tbuckley/cabot-search huggingface dataset:
Abstract 16640: Neutrophil Expansion is Essential for Adverse Left Ventricular Remodeling and Dysfunction in Chronic Ischemic Heart Failure
Authors: Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Sumanth D Prabhu, Gregg Rokosh
Journal: Circulation (2020)

Chronic inflammation contributes significantly to disease progression in heart failure (HF), and is characterized by expansion of activated macrophages, dendritic cells, and T cells in the failing heart. Neutrophils play a well-known role as the initial drivers of inflammatory response to myocardial infarction (MI), thereby providing the platform for the subsequent recruitment of macrophages and T cells. However, whether and how neutrophils contribute to inflammation and adverse LV remodeling in chronic HF are unknown. We tested the hypothesis that activated neutrophils are required for tissue remodeling and disease progression in HF. Male C57Bl/6 mice were studied 4 and 8 weeks after left coronary artery ligation during established ischemic HF (sham-operated controls). As assessed by flow cytometry, CD11b + Ly6G + neutrophils were expanded in the peripheral blood (4 w post-MI), and in the bone marrow, spleen, and heart at 8 w post-MI. Immunostaining revealed that in the failing heart, neutrophils were primarily localized to the MI border zone, but also augmented in remote zone myocardium. CXCL1 and CXCL5 chemokine expression was increased in the failing heart, consistent with chemotactic signals for myocardial neutrophil recruitment. Isolated naïve neutrophils also exhibited increased chemotaxis in response to plasma from HF mice (versus plasma from naïve mice), as assessed by time-lapse video microscopy. Moreover, blood neutrophils isolated from HF mice exhibited significantly increased neutrophil extracellular trap (NET) production as compared to control neutrophils, whereas plasma NETs (histone-DNA complexes) were increased in HF mice. Finally, the in vivo role of neutrophils in chronic HF (8 w post-MI) was determined via depletion studies using genetic (Ly6G-diptheria toxin receptor mice) and antibody (1A8) based approaches. In both models, 2 and 4 w of neutrophil depletion, respectively, significantly improved LV systolic function and reduced end systolic volume. 1A8 treated HF mice also exhibited reduced remote zone fibrosis. We conclude: neutrophil expansion and activation are important components of the chronic inflammatory response in HF, and play an obligatory role in the progression of LV remodeling in ischemic cardiomyopathy.
Abstract 16229: Nonsteroidal Anti-inflammatory Drug Use and Heart Failure Hospitalizations: Are Patients Being Screened?
Authors: Evan D Levine, Kevin Rabii, Shankar Thampi, Khalid Pasha, Neil Coplan
Journal: Circulation (2020)

Introduction: There is strong evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of heart failure (HF) and mortality in HF patients. Patients admitted with decompensated HF should be screened for NSAID use. Hypothesis: NSAID use in patients admitted with HF is often overlooked due to inadequate screening by clinicians. Methods: We performed a prospective study of all patients admitted to the cardiology service with a primary diagnosis of decompensated HF. All patients were evaluated for enrollment within 48 hours of admission. Exclusion criteria included shock, cardiac arrest, respiratory failure requiring positive pressure ventilation, altered mental status or toxic metabolic encephalopathy, dementia, cognitive deficit, acute gastrointestinal bleed, acute blood loss anemia, and NSAID allergy. Electronic Medical Record review and in-person interviews were performed to determine if subjects had been screened for NSAID use. Positive screening included: documentation of NSAID use or absence of NSAID use in the admission note, medication reconciliation documenting NSAID use, or answering yes to the interview question “Were you asked if you take NSAIDs or over-the-counter pain medication?” Results: The study included 151 subjects (78 men/73 women); mean age 71.7 years. The number of patients who were taking NSAIDs was 34 (22.5%); there was no variation in prevalence between genders. NSAID screening occurred in 15.9% of patients (24/151). Of those taking NSAIDs, 88.3% had not been screened by their providers and 29% had no documented etiology for their HF exacerbation or had documented HF of “unclear etiology.” 56% of patients taking NSAIDs had self-prescribed, while 44% reported prescription by a physician. 82% had been taking NSAIDs regularly for over 1 month. Additionally, of patients on NSAIDs, 53% had coronary artery disease, 56% had hypertension, and 50% had chronic kidney disease. Conclusions: Despite strong evidence that NSAIDs are harmful and contraindicated in many cardiovascular conditions, NSAID use in patients with HF is still prevalent. This study highlights the importance of vigilant screening by clinicians and the need for improved patient education on the risks associated with this class of medication.
Long-term treatment-free remission in patients with chronic myeloid leukemia after second-line nilotinib: ENESTop 5-year update
Authors: Timothy P. Hughes, Nelma Cristina D. Clementino, Mikhail Fominykh, Jeffrey H. Lipton, Anna G. Turkina, Elena Beatriz Moiraghi, Franck E. Nicolini, Naoto Takahashi, Tomasz Sacha, Dong-Wook Kim, Rafik Fellague-Chebra, Ranjan Tiwari, Catherine Bouard, Francois-Xavier Mahon
Journal: Leukemia (2021)
Abstract P011: Serum Adiponectin And Risk Of Incident Hypertension: The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study.
Authors: Aneesh Singal, Mary Cushman, Neil A Zakai, Nels C Olson, George Howard, Virginia J Howard, Suzanne E Judd, April P Carson, Timothy B Plante
Journal: Circulation (2021)

Background: Hypertension is a leading cause of disability-adjusted life years lost in the United States. Adiponectin is a cytokine secreted by adipocytes that increases insulin sensitivity, maintains vascular homeostasis, and is inversely associated with adiposity. We sought to determine the risk of incident hypertension by level of adiponectin at baseline. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black and White US adults in 2003-2006, with a second visit ~9 years later. Adiponectin was measured at the baseline visit among a random sample of 4,400 participants who attended the second visit. Modified Poisson regression estimated the relative risk (RR) for incident hypertension by each 1 SD higher of log-transformed adiponectin level adjusting for age, race, and sex in a minimally adjusted model. The fully adjusted model added Southern Diet pattern, dietary ratio of sodium to potassium, BMI, waist circumference, and systolic blood pressure. Restricted cubic splines visualized RR of hypertension by level of adiponectin, relative to the median. Results: After excluding those with prevalent hypertension (threshold 140/90 mm Hg or blood pressure medication use; n=2477) and missing adiponectin (n =129), 1,877 participants remained (mean age 62 years, 49% male, 36% Black, with lower adiponectin in Black participants p&lt;0.001). Incident hypertension occurred in 46% (95% CI 43, 50%) of Black adults and 32% (29, 34%) of White adults. The RR for incident hypertension for each 1-SD higher log adiponectin was 0.91 (0.83, 1.00) in the demographic model and 0.99 (0.89, 1.10) in the fully adjusted model. Hypertension risk was similar across the continuum of adiponectin ( Figure ). Conclusions: In a cohort of Black and White US adults without hypertension, level of adiponectin did not associate with risk of incident hypertension 9 years later after adjusting for other hypertension risk factors.
Abstract 13136: Left Atrial Appendage Structural Characteristics Predict Thrombus Formation
Authors: Hyun Kim, John Ning, Kaiwei Lu, Colton Thompson, Sudhi Tyagi, Marcie Berger
Journal: Circulation (2020)

Introduction: Atrial fibrillation remains highly prevalent in the US with over 6 million diagnosed individuals. Discordant atrial contraction inherent to atrial fibrillation results in stagnant blood flow and increases the risk for thrombus formation particularly within the left atrial appendage (LAA). Anticoagulation is the mainstay of intracardiac thrombus prevention and is initiated based on the CHAD 2 S 2 -VASc risk score that does not account for LAA morphology. The relationship between LAA structural characteristics and thrombus development remains poorly understood. Hypothesis: We hypothesized that in patients with atrial fibrillation, LAA structural characteristics correlate with the presence of thrombus. Methods: We performed a retrospective case-control study of 151 subjects with a history of atrial fibrillation who underwent transesophageal echocardiogram (TEE) to evaluate the LAA for pre-cardioversion indication or Watchman screening evaluation. Subjects discovered to have LAA thrombus on TEE defined the study case group (n = 74) while control subjects did not have LAA thrombus (n = 77). Baseline demographics and echocardiographic characteristics were collected for all subjects. Results: Subjects without thrombus were older than those with thrombus (thrombus: 68.6 ± 13.1 years, no thrombus: 74.7 ± 9.2 years, p = 0.001 ). LAA ostial cross-sectional area was smaller in subjects with thrombus than those without thrombus (thrombus: 251.1 ± 117.4 mm 2 , no thrombus: 332.9 ± 171.2 mm 2 , p &lt; 0.001 ). This finding remained significant in both unadjusted and adjusted logistic regression models ( Table 1 ). CHA 2 DS 2 -VASc score did not significantly differ in those with or without thrombus (thrombus: 4.4 ± 1.8, no thrombus: 4.3 ± 1.7, p = 0.822). Conclusions: Smaller LAA ostial cross-sectional area correlates with thrombus formation. Consideration of LAA structural characteristics may improve precision of anticoagulation management.
Abstract 13583: Secondary Findings of Loss-of-function Variants in <i>FLNC</i> Are Associated With Arrhythmogenic Cardiomyopathy Phenotypes in a General Clinical Population
Authors: Christopher M Haggerty, Melissa Kelly, Crystal Tichnell, Brittney Murray, Amy C Sturm, Brandon Fornwalt, Cynthia James
Journal: Circulation (2020)

Introduction: The FLNC gene, encoding the Filamin C sarcomere protein, has gained recent attention as a potential cause of severe cardiomyopathy and arrhythmia phenotypes through genetic testing of individuals with known inherited heart disease. We sought to characterize the phenotypes associated with rare, putative loss-of-function variants in FLNC ascertained through secondary findings of exome sequencing in a large clinical population. Methods: We reviewed exome data from the first 135,878 sequenced participants in the Geisinger MyCode Community Health Initiative with linked electronic health records (EHR; the DiscovEHR cohort) to identify rare frameshift, stop gain, or canonical splice site variants in FLNC (FLNC LOF ). We compared data on diagnoses and cardiac diagnostic testing (i.e., ECG and echocardiography, when available) from the EHR between individuals with and without FLNC LOF using SAIGE mixed linear models adjusted for age, sex, and ancestry. Results: We observed 46 individuals (0.03%) carrying one of 24 distinct FLNC LOF variants. These individuals had significantly increased odds for diagnoses of dilated cardiomyopathy (OR: 49, 95% CI: [4-560]), ventricular tachycardia (OR: 170, [5-6317]), and supraventricular tachycardia (OR: 11, [2-77]). We also observed significantly increased left ventricular (LV) diameter (5.1 ± 0.8 cm vs. 4.6 ± 0.7 cm, p = 0.001) and decreased LV ejection fraction (Figure) by echocardiography (available in 50% of FLNC LOF individuals), and a trend toward higher prevalence of inverted T waves in any precordial lead beyond V2 (23% vs. 7%, p = 0.06). Conclusion: Loss-of-function variants in FLNC are extremely rare in a general clinical population but are associated with a clinically significant and potentially actionable, yet incompletely penetrant, cardiac phenotype marked by ventricular dysfunction and dysrhythmia. Consideration for screening and return of secondary findings may be warranted.
Abstract 14240: Thoracic Aortic Calcium for the Prediction of Stroke Mortality: The Coronary Artery Calcium Consortium
Authors: Olufunmilayo H Obisesan, Albert D Osei, Daniel Berman, Zeina Dardari, S M Iftekhar Uddin, Omar Dzaye, Olusola A Orimoloye, Matthew J Budoff, Michael D Miedema, John A Rumberger, Mohammadhassan Mirbolouk, Alan Rozanski, Leslee J Shaw, Khurram Nasir, Michael J Blaha
Journal: Circulation (2020)

Introduction: Thoracic aortic calcium(TAC) is an important marker of extra-coronary atherosclerosis with known predictive value for all-cause mortality. We sought to explore the predictive value of TAC for stroke mortality, independent of the more established coronary artery calcium score. Methods: The Coronary Artery Calcium(CAC) Consortium is a retrospectively assembled database of 66,636 patients aged ≥18 years with no prior history of cardiovascular disease, who had CAC scans done for risk stratification and were followed-up for an average of 12±4years. CAC scans capture a view of the adjacent thoracic aorta, enabling us to assess TAC at no extra cost. TAC was analyzed as present or not present and we restricted analysis to those with this information available. To account for competing risks for death from other causes, we utilized multivariable-adjusted competing risk regression models adjusted for traditional cardiovascular risk factors (age, sex, hypertension, hyperlipidemia, cigarette smoking, diabetes, family history of CHD) and CAC score. We report the relationship between TAC and stroke mortality using sub-distribution hazard ratios(SHR) with 95% CI. Results: There were 41,066 patients with information on TAC, 110 of whom had stroke mortality. The mean age of participants was 53.8±10.3 years, with 34.4% female. The unadjusted SHR for stroke mortality among those who had TAC compared to those who did not was 8.80(95%CI:5.97,12.98). After adjusting for traditional risk factors and CAC score, the SHR was 2.21(95%CI:1.39,3.49). The fully adjusted SHR for females was 3.42(95%CI:1.74,6.73) while for males it was 1.55(95%CI:0.83,2.90). Conclusion: TAC was predictive of stroke mortality independent of traditional risk factors and CAC, more so in females. The presence of TAC appears to be an independent marker of stroke mortality risk though further research is needed to study its incremental value over existing cardiovascular risk prediction models.
Abstract 15321: Complications of Drug Challenge Testing in Brugada Syndrome: A Systematic Review and Meta-analysis
Authors: Pattara Rattanawong, Wasawat Vutthikraivit, Jakrin Kewcharoen, Patrick Hooke, Komandoor S Srivathsan, Win K Shen, Dan Sorajja
Journal: Circulation (2020)

Introduction: Drug challenge testing is performed to unmask Type-1 Brugada pattern. The safety and prevalence of its complications during the test are unclear. We aimed to assess the relation of complications in patients with positive and negative results by a systematic review and meta-analysis. Hypothesis: The prevalence of arrhythmic complications is higher in patients with positive drug challenge testing. Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to June 2020. Included studies were cohort studies that reported ventricular arrhythmia that required interventions (VAI) (sustained ventricular tachycardia [VT], polymorphic VT, ventricular fibrillation, appropriate implantable cardioverter defibrillator [ICD] shock, or sudden cardiac arrest) and ventricular arrhythmias that did not required interventions (VANI) (premature ventricular complexes and non-sustained VT) during drug challenge testing. Data were combined using the random-effects model. Results: Thirteen studies involving 2,688 patients (62.7% positive) were included. The overall prevalence of VAI and VANI were 3.7% (95% confidence interval [CI]: 1.8-5.7) and 0.5% (95% CI: 0.1-0.9), respectively. VAI were more common in positive when compared to negative test result patients (1.5% [95% CI: 0.6-2.4] and 0%, respectively) but the prevalence of VANI were similar (2.7% [95% CI: 0.8-4.6] and 2.6% [95% CI: 0.8-4.6], respectively). VAI in positive result patients were more common with flecainide followed by pilsicainide and ajmaline (2.4% [95% CI: -4.3 to 9.2], 2.2% [95% CI: 0.5-4.0], and 1.5% [95% CI: 0.6 to 2.4], respectively). Most of patients with VAI during drug challenge testing underwent ICD implantation (94%). VAI during drug challenge testing in positive result patients carries an increased risk of VAI during 8.6 ± 4.9 years follow-up (odds ratio 3.73, 95% CI: 1.77-7.86, p=0.001). Conclusions: VAI were more common in patients with positive drug challenge testing, more often occurring with positive flecainide challenge, and carries an increased risk of VAI over long-term follow-up in patients with positive drug challenge testing.
The rise of affectivism
Authors: Daniel Dukes, Kathryn Abrams, Ralph Adolphs, Mohammed E. Ahmed, Andrew Beatty, Kent C. Berridge, Susan Broomhall, Tobias Brosch, Joseph J. Campos, Zanna Clay, Fabrice Clément, William A. Cunningham, Antonio Damasio, Hanna Damasio, Justin D’Arms, Jane W. Davidson, Beatrice de Gelder, Julien Deonna, Ronnie de Sousa, Paul Ekman, Phoebe C. Ellsworth, Ernst Fehr, Agneta Fischer, Ad Foolen, Ute Frevert, Didier Grandjean, Jonathan Gratch, Leslie Greenberg, Patricia Greenspan, James J. Gross, Eran Halperin, Arvid Kappas, Dacher Keltner, Brian Knutson, David Konstan, Mariska E. Kret, Joseph E. LeDoux, Jennifer S. Lerner, Robert W. Levenson, George Loewenstein, Antony S. R. Manstead, Terry A. Maroney, Agnes Moors, Paula Niedenthal, Brian Parkinson, Ioannis Pavlidis, Catherine Pelachaud, Seth D. Pollak, Gilles Pourtois, Birgitt Roettger-Roessler, James A. Russell, Disa Sauter, Andrea Scarantino, Klaus R. Scherer, Peter Stearns, Jan E. Stets, Christine Tappolet, Fabrice Teroni, Jeanne Tsai, Jonathan Turner, Carien Van Reekum, Patrik Vuilleumier, Tim Wharton, David Sander
Journal: Nature Human Behaviour (2021)
γ-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy
Authors: Fangyuan Zhou, Shikui Yang, Chao Zhao, Wangwang Liu, Xufeng Yao, Hui Yu, Xiaolian Sun, Yi Liu
Journal: Theranostics (2021)

Precise treatment of tumors is attracting increasing attention. Molecular probes simultaneously demonstrating the diagnostic signal and pharmacological effect in response to tumor microenvironment are highly desired. γ-glutamyl transpeptidase (GGT) is a biomarker with significantly up-regulated expression in the tumor area. We developed a GGT responsive near-infrared (NIR) nanoassembly for tumor-specific fluorescence imaging-guided photothermal therapy.
Abstract 13080: Clinical Significance of Clonal Hematopoiesis With JAK2V617F in Patients With Cardiovascular Diseases
Authors: Kento Wada, Tomofumi Misaka, Tetsuro Yokokawa, Yusuke KIMISHIMA, Keiji Minakawa, Takashi Kaneshiro, Akiomi YOSHIHISA, Kazuhiko Ikeda, Yasuchika Takeishi
Journal: Circulation (2020)

Background: It becomes increasingly clear that age-related clonal hematopoiesis (CH) is associated with cardiovascular diseases. However, CH with a driver mutation that causes myeloproliferative neoplasm (MPN) is not fully understood. Objective: To determine the clinical relevance of CH with MPN-driving mutations on cardiovascular diseases. Methods: This study prospectively enrolled 832 patients with cardiovascular diseases who did not show any hematological disorders. We examined the presence of the known MPN-driving mutations including JAK2V617F, CALRdel52, CALRins5, MPLW515L, and MPLW515K by an allele-specific polymerase chain reaction. Results: Out of 832 patients, 16 patients (1.9%) exhibited MPN-driving mutations including 15 patients with JAK2V617F (1.8%) and 1 patient with CALRins5 (0.1%). We divided the patients into two groups: vascular diseases including coronary artery disease, stroke, aortic aneurysm, aortic dissection, peripheral artery disease, deep vein thrombosis, and pulmonary thromboembolism (n=462, 55%) and non-vascular diseases (n=370, 45%). The prevalence of JAK2V617F-positive CH was significantly higher in patients with vascular diseases than in those with non-vascular diseases (2.8% vs. 0.5%, P = 0.014). In a multivariable analysis adjusted for known classic-atherosclerotic risk factors (age, male, obesity, smoking, hypertension, diabetes mellitus, dyslipidemia), the presence of JAK2V617F-positive CH was independently associated with vascular diseases (odds ratio, 5.448; P = 0.043). Additionally, peripheral leukocyte IL1B mRNA expressions as well as plasma interleukin-1β concentrations were significantly increased in patients with JAK2V617F-positive CH compared to those without JAK2V617F (P = 0.040 and P = 0.030, respectively). Conclusions: CH with JAK2V617F, but not CALR or MPL mutations, was significantly associated with vascular diseases independently on classic-atherosclerotic risk factors, in relation to interleukin-1β-related inflammatory mechanisms. JAK2V617F is a potential diagnostic and therapeutic target for vascular diseases.
Further evidence that sex matters in lung development: maternal asthma and infant lung function
Authors: Lauren Deanna Benton, Wayne Morgan
Journal: Thorax (2021)

Over the last four decades, birth cohort studies have materially improved our understanding of the early origins of respiratory disease. In this issue, Belinelo et al present evidence from the bern infant lung development (BILD) and breathing for life trial (BLT) cohorts demonstrating that maternal asthma is associated with altered tidal breathing patterns in male infants.1 The BILD cohort recruited healthy neonates from 1999 to 2010 to further understand the complex interactions of environment and genetics on lung development and respiratory disease. In contrast, the BLT was a clinical trial to investigate the utility of the fractional concentration of exhaled nitric oxide in guiding medical management of asthma in pregnant women which included prospective infant follow-up. This analysis uses a combined data set of the two cohorts to look at the link between maternal asthma and tidal breathing parameters in young infants.1 The authors found that male infants born to mothers with asthma had a lower ratio of the time to peak tidal expiratory flow to total expiratory time (tPTEF/tE%).1 This breathing pattern is compatible with a longer respiratory system time constant and has been shown to be associated with later wheezing in early life2 and asthma up to age 36.3 Low lung function in infancy not only precedes and predicts later respiratory problems it also seems to partly determine …
간세포암종에 대한 간동맥화학색전술후 생존율과 관련된 예후 요인 분석
Authors: 김성우(Sung Woo Kim), 이숭환(Soong hwan Lee), 노병주(Byung Joo Roh), 김종철(Jong Cheol Kim), 박성수(Sung Soo Park), 이동후(Dong Hoo Lee)
Journal: Clinical and Molecular Hepatology (2000)

목적: 간세포암종 환자에서 보다 적극적인 치료법으로서 간동맥화학색전술 후 생존율을 파악하고 예후에 영향을 미치는 인자들을 조사하여 그들의 임상적 의의를 파악하고자 하였다. 대상과 방법: 1986년 2월부터 1999년 11월까지 본원에 입원하여 간세포암종으로 진단받고 간동맥화학색전술을 시행한 241명을 대상으로 후향적으로 분석하였다. Kaplan-Meier법으로 생존율을 조사하고 예후에 영향을 미치는 여러 인자를 선택하여 log-rank test로 단변량 분석을 하였고, Cox proportional hazard model을 이용하여 다변량 분석을 하였다. 결과: 대상환자의 연령은 평균 54.77±9.32세였으며, 남녀 비는 4.7:1이였다. 평균 추적기간은 13.98개월이고, 최장 생존은 101개월이었다. Kaplan-Meier분석 방법에 의한 6개월, 1년, 2년의 누적 생존율은 각각 58.28%, 41.54%, 20.06%이었다. 생존율에 영향을 주는 인자를 단변량 분석한 결과 성별, 간경변증, Child-Pugh 분류, 종양의 유형, 종양의 위치, 종양의 크기, TNM 병기, 종양의 전이유무, 문맥 혈전, 동맥문맥단락, 복수, AFP, protein, albumin, total bilirubin, AST, AST/ALT, alkaline phosphatase, Na 등이 유의한 인자로 나타났다. 이들을 Cox proportional hazard model로 다변량 분석한 결과 종양의 유형, 문맥 혈전, Child-Pugh 분류 등이 중요한 독립된 예후 인자로 나타났다. 결론: 이상의 결과에서 간세포암종 환자들은 동반 간경변의 보상성이 좋고, 문맥 혈전이 없으며 종양의 유형이 단일 결절형이라면, 반복적인 간동맥화학색전술로 비교적 높은 생존율을 보일 것으로 판단되며 조기 발견 치료를 위한 노력이 경주되어야 할 것이다.