tbuckley/cabot-search huggingface dataset:
Abstract 10877: Heterogeneity and Overlap of the Relationships Between Progression of Arterial Stiffness with the Development of Hypertension as Well as with That of Diabetes
Authors: Hiroki Nakano, Kazuki Shiina, taka taka, Masatsune Fujii, YOICHI IWASAKI, Chisa Matsumoto, Akira Yamashina, Taishiro Chikamori, Hirofumi Tomiyama
Journal: Circulation (2021)

Background: While co-existence of hypertension and diabetes is frequent, it has not been clarified whether arterial stiffness, a risk for cardiovascular disease, has independent bi-directional relationships with the development of hypertension and with that of diabetes. The present prospective observational study examined whether the increased arterial stiffness is independently related to the development of hypertension alone, that of diabetes mellitus alone and their coexistence and also examined vis versa. Methods: A total of 3194 Japanese middle-aged men without hypertension and diabetes at the start of this study (41±9 years old) were included. At the annual health check-ups, the blood pressure, serum glycohemoglobin A1c levels (HbA1c), and brachial--ankle pulse wave velocity (baPWV) were measured annually for 9 years’ period. Results: At the end of the study period, 434 participants were diagnosed as having hypertension alone, 19 as having diabetes (HbA1c &gt; 6.5%) alone / 90 as having impaired glucose metabolism (impG) (HbA1c &gt; 6.1%) alone, and those as having both co-existence (19 for diabetes / 41 for impG). The baPWV showed significant odds ratios for new onset of hypertension alone (1.53, P&lt;0.01) and new onset of both co-existence (1.81, P=0.05), but not for that of diabetes alone / impG alone. Conversely, mean blood pressure, but not HbA1c, had a significant odds ratio for the high baPWV ( &gt; 1400cm/sec) at the end of study period (1.33, P&lt;0.01). The generalized linear model analyses demonstrated a significant longitudinal association of the baPWV with the presence of hypertension alone (beta = 5.0 x 10 -3 , P&lt;0.01) and both co-existence (beta = 8.0 x 10 -3 , P&lt;0.01), but not that of diabetes / impG alone. The mean blood pressure, but not HbA1c, also have a longitudinal association with high baPWV (beta = 0.11, P&lt;0.01). Conclusions: In Japanese middle-aged men, the elevated blood pressure and increased arterial stiffness may have a vicious cycle in the development of hypertension, and the precede of arterial stiffness for the development of diabetes may be a crossing phenomenon for this vicious cycle. Thus, arterial stiffness may be a key element to increase cardiovascular risks in hypertension rather than in diabetes mellitus.
Abstract P475: Microrna-129-5p Rescues Myocardial Fibrosis And Calcification By Targeting Asporin And Sox9 In Cardiac Fibroblasts
Authors: Lejla Medzikovic, Laila Aryan, Gregoire Ruffenach, Min Li, Nicoletta Savalli, Riccardo Olcese, JASON HONG, Salil Sharma, Gregory Fishbein, Mansoureh Eghbali
Journal: Circulation Research (2021)

Myocardial fibrosis promotes heart failure (HF) progression by impairing myocardial compliance, but also may predispose to myocardial calcification, further impairing cardiac function. Transition of resident cardiac fibroblast (CF) to pro-fibrotic myofibroblasts (MF) and osteogenic cell fates (OF) are key events which are partially controlled by microRNAs (miRs). To discover novel miRs involved in myocardial fibrosis and calcification, we compared online-available microarray datasets of left ventricles (LV) from failing human and mouse hearts. Assessing differentially-expressed miRs known to regulate fibrosis and calcification genes revealed that miR-129-5p is significantly downregulated in HF LV. Bioinformatic target analysis revealed small leucin-rich proteoglycan Asporin (Aspn) and SRY-Box Transcription Factor 9 (Sox9) as two novel miR-129-5p targets upregulated in both mouse and human diseased LV. Thus far, nothing is known about miR-129-5p in cardiac fibrosis and calcification. Additionally, the role of Asporin in myocardial fibrosis and the roles of either Asporin or Sox9 in myocardial calcification remain undiscovered. We show that miR-129-5p is expressed in CF in mouse and human hearts and is downregulated in CF of both HF patients and Angiotensin II (AngII)-injured mice, while Asporin and Sox9 are upregulated in CF of HF LV. In vitro , AngII or transforming growth factor-β downregulated miR-129-5p expression in primary adult mouse CF. Overexpression of miR-129-5p in CF inhibited expression of MF and OF transition markers, reduced migration, collagen production and calcium deposition. We validated Asporin and Sox9 as direct targets of miR-129-5p. Accordingly, silencing of Asporin and Sox9 in CF attenuated molecular and functional characteristics of MF and OF transition. Strikingly, systemic delivery of miR-129-5p mimics in mice directly targets CF and is sufficient to rescue preexisting AngII-induced myocardial fibrosis, calcification, diastolic- and systolic dysfunction. In conclusion, miR-129-5p rescues myocardial fibrosis and calcification by attenuating MF and OF transition via inhibition of Asporin and Sox9 in CF and is a promising therapeutic target.
Abstract 9493: Differences in Prognostic Implications of Changes in Echocardiography in Asymptomatic Severe Aortic Stenosis Managed Conservatively
Authors: Eri Muta, Takao Kato, Tomohiko Taniguchi, Takeshi Kimura
Journal: Circulation (2021)

Background: No previous study has explored the association between the changes in echocardiographic parameters during follow-up and clinical outcomes in patients with asymptomatic severe aortic stenosis (AS) and who were managed conservatively. Objective: This study aimed to investigate the prognostic impact of the changes in echocardiographic parameter at 1-year follow-up in asymptomatic severe AS patients managed conservatively. Methods: Among 3815 patients with severe AS enrolled in the multicenter CURRENT AS registry in Japan, we analyzed conservatively managed 555 patients who underwent echocardiography at 1-year follow-up and remained asymptomatic. The primary outcome measure was a composite of AS-related deaths and hospitalization due to heart failure. A decline in left ventricular ejection fraction (LVEF), an increase in left ventricular end-diastolic dimension (LVEDD), and an increase in aortic valve pressure gradient (PG) were defined as above 10%, 5mm, and 30mmHg, respectively, based on the clinically relevant values. Results: There were 61 patients (11.0 %) with &gt;10% decline in LVEF and 494 patients (89.0%) without decline. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the decline in LVEF group than in no decline in LVEF group. After adjusting for confounders, the excess risk of the decline in LVEF relative to no decline in LVEF for the primary outcome measure remained significant (hazard ratio; 2.76, 95% confidence interval 1.66-4.45). The cumulative 3-year incidence of the primary outcome measure was significantly higher in the increase in LVEDD group than in no increase in LVEDD group. In contrast, there were no difference in cumulative 3-year incidence of the primary outcome measure between the increase in aortic valve PG and no increase group. Conclusions: Severe asymptomatic AS patients with a &gt;10% LVEF decline or &gt;5mm increase in LVEDD at 1-year after diagnosis had worse AS-related clinical outcome than those without under conservative management, whereas there were no differences in the outcomes stratified by changes in aortic valve PG. This indicated the importance in the LV morphology and function during follow-up in asymptomatic severe AS patients when managed conservatively.
Tagraxofusp (SL-401) in Patients with Chronic Myelomonocytic Leukemia (CMML): Updated Results of an Ongoing Phase 1/2 Trial
Authors: Mrinal M. Patnaik, Haris Ali, Eunice S. Wang, Abdulraheem Yacoub, Vikas Gupta, Sangmin Lee, Gary J. Schiller, James M. Foran, Ayalew Tefferi, Christopher L Brooks, Guillermo Garcia-Manero, Tariq I. Mughal, Naveen Pemmaraju
Journal: Blood (2021)
Abstract 14354: Optimal Anticoagulation Use in Patients Undergoing Transcatheter Mitral Valve Replacement a Quest for More Data
Authors: Kirtivardhan Vashistha, Amel Tobaa, Adee Elhamdani, Adnan Khalif, Mark Doyle, ramzi khalil
Journal: Circulation (2021)

Background: Multiple studies have demonstrated an increased risk of valve thrombosis in patients with mitral valve prostheses. Data to guide decision-making in regards to the choice of anticoagulation agent and duration of the therapy is lacking. We present our single-center experience with oral anticoagulation use in patients undergoing transcatheter mitral valve replacement (TMVR). Methods: 32 patients underwent the TMVR procedure at our center from 1/1/2017 to 12/31/2020. Data points on baseline characteristics, STS-PROM, functional status (NYHA and KCCQ), baseline laboratory values, echocardiographic parameters (including LVEF, MV area, gradient, grading of MS, and MR was collected. We analyzed patterns of anticoagulation therapy including the type of agent, duration of therapy, and complications occurring related to anticoagulation use. Results: Our registry included 32 patients that underwent TMVR. 70.5 % were females, 96.8 % Caucasian with a mean NYHA class of 3.25. STS-PROM of 6.25 (5.56-9.43) and KCCQ score of 38.04 (SD 19.9). Out of 32 patients, 31 had retrievable data. Vitamin K antagonist (VKA) was used in 60 % (18), apixaban in 26.6 % (8), rivaroxaban in 16.6 % (3), and no anticoagulation was used in 0.03 % (1) of patients.74 % (22) of the patients were on anticoagulation at the time of TMVR for another indication. 33.3% (6) of patients on VKA suffered a complication such as gastrointestinal/genitourinary bleed, while 54.45% (6) of patients on DOAC reported similar complications. Conclusion: The choice of anticoagulant and optimal duration of anticoagulation in patients undergoing TMVR remains a gap in our evidence base. We present our single-center experience of anticoagulant use in this patient population. Further randomized studies are needed to address this knowledge gap.
NIMG-74. RESPONSE ASSESSMENT AFTER DOSE-ESCALATED RADIOTHERAPY: IMAGING PROTOCOL OF A MULTICENTER PHASE III TRIAL ON INTRAOPERATIVE RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA (INTRAGO-II;ARO2016-1;AG-NRO-03)
Authors: Whitney Pope, Kevin Petrecca, Alexander Radbruch, Frank Giordano
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Reliable response assessment of irradiated glioblastomas remains challenging. In an attempt to better distinguish post-therapeutic alterations (such as reactive gliosis, pseudoprogression and radionecrosis) from tumor progression, especially after (local) RT dose escalation as performed in the multinational INTRAGO-II trial, we modified the classical RANO criteria and developed a protocol and workflow for uniform assessment of post-irradiation tumor response. METHODS INTRAGO-II is a multinational randomized phase III trial (9 nations, 19 centers) that evaluates the benefit of intraoperative radiotherapy (IORT) with 20-30 Gy to the tumor bed after resection of glioblastoma in addition to standard of care (NCT02685605). Within this trial, advanced imaging is mandatory in addition to standard sequences and measurements (such as the sum of the products of perpendicular diameters, SPD). Specifically, the acquisition of dynamic susceptibility contrast (DSC) sequences as well as the calculation of the normalized relative cerebral blood volume (rCBV) is required. All local assessments are subjected to a central neuroradiology read, which is conclusive. The key modifications to RANO are that (i) an ≥25% increase SPD of the target lesions should be associated with a rCBV≥1 of at least one lesion to be considered radiological progression, (ii) new enhancing lesions should become measurable before they can constitute to radiological progression, (iii) rCBV is normalized against normal appearing white matter from the contralateral brain by reference ROI (with a minimal sphere size of 5x5mm) and (iv) confirmatory scans are mandatory for defining progressive disease. CONCLUSION/SUMMARY We present an imaging protocol based on updated RANO that accounts for post-irradiation image alterations. Funding: Carl Zeiss Meditec AG, Germany and MedWave Medical Imaging BV; Registered with ClinicalTrials.gov, number NCT02685605.
Abstract 14224: JAK2V617F Red Blood Cells Promote Atherosclerosis and Thrombosis
Authors: Wenli Liu
Journal: Circulation (2021)

Elevated hematocrit is associated with cardiovascular risk; however, the causality and mechanisms are unclear. The JAK2V617F (JAK2VF) mutation markedly increases cardiovascular risk both in myeloproliferative disorders with elevated blood cell counts and in the much more prevalent clonal hematopoiesis of indeterminate potential with normal blood cell counts. Jak2VF mouse models with elevated white blood cells (WBC), platelets and red blood cells (RBCs) display accelerated atherosclerosis. However, whether Jak2VF RBCs promote atherogenesis and thrombosis independently from increased WBC and platelets remains uncertain. We used Erythropoietin Receptor (EpoR) Cre recombinase to generate a conditional knock-in of murine Jak2VF (VFEpoR) in the RBC lineage. Hyperlipidemic VFEpoR mice without elevated blood cell counts showed accelerated arterial thrombosis and increased atherosclerotic plaque necrosis. Induction of erythrocytosis with low dose erythropoietin (EPO) without concomitant leukocytosis or thrombocytosis further worsened thrombosis and atherosclerosis. VFEpoR atherosclerotic lesions featured endothelial barrier breakdown, RBC infiltration, iron deposition, lipid peroxidation, macrophage erythrophagocytosis and macrophage ferroptosis. VFEpoR RBCs had reduced antioxidant defenses and contained increased ROS and lipid hydroperoxides. Phagocytosis of murine or human WT or Jak2 VF RBCs by WT macrophages induced lipid peroxidation and ferroptotic death that was prevented by the ferroptosis inhibitor Liproxstatin-1. Ferroptosis inhibition reversed increased atherosclerosis and necrotic core formation in VFEpoR mice but had no impact in controls. These studies demonstrate that both qualitative and quantitative defects in Jak2VF RBCs accelerate atherosclerosis and thrombosis. Phagocytosis of WT or Jak2VF RBCs by macrophages leads to ferroptotic cell death, suggesting ferroptosis as a new therapeutic target to reduce RBC-mediated cardiovascular risk.
Abstract 11260: Psychosocial Factors Amongst Women with MINOCA
Authors: Anais Hausvater, Tanya Spruill, Ki Park, Nathaniel Smilowitz, Binita Shah, Kevin Marzo, Nisha Jhalani, Caitlin Giesler, Laxmi S Mehta, Bina Ahmed, C Noel Bairey Merz, Dwithiya Thomas, Jeff Trost, Puja Mehta, Bryan Har, Kevin R Bainey, Yuhe Xia, Hua Zhong, Ellen Hada, Judith S Hochman, Harmony Reynolds
Journal: Circulation (2021)

Introduction: Women are particularly vulnerable to high stress and depression after myocardial infarction (MI), and both are associated with increased post-MI mortality. MI with non-obstructive coronary arteries (MINOCA) disproportionately affects women. Little is known about the degree to which stress and depression levels around the time of MI relate to the type of MI in women. We aimed to determine whether psychosocial factors differ between women with MINOCA and those with MI and obstructive CAD (MI-CAD). Methods: Women with MI enrolled in a multicenter study completed baseline measures of perceived stress (Perceived Stress Scale [PSS-4]), depressive symptoms (Patient Health Questionnaire [PHQ-2]), major life stressors (life events checklist [LEC]) and psychological resilience (Brief Resilience Scale [BRS]) at the time of hospitalization for acute MI. PSS-4 and PHQ-2 were repeated at 2-months post-MI. Psychosocial measures were compared between patients with MINOCA and those with MI-CAD at baseline and 2-month follow-up using t-test and chi-square. Results: This study compared 172 MINOCA patients and 314 MI-CAD patients. Women with MINOCA were younger (59.4±12.5 vs 64.2±12.9 years, p&lt;0.001) and less likely to be non-Hispanic white (52.3% vs 64.3%, p=0.004). Women with MINOCA were less likely to have high stress (PSS-4 ≥6) at the time of MI (51.0% vs 63.0% vs, p=0.021) and at 2-months post-MI (32.5% vs 46.3%, p=0.019) compared to women with MI-CAD. There was no difference in the proportion with depressive symptoms (PHQ-2 ≥2) at the time of MI (36.2% MINOCA vs 42.7% MI-CAD, p=0.23) or at 2-months post-MI (39.0% vs 39.5%, P&gt;0.99). MINOCA patients reported fewer major life stressors than MI-CAD patients (LEC 2.67±1.93 vs 3.13±1.80, p=0.015). The frequency of low psychological resilience (BRS&lt;18) (24.3% vs 21.6%, p=0.60) did not differ between MINOCA and MI-CAD patients. Conclusions: Stress and depression are common among women at the time of, and 2-months post-MI. MINOCA patients reported lower stress levels at the time of and following MI compared to MI-CAD patients and fewer traumatic life events, but depressive symptoms and resilience did not differ by MI type.
Abstract 6937: Atrial Fibrillation in Breast Cancer Patients: Incidence, Prevalence, Risk Factors, and Mortality: Longitudinal Seer-Medicare Analysis
Authors: Avirup Guha, Michael Fradley, Susan F Dent, Neal L Weintraub, Maryam Lustberg, Alvaro Alonso, Daniel Addison
Journal: Circulation (2021)

Background: The national incidence, risk factor, and associated mortality of atrial fibrillation (AF) in early or advanced breast cancer patients are unknown. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified females, ≥ 66-year-old, with a new primary diagnosis of breast cancer from 2007 through 2014. These patients were individually matched 1:1 to Medicare enrollees without cancer, and each pair was followed for one year to identify a primary outcome of AF. Cumulative incidence rates were calculated using competing risk survival statistics. Following this, risk factor analysis was conducted using the adjusted Cox proportional hazards model. Finally, Kaplan-Meier methods and adjusted Cox proportional hazards modeling were performed to estimate mortality in breast cancer patients with incident and AF prior to breast cancer diagnosis. Results: This study included 85,423 breast cancer patients. Among these 9,425 (11.0%) had AF diagnosis prior to the breast cancer diagnosis. New AF was diagnosed in 2,993 (3.9%) patients in a 1-year period after the breast cancer diagnosis [incidence rate = 3.3% (95% CI = 3.0% - 3.5%) at 1-year; highest rate in the first two months (0.6%/month)]. The population standardized AF incidence was higher in Black compared to White females (58.8 vs. 49.9 per 1000 person-years in 2014, respectively). Apart from traditional demographic and cardiovascular risk factors, breast cancer stage was strongly associated with development of AF [AJCC Stage II vs. I: adjusted HR (aHR)= 1.51 (95% CI= 1.37 - 1.65); AJCC Stage III vs. I: aHR= 2.63 (95% CI= 2.35 - 2.94); AJCC Stage IV vs. I: aHR= 4.21 (95% CI= 4.04 - 5.48)]. New onset AF after breast cancer diagnosis [aHR = 3.51 (95% CI = 1.69 - 7.32)] and AF prior to breast cancer diagnosis [aHR = 1.70 (95% CI = 1.26 - 2.29)] was associated with increased 1-year- cardiovascular mortality. Conclusion: AF incidence is significantly higher in women after a breast cancer diagnosis. Apart from traditional risk factors, higher breast cancer stages at diagnosis are significantly associated with a higher risk of AF. New or prior AF in the setting of new breast cancer increases 1-year cardiovascular mortality.
Phase I Study of PHE885, a Fully Human BCMA-Directed CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma Manufactured in &amp;lt;2 Days Using the T-Charge TM Platform
Authors: Adam S. Sperling, Sarah Nikiforow, Omar Nadeem, Clifton C Mo, Jacob P. Laubach, Kenneth C. Anderson, Alejandro Alonso, Shuntaro Ikegawa, Rao Prabhala, Diego Hernandez Rodriguez, Heather Daley, Kit L. Shaw, Yohei Arihara, Soudeh Ansari, David S Quinn, David Pearson, Anniesha Hack, Louise M Treanor, Dexiu Bu, Jennifer Mataraza, Lawrence Rispoli, Marc Credi, Jerome Ritz, Serena De Vita, Nikhil C. Munshi
Journal: Blood (2021)
Abstract 11705: Comparing Healthcare Utilization and Health Outcomes of Infective Endocarditis Between People Experiencing Homelessness and People With Secure Housing
Authors: Christopher Lynch, Rie Sakai-Bizmark
Journal: Circulation (2021)

Introduction: Infective endocarditis (IE) is uniformly fatal if left untreated. Lower socioeconomic status has been shown to increase risk for community-acquired bacteremia, leading to possible IE. People experiencing homelessness (PEH) face risk factors for IE, such as inadequate access to personal hygiene, lack of consistent resting places to prevent skin breakdown, substance use, and inadequately treated comorbidities. This study seeks to compare characteristics of health utilization and outcomes for PEH hospitalized for IE with people with secure housing (PSH). Hypothesis: Mortality rate and healthcare utilization due to IE are higher for PEH compared to PSH. Methods: We used New York Statewide Inpatient Database between 2009 and 2014 to identify patients over 18 years of age admitted with the diagnosis of IE. With homelessness as the exposure variable, outcomes included 1] hospitalization cost per day, 2] length of stay (LOS), and 3] in-hospital mortality. Multivariate regression models, adjusted by patient characteristics, were used to explore the associations between homelessness and outcomes. Results: We identified 809,491 IE hospitalizations (25,968 homeless and 783,523 non-homeless). PEH were significantly more likely to be white (16.9% in PEH and 62.6% in PSH, p&lt; .001). Homelessness was significantly associated with lower odds of in-hospital mortality (adjusted Odds Ratio [aOR] 0.88, p &lt; .001), lower means ratio of cost (Means Ratio 0.99, p &lt; .001), longer LOS (Incidence Rate Ratio=1.03, p &lt; .001), and increased risk for readmission within 30 days of hospital discharge (aOR 1.1, p&lt;.01). Conclusions: The lower risk of hospital mortality for IE amongst PEH is unexpected given the higher burden of comorbidities and risk factors in this vulnerable group. It is possible that a significant proportion of PEH are dying outside hospital walls due to barriers in connecting with medical care. Lower hospitalization cost per day along with longer LOS could also reflect the time intensive but lower cost services required for complex discharge planning efforts for PEH. These results quantify and highlight the need for further study to understand overall mortality in PEH along with effective discharge planning strategies that address these disparities.