tbuckley/cabot-search huggingface dataset:
Abstract 11586: Diagnostic Tests Used to Identify Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in the United States
Authors: Sarah Brown, Wei Yen Chung, James Deemer, Niya Melinis, Devon Wright
Journal: Circulation (2021)

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed, progressive disease characterized by amyloid protein deposits building in the left ventricle. The deposition of transthyretin (TTR) amyloid causes the heart walls to weaken and specialized tests are needed to identify ATTR-CM. Hypothesis: This paper examines the tests used to identify ATTR-CM in the US. Methods: Ipsos’ ATTR-CM Therapy Monitor was fielded monthly between February 2021 and April 2021, with ~100 treating doctors providing data online on &gt;200 ATTR-CM patients seen in consultation per wave. Ipsos analyzed information provided on the diagnostic tests ordered for the total 665 patients to understand how ATTR-CM is diagnosed and tracked the order in which the tests were conducted, across four batteries, to understand the flow of the diagnostic procedures. Results: The patients in our study went through 5 diagnostic tests on average before receiving a confirmed ATTR-CM diagnosis via Echocardiogram (ECHO) with strain imaging (91%), Genetic tests (75%), Scintigraphy tests (60%), Cardiac Magnetic Resonance Imaging (MRI) (55%), Laboratory tests (51%), and Biopsy tests (30%) as the top tests ordered. Overall, 19% of the reported patients had an unknown order of tests. ECHOs were most ordered in the 1st battery of tests (92%), Cardiac MRIs in the 2nd battery (39%), and Scintigraphy tests in the 2nd (33%) and 3rd batteries (26%). Biopsy tests were ordered in the 3rd battery (18%) and Genetic tests in the 4th+ battery (25%), while laboratory tests were ordered throughout the batteries (1st: 19%, 2nd: 14%, 3rd: 19%, 4th+: 11%). Patients experienced a delay of 3.7 weeks between the 1 st and 2 nd batteries of tests on average, and 3.8 weeks between the 2 nd and 3 rd batteries. Once ATTR-CM was suspected, it took physicians 6.5 weeks on average to run all necessary tests and arrive at a confirmed ATTR-CM diagnosis. Conclusion: Our data indicate that, patients go through a long journey before receiving a confirmed ATTR-CM diagnosis, taking 6.5 weeks on average once ATTR-CM is suspected and requiring many tests over 4+ batteries. Further research is needed to figure out how to encourage early suspicion of ATTR-CM and increase the speed of the diagnostic process.
Abstract 13417: Fluid-Structure Interaction Simulations of Bicuspid Aortic Valve Disease
Authors: Alexander D Kaiser, Rohan Shad, Nicole Schiavone, William Hiesinger, Alison L Marsden
Journal: Circulation (2021)

Introduction: Aortic dilation and aneurysm formation is common in patients with a bicuspid aortic valve. Hemodynamics and genetics are both believed to cause dilation, but the relative contributions remain controversial. Further, retrospective studies assess hemodynamics when dilation has already set in. We simulate flows through a tricuspid and three bicuspid aortic valves and study their hemodynamics from a baseline non-dilated aorta. Hypothesis: We hypothesize that the bicuspid phenotype determines flow in the ascending aortic, and high velocity jets will correlate with known regions of dilation in patients with bicuspid valves. Methods: Using methods we recently developed, we constructed a tricuspid valve and bicuspid valves with left/right (LR), right/non (RN) and non/left (NL) coronary cusp fusion. To isolate the effect of leaflet fusion phenotype, we use one healthy, patient-specific aortic geometry throughout. Fluid-structure interaction simulations were performed. Results: Dramatic differences in flow occur between all cases. The tricuspid case shows a relatively uniform flow profile, velocities of ~200cm/s, normalized streamwise momentum &lt;1.5, normalized tangential flow strength of &lt;1.6, &lt;20% reverse flow away from the sinus and sustained pressure gradients &lt;2 mmHg. All bicuspid cases show a localized jet, peak velocities &gt;300cm/s, normalized streamwise momentum &gt;2.0, normalized tangential flow strength &gt;1.0, &gt;50% transient reverse flow and sustained pressure gradients &gt;18 mmHg. With LR fusion, the jet hugs the outer curvature of the aorta from the sinotubular junction through the ascending aorta. With RN fusion, the jet moves from the inner to outer curvature of the aorta. Conclusions: With LR and RN cusp fusion, high flow rate jets occur at regions that generally correlate with dilation in prior studies, suggesting that hemodynamic factors alone may be sufficient to cause aortic dilation. This hypothesis should be tested in an animal model.
BIOM-15. SERUM AMYLOID-β42 AS A NONINVASIVE BIOMARKER FOR PROGNOSIS AND HISTOLOGIC FEATURES OF GLIOMA
Authors: Kihwan Hwang, Minhee Noh, Jay Park, So Young Ji, Jung Ho Han, Kwang Sung Ahn, Chae-Yong Kim
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Glioma is the most common primary tumor in central nervous system and is often refractory. Histopathologic examination is essential to establish initial diagnosis, and multiple imaging studies are conducted to assess for treatment response. However, those conventional approaches usually accompanies high risks and costs during treatment. The purpose of this study is to find a novel candidate of noninvasive biomarker for histologic prediction and prognostic assessment of glioma. METHODS Serum was prepared from blood samples collected preoperatively from 65 patients with WHO grade II–IV glioma from October 2004 to December 2017 in a single tertiary-level institution. Concentration of amyloid beta-42 (Aβ42) was measured by SMCxPRO (Merck) immunoassay. Clinical characteristics and histologic features of the patients including the molecular subtype were reviewed. Progression-free survival has been evaluated for the primary outcome. RESULTS The mean age of the patients was 53.7±12.2 years. 37 (56.9%) patients were males and 21 (32.3%) cases were primary tumors. In Kaplan-Meier survival analysis, higher serum Aβ42 (&amp;gt;5.7 pg/ml) group showed poor outcome with a statistical significance (p=0.014). In multivariate regression analysis, the concentration of serum Aβ42 showed a significant association with EGFR expression, or Ki-67 labeling index. The higher concentration of serum Aβ42 was associated with EGFR wild type (odds ratio 0.237, p=0.022), high cell proliferation (β=0.339, p=0.007) and poor outcome (hazard ratio 0.339, p=0.046). CONCLUSION Serum Aβ42 level is a possible good candidate of noninvasive biomarkers for prediction of histologic features and prognosis in glioma patients. Further studies with large cohorts might be mandatory for the clinical use of Aβ42.
Abstract 12060: Comparison of Sites of Wall Thickening and Abnormal Late Enhancement on Cardiac CT and Magnetic Resonance Imaging with Electrocardiography Findings in Patients with Confirmed Cardiac Amyloidosis
Authors: Nobusada Funabashi, Kohki Nakamura, takehio sasaki, Shigeto Naito, Yoshio Kobayashi
Journal: Circulation (2021)

Introduction: Left ventricular (LV) wall thickening and diastolic dysfunction on a TTE without a high voltage R wave on V5 leads on an ECG to a diagnosis of cardiac amyloidosis (CA). However, amyloid sometimes invades right ventricle (RV), and left (LA) and right (RA) atria, causing ECG changes such as sick sinus syndrome (SSS), arrhythmia, and QRS wave axis deviation. Hypothesis: We hypothesize that there is the relationship between sites of wall thickening and abnormal late enhancement (LE) on cardiac CT and MRI, suggesting amyloid invasion, with ECG findings in patients with CA confirmed by biopsy. Methods: A total of 26 patients (11 females) with suspected CA, who had LV wall thickening by TTE without a high voltage R wave in V5 leads, underwent cardiac CT. 5 patients (3 females, mean age 73 years) were diagnosed with CA. 4 patients underwent MRI. Results: Case 1 had wall thickening in the basal interventricular septum (IVS), LV inferior-posterior wall, LA on CT, LE in endocardium in whole LV, RV, and RA on CT, and LE in endocardium in whole LV, RV, LA, and IVS on MRI. ECG showed SSS (junctional rhythm), left QRS axis deviation, no low voltage R wave in limb leads, and a mild LA load. Case 2 had wall thickening in whole LV, RV, LA, and IVS on CT, and unclear (CT) or no (MRI) LE. ECG revealed SSS (junctional rhythm), a normal QRS axis, no low voltage R wave in limb leads, and no LA load. Case 3 had wall thickening in LA and basal IVS on CT, abnormal LE in the LA and basal IVS on CT, and LE in the LA only on MRI. ECG revealed atrial tachycardia, a normal QRS axis with low voltage R wave in limb leads, and no LA load. Case 4 had wall thickening in the LA, an RV moderator band on CT, an unclear LE on CT, and LE in whole LV, endocardium in the RV, and whole IVS on MRI. ECG showed a normal sinus rhythm, left QRS axis deviation, with low voltage R wave in limb leads, and no LA load. Case 5 had wall thickening in the IVS, LV lateral wall, LV anterior wall, RA, RV outflow tract, and RA appendage, and no abnormal LE on CT (MRI not performed). ECG revealed a normal sinus rhythm, right QRS axis deviation, with low voltage R wave in limb leads, and a mild LA load. Conclusions: This pilot study revealed the presence of wall thickening and abnormal LE in RV, LA, and RA in addition to LV would be important which may influence ECG changes in patients with CA.
Abstract 10157: Incremental Medical Expenditure and Effectiveness of Early Non-invasive Cardiac Testing in Suspected Acute Coronary Syndrome
Authors: Aniket Kawatkar, Adam Sharp, Aileen Baecker, Rita F Redberg, Mingsum Lee, Maros Ferencik, Yi-Lin Wu, Ernest Shen, chengyi zheng, Visanee Musigdilok, Steve Goodacre, Praveen Thokala, Benjamin Sun
Journal: Circulation (2021)

Introduction: The relationship between medical expenditure and long-term effectiveness of early (within 72 hours) non-invasive cardiac stress testing (NIT) in reducing future acute myocardial infraction (AMI) is not well understood. We estimated the value of early NIT after an emergency department (ED) evaluation for suspected acute coronary syndrome (ACS). Methods: This was a retrospective cohort study of adult (18+) patients with chest pain, presenting at EDs within the Kaiser Permanente Southern California health system from 10/2015-12/2018. We analyzed the direct medical expenditure associated with medical office visits, hospital facility and ED visits, pharmacy utilization, hospice stays, skilled nursing stays, home health, dialysis, laboratory and radiology utilization during the one year following the index chest pain ED visit. We also identified incidence of AMI during the 1-year follow-up. We used 2-stage residual inclusion instrumental variables (IV) techniques to evaluate the marginal effect of early NIT on total all cause expenditure as well as subgroups of utilization. We used control functions IV techniques to evaluate the marginal effect of NIT on AMI and calculated the number needed to treat (NNT) as the inverse of the absolute risk reduction. All models adjusted for socio-demographics, cardiovascular disease (CVD) history and treatment and non-CVD comorbidities. Results: The cohort included 91250 patients (mean age 58 years, female 58%) and 19% received early NIT. The marginal difference in total expenditure between the early NIT vs controls was $2,583 (95% CI $591 to $4,575) and was mainly related to the index ED visit (Table 1). Those who received early NIT had slightly lower risk of AMI during the 1-year follow-up (risk reduction 1.3% (-1.9% to -0.7%) resulting in NNT of 75. Conclusions: Early NIT offers minor risk reduction of AMI but with an increase of $2583 in expenditure. With a NNT of 75, the cost to avoid one AMI is estimated to be $193,725.
Correction to: ciRS-7 is a prognostic biomarker and potential gene therapy target for renal cell carcinoma
Authors: Weipu Mao, Keyi Wang, Bin Xu, Hui Zhang, Si Sun, Qiang Hu, Lei Zhang, Chunhui Liu, Shuqiu Chen, Jianping Wu, Ming Chen, Wei Li, Bo Peng
Journal: Molecular Cancer (2021)

An amendment to this paper has been published and can be accessed via the original article.
Abstract 11941: Feasibility of a Novel Cardiac Scale in Measuring Blood Pressure
Authors: Corey Centen, Sarah Smith, Sarin Patel, Marat Fudim, Daniel Yazdi
Journal: Circulation (2021)

Introduction: There is a need for simple and frictionless methods for measuring blood pressure in the home setting. In this proof-of-concept study we investigated the ability of the Bodyport Cardiac Scale to measure central mean arterial pressure (cMAP). The scale can measure electrocardiography (ECG), impedance plethysmography (IPG), and ballistocardiography (BCG) signals from the user’s feet (Figure 1). Hypothesis: Scale-derived biosignals can be used to approximate cMAP. Methods: In this single-center, non-randomized, IRB approved study, 87 subjects underwent three paired readings from the reference device, SphygmoCor XCEL, and the Bodyport Cardiac Scale following the ISO 81060-2 standard. A lasso regression model was developed using biosignals derived from the scale including pulse transit time, pulse rate, weight, and other signal features to approximate cMAP obtained from the reference device. The model was trained on 60 subjects (70% of subjects) and independently validated on the remaining unseen 27 subjects. Results: The study population had a mean age (standard deviation) of 41.6 years (13.4), mean weight of 178 lbs (50.5), mean cMAP of 91.4 mmHg (18.3), cMAP range of 63-147 mmHg, and 56% were male. The scale estimate for cMAP had a mean error of -1.7 mmHg, standard error of 12.2 mmHg, 95% limits of agreement of -25.63 to 22.23 mmHg, and a Pearson correlation of 0.74, p &lt; 0.0001 (Figure 2). Conclusions: This study demonstrates the feasibility of using biosignals from this cardiac scale to predict cMAP without calibration. Future studies would seek to further improve the accuracy of the model and assess longitudinal changes in the blood pressure measurement.
Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody?negative primary biliary cirrhosis*1
Authors: K TSUNEYAMA
Journal: Hepatology (1995)

The presence of antimitochondrial antibodies (AMA) is a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, the study of these autoantibodies has enabled much information to be accumulated about the specificity of this response. The autoantigens have been identified as components of a functionally related enzyme family, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E2 subunit (PDC-E2) has been determined to be the immunodominant autoantigen. Using a panel of mouse monoclonal antibodies and human combinatorial autoantibodies, it has been demonstrated that patients with PBC, but not controls, have an abnormal expression of either PDC-E2 or a cross-reacting molecule in the apical region of biliary epithelium. Others have shown a similar reaction using rabbit sera directed to PDC-E2. Our previous studies have concentrated on AMA-positive patients. In this study, the presence of PDC-E2, class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells of AMA-positive as well as AMA-negative patients is addressed. Most patients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region of the bile duct epithelial cells for “PDC-E2,” increased IgA expression, and little major histocompatibility complex (MHC) class II staining in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E2 on the apical side of their biliary epithelium had anticentromere antibodies and Sjogren's syndrome. Based on these data, it can be concluded that the disease process for both AMA-positive and AMA-negative patients with PBC has a similar pathogenic mechanism, which is likely to involve the abnormal expression of PDC-E2 or a molecular mimic of PDC-E2, and does not require MHC class II expression.
Abstract 9850: Association Between Matrix Metalloproteinase-2 Activity, Heart Failure and Adverse Cardiac Remodeling: The Atherosclerosis Risk in Communities Study
Authors: Leo F Buckley, Ali M Agha, Pranav Dorbala, Brian Claggett, Bing Yu, Aliza Hussain, VIJAY NAMBI, Kuni Matsushita, Ron C Hoogeveen, Christie M Ballantyne, Amil M Shah
Journal: Circulation (2021)

Introduction: MMP-2, an extracellular matrix regulator, is overexpressed in the myocardium of patients with dilated cardiomyopathy and predicts adverse outcomes in patients with heart failure (HF). Whether circulating MMP-2 associates with incident HF with reduced and preserved ejection fraction (HFrEF, HFpEF) and with cardiac structure and function among persons free of HF remains unclear. Methods: Among 4471 participants in the community-based ARIC study who were free of HF, had aptamer-based MMP-2 measurements (SomaLogic), and underwent echocardiography at Visit 5 (2011-2013), we assessed the association of MMP-2 with adjudicated HF, HFrEF (LVEF&lt;50%) and HFpEF using multivariable Cox proportional hazards regression and with cardiac structure and function using multivariable linear regression. MMP-2 levels and echocardiographic parameters were standardized before analysis. All models adjusted for demographics, field center, coronary artery disease, diabetes, hypertension, atrial fibrillation, smoking status, body mass index and eGFR, and, in linear regression models, systolic blood pressure and heart rate. Results: The mean age was 75±5 years and 57% were women. Higher MMP-2 level associated with older age, male sex, and coronary artery disease, and with lower BMI, higher eGFR, and lower diabetes and hypertension prevalence. Higher MMP-2 levels associated with larger LV volume (standardized β=0.13; P&lt;.001), mass (β=0.08; P&lt;.001), E/e’ (β=0.12; P&lt;.001) and LA volume index (β=0.19; P&lt;.001). Over a median follow-up of 7 (IQR 6-8) years, 204 HFpEF, 180 HFrEF, and 55 unknown LVEF events occurred. Higher plasma MMP-2 level associated with greater risk of HF (HR per 1 SD: 1.30 [1.18-1.43]; P&lt;.001), HFrEF (1.23 [1.06-1.43]; P=.007), and HFpEF (1.33 [1.16-1.54]; P&lt;.001) post-Visit 5 ( Figure ). Conclusions: Higher circulating MMP-2 is independently associated LV remodeling and diastolic dysfunction, and with risk of incident HFrEF and HFpEF.
NCOG-43. RELATIONSHIPS BETWEEN MOOD DISTURBANCE, SYMPTOM INTERFERENCE, AND DISEASE PROGRESSION IN GLIOMA PATIENTS
Authors: Kayla Roche, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Anna Choi, Alexa Christ, Ewa Grajkowska, Varna Jammula, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Lily Polskin, Marta Penas-Prado, Valentina Pillai, Brett Theeler, Jing Wu, Mark Gilbert, Terri Armstrong, Amanda King
Journal: Neuro-Oncology (2021)

Abstract Cross-sectional studies indicate that patients with gliomas report significant depressive/anxiety symptoms and symptom-related interference with daily activities at diagnosis and throughout the illness trajectory. Our study aimed to explore relationships between these mood disturbances and symptom interference with respect to progressive disease (PD) in glioma patients. Demographic, clinical characteristics, MDASI-Brain Tumor (interference items), and PROMIS Anxiety and Depression Short-Forms were collected at the time of imaging surveillance, before discussing imaging results. Comparisons between patients with/without PD and respective change scores were calculated at study entry and at subsequent assessments. Independent t-tests, Chi-square tests, and paired sample t-tests were used to report results. The sample included 438 glioma patients (62% male, 84% Caucasian, 82% high-grade) with median age of 51 years (range 18-82); 42% had PD with 60% reporting past recurrence(s); 45% had poor Karnofsky Performance Status (KPS); and median time from diagnosis was 2 years (range: 0-30). On average, patients with PD on imaging at time of assessment reported significantly greater anxiety (p = 0.008), depression (p &amp;lt; 0.001), and symptom interference (p &amp;lt; 0.001) than those with stable disease. Additionally, more patients with PD reported moderate-severe anxiety (25%) and depression (22%) than patients with stable disease (15% and 12%, respectively). When evaluating change scores, patients with PD reported worse symptom interference (p &amp;lt; 0.001) but stable mood disturbance, while patients with stable disease reported improved depression (p = 0.018) and unchanged anxiety symptoms compared to baseline. Although mood disturbance is higher for patients with PD, some of these patients do not experience worsening, but rather a continuation of ongoing psychological symptoms, which may portend a worse illness trajectory. Identifying these patients early in this trajectory to evaluate potential biologic correlates between mood and prognosis is warranted to validate these findings.
Abstract P333: The Vascular Barrier: A Common Anti-arrhythmic Target In Atrial Fibrillation And Myocardial Infarction
Authors: Louisa Mezache, Gerard Nuovo, Rengasayee Veeraraghavan
Journal: Circulation Research (2021)

Vascular leak is a major sequela of inflammation, which is associated with arrhythmic pathologies such as atrial fibrillation (AF) and myocardial infarction (MI). We recently demonstrated that the vascular leak-inducing cytokine vascular endothelial growth factor (VEGF; 90-580 pg/ml - levels found in AF patients) induces acute remodeling (30-60 minutes) of sodium channel (Na V 1.5) -rich intercalated disk (ID) nanodomains, disrupting their ultrastructure and prompting translocation of Na V 1.5 from these sites. This in turn disrupted impulse propagation and promoted arrhythmias in murine atria. Here, we tested the hypotheses that i) similar acute pro-arrhythmic remodeling occurs in the ventricles of MI patients, and ii) protecting the vascular barrier may prevent arrhythmias following an acute inflammatory insult. First, we examined myocardial samples from five human MI patients. VEGF was overexpressed in both cardiomyocytes and vascular endothelium in the border zone surrounding &lt;6 month-old infarcts. Notably, co-localization analysis showed significantly reduced Na V 1.5 near both connexin43 and N-cadherin within the border zone in 1-, 3-, and 9-day-old infarcts, paralleling our observations in mouse atria. Next, we returned to our murine model of AF induced by acute inflammatory insult (100 pg/ml VEGF for 60 minutes) to test the antiarrhythmic efficacy of protecting the vascular endothelial barrier. Overall, median in vivo arrhythmia burden was higher in VEGF-treated mice relative to vehicle controls (7.5±11 vs. 0±6 s/hr). We tested two strategies shown to prevent vascular barrier breakdown: Blocking connexin43 hemichannels (αCT11 peptide) decreased in vivo arrhythmia burden to 0 ± 6.07 s/hr. Panx1-IL2 (a peptide inhibitor of Panx1 channels) treatment decreased also in vivo arrhythmia burden (0 ± 15.57 s/hr with 1.6 μM Panx1-IL2). Similar antiarrhythmic efficacy was also achieved with small molecule inhibitors of Cx43 and Panx1. These results highlight VEGF-induced vascular leak as a novel mechanism for acute arrhythmias both in the early stage AF and following MI. Indeed, this mechanism may contribute to post-MI AF. Importantly, vascular-barrier protection may be a viable strategy to prevent these arrhythmias.