tbuckley/cabot-search huggingface dataset:
Abstract 113: Targeting Receptor-interacting Protein 140 (RIP140) To Modulate Energy Metabolism In The Failing Heart
Authors: Tsunehisa Yamamoto, Kirill Batmanov, Elizabeth Pruzinsky, Yang Xiao, Swapnil V Shewale, Kendra McDaid, Teresa C Leone, Santosh K Maurya, E Douglas D Lewandowski, Daniel P Kelly
Journal: Circulation Research (2021)

During the development of heart failure (HF), the PPAR/ERR complex becomes deactivated resulting in diminished capacity for mitochondrial fatty acid oxidation (FAO) and ATP production leading to an “energy-starved” state that contributes to progression of HF. Receptor-Interacting protein 140 (RIP140) serves as a co-repressor of PPAR/ERR in some extra-cardiac tissues. We hypothesized that inhibition of RIP140 would re-activate PPAR/ERR enhancing capacity for fuel catabolism and ATP production in the failing heart. Heart and skeletal muscle-specific RIP140 knockout mice (strRIP140KO) were resistant to the development of cardiac hypertrophy and diastolic dysfunction in response to chronic pressure overload that mimicked features of HF with preserved ejection fraction (HFpEF). To further evaluate the role of RIP140 in heart, cardiac-specific (cs) RIP140KO mice were generated. 13 C-substrate NMR studies demonstrated that palmitate oxidation and triglyceride turnover rates were significantly accelerated in isolated perfused csRIP140KO hearts. csRIP140KO were subjected to transverse aortic constriction/apical myocardial infarction surgery (TAC/MI), to produce HF with reduced EF (HFrEF). Compared to controls, csRIP140KO exhibited reduced left ventricular remodeling and systolic dysfunction when subjected to TAC/MI. RNA-sequence analysis demonstrated that many genes involved in FAO, branched-chain amino acid catabolism, oxidative phosphorylation, and adult muscle contraction programs were significantly “protected” (less downregulation) by RIP140 deletion in the context of TAC/MI. To identify candidate cardiac RIP140 targets, “CUT&amp;RUN”-sequencing was conducted on cardiomyocytes (CM) from csRIP140KO and controls to identify changes in enhancer regions. Motif analysis of peaks with increased H3K27ac deposition in the csRIP140KO CM identified ERR, PPAR, myocyte enhancer 2 (MEF2), glucocorticoid receptor (GR), and kruppel-like factor (KLF) binding sites. We conclude that RIP140 serves as a global co-repressor of a network of transcription factors that control cardiac energy metabolic and contractile function, and that inhibition of RIP140 could prove to be a novel therapeutic approach for HF.
Dynamic models of stress-smoking responses based on high-frequency sensor data
Authors: Sahar Hojjatinia, Elyse R. Daly, Timothy Hnat, Syed Monowar Hossain, Santosh Kumar, Constantino M. Lagoa, Inbal Nahum-Shani, Shahin Alan Samiei, Bonnie Spring, David E. Conroy
Journal: npj Digital Medicine (2021)

Abstract Self-reports indicate that stress increases the risk for smoking; however, intensive data from sensors can provide a more nuanced understanding of stress in the moments leading up to and following smoking events. Identifying personalized dynamical models of stress-smoking responses can improve characterizations of smoking responses following stress, but techniques used to identify these models require intensive longitudinal data. This study leveraged advances in wearable sensing technology and digital markers of stress and smoking to identify person-specific models of stress and smoking system dynamics by considering stress immediately before, during, and after smoking events. Adult smokers ( n = 45) wore the AutoSense chestband (respiration-inductive plethysmograph, electrocardiogram, accelerometer) with MotionSense (accelerometers, gyroscopes) on each wrist for three days prior to a quit attempt. The odds of minute-level smoking events were regressed on minute-level stress probabilities to identify person-specific dynamic models of smoking responses to stress. Simulated pulse responses to a continuous stress episode revealed a consistent pattern of increased odds of smoking either shortly after the beginning of the simulated stress episode or with a delay, for all participants. This pattern is followed by a dramatic reduction in the probability of smoking thereafter, for about half of the participants (49%). Sensor-detected stress probabilities indicate a vulnerability for smoking that may be used as a tailoring variable for just-in-time interventions to support quit attempts.
Lymphocyte Ratios Progressively Worsen in Non-Survivors of COVID-19
Authors: Adekunle Emmanuel Alagbe, Gisele Audrei Pedroso, Beatriz Benedetti de Oliveira, Edivilson de Costa, Gisélia Aparecida Freire Maia, Bruna Facanali Piellusch, Dulcinéia Martins Albuquerque, Angelica Zaninelli Schreiber, José Luiz Proença Modena, Susan Elisabeth Domingues Costa Jorge, Fernando Ferreira Costa, Maria de Fátima Sonati, Magnun Nueldo Nunes Santos
Journal: Blood (2021)
Abstract 11190: Impact of the Use of Platelet Function Testing to Guide P2Y12 Inhibitor Usage After Percutaneous Coronary Intervention (PCI): Results of a Large Real-World Experience
Authors: Joseph B Muhlestein, Heidi T May, Jeffrey L Anderson, Tami L Bair, Viet T Le, Benjamin D Horne, Stacey Knight, Brian K Whisenant, Kirk U Knowlton
Journal: Circulation (2021)

Background: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains standard treatment for patients undergoing PCI, and clopidogrel remains the most used agent. Many patients (pts) are genetically resistant to clopidogrel and may not receive its full benefit. However, the use of platelet function testing to provide individualized management of P2Y12 inhibitor therapy remains controversial. Therefore, we analyzed the impact of the use of platelet function testing after PCI in a large real-world experience. Methods: We searched Intermountain Healthcare medical records for pts who underwent PCI followed by DAPT. We compared 1-year outcomes (MACE=death, MI, stroke; and repeat revascularization and major bleeding) in those who did, or did not, receive P2Y12 platelet function testing within 90 days. Cox hazard regression analysis was used to determine multivariable hazard ratios. Results: A total of 11,561 pts were included, of which 650 (5.6%) received P2Y12 platelet function testing. Baseline demographics, discharge P2Y12 inhibitor and outcomes are shown in the Table. Conclusion: In this real-world analysis of patients undergoing PCI, a small proportion of the patients received P2Y12 platelet function testing. Platelet function testing was associated with increased utilization of prasugrel or ticagrelor and a statistically lower incidence of 1-year MACE (10.8% vs. 12.4%, adjusted odds ratio = 0.69, p=0.03), with a very low incidence of major bleeding. Further investigation regarding the potential benefits of individualized management of DAPT therapy through P2Y12 platelet function testing may be justified.
Biosensors and Point‐of‐Care Devices for Bacterial Detection: Rapid Diagnostics Informing Antibiotic Therapy
Authors: Ashna Gopal, Li Yan, Saima Kashif, Tasnim Munshi, Vellaisamy A. L. Roy, Nicolas H. Voelcker, Xianfeng Chen
Journal: Advanced Healthcare Materials (2021)

Abstract With an exponential rise in antimicrobial resistance and stagnant antibiotic development pipeline, there is, more than ever, a crucial need to optimize current infection therapy approaches. One of the most important stages in this process requires rapid and effective identification of pathogenic bacteria responsible for diseases. Current gold standard techniques of bacterial detection include culture methods, polymerase chain reactions, and immunoassays. However, their use is fraught with downsides with high turnaround time and low accuracy being the most prominent. This imposes great limitations on their eventual application as point‐of‐care devices. Over time, innovative detection techniques have been proposed and developed to curb these drawbacks. In this review, a systematic summary of a range of biosensing platforms is provided with a strong focus on technologies conferring high detection sensitivity and specificity. A thorough analysis is performed and the benefits and drawbacks of each type of biosensor are highlighted, the factors influencing their potential as point‐of‐care devices are discussed, and the authors' insights for their translation from proof‐of‐concept systems into commercial medical devices are provided.
Abstract 9833: Incidence and Predictors of Acute Limb Ischemia in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock - Insight from National Readmission Database
Authors: Carlos Manuel Romero, Irfan Shafi, Aadhar Patil, Maninder Singh, Vladimir Lakhter, Riyaz Bashir
Journal: Circulation (2021)

Introduction: Cardiogenic shock (CS) is an ominous complication of acute myocardial infarction (AMI) that has a mortality as high as 50%. Use of percutaneous mechanical circulatory support devices (MCSD) has increased in attempts to improve outcomes, however its use can be complicated by acute limb ischemia (ALI). In contemporary clinical practice the incidence and predictors of this complication not known. Methods: Patients with index hospitalizations for AMI complicated by CS in the U.S. Nationwide Readmissions Database were identified from January 2016 to December 2018 using International Classification of Diseases (ICD) 10 codes (“I21-”, “I214”, “R57-”). We evaluated the incidence of ALI and its impact on mortality, length of stay, and cost of hospitalization. We used logistic regression analysis to determine independent predictors of ALI in this population. Results: Amongst a total of 61,950 patients had AMI complicated by CS and 922 (1.49%) developed ALI. The rates of ALI increased from 1.29% in 2016 to 1.66% in 2018. Utilization of microaxial MCSD increase from 2.245% in 2016 to 14.03% in 2018. The major predictors of ALI included peripheral arterial disease (PAD) (OR, 7.86, 95% CI 6.34 to 9.76), veno-arterial extracorporeal membrane oxygenation (ECMO-VA) cannulation (OR, 2.96, 95% CI of 1.53 to 5.73), and microaxial MCSD implantation (OR, 2.91, 95% CI of 2.48 to 3.41). (Figure 1). ALI patients had higher mortality (41.37% vs 34.07%, p=&lt;0.001), longer length of stay (17.33 ± 17.92 vs 9.73 ± 11.43) and higher charges (507,955 ± 610,337 vs 249,904 ± 305,385). Conclusions: This nationwide observational study shows that ALI is not an infrequent complication in patients with AMI complicated by CS. This complication is associated with higher mortality, and longer length of stay. Presence of PAD and use of MCSD is associated with significantly higher risk of ALI.
Abstract 13712: Clinical Predictive Tool for Pediatric Cardiac Patients on Extracorporeal Membrane Oxygenation Therapy and Ultrafiltration
Authors: Jennifer Sedler, Scott M Sutherland, vamsi V yarlagadda, Ozzie Jahadi, Amanda M Uber, David Kwiatkowski
Journal: Circulation (2021)

Introduction: Fluid overload is common among pediatric cardiac patients receiving ECMO. It is often treated with in-line ultrafiltration (UF) with some patients progressing to continuous renal replacement therapy (CRRT). We assessed whether requiring CRRT was associated with increased morbidity and mortality compared to UF alone. Additionally, we evaluated characteristics associated with the progression from UF to CRRT to create a clinical decision support tool to help identify patients likely to require CRRT. Hypothesis: Pediatric cardiac patients on ECMO who require CRRT have increased morbidity and mortality compared to UF alone and can be identified at the time UF is initiated. Methods: Retrospective chart review of patients age ≤18 years treated with ECMO from 1/14-12/19 at a single quaternary care cardiac ICU. Bivariate comparisons using Chi-square or Fisher’s Exact and Mann-Whitney U tests were used as appropriate. ROC curve was used to create a tool predictive of the need for CRRT at the time of initiation of UF. Results: Of 131 ECMO patients, 45 (32%) underwent UF and 13 (10%) UF then CRRT. Patients who required CRRT had a higher creatinine and BUN at time of UF initiation (p=0.04 and p=&lt;0.01), longer time on ECMO (p=&lt;0.01), a lower rate of renal recovery (p=0.02), and higher mortality (p=0.01). Using ROC analysis, presence of ≤3 of 7 variables (BUN &gt;20 and GFR &lt;60 at UF initiation, low MAP and RPP 12 hours before initiation of UF, total fluid overload &gt; 10%, daily fluid balance &gt; 50mL/kg in the 24 hours prior to UF initiation, and urine output &lt;1ml/kg/hr in the day prior to UF initiation) had a positive predictive value of 87.5% and negative predictive value of 50.0% for the use of UF alone (AUC 0.801; p=0.002). Conclusions: Pediatric cardiac patients treated with ECMO and UF who require CRRT demonstrate increased morbidity and mortality compared to UF alone. A novel clinical tool may assist in stratifying patients at UF initiation.
Abstract 10950: Real-World Practice of Reperfusion and Revascularization in Patients with St-Segment Elevation Myocardial Infarction in China: Findings from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome Project
Authors: Yiqian Yang, Yongchen Hao, Jun Liu, Na Yang, Yong Huo, Sidney C Smith, Junbo Ge, Gregg C Fonarow, Louise Morgan, Chang-Sheng Ma, Han Yaling, Dong Zhao, Jing Liu
Journal: Circulation (2021)

Introduction: Reperfusion and revascularization therapies are key treatments of ST-segment elevation myocardial infarction (STEMI). However, little is known about the contemporary practice among Chinese patients with STEMI. We aimed to explore the recent practice of reperfusion and revascularization among hospitalized patients with STEMI in China. Methods: A total of 59442 STEMI patients admitted to 159 tertiary hospitals from 30 provinces in China were included in the Improving Care for Cardiovascular Disease in China (CCC)-ACS project from November 2014 to December 2019. The practice of reperfusion and revascularization were assessed. Associations between therapies and in-hospital MACE after 1 day of admission were examined with multivariate Cox regression. Results: Among the 59442 patients, 48897 (82.3%) underwent reperfusion/ revascularization, including 28280 (47.6%) received pPCI within 12 hours, 4649 (7.8%) received pPCI between 12 to 24 hours, 1314 (2.2%) received fibrinolysis alone, and 1751 (2.9%) received pharmaco-invasive strategy. A total of 12903 patients (21.7%) received elective PCI, among which 1486 (11.5%) initially received fibrinolysis. Overall, 37480 patients (63.1%) received reperfusion therapy, including 32929(55.4%) received pPCI, which was 7.2-fold higher than that of fibrinolysis (4551, 7.7%). Among patients receiving fibrinolysis, only 38.4% (1751/4551) received pharmaco-invasive strategy, including 25.2% for pharmaco-invasive PCI and 13.3% for rescue PCI. All PCI strategies, but not fibrinolysis alone, were associated with decreased risk of in-hospital MACE compared with no reperfusion/ revascularization, with the adjusted HR (95% CI) of 0.46(0.38, 0.56) for pPCI&lt;12h, 0.38(0.27, 0.55) for pPCI 12-24h, 0.38(0.16, 0.95) for rescue PCI, 0.27(0.13, 0.59) for pharmaco-invasive PCI, 0.28(0.21, 0.37) for elective PCI, and 0.86(0.57, 1.29) for fibrinolysis alone. Conclusions: Revascularization therapies are widely used in patients with STEMI in China. However, there are notable gaps between guideline recommendations and the clinical practice in terms of timely reperfusion, especially pharmaco-invasive strategy. Early reperfusion therapies should be further strengthened.
Abstract 11988: Trends and Variation of Red Blood Cell Transfusion in Coronary Artery Bypass Grafting in China, 2014-2019
Authors: Danwei Zhang, Jianyu Qu, Zhe Zheng
Journal: Circulation (2021)

Introduction: Red blood cell (RBC) transfusion is common for cardiac surgeries, but safety problems are of concern, and some countries have taken initiatives to limit RBC use. The trends and variation of RBC transfusion in coronary artery bypass grafting (CABG) across China remain unknown, which is essential for quality control on reducing unnecessary transfusion. Hypothesis: To assess recent trends of perioperative RBC transfusion and variation across hospitals and surgeons among patients undergoing elective isolated CABG. Methods: We used data from a national CABG registry with detailed clinical information of patients undergoing elective isolated CABG between 2014 and 2019. The overall and hospital-level rates of perioperative RBC transfusion were described and compared across study years. Hierarchical models were used to make risk-adjusted between-hospital comparison, and to quantify variations derived from hospitals and surgeons. Results: A total of 47554 CABG patients from 72 hospitals were included, with a mean age of 62.7 (standard deviation [SD]: 8.8) years and 75.4% were male. The overall perioperative RBC transfusion rate was 43.9% during the study period. A remarkable decline of RBC transfusion from 51.6% in 2014 to 39.8% in 2019 (P for trend&lt;0.001) was observed, along with the mean hospital-level transfusion rate declined from 56.6% (SD: 26.9%) to 48.1% (SD: 26.1%), and minimal amounts (1-2 units) of RBC declined from 21.9% (SD: 16.3%) to 18.3% (SD: 13.1%). Hospital-level intraoperative transfusion had a similar decreasing amplitude (from 34.8% to 28.7%) with postoperative transfusion (from 38.7% to 32.4%), and the Pearson correlation coefficient was 0.32 (P&lt;0.01). After risk adjustment of patient characteristics, the median odds ratio (MOR) of perioperative RBC transfusion between hospitals was 3.9 in 2014 and reduced to 3.2 in 2019. Furtherly, the relative proportion of variation hospitals explained decreased from 88.0% to 76.0% while increased for surgeons from 12.0% to 24.0%. Conclusions: There is a considerable decline of perioperative RBC transfusion in CABG patients in China during last few years, with notable reductions in between-hospital variation. However, strategies to narrow between-surgeon variation are required.
Abstract 12626: Valvosoft Non-Invasive Ultrasound Therapy (NIUT) in Patients With Severe Symptomatic Aortic Valve Stenosis: First-in-Human Study - Twelve-Months Safety Update
Authors: Emmanuel Messas, Guillaume Goudot, Alexander Ijsselmuiden, Peter den Heijer, Danijela Trifunovic, Petrovic Olga, Etienne Puymirat, Bernard CHOLLEY, Christian Spaulding, Eloi Marijon, Menno van Gameren, Milos Velinovic, Natasa Kovacevic-Kostic, Dusko Terzic, Vladimir Milicevic, Radmila Karan, Mathieu Rémond, Robin Penot, Mathieu Pernot, Mickael Tanter, Benjamin BERTRAND, Rene Spaargaren
Journal: Circulation (2021)

Background: While aortic valve replacements (AVR) generally present favorable outcomes in severe calcific aortic stenosis (CAS), not all patients are eligible for an invasive treatment.Cardiawave © developed a novel non-invasive ultrasound therapy (NIUT) device, Valvosoft, to treat CAS. A prospective first-in-human study was conducted in two centers (Hôpital Européen Georges-Pompidou, France and Heart Center, Amphia Hospital, Netherlands) in 10 patients and a second study (University Clinical Center of Serbia) involving brain-MRI in 4 patients. All patients had symptomatic severe CAS and were ineligible for SAVR or TAVR according to local heart teams. Methods: Transthoracic NIUT was delivered on all 14 patients with Valvosoft. Clinical and echocardiographic evaluation was performed at baseline, discharge, 1-, 3-, 6- and 12-months follow-up (FUP). Additionally, the 4 patients of the second study had a brain-MRI performed before and after treatment. Results: Patients were advanced in age (82.4±5.3 years) with severe comorbidities (57% with heart failure and 50% with coronary heart disease). No adverse events (AE) occurred during the procedure other than isolated ventricular extrasystoles. No serious AE were adjudicated by a Clinical Event Committee (CEC) as device- or procedure-related at 1-month FUP. No death, stroke or transient ischemic attack or deterioration of neurological status were observed at 1-month FUP.During 12-months FUP, 5 deaths were reported (between 2 to 7 months after the procedure), all were adjudicated by CEC as non-procedure related. The survival rate was 100%, 93%, 79%, 64% at 1-, 3-, 6 and 12-months (to compare to the classic natural evolution of the disease survival rate of 94%, 73%, 73%, 54% respectively). No sign of cerebrovascular accident was detected in any of the 4 patients who had a brain-MRI before and after treatment. Conclusions: NIUT was feasible and safe in this small cohort of very frail, severe symptomatic CAS patients with severe comorbidities. Brain-MRIs performed before and after treatment ruled out silent cerebrovascular events. The survival rate of this cohort suggests that NIUT is beneficial for these patients and serves an unmet medical need.
Abstract 11667: Factors Associated With No-Show and Cancellations at Adult Congenital Heart Disease Clinic
Authors: Karishma Patel, Evan F Shalen, Lidija B McGrath, Yunwoo Burton, Abigail Khan
Journal: Circulation (2021)

Introduction: Many adults with congenital heart disease (ACHD) do not regularly access cardiology care; this has been associated with adverse outcomes. Clinic no-shows and cancellations limit access to care, and identify a population in need of intervention to improve engagement with care. We investigated factors associated with no-shows and cancellations in our academic ACHD clinic which draws from a large catchment area in Oregon, Washington, Idaho and California. Methods: The electronic medical record was queried to identify individuals ≥ 18 years of age with a scheduled appointment in the ACHD clinic from 2017-2020. Demographic and scheduling characteristics were recorded. Multivariate logistic regression was used to test for an association between variables and either no-show or patient-initiated cancellation. Results: Our sample included 7616 scheduled visits, and 4191 (55.0%) were completed. There were 332 (4.4%) no-shows and 1320 were canceled by the patient (17.3%). Factors associated with an increased risk of no-show to clinic were Medicaid (OR=1.86 (95% CI: 1.39, 2.49), p&lt;0.001), prior no-show (OR per 1% increase in prior no-show rate 1.13 (95% CI: 1.13, 1.45), p&lt;0.001), and an appointment at an off-site clinic (OR 2.16 (95% CI: 1.32, 3.45), p=0.002). Factors associated with an increased risk of a cancellation were in-person vs. virtual visits (OR 1.89 (95% CI 1.44, 2.53), p&lt;0.001) and being an established patient (OR 1.38 (95% CI 1.17, 1.63), p&lt;0.001). Patient age, day of the week, and appointment time were not associated with no-shows or cancellations. Discussion: Medicaid insurance, prior no-show, and off-site clinics are associated with a higher risk of no-show to ACHD clinic. As ACHD remains a limited resource, and lack of ACHD follow-up is associated with adverse events, limiting no-shows and canceled visits is an important goal. This study identifies a high-risk population which may benefit from targeted interventions to improve access to care.