tbuckley/cabot-search huggingface dataset:
Abstract 14177: Low Cholesterol Level Was a Risk for Stroke or Systemic Embolism in Elderly Patients With Atrial Fibrillation: The Fushimi AF Registry
Authors: Moritake Iguchi, Nobutoyo Masunaga, MITSURU ISHII, Yoshimori An, Yuya Ide, Akiko Fujino, Yasuhiro Hamatani, KOSUKE DOI, Syuhei Ikeda, Kenjiro Ishigami, Masahiro Esato, Hiromichi Wada, Koji Hasegawa, Hisashi Ogawa, Mitsuru Abe, Masaharu Akao
Journal: Circulation (2020)

Introduction: Hyperlipidemia is a well-established risk factor for cardiovascular disease. However, low cholesterol is also reported to be associated with poor outcome in chronic disease, which is called “cholesterol paradox”, and the impact of cholesterol level on the incidence of stroke or systemic embolism (SE) in atrial fibrillation (AF) remains unclear. Methods: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. We obtained baseline total cholesterol level (TC) in 3,051 patients, and examined the relationship between TC and incidence of stroke/SE. Results: TC was inversely correlated with age and positively correlated with body weight. Patients with lower TC were more likely to be male, and had more diabetes, coronary artery disease, heart failure, prior stroke/SE, chronic kidney disease, and anemia. CHA 2 DS 2 -VASc score was inversely correlated with TC. Prescription of statin was higher in patients with lower TC, but that of oral anti-coagulants was not associated with TC. During the median follow-up of 1,476 days, stroke/SE occurred in 277 (9.1%) patients. After adjustment for the components of CHA 2 DS 2 -VASc score, body weight, and prescription of oral anti-coagulants and statins, TC had significant inverse association with the incidence of stroke/SE (hazard ratio (HR), 0.94; 95% confidence interval (CI) 0.91-0.98 for 10-mg/dl increase) (Table). TC was significantly associated with ischemic stroke/SE (HR, 0.95; 95% CI 0.91-0.99 for 10-mg/dl increase), but was not associated with intracranial bleeding (HR, 0.95; 95% CI 0.88-1.02 for 10-mg/dl increase). When we divided the patients into the elderly (≥75 years) and the young, low TC was a predictor for stroke/SE in the elderly (HR, 0.94; 95% CI 0.90-0.99 for 10-mg/dl increase), but was not in the young (HR, 0.95; 95% CI 0.90-1.01 for 10-mg/dl increase). Conclusions: Low TC might be an independent predictor for stroke/SE in elderly patients with AF.
Abstract 15888: Platelet Activation is Associated With All-cause Mortality in Patients With Covid-19
Authors: Tessa J Barrett, Angela Lee, Yuhe Xia, Lawrence Lin, Margaret Black, Paolo Cotzia, Judith S Hochman, Jeffrey S Berger
Journal: Circulation (2020)

Background: COVID-19 is a global pandemic with patients at increased risk for all-cause mortality. Virus-platelet interactions are linked to viral pathogenesis and increased risk of adverse events. Aim: To investigate the relationship between in vivo platelet activity markers and all-cause mortality in hospitalized patients with COVID-19. Method: Plasma samples were collected from 100 hospitalized patients on the day of PCR-confirmed COVID-19 diagnosis. Thromboxane B 2 (TxB 2 ), P-selectin, and soluble CD40 ligand (sCD40L) were measured in plasma, and mean platelet volume (MPV) assessed. Subjects were followed until discharge or death. Results: Among 100 patients, the median age was 65 years (IQR: 55, 75), 39% were female, and 32 died or experienced a thrombotic event. The baseline platelet activation markers, P-selectin (p=0.02), sCD40L (p=0.03) and MPV (p=0.005) were higher in patients who died. After adjustment for age, sex, race/ethnicity, platelet count, antiplatelet therapy, and chronic obstructive pulmonary disease, TxB 2 (p=0.036), P-selectin (p=0.007), sCD40L (p=0.02) and MPV (p=0.01) were each independently associated with death after multivariable adjustment ( Table 1 ). Conclusions: Biomarkers of platelet activation are significantly associated with death or thrombosis in patients hospitalized with COVID-19. Our findings suggest multiple platelet activation mechanisms may contribute to adverse events. Further investigation into the mechanistic role of platelets in COVID-19 pathogenesis and the potential role of antiplatelet therapy is warranted. Table 1. Multivariable regression models of all-cause mortality. Odds ratios (OR) from logistic regression analysis per SD increase for biomarker levels adjusted for age, sex, race, antiplatelet therapy, platelet count, and chronic obstructive pulmonary disease (COPD).
circIGHG-Induced Epithelial-to-Mesenchymal Transition Promotes Oral Squamous Cell Carcinoma Progression via miR-142-5p/IGF2BP3 Signaling
Authors: Jingpeng Liu, Xiao Jiang, Ailing Zou, Zhaoyi Mai, Zhijie Huang, Liying Sun, Jianjiang Zhao
Journal: Cancer Research (2020)

Abstract Circular RNAs (circRNA) are a new member of endogenously produced noncoding RNAs that have been characterized as key regulators of gene expression in a variety of malignances. However, the role of circRNA in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we identified unique circRNA that regulate OSCC progression and metastasis and pave roads for future research in early diagnosis, prevention, and treatment of OSCC. Transcriptomic analyses identified a circRNA derived from IGHG locus (circIGHG) as significantly upregulated in OSCC and positively associated with poor prognosis of OSCC. circIGHG directly bound miR-142-5p and consequently elevated IGF2BP3 activity. Knockdown of circIGHG led to impaired expression of IGF2BP3 and attenuated aggressiveness of OSCC cells. Epithelial–mesenchymal transition was the main mechanism through which circIGHG/IGF2BP3 promotes metastasis of OSCC. Overall, these results demonstrate that circIGHG plays a pivotal role in OSCC development and metastasis and has potential to serve as a biomarker and therapeutic target for early-stage diagnosis and treatment of OSCC. Significance: These findings broaden our insights regarding regulation of OSCC progression by circular RNA and serve as a reference for future clinical research in OSCC diagnosis and treatment.
Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve
Authors: Helio P. Guimarães, Renato D. Lopes, Pedro G.M. de Barros e Silva, Idelzuita L. Liporace, Roney O. Sampaio, Flávio Tarasoutchi, Conrado R. Hoffmann-Filho, Rodrigo de Lemos Soares Patriota, Tiago L.L. Leiria, Diana Lamprea, Dalton B. Precoma, Fernando A. Atik, Fabio S. Silveira, Fabio R. Farias, Diogo O. Barreto, Adail P. Almeida, Alexandre C. Zilli, João D. de Souza Neto, Margaret A. Cavalcante, Fernando A.M.S. Figueira, Flávia C.S. Kojima, Lucas Damiani, Renato H.N. Santos, Nanci Valeis, Viviane B. Campos, Jose F.K. Saraiva, Francisco H. Fonseca, Ibraim M. Pinto, Carlos C. Magalhães, Joao F.M. Ferreira, John H. Alexander, Ricardo Pavanello, Alexandre B. Cavalcanti, Otavio Berwanger
Journal: New England Journal of Medicine (2020)

The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.
Abstract 17205: The Association of Cerebrovascular Autoregulation With Neurodevelopmental Delays Between Infants With and Without Congenital Heart Disease
Authors: Nhu Tran, Jodie Votava-Smith, Michelle Tran, Ashok Panigrahy, Brad Peterson
Journal: Circulation (2020)

Background: Children with Congenital Heart Disease ( CHD ) are 5 times more likely to develop neurodevelopmental impairment lasting into adulthood compared to their peers. One theory is that hypoxemia associated with CHD contributes to impaired cerebrovascular autoregulation ( CA ), which in turn may contribute to neurological injuries and impaired neurodevelopmental outcome ( NDO ) in CHD. This study examined the association of CA and NDO between CHD and healthy infants. Hypothesis: Impaired CA will be associated with poorer NDO in CHD infants through 9-month development. Methods: A prospective, longitudinal study was performed at 3, 6, &amp; 9-month time points. CA was indexed by calculating the difference between 2-minute averaged supine and sitting cerebral oxygenation (rcSO 2 ) measured by near-infrared spectroscopy for 3 consecutive tilts (0-90°), resulting in change scores. The Bayley Scales of Infant and Toddler Development III measured NDO. Multiple linear regressions quantified the group-by-CA interaction on NDO at each age. Results: We enrolled 35 CHD and 26 healthy control ( HC ) infants. 3 months: As CA worsened (change score in rcSO 2 increased by 1-unit), cognitive compositive scores decreased by 2.6% in the CHD group compared to the HC during the 3 rd postural change (P=0.003). 6 months: As CA worsened, the language composite scores decreased by 3.7% in the CHD group at compared to the HC for the 1 st postural change (P=0.041). 9 months: As CA worsened, the cognitive composite scores decreased by 2.7% in the CHD group compared to the HC during the 3 rd postural change (P=0.046). See Table 1. Conclusion: We found poorer CA to be significantly associated with worse NDO in CHD infants. These initial results demonstrate the persistence of impaired CA even after surgical repair of CHD, which may be a mechanism of brain injury. Future directions include larger studies and targeted interventions to improve CA to reduce developmental delays in CHD children.
Abstract 13218: Machine Learning Can Identify Cardiology Patients With High Future Healthcare Utilization in a Large Regional Health System
Authors: Linyuan Jing, Rameswara S Challa, Alvaro Ulloa, William C Cauthorn, Dustin Hartzel, Joseph Leader, Daniel B Rocha, Christopher M Haggerty, Brandon Fornwalt
Journal: Circulation (2020)

Introduction: Healthcare cost has increased drastically in the last decade, and over 50% of the cost can be attributed to a small portion (5-10%) of the population. Certain clinical programs, such as home-based care, aim to reduce this utilization but need methods to identify the most appropriate patients to enroll. We hypothesized that machine learning can predict patients with high future utilization with good accuracy. Methods: 683,160 cardiology patients (defined broadly as those with an ECG, echocardiogram or cardiology visit) with ~17 million clinical episodes since 2004 were identified from Geisinger’s electronic health records. Utilization was estimated as total cost of care for outpatient, inpatient and emergency department visits. Patients with the highest 10% utilization in a given year were defined as high utilizers. Machine learning models were used to predict high utilization over the next 3, 6 and 12 months. Input variables (n=191) included age, sex, smoking, 5 vital signs, 21 labs, 18 medications (current and past), 40 ECG and 44 echocardiographic measurements, 43 comorbidities, 7 time / cyclical features, 6 past utilization metrics and 4 social metrics (e.g. distance to healthcare facilities). Results: XGBoost achieved the best performance with areas under the ROC curve (AUC) of 0.82, 0.81 and 0.78 for 3, 6, 12-month models, and average precision scores (AP) of 0.31, 0.36 and 0.37, respectively, while the commonly used Charlson Comorbidity Index had poor performance with AUCs of 0.63 - 0.64 and APs of 0.1 - 0.17. Past utilization was the best predictor of future utilization. Targeting patients with the top 5 and 10% highest risk for utilization achieved sensitivities of 26 and 40% and positive predictive values of 50 and 38% (12-month model, Figure). Conclusions: Machine learning can be used to predict which patients will have high future healthcare utilization. This may help target populations for intervention programs aimed at reducing utilization.
Abstract 15266: The Associations Between Pectoralis Muscle Area and Texture on Computed Tomography With Metabolic Syndrome: The Multi-ethnic Study of Atherosclerosis - Arthritis (MESArthritis) Study
Authors: Farhad Pishgar, Mahsima Shabani, Thiago Quinaglia A. C. Silva, Matthew J Budoff, David A Bluemke, Graham Barr, Colin Wu, Joao A Ac Lima, Shadpour demehri
Journal: Circulation (2020)

Introduction: Metabolic syndrome (MetS) has been cited as a potentially modifiable risk factor for the cardiovascular outcomes. Hypothesis Pectoralis muscle (PM) and intermuscular adipose tissue (IntM AT) areas on chest CT images may be readily obtainable soft tissue biomarkers for MetS screening. Methods: Out of 3,204 subjects in the MESA study with available chest CT scan in the exam 5 (4/2010 to 2/2012), 2,975 subjects had quality-essential images and were included in this analysis. The PM and IntM AT areas in the CT images were measured using a framework for image segmentation in the slice above the aortic arch.The presence of MetS subcomponents and the MetS diagnosis for this sample were determined using the NCEP ATP III. The associations between PM and IntM AT areas with MetS subcomponents and diagnosis were studied using regression (adjusted for relevant confounders). The ROC curves were used to defining the optimal cut-off points (using the Youden’s Index) for MetS diagnosis. Results: The mean age of subjects was 69.29±9.26 (1,434 men and 1,541 women). In this sample, 1,065 (35.80%) subjects were diagnosed with MetS. IntM AT (OR:1.07(1.02-1.13)), but not the PM (OR:0.98(0.97-1.00)) area, was associated with MetS. Using the ROC curve, the optimal cut-off points of the IntM AT areas and PM for MetS diagnosis were 16.22 and 1.87, respectively. The cut-off point for the PM were highly sensitive (87.1%) but not specific (16.4%). Conclusion: Quantitative analysis of PM and IntM AT areas, measured in a predefined “single slice” of the chest CT image using an in-house semiautomatic framework, may be used as an imaging biomarker for MetS.
Abstract 14065: Effectiveness and Tolerability of Perindopril 3.5 Mg/amlodipine 2.5 Mg Single Pill Combination in Newly Diagnosed Patients With Hypertension. The Simple National Study Across Canada
Authors: Stella S DASKALOPOULOU, Romualda VILLATTE
Journal: Circulation (2020)

Introduction: The perindopril 3.5 mg /amlodipine 2.5 mg is the only available angiotensin converting enzyme inhibitor and a calcium channel blocker single pill combination (SPC) with market approval as a first-line therapy indication for hypertension. Hypothesis: Effectiveness, tolerability of, and the compliance to this SPC in patients with newly diagnosed hypertension. Methods: National, prospective, open-label, non-interventional study. Patients (n=1179) were initially prescribed the lowest dose SPC perindopril 3.5 mg/amlodipine 2.5 mg with possible up-titration after 4-weeks treatment (to 7/5 mg up to 14/10 mg). Office blood pressure (BP) at baseline, 3 months (M3), 6 months (M6), and the percentage of patients with normalized BP were assessed. Data were stratified by age, systolic BP category at baseline, and diabetic status. Results: Significant early systolic/diastolic BP decreases from baseline (mean±SD) were observed since the first visit: -20.8±14.7/-11.7±9.2 (P&lt;0.001) at M3 and was slightly greater at M6: -22.9±14.5/-13.4±9.1, (P&lt; 0.001), suggesting that the majority of the effect was obtained within the first 3 months; 82% of patients continued at the same dose, 17.5% were up-titrated. BP target was achieved in 61.4% of patients at M3, in 70.2% at M6. Significant BP decreases were observed in all age subgroups, in diabetic and non-diabetic patients. At both visits, significantly higher efficacy was observed in patients with stage 2 hypertension ( -27.0±15.3/-13.2±9.6, at M3 and -29.6±15.4/-15.0±9.2, at M6; p&lt;0.002 for all) than stage 1. The greatest efficacy was observed in non-diabetic patients with stage 2 hypertension at M6 (-35.0±12.5/-17.2±8.9; P&lt;0.001). Good compliance was reported in 95% of patients. During the study, emergent adverse events were reported in 95 (7.2%) patients, with no severe safety concerns raised; the intensity was mostly mild (76.8%) or moderate (21.1%) Conclusions: The Canadian SIMPLE study confirms the early benefits, tolerability of and compliance to the SPC perindopril/amlodipine 3.5 mg/2.5 mg, with a possibility of up-titration. This supports the guidelines recommendation for SPC use in newly diagnosed patients with hypertension as a first-line therapeutic option in clinical practice.
A randomized double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis
Authors: Melody C. Carter, Irina Maric, Erica H. Brittain, Yun Bai, Keith Lumbard, Hyejeong Bolan, Daly Cantave, Linda M. Scott, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2020)
ATF4 activation promotes hepatic mitochondrial dysfunction by repressing NRF1–TFAM signalling in alcoholic steatohepatitis
Authors: Liuyi Hao, Wei Zhong, Haibo Dong, Wei Guo, Xinguo Sun, Wenliang Zhang, Ruichao Yue, Tianjiao Li, Alexandra Griffiths, Ali Reza Ahmadi, Zhaoli Sun, Zhenyuan Song, Zhanxiang Zhou
Journal: Gut (2020)

Objective Mitochondrial dysfunction plays a dominant role in the pathogenesis of alcoholic liver disease (ALD); however, the underlying mechanisms remain to be fully understood. We previously found that hepatic activating transcription factor 4 (ATF4) activation was associated with mitochondrial dysfunction in ALD. This study aimed to investigate the function and mechanism of ATF4 in alcohol-induced hepatic mitochondrial dysfunction. Design ATF4 activation was detected in the livers of patients with severe alcoholic hepatitis (AH). The role of ATF4 and mitochondrial transcription factor A (TFAM) in alcohol-induced liver damage was determined in hepatocyte-specific ATF4 knockout mice and liver-specific TFAM overexpression mice, respectively. Results Hepatic PERK-eIF2α-ATF4 ER stress signalling was upregulated in patients with AH. Hepatocyte-specific ablation of ATF4 in mice ameliorated alcohol-induced steatohepatitis. ATF4 ablation also attenuated alcohol-impaired mitochondrial biogenesis and respiratory function along with the restoration of TFAM. Cell studies confirmed that TFAM expression was negatively regulated by ATF4. TFAM silencing in hepatoma cells abrogated the protective effects of ATF4 knockdown on ethanol-mediated mitochondrial dysfunction and cell death. Moreover, hepatocyte-specific TFAM overexpression in mice attenuated alcohol-induced mitochondrial dysfunction and liver damage. Mechanistic studies revealed that ATF4 repressed the transcription activity of nuclear respiratory factor 1 (NRF1), a key regulator of TFAM, through binding to its promoter region. Clinical relevance among ATF4 activation, NRF1–TFAM pathway disruption and mitochondrial dysfunction was validated in the livers of patients with AH. Conclusion This study demonstrates that hepatic ATF4 plays a pathological role in alcohol-induced mitochondrial dysfunction and liver injury by disrupting the NRF1–TFAM pathway.
Abstract 14603: Arterial Vascular Events in Men With Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)
Authors: Kathleen W Zhang, Michael G Fradley, Daniel Addison, Courtney Campbell, Arjun K Ghosh, Adam C Calaway, Jorge Alberto Garcia, Lee Ponsky, Daniel Lenihan, Nihar R Desai, Neal L Weintraub, Avirup Guha
Journal: Circulation (2020)

Introduction: Hormone therapy has been associated with adverse cardiovascular events including arterial vascular events in men with prostate cancer. It is unclear if the risk of arterial vascular events varies by type of hormone therapy used. Methods: The Food and Drug Administration’s Adverse Event Reporting System (FAERS) was used to compare arterial vascular event reporting in men receiving hormone therapy from 01/01/2000 to 04/30/2020 for prostate cancer. Therapies evaluated were gonadotrophin-releasing hormone (GnRH) agonists (i.e. leuprolide), GnRH antagonists (i.e. degarelix), androgen receptor (AR) antagonists (i.e. bicalutamide) and abiraterone. Arterial vascular events included coronary artery disease, myocardial infarction, ischemic stroke, peripheral vascular disease, and hypertension requiring hospitalization. Polytomous logistic regression (adjusted for age, need for hospitalization, and event reporting source) was performed for non-GnRH agonists as compared to GnRH agonists. Results: Among 34,466 events reported during the study period on single agent therapy, 10.6% were arterial vascular events (5.9% hypertension requiring hospitalization, 2.3% coronary artery disease or myocardial infarction, 2.1% ischemic stroke, and 0.3% peripheral vascular disease). Median age of those with reported arterial vascular events was 76 years (IQR 70 - 82). Arterial vascular events were reported less commonly in men receiving AR antagonists (adjusted reporting odds ratio [ROR] 0.7 [95% CI 0.7-0.8], p&lt;0.0001), abiraterone (ROR 0.9 [0.8-0.98], p=0.02), and GnRH antagonists (ROR 0.9 [0.7-1.1], p=0.15) as compared to those receiving GnRH agonists. Conclusion: Arterial vascular events are reported more commonly in men receiving GnRH agonists for prostate cancer as compared with other types of hormone monotherapy. Use of non-GnRH agonists may reduce the risk of adverse cardiovascular events on hormone therapy in men with prostate cancer.
Abstract IA-11: An exception to the rule: A coding functional variant at a pancreatic cancer GWAS locus
Authors: Ashley Jermusyk, Jun Zhong, Naomi Gordon, Katelyn Connelly, Sumeth Perera, Ehssan Abdolalizadeh, Tongwu Zhang, Aidan O'Brien, Jason Hoskins, Irene Collins, Daina Eiser, Chen Yuan, Harvey Risch, Eric J. Jacobs, Donghui Li, Mengmeng Du, Rachael Stolzenberg-Solomon, Alison P. Klein, Jill P. Smith, Brian M. Wolpin, Stephen J. Chanock, Jianxin Shi, Gloria M. Petersen, Christopher Westlake, Laufey T. Amundadottir
Journal: Cancer Research (2020)

Abstract Genome wide association studies (GWAS) in 9,013 pancreatic cancer patients and 12,452 controls of European ancestry have discovered over 20 risk loci in the human genome. Here, we fine mapped one such locus on chromosome 16q23.1 in the vicinity of two Chymotrypsinogen precursor genes, CTRB1 and CTRB2. We fine-mapped this locus to rs72802365 (P=2.51x10-17, OR=1.36, 95% CI=1.31-1.40) and identified colocalization (PP=87%) with aberrant exon 5→7 CTRB2 splicing in pancreatic tissues. Imputation of a 584 bp insertion/deletion variant overlapping exon 6 of CTRB2 into the GWAS datasets resulted in a highly significant association with pancreatic cancer risk (P=2.83x10-16, OR=1.36, 95% CI=1.31-1.42), indicating that it may underlie this signal. Exon skipping attributable to the deletion (risk) allele introduces a premature stop codon in exon 7 of CTRB2, yielding a truncated chymotrypsin B2 protein that lacks chymotrypsin activity, is poorly secreted, and accumulates intracellularly in the endoplasmic reticulum (ER). The intracellular accumulation of a nonfunctional chymotrypsinogen B2 protein may lead to ER stress and pancreatic inflammation, which in turn, may explain the increased pancreatic cancer risk in carriers of CTRB2 exon 6 deletion alleles. Citation Format: Ashley Jermusyk, Jun Zhong, Naomi Gordon, Katelyn Connelly, Sumeth Perera, Ehssan Abdolalizadeh, Tongwu Zhang, Aidan O'Brien, Jason Hoskins, Irene Collins, Daina Eiser, Chen Yuan, Harvey Risch, Eric J. Jacobs, Donghui Li, Mengmeng Du, Rachael Stolzenberg-Solomon, Alison P. Klein, Jill P. Smith, Brian M. Wolpin, Stephen J. Chanock, Jianxin Shi, Gloria M. Petersen, Christopher Westlake, Laufey T. Amundadottir. An exception to the rule: A coding functional variant at a pancreatic cancer GWAS locus [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-11.
Video consultations will increase health inequality without the correct infrastructure put in place
Authors: Ashley K Mehmi, David Winters, James S A Green
Journal: BMJ (2020)

We write to comment on two articles, the first explaining the benefits and practicalities of video consultations1 and the second warning of the health inequalities exposed by the pandemic.2

Although video consultation has many benefits, it may also increase health inequality without the correct infrastructure and processes put in place.3

The overriding problem concerns access, as many patients simply cannot engage …