tbuckley/cabot-search huggingface dataset:
Abstract 15194: Multiple Co-morbidities Produce Left Ventricular Diastolic Dysfunction in a Large Animal Model
Authors: Oana Sorop, Ilkka Heinonen, Matthijs van Kranenburg, Vincent J de Beer, Yanti Octavia, Robert-Jan M van Geuns, Anton H van den Meiracker, Jolanda van der Velden, Jan A Danser, Daphne Merkus, Dirk J Duncker
Journal: Circulation (2015)

More than 50% of patients with heart failure have preserved ejection fraction (HFpEF) characterized by diastolic dysfunction. HFpEF usually occurs in female patients with multiple comorbidities such as obesity, hypercholesterolemia, diabetes mellitus (DM) and hypertension. Here we studied the effects of DM, high fat diet (HFD), and chronic kidney disease (CKD) on diastolic dysfunction in swine. In 11 female swine, DM type 2 (3x50mg/kg iv streptozotocin), hypercholesterolemia (HFD 1% cholesterol) and CKD by renal artery embolization (38-42μm polyethylene beads), were induced (DM+HFD+CKD). Swine were followed for 6 months. Eight female healthy swine on normal pig-chow, matched for age were used as controls (CON). The DM+HFD+CKD showed hyperglycemia (22.7±0.9mmol/l in DM+HFD+CKD vs 6.1±0.67mmol/l in CON), hypercholesterolemia (16.9±3.4 vs 2.2±0.1mmol/l), hypertriglyceridemia (1.20±0.36 vs 0.28±0.05mmol/l) and hypertension (awake mean arterial pressure: 108±6 vs 84±3mmHg; all P≤0.05). These co-morbidities resulted in chronic systemic inflammation (TNF-α: 231±64 vs 74±24pg/ml), impaired coronary small artery endothelium-dependent vasodilation to bradykinin, capillary rarefaction (cap./fiber ratio 0.58 vs 0.99) and increased myocardial superoxide production (14.8±0.9 vs 6.4±0.3 RLU/sec/g), due to increased NOX activity (all P≤0.05). The coronary microvascular abnormalities were associated with increased myocardial collagen content (4.7±0.3 vs 2.4±0.2%) and elevated passive cardiomyocyte force, (both P≤0.05), resulting in reduced E/A ratio (0.99±0.14 vs 1.53±0.23), measured with cardiac MRI, and increased LV end-diastolic stiffness (0.79±0.19 vs 0.29±0.03 mmHg/ml/mg) derived from LV pressure-volume relations obtained with a conductance catheter (both P≤0.05). In contrast, ejection fraction was maintained, (45±4 vs 54±3%, P=NS). In summary, multiple comorbidities, including DM, hypercholesterolemia, CKD and hypertension in female swine trigger a series of events, starting with systemic inflammation, increased oxidative stress and coronary microvascular dysfunction, resulting in myocardial stiffening, and leading to diastolic dysfunction.
The 2016 Melbourne thunderstorm asthma epidemic: Risk factors for severe attacks requiring hospital admission
Authors: Mark Hew, Joy Lee, Nugroho H. Susanto, Shivonne Prasad, Philip G. Bardin, Sara Barnes, Laurence Ruane, Anne M. Southcott, Andrew Gillman, Alan Young, Kanishka Rangamuwa, Robyn E. O'Hehir, Christine McDonald, Michael Sutherland, Matthew Conron, Sarah Matthews, Nur‐Shirin Harun, Philippe Lachapelle, Jo A. Douglass, Louis Irving, David Langton, Jennifer Mann, Bircan Erbas, Francis Thien
Journal: Allergy (2018)

Abstract Background The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016. Objective Among thunderstorm‐affected patients presenting to emergency rooms ( ER s), we investigated risk factors predicting severe attacks requiring admission to hospital. Methods Thunderstorm‐affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed. Results We interviewed 1435/2248 (64%) of thunderstorm‐affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [ aOR ] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission ( aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non‐Asian patients ( aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia ( OR = 5.42, 95% CI 1.56, 18.83). Conclusions In epidemic thunderstorm asthma patients who presented to the ER , higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non‐Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene‐environment interactions.
Effective doxorubicin-based nano-therapeutics for simultaneous malignant lymphoma treatment and lymphoma growth imaging
Authors: Tomáš Etrych, Lenka Daumová, Eva Pokorná, Diana Tušková, Ondřej Lidický, Věra Kolářová, Jan Pankrác, Luděk Šefc, Petr Chytil, Pavel Klener
Journal: Journal of Controlled Release (2018)
Letting Her Be in Charge
Authors: Lynn E. Fiellin
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Building a novel near real-time multisource database to assess and improve infusion wait time at a comprehensive cancer center.
Authors: Jing Jing Wang Yakowec, Mark Pettengill, Sadiqa Mahmood, Belen Fraile, Hakim Lakhani
Journal: Journal of Clinical Oncology (2018)

4 Background: Evidence has shown that long infusion wait time is one of the main contributors to oncology patient dissatisfaction. To identify bottlenecks and inefficient processing, a comprehensive understanding of the infusion workflow at Dana-Farber Cancer Institute was explored. The goal of the project is to leverage existing data sources to quantify time to process completion and to serve as the database for multiple wait time improvement projects. Methods: Infusion workflow from patient check-in or appointment time to first infusion medication administration (wait time) was mapped. Data from Epic and Real-Time Locating System (RTLS) were pulled into a single integrated source in Tableau and SAS for analysis. Using a custom SQL query, the following tables including crucial timestamps were pulled and pooled: encounters, pharmacy processing and dispense, treatment plan and protocol, RTLS events related to infusion chair occupancy, and medication administration records. Further programming was written to flag categories such as investigational versus non-investigational drugs, linked versus un-linked to exam appointments, and inclusion and exclusion criteria regarding date range, infusion floor, and encounter type. Results: The final clean infusion database includes data from September 1, 2017 through the day before current day via automatic data pull. Processing and wait times were analyzed at multiple levels by drug, encounter, department, staff, and protocol. To date, four known wait time improvement projects that aim to shorten processing time, such as early signing of orders by providers, have leveraged this near real-time dataset to monitor and evaluate the impact of the projects. The automation of data to pre-built visualizations in Tableau comparing baseline processing time to post-pilot impact and overall wait time trends has been extremely well received by all improvement stakeholders at the institute. Conclusions: A novel database merging Epic and RTLS data was successfully built to explore and improve infusion patient wait time. This technique can be applied at other institutions interested in reducing wait times and improving patient satisfaction.
Triacetylfusarinine C: A urine biomarker for diagnosis of invasive aspergillosis
Authors: Martin Hoenigl, Thomas Orasch, Klaus Faserl, Juergen Prattes, Juergen Loeffler, Jan Springer, Fabio Gsaller, Frederike Reischies, Wiebke Duettmann, Reinhard B. Raggam, Herbert Lindner, Hubertus Haas
Journal: Journal of Infection (2018)

Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C, a fungal siderophore that has been shown to accumulate in urine in animal models, is a potential new biomarker for diagnosis of IA.
Dose-Dependent Associations Between Sleep Duration and Unsafe Behaviors Among US High School Students
Authors: Matthew D. Weaver, Laura K. Barger, Susan Kohl Malone, Lori S. Anderson, Elizabeth B. Klerman
Journal: JAMA Pediatrics (2018)

School StudentsYouths in America are sleeping less than ever before.More than 70% of high school students average less than 8 hours of sleep, 1 falling short of the 8 to 10 hours that adolescents need for optimal health. 2 Insufficient sleep negatively affects learning and development and acutely alters judgment, particularly among youths. 3We estimated associations between sleep duration and personal safety risk-taking behaviors in US high school students.Methods | We used data from high school students who responded to the Youth Risk Behavior Survey between February 2007 and May 2015. 4 The Youth Risk Behavior Survey is administered biannually to a nationally representative sample of students of all ages enrolled in grades 9 to 12 at public and private schools.Sleep duration on an "average" school night was categorized as 8 hours or more, 7 hours, 6 hours, or less than 6 hours.Personal safety risk-taking behaviors were examined individually and as composite categories.We weighted all analyses to account for the complex survey design and controlled for age, sex, race/ethnicity, and year of survey in weighted logistic regression models to test the association between sleep duration and each outcome of interest.The study was exempt from institutional review board review, as this analysis used publicly available data without identifiable information and these activities are not considered human participants research.
O2⋅− and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate
Authors: Joshua D. Schoenfeld, Zita A. Sibenaller, Kranti A. Mapuskar, Brett A. Wagner, Kimberly L. Cramer-Morales, Muhammad Furqan, Sonia Sandhu, Thomas L. Carlisle, Mark C. Smith, Taher Abu Hejleh, Daniel J. Berg, Jun Zhang, John Keech, Kalpaj R. Parekh, Sudershan Bhatia, Varun Monga, Kellie L. Bodeker, Logan Ahmann, Sandy Vollstedt, Heather Brown, Erin P. Shanahan Kauffman, Mary E. Schall, Ray J. Hohl, Gerald H. Clamon, Jeremy D. Greenlee, Matthew A. Howard, Michael K. Schultz, Brian J. Smith, Dennis P. Riley, Frederick E. Domann, Joseph J. Cullen, Garry R. Buettner, John M. Buatti, Douglas R. Spitz, Bryan G. Allen
Journal: Cancer Cell (2017)
An improved formula for standard hypoxia tolerance time (STT) to evaluate hypoxic tolerance in mice
Authors: Gang Xu, Yu-Qi Gao, Yi-Xing Gao, Gang Wu, Jian-Yang Zhang, Wen-Xiang Gao
Journal: Military Medical Research (2018)

Hypoxia is a primary cause of mountain sickness and a common pathological condition in patients with heart failure, shock, stroke, and chronic obstructive pulmonary disease (COPD). Thus far, little advancement in countering hypoxic damage has been achieved, and one of the main reasons is the absence of an ideal algorithm or calculation method to normalize hypoxia tolerance scores when evaluating an animal model. In this study, we improved a traditional calculation formula for assessment of hypoxia tolerance. We used a sealed bottle model in which the oxygen is gradually consumed by a mouse inside. To evaluate the hypoxia tolerance of mice, the survival time (ST) of the mouse is recorded and was used to calculate standard hypoxia tolerance time (STT) and adjusted standard hypoxia tolerance time (ASTT). Mice administered with methazolamide and saline were used as positive and negative controls, respectively. Since mice were grouped according to either body weight (BW) or bottle volume, we found a strongly negative correlation between STT and BW instead of between STT and bottle volume, suggesting that different BWs could cause false positive or negative errors in the STT results. Furthermore, both false positive and negative errors could be rectified when ASTT was used as the evaluation index. Screening for anti-hypoxic medicines by using mice as the experimental subjects would provide more credible results with the improved ASTT method than with the STT method. ASTT could be a better index than STT for the evaluation of hypoxia tolerance abilities as it could eliminate the impact of animal BW.
Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration
Authors: Katherine G. Chen, Jason A. Alvarez, Mohammad Yazdanie, Chandana Papudesu, Wai T. Wong, Henry E. Wiley, Tiarnan D. Keenan, Emily Y. Chew, Frederick L. Ferris, Catherine A. Cukras
Journal: Ophthalmology (2018)
Primary Whole-gland Cryoablation for Prostate Cancer: Biochemical Failure and Clinical Recurrence at 5.6 Years of Follow-up
Authors: Masakatsu Oishi, Inderbir S. Gill, Akbar N. Ashrafi, Michael Lin-Brande, Nima Nassiri, Toshitaka Shin, Alfredo Bove, Giovanni E. Cacciamani, Osamu Ukimura, Duke K. Bahn, Andre Luis de Castro Abreu
Journal: European Urology (2018)
Phase 2b Controlled Trial of M72/AS01<sub>E</sub>Vaccine to Prevent Tuberculosis
Authors: Olivier Van Der Meeren, Mark Hatherill, Videlis Nduba, Robert J. Wilkinson, Monde Muyoyeta, Elana Van Brakel, Helen M. Ayles, German Henostroza, Friedrich Thienemann, Thomas J. Scriba, Andreas Diacon, Gretta L. Blatner, Marie-Ange Demoitié, Michele Tameris, Mookho Malahleha, James C. Innes, Elizabeth Hellström, Neil Martinson, Tina Singh, Elaine J. Akite, Aisha Khatoon Azam, Anne Bollaerts, Ann M. Ginsberg, Thomas G. Evans, Paul Gillard, Dereck R. Tait
Journal: New England Journal of Medicine (2018)

A vaccine to interrupt the transmission of tuberculosis is needed.We conducted a randomized, double-blind, placebo-controlled, phase 2b trial of the M72/AS01E tuberculosis vaccine in Kenya, South Africa, and Zambia. Human immunodeficiency virus (HIV)-negative adults 18 to 50 years of age with latent M. tuberculosis infection (by interferon-γ release assay) were randomly assigned (in a 1:1 ratio) to receive two doses of either M72/AS01E or placebo intramuscularly 1 month apart. Most participants had previously received the bacille Calmette-Guérin vaccine. We assessed the safety of M72/AS01E and its efficacy against progression to bacteriologically confirmed active pulmonary tuberculosis disease. Clinical suspicion of tuberculosis was confirmed with sputum by means of a polymerase-chain-reaction test, mycobacterial culture, or both.We report the primary analysis (conducted after a mean of 2.3 years of follow-up) of the ongoing trial. A total of 1786 participants received M72/AS01E and 1787 received placebo, and 1623 and 1660 participants in the respective groups were included in the according-to-protocol efficacy cohort. A total of 10 participants in the M72/AS01E group met the primary case definition (bacteriologically confirmed active pulmonary tuberculosis, with confirmation before treatment), as compared with 22 participants in the placebo group (incidence, 0.3 cases vs. 0.6 cases per 100 person-years). The vaccine efficacy was 54.0% (90% confidence interval [CI], 13.9 to 75.4; 95% CI, 2.9 to 78.2; P=0.04). Results for the total vaccinated efficacy cohort were similar (vaccine efficacy, 57.0%; 90% CI, 19.9 to 76.9; 95% CI, 9.7 to 79.5; P=0.03). There were more unsolicited reports of adverse events in the M72/AS01E group (67.4%) than in the placebo group (45.4%) within 30 days after injection, with the difference attributed mainly to injection-site reactions and influenza-like symptoms. Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two groups.M72/AS01E provided 54.0% protection for M. tuberculosis-infected adults against active pulmonary tuberculosis disease, without evident safety concerns. (Funded by GlaxoSmithKline Biologicals and Aeras; ClinicalTrials.gov number, NCT01755598 .).
How nonrandomized trials (NRT) inform pan-Canadian Oncology Drug Review (pCODR) expert review committee (pERC) recommendations in blood cancer.
Authors: Missale Tiruneh, Stephanie Ross, Kristina Ellis, Maureen E. Trudeau, Catherine Moltzan, Valerie McDonald, Alexandra Chambers, Adam E. Haynes
Journal: Journal of Clinical Oncology (2018)

100 Background: In Canada, the Canadian Agency for Drugs and Technologies in Health’s pERC makes reimbursement recommendations for cancer drugs based on pCODR reviews of best available evidence, which in some circumstances, is from Phase II NRTs. To date, the majority of pERC recommendations based on NRT evidence have been for blood cancers. Objective: To examine aspects of NRT evidence that may influence pERC reimbursement recommendations for blood cancers. Methods: Final pERC Recommendations on blood cancer reviews supported by NRTs were included (July 2011 to June 2018). Factors that influenced Final Recommendations, such as clinical benefit, alignment with patient values and cost-effectiveness, were extracted. Results: As of June 2018, 10 conditional and 6 negative decisions were made in 13 Final Recommendations. Among conditional reimbursement recommendations, substantial need for treatment options and poor prognosis with available therapies were commonly noted. Assessment of the feasibility of randomized controlled trials (RCT) varied. The magnitude of benefit was impressive or a substantial benefit was seen in subgroups with greater need. Some recommendations noted benefit above historical outcomes or consistent evidence with other indications or trials. Most recommendations reported an improvement in quality of life (QoL) and a manageable toxicity profile. Limitations included short trial follow-up. Factors affecting cost-effectiveness and alignment with patient values varied. Among negative recommendations, there was less certainty about burden of illness and need. Uncertainty about magnitude of clinical benefit was attributed to lack of direct or indirect comparison to available options, lack of long term data or comparison to historical evidence, limited QoL data, and variability in toxicity. All cases were not cost-effective and partially aligned with patient values. Conclusions: pERC may accept evidence from NRTs to make reimbursement recommendations for blood cancers when there is a high burden of illness, unmet need, reasonable demonstration of efficacy and manageable toxicities. Feasibility of RCT was not a consistent factor.
PLK1 stabilizes a MYC-dependent kinase network in aggressive B cell lymphomas
Authors: Yuan Ren, Chengfeng Bi, Xiaohong Zhao, Tint Lwin, Cheng Wang, Ji Yuan, Ariosto S. Silva, Bijal D. Shah, Bin Fang, Tao Li, John M. Koomen, Huijuan Jiang, Julio C. Chavez, Lan V. Pham, Praneeth R. Sudalagunta, Lixin Wan, Xuefeng Wang, William S. Dalton, Lynn C. Moscinski, Kenneth H. Shain, Julie Vose, John L. Cleveland, Eduardo M. Sotomayor, Kai Fu, Jianguo Tao
Journal: Journal of Clinical Investigation (2018)

Concordant activation of MYC and BCL-2 oncoproteins in double-hit lymphoma (DHL) results in aggressive disease that is refractory to treatment. By integrating activity-based proteomic profiling and drug screens, polo-like kinase-1 (PLK1) was identified as an essential regulator of the MYC-dependent kinome in DHL. Notably, PLK1 was expressed at high levels in DHL, correlated with MYC expression, and connoted poor outcome. Further, PLK1 signaling augmented MYC protein stability, and in turn, MYC directly induced PLK1 transcription, establishing a feed-forward MYC-PLK1 circuit in DHL. Finally, inhibition of PLK1 triggered degradation of MYC and of the antiapoptotic protein MCL-1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL cell growth, survival, and tumorigenicity, supporting clinical targeting of PLK1 in DHL.
Abstract 13975: Association of In-Hospital Acute Kidney Injury With Long-term Outcomes in Survivors of Acute Myocardial Infarction: Insight From the NCDR
Authors: Purav Mody, Tracy Wang, Robert McNamara, Sandeep Das, Dharam Kumbhani, Matthew Roe, Stephen Wiviott, Thomas Tsai, James De Lemos
Journal: Circulation (2015)

Background: Chronic kidney disease (CKD) and acute kidney injury (AKI) have both been associated with adverse short-term outcomes after MI. However, the impact of AKI on long-term outcomes and the interaction of AKI with baseline renal function have not been well described. Methods: ACTION Registry®-GWTGTM records from 2008-2012 were linked to Medicare data yielding a population of 76,500 acute MI patients from 581 hospitals who survived to hospital discharge. We excluded patients with cardiogenic shock, cardiac arrest, and those undergoing CABG or currently on dialysis. CKD status was defined using the Kidney Disease Outcome Quality Initiative criteria based on admission GFR estimated using the MDRD equation. No, mild, moderate and severe AKI were defined as changes in creatinine (Cr) from baseline to peak of &lt; 0.3, 0.3 to &lt; 0.5, 0.5 to &lt; 1.0 and ≥ 1.0 mg/dl respectively. Cox proportional hazard modeling was used to examine associations between AKI and 1-year mortality. Covariates for risk adjustment were adapted from the CRUSADE long-term mortality risk model. Results: The median age was 77 years, 30% had STEMI and 78% underwent diagnostic angiography.The incidence of mild, moderate and severe AKI was 7.5%, 6.0% and 3.0%. CKD stages 3, 4, and 5 were present in 41.2%, 6.7%, and 1.0% of patients. Both CKD and AKI were significantly associated with 1-year mortality (p&lt; 0.0001 for each). A significant interaction was noted between CKD and AKI with respect to 1-year mortality (p-interaction&lt;0.0001). Adjusted 1-year mortality increased in a dose-dependent manner across increasing severity of AKI, but this association was attenuated among individuals with more severe baseline CKD (Figure). Conclusion: One-year mortality increased in proportion to severity of AKI, with even a small increase in Cr associated with worse outcomes. The association of AKI with outcomes was modified by baseline Cr, with a greater impact of AKI observed among patients with higher baseline eGFR.