tbuckley/cabot-search huggingface dataset:
Abstract 11520: Cost-Related Medication Nonadherence in Adults with Diabetes Mellitus in the United States
Authors: Mohamad Taha, Javier Valero Elizondo, Cesar Caraballo, Tamer Yahya, Rohan Khera, Priyanka Satish, Isaac Acquah, Kobina Hagan, Kershaw Patel, Elias Mossialos, Miguel Cainzos Achirica, Khurram Nasir
Journal: Circulation (2021)

Background: Health-related expenditures due to diabetes mellitus (DM) are rising in the US. Medication nonadherence is associated with worse health outcomes, particularly among individuals with DM who require uninterrupted treatment. We sought to determine whether patients with DM in the US report cost-related nonadherence (CRN), a potential consequence of rising drug costs. Methods: We used the National Health Interview Survey (2013-18), a nationally representative study, to identify participants with and without self-reported DM. Participants were considered to have experienced CRN if during the preceding year they reported skipping doses, taking less medication, or delaying filling a prescription to save money. Results: Of the 20,326 participants with DM, a weighted 14% (or 3 million annually) experienced CRN, including 9.5% skipping doses, 9.9% taking less medicine, and 11.8% delaying prescription filling to save money. Compared to those without DM (N=145,186), participants with DM reported a higher prevalence of CRN, with the largest differences being observed among non-elderly adults (Figure). Among non-elderly adults with DM, a weighted 19.4% (or 2.3 million annually) reported CRN. In multivariable logistic regression models, the main drivers of CRN among participants with DM were lack of insurance (OR 4.34, 95% CI 3.49, 5.39), younger age (OR 3.43, 95% CI 2.65, 4.44), low income (OR 1.82, 95% CI 1.58, 2.09), use of insulin (OR 1.19, 95% CI 1.04, 1.35), and unfavorable risk factor profile (OR 1.53, 95% CI 1.21, 1.93) (Table). Conclusion: In the US, 1 in 7 adults with DM reported CRN, and the burden was highest among non-elderly adults. Cost represents a serious barrier for therapy adherence among individuals with DM in the US, particularly among the most vulnerable. Removing financial barriers to accessing medications may improve adherence to essential therapies among individuals with DM, and ultimately improving outcomes.
Abstract 14261: Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia: A Standardized Mapping System Protocol
Authors: Francesca Bulian, Massimiliano Manfrin, Werner Rauhe
Journal: Circulation (2021)

Introduction: according to European guidelines, ablation has become the treatment of choice in patients with symptomatic atrioventricular nodal reentry tachycardia (AVNRT). Despite the high procedure success rate, anatomical variations can affect the outcome in terms of relapses and complications. As recently demonstrated, low-voltage bridge visualization allows low pathway identification and therefore a new ablation strategy. Hypothesis: our purpose was the validation of standardized ablation protocol within the low-voltage bridge area. Methods: 70 consecutive patients with inducible AVNRT were evaluated and a three-dimensional voltage map of the right atrial septum and Koch Triangle was constructed by means of contact mapping. Ablation site was identified as the low-voltage area below the His bundle, adjusting the high-voltage slider to 1,5 mV and dynamically adjusting the slider of low-voltage. Radio-frequency energy (with an average number of nine lesions per patient) was then delivered within this area until the appearance of junctional beats. The results were tested at the end of the procedures and during the observational period (the mean follow-up was 10,5 months). Results: the slow pathway was identified by the low-voltage bridge in 60 patients (85,6%) and in these patients, the target lesions in that area finally prevented induction of AVNRT in 100% of cases. A zero-fluoroscopy approach was possible for 50 patients (83%). Compared with standard AVNRT ablation, no complications as well as no statistical differences in terms of total procedure time were observed (p=0,056). 59 patients (98%) had no relapses during the follow-up. Conclusions: voltage gradient mapping successfully targeted the slow pathway in most of our cases. Lesions on the voltage bridge led to effective ablation of AVNRT and to a drastic x-ray exposure reduction in the absence of acute or long-term complications.
TAMI-60. MODULATION OF CELL BIOMECHANICS THROUGH GUIDANCE RECEPTOR PLEXIN-B2 FACILITATES GLIOBLASTOMA INFILTRATION
Authors: Roland Friedel, Yong Huang, Rut Tejero, Chrystian Junqueira Alves, Concetta Brusco, Theodore Hannah, Vivian Lee, Guohao Dai, Hongyan Zou
Journal: Neuro-Oncology (2021)

Abstract Infiltrative growth is a major cause of the high lethality of malignant brain tumors such as glioblastoma (GBM). The study of the contribution of biomechanical processes to GBM invasion is an emerging field. We show here that GBM cells upregulate the guidance receptor Plexin-B2 to gain invasiveness by modulating their biomechanical properties. Deletion of Plexin-B2 in GBM stem cells limited tumor spread and shifted invasion paths from axon fiber tracts to perivascular routes. On a cellular level, Plexin-B2 adjusts cell adhesiveness, migratory responses to different matrix stiffness, and actomyosin dynamics, thus empowering GBM cells to leave stiff tumor bulk and infiltrate softer brain parenchyma. Correspondingly, gene signatures affected by Plexin-B2 were associated with locomotor regulation, matrix interactions, and cellular biomechanics. On a molecular level, the intracellular Ras-GAP domain contributed to Plexin-B2 function, while the signaling relationship with downstream effectors Rap1/2 appeared variable between GBM stem cell lines, reflecting intertumoral heterogeneity. Our studies have established Plexin-B2 as a modulator of cell biomechanics that is usurped by GBM cells to gain invasiveness. Ongoing investigations focus on the regulation of the biomechanical properties of cell membrane and cell actomyosin cortex through plexins that provide GBM cells with the mechanical dynamics to penetrate to restricted space.
Diffuse Large B Cell Pdtx in Humanized Mice Are Valuable Models to Study Host-Lymphoma Interactions and Immune-Modulating Agents
Authors: Giorgia Zanetti, Giuseppina Astone, Luca Cappelli, William Chiu, Maria Teresa Cacciapuoti, Clarisse Kayembe, Danilo Fiore, Wayne Tam, Joseph Scandura, Silvana Di Giandomenico, Lorenzo Galluzzi, Lisa Giulino Roth, Giorgio Inghirami
Journal: Blood (2021)
Abstract 9856: Associations of a Polygenic Risk Score (PGS) with High Risk Coronary Artery Disease (CAD) in PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain)
Authors: Jonathan D Newman, Pamela S Douglas, Ilya Zhbannikov, Maros Ferencik, Borek Foldyna, Udo Hoffmann, Svati H Shah, Geoffrey S Ginsburg, Michael T Lu, Deepak Voora
Journal: Circulation (2021)

Introduction: PGSs summarize the polygenic risk for CAD and may have clinical utility. We tested whether a previously validated PGS for CAD is associated with coronary CT angiography (CTA) findings predictive of future cardiovascular events in the PROMISE trial, which randomized individuals with stable outpatient chest pain to standard of care vs. CTA. Methods: This nested case-control study compared genotyped PROMISE participants with no CAD (0% stenosis), obstructive CAD (oCAD, ≥50% stenosis) or high-risk CAD defined as either oCAD ≥70% stenosis, CAC &gt;400, Leaman Score &gt; 5 (measure of stenosis and plaque burden), or any high-risk plaque feature (positive remodeling, low attenuation, napkin ring sign) on CTA. The Illumina Global Screening Array with imputation from the 1000 Genomes reference panel was used with LDpred to calculate ancestry-adjusted PGS. We calculated adjusted odds ratios (aORs) of oCAD and high-risk CAD for PGS quintiles 2-5 with quintile 1 as the referent using logistic regression and age, sex, and European Society of Cardiology pre-test probability (PTP) for obstructive CAD as covariates. Results: Among the 518 participants, 414=no CAD, 86=oCAD, and 103=high risk CAD (overlap of oCAD and high-risk CAD=85), the median age (±S.D.) was 58 (±7) years, 58% were female, and 13% were of non-white race or Hispanic ethnicity. Baseline characteristics, family history of premature CAD, PTP risk score and medications were similar across PGRS quintiles (all P&gt;0.2). After multivariate adjustment, PGRS quintile 5 was associated with significantly increased odds of oCAD ≥50% (aOR 6.09) and high-risk CAD (aOR 6.13) as compared with quintile 1. Conclusions: In a population of stable symptomatic outpatients, higher PGS was associated with oCAD and high-risk CAD on CTA, even after adjustment for age, sex and pretest probability of CAD. The PGS may be useful for risk stratification of outpatients with suspected CAD.
Abstract 10455: HFA-PEFF Score: A Prognostic Value in Heart Failure with Preserved Left Ventricular Ejection Fraction Patients
Authors: Koichi Egashira, Kenichi Tsujita, Eiichiro Yamamoto, Daisuke Sueta
Journal: Circulation (2021)

Introduction: The HFA-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved left ventricular ejection fraction (HFpEF). This study aimed to evaluate the relationship between the score and cardiovascular outcomes in HFpEF patients. Methods: 505 consecutive HFpEF patients were prospectively observed for up to 1,500 days or until the occurrence of cardiovascular events. Cardiovascular outcomes were compared between the HFA-PEFF score 0-4 group (low-intermediate score group) and the HFA-PEFF score 5-6 group (high score group). Overall, 237 cardiovascular events were observed during the follow-up period (median: 1,154 days). Results: Kaplan-Meier analysis showed that there was no significant difference about composite cardiovascular events between low-intermediate score group and high score group (P=0.251), whereas the high score group was at higher risk of HF-related events than the low-intermediate score group (P&lt;0.001). Multivariable Cox proportional hazards analysis with the significant factors from the univariate analysis showed that the HFA-PEFF score (hazard ratio: 1.20, 95% confidence interval: 1.01-1.42, P=0.036) significantly predicted future HF-related events. Receiver operating characteristic analysis showed that the HFA-PEFF score significantly predicted HF-related events (area under the curve, 0.634; 95% CI, 0.575-0.693; P&lt;0.001). The cutoff HFA-PEFF score was 4.5 for the identification of HF-related events. Decision curve analysis revealed that combining HFA-PEFF score with conventional prognostic factors ameliorated risk-prediction of HF-related events. Conclusions: HFA-PEFF score may be useful for predicting HF-related events in HFpEF patients.
Abstract 12174: Valsartan Protects Both Cardiac and Lung Cells From SARS-CoV-2 Infection
Authors: Francesca Bastaroli, Manuela Mura, JOSE' CAMILLA SAMMARTINO, alessandro ferrari, MARZIA CORLI, Chiara Guarona, Elena Percivalle, Massimiliano Gnecchi
Journal: Circulation (2021)

Background: Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) disease (COVID-19) mainly affects the respiratory system, but cardiac complications occur very often. SARS-CoV-2 entry in host cells is mediated by the interaction between the viral Spike (S) glycoprotein and the host angiotensin-converting enzyme 2 (ACE2). The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) might influence the expression of ACE2 and viral infection, but not much is known about these interactions. Aim: To evaluate the effects of ACEIs and ARBs during active viraemia. Methods: We tested the ACEI Lisinopril (at 100nM and 500nM) and the ARB Valsartan (at 10uM and 50uM) for one week on two cell types: cardiomyocytes derived from hiPSC (hiPSC-CMs) as heart model and a lung epithelial cancer cell line (16HBE) as pulmonary model. The SARS-CoV-2 wild strain was inoculated in the two treated cell types for one hour. Cell viability was measured 72 hours after infection. Supernatants were collected and titrated to verify the presence of infectious virus using a micro-neutralization assay on VERO-E6 cells. Levels of ACE2 mRNA and protein content on cell lysates were quantified after each treatment by RT-qPCR and western blot, respectively. Results: ACEI and ARB at both concentrations affected the viability of neither hiPSC-CMs nor 16HBE cells in the absence of virus. Vice versa, viral infection significantly decreased viability of both hiPSC-CMs (-46%; p&lt;0,01) and 16HBE (-19%; p&lt;0,05). Viral titration revealed that SARS-CoV-2 replicated in both cell lines and was actively released in supernatants. Importantly, pre-treatment with Valsartan 50uM increased the viability of both hiPSC-CMs and 16HBE after infection, while Lisinopril and the lower dose of Valsartan had neutral effect. Of note, Valsartan 50uM treatment decrease ACE2 mRNA level in both hiPSC-CMs (-47%, p&lt;0,01) and 16HBE (-37%, p&lt;0,01). Also ACE2 protein levels were reduced in cell lysates of hiPSC-CMs and 16HBE treated with Valsartan 50uM. Conclusion: These data suggest that ACEIs and ARBs do not worsen the SARS-CoV-2 infection. On the contrary, Valsartan seems to be protective against SARS-CoV-2 infection, possibly by reducing ACE2 expression.
Abstract 13806: In-Hospital Outcomes Among Patients With Septic Shock and Underlying Chronic Atrial Fibrillation
Authors: Mohinder R Vindhyal, Rhythm Vasudeva, Suveenkrishna Pothuru, Elizabeth Ablah, Won Choi, K James Kallail, Zubair Shah, Kamal gupta
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is the leading cause of arrhythmia among hospitalized patients. Altered hemodynamics with new-onset non-valvular atrial fibrillation, especially during sepsis/septic shock, causes decreased organ perfusion, lowers cardiac output, and increases the risk of organ dysfunction leading to increased intensive care unit (ICU) length of stay and mortality. However, little is known about the outcomes of patients hospitalized with septic shock and underlying chronic atrial fibrillation (UCAF). Hypothesis: Does UCAF increase in-hospital mortality in patients who have a diagnosis of septic shock during hospitalization. Methods: This was a retrospective analysis of the 2016 and 2017 Nationwide Readmission Database. ICD-10 codes were used to identify patients with septic shock, and these patients were stratified into those with and without a UCAF. Propensity matching analyses were performed to compare in-hospital mortality and clinical cardiovascular outcomes between the two groups. Results: A total of 353,422 patients with hospitalization for septic shock were identified, 5.8% of whom (n=20,772) had UCAF. After 2:1 propensity matching, 41,438 patients were identified as having septic shock without UCAF, and 20,719 patients were identified as having septic shock with UCAF. In hospital mortality [34.4% vs. 34.1%, p= 0.049], incidence of ischemic stroke [2.5% vs. 2.2%, p = 0.012], acute heart failure [1.8% vs. 1.4%, p &lt; 0.001], length of stay [11.46 days vs. 10.93 days, p&lt; 0.001], mean total charges [$150 4094 vs. $140 4037, p &lt; 0.001] were significantly higher in patients with septic shock and UCAF compared to patients with septic shock without UCAF. Conclusions: The study identified UCAF as an adverse prognosticator for inpatient mortality and severe cardiovascular clinical outcomes. The study suggests the need for future research to improve patient outcomes of patients with septic shock and UCAF.
Abstract 11811: Impact of Anemia on the Outcomes of Hospitalizations for Atrial Fibrillation: Analysis of National Inpatient Sample
Authors: Muhammad Almani, Muhammad Usman, Trohman Richard, Annabelle Santos Volgman, Muhammad Ayub
Journal: Circulation (2021)

Introduction: Anemia is a known adverse prognostic factor among patients with cardiovascular diseases. We sought to determine the impact of anemia on hospitalizations for atrial fibrillation (AF). Methods: Data were extracted from the National Inpatient Sample (NIS) 2016 - 2018 Database. The NIS was searched for hospitalizations for adult patients with AF as principal discharge diagnosis with and without anemia as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Multivariate logistic and linear regression analysis were used accordingly to adjust for confounders. STATA software was used for analysis. Results: Of the 1,236,549 patients admitted for AF, 196,430 (15.9%) had anemia. The mean age of patients with anemia was 74 years (95% CI 73.8 - 74.1) vs. 70 years (95% CI 70.2 - 70.3) at the time of admission for AF (p&lt;0.001). There were 56.6% females in the Anemia group vs. 50.3% in the other group (p&lt;0.001). The adjusted odds ratio (aOR) for inpatient mortality for AF with anemia compared to AF without anemia was 1.53 (95% CI 1.388 - 1.686, p&lt;0.001). Patients with anemia averaged 1.23 days longer length of stay (95% CI 1.182 - 1.287, p&lt;0.001) and 14112 USD higher mean hospitalization charge (95% CI 13179 - 15046, p&lt;0.001). Comorbid anemia in AF patients was associated with higher risks of cardiac arrest (aOR 1.61; 95% CI 1.38 - 1.87, p&lt;0.001) and cardiogenic shock (aOR 1.84; 95% CI 1.61 - 2.10, p&lt;0.001) and a lower likelihood of cardioversion (aOR 0.73; 95% CI 0.71 - 0.76, p&lt;0.001). Detailed outcomes are listed in Table 1. Conclusions: Comorbid anemia leads to worse outcomes in patients with AF. Early detection and treatment of anemia in at-risk patients may improve clinical outcomes in AF.
EPCO-19. SYSTEMS BIOLOGY APPROACH ON MGMT-METHYLATED, IDH WILD-TYPE SHORT-TERM SURVIVORS REVEALS MUTATIONS IN THE BRCA1-MEDIATED DNA REPAIR SIGNALING PATHWAY
Authors: Cameron Noorbakhsh, Yang Liu, Frederick Lang, John DeGroot, Kadir Akdemir, Kristin Alfaro-Munoz, Brittany Parker-Kerrigan, David Jaffray, Jason Huse, Krishna Bhat, Vinay Puduvalli, Kasthuri Kannan
Journal: Neuro-Oncology (2021)

Abstract Numerous multi-omic studies have revealed the vast molecular complexity of glioblastoma; however, these studies have failed to identify actionable drivers for definitive therapy. Unlike conventional relational data analysis methods used to examine such data, systems biology approaches using graph databases have emerged as powerful tools with flexibility and scalability needed to reveal specific vulnerabilities. Here we demonstrate the utility of a patient-centric graph database in identifying novel factors associated with poor outcome (survival &amp;lt; 8 months) in patients with MGMT promoter methylated glioblastoma. Using a cohort of 112 patients from the TCGA database, we integrated high-impact mutations with MGMT methylation status. Network analysis revealed three subnetworks, consisting of (a) methylated patients, the M-network, (b) methylated and unmethylated patients, the MU-network, and (c) unmethylated patients, the U-network. In addition, querying the genes in the M-network revealed three key molecules in the DNA repair pathway, namely, FANC-A, FANC-E, and MYUTH, mutated in five patients (q-value &amp;lt; 2.3E-02). Moreover, we observed that BRCA1 mediates other critical signaling molecules in the MU-network. Interestingly, in intermediate (8-24 months) or long-term ( &amp;gt;24 months) survivors networks, this pathway is not implicated. In light of recent studies implicating BRCA1 modulating temozolomide resistance in GBM sphere-forming cells and BRCA1’s protein expression predicting survival in patients, this result suggests that mutations in BRCA1-mediated DNA repair pathways hinder response to chemotherapy despite methylated MGMT, reducing the survival in patients. Besides this novel result explaining low survival in MGMT methylated patients through a synthesis of epigenetic and genetic data, our framework provides a novel and compelling paradigm for data integration at various scales from molecular events in a single patient’s tumor to integrating the molecular profile (or genotype) with phenotypic characteristics at the population level. We will present additional insights derived from this analysis at the SNO annual meeting.
Abstract 14422: Molecular Pathogenesis of Cardiac Microthrombi in Fatal Covid-19: Insights from Clinico-histopathologic and Single Nuclei RNA Sequencing Analyses
Authors: Nobuaki J Fukuma, Michael Brener, Michelle Hulke, Nobuaki Fukuma, Stephanie Golob, Robert Zilinyi, Zhipeng Zhou, Christos Tzimas, Ilaria Russo, Claire McGroder, Alexander Chong, Ryan Pfeiffer, Zhang Geping, Anne-Catrin Uhlemann, Jeffrey Moses, Martin Leon, Daniel Burkhoff, Mathew Maurer, Bjorn Redfors, Nir Uriel, Matthias Szabolcs, Charles C Marboe, Matthew Baldwin, Nathan R Tucker
Journal: Circulation (2021)

Cardiac microthrombi are postulated to underlie cardiac injury in critical COVID-19. To determine pathogenic mechanism(s) of cardiac injury in fatal COVID-19, we conducted a single-center prospective cohort study of 69 consecutive COVID-19 decedents. Microthrombi was the most commonly detected acute cardiac histopathologic feature (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi (ESR, P non-linearity 0.015, P association =0.008; CRP per 20mg/L increase, OR 1.17, 95%CI 1.00-1.36). Using single nuclei RNA-sequence analysis, we discovered an enrichment of prothrombotic, anti-fibrinolytic, and extracellular matrix signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts, compared with microthrombi-negative COVID-19 hearts and non-COVID-19 donor hearts. Our cumulative findings identify these specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.