tbuckley/cabot-search huggingface dataset:
Abstract 749: Circulating miRNAs and Apoptosis Genes With Hyperglycemia in Ischemic Stroke Patient
Authors: Yi-Chen Hsieh, Nai-Fang Chi, Hung-Yi Chiou
Journal: Circulation Research (2019)

Stroke is the third cause of death and the leading cause of adult disability in Taiwan. More than half of acute ischemic stroke patients had hyperglycemia, which is one of the major reason for unfavorable outcomes. However, the physiopathology is remain unclear and better knowledge of underlying genetic mechanisms is needed to improve prognosis. This study aimed to identify possible genes and its regulated miRNA involving in hyperglycemia-induced unfavorable stroke outcomes. This is a two-stage study design. In the first screening stage, 3 hyperglycemia ischemic stroke patients and 3 normal-glycemia cases were recruited. MiRNA sequencing and PCR profile arrays were conducted. Messenger RNA with significant differences and miRNA were analyzed using miRSystem database and Cytoscape. The results showed that apoptosis regulatory pathway genes (FAS and BCL2L1) and its related microRNAs (has-let-7i-5p,has-let-7b-5p,has-let-7a-5p,has-let-7f-5p,has-let-7g-5p,has-let-7e-5p,has-miR-98-5p) were highly associated with acute hyperglycemia ischemic stroke. In the second validation stage, we then verified the above mentioned apoptosis regulatory pathway genes and its related miRNAs using middle cerebral artery occlusion (MCAO) mice model and validate in 143 ischemic stroke patients. From the animal model, the results showed that the FAS gene of hyperglycemic rats exhibited a higher performance than that of normal glycemic rats. The results of miRNAs indicated that the expression of has-let-7a-5p, has-let-7b-5p, has-let-7e-5p, and has-let-7i-5p was lower in hyperglycemia rats than those belonged to normal glycemic rats. For ischemic stroke patients, unfavorable outcome patients had higher FAS expression. Furthermore, there is a significant group-by-time interactions in FAS expression, with unfavorable outcome patients having increasing expression in FAS gene (p=0.0208). A remarkable group-by-time interaction in has-let-7e-5p expression was also observed, with unfavorable outcome patients having decreasing expression in has-let-7e-5p (p=0.0128). Our study uncovers FAS gene play an important role in hyperglycemia resulting in poor outcomes in ischemic stroke patients, and might provide new direction for treatment in the future.
Helen Salisbury: Reasons to be fearful
Authors: Helen Salisbury
Journal: BMJ (2019)

Most doctors their work home with them-literally, in the shape of emails to write and results to check, or figuratively, in their heads.We worry about patients at risk and whether we've taken the right decisions.It's often disrupting our sleep or intruding into our time off, when we should be attending to friends or family.How do we develop the confidence that we're good enough doctors?We've been adequately trained, we've passed our exams, and we make the best decision we can with the available evidence.We know that continuing to worry once we've closed the surgery door can be a recipe for burnout.So, how can we learn to let go?Experience helps: the longer you practise without major error, the more the fear recedes, but for some doctors it never goes away.
Therapeutic inhibition of mTORC2 rescues the behavioral and neurophysiological abnormalities associated with Pten-deficiency
Authors: Chien-Ju Chen, Martina Sgritta, Jacqunae Mays, Hongyi Zhou, Rocco Lucero, Jin Park, I-Ching Wang, Jun Hyoung Park, Benny Abraham Kaipparettu, Loredana Stoica, Paymaan Jafar-Nejad, Frank Rigo, Jeannie Chin, Jeffrey L. Noebels, Mauro Costa-Mattioli
Journal: Nature Medicine (2019)
Abstract 220: Gut Microbiota Alterations Associate With T Cell Activation and Adverse Cardiac Remodeling in Response to Cardiac Pressure Overload
Authors: Francisco J Carrillo-salinas, Njabulo Ngwenyama, Marina Anastasiou, Kuljeet Kaur, Mark Aronovitz, Pilar Alcaide
Journal: Circulation Research (2019)

Background: The complex syndrome of heart failure (HF), a leading cause of morbidity and mortality affecting more than 24 million people worldwide, is recently becoming associated with alterations in gut microbiota, also known as gut dysbiosis, as well as with T cell mediated systemic inflammation and T cell infiltration in the heart. Specifically, certain bacteria promote T cell activation, and T cell activation contributes to adverse cardiac remodeling and cardiac dysfunction in HF. We hypothesize that gut dysbiosis modulates cardiac remodeling and function in a T cell-dependent manner. Results: C57/BL6 mice were orally treated with a well-stablished wide spectrum antibiotic cocktail (ABX) and subjected to transverse aortic constriction (TAC), a model of non-ischemic HF. ABX was present during the duration of TAC (4 weeks), thus sterilizing the gut completely, or during 3 weeks before TAC followed by removal during the 4 weeks of TAC duration for spontaneous recovery of the gut microbiota (TAC-REC). The lack of gut microbiota showed a reduced T cell activation in the mediastinal lymph nodes and heart T cell infiltration, as well as cardiac fibrosis and cardiac hypertrophy were prevented in response to TAC. Nevertheless, gut dysbiosis induced by bacterial recolonization only partially recovered this phenotype. In addition, we sequenced 16S RNA to study the changes in bacterial populations in Sham, TAC, and TAC-REC. TAC induced changes in the gut microbiota compared to Sham surgery, which resulted in a higher relative abundance of several genera, such as Bacteroides, and lower relative abundance of Coprococcus, Lactobacillus and Bifidobacterium, these last two normally associated to an anti-inflammatory response. At the end of the experiment, bacterial recolonization in TAC-REC mice showed different relative bacterial abundance between TAC and TAC-REC, although there were no significant changes in diversity at 4 weeks post-TAC. Conclusion: Collectively, our findings suggest that changes in gut microbiota constitution modify T cell activation and migration to the heart in the TAC model. Exploring the role of gut microbiota in modulating adverse cardiac remodeling and cardiac function can become an optimal therapeutic target to treat HF patients.
Reducing emergency department utilization by improving patient access to their oncology care team.
Authors: Tony Philip, Karen Gleason, Claire Nekola, Todd Tucker, Jenny Paul Valadez, Shreya Prasad-Goyal, Samantha Meisels, Ronda Marie Bowman, Laura Kaufman
Journal: Journal of Clinical Oncology (2019)

77 Background: At Monter Cancer Center, we observed that when patients on active intravenous chemotherapy presented to our local ED about 70% arrived during the hours of 8am and 6pm. ED utilization by active chemotherapy patients results in cancer care by providers not familiar with their disease or treatment, increased costs, poor patient experience and potential treatment delays. Our goal was to create 20% reduction in daytime ED utilization, compared to Q4 2018, by patients that received intravenous chemotherapy within 30 days of their ED visit. Methods: Through the ASCO Quality Training program, a multidisciplinary team of frontline staff was formed to create a Process map, Cause and effect diagram and Priority Matrix to develop solutions. Our first PDSA created a simplified criteria to help office secretaries triage urgent and non-urgent calls to providers. This allowed patients with urgent issues to speak to their care team on first call rather than await a callback. In our second PDSA, our treatment room nurses emphasized to patients on their treatment discharge to contact their care team first for symptom management rather than going to the ED. Results: Compared to our baseline, we have seen a 33% decrease in ED utilization by re-educating patients to call us first for symptoms and providing a clear tool to help secretaries triage calls to the care team. Conclusions: Our study shows improving patient access to their oncology care teams can decrease ED utilization, increase cancer center utilization while improving patient safety across multiple disease types.
Abstract 569: Functional Benefits of Muscle PGC-1alpha in Aged Animals
Authors: Steven Yang, Emanuele Loro, Shogo Wada, Tejvir S Khurana, Zoltan Arany
Journal: Circulation Research (2019)

Metabolic homeostasis requires a complex network of transcriptional programs. PGC-1 (peroxisome-proliferator-activated receptor-γ coactivator-1) alpha is a potent transcriptional coactivator that coordinates the activation of a large number of nuclear-encoded genes, which, in turn, regulate numerous metabolic processes. Exercise strongly induces muscle PGC-1alpha in both humans and rodents. Over-expression of PGC-1alpha in skeletal muscle activates mitochondrial oxidative metabolism, fast-to-slow fiber-type switching, and neovascularization, leading to markedly increased endurance. In light of these findings, PGC-1alpha has been proposed to protect from age-associated sarcopenia, bone loss, and whole-body metabolic dysfunction, although these findings have been controversial. We therefore comprehensively evaluated muscle and whole-body function and metabolism in 24 month-old transgenic mice that over-express PGC-1alpha in skeletal muscle. We find that the powerful effects of PGC-1alpha on promoting muscle oxidative capacity and protection from muscle fatigability persist in aged animals, although at the expense of muscle strength. However, skeletal muscle PGC-1alpha does not prevent bone loss and in fact accentuates it, nor does it have long-term benefit on whole-body metabolic composition or insulin sensitivity. Interestingly, we see protection from sarcopenia in male animals with over-expression of PGC-1alpha in skeletal muscle but not in female animals. In summary, muscle-specific expression of PGC-1alpha into old age has beneficial effects on muscle fatigability and may protect from sarcopenia in males, but does not improve whole-body metabolism and appears to worsen age-related trabecular bone loss.
PCR Screening for Epstein-Barr Virus-Related Lymphoproliferative Disease (EBV-LPD) among Allogeneic Stem Cell Transplant (AlloSCT) Recipients: The Importance of T Cell Depletion.
Authors: Giannina Garces Ambrossi, Ann Jakubowski, Carrie Brennan, Timothy E. Kiehn, David M. Weinstock
Journal: Blood (2005)
Evaluating uptake and patient satisfaction with an out-of-pocket cost tracker for gynecologic cancer patients undergoing treatment.
Authors: Margaret Liang, Sarah S. Summerlin, Teresa KL Boitano, Christina T. Blanchard, Smita Bhatia, Warner King Huh, Maria Pisu
Journal: Journal of Clinical Oncology (2019)

101 Background: Tracking expenses may be useful to minimize financial distress in cancer patients. Our objective was to evaluate uptake and satisfaction with an out of pocket (OOP) cost tracker for gynecologic cancer patients on treatment. Methods: Within a longitudinal survey to assess financial burden among gynecologic cancer patients starting a new line of systemic therapy at a tertiary-care cancer center, we provided worksheets for participants to track their OOP expenses voluntarily. We assessed patient usage and satisfaction at 3 and 6 months. Financial distress was measured using Comprehensive Score for Financial Toxicity &lt; 26. Results: Among 121 participants with an average age of 59 years, 34 (28%) were African-American and 33 (27%) had a high school diploma or less. Half (55/110, 50%) of participants reported annual income &lt; $40,000. Most participants had health insurance (113/121, 93%) and were unemployed (77/118, 65%). Forty-nine of 121 (40%) participants reported ever using the OOP cost tracker at 3 or 6 months. Those who used the cost tracker stated it was helpful to track costs (86%, 73%), easy to use (97%, 100%), and useful for budgeting (42%, 24%) at 3 and 6 months. Participants reported using the cost tracker at least weekly (33%, 19%), every 2 weeks (36%, 27%), or monthly (31%, 54%) at 3 and 6 months. Twelve participants returned their OOP cost trackers for review with a median use of 5.5 months (range 3-10). Average monthly patient-reported OOP costs (range) were: $41 ($0-$584) for direct non-medical costs (i.e., transportation, lodging), $15 ($0-$120) for outpatient services, $13 ($0-$150) for medications/supplies, and $9 ($0-$100) for hospital services. Use of the OOP cost tracker at 3 months was not associated with financial distress at baseline (p = 0.30) or at 3 months (p = 0.89). Qualitative analysis showed the OOP cost tracker reminded patients to save receipts and to track categories of cost they would not have otherwise considered. Conclusions: 40% of gynecologic cancer patients undergoing treatment used an OOP cost tracker worksheet and found it helpful and easy to use. Direct non-medical costs accounted for the highest average monthly patient-reported OOP cost.
Can we promote physical activity to patients if we’re not physically active ourselves?
Authors: David J Jones
Journal: BMJ (2019)

Haseler and colleagues’ article on discussing physical activity with patients is helpful.1 Doctors of all specialties, myself included, ought to be more proactive in encouraging patients to exercise more, eat more healthily, lose weight, and so on. Every presentation—be it to a general practitioner, to the emergency department, …
Anti-AML Activity of Combined Epigenetic Therapy with Novel DNMT1 Inhibitors SGI-110 or SGI-1036 and Histone Deacetylase Inhibitor Panobinostat.
Authors: Warren Fiskus, Pace Johnston, Rajeshree Joshi, Rekha Rao, Celalettin Ustun, Anand Jillella, Peter Atadja, Stuart Hwang, Sanjeev Redkar, Kapil N. Bhalla
Journal: Blood (2008)
Abstract 522: IL-10 Knockout Bone Marrow Fibroblast Progenitor Cells-derived Exosomes Activate Cardiac Fibroblast and Exaggerate Pressure Overload-induced Fibrosis in Mice Heart
Authors: Rajesh Kumari, Prabhat Ranjan, Prasanna Krishnamurthy, Raj Kishore, Suresh K Verma
Journal: Circulation Research (2019)

Background: Inflammatory mediators play important role in cardiac remodeling. In heart, fibrosis is mainly mediated by activated fibroblasts (myofibroblasts), however, origin of myofibroblasts in diseased heart remains unclear. Recently, we have shown that bone marrow fibroblast progenitor cells (FPCs) significantly contribute in cardiac fibrosis in IL10 KO (KO) mice, but its molecular mechanism is not known. Here, we hypothesize that BM-FPCs activate resident cardiac fibroblast via their paracrine mediators (packaged in exosomes) to exaggerate the cardiac fibrosis in KO mice post- transverse aortic constriction (TAC). Method and Results: Cardiac hypertrophy and fibrosis was induced in Wild-type (WT) and IL10-knockout (IL10KO) mice by TAC surgery. TAC-induced left ventricular (LV) dysfunction and fibrosis were further exaggerated in KO mice. Recombinant IL10 administration markedly improved LV function and inhibited PO-induced cardiac fibrosis. PO enhanced FPC mobilization and homing in KO mice compared to WT mice. Furthermore, to identify the paracrine signaling, exosomes were isolated from WT and KO-FPCs culture media and characterized for fibrotic miRNA and proteins. Our data suggests that KO-FPC-exosomes are enriched with profibrotic miRs (miR21 and miR27) and proteins (RhoA). To explore whether KO-FPC-exosomes modulates resident fibroblasts biology and activation, adult cardiac fibroblasts (WT) were isolated and treated with WT and IL10KO-BMFPC-exosomes for 48 hrs. myoFB-associated gene (Collagen1α, Collagen3α and α- SMA) expression was notably increased in KO-FPC-exosome treated cells. Finally, immunostaining data further corroborated with our gene expression data and showed significantly enhanced α-SMA expression after KO-FPCs exosome treatments in cFBs. Conclusion: In conclusion, our data suggest that fibrotic remodeling factors (miRs and/or proteins) packaged in KO-FPC exosomes are sufficient to enhance the resident cardiac fibroblast activation and mediate cardiac fibrotic remodeling. Acknowledgement: NIH (RO1-135060) and AHA (14SDG20480104) SKV
Increased Angiogenic Activity of Plasma From Sickle Cell Disease Patients and Anti-Angiogenic Effects of Hydroxyurea: Evaluation of Capillary-Like Structure Formation of Human Umbilical Vein Endothelial Cells on Matrigel
Authors: Flávia Cristine Mascia Lopes, Kleber Yotsumoto Fertrin, Sara T. Olalla-Saad, Fernando Ferreira Costa, Nicola Conran
Journal: Blood (2011)
Improving implementation of standardized structured reporting: Development of an implementation toolkit.
Authors: Rosella Hermens, Julie Elisa Maria Swillens, Rinus Voorham, Iris D. Nagtegaal
Journal: Journal of Clinical Oncology (2019)

265 Background: Although standardized structured reporting (SSR) usage is recommended in national and international evidence-based guidelines (warranting quality &amp; safety), actual use varies widely in oncology related medical disciplines. Previous research showed multiple impeding factors regarding SSR-implementation. The aim of this study is to develop an implementation toolkit, based on the impeding factors found. Methods: We organized an expert meeting a. to explore experts’ opinions on the impeding factors found in a previous study; and b. to discuss possibilities for a tailored implementation toolkit. The expert-panel consisted of three pathologists, three multidisciplinary-team (MDT) members, three patient organization delegates, two delegates of the Dutch nationwide network and registry of histo- and cytopathology(PALGA), two delegates of the Netherlands Comprehensive Cancer Organization (IKNL), one PALGA-liaison, and one implementation expert. A literature study was performed to obtain evidence on the most effective implementation tools. All selected tools were included in an implementation toolkit. Results: The expert meeting and literature study yielded eight tools to be developed: 1. Two communication tools of both the benefits of SSR and of the development and updates of SSR-templates; 2. Consultation and simulation sessions with MDT-members to optimize the development and feedback process of the standardized structured reports and to increase familiarity with these reports; 3. A tailored e-learning for pathologists to increase the familiarity, knowledge and skills of SSR-usage; 4. IT-solutions, such as incorporation of speech recognition to improve the usability and content of both the SSR templates and the generated reports; 5. A sustainable feedback-system to support SSR-template usage; 6. Agenda setting success to encourage use of SSR. Conclusions: Experts proposed several tools to improve the implementation of SSR. The next step is to test this toolkit in a pilot study.
Use of nonclinical staff to coordinate oral anticancer drug prescriptions.
Authors: Daniel O'Neil, Melissa Kate Accordino, Jason Dennis Wright, Cynthia Law, Suzuka Nitta, Donna Buono, Maura Abbott, Yelena Ustoyev, Jianhua Hu, Alfred I. Neugut, Chin Hur, Khilna Patel, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2019)

72 Background: In September 2018, Herbert Irving Comprehensive Cancer Center (HICCC) began using non-clinical pharmacy liaisons to oversee coordination of oral anticancer drug (OACD) prescriptions (RXs), a task previously performed by clinical staff. Liaisons interact with payers, specialty pharmacies and financial assistance (FA) groups. We assessed the impact of this strategy on time to receipt of OACDs. Methods: We collected prospective data on all new OACD RXs from HICCC’s medical oncology practice from 1/1/2018 to 9/17/2018 (pre-liaisons) and 9/17/2018 to 5/1/2019 (post-liaisons). We collected patient demographic and insurance data; date of prescription; date of drug delivery; and interactions with payers and FA groups. Federal Drug Association labels were reviewed for drug approval dates and indications. Daily drug cost was defined according to average wholesale price. We define time to receipt (TTR) as days from RX to OACD delivery and used multivariable linear regression to determine factors associated with TTR (log transformed). Results: Over the study period, we evaluated 707 RXs; 93 (13%) were never filled. Of 614 filled RXs, 350 (57%) were placed in the pre-liaison period and 264 (43%) in the post-liaison period. After introduction of liaisons, FA was pursued for more RXs (17% vs 25%, p = 0.007); there was no difference pre- and post-liaisons in patient demographics, distribution of payers, RXs needing prior authorization (PA) (76% vs 77%), off-label RXs (14% vs 16%), RXs for drugs approved &lt; 2 years earlier (5% vs 3%) or mean daily cost ($471 vs $470). Mean TTR before and after liaisons were 11.9 and 11.6 days, respectively. Linear regression showed longer TTR was associated with commercial payers (p = 0.02), need for PA (p = 0.03), FA pursuit (p ≤ 0.0001) and daily OACD cost (p = 0.03); no association was seen with use of liaisons, patient age, off-label use or OACDs approved &lt; 2 years earlier. Conclusions: Implementation of pharmacy liaisons to coordinate OACD prescriptions did not impact the time to OACD receipt, though liaisons were able to pursue financial assistance for more patients. Insurance and cost factors had the greatest impact on time to drug receipt. Task shifting may reduce the clerical workload for providers.
Peripheral Neuropathy Is Associated with an Increased Risk of Fractures in Individuals with Monoclonal Gammopathy of Undetermined Significance: A Population-Based Study Including 15,351 MGUS Cases
Authors: Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Ingemar Turesson, Magnus Björkholm, Ola Landgren, Sigurður Yngvi Kristinsson
Journal: Blood (2018)
Rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: long-term follow-up of a phase 2 study from the German Hodgkin Study Group
Authors: Dennis A. Eichenauer, Annette Plütschow, Michael Fuchs, Sylvia Hartmann, Martin-Leo Hansmann, Boris Böll, Bastian von Tresckow, Peter Borchmann, Andreas Engert
Journal: Leukemia (2019)
Simulation of Chemotherapy Effects in Older Breast Cancer Patients With High Recurrence Scores
Authors: Young Chandler, Jinani C Jayasekera, Clyde B Schechter, Claudine Isaacs, Christopher J Cadham, Jeanne S Mandelblatt
Journal: JNCI Journal of the National Cancer Institute (2019)

Tumor genomic expression profile data are used to guide chemotherapy choice, but there are gaps in evidence for women aged 65 years and older. We estimate chemotherapy effects by age and comorbidity level among women with early-stage, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers and Oncotype DX scores of 26 or higher.A discrete-time stochastic state transition simulation model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups based on age (65-69, 70-74, 75-79, and 80-89 years) and comorbidity levels (no or low, moderate, severe). Outcomes were discounted at 3%, and included quality-adjusted life-years (QALYs), life-years, and breast cancer and other-cause mortality with chemoendocrine vs endocrine therapy. Sensitivity analysis tested the effect of varying uncertain parameters.Women aged 65-69 years with no or low comorbidity gained 0.16 QALYs with chemo-endocrine and reduced breast cancer mortality from 34.8% to 29.7%, for an absolute difference of 5.1%; this benefit was associated with a 12.8% rate of grade 3-4 toxicity. Women aged 65-69 years with no or low or moderate comorbidity levels, and women aged 70-74 years with no or low comorbidity had small chemotherapy benefits. All women aged 75 years and older experienced net losses in QALYs with chemo-endocrine therapy. The results were robust in sensitivity analyses. Chemotherapy had greater benefits as treatment effectiveness increased, but toxicity reduced the QALYs gained.Among women aged 65-89 years whose tumors indicate a high recurrence risk, only those aged 65-74 years with no or low or moderate comorbidity have small benefits from adding chemotherapy to endocrine therapy. Genomic expression profile testing (and chemotherapy use) should be reserved for women aged younger than 75 years without severe comorbidity.