tbuckley/cabot-search huggingface dataset:
Abstract 6977: Thrombi Located at the Apex of Left Atrial Appendage Tend to Disappear in Patients with Atrial Fibrillation
Authors: Miho Sugitani, Takanao Mine, Masaharu Ishihara
Journal: Circulation (2021)

Background: Catheter ablation (CA) for atrial fibrillation (AF), or left atrial appendage (LAA) occlusion device to prevent stroke are contraindicated in patients with left atrial appendage thrombus (LAAT), and LAAT is required to disappear. However, LAAT do not disappear in some people, and the predictors for LAAT disappearance remains unclear. Methods: We retrospectively studied 65 LAAT patients taking anticoagulants out of 1381 consecutive patients who underwent transthoracic echocardiography (TEE) prior to cardioversion or CA for AF. Patients with significant valvular disease and coagulation disorder were excluded. Clinical data were evaluated at the time of TEE. The LAA was divided into three parts (the apex, middle and base), and the position of the LAAT were classified by three independent observers, and the size, shape and movability of LAAT were also evaluated. Results: Forty-six of 65 LAAT patients underwent re-TEE during follow-up (6.4±14.4 months), and LAAT disappeared in 20 out of 46 patients. Patients with disappearance of LAAT had LAAT located at the apex of LAA (apex: 16/24, 67%, middle: 2/10, 20%, base 2/12, 17%, p=0.0041), shorter left atrial dimension (LAD) (46.1±5.4 vs. 50.2±5.5 mm, p=0.0264) and longer period to re-TEE (9.6±20.5 vs. 4.0±6.4 months, p=0.0046). On multivariate analysis, LAAT located at the apex of LAA (p=0.0057, OR 6.9844833, 95%CI 1.6144805-30.215916) and smaller LAD (p=0.07614, OR 3.1453251 for each 10 mm decrease in LAD, 95%CI 0.8785845-0.988234) were associated with disappearance of LAAT. Disappearance rate of LAAT in patients with LAAT located at the apex of LAA and small LAD (&lt;48mm) was 82% (9/11) [Figure]. Conclusion: Thrombi located at the apex of LAA might be easy to disappear in patients with atrial fibrillation.
Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES
Authors: Shanjie Wang, Ye Wang, Xin Wan, Junchen Guo, Yiying Zhang, Maoyi Tian, Shaohong Fang, Bo Yu
Journal: Diabetes Care (2021)

OBJECTIVE Despite that periodical monitoring of cobalamin (vitamin B12) in metformin-treated patients with diabetes is recommended, cobalamin-associated mortality benefits or risks remain unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in adults with diabetes using metformin or not. RESEARCH DESIGN AND METHODS This study included 3,277 adults with type 2 diabetes from the National Health and Nutrition Examination Survey (NHANES) and followed up until 31 December 2015. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk. RESULTS Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin or intake of foods or cobalamin supplements, regardless of metformin treatment (each P ≥ 0.120). The doubling of methylmalonic acid (MMA), a cobalamin-deficiency marker, was significantly associated with higher all-cause (HR 1.31 [95% CI 1.18–1.45], P &amp;lt; 0.001) and cardiac (HR 1.38 [95% CI 1.14–1.67], P = 0.001) mortality. Cobalamin sensitivity was assessed by the combination of binary B12low/high and MMAlow/high (cutoff values: cobalamin 400 pg/mL, MMA 250 nmol/L). Patients with decreased cobalamin sensitivity (MMAhighB12high) had the highest mortality risk. The multivariable-adjusted HRs (95% CIs) of all-cause mortality in MMAlowB12low, MMAlowB12high, MMAhighB12low, and MMAhighB12high groups were 1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers. CONCLUSIONS Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.
Existence of a differentiation blockage at the stage of a megakaryocyte precursor in the thrombocytopenia and absent radii (TAR) syndrome
Authors: Rémi Letestu, Natacha Vitrat, Aline Massé, Jean-Pierre Le Couedic, Vladimir Lazar, Philippe Rameau, Françoise Wendling, Jacqueline Vuillier, Patrick Boutard, Emmanuel Plouvier, Mireille Plasse, Rémi Favier, William Vainchenker, Najet Debili
Journal: Blood (2000)
Abstract 12210: Long-Term Efficacy and Safety of ARRY-371797 (PF-0765803) in an Open-Label Rollover Study in Patients With Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
Authors: Daniel P Judge, Neal K Lakdawala, Matthew R Taylor, Luisa Mestroni, Huihua Li, Colleen Oliver, Franca S Angeli, Patrice A Lee, Calum Macrae
Journal: Circulation (2021)

Introduction: Dilated cardiomyopathy due to LMNA gene mutations ( LMNA -DCM) accounts for ~6% of DCM cases and is a life-threatening condition with a high unmet need. No disease-specific treatment targeting the underlying mechanism of disease is currently available. ARRY-371797 (PF-0765803), a potent, selective, oral, small-molecule inhibitor of the p38α MAPK pathway, improved exercise capacity (6MWT) in symptomatic LMNA -DCM patients (n=12) in a 48-week, open-label, Phase 2 study. Methods: This was an open-label rollover study of the long-term safety and efficacy of ARRY-371797 in symptomatic LMNA -DCM patients previously participating in the Phase 2 parent study, with eligible patients continuing on the same dose. Safety and efficacy assessments (6MWT, NT-proBNP, and KCCQ) were performed at Weeks 48, 72, 96, 120, and 144 from treatment initiation in the parent study. Results: Eight patients were enrolled (mean [SD] age, 51 [10] years; 4 males). There was a &gt;30 m mean improvement and &gt;10% mean increase in 6MWT distance from parent study baseline up to Week 120 ( Table ), with 3 patients (37.5%) having ≥10% improvement from baseline to Week 144. The decrease in mean NT-proBNP concentration in the parent study was maintained ( Table ). KCCQ Physical Limitation score increased at all visits except Week 48. Changes in KCCQ Clinical Summary and Overall Summary scores were variable. Treatment was generally well tolerated: 3 patients discontinued due to causes not considered treatment-related (UTI and nausea, CRT-D, and LVAD implantation); 2 experienced Grade 1 adverse events considered treatment-related. There were no deaths. Conclusions: ARRY-371797 was generally well tolerated, with evidence suggesting preserved exercise capacity over &gt;2 years’ follow-up. Efficacy and safety of ARRY-371797 is being investigated in the REALM-DCM trial, an ongoing, pivotal, Phase 3, randomized, placebo-controlled study in LMNA -DCM.
Abstract 11883: Mineral Metabolism Predictors of Poor Outcomes in Stable Coronary Artery Disease With and Without Impaired Renal Function
Authors: Alvaro Acena, Marta Lopez-Castillo, Ana M Pello, Juan Martinez-milla, Hans P Gaebelt, Carlos Gutierrez Landaluce, Carmen Cristobal, Nieves Tarin, Ana Huelmos, Maria L Gonzalez Casaus, oscar lorenzo, Ester Canovas, Andrea Kallmeyer, Joaquin Alonso, Jose tunon
Journal: Circulation (2021)

Background: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts with SCAD has not been shown yet. Our aim is to assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. Methods: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D3], and fibroblast growth factor-23 [FGF-23]) in 964 pts. with SCAD and eGFR&lt;60 ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60 ml/min/1.73 m2 (HGFR) included in five hospitals of Spain. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results: There were 790 pts. with HGFR and 174 with LGFR. Median follow-up was 5.1 years. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR= 0.023 (0.94-0.99) p=0.023], FGF23 [HR= 1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR= 1.01 (1.00-1.01) p=0.026] and high sensitivity troponin [HR= 5.12 (1.67-15.59) p= 0.004], along with age [HR= 1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR= 1.13 (1.07-2.79) p=0.027], dihydropyridines [HR= 1.71 (1.05-2.77) p= 0.032], verapamil [HR= 5.71 (1.35-24.1) p= 0.018], and Proton-pump inhibitors [HR= 2.23 (1.36-3.68) p= 0.002]. In the LGFR subgroup, predictors of death or ischemic events were PTH plasma levels, [HR=1.01 (1.00-1.01) p=0.005], the eGFR [HR=0.96 (0.94-0.99) p=0.004], age [HR=1.06 (1.02-1.10) p=0.003], caucasian race [HR=0.04 (0.004-0.380) p=0.005], and treatment with insulin [HR=2.6 (1.20-5.63) p=0.015]. Conclusions: In pts. with SCAD, PTH is an independent predictor of poor outcomes only in those with eGFR&lt;60 ml/min/1.73 m2 , while in pts. with eGFR≥60 ml/min/1.73 m2 calcidiol and FGF-23 become the only components of MM that may predict prognosis. Then, renal function influences the predictive power of MM markers in pts. with SCAD.
Abstract 11393: Lipidomics Profiling and Risk for Cardiovascular Disease: A Longitudinal Study in American Indians
Authors: Wenjie Zeng, Guanhong Miao, Mingjing Chen, Ying Zhang, Jason G Umans, Shelley A Cole, Elisa T Lee, Barbara Howard, Oliver Fiehn, Jinying Zhao
Journal: Circulation (2021)

Background: Dyslipidemia is an established risk factor for CVD. Standard lipid panel lacks description of the full spectrum of blood lipids. A longitudinal profiling of blood lipidome in relation to the risk of CVD is lacking in any racial/ethnic groups. Objective: Identify novel lipid species associated with risk of CVD in American Indians, independent of traditional risk factors (TRFs). Method: Using untargeted LC-MS, we repeatedly measured 1,542 lipid species in 3,916 fasting plasma samples from 1,958 participants who attended two exams (~5.5 years apart) and were followed up to 18 years in the Strong Heart Study. Elastic net was used to select baseline lipids and change in lipids (baseline to 5-year follow-up) associated with 18-year risk of CVD. Multivariate and network analyses were conducted to identify discriminatory lipidomic signatures and differential lipid networks associated with risk of CVD. Results: Of 1,911 participants free of CVD at both baseline (2001-2003) and 5-year follow-up (2006-2009), 222 developed CVD after 18 years of follow-up. High-resolution LC-MS detected 1,542 lipid species (518 known). After adjusting for TRFs (age, sex, center, smoking, BMI, hypertension, diabetes, LDL-c, and albuminuria), elevated baseline levels of 21 known lipids, including cholesterol esters, sphingolipids, glycerophospholipids, and fatty acids, were significantly associated with increased (HR: 1.08 to 1.26) or decreased (HR: 0.81 to 0.91) risk of CVD. Longitudinal change in 13 lipids, including cholesterol esters, sphingolipids, glycerophospholipids, and fatty acids, were either positively (HR: 1.03 to 1.28) or inversely (HR: 0.75 to 0.92) associated with risk of CVD at 18-year follow-up. A lipid score comprising 10 baseline lipids significantly improved risk prediction beyond TRFs (ROC increases from 0.823 to 0.837, P = 0.009). Multivariate and network analyses identified distinct lipidomic signatures and lipid networks associated with risk of CVD. Conclusion: Novel molecular lipids significantly predict risk of CVD beyond TRFs in American Indians. Our findings provide novel lipid molecules for risk stratification and shed light on the mechanism linking lipid dysregulation to CVD in American Indians.
Abstract 11515: Noninvasive Quantitation of Coronary Collateral Flow Capacity in Patients with Chronic Total Occlusion Treated with External Counter Pulsation: Dobutamine Compared with Vasodilator Stress Pet Identifies Collaterogenesis
Authors: Michael E Merhige, Cory Davis, Julia Keppler, Connor Knapp, Kevin Wilson
Journal: Circulation (2021)

Introduction: FDA approved external counterpulsation (ECP) improves coronary collateral flow index measured invasively, using intracoronary wedge pressure beyond a severe stenosis. However, there is presently no noninvasive method to measure coronary collateral flow capacity (CCFC), in patients with total coronary occlusion (CTO). Hypothesis: CCFC can be measured noninvasively by comparing the improvement in flow in the ischemic bed beyond CTO, using dobutamine stress (DBT), which supports supply side pressure, compared with vasodilator stress (DIP), which lowers supply side pressure, causing coronary steal. Methods: Seven patients with CTO were treated with 35 sessions of ECP, and studied with both DIP and DOB stress PET myocardial perfusion imaging. Coronary flow capacity (CFC), which integrates absolute rest and stress flow with coronary flow reserve on a per pixel basis, was measured objectively with FDA approved HeartSee software. Results: As shown in the Table, all patients demonstrated a decrease in the size of the ischemic zone at risk, defined as moderate or severely reduced CFC, when CFC with DIP was compared with DOB: 28% LV mass vs. 5%; p &amp;lt 0.01. Five of 7 patients also demonstrated significant improvement in global CFC by Kolmogorov-Smirnoff analysis. Absolute stress flow into the ischemic zone improved significantly in all ECP treated patients during demand ischemia compared with vasodilator stress (1.9 vs. 1 ml/min/g; p &amp;lt 0.01). One of the two patients who did not improve global CFC, despite ECP treatment, underwent coronary arteriography demonstrating a new flow limiting stenosis in the supply side vessel, which was successfully stented. Conclusion: ECP treatment is associated with improved coronary collateralization in patients with CTO, which can be identified noninvasively with quantitative PET myocardial perfusion imaging.
RADT-17. FOCUSED ULTRASOUND MEDIATED BLOOD–BRAIN BARRIER OPENING IS SAFE AND FEASIBLE CONCURRENT WITH AND ADJUVANT TO A CLINICAL RADIATION SCHEME FOR BRAINSTEM DMG
Authors: Masih Tazhibi, Nicholas McQuillan, Hong-Jian Wei, Antonios Pouliopoulos, Ethan Bendau, Zachary Englander, Andrea Webster, Nina Yoh, Stergios Zacharoulis, Elisa Konofagou, Cheng-Chia Wu
Journal: Neuro-Oncology (2021)

Abstract Diffuse midline gliomas (DMG) are pediatric tumors with dismal prognosis. When these tumors emerge in the brainstem, there exists no feasible method of surgical resection or systemic intervention, making ionizing radiation the sole therapeutic avenue to date. However, radiotherapy (RT) provides only marginal survival benefit as the topographically diffuse and highly infiltrative tumors spread in areas in which the blood-brain barrier (BBB) is relatively intact. Focused ultrasound (FUS) with intravenous microbubbles provides a compelling solution, transiently and non-invasively opening the BBB to allow drug delivery across the cerebrovasculature. Nonetheless, it remains unclear whether FUS can be safely administered at the brainstem in patients receiving RT. Therefore, the goal of this study was to assess the safety and feasibility of FUS administered concurrent with and adjuvant to a clinical hypofractionated radiation scheme for brainstem DMG. Non-tumor bearing B6 albino mice were randomly assorted into control, RT, FUS, and RT+FUS groups. Mice designated RT+FUS received 39Gy/13fx (hypofractionated RT scheme) to the brainstem with two sessions of FUS approximately 1 week apart. A single-element, spherical-segment FUS transducer driven by a function generator through a power amplifier was used with concomitant microbubble injection to sonicate the brainstem. Magnetic resonance imaging (MRI) was used to confirm BBB opening and cardiopulmonary measures were recorded throughout sonication. Vitals were assessed daily, and all treatment animals underwent Kondziela inverted screen testing and sequential weight lifting to assess brainstem-related strength and motor coordination deficits. In both FUS and RT+FUS mice, MRI confirmed brainstem BBB opening and subsequent closure within 96 hours. Mouse weights were stable, with slight drops (mean=5.5%) following FUS that resolved within three days. No attenuation in cardiorespiratory, strength, and motor coordination measurements was observed from FUS. FUS is a safe and feasible technique for brainstem BBB opening concurrent with and adjuvant to clinical hypofractionated RT.
Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains
Authors: Baoling Ying, Bradley Whitener, Laura A. VanBlargan, Ahmed O. Hassan, Swathi Shrihari, Chieh-Yu Liang, Courtney E. Karl, Samantha Mackin, Rita E. Chen, Natasha M. Kafai, Samuel H. Wilks, Derek J. Smith, Juan Manuel Carreño, Gagandeep Singh, Florian Krammer, Andrea Carfi, Sayda M. Elbashir, Darin K. Edwards, Larissa B. Thackray, Michael S. Diamond
Journal: Science Translational Medicine (2022)

Although mRNA vaccines encoding the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevent COVID-19, the emergence of new viral variants jeopardizes their efficacy. Here, we assessed the immunogenicity and protective activity of historical (mRNA-1273, designed for Wuhan-1 spike protein) or modified (mRNA-1273.351, designed for B.1.351 spike protein) Moderna mRNA vaccines in 129S2 and K18-hACE2 mice. Mice were immunized with either high-dose or low-dose formulations of the mRNA vaccines, where low-dose vaccination modeled suboptimal immune responses. Immunization with formulations at either dose induced neutralizing antibodies in serum against ancestral SARS-CoV-2 WA1/2020 and several virus variants, although serum titers were lower against the B.1.617.2 (Delta) virus. Protection against weight loss and lung pathology was observed with all high-dose vaccines against all viruses. However, low-dose formulations of the vaccines, which produced lower magnitude antibody and T cell responses, showed breakthrough lung infections with B.1.617.2 and development of pneumonia in K18-hACE2 mice. Thus, in individuals with reduced immunity after mRNA vaccination, breakthrough infection and disease may occur with some SARS-CoV-2 variants.
QOLP-33. EVIDENCE OF FINANCIAL TOXICITY IN PRIMARY CENTRAL NERVOUS SYSTEM TUMOR PATIENTS: CORRELATIONS BETWEEN EMPLOYMENT STATUS, SYMPTOM BURDEN AND HEALTH-RELATED QUALITY OF LIFE
Authors: Alexa Christ, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Anna Choi, Ewa Grajkowska, Varna Jammula, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Valentina Pillai, Lily Polskin, Brett Theeler, Jing Wu, Mark Gilbert, Terri Armstrong, Heather Leeper
Journal: Neuro-Oncology (2021)

Abstract SIGNIFICANCE AND AIMS Financial toxicity (FT) after a cancer diagnosis is the consequence of decreased earnings and increased spending. In patients with primary central nervous system (PCNS) tumors, the correlation between FT and factors such as symptom burden, psychological distress, and health-related quality of life has not been extensively studied. We assessed employment status and several patient illness factors in a PCNS tumor cohort. METHODS Patient and disease characteristics and patient-reported outcomes (PROs) were collected from adults diagnosed with PCNS tumors between 9/2016-12/2019. Descriptive statistics and regression analyses were used to describe PROs. RESULTS Of 277 patients, 77 (28%) reported being unemployed due to tumor diagnosis. They reported difficulty walking (64%) and performing usual activities (64%). This group had lower general health status (p&amp;lt; 0.001) and higher tumor-related symptom severity (p=0.004) than employed patients. Unemployed patients reported high symptom burden with an average of 6 moderate-severe symptoms for those with brain tumors and 10 for those with spine tumors. Both brain and spine tumor patients who were unemployed reported increased mood-related interference (p=0.020), as well as moderate-severe anxiety (30%) and depression (25%) compared to employed patients (15% vs 8%, respectively). Unemployed brain tumor patients reported worse scores in cognitive and neurologic symptom subscales (p&amp;lt; 0.001). CONCLUSIONS AND IMPLICATIONS These data provide indirect evidence that financial toxicity that correlates with high symptom burden across several domains and lower health-related quality of life. Future research work will include the COST questionnaire to further evaluate the implications of FT in the PCNS tumor patient population.
Recent Evidence Supporting Psychologic and Social Risk Factors for Coronary Disease
Authors: C. David Jenkins
Journal: New England Journal of Medicine (1976)

Past epidemiologic studies of coronary disease have shown such variables as elevated blood pressure, elevated serum cholesterol, cigarette smoking, obesity, diabetes and family history of coronary disease to be factors predictive of elevated risk of incidence of this disease in groups and in individuals. Enthusiasm over these positive results should not obscure the fact that these risk factors, taken together, provide an incomplete estimate of the coronary-disease burden of a population and an insensitive prediction of the risks of individuals.Keys and his colleagues1 applied multiple logistic riskfactor equations derived in Framingham to European data and then reversed the process, . . .
Abstract 13344: Racial Differences in Baseline Characteristics Among Adult Women Presenting With ST Elevation Myocardial Infarction
Authors: Sriviji Senthil Kumaran, Juan Del Cid Fratti, Anjali R Desai, Sudhir Mungee, Ekanka Mukhopadhyay, Tinoy J Kizhakekuttu
Journal: Circulation (2021)

Background: Race related differences in baseline characteristics among women presenting with ST Elevation Myocardial Infraction (STEMI) has not been well studied. Methods: We used the National inpatient sample database to identify women who were admitted with STEMI as the primary diagnosis from 2016 to 2018. We evaluated the differences in comorbid conditions among different races - Caucasians, African Americans, Hispanics, Asian and other minority races including native Americans. Results: Of 208,223 female patients with STEMI, 75.7% were Caucasians, 11.3% African American, 7.4% Hispanic, 2.4% Asian, and 4.3% other races. African Americans had the highest percentage of obesity (23%), Obstructive Sleep Apnea (6%) and Tobacco use. Overall, Diabetes mellitus was more common among the racial minorities with the highest among Hispanics (52.3%) followed by Asians (47.8%) and then African Americans (41.2%). All racial minorities had higher incidence of Chronic kidney disease (CKD) when compared to Caucasians. Despite similar prevalence of Coronary artery disease, Asians had lower rates of prior revascularization procedures compared to other subgroups. Conclusion: The differences in prevalence of the various comorbidities among racial subgroups is crucial to note. This will determine outcomes in these patients. CKD is a key association that plays an important role in the pathogenesis of multiple cardiac diseases, including STEMI. Our study underscores the increased prevalence of CKD among racial minorities. Our findings will help guide the management of these populations and make long term management more patient centered.