tbuckley/cabot-search huggingface dataset:
Abstract 12427: Insertable Cardiac Monitors for Atrial Fibrillation Detection in Patients With Ischemic Stroke: A Meta-Analysis of Randomized Clinical Trials
Authors: Babikir Kheiri, Saket Sanghai, Hani Alhamoud, Mohammed Osman, Eric Stecker, Charles Henrikson, Babak Nazer
Journal: Circulation (2021)

Introduction: The benefits of insertable cardiac monitor (ICM) in patients with recent strokes remains unknown.. Objective: To evaluate the role of ICM for AF detection in patients with recent stroke. Methods: Database search was performed for RCTs. The primary outcome was the time to first detection of AF at 1-year follow-up. Secondary outcomes included the rates of recurrent stroke/TIA and deaths. We calculated the hazards ratios from the extracted Kaplan-Meier curves reported by each trial. Cox proportional hazards model was analyzed following testing of the proportional-hazards assumption (residual Schoenfeld test). Results: We included 3 RCTs with a total of 1,233 patients (613 ICM group vs 620 control group who received routine clinical care of ECGs and ambulatory ECG monitoring ranging from 24 hour to 30 days). The mean age was 64.5 ± 11.3 yrs, 37.9% female, 69.3% hypertensive, and 25.9% diabetic with CHA 2 DS 2 -VASc score of 4.6 ± 1.6. The time from index event to randomization was 31.8 ± 42 days. The threshold for AF detection was &gt;30 sec. At 1-year, AF was detected in 12.9% of patients in the ICM group versus 2.4% in the control group (HR=5.3; 95% CI=3.1 - 9.2; p&lt;0.01; NNT 10). There were no significant differences between groups in terms of recurrent stroke/TIA and death (p&gt;0.05). Of the 94 patients with detected AF, 83 patients (88.3%) received oral anticoagulants. Among the 560 ICMs that were inserted, 6 (1.1%) devices were removed due to infection at the insertion site or pocket erosion. Conclusions: Among patients with ischemic stroke and no prior evidence of AF, ICM was associated with a significantly higher rate of AF detection over 1-year follow-up. Further large trials with long-term follow-up are needed to establish the association of ICM-detected AF with recurrent strokes, to determine the effect of subsequent anticoagulation in this scenario, and to validate their cost-effectiveness.
PATH-07. INFRATENTORIAL HIGH-GRADE GLIOMAS: NEUROSURGICAL CASE SERIES WITH MOLECULAR ANALYSIS
Authors: Brittany Stopa, Kyla Truman, Genaro Villa, Pierpaolo Peruzzi, William Gormley, Bryan Iorgulescu, Timothy Smith
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Most high grade gliomas (HGG) are located supratentorially, while less than 1% arise infratentorially. Growing evidence suggests that infratentorial HGGs (iHGG) represent a collection of distinct molecular entities and that further elucidation of their molecular features can help guide management. We perform here a clinical and molecular analysis of our institutional iHGG case series. METHODS We retrospectively reviewed iHGG patients treated surgically at Brigham and Women’s Hospital (1992-2020), and evaluated their history of prior malignancies, tumor location, treatment, molecular profile, tumor recurrence, and survival. iHGG were identified by review of pathology records, using WHO Histologic Grading Criteria as grade III-IV gliomas located infratentorially. Molecular analysis data was obtained from pathology records. RESULTS Among 37 iHGGs, 16 (43%) were glioblastomas, 11 (30%) were anaplastic astrocytomas, 2 (5%) were diffuse midline gliomas, 2 (5%) were infiltrating gliomas, 2 (5%) were anaplastic ependymomas, 1 (3%) was an anaplastic oligodendroglioma, and 3 (8%) were HGG not otherwise specific. Sixteen (43%) patients were female, median age was 49 years. Fifteen patients had history prior malignancy, 11 of which received radiation and 8 chemotherapy. Surgical resection of iHGG included gross total resection in 4 (11%) and subtotal in 33 (89%). Twenty-one patients (57%) received adjuvant radiation and 19 (51%) chemotherapy. At follow-up, 13 (35%) patients demonstrated symptomatic deterioration, 15 (41%) were stable, and 7 (19%) were improved. Seven patients (19%) experienced recurrence at a mean time of 19 months, and one-year survival was 35%. Molecular analysis revealed 7/15 (47%) tumors were MGMT promoter methylated, IDH was mutated in 3/24 (13%), EGFR was amplified in 3/10 (30%), CDKN2A/B homozygous deletion in 4/7 (57%), TP53 was mutated in 14/15 (93%), and H3K27M was present in 4/10 (40%). CONCLUSIONS iHGGs demonstrate substantial distinction from their supratentorial counterparts. Herein we examined their clinical course, molecular features, management, and outcomes.
Keratinocyte-intrinsic BCL10/MALT1 activity initiates and amplifies psoriasiform skin inflammation
Authors: Zsuzsanna Kurgyis, Larsen Vornholz, Konstanze Pechloff, Lajos V. Kemény, Tim Wartewig, Andreas Muschaweckh, Abhinav Joshi, Katja Kranen, Lara Hartjes, Sigrid Möckel, Katja Steiger, Erik Hameister, Thomas Volz, Mark Mellett, Lars E. French, Tilo Biedermann, Thomas Korn, Jürgen Ruland
Journal: Science Immunology (2021)

BCL10/MALT1 signaling in keratinocytes is altered in human sporadic psoriasis and is a critical initiator and amplifier of skin inflammation in mouse models.
Abstract 10513: Early Follow-Up After Heart Failure Hospitalizations Remains Low and Variable Across Hospitals: Insights from the Michigan
Authors: Mike P Thompson, Chelsea Abshire, Thomas Cascino, John Syrjamaki, Hari Nathan
Journal: Circulation (2021)

Introduction: Early outpatient follow-up may improve outcomes for hospitalized heart failure patients, and is being considered as an ACC/AHA heart failure performance measure. Hypothesis: We evaluated patterns and determinants of early outpatient follow-up after heart failure hospitalization across Michigan hospitals. Methods: The sample used in this analysis included all patients hospitalized with a primary diagnosis of heart failure between January 1, 2017 and December 31, 2019 in the Michigan Value Collaborative statewide multipayer claims data registry. Early follow-up was defined as an outpatient evaluation and management visit within 7 days of discharge. Multilevel mixed-effects models were used to evaluate risk-adjusted early follow-up rates after heart failure hospitalization, adjusting for patient and discharging hospital factors. Results: A total of 17,203 of 39,505 (43.6%) patients hospitalized for heart failure had an early follow-up visit after discharge, which increased from 41.3% in 2017 to 43.0% in 2018 and 46.1% in 2019 (p&lt;0.001). Predictors of early follow-up include male sex, increasing age, commercial insurance coverage, angina, coagulopathy, lung disease, metabolic disorders, arrhythmia, vascular disease, hospital not-for-profit status, non-teaching hospital, and non-rural location. After adjustment, hospital-level rates of early follow-up ranged from 18.1% to 65.7%, with a median of 42.0% (Figure). Patient and hospital factors account for 1.4% and 36.3% of the variation in hospital-specific rates of early follow-up, with 62.3% of the variation left unexplained. Conclusions: Less than half of hospitalized heart failure patients have an early follow-up after discharge, with patient factors accounting 2% of the variation. A more thorough understanding of the determinants of successful early follow-up after heart failure hospitalization and its impact on outcomes will better inform quality improvement efforts.
Publisher Correction: Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection
Authors: Martina Patone, Lahiru Handunnetthi, Defne Saatci, Jiafeng Pan, Srinivasa Vittal Katikireddi, Saif Razvi, David Hunt, Xue W. Mei, Sharon Dixon, Francesco Zaccardi, Kamlesh Khunti, Peter Watkinson, Carol A. C. Coupland, James Doidge, David A. Harrison, Rommel Ravanan, Aziz Sheikh, Chris Robertson, Julia Hippisley-Cox
Journal: Nature Medicine (2021)
Genomic Landscape and Molecular Risk in Patients with Advanced Myelofibrosis Treated within the Multicenter Phase Ib/II MPNSG0212 (POMINC) Trial
Authors: Ekaterina Panina, Steffen Koschmieder, Florian H. Heidel, Andreas Hochhaus, Holger Hebart, Susanne Isfort, Frank G. Rücker, Andreas Reiter, Markus Bangerter, Cornelius Waller, Christoph Scheid, Denise Wolleschak, Joachim R. Goethert, Philippe Schafhausen, Thomas Kindler, Markus P. Radsak, Norbert Gattermann, Robert Möhle, Nikolas von Bubnoff, Tim H Brümmendorf, Hartmut Döhner, Martin Griesshammer, Frank Stegelmann, Konstanze Döhner
Journal: Blood (2021)
Abstract 12526: T Cell Response to Influenza Vaccination Remains Intact in Adults With Congenital Heart Disease Who Underwent Early Thymectomy
Authors: David M Leone, Hong-Jai Park, Serhan Unlu, Michelle Z Gurvitz, Insoo Kang, Robert W Elder
Journal: Circulation (2021)

Introduction: Thymectomy is routine during surgery for congenital heart defects to access to the heart. T cells developed in the thymus play a key role in immunity. Individuals with thymectomy in infancy have altered T cell populations suggesting early immunosenescence. Hypothesis: Adults with Congenital Heart Disease (ACHD) who underwent thymectomy in the first year of life have an altered response to influenza vaccination due to T cell immunosenescence. Methods: We recruited ACHD with early thymectomy ≤ 1 year of age (ACHD-ET; n = 12), ACHD and no thymectomy (ACHD-NT; n = 8), and healthy controls (HC; n = 14). Peripheral blood was collected prior to influenza vaccine and 4 weeks following administration. Flow cytometry of T cell subsets and intracellular cytokine staining of CD4 + T cells was done following in vitro stimulation with influenza viral antigen. Results: Subject's mean age was 34 ± 10.6 years with no difference between the groups. At baseline, the median (IQR) frequency of naïve CD4 + T cells was 24.7% (15.9) in ACHD-ET vs. 43.6% (16.9) in HC ( P =0.01). Similarly, naïve CD8 + T cells were lower with 37.5% (25.7) in ACHD-ET vs 62.8% (22.9) in HC ( P =0.02). This also resulted in a reciprocal increase in memory CD4 + and CD8 + T Cells in the ACHD-ET group. The ACHD-NT was not significantly different than the other groups. The frequencies of influenza antigen-specific memory CD4 + T cells expressing IFN-γ and TNF-α were significantly increased in post-vaccine blood samples compared to pre-vaccine samples across all 3 groups ( P &lt;0.05). Conclusions: ACHD-ET have a smaller population of naïve T cells, suggestive of immunosenescence. Despite this they have an equivalent cytokine response suggesting that early thymectomy does not inhibit the response to vaccination in young adulthood. Our findings support the recommendation that preventative vaccination against pathogens including influenza virus and the newly emerging SARS-CoV-2 should continue to be routinely performed in ACHD.
Abstract 14127: Gene Level Data Extraction, Integration and Comparison of Preclinical Atherosclerosis Investigations in the ApoE and LDLR Knockout Mouse Models
Authors: Rachel R Xiang, M. Elizabeth Moss, Brigett V Carvajal, Yihua Wang, Nicholas Camarda, Alec Stepanian, Jacob Ramsey, Megan M Shuey, Quinn Wells, Joshua A Beckman, Iris Z Jaffe
Journal: Circulation (2021)

Introduction: Animal models are extensively used to interrogate molecular mechanisms of disease. The apolipoprotein E knockout (ApoE-KO) and low-density lipoprotein receptor (LDLR)-KO mouse models are well established preclinical models of atherosclerosis. Hypothesis: We hypothesized that integrated analysis of preclinical data will identify novel signaling pathways and regulatory networks driving atherogenesis. Comparison of findings between models may implicate model-specific mechanisms of atherosclerosis. Methods: Data were extracted from 716 ApoE KO and 422 LDLR KO manuscripts published in ATVB journal from 1995-2020. Extracted data described the impact of an experimental gene perturbation on atherosclerotic phenotypes. Impacts on plaque size and composition were analyzed using Ingenuity Pathway Analysis, separately for each model and as an aggregate dataset. Results: Distinct regulatory pathways and networks were identified across models and in early versus late stages of atherosclerosis. Of top networks in each model, 8/10 were inflammatory and cell growth networks in the ApoE-KO whereas 6/10 were lipid and carbohydrate metabolism networks in the LDLR-KO dataset. Integration of data identified SC-58125, a cyclooxygenase-2 inhibitor, as the top regulatory network that linked 53% (n=168) of genes implicated in atherosclerosis into a single network. Aggregate data from early atherogenesis (&lt;11 wks. high fat diet (HFD)) was enriched in inflammatory functions, whereas late atherosclerosis (14+ wks. HFD) was associated with cell growth and metabolic pathways. Conclusion: Integration of data from two genetic KO mouse models identified distinct gene programs driving atherosclerosis in each model system. Aggregation of data from two models strengthened key findings and identified novel associations. Finally, combining datasets provided greater power to identify distinct gene pathways and networks in early versus late atherosclerosis.
Abstract 11382: Left and Right Ventricular Strain Mechanics in Fetal Arrhythmia
Authors: Geetha Haligheri, Neha Chellu, Rukmini R Komarlu
Journal: Circulation (2021)

Introduction: Assessment of ventricular mechanics in fetuses with tachyarrhythmia poses significant challenges. Strain analysis measures myocardial deformation and has been shown to be a very sensitive marker of ventricular systolic dysfunction compared to traditional measurements. Global and regional myocardial deformation has not been well described in fetuses with arrhythmias. Hypothesis: We hypothesize that left and right ventricular myocardial mechanics are impaired in fetuses with tachyarrhythmias compared to normal fetuses in sinus rhythm. Methods: Retrospective review of fetuses with tachyarrhythmia (groups 1 and 2) and gestational age (GA) matched normal fetuses with normal cardiac anatomy (group 3) from 2000 to 2018 at a single institution, with IRB approval. Fetuses with isolated ectopy and congenital heart disease were excluded from all groups. Strain analysis was performed using VVI software. Arrhythmia type, medications, cardiovascular profile score and postnatal outcome were collected. Results: 18 fetuses with tachyarrhythmia with GA between 21 to 36.5 weeks were analyzed; 18 fetuses of similar GA with normal cardiac anatomy in sinus rhythm served as controls. 3 fetuses were delivered close to term and did not have strain assessment in sinus rhythm. Both LV global longitudinal strain (-4.44 ± 2.82%) and strain rate (-1.24 ± 0.85%) and RV global longitudinal strain (-6.76 ± 2.09%) and strain rate (-1.41 ± 0.55%) were reduced in tachyarrhythmia (Group 1) and recovered when in sinus rhythm (Group 2) but still reduced compared to controls (Group 3). Global longitudinal velocity was not different between patients in Group 2 and 3 (Table &amp; Fig 1). Conclusions: Strain parameters remain abnormal in fetuses with tachyarrhythmia despite conversion to sinus rhythm when compared to GA matched controls. Serial evaluation of strain will help guide therapy and monitor ventricular function in this patient population.
Pathway Analysis Provides Mechanistic Insights into Navtemadlin (KRT-232) Activity and Synergy with Decitabine in Acute Myeloid Leukemia Preclinical Models
Authors: Jin Wang, Venu Valmeekam, Kaijin Wu, Jiang F. Zhong, Andres Stucky, Xuelian (Lili) Chen, Alex Duong, Jude Canon, Cecile Marie Krejsa, Kevin R. Kelly
Journal: Blood (2021)
Abstract 10682: Peripartum Myocardial Strain Analysis: A Marker for Adverse Cardiovascular Outcomes?
Authors: Ronit Zadikany, Marie Lauzon, Sarah Kilpatrick, Janet Wei
Journal: Circulation (2021)

Introduction: Hypertensive disorders of pregnancy (HDP) contribute significantly to adverse cardiovascular (CV) outcomes in peripartum women, and echocardiography helps stratify risk and guide management. Global longitudinal strain (GLS), a marker of left ventricular (LV) systolic function, has not been well-characterized in peripartum women with or without HDP. Hypothesis: We hypothesized that GLS is abnormal in women with prior HDP and may predict adverse CV outcomes. Methods: We retrospectively analyzed 141 women with echocardiograms performed during the peripartum period (6 weeks antepartum to 8 weeks postpartum). We investigated relationships between adverse CV outcomes and clinical and echocardiographic variables, including peak systolic GLS. Prior HDP was defined as a preceding diagnosis of gestational hypertension (HTN), chronic HTN or preeclampsia. Results: Women with prior HDP (72/141, 51%) were older (35 vs 32 years), more often obese (61% vs 34%) and had higher mean arterial pressure (96 vs 82 mmHg) compared to those without prior HDP (p&lt;0.01 for all). Women with prior HDP had greater LV thickness (1.0 vs 0.9 cm) and more frequently abnormal inferior vena cava (IVC) size and collapsibility (p&lt;0.01 for all), although median LV ejection fraction (64% vs 65%) and GLS (-19.6 vs -20.2) were similar. During follow-up of 2.5 years, women with prior HDP had more CV-related emergency department (ED) visits (36% vs 16%, p&lt;0.01) and hospitalizations (32% vs 12%, p&lt;0.01). Using multivariable modeling, left atrial area (LAA) and IVC size better predicted CV-related ED visits and hospitalizations when compared to age, obesity and history of gestational HTN ( Figure ). Conclusions: Although GLS did not predict CV outcomes, abnormal LAA and IVC suggest elevated left and right atrial pressure is related to HDP and CV outcomes. Further study of LV diastolic or right ventricular dysfunction may elucidate mechanisms contributing to adverse outcomes in this population.
Abstract 9110: Use of a Genetic Risk Score to Predict Atrial Fibrillation in Patients With Cardiovascular Disease
Authors: Amanda C Garfinkel, Nicholas A Marston, Frederick K Kamanu, Giorgio M Melloni, Carolina Roselli, Deepak L Bhatt, Marc P Bonaca, Christopher P Cannon, Robert P Giugliano, Michelle L Odonoghue, Itamar RAZ, Benjamin M Scirica, Eugene Braunwald, Patrick T Ellinor, Steven A Lubitz, Marc S Sabatine, Christian T Ruff
Journal: Circulation (2021)

Background: Early detection of atrial fibrillation (AF) could permit earlier anticoagulation and thus potentially reduce risk of embolic stroke. A validated genetic risk score (GRS) has been shown to predict AF risk but its clinical utility beyond established AF risk factors is unclear. Methods: We performed a prospective cohort analysis in pts w/o prior AF from 4 TIMI trials [SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, FOURIER (TIMI 59)]. Pts were divided into genetic risk quintiles using a validated 1,018 SNP GRS for AF. Clinical risk for AF was also calculated using the validated CHARGE-AF model (age, ht, wt, SBP, DBP, anti-HTN med, DM, CHF, MI, smoking). 3-year KM rates and adjusted HRs were calculated across clinical and genetic risk groups. C-index was used to determine if the addition of GRS improved AF prediction compared with clinical risk and NT-proBNP. Results: In 36,663 pts followed for a median of 2.3 yrs, 1,018 new AF cases (2.8%) were identified. AF GRS predicted a significant risk gradient for AF with a 33% increased risk per 1-SD increase in GRS (HR 1.33 [95%CI 1.26-1.41]; p&lt;0.001). Those in the top quintile of AF GRS were more than 2-fold more likely to develop AF (HR 2.26 [1.84-2.78], p&lt;0.001) compared with the bottom quintile. This risk prediction was on par with age and stronger than any other clinical risk factor. Further, GRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, such that pts with high GRS and CHARGE-AF score had an 8.1% 3-year AF risk (Fig) . The C-index for CHARGE-AF was 0.64 (0.63-0.66); addition of NT-proBNP raised the C-index to 0.67 (0.65-0.69), and inclusion of GRS increased it further to 0.69 (0.67-0.71) (p&lt;0.001). Conclusion: In pts with CV disease, AF GRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score. AF GRS may be a clinically useful tool to identify very high-risk pts for consideration of AF screening.
Abstract 12904: National Trends in Aortic Aneurysm and Dissections in Patients With Marfans and Ehlers Danlos Syndrome
Authors: Edgar Aranda-Michel, James Brown, Derek Serna-Gallegos, Sarah Yousef, Yancheng Dai, Yisi Wang, Ibrahim Sultan
Journal: Circulation (2021)

Introduction: Marfans (MFS) and Ehlers Danlos syndrome (EDS) predispose patients to acute aortic dissections and aneurysms. Given their low incidence, there are limited large cohort data on mortality. Hypothesis: Type of connective tissue disorder will predict mortality in patients with Marfans or Ehlers Danlos Syndrome. Methods: The National Inpatient Sample (NIS) was reviewed for adults (&gt;18 years) with MFS and EDS between 2010-2017 via ICD9 and 10 diagnosis codes. Procedure codes were used to distinguish patients undergoing open aortic repair or TEVAR (thoracic endovascular aortic repair) for either a type A aortic dissection or an aortic aneurysm. NIS weights were used to project the 20% NIS volume to national volumes. Univariable logistic regression was used to determine independent predictors of mortality. Results: A total of 19,567 patients were identified. The incidence of MFS and EDS was 18 and 22.4 per 100k, respectively. After applying the inclusion criteria, there were 2,553 MFS and 180 EDS patients. EDS patients were more likely older (50 vs 42, P&lt;0.001) and women (47% vs 33%, P&lt;0.001). MFS patients were more likely to have a type A aortic dissection (44% vs 31%, P&lt;0.001). However, in the total cohort, aortic aneurysm was more frequent (56%). EDS patients were more likely to undergo TEVAR (2.8% vs 1.0%, P=0.03). MFS patients were more likely to have a complication of acute kidney injury (P=0.02) whereas EDS patients were more likely to have bowel ischemia (P=0.05). The majority of patients (89%) were treated at urban teaching hospitals. There was no statistical difference in mortality between the MFS and EDS cohorts (4.6% vs 2.8%, P=0.26). In logistic regression for death, aortic aneurysm (HR 0.14, P&lt;0.001) and elective admission (OR 0.28, P=0.003) were protective for death whereas aortic dissection was a predictor for mortality (OR 7.31, P&lt;0.001). Type of connective tissue disease or sex were not significant predictors. Conclusions: National level estimates show low mortality for patients with MFS and EDS presenting to the hospital with an aortic dissection or aneurysm. Differences in age and sex can guide aortic surveillance for these patient populations, leading to potentially decreased risk of acute aortic dissections and hospital mortality.
The Determinative Role of Hematopoietic Stem and Progenitor Cell Graft Composition on the Engraftment Kinetics after HSCT
Authors: Giulia Barbarito, Beruh Dejene, Gopin Saini, Rachana Patil, David C. Shyr, Robertson Parkman, Alice Bertaina, Kenneth I. Weinberg
Journal: Blood (2021)