tbuckley/cabot-search huggingface dataset:
Abstract 17201: TEG R-time as a Comparable Method to aPTT and Heparin Levels in Pediatric Patients on Heparin Therapy
Authors: Mamadou Diallo, Fatoumata Diallo, Andrew Torres, Sitaram Emani, Sirisha Emani
Journal: Circulation (2020)

Introduction: Hemorrhage post cardiac surgery continues to be a common morbidity despite the advancement in technology in coagulation diagnostics. Although, activated partial thromboplastin time (aPTT) and FXa function (heparin levels) are commonly used methods, there is often discrepancy in results between the methods. Hypothesis: In this study, we analyzed the use of Thromboelastography (TEG) reaction-time (R-time) as an additional diagnostic method for comparison to help guide blood product management. Methods: In a retrospective study of pediatric patients (N=292) who were given heparin, TEG R-time results along with aPTT and heparin levels were collected from the electronic patient records after the approval from our institution review board. Comparisons were made between the three methods using Pearson r correlations. Correlations between the three methods and bleeding events was also analyzed. Results: There were positive moderate correlations between R-time ≥15 min vs. aPTT ≥50s ( r =0.51), R-time ≥15min, vs. heparin levels ≥0.1 IU/ml ( r =0.54); and aPTT ≥50s vs. heparin levels ≥0.1 IU/ml ( r =0.55). When R-time was ≥15min, 74% of the patients had aPTT ≥50s ( p &lt;0.001) and 81% of the patients had heparin levels ≥0.1 IU/ml ( p &lt;0.001). When aPTT was ≥50s, 78% of the patients had heparin levels ≥0.1 IU/ml ( p &lt;0.001). However, no correlation was found between bleeding events vs. R-time ≥15min, aPTT ≥50s and heparin levels ≥0.1 IU/ml. Conclusions: Correlation between TEG R-time versus aPTT or heparin levels was comparable to the correlation between aPTT versus heparin levels. In conclusion, TEG R-time could be used as an additional diagnostic method to help guide blood product management.
<i>Gga3</i> deletion and a <i>GGA3</i> rare variant associated with late onset Alzheimer’s disease trigger BACE1 accumulation in axonal swellings
Authors: Selene Lomoio, Rachel Willen, WonHee Kim, Kevin Z. Ho, Edward K. Robinson, Dmitry Prokopenko, Matthew E. Kennedy, Rudolph E. Tanzi, Giuseppina Tesco
Journal: Science Translational Medicine (2020)

GGA3-mediated BACE1 accumulation in dystrophic neurites is an early pathogenic event and is independent of Aβ extracellular deposition.
Abstract 16363: An 18-month Smoking Cessation Intervention Incorporating Pharmacotherapy and Behavioral Counseling Improves Tobacco Abstinence Rates in Adult Smokers With Serious Mental Illness (smi) in Community Mental Health Settings: Results of a Randomized Clinical Trial
Authors: Gail Daumit, A. Eden Evins, Corinne Cather, Arlene Dalcin, Faith Dickerson, Edgar R Miller, Lawrence J Appel, Gerald J Jerome, Una McCann, Jeanne Charleston, Deborah Young, Joseph Gennusa, Stacy Goldsholl, COURTNEY COOK, Tyler Fink, Nae Yuh Wang
Journal: Circulation (2020)

Introduction: Tobacco smoking is the largest contributor to markedly elevated CVD and preventable death in persons with SMI. Trials of combined pharmacologic and behavioral treatments improve abstinence rates, but have targeted those ready to quit right away, and evidence-based treatments are rarely used in the community. Weight gain often accompanies abstinence. Our objective was to determine the effectiveness of an 18m smoking cessation pharmacotherapy and behavioral counseling intervention incorporating weight management and physical activity in persons with SMI. Hypothesis: The active intervention is more effective than control in achieving biochemically validated, 7-day point prevalence smoking abstinence at 18m. Methods: We conducted an RCT in 4 community mental health settings in 192 smokers with SMI, stratified by readiness to quit within 30d or in 1 to 6m. The active intervention group was offered 18m of 1 st -line cessation pharmacotherapy, smoking cessation and weight management counseling tailored to readiness to quit, and support for physical activity. Controls received a quit line referral. Results: Mean(SD) age was 49.6(11.7); cigarettes/day 12.1(9.5); BMI 32.0(7.6) kg/m 2 ; 49% were male, 48% African-American, 62% willing to quit in 30d, 95% completed 18m follow-up. At 18m, 27.8% of active group and 6.3% of controls achieved 7d smoking abstinence (p&lt;0.0001); adjusted odds ratio 6.0 (95% CI: 2.3 –15.6; p=0.0002). There was no significant modification of intervention effect on abstinence by readiness to quit. Mean difference in weight change over 18m between active and control was not significant (3.5 lbs, 95% CI: -3.3 –10.3; p=0.32). Conclusions: Offering 18m of evidence-based cessation treatment in the community substantially increased smoking abstinence without significant weight gain in SMI. Implementing best practice guidelines to treat all smokers regardless of readiness to quit should improve CVD health in this high-risk population.
Abstract 16240: Knowledge of Clinical Presentation and Diagnostic Pathways for Cardiac Amyloidosis Among Physicians in the Middle East-Gulf Region: on Behalf of the Gulf Cardiac Amyloidosis Working Group
Authors: Firas Al Badarin, Juwairia Al Ali, Feras Bader, Abdulla M Shehab, Said AlSaid, Khadim Sulaiman, Adel Khalifa, Hani Sabbour, Amr Badr, Basma Alzadjali, Haluk Alibazoglu, NOOSHIN BAZARGANI, Khaldoon Al Humood, Stefano Perlinin
Journal: Circulation (2020)

Background: There is a growing interest in raising awareness about amyloidosis as an under-recognized cause of heart failure and preserved ejection fraction (HFpEF). Recently, the prevalence of cardiac amyloidosis in the United States has increased, which may partly be attributed to initiatives from major professional societies aimed to improve patient identification and disease detection. Whether this has also impacted physicians’ knowledge about cardiac amyloidosis in the Middle East-Gulf region is unknown but critical to assess, as it would identify a need for dedicated regional educational activities. Methods: Physicians practicing in 5 Gulf countries (UAE, Bahrain, Qatar, Oman and Kuwait) were invited to participate in this anonymous, online survey by receiving a unique survey link by email. We assessed awareness of cardiac amyloidosis, knowledge of disease manifestations and approach to diagnosis. Responses to the survey were recorded using a 4- or 5-point Likert scale. Results: A total of 272 physicians participated in the survey. Most participating physicians were men (82%) and have been practicing cardiology (71%) for &gt;10 years (65%). Whereas 83% of responders considered themselves to be somewhat or extremely familiar with signs and symptoms of cardiac amyloidosis, only 63% would consider cardiac amyloidosis as a cause of HFpEF, 59% would consider it in patients with heart failure and orthostatic hypotension while only 39% consider cardiac amyloidosis in patients with low-flow, low-gradient severe aortic stenosis. Furthermore, cardiac MRI was found to be useful for diagnosis of cardiac amyloidosis by 92% of responders, while echocardiography, cardiac scintigraphy with bone-seeking radiotracers and biomarkers were felt to be useful by only 81%, 60% and 31% of survey participants, respectively. Conclusion: Despite perceived familiarity with cardiac amyloidosis among a group of mid-career cardiologists, there is need to raise awareness about the heterogenous manifestations of the disease and about the respective roles of testing modalities in making this diagnosis.
A Data-Driven Argument in Bioethics: Why Theologically Grounded Concepts May Not Provide the Necessary Intellectual Resources to Discuss Inequality and Injustice in Healthcare Contexts
Authors: Tomasz Żuradzki, Karolina Wiśniowska
Journal: The American Journal of Bioethics (2020)

This article refers to:There's No Harm in Talking: Re-Establishing the Relationship Between Theological and Secular Bioethics
Abstract 12910: Use of Optimal Medical Therapy in Patients With Cardiovascular Disease Undergoing Cardiac Rehabilitation
Authors: S Hammad Jafri, Pavel Huschsa, Gisele Bousquet, Sonis Lindsay, Lutfy Christine, Pranav Dorbala, Ron Blankstein, Christopher P Cannon, Jorge Plutzky, Donna Polk, Hicham Skali
Journal: Circulation (2020)

Introduction: Optimal Medical Therapy (OMT) in patients with Coronary Artery Disease (CAD) or Heart Failure (HF) is underused despite known benefits. The rate of OMT use among patients enrolled in Cardiac Rehabilitation (CR) is not well known. Purpose: To describe prevalence and characteristics of OMT use in patients with CAD or HF undergoing CR. Methods: CAD patients were defined as those with prior MI, PCI, CABG, or angina. OMT for CAD patients required all currently guideline-recommended medications (aspirin or antiplatelet, statins, beta-blockers (BB); and ACEi/ARB for concurrent HF or DM). The HF group included patients referred to CR for HFrEF or for another indication and had documented left ventricular systolic dysfunction (LVEF&lt;40%, echocardiography). OMT for HF required BB, spironolactone and either ACEi/ARB or Angiotensin Receptor Neprilysin Inhibitor (ARNI) use. Predictors of OMT were identified using with multivariable logistic regression. Results: From January 2015 to December 2019, 612 patients (mean age: 65, 23% female) with CAD were enrolled in CR, with 483 (79%) patients meeting all OMT criteria. CAD patients on OMT were more likely to have hypertension (85%), hyperlipidemia (94%) but less angina (8%). Prior MI, hypertension, hyperlipidemia, and 6-minute walk distance were significantly associated with OMT use.Of 131 HF patients (mean age: 64, 21% female) enrolled in CR, 23 (18%) met all 3 OMT criteria—99 (76%) and 128 (98%) patients met only 2 or 1 of OMT criteria, respectively. Use of spironolactone (least prescribed), ARNI, and ACEi/ARBs all increased over the study period. Study limitations include lack of control for contraindications to medications. Conclusion: Although it has improved over time, OMT use remains low (HF 18%, CAD 79%) among patients enrolled in CR. CR may represent a unique opportunity to enhance OMT use.
Abstract 15056: Machine Learning Prediction of Long QT Syndrome
Authors: Steven Simon, Divneet Mandair, Michael A Rosenberg, Premanand Tiwar
Journal: Circulation (2020)

Introduction: Drug-induced QT prolongation causes significant morbidity and mortality but could be preventable with prediction of susceptible individuals. Machine learning (ML) algorithms applied to electronic health record (EHR) data may provide a method for identifying these individuals and could be automated to directly alert providers of risk. This study applies ML techniques to EHR data to identify an integrated model that can be deployed to predict risk of drug-induced QT prolongation. Methods: We examined data from the UCHealth EHR that has been harmonized to the Observational Medical Outcomes Partnership common data model and identified inpatients who had received a medication known to prolong the QT interval and had an electrocardiogram (ECG) performed within 24 hours. We used a binary outcome of the development of a QTc interval &gt; 500 ms by ECG within 24 hours of medication initiation or no ECG with a QTc interval &gt; 500 ms throughout the encounter. We compared multiple machine learning methods (logistic regression, random forest, naïve Bayes, and deep neural network (DNN)) by classification accuracy as assessed by AUC and F 1 score. We performed calibration and scaling of the final model. Results: We identified 35639 inpatients who received a known QT-prolonging medication and had an ECG within 24 hours. Of those, 4558 patients developed a QTc &gt; 500 ms and 31081 patients did not. The DNN model provided reasonable classification accuracy (F1 score 0.404; AUC 0.71) and was the most accurate method tested. A range of decision cutpoints were plotted with respective sensitivity/specificity (Figure 1). Conclusions: We found that by applying a DNN to EHR data, we could reasonably predict individuals susceptible to drug-induced QT prolongation. Varying cutpoints can be used to tailor the model to the desired sensitivity. Future studies are needed to validate this model in novel EHRs and within the physician order entry system to assess ability to improve patient safety.
Abstract 15013: Ischemic Mitral Regurgitation is Associated With Impaired Transforming Growth Factor/Bone Morphogenic Protein Signaling and Increased CD45+ Cell Presence in the Mitral Valve Interstitial Cell Population
Authors: Estibaliz Castillero, Daniel P Howsmon, Bruno V Rego, Yingfei Xue, Robert C Gorman, Michael Sacks, Robert LEVY, Giovanni Ferrari
Journal: Circulation (2020)

Introduction: Ischemic mitral regurgitation (IMR) develops in a fraction of patients in response to left ventricular (LV) remodeling after ischemia. IMR independently predicts adverse events and doubles mortality. While largely driven by LV distortion, the susceptibility of the mitral valve (MV) to undergo remodeling may play a role in determining whether MR develops. We hypothesized that impaired cellular response in MV cells may contribute to MR development by inducing maladaptive tissue remodeling. Methods: Dorsett hybrid sheep (n=32) were subjected to ligation of the circumflex coronary artery to induce myocardial infarction (MI). Development of MR was reported by echocardiography. MV leaflets and isolated MV interstitial cells (MVIC) were collected at baseline (Control), 4-, and 8-weeks post MI. RNAseq (150 paired end reads, 20 million reads/sample) was performed on MV leaflets from all groups. MVICs were treated with for 24h with 10ng/ml TGFβ1 of 50ng/ml BMP4. Results: Gene set enrichment analysis using pre-defined gene sets from the Gene Ontology project, considering genes with significant changes (p&lt;0.05) between MV with/without MR showed enrichment of cardiac contraction biological processes. TGFβ/BMP-dependent SMAD7 was the main hub in the protein-protein-interaction network of the top contributing genes to the enriched pathways in MR. In vitro, collagen matrix-contracting ability of MR MVICs was higher than non-MR MI MVICs. MVICs from MI sheep were less responsive to BMP4 pro-osteogenic stimulation (as reflected by blunted increased in ID2, osteopontin and osteocalcin mRNA) than control. MVICs from sheep with MR had a diminished COL1A1 mRNA response to TGFβ1 and enhanced pro-chondrogenic RUNX2 and SOX9 mRNA response to BMP4 vs. non-MR MVICs. Baseline CD45 expression was detectable only in MR MVICs. Upon TGFβ1 stimulation, CD45 expression was detected in all groups. Immunostaining confirmed increased presence of CD45+ cells in IMR MV interstitium. Conclusions: MVs from sheep developing MR had altered TGFβ/BMP response, which may be partially mediated by increased CD45+ fibrocyte presence. Pharmacological strategies aimed to modulate TGFβ/BMP signaling after MI may protect from pathological MV remodeling leading to IMR.
Abstract PO-034: Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation
Authors: Valentina Pita-Grisanti, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Myrriah Chavez-Tomar, Samantha Terhorst, Sue Knoblaugh, Christopher Coss, Thomas Mace, Fouad Choueiry, Alice Hinton, Jennifer M Mitchell, Karen Basen-Engquist, Zobeida Cruz-Monserrate
Journal: Cancer Research (2020)

Abstract Background: Obesity is a risk factor for pancreatic ductal adenocarcinoma (PDAC), a deadly disease with no preventive strategies. Lifestyle interventions to decrease obesity might serve to prevent obesity-induced PDAC. We examined whether decreasing obesity via increased physical activity (PA) and/or diet-induced weight loss could prevent PDAC in mice and compared the levels of systemic inflammatory-associated cytokines in human subjects undergoing a PA intervention. Methods: Obesity-induced PDAC mouse models were exposed to various interventions before and after cancer initiation, that included increased PA, diet-induced weight loss, and/or chemotherapy. We evaluated body composition, tumor progression, growth, fibrosis, and inflammation. Circulating inflammatory-associated cytokines of overweight/obese human subjects before and after a PA intervention were also compared. Results: Genetically engineered PDAC mice on a PA intervention while on a HFD, gained less weight, displayed lower grade pancreatic intraepithelial neoplasias lesions, and fewer mice developed PDAC compared to controls. Similar results were observed in PDAC mice given a HFD to induce obesity, prior to a control diet (CD) and PA intervention, compared to mice given a CD after the HFD. PA alone or with a CD intervention decreased body weight but did not prevent tumor growth in an orthotopic mouse model of PDAC. PA combined with chemotherapy increased the percentage of splenic cluster of differentiation 8+ (CD8+) T cells in PDAC mice. Finally, PA prevented the increase of systemic inflammatory-associated cytokines in PDAC mice and in overweight/obese control human subjects. Conclusions: PA alone or with diet-induced weight loss delayed the progression of PDAC in genetically engineered mice and reduced inflammation. While these interventions did not prevent tumor growth in the orthotopic mouse model, it did modulate immune responses. Reducing obesity by increasing PA and decreasing dietary fat intake could be a way of reducing the incidence of PDAC in high-risk obese individuals. Citation Format: Valentina Pita-Grisanti, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Myrriah Chavez-Tomar, Samantha Terhorst, Sue Knoblaugh, Christopher Coss, Thomas Mace, Fouad Choueiry, Alice Hinton, Jennifer M Mitchell, Karen Basen-Engquist, Zobeida Cruz-Monserrate. Increased physical activity delays development of obesity-induced pancreatic ductal adenocarcinoma in mice and modulates inflammation [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-034.
Abstract 13645: Cardiologist Evaluation of Patients With Type 2 Myocardial Infarction
Authors: Cian P McCarthy, David S Olshan, Saad Rehman, Maeve Jones-O’Connor, Sean Murphy, Joshua A Cohen, Jinghan Cui, Avinainder Singh, Muthiah Vaduganathan, James L Januzzi, Jason H Wasfy
Journal: Circulation (2020)

Introduction: Type 2 myocardial infarction (T2MI) is common and associated with recurrent cardiovascular events. How often T2MI patients are evaluated by a cardiologist and the association between these evaluations and diagnostic testing and treatments are unknown. Hypothesis: T2MI patients evaluated by a cardiologist are more likely to undergo cardiovascular testing and be placed on therapies for ischemic heart disease (IHD). Methods: We identified adjudicated patients with T2MI at Massachusetts General Hospital between October 2017 and May 2018. We examined baseline characteristics, diagnostic testing performed, and discharge medications, stratified by cardiologist evaluation during their admission. Results: We identified 359 patients with T2MI. During admission, 207 patients (57.7%) were evaluated by a cardiologist; 120 (33.4%) received a cardiology consultation and 87 (24.2%) were admitted to a cardiology service. Patients evaluated by a cardiologist were more likely to have hyperlipidemia (67.1% vs 52%, p=0.005), known CAD (58.9% vs. 38.8%, p&lt;0.001), prior MI (27.1% vs. 14.5%, p=0.006), and HF (56.5% vs. 44.1%, p=0.03). Patients evaluated by a cardiologist were more likely to undergo stress testing (13.5% vs 3.3%, p=0.002), transthoracic echocardiography (80.2% vs. 50.7%, p&lt;0.001), and coronary angiography (21.3% vs. 0%, p&lt;0.001) during their index admission. There was no difference in mortality among those who were or were not evaluated by a cardiologist (11.6% vs. 9.2%, p=0.58). Patients evaluated by a cardiologist were more likely to be discharged on a statin (74.5% vs 64.5%, p=0.04) and a beta blocker (72% vs. 55.9%, p=0.002). Only new prescriptions of beta blockers were more commonly prescribed among those evaluated by a cardiologist (20.3% vs. 7.9%, p=0.002). Among those with available follow-up data (N=289), 111 patients (38.4%) had an outpatient cardiology follow-up visit within 6 months of discharge. Conclusions: Fewer than 60% of patients with T2MI were evaluated by a cardiologist during their admission and those that did were more likely to undergo further cardiovascular testing and to be discharged on therapies for IHD. Most T2MI patients did not have an outpatient cardiology follow-up visit after their event.
Macrolide and Nonmacrolide Resistance with Mass Azithromycin Distribution
Authors: Thuy Doan, Lee Worden, Armin Hinterwirth, Ahmed M. Arzika, Ramatou Maliki, Amza Abdou, Lina Zhong, Cindi Chen, Catherine Cook, Elodie Lebas, Kieran S. O’Brien, Catherine E. Oldenburg, Eric D. Chow, Travis C. Porco, Marc Lipsitch, Jeremy D. Keenan, Thomas M. Lietman
Journal: New England Journal of Medicine (2020)

Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear.