tbuckley/cabot-search huggingface dataset:
Abstract 12516: Vascular Calcification Does Not Affect Cardiovascular Structure and Function During the Reversal of Atherosclerosis
Authors: Daniel M Kalta, Xin Lin, Mohnish Singh, Olga V Savinova
Journal: Circulation (2021)

Introduction: Animal models are used to study the mechanisms of reversal of atherosclerosis. Due to the minimal extent of plaque calcification, commonly used mouse models do not provide good insight into the regression of calcified plaques. To address this question, we developed a mouse strain that is genetically predisposed to atherosclerotic calcification. Hypothesis: The purpose of this study was to compare the effects of the reversal of atherosclerosis on cardiovascular physiology between mice predisposed to calcification and control mice. Methods: All mice (n=35) had a mutation of a low-density lipoprotein receptor and developed atherosclerosis over a course of 15 weeks while on a Western diet. The experimental groups consisted of mice overexpressing TNAP (tissue-nonspecific alkaline phosphatase) in macrophages under the control of LysM-Cre recombinase, and the control littermates. After 23 weeks of age (baseline), mice were switched to a normal diet. Echocardiographic studies were performed to assess cardiac structure and function at baseline and at 52 weeks of age at the completion of the diet reversal protocol. MicroCT analysis of calcification was performed ex vivo . Data were analyzed via 2-way ANOVA to calculate the effect of diet (atherosclerotic baseline vs reversal) while adjusting for sex. Results: Cardiac parameters including left ventricular (LV) mass, LV internal diameter and wall thickness, ejection fraction, fractional shortening, and aortic valve flow velocity were within the normal range and not statistically different between the two genotypes. CT data confirmed an increase in calcium volume in TNAP overexpressor mice compared to controls. Conclusions: Our data suggest that under conditions of the reversal of atherosclerosis, plaque calcification at baseline is not associated with the deterioration of cardiac structure and function in a mouse model.
Abstract 12536: Nanoliposomal Treatment Reduces Stroke Injury Following Middle Cerebral Artery Occlusion in Mice
Authors: Saif Ahmad, Adam Kindelin, Seth Truran, Nina Karamanova, Maria Lozoya, Volkmar Weissig, Daniel Griffiths, Jonathan Lifshitz, Andrew F Ducruet, Raymond Q Migrino
Journal: Circulation (2021)

Introduction: Neuroprotective strategies for stroke are lacking leading to significant disability and death. Liposomes (phospholipid particles) are commonly used as molecular carriers of therapeutic agent cargos. We previously showed that cargo-less nanoliposomes (NL, &lt;100 nm size particles) composed of phosphatidylcholine, cholesterol and monosialoganglioside (70:25:5 molar ratios) induced an antioxidant protective response in endothelial cells exposed to oxidative stress-mediated amyloid injury. Hypothesis: NL will preserve neuroblastoma cell viability in the setting of hypoxic injury and will reduce functional and histologic injury in mice following middle cerebral artery occlusion (MCAO). Methods: SH-SY5Y neuroblastoma cells were exposed to 20-hour physoxic (5% oxygen) condition or hypoxic (1% oxygen) condition without or with NL (100 or 300 μg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment scoring was compared as well as post-mortem brain infarction size. Results: Neuroblastoma cells showed reduced viability following hypoxia that was reversed by treatment with NL. NL increased gene expression of HO-1, NQO1 and SOD1 compared to untreated controls. NL-treated mice showed reduced neurologic function impairment and reduced brain infarct size compared to controls (18.8±2% versus 27.3±2.3%, p=0.017, see Figure). Conclusions: Cargo-less NL reduced functional and structural stroke injury in mice subjected to MCAO likely mediated in part through induction of an antioxidant stress response. NL is a candidate novel agent to mitigate stroke injury.
Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in Czech Republic
Authors: Tereza Popkova, Ludek Pour, Ivan Spicka, Jakub Radocha, Alexandra Jungova, Jiri Minarik, Tomas Jelinek, Petr Pavlicek, Marta Krejci, Jan Straub, Vladimir Maisnar, Tereza Dekojova, Tomas Pika, Jan Soukup, Lenka Capkova, Roman Hájek
Journal: Blood (2021)
Abstract 15517: Effect of Glucose Control on Clinical Outcomes After Endovascular Treatment in Diabetic Patients With Peripheral Artery Disease: Analysis From the K-VIS ELLA Registry
Authors: Jung-Joon Cha, Hyoeun Kim, Young-Guk Ko, Jae-Hwan Lee, Chang-Hwan Yoon, Cheol Woong Yu, Seung Whan Lee, Sang-Rok Lee, Seung Hyuk Choi, Yoon Seok Koh, Pil-Ki Min
Journal: Circulation (2018)

Background: The Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) registry is a multicenter retrospective observational study in patients with low...
Previously Unknown Stage of TCR Beta VDJ Recombination As a Novel Rich Source of Markers for Clonality Assessment and MRD Monitoring in T-ALL
Authors: Alexander Y Komkov, Anastasia O Smirnova, Anna M Miroshnichenkova, Alexander M Popov, Alexander I Karachunskiy, Yulia V Olshanskaya, Michael A Maschan, Ilgar Z Mamedov
Journal: Blood (2021)
TWMP-02. Supplementary motor area syndrome in glioma surgery - towards a classification system based on clinical and imaging data
Authors: Mehmet Salih Tuncer, Lucius Fekonja, Stefanie Ott, Andreas Pfnür, Anna-Gila Karbe, Melina Engelhardt, Katharina Faust, Thomas Picht, Jan Coburger, Lasse Dührsen, Peter Vajkoczy, Julia Onken
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVES Surgical resection of gliomas involving the supplementary motor area (SMA) frequently results in a symptom complex commonly described as „SMA syndrome“, which is characterized by transient contralateral akinesia and mutism. As factors potentially influencing the severity and duration of symptoms still remain elusive, we aim to further investigate potential predictors in a multicentric cohort of glioma patients. METHODS Fifty patients with gliomas located in the superior frontal gyrus from 3 centers were included in this retrospective study. Patients with injury of M1 and/or the corticospinal tract were excluded. Early postoperative motor outcome, the occurrence of mutism and duration of acute symptoms in days were assessed. The long-term outcome was assessed in follow-up examinations 3 months after surgery. Atlas-based lesion-symptom mapping was performed using postoperative MR imaging estimating surgical grey matter damage as well as white matter disconnection severity. Associations between functional outcome and imaging findings were analyzed using group tests and correlation analyses. RESULTS Median duration of symptoms in the cohort was 3 days (range: 1 – 42 days). Persistent deficits concerning fine motor movements and speech after initial recovery were found in 27 patients (54%). Disconnection of the central segment of the corpus callosum was associated with longer symptom duration (FDR corr. p &amp;lt; 0.05), while disconnection of the mid-posterior segment of the corpus callosum was associated with persistent deficits at follow-up (FDR corr. p &amp;lt; 0.05). CONCLUSIONS The present study shows a high variability regarding the recovery time of postoperative SMA syndrome and a high prevalence of persistent deficits in fine motor movements and speech after initial recovery of acute symptoms. The pivotal role of interhemispheric connectivity in the recovery process is reinforced. These findings will help neurosurgeons in patient consultation and provide a foundation for future studies aiming to establish prediction models of the SMA syndrome.
High-throughput and high-dimensional single-cell analysis of antigen-specific CD8+ T cells
Authors: Ke-Yue Ma, Alexandra A. Schonnesen, Chenfeng He, Amanda Y. Xia, Eric Sun, Eunise Chen, Katherine R. Sebastian, Yu-Wan Guo, Robert Balderas, Mrinalini Kulkarni-Date, Ning Jiang
Journal: Nature Immunology (2021)
Discordant and inappropriate discordant recommendations in consensus and evidence based guidelines: empirical analysis
Authors: Liang Yao, Muhammad Muneeb Ahmed, Gordon H Guyatt, Peijing Yan, Xu Hui, Qi Wang, Kehu Yang, Jinhui Tian, Benjamin Djulbegovic
Journal: BMJ (2021)

Abstract Objective To investigate whether alignment of strength of recommendations with quality of evidence differs in consensus based versus evidence based guidelines. Design Empirical analysis. Data source Guidelines developed by the American College of Cardiology and the American Heart Association (ACC/AHA) and the American Society of Clinical Oncology (ASCO) up to 27 March 2021. Study selection Recommendations were clearly categorised as consensus or evidence based, were separated from the remainder of the text, and included both the quality of evidence and the strength of the recommendations. Data extraction Paired authors independently extracted the recommendation characteristics, including type of recommendation (consensus or evidence based), grading system used for developing recommendations, strength of the recommendation, and quality of evidence. The study team also calculated the number of discordant recommendations (strong recommendations with low quality evidence) and inappropriate discordant recommendations (those that did not meet grading of recommendations assessment, development, and evaluation criteria of appropriateness). Results The study included 12 ACC/AHA guidelines that generated 1434 recommendations and 69 ASCO guidelines that generated 1094 recommendations. Of the 504 ACC/AHA recommendations based on low quality evidence, 200 (40%) proved to be consensus based versus 304 (60%) evidence based; of the 404 ASCO recommendations based on low quality evidence, 292 (72%) were consensus based versus 112 (28%) that were evidence based. In both ACC/AHA and ASCO guidelines, the consensus approach yielded more discordant recommendations (ACC/AHA: odds ratio 2.1, 95% confidence interval 1.5 to 3.1; ASCO: 2.9, 1.1 to 7.8) and inappropriate discordant recommendations (ACC/AHA: 2.6, 1.7 to 3.7; ASCO: 5.1, 1.6 to 16.0) than the evidence based approach. Conclusion Consensus based guidelines produce more recommendations violating the evidence based medicine principles than evidence based guidelines. Ensuring appropriate alignment of quality of evidence with the strength of recommendations is key to the development of “trustworthy” guidelines.
New Settings for Immune Checkpoint Inhibitors in Urothelial Cancer
Authors: Arlene O. Siefker-Radtke
Journal: Journal of the National Comprehensive Cancer Network (2021)

The advent of immune checkpoint inhibitors (ICIs) has changed the game in cancer immunotherapy, specifically in the treatment of urothelial bladder cancer. Several clinical trials combining chemotherapy with ICIs have resulted in approvals from the FDA and subsequent revisions within the NCCN Guidelines. The current NCCN Guidelines for Bladder Cancer reflect the most up-to-date, evidence-based data relating to the evaluation and management of urothelial bladder cancer. ICIs have been incorporated into the guidelines as maintenance therapy in response to chemotherapy, sequencing after disease progression from frontline chemotherapy, and for the treatment of non–muscle-invasive bladder cancer.
Abstract 14304: Incident Dialysis and Acute Kidney Injury Among Medicare Beneficiaries After Hospitalization for Heart Failure in the US
Authors: Muthiah Vaduganathan, Stephen J Greene, Ravi B Patel, Shuaiqi Zhang, Karen Chiswell, Adam D Devore, Javed Butler, Paul A Heidenreich, Joanna Huang, Michelle M Kittleson, Karen E Joynt Maddox, James J McDermott, Anjali T Owens, Pamela Peterson, Scott Solomon, Orly Vardeny, Clyde Yancy, Gregg C Fonarow
Journal: Circulation (2021)

Background: Recent therapies in heart failure (HF) have been shown to slow kidney disease progression, yet the trajectory of clinically relevant kidney events in real-world HF care is not well described. Methods: We identified Medicare beneficiaries hospitalized for HF at 240 US sites in the GWTG-HF registry in 2016 who did not require dialysis prior to or during hospitalization and followed them through 1-year post-discharge for incident kidney events, all-cause and HF readmissions, and death. Associations between discharge CKD-EPI-derived eGFR and time-to-first events were modeled adjusting for demographics, medical history, LVEF, discharge vital sign and laboratory measures, and hospital characteristics. Results: Among 20,927 Medicare beneficiaries (age 81±9y; 53% women; 10% Black), discharge eGFR was ≥90, 60-89, 45-59, 30-44, and &lt;30 mL/min/1.73 m 2 in 4%, 27%, 23%, 25%, and 21%, respectively. By 1 year, 37% had died and 65% were readmitted (including 31% for HF, 7% for AKI, and 5% for dialysis/end-stage kidney disease [ESKD]). Lower discharge eGFR (per 10 mL/min/1.73 m 2 decrease) was independently associated with increased mortality (aHR 1.08[1.05-1.10]), all-cause readmission (aHR 1.04[1.02-1.06]), HF readmission (aHR 1.09[1.06-1.12]), readmission for AKI (aHR 1.20[1.15-1.25]), and progression to dialysis/ESKD (aHR 2.22 [1.93-2.55]); all P&lt;0.001. Categorical analyses consistently demonstrated heightened risks of HF and kidney events at lower eGFR. A potential J-shaped relationship was observed for mortality &amp; dialysis/ESKD. Conclusions: Older adults hospitalized for HF face broad post-discharge risks of recurrent HF events, kidney events, and death. One in 20 Medicare beneficiaries are estimated to progress to dialysis/ESKD within 1-year of hospital discharge. These data may inform shared decision-making and highlight the need to prioritize comprehensive HF care that simultaneously improve outcomes in diverse disease pathways.
Abstract 13428: Mid-Life and Late-Life Exposure to Traditional Cardiovascular Risk Factors and Zero Coronary Artery Calcium: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Frances M Wang, Shoshana Ballew, Aaron R Folsom, Lynne E Wagenknecht, Candace M Howard-Claudio, Josef Coresh, Matthew J Budoff, Michael J Blaha, Kuni Matsushita
Journal: Circulation (2021)

Introduction: Our understanding of traditional atherosclerotic risk factors is largely based on their contributions to adverse atherosclerotic events. However, the relative contributions of mid-life and late-life risk factor exposures to persistent zero coronary artery calcium (CAC=0) in older adulthood, a representative healthy vascular aging phenotype, have not been fully examined. Hypothesis: Both mid-life and late-life risk factors are associated with CAC=0, with stronger results for the former. Methods: Using data from 2,035 community-dwelling participants free of coronary heart disease in the ARIC study, we evaluated traditional modifiable risk factors (i.e., lipids, systolic blood pressure, obesity, smoking, and diabetes) at mid-life (median age 49, visit 1 from 1987-1989) and late-life (median age 73, visit 5 from 2011-2013) and their associations with CAC=0 at visit 7 (median age 80, from 2018-2019), using multivariable logistic regression models adjusted for within-visit factors. Results: There were 204 participants (10.0%) with CAC=0. Compared with participants with any CAC, those with CAC=0 had more favorable values for most traditional risk factors (lower cholesterol, BMI, and systolic blood pressure, higher HDL-C, and not smoking) in both mid-life and late-life, with the exception of fasting glucose ( Table ). The results were similar when we modeled diabetes instead of fasting glucose. Lower total cholesterol in mid-life, but not late-life, was associated with CAC=0. Conclusions: Having favorable modifiable risk factors both at mid-life and late-life were independently associated with CAC=0 in older adults free of clinical coronary heart disease. These results highlight the importance of maintaining a healthy risk factor profile from mid-life, with implications on public health promotion and strategy.
Optimal Anticoagulant Dosing in Patients with COVID-19, a Retrospective Review
Authors: Alessandra Carrillo, Shil Punatar, Sushma Pavaluri, Madeline Jentink, Dixita Patel, Joseph Braun, Tsvetelina Todorova, Damoun Safarpour, Marwah W Farooqui, Masood Ghouse, Krishnan Srinivasan
Journal: Blood (2021)
Abstract 10066: Right Ventricular Function as a Predictor of Mortality in Patients with Sepsis: A Systematic Review and Meta-Analysis
Authors: Gaspar Del Rio-Pertuz, Juan Toro, Abel Triana, Sneha Singh, Hernando Gomez
Journal: Circulation (2021)

Introduction: Sepsis-associated myocardial dysfunction has been described in relation to left ventricular function and reported to have a variable correlation with mortality. However, the extent to which right ventricular (RV) dysfunction contributes to myocardial dysfunction and a poor prognosis in sepsis remains unknown. Our aim is to investigate the association between RV dysfunction and mortality in patients with sepsis. Methods: We performed a systematic review of the literature. We systematically searched Cochrane, Embase, MEDLINE, Scopus and Web of Science for full-text articles from inception to June 2020. Studies were included if they reported RV function and mortality in patients with sepsis using echocardiography. Data was extracted using a collection form designed a priori . Significance was determined by a two-tailed p value &lt; 0.05. The present study was registered in the PROSPERO (CRD42020204423). Hypothesis: RV dysfunction is associated to mortality in adult patients with sepsis. Results: Six studies including 526 patients were selected for final analysis. Patients had a mean age of 57 years, 45% were females, and there was an overall mortality of 37%. In three studies, transthoracic echocardiography was performed within 24h of sepsis diagnosis, and reported Tricuspid annular plane systolic excursion (TAPSE) in a total of 366 patients. In pooled analysis, survivors had a higher TAPSE compared to non-survivors ((SMD):1.89 (95%CI 0.14-3.655) p=0.03, Figure1). All other parameters of RV dysfunction assessed did not have a statistically significant difference between survivors and non-survivors (Figure 2-6). Conclusion: RV dysfunction as demonstrated by a lower TAPSE is associated with higher mortality in patients with sepsis and/or septic shock. This data suggest that RV dysfunction is an important contributor to sepsis-associated myocardial dysfunction and worsening prognosis in patients with sepsis.
Abstract 13848: Establishing an Optogenetic <i>in vitro</i> Model to Study Atrial Fibrillation Based on Human Engineered Heart Tissue
Authors: Bangfen Pan, Julius Hansen, Grit Höppner, Tim Stüdemann, Aaltje Maria Stella Stoter, Torsten Christ, Marc D. Lemoine, Roger Foo, Thomas Eschenhagen, Justus Stenzig
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is a type of sustained cardiac tachyarrhythmia in which the atrial rate can reach up to 300-600 beats per minute (BPM). The elucidation of the mechanisms of AF and the search for new therapeutic methods is hampered by a lack of suitable in vitro models. In previous studies, chronic optical tachypacing induced arrhythmia vulnerability in ventricular-like human engineered heart tissue (EHT). Here, we aimed to optimize an AF in vitro model based on optogenetics, EHT and a novel optogenetic pacing platform. Methods: Human induced pluripotent stem cells (hiPSC) stably expressing Volvox-Channelrhodopsin-1 (VChR1) were differentiated into atrial-like cardiomyocytes (CM) by treatment with 1 μM retinoic acid (RA) at the cardiac induction stage. CMs were used to cast fibrin-based 24-well format EHTs. The expression of atrial/ventricular markers was validated by qPCR, and action potential (AP) recordings with atrial-specific channel inhibitors were performed on at least one-month-old EHTs. A novel custom-designed circuit board with a programmable microcontroller and 24 RGB addressable light-emitting diodes (LED) was used for optical tachypacing. 25-30 days old EHTs were stimulated by 90 s bursts of blue light pulses (5 Hz), separated by 10 s breaks for 35-40 days. Non-paced and paced EHTs were characterized regarding contractility and gene expression. Results: EHTs had a high expression of atrial mRNA markers and displayed atrial-like AP. A flexible and straightforward optogenetic tool was built to make chronic tachypacing feasible. Using this novel platform, EHTs were successfully paced at 5 Hz for up to 40 days. Compared with non-paced EHTs, paced EHTs showed a different spontaneous contractility profile, higher expression of stress genes, and released more troponin I into the medium. Conclusions: We have successfully generated an in vitro model to mimic the status of atria with a high frequency (300 BPM) during AF. Paced EHTs displayed stress signs, partially resembling the changes of atria in AF. In the future, we could utilize this model to study the underlying mechanisms and assess proarrhythmic and antiarrhythmic drug effects.
The First Real-World Experience with Betibeglogene Autotemcel (beti-cel) Gene Therapy Treatment for Transfusion-Dependent β-Thalassemia (TDT)
Authors: Joachim B. Kunz, Eva Roth, Adil Mirza, Johann Greil, Petra Pavel, Anita Schmitt, Michael Schmitt, Alexander Kunz, Andreas E. Kulozik
Journal: Blood (2021)
Abstract 10484: Cardiac Adaptation to Acute Haemodynamic Stress in Patients with Type 2 Diabetes
Authors: Amrit Chowdhary, Sharmaine Thirunavukarasu, Nicholas Jex, Lauren Coles, Hui Xue, Peter Kellman, John GREENWOOD, Sven Plein, Eylem Levelt
Journal: Circulation (2021)

Background: Due to varying cardiac workloads, efficient demand-supply matching is crucial for maintaining normal cardiac function. Cardiac metabolism is profoundly affected by changes in cardiac workload. There is scarcity of non-invasive studies evaluating how the heart adapts to hemodynamic stress in type 2 diabetes (T2D) patients. Objectives: Using cardiovascular magnetic resonance (CMR) and 31 Phosphorus MR spectroscopy ( 31 P-MRS) we assessed changes in cardiac energetics, perfusion, strain, systolic and diastolic function in response to increases in cardiac workload with dobutamine stress in T2D patients and healthy volunteers (HV). Methods: 24 T2D patients and 18 matched HV were recruited. Participants with ischemic heart disease were excluded. Results: Table-1 shows clinical and CMR/ 31 P-MRS data. Compared to HV, T2D patients showed reductions in left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at rest, and a blunted increase in LVEF and GLS during stress. Diastolic function was impaired in T2D with lower mitral in-flow E/A ratio compared to HV at rest, which was further reduced during stress in both groups. Stress myocardial blood flow was lower in T2D patients.Compared to HV, rest phosphocreatinine (PCr)/ATP ratio was 17% lower in T2D patients, with a further 8% reduction during stress. However, there was a more pronounced reduction in the PCr/ATP with stress in HV (33% relative reduction), although stress PCr/ATP remained numerically higher in HV compared to T2D patients. Conclusions: T2D is associated with blunted ability of the myocardium to significantly increase contractile function from rest to stress. Moreover, T2D patients show exacerbated reductions in myocardial energetics and diastolic function during stress. Although reductions in myocardial energetics and diastolic function in response to acute stress were also detected in HV, these assessments remained higher in HV at stress compared to T2D patients.