tbuckley/cabot-search huggingface dataset:
Abstract P414: Systems Genetics Analysis Reveals Significant Eqtls Associated With Echocardiography Parameters In Genetic Reference Population Of Bxd Strains.
Authors: Buyan-Ochir Orgil, Fuyi Xu, Undral Munkhsaikhan, Neely R Alberson, Jason Johnson, Jeffrey A Towbin, Lu Lu, Enkhsaikhan Purevjav
Journal: Circulation Research (2021)

Background: Causal and modifier genes, genetic background and environment underlie clinical heterogeneity in cardiomyopathy (CM). The BXD recombinant inbred (RI) family represents a murine genetic reference population (GRP) that are descendants from crosses between C57BL/6J (B6) and DBA/2J (D2) mice. The parental D2 mouse is a natural model of hypertrophic CM (HCM). The study aimed to dissect genetic architecture of cardiac traits in BXD GRP using systems genetics analysis. Methods: Echocardiography was performed in 88 strains of male (M) and female (F) BXDs (N&gt;5/sex) at 4-5 months of age. Cardiac traits were then associated with heart transcriptome, and expression quantitative trait loci ( eQTL) mapping was performed. Results: More than 2-fold variance in ejection fraction (EF%), fractional shortening (FS%), left ventricular (LV) volumes at end-systole and end-diastole (Vol;s and Vol;d), internal dimensions (ID;s and ID;d), posterior wall (PW), and interventricular septum (IVS) thickness was found among BXDs. Traits seen in dilated CM (DCM) patients such as reduced EF%, FS%, and LVPW and increased Vol;s and ID;s are found in BXD78 (M, F), BXD32, 111, and 68 (F) strains. Strains D2, BXD90 and 155 (M, F), BXD44 and 65 (M), and BXD113, 16, 77 (F) had significantly greater LV mass, LVPW and IVS thickness compared to sex-matched controls, suggestive for traits seen in HCM patients. A 6.4 Mb QTL (peak LRS=18.50) was identified on chromosome (Chr) 8 to be significantly associated with ID;s, ID;d, Vol;s and Vol;d among male BXDs. eQTL mapping for each of 131 genes on Chr8 QTL identified 6 genes ( Coq9 , Ndrg4 , Crnde, Irx3, Rpgrip1l, and Rbl2 ) being cis -regulated and Ndrg, Slc6a2 and Ces1d being significantly (p &lt; 0.05) correlated with LV volumes. In female BXDs, a significant QTL on Chr7 (40.2 Mb) with 9 genes that significantly correlated with LVPW;d was identified. A suggestive 92.6 Mb QTL on Chr3 with Snapin , Tpm3 , and Wars2 correlated with EF% and FS% (p &lt; 0.05). Conclusions: Our study found cardiomyopathy-associated traits are segregated among BXD family and these traits vary among BXD lines. Multiple associated QTLs demonstrate that the BXD family is suitable to map gene variants and identify genetic factors and modifiers that influence cardiomyopathy phenotypes.
Abstract 10101: Obstructive Sleep Apnea Syndrome Attenuates HDL Functions
Authors: Yasuhiro Endo, Makoto Sasaki, Manami Teramoto, Makoto Ayaori, Hideaki Nakayama, Yuichi Inoue, Katsunori Ikewaki
Journal: Circulation (2021)

Background: High density lipoprotein (HDL) exerts anti-atherogenic functions including cholesterol efflux capacity and anti-oxidative activities. Obstructive sleep apnea (OSA) is associated with increased risk for cardiovascular disease via inflammation and oxidative stress. However, HDL functions in patients with OSA remains to be elucidated. We therefore investigated cholesterol efflux capacity and anti-oxidative activity in order to assess whether OSA would affect HDL functions. Methods and Results: A total of 116 OSA patients who underwent polysomnography tests from April 2017 to April 2019 were enrolled in this cross-sectional study. Blood samples were obtained at the next day of polysomnography test. We measured cholesterol efflux capacity in OSA patients and found that CEC was significantly lower in SAS groups (apnea hypoxia index (AHI)≧5) compared with non-SAS groups.(AHI&lt;5)(1.06±0.15 vs 0.96±0.14 p=0.01) Among OSA parameters, minimal pulse oxygen saturation(minSpO2), a highly correlated parameter with AHI (r=-0.76 p&lt;0.001), was found to be positively correlated with CEC (r=0.19 p=0.034) In multiple regression analysis , CEC was associated with minSpO2 independently of several clinical parameters including BMI, age, PON1, smoking, hypertension, dyslipidemia, diabetes mellitus, TC, logTG, HDL-C.(β=0.25 p=0.02) Further, CEC was inversely correlated with log hsCRP adjusted with the same model.(β=-0.25 p=0.01).With regard to anti-oxidative function, assessed by AAPH and PON1 activity, AHI or min SpO2 did not correlate with anti-oxidaitive activity by AAPH or PON1 activity. Conclusion: Obstructive sleep apnea syndrome attenuated cholesterol efflux capacity. Min SpO2 may be a good predictor of HDL dysfunction in OSA.
Abstract 14281: Comparative Visualization of Left Ventricular Segments With and Without Intravenous Contrast During Dobutamine Stress Echocardiography in Class III Obese Patients
Authors: Carl Carlino, Saravanan Kuppuswamy, Lerin McCray, Kul Aggarwal, Martin A Alpert
Journal: Circulation (2021)

Introduction: Concern exists regarding adequacy of visualization of stress echocardiograms performed without intravenous contrast (IVC) enhancement in patients with Class III obesity (body mass index ≥ 40 kg/m 2 ). Hypothesis: Use of (IVC) enhancement will significantly improve visualization and interpretability for ischemia of left ventricular (LV) segments during dobutamine stress echocardiography (DSE) at baseline and at peak stress compared to non-use of IVC enhancement. Methods: DSE was performed on 128 candidates for bariatric surgery with class III obesity without chest pain or pre-existent coronary artery disease. DSE without IVC was initially performed on 62 patients with class III obesity, then was subsequently was performed with IVC on 66 patients with class III obesity. LV regional wall motion was assessed at baseline and peak stress using the 16-segment model. Results: In the IVC group 1046 of 1056 LV segments studied (99.1%) were well-visualized and interpretable at baseline and 1044 of 1056 LV segments studied (98.9%) were well-visualized and interpretable at peak stress. In the non-IVC group 905 of 992 LV segments studied (91.2%) were well-visualized and interpretable at baseline and 886 of 992 LV segments studied (89.3%) were well-visualized and interpretable at peak stress. A significantly greater number of LV segments were well-visualized and interpretable in the IVC group compared to the non-contrast group, at baseline and at peak stress (p &lt; 0.00001 for both). DSE was positive for ischemia in 1 patient. All patients eventually underwent bariatric surgery without cardiovascular complications. Six months after surgery, all patients were alive; none developed cardiovascular events. Conclusion: The use of IVC enhancement during DSE significantly improves visualization and interpretability of lLV segments in patients with class III obesity and relatively low cardiovascular risk.
Abstract 13000: Quality of Care and In-Hospital Outcomes of Patients Hospitalized for Heart Failure With Reduced Ejection Fraction During the COVID-19 Pandemic: Findings From the Get With the Guidelines-Heart Failure Registry
Authors: Neil Keshvani, Anurag Mehta, Heather Alger, Christine Rutan, Joseph H Williams, Shuaiqi Zhang, Rebecca Young, Brooke Alhanti, Karen Chiswell, Stephen J Greene, Adam D Devore, Gregg C Fonarow, Ambarish Pandey
Journal: Circulation (2021)

Introduction: COVID-19’s impact on in-hospital care quality and outcomes of patients hospitalized with acute heart failure (HF) has not been systematically evaluated nationally. Methods: Patients hospitalized with HF with ejection fraction (EF) &lt;40% in the AHA GWTG-HF registry during the pandemic (3/1/2020 - 4/1/ 2021) and pre-pandemic (2/1/2019 - 2/29/2020) periods were included. Adherence to HF process of care measures, in-hospital mortality, and length of stay (LOS) were compared in the pre-pandemic vs pandemic period and among hospitalized HF patients with vs without COVID-19 across both periods. Results: 40,005 pre-pandemic and 35,561 pandemic period patients admitted across 346 centers (median age 68, 33% women, 58% White) were included. There were no differences in clinical characteristics, comorbidities, presentation vital signs, or EF during the pandemic vs pre-pandemic periods. Among process of care measures, utilization of guideline-directed medical therapy at discharge was comparable across both periods. In contrast, rates of ICD placement or prescription and blood pressure control at discharge were lower during the pandemic (vs pre-pandemic period) ( Table ). In-hospital death (2.5% vs. 3.0%, p&lt;0.001) and LOS (mean 5.4 vs. 5.7 days, p=0.008) were higher during the pandemic vs pre-pandemic. Substantial geographic variation was seen in the in-hospital death rates during the pandemic, with highest rates among patients hospitalized in the Northeast region (3.36%). Among HF patients hospitalized during the pandemic with COVID-19 (N = 527 [1.5%]), adherence to ICD placement or prescription at discharge and prescription of aldosterone antagonist or ACE/ARB/ARNi were lower, and risk of in-hospital death and length of stay were significantly higher than those without COVID-19. Conclusion: In-hospital mortality and adherence to certain quality measures worsened during COVID-19 pandemic among patients admitted for acute decompensated HFrEF.
Tandem CD19/CD22 Dual Targets CAR T-Cells Bridging Hematopoietic Stem Cells Transplantation Acquires Robust Remission for Relapsed and Refractory B Acute Lymphoblastic Leukemia Patients
Authors: Wei Cui, Xinyue Zhang, Haiping Dai, Qingya Cui, Jia Yin, Zheng Li, Lei Yu, Liqing Kang, Depei Wu, Xiaowen Tang
Journal: Blood (2021)
Six-Month Follow-up for Infectious Complications after Lymphodepletion and Application of CD19-Chimeric Antigen Receptor T (CAR-T) Cell Therapy
Authors: Felix Korell, Maria-Luisa Schubert, Tim Sauer, Anita Schmitt, Patrick Derigs, Tim Frederik Weber, Paul Schnitzler, Carsten Müller-Tidow, Peter Dreger, Michael Schmitt
Journal: Blood (2021)
Abstract 10114: Secondhand Tobacco Smoke Exposure, Urine Cotinine, and Risk of Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis
Authors: Gen-min Lin, Don Lloyd-jones, Laura A Colangelo, R. Graham Barr, Moyses Szklo, Susan Heckbert, Lin Y Chen, Joao A Lima, Kiang Liu
Journal: Circulation (2021)

Importance: Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and has been associated with atrial fibrillation (AF), but the association of SHS with AF has not been confirmed using objective measures for both SHS and incident AF events. Objectives: To investigate the association of self-reported and objective SHS exposure amounts with incident AF. Design: Cohort study. Setting: The Multi-Ethnic Study of Atherosclerosis (MESA) included 6 USA sites. We used follow-up data from the first visit (2000-2002) through 2015. Participants: The study sample consisted of 5,730 participants, aged 45-84 years and free of known AF and other cardiovascular diseases at baseline, who self-reported SHS exposure time in hours per week. We also selected a cohort subset of 3,237 current non-smoking participants who received spot urine cotinine measurements at baseline (2000-2002). Exposures: Self-reported SHS exposure time (whole cohort) and urine cotinine levels (cohort subset). Main Outcomes and Measures: AF events were identified using Medicare claims, hospital records and electrocardiographic findings. A multivariable Cox proportional hazards regression model was used with simultaneous adjustment for demographic factors, educational level, health insurance status, active smoking status, tobacco pack-years, traditional cardiovascular risk factors, depressive symptoms and medications. Results: During a median follow-up of 14.0 years, 856 and 452 AF events were identified in the overall and the cohort subset, respectively. No association of SHS exposure time or urine cotinine with incident AF was found. However, a higher AF risk with greater urine cotinine (8.53-442.0 ng/mL) compared with lower urine cotinine (≤7.07 ng/mL) was observed in never smokers [hazard ratios (HR): 1.60 (95% confidence intervals (CI): 1.16, 2.19)], but not in former smokers [HR: 0.88 (95% CI: 0.63, 1.23)] (p-value for multiplicative interaction: 0.009 and for additive interaction: 0.017, respectively). Conclusions and Relevance: Objectively measured greater SHS exposure expressed by urine cotinine might be associated with 1.6-fold higher risk of incident AF in never smokers.
Abstract 11895: Impact of Prehospital Mobile Cloud ECG System to Reduce Door to Balloon Time and Onset to Recanalization Time in STEMI
Authors: Takashi Unoki, Motoko Kametani, Junya Matsura, Tomoko Nakayama, Yutaka Konami, Hiroto Suzuyama, Masayuki Inoue, eiji horio, Tetsuo Yufu, Kazuhisa Kodama, Megumi Yamamuro, Eiji Taguchi, Tadashi Sawamura, KOICHI NAKAO, Tomohiro Sakamoto
Journal: Circulation (2021)

Background: Clinical guidelines strongly recommend patients with ST-elevation myocardial infarction (STEMI) receive timely mechanical reperfusion, defined as door-to-balloon time (DTBT) ≤90 minutes. Recently, mobile cloud 12-lead ECG transmission system (C-ECG) were becoming popular at low cost. Medical staff can immediately review the ECG via PC or personal hand-held devices, and also track the location of the ambulance in a real time manner. Objective: Evaluate the impact of the prehospital C-ECG on DTBT and mortality in patients with STEMI. Methods: In June 2018, eight mobile C-ECG systems (SCUNA®, MEHERGEN GROUP) were integrated into the Uki city and Kamimashiki city regional EMS departments in Kumamoto Prefecture, We compared the DTBT, onset to recanalization time (OTRT) and mortality rates of STEMI cases for 3 years prior to and 3 years after the C-ECG system. Results: For 6 years study period, 267 STEMI patients were transferred by ambulances from two EMS departments. After excluding 14 patients with onset to arrival time more than 24 hours and 54 patients who were transferred without C-ECG, 199 consecutive STEMI cases underwent emergency PCI in which 100 were prior to C-ECG introduction (Pre-C-ECG, from June 2015 to May 2018) and 99 were after C-ECG (Post-C-ECG, from June 2018 to May 2021). Results: No significant differences were found in age, gender, and Killip classification between the groups. The DTBT and OTRT were significantly shorter in the post-C-ECG compared to the pre-C-ECG (Pre: 68 min [IQR; 43-76] vs. Post: 50 min [IQR; 43-76]; p=0.005, Pre: 190 min [IQR; 138-294] vs. Post: 157 min [IQR; 112-276]; P=0.04, respectively). However, peak-CPK and the in-hospital mortality were not significantly different (Pre: 2068 IU/L [IQR; 1168-4200] vs. Post: 2105 IU/L [IQR; 872-4528]; p=0.8, Pre: 7.0% vs. Post: 5.1%; p=0.6, respectively). Conclusion: Although the prehospital mobile C-ECG system significantly reduced both DTBT and OTRT, the DTBT at our institution was short enough that C-ECG did not reduce the peak CPK or mortality.
QOLP-32. EFFECT OF CANNABIS USE ON QUALITY OF LIFE AMONG GLIOMA PATIENTS: A LONGITUDINAL PERSPECTIVE
Authors: Eduardo Rodriguez Almaraz, Susan Chang, Nancy Ann Oberheim-Bush, Jennifer Clarke, Jennie Taylor, Jessica Schulte, Mariza Daras, Laura Busby, David Gibson, Nicholas Butowski
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Gliomas are devastating primary tumors of the central nervous system that often present with difficult to manage symptoms in addition to the antineoplastic tumor itself. Due to recent increase in popularity and societal acceptance of cannabis products, their use by glioma patients has increased. METHODS We conducted a single center, prospective study: patients with glioma answered a locally validated survey to inquire about their cannabis use at baseline and every three months. Quality of Life was measured using the EORTC QLQ-C30, its complementary module BN-20 and the EQ-5D-5L instrument. Eligible participants were classified as cannabis users or non-users. We performed linear regression clustered by subjects to see differences by user group and trends overtime. RESULTS To date, 89 patients agreed to participate, enrolled, and answered the baseline questionnaires, and 64 have answered the 3 month follow up survey. The mean age was 49.7(SD 13.74), 55 were male, 55 were cannabis users at baseline (61.8%) and 34 at 3 months (53.13%). Patients who were cannabis users scored 11.73 lower points at baseline when compared to non-users (79.65 [SD 18.93] vs 67.92 [SD 19.22]) in the QLQ-C30 instrument. Similarly, cannabis users recorded 9.624 lower points at 3 months compared to non-users (70.1 [SD 21.33] vs 79.72 [SD13.95]). The difference-in-difference estimator was 2.108 (p&amp;lt; 0.7). CONCLUSION Although we observed cannabis users scoring lower QoL measurements (p&amp;lt; 0.05) at baseline and 3 months, we observed a slight improvement in QoL of cannabis users while observing no change or decline (in some measures) among non-users. Our findings provide insight to the impact that cannabis has in QoL over time. While not conclusive, these preliminary results need to be studied on a longer-term basis with a larger sample size in order to detect trends on quality of life among patients with different tumor types.
Abstract 12967: Deletion of G Protein-Coupled Receptor 39 Protects Angiogenesis in Hyperglycemia
Authors: Sai Meda Venkata, Hainan Li, Huong Nguyen, Jia Yi Koh, Jie-mie Wang
Journal: Circulation (2021)

Introduction: Endothelial cells (ECs) are essential to vascular homeostasis and angiogenesis. Endothelial dysfunction significantly contributes to critical limb ischemia in patients with diabetes. G protein-coupled receptor (GPR) 39 is an orphan receptor whose role in EC functions is unknown. We hypothesize that inhibition of GPR 39 protects angiogenesis under hyperglycemic conditions. Methods and Results: Healthy human aortic endothelial cells (H-HAECs) and diabetic human aortic endothelial cells (D-HAECs) were cultured in vitro . The migration (Modified Boyden Chamber assay) and tube formation capacity of H-HAECs were impaired by the transfection of adenovirus carrying human GPR39 or by a GPR39 agonist, TC-G-1008 (both n=5, p&lt;0.05). Conversely, GPR39 siRNA improved D-HAEC migration (n=4 per group, p&lt;0.05). In an angiogenesis protein profiler array, GPR39 overexpression has significantly reduced vascular endothelial growth factor (VEGF), Interleukin-8, monocyte Chemoattractant Protein-1 (MCP1), and Angiopoietin-2 in H-HAECs (n=5 per group, p&lt;0.05). Adult male GPR39 global knockout (GPR39 KO ) mice and age- and sex-matched wild-type (GPR39 WT ) litters were rendered diet-induced obese (DIO) by a 10-week high-fat and an add-on 8-week hyperglycemia by low-dose streptozotocin (STZ) injections chow as they reflect the human condition where obesity is closely linked to type 2 diabetes development. Hind limb ischemia was created by left femoral artery ligation. Laser Doppler imaging showed that GPR39 KO mice had a faster blood perfusion recovery from ischemia than GPR39 WT mice (n=5 per group, p&lt;0.05). In adult male C57BL/6 with DIO-STZ, intramuscular injection of EC-affinitive AAV-mediated shRNA against GPR39 significantly accelerated blood perfusion recovery and prevented tissue necrosis compared to empty AAV treatment (n=5 per group, p&lt;0.05). Conclusion: Our data indicated that genetic inhibition of GPR39 improved EC functions and accelerated angiogenesis from ischemia. We believe that the investigations in endothelial GPR39 may help better identify the novel therapeutic potential of targeting GPR39 in treating vascular complications in hyperglycemia.
EPID-21. EPIDEMIOLOGY AND RISK FACTORS OF PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS IN CHILDREN AND ADULTS IN THE MIAMI CANCER INSTITUTE (MCI) COHORT
Authors: Miguel Ramirez-Menendez, Shirlinka Israel, Muni Rubens, Alejandra Fernandez, Zuanel Diaz, Matthew Hall, Alexander Mohler, Rupesh Kotecha, Yazmin Odia
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Many epidemiological studies assess risk factors and incidence of primary CNS tumors in the United States; few describe the incidence in specific geographic locations. Environmental or ethnic/racial factors may affect the incidence of primary CNS tumors. Miami-Dade County (MDC) is an ethnically-diverse US county, with 69.4% Hispanic, 12.9% White Non-Hispanic, 15.5% Black Non-Hispanic, Asian 1.6%, 0.3% Native, and 0.3% other. We characterized primary CNS tumors at Miami Cancer Institute (MCI) relative to national reports. METHODS We reviewed electronic medical records for all patients (n=1221) diagnosed with CNS tumors at MCI from 2017 to 2021. Descriptive and statistical analyses assessed environmental and clinical variables. RESULTS Malignant CNS tumors account for 74% of MCI primary CNS tumors. Diffuse gliomas (41%), meningiomas (26%), and embryonal tumors (5%) were the most common histologies; embryonal tumors most common at younger ages (median: 18 years). The most abundant histological subtypes were glioblastoma (54%), benign meningioma (92%), and medulloblastoma (73%), respectively. Ethnic/racial composition of glioma patients at MCI was 55.9% Hispanic, 24.6% White Non-Hispanic, 6.4% Black Non-Hispanic, 1.8% Other Non-Hispanic, 1.3% Asian, 10% unreported, comparable to MDC. Compared to national averages, the age distribution at MCI was higher among lower grade gliomas (range: 15-96, Median: 61 years), yet lower for malignant gliomas (range: 1-93, median: 47 years). The incidence of malignant CNS tumors did not differ by gender; benign primary CNS tumors were significantly more frequent in females (245/324, 76%; p&amp;lt; 0.001). Smoking history did not associate with incidence of primary CNS tumors; 793/1221 (65%) self-reported as non-smoker. CONCLUSION The ethnic/racial composition and incidence of primary CNS tumors by histology at MCI significantly differs from national CBTRUS database (Ostrom et al). This cohort will be further characterized by genetic profiles, race, diet, allergies, family history, substance use, clinical trial enrollment, therapeutic modalities, and overall survival rate.
Abstract 10384: Continuous Blood Pressure Monitoring During Six-Minute Walk Test and the Hemodynamic Response in Patients with Pulmonary Hypertension
Authors: Andrew M Pattock, Cooper B Kersey, Michelle M Kim, Kayvon Ghoreshi, Patrick Stafford, Domitilo Gomez, Martin Baruch, Andrew Mihalek, Sula Mazimba, Younghoon Kwon
Journal: Circulation (2021)

Introduction: The six-minute walk test (6MWT) is frequently performed in patients with pulmonary hypertension (PH) to assess exercise capacity. Systolic blood pressure (SBP) values and variation during 6MWT may hold prognostic significance, but technologic limitations have precluded routine measurement. We used a novel device for continuous SBP monitoring during 6MWT and analyzed the relationship with PH severity. Methods: Caretaker®, an FDA-approved wireless continuous noninvasive BP device that uses pulse decomposition analysis was worn during 6MWT in patients with and without PH. We compared SBP values before, during, and after 6MWT. A repeated-measures ANOVA was used to compare SBP between groups. Results: Of the 80 patients tested, fifty patients (62.5%) demonstrated adequate signal quality for SBP monitoring. SBP varied significantly with the 6MWT in the PH group (N = 26; before vs. during vs. after; 129.1 [18.7] vs. 126.7 [18.6] vs. 140.3 [23.5] mmHg, p = 0.0006), but not in the non-PH group (N = 24; 136.1 [17.6] vs. 137.8 [17.9] vs. 143.1 [20.0] mmHg, p = 0.16). In the PH group, SBP variation while walking was inversely correlated with baseline pulmonary artery systolic pressure (PASP) (R = -0.47, p = 0.039, Figure 1 ). Conclusions: Continuous, clinic based SBP monitoring was feasible in nearly two-thirds of patients undergoing 6MWT. SBP response during walking differed between patients with and without PH and may provide clinically relevant insight into a patients exercise response. In patients with PH, change in SBP during 6MWT was inversely correlated with baseline PASP, suggesting dysregulated exertional hemodynamic response in patients with severe PH.