer, Musa M. Mhlanga, Willem J. M. Mulder, Niels P. Riksen, Andreas Schlitzer, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Ramnik J. Xavier, Eicke Latz
Journal: Nature reviews. Immunology (2020)
Abstract P252: Passive Smoking in Childhood and Mortality From Coronary Heart Disease in Adulthood Among Japanese Men and Women: The Jacc Study
Authors: Masayuki Teramoto, Hiroyasu Iso, Isao Muraki, Kokoro Shirai, Akiko Tamakoshi
Journal: Circulation (2020)

Background: Secondhand smoke exposure among adults is an established risk factor for cardiovascular disease, but little is known about the impact of passive smoking in childhood on risk of adverse cardiovascular outcome in adulthood. We examined whether childhood exposure to secondhand smoke is associated with mortality from coronary heart disease(CHD) in adulthood among Japanese men and women. Methods: We analyzed the data for 71,459 participants ( 31,027 men and 40,432 women) aged 40-79 years, with no history of CHD, stroke, or cancer at the baseline (1988-1990) and who completed a lifestyle questionnaire including the number of family members who smoked at home in childhood(0,1,2 and 3+ members) under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). Results: The sex-specific proportions of current smokers were 49.0% for 0 member, 54.3% for 1 member, 56.8% for 2 members and 59.3% for 3+members among men, and the respective proportions among women were 3.3%, 5.2%, 7.2%, and 11.2%.During the median follow-up of 18.9 years, a total of 955 (589 men and 366 women) deaths from CHD were reported. There was a dose-response relationship between the number of smoking family members at home and CHD mortality at adulthood among the middle aged (40-59 years); the multivariable HRs, adjusting for age, sex, history of hypertension and diabetes, body mass index, smoking status, alcohol consumption, hours of exercise and walking, perceived mental stress, educational level and employment status, were 1.05 (95% CI: 0.74, 1.48) for 1 family member, 1.27(0.83, 1.94) for 2 family members and 2.34(1.17, 4.68) for 3+ family members compared with no family member(p for trend=0.04). Such an association was not observed for the older persons aged 60-79 years.The excess CHD mortality associated with 3+ family members among the middle-aged was more evident among never or ex-smokers than among current smokers: the respective multivariable HRs were 3.74(1.40, 10.01) and 1.90(0.72, 5.06). Conclusions: Passive smoking exposure in childhood was associated with increased risk of mortality from CHD in adulthood, primarily for the middle aged men and non-current smokers.
Informed Consent for Stem Cell–Based Interventions
Authors: Zubin Master, Cambray Smith, Jon C. Tilburt
Journal: JAMA (2020)

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Abstract P197: Health Information Technology Use Among Patients With Diagnosed Atherosclerotic Cardiovascular Disease: Evidence From The 2010-2018 National Health Interview Survey
Authors: Uchenna Nwokeji, Erin Spaulding, Rongzi Shan, Ruth-Alma N Turkson-Ocran, Diana Baptiste, Binu Koirala, Timothy B Plante, Seth S Martin, Yvonne Commodore-Mensah
Journal: Circulation (2020)

Introduction: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality worldwide. Health Information Technologies (HIT) have recently emerged as a viable intervention to mitigate the burden of ASCVD. At least 60% of US adults report searching the internet for health information; however, previous research has not examined prevalence and sociodemographic differences in HIT use among adults with ASCVD. Objective: To evaluate the prevalence and sociodemographic differences in HIT use among U.S. adults with a history of diagnosed ASCVD. Methods: We pooled cross-sectional data from the 2010-2018 National Health Interview Survey (NHIS) to examine HIT use among adults aged ≥18 years (N=2,410) who self-reported being diagnosed with ASCVD (coronary heart disease (CHD) and/or stroke). We evaluated sociodemographic differences in HIT use among respondents with generalized linear models using Poisson distribution. Analyses were weighted according to NHIS standards. Results: The mean (±sd) age was 70 (±0.2) years, and 47.7% were female. Among US adults with a history of ASCVD, 22.6% of respondents utilized some form of HIT. HIT users with a history of ASCVD were more likely to be younger in age, have at least some college education, be employed, and be married ( Table 1 ). Conclusion: HIT use was low among adults with a history of ASCVD, which may represent a barrier to delivering care via emerging HIT. Given the association with sociodemographic factors such as education and employment, there is a need to develop targeted strategies to address sociodemographic barriers that impact HIT usage.
Clinical factors associated with outcome in metastatic renal cell carcinoma patients treated with VEGF-targeted therapy
Authors: A. Golshayan, T. K. Choueiri, P. Elson, J. A. Garcia, M. Khaswneh, S. Usman, I. Tamaskar, L. Wood, B. I. Rini, R. M. Bukowski
Journal: Journal of Clinical Oncology (2007)

5046 Background: Therapy targeted against the vascular endothelial growth factor (VEGF) pathway is a standard of care in metastatic renal cell carcinoma (RCC). Identification of clinical features of patients more likely to benefit from these agents would aid in patient selection and interpretation of clinical trial results. Methods: We reviewed 120 metastatic RCC patients receiving bevacizumab, sorafenib, sunitinib or axitinib on one of eight prospective clinical trials at the Cleveland Clinic Taussig Cancer Center. Clinical features associated with outcome were identified by univariate analysis, and then a stepwise modeling approach based on Cox proportional hazards regression was used to identify independent prognostic factors and form a model for progression-free survival (PFS). A bootstrap algorithm was used to provide internal validation. Results: Forty-one patients (34%) achieved an objective response by RECIST criteria (95% C.I. 27–44%). The median PFS for the entire group was 13.8 months (m) (95% C.I. 10.7–19.0 m). Multivariate analysis identified the following independent adverse prognostic factors (PF) for PFS: time from diagnosis to current treatment &lt;2 years, baseline platelet count &gt;300 K/μL, baseline neutrophil count &gt;4.5 K/μL, baseline corrected serum calcium &lt;8.5 or &gt;10.0 mg/dL and initial ECOG performance status &gt;0. Using these factors three prognostic subgroups were formed based on the number of adverse PF present . Median PFS in patients with 0 or 1 adverse PF was 20.1 m (95% C.I. 19.0–22.3 m) compared to 13 m (95% C.I. 8.6–17.6 m) in patients with 2 adverse PF and 3.9 m (95% C.I. 1.8–7.2 m) in patients with &gt;2 adverse PF. Conclusions: Five independent prognostic factors for predicting PFS were identified and used to categorize patients with metastatic RCC receiving VEGF-targeted therapies into three risk groups. These factors can be readily incorporated to clinical patient care, stratification schema for clinical trials utilizing these novel agents and for interpretation of clinical trial results using VEGF-targeted agents therapy. No significant financial relationships to disclose.
Tumor‐Oriented Telomerase‐Terminated Nanoplatform as Versatile Strategy for Multidrug Resistance Reversal in Cancer Treatment
Authors: Yahui Wu, Dan Zhong, Yachao Li, Huayu Wu, Xianghui Xu, Jun Yang, Zhongwei Gu
Journal: Advanced Healthcare Materials (2020)

Multidrug resistance is one of the major problems in chemotherapy, and exploiting impactful targets to reverse drug resistance of most tumors remains a difficult problem. In this study, the tumor-oriented nanoparticle, BIBR1532-loaded peptide dendrimeric prodrug nanoassembly (B-PDPN), is used to assist telomerase inhibition for multidrug resistance reversal. B-PDPN possesses the characteristics of an acid-activated histidine to promote cellular uptake, a redox-sensitive poly(ethylene glycol) (PEG) layer to actualize endosomal escape and telomerase inhibitor release, and an acid sensitive chemical bond to facilitate chemotherapeutic drug release. Telomerase termination weakens the protective effect of hTERT protein on mitochondria and enhances reactive oxygen species (ROS) production, which increases DNA damage and apoptosis. The tumor-oriented nanoparticle B-PDPN achieves a broad-spectrum telomerase inhibition to combat multidrug resistance. In vivo experiments support the evidence that B-PDPN accumulates in the tumor site and reduces the expression of hTERT in tumor tissues to inhibit drug resistant tumor growth. This work introduces an innovative strategy of utilizing features of tumor-activated nanoplatform to assist telomerase termination. The nanoplatform enhances intracellular drug concentration and nucleus delivery of doxorubicin (DOX), and promotes DNA damage to combat multidrug resistance.
Covid-19: Trump says risk to Americans is “very low”
Authors: Janice Hopkins Tanne
Journal: BMJ (2020)

President Donald Trump described the US response to the covid-19 outbreak as “a tremendous success” and asserted that the risk to Americans was “very low” during a rare nationally televised press conference on Wednesday 27 February.

He said that the 60 covid-19 patients in the US were mostly doing well, although one remained seriously ill.

To combat covid-19 he advocated screening people from infected areas, quarantining those at risk, and developing a vaccine, which was advancing “rapidly.” He said the country was “very ready” and was the best prepared country in the world to deal with the outbreak.

Trump said he had asked Congress for $2.5bn (£1.94bn; €2.29bn) to fight the virus (from the Ebola response budget), but Congressional Republicans had suggested $4bn and Democrats had pushed for $8.5bn. He indicated he would accept whatever Congress decided.

Shortly afterwards, the Centers for Disease Control and Prevention reported apparent local transmission of covid-19 to a person in northern California with no …
Correlative analyses of plasma cytokine/angiogenic factor (C/AF) profile, gender and outcome in a randomized, three-arm, phase II trial of first-line vandetanib (VAN) and/or carboplatin plus paclitaxel (CP) for advanced non-small cell lung cancer (NSCLC)
Authors: E. O. Hanrahan, H. Y. Lin, D. Z. Du, S. Yan, E. S. Kim, J. J. Lee, A. J. Ryan, H. T. Tran, B. E. Johnson, J. V. Heymach
Journal: Journal of Clinical Oncology (2007)

7593 Background: VAN (ZD6474) is an oral inhibitor of VEGFR, EGFR and RET. In a phase II trial, 181 patients with advanced NSCLC were randomized to 1st-line treatment with VAN, CP or VAN + CP. Progression free survival (PFS) was prolonged for VAN + CP vs CP (Heymach et al, submitted for ASCO 2007). Exploratory subgroup analyses suggest gender differences in PFS benefit for VAN + CP vs CP (HR 0.47 in females vs 1.05 in males). We performed exploratory analyses of plasma levels of 35 C/AFs to investigate gender differences and potential prognostic or predictive markers. Methods: Plasma was collected at baseline (n = 123; VAN 55, CP 32, VAN + CP 36), day (D) 8 (n = 104), D22 (n = 95), and D43 (n = 83). We used multiplex bead assays to measure 33 plasma C/AFs, including VEGF, basic FGF, EGF, HGF, E-selectin, ICAM-1, MMP-9, multiple chemokines and interleukins (IL). Osteopontin and sVEGFR-2 were measured by ELISA. Cox models were applied on PFS to identify prognostic/predictive markers after rank transformation and adjusted for covariates. Results: Significant gender differences in baseline C/AF levels were seen for IL-15, IL-1RA, IL-2R, MIG, and MIP-1A (all higher in females, all p = 0.022). Controlling for gender and treatment, high baseline E-selectin (p = .01), IL-6 (p = 0.018), and IL-2R (p = 0.008) were adverse prognostic indicators for PFS. Controlling for gender, the tests for treatment by factor interactions (to assess whether treatment effect was different in patients with low and high C/AF levels) were significant for baseline HGF (p = 0.04) and IL-2R (p = 0.008). For both HGF and IL- 2R, low levels were associated with prolonged PFS in the VAN arm, but were not associated with differences in the CP or VAN + CP arms. Significant changes in VEGF (rise) and sVEGFR-2 (decrease) occurred with treatment in the VAN arm; IL12, IL-1RA, MMP-9 and MCP-1 changed in the CP and VAN + CP arms. Conclusions: There are gender differences in PFS benefit from VAN and in plasma C/AF profile. Several C/AFs were of prognostic value, whereas low HGF and IL-2R were predictive of benefit in the VAN but not CP and VAN + CP arms. These gender differences and markers warrant further investigation. [Table: see text]
Abstract P515: Comparison of Dietary Measures Association With Incident Type 2 Diabetes: The Reasons for Geographic and Racial Differences in Stroke (regards) Study
Authors: Stephanie Tison, April P Carson, James M Shikany, Keith Pearson, George Howard, Suzanne E Judd
Journal: Circulation (2020)

Background: Previous studies have investigated the association of dietary patterns with risk of diabetes, but have not compared a priori and a posteriori dietary scores in the same diverse population. The objective of this study was to evaluate a priori and a posteriori dietary patterns associations with incident diabetes in the REGARDS study. Methods: This study included 8,875 Black and White adults with available dietary data, without diabetes (defined as fasting glucose&gt;=126 mg/dL, random glucose&gt;=200 mg/dL, or use of diabetes medications) at baseline (2003-2007), and with follow-up (2013-2016) status of diabetes. Dietary patterns were examined by quintile and included a posteriori Plant-based and Southern, as well as a priori scores of Mediterranean Diet Score, Dietary Approaches to Stop Hypertension (DASH) Diet Score, Dietary Inflammatory Index (DII) and Dietary Inflammation Score (DIS). Modified Poisson regression was used to obtain risk ratios for incident diabetes with models adjusted for total energy intake, demographics, and lifestyle factors. Results: The mean (SD) age at baseline was 63.2 (8.5) years, 27.1% were Black, 56.2% were female, and 11.7% had incident diabetes at follow-up. Adherence to the Southern dietary pattern was positively associated with incident diabetes for all models (figure). After adjustment for demographic factors, the highest quintiles of DII and DIS were associated with incident diabetes and the highest quintiles of DASH scores were protective of development of incident diabetes. Conclusion: The Southern dietary pattern derived in REGARDS showed the strongest association with incident diabetes of all the dietary scores and of the a priori scores the DIS showed the strongest association with incident diabetes. The lack of association in adjusted models with the Mediterranean Diet and Plant-based pattern show these scores to be less pertinent. The DIS demonstrates food based dietary inflammation as one of the potential pathways for incident diabetes.