tbuckley/cabot-search huggingface dataset:
Coffee Consumption and Risk of Adverse Outcomes
Authors: Paolo Palatini
Journal: JAMA Internal Medicine (2021)

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Abstract 9722: P53-phlda3 Signaling Induced by Carbon-Ion Irradiation is a Novel Therapeutic Target to Suppress Cardiac Hypertrophy in Mice
Authors: Nozomi Furukawa, Naoko Okano, Yukari Yoshida, Takashi Shimokawa, Akinori Kanai, Tatsuya Ohno, Norimichi Koitabashi
Journal: Circulation (2021)

Background: Irradiation to the heart increases the risk of several cardiac disease including coronary artery disease, heart failure, pericardial disease and cardiac arrythmia, therefore, the heart has been considered one of the organs at risk in thoracic irradiation. On the other hand, recent experimental studies suggested irradiation may ameliorate cardiac injury and arrhythmia after myocardial infarction. To test irradiation effects on pathological cardiac remodeling, we examine the effects from irradiation in a mouse model of heart failure. Methods and Results: We used cardiac hypertrophy and heart failure mice model induced by transverse aortic constriction (TAC), irradiated by X-ray (20, 30 Gy) or carbon-ion beam (10, 30 Gy) at 2 weeks after pressure overload, and examined the changes in cardiac function by echocardiography. Concerning to the X-ray, 1 week after irradiation, ventricular systolic dysfunction induced by TAC was attenuated compared with control group. Among the X-irradiated groups, the higher dose improved cardiac function better. However, at 2 weeks post-irradiation, the cardiac function decreased again. On the other hand, carbon-ion irradiation improved left ventricular function and cardiac hypertrophy even at 2 weeks post-irradiation. The BNP expression was increased in TAC-treated mice and markedly decreased in irradiated mice, suggesting improvement of cardiac hypertrophy and cardiac remodeling. Cardiac p53 phosphorylation is markedly induced by cardiac irradiation. RNA sequencing using irradiated heart revealed pleckstrin homology-like domain family A, member 3 (PHILDA3), a downstream of p53 was significantly upregulated after X-ray or carbon-ion irradiation. PHLDA3 was decreased by TAC treatment, but improved especially in 30 Gy carbon-ion irradiation group. Akt phosphorylation, a hypertrophic signal and downstream target of PHLDA3, was suppressed by irradiation after TAC. Conclusion: Irradiation, especially with carbon-ion beam, brought a beneficial effect on pathological cardiac remodeling. Irradiation induced p53-PHLDA3-Akt signaling might be novel therapeutic target in the pathogenesis of heart failure.
Subgroup analysis of patients with metastatic colorectal cancer (mCRC) treated with regorafenib (REG) in the CORRECT trial who had progression-free survival (PFS) longer than 4 months.
Authors: Axel Grothey, Alfredo Falcone, Yves Humblet, Olivier Bouche, Laurent Mineur, Antoine Adenis, Josep Tabernero, Takayuki Yoshino, Heinz-Josef Lenz, Richard M. Goldberg, Lei Xu, Andrea Wagner, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2015)

710 Background: In the CORRECT phase III trial (NCT01103323), the multikinase inhibitor REG significantly improved overall survival (OS) and PFS vs placebo in patients with mCRC who had disease progression after other standard therapies (HR for OS: 0.77; 1-sided p =0.0052; Grothey 2013). A post-hoc exploratory subgroup analysis was conducted to evaluate patients in the REG treatment group who had a PFS longer than 4 months (long-PFS) defined as patients who progressed, died, or discontinued treatment for other reasons after 4 months. Methods: Of the505 patients randomized to REG in CORRECT, 98 (19.4%) were classified as having a long-PFS benefit. Baseline characteristics, safety, and dosing parameters were analyzed descriptively. Results: The long-PFS subpopulation was representative of the overall study population (Table). Long-PFS patients received a median of 6 cycles of REG (1-12), 92% received ≥5 cycles, and 20% had &gt; 8 cycles. Overall 34% of patients had dose reductions and 87% had dose interruptions. The actual mean daily dose was 139 mg and the mean percent of the planned dose was 81%. Adverse events (AE) of any grade were experienced by all long-PFS patients, and the most common grade ≥3 AEs were hand-foot skin reaction (20%), hypertension (17%), diarrhea (17%), and fatigue (16%). Conclusions: A subset of 98 (19.4%) patients treated with REG in the CORRECT study had a PFS &gt; 4 months, confirming the clinical benefit and tolerability of REG as a treatment option for patients with mCRC. Prospective validation of these findings in conjunction with biomarker analysis from real-life clinical experience is needed. Clinical trial information: NCT01103323. [Table: see text]
NIMG-42. MP-MRI-BASED TUMOR PROBABILITY MAPS TRAINED USING AUTOPSY TISSUE SAMPLES AS GROUND TRUTH NON-INVASIVELY PREDICT INFILTRATIVE TUMOR BEYOND THE CONTRAST ENHANCING REGION
Authors: Samuel Bobholz, Allison Lowman, Michael Brehler, John Sherman, Savannah Duenweg, Fitzgerald Kyereme, Jennifer Connelly, Elizabeth Cochran, Wade Mueller, Anjishnu Banerjee, Peter LaViolette
Journal: Neuro-Oncology (2021)

Abstract Infiltrative glioma beyond contrast enhancement on MRI is often difficult to identify with conventional imaging. In this study, we use large-format autopsy samples aligned to multi-parametric MRI to test the hypothesis that radio-pathomic machine learning models are able to accurately identify areas of infiltrative tumor beyond the contrast enhancing region. At autopsy, 140 tissue samples from 62 brain cancer patients were collected from brain slices sectioned to align with the patients’ last clinical MRI prior to death. Cell, extra-cellular fluid (ECF), and cytoplasm densities were computed from digitized, hematoxylin and eosin-stained samples, and a subset of 20 slides from 9 patients were annotated for tumor presence by a pathologist-trained technician. In-house custom software was used to align the tissue samples to the patients’ last clinical imaging, which included pre- and post-contrast T1, FLAIR, and ADC images. Bagging random forest models were then trained to predict cellularity, ECF, and cytoplasm density using 5-by-5 voxel tiles from each MRI as input. A 2/3-1/3 train-test split was used to validate model generalizability. A naïve Bayes classifier was trained to predict tumor class using cellularity, ECF, and cytoplasm segmentations within the annotation data set, again using a 2/3-1/3 train-test split to validate performance. The random forest models each accurately predicted cellularity, ECF, and cytoplasm density within the test data set, with root-mean-squared error values for each falling within one standard deviation of the ground truth. The histology-based tumor prediction model accurately predicted tumor, with a test set ROC AUC of 0.86. When using whole brain cellularity, ECF, and cytoplasm predictions from the random forest models as inputs for the naïve Bayes classifier, tumor probability maps identified regions of infiltrative tumor beyond contrast enhancement. Our results suggest that radio-pathomic maps of tumor probability accurately identify regions of infiltrative tumor beyond currently accepted MRI signatures.
Abstract 11682: Race, Sex, and Socioeconomic Disparities in Hospitalization With Ventricular Tachycardia or Cardiac Arrest in a National Medicare Cohort
Authors: Ryan T Kipp, Matthew Kalscheur, Ann Sheehy, Christie Bartels, Amy J Kind, Ryan Powell
Journal: Circulation (2021)

Introduction: Significant disparities by race, sex, and socioeconomic status exist in cardiovascular care. Yet little is known regarding the disparities in patients hospitalized with life-threatening arrhythmias. Hypothesis: We hypothesize that there are differences in race, sex, and socioeconomic status between patients who develop ventricular tachycardia (VT) or cardiac arrest (CA). Methods: Using the national 100% U.S. Medicare inpatient dataset of fee-for-service beneficiaries admitted with VT or CA from January 1, 2014 through November 30, 2014, multivariable logistic regression was constructed to examine the characteristics associated with hospitalization with VT compared to those with CA. Neighborhood-level socioeconomic disadvantage for each patient was measured by the Area Deprivation Index which reflects 17 dimensions related to education, income, housing, and employment factors. Results: Of 195,806 patients admitted with VT or CA, 117,930 (60%) were admitted with VT and 77,876 (40%) with CA. Those residing in the most disadvantaged neighborhoods had a significantly lower rate of hospitalization with VT, and a higher rate of hospitalization with CA (Figure 1). After adjustment for baseline demographics, comorbidities, and hospital characteristics, living in one of the top 20% most disadvantaged US neighborhoods (OR 1.09, 95% CI 1.05-1.12), female sex (OR 1.27, 95% CI 1.24-1.29), non-White race (OR 1.16, 95% CI 1.12-1.20), and non-urban residence (OR 1.10, 95% CI 1.06-1.14) were associated with greater odds of hospitalization with CA. Conclusion: Significant differences exist in the race, sex, and neighborhood socioeconomic characteristics for patients hospitalized with VT compared to those with CA. Possible etiologies for these differences include geographic or economic barriers in accessing acute medical care or trust in the medical system. Further studies are needed to investigate the drivers and solutions to this difference.
Abstract 12141: Echocardiographic Characteristics and Outcomes Between African American and Caucasians in Acute Pulmonary Embolism
Authors: Rafael S Cires-drouet, Jacob Sama, Paul Han, Taylor Miller, Lateaqua Alston, Rafael Cires-Drouet, Minerva Mayorga-Carlin, John Sorkin, Susie Hong, Gautam Ramani, Daniel Haase, Brajesh Lal, Bradley Taylor
Journal: Circulation (2021)

Introduction: Socio-economical differences and delayed medical care have been associated to a higher mortality in African American (AA) PE patients. Hypothesis: Peri-PE mortality is higher in AA than Caucasian (CC) patients in a single medical center. Methods: A 26 months retrospective review of AA and CC patients admitted with an acute PE. Results: A total of 303 AA and 343 CC were identified. African Americans were younger, had more females, diabetes, chronic kidney disease and smokers than CC. A history of recent surgery and trauma were more common in CC. (Table I) Both groups had similar clinical presentations, biomarkers, and radiologic characteristics (CTA); except for RV strain that was more common among AA. In the initial echocardiogram, LV function was similar in both groups, although, AA had more often an underfilled LV and an abnormal RV. (Table II) There was no difference in hospital mortality between AA (n=21[6.9%]) and CC (n=21[6.1%]), p=0.67. Among 107 (AA=54, CC=53) patients who received advanced therapies, the mortality was higher in AA (18.5% vs.3.8% p=0.01). In a logistic regression analysis, the risk of death was increased by age (OR 1.04; 95%CI 1.020-1.073) and the need of advanced therapies (OR 2.43; 95%CI 1.029-5.769). Although AA race (OR 1.77; 95%CI 0.862-3.647), BMI (OR 0.99; 95%CI 0.950-1.038), abnormal RV (OR 0.71; 95%CI 0.321-1.601) and abnormal LV function (OR 1.737; 95%CI 0.754-4.005) did not increase significantly the risk of death. Conclusion: Despite hemodynamic changes of the LV and RV appreciated in AA, there was no difference in overall mortality. The risk of death was increased by age and need for advanced therapies.
Abstract 12619: Macrophage-Dependent Interleukin-1 Beta Secretion (IL-1β) Induces Diabetic Diastolic Dysfunction
Authors: Hong Liu, Yimao Huang, Gyeoung-Jin Kang, Feng Feng, Deborah Dickey, Samuel C Dudley
Journal: Circulation (2021)

Introduction: Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD), the underlying pathological condition of heart failure with preserved ejection fraction (HFpEF). Nevertheless, the mechanism linking DM and DD is unclear. DM causes a low level inflammatory response, and we tested whether macrophage-dependent IL-1β secretion was the cause of DM-associated DD. Methods: Type II diabetic mice were induced by feeding 60% kcal high fat diet (HFD) for at least 20 weeks. Cardiac macrophage accumulation was assessed by flow cytometry. Diabetic mice were subjected to IL-1β suppressing treatment with IL-1 receptor antagonist (IL-1RA) or macrophage depletion by Clodronate liposome, and mouse cardiac diastolic function was evaluated by echocardiogram (E/E’). To determine the role of macrophage-dependent IL-1β in the DD development, fatty acid binding protein 4 knockout (FABP4 KO) mice were employed, and the secretory profile of isolated macrophages was examined by microarray and ELISA. The relation between IL-1β and the cardiac mitochondrial oxidative stress was investigated to explore the potential mechanism of IL-1β mediated DD. Results: Diabetic mice presented DD (E/E’, 19.6 ± 0.8 in control vs. 26.8 ± 0.8 in DM, p&lt;0.05), higher IL-1β level (3.7 ± 0.6 pg/ml in control vs. 9.1 ± 0.8 pg/ml in DM, p&lt;0.05), and increased macrophage accumulation in the hearts (F/80 + cells, 15.7 ± 0.8% in control vs. 19.6 ± 1.3% in DM, p&lt;0.05). DD was significantly ameliorated by suppressing IL-1β (E/E’, 22.2 ± 1.5, p&lt;0.05 vs. control) or depleting macrophages (E/E’, 15.8 ± 0.7, p&lt;0.05 vs control) in DM mice. Confirming the central role of macrophages and IL-1β, mice with fatty acid binding protein 4 knockout (FABP4 KO) were unable to secrete IL-1β and were resistant to diabetes-induced DD (E/E’, 17.2 ± 1.3 in KO+HFD vs. 22.1 ± 1.1 in wildtype+HFD, p&lt;0.05). IL-1β regulated the mitoROS generation in cardiomyocytes, and a mitochondrially targeted antioxidant (mitoTempo) prevent diabetic-associated DD (E/E’, 20.7 ± 1.6, p&lt;0.05 vs. control). Conclusions: DM-associated DD was mediated by macrophage-dependent IL-1β secretion. MitoROS provided a mechanistic link between macrophage secreted IL-1β and diabetic DD.
Abstract 13628: Cardiovascular Toxicity Associated With Vascular Endothelial Growth Factor Receptor Inhibitors Use in Oncology: A Network Meta-Analysis of Phase 3 Clinical Trials
Authors: saad ullah malik, Asad Ullah Malik, Ebubechukwu Ezeh, Yury Kachynski, Kemnasom Nwanwene, Esiemoghie Akhigbe, Mackenzie Hamilton, Ameer Quadri, Russell Nogot, Maria Tria Tirona, Ellen Thompson
Journal: Circulation (2021)

Introduction: Which vascular endothelial growth factor receptor inhibitor (VEGFRi) is less cardiotoxic compared to others in same class is not well known. We compared cardiovascular safety profile of all FDA approved VEGFi used as chemotherapy for cancers. Methods: We performed PRISMA compliant literature search on PubMed, Embase, Cochrane, Web of Science, Scopus and Clinicaltrials.gov (inception-6/12/2021). Only phase 3 RCTs were included. Primary outcomes were hypertension (HTN), myocardial infarction (MI), heart failure (HF), conduction abnormalities, dyspnea and pedal edema. Random-effects meta-analysis (MA) was conducted followed by frequentist network meta-analysis (NMA). Results were reported as RR with 95% CI and OR with 95% credible intervals (CrI). Quality and risk of bias assessment were done using GRADE and Cochrane risk of bias assessment tools respectively. Results: This analysis included 20426 patients from 32 RCTs. There was a very high risk of HTN associated with VEGFi compared to placebo (RR: 4.36, 95% CI:3.5-5.4, I2:69%, p-value:&lt;0.05). Among VEGFi, lenvatinib was associated with slightly higher risk of HTN (Figure 1). There was no difference between VEGFi and placebo in risk of MI (RR: 1.25, 95% CI:0.86-1.83, I2:0%, p-value:0.48), conduction abnormalities (RR: 2.49, 95% CI:0.54-11.58, I2:37%, p-value:0.19), HF (RR: 1.24, 95% CI:0.52-2.93, I2:40%, p-value:0.18), dyspnea (RR: 1.16, 95% CI:0.95-1.43, I2:27%, p-value:0.22) and pedal edema (RR: 3.1, 95% CI: 0.86-11.23, I2:70%, p-value:0.01). Same was true when VEGFi were compared (Figure 2). Risk of bias was low and studies were of moderate to high quality. Conclusions: VEGFi are associated with significantly higher risk of HTN compared to placebo. Among VEGFi, Lenvatinib is associated with slightly higher risk of HTN and there is no difference in risk of MI, HF, conduction abnormalities, dyspnea and pedal edema among VEGFi. Study is limited by heterogeneous patient population.
Ex Vivo Evaluation of the Effect of Plasma-Derived Factor VIII/Von Willebrand Factor in Patients with Severe Hemophilia_A on Prophylaxis with Emicizumab By Thrombin Generation Assay
Authors: Maria-Isabel Bravo, Aida Raventós, Alba Pérez, Elena G Arias-Salgado, María Teresa Alvarez Román, Nora V. Butta, Víctor Jiménez-Yuste, Montserrat Costa, Todd Willis
Journal: Blood (2021)
Abstract 14160: Trends in Racial and Ethnic Differences in Adiposity and Association With All-Cause Mortality in Adults in the United States: A 20-year National Health and Nutrition Examination Survey Analysis, 1999-2018
Authors: Yuan Lu, Yuntian Liu, Cesar Caraballo, Daisy Massey, Shiwani Mahajan, Jeph Herrin, Harlan M Krumholz
Journal: Circulation (2021)

Introduction: Reducing overall rates of and the racial/ethnic differences in obesity is a public health priority in the US. However, it is unknown how the racial/ethnic differences in different adiposity measures changed in the US population over recent decades Methods: Using data from the National Health and Nutrition Examination Survey 1999-2018, we determined trends in the racial/ethnic differences of several adiposity measures and whether race/ethnicity moderates the associations between these measures and all-cause mortality. Adiposity measures included overweight (body mass index [BMI] of 25.0-29.9 kg/m 2 ), overall obesity (BMI ≥30.0 kg/m 2 ), abdominal obesity (waist circumference [WC] ≥88 cm for women or ≥102 cm for men), and high body fat (body fat mass percentage [FM] ≥35% for women or ≥25% for men). Results: The study included 49,629 adults aged 18-79 years (mean age 45.3 [SD, 17.9] years, 51.3% women), of whom 12.5% were Black, 15.5% were Latino/Hispanic, and 72.0% were White. Between 1999 and 2018, Latino/Hispanic people had a higher prevalence of overweight, overall obesity, abdominal obesity, and high body fat than White people. The gaps between Latino/Hispanic and White people significantly increased for all adiposity measures (P&lt;0.01 for all measures) during this time. Black people had a higher prevalence of overweight, overall obesity, and abdominal obesity, but a similar prevalence of high body fat compared with White people. There were no significant changes in the gaps between Black and White people for any adiposity measures. For all adiposity measures, the associations between adiposity measures and mortality did not differ by race/ethnicity. Conclusions: Racial/ethnic differences in the prevalence of overweight, overall obesity, abdominal obesity, and high body fat persisted or increased over 20 years, with the differences increasing between Latinos/Hispanics and Whites and not changing between Blacks and Whites.
Abstract 11166: Can Claims Diagnoses Accurately Identify Heart Failure with Reduced and Preserved Ejection Fraction in Medicare Data?
Authors: Benjamin Bates, Ehimare Akhabue, Abhigyan Mukherjee, Meghan Nahass, Emily P Hiltner, Joanna Rock, Brandon Wilton, Chintan Dave, Soko Setoguchi
Journal: Circulation (2021)

Background: Medicare claims data have been widely used to describe the management and outcomes of patients with heart failure (HF). While the management of HFrEF vs HFpEF differs, the usefulness of ICD10 codes to differentiate HFrEF and HFpEF in Medicare data is not well characterized. Thus, we assessed if ICD10 codes can accurately identify HFrEF and HFpEF in Medicare data. Methods: Among 314,221 Medicare patients hospitalized for HF (defined as primary or secondary ICD10 I50.x) between 10/2015 and 12/2017, we randomly sampled 200 charts in a 1:1:2 ratio for systolic dysfunction (I50.2), diastolic dysfunction (I50.3), and other I50.x HF. Cardiology trained physicians extracted and adjudicated clinical information. We calculated positive predictive values (PPV) with 95% confidence interval (CI) of the ICD10 codes for HFrEF and HFpEF. HFrEF was assessed using varying ejection fraction (EF) cut-offs of 40% and 50% or in combination with qualitative EF assessment. Results: Among the 314,221 HF patients, 80% had codes for systolic/diastolic dysfunction (I50.2 or 3) and 20% had codes for combined dysfunction or unspecified HF. The 200-chart-validation-sample (mean age 81, 43% male and 90% white) included 50 systolic (I50.2), 50 diastolic (I50.3), 47 combined (I50.4) and 53 unspecified HF (I50.9) patients. EF was recorded in ≥80% of patients with systolic, diastolic, and combined dysfunction. For systolic HF code, the PPV for HFrEF was 80% and 92% using EF≤40% and ≤50%, respectfully. For diastolic HF code, the PPV for HFpEF was 96% (Table). The ICD10 code for combined or unspecified HF did not predict either HFrEF or HFpEF well. Conclusion: ICD10 codes that specify systolic or diastolic HF were used in 80% of hospitalized HF patients, had EF recorded in ≥80% of patients, and predicted reduced and preserved EF with high validity. Specific ICD10 HF codes alone may be useful in identifying populations with HFrEF or HFpEF in hospitalized Medicare patients.