tbuckley/cabot-search huggingface dataset:
Achieving Adherence With NCCN Guidelines for Nonmelanoma Skin Cancer Regarding Peripheral and Deep En Face Margin Assessment (PDEMA)
Authors: Yaohui G. Xu, Young Lim, Jeremy S. Bordeaux, Sumaira Z. Aasi, Murad Alam, Pei-Ling Chen, Carlo M. Contreras, Dominick DiMaio, Jessica M. Donigan, Jeffrey M. Farma, Roy C. Grekin, Lawrence Mark, Kishwer S. Nehal, Paul Nghiem, Kelly Olino, Tejesh Patel, Jeffrey Scott, Ashok R. Shaha, Divya Srivastava, Chrysalyne D. Schmults
Journal: Journal of the National Comprehensive Cancer Network (2024)

Peripheral and deep en face margin assessment (PDEMA), formerly termed by NCCN as complete circumferential peripheral and deep margin assessment (CCPDMA), has the advantages of histologic visualization of the entire marginal surface, highly accurate resection of involved tissue, and sparing of uninvolved tissue. Owing to its highest reported cure rates, PDEMA is the NCCN-preferred treatment for dermatofibrosarcoma protuberans, high-risk basal cell carcinoma, and very-high-risk cutaneous squamous cell carcinoma. In the United States, Mohs micrographic surgery (Mohs) is the most common method of PDEMA. In Germany and some other countries, non-Mohs methods of PDEMA referred to as the Tubingen torte and muffin techniques are more widely used. The Tubingen methods of PDEMA require close communication between surgeon and pathologist. This article describes the background of both Mohs and Tubingen PDEMA, reviews what constitutes PDEMA, and provides a protocol for Tubingen PDEMA detailing critical components in a stepwise fashion using illustrative photos and diagrams. We hope to broaden understanding of the NCCN Guidelines and their rationale, align practice, and optimize patient outcomes.
Abstract 4137878: Trends in Survival After Out-of-Hospital Cardiac Arrest Across Community Demographics Since the COVID-19 Pandemic
Authors: Eric Hall, Qiang Li, Paul Chan, Bryan McNally, Rabab Al-Araji, James de Lemos, Saket Girotra
Journal: Circulation (2024)

Background: The COVID-19 pandemic in 2020 was marked by a sharp decrease in out-of-hospital cardiac arrest (OHCA) survival. Whether OHCA survival has recovered to pre-pandemic levels, and whether changes in OHCA survival are similar across communities of different racial and ethnic composition, is unknown. Methods: We included adult patients with non-traumatic OHCA from 2015-2022 in the Cardiac Arrest Registry to Enhance Survival registry. Using hierarchical multivariable regression, we calculated risk-adjusted rates of survival to hospital discharge during 2015-2019 (reference period) and compared this to survival rates during 2020, 2021, and 2022. We also examined whether the trajectory of survival over this period differed based on the racial/ethnic composition of the community served by the emergency medical service (EMS) agency, defined as predominantly White (&gt;80% White residents), majority Black or Hispanic (&gt;50% Black or Hispanic residents), or integrated (neither). Results: Of 485,079 patients with OHCA, mean age was 61.9 years; 64% were male, and 22% were of Black race with 7% of Hispanic ethnicity. Overall, risk-adjusted survival rates to hospital discharge for OHCA decreased from 10.1% in 2015-2019 to 8.4% in 2020 (P&lt;0.0001). The relative decrease was similar at EMS agencies serving predominantly Black and Hispanic communities (-17.2%) as compared to predominantly White (-17.5%) or integrated communities (-16.8%). Risk-adjusted survival rates recovered partially in 2021 (8.7%) and 2022 (8.9%) but remained below the pre-pandemic period. As of 2022, OHCA survival in majority Black and Hispanic communities was still 9.7% lower, as compared to pre-pandemic years, whereas it was 10.9% lower in integrated communities and 13.6% lower in predominately White communities. Moreover, the survival disparity for OHCAs in Black/Hispanic vs. White communities narrowed to 0.4% (8.4% vs. 8.8%) in 2022, as compared to 1.0% (9.3% vs. 10.3%) prior to the pandemic. Conclusions: OHCA survival has improved in the U.S. since the initial pandemic year of 2020, but remains lower than the pre-pandemic years. The survival disparity for OHCAs occurring in majority Black and Hispanic relative to predominately White communities decreased since 2020, although absolute survival remained lower in majority Black and Hispanic communities throughout the study period.
Abstract 4137796: Novel Deep Learning Aligned Strain Techniques in Repaired Tetralogy of Fallot
Authors: Sven Koehler, Lifu Deng, Ansh Shah, Edward Mascha, Shuyi Li, Christopher Nguyen, Tara Karamlou, Tal Geva, Anne Valente, Ji Hae Lee, Heiner Latus, Thomas Pickardt, F. Gerald Greil, Philipp Beerbaum, Samir Sarikouch, Mohammad Hussain, Sandy Engelhardt, Animesh Tandon
Journal: Circulation (2024)

Introduction: Multicenter studies show that demographic and CMR-based volumetrics and strain predict death, ventricular tachycardia and fibrillation (DVTF) in repaired tetralogy of Fallot (rTOF). We developed a novel deep learning method to calculate radial (RS) and circumferential strain (CS) from end-diastole (ED) to other key frames: mid systole (MS), end-systole (ES), peak flow (PF) in diastole, and mid-diastole (MD) (called ED2K), as well as from each key frame to the next (called K2K strain), for each left ventricle (LV) segment. Hypothesis: We hypothesized that: H1) ED-ES strain; H2) septal strain; and H3) diastolic strain would be additionally predictive of DVTF as compared to a traditional model. Approach: 704 patients combined from the German Competence Network and INDICATOR cohorts had ED2K and K2K strain values calculated using CMR short axis stack. We first created a 4-variable “traditional” logistic regression model including age at CMR, RVEF%, LVEF% and RVESVi. We then separately added ED2K and K2K parameters to assess increased ability to discriminate DVTF, measured by the c-statistic. Results: In univariate analyses, H1: ED to ES RS and CS; H2: multiple systolic septal and non-septal variables; and H3: overall diastolic RS and CS were significantly associated with DVTF, with c-statistics between 0.65 and 0.73 (n=56, Table 1). When added to the traditional model, H1: ED to ES CS; and H2: septal and non-septal CS slightly improved model performance (Table 2). Model calibration was adequate for all models. Conclusion: Our key-frame specific strain recapitulates the CS prediction of adverse events in rTOF, and slightly improves prediction in a multiparameter model. Future work includes external validation.
Abstract 4137900: Differences in Echocardiographic Findings Between Epicardial Vasospastic Angina Phenotypes Affect Response to Medical Therapy
Authors: Keita Shibata, Naoko Ikeda, takahiro furuya, Chisato Sato, Tenjin Nishikura, Kohei Wakabayashi, Kaoru Tanno
Journal: Circulation (2024)

Background: The phenotype of epicardial vasospasm is classified as focal or diffuse. However, its echocardiographic characteristics are unknown. Furthermore, patients with diffuse vasospasms have poorer responses to medical therapy than patients with focal spasms because of more extensive areas of endothelial dysfunction. We hypothesized that there are differences in echocardiographic findings between the patients with diffuse and focal vasospasm, which might affect response to medical therapy. Methods: The present study was a single-center retrospective cohort study that included 77 consecutive patients diagnosed with vasospastic angina (VSA) undergoing coronary spasm provocation test using acetylcholine from 2014 to 2024. The patients with a history of cardiomyopathy and significant obstructive coronary artery disease were excluded. Diffuse VSA was defined as vasospasm in 2≧ adjacent coronary segments, and focal VSA was defined as vasospasm in one isolated coronary segment. Patients were divided into diffuse VSA group (n=45) and focal VSA group (n=32). Left ventricular function was assessed using 2D speckle tracking echocardiography. After the diagnosis of VSA and the administration of medical treatment for VSA, an emergency room (ER) visit with a chest pain attack was recorded as the event of poor response to medical therapy. Results: There was no significant difference in the follow-up period and baseline characteristics (Table). LVEF was similar between the two groups (63.1±5.8% vs. 62.9±7.6%, p =0.87). In contrast, the left ventricular global longitudinal strain (LV-GLS) was significantly lower in the diffuse VSA group than in the focal VSA group (17.4±2.8% vs. 20.2±2.4% p &lt;0.001). There is no difference in medical therapy for VSA (Table). Observation of ER visits with a chest was more frequent in the diffuse VSA group [diffuse VSA group (20/45, 44.4%) vs. focal VSA group (3/29, 9.3%), p &lt;0.001]. Kaplan-Meier curves showed that the diffuse VSA group had a higher cumulative rate of ER visits with a chest pain attack (Log-rank p &lt;0.001). On multivariable Cox regression analysis, diffuse VSA (HR=4.2, 95% CI: 1.10-16.06, p =0.030) and low LV-GLS (HR =1.16, 95%CI: 1.01-1.34, p =0.031) were an independent risk factor for poor response to medical therapy. Conclusion: Patients with diffuse VSA had lower LV-GLS than patients with focal VSA. Moreover, diffuse VSA and lower LV-GLS were associated with poor response to medical therapy after diagnosis of VSA.
Abstract 4137919: Electrical Storm Caused by Chagasic Cardiomyopathy Successfully Treated with Ventricular Aneurysmectomy
Authors: Juan Manuel Munoz-Moreno, Carlos Jhonatan Lobato-Jeri, Carlos Requena Armas, Victor Becerra-Gonzales, Cesar Mendoza
Journal: Circulation (2024)

Introduction: Chronic Chagasic cardiomyopathy (CCC) is a serious complication of Chagas disease that can manifest as LV dysfunction, ventricular aneurysms, and ventricular arrhythmias. Management of the electrical storm in CCC is challenging, especially when it is refractory to catheter ablation. Case Presentation: A 59-year-old woman from southern Peru presented to the ED with palpitations and dyspnea for 1 week. Physical exam was normal. ECG showed Q waves in III and AVF leads. TTE revealed an LVEF of 45% with an inferolateral LV aneurysm. Coronary angiography showed no lesions. CCC was suspected and serology was ordered, which was positive for T. cruzi . Cardiac MRI confirmed the presence of a 32x22mm basal inferolateral LV aneurysm. During hospitalization, she experienced 4 episodes of unstable monomorphic ventricular tachycardia (VT) within 24 hours, requiring defibrillation with 200J, vasopressor support, and invasive mechanical ventilation. The diagnosis of electrical storm secondary to CCC was proposed, for which amiodarone infusion was started until complete impregnation was achieved. Additionally, support was provided with IABP and specific antiparasitic treatment with benznidazole. Electrophysiology determined that the probable focus of the VT was situated at the level of the LV aneurysm. Therefore, ablation with endocardial-epicardial mapping was performed. However, the patient continued to experience recurrent episodes of VT. Consequently, in a multidisciplinary discussion, it was decided to perform a ventricular aneurysmectomy, which was successful. The patient's clinical progress was favorable, with initiation of GDMT and placement of a single-chamber ICD for secondary prevention. After one year of outpatient follow-up, the patient remains free of VT recurrences. Conclusion: Ventricular aneurysmectomy is a successful management approach for patients with CCC who present with electrical storm refractory to antiarrhythmic drugs and catheter ablation, and whose VT is believed to originate from the aneurysm. The diagnosis of CCC is highly arrhythmogenic and should be suspected at an early stage, given the patient's demographics and the presence of LV aneurysm in the absence of coronary artery disease.
Abstract 4137927: Physicians’ Misrecognition of Stroke Risk in Patients with Atrial Fibrillation
Authors: Hiroshi Miyama, Nobuhiro Ikemura, Takehiro Kimura, Yoshinori Katsumata, Ikuko Ueda, Kojiro Tanimoto, Seiji Takatsuki, Shun Kohsaka, Masaki Ieda
Journal: Circulation (2024)

Background: Current clinical practice guidelines for atrial fibrillation (AF) recommend stroke risk stratification and the use of oral anticoagulants (OACs) for patients at risk. However, physicians’ recognition of patients’ stroke risk may differ from the calculated risk, and the effect of this discrepancy on subsequent care remains unknown. Aims: We aimed to document treating physicians’ estimations of individual patients' stroke risk and assess its association with OAC utilization. Methods: A multicenter, prospective cohort study was conducted in two outpatient practices in Tokyo, Japan, between 2018 to 2020. Participants included patients with newly diagnosed AF or those referred for initial treatment for AF. Treating physicians were asked to document the patient's estimated risk of stroke in numbers. The estimations were categorized as low risk (&lt;1.0%/year), intermediate risk (1.0%≤ to &lt;2.0%/ year), and high risk (2.0%≤/year). We then calculated patients’ baseline CHA 2 DS 2 -VASc scores and divided them into three risk groups: 0 or 1 point as low risk, 2 points as intermediate risk, and 3 or more points as high risk. Higher risk categorization by physicians was defined as "overestimation," while lower risk categorization was defined as "underestimation." The independent association of physician-patient risk concordance with OAC use was explored by multivariable Logistic regression models. Results: Among the 285 patients enrolled in this study (mean age 68±12 years, male 72.6%), the mean CHA 2 DS 2 -VASc score was 2.3±1.6. Physicians correctly estimated stroke risk in 147 patients (51.6%), underestimated it in 25 patients (8.8%) and overestimated it in 113 patients (39.6%). OACs were used in 89.8% of patients whose stroke risk was correctly estimated, 72.0% of those whose stroke risk was underestimated, and 84.1% of patients whose health status was overestimated. After multivariable adjustment, the underestimation of stroke risk was independently associated with less use of OACs (adjusted odds ratio 0.23, 95% CI 0.061-0.85, P=0.028). Conclusions: In this cohort study, physician underestimation of stroke risk was not rare and associated with less use of OACs.
Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy
Authors: Yumi Kashima, Masashi Nakagawa, Yusuke Kure, Masanori Matsuo, Yuya Sakamoto, Kenji Shimeno, Ryo Matsumoto, Yoshiki Matsumura, Yukio Abe, Takahiko Naruko
Journal: Circulation (2024)

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease. Methods: Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry. Results: Plasma neopterin levels were significantly higher in TC patients compared with SAP patients ( P &lt;0.0001) or UAP patients ( P &lt;0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P&lt;0.05) and serum C-reactive protein levels (R=0.38, P&lt;0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC. Conclusions: This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.
Abstract 4137869: Ross Procedure for Correction of Congenitally Unicuspid Aortic Valve: A Paradigm Shift?
Authors: Ahmed Wahaj, Naima Maqsood, Yoshiya Toyoda, Sabrina Islam
Journal: Circulation (2024)

Case 1: A 54-yr-old man reported exertional dyspnea for 3 months, with a systolic murmur on exam. TTE noted severe aortic stenosis, moderate insufficiency and possible bicuspid valve morphology. Coronary angiogram showed no obstructive disease. CT chest showed a 5-cm ascending aortic aneurysm. CT surgery evaluation was sought, and patient had a Ross procedure with aortic hemiarch repair. Intra-operative TEE confirmed a congenitally unicommissural, unicuspid aortic valve (UAV). A 7-month follow-up TTE showed a normal aortic and pulmonic prosthetic gradient. Case 2: A 46-yr-old lady reported progressive exercise intolerance, with a systolic murmur and faint S2 noted on exam. TTE showed severe aortic stenosis. MR angiogram showed a unicuspid valve and a mildly dilated aortic root. The patient was evaluated by CT surgery and underwent Ross procedure. TTE 4 years later showed a normal aortic and a moderately elevated pulmonic prosthetic gradient. Patient continues to exercise without limitations. Discussion: UAV is a rare entity with an incidence of 0.02%. It has a bimodal distribution, in infants and adults, with the unicommissural type more common in adults. Due to rapid progression of valvular disease, the mean age at diagnosis is 42 years. Concurrent aortic dilatation is present in 48% patients. Management of UAV is a matter of ongoing investigation. Classically, young patients with aortic valve disease underwent mechanical AVR. Ross procedure was under-utilized due to concerns about the surgical complexity and potential need for re-operation of the aortic and pulmonic grafts. However, recent studies show promising results. Patients with UAV have lower reoperation rates after a Ross procedure compared to a repair alone. Furthermore, a Ross procedure confers mortality benefit over mechanical AVR with no significant difference in immediate perioperative complications and mortality, although, this needs further investigation in a UAV cohort. Our cases support the feasibility of a Ross procedure for UAV, in providing a durable solution while avoiding anticoagulation in young patients. As Ross procedure is performed in limited centers, patients with UAV should be referred to such centers for definitive management.
Abstract 4137829: Comprehensive Single-Cell Atlas of the Human Lung in Pulmonary Arterial Hypertension
Authors: Jason Hong, Brenda Wong, Adam Brownstein, Tammy Graves, Micheala Aldred, Zhiyu Dai, Xia Yang, Mansoureh Eghbali
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disease characterized by progressive vascular remodeling. Although various immune and vascular cell populations have been implicated in the pathobiology of PAH, a comprehensive assessment of the various cell types in human PAH lungs is still lacking. Methods: Single-nucleus RNA sequencing was performed on lung samples from the Pulmonary Hypertension Breakthrough Initiative using the 10x Genomics Chromium Fixed RNA Profiling workflow. Rigorous quality control measures were implemented, including the detection and removal of ambient RNA using CellBender and doublets using scDblFinder. Data normalization and dimensionality reduction were performed using Seurat, and alignment by sample and sequencing batch was conducted using Harmony. Cells were annotated by mapping onto the Human Lung Cell Atlas using Azimuth. Differential gene expression analysis was conducted using a robust pseudobulk approach with edgeR to limit false positive findings. Gene set enrichment analysis was performed using the Hallmark pathways. Results: Lung samples from a total of 67 individuals were profiled, including 42 PAH and 25 age- and sex-matched control lungs. After quality control filtering, over 800,000 cells were captured, with a median of 12,000 cells per sample. Clustering uncovered over 30 cell types, representing endothelial, stromal, immune, and epithelial lineages of the lung. A median of 2,500 transcripts and 1,500 genes were detected per cell. Differentially expressed genes between PAH and control were detected in all major cell populations (FDR &lt; 0.05). Comparative analysis across all cell types revealed interferon response in monocyte subpopulations and endothelial-to-mesenchymal transition in endothelial subpopulations as top upregulated pathways. Conclusion: Comprehensive single-nucleus profiling of human lungs in PAH revealed extensive gene and pathway dysregulation across diverse cell types. This rich dataset provides a valuable resource for the research community, offering opportunities to advance and refine our understanding of the cellular pathobiology of PAH.
Abstract 4137735: Chronic Oxidative Stress Induces Hypertension and Abdominal Aortic Aneurysm in Chemogenetic Mice Model
Authors: Apabrita Das, Markus Waldeck-Weiermair, Shambhu Yadav, Taylor Covington, Fotios Spyropoulos, Arvind Pandey, Thomas Michel
Journal: Circulation (2024)

Background: Aortic aneurysms account for ~10,000 deaths annually in the USA. Oxidative stress is implicated in both abdominal (AAA) and thoracic (TAA) aneurysm formation, but the mechanisms are incompletely understood. We used a chemogenetic approach to modulate oxidative stress in the vascular wall by creating a transgenic mouse (DAAO-TG Tie2 ) that expresses yeast D-amino acid oxidase (DAAO) driven by the endothelial Tie2 promoter. DAAO generates the reactive oxygen species hydrogen peroxide from D-amino acids. Vascular tissues contain L-amino acids, so yeast DAAO is quiescent until DAAO-TG Tie2 mice are provided with D-amino acids. Here we characterize the cellular and molecular consequences of vascular oxidative stress in DAAO-TG Tie2 mice. Hypothesis: Chronic oxidative stress in the vascular wall causes arterial dysfunction. Aim: To characterize the phenotype of DAAO-TG Tie2 mice after oxidative stress induction in vascular endothelium. To identify the mechanisms whereby vascular oxidative stress causes arterial dysfunction and hypertension. Methods: Systolic blood pressure and aortic sonography were measured weekly in D-alanine-fed DAAO-TG Tie2 . Proteomic analyses were used to identify mechanistic targets, which were validated using biochemical and immunohistochemical methods. Results: D-alanine-fed DAAO-TG Tie2 mice develop systolic hypertension and abdominal but not thoracic aortic aneurysms; treated mice die in &gt;3 months with burst abdominal aortic aneurysms. Transgene expression is similar in abdominal and thoracic endothelium. Levels of oxidative stress markers (oxidized proteins, lipid, and DNA) were similar in thoracic and abdominal aorta. Proteomic analyses established phenotypic switching in abdominal but not thoracic aorta, and also revealed activation of the oxidant-activated kinase ASK1 and of the MAP kinase cascade in abdominal but not thoracic aorta. Immunoblot analyses showed a marked decrease in JNK1 phosphorylation by phosphatase DUSP3 and an increase in vascular KLF4, leading to phenotypic switching of contractile to synthetic VSMCs. Conclusion: Chronic chemogenetic oxidative stress induces hypertension and abdominal aortic aneurysm formation caused by KLF4-dependent VSMC phenotypic switching.