tbuckley/cabot-search huggingface dataset:
Abstract 10037: Cerebral Embolic Protection During Transcatheter Aortic Valve Implantation: Updated Systemic Review and Meta-Analysis
Authors: Salman Zahid, AAMER UBAID, Muhammad Atif Khan, Mian Tanveer Ud Din, Hamza Zahid Ullah Muhammadzai, Muhammmad Khan, Muhammad Faisal Uddin, Waqas Ullah, Muhammad U Khan, Abid Nawaz Khan Adil, Abdul Baqi, Sakina Abbas, Arslan Inayat, Fnu Salman, Jeremiah Depta
Journal: Circulation (2021)

Introduction: In patient undergoing transcatheter aortic valve implantation (TAVI), stroke remains a potentially devastating complication associated with significant morbidity and mortality. Hypothesis: To reduce the risk of stroke, cerebral protection devices (CPD) were developed to prevent debris from embolizing to the brain during TAVI.The data on the safety and efficacy of cerebral protection devices (CPD) remains limited. Methods: We performed a systemic review and meta-analysis to determine the safety and efficacy of CPD in TAVI. The MEDLINE (PubMed, Ovid) and Cochrane databases were queried with various combinations of medical subject headings to identify relevant articles. Statistical analysis was performed using a random-effects model to calculate unadjusted odds ratio (OR). Results: Using a pooled analysis, CPD was associated with a significant reduction in major adverse cardiovascular events (MACE) (OR 0.69, 95% CI 0.50-0.96, p=0.03) and stroke (OR 0.61, 95% CI 0.42-0.90, p=0.08) in patients undergoing TAVI. Similarly, on MRI volume per lesion were lower for patients with CPD use (SMD -0.79 [-1.30,-0.28], p&lt;0.01). No significant difference were observed in mortality (OR 0.97, 95% CI 0.60-1.55, p=0.88), acute kidney injury (OR 0.75, 95% CI 0.42-1.37, p=0.68), bleeding (OR 0.93, 95% CI 0.52-1.65, p=0.80) or vascular complications (OR 0.90, 95% CI 0.62-1.31, p=0.6) for patients undergoing TAVI with CPD. Conclusions: In conclusion, CPD device use in TAVI is associated with a reduction of MACE and stroke compared with patients undergoing TAVI without CPD.
Abstract 12984: Technology-Delivered Motivational Interviewing Interventions for Patients With Cardiovascular Diseases - A Systematic Review
Authors: Paolo Iovino, Marina Baricchi, Greta Ghizzardi, Alessia Martina Trenta, rosario caruso, Cristina Arrigoni, cristina pedroni, federica dellafiore, Gianluca Pucciarelli, Ercole Vellone
Journal: Circulation (2021)

Introduction: Cardiovascular diseases (CVD) are a major source of burden worldwide. COVID-19 pandemic has renewed the importance of remote psychoeducational interventions to improve outcomes in these patients. Technology-delivered motivational interviewing (TD-MI) has proven to be effective in chronic disease populations, yet there has been no attempt to summarize TD-MI characteristics and effectiveness in CVD populations. Methods: We searched PubMed, CINHAL, PsychInfo and Web of Science (from inception to May 1, 2021) for randomized controlled trials that enrolled adults with CVD. Record screening, data extraction and risk of bias assessment were performed in duplicate. This review is registered in PROSPERO, CRD42021241516. Results: Of the 2,742 records identified, 7 studies were eligible for qualitative synthesis. Participants (n=12,053, mean age = 62.25, 37.5% females) enrolled from community settings and prevalently affected by coronary artery disease (n. studies=5), hypertension (n=3) and heart failure (n=3), received an average of 11 phone (n=6) or video calls (n=1) over an average of 7 months. Interventionists were mostly nurses (n=4), followed by psychologists (n=2) and a social worker (n=1). Treatment fidelity was assessed in 5 trials; 2 trials reported the intervention to be based on a theoretical framework, and 2 studies specified if the interventionist underwent some training before TD-MI administration. Caregivers were never involved. Most targeted outcomes were medication adherence (n=5), quality of life (n=4), disease-related parameters (n=4), and depression (n=3). Risk of bias varied markedly, with the largest source resulting from lack of blinding of participants and assessors (performance bias). The only feasible meta-analysis showed no significant effects of TD-MI on depression (n=3; Z=1.18, p=0.24; I 2 =42%). Conclusions: The number of trials involving TD-MI interventions across CVD populations is scarce and their effectiveness is inconclusive. There was lack of reporting of interventionists’ training, description of treatment fidelity, and blinding procedures. More trials with stronger designs and better reporting are needed in the CVD field to inform clinical decision making and research.
Abstract 10817: Association of Hospital Procedural Volumes with Outcomes of Left Ventricular Assist Devices
Authors: Tayyab Ali Waheed, Usama Nasir, Keerat Ahuja, Jared Green, Mochon Agnieszka
Journal: Circulation (2021)

Introduction: Left Ventricular Assist Devices (LVADs) are effective and feasible options for stage D heart failure. The impact of procedural volumes on LVAD outcomes has been seldomly investigated. Methods: We investigated the Nationwide Readmission Database for the impact of different institutional LVAD volumes on clinical outcomes in 2018. Institutional procedural volumes were stratified into Low (1-7/year), medium (8-24/year) and high (&gt;25/year). Multivariant analysis and adjusted odds ratio was performed to examine association between LVAD hospital volumes and outcomes. Primary outcome was major adverse events (MAE) defined as a composite of mortality, myocardial infarction, stroke or TIA, bleeding requiring transfusion, acute kidney injury, vascular complications and pericardial effusion or tamponade requiring pericardiocentesis or surgery. Results: A total of 2315 patients underwent LVAD placement, with a mean age of 57. No difference in age, sex or presence of chronic disease was noted among patient in different procedural volume tiers. There was statistically significant difference in MAE in medium-volume center when comparing to low volume centers. No difference in MAE was present in low and high-volume center. No significant difference was noted in 30-day all cause readmission, 30-day heart failure readmission or in individual components of MAE across different hospital procedural volumes. Conclusions: Medium-volume centers are associated with better composite clinical outcomes. Overall, no difference in mortality, stroke or myocardial infarction exists among different volume centers. Further clinical research is warranted to clarify the appropriate minimum LVAD procedural volumes required for accreditation.
Abstract P386: Supplementation Of Tyrode With Fatty Acids And 3-hydroxybutyrate Improves Adult Cardiomyocytes Contractility Of Failing Human Hearts.
Authors: Alexia Vite, Timothy Matsuura, Ling Lai, Kenneth Bedi, Daniel P Kelly, Kenneth B Margulies
Journal: Circulation Research (2021)

Due to its high energy consumption and limited ability to store ATP, the heart is highly dependent of exogenous metabolic substrates. Prior in vivo studies have reported that the development of heart failure is accompanied by a transition from the normal preferential metabolism of free fatty acids (FFA) to increases in glucose utilization and even ketone bodies, which normally provide a modest contribution to energy balance. However, the functional significance of the upregulated ketone metabolism in the failing heart is poorly understood. Recognizing that nearly all prior studies examining isolated cardiomyocyte physiology have used glucose as the sole metabolic substrate, we initiated studies to examine the impact of alternative metabolic substrates on contractility in isolated human cardiomyocytes. To understand the role of substrate alteration cardiomyocyte functionalities, we employed freshly isolated adult human left ventricular cardiomyocytes from 11 non-failing hearts (NF) obtained from organ donors and 13 failing hearts (HF) obtained from transplant recipients. Cardiomyocytes were resuspended in a conventional 5mM Glucose Tyrode solution with alternative substrates (Glucose, FFA, R-3-OHB or Mix (Glucose + FFA + 3-OHB)). Myocytes were field stimulated at 1 Hz and sarcomere length, fractional shortening, contraction velocity and relaxation velocity were measured using a video-based sarcomere length detection system (IonOptix Corp). Studies using isolated cardiac myocyte contractility as readout confirm that myocytes from NF human hearts are omnivorous: high levels of myocyte fractional shortening (FS) can be achieved under unstressed conditions (1 Hz, unloaded) with any substrate (FS Glucose : 0.1315±0.012; FS FFA : 0.1428±0.0127; FS 3OHB : 0.1343±0.014; FS MIX : 0.15467±0.02). In the failing heart, glucose alone is insufficient to produce normal unstressed myocyte fractional shortening (FS Glucose : 0.088±0.009***, p&lt;0.001 compare to NF). However, in failing myocytes, supplementation of physiological levels of glucose with FFA or ketones each enhances myocyte contractility and rates of shortening and re-lengthening (FS FFA : 0.109±0.0127; FS 3OHB : 0.107±0.012; FS MIX : 0.112±0.016). These results suggest that future comparisons of NF vs. HF human myocyte contractility should include conditions with a physiological mix of metabolic substrates.
Mutation Analysis and Effect on Prognosis of Direct Antiglobulin Test Positivity in Diffuse Large B-Cell Lymphoma
Authors: Caitlin Coombes, Joshua W. D. Tobin, Kartik Saxena, Jun Hee Lim, Bruce Shadbolt, Yogesh Jeelall, Chris Goodnow, Andrews Daniel Thomas, Sanjiv Jain, Simon Jiang, Keisuke Horikawa, Dipti Talaulikar
Journal: Blood (2017)
Inhibition of Factor XII Attenuates Prothrombotic Complications in Sickle Cell Mice
Authors: Erica Sparkenbaugh, Christina M Abrams, Megan D Miller, Brian C Cooley, Anton Ilich, Shreya Yadav, Michael Wallisch, Nigel S Key, Andras Gruber, Felicity N. E. Gavins, Rafal Pawlinski
Journal: Blood (2021)
NCOG-23. PATIENT-REPORTED SYMPTOM BURDEN AND INTERFERENCE: A COMPARISON BETWEEN COVID-19 PANDEMIC YEAR AND NORMATIVE DATA IN PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Valentina Pillai, Lily Polskin, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Anna Choi, Alexa Christ, Ewa Grajkowska, Varna Jammula, Heather Leeper, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Brett Theeler, Jing Wu, Mark Gilbert, Terri Armstrong, Amanda King
Journal: Neuro-Oncology (2021)

Abstract CNS tumor patients are highly symptomatic causing interference with activity and worse quality of life. Social distancing due to the COVID-19 pandemic increased demands on the patient, caregivers, clinicians, and the health care system. The NCI’s Neuro-Oncology Branch Natural History Study (NHS) systematically collected patient-reported outcomes (PROs) provide insight into how these challenges influenced symptom burden and interference during the COVID year. METHODS: Patient and disease characteristic as well as patient-reported symptoms and interference (MDASI-BT/-SP) and general health status (EQ-5D-3L) from 3/2020-2/2021) were compared to NHS normative sample collected prior to 3/2020. RESULTS: The sample (n = 178) was primarily White (82%), male (55%), median age of 45 (range 18 – 79) and KPS ³ 90 (51%). The majority had high-grade (70%) brain (83%) tumors (BT) with ≥ 1 prior recurrence (60%) and 25% were on active treatment. Clinical visits were primarily conducted via telehealth (64%) and 20% of all patients were diagnosed with progression at the time of assessment. Most commonly reported moderate-severe symptoms among BT patients were fatigue (30%), difficulty remembering (28%), feeling drowsy (22%). Among spinal cord tumor patients, fatigue (39%), pain (35%) and numbness/tingling in arms/legs/trunk (35%) were most frequently reported. These symptoms were reported in similar frequencies by the normative sample. Nearly half of the COVID year sample (48%) reported moderate-severe activity-related interference. Reported problems with mobility (38%), self-care (19%), pain/discomfort (40%), and usual activities (50%) were similar in both groups except for increased mood disturbance (53%) was reported during the COVID year. CONCLUSION: These findings support CNS tumor patients remained highly symptomatic with significant impact on health-related quality of life during the COVID year. Clinicians should develop timely individual care plans to help BT patients navigate their disease course. Evaluation of risk associated with more severe symptoms and functional limitations are ongoing.
Abstract 10415: Dysregulation of FOXO-FOXM1 Signaling Inhibits Maturation of IPSC-Derived Cardiomyocytes in 3D Suspension Culture
Authors: Jessica C Garbern, Hannah L Elwell, Estela Mancheno Juncosa, Daphne van den Berg, Morgan K Sokol, Richard T Lee
Journal: Circulation (2021)

Directed differentiation of human pluripotent stem cells (PSC) into cardiomyocytes via manipulation of Wnt signaling leads to generation of immature cardiomyocytes, more closely resembling a fetal state. It has become increasingly apparent that metabolic parameters regulate of cardiomyocyte maturation. The forkhead box (FOX) family of transcription factors has previously been shown to regulate metabolic phenotype in neonatal cardiomyocytes through a balance between FOXO and FOXM proteins. Therefore, we hypothesized that dysregulation of FOXO-FOXM1 signaling inhibits maturation of iPSC-derived cardiomyocytes (iPSC-CMs). We cultured iPSC-CMs in 3D suspension culture using an orbital shaker. iPSC-CMs were treated with RCM-1 (FOXM1 inhibitor), LOM612 (FOXO nuclear translocator), or AS1842856 (FOXO inhibitor) starting 2 days after onset of beating. We found that inhibition of FOXO with AS1842856 resulted in loss of expression of cardiac-specific markers such as cardiac troponin T as well as loss of spontaneous beating. In contrast, inhibition of FOXM1 with RCM-1 or activation of FOXO with LOM612 resulted in retention of a cardiomyocyte phenotype with continued expression of cardiac troponin T but with significantly increased expression membrane protein expression of Kir2.1 (Figure), the protein largely responsible for maintaining the resting membrane potential in cardiomyocytes. These results suggest that inhibition of FOXM1 and/or activation of FOXO signaling may facilitate maturation of iPSC-derived cardiomyocytes. Figure. (A) % of TNNT2+ iPSC-derived cardiomyocytes that express Kir2.1 and (B) Mean fluorescence intensity of Kir2.1 in iPSC-derived cardiomyocytes after treatment with DMSO (vehicle control), RCM-1, LOM612, or AS1842856. *p&lt;0.05, ***p&lt;0.001, ****p&lt;0.0001 by one-way ANOVA with Dunnett’s multiple comparisons test.
Is PFS the Right Endpoint to Assess Outcome of Maintenance Studies in Multiple Myeloma? Results of a Patient Survey Highlight Quality-of-Life As an Equally Important Outcome Measure
Authors: Anna Fleischer, Larissa Heimeshoff, Johannes Allgaier, Karin Jordan, Götz Gelbrich, Rüdiger Pryss, Johannes Schobel, Hermann Einsele, Martin Kortuem, Imad Maatouk, Niels Weinhold, Leo Rasche
Journal: Blood (2021)
Abstract 10512: Sialic Acid-rich Fc Having A Strong Anti-inflammatory Effect In Kawasaki Disease Model
Authors: Yukako Yoshikane, Tatsuki Miyamoto, Mitsuhisa Koga, seiji haraoka, Tamaki Cho, Shinichiro Nagamitsu
Journal: Circulation (2021)

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery (CA) aneurysms. High-dose intravenous immunoglobulin (IVIG) is the most standard treatment. However, the problem with current high-dose IVIG therapy is that it is inefficient for both patients and cost because it contains ineffective parts and requires a high total dose. It has recently been reported that sialic acid in the fragment crystallizable (Fc) region has an anti-inflammatory effect. Hypothesis: In the KD model, a small amount of sialic acid-rich (SR-)Fc has an anti-inflammatory effect equivalent to that of high-dose IVIG. Methods: A Candida albicans cell wall extract (CAWE)-induced KD-like vasculitis model was established in DBA/2 mice. IgG, antigen-binding fragment (Fab), and Fc with 2g/kg/0.5ml, and IgG, SR-IgG, and SR-Fc with 0.2g/kg/0.5ml, and placebo 0.5ml were administered intraperitoneally 3 times every other day (n=5, respectively). Four weeks after treatment, we compared the incidence of CA inflammation between each group. Histological analysis was performed by using a quantified scoring system: grade 1; &amp;lt;20 cells /HPF, grade 2; &amp;lt;100cells/HPF, grade 3; &amp;gt;100cels/HPF, grade 4; distraction of elastic lamina, grade 5; neointimal proliferation. Results: All five mice in placebo group had the infiltration grade 3 or higher (100%), whereas none of the mice in IgG group had the infiltration (0%). In Fab group, three out of four had the infiltration (75%, one mouse died), whereas in Fc group, only one out of five had the infiltration (20%). In one-tenth dose IgG group, two out of four had the infiltration (50%, one mouse died), whereas in one-tenth dose SR-IgG and SR-Fc group, 20% or less of them had the infiltration (one out of five, zero out of five, respectively). Treatment with one-tenth dose SR-IgG and SR-Fc significantly suppressed CAWE-induced vasculitis ( p &amp;lt;0.05 and 0.01, respectively). Conclusions: It was shown that the immunoglobulin effect was mainly in the Fc region and one-tenth dose SR-Fc had an anti-inflammatory effect equivalent to that of high-dose IgG in a Candida -induced KD mouse model. One-tenth doses SR-Fc may be an alternative treatment to high-dose IVIG in KD patients.
TP53 and MYD88 Mutations As Detected By Liquid Biopsy in the Prediction of Progression-Free Survival in Patients with Diffuse Large B-Cell Lymphoma
Authors: Maher Albitar, Andrew Ip, Hong Zhang, Andrew L. Pecora, Jeffrey Justin Estella, Ivan De Dios, Wanlong Ma, Lori A. Leslie, Tatyana A. Feldman, Andre H. Goy
Journal: Blood (2021)
CTIM-24. RANDOMIZED TRIAL OF NEOADJUVANT VACCINATION WITH TUMOR-CELL LYSATE INDUCES T CELL RESPONSE IN LOW-GRADE GLIOMAS
Authors: Jennie Taylor, Hirokazu Ogino, Takahide Nejo, David Gibson, Payal Watchmaker, Kaori Okada, Atsuro Saijo, Meghan Tedesco, Anny Shai, Cynthia Wong, Jane Rabbitt, Michael Olin, Christopher Moertel, Yasuhiko Nishioka, Andres Salazar, Annette Molinaro, Joanna Phillips, Nicholas Butowski, Jennifer Clarke, Nancy Ann Oberheim-Bush, Shawn Hervey-Jumper, Philip Theodosopoulos, Susan Chang, Mitchel Berger, Hideho Okada
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The prognosis of WHO grade II low-grade gliomas (LGG) is varied with potential for long survival.Given their relatively intact immune system and slow growth rate, vaccines are an attractive treatment strategy for LGG in an attempt to defer more toxic treatments. The goals of this pilot study were to evaluate safety and immunological effects of vaccination with GBM6-AD, an allogeneic glioblastoma stem cell line lysate, with poly-ICLC in LGG. METHODS Eligible patients were ≥ 18 years old, ≥ 70 KPS, with recurrent LGG or imaging consistent with LGG, and amenable to resection. Patients were randomized to vaccine prior to surgery (Arm 1) or not (Arm 2) and all received adjuvant vaccine. Co-primary outcomes were safety and immune response in the tumor, with exploratory outcomes of survival and immunologic effects in peripheral blood. RESULTS A total of 17 eligible patients were evaluable – nine into Arm 1 and eight into Arm 2. Median age was 33 years, with median time from initial diagnosis of 4.7 years (0 – 20). Two patients (11.8%) previously received radiotherapy and seven (41.2%) prior systemic therapy. No dose limiting toxicities or grade 3 AEs were observed. Neoadjuvant vaccination induced up regulation of type-1 cytokines and chemokines in peripheral blood, and CD8+ T cell clones that reacted to the vaccine were also detected in the tumor. Median follow-up time from first post-operative vaccine was 20.8 months with median PFS of 11.0 months and time to change in therapy of 23.7 months. Of the six patients to receive additional treatment, three had second surgery only one confirming malignant progression to anaplastic oligodendroglioma. CONCLUSION Treatment was well-tolerated with no regimen-limiting toxicity. GBM6-AD plus poly-ICLC induced effector CD8+ T cell response in peripheral blood and enables some vaccine-reactive CD8+ T cells to migrate into the TME. Further investigation is warranted.
Abstract 10789: Effect of Sacubitril-Valsartan on Incidence of Atrial Fibrillation: A Meta-Analysis
Authors: Javaria Ahmad, Ali Sultan, Paari Dominic
Journal: Circulation (2021)

Introduction: Sacubitril/valsartan reduces all cause mortality in heart failure (HF) patients compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). ACEIs/ARBs have been shown to decrease the incidence of atrial fibrillation (AF). Hypothesis: Sacubitril-Valsartan decreases the incidence of AF compared to ACEis/ARBs. Methods: Clinicaltrials.gov was searched for trials by terms sacubitril/valsartan, entresto, sacubitril, valsartan. Randomized controlled human trials of sacubitril/valsartan reporting AF were included. Data were extracted independently by two reviewers. Data was pooled using a random effect model. Publication bias was evaluated by funnel plots. Results: A total of 11 trials including 11474 patients on sacubitril/valsartan and 10145 patients on ACEI/ARBs were identified. 304 AF events were reported in the sacubitril/valsartan group compared to 284 AF events in ACEIs/ARBs. Patients on sacubitril/valsartan were as likely as patients on ACEIs/ARBs to develop AF (pooled OR=1.054, (95% CI= 0.893 - 1.244), p=0.536). Atrial flutter (AFl) events were reported in 6 trials; 48 out of 9165 patients in the sacubitril/valsartan group developed AFl compared to 46 out of 8759 in ACEi/ARBs group. There was no difference in AFl risk between the two groups (pooled OR=1.028, (95% CI=0.681 - 1.553), p=0.894). Finally, sacubitril/valsartan did not reduce the risk of atrial arrhythmias (AF+AFl) compared to ACEi/ARBs (pooled OR=1.050 (95% CI= 0.900 - 1.225), p=0.533). Conclusion: Although sacubitril/valsartan reduces mortality compared to ACEIs/ARBs in HF patients, they do not reduce AF risk compared to these drugs.