tbuckley/cabot-search huggingface dataset:
Initiation of family-centered bedside rounds at Phoenix Children's Hospital Center for Cancer and Blood Disorders.
Authors: Cathy A Lee-Miller, Renee Connor, Lynnette Acosta, Cynthia Wetmore
Journal: Journal of Clinical Oncology (2018)

170 Background: There has been a national trend towards a family/patient-centered care model in an effort to achieve many goals: earlier discharges, enhanced collaboration and patient safety, and improved satisfaction among medical care teams, patients and families. While most of the services at Phoenix Children’s Hospital (PCH) utilized a family-centered rounding model, the hematology/oncology service used table rounds. In December 2017, the Center for Cancer and Blood Disorders (CCBD) initiated family-centered rounds (FCR) on the inpatient service. Methods: FCR participants include patient, parent(s), bedside nurse, clinical supervisor, residents, fellow, attending, nurse practitioners, pharmacist, dietitian and child life specialist. One unique aspect of our FCR model is using scheduled rounds, whereby each patient is allotted a specific length of time and each family is given a time range within which to expect the team. Patients are scheduled every 10 minutes and if more time is needed, the attending/fellow return later for discussion. Staying on a schedule allows for improved nursing workflow and for consulting teams and interpreters to join rounds for specific patients. Outcome measures include patient, family and employee satisfaction. Results: Patient satisfaction is measured using NRC Real-time electronic survey. Scores have increased from a baseline of 70% (Oct/Nov 2017) to 87.5% (April 2018) after the initiation of FCR. From a qualitative standpoint, families have expressed gratitude for the new rounding model. Staff have expressed increased satisfaction at the efficiency and thoroughness of communication on rounds and the multidisciplinary team allows for real-time collaboration. Conclusions: FCR have led to increases in patient satisfaction both quantitatively and qualitatively. Ongoing initiatives include adding family-centered night rounds and a more extensive evaluation of FCR’s impact on employee satisfaction, patient safety, length of stay and lower overall costs. We are continuously evaluating the structure and efficacy of FCR to achieve the best possible care for our patients.
Abstract 15325: Overexpression of MicroRNA-126 Promotes Angiogenesis in a Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) and Tyrosine Kinase with Immunoglobulin-like and EGF-like Domains 2 (Tie2) Dependent Manner in Hindlimb Chronic Ischemia
Authors: Pratiek N Matkar, Wei J Cao, Dmitriy Rudenko, Hao H Chen, Michael A Kuliszewski, Howard Leong-Poi
Journal: Circulation (2014)

Introduction: The endothelial specific microRNA-126 (miR-126) regulates angiogenesis primarily by blocking endogenous inhibitors of VEGF, Sprouty-related protein and phosphoinositol-3 kinase regulatory subunit 2. We hypothesized that ultrasound-mediated delivery of miR-126 contributes to neovascularization through VEGFR-2 and Tie2 pathway at an early and late stage respectively in chronic ischemia. Methods: F-344 rats (n=4) were delivered with fluorescently labeled miR by ultrasound-mediated gene delivery (UMGD) to determine the miR cellular localization. Unilateral hindlimb ischemia was created by left femoral artery ligation (n=92). At day 14 post-ligation, microvascular blood flow (MBF) was assessed by contrast-enhanced ultrasound (CEU). UMGD of miR-126 (n=35) or scrambled miR (n=25) was performed, with control animals (n=32) receiving no treatment. Perfusion was re-assessed and Tie2 and pTie2 levels were quantified by western blotting at day 28. For in vitro studies, human umbilical vascular endotheli...
Heart failure with reduced ejection fraction: comparison of patient characteristics and clinical outcomes within Asia and between Asia, Europe and the Americas
Authors: Pooja Dewan, Pardeep S. Jhund, Li Shen, Mark C. Petrie, William T. Abraham, M. Atif Ali, Chen‐Huan Chen, Akshay S. Desai, Kenneth Dickstein, Jun Huang, Songsak Kiatchoosakun, Kee‐Sik Kim, Lars Køber, Wen‐Ter Lai, Yuhua Liao, Ulrik M. Mogensen, Byung‐Hee Oh, Milton Packer, Jean L. Rouleau, Victor Shi, Antonio S. Sibulo, Scott D. Solomon, Piyamitr Sritara, Karl Swedberg, Hiroyuki Tsutsui, Michael R. Zile, John J.V. McMurray
Journal: European Journal of Heart Failure (2018)

Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world.We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan.Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences.
Abstract P278: Metabolomic Profiles Associated with Dietary Patterns in Women
Authors: Paulette D Chandler, Raji Balasubramanian, Nina Paynter, Franco Giulianini, Linda G Snetselaar, Simin Liu, Charles Eaton, Deirdre Tobias, JoAnn E Manson, Edward Giovannucci, Clary Clish, Kathryn E Rexrode
Journal: Circulation (2016)

Background: Dietary patterns have a complex impact on metabolism with certain foods increasing specific metabolite levels. Metabolomic profiling, an emerging technology, may offer insights into the biological mechanisms linking the Western dietary pattern (WD) with cardiovascular disease and cancer. Methods: Metabolomic profiling of 371 metabolites by tandem quadrapole liquid chromatography/ mass spectroscopy was available on 1153 healthy, control subjects in the Women’s Health Initiative. Metabolites were log-transformed and standardized and each considered individually in statistical models. Using factor analyses, we analyzed dietary data and identified two major dietary patterns: WD (high in meat, poultry, fish, solid fat, oils, cheese, processed meats, refined grains, and added sugars) and Prudent dietary pattern (PD) (high in fruits and vegetables). Linear regression models were created with the dietary pattern scores (WD or PD) as a continuous variable for the primary exposure and each metabolite as the outcome. Models were adjusted for matching factors in the primary study (race, time period, hysterectomy status), as well as for body mass index and medications (antihypertensives, anti-diabetic drugs, aspirin and statins). Significant results were defined as FDR adjusted p&lt;0.05. Results: Median age was 68 years (interquartile range 62-72). After multivariable adjustment, WD was inversely associated with 2 metabolites: eicosapentaenoic acid (EPA) and docosahexaenoic acid DHA (FDR p=0.01); these were positively associated with the PD, (FDR p&lt;0.0001). PD was significantly associated with 85 metabolites (mostly lipids) including 4 phosphatidylcholines (FDR p&lt;0.0001); among significant inversely associated metabolites were 11 acylcarnitines (e.g.C4-OH-carnitine, FDR p &lt;0.0002), 2 polyunsaturated fatty acids (docosatrienoic acid, FDR p=0.0004 and myristoleic acid, FDR p=0.049), and 12 plasmalogens (e.g. C36.2, C36.3, C36.4 phosphatidylethanolamines,FDR p&lt;0.0001). Conclusions: PD is associated with multiple metabolites involved in mitochondrial fatty acid oxidation, as well as several associated with insulin resistance. EPA and DHA levels were lower in those with WD and higher among those with PD. These metabolites may be involved in how dietary patterns impact chronic disease.
Uncovering oncologists’ gaps and attitudes toward biosimilars: Impact of a two-phase educational program.
Authors: Zachary Schwartz, Jenny Schulz, Angelique Vinther, Sanjiv S. Agarwala, Alyce Kuklinski
Journal: Journal of Clinical Oncology (2018)

91 Background: Biosimilar agents are changing the clinical landscape in oncology. We sought to measure oncologists’ competence and knowledge of biosimilars and to address identified educational gaps related to biosimilars’ clinical application. Methods: We designed a 2-phase online educational program focused on biosimilars that included questions to measure oncologists’ knowledge and competence. These questions were administered before and then repeated after the education was delivered. Oncologists were also invited to submit their own questions about biosimilars and their use in clinical practice. To uncover key educational gaps, we identified questions with high incorrect responses at baseline, persistence of incorrect responses, and questions submitted by learners during Phase 1 of the education. These gaps were used to refine the teaching in Phase 2 of the education. Results: Between March and December 2017, a total of 1616 oncologists participated in the education. Among the subset of oncologists who answered at least 1 question, we identified persistent misunderstandings about biosimilars at baseline: 59% incorrectly believed a biosimilar could have efficacy that differs from its reference agent; a further 15% were unsure (n = 238) Absolute improvement in optimal response was 19% over baseline ( P = .0002) after Phase 1 of the education and 42% ( P &lt; .0001) after Phase 2 66% did not understand that, in the US, biosimilars cannot be substituted at the pharmacy without the prescriber’s approval (n = 220) Absolute improvement in optimal response was 13% over baseline ( P = .0571) after Phase 1 of the education and 33% ( P &lt; .0001) after Phase 2 82% did not understand extrapolation of indications among biosimilars (n = 114) Absolute improvement in optimal response was 41% over baseline ( P &lt; .0001) after the education Oncologists’ willingness to prescribe biosimilars also increased. Conclusions: We uncovered gaps in oncologists’ understanding of the efficacy, substitution, and indications of biosimilars, which may explain some oncologists’ reluctance to consider biosimilars as a treatment option for their patients. This educational program increased oncologists’ competence with biosimilars.
Abstract 16301: Oxidative Mitochondrial DNA Damage Affects Mitochondrial Respiration and Cardiac Development in Mice With Altered DNA Repair
Authors: Jared M McLendon, Diego F Alvarez, Olena M Gorodnya, Sergiy Sukhanov, Lyudmila I Rachek, Mark N Gillespie, Mykhaylo V Ruchko
Journal: Circulation (2015)

Impaired mitochondrial proliferation and function may lead to heart failure. Mitochondrial biogenesis during postnatal cardiac development in rodents is accompanied by oxidative mitochondrial (mt) DNA damage and repair. How mtDNA damage is linked to mitochondrial biogenesis is unknown, but our previous data suggest that site-specific mtDNA oxidation is involved in regulation of mtDNA replication. Here we tested the hypothesis that modulation of Ogg1, a DNA glycosylase mediating the first step in the base excision repair of oxidative mtDNA damage, coordinately affects mitochondrial function and cardiac development. Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KOTG) were analyzed for mtDNA damage and replication using Southern and slot-blot analyses; mitochondrial respiration using oxygraph; and cardiac function using echocardiography. Compared to WT, KO mice showed increased oxidative mtDNA damage in cardiac tissue, (0.18 ± 0.04 vs. 0.35 ± 0.04 lesions/104 bp respectively, p&lt;0.05), 2-fold decrease in mtDNA copy number (p&lt;0.05) and increased heart:body mass ratio (4.96 ± 0.11 vs. 5.70 ± 0.10 mg/g respectively, p&lt;0.05). Conversely, KOTG mice showed decreased mtDNA oxidation, restored mtDNA copy number and blunted elevation in cardiac mass. Echocardiography confirmed increased cardiac mass in KO mice with a trend towards decrease of cardiac contractility. Compared to hearts from WT mice, KO animals displayed significant increase in mitochondrial oxygen flux at state III (54.0 ± 8.1 vs. 93.9 ± 9.2 pmol/sec/ml/10 mg respectively, p&lt;0.05) with concurrent decrease in respiratory ratio (2.56 ± 0.42 vs. 1.46 ± 0.27 respectively), indicating constitutive uncoupling in the cardiac tissue. Mitochondrial bioenergetics of KOTG mice did not differ from WT animals. In summary, Ogg1 deficiency in mice leads to elevated oxidative mtDNA damage; decreased mtDNA copy number and respiration; and cardiac hypertrophy. Restored mtDNA repair completely eliminated these effects on mitochondrial function and cardiac development. These results suggest that abnormalities in mitochondrial function and cardiac development can be manipulated by altering mtDNA damage and repair.
A Novel Angiotensin II–Induced Long Noncoding RNA <i>Giver</i> Regulates Oxidative Stress, Inflammation, and Proliferation in Vascular Smooth Muscle Cells
Authors: Sadhan Das, Erli Zhang, Parijat Senapati, Vishnu Amaram, Marpadga A. Reddy, Kenneth Stapleton, Amy Leung, Linda Lanting, Mei Wang, Zhuo Chen, Mitsuo Kato, Hyung Jung Oh, Qianyun Guo, Xinyue Zhang, Bin Zhang, Haitong Zhang, Qinghao Zhao, Wei Wang, Yongjian Wu, Rama Natarajan
Journal: Circulation Research (2018)

Rationale: AngII (angiotensin II)-mediated vascular smooth muscle cell (VSMC) dysfunction plays a major role in hypertension. Long noncoding RNAs have elicited much interest, but their molecular roles in AngII actions and hypertension are unclear. Objective: To investigate the regulation and functions of a novel long noncoding RNA growth factor– and proinflammatory cytokine–induced vascular cell-expressed RNA ( Giver ), in AngII-mediated VSMC dysfunction. Methods and Results: RNA-sequencing and real-time quantitative polymerase chain reactions revealed that treatment of rat VSMC with AngII increased the expression of Giver and Nr4a3 , an adjacent gene encoding a nuclear receptor. Similar changes were observed in rat and mouse aortas treated ex vivo with AngII. RNA-FISH (fluorescence in situ hybridization) and subcellular fractionation showed predominantly nuclear localization of Giver . AngII increased Giver expression via recruitment of Nr4a3 to Giver promoter. Microarray profiling and real-time quantitative polymerase chain reaction validation in VSMC showed that Giver knockdown attenuated the expression of genes involved in oxidative stress ( Nox1 ) and inflammation ( Il6 , Ccl2 , Tnf ) but increased Nr4a3 . Conversely, endogenous Giver overexpression showed opposite effects supporting its role in oxidative stress and inflammation. Chromatin immunoprecipitation assays showed Giver overexpression also increased Pol II (RNA polymerase II) enrichment and decreased repressive histone modification histone H3 trimethylation on lysine 27 at Nox1 and inflammatory gene promoters. Accordingly, Giver knockdown inhibited AngII-induced oxidative stress and proliferation in rat VSMC. RNA-pulldown combined with mass spectrometry showed Giver interacts with nuclear and chromatin remodeling proteins and corepressors, including NONO (non-pou domain-containing octamer-binding protein). Moreover, NONO knockdown elicited similar effects as Giver knockdown on the expression of key Giver -regulated genes. Notably, GIVER and NR4A3 were increased in AngII-treated human VSMC and in arteries from hypertensive patients but attenuated in hypertensive patients treated with ACE (angiotensin-converting enzyme) inhibitors or angiotensin receptor blockers. Furthermore, human GIVER also exhibits partial functional conservation with rat Giver . Conclusions: Giver and its regulator Nr4a3 are important players in AngII-mediated VSMC dysfunction and could be novel targets for antihypertensive therapy.
Cyclin F-Dependent Degradation of RBPJ Inhibits IDH1R132H-Mediated Tumorigenesis
Authors: Ruhi S. Deshmukh, Shalakha Sharma, Sanjeev Das
Journal: Cancer Research (2018)

Cyclin F is a substrate recognition subunit of Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role of cyclin F in the genotoxic stress response, its function under conditions of altered metabolic homeostasis remain unexplored. Here we report that cyclin F is induced upon metabolic stress in a FOXO1-dependent manner. Under metabolic stress conditions, cyclin F mediated polyubiquitylation of RBPJ at Lys315, leading to its proteasomal degradation. RBPJ regulated the expression of IDH1, which is often mutated to an oncogenic form IDH1R132H in cancers. Thus, metabolic stress-induced cyclin F attenuated the oncogenic functions of IDH1R132H in an RBPJ-dependent manner. Studies in mouse tumor models indicated that abrogation of cyclin F expression facilitates IDH1R132H-mediated tumorigenesis and metastasis. In addition, increased IDH1R132H levels correlated with reduced cyclin F levels in increasing grades of glioma. These findings highlight a novel aspect of cyclin F functions in inhibiting tumorigenesis and provide mechanistic insights into regulation of IDH1R132HSignificance: These findings reveal mechanistic insights into the key role of the cyclin F-RBPJ axis in response to metabolic stress in cancer cells. Cancer Res; 78(22); 6386-98. ©2018 AACR.
Abstract 18529: Trends in Direct Healthcare Expenditures Among US Adults With Atherosclerotic Cardiovascular Disease: Analysis of the Medical Expenditure Panel Survey From 2002 to 2013
Authors: Javier Valero-Elizondo, Joseph A Salami, Haider J Warraich, Chukwuemeka U Osondu, Erica S Spatz, Nihar Desai, Jamal S Rana, Salim S Virani, Ron Blankstein, Michael J Blaha, Amit Khera, Khurram Nasir
Journal: Circulation (2016)

Introduction: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the US with substantial financial burden at an individual and national level. We aimed to explore ...
Identifying delays in care for patients with NSCLC using value-stream mapping.
Authors: Chad W. Cummings, Becky Habecker, Katherine Tullio, Andrew Rothacker, Nathan A. Pennell, Gregory M.M. Videtic, Daniel Raymond, Peter J. Mazzone, Alison Ibsen
Journal: Journal of Clinical Oncology (2018)

136 Background: Value-Stream Mapping (VSM) was employed to evaluate non-value added activities focused on minimizing time between pathological diagnosis and first treatment (Time-To-Treat or TTT). Objective is to identify unnecessary delays in care for NSLC patients treated at a large academic medical center. Methods: A total of 253 patient records were examined between 1/15/2015 and 7/19/2016 and divided into stages: Stage I (Non-Surgical), Stage I-II (Surgical), Stage III, and Stage IV. Selection criteria required a min. of 50 patients/stage, including internally and externally diagnosed patients. A VSM was developed for each stage. Spreadsheets were used to detail dates and sequences of events, including consults, E&amp;M visits, imaging, procedures, and testing. Results: Overall TTT results by stage (median days) are as follows: Stage I (Non-Surgical) = 46 days (n = 55), Stage I-II (Surgical) = 35 days, n = 50), Stage III = 34 days (n = 71), Stage IV = 19 days (n = 77). Consults were reviewed among 4 specialties (Med/Onc, Rad/Onc, Surgical, Pulmonary), revealing Pulmonary Consults most common regardless of stage, 38%, 40%, 49%, 29%, respectively. It was found consults among specialties were rarely coordinated (stage III: 11/70 patients had consults same day between 2 specialties). Bronchoscopy procedures were most common method of Dx; sampling (n = 60, all stages) revealed MD orders are placed within 1 median day for each stage (15% ≥ 5days), but lead time to procedure ranged 7-12 median days depending on stage. Comorbidities for surgical patients (n = 46) were reviewed and found TTT delays correlates with number of comorbidities and FEV1 test results. Interventions included weekly, multi-disciplinary identification and review of patients across the 4 specialties, development of a TTT visual dashboard, and creation of communication standards across specialties. Conclusions: A VSM will identify areas where excessive delays occur. Opportunities exist to combine activities (same-day appointments/consults), reduce delays between activities, and/or improve communication. Decision-making can be accelerated when time between events (consults, staging, procedures, and tests) is minimized, regardless of diagnosis origin.
Extent of Risk-Aligned Surveillance for Cancer Recurrence Among Patients With Early-Stage Bladder Cancer
Authors: Florian R. Schroeck, Kristine E. Lynch, Ji won Chang, Todd A. MacKenzie, John D. Seigne, Douglas J. Robertson, Philip P. Goodney, Brenda Sirovich
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Cancer care guidelines recommend aligning surveillance frequency with underlying cancer risk, ie, more frequent surveillance for patients at high vs low risk of cancer recurrence. <h3>Objective</h3> To assess the extent to which such risk-aligned surveillance is practiced within US Department of Veterans Affairs facilities by classifying surveillance patterns for low- vs high-risk patients with early-stage bladder cancer. <h3>Design, Setting, and Participants</h3> US national retrospective cohort study of a population-based sample of patients diagnosed with low-risk or high-risk early-stage bladder between January 1, 2005, and December 31, 2011, with follow-up through December 31, 2014. Analyses were performed March 2017 to April 2018. The study included all Veterans Affairs facilities (n = 85) where both low- and high-risk patients were treated. <h3>Exposures</h3> Low-risk vs high-risk cancer status, based on definitions from the European Association of Urology risk stratification guidelines and on data extracted from diagnostic pathology reports via validated natural language processing algorithms. <h3>Main Outcomes and Measures</h3> Adjusted cystoscopy frequency for low-risk and high-risk patients for each facility, estimated using multilevel modeling. <h3>Results</h3> The study included 1278 low-risk and 2115 high-risk patients (median [interquartile range] age, 77 [71-82] years; 99% [3368 of 3393] male). Across facilities, the adjusted frequency of surveillance cystoscopy ranged from 3.7 to 6.2 (mean, 4.8) procedures over 2 years per patient for low-risk patients and from 4.6 to 6.0 (mean, 5.4) procedures over 2 years per patient for high-risk patients. In 70 of 85 facilities, surveillance was performed at a comparable frequency for low- and high-risk patients, differing by less than 1 cystoscopy over 2 years. Surveillance frequency among high-risk patients statistically significantly exceeded surveillance among low-risk patients at only 4 facilities. Across all facilities, surveillance frequencies for low- vs high-risk patients were moderately strongly correlated (<i>r</i> = 0.52;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Patients with early-stage bladder cancer undergo cystoscopic surveillance at comparable frequencies regardless of risk. This finding highlights the need to understand barriers to risk-aligned surveillance with the goal of making it easier for clinicians to deliver it in routine practice.