tbuckley/cabot-search huggingface dataset:
Abstract 14221: The Role of Left Ventricular Dysfunction in Children With Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Alison J Howell, Aamir Jeewa, Dawn Nicholson, Emilie M Jean-st-michel, Eric Minn
Journal: Circulation (2021)

Introduction: We sought to evaluate the impact of left ventricular dysfunction (LVDfx) in children with a definite arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. Methods: We retrospectively reviewed patients 0-18 years of age diagnosed with ARVC at our institution between 2001-2018. Patients with LVDfx, defined as an ejection fraction of &lt;55% on echocardiogram, were identified and their outcomes compared to ARVC patients without LVDfx. Kaplan-Meier transplant-free survival curves were utilized. Results: Thirty-five children with a diagnosis of ARVC were identified. Twelve patients (34%) had LVDfx, of which 7 (20%) had moderate-severe LVDfx. The median age at diagnosis was 15 years (IQR 13.2 - 15.8) with a median follow-up time of 2.1 years (IQR 1.1 - 4.3). There was no association with increased left ventricular dimension or mitral regurgitation in either group. Cardiac magnetic resonance imaging demonstrated that LVDfx was associated with moderate to severe right ventricular dysfunction (41.6% vs 17.4% p = 0.009) and late gadolinium enhancement (58.3% vs 8.7% p = 0.004). Arrhythmia burden was greater in the LVDfx group with a higher incidence of ectopy (83% vs 50% p = 0.04) and non-sustained ventricular tachycardia (83% vs 22% p = 0.0009). The LVDfx group was significantly more likely to receive an angiotensin converting enzyme inhibitor (41.6% vs 0% p = 0.002) or a beta-blocker (75% vs 8.7% p = 0.0001). Total length of hospital stay was significantly longer in the LVDfx cohort (median 2 days vs 0 days p = 0.001). The two-year transplant free survival was significantly worse in the LVDfx group (88% vs. 100%, p=0.04, figure 1). Conclusions: ARVC is not always confined to a single chamber and LVDfx confers a greater risk to the healthcare trajectory of children with ARVC. Therapeutic strategies for LVDfx may have a substantial impact on outcomes in this population.
Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics: Erratum
Authors: Ju Huang, Fengqiu Liu, Xiaoxia Han, Liang Zhang, Zhongqian Hu, Qinqin Jiang, Zhigang Wang, Haitao Ran, Dong Wang, Pan Li
Journal: Theranostics (2021)

[This corrects the article DOI: 10.7150/thno.29569.].
Abstract 13990: Tightly Connected Provider Networks Are Associated With Lower Spending for Patients Undergoing Left Ventricular Assist Device Implantation
Authors: Dennie Kim, Russell Funk, Hechuan Hou, Austin Airhart, Khalil Nassar, Francis D Pagani, Min Zhang, Paul Chandanabhumma, Keith D Aaronson, Carol Chenoweth, Ahmad Hider, Lourdes Cabrera, Donald S Likosky
Journal: Circulation (2021)

Introduction: Patients receiving a durable left ventricular assist device (LVAD) implant for advanced heart failure require multidisciplinary care but integration of care delivery may vary among provider groups. Prior studies found that greater provider network connectivity may be associated with more integrated care and better clinical outcomes. Hypothesis: Greater connectedness in provider networks is associated with lower LVAD payments. Methods: Drawing on social network theory, a measure of connectedness was developed based on the number of shared patients among providers (e.g. primary care physicians, cardiologists, surgeons) caring for 4,985 Medicare beneficiaries, starting 180 days prior to LVAD admission until 180 days post-discharge, from July 2009-April 2017. Connectedness was measured as average network path length, with shorter path lengths indicating more connected networks. Total payments were captured from admission to 180 days post-discharge. Multivariable regression was used to analyze the relationship between connectedness and LVAD payments. Results: The patient cohort was 81% male, 73% white, 11% Intermacs Profile 1 with a mean age of 63.1 years (SD 11.1). The median path length (IQR) for a provider network was 1.7 (1.6, 1.8) and median (IQR) payments from admission to 180 days post-discharge was $162,774 ($151,279, $202,932). Median (IQR) payments at the lower, middle, and upper terciles of connectedness were $162,249 ($150,543, $198,709), $162,577 ($151,424, $199,471), and $163,922 ($152,263, $212,072), respectively. After adjusting for center, patient demographics, and clinical factors, greater connectedness was associated with lower payments (β=-22097.88, p&lt;0.01), Figure. Conclusions: Greater provider network connectedness is associated with lower payments for Medicare beneficiaries receiving durable LVAD implants. Interventions to improve network connectedness may improve the value of care in this population.
Abstract 13408: Have We Improved? Right Bundle Branch Block and Transcatheter Aortic Valve Replacement: An Analysis of the National Inpatient Database
Authors: Juliann Gilchrist, Jennifer Maning, Jelani Grant, Louis T Vincent, Bertrand Ebner, Rafael Hernandez, Neal Olarte, Odunayo Olorunfemi, Rosario A Colombo
Journal: Circulation (2021)

Background: Pre-existing right bundle branch block (pRBBB) is recognized as a significant risk factor for the need of permanent pacemaker (PPM) therapy after TAVR, with early studies suggesting additional risk of mortality and hospitalization. This study aims to explore contemporary in-hospital outcomes of TAVR patients with pRBBB. Methods: Using the National Inpatient Database (NIS) we identified patients 18 years and older hospitalized for index TAVR procedure from 2016 to 2018. Primary outcome was incidence of PPM implant post-TAVR. Secondary outcomes included in-hospital mortality and length of stay (LOS). Multivariate analysis model was used to adjust for statistically significant differences in baseline characteristics between the groups. Results: A total of 152,490 patients underwent TAVR. Pre-existing RBBB was present in 7090 (4.6%) patients. Patients with pRBBB were less likely to be women (34.6% vs 46.8%, p &lt; 0.001) and more likely to suffer from heart failure (76.9% vs 74.3%, p &lt; 0.001) and diabetes (40.2% vs 37.3%, p &lt; 0.001). Those with pRBBB were more likely to undergo PPM implant (29.4% vs 9.1%, OR 3.776, p &lt; 0.001). There was no significant difference in in-hospital mortality (1.3% vs 1.5%, p = 0.203) or LOS (4.51 ± 5.15 vs 4.38 ± 5.54 days, p= 0.062) between the groups. Subgroup analysis showed that the incidence of PPM implant (29.1% vs 14.6%, p &lt; 0.001), in-hospital mortality (1.4% vs 0.7%, p &lt; 0.001), cardiogenic shock (2.1% vs 1.5%, p &lt; 0.001) and mechanical ventilation (3.1% vs 2.0%, p &lt; 0.001) was higher among patients with pRBBB compared to those with pre-existing LBBB (pLBBB). Conclusions: Contrary to previous reports, patients with pRBBB did not show increased risk of in-hospital mortality or LOS compared to those without RBBB. pRBBB was, as expected, associated with increased risk for PPM implant post-TAVR. When compared to patients with pLBBB, those with pRBBB appear to experience worse in-hospital outcomes, suggesting an area for further research.
An Imaging Biomarker of Tumor-Infiltrating Lymphocytes to Risk-Stratify Patients With HPV-Associated Oropharyngeal Cancer
Authors: Germán Corredor, Paula Toro, Can Koyuncu, Cheng Lu, Christina Buzzy, Kaustav Bera, Pingfu Fu, Mitra Mehrad, Kim A Ely, Mojgan Mokhtari, Kailin Yang, Deborah Chute, David J Adelstein, Lester D R Thompson, Justin A Bishop, Farhoud Faraji, Wade Thorstad, Patricia Castro, Vlad Sandulache, Shlomo A Koyfman, James S Lewis, Anant Madabhushi
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background Human papillomavirus (HPV)–associated oropharyngeal squamous cell carcinoma (OPSCC) has excellent control rates compared to nonvirally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment-related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials. Methods Association between OP-TIL and patient outcome was explored on whole slide hematoxylin and eosin images from 439 stage I HPV-associated OPSCC patients across 6 institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence or death in the remaining 5 cohorts (n = 345). All statistical tests were 2-sided. Results OP-TIL separated stage I HPV-associated OPSCC patients with 30 or less pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS = 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52 to 4.32; P &amp;lt; .001), even after adjusting for age, smoking status, T and N classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32 to 3.94; P = .003). Conclusions OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.
Abstract 13041: Differences In Systemic Fatty Acids Between Coronary Heart Disease Patients And Controls From The Middle East Favors Inflammation
Authors: Ehsan Ullah, Khalid Kunji, Ayman El-Menyar, Reem Elsousy, Maryam Al-Nesf, Alka Beotra, Mohammed Al-Maadheed, Vidya Mohamed-Ali, Mohamad Saad, Jassim Al Suwaidi
Journal: Circulation (2021)

Introduction: Fatty acids (FAs) have been of interest as biomarkers and as mechanistic signaling modulators of inflammation for the progression of coronary heart disease (CHD). Short chain FAs (SCFA) play a role in two inflammation mediating signaling mechanisms: inhibition of histone deactylase and activation of G-protein-coupled receptors. The omega-3 FAs are important in the generation of resolvins, which are active in the resolution of inflammation. Medium chain FAs (MCFA) play an important role in decreasing cholesterol by inhibiting bile acid reabsorption. In this study we investigated changes of FAs in CHD. Methods: Samples from the Qatar Cardiovascular Biorepository and Qatar Biobank (CHD n=1,001, controls n=2,999) were used for the quantitative analysis of serum FAs by liquid chromatography-mass spectrometry. Data were curated by Metabolon Inc. Standard quality control steps were performed. Logistic regression, adjusting for age, BMI, and sex, was conducted to test association between CHD and FAs. Results: Overall 289 lipid metabolites including 27 long chain FAs (LCFA), 9 MCFA, and one SCFA (caproate) were analyzed. The significant metabolites at P &lt;0.05 were 25 LCFA (20 were higher in CHD), 7 MCFA (4 were higher in CHD), and one SCFA (higher in CHD, P =1.64х10 -87 ). MCFA heptanoate (7:0, P =1.67х10 -26 ), LCFA erucate (22:1n9, P =5.5х10 -8 ) and docosadienoate (20:2n6, P =1.25х10 -5 ) were higher in CHD than controls. Among the FAs that were lower in CHD, there were the long chain omega-3 FAs eicosapentaenoate (EPA, 20:5n3, P =1.6х10 -3 ), docosahexaenoate (DHA, 22:6n3, P =1.45х10 -10 ), and docosapentaenoate (DPA, 22:5n3, P =1.64х10 -11 ), and the MCFA 5-dodecenoate (12:1n7, P =3.5х10 -4 ) and 10-undecenoate (11:1n1, P =3.79х10 -11 ). Conclusions: Our results show that changes in the FAs profile of the CHD patients in this study may mechanistically contribute to the increased prevalence of inflammatory diseases such as CHD in the Middle East.
QOLP-28. COMPARING KNOWLEDGE OF AND BELIEFS ABOUT PALLIATIVE CARE AMONG NEURO-ONCOLOGY PATIENTS, CAREGIVERS, PROVIDERS AND A NATIONALLY-REPRESENTATIVE U.S. SAMPLE
Authors: Margaret Johnson, Mustafa Khasraw, Jung-Young Kim, Nicole Cort, James Herndon, Luis Ramirez, Eric Lipp, Daniel Landi, Annick Desjardins, Henry Friedman, David M Ashley, Mary Affronti, David J Casarett, Katherine B Peters
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION There is increasing recognition that palliative care (PC) can benefit patients with advanced cancers. However, early referral to PC is not yet a reality for patients diagnosed with a primary brain tumor. We hypothesize that lack of knowledge and/or misperceptions regarding PC by patients, caregivers, or their providers remain barriers. METHODS This is an IRB-exempt, one-time QR-accessible REDcap questionnaire administered to patients, caregivers, and providers at the Preston Robert Tisch Brain Tumor Center between September 2020 and May 2021. We administered 9 questions regarding knowledge and beliefs about PC from the Health Information National Trends Survey 5, Cycle 2: results of this nationally representative U.S. sample are publicly available and used for comparison. RESULTS We had 141 survey respondents: 25 providers, 59 patients, and 57 caregivers. The median patient and caregiver ages were 49 (21-74) and 50 years (24-73), respectively. Caregivers were more likely female (55.2 %) and identified as a spouse or domestic partner (58.2%). Providers, were equally distributed by years of experience. Compared to patients and caregivers, providers reported more baseline knowledge of PC (p&amp;lt; 0.0001, p&amp;lt; 0.0001) and better understood the role of PC in pain/symptom management (p=0.0038, p=0.0087) and social/emotional support (p=0.0044, p=0.0279). Interestingly, most providers (76.0%) disagreed with the statement “the goal of palliative care is to give patients more time at the end of life.” Compared to a general U.S. sample (n=1,162) our patients (n=39) were better informed in only 2 of 9 questions. Whereas, caregivers (n=48) were better informed in 6 of 9 questions. CONCLUSION Neuro-oncology providers were knowledgeable, but a minor gap in understanding the goal of PC was identified. Caregivers were overall more knowledgeable than patients. However, Neuro-oncology patients, had similar knowledge and beliefs compared to a nationally representative sample. PC interventions should prioritize filling knowledge gaps for Neuro-oncology patients.
Abstract 10973: Tenascin-C Deficiency Rescues the Effect of Diabetes on Cardiac and Vascular Dysfunction in Mice
Authors: Attila K, Zsuzsanna Arnold, Ibrahim Aykac, Eylem Acar, Petra L Szabó, Alexander Fee, Maria Szekeres, Simon Watzinger, György Nádasy, Nazha Hamdani, Bruno K Podesser
Journal: Circulation (2021)

Introduction: Tenascin-C (TN-C) upregulation is linked to worse clinical outcome in diabetic patients. However, the role of TN-C in the development of diabetic cardiomyopathy is still unknown. Hypothesis: Whether TN-C plays a maladaptive role in diabetic cardiomyopathy. Methods: AJ (n=14) and TNC-KO (n=16) adult male mice were injected with streptozotocin (50mg/kg) to induce diabetes. Cardiac function was measured by echocardiography at 16-18 weeks follow-up. Additionally, cardiomyocyte passive stiffness , vascular endothelial function (aorta), and cardiac fibrosis were assessed. In addition, the hemodynamic effect of human recombinant TN-C (hrTN-C; 80 ng/ml) on the isolated working rat heart (n=3) was evaluated. Isolated primary mouse cardiomyocytes (IPMC) were used to assess TN-C expression. Human ventricular cardiac fibroblasts (HCF) were cultured and treated with 1) TGF-β (20ng/ml); 2) rhTN-C (10μg/ml) and TLR4 inhibitor (TAK-242, 50 mM) in combination with TN-C and mRNA expression of α-SMA, TN-C, Col-1, Col-3 and ACE1 were assessed by RT-qPCR. Finally, HUVEC were treated either with rhTN-C (10μg/ml) or combination with TLR-4 inhibitor and analysed of the expression of NADPH oxidase 1 and 4 (NOX1, NOX4). Results: TN-C deficiency was accompanied by preserved LV ejection fraction and endothelium function in aorta (p&lt;0.05, respectively). Diabetic TN-C KO mice show reduction in cardiomyocyte stiffness and diastolic dysfunction as compared to AJ diabetic group (p&lt;0.01). Histology revealed less cardiac and perivascular fibrosis in diabetic TN-C KO animals than in the AJ diabetic group (p&lt;0.01). In addition, rhTN-C resulted in reduction in cardiac function in isolated rat hearts. mRNA expression of TN-C was increased in IPMC. Moreover, TGF-β treatment markedly upregulated TN-C expression (p&lt;0.01) and rhTN-C promoted pro-fibrotic genes expression (p&lt;0.05, respectively). HUVEC incubated with rhTN-C showed increased expression of IL-6 and NOX4 via TLR-4 signalling. Conclusions: TN-C promotes a hostile environment that facilitates fibrosis and oxidative stress leading to cardiomyocyte and endothelial cell dysfunction. Thus, TN-C may play a crucial role in cardiovascular dysfunction in diabetes as well as a potential target for therapy.
Abstract 12266: Endothelial Cells Senescence Exacerbates Pulmonary Hypertension Through Notch-Induced Pulmonary Arterial Smooth Muscle Cells Proliferation and Migration
Authors: Risa Ramadhiani, Koji Ikeda, Kazuya Miyagawa, Gusty Rizky Teguh Ryanto, Naoki Tamada, Yoko Suzuki, Ken-Ichi Hirata, Noriaki Emoto
Journal: Circulation (2021)

Background: Endothelial cell (EC) dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) by mediating structural changes in vasculatures. Various stress that promotes EC dysfunction also induces premature senescence in EC; however, the role of EC senescence in the development of PAH remains unknown. Hypothesis: We hypothesized that senescent ECs play a significant role in the development of PAH. Methods: We generated EC-specific progeroid mice that overexpress the dominant-negative form of telomere repeat binding factor 2 under the control of the VE-cadherin promoter. Following chronic hypoxia exposure, PH phenotypes were assessed by RVSP and lung histology. Gene expression was assessed by RT-qPCR. The interaction of pulmonary artery ECs (PAECs) and pulmonary artery smooth muscle cells (PASMCs) was analyzed using indirect and direct co-culture systems. In addition, gamma-secretase inhibitor (DAPT) was used to inhibit Notch signaling both in the in-vitro and in-vivo studies. Results: The transgene expression was specifically expressed and fairly distributed in various pulmonary blood vessels in EC-specific progeroid mice. After three weeks of hypoxia exposure, EC-specific progeroid mice exhibited exacerbated pulmonary hypertension (PH) phenotype, accompanied by the prominent medial thickening and enhanced proliferation capacity of SMCs in the distal pulmonary arteries. Interestingly, contact-mediated interaction with senescent ECs increased proliferation and migration capacities in SMCs, while the absence of EC-SMC contact abolished those effects. Mechanistically, senescent ECs expressed higher Notch ligands than in young ECs, leading to the enhanced Notch signaling in PASMCs. Consistently, pharmacological inhibition of Notch signaling attenuated senescent ECs’ effects on SMCs in vitro and the PH phenotype in EC-specific progeroid mice in vivo. Conclusions: These findings established the critical roles of senescent ECs in the PAH pathogenesis, suggesting a novel pathological-targeted therapeutic approach for PAH.
EXTH-36. ELECTROCONVULSIVE SEIZURE-INDUCED CHANGES IN THE TUMOR MICROENVIRONMENT PROMOTE SURVIVAL IN GLIOMA-BEARING MICE
Authors: Timothy Sita, Lisa Hurley, Michael Drumm, Serena Tommasini-Ghelfi, Akanksha Mahajan, Corey Dussold, Kevin Murnan, Sean Sachdev, Craig Horbinski, Roger Stupp, Alexander Stegh
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Growing evidence indicates that the neurotransmitters dysregulated in psychiatric disorders are similarly dysregulated in glioblastoma (GBM) biology. GBM cells are dependent on bountiful neuronal glutamate, utilize elevated dopamine receptor expression to augment progression, and catabolize serotonin to drive proliferation and inhibit anti-tumor immunity. The clinical induction of seizure, known as electroconvulsive therapy (ECT), has been used by psychiatrists since the 1930s to correct these dysregulations and can additionally improve medication blood-brain barrier (BBB) penetrance. We hypothesized that seizure-induced changes in the glioma microenvironment occur with ECT, slowing tumor progression, increasing BBB permeability, and prolonging overall survival in glioma-bearing mice. METHODS C57BL6 mice were orthotopically injected with CT-2A-Luc mouse glioma cells. Mice were randomized to receive ECT via ear-clip electrodes or sham treatment daily up to five times per week. Intracranial progression was monitored via bioluminescent signal from CT-2A-Luc xenografts. BBB permeability was assessed by subjecting mice to ECT or sham treatment immediately following intravenous injection of sodium fluorescein. RESULTS Intracranial progression was maximally reduced in ECT-treated mice relative to sham-treated mice after 17 ECT treatments (ECT radiance 2.6 x 109 photons/second versus sham 4.7 x 109 photons/second, p=0.013), which was further confirmed by both decreased tumor weight and tumor size on histologic evaluation. This translated into an improvement in overall survival from median 29 days in sham-treated mice to 38 days in ECT-treated mice (p=0.0018). Mean seizure duration was 41.8 seconds and positively correlated with overall survival (Pearson coefficient r=0.63, p=0.028). Brain parenchymal uptake of sodium fluorescein was significantly higher in ECT-treated mice (mean relative increase in ECS to sham radiance of 1.47, p&amp;lt; 0.05). CONCLUSION Repeated ECT slows tumor progression and prolongs overall survival in C57BL6 mice bearing CT-2A-Luc xenografts. The BBB is compromised immediately following ECT. ECT merits further oncologic investigation as a potential therapeutic in GBM.