tbuckley/cabot-search huggingface dataset:
Abstract 12308: Stress-Related Neural Activity Predicts Subsequent Heart Failure
Authors: Charbel Gharios, Shady Abohashem, Hadil Zureigat, Taimur Abbasi, Kenechukwu Mezue, Alexander Cardeiro, Michael Osborne, Ahmed A Tawakol
Journal: Circulation (2021)

Introduction: Higher stress-related neural activity (SNA) associates with subsequent risk of cardiovascular disease. We investigated whether heightened SNA predicts subsequent heart failure (HF). Methods: Individuals (N=2,112; median age 69 years; 48% female) enrolled in the Mass General Brigham Biobank without baseline HF who underwent clinically indicated 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging were retrospectively identified. SNA was measured using validated methods, as amygdalar metabolic activity corrected for regulatory brain (i.e., medial prefrontal cortical) activity. Subsequent development of HF was determined via medical record review using International Classification of Diseases 10 (ICD-10) codes. Survival analyses using Cox and Kaplan-Meier models were performed. Results: Over a median follow-up period of 3.9 years after imaging, 210 individuals developed HF (57 systolic, 93 diastolic). Individuals with subsequent HF (versus no HF) had higher baseline SNA (mean Z-score 0.19 ± 1.07 versus -0.08 ± 0.99; p=0.005, adjusted for age and sex). SNA associated with subsequent HF when divided into tertiles (Figure) and as a continuous measure (standardized HR [95% CI]: 1.38 [1.11-1.70], p=0.003, adjusted for age, sex, hypertension, hyperlipidemia, diabetes and smoking). The association between SNA and HF subtype was stronger for diastolic HF (1.37 [1.00-1.88], p=0.047) than for systolic HF (1.14 [0.87-1.49], p=0.348) in models additionally adjusting for history of myocardial infarction. Conclusion: In this retrospective study of individuals with clinical FDG-PET/CT imaging, higher SNA predicted subsequent HF with a somewhat stronger association for diastolic HF. Understanding the link between heightened stress-associated neural activity and subsequent HF may provide important insights into better HF prevention and management strategies.
Abstract 12956: Prediction of True Worsening Renal Failure Which Were Associated With Poor Long-Term Outcome in Patients With Acute Heart Failure. The Importance of Cardiac Biomarkers Based on Cardio Renal Syndrome
Authors: Akihiro Shirakabe, Noritake Hata, Nobuaki Kobayashi, Hirotake Okazaki, Masato Matsushita, Yusaku Shibata, Tomofumi Sawatani, Saori Uchiyama, Kenichi Tani, Kuniya Asai, Wataru Shimizu
Journal: Circulation (2018)

Background: Whether or not the definition of a worsening renal function (WRF) is adequate for the evaluation of acute renal failure in patients with acute heart failure (AHF) is unclear. The biomar...
Abstract 9938: Genetic Architecture and Precision Medicine of Atrial Fibrillation
Authors: Kazuo Miyazawa, Kaoru Ito, Zhaonan Zou, Hiroshi Matsunaga, Satoshi Koyama, Hirotaka IEKI, Kouichi Ozaki, Yoshihiro Onouchi, Shinya Oki, Hiroshi Akazawa, Issei Komuro
Journal: Circulation (2021)

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with increased risks of morbidity and mortality. We performed a large-scale genome-wide association study (GWAS) of 150,272 individuals of Japanese ancestry (9,826 cases and 140,446 controls) and identified five new susceptibility loci including Japanese-specific rare variants associated with the pathogenesis of cardiomyopathy. We then conducted a trans-ancestry meta-analysis of more than 1 million individuals including 77,690 cases and discovered 35 novel loci in total. Using the GWAS result, epigenetic-feature and gene-set analyses revealed the transcriptional landscape of AF, elucidating the underlying biological pathways. Additionally, we created polygenic risk scores (PRS) for AF, where PRS derived from trans-ancestry GWAS surpassed those derived from a single population. The PRS was associated with increased risk of long-term cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients, suggesting that it may play an important role in early detection of subclinical AF or the pathophysiology underlying thromboembolism. Our results provide novel biological and clinical insights into AF genetics and broaden its clinical applications.
Abstract 12172: Relationship Between Increased QTc Risk Score and In-Hospital Mortality
Authors: James E Tisdale, Malinda Tan, C. W Heise, Tyler Gallo, Raymond L Woosley, Corneliu Antonescu, Sheila Gephart, Daniel Malone
Journal: Circulation (2021)

Introduction: Torsades de pointes (TdP) is a life-threatening arrhythmia associated with prolongation of the heart rate-corrected QT (QTc) interval. QTc prolongation is associated with increased mortality. A QTc Risk Score (QTc-RS) advisory has been developed, but the ability of the QTc-RS to predict mortality is unknown. Objective: To evaluate the relationship between a validated QTc-RS and mortality among hospitalized patients. Methods: An advisory incorporating a previously validated QTc-RS was implemented as a clinical decision support tool at 28 inpatient facilities. When an order was initiated for a known QTc-prolonging medication, a QTc-RS (maximum score = 21) was electronically calculated and, if the score was &gt; 11, prescribers received a warning that included patient-specific risk factors. The advisory also provided single click actions for laboratory tests, electrocardiogram orders, cancelling incoming medication orders or discontinuing existing QTc-prolonging medications. Results: Between April and November 2020, there were 144,148 QTc-RS scores calculated. Among the 7923 warnings with a score &gt;11, the majority (51%) had a score of 12, 29% had a score of 13, 12% had a score of 14, and 8% had a score ≥ 15. The most common risk factors were: age &gt; 67 years (66%); sepsis (65%); ≥ 1 QTc-prolonging medication(s) (60%); female (59%); heart failure (34%); serum potassium &lt; 3.5 mEq/L (28%); and a loop diuretic (21%). Among those with a QTc-RS &gt;11, 11.9% (944/7923) expired during the inpatient encounter. The proportion of deaths increased as the risk score increased (Table 1). Relative to individuals with QTc-RS 12-14, the odds ratio for inpatient mortality in those with scores &gt;17 was 3.0 (95% CI:1.7-5.5). Conclusions: An increasing QTc-RS was associated with an increased likelihood of in-hospital mortality
Abstract 10224: What Are the Effects of a Gradual Taste Adaptation Approach in Patients with Heart Failure and Family Caregivers?
Authors: Misook L Chung, Terry A Lennie, Jennifer Miller, Debra K Moser
Journal: Circulation (2021)

Introduction: Adherence to the sodium-restricted diet (SRD) remains poor due to multiple barriers. We developed a dyadic intervention, a gradual taste adaptation to SRD to improve adherence to the SRD by overcoming sensory and family barriers. The purpose was to determine the efficacy of the gradual taste adaptation approach on dietary sodium intake, preferences for salty food, and enjoyment of SRD. Hypothesis: There will be a greater decline in dietary sodium intake and preference for salty food and an increase in the enjoyment of SRD at 4 and 12 months in dyads receiving the intervention compared to the dyads receiving usual care. Methods: A total of 158 patients with HF and caregiver dyads were randomly assigned to either the intervention (n=79 dyads) or a usual care control group (n=79 dyads). The 12-week intervention was delivered remotely using video conferencing. Outcomes were measured at 4 and 12 months for dyads, including dietary sodium intake using 24-hour urinary sodium excretion and self-reports on preference for salty food and enjoyment of SRD. Repeated measures ANOVA was used to determine intervention effects. Results: There was no difference in patients’ dietary sodium intake at baseline between the groups. Compared to the control group, patients in intervention significantly reduced dietary sodium intake and greater enjoyment of SRD. Sodium was reduced by 1,144 mg sodium at 4 months and 960 mg at 12 months while ratings of enjoyment of SRD increased at 4 and at 12 months (Figure 1). The intervention was not effective in decreasing the preference for salty food. There were also no significant intervention outcomes effects for caregivers. Conclusions: An innovative approach of gradual taste adaptation demonstrated significant short and long-term effects on reducing dietary sodium intake and enjoyment of SRD for patients. The intervention has the potential to expand the application to individuals who need to follow a SRD.
Abstract 12860: Effects of Marine Omega-3 and Vitamin D Supplementation on Circulating Biomarkers of Glucose-Insulin Homeostasis and Incident Cardiovascular Disease in the Vitamin D and Omega-3 Trial (VITAL)
Authors: Frank Qian, Yanjun Guo, Heike Gibson, Natalya Gomelskaya, Yanyan Liu, Olga Demler, Nancy R Cook, I-min M Lee, Julie E Buring, Julia A Larsen, Jennifer Boring, Michael J Mcphaul, Joann E Manson, Aruna D Pradhan, Samia Mora
Journal: Circulation (2021)

Introduction: Dysglycemia and insulin resistance increase cardiovascular disease (CVD) risk. Associations between specific glucose-insulin biomarkers and CVD have been inconsistent. Hypothesis: We hypothesized that higher insulin, C-peptide, insulin resistance score (IRS), and HbA1c are associated with incident CVD and coronary heart disease (CHD) events and that both vitamin D and omega-3 fatty acids (n-3 FA) would improve these biomarkers and attenuate their risks with CVD. Methods: VITAL (NCT01169259) was a 2x2 factorial design RCT testing vitamin D (cholecalciferol, 2000 IU/d) and n-3 FA (EPA+DHA, 1 g/d) for the primary prevention of CVD. Incident CVD cases [non-fatal myocardial infarction (MI), non-fatal stroke, or CV death] were matched 1:1 on age and sex to healthy controls (n=715 CVD pairs including 423 CHD [MI, revascularization, CHD death] pairs). Conditional logistic regression adjusting for demographics, CV risk factors, and randomized treatment was used to assess the adjusted odds ratio (aOR) and 95% CI between baseline levels of insulin, C-peptide, IRS (Insulinх0.0265+C-peptideх0.00511+Creatinineх-3.2641), and HbA1c with risk of CVD and CHD events. In control participants, we examined the randomized effects of vitamin D or n-3 FA on changes in these biomarkers at 1- or 2-years follow-up. Results: Mean age of participants was 71 years, approximately 42% were female, and 12% were African American. Baseline insulin, C-peptide, and IRS were not associated with CVD ( Figure 1 ). HbA1c was associated with CVD risk, aOR (95% CI) per SD increment, 1.17 (1.01, 1.38). Of the 4 biomarkers, only IRS was associated with CHD risk, aOR (95% CI): 1.22 (1.01, 1.46). Randomization to vitamin D or n-3 FA did not modify levels of these biomarkers or their associations. Conclusions: HbA1c was significantly associated with CVD risk, whereas IRS was associated with CHD risk. Neither vitamin D nor n-3 FA appreciably modified these biomarker levels or their risk associations.
Real-World Use of FLT3 Tyrosine Kinase Inhibitors in Patients with Relapsed/Refractory <i>FLT3</i> mutation-Positive Acute Myeloid Leukemia in the United States
Authors: David L. Grinblatt, Wei Han, David Nimke, Qi Feng, Loretta Sullivan, Bhavik J. Pandya
Journal: Blood (2021)
Abstract 12503: A Randomized Controlled Trial of Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease
Authors: Andrea Z Beaton, Emmy Okello, Joselyn Rwebembera, Anneke Grobler, Daniel Engelman, Jonathan Carapetis, Lesley Canales, ALYSSA DEWYER, Peter Lwabi, Mariana Mirabel, Ana O Mocumbi, Meghna Murali, miriam nakitto, Emma Ndagire, Maria Nunes, Isaac Omara, Rachel Sarnacki, Amy Scheel, Nigel Wilson, Meghan Zimmerman, Liesl Zuhlke, Ganesan Karthikeyan, Craig A Sable, Andrew Steer
Journal: Circulation (2021)

Introduction: Rheumatic heart disease affects 40.5 million people globally and causes 306,000 annual deaths. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. However, it is unknown if secondary antibiotic prophylaxis is effective at preventing progression of latent rheumatic heart disease. Methods: We conducted a randomized controlled trial of secondary antibiotic prophylaxis among Ugandan children (5-17 years) with latent rheumatic heart disease. We randomized children to receive either 4-weekly injections of benzathine benzylpenicillin G or no prophylaxis. All children underwent echocardiography at baseline and 2 years after randomization. Changes from baseline were adjudicated by a panel blinded to treatment allocation. The primary outcome was rheumatic heart disease progression. The trial was registered at ClinicalTrials.org (NCT03346525) on November 17, 2017. Results: 818 were included in the modified intention to treat analysis and 799 participants (97.7%) reached study completion. Three participants in the prophylaxis group (0.8%) demonstrated echocardiographic progression, compared to 33 (8.3%) in the control group (risk difference -7.5%, 95%CI, -10.2 to -4.7, p&lt;0.001). The number of children with latent rheumatic heart disease needed to receive prophylaxis to prevent one child from developing progression was 13 (95%CI, 10 to 21). There were 2 serious adverse events in the prophylaxis group, including one episode of a mild anaphylactic reaction (0.01% of all treatment doses). Conclusions: Secondary antibiotic prophylaxis reduces the risk of latent rheumatic heart disease progression at 2 years. These data provide new information for our understanding of the role of screening for latent rheumatic heart disease. Further research is needed before the implementation of population-level screening can be recommended.
A qualitative interview study to explore adolescents’ experience of alopecia areata and the content validity of sign/symptom patient‐reported outcome measures*
Authors: Jake Macey, Helen Kitchen, Natalie V.J. Aldhouse, Emily Edson‐Heredia, Russel Burge, Apurva Prakash, Brett A. King, Natasha Mesinkovska
Journal: British Journal of Dermatology (2021)

The content validity (appropriateness and acceptability) of patient-reported outcome (PRO) measures for scalp hair loss, eyebrow loss, eyelash loss, nail damage and eye irritation has been demonstrated in adults with alopecia areata (AA) but not adolescents.To explore the content validity of the suite of AA PRO measures and accompanying photoguides in an adolescent sample.Semi-structured, 90-min, combined concept elicitation and cognitive interviews were conducted face-to-face with adolescents who experienced ≥ 50% AA-related scalp hair loss. Transcripts underwent thematic and framework analysis.Eleven adolescents (aged 12-17 years, 55% female, 45% nonwhite) diagnosed with AA for 5·9 years (mean) participated. Participants had 69·6% scalp hair (mean) and current eyebrow (82%) and/or eyelash loss (82%) and/or nail involvement (36%). Adolescents reported scalp, eyebrow and eyelash hair loss as their top three most bothersome signs/symptoms. Despite mostly accepting their AA, impacts related to visible areas of hair loss were prominent. Participants demonstrated good understanding and appropriate use of the PRO measures, and advocated including hair loss percentages alongside descriptive categories in the Scalp Hair Assessment PRO™. Results confirmed treatment success thresholds established with adults: achievement of ≤ 20% scalp hair loss, no/minimal eyebrow and eyelash loss, no/a little nail damage and eye irritation (PRO measure categories 0 or 1).The Scalp Hair Assessment PRO™, PRO Measure for Eyebrows™, PRO Measure for Eyelashes™, PRO Measure for Nail Appearance™ and PRO Measure for Eye Irritation™ and accompanying photoguides are fit-for-purpose self-reported measures of AA signs/symptoms that are impactful to adolescents with AA.
Abstract 11297: Longitudinal Lipidomics Profiling of Risk for Hypertension in American Indians: The Strong Heart Study
Authors: Wenjie Zeng, Guanhong Miao, Mingjing Chen, Zhang Ying, Jason Umans, Shelley Cole, Elisa T Lee, Barbara Howard, Oliver Fienhn, Jinying Zhao
Journal: Circulation (2021)

Background: Dyslipidemia is an important risk factor for hypertension (HTN). Routine clinical tests cannot capture all molecular lipid species in blood (i.e., lipidome). Moreover, a longitudinal lipidomic profiling of risk for HTN is still lacking in any racial/ethnic groups. Objective: Identify novel lipid species and lipidomic signatures associated with risk of HTN in American Indians, independent of traditional risk factors (TRFs). Methods: Using an untargeted LC-MS, we repeatedly measured 1,542 lipids in 3,916 fasting plasma samples from 1,958 American Indians attending two clinical examinations (~5.5 years apart) in the SHS. Elastic net was used to select baseline lipids associated with risk of HTN. Longitudinal associations between changes in lipidome and changes in blood pressure measures, e.g., SBP, DBP, mean arterial pressure (MAP), were examined by mixed-effect linear model, adjusting for TRFs and baseline lipids. Multivariate and network analysis was used to identify lipidomic signatures and differentially co-regulated lipid pairs associated with risk of HTN. Results: Of 905 normotensive participants at baseline, 276 developed HTN after 5-year follow-up. After adjusting for TRFs (age, age 2 , sex, center, BMI, smoking, and diabetes), higher baseline levels of 144 lipids (38 known), including glycerophospholipids, glycerolipids, acylcarnitines, sphingolipids, and fatty acids, were significantly associated with increased (HRs:1.03- 2.07) or decreased (HRs: 0.80 - 0.94) risk of HTN. A lipid score comprising 38 baseline lipids significantly improved risk prediction beyond TRFs (ROC increases from 0.678 to 0.725, P&lt;0.001). Longitudinal change in plasma lipidome explains up to 3.2% variability in changes of BP measures. Multivariate and network analysis identified lipidomic signatures and differentially regulated lipid networks associated with risk of HTN. Conclusion: We identified novel molecular lipids and lipidomic signatures associated with risk of HTN, independent of TRFs. If replicated, the newly identified molecular lipids may serve as novel biomarkers for risk stratification and provide therapeutic targets for early intervention tailored to American Indians.
Abstract 11502: Elevations in Proinflammatory Cytokines Il-1β and Il-12 in the Transgenic (mren2)27 Rat: A Clinically-Relevant Animal Model of Metabolic Syndrome
Authors: Nathan P McMullen, Nicholas Contillo, Stacey Wolfe, Fatima Ryalat, Anthony Anzalone, Stephanie Coffman, Christine Tschoe, Debra I DIZ, zhidan xiang, Keyan Peterson, Jack Jestus
Journal: Circulation (2021)

Introduction: Spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of strokes and carries a 40% mortality rate within one month. Neuroinflammation plays a key role in secondary brain injury after ICH and inflammatory pathways may represent important therapeutic targets. A major obstacle in developing novel therapeutics is the lack of a translatable animal model that recapitulates the comorbidities of patient’s that suffer from ICH. Hypertension, diabetes, and obesity are components of the metabolic syndrome often seen in ICH patients, and may modulate the neuroinflammatory response to ICH. Thus, we aimed to characterize peripheral markers of systemic inflammation in a transgenic hypertensive (mRen2)27 rat model of metabolic syndrome. Methods: Serum proinflammatory cytokines IL-1β and IL-12 were measured using ELISA in naïve male and female (mRen2)27 (n=15) and healthy SD rats at 32 weeks of age (n=14). Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. Statistical analyses of group differences were conducted using two-sample t-tests. Results: SBP (mm Hg) was significantly higher in the (mRen2)27 transgenic rats compared to SD rats, in both males (195 ± 4, n=8 vs. 125 ± 4, n=6, p&lt; 0.05) and females (183±7, n=7 vs. 114±10, n=8, p&lt; 0.05). Female (mRen2)27 rats had significantly higher serum concentrations (pg/mL) of IL-12 (1073±47, n=7 vs. 438±101, n=8, p&lt; 0.05) and IL-1β (pg/mL) (11±3, n=7;. 4±1 , n=8, p&lt; 0.05). Similarly, male (mRen2)27 rats had significantly higher levels of IL-12 compared to SD rats (825±58 , n=8 v. 582±90 , n=6, p&lt; 0.05). IL-12 levels were higher in mRen female rats compared with males (1073±47, n=7 v. 825±58 , n=8, p&lt; 0.05). Serum levels of IL-1β was not significantly different between male SD and (mRen2)27 rats. Conclusion: Compared to healthy SD rats, the pro-inflammatory cytokines IL-1β and IL-12 are elevated in a clinically-relevant animal model of spontaneous hypertension. These findings simulate human studies that have linked cardiometabolic disease with elevated levels of pro-inflammatory cytokines. Future studies using this animal model will seek to further characterize changes in perihematomal and peripheral levels of proinflammatory and inflammation-resolving cytokines following ICH.
Central Line Associated Bloodstream Infection Rate Among Hematologic Malignant Patients Who Received Antimicrobial Prophylaxis in the Inpatient Setting
Authors: Sujith Abbagoni, Thuy Le, Locke J. Bryan, Mohammad A. H. Mian, Danielle Bradshaw, Ashley D Fox, Anand P Jillella, Chijioke Okereke, Ravindra Kolhe, Natasha M. Savage, Vamsi Kota
Journal: Blood (2021)
Abstract 11825: The Association Between Frailty and Vascular Endothelial Growth Factor Families in Patients With Heart Failure: The PREHOSP-CHF Study
Authors: Moritake Iguchi, Hiromichi Wada, Tsuyoshi Shinozaki, masahiro suzuki, Yoichi Ajiro, Morihiro Matsuda, Akihiro Koike, Tomomi Koizumi, masatoshi shimizu, Yujiro Ono, Takashi Takenaka, Satoru Sakagami, Yukiko Morita, Kazuteru Fujimoto, Kazuya Yonezawa, Kazuro Yoshida, Akiyo Ninomiya, Toshihiro Nakamura, JUNICHI FUNADA, Yutaka Kajikawa, Yoshifumi Oishi, Toru Kato, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2021)

Background: Frailty is a complex clinical syndrome associated with ageing and chronic illness, and is common in heart failure (HF). Vascular endothelial dysfunction including maladaptive angiogenesis and lymphangiogenesis is involved in the pathogenesis of HF, and is also considered to be the causes of frailty. We investigated the association of vascular endothelial growth factor (VEGF) families, central regulators of angiogenesis and lymphangiogenesis, with frailty, and prognostic role of these cytokines in frail HF patients. Methods: We performed a multicenter prospective cohort study to determine the predictive value of VEGF families for prognosis among patients with HF. A total of 1,024 patients (mean age, 75.5 years, 58.7% male) were included in the analyses. Serum levels of VEGF, VEGF-C, VEGF-D, and soluble VEGF receptor-2 (sVEGFR-2) were measured. Frailty was assessed by Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Results: A total of 256 (25.1%) patients had frailty (CFS≥5) at baseline. Frail patients were older, more likely female, and had lower body mass index, higher NYHA class, and higher rates of prior hospitalization for HF, HF with preserved ejection fraction, anemia, cerebrovascular disease, and dementia. N-terminal pro brain natriuretic peptide, high sensitivity troponin I, and high sensitivity C-reactive protein levels were higher in frail patients. During the 2-year follow-up, 211 all cause death occurred. In Kaplan-Maier analysis, frail patients showed significantly higher incidence of all-cause (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.14-5.42). Regarding VEGF families, frail patients had significantly lower levels of sVEGFR-2 and VEGF-C, and higher levels of VEGF-D. Multiple regression analysis revealed that VEGF-C had inverse correlation with CFS (P, 0.03). After adjusting for clinical confounders, a low VEGF-C level was independently associated with all-cause death in frail patients (HR, 0.74; 95%CI, 0.58-0.94 for 1-SD increase), but was not in non-frail patients (HR, 0.87; 95%CI, 0.64-1.14 for 1-SD increase) (P for interaction, 0.09). Conclusions: In HF patients, a low VEGF-C value was associated with frailty and was independent risk for all-cause death in frail patients.