tbuckley/cabot-search huggingface dataset:
Abstract 13434: Improved Diagnostic Performance of Contemporary Transesophageal Echocardiography With Three-dimensional Imaging for Infective Endocarditis
Authors: Johnny Chahine, Bryce Montane, Jafar Alzubi, Hanan Alnajjar, Andrew Fiore, jasmine mutti, Beni Verma, Mohamed M Gad, Emily Reznicek, Richard A Grimm, Brian P Griffin, Bo Xu
Journal: Circulation (2020)

Introduction: Infective endocarditis (IE) is associated with high morbidity and mortality. Conventionally, a repeat transesophageal echocardiogram (TEE) is necessary if the first TEE is negative, and there is high clinical suspicion. We aimed to investigate the diagnostic performance of contemporary TEE for IE. Hypothesis: We hypothesize that with advancements in TEE imaging, including three-dimensional (3D) imaging, the diagnostic performance of TEE for IE would be improved. Methods: Patients who had two or more TEEs at our center, within 6 months, for evaluation of IE in 2011 (pre-3D imaging) and 2019 (post-3D imaging) were included. Patients not meeting the Duke criteria for IE (n=899) were excluded. The primary endpoint was the sensitivity of TEE to detect IE. TEE sensitivity was also compared among the different subtypes of IE (native valve, prosthetic valve, device-related, central line-related, and aortic prosthetic graft-related). Results: 242 patients were included: 70 in 2011 and 172 in 2019. In 2011, there were more smokers and a lower rate of pacing devices; otherwise, there were no significant differences in baseline characteristics, including intravenous drug use. The sensitivity of the initial TEE for IE was 85.7% in 2011, improving significantly to 95.3% in 2019 (p=0.01). The improved diagnostic performance in 2019 was mainly driven by the improved detection of prosthetic valve IE (70.8% vs. 93.7%, p=0.009). There were no significant differences for the other subtypes of IE (Figure). In 2019, patients had a higher rate of IE diagnosis within 15 days of index admission, which did not reach statistical significance (n=161, 93.6% vs. n=62, 88.6% in 2011, p=0.19). Kaplan Meier analysis demonstrated that patients in 2019 had a higher rate of procedures for endocarditis (p=0.01). Conclusions: Contemporary TEE imaging including 3D technology improved the detection of IE on the initial TEE, mainly driven by improved detection of prosthetic valve IE.
Biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of the quinone‐methide triterpenoid celastrol
Authors: Yun Lu, Yuan Liu, Jiawei Zhou, Dan Li, Wei Gao
Journal: Medicinal Research Reviews (2020)

Abstract Celastrol, a quinone‐methide triterpenoid, was extracted from Tripterygium wilfordii Hook. F. in 1936 for the first time. Almost 70 years later, it is considered one of the molecules most likely to be developed into modern drugs, as it exhibits notable bioactivity, including anticancer and anti‐inflammatory activity, and exerts antiobesity effects. In addition, the molecular mechanisms underlying its bioactivity are being widely studied, which offers new avenues for its development as a pharmaceutical reagent. Owing to its potential therapeutic effects and unique chemical structure, celastrol has attracted considerable interest in the fields of organic, biosynthesis, and medicinal chemistry. As several steps in the biosynthesis of celastrol have been revealed, the mechanisms of key enzymes catalyzing the formation and postmodifications of the celastrol scaffold have been gradually elucidated, which lays a good foundation for the future heterogeneous biosynthesis of celastrol. Chemical synthesis is also an effective approach to obtain celastrol. The total synthesis of celastrol was realized for the first time in 2015, which established a new strategy to obtain celastroid natural products. However, owing to the toxic effects and suboptimal pharmacological properties of celastrol, its clinical applications remain limited. To search for drug‐like derivatives, several structurally modified compounds were synthesized and tested. This review focuses primarily on the latest research progress in the biosynthesis, total synthesis, structural modifications, bioactivity, and mechanism of action of celastrol. We anticipate that this paper will facilitate a more comprehensive understanding of this promising compound and provide constructive references for future research in this field.
Acute Kidney Injury After Percutaneous Edge-to-Edge Mitral Repair
Authors: Germán Armijo, Rodrigo Estevez-Loureiro, Fernando Carrasco-Chinchilla, Dabit Arzamendi, Felipe Fernández-Vázquez, Pilar Jimenez-Quevedo, Xavier Freixa, Isaac Pascual, Ana María Serrador, Dolores Mesa, Juan H. Alonso-Briales, Javier Goicolea, Rosana Hernández-Antolin, Estefania Fernández-Peregrina, Ana Belen Cid Alvarez, Leire Andraka, Ignacio Cruz-Gonzalez, Alberto Berenguer, Juan Sanchis, Jose Luis Diez Gil, Jose M. Hernández-García, Chi-Hion Li, Tomas Benito-González, Jose A. de Agustin, Pablo Avanzas, Ander Regueiro, Ignacio Amat-Santos, Manuel Pan, Luis Nombela-Franco
Journal: Journal of the American College of Cardiology (2020)
Abstract 279: Multi-task Learning Improves Model Performance in Predicting Rare Catastrophic Events in Healthcare Claims Dataset
Authors: ChienYu Chi, Yen-Pin Chen, Adrian Winkler, Kuan-Chun Fu, Fie Xu, Rohollah Soltani, Chien-Hua Huang
Journal: Circulation (2020)

Introduction: Predicting rare catastrophic events is challenging due to lack of targets. Here we employed a multi-task learning method and demonstrated that substantial gains in accuracy and generalizability was achieved by sharing representations between related tasks Methods: Starting from Taiwan National Health Insurance Research Database, we selected adult people (&gt;20 year) experienced in-hospital cardiac arrest but not out-of-hospital cardiac arrest during 8 years (2003-2010), and built a dataset using de-identified claims of Emergency Department (ED) and hospitalization. Final dataset had 169,287 patients, randomly split into 3 sections, train 70%, validation 15%, and test 15%.Two outcomes, 30-day readmission and 30-day mortality are chosen. We constructed the deep learning system in two steps. We first used a taxonomy mapping system Text2Node to generate a distributed representation for each concept. We then applied a multilevel hierarchical model based on long short-term memory (LSTM) architecture. Multi-task models used gradient similarity to prioritize the desired task over auxiliary tasks. Single-task models were trained for each desired task. All models share the same architecture and are trained with the same input data Results: Each model was optimized to maximize AUROC on the validation set with the final metrics calculated on the held-out test set. We demonstrated multi-task deep learning models outperform single task deep learning models on both tasks. While readmission had roughly 30% positives and showed miniscule improvements, the mortality task saw more improvement between models. We hypothesize that this is a result of the data imbalance, mortality occurred roughly 5% positive; the auxiliary tasks help the model interpret the data and generalize better. Conclusion: Multi-task deep learning models outperform single task deep learning models in predicting 30-day readmission and mortality in in-hospital cardiac arrest patients.
Abstract 13812: Pulmonary Function Predicts Cardiac Function, Structure &amp; Clinical Outcome in Chronic Heart Failure: Results From the Myovasc Study
Authors: Marc W Heidorn, Felix Müller, Stefanie Steck, Alexander Schuch, Sven O Tröbs, Gregor Buch, Göbel Sebastian, Andreas Schulz, Marina Panova-Noeva, Bianca Wagner, Karl J Lackner, Tommaso Gori, Thomas Muenzel, Philipp Wild, Jürgen Prochaska
Journal: Circulation (2020)

Introduction: A growing body of evidence suggests a relevance of pulmonary function in the pathophysiology of heart failure (HF). Comprehensive data on the role of forced expiratory volume in 1 second (FEV1) in the development &amp; progression of HF is limited. Hypothesis: Given this background, we hypothesized, that (FEV1) is associated with deteriorated left ventricular (LV) functional as well as structural status, &amp; predicts specific clinical outcome in HF. Methods: Data from the MyoVasc Study (n=3,289) were analysed. Comprehensive clinical phenotyping including body plethysmography for the evaluation of FEV1 &amp; standardized echocardiography were performed during a five-hour investigation in a dedicated study center. Worsening of HF (comprising transition from asymptomatic to symptomatic HF, HF hospitalization, &amp; cardiac death) was assessed during a structured follow-up with subsequent validation &amp; adjudication of endpoints. Results: Information on FEV1 was available in 2,998 individuals (age 35-84 years; 34.1% female, mean FEV1 92.4[% predicted]). In multivariable regression analysis adjusted for age, sex, height, cardiovascular risk factors (CVRF) &amp; clinical profile, FEV1 per-1SD was an independent predictor of reduced LV ejection fraction (β:-1.6[95%CI -2.0;-1.3]), elevated E/E’-ratio (β:0.82[0.64;0.99]), &amp; increased LV mass/Height 2.7 (β:1.6[1.1;2.1]) (for all, P&lt;0.001). During a median follow-up of 2.3 (interquartile range 1.1; 4.0) years, FEV1 per-1SD predicted worsening of HF (hazard ratio(HR) 1.46[1.30;1.65], P&lt;0.001) independent of age, sex, height, CVRF &amp; comorbidities. This finding was consistent among the single components of the primary study endpoint: FEV1 per-1SD predicted an increased risk for transition to symptomatic HF (HR 1.57[1.19;2.06]), HF hospitalization (HR 1.35[1.16;1.57]) &amp; for cardiac death (HR 1.84[1.49;2.26]) (for all, P&lt;0.001). FEV1 per-1SD remained an independent predictor of worsening of HF after additional adjustment for NT-proBNP (HR 1.25[1.08;1.45], P=0.002). Conclusion: Impaired FEV1 is directly linked to the pathophysiology of HF &amp; represents a strong &amp; independent predictor of HF outcome highlighting its potential value to advance risk prediction in HF.
Abstract 16072: Cellular Contraction is Required for Hyperglycemia-Induced Vascular Calcification
Authors: Hooi Hooi Ng, Daniela Medina, Amirala Bakhshian Nik, Joshua D Hutcheson
Journal: Circulation (2019)

Introduction: Diabetes-related cardiovascular disease is associated with the development of vascular calcification. Therapeutic intervention for the prevention or treatment of hyperglycemia-induced...
Abstract 15379: A Novel Acoustic Biomarker of Quality of Life in Left Ventricular Assist Device Recipients
Authors: Boyla O Mainsah, Priyesh A Patel, Xinlin Chen, Cameron Olsen, Leslie Collins, Ravi - Karra
Journal: Circulation (2020)

Introduction: Left ventricular assist device (LVAD) recipients experience variable improvements in quality of life (QoL). Methods for optimizing LVAD support to improve QoL are needed. Hypothesis: We hypothesized that acoustic signatures obtained from digital stethoscopes can predict patient-centered outcomes in LVAD recipients. Methods: Subjects were recruited from the LVAD clinic at Duke University Medical Center. Subjects were trained to use a digital stethoscope and recorded their precordial sounds weekly for 6 months. Subjects also completed a Kansas City Cardiomyopathy Questionnaire (KCCQ) weekly. The primary outcome for this study was QoL, as measured by the KCCQ summary score. Results: Twenty-four subjects, 8 supported by a HeartWare LVAD and 16 supported by a HeartMate3 (HM3) LVAD, were enrolled. We developed a novel algorithm to filter LVAD sounds from recordings. Unsupervised clustering of LVAD-mitigated sounds revealed discrete groups of acoustic features. Six out of 16 [38%] HM3 recipients made up a unique cluster and shared a common acoustic feature that we have termed the pulse synchronized sound (PSS) based on its temporal association to the artificial pulse of the HM3. Subjects with the PSS had significantly better KCCQ scores at baseline (median, 89.1 [IQR, 86.2-90.4] vs 66.1 [IQR, 31.1-73.7], P = 0.03) and over the 6 months of the study (mean = 79.67 [95% CI, 74.55 - 84.78] vs 60.57 [95% CI, 55.58 - 65.55], P &lt; .001). Mechanistically, the PSS shares acoustic features with patient-derived intrinsic sounds. Because the PSS cannot be detected by routine auscultation, we developed a robust machine learning algorithm to detect the PSS in precordial sound recordings (AUC = 0.95 by leave-one-subject out cross-validation). Conclusions: We have identified a novel acoustic feature associated with better QoL in HM3 recipients. This novel biomarker is the first of its kind in LVAD recipients and may provide a method for assaying optimized LVAD support.
Association Between Adherence to Fractional Flow Reserve Treatment Thresholds and Major Adverse Cardiac Events in Patients With Coronary Artery Disease
Authors: Maneesh Sud, Lu Han, Maria Koh, Peter C. Austin, Michael E. Farkouh, Hung Q. Ly, Mina Madan, Madhu K. Natarajan, Derek Y. So, Harindra C. Wijeysundera, Jiming Fang, Dennis T. Ko
Journal: JAMA (2020)

<h3>Importance</h3> Fractional flow reserve (FFR) is an invasive measurement used to assess the potential of a coronary stenosis to induce myocardial ischemia and guide decisions for percutaneous coronary intervention (PCI). It is not known whether established FFR thresholds for PCI are adhered to in routine interventional practice and whether adherence to these thresholds is associated with better clinical outcomes. <h3>Objective</h3> To assess the adherence to evidence-based FFR thresholds for PCI and its association with clinical outcomes. <h3>Design, Setting, and Participants</h3> A retrospective, multicenter, population-based cohort study of adults with coronary artery disease undergoing single-vessel FFR assessment (excluding ST-segment elevation myocardial infarction) from April 1, 2013, to March 31, 2018, in Ontario, Canada, and followed up until March 31, 2019, was conducted. Two separate cohorts were created based on FFR thresholds (≤0.80 as ischemic and &gt;0.80 as nonischemic). Inverse probability of treatment weighting was used to account for treatment selection bias. <h3>Exposures</h3> PCI vs no PCI. <h3>Main Outcomes and Measures</h3> The primary outcome was major adverse cardiac events (MACE) defined by death, myocardial infarction, unstable angina, or urgent coronary revascularization. <h3>Results</h3> There were 9106 patients (mean [SD] age, 65 [10.6] years; 35.3% female) who underwent single-vessel FFR measurement. Among 2693 patients with an ischemic FFR, 75.3% received PCI and 24.7% were treated only with medical therapy. In the ischemic FFR cohort, PCI was associated with a significantly lower rate and hazard of MACE at 5 years compared with no PCI (31.5% vs 39.1%; hazard ratio, 0.77 [95% CI, 0.63-0.94]). Among 6413 patients with a nonischemic FFR, 12.6% received PCI and 87.4% were treated with medical therapy only. PCI was associated with a significantly higher rate and hazard of MACE at 5 years compared with no PCI (33.3% vs 24.4%; HR, 1.37 [95% CI, 1.14-1.65]) in this cohort. <h3>Conclusions and Relevance</h3> Among patients with coronary artery disease who underwent single-vessel FFR measurement in routine clinical practice, performing PCI, compared with not performing PCI, was significantly associated with a lower rate of MACE for ischemic lesions and a higher rate of MACE for nonischemic lesions. These findings support the performance of PCI procedures according to evidence-based FFR thresholds.
Abstract 13815: Prognostic Impact of Sleep Disordered Breathing in Hospitalized Patients Following Acute Heart Failure
Authors: Sayaki Ishiwata, Takatoshi Kasai, Shoko Suda, Akihiro Sato, Hiroki Mastumoto, Jun Shitara, Shoichiro Yastu, Megumi Shimizu, Azusa Murata, Takao Kato, Masaru Hiki, Yuya Mastue, Ryo Naito, Hiroyuki Daida
Journal: Circulation (2020)

Introduction: Identifying hospitalized patients at a high risk for worse long-term clinical outcomes following acute heart failure (AHF) is important. However, limited data regarding influence of sleep-disordered breathing (SDB) and its treatment by positive airway pressure (PAP) on post-discharge clinical outcomes in hospitalized patients following AHF are available. Hypothesis: Presence of SDB may be associated with worse long-term clinical outcomes, which may be reversible by PAP therapy in patients with AHF. The aim of this study is to investigate relationship between SDB, its treatment by PAP and long-term clinical outcomes. Methods: After the initial improvement of AHF, overnight polysomnography was performed on consecutive hospitalized patients whose left ventricular (LV) ejection fraction ≤45% between May 2012 and April 2018. In the present study, SDB was defined as an apnea-hypopnea index ≥15. Patients with SDB were subdivided as those with or without PAP treatment. The incidence of deaths and re-hospitalizations due to exacerbation of heart failure until April 2019 were assessed by stepwise multivariable Cox proportional model. Results: Overall, 241 patients were enrolled. Among them, 73% had SDB and 29% were initiated into PAP. At a median follow-up of 1.7 years, 89 patients had clinical events (36.9%). In the stepwise multivariable analysis, SDB was associated with increased risk of clinical events (hazard ratio [HR], 2.20; P=0.007). Among SDB patients, stepwise multivariable analysis showed that PAP treatment was associated with reduced risk of clinical events (HR 0.45; P=0.022). Conclusions: In hospitalized patients following AHF, presence of SDB was associated with worse long-term clinical outcomes, which may be reversible by PAP therapy. Thus, following AHF, hospitalized patients with LV systolic dysfunction should be evaluated whether they have SDB and considered for SDB treatment before discharge.
Pre-depletion of TRBC1+ T cells promotes the therapeutic efficacy of anti-TRBC1 CAR-T for T-cell malignancies
Authors: Chaoting Zhang, Heyilimu Palashati, Zhuona Rong, Ningjing Lin, Luyan Shen, Ying Liu, Shance Li, Bentong Yu, Wenjun Yang, Zheming Lu
Journal: Molecular Cancer (2020)

Targeting T cell receptor β-chain constant region 1 (TRBC1) CAR-T could specifically kill TRBC1+ T-cell malignancies. However, over-expressed CARs on anti-TRBC1 CAR transduced TRBC1+ T cells (CAR-C1) bound to autologous TRBC1, masking TRBC1 from identification by other anti-TRBC1 CAR-T, and moreover only the remaining unoccupied CARs recognized TRBC1+ cells, considerably reducing therapeutic potency of CAR-C1. In addition, co-culture of anti-TRBC1 CAR-T and TRBC1+ cells could promote exhaustion and terminal differentiation of CAR-T. These findings provide a rationale for pre-depleting TRBC1+ T cells before anti-TRBC1 CAR-T manufacturing.
Abstract 16847: Comparison of Urine Output and Creatinine as Markers for Severe Acute Kidney Injury in the Immediate Post-Operative Period After Pediatric Heart Transplant
Authors: Alexander Alali, Sebastian Acosta, Mubbasheer Ahmed, Ayse Akcan Arikan, Shaine A Morris, Parag Jain
Journal: Circulation (2020)

Background: Urine output (UOP) is an important indicator for acute kidney injury (AKI) in the pediatric critical care setting as it captures approximately 20% of patients who would go undiagnosed with creatinine data alone. We hypothesized that UOP remains clinically relevant indicator of severe AKI in the immediate post-operative period after pediatric heart transplant (HT). Methods: We performed a retrospective descriptive study of all patients who underwent HT at a single, quaternary care pediatric institution between 1/2016-11/2019. Severe AKI was defined as &amp;gt= stage 2 using the Kidney Disease Improving Global Outcomes (KDIGO) criteria and measured at POD 1, 2 and 3, respectively. Baseline creatinine was defined as the lowest creatinine value in the 3 months preceding HT. Results were then subdivided into those who met severe AKI based on KDIGO creatinine criteria alone versus and those meeting criteria only by UOP. Results: During the study period, 94 patients underwent HT. Median age at HT was 7 years (range 1 month - 23 years). Criteria for severe AKI was met by 40%, 49%, and 52% at POD 1, 2 and 3 respectively. Of these, 95%, 93%, and 94% were captured with creatinine criteria (Figure 1.) Comparatively, only 3%, 3% and 4% were captured with only UOP criteria at POD 1, 2 and 3 respectively. Figure 2 illustrates an almost uniform decrease in UOP at hour 11 (median 0.83 ml/kg/hr, IQR 0.59-1.36 ml/kg/hr) with subsequent dispersion over time. Conclusions: Severe AKI is common after OHT and is largely nonoliguric, with significant less capture of severe AKI based on UOP alone. Most patients experience a decline in UOP in the first 12h but were rarely oliguric in the first 48h.
Abstract 16650: Segmental and Global Longitudinal Strain Differences Between Children With Paediatric Inflammatory Multisystem Syndrome Temporally Associated With Sars-cov-2 Pandemic and Kawasaki Disease: Preliminary Data From an Ongoing Study
Authors: Enrico Piccinelli, jethro herberg, Heechan Kang, alain fraisse, Sylvia Krupickova, Ivan Bermejo Altamar, Jolanda Sabatino, Yogen Singh, Carles Bautista-Rodriguez, Giovanni Di Salvo
Journal: Circulation (2020)

Introduction: The paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and Kawasaki disease (KD) have overlapping features. This study aimed to describe the strain segmental analysis among both entities. Methods: Retrospective review of strain segmental analysis within 4 weeks of presentation of symptoms among children diagnosed with PIMS-TS between April and June 2020 and a historic cohort of typical KD from the Royal Brompton Hospital, London. Results: We included 33 PIMS-TS patients (23 males, 69.7%) at a mean age of 8 ± 4,9 years old and 45 KD patients (31 males, 68,9%) at a mean age of 5,8 ± 4,5 years old. PIMS-TS patients were older at presentation (p = 0.038). Left ventricle ejection fraction (LVEF) was normal in both groups (63,3% vs 63,5%; p= 0,89), 4/33 PIMS-TS children (12,1%) had coronary arteries abnormalities (CAA), whereas 100% of KD cohort had CAA. Both groups had a normal global longitudinal strain (GLS), but in PIMS-TS it was significantly reduced compared to the KD group (-20% vs -22%; p=0,008). Basal segments were the most affected in PIMS-TS with significant difference in the basal anterior and anterolateral strain compared to KD (respectively -18,2% vs -23,4%; p &lt; 0,001 and - 16,7% vs -22,7%; p &lt; 0,001). PIMS-TS had a greater anterior, anterolateral and posterior segments involvement with a significant reduction in the anterolateral mid-wall longitudinal strain (-18,3% vs -22%; p=0,002). Apical segments were less involved, with a significant difference only in the septal and inferior apical strain (respectively p=0.001 and p=0,032). Conclusions: These preliminary data showed that after 4 weeks from the onset of symptoms, all PIMS-TS patients had a normal LVEF but they had a significant reduction in GLS and different segmental involvement compared to KD cohort. We hypothesize that these findings may be related to direct myocardial damage in PIMS-TS rather than caused by coronaries perfusion abnormalities.
Abstract 12678: Lithium Toxicity Presenting as 2:1 Atrioventricular Block
Authors: Jin Ei Chan, Voravech Nissaisorakarn, Michael J Grushko
Journal: Circulation (2019)

Case presentation: A 60 year-old female with history of bipolar disorder presented with behavioral changes. Her home medications included lithium 300 mg twice daily. Blood pressures were stable and...