tbuckley/cabot-search huggingface dataset:
Abstract 13045: Myofibroblasts Revert to an Inactive Phenotype During Regression of Heart Failure
Authors: Chao Yang, Yuxing Chen, Lianlian Zhu, Lan Zhang, Xiangmin Kong, Qiyu Chen, Xue Liu, Yue Wu, Xinyang Hu, Wei Zhu, Jian'an Wang
Journal: Circulation (2023)

Introduction: The therapy of left ventricular mechanical unloading, such as transcatheter aortic valve replacement(TAVR)and left ventricular assist devices(LVAD)has significantly improved prognosis for patients with heart failure. However, the detailed cellular and/or molecular mechanisms of recovery of cardiac function remain unknown. Objective: We aimed to build a cellular atlas of the heart that experienced stress and de-stress process, with a focus on myofibroblasts, specifically its cell fate of differentiation and function. Methods: We conducted single-cell and ATAC sequencing on non-myocardial cells from mouse heart samples of pressure overload-induced heart failure and recovery, using TAC (transverse aortic arch constriction)/deTAC (with suture for the constriction removed 2 weeks after TAC) model to identify the dynamic changes. Lineage tracing technique was also used to gain further insight into cell fate and reciprocal interactions. Macrophage subgroup was cleared using various approaches to investigate the cross-talk between myofibroblast and macrophage. Results: We generated a TAC/deTAC mouse model which can faithfully simulate a reversal process of functioning for the heart that underwent a pressure overload stress. Multi-omics sequencing reveals the genetic changes and transcriptional regulation of cell populations at different stages. Among the different cell types, significant changes in the gene expression pattern were observed in fibroblasts. Aided by myofibroblast lineage tracing, flow cytometry examinations suggested that remaining in a quiescent state rather than showing a decrease in its number appeared as the main fate of myofibroblasts. Surprisingly, however, simultaneous pressure unloading and macrophage clearance resulted in a significant reduction in the number of myofibroblasts. Conclusions: With a reliable TAC/deTAC mouse model, our multi-omics data revealed dynamic changes in cell populations of the heart that underwent pressure overload followed by unloading, our data demonstrated a quiescent state rather than a reduction in number was the major fate for the activated myofibroblasts for which macrophages were involved. These findings provide a theoretical basis for further treatment.
Abstract 11422: The Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Stroke in Patients With Heart Failure With Preserved Ejection Fraction: A Meta-Analysis of Randomized Controlled Trials
Authors: SHARATH KOMMU
Journal: Circulation (2023)

Background: Randomized controlled trials on sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) have shown them to be beneficial in improving cardiovascular outcomes, including improvement in heart failure parameters and reduced risk of major adverse cardiovascular events (MACE). Positive results are also noted in patients with heart failure with preserved ejection fraction (HFpEF). However, it is unclear if they have any additional benefit of decreased risk of stroke in this patient population of HFpEF. Methods: We performed MEDLINE (via PubMed) and ClinicalTrials.gov searches using the search words - SGLT2 inhibitors and heart failure. Among the reports identified, we screened for randomized controlled trials on HFpEF, that had stroke as one of their outcomes or side effects. We identified three studies that can be included in our meta-analysis. Results: 12,553 (6279 in the treatment group and 6274 in the placebo group) are included in the meta-analysis. The baseline characteristics in both groups were similar. Among the patients treated for HFpEF, the total number of patients who had an ischemic stroke in the SGLT2 inhibitor group was 113 out of 6279 (1.8%), while in the placebo group, 101 out of 6274 (1.6%). We found that SGLT2 inhibitors did not significantly decrease the risk of ischemic stroke in patients treated for heart failure with preserved EF with a relative risk of 1.12 and 95% CI of 0.86 to 1.46. Conclusion: Our meta-analysis shows that in patients treated for HFpEF, SGLT2 inhibitors have a neutral effect on the risk of ischemic stroke.
Abstract 18538: Results of a Self-Management Intervention to Improve Hypertension in Black Patients Using the Electronic Health Record Patient Portal
Authors: Charmaine Duckie, Karen Boston, Brittney Champagne, David Halpern, Bradi B Granger
Journal: Circulation (2023)

Introduction: Nearly half of American adults (47%) have hypertension (HTN), and non-Hispanic Black patients are disproportionately represented among those diagnosed (56% versus 48% for White, 46% for Asian, and 39% Hispanic adults). Models of care to reduce blood pressure for the Black patient population are not consistently implemented, in large part due to systemic and structural barriers to care. Hypothesis: The purpose of this study was to improve access to and use of digital education, skills for self-measured blood pressure (SMBP) monitoring, use of the electronic health record (EHR) patient portal, and blood pressure from baseline to 3 months in a cohort of Black Americans. Methods: A pre-post intervention design was used to evaluate the team-based, nurse-led intervention. Patients received coaching on HTN goals, screening for social determinants of health (SDOH), medication review, self-paced portal-based videos, and teach-back for BP cuff use. Post-implementation blood pressure (BP) and self-management (knowledge, cuff-use, patient portal use, and attendance at follow-up) were measured using the HELM tool, Chronic Care Model (CCM) and American Heart Association (AHA) HTN toolkit. 12-month follow-up is ongoing. Results: Black participants (n=80) averaged 59 (SD 10) years of age; most were female (n=58, 73%), employed (n=59, 75%), non-smokers (n=66, 84%), with average BMI 34.5 (SD8). From 0-3-months, views of portal-pushed videos increased to 69%, knowledge scores improved pre- (M = 67.9, SD = 16.7 to post (M = 75.2, SD = 17.4), and mean systolic BP was significantly reduced by 20.3mmHg (95%CI 16.11, 24.44). Average systolic BP pre was 152.13 (SD = 16.87) and post was 131.85 (SD = 13.13), t (79) = 9.71, p&lt; .001. Sustainability at 12-months is ongoing. Conclusions: A team-based, nurse-led model improves patient engagement, adoption of portal-prescribed education, skills for SMBP, EHR-reported BP, and visit follow-up for Black patients with uncontrolled BP.
Abstract 16840: A Novel Long-Acting CRF2 Receptor Agonist COR-1167 Improves Cardiac and Renal Function on Top of Furosemide in a Sheep Model of Pacing Induced Heart Failure
Authors: Mark C Kowala, Miriam T Rademaker, Nicola J Scott, Chris J Charles, Francesca C Lawson, Marie-Laure Ozoux, Philip Janiak
Journal: Circulation (2023)

Urocortin-2 (UCN-2), a member of the corticotrophin releasing factor family, has cardiovascular protective effects mediated via activation of CRF2 receptors. Exploratory studies in ovine heart failure (HF) and in HF patients demonstrated that acute intravenous (IV) infusion of UCN-2 (1-4hrs), on top of standard of care, temporarily improved cardiac function. However, the short t 1/2 of recombinant UCN-2 (~15 min) limits its therapeutic utility. A stable CRF2 peptide agonist was developed, named COR-1167, that is potent and selective for CRF2 versus CRF1 receptors and it was tested chronically in vivo. Adult female sheep were anesthetized, and instrumented with 7F His bundle electrodes, arterial, venous and Swan-Ganz catheters, pressure transducers, and flow probes. After recovery, HF was induced by rapid cardiac pacing that was maintained during the study. COR-1167 (5 μg/kg/day SC) in combination with furosemide (0.35 mg/kg/day IV) versus furosemide alone was administered for 5 days and cardiorenal parameters were constantly monitored in conscious sheep. Furosemide had no effect on cardiac function while it increased urine Na + , when compared to pre-treatment measurements. Compared to furosemide, COR-1167 plus furosemide significantly enhanced cardiac and renal function parameters (Table). Mean + SEM for Days 1-5 (CV, biomarker and renal parameters), F (n=5-7), F + COR-1167 (n=6-7), Repeated Measures ANOVA; *BW Day 0 minus Day 5 = BW change, Unpaired t test. COR-1167 cardiorenal benefits occurred within 2 hours of the first dose and were sustained, without changing SBP. It increased natriuresis and decreased net fluid balance (water intake minus urine volume) and BW (reflecting a reduction in congestion). In conclusion, chronic CRF2 receptor activation by COR-1167 significantly improved both cardiac and renal function on top of furosemide in ovine HF and potentially is a unique therapy for HF patients.
Abstract 18545: GSK-3β Prevents Lipotoxicity in Obesity Cardiomyopathy Through Upregulation of ATGL
Authors: Koichiro Takayama, Yasuki Nakada, Yasuhiro Maejima, Junichi Sadoshima
Journal: Circulation (2023)

Introduction: Obesity induces accumulation of lipids in cardiomyocytes, leading to cardiac dysfunction, termed lipotoxic cardiomyopathy. We have shown previously that GSK-3α promotes fatty acid uptake in the heart. In contrast, GSK-3β may mediate lipid catabolism. In this study, we aimed to elucidate the role of GSK-3β in lipolysis, primarily focusing on the post-translational regulation of FoxO1 and its association with ATGL, which is the first lipase to hydrolyze lipids. Methods: Wild-type (WT) and homozygous cardiac-specific GSK-3β knock-out (GSK-3β-cKO) mice were fed a normal diet (ND) or a high fat diet (HFD) for 3 months. Results: HFD consumption in WT mice activated GSK-3β in the heart, as indicated by decreases in Ser9-phosphorylated GSK-3β/total GSK-3β (0.5-fold, p&lt;0.05 compared to ND consumption), and upregulated ATGL (2.4-fold, p&lt;0.05) in the heart. Echocardiographic analyses showed preserved systolic and diastolic function in WT mice at this time point (LVEF: 56.3 ± 1.5 %, E/A: 2.06 ± 0.22, n = 13). However, ATGL was not increased (1.6-fold) and both systolic and diastolic dysfunction were observed (LVEF: 45.8 ± 1.5 %, p&lt;0.01 compared to WT, E/A: 1.43 ± 0.20, p&lt;0.05, n =12) in GSK-3β-cKO mice fed a HFD. GSK-3β overexpression in neonatal rat ventricular cardiomyocytes increased ATGL in a dose-dependent manner (p&lt;0.05). FoxO1 knock-down on this background inhibited upregulation of ATGL, suggesting that GSK-3β-induced upregulation of ATGL is mediated through a FoxO1-dependent mechanism. Immunoprecipitation showed that GSK-3β interacts with FoxO1, while mass spectrometry analyses revealed that GSK-3β phosphorylates FoxO1 at 8 Serine/Threonine residues. A FoxO1 mutant in which Serine/Threonine residues at the GSK-3β phosphorylation sites are mutated to Alanine was excluded from the nucleus, and its overexpression prevented upregulation of ATGL in the presence of GSK-3β overexpression. Conclusions: GSK-3β is activated in the presence of HFD consumption in the heart, which may, in turn, prevent lipotoxic cardiomyopathy through phosphorylation of FoxO1 and upregulation of ATGL.
The burden of atopic dermatitis across paediatric populations: ‘it’s not just an itch that rashes’
Authors: Zelma C Chiesa Fuxench
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof The burden of atopic dermatitis across paediatric populations: 'it's not just an itch that rashes' Get access Zelma C Chiesa Fuxench Zelma C Chiesa Fuxench Conceptualization, Writing - original draft, Writing - review & editing Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Email: zchi@pennmedicine.upenn.edu https://orcid.org/0000-0003-0023-4176 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad521, https://doi.org/10.1093/bjd/ljad521 Published: 19 December 2023 Article history Received: 12 December 2023 Accepted: 15 December 2023 Published: 19 December 2023 Corrected and typeset: 23 January 2024
Abstract 311: Accuracy of Automated External Defibrillator Pad Placement During Out-of-Hospital Cardiac Arrest Resuscitation Simulations
Authors: Amanda L Missel, Daniel Rizk, Stephen R Dowker, Isabella G Scott, Noor K Majhail, Nathaniel Hunt, Robert W Neumar
Journal: Circulation (2023)

Introduction: Out-of-hospital cardiac arrest (OHCA) victims receiving defibrillation from an automated external defibrillator (AED) placed early in the chain of survival are more likely to survive. Aim: We sought to explore the accuracy of AED pad placement for lay rescuers (LR) and first responders (FR). Methods: We conducted a secondary analysis of data collected during randomized OHCA simulation trials involving LR and FR. LR received hands-only CPR and AED guidance from a simulated 9-1-1 telecommunicator. FRs did not receive telecommunicator instruction. Participants were surveyed about medical training and experience. Correct AED pad placements (anterior: AP, lateral: LP) were individually determined from video abstraction based on manufacturer’s recommendations and distance to anatomical landmarks (mid, nipple, and naval lines). Incorrect AP placement was defined as more than 6 cm medial or 10 cm inferior. Incorrect LP placement was defined as more than 6 cm superior, 9 cm inferior, or 10 cm medial. We examined the association between correct pad placement and previous CPR training (current, expired, or never) for LR and correct pad placement and self-reported recent field experience (&lt; 1 year) with AED application for FR using Chi-square tests. Results: LR correctly placed the AP in 30/38 (79%) and the LP 30/38 (79%) simulations. Application did not differ significantly based on previous CPR training (AP p= .187, LP p=.578). The most common incorrect placement was too low for both AP (5/8, 63%) and LP (4/8, 50%). FRs applied the AP correctly in 31/36 (86%) and the LP in 22/36 (61%) simulations. Among FRs, correct pad application did not differ significantly based on recent field experience (AP p=.29, LP p=.563). The most common incorrect placement was too low for both AP (5/5, 100%) and LP (12/14, 86%). Conclusion: Both LRs and FRs may not apply AEDs per manufacturer’s recommendations. Further research is needed to improve instructions and follow-up training to ensure appropriate placement of AEDs, and to understand how improper AED placement impacts the accuracy of rhythm analysis and defibrillation success.
Abstract 13013: Predictors of Mortality in Elderly Patients Admitted With Takotsubo Cardiomyopathy and a History of Depression
Authors: Kamleshun Ramphul, Shruti Aggarwal, Sudhamai Akkaramani, Jasninder S Dhaliwal, Rahat A Memon, Prince K Pekyi-Boateng, Shaheen Sombans, Nomesh Kumar, Fnu Bawna, Abhimanyu Ravalani, Hemamalini Sakthivel
Journal: Circulation (2023)

Introduction: Takotsubo cardiomyopathy(TC) (broken heart syndrome or stress-induced cardiomyopathy) is usually a catecholamine-driven weakening of the left ventricle wall motion due to severe emotional or physical stress. It presents as an acute onset of reversible symptoms resembling acute coronary syndrome without occluded coronary arteries. As emotional stressors often trigger the condition, we aim to evaluate factors that can cause hospital death following admission for TC among elderly patients with depression. Methods: Our study group assessed mortality risk factors in patients ages ≥60 years with a diagnosis of TC and depression from the 2016-2020 National Inpatient Sample. Results: There were a total of 26375 elderly patients who had a diagnosis of TC. Amongst them, 25225 (95.6%) did not survive their hospitalization. After adjusting for variables, we found several factors that increased the odds of all-cause mortality in these patients, such as cirrhosis (aOR 2.093, p&lt;0.01), peripheral vascular disease (PVD)(aOR 1.319, p=0.017), and events of Acute Kidney Injury (AKI)(aOR 3.072, p&lt;0.01). Meanwhile, Females (vs. Males, aOR 0.597, p&lt;0.01), the presence of hypertension(aOR 0.854, p=0.029), lipid disorder (aOR 0.696, p&lt;0.01), smoking (aOR0.74, p&lt;0.01), history of stroke (aOR 0.612, p&lt;0.01) or history of myocardial infarction (aOR 0.536, p&lt;0.01) showed lower odds of mortality among elderly patients admitted with TC. No disparities based on race or insurance forms were observed (Table 1). Conclusions: Our analysis found that patients ages ≥ 60 years with TC had poorer outcomes if they had cirrhosis, PVD, or AKI. While reduced odds of death were seen in females and patients with specific comorbidities such as smoking, hypertension, lipid disorder, history of stroke, or myocardial infarction, further studies, adjusting for the length of diagnosis and the medications being used, should be encouraged to expand and understand our results better.
Patient-Reported Impact of Dermatological Diseases (PRIDD) is a new patient-reported outcome measure for dermatology: why is it needed?
Authors: Laura Howells
Journal: British Journal of Dermatology (2023)

A commentary piece on the BJD published article 'Further refinement of the Patient-Reported Impact of Dermatological Diseases (PRIDD) measure using classical test theory and item response theory'. The commentary aims to contextualise the study and describe the benefits of PRIDD for the dermatology community.
Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience
Authors: Sara A. Scott, Ellen M. Marin, Kathryn T. Maples, Nisha S. Joseph, Craig C. Hofmeister, Vikas A. Gupta, Madhav V. Dhodapkar, Jonathan L. Kaufman, Sagar Lonial, Ajay K. Nooka
Journal: Blood Cancer Journal (2023)
Abstract 14119: Association of Electrophysiologic Characteristics of Extra Pulmonary Vein Triggers With Atrial Fibrillation Recurrence
Authors: Young Shin Lee, Daehoon Kim, Hui-Nam Pak
Journal: Circulation (2023)

Introduction: The objective of this study was to investigate the mechanisms underlying the effects of extra pulmonary vein triggers (ExPVTs) on atrial fibrillation (AF) recurrence after catheter ablation (AFCA). We aimed to assess whether there are differences in electrophysiologic characteristics based on the location of ExPVTs and whether the location of ExPVTs is associated with AF recurrence. Methods: Among 2,625 patients who underwent de novo AFCA and subsequently underwent isoproterenol provocation tests, ExPVTs were identified in 311 cases. We categorized the location of ExPVTs as left atrium (LA), right atrium (RA), or septum, and vascular or non-vascular origins. Results: Patients with ExPVTs in the LA exhibited a larger LA diameter (42.2±6.8 vs. 40.4±6.9, p=0.035), a higher LA volume index (LAVI) (43.1±17.1 vs. 37.9±12.2, p=0.006), as well as significantly higher LA wall stress (193.2±106.7 vs. 154.9±74.6, p=0.001) compared to patients with ExPVTs in the RA. Multivariable logistic regression analysis revealed that male sex (p=0.032), diabetes mellitus (p=0.008), and higher LAVI (p=0.021) were associated with the presence of ExPVTs in the LA. No significant difference was observed in AF recurrence rate based on the location of ExPVTs when categorized as LA, RA, or both (Log-rank p=0.087), or when categorized as vascular versus non-vascular origin (p=0.528). However, when ExPVTs were classified as LA, RA, or septum, a significant difference in AF recurrence among the three groups was observed (p=0.047), with a higher recurrence rate in patients with ExPVTs in the LA compared to those with ExPVTs in the RA (p=0.018). Conclusions: Categorizing the location of ExPVT as LA, RA, or septum revealed a significantly higher AF recurrence rate in patients with ExPVTs in the LA compared to those with ExPVTs in the RA.
Abstract 11428: A Spot(s) Diagnosis: A Rare Cause of Effusive-Constrictive Pericarditis
Authors: Brian K Mitchell, Aaron Schatz, Michael Patrone, Kylie Weigel, Hem Bhardwaj, Georgia Thomas, Antonio Abbate, Zachary M Gertz
Journal: Circulation (2023)

Introduction: Effusive-constrictive pericarditis (ECP) is a rare cause of heart failure characterized by impaired cardiac filling due to pericardial compression. Cutibacterium acnes (C. acnes) is an indolent bacteria and uncommon cause of pericarditis, occurring predominantly in older, immunocompromised, and post-surgical patients. This report describes a rare case of ECP due to C. acnes in a young, immunocompetent male. Case Description: A 26 year old male with a history of acne treated with clindamycin wash presented with progressive dyspnea, orthopnea and lower extremity edema. Exam found a pericardial friction rub and knock, and Kussmaul sign. Electrocardiogram met low voltage criteria. Chest CT demonstrated bilateral pleural effusions, pericardial effusion, and ascites. Transthoracic echocardiogram showed a complex pericardial effusion with evidence of tamponade physiology. An emergent pericardial window was performed revealing thickened pericardium, pericardial adhesions, and 200 mL of sanguineous fluid. Pericardial biopsy was consistent with chronic fibrosing pericarditis. Tissue culture isolated C. acnes. Subsequent right heart catheterization confirmed constrictive physiology with diastolic equalization of intracardiac pressures and ventricular interdependence. Cardiac MRI noted intense pericardial enhancement, septal bounce, and biventricular fixation. Rheumatologic, HIV, viral hepatitis, EBV and CMV panels were negative. ESR was normal and CRP mildly elevated. The patient was treated with diuretics, colchicine, metoprolol, and antibiotics. Subsequent imaging showed marked improvement (Figure 1). Discussion: This case demonstrates that ECP due to C. acnes can occur in an immunocompetent patient without traditional risk factors or exposures. Since bacterial pericarditis is associated with a significant risk of mortality, it is important to have a high suspicion for this pathogen to avoid delay of appropriate treatment.