tbuckley/cabot-search huggingface dataset:
Abstract 9596: Presence and Extent of Aortic Arch Plaques for the Prediction of Cardiovascular Outcomes in Patients with Suspected Coronary Artery Disease Undergoing Wide Volume Scanning Coronary Computed Tomography Angiography
Authors: Kenichiro Otuska, Hiroki Yamaura, Hirotoshi Ishikawa, Kuniyuki Shirasawa, Kumiko Hirata, Noriaki Kasayuki
Journal: Circulation (2021)

Introduction: Wide volume scanning with 320-row multidetector CT coronary angiography (WVS-CCTA) enables comprehensive assessment of aortic arch together with coronary artery disease (CAD), without additional contrast media injection (Figure A-E). This study investigated prognostic implication of the presence and extent of aortic arch plaques (AAPs) and coronary high-risk plaque burden, as assessed by low-attenuation plaque (LAP) volume, on major cardiovascular events (MACE). Methods: This study consisted of patients with suspected CAD undergoing WVS-CCTA (n=529, mean age 64 yo, 57% of male). Conventional CCTA analysis included the assessment of coronary artery calcium score (CACS), obstructive CAD (diameter stenosis &amp;lt;50%), and %LAP volume (&amp;lt;30 HU). AAP score was defined as the sum of AAP thickness (0: no plaque, 1: &amp;lt;3 mm, 2: 3-5 mm, 3: &amp;gt; 5 mm) and AAP maximum angle (0: no plaque, 1: &amp;lt;120°, 2: 120-240°, 3: &amp;gt; 240°), resulting in a total of 0-6 point(s). The primary endpoint was a MACE composed of all-cause mortality, coronary revascularization, heart failure hospitalization, stroke, and vascular disease requiring invasive treatment. Results: The mean AAP score was 2.0 points (&amp;gt; 2 points in 56% and &amp;gt; 4 points in 27%), which is well correlated with CAD extent and severity. During a follow-up period of 2 years, MACE was observed in 15% of the study patients. In Cox hazard model analysis adjusted by age, gender, chronic kidney disease, and left ventricular ejection fraction &amp;lt;50%, the independent factors associated with MACE were diabetes mellitus [hazard ratio (HR), 1.9; p=0.009], obstructive CAD (HR, 3.8; p &amp;lt;0.001), the 4 th quartile of %LAP volume (HR, 1.8; p=0.016), and AAP score per 1 point increase (HR, 1.2; p=0.008). Conclusion: This study demonstrates unique opportunity for comprehensive evaluation of the presence and extent of AAPs together with CAD, providing prognostic implication of AAP score on MACE in patients with suspected CAD.
Sequential immunization of macaques elicits heterologous neutralizing antibodies targeting the V3-glycan patch of HIV-1 Env
Authors: Amelia Escolano, Harry B. Gristick, Rajeev Gautam, Andrew T. DeLaitsch, Morgan E. Abernathy, Zhi Yang, Haoqing Wang, Magnus A.G. Hoffmann, Yoshiaki Nishimura, Zijun Wang, Nicholas Koranda, Leesa M. Kakutani, Han Gao, Priyanthi N. P. Gnanapragasam, Henna Raina, Ana Gazumyan, Melissa Cipolla, Thiago Y. Oliveira, Victor Ramos, Darrell J. Irvine, Murillo Silva, Anthony P. West, Jennifer R. Keeffe, Christopher O. Barnes, Michael S. Seaman, Michel C. Nussenzweig, Malcolm A. Martin, Pamela J. Bjorkman
Journal: Science Translational Medicine (2021)

Sequential immunization elicits antibodies against the V3-glycan patch of HIV-1 Env in rhesus macaques and also induces off-target antibody responses.
Abstract 10226: Bioactive Adrenomedullin for Assessment of Venous Congestion in Heart Failure
Authors: Anna Egerstedt, Tomasz Czuba, Kevin Bronton, Carl Lejonberg, Toralph Ruge, Torgny Wessman, Goran Radegran, Janin Schulte, Oliver Hartmann, Olle MELANDER, Gustav Smith
Journal: Circulation (2021)

Introduction: Bioactive adrenomedullin (bio-ADM) is a vascular-derived peptide hormone that has emerged as a promising biomarker for assessment of congestion in decompensated heart failure (HF). Hypothesis: We aimed to evaluate diagnostic and prognostic performance of bio-ADM for HF in comparison to amino-terminal pro-B-type natriuretic peptide (NT-proBNP), with decision thresholds derived from invasive hemodynamic and population-based studies. Methods and Results: Normal reference ranges (95% prediction interval) for bio-ADM were derived from a community-based cohort (n=5060): 8-39 pg/mL. In a cohort of HF patients undergoing right heart catheterization (n=346), bio-ADM was correlated with mean right atrial pressure (mRAP, r=0.55) and followed a concordant trajectory to mRAP after heart transplantation. In contrast, NT-proBNP was correlated with pulmonary arterial wedge pressure (PAWP). The area under the receiver operating characteristic curve (AUROC) for discrimination of elevated mRAP and PAWP was 0.74 (95%CI=0.67-0.79) and 0.70 (95%CI=0.64-0.75), respectively, with optimal bio-ADM decision cutoff of 39 pg/mL, concordant with cubic spline analyses. NT-proBNP discriminated PAWP slightly better than mRAP (AUROC 0.73 [95%CI=0.68-0.79] and 0.68 [95%CI=0.61-0.75]). In a cohort of patients presenting with acute dyspnea (n=1534), including patients with decompensated HF (n=570), a bio-ADM decision cutoff of 39 pg/mL was associated with 30- and 90-day mortality and conferred a 2-fold increased odds of HF diagnosis, independently from NT-proBNP. Conclusions: Bio-ADM tracks with mRAP and associates with measures of systemic congestion and with mortality in decompensated HF independently from NT-proBNP. Our findings support utility of bio-ADM as a biomarker of systemic venous congestion in HF and nominate a decision threshold.
Abstract 13869: The Impact of Genotype on Aortic Dilation in Pediatric Patients With RASopathy
Authors: Rabia S Khan, Kathryn N Weaver, Lisa Martin, Carlos Prada, Chet Villa
Journal: Circulation (2021)

Introduction: Proximal aortic dilation is an important cause of morbidity and mortality secondary to rupture, dissection, and complications of repair. It has been described as a rare finding in RASopathy, but data is limited regarding prevalence, severity, and genetic factors. This study aims to examine outcomes and genotype associations in pediatric patients with aortic dilation and RASopathy. Methods: A retrospective review performed at a single pediatric referral center. Study population included children with a molecularly confirmed RASopathy diagnosis evaluated between January 2000 and August 2019. Baseline data included demographics, genetic data, cardiac diagnostic data, clinical course, and mortality outcome. Results: Ninety patients were identified (mean age 10.4, female 48%). Aortic dilation was found in 28%. Of these, 68% had mild dilation, while moderate and severe dilation were each seen in 16%. Aortic dilation occurred in all major RASopathy types (Noonan, Noonan with Multiple Lentigenes, Costello, and Cardiofaciocutaneous). Hypertrophic cardiomyopathy was seen in 30% and pulmonary stenosis in 53% of RASopathy patients, with similar prevalence among those with aortic dilation (p=1 and 0.45, respectively). Aortic dilation was more prevalent in RAS ( KRAS , HRAS , NRAS ) variants (4/9 versus 12/81, p=0.0494). It was also seen in 16 of 60 patients with PTPN11 variants in association with all three commonly involved regions (exon 3 of N-SH2 region and exons 8 and 13 of PTP domain). The two patients with extreme dilation (z-score &gt; 6) had variants of amino acids 61 and 63 in exon 3 of PTPN11 . No surgical interventions targeting aortic dilation were performed in any patient, and there were no reports of dissection or rupture. There was no clear progression of dilation, and two patients had complete resolution with time. Discussion: Aortic dilation occurred in all four major types of RASopathy and was associated with most of the affected genes, with distribution along the PTPN11 gene being similar to the distribution of RASopathy. The dilation was not progressive and there were no complications or interventions. RAS genes and exon 3 of the PTPN11 gene demonstrated a possible higher association with aortic dilation and warrant further investigation.
NIMG-38. MEASURING ADHERENCE TO TRIPOD OF ARTIFICIAL INTELLIGENCE PAPERS IN THE GLIOMA SEGMENTATION
Authors: Niklas Tillmanns, Avery Lum, W R Brim, Harry Subramanian, Ming Lin, Khaled Bousabarah, Ajay Malhotra, Jin cui, Alexandria Brackett, Sam Payabvash, Ichiro Ikuta, Michele Johnson, Bernd Turowski, Mariam Aboian
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Generalizability, reproducibility and objectivity are critical elements that need to be considered when translating machine learning models into clinical practice. While a large body of literature has been published on machine learning methods for segmentation of brain tumors, a systematic evaluation of paper quality and reproducibility has not been done. We investigated the use of “Transparent Reporting of studies on prediction models for Individual Prognosis Or Diagnosis” (TRIPOD) items, among papers published in this relatively new and growing field. METHODS According to PRISMA a literature review was performed on four databases, Ovid Embase, Ovid MEDLINE, Cochrane trials (CENTRAL) and Web of science core-collection first in October 2020 and a second time in February 2021. Keywords and controlled vocabulary included artificial intelligence, machine learning, deep learning, radiomics, magnetic resonance imaging, glioma, and glioblastoma. The publications were assessed in order to the TRIPOD items. RESULTS 37 publications from our database search were screened in TRIPOD and yielded an average score of 12.08 with the maximum score being 16 and the minimum score 7. The best scoring item was interpretation (item 19) where all papers scored a point. The lowest scoring items were the title, the abstract, risk groups and the model performance (items number 1, 2, 11 and 16), where no paper scored a point. Less than 1% of the papers discussed the problem of missing data (item 9) and the funding of research (item 22). CONCLUSION TRIPOD analysis showed that a majority of the papers do not score high on critical elements that allow reproducibility, translation, and objectivity of research. An average score of 12.08 (40%) indicates that the publications usually achieve a relatively low score. The categories that were consistently poorly described include the ML network description, measuring model performance, title details and inclusion of information into the abstract.
Enterococcal bacteremia in mice is prevented by oral administration of probiotic <i>Bacillus</i> spores
Authors: Pipat Piewngam, Janice Chiou, Joie Ling, Ryan Liu, Pawiya Pupa, Yue Zheng, Michael Otto
Journal: Science Translational Medicine (2021)

Quorum sensing contributes to systemic Enterococcus infection in mice and is inhibited by oral administration of Bacillus spores.
Practice Gaps and Barriers in Optimal Care Among Healthcare Providers Treating Patients with Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Results of a Two-Phase Qualitative/Quantitative Study
Authors: Marie N Becker, Alexandra Howson, Timothy A. Quill, Naval Daver, Eytan M. Stein
Journal: Blood (2021)
Abstract 14412: Endothelial Cell-Selective Adhesion Molecule Deficiency in Mice Causes Vascular Endothelial Dysfunction and Impairs Left Ventricle Diastolic Function
Authors: Vadym Buncha, Katie Fopiano, Yanna Tian, Liwei Lang, Zsolt A Bagi
Journal: Circulation (2021)

Dysfunction of vascular endothelium plays a key role in the development of left ventricular diastolic dysfunction (LVDD) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). Recently, Endothelial Cell-Selective Adhesion Molecule (ESAM) was proposed as a novel biomarker in HFpEF. We hypothesized that ESAM plays a mechanistic role in the development of both microvascular dysfunction and LVDD. ESAM knockout and wild type (WT) mice were employed. Using transthoracic echocardiography it was found that ESAM knockout mice displayed LV diastolic dysfunction, as indicated by a significantly reduced E/A ratio (E=early, A=late mitral inflow peak velocities), increased E/e’ ratio, isovolumic relaxation time (IVRT) and increased E wave deceleration time, with no change in the ejection fraction. The systolic blood pressure, as measured by tail-cuff plethysmography, was not different between ESAM knockout and WT mice; and no cardiac hypertrophy was detected in the ESAM knockout mice. Vasodilator function of the pulmonary artery and aorta was assessed using wire myography. We found that the endothelium-dependent, acetylcholine-induced relaxation of the aorta and pulmonary artery was significantly reduced in ESAM knockout mice, whereas endothelium-independent, nitric oxide donor, sodium nitroprusside-induced relaxation was similar in the two groups. Thus, we concluded that ESAM deficiency in mice display a HFpEF phenotype, in that ESAM knockout mice develop endothelial dysfunction and LVDD.
Exposure-Response Relationship between Von Willebrand Factor (VWF) Activity and Bleeding Events Following Prophylaxis with Recombinant VWF (rVWF, vonicog alfa) in Patients with Severe Von Willebrand Disease (VWD)
Authors: Yi Wang, Gülden Özen, Björn Mellgård, Jean Francois Marier, Olivier Barriere, Grygoriy Vasilinin, Indranil Bhattacharya
Journal: Blood (2021)
Abstract 9649: Challenging The Dogma: Increasing Cardiac Fatty Acid Rather Than Glucose Utilisation Improves Cardiac Function in Severe Non-Ischaemic Heart Failure With Reduced Ejection Fraction (HFrEF)
Authors: William Watson, Peregrine Green, Andrew J Lewis, Stefan Neubauer, Giovanni Luigi De Maria, Neil Herring, Oliver J Rider
Journal: Circulation (2021)

Introduction: Based on the premise that in HFrEF the heart is metabolically inflexible and oxygen limited, current metabolic therapies aim to increase glucose oxidation. However, if the human failing heart is neither inflexible nor oxygen limited, this approach is called into question. Methods: During either insulin-glucose (GI) or Intralipid infusion (IL) (random order), 20 non-ischaemic HFrEF patients underwent cardiac magnetic resonance imaging and 31 P-spectroscopy at rest and during dobutamine infusion (mean 100 bpm). 10 patients underwent invasive arteriovenous blood sampling (left main–coronary sinus), coronary flow and left ventricular (LV) pressure-volume loop measurements, during GI and IL infusion, at rest and during rapid atrial pacing (100 bpm). Results: At rest, during IL fatty acid (FA) uptake was higher (61±53 vs 5±13 μmol/min, p=0.03) and during GI, glucose uptake was higher (97±53 vs 45±36 μmol/min, p=0.04). Compared to fasting conditions, LV ejection fraction was higher during IL (40±9 vs 35±9%, p&lt;0.001), but unchanged during GI (34±8%). Cardiac work was higher during IL (466±148 vs 549±163 mmHg.L/min, p=0.02), as was LV developed pressure (by 6mmHg, p=0.049). At rest, during IL, myocardial oxygen uptake (MVO 2 20±9 vs 15±9 ml/min, p=0.05) and phosphocreatine/ATP ratio (PCr/ATP 2.01±0.33 vs 1.86±0.25, p=0.02) were higher and lactate was consumed. Stress cardiac work was again higher during IL (by 62mmHg.L/min, p=0.009). Despite higher cardiac work and MVO 2 during IL at stress, PCr/ATP was again unchanged and lactate consumed. During GI, with atrial pacing (100 bpm) FA uptake was increased &gt;4 fold (5±14 vs 24±32 μmol/min, p=0.04), suggesting selective FA preference. Conclusions: In severe HFrEF cardiac metabolic flexibility is retained changing substrate use to match arterial supply and workload. At rest and stress, increased FA uptake, but not glucose is associated with increased contractility. Cardiac preference to FA was observed during stress. Despite increased MVO 2 , the phosphocreatine pool remains stable and lactate is consumed, showing that mitochondrial oxygen supply was not fixed or limited. This challenges existing dogma, suggesting increasing FA oxidation and not glucose should be the therapeutic target in HFrEF.
Abstract 11691: Deep Learning Predicts Need for Permanent Pacemaker Following Transcatheter Aortic Valve Replacement
Authors: Demilade A Adedinsewo, Parth Patel, Alexander Weston, Julio Perez-Downes, Najiyah Salwa, Rayan Suliman, Peter Pollak, Abdallah El Sabbagh, Mohamad H Yamani, Rickey Carter
Journal: Circulation (2021)

Introduction: Conduction disturbance after transcatheter aortic valve replacement (TAVR) remains a common complication. Predictive tools to identify conduction disturbance requiring pacing are limited. Our main objective was to develop a deep learning model to predict the need for a permanent pacemaker. Hypothesis: An electrocardiogram (ECG) based deep learning algorithm can predict the need for permanent pacemaker post TAVR. Methods: We evaluated patients who had TAVR at Mayo Clinic between June 2010 and May 2021. Digital ECGs done on the TAVR date or within 24 hours post procedure were partitioned into training, validation, and testing datasets. We trained a deep learning algorithm on the training data and optimized hyperparameters against the validation data. All model performance metrics are based on the reserved test data that were estimated once model architecture was optimized. Need for permanent pacemaker, defined as pacemaker placement due to development of conduction disturbance post TAVR and at least 1% ventricular pacing on device interrogation done at least 2 weeks post pacemaker implantation, was the training target. Results: A total of 3021 patients were evaluated for inclusion and 2,407 cases were available for modeling (exclusions: prior pacemaker (n=419), unsuccessful TAVR (n=27) and no ECG within the pre-specified period (n=168)). Overall, the median age was 82 (Q1: 76, Q3: 86) and 41% were female. In the withheld test data, 15% had a permanent pacemaker with at least 1% ventricular pacing. The algorithm detected the need for pacemaker in the test set with an AUC of 0.83 (95% CI: 0.73 to 0.92). Accuracy, sensitivity, specificity, positive and negative predictive were 80%, 72%, 81%, 41% and 94%, respectively. Conclusions: This study demonstrates the ability of a deep learning model based on ECG data to assist in making the decision to implant a pacemaker following TAVR with a high negative predictive value. Larger validation studies are warranted.
Leukaemia Cells Induced Metabolic Alterations in AML Associated Mesenchymal Stem Cells Via Notch Signalling
Authors: Helal Mohammed Mohammed Ahmed Noman, Yahya Saleh Al-Matary, Subbaiah Chary Nimmagadda, Pradeep Kumar Patnana, Longlong Liu, Lanying Wei, Daria Frank, Georg Lenz, Cyrus Khandanpour
Journal: Blood (2021)
Abstract 11108: Association of a Virtual Career Development Forum with Confidence and Presentation Performance in Early-Career Academic Cardiologists During Covid-19
Authors: Bryan C Taylor, Joan B Fowler, Rebecca Weaver, Robert O Bonow, Don Lloyd-jones, Sadiya Khan
Journal: Circulation (2021)

Introduction: Academic cardiology continues to face significant challenges in retaining physician-scientists with attrition occurring at key steps in career development progression, particularly in the transition from fellow to faculty. Available data demonstrate that factors that may promote retention and support success for early-stage investigators (ESIs) include structured mentorship, networking and peer collaboration, and didactics on scientific writing. However, the impact of the COVID-19 pandemic on career development activities, such as the Northwestern Cardiovascular Young Investigators’ Forum (NCYIF), is not known. Hypothesis: An adaptive, virtual NCYIF format, delivered on a remote basis, can still achieve important educational and career development outcomes metrics, including confidence and performance by ESIs. Methods: In 2020, the NCYIF pivoted its in-person content to an online, virtual delivery using the following elements: pre-meeting technical skills and Zoom trainings, virtual presentation coaching sessions, interactive Zoom breakouts for mentoring (including near-peer alumni mentoring), and a downloadable mobile app. We conducted a pre- and post-meeting survey-based analysis to examine outcomes for ESIs who attended the virtual NCYIF meeting, including confidence in presentation skills and responding to questions by meeting judges (5-point Likert scale). All participants had an opportunity to meet 1:1 with a pre-meeting public speaking coach. Results: Of 31 attendees, 44% were fellows, 20% were women, and 61% were non-White. From pre- to post-meeting assessment, change in confidence increased significantly for presentation skills (3.07 vs. 3.46, p=0.009) and for ability to respond to questions and comments during the judging session (2.76 vs. 3.17, p=0.025). 68% of individuals completed pre-meeting coaching. Performance improvements were significant regardless of use of pre-meeting coaching support. Conclusions: Online-based delivery of a multi-day professional skills and career development forum for ESIs in academic cardiology resulted in significant improvements in confidence and presentation performance and supports the scalability of future content through a virtual platform.
小児急性骨髄性白血病(AML)におけるWT1突然変異の有病率と予後的意味:小児腫瘍学グループの報告
Authors: A Ho Phoenix, Zeng Rong, A Alonzo Todd, B Gerbing Robert, L Miller Kristen, A Pollard Jessica, L Stirewalt Derek, A Heerema Nyla, C Raimondi Susana, Hirsch Betsy, L Franklin Janet, Lange Beverly, Meshinchi Soheil
Journal: Blood (2010)
PATH-15. NON-CANONICAL IDH 1 AND IDH 2 MUTATIONS ARE ASSOCIATED WITH IMPROVED SURVIVAL IN PATIENTS WITH GLIOMAS: RESULTS OF A META-ANALYSIS
Authors: Vincenzo Di nunno, Enrico Franceschi, Alicia Tosoni, Lidia Gatto, Antonella Mura, Giorgia Acquaviva, Dario De Biase, Stefania Bartolini, Alba Ariela Brandes
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Non-canonical isocitrate dehydrogenase (IDH) mutations are uncommon among patients with grade 2 and 3 gliomas and their clinical significance is still unclear. METHOD We carried out a systematic review and meta-analysis to evaluate the prognostic impact of IDH1 and IDH2 non-canonical mutations. We searched English-written articles published on PubMed/Medline, Cochrane library, and Scopus until the 1st May 2021. Keywords adopted for the research were: ‘’IDH’’ OR ‘’IDH1’’ OR ‘’IDH2’’ OR ‘’Isocitrate dehydrogenase’’ AND ‘’glioma’’. RESULTS We selected 13 of 3513 studies reporting data of 4007 patients with a diagnosis of grade 2 and grade 3 including 3091 patients with a molecular proven IDH 1 or IDH 2 mutations. Between patients with IDH mutated gliomas, 479 (15.5%) patients showed non-canonical IDH 1 or IDH 2 mutations. The presence of IDH 1 non-canonical mutation occurred in younger age and in non codeleted 1p19q as compared to canonical IDH 1 mutation. However, patients with IDH 2 mutations showed more frequently 1p19q codeletion as compared to those with canonical IDH 1 mutated glioma. Four studies reported complete data survival for patients with non-canonical (n= 160) and canonical mutations (n= 1019). The pooled HR of these studies was 0.47 (95% CI, 0.28-0.81) confirming a positive prognostic role for non-canonical IDH 1 and IDH 2 mutations. CONCLUSION The presence of non-canonical IDH 1 and IDH 2 mutations defines a specific subgroup of gliomas occurring at younger age with improved survival. Patients with a non-canonical IDH 1 mutation showed less frequently 1p19q codeletion as compared to those patients harboring a canonical or IDH 2 mutation.