tbuckley/cabot-search huggingface dataset:
PDTM-08. SINGLE-CELL GENOMICS REVEALS TUMOR-INITIATING PROGENITORS AND ONCOGENIC CASCADES DURING TUMORIGENESIS AND RELAPSE IN MEDULLOBLASTOMA
Authors: Liguo Zhang, Xuelian He, Xuezhao Liu, Kalen Berry, Richard Lu
Journal: Neuro-Oncology (2019)

Abstract Progenitor heterogeneity and identities underlying tumor initiation and relapse in medulloblastomas, the most common malignant pediatric brain tumor, remain elusive. Here, by utilizing single-cell analysis at different stages of tumorigenesis, we demonstrated a developmental hierarchy of diverse progenitor pools in sonic hedgehog (SHH)-medulloblastomas. Unexpectedly, we identified Olig2-expressing progenitors as transit-amplifying cells at the onset of tumorigenesis. Although Olig2+ cells become quiescent stem-like progenitors in full-blown tumors, they are highly enriched in therapy-resistant and recurrent medulloblastomas. High-level OLIG2 expression is associated with poor outcome in human SHH-medulloblastomas. Depletion of mitotic Olig2+ progenitors or Olig2-ablation impeded tumorigenesis. Transcriptome and chromatin-occupancy profiling revealed that Olig2 modulates the chromatin landscape and activates oncogenic networks including HIPPO-Yap/Taz and Aurora-A/MycN pathways. Co-targeting these oncogenic pathways induced tumor growth arrest. Together, our results raise the unanticipated possibility that glial lineage-associated Olig2-expressing progenitors are tumor-initiating cells during medulloblastoma tumorigenesis and relapse, suggesting Olig2-driven oncogenic networks as potential therapeutic targets.
Case Management Featuring Community Health Workers Reduces Inpatient Health Care Utilization in Adults with Sickle Cell Disease
Authors: Wally R Smith, Daniel Sop, Shirley Johnson, Thokozeni Lipato, Mica Ferlis, Caitlin Mcmanus, Margaret Guy, Sarah Hartigan, Emily Holt, Chantal McHenry, John D. Roberts
Journal: Blood (2019)
Risk Factors and Trends for Incidence of Acute Coronary Syndrome after Hematopoietic Stem Cell Transplant - a 15-Year Experience with National Inpatient Sample
Authors: Jasdeep Singh Sidhu, Jeevanjot Kaur Virk, Shivani Handa, Amrendra Mandal, Sridevi Rajeeve
Journal: Blood (2019)
Dose Optimization in Elderly CML Patients Treated with Bosutinib after Intolerance or Failure of First-Line Tyrosine Kinase Inhibitors
Authors: Fausto Castagnetti, Gabriele Gugliotta, Monica Bocchia, Malgorzata Monika Trawinska, Isabella Capodanno, Massimiliano Bonifacio, Giovanna Rege Cambrin, Monica Crugnola, Gianni Binotto, Chiara Elena, Alessandro Lucchesi, Micaela Bergamaschi, Francesco Albano, Luigiana Luciano, Federica Sorà, Francesca Lunghi, Fabio Stagno, Patrizia Pregno, Alessandra Iurlo, Anna Rita Scortechini, Michele Cedrone, Raffaele Spadano, Elena Trabacchi, Monia Lunghi, Giuseppina Spinosa, Dario Ferrero, Massimo Pini, Davide Rapezzi, Laura Nocilli, Michele Cavo, Giuseppe Saglio, Fabrizio Pane, Michele Baccarani, Gianantonio Rosti
Journal: Blood (2019)
Oral Azacitidine and Cedazuridine Approximate Azacitidine Efficacy in a Murine Model
Authors: Haley E. Ramsey, Maria Arrate, Londa Fuller, Agnieszka E. Gorska, Kelli Boyd, Melissa A. Fischer, Aram Oganesian, Mohammad Azab, Michael R. Savona
Journal: Blood (2019)
Long Non-Coding RNAs As Novel Therapeutic Targets in Juvenile Myelomonocytic Leukemia: Proof of Concept Study
Authors: Mattias Hofmans, Barbara Depreter, Tim Lammens, Helene Cave, Christian Flotho, Henrik Hasle, Valerie de Haas, Charlotte M. Niemeyer, Jan Stary, Pieter Van Vlierberghe, Jan Philippé, Barbara De Moerloose
Journal: Blood (2019)
NIMG-30. REPRODUCIBLE RADIOMIC MAPPING OF TUMOR CELL DENSITY BY MACHINE LEARNING AND DOMAIN ADAPTATION
Authors: Lujia Wang, Hyunsoo Yoon, Andrea Hawkins-Daarud, Kyle Singleton, Kamala Clark-Swanson, Bernard Bendok, Maciej Mrugala, Jenny Eschbacher, Kris Smith, Peter Nakaji, Ashlyn Gonzalez, Ashley Nespodzany, Leslie Baxter, Teresa Wu, Kristin Swanson, Leland Hu, Jing Li
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND An important challenge in radiomics research is reproducibility. Images are collected on different image scanners and protocols, which introduces significant variability even for the same type of image across institutions. In the present proof-of-concept study, we address the reproducibility issue by using domain adaptation – an algorithm that transforms the radiomic features of each new patient to align with the distribution of features formed by the patient samples in a training set. METHOD Our dataset included 18 patients in training with a total of 82 biopsy sample. The pathological tumor cell density was available for each sample. Radiomic (statistical + texture) features were extracted from the region of six image contrasts locally matched with each biopsy sample. A Gaussian Process (GP) classifier was built to predict tumor cell density using radiomic features. Another 6 patients were used to test the training model. These patients had a total of 31 biopsy samples. The images of each test patient were purposely normalized using a different approach, i.e., using the CSF instead of the whole brain as the reference. This was to mimic the practical scenario of image source discrepancy between different patients. Domain adaptation was applied to each test patient. RESULTS Among the 18 training patients, the leave-one-patient-out cross validation accuracy is 0.81 AUC, 0.78 sensitivity, and 0.83 specificity. When the trained model was applied to the 6 test patients (purposely normalized using a different approach than that of the training data), the accuracy dramatically reduced to 0.39 AUC, 0.08 sensitivity, and 0.61 specificity. After using domain adaption, the accuracy improved to 0.68 AUC, 0.62 sensitivity, and 0.72 specificity. CONCLUSION We provide candidate enabling tools to address reproducibility in radiomics models by using domain adaption algorithms to account for discrepancy of the images between different patients.
Amnion Implantation in Peripheral Vascular Disease
Authors: A. Webb-Jones
Journal: BMJ (1958)

<h3>Introduction</h3> SCFN of the newborn is an uncommon, self-limiting panniculitis characterized by development of erythematous, firm, indurated plaques or nodules commonly over the extremities, back, buttocks and thighs, mostly occurring in term or post term babies within the first few weeks after birth. Hypercalcaemia is a life threatening complication which requires monitoring for several months.Perinatal mechanical stress, tissue hypoxia, and hypothermia may contribute to the pathogenesis. Exact incidence is unknown with a nearly equal male to female ratio. <h3>Case Background</h3> We report a neonate presenting to emergency department by parents at 10 days of life from home with a sudden onset bruise-like linear lesion 6 cm long and 1.5 cm wide extending from the midline of upper part of the back to the right axilla. There was no history of trauma and baby was born via NVD. The skin lesion was red/purple in colour, non tender and palpable on examination. Clinical examination was otherwise unremarkable. As the marks on the back were suggestive of bruising, the baby underwent detailed Non Accidental Injury (NAI) investigations and social services assessment. Coagulation studies and FBC were normal. MRI brain reported subdural haematoma and suspected skull fracture, making NAI a strong consideration. Ophthalmology assessment and skeletal survey were normal. CT Skull was advised and this excluded skull fracture in favour of vermian skull bones. The origin of the subdural haematoma was then deemed uncertain but reported to be likely associated with vaginal delivery. Dermatology consultation confirmed the clinical diagnosis of SCFN of newborn. <h3>Conclusion</h3> SCFN is a rare but important condition to consider in young infants who present with unexplained bruise-like lesions which require thorough investigation and consideration of possible NAI. Dermatology opinion was very helpful and should be sought if there is uncertainty about differential diagnosis.
Characterization of Bypassing Kinases Inferred By Phosphoproteomics in a Midostaurin Resistant Myeloid Cell Line Model
Authors: Mahmoud Hallal, Sophie Braga-Lagache, Jovana Jankovic, Rémy Bruggmann, Ramanjaneyulu Allam, Mario P. Tschan, Cédric Simillion, Manfred Heller, Nicolas Bonadies
Journal: Blood (2019)
Achievement of Complete Remission (CR) with Measurable Residual Disease (MRD) Negativity Is Highly Prognostic in Patients (pts) with Relapsed or Refractory (R/R) Acute Myeloid Leukemia (AML) Receiving First Salvage Chemotherapy
Authors: Nicholas J. Short, Hind Rafei, Naval G. Daver, Hyunsoo Hwang, Jing Ning, Jorge E. Cortes, Jeffrey L. Jorgensen, Tapan M. Kadia, Courtney D. DiNardo, Sa A Wang, Elias Jabbour, Uday Popat, Betul Oran, Marina Y Konopleva, Guillermo Garcia-Manero, Gautam M. Borthakur, Kapil N. Bhalla, Ghayas C. Issa, Hagop M. Kantarjian, Farhad Ravandi
Journal: Blood (2019)
Controlled Growth Factor Release in 3D‐Printed Hydrogels
Authors: Pengrui Wang, David Berry, Amy Moran, Frank He, Trevor Tam, Luwen Chen, Shaochen Chen
Journal: Advanced Healthcare Materials (2019)

Abstract Growth factors (GFs) are critical components in governing cell fate during tissue regeneration. Their controlled delivery is challenging due to rapid turnover rates in vivo. Functionalized hydrogels, such as heparin‐based hydrogels, have demonstrated great potential in regulating GF release. While the retention effects of various concentrations and molecular weights of heparin have been investigated, the role of geometry is unknown. In this work, 3D printing is used to fabricate GF‐embedded heparin‐based hydrogels with arbitrarily complex geometry (i.e., teabag, flower shapes). Simplified cylindrical core–shell structures with varied shell thickness are printed, and the rates of GF release are measured over the course of 28 days. Increasing the shell layers' thickness decreases the rate of GF release. Additionally, a mathematical model is developed, which is found capable of accurately predicting GF release kinetics in hydrogels with shell layers greater than 0.5 mm thick ( R 2 &gt; 0.96). Finally, the sequential release is demonstrated by printing two GFs in alternating radial layers. By switching the spatial order, the delivery sequence of the GFs can be modulated. This study demonstrates how 3D printing can be utilized to fabricate user‐defined structures with unique geometry in order to control the rate of GF release in hydrogels.
EXTH-11. TREATMENT WITH DELTA-24-RGDOX OF SUBCUTANEOUS TUMORS RESULTS IN ABSCOPAL EFFECT ERADICATING INTRACRANIAL MELANOMAS
Authors: Hong Jiang, Dong Ho Shin, Teresa Nguyen, Marta M Alonso, Frederick Lang, Candelaria Gomez-Manzano, Juan Fueyo
Journal: Neuro-Oncology (2019)

Abstract Immune checkpoint blockade has revolutionized cancer therapy; however the therapeutic benefit is limited to only a subset of patients with immunogenic (“hot”) tumors and is compromised by immune-related adverse events. We have reported the efficacy of oncolytic adenovirus Delta-24-RGDOX (DNX-2440) in syngeneic glioma mouse models. We hypothesized that localized treatment with the virus is effective against disseminated melanomas, including intracranial melanomas. We tested the hypothesis in the subcutaneous (s.c.)/s.c. and s.c./intracranial (i.c.) melanoma models derived from luciferase-expressing B16-Red-FLuc cells in C57BL/6 mice. First, through monitoring tumor growth with bioluminescence imaging, we found that, in both s.c./s.c. and s.c./i.c. models, three injections of Delta-24-RGDOX significantly inhibited the growth of both the virus-injected s.c. tumor and untreated distant s.c. or i.c. tumor, thereby prolonging survival. Next, through cell profiling with flow cytometry, we observed that the virus increased the presence of T cells and effector T cell frequency in the virus-injected tumor and mediated the same changes in T cells from peripheral blood, tumor-draining lymph nodes (TDLNs), spleens, and brain hemispheres with untreated tumor. Moreover, Delta-24-RGDOX decreased the frequency of exhausted T cells and regulatory T cells in the virus-injected and untreated i.c. tumors. Consequently, the virus promoted recruitment and/or in situ expansion of antigen-specific T cells in tumors expressing the target antigen. Therefore, we concluded that local intratumoral injection of Delta-24-RGDOX resulted in systemic immune activity against the disseminated tumors. Furthermore, we speculate that given the immunogenicity, cancer-selectivity and intratumoral administration of the virus, Delta-24-RGDOX is expected to have an improved safety profile when compared to immune checkpoint blockade treatment strategies. This is the first report demonstrating that local administration of oncolytic adenovirus results in eradication of intracranial tumors, suggesting Delta-24-RGDOX could be used to manage brain metastases of melanoma.
Safety and Efficacy of Combined Ruxolitinib and Thalidomide in Patients with Myelofibrosis: A Phase II Study
Authors: Raajit K. Rampal, Srdan Verstovsek, Sean M. Devlin, Amber C. King, Eytan M. Stein, Naveen Pemmaraju, Michael J. Mauro, Tapan M. Kadia, Guillermo Montalban-Bravo, Kelsey Alvarez, Nicole Ard, Tawni Goodman, Bria Taylor, Prithviraj Bose
Journal: Blood (2019)
QOLP-37. QUALITATIVE RESEARCH IN LOWER GRADE GLIOMA: UNDERSTANDING SIGNS, SYMPTOMS, AND DISEASE IMPACTS DURING EXPECTANT MANAGEMENT
Authors: Audra Boscoe, Ted Wells, Christina Graham, Caitlin Pohl, Brooke Witherspoon, Christa Kerkorian, Lori Steelman, Shuchi S Pandya
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with lower grade glioma (LGG) (i.e., grade II or III) have limited treatment options. After surgical resection of their tumor, patients will undergo either a period of expectant management (watch and wait) or treatment with adjuvant chemotherapy and/or radiotherapy. Approximately 80% of patients with LGG have an isocitrate dehydrogenase mutation, which is a viable target for molecular therapy. This offers a therapeutic intervention that could potentially delay the need for chemotherapy and/or radiotherapy in select patients. Several prognostic and patient-specific factors contribute to the decision to recommend expectant management, including concerns about the side effects of chemotherapy and radiotherapy. The aim of this project was to understand patients’ signs and symptoms during the expectant management period and how LGG impacts their lives. METHODS Concept elicitation interviews were conducted in the US with patients with LGG as well as key opinion leaders (KOLs) with experience treating patients with LGG. Interview data were analyzed using Atlas.ti, and patient data were reviewed against KOL data. RESULTS Seven patients with ≥ 3 months of expectant management experience and three KOLs were interviewed. During their expectant management periods, patients reported 12 signs/symptoms, mostly related to deficits in cognition. Patients reported 16 impacts across four categories, with a substantial proportion of the impacts identified as negatively affecting emotional function. The signs/symptoms and impacts reported by patients were generally also reported by KOLs. During expectant management, patients typically resume their original quality of life post-surgery, but may also experience anxiety. Patients and KOLs indicated a preference for expectant management and delaying chemotherapy or radiotherapy. CONCLUSIONS Patient and KOL interviews characterized the LGG experience and indicated a preference for expectant management, which may be supported by therapies that delay the initiation of chemotherapy and/or radiotherapy.
RARE-23. HIGH DOSE METHOTREXATE WITH OR WITHOUT VINCRISTINE FOR PRIMARY CNS LYMPHOMA, THE OHIO STATE UNIVERSITY EXPERIENCE
Authors: Tracelyn Freeman, Carlo Legasto, Alex Schickli, Eric McLaughlin, Pierre Giglio, Vinay Puduvalli, Javier Gonzalez
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES 1) Determine the response rate (RR) after chemotherapy with high-dose methotrexate with or without vincristine in patients with primary CNS lymphoma. 2) Determine the difference in adverse effects with the use of vincristine. 3) Determine the difference in progression-free survival (PFS) and overall survival (OS) between the 2 groups. METHODS Retrospective study in patients 18–89 years with primary CNS lymphoma that received chemotherapy with rituximab (R), methotrexate (M), procarbazine (P), and vincristine (V) R-MPV, R-MV, R-MP, or R-M between 2010 and 2018 at The Ohio State University. Response rate by cycle 7 was compared with odds ratio. Kaplan-Meier curves were used to compare OS and PFS. RESULTS 29 patients were included: 16 (55%) received vincristine. 14/16 patients treated with vincristine and 4/13 in the other group also had procarbazine. 12/29 patients had a complete response after a maximum of 7 cycles. The odds of complete response were 24% higher in patients treated with vincristine but the difference did not reach statistical significance. Side effects were higher in the vincristine arm. The most common was peripheral neuropathy (75% vs 8% - all grades). Median PFS was 60.7 months for the vincristine group and 23.7 months for the non-vincristine group. Median OS was 85.3 months for the vincristine group and 67.1 months for the non-vincristine group. OS and PFS curves did not differ significantly. CONCLUSIONS The use of vincristine in high-dose methotrexate chemotherapy regimens for CNS lymphoma was not associated with a statistically significant difference in RR. Patients who received vincristine had more side effects and there were no significant differences in OS and PFS. The sample size and rate of procarbazine use may be confounding factors. Further studies are necessary to determine the effect of vincristine in RR and OS in these patients.
A novel cryoballoon ablation system for eradication of dysplastic Barrett’s esophagus: a first-in-human feasibility study
Authors: Sanne Noortje van Munster, Anouk Overwater, Mihaela G. M. Raicu, Kees C. A. Seldenrijk, Wouter B. Nagengast, Erik J. Schoon, Jacques J. G. H. M. Bergman, Bas L. A. M. Weusten
Journal: Endoscopy (2019)

Abstract Background Endoscopic cryoablation for Barrett’s esophagus (BE) might offer advantages over heat-based ablation. Focal cryoballoon ablation has been promising for short-segment BE, whereas the novel 90°-swipe cryoballoon ablation system (CbSAS90) ablates larger areas in a single step (90° over 3 cm). The system allows for dose adjustment. CbSAS90 has been feasible and safe in animal and pre-esophagectomy studies. This is the first clinical study to assess feasibility, safety, and efficacy of CbSAS90 for eradication of dysplastic BE. Methods In this prospective study in dysplastic BE patients, dose finding started with semi-circumferential treatment at 0.8 mm/s (dose 1). The dose was escalated by reducing speed by 0.1 mm/s in six patients until BE surface regression was ≥ 80 % without complications (“effective dose”). The effective dose was subsequently confirmed with circumferential treatment in 12 new patients. Post-procedural pain (0 – 10) and dysphagia (0 – 4) were evaluated. Outcomes were feasibility, safety, and BE surface regression. Results 25 patients were included, with technically successful treatment in 92 % (95 %CI 73 % – 99 %). Median (95 %CI) BE surface regression was 78 % (50 % – 85 %) for dose 1 and 85 % (55 % – 95 %) for dose 2 (0.7 mm/s), which was defined as the effective dose. Circumferential treatment resulted in 93 % (88 % – 96 %) regression. Two of 12 patients with circumferential treatment developed strictures that required dilation. Median pain and dysphagia scores were low (0 – 3 and 0, respectively). Conclusions CbSAS90 was feasible and effective for ablating larger BE areas. The optimal dose for circumferential treatment that balances safety and efficacy requires further evaluation.
Long-Term Outcomes of Chronic Myeloid Leukemia Patients Who Lost Undetectable Molecular Residual Disease (UMRD) after Imatinib Discontinuation: Korean Imatinib Discontinuation Study (KIDS)
Authors: Sung-Eun Lee, Joon Seong Park, Hyeoung-Joon Kim, Sung-Hyun Kim, Dae Young Zang, Sukjoong Oh, Young Rok Do, Yunsuk Choi, Jae-Yong Kwak, Jeong-A Kim, Kyoo Hyung Lee, Yeung-Chul Mun, Won Sik Lee, Myung Hee Chang, Jinny Park, Jihyun Kwon, Dong-Wook Kim
Journal: Blood (2019)
Understanding How Fc-Modification Transforms a Pathogenic Heparin-Induced Thrombocytopenia (HIT)-like Monoclonal Antibody into a Novel Treatment for Sepsis
Authors: Kandace Gollomp, Amrita Sarkar, Gowthami Arepally, Douglas B. Cines, M. Anna Kowalska, Lubica Rauova, Mortimer Poncz
Journal: Blood (2019)
FDA Analysis: Impact of Body Mass Index (BMI) on Outcomes in Relapsed-Refractory Multiple Myeloma
Authors: Rachel Ershler, Bindu Kanapuru, Yutao Gong, Urvi A Shah, Sham Mailankody, Ola Landgren, Marc Theoret, Nicole J Gormley, Ann T. Farrell, Richard Pazdur
Journal: Blood (2019)
INNV-09. CLINICAL EFFICACY OF TUMOR TREATING FIELDS FOR NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Yang Liu, Myla Strawderman, Kwanza Warren, Margie Richardson, Jennifer Serventi, Nimish Mohile, Michael Milano, Kevin Walter
Journal: Neuro-Oncology (2019)

Abstract Recent clinical trials demonstrated that adding tumor treating fields (TTF) to radiotherapy and temozolomide chemotherapy (the Stupp protocol) increased survival for glioblastoma (GBM) patients. However, data is lacking on the magnitude of this survival effect when the regimen is used outside of a clinical trial as part of routine clinical practice. In the present study, we retrospectively identified adult patients with newly diagnosed GBM (n = 240) treated with the Stupp protocol at our institution from January 2005 to July 2017. We grouped patients into two time periods for comparison: 2005–2013 (group 1, Stupp protocol) and 2014–2017 (group 2, TTF+ Stupp protocol). Thirty-six percent (37/104) of patients in group 2 received TTF in conjunction with the Stupp protocol. Within group 2, the 37-patients who received TTF + Stupp had increased 6-month and 1-year survival rates compared to the 67-patients who received Stupp alone (97.1% vs. 75.7%, p = 0.006; 67.6% vs. 53.7%, p = 0.170, respectively). The improvement of survival rate at 6-month was further confirmed by a modified Poisson model (RR: 1.23, p = 0.010) adjusting for sex, age, performance status and extent of resection. However, we did not observe improvements in overall survival (OS) with a Cox model with TTF treatment modeled as a time-dependent covariate (HR = 0.87, p = 0.599). Furthermore, we did not find that the addition of TTF as a treatment option in our center significantly improved OS for patients in group 2 when compared to those in group 1 (429.0 vs. 395.0 days, p = 0.138). Therefore, while adding TTF to the Stupp protocol appeared to benefit patients with newly diagnosed GBM, this effect may be largely due to selection bias. Comprehensive studies including large number of patients as well as longer follow-up time are needed to validate our results.
Adiponectin Inhibits the Differentiation and Maturation of Osteoclasts Via mTOR Pathway in Multiple Myeloma
Authors: Rong Fu, Liu Zhaoyun, Hui Liu, Yanqi Li, Yangyang Wang, Rui Xing, Fu Mi, Zonghong Shao, Jia Song, Chenhuan Xiang
Journal: Blood (2019)
In Systemic Light-Chain Amyloidosis Complete and Very Good Partial Responses Are Not Enough: Involved Free Light Chain (iFLC) Levels &lt; 10mg/L Are Associated with Optimal Long-Term Survival
Authors: Amandeep Godara, Denis Toskic, Benjamin Rosenthal, Cindy Varga, Adin Kugelmass, Ping Zhou, Teresa Fogaren, Raymond L Comenzo
Journal: Blood (2019)
Cardiac Pacing in Sub-Saharan Africa
Authors: Xavier Jouven, Bara I. Diop, Kumar Narayanan, Anicet Adoubi, Serigne Abdou Ba, Dahdi Balde, Jean-Marie Damorou, Mamadou Bacary Diarra, Anastase Dzudie, Beatriz Ferreira, Sedonougbo Martin Houenassi, Meo-Stephane Ikama, Abdoul Kane, Adama Kane, Samuel Kingue, Jean-Bruno Mipinda, Ana-Olga Mocumbi, Ali Niakara, Merimee Ouankou, Abdallahi Aly Sidi, Jean-Laurent Takombe, Ibrahim Ali Toure, Patrice Zabsonré, David S. Celermajer, Antoine Lafont, Bernard Dodinot, Pascal Sagnol, Eloi Marijon
Journal: Journal of the American College of Cardiology (2019)