tbuckley/cabot-search huggingface dataset:
Abstract 13624: Rates of Depression, Anxiety and Stress in Parents of Children With Congenital Heart Disease Using the DASS
Authors: Brian Lee, rohit S loomba
Journal: Circulation (2021)

Introduction: There have been many studies investigating the rate of mental health disorders for caregivers of children with congenital heart disease (CHD) but the types and timing of evaluation vary. The Cardiac Neurodevelopmental Outcome Collaborative recommends using the Depression Anxiety Stress Scale (DASS) to evaluate parents between 6-36 months of age. The DASS is a self-completed questionnaire that evaluates for depression, anxiety and stress. There has not been a study investigating the use of DASS in parents of children with CHD. Hypothesis: Our hypothesis was that DASS scores would peak initially and improve with time. Methods: This study was a single centered, retrospective review from January 1, 2018 to June 1, 2020. Eligible subjects were parents of CHD patients seen in our Neurodevelopmental clinic who completed the DASS. Demographic data, clinical history of the child and DASS scores were recorded. Cox-regression analysis was conducted using a composite end point of having an abnormal score in any of the three DASS domains, depression, anxiety or stress. Data for mothers and fathers were analyzed separately. Results: 273 mothers and 139 fathers were enrolled. For mothers, elevated scores in each domain were increased at the 12 and 24 months appointments. For fathers, scores for each domain were elevated initially, followed by a decrease before peaking later on. Paternal scores for depression were increased at 36 months and paternal scores for anxiety and stress were increased at 30 months. Increased length of stay for the index surgery was associated with an abnormal DASS score for mothers (B 0.02, p&lt; 0.01) and fathers (B 0.01, p=0.04). Being in a relationship with the father (B -0.8, p&lt;0.01) was associated with freedom of an abnormal DASS score for mothers. Conclusions: Abnormal DASS scores peak at different time points for mothers and fathers. These time points may be critical time points to offer social support for parents. In addition, increased length of stay for the child’s index surgery and the parents being in a relationship are important factors in the development of mental distress in parents.
Abstract 11653: Intravascular Targeted Photoactivation Guided by Optical Coherence Tomography-Near Infrared Fluorescence (OCT-NIRF) Imaging Promotes Stabilization of Atherosclerotic Plaques
Authors: Joon Song, Yeon Hoon Kim, Jae Won Ahn, Hyeong Soo Nam, JIN HYUK KIM, Hyun Jung Kim, Ryeong Hyun Kim, Dong Kang, Ye Hee Park, Jeonggeun Song, Kyeongsoon Park, Hongki Yoo, Kim Jin Won
Journal: Circulation (2021)

Introduction and Hypothesis: Photoactivation has emerged as an innovative therapeutic strategy for coronary high-risk plaque without metallic remnants, however, limited targetable ability of photoactivator and lack of imaging guidance hinders its application to clinics. To solve these unmet needs, we developed intravascular photoactivation strategy guided by dual-modal OCT-NIRF structural-molecular imaging using a novel theranostic NIRF-emitting photoactivator. Methods and Results: Photoactivatable NIRF-emitting theranostic agent targeting scavenger receptors on macrophages was newly synthesized. The intravascular photoactivation system based on fiber type cylindrical diffuser was newly fabricated for the therapeutic light delivery to the plaques. Forty-eight hours after intravenous injection of scale-up NIRF-emitting photoactivator (equivalent Ce6 dose of 2 mg/kg), OCT-NIRF imaging was able to exactly identify the highly inflamed targets in OCT-delineated plaques of rabbit arteries. Two weeks after therapeutic light irradiation through the catheter to the NIRF enhanced macrophages, the inflammatory NIRF signals of targeted atheroma markedly decreased as compared to the controls (Figure). By comprehensive immunofluorescence analysis, photoactivation produced a prominent increase in macrophage-associated apoptotic bodies and also induced autophagy with an enhanced efferocytosis, resulting in stabilization of the atheroma. Conclusions: Intravascular photoactivation using targeted NIRF emitting photosensitizer could stabilize the inflamed plaque under the guidance of OCT-NIRF imaging. This imaging guided therapeutic innovation will be a promising theranostic strategy for the high-risk coronary plaques.
Abstract 11231: Rethinking the Disconnect in Patient Outreach: Key Considerations in Addressing Racial Disparities in Hypertension
Authors: Sandra Au, Xu Katie, Irene Jonathan, Dakota Douglas, Evan M Murray, Unique Whitehurst, Daniel Tounsel, Holly Biola, Bradi B Granger
Journal: Circulation (2021)

Background: Disparities in hypertension and cardiovascular outcomes among Black men in the US are influenced by social determinants of health (SDOH) and systemic inequity. Self-measured blood pressure (SMBP) monitoring programs may be an efficacious strategy to combat these disparities in the community setting. Leveraging the advantages of SMBP, however, requires improved understanding of barriers to engagement in this population. Methods: A total of 258 Black male patients of a Federally Qualified Health Center, with severe hypertension ( &gt; 160mm Hg systolic or &gt; 100mm Hg diastolic) were eligible. Patients were called using the phone number(s) in the electronic health record (EHR), and callers documented brief summaries of the call. At least 3 attempts were made to offer a free BP cuff, and provide longitudinal SMBP education and heart-healthy lifestyle counseling. NVivo was used for coding and content analysis, employing mixed inductive and deductive approaches to identify barriers to engagement. Coding structure included ‘communication’ and ‘engagement’, stratified by positive and negative attributes. Results: Analysis of initial outreach data (n=172) highlighted themes of unfavorable engagement to include excessive burden from competing health priorities and socioeconomic stress, and communication themes included unreliable phone numbers in the EHR hindering contact, and skepticism/mistrust of the caller by those patients reached. (Table). Conclusion: Optimizing engagement in SMBP programs to address hypertension disparities remains challenging, however improved SDOH screening and resource connection, system practices in EHR integrity, and understanding of patient mistrust of the health system may be key considerations. Ongoing thematic analyses on sustained SMBP skill-building and patient trust in care navigation may provide further insight on strategies to improve racial disparities in cardiovascular health outcomes.
Abstract 12425: Troponin Kinetics and Cardiovascular Events in Patients With Myocarditis After Immune Checkpoint Inhibitors Use
Authors: Thiago Silva, Zsofia Drobni, Amna Zafar, Carlos Gongora, Leyre Zubiri, Daniel Zlotoff, Jingyi Gong, Charlotte Lee, Sarah Hartmann, Hannah Gilman, Alexandra-Chloe Villani, Ryan Sullivan, Kerry Reynolds, Lili Zhang, Anju Nohria, Tomas Neilan
Journal: Circulation (2021)

Introduction: Immune checkpoint inhibitors (ICI) leverage the immune system against cancer. Myocarditis is an uncommon but serious complication of ICI use. There are limited data on the utility of serum troponin levels in this setting. We assessed whether troponin values measured at different time points during admission have prognostic significance. Hypothesis: Baseline (admission), peak and inter-value trajectory (slope) of high-sensitivity cardiac Troponin T (hs-cTnT) levels predict cardiovascular events in ICI-myocarditis. Methods: A retrospective cohort of all patients admitted with ICI-myocarditis in a single integrated academic network was performed. Troponin measures were included from the 24 hours preceding admission until time of event/censoring. Optimal threshold values for baseline, peak hs-cTnT, and slope changes were obtained through ROC curves (Youden index). Major adverse cardiac event (MACE) was defined as a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: A total of 980 hs-cTnT measures from 63 patients were identified (figure 1). Over a median follow-up period of 16 days, 24 events occurred. A higher baseline (&gt;1248 ng/l, HR: 3.75, 95% CI: 1.57–9.00, p= 0.003) (figure 2) and peak hs-cTnT (&gt;1959 ng/l, HR: 3.66, 95% CI: 1.49–8.98, p= 0.01) were associated with MACE adjusted for age and left ventricular ejection fraction (LVEF). Additional optimal threshold hs-cTnT values based on LVEF were also identified. For those with an LVEF &lt; 50%, a baseline value &gt;265 ng/l (HR: 4.9, 95% CI: 1.5-15.8, p&lt; 0.01) and for those with an LVEF &gt;50%, a baseline value &gt;780 ng/l (HR: 3.6, 95% CI: 1.03-12.4, p=0.04) were associated with MACE. The hs-cTnT trajectory slope changes (baseline-to-peak, slope in first 24 hours, slope in first 48 hours) were not associated with events. Conclusion: Baseline and peak hs-cTnT during admission for ICI-related myocarditis associated with MACE. Cutoff values may vary by LVEF strata.
Abstract 13413: Obstructive Sleep Apnea Increases Costs but Not Length of Stay in First Instance Heart Failure Hospitalizations
Authors: Ashvin Zachariah, Joshua Larned
Journal: Circulation (2021)

Introduction: Sleep-related breathing disorders have a high prevalence in the heart failure (HF) population. Although causality has not explicitly been established, obstructive sleep apnea (OSA) appears to increase risk for the development and progression of heart failure. A single-center study by Sommerfeld et. al. reported OSA as the strongest predictor for hospital readmission among HF patients. The goal of this study was to employ the use of a nationwide database to evaluate the possible effect of OSA on length of stay and costs associated with HF hospitalization. Hypothesis: Patients with history of OSA admitted for HF will have higher costs and longer length of stay associated with hospitalization, compared to controls without history of OSA hospitalized for HF. Methods: We conducted a retrospective matched cohort analysis using records from the Medicare Standard Analytical Files in the PearlDiver database. Using the International Classification of Diseases, ninth revision (ICD-9) codes, we queried for patients with history of obstructive sleep apnea hospitalized for heart failure from 2005-2014. We matched to controls (without history of OSA) based on age, gender, and Elixhauser Comorbidity Index. We sought to compare length of stay (LOS) and costs attributed to first-instance HF exacerbation. Costs were reported as the average amount paid per patient, as this more accurately reflects cost rather than amount billed by the hospital. Results: Matching yielded two cohorts of 464,620 patients in each group. Average amount paid per patient in the OSA group was greater by a statistically significant amount when compared to the group without OSA hospitalized for HF ($15,447 vs $9,555, p&lt;0.0001). Length of stay was however noted to be shorter in the OSA cohort compared to the non-OSA cohort (5.7 days vs 8.1 days, p&lt;0.0001). Conclusions: Patients with OSA who were hospitalized for HF suffered higher cost of hospitalization, although length of stay was not impacted. The effect on costs is in line with existing literature regarding the relationship between OSA and HF. Possible reasons for decreased LOS in the sleep apnea cohort include more rapid/aggressive treatment course, respiratory support, or death leading to reduction of LOS.
Abstract 10479: Genome Wide Association Study For Acute Kidney Injury In Patients Undergoing Off-pump Coronary Artery Bypass Graft Surgery
Authors: Muralidhar Kanchi, Ramesh Menon, Sangamitra Mishra, Ramprasad Vedam
Journal: Circulation (2021)

Introduction: In this study, we evaluated the genetic predisposition to AKI using genome-wide association study (GWAS) in patients undergoing elective off-pump-CABG (OP-CABG). Methods: Patients of South Asian ancestry were categorized into four cohorts as follows: (A) patients with normal renal function undergoing OP-CABG (eGFR&gt;60ml/min/m2) (n=754; AKI - 81, Non-AKI-673); (B) patients with renal dysfunction (eGFR&lt;60ml/min/m2; not needing dialysis) undergoing OP-CABG (n=263; AKI-169, non-AKI-89); (C) patients with renal dysfunction with no symptomatic/known heart disease (n=92); (D) age-matched healthy control population (with normal kidney function, without symptomatic/known heart disease) (n=826). Renal function was considered to be normal, if the serum creatinine was less than 1.3mg% and/or estimated glomerular filtration rate was greater than 60ml/min/1.7 m 2 . Genotyping was performed using Infinium Global Screening Array-24 v3.0 BeadChip from Illumina, which included 6,54,027 markers. GWAS analysis was performed using age, genders and top10 principal components as covariates using logistic regression using PLINK 2.0. Postoperative AKI was defined based on Kidney Disease Improving Global Outcomes guidelines. Results: There were 754 participants with good renal function undergoing OP-CABG; among them, 81 subjects developed AKI postoperatively. The GWAS analysis revealed 607 markers with a suggestive significance p-value threshold of 1e-4. A modest signal was observed on chromosome 11 region, covering genes such as COX8A, NAA40, RCOR. The gene-based test in FUMA annotation revealed genes, MARCOD2, CNTN4, MAGI2 etc. as top hits. However, none of the markers remained significant after multiple testing corrections using Bonferroni and Benjamini-Hochberg. Conclusions: The GWAS revealed an association signal on chromosome 11, which is suggestive and needs to be pursued further in a larger sample set.
Abstract 14353: Feminizing Hormone Therapy and Subclinical Indicators of CVD Risk in Transgender Women With HIV
Authors: Nicholas Fonseca Nogueira, Ana S Salazar, MA Ruixuan, Natalie Aguilar, Alex Gonzalez, Valeria Porras, Meela Parker, Alejandro Mantero, Barry E Hurwitz, Maria L Alcaide, Claudia Martinez
Journal: Circulation (2021)

Introduction: Transgender women (TW) are at higher risk of HIV infection compared to cisgender groups and HIV is associated with accelerated cardiovascular disease (CVD) complications. A high proportion of TW use feminizing hormone therapy (FHT), particularly estrogen. However, there is a scarcity of data about the cardiovascular impact of FHT in TW with HIV (TWH). Subclinical indicators of CVD risk, arterial stiffness and endothelial progenitor cells colony forming units (EPC-CFUs), were examined in TWH with and without FHT. Hypothesis: Estrogen use in FHT reduces arterial stiffness and induces EPC proliferation. Methods: This pilot included adults 20-60 years old, identifying as TW, with a documented HIV-1 diagnosis, stable ART ≥ 6 months, and without history of CVD. Sociodemographic questionnaire was completed prior to an in-person blood collection and applanation tonometry assessment. Groups were stratified by estrogen levels (normal: 1-82pg/ml vs high: &gt;82pg/ml) and relationships with EPC-CFUs and arterial stiffness were examined using t-test and Pearson’s correlation. Results: Median age was 42 yrs. (IQR 34-52) with mean glucose 105.70 mg/dl (± 58.07), triglycerides 138.52 mg/dl (± 69.61), LDL 82.38 mg/dl (± 35.01), and CRP 3.45 mg/L (±3.57). TW with high (n=5) and normal (n=12) estrogen levels had similar values in EPC-CFUs counts (p=0.99), central augmentation index (cAIx; p=0.27), carotid to radial pulse wave velocity (CR-PWV; p=0.20), and carotid to femoral PWV (CF-PWV; p=0.87). A positive trend appeared in log-transformed estradiol across cAIx (r=0.32, p=0.21); negative trends in CR-PWV (r=-0.11, p=0.70) and CF-PWV (r=-0.19, p=0.48), and no relationship with EPC-CFUs (r=0.05, p=0.86). There were non-significant negative weak trends between EPC-CFUs and cAIx (r=-0.32, p=0.21), CR-PWV (r=-0.2, p=0.48), and CF-PWV (r =-0.29, p=0.27). Conclusions: An inverse correlation between EPC-CFUs and arterial stiffness measurements was observed. Considering these test modalities have a strong correlative potential with CVD risk, FHT does not appear to confer higher CVD risk through these mechanisms. Further research to understand the mechanisms underlying HIV related CVD pathophysiology is critically needed especially in TWH.
Abstract 10329: Health Status Outcomes of Percutaneous Coronary Intervention and Coronary Artery Bypass Grating in Stable Coronary Disease: Secondary Analysis of the ISCHEMIA Trial
Authors: Chetan Huded, John Spertus, Philip Jones, Daniel B Mark, Sripal Bangalore, Gregg W Stone, T Bruce B Ferguson, David O Williams, William E Boden, Harmony Reynolds, Judith S Hochman, David J Maron
Journal: Circulation (2021)

Introduction: In ISCHEMIA, participants (pts) with stable CAD and moderate/severe ischemia had better angina-related health status (symptoms, function, and quality of life) following an initial invasive strategy (INV), which could have been either PCI or CABG. In this analysis we describe the health status outcomes of INV pts, stratified by revascularization with PCI or CABG. Methods: We performed a descriptive analysis of unadjusted health status outcomes due to the non-randomized selection of PCI vs. CABG with inherent differences in groups. In 4617 out of 5179 pts in the trial, health status was assessed at baseline, 1.5 mos, 3 mos, 6 mos, and every 6 mos thereafter. The Seattle Angina Questionnaire (SAQ) summary score (SS) was the primary outcome, with higher scores indicating better health status. Results: Among 2295 INV pts with health status assessments,1257 underwent PCI and 350 CABG, while the remaining 688 were not revascularized within 3 mos. Initial conservative (CON) strategy was assigned in 2322 pts. Baseline SAQ SS was 72.1±19.2 in PCI, 73.4±17.8 in CABG, and 74.8±18.8 in CON groups. At 3 mos, SAQ SS was highest in PCI-treated pts (PCI 86.7±14.1, CABG 84.3±15.8, CON 81.8±17.0). Longer-term SAQ SS was consistently highest in CABG-treated pts at 1 year (Figure, PCI 87.5±14.8, CABG 89.8±13.2, CON 84.2±16.1), and 4 years (PCI 88.1±15.0, CABG 91.6±13.8, CON 86.9±15.4). Freedom from angina at 4 years was achieved in 75.9% of those treated with PCI, 82.8% with CABG, and 70.7% of CON pts. Conclusions: In this unadjusted non-randomized analysis from ISCHEMIA, those selected for PCI had the most favorable short-term health status, and those selected for CABG had the most favorable long-term health status. A fully risk-adjusted analysis is forthcoming to account for differences in patient selection and to facilitate between group comparisons.
A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes
Authors: Mahmoud I. Abdel-Aziz, Susanne J.H. Vijverberg, Anne H. Neerincx, Paul Brinkman, Ariane H. Wagener, John H. Riley, Ana R. Sousa, Stewart Bates, Scott S. Wagers, Bertrand De Meulder, Charles Auffray, Åsa M. Wheelock, Aruna T. Bansal, Massimo Caruso, Pascal Chanez, Mohib Uddin, Julie Corfield, Ildiko Horvath, Norbert Krug, Jacek Musial, Kai Sun, Dominick E. Shaw, Thomas Sandström, Paolo Montuschi, Stephen J. Fowler, René Lutter, Ratko Djukanovic, Peter Howarth, Paul Skipp, Marek Sanak, Ian M. Adcock, Kian Fan Chung, Peter J. Sterk, Aletta D. Kraneveld, Anke H. Maitland-van der Zee
Journal: European Respiratory Journal (2021)

<b>A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.</b>https://bit.ly/3FWuJqS
Abstract 12625: Troponin I3 A157V Homozygous Mutation Induces Diastolic Dysfunction
Authors: Jason M Duran, Paul Bushway, Maria Manso, Yusu Gu, Yoshitake Cho, Joshua Fong, Robert S Ross, Eric D Adler
Journal: Circulation (2021)

Introduction: Previous studies describe a morbid restrictive cardiomyopathy in patients with substitution of alanine with valine at amino acid 157 (A157V) within the calcium-binding domain of the inhibitory subunit of cardiac troponin (TNNI3); yet the precise mechanism of disease remains unknown. Hypothesis: A murine model of A157V TNNI3 would recapitulate key features of disease and serve as a model of cardiac restriction. Methods: TNNI3 A157V mice were generated using a cloning-free CRISPR/Cas-9 system to introduce a point mutation (c.470c&gt;T) resulting in missense substitution of valine for alanine at amino acid 157 in Exon 7 of TNNI3 . Heterozygous and homozygous mice were generated in a C57BL/6 background. At one year of age animals had echocardiography and electrocardiogram (ECG) performed, followed by invasive hemodynamics. Mice were then sacrificed for cardiac morphometry and hearts were fixed and embedded for histology. TNNI3 A157V adeno-associated virus-9 (AAV-9) construct was generated and injected retro-orbitally into 8-12 week old wild-type mice. Results: Serial echocardiography at 2, 4, 6 and 12 months of age demonstrated normal wall thickness, ejection fraction and strain. No differences were noted in cardiac arrhythmias assessed using ECG. Hemodynamics performed at 15 months of age demonstrated significantly reduced minimum derivative of pressure/time (dP/dT) and Tau in response to dobutamine in TNNI3 A157V mice v. controls. No significant differences between genotypes were detected in cardiac morphometry (heart weight and heart weight normalized to body weight or tibia length), myocyte cross sectional area measured on trichrome-stained heart sections, or myocardial oxygen consumption rate measured by oroboros. Mice injected with TNNI3 A157V AAV-9 demonstrated expression of the mutant TNNI3 construct on western analysis and immunohistochemistry. Conclusions: We have developed a novel mouse model in which substitution of valine for alanine at amino acid 157 in TNNI3 induces diastolic dysfunction despite the absence of cardiac hypertrophy that recapitulates key features of human disease and can serve as a platform for further mechanistic and translational studies.
LC3-Associated Phagocytosis in Bone Marrow Macrophages Suppresses AML Progression through Mitochondrial DAMP Induced Sting Activation
Authors: Jamie A Moore, Jayna J Mistry, Charlotte Hellmich, Rebecca H Horton, Edyta Wojtowicz, Aisha Jibril, Tom Wileman, Matthew Jefferson, Naiara Beraza, Kristian M Bowles, Stuart A Rushworth
Journal: Blood (2021)
SETD2はEZH2とAMPKシグナル伝達経路の統合により前立腺癌転移を制限する【JST・京大機械翻訳】
Authors: Yuan Huairui, Han Ying, Wang Xuege, Li Ni, Liu Qiuli, Yin Yuye, Wang Hanling, Pan Lulu, Li Li, Song Kun, Qiu Tong, Pan Qiang, Chen Qilong, Zhang Guoying, Zang Yi, Tan Minjia, Zhang Jian, Li Qintong, Wang Xiaoming, Jiang Jun, Qin Jun
Journal: Cancer Cell (2020)