tbuckley/cabot-search huggingface dataset:
Abstract 11833: Prognostic Value of Diffusion-Weighted Cardiac Magnetic Resonance Imaging in Hospitalized Heart Failure Patients
Authors: Kazuki Kagami, Takumi Toya, Shunpei Kuwaki, Atsushi Sato, Yusuke Yumita, Ayumu Osaki, Midori Iwashita, Risako Yasuda, Yukinori Ikegami, Takayuki Namba, Nobuyuki Masaki, Yuji Nagatomo, John Steiner, Takeshi K Adachi
Journal: Circulation (2021)

Introduction: Diffusion-weighted imaging (DWI) has been recognized as the golden standard to detect acute phase cerebral infarction; however, there is a paucity of data regarding its utility in cardiac magnetic resonance (CMR). Hypothesis: We hypothesized that contrast-free DWI could detect underlying myocardial pathophysiology in patients with heart failure (HF). Methods: We included 90 hospitalized HF patients (mean age 62±13 years, 67% males, HFpEF/HFmrEF/HFrEF [N] 21/7/62) who underwent CMR with DWI and late gadolinium enhancement (LGE). We acquired 2 diffusion-weighted images (b=0 and 800 s/mm 2 ) to constitute apparent diffusion coefficient (ADC) map (Figure 1). ADC values were automatically calculated for five segments (basal septal, mid septal, apical, mid lateral, basal lateral) on 4-chamber planes. The association between minimum ADC values and major adverse cardiac events (MACE: all-cause mortality, HF hospitalization, or sustained ventricular arrhythmia/ICD shock) was investigated. Results: During a median follow-up of 18.1 months (IQR 9.3-32.1), 26 adverse events (8 all-cause deaths, 13 HF hospitalizations, and 5 ventricular arrhythmias) were detected in 20 patients. Event-rates were significantly higher in patients with minimum ADC value lower than median (=3490 mm 2 /s) than those with minimum ADC value higher than median (log-rank p=0.003) (Figure B). Lower minimum ADC value was associated with an increased risk of MACE (unadjusted HR 4.45, 95% confidence interval: [1.49-13.32]) and it remained significant even after adjustment for LGE. Minimum ADC values improved discrimination of risk for MACE after adding it to LGE (Figure C). Conclusions: Patients with lower minimum ADC values had an increased risk of MACE. DWI may potentially provide with incremental prognostic values over LGE in HF patients.
Cerebral Sinovenous Thrombosis in Greek Children: A Single Centre Experience
Authors: Athina Dettoraki, Aikaterini Michalopoulou, Maria Gavra, Loukia Ioannidou, Zoey Kapsimali, Sotiria Thymianou, Sophia Vassilopoulou, Ioannis Papassotiriou, Antonis Kattamis, Eleni Pergantou
Journal: Blood (2021)
Abstract 12102: TNNI3-K183del Mutation in Dilated Cardiomyopathy Patient-Specific iPSC-Derived Cardiomyocytes Affects Structural Proteins and Ion Channels, Leading to Impair the Function of Cardiomyocytes
Authors: Nagako Sougawa, Takuji Kawamura, Ryohei Matsuura, Junjun Li, Li LIU, Akima Harada, Maki Takeda, Noriko Oda-Mochizuki, Yoshiki Sawa, Shigeru Miyagawa
Journal: Circulation (2021)

Background: One of the causes for Dilated cardiomyopathy (DCM) are thought to be genetic defect. One mutation, Lys183 del mutation of the TNNI3, is suggested to be associated with left ventricular systolic dysfunction and transition from hypertrophic cardiomyopathy to DCM. However, the precise disease mechanism is not fully understood. Because cardiomyocytes derived from induced pluripotent stem cells (hiPSC-CMs) possess many of the same characteristics as primary human CMs and can be generated in unlimited quantities from pluripotent cell sources, they are thought to be a promising research tools to model genetic cardiomyopathies. Therefore, we hypothesized that iPS-CMs with mutations in TNNI3 is useful for elucidating the pathological mechanism of DCM and examined the phenotype of iPS-CMs with mutations in TNNI3. Methods and Results: We generated iPSCs from the patient with Lys183 del mutation of the TNNI3, and simultaneously induced iPS-CMs. By immunofluorescence stain analysis, we identified well-formed parallel arrays of repeating sarcomeres in myofibrils from WT iPS-CMs. On the other hand, iPS-CMs with Lys183 del mutation of the TNNI3 had fewer myofibrils and abnormal, irregular sarcomeres. In addition, sarcomere length was shorter in iPS-CMs with mutation in TNNI3 than in WT iPS-CMs. By gene expression analysis, we identified that iPS-CMs with mutation in TNNI3 had lower expression of some molecules including structural proteins or ion channels than WT iPS-CM. Cell motion analysis revealed that WT iPS-CMs were synchronously beating in multi wells, whereas iPS-CMs with mutation in TNNI3 were not. In addition, contraction velocity (CV) and relaxation velocity (RV) were significantly lower in iPS-CMs with mutation in TNNI3 (CV; 4.98±0.05 μm/sec, RV; 4.01±0.01 μm/sec) compared with WT iPS-CM (CV; 14.25±0.03 μm/sec, RV; 7.04±0.03 μm/sec). Moreover, significant decrease in contraction deformation distance and relaxation deformation distance were observed in iPS-CMs with mutation in TNNI3 (0.96±0.004 μm, 0.91±0.01 μm, respectively), compared to WT iPS-CMs (2.56±0.004 μm, 2.18±0.008 μm, respectively). Conclusion: iPS-CMs with Lys183 del mutation of the TNNI3 showed the morphological and functional phenotypes of DCM at a cellular level.
Abstract 10330: Intermittent Fasting Interacts with Red Cell Distribution Width to Differentially Improve Cardiometabolic Health
Authors: Benjamin D Horne, Joseph B Muhlestein, Heidi T May, Viet T Le, Tami L Bair, Kirk U Knowlton, Jeffrey L Anderson
Journal: Circulation (2021)

Introduction: Intermittent fasting reduces weight and cardiometabolic risk factors. In the WONDERFUL Trial (NCT02770313), intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) and the Metabolic Syndrome Score (MSS), with insulin having the largest decline. The red cell distribution width (RDW) measures the dispersion of red blood cell size, is strongly predictive of mortality and major adverse events, and may be a biomarker of general health. This post hoc study of subjects from the WONDERFUL Trial examined the interactive effect of intermittent fasting and baseline RDW on changes in insulin, glucose, HOMA-IR, and MSS. Methods: Subjects aged 21-70 years who had pre-diabetes, diabetes, or ≥1 other metabolic syndrome factor and modestly elevated LDL-C were enrolled if they were not taking anti-diabetic or statin medications and were free of chronic diseases (N=71; n=38 intermittent fasting, n=33 controls). Subjects were randomized to 24-hour water-only fasting (twice-weekly for 4 weeks followed by once-weekly for 22 weeks) or ad libitum eating (control) for 26 weeks. Results: Age averaged 49.1±11.1 years and 64.8% were female. Change scores stratified by RDW size distribution (RDW-SD) are shown in the Table. Results were similar when the RDW coefficient of variation (RDW-CV) was used. Intermittent fasting did not change RDW-SD (1.27±9.6 fL vs. control: -0.37±1.76 fL, p=0.34) or RDW-CV (-0.15%±0.55% vs. control: -0.11%±0.45%, p=0.76) over the 26-week trial. Conclusions: Compared to controls, intermittent fasting significantly decreased insulin more in subjects with higher baseline RDW than those with RDW ≤median. This differential effect may also apply to changes in HOMA-IR, glucose, and MSS. These findings should be validated and expanded in larger studies since RDW may identify people who would derive the most cardiometabolic benefit from engaging in intermittent fasting.
Abstract 11272: Barriers and Enablers of Rheumatic Heart Disease Care in a Resource Limited Setting
Authors: Jafesi Pulle, Hadija Nalubwama, JENIFER ATALA, Rebecca Namara, Rachel Sarnacki, Emma Ndagire, andrea beaton, Craig A Sable, David Watkins, Emmy Okello
Journal: Circulation (2021)

Introduction: Rheumatic heart disease (RHD) has nearly been eradicated in wealthy nations but remains a significant public health concern in low-resource countries like Uganda. Many people living with RHD is these settings have not been diagnosed and many who are diagnosed have late-stage disease requiring surgery, an expensive intervention. Objectives: To explore the barriers and enablers to RHD care in a resource limited setting. Methods: This was a qualitative study. We held in-depth interviews among 36 RHD patients randomly selected from a computer-generated list of patients enrolled in the RHD registries in the Northern, Central, and South-western regions. The selected participants were interviewed by trained qualitative research staff. All interviews were tape recorded and transcribed verbatim. Data were analyzed by thematic content analysis and useful codes were generated by both inductive and deductive approaches. Generated codes were collapsed into themes. Coding was done by 3 independent researchers who compared their results and agreed on one codebook which was updated iteratively. Results: Barriers to care included financial constraints, high cost of medicines, poor access to RHD diagnostics, misdiagnosis, poor access to drugs, high cost of cardiac medicines and high costs of travel to health facilities. Enablers of RHD care included the desire to live, availability of drugs, diagnostics and healthcare workers at RHD clinics, good attitude, counseling and education by health workers, subsidised costs of services at RHD clinics, reminder systems and access to RHD services at nearer facilities. Conclusion: Enhancing enablers and mitigating barriers may improve access to RHD care in resource limited settings and significantly reduce the burden of disease.
Abstract 15315: Efficacy and Safety of Four-Factor Prothrombin Complex Concentrate in the Patients With Mechanical Circulatory Support for Life-Threatening Bleeding or Emergent Surgery
Authors: Keitaro Domae, Yukitoshi Shirakawa, Ryo Kawasumi, Fumio Yamana, Kana Shibata, Koichi Toda, Shigeru Miyagawa, Daisuke Yoshioka, Toshiki Takahashi, Yoshiki Sawa
Journal: Circulation (2019)

Introduction: Anti-coagulation therapy with vitamin K antagonist (VKA) is necessary for preventing thromboembolic event in the patients with mechanical circulatory support (MCS) although, in case o...
Pneumocystis Jirovecii Infection in Autologous Hematopoietic Stem Cell Transplant Recipients
Authors: John E Coda, Kadee Raser, Sarah M. Anand, Monalisa Ghosh, John Maciejewski, Attaphol Pawarode, Mary Mansour Riwes, Christina Tillman, Gregory Yanik, John M. Magenau, Matthew J. Pianko
Journal: Blood (2021)
QOLP-27. NEURO-ONCOLOGICAL PATIENTS' AND CAREGIVERS' PSYCHOSOCIAL BURDEN DURING THE COVID-19 PANDEMIC – A PROSPECTIVE STUDY WITH QUALITATIVE CONTENT ANALYSIS
Authors: Mirjam Renovanz, Julia Binswanger, Carolin Kohl, Felix Behling, Susan Noell, Sophie Hirsch, Anne-Katrin Hickmann, Marcos Tatagiba, Melina Hippler, Ghazaleh Tabatabai
Journal: Neuro-Oncology (2021)

Abstract OBJECTIVE The COVID-19 pandemic may reinforce psychosocial distress of neuro-oncological patients. We aimed to 1) differentiate the burden caused by the pandemic vs. the tumor and 2) establish topics relevant for brain tumor patients (BTPs) and caregivers. METHODS Patients and caregivers were prospectively assessed from April 2020 – July 2020 by a 10-item comprising interview over the phone, including qualitative and quantitative questions. They were quantitatively evaluated i.a. by the Distress Thermometer (DT, score 1-10). The qualitative questions were analyzed using structured content analysis: The interview questions defined the main categories. Subcategories were derived by an inductive approach assessing the frequency of patients' and caregivers' answers. RESULTS A total of 69 patients and 20 caregivers were interviewed; n= 36 were female (49%), mean age was 53 years (range 32-81). Patients' disease-related DT scores were higher than the COVID-19-related DT scores: the median of the disease-related DT score was 7 (range 2-10) vs. median of COVID-19-related distress: 5.0 (range 2-7). Caregivers perceived a higher burden due to the disease (DT median disease: 8; range 2-10 vs. DT pandemic: 3, range 0-10). A total of 5 main and 21 subcategories were elaborated, most frequently mentioned were "restrictions in public and private affairs" (28%), "changes in the psychological well-being" (23%), "limited social interaction by contact restriction" (25%). Subcategories relevant for caregivers were similar to those of BTPs. CONCLUSION A considerable proportion of patients and caregivers still perceived the brain tumor disease as more burdensome than the pandemic. We established main and subcategories of interview items possibly of great relevance to patients during these difficult times, which could be implemented in the content-related adaption of the psychosocial assessment.
Abstract 9685: Long-Term Efficacy and Safety of Mavacamten in Patients with Non-Obstructive Hypertrophic Cardiomyopathy: Interim Results from the MAVERICK-LTE Cohort of the MAVA-LTE Study
Authors: Anjali Owens, Mark V Sherrid, Timothy C Wong, Richard G Bach, Omar Wever-Pinzon, Marzia Rigolli, Ganesh Balaratnam, Grace Ma, Matthew E Mealiffe, Jay M Edelberg, Neal K Lakdawala, Ahmad Masri, Andrew Wang
Journal: Circulation (2021)

Introduction: In the phase 2 MAVERICK-HCM study in patients (pts) with non-obstructive hypertrophic cardiomyopathy (nHCM), mavacamten, a cardiac myosin inhibitor, was well tolerated and associated with significant reduction in biomarkers of myocardial wall stress and injury over 16 weeks (wks). Long-term efficacy and safety of mavacamten are being evaluated in MAVA-LTE. Methods: Pts who completed MAVERICK-HCM were eligible to enroll in the MAVERICK-LTE cohort of MAVA-LTE. Pts who received mavacamten in MAVERICK-HCM continued on the same dose; pts on placebo were randomized (1:1) to 1 of 2 target mavacamten plasma concentration groups (~200 or ~500 ng/mL) and started on 5 mg, with dose titration at Wk 6 (dosing not based on clinical response). Pts were evaluated at Wks 8, 12, 16, 24, and every 12 wks thereafter. An interim analysis was performed (longest follow-up at data cutoff, 96 wks; efficacy data presented through Wk 48). Results: At the data cutoff, 43 pts were enrolled in MAVERICK-LTE (mean age, 54 yrs; 65% female; mean dose, 7.6 mg/day). Median NT-proBNP significantly decreased by 58% at Wk 24 and by 67% at Wk 48 (Table). Significant reductions were also observed in tissue Doppler E/e’ at Wks 24 and 48 and in left atrial volume index (LAVI) at Wk 48. There was a modest reduction in left ventricular ejection fraction (LVEF) of 5.4% at Wk 48 without significant changes in LV stroke volume (Wk 48 mean ± SD change, 0.0 ± 8.5 mL). Most treatment-emergent adverse events were considered mild or moderate and unrelated to treatment. Nine pts temporarily discontinued treatment due to LVEF &lt;50% (range, 36%-49%); 7 were asymptomatic, 8 resumed treatment at a lower dose after recovery of LVEF ≥50%, and 1 permanently discontinued. Conclusions: Consistent with the parent study, longer-term mavacamten was well tolerated and demonstrated sustained reduction in NT-proBNP in pts with nHCM. Improvements in LV relaxation and diastolic function by mavacamten were evidenced by lower E/e’ and LAVI.
Abstract 14076: Freeze-Dried Human Placental Mesenchymal Stem Cell Prevents the Progression of Acute Respiratory Distress Syndrome in Rats
Authors: Nodar Kipshidze, Zurab Kakabadze, Tea Paresishvili, David Chakhunashvili, Nicholas Kipshidze
Journal: Circulation (2021)

Introduction: Acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in patients with COVID-19. Despite numerous studies, therapies for ARDS in COVID-19 remain significantly limited. Currently, there have been reports of the efficient use of mesenchymal stem cell (MSC) for the treatment of ARDS. Several studies have reported that MSC produces anti-inflammatory cytokines, promotes the maturation of dendritic cells, and modulates NK cells. The safety of MSC therapy has been demonstrated in early-stage clinical studies with a relatively small number of patients. We investigated the influence of freeze-dried human placental mesenchymal stem cells (HPMSC) in a preclinical rodent model of ARDS. Methods: Sixty rats were randomly divided into three groups of 20: the first group was the control, the second group received dexamethasone, and the third group received HPMSC. Results: Survival was highest in the HPMSC group (75%, 95%CI: 50, 88) when compared to the control group. In a cox regression model, mortality of HPMSC group (HR: 11.30 [95% CI: 4.05, 31.50]) when compared to control was statistically significant (p &lt; 0.001). Mortality in the dexamethasone (HR: 64.25 [95% CI: 32.71, 126.19]) was not statistically significant (p = 0.199). Plasma serum TNF-α levels were statistically significant in the HMPSC group when compared to the control (p &lt; 0.001) and dexamethasone group (p &lt; 0.001). Single factor ANOVA comparing TNF-α levels between all groups was also significant (p &lt; 0.0001). Trends (Table 1) indicated that plasma serum cytokine levels for TNF-α, IL-1β, and Il-6 were less in the HPMSC group than the control and dexamethasone groups. Conclusions: These experiments demonstrated that HPMSC significantly decreased mortality, endogenous intoxication, and a reduction in the release of pro-inflammatory cytokines. The freeze-dried placental stem cell is a promising biomaterial that can be used nebulized for the treatment of coronavirus disease.
Abstract 12954: A Genotype-Phenotype Link Between Cardiac Monoamine Oxidase Activity and Arrhythmogenic Potential Using a Translational Approach
Authors: Qian Shi, Alexander Hart, Andrew Jatis, Nathan Karlan, Shahab Akhter, Jean C Shih, Ryan M Smith, Long-sheng Song, Ethan J Anderson
Journal: Circulation (2021)

Introduction: Monoamine oxidase (MAO) has emerged as an intriguing drug target for heart disease because of the toxicity of the oxidative catechol metabolites produced. Our group has recently shown that a high rate of MAO activity in atrial myocardium is associated with a greater incidence of postoperative atrial fibrillation (POAF) following coronary artery bypass graft surgery (CABG). Hypothesis: Cardiac MAO deficiency lowers arrhythmogenic potential. Methods and Results: In a cohort of age-matched CABG patients (N=288, 26% female, 20% African-American), we performed DNA-sequencing analysis of maoA,B while assessing maximal MAO-A and -B enzyme activity with norepinephrine (NE) in fresh atrial tissue from a subset (N=110) of these patients. Patients homozygous for maoA synonymous variant rs1800464, and maoB intron variant rs5905512, had lower NE-supported MAO activity ( Figure 1 , 0 = ref, 1=het, 2=homoz) and lower incidence of POAF (OR 0.6 ± 0.1 and 0.9 ± 0.02, respectively). Mice with cardiomyocyte-specific MAO-A deficiency (cMAOA -/- ) had 2-fold lower rates of epinephrine/caffeine-induced ventricular tachycardia (VT) compared with wild-type ( Figure 2 , *P&lt;0.05). Moreover, cardiomyocytes from cMAOA -/- mice had increased fractional shortening, faster relaxation and shorter Ca 2+ transient duration (P&lt;0.05). Alterations in Ca 2+ handling in the cMAOA -/- mice were accompanied by decreased epinephrine-induced phosphorylation of CamKII and ryanodine receptor (P&lt;0.05). Conclusions: Collectively, these findings suggest that decreasing MAO activity lowers arrhythmogenic potential in the heart, and that cardiac MAO may be a therapeutic target for POAF.
EXTH-46. MRS BASED BIOMARKERS OF IDH1 MUTANT GLIOMA RESPONSE TO THE IDH INHIBITOR BAY-1436032
Authors: Donghyun Hong, Noriaki Minami, Céline Taglang, Georgios Batsios, Anne Marie Gillespie, Russell Pieper, Joseph Costello, Pavithra Viswanath, Sabrina Ronen
Journal: Neuro-Oncology (2021)

Abstract Gliomas are the most prevalent type of brain tumor in the central nervous system. Mutations in the cytosolic enzyme isocitrate dehydrogenase 1 (IDH1) are a common feature of primary low-grade gliomas, catalyzing the conversion of α-ketoglutarate (αKG) to the oncometabolite 2-hydroxyglutarate (2HG), and mutant IDH1 is a therapeutic target for these tumors. Several mutant IDH inhibitors are currently in clinical trials, nonetheless, complementary non-invasive early biomarkers to assess drug delivery and potential therapeutic response are still needed. The goal of this study was therefore to determine the potential of 1H and hyperpolarized 13C magnetic resonance spectroscopy (MRS)-based biomarkers as indicators of mutant IDH1 low-grade glioma response to treatment with the clinically-relevant IDH1 inhibitor BAY-1436032 in cells and animal models. Immortalized human astrocytes engineered to express mutant IDH1 were treated with 500nM (IC50 value) of BAY-1436032 and BT257 tumors implanted in rats were treated with 150mg/kg of BAY-1436032. To assess steady-state metabolite levels, 1H MRS spectra were acquired on a 500 MHz MRS cancer for cells and a 3 T scanner for animal studies. To assess metabolic fluxes, we used hyperpolarized 13C MRS and probed the fate of hyperpolarized [1-13C]αKG. 1H MRS showed a significant decrease in 2HG as well as a significant increase in glutamate (Glu) and phosphocholine (PCh) following BAY-1436032 treatment in both cell and animal models compared to controls. Furthermore, hyperpolarized 13C MRS showed that hyperpolarized 2HG production from hyperpolarized [1-13C]αKG was decreased and hyperpolarized glutamate production from hyperpolarized [1-13C]αKG was increased in the BAY-1436032 treated groups compared to controls. These findings are consistent with our previous study, which investigated the MRS-detectable consequences of two other mutant IDH inhibitors: AG120 and AG881. Collectively, our work identifies translatable MRS-based metabolic biomarkers of mutant IDH1 inhibition.
CTNI-34. TOXICITY PROFILE AND COMPLIANCE OF PATIENTS WITH HIGH RISK GRADE 2 OR GRADE 3 GLIOMAS RECEIVING ADJUVANT PCV VERSUS ADJUVANT TEMOZOLOMIDE
Authors: Nandini Menon, Abhishek Chatterjee, Tejpal Gupta, Jayant Sastri Goda, Epari Sridhar, Ayushi Sahay, Amit Janu, Abhishek Mahajan, Ameya Puranik, Aliasgar Moiyadi, Prakash Shetty, Vikas Singh, Rakesh Jalali, Vijay Patil
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION The NCCN recommends either PCV (Procarbazine, CCNU and vincristine) or Temozolomide (TMZ) as adjuvant therapy in high-risk grade 2 &amp; grade 3 gliomas. In this ongoing study we are comparing PCV with TMZ as adjuvant therapy in this setting. METHODS This is a randomised phase 3 study that includes patients with high risk (as per RTOG) grade 2 gliomas and grade 3 gliomas after surgery. Patient are randomly assigned in 1: 2 to receive either adjuvant PCV or TMZ after adjuvant RT. The primary end-point is progression-free survival &amp; key secondary end points are overall survival, toxicity and quality of life. The current analysis focuses on the compliance and adverse events seen in patients enrolled till 30th April 2020. RESULTS 46 patients were enrolled, with 30 patients in TMZ arm. The median age of patients was 37 years (range 23-64). The ECOG PS was 1 in 45 (97.8%) patients and 2 in 1(2.2%) patient at enrolment. The number of patients who have completed all planned cycles of chemotherapy in the PCV arm is 62.5% (10, n=16) as compared to 90% (27, n=30) in the TMZ arm (P=0.047). The incidence of grade 3 or higher adverse events is 68.8% (n=11) in the PCV arm and 16.7% (n=5) in the TMZ arm (P=0.001). The most common grade 3 or higher toxicities noted are lymphopenia in 50% (n=8), neutropenia in 37.5% (n=6), and thrombocytopenia in 25% (n=4) in the PCV arm; while the corresponding numbers in the TMZ arm are 13.3% (n=4), 3.3% (n=1) and 10% (n=3) respectively. CONCLUSION In the current study the chemotherapy completion rates are higher with TMZ and it is associated with lower grade 3-4 events, whether this will lead to an improvement in outcomes remains to be seen.