tbuckley/cabot-search huggingface dataset:
Abstract 14379: Implementation of Pharmacist-led Antithrombotic Medication Management for Elective Endoscopic Procedures
Authors: Henry Han, Emily Sippola, Wilson Chen, Spencer Morgan, Elizabeth Renner, Allison Ruff, Anne Sales, Jacob Kurlander, Geoffrey D Barnes
Journal: Circulation (2020)

Introduction: Mismanagement of antithrombotic medications often leads to cancelled elective procedures. Pharmacist-led anticoagulation management prior to elective procedures is not well studied. Methods: We implemented a best practice advisory (BPA) that offered referral to a pharmacist-led medication management service prior to elective outpatient gastrointestinal endoscopies. Eligible patients were taking warfarin, a direct oral anticoagulant, and/or a P2Y12 inhibitor for management of atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), peripheral arterial disease (PAD), and/or mechanical heart valve. Patients referred to the antithrombotic service were compared to those managed by the ordering provider. Outcomes assessed included documentation of a medication management plan, guideline-appropriateness of drug cessation prior to endoscopy, and guideline-appropriate rates of enoxaparin bridging for high risk warfarin patients. Results: Seventy-four percent of patients (448/645) were referred to the antithrombotic service. These patients were more likely to have had VTE (33.0% vs. 18.2%), less likely to have CAD (31.9% vs. 40.9%; p=0.009 for indication category), and more likely to be prescribed warfarin (32.8% vs 20.9%, p&lt;0.001). After adjusting for baseline differences, patients referred to the antithrombotic service were more likely to have had pre-procedure medication plan documentation (98.7% vs 56.1%, p &lt;0.001), and pre-procedure antithrombotic management was more likely to follow guidelines (97.5% vs. 91.5%, p=0.024). Guideline-appropriate use of bridging enoxaparin for warfarin patients was not different (10/16 [62.5%] vs. 2/6 [33.3%], p=0.221). Conclusion: Pre-procedural antithrombotic medication management by a pharmacist-led team for elective endoscopies was associated with more guideline-adherent management and better documentation of the medication plans.
Microstructure evolution and texture tailoring of reduced graphene oxide reinforced Zn scaffold
Authors: Youwen Yang, Yun Cheng, Shuping Peng, Liang Xu, Chongxian He, Fangwei Qi, Mingchun Zhao, Cijun Shuai
Journal: Bioactive Materials (2020)

Zinc (Zn) possesses desirable degradability and favorable biocompatibility, thus being recognized as a promising bone implant material. Nevertheless, the insufficient mechanical performance limits its further clinical application. In this study, reduced graphene oxide (RGO) was used as reinforcement in Zn scaffold fabricated via laser additive manufacturing. Results showed that the homogeneously dispersed RGO simultaneously enhanced the strength and ductility of Zn scaffold. On one hand, the enhanced strength was ascribed to (i) the grain refinement caused by the pinning effect of RGO, (ii) the efficient load shift due to the huge specific surface area of RGO and the favorable interface bonding between RGO and Zn matrix, and (iii) the Orowan strengthening by the homogeneously distributed RGO. On the other hand, the improved ductility was owing to the RGO-induced random orientation of grain with texture index reducing from 20.5 to 7.3, which activated more slip systems and provided more space to accommodate dislocation. Furthermore, the cell test confirmed that RGO promoted cell growth and differentiation. This study demonstrated the great potential of RGO in tailoring the mechanical performance and cell behavior of Zn scaffold for bone repair.
Abstract 360: Metformin Confers Cardiac and Renal Protection in Sudden Cardiac Arrest
Authors: Cody A Rutledge, Takuto Chiba, Kevin Redding, Sunder Sims-lucas, Jonathan Elmer, Cameron Dezfulian, Brett A Kaufman
Journal: Circulation (2020)

Introduction: Sudden cardiac arrest (SCA) affects over 600,000 Americans yearly with substantial mortality. After resuscitation, multiple system organ damage is common. Metformin has previously demonstrated ischemic protection in cardiac and renal tissues. We retrospectively evaluated kidney damage and cardiac function in a cohort of diabetic SCA patients. We also developed a mouse model of SCA that replicates human pathology and pretreated with metformin to evaluate the molecular changes driving these outcomes. Methods: We performed a retrospective analysis of patients admitted to a single center from 2010 to 2019 after resuscitation from SCA. We included those with a known diabetes prior to arrest. We extracted home medications from nursing and pharmacy medication reconciliations. Our primary exposure of interest was pre-arrest metformin use (vs no or other medications). We compared first day and maximum serum creatinine (SCr) during hospitalization, as well as cardiac ejection fraction (EF) after arrest. To explore the mechanisms underlying these changes, we developed a mouse model of SCA to compare metformin vs non-treated SCA mice. We evaluated EF and renal endpoints including SCr, BUN, and tubular damage 1-day after SCA. Tissues were collected for molecular and histologic studies. Results: We identified 360 diabetic patients of whom 151 (42%) were prescribed metformin at the time of SCA. There were no differences in age, sex, pre-arrest SCr or pre-arrest A1c between metformin and non-metformin treated patients. After SCA, metformin-treated patients had significantly lower initial SCr when compared to non-metformin patients (1.5±0.1 vs 1.7±0.1), 1-day SCr (1.4±0.1 vs 1.7±0.1), max creatinine (1.9±0.1 vs 2.2±0.1 ), and higher EF (49±2 vs 43±2). In the mouse study, pretreatment with metformin group found significantly lower 1-day SCr than non-treated mice (0.40±0.05 vs 1.52±0.22), BUN (64.8±8.2 vs 156.0±39.8), and histologic injury score (0.17±0.71 vs 3.33±0.29), as well as improved 1-day EF (49.6±3.7 vs 38.8±4.5). Conclusions: Our data support a renal- and cardio-protective role for metformin after SCA. Future studies will explore biochemical changes driving protection in the mouse with the goal of discovering translatable therapies.
The BET Inhibitor, CPI-0610, Promotes Myeloid Differentiation in Myelofibrosis Patient Bone Marrow and Peripheral CD34+ Hematopoietic Stem Cells
Authors: Jennifer A Mertz, Patricia J Keller, Rosana D Meyer, Oksana Zavidij, Jike Cui, Jean-Jacques Kiladjian, Srdan Verstovsek, Vikas Gupta, Moshe Talpaz, Claire Harrison, Adam J. Mead, Ruben Mesa, John Mascarenhas, Adrian Senderowicz, Gozde Colak, James Shao, Katarina Luptakova, Jeffrey S Humphrey, Jing Wang, Patrick Trojer, Mohamed E Salama
Journal: Blood (2020)
Abstract 236: Gender Disparities in Bystander CPR and Defibrillation Persist in Black and Hispanic Neighborhoods in the US
Authors: Audrey L Blewer, Monique A Starks, Carolina Malta Hansen, Marcus E Ong, Anthony J Viera, Rabab Al-Araji, Bryan F McNally, Christopher B Granger
Journal: Circulation (2020)

Introduction: Bystander CPR (B-CPR) and defibrillation for sudden cardiac arrest (SCA) vary by gender with females being less likely to receive these interventions. Despite known differences by race and ethnicity, it is unknown whether gender disparities in B-CPR and defibrillation persist by neighborhood race and ethnicity. Objectives: We examined the likelihood of receiving B-CPR and defibrillation by gender stratified by public location and neighborhood racial/ethnic composition. We hypothesized that in public locations within Black neighborhoods, females will have a lower likelihood of receiving B-CPR compared to males. Methods: We conducted a retrospective cohort study using data from the US Cardiac Arrest Registry to Enhance Survival (CARES) registry. Neighborhoods were classified by census tract based on percent of Black or Hispanic residents using the threshold in the definition of “White flight” where Whites leave a neighborhood when it exceeds &gt;30% of a minority population. We independently modeled the likelihood of receipt of B-CPR and defibrillation by gender stratified by public location and neighborhood racial/ethnic composition controlling for confounding variables. Results: From 2013-2018, CARES collected 350,722 US arrests; after excluding pediatric arrests, those witnessed by EMS, or those that occurred in a healthcare facility, 214,464 were included. Mean age was 64±16 and 65% were male; 39% received B-CPR, 9% received bystander defibrillation prior to 9-1-1 responders arrival, and 18% occurred in the public. In Black neighborhoods, females who had SCA in public locations were 22% less likely to receive B-CPR (OR: 0.78 (0.64-0.95), p=0.01) and 42% less likely to receive defibrillation (OR: 0.58 (0.45-0.74), p&lt;0.01) compared to males. In Hispanic neighborhoods, females who had SCA in public locations were also less likely to receive B-CPR (OR: 0.72 (0.59-0.87), p&lt;0.01) and less likely to receive defibrillation (OR: 0.62 (0.48-0.80), p&lt;0.01) compared to males. Conclusion: Females with public SCA have a decreased likelihood of receiving B-CPR and defibrillation, and these findings persist in Black and Hispanic neighborhoods. This has implications for strategies to reduce disparities around bystander response to SCA.
The Spectrum of<i>Helicobacter</i>-Mediated Diseases
Authors: Karen Robinson, John C. Atherton
Journal: Annual Review of Pathology Mechanisms of Disease (2020)

Helicobacter pylori is the leading cause of peptic ulcer disease. The infection has been implicated in more than 75% of duodenal ulcer cases and 17% of gastric ulcer cases. H. pylori has been classified as a human carcinogen, since it is the main cause of distal gastric adenocarcinoma and B cell mucosa-associated lymphoid tissue lymphoma. Evidence also links H. pylori with extragastric conditions including iron deficiency anemia, idiopathic thrombocytopenic purpura, and vitamin B12 deficiency. Studies indicate that H. pylori may be protective against other conditions of the gastrointestinal tract (e.g., reflux esophagitis and related pathologies) and elsewhere in the body (e.g., asthma). The infection is asymptomatic in the vast majority of cases; more serious outcomes occur in only 10-15% of infected individuals. Despite extensive research over the past 3 decades, there is no effective vaccine, and the circumstances leading to disease development remain unclear. In addition, there is now a growing prevalence of antimicrobial resistance in H. pylori. This review discusses these important issues.
Abstract PO-043: Interception of pancreatic cancer progression
Authors: Matthew L. McDermott, Lesley P. Ferguson, Kendall Chambers, Nirakar Rajbhandari, Tannishtha Reya
Journal: Cancer Research (2020)

Abstract Pancreatic Cancer (PC) is projected to be one of the leading causes of cancer related death by 2030. Although other cancers have made significant strides towards improved treatment, PC still remains at a 9% fiver year survival rate due to end-stage diagnosis, aggressive metastasis, and a protective stromal wall. Therefore, to identify novel therapeutic targets, our lab focuses on studying cancer stem cells, a highly chemo-resistant sub-population of pancreatic cancer cells. RNA-seq analysis of these cancer stem cells has revealed a number of genes that are enriched compared to non-therapy resistant cells and normal pancreas. We hypothesize that genes turned on through pancreatic cancer progression contribute to therapy resistance. If PC could be targeted at earlier stages, it would be possible for therapeutics to bypass the wealth of issues that occur as it advances. By cross referencing our RNA-seq analysis to sequencing performed at various stages of pancreatic cancer development in mice, a subset of genes is not only up-regulated in therapy resistant cells, but increases in expression as normal pancreas progresses to an end stage tumor. Preliminary studies have shown that inhibition of these select genes reduces growth of mouse pancreatic cancer in vitro and in vivo. Ongoing studies are to (1) test if inhibition of these genes reduces early stage PC growth in vitro and in vivo, and (2) test how gene knockdown affects human pancreatic cancer cell growth in vitro and in vivo. Citation Format: Matthew L. McDermott, Lesley P. Ferguson, Kendall Chambers, Nirakar Rajbhandari, Tannishtha Reya. Interception of pancreatic cancer progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-043.
Abstract 15396: Atrial Fibrillation Bleeding Risk and Prediction While Treated With Direct Oral Anticoagulants in Warfarin Naïve and Experienced Patients
Authors: Alexander C Perino, Krishna Pundi, Jun Fan, Susan K Schmitt, Mitra Kothari, Paul A Heidenreich, Mintu Turakhia
Journal: Circulation (2020)

Introduction: Direct oral anticoagulants (DOAC) are guideline-recommended over warfarin for stroke prevention in atrial fibrillation (AF). However, patients who are DOAC eligible are commonly maintained on warfarin. We sought to evaluate bleeding risk and prediction while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin. Methods: We performed a retrospective cohort study using data from the Veteran Affairs health care system. We included patients with a prescription for warfarin and/or DOAC from 10/1/2010 to 9/30/2017 with an AF encounter in the 90 days prior to 30 days after prescription. We categorized DOAC treated patients as warfarin-naïve or -experienced and performed an on-treatment analysis to determine bleeding incidence and HAS-BLED score discrimination. In adjusted analyses, we compared risk of bleeding while treated with DOAC (both for warfarin-naïve and -experienced patients) to warfarin. Results: The analysis cohort included 99,143 patients treated with warfarin (71±10 years, HAS-BLED 2.6±1.2) and 73,732 and 26,760 patients treated with DOAC who were warfarin-naïve (74±10 years, HAS-BLED 2.4±1.0) and -experienced (71±9 years, HAS-BLED 2.8±1.1), respectively. DOAC patients with warfarin experience had more prior bleeds (DOAC, warfarin-experienced: 11.9%; DOAC, warfarin-naïve: 4.5%; warfarin: 6.2%; p&lt;0.001 for both). Risk of intracranial bleeding was substantially lower while on DOAC treatment (both for warfarin-naïve and -experienced patients) as compared to warfarin ( Table ). HAS-BLED discrimination for bleeding outcomes, intracranial or any bleeding, was modest ( Table ). Conclusion: DOAC treatment had a favorable safety profile compared to warfarin treatment, even for DOAC treated patients with warfarin-experience who had more prior bleeds. These data argue against maintaining DOAC eligible patients on warfarin therapy regardless of HAS-BLED score.
Abstract 16602: Mitolamban is a Novel Cardiac-Enriched Mitochondrial Microprotein That Regulates Respiratory Complex III
Authors: Catherine A Makarewich, Amir Z Munir, Svetlana Bezprozvannaya, Aaron M Gibson, Thomas P Matthews, Misty Martin, John R McAnally, Sean J Morrison, Rhonda S Bassel-Duby, Eric N Olson
Journal: Circulation (2020)

Introduction: Emerging evidence suggests that many RNA molecules currently annotated as noncoding contain short open reading frames that code for functional small proteins called microproteins. Microproteins play critical roles in a diverse range of essential biological processes. To identify novel cardiac-expressed microproteins, we used a comparative genomics approach and identified mitolamban (Mtlbn) as a highly conserved 47-amino acid transmembrane protein that is abundantly expressed in the heart. Methods and Results: Subcellular localization studies showed that Mtlbn localized specifically to the inner mitochondrial membrane. Immunoprecipitations and mass spectrometry analysis indicated that Mtlbn interacted with subunits of complex III of the electron transport chain (ETC) and we observed the presence of Mtlbn in complex III respiratory supercomplexes (SCs) by blue native polyacrylamide gel electrophoresis (BN-PAGE). Cardiac-specific Mtlbn overexpressing transgenic (TG) mice and Mtlbn gene-deleted (knockout, KO) mice were generated to dissect the molecular function of this protein in the heart. Mtlbn TG mice developed cardiomyopathy and died prematurely with histological, biochemical and ultrastructural pathologic features. Metabolomic analysis indicated that hearts from TG mice had signs of increased oxidative stress and mitochondrial dysfunction. While Mtlbn KO mice had normal cardiac function and histological appearance, BN-PAGE analysis of purified mitochondria from KO hearts showed altered complex III composition. Functional assessment of purified heart mitochondria from Mtlbn KO mice revealed a reduction in complex III activity and metabolomic analysis of KO heart tissue indicated an altered metabolite profile consistent with deficiencies in complex III activity. Conclusions: Mtlbn is a novel heart-enriched microprotein that localizes to the inner mitochondrial membrane where it interacts with complex III of the ETC. Our data indicate that Mtlbn serves as a critical regulator of mitochondrial ETC activity through a direct role in affecting complex III function.
Abstract 13480: High Density Lipoprotein Promotes Angiogenesis by Suppressing Mir-24-3p Expression
Authors: Zhijun OU, Hua-Ming Li, Zhi-Wei Mo, Yue-Ming Peng, Yan Li, Wei-Ping Dai, Jingsong Ou
Journal: Circulation (2020)

Introduction: Previous studies showed that high density lipoprotein (HDL) can stimulate angiogenesis. However, the mechanisms by which HDL promotes angiogenesis remains unclear. Hypothesize: HDL may promote angiogenesis by regulating miRNAs expression. Methods: HDL was isolated from healthy subjects. Human umbilical vein endothelial cells (HUVECs) were cultured with vehicle or HDL (100 μg/ml), and the differential miRNAs expression were indentified by miRNA array and verified by qRT-PCR. HUVECs were treated with vehicle or HDL (100 μg/ml) with or without miRNAs mimic, endothelial cells proliferation, migration and tube formation were detected. The production of nitric oxide(NO) was measured. The expression and phosphorylation of endothelial nitric oxide synthase (eNOS) was determined. Results: The miRNAs profile of HDL-treated HUVECs is significantly different from control group. HDL significantly downregulated miR-24-3p expression. HDL significantly promoted HUVECs proliferation, migration and tube formation. HDL also significantly stimulated NO production and up-regulated the expression and phosphorylation of eNOS. However, HDL did not stimulated HUVECs proliferation, migration, tube formation and NO production as well as the expression and phosphorylation of eNOS after pretreated with miR-24-3p mimic. Conclusions: HDL can promote angiogenesis by suppressing miR-24-3p expression.
Interpreting the Kansas City Cardiomyopathy Questionnaire in Clinical Trials and Clinical Care
Authors: John A. Spertus, Philip G. Jones, Alexander T. Sandhu, Suzanne V. Arnold
Journal: Journal of the American College of Cardiology (2020)

To improve the patient-centeredness of care, patient-reported outcomes have been increasingly used to quantify patients’ symptoms, function, and quality of life. In heart failure, the Kansas City Cardiomyopathy Questionnaire (KCCQ) has been qualified by the U.S. Food and Drug Administration as a Clinical Outcome Assessment and recommended as a performance measure for quantifying the quality of care. By systematically asking the same questions reproducibly over time, the KCCQ can validly and sensitively capture the impact of heart failure on patients’ lives and is strongly associated with clinical events over time. This review describes how to interpret the KCCQ, how it should be analyzed in clinical trials to maximize the interpretability of results, and how it can be used in clinical practice and population health. By providing a deeper understanding of the KCCQ, it is hoped that its use can further improve the patient-centeredness of heart failure care.
NT-proBNP: Can We Better Utilize Biomarkers in Patients With Diabetes?
Authors: Matthew A. Cavender, Benjamin M. Scirica
Journal: Diabetes Care (2020)

B-type natriuretic peptide (BNP) is secreted from the atria of the heart as a response to myocardial stretch that occurs with increases in volume, afterload, and other hemodynamic changes that result in increased cardiovascular stress. The atria of the heart secrete BNP in its proform and it is subsequently cleaved into an inactive form (N-terminal [NT]-proBNP) and an active form (BNP) (1). Although there are some differences with regard to interpretation of the assays for these different metabolites, both NT-proBNP and BNP (referred to collectively as natriuretic peptides [NP]) can be measured and quantified and play an important role in the diagnosis and management of both acute and chronic heart failure.

While the role of NP in the management of heart failure is well established, the role of NP outside of heart failure is less well defined. Prior studies consistently show a clear relationship between elevated levels of NP and subsequent risk of cardiovascular events, including atrial fibrillation (2), diastolic dysfunction (3), coronary heart disease, and stroke (4), and the development of diabetes (5). Given these associations, it is possible to use NP to assist in the risk stratification of patients into those who are at high and low risk of cardiovascular events in populations at risk for cardiovascular disease, with stable coronary artery disease, or following a myocardial infarction (6). Furthermore, it is possible that these biomarkers could also help to tailor therapy such that patients at high risk have intensification of …
Abstract 282: In Hospital Outcomes of Cardiac Arrest in Patient with End Stage Renal Disease
Authors: Muhammad Khan, Muhammad U Khan, Muhammad Munir
Journal: Circulation (2020)

Background: End stage renal disease (ESRD) is a well-recognized risk factor for development of sudden cardiac arrest(SCA). There is limited data on outcomes after an in-hospital SCA event in ESRD patients. Methods: Data were obtained from National Inpatient Sample from January 2007 to December 2017. In-hospital SCA was identified using International Classification of Disease, 9th Revision, Clinical Modification, and International Classification of Disease, 10th Revision, Clinical Modification codes of 99.60, 99.63, and 5A12012. ESRD patients were subsequently identified using codes of 585.6 and N18.6. Propensity -matched analysis using logistic regression with SD caliper of 0.2 was used to match patients with and without ESRD. Crude and propensity-matched (PS) cohorts outcomes were calculated. Results: A total of 1,412,985 patients sustained in-hospital SCA during our study period. ESRD patients with in-hospital SCA were younger and had a higher burden of key co-morbidities. Mortality was similar in ESRD and non-ESRD patients in PS matched cohort (70.4% vs. 70.7%, p = 0.45, figure 1) with an overall downward trend over our study years (figure 2). Conclusion: In the context of in-hospital SCA, mortality is similar in ESRD and non-ESRD patients in adjusted analysis. Adequate risk factor modification could further mitigate the risk of in-hospital SCA among ESRD patients