tbuckley/cabot-search huggingface dataset:
Abstract 10633: Deep Learning Model Accurately Quantifies LA Volumes on Routine Non-Contrast Chest CTs and Predicts Adverse Outcomes
Authors: Gilberto Aquino, Jordan Chamberlin, Megan Mercer, Madison Kocher, Ismail Mikdat Kabakus, Selcuk Akkaya, Matthew Fiegel, Sean Brady, Nathan Leaphart, Andrew Dippre, Vincent Giovagnoli, Basel Yacoub, Athira Jacob, Mehmet Gulsun, Pooyan Sahbaee, Puneet Sharma, Jeffrey Waltz, Joseph Schoepf, dhiraj baruah, Tilman Emrich, Stefan Zimmerman, Ali Agha, Jeremy R Burt
Journal: Circulation (2021)

Introduction/Hypothesis: To develop and validate a deep learning model to automatically segment and measure left atrial (LA) volumes from routine noncontrast chest CTs and evaluate for outcomes prognosis. Methods: A prototype AI algorithm, with a conditional variational auto-encoder architecture, was initially developed and trained using training data from 1313 patients (paired CTA and non-contrasted exams; “training group”). Left atrium contours from contrasted cases were used to train the model on corresponding non-contrasted dataset. We then retrospectively evaluated 274 patients (mean age 67.9 years, 54.6% male, 57.2% caucasian) who underwent a routine non ECG-gated, noncontrast chest CT for coronary artery calcium or lung cancer screening for validation of the AI model (“validation group”). Outcomes included heart failure (HF) hospitalization and new-onset atrial fibrillation within 5 years. Simple logistic regressions with appropriate univariate statistics were used for modelling outcomes. Results: In the validation group, there was excellent correlation between AI and expert results with a LA volume index (LAVi) intraclass correlation coefficient of 0.950 (0.936-0.960). Bland-Altman plot demonstrated that the AI underestimated LAVi by a mean 5.86 mL/m2. AI-LAVi independently predicted new-onset atrial fibrillation (AUC = 0.855, OR = 1.12, 95% CI 1.08 - 1.18; p&lt;0.0001). AI-LAVi was independently associated with HF hospitalization (AUC = 0.903, OR = 1.08, 95% CI 1.04 - 1.13, p = 0.0009). Conclusion: In this large validation cohort, AI for automated measurement of LA volume on routine noncontrast chest CTs had excellent agreement with manual quantification. AI-LAVi is independently predictive for new-onset atrial fibrillation and HF hospitalization within 5 years.
Abstract 9290: Relationship Between Body Weight and Pharmacokinetics of Apixaban in Patients With Atrial Fibrillation: Insights from the ARISTOTLE Trial
Authors: Josephine Harrington, Anna Giczewska, Daniel Wojdyla, Jeffrey B WASHAM, Marat Fudim, Ziad Hijazi, Renato D Lopes, Elaine Hylek, Stefan H Hohnloser, Shinya Goto, Maria Bahit, Lars C Wallentin, Christopher B Granger, John H Alexander
Journal: Circulation (2021)

Introduction: Apixaban dosing in atrial fibrillation (AF) is 5 mg BID or 2.5 mg BID in patients with ≥2 dose-reduction criteria: age &gt;80 years, weight &lt;60 kg, or creatinine &gt;1.5 mg/dl. There is a question of whether drug monitoring might be useful to guide dosing, particularly in patients with extremely high or low body weight (BW). Previous work has demonstrated that the effects of apixaban versus warfarin are similar across BWs. We aimed to investigate the relationship between BW and exposure to apixaban in patients with AF. Methods: Exposure to apixaban was assessed as area under the curve steady state (AUC SS ) using population pharmacokinetics (PK) data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. The relationship between BW and AUC SS was assessed continuously and by BW categories of ≤60kg, &gt;60-120kg, or &gt;120kg overall and by apixaban dose. Results: Of patients with PK data (n=2924), 8.9% were ≤60kg, and 5.8% &gt;120kg. Compared to the overall group, patients ≤60kg were more likely to be older (74 vs 70 years), female (67 vs 33%), had lower creatinine (0.92 vs 1.02 mg/dL) and higher CHA 2 DS 2 -VASc scores (3.9 vs 3.4). There was a weak but significant correlation between BW and AUC SS assessed continuously (correlation -0.38, p&lt;0.001) and by BW group: ≤60kg [median AUCSS 4089 (25 th 3073, 75 th 5148 ng•hr/ml)], &gt;60-120kg [3566 (2926, 4286 ng•hr/ml)], and &gt;120kg [2699 (2284, 3226 ng•hr/ml)] (p&lt;0.001) (Figure). This relationship persisted with stratification by apixaban dose (data not shown). Conclusions: There is a significant relationship between body weight and predicted exposure to apixaban, including at the extremes of BW, but with wide variation in exposure at every weight. This variation, and the absence of an association between body weight and apixaban’s observed safety and efficacy compared with warfarin, make it unlikely that routine therapeutic monitoring of apixaban will be clinically useful.
Abstract 10706: Alpha Aminoadipic Acid Down-Regulates Sr-bi Abca1 and Abcg1 Expression and May Regulate Plasma Lipid Profiles, Cellular Cholesterol Efflux, and Efferocytosis
Authors: Chuan Wang, Doran Amanda C, Macrae F Linton, Ferguson Jane
Journal: Circulation (2021)

Introduction: The metabolite α-aminoadipic acid (2-AAA) has been identified as a predictor of diabetes and atherosclerosis in large human prospective studies. However, the mechanisms linking this metabolite to disease pathophysiology remain unknown. Efferocytosis, a macrophage-mediated process for clearance of apoptotic cells (ACs), is critical in preventing necrosis of dead cells and triggers anti-inflammatory and pro-resolving responses in phagocytes. Cholesterol efflux from peripheral cells in atherosclerotic plaque is a critical step in Reverse Cholesterol Transport (RCT). We hypothesized that the 2-AAA pathway relates to atherosclerosis through modulation of plasma lipid profiles, cholesterol efflux, and macrophage efferocytosis. Results: We found a significant negative correlation between plasma 2-AAA and HDL cholesterol (r=-0.53, P&lt;0.0001), and a significant positive correlation with triglycerides (r=0.35, P=0.006), in two separate samples of individuals with and without cardiometabolic disease (N=98), suggesting a relationship between 2-AAA and cardiovascular risk. We investigated the consequences of 2-AAA stimulation in several primary cells and cell lines. We found that 2-AAA stimulation downregulates three key genes (SR-BI (up to 86% reduction, P=0.005), ABCA1 (up to 92% reduction, P=0.007), ABCG1 (up to 94% reduction, P=0.008)) that directly relate to cholesterol efflux in THP-1 macropohages, suggesting an important role of 2-AAA in cholesterol efflux. Next, we found that treatment with 2-AAA at physiologically-relevant doses (30μM and 100μM) for times ranging from 30 minutes to 6 hours led to consistent reductions of efferocytosis of up to 60% (P&lt;0.001) in mouse macrophages, J774 cells and Raw 264.7 cells, suggesting a pivotal role of 2-AAA in efferocytosis. Conclusions: Our data suggest 2-AAA is associated with plasma lipid profiles (HDL, triglycerides), cholesterol efflux, and macrophage efferocytosis. These novel data could provide a new target for the treatment of atherosclerosis.
REALM (OP-RW001): Comparing the Characteristics and Clinical Outcomes of Patients with Relapsed/Refractory Multiple Myeloma in the Real World to Patients Receiving Melflufen in the Horizon Study
Authors: Sikander Ailawadhi, Ching-Kun Wang, Andrew J. Belli, Catarina Jansson Blixt, Diana Cripps, Stojan Zavisic, Karthik Ramasamy
Journal: Blood (2021)
Abstract P418: Transcriptomic And Genomic DNA Accessibility Dynamics During Differentiation Of Induced Pluripotent Stem Cells Derived Smooth Muscle Cells And Acquisition Of Contractile Phenotype
Authors: LU LIU, Adrien Georges, Nabila Bouatia-Naji
Journal: Circulation Research (2021)

Introduction: Smooth muscle cells (SMCs) capacity to phenotype switching between proliferative and quiescent (contractile) is a widely studied mechanism in cardiovascular disease. Primary SMCs tend to lose many physiological features in culture, which makes the study of their contractile function challenging. Recently, an optimized protocol of induced pluripotent stem cells (iPSCs) differentiation into contractile SMCs was described. Here we aimed at defining the transcriptomic and open chromatin dynamics during the acquisition of SMCs phenotypes. Methods: We differentiated 4 human iPSC lines (2 males, 2 females) towards either contractile (Repsox induced) or synthetic (PDGF-BB/TGF-β induced) SMC phenotypes using a 24-days protocol. We performed RNA-Seq and assay for transposase accessible chromatin (ATAC)-Seq at 5 time points of differentiation. We analyzed gene expression profiles and compared them to existing dataset of human aorta by principle component analyses (PCA) and gene set enrichment analyses using GO terms. Results: iPSCs derived SMCs showed expected morphology and positive expression of SMC markers. Synthetic SMCs (SSMCs) exhibited greater capacity of proliferation, migration and lower calcium release capacity, compared to contractile SMCs (CSMCs). RNA-Seq results showed that multiple genes involved in the contractile function of arteries, including myosin light chain kinase (MYLK) and angiotensin type 1 receptor ( AGTR1 ) genes were highly expressed in CSMCs compared to SSMCs. Overall, CSMCs conserved SMC properties beyond 24 days and their gene expression profile clustered near human aorta. During late differentiation stages, CSMCs showed an upregulation of genes involved in cardiovascular system development, whereas genes involved in cell stress were upregulated in SSMCs. Conclusions: We describe global genomic profiles of iPSCs derived CSMCs that presented comparable gene expression profiles to mature artery tissue. Combination with upcoming DNA accessibility maps is expected to allow the functional exploration of genetic risk variation involved in several arterial diseases involving the impairment of the SMCs contractile function.
Abstract P458: Myosin Light Chain Dephosphorylation By Ppp1r12c Promotes Atrial Hypocontractility In Atrial Fibrillation
Authors: Francisco J Gonzalez-Gonzalez, Srikanth Perike, Frederick Damen, Andrielle Capote, Katherina M Alsina, Benjamin Levin, Arvind Sridhar, Jacob Grand, Jody Martin, Joseph Akar, Chad M Warren, John Solaro, Dawood Darbar, Craig Goergen, Beata M Wolska, Xander H Wehrens, Mark McCauley
Journal: Circulation Research (2021)

Introduction: Atrial fibrillation (AF), is the most common sustained arrhythmia, with an estimated prevalence in the U.S. of 2.7 million to 6.1 million and is predictive to increase to 12.1 million in 2030. AF increases the chances of a thromboembolic stroke in five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function in AF remains unknown. Objective: The overexpression of PPP1R12C, causes hypophosphorylation of atrial myosin light chain 2 (MLC2a), decreasing atrial contractility. Methods and Results: Left and right atrial appendage tissues were isolated from AF patients versus sinus rhythm (SR). To evaluated the role of PP1c-PPP1R12C interaction in MLC2a de-phosphorylation we used Western blots, coimmunoprecipitation, and phosphorylation assays. In patients with AF, PPP1R12C expression was increased 3.5-fold versus SR controls with an 88% reduction in MLC2a phosphorylation. PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF. In vitro studies of either pharmacologic (BDP5290) or genetic (T560A) PPP1R12C activation demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Additionally, to evaluate the role of PPP1R12C expression in cardiac function, mice with lentiviral cardiac-specific overexpression of PPP1R12C (Lenti-12C) were evaluated for atrial contractility using echocardiography, versus wild-type and Lenti-controls. Lenti-12C mice demonstrated a 150% increase in left atrium size versus controls, with reduced atrial strain and atrial ejection fraction. Also, programmed electrical stimulation was performed to evaluate AF inducibility in vivo. Pacing-induced AF in Lenti-12C mice was significantly higher than controls. Conclusion: The Overexpression of PPP1R12C increases PP1c targeting to MLC2a and provokes dephosphorylation, that cause a reduction in atrial contractility and increases AF inducibility. All these discoveries advocate that PP1 regulation of sarcomere function at MLC2a is a main regulator of atrial contractility in AF.
Abstract 10109: High Prevalence and Significant Impact of Arrhythmias on Healthcare Resource Utilization in Hospitalizations of Patients with Prior (corrected) Congenital Heart/Circulatory Disease
Authors: Dipen Zalavadia, Srija Shanker, Ashish Nepal, Bushra Fatima, Tanvi Singla, Aamer R Mohammad, Deepu Joseph, Sonali Sachdeva, Rupak Desai
Journal: Circulation (2021)

Introduction: Even after surgical correction, adults with a previously corrected Congenital Heart Disease (CHD) may remain at a significantly elevated risk of arrhythmias. However, there is not much known about the prevalence, comorbidity burden, and impact of arrhythmia in these patients. Methods: Using the National Inpatient Sample (2015 Oct-2017), adult admissions with previously corrected CHD were identified. The primary outcome was the prevalence of arrhythmia and secondary outcomes included comorbidities and outcomes between the arrhythmic vs. non-arrhythmic cohort. Results: Of 19,395 admissions with previously corrected CHD, 7675 (39.6%) patients experienced arrhythmias [median age 55 (39-68) years, male 51.7%, white 75%] (Table 1). The arrhythmic cohort often consisted of relatively older, male, white patients and had higher rates of hypertension (56.4% vs. 41%), hyperlipidemia (33.1% vs. 23%), diabetes (9% vs. 6.5%), renal failure (14% vs. 7.8%), and congestive heart failure (17.6% vs. 9.2%) compared to the non-arrhythmic cohort. The arrhythmic cohort had a higher frequency of patients with at least one CVD risk factor (75.5% vs. 65.4%). All-cause mortality was non-significantly higher in the cohort with arrhythmia (1.6% vs. 1.3%). Furthermore, the arrhythmic cohort was less often routinely discharged and had more frequent transfers/home healthcare requirements, prolonged hospital stay, and higher hospital charges. Conclusions: Nearly 40% of admissions among patients with a prior history of surgically corrected CHD experienced arrhythmias which were associated with a considerably higher comorbidity burden and healthcare resource utilization with non-significantly higher all-cause mortality.
Medical Violence
Authors: Ian Jenkins
Journal: Annals of Internal Medicine (2021)

On Being a DoctorOctober 2021Medical ViolenceIan Jenkins, MDIan Jenkins, MDUniversity of California, San Diego, San Diego, CaliforniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-2188 Audio Reading - “Medical Violence” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Medical Violence” by Ian Jenkins, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail His name was one of these: Raul, Ryan, or Rakim. It doesn't matter. The sheriff's deputy sat him on the edge of the examination table and left. He was the last patient of my shift at a county jail. The 22-year-old man sat there, waiting for me to initiate the encounter, taking disturbingly fast, deep breaths.“Whoa, what's happening?” I asked.“Diabetic,” he panted. “Been asking for insulin since I got arrested.”I asked for a fingerstick blood sugar while I interviewed him. He had one problem: a 5-year history of type 1 diabetes. He took long-acting insulin and four ... Author, Article, and Disclosure InformationAffiliations: University of California, San Diego, San Diego, CaliforniaCorresponding Author: Ian Jenkins, MD, Department of Medicine, University of California, San Diego, 200 West Arbor Drive, MC 8485, San Diego, CA 92123; e-mail, [email protected]ucsd.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Medical Violence” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “Medical Violence” by Ian Jenkins, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics October 2021Volume 174, Issue 10Page: 1472-1473 ePublished: 19 October 2021 Issue Published: October 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Publication Productivity and Bibliometric Profiling—A Potentially Gender-Biased Approach—Reply
Authors: Torbjorg Holtestaul, Jason Bingham, Christopher Yheulon
Journal: JAMA Surgery (2021)

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Abstract 14477: Meta-Analysis of Studies Comparing Multivessel Percutaneous Coronary Intervention and Culprit Vessel Only Intervention Among Patients With Acute Myocardial Infarction and Cardiogenic Shock
Authors: Gauravpal S Gill, Jorge Sanz Sanchez, Waiel Abusnina, Arun K Kanmanthareddy, Hector Garcia-Garcia
Journal: Circulation (2021)

Background: Studies investigating mortality and adverse event outcomes in patients presenting with acute myocardial infarction (MI) in cardiogenic shock (CS) have reported conflicting results, and have primarily included patients with ST elevation MI. This meta-analysis investigates appropriate revascularization strategy in these patients. Methods: PubMed, Google Scholar, CINAHL and Cochrane databases were queried for studies comparing multivessel (MV) percutaneous coronary intervention (PCI) and culprit vessel (CV) PCI in patients with MI in CS. Data on outcomes from the selected studies were extracted and analyzed by means of random effects model. Two tailed p-value less than 0.05 was considered significant. Heterogeneity was assessed using I 2 test. Results: Twelve studies were included in the final analysis. There was no significant difference in short-term (OR 0.95, 95% CI [0.90-1.01]; p=0.09) or long-term (1.16 [0.95-1.41]; p=0.14) mortality between MV PCI and CV PCI ( Figure) . Similarly, the odds of reinfarction (1.04 [0.58-1.85]; p=0.90) and stroke (1.08 [0.88-1.33]; p=0.46) were similar between the two groups. Although patients with MV PCI had lower odds of revascularization (0.46 [0.34-0.62]; p&lt;0.01), they carried higher odds of new renal replacement therapy (1.30 [1.14-1.48]; p&lt;0.01) and bleeding (1.25 [1.14-1.36]; p&lt;0.01). Interestingly, on exclusion of study exclusively containing patients with non-ST elevation MI, odds of short-term mortality were higher (1.44 [1.28-1.62]; p&lt;0.01) in the MV PCI group. Conclusions: Among patients with AMI and cardiogenic shock, there was no difference observed in short-term or long-term all-cause mortality, between MV PCI and CV PCI revascularization strategies. However, adopting the MV PCI strategy may lead to higher odds of bleeding and renal replacement therapy.
Functional Genomic Landscape of Natural Killer Cell Evasion in Multiple Myeloma
Authors: Sara Gandolfi, Olli Dufva, Jani Huuhtanen, Olga Dashevsky, Jay Klievink, Jonas Bouhlal, Michal Sheffer, Matti Kankainen, Ricardo De Matos Simoes, Satu Mustjoki, Constantine S. Mitsiades
Journal: Blood (2021)
Abstract 11557: Rates of Early Target Vessel Revascularization and Target Lesion Revascularization Amongst Third Generation Drug-Eluting Stents
Authors: Christopher Chew, Michael Hendrickson, Hannan Yang, George A Stouffer, Joseph Rossi
Journal: Circulation (2021)

Background: While the benefits of drug-eluting stents (DES) during percutaneous coronary intervention (PCI) are well established, the frequency and timing of repeat revascularization events, particularly early events, is not well described in contemporary clinical practice. Methods: Patients undergoing PCI at two large tertiary centers in a single health system from April 2014 to December 2019 were prospectively enrolled into the NCDR CathPCI Registry. Target vessel revascularization (TVR) and target lesion revascularization (TLR) were defined as a repeat intervention to the index vessel or lesion respectively and determined by linking to subsequent PCI events and CABG admissions in the EMR. Early TVR and TLR rates were identified at 30 days, 90 days, six months, and one year. Logistic regression was used to estimate the association between stent type and TVR/TLR at the pre-specified time points. Generalized estimating equations with nested modeling were used to account for patients with multiple vessels and lesions. Results: Overall, 8,221 PCI procedures were identified in 7,128 patients with 9,558 vessel interventions and 12,019 lesion interventions. There were similar rates of TVR for Zotarolimus eluting durable polymer stents (ZES-DP), Everolimus eluting bioabsorbable polymer stents (EES-BAP), and Everolimus eluting durable polymer stents (EES-DP) at 30 days (p=0.61), 90 days (p=0.79), six months (p=0.58), and one year (p= 0.35). There were similarly no differences in TLR between stent types at each time point (p= 0.57, 0.79, 0.16, 0.13 respectively). The total rates of TLR and TVR progressed linearly throughout the year following PCI with nearly half of all repeat revascularization events occurring within 6 months. Table 1. Conclusions: Within a single health system from 2014 to 2019, ZES-DP, EES-BAP, and EES-DP were associated with similar rates of TVR and TLR. These events appear to occur earlier than typically reported in clinical trials.