tbuckley/cabot-search huggingface dataset:
Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study
Authors: Shelly L Gray, Sascha Dublin, Onchee Yu, Rod Walker, Melissa Anderson, Rebecca A Hubbard, Paul K Crane, Eric B Larson
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. <b>Design</b>&nbsp;Prospective population based cohort. <b>Setting</b>&nbsp;Integrated healthcare delivery system, Seattle, Washington. <b>Participants</b>&nbsp;3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. <b>Main outcomes measures</b>&nbsp;The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer's disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. <b>Results</b>&nbsp;Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer's disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer's disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. <b>Conclusion</b>&nbsp;The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia.
Action of Snake Venom on Rauscher Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J H Monroe, G P Shibley, G Schidlovsky, T Nakai, A F Howatson, N W Wivel, T E O'Connor
Journal: JNCI Journal of the National Cancer Institute (1968)

Journal Article Action of Snake Venom on Rauscher Virus Get access J. H. Monroe, J. H. Monroe Search for other works by this author on: Oxford Academic PubMed Google Scholar G. P. Shibley, G. P. Shibley Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Schidlovsky, G. Schidlovsky Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Nakai, T. Nakai Search for other works by this author on: Oxford Academic PubMed Google Scholar A. F. Howatson, A. F. Howatson Search for other works by this author on: Oxford Academic PubMed Google Scholar N. W. Wivel, N. W. Wivel Search for other works by this author on: Oxford Academic PubMed Google Scholar T. E. O'Connor T. E. O'Connor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 40, Issue 1, January 1968, Pages 135–145, https://doi.org/10.1093/jnci/40.1.135 Published: 01 January 1968 Article history Received: 16 May 1967 Accepted: 16 August 1967 Published: 01 January 1968
GW26-e4017 Intravenous infusion of drag-reducing polymers protects against acute myocardial ischemia and reperfusion injury
Authors: Feng Hu, Daogang Zha, Yili Liu, Kaizheng Gong, Gaoyuan Ge, Pei Zhao, Lin Du, Xiaoning Sun, Zhengang Zhang
Journal: Journal of the American College of Cardiology (2015)
Incidence of gastrointestinal stromal tumors (GISTs) in France: Results of the PROGIST survey conducted among pathologists
Authors: G. Monges, J. Coindre, J. Scoazec, A. Bouvier, J. Blay, Y. Loria-Kanza, A. Mathieu-Boue, S. Bisot-Locard
Journal: Journal of Clinical Oncology (2007)

10047 Background: GISTs are the most common mesenchymal tumors of the gastrointestinal tract but data on the annual incidence of this tumor is scarce due to previous lack of well-defined pathologic criteria. The aim of this study was to investigate the incidence of GISTs in France and describe the distribution according to age, sex, circumstances of discovery, localization and risk categories. Methods: This prospective epidemiologic study was performed among pathologists who were asked to declare all the cases of GIST over a one year period. All pathology centers (330 centers) in France were proposed to participate and asked to report exhaustively the cases diagnosed from 1 December 2004 to 30 November 2005. Results: 591 cases of GISTs were reported, 535 new cases and 56 cases of relapse. However, some large centers were not able to participate. So, the annual estimated incidence was 12 cases/million inhabitants in France. The main characteristics of the new cases of GIST were as follows: mean age 65 (± 13.2) (range: 16–93) years, 48.6% men and 51.4% women, circumstances of discovery: fortuitous 163 (30.5%), symptomatic 249 (46.5%), unknown 123 (23%). The primary tumor locations were: stomach 341 (63.7 %), small intestine 115 (21.5%), mesentery 35 (6.5%), colon/rectum 17 (3.2%), esophagus 4 (0.7%), unknown 23 (4.3%). 95.3% of GISTs were cKIT (CD117) + and 3.7 % were cKIT -. According to the Fletcher consensus criteria, based on tumor size and mitotic rate, among the 490 localized GISTs 14.7% were considered to be at very low prognostic risk, 25.5% at low-risk, 23.1 % at intermediate risk and 23.1 % at high-risk. For 13.6 % data were missing. Conclusions: This study is providing for the first time an estimation of the annual incidence of GISTs and a description of the characteristics of these tumors in France based on pathology registration. The true incidence may be slightly higher as some large centers were not able to reported their cases. These results are comparable to what has been reported in recent studies in other European countries. No significant financial relationships to disclose.
The optimal length of the proximal resection margin in patients with proximal gastric adenocarcinoma: A multi-institutional study of the U.S. Gastric Cancer Collaborative.
Authors: Lauren McLendon Postlewait, Malcolm Hart Squires, David A. Kooby, George A. Poultsides, Sharon M. Weber, Mark Bloomston, Ryan C. Fields, Timothy M. Pawlik, Konstantinos Ioannis Votanopoulos, Carl Richard Schmidt, Aslam Ejaz, Alexandra W. Acher, David J. Worhunsky, Neil Saunders, Doug S. Swords, Linda X. Jin, Clifford Suhyun Cho, Kenneth Cardona, Charles A. Staley, Shishir Kumar Maithel
Journal: Journal of Clinical Oncology (2015)

108 Background: A 5cm margin is advocated for distal gastric cancers. The optimal length of the proximal resection margin (PM) for proximal (GEJ Siewert II and III, cardia, and fundus) gastric adenocarcinoma (GAC) is not established. Methods: Patients who underwent curative intent abdominal-approach resection for proximal GAC from 2000-2012 at 7 academic US institutions were included. Patients with positive distal margins were excluded. PM length was analyzed by 0.5cm increments and was also dichotomized at the mean and median value. Primary endpoints were local recurrence (LR), recurrence-free survival (RFS) and overall survival (OS). Results: Out of 965 patients, 211 had proximal GAC, and 162 had data available on PM length. 151 patients had negative microscopic margins with a mean value of 2.6cm and a median of 1.7cm (range 0.1-15cm). When PM length was sequentially dichotomized and analyzed at 0.5cm increments (0.5-6.5cm), a greater margin distance for each analysis was not associated with LR, RFS, or OS. Similarly, a PM distance greater than the mean or median value was not associated with LR, RFS, or OS. 11 patients had a positive PM (R1), which was associated with higher N-stage (N3: 73% vs 26%; p=0.007) and increased LR (HR6.1; p=0.009). When accounting for other adverse prognostic factors (grade, lymphovascular invasion, tumor size, T-stage, and N-stage), a positive PM was not independently associated with LR. A positive PM was also not associated with decreased RFS or OS. Conclusions: For an abdominal-approach resection of proximal gastric adenocarcinoma, the length of the proximal margin is not associated with local recurrence, recurrence-free survival, or overall survival. A positive microscopic margin is associated with advanced N-stage but is not independently associated with recurrence or survival. When performing an abdominal-approach resection of proximal gastric adenocarcinoma, a grossly negative proximal margin is sufficient. Efforts to achieve a specific margin distance, especially if it necessitates an esophagectomy, should be abandoned.
Integration of 2-hydroxyglutarate-proton magnetic resonance spectroscopy into clinical practice for disease monitoring in isocitrate dehydrogenase-mutant glioma
Authors: Macarena I de la Fuente, Robert J Young, Jennifer Rubel, Marc Rosenblum, Jamie Tisnado, Samuel Briggs, Julio Arevalo-Perez, Justin R Cross, Carl Campos, Kimberly Straley, Dongwei Zhu, Chuanhui Dong, Alissa Thomas, Antonio A Omuro, Craig P Nolan, Elena Pentsova, Thomas J Kaley, Jung H Oh, Ralph Noeske, Elizabeth Maher, Changho Choi, Philip H Gutin, Andrei I Holodny, Katharine Yen, Lisa M DeAngelis, Ingo K Mellinghoff, Sunitha B Thakur
Journal: Neuro-Oncology (2015)

The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but the sensitivity of this methodology and its clinical implications are unknown.We developed an MR imaging protocol to integrate 2HG-MRS into routine clinical glioma imaging and examined its performance in 89 consecutive glioma patients.Detection of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas was closely linked to tumor volume, with sensitivity ranging from 8% for small tumors (<3.4 mL) to 91% for larger tumors (>8 mL). In patients undergoing 2HG-MRS prior to surgery, tumor levels of 2HG corresponded with tumor cellularity but not with tumor grade or mitotic index. Cytoreductive therapy resulted in a gradual decrease in 2HG levels with kinetics that closely mirrored changes in tumor volume.Our study demonstrates that 2HG-MRS can be linked with routine MR imaging to provide quantitative measurements of 2HG in glioma and may be useful as an imaging biomarker to monitor the abundance of IDH-mutant tumor cells noninvasively during glioma therapy and disease monitoring.
Assessment of trastuzumab-related cardiac dysfunction in the Herceptin Adjuvant (HERA) Trial with 3.6 years median follow- up
Authors: M. J. Procter, T. Suter, E. de Azamuja, S. Muehlbauer, U. Dafni, D. J. van Veldhuisen, M. Muscholl, M. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2009)

540 Background: The Herceptin Adjuvant (HERA) Trial is a three-group randomized trial that compared 1 year or 2 years trastuzumab with observation. We investigated cardiac dysfunction in HERA patients randomized to observation or 1 year trastuzumab and report results at a median follow-up of 3.6 years. Methods: Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF &gt; 55%) were eligible. Cardiac function was monitored throughout the trial. A repeat LVEF assessment was required in case of cardiac dysfunction. Results: There were 1,698 patients randomized to observation and 1,703 randomized to 1 year trastuzumab. The incidence of discontinuation of trastuzumab due to cardiac disorders was low (5.1%). The incidence of cardiac endpoints was low (severe CHF 0.77% in the trastuzumab group). The incidence of cardiac endpoints was higher in the trastuzumab group compared to observation (severe CHF 0.77% vs 0.00%; confirmed significant LVEF drops 3.57% vs 0.64%). In the trastuzumab group, there were no occurrences of severe CHF after the end of the scheduled treatment period of 1 year. Among the patients in the trastuzumab group with confirmed significant LVEF drop, the first occurrence was within the scheduled treatment period of 1 year for 55 out of 60 patients (91.7%). In the trastuzumab group, 59 of 73 patients (80.8%) with a cardiac endpoint reached acute recovery and of these 59 patients 52 (88.1%) were consider to have a favourable long term outcome. Conclusions: The incidence of cardiac endpoints remains low even with longer term follow-up. The cumulative incidence of any type of cardiac endpoint increases during the scheduled treatment period of 1 year, but appears to remain approximately constant after the scheduled treatment period of 1 year is completed. [Table: see text]
Abstract 20452: Microrna-200b Induces Endothelial Progenitor Cell Apoptosis and Senescence by Targeting Cjun Expression
Authors: Shoukang Zhu, Shanming Deng, Chunling Jia, Qi Ma, Emily Chen, Wei Zhu, Pascal J Goldschmidt-Clermont, Chunming Dong
Journal: Circulation (2014)

Introduction: Lineage negative bone marrow cells (Lin - BMCs) mediate vascular repair. Aging-associated apoptosis and senescence result in reduced number and impair Lin - BMCs’s pro-repair capacity. Molecular mechanisms underlying lin - BMCs apoptosis and senescence remain poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin - BMCs is a critical step in understanding the process of vascular repair. Hypothesis: miR-200b-cJun network plays a vital role in regulating Lin - BMCs apoptosis, senescence and self renewal in angiogenesis. Methods: Lin - BMCs were isolated from young (3-week-old) wild type (WT), young apoE -/- , aged WT (29-month-old) and aged apoE -/- (12 month-old) C57BL/6 mice. Global miRNA and gene expression profiling were analyzed. Results: Transcriptome analysis in Lin - BMCs isolated from young and aged WT and apoE -/- mice showed a significant aging-associated increase in miR-200b expression. We found that C-Jun was predicted to be a miR-200b target and c-Jun expression was reversely correlated with miR-200b levels. Luciferase reporter assays confirmed c-Jun as a direct target of miR-200b. MiR-200b overexpression in young lin-BMCs inhibited c-Jun expression, resulting in increased senescence and apoptosis in vitro and impaired angiogenic capacity in vivo . In contrast, suppression of miR-200b or overexpression of c-Jun in aged lin - BMCs increased c-Jun expression rejuvenated Lin - BMCs with decreased senescence and apoptosis, leading to improved angiogenesis in vitro and in vivo . Conclusions: Using genomic and functional studies, we discovered that miR-200b regulates apoptosis and senescence of age-associated lin - BMCs by suppressing c-Jun expression, thus negatively affecting vascular repair capacity of those cells in atherogenesis. Modulation of miR-200b and/or its target c-Jun may suggest a potential therapeutic intervention to improve Lin - BMCs-mediated angiogenesis and vascular repair.
Safety of low-dose aspirin (ASA) in a pooled analysis of 3 randomized, controlled trials (RCTs) of bevacizumab (BV) with chemotherapy (CT) in patients (pts) with metastatic colorectal cancer (mCRC)
Authors: J. Hambleton, J. Skillings, F. Kabbinavar, E. Bergsland, E. Holmgren, S. N. Holden, H. Hurwitz, F. Scappaticci
Journal: Journal of Clinical Oncology (2005)

3554 Background: BV (Avastin™) increases overall survival from 15.6 to 20.3 months in pts with mCRC when added to first-line irinotecan, fluorouracil, and leucovorin. In a subsequent larger pooled analysis, adding BV to CT was found to increase the risk of arterial thromboembolic events (ATEs), particularly in pts ≥65 years old with a history of atherosclerosis (Genentech, Inc., DDL, Aug 2004). Low-dose ASA is a standard therapy for primary and secondary prophylaxis of ATEs in pts at high risk of such events, and use of ASA ≤325 mg daily has been permitted in BV trials. We explored the bleeding risk associated with ASA use in mCRC trials. Methods: Analyses of pts with mCRC pooled from 3 RCTs of BV with CT were performed to explore a potential relationship between ASA use and incidence of bleeding events. ASA users were defined in 2 ways: Group A, those who reported ASA use at study enrollment (N=108); Group B, those in Group A plus those who used ASA at any time on study (N=195). Bleeding event rates by NCI-CTC grade were calculated as percent incidence unadjusted for a pt’s duration of study treatment. Conclusion: In this analysis, the use of low-dose ASA by pts with mCRC who receive CT alone or in combination with BV does not appear to increase the risk of bleeding of any severity. An exploratory analysis of the treatment effect of ASA on ATE risk in mCRC will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, GlaxoSmithKline, ImClone, Pfizer Genentech Genentech Genentech
A study of feasibility for setting up a dedicated brain tumor registry
Authors: S. J. Davidson, K. O’Neal, J. van Dellen, F. Roncaroli, C. Brock, A. Waldman
Journal: Journal of Clinical Oncology (2007)

12514 Background: Population-based tumor registries represent an invaluable resource for monitoring incidence and prevalence of cancer. Nevertheless, data generated is not always useful for deciding treatment protocols or running translational/clinical research. This is particularly true for rare cancers such as primary brain tumors. Moreover, benign or low grade tumors are usually excluded and information such as quality of life and efficacy of treatment not followed up. Finally, there is no agreement on the minimum dataset required. Here, we investigated the difficulties of setting up a dedicated BTR that can be supportive of research. Methods: We audited 1000 consecutive histologically proven adult cases operated between 1995–2005. This group included 734 gliomas, 246 meningiomas and 20 ependymomas. As minimum dataset, we considered demographics, presenting symptoms, site, neuroimaging findings, pathology/WHO grade, extent of surgery, post-operative treatment, relapses and cause of death. To avoid capture/recapture errors we cross-referenced four independent databases (histopathology, imaging, Cancer Specialist and hospital patient database). Results: Overall availability of data was 80% in 1995–2000 and 95% in 2000–2005 when electronic notes were introduced. Missing data were as follow: demographics: 0%; symptoms: 20%; site and neuroimaging 15%; incorrect diagnosis or grade update; 20%; extent of surgery: 5%; post-operative treatment: 15%; follow-up: 10%: cause of death: 15%. Data could not be interpreted in 20% of cases due to transcription errors and use of abbreviations. Conclusion: To fulfil requirements for clinical/translational research (GNOSIS), BTR needs i) dedicated national registries; ii) specialist and professional data collection; iii) registration at the time of pathological diagnosis. No significant financial relationships to disclose.
Acute Reduction in Strain Dyssynchrony Index with Cardiac Resynchronization Therapy Predicts Mid-Term Left Ventricular Reverse-remodeling and Long-Term Outcome: Using Two-dimensional Speckle-tracking Study
Authors: Kazuhiro Tatsumi, Hidekazu Tanaka, Kensuke Matsumoto, Takuma Sawa, Yasuhide Mochizuki, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Keiko Ryo-Koriyama, Yuko Fukuda, Akihiro Yoshida, Hiroya Kawai, Ken-Ichi Hirata
Journal: Circulation (2012)
Addressing Skyrocketing Cancer Drug Prices Comes With Tradeoffs
Authors: Scott D. Ramsey, Gary H. Lyman, Rick Bangs
Journal: JAMA Oncology (2016)

This Viewpoint asserts that the current model for cancer drug pricing in the United States is not sustainable, harms patients and families and the health care system, and calls for solutions that better balance access, affordability, and incentives to innovate.
Use of a USA population survey to describe tobacco exposure, respiratory symptoms, and chronic diseases among smokers
Authors: Yong Liu, Roy Pleasants, Janet Croft, Anne Wheaton, Khosrow Heidari, Jill Ohar, Monica Kraft, David Mannino, Charlie Strange
Journal: European Respiratory Journal (2014)

Purpose:  We used the Behavioral Risk Factor Surveillance System (BRFSS), an annual USA health survey, to assess relationships among years of tobacco use, respiratory symptoms, and major chronic diseases.  Methods : Questions addressing duration of tobacco use and frequency of cough as well as shortness of breath were added to the 100+ question 2012 South Carolina BRFSS. Data were analyzed to assess the relationships of years of tobacco use, respiratory symptoms, and comorbidities (accounting for age and complex sampling design).  Results : Among ever smokers(n=5462 adults), the distribution of years of tobacco use was 33.0% for 1-9, 25.6% for 10-19, 19.3% for 20-29, 12.4% for 30-39, and 9.6% for >40 years. Regarding respiratory symptoms in these persons, 13.6% had a productive cough most or every day each week, 5.7% had shortness of breath (SOB) most or all of the time, and 9.2% strongly agreed that SOB affected physical activity in the last year. Furthermore, 10.6% had COPD, 8.6% had coronary heart disease (CHD), 10.9% had diabetes, 30.3% had arthritis, 11.1% had any cancer, 38.1% had high blood pressure (HBP), 3.6% had stroke, and 2.6% had kidney disease. After controlling for age, dose-response relationships of tobacco use were observed for the likelihood of having COPD, CHD, diabetes, arthritis, and all three respiratory symptoms(p Conclusion : Our population-based data shows a significant relationship between prolonged tobacco use and frequency of respiratory symptoms as well as some chronic diseases.