tbuckley/cabot-search huggingface dataset:
PATH-29. GLIOBLASTOMA TUMOR CLASSIFICATION BASED ON SPATIAL ANALYSIS OF ONCOGENIC AMPLIFICATIONS AND PROTEIN EXPRESSION
Authors: Kacper Walentynowicz, Dalit Engelhardt, Shreya Yadav, Ugoma Onubogu, Roberto Salatino, Cristina Vincentelli, Thomas McDonald, Franziska Michor, Michalina Janiszewska
Journal: Neuro-Oncology (2021)

Abstract Heterogeneity of glioblastoma (GBM) has been extensively studied in recent years with identification of oncogenic drivers of GBM cellular subtypes. However, little is known about how these cells interact with each other or with the surrounding tumor microenvironment (TME). We employed spatial protein profiling targeting immune and neuronal markers (79 proteins) coupled with single-cell spatial maps of fluorescence in situ hybridization (FISH) for EGFR, CDK4, and PDGFRA on human GBM tissue sections. Several cores from 20 GBM samples were collected to create a tissue microarray, and 96 regions of interests were profiled with 37,844 nuclei for oncogenic amplification screen. Spatial protein profiling identified strong correlation of certain immune markers, TAU-associated proteins, and oligodendrocyte-enriched protein groups and overall high intratumor heterogeneity of TME. Our single-cell quantification of FISH signals showed differences among tumors based on the prevalence of dual amplification of EGFR and CDK4 within a cell relative to single oncogene amplified cells. High relative frequency of dual amplification was associated with increased expression of immune-related markers and decreased expression of EGFR protein. Moreover, this protein expression signature was associated with survival in another GBM dataset. Here, we present spatial genetic analysis at the single cell level coupled with protein expression profiles associated with tumor microenvironment. Our results suggest that assessment of genetic heterogeneity in GBM could potentially drive improved patient stratification and treatment.
Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19
Authors: Brian M. Clemency, Renoj Varughese, Yaneicy Gonzalez-Rojas, Caryn G. Morse, Wanda Phipatanakul, David J. Koster, Michael S. Blaiss
Journal: JAMA Internal Medicine (2021)

Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear.
Third-Party Partially HLA Matched Fungus-Specific T-Cells (FSTs) Used to Treat Invasive Fungal Infection (IFI) with <i>Scedosporium Aurantiacum</i> after Allogeneic Hemopoietic Stem Cell Transplant (aHSCT)
Authors: Shafqat Inam, Gaurav Sutrave, Selmir Avdic, Janine Street, Elissa Atkins, Leighton Edward Clancy, David J Gottlieb
Journal: Blood (2021)
Abstract 12314: Clinical Determinants of Low Attenuation Epicardial Adipose Tissue Volume in Type 2 Diabetes
Authors: Sarah L Ayton, Jian L Yeo, Gaurav S Gulsin, Emer M Brady, Jayanth R Arnold, Matthew P Graham-Brown, Anvesha Singh, Damini Dey, Gerry P McCann, Alastair J Moss
Journal: Circulation (2021)

Introduction: The accumulation of excess epicardial adipose tissue (EAT) is associated with the onset of specific heart failure phenotypes. Subsets of adipocytes in EAT produce an inflammatory secretome which alters the extracellular matrix of the epicardium and impairs myocardial contractility. Lipid-laden adipocytes have a low computed tomography (CT) attenuation and can be readily identified using cardiac CT. Objective: This study sought to identify the clinical and biomarker determinants of low attenuation EAT in participants with Type 2 diabetes (T2D) at risk of heart failure. Methods: Participants with T2D and non-diabetic controls were prospectively recruited to an observational multi-modality cardiovascular imaging study. Deep learning analytics (QFAT, Cedars-Sinai) measured EAT volume and CT attenuation from cardiac CT datasets. Adipose tissue with CT attenuation values of -90 to -190 Hounsfield Units (HU) were classified as low attenuation EAT regions. Comparison was made with anthropometric and blood biomarkers to evaluate determinants of low attenuation EAT. Results: Type 2 diabetic (n=151, median age 64 (59, 69) years, 65% male) and non-diabetic individuals (n=39, median age 59 (54, 66.5) years, 59% male) were recruited. Total EAT volume indexed to body surface area was 1.6-fold higher in diabetics (62.4 (49.1, 77.7) cm 3 /m 2 vs 38.8 (29.6, 51.9) cm 3 /m 2 , p &lt;0.01) and mean CT attenuation was lower (-77.4 +/- 5.2 HU vs -70 +/- 5.4 HU, p &lt;0.01). Larger indexed EAT volume was associated with a lower mean CT attenuation in all participants (r = -0.839, p &lt;0.01). Multivariate analysis identified increasing age, white ethnicity and waist circumference as independent determinants of low attenuation EAT (adjusted R 2 = 0.2003, p &lt;0.01). No association was found with dysglycemia (HbA1c, p = 0.2), dyslipidemia (Triglycerides, p = 0.1) and subclinical inflammation (neutrophil:lymphocyte ratio, p = 0.4). Conclusions: In patients with T2D, indexed EAT volumes are 1.6-fold higher with a lower mean CT attenuation. Age, white ethnicity and waist circumference are associated with low attenuation EAT. Prospective studies are required to determine whether interventions to reduce low attenuation EAT will prevent the onset of heart failure.
Identifying Top Talent to Improve Prostatectomy Sexual Outcomes
Authors: Jeffery Vehawn, Brock O’Neil
Journal: JAMA Surgery (2021)

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Abstract 13422: The Impact of Cardiac Resynchronization Therapy With Defibrillator in Patients With Nonischemic Cardiomyopathy
Authors: Harsh P Patel, Samarthkumar J Thakkar, N. Gurukripa Kowlgi, Ashish Kumar, Rohan Parikh, Justin Z Lee, Vishal Parikh, Scott Feitell, Sourbha Dani, Christopher V Desimone, Abhishek Deshmukh
Journal: Circulation (2021)

Introduction: Real-world data on the significance of adding a defibrillator to cardiac resynchronization therapy (CRT-D) in patients with nonischemic cardiomyopathy (NICM) are limited. Hypothesis: CRT-D is associated with a lower risk of mortality and heart failure (HF) readmissions compared to CRT-P in NICM. Methods: We identified patients with NICM who underwent CRT-D and CRT without an ICD (CRT-P) by analyzing the nationwide readmission database from October 2015- December 2018 and using appropriate ICD-10 CM codes. Propensity score matching was performed to adjust for the confounders. Kaplan Meier curves were utilized for time to event analysis. Cox proportional hazard regression was used to generate hazard ratios. All-cause mortality at 6 months was the primary outcome whereas readmission due to HF and any other cause at 6 months were defined as secondary outcomes. Results: Post-PSM, 3054 patients with NICM underwent CRT-P, and 2863 patients underwent CRT-D placement. CRT-D did not show any benefit over CRT-P in reducing all-cause mortality at 6 months (2.92% vs. 2.79%, HR: 0.84, 95% CI: 0.61-1.16, p=0.29). Similarly, there was no difference in terms of readmissions due to other causes among both groups of patients (36.25% vs. 31.85%, HR: 0.98, 95% CI: 0.89-1.08, p=0.77). However, patients with CRT-P implantations had a lower risk of HF readmissions compared to the CRT-D group (10.05% vs. 14.25%, HR: 0.67, 95% CI: 0.58-0.79, p&lt;0.0001). Conclusions: The addition of a defibrillator to CRT failed to show a survival benefit in patients with NICM. Moreover, HF readmissions were higher in CRT-D patients compared to CRT-P.
Abstract 13186: A Machine Learning Evaluation of Patient Characteristics Associated With Guideline-Directed Prescribing for Heart Failure and Reduced Ejection Fraction
Authors: Katy Trinkley, Krithika Suresh, Rachel Kim, Michael Rosenberg, Malinda Tan, Heather Anderson, Larry A Allen, David P Kao, Premanand Tiwari, Daniel Malone
Journal: Circulation (2021)

Introduction: Patients with heart failure and reduced ejection fraction (HFrEF) are consistently under-prescribed guideline-directed medications. Many barriers to prescribing are known, including patient characteristics (e.g., higher potassium values within normal limits predict under-prescribing of some medications). However, identification of these barriers has relied on traditional a priori hypotheses or qualitative methods. To overcome the limitations of traditional methods, we used a supervised machine learning (ML) approach to identify potential new barriers to prescribing. Methods: We used electronic health record data to evaluate characteristics of adults with HFrEF within the UCHealth system. Characteristics evaluated included insurance type, medications, diagnoses and lab values. We evaluated the predictive performance of ML algorithms and statistical models based on area under the receiver operating characteristic curve (AUC) to predict prescription of 4 types of medications: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). We identified top characteristics associated with prescribing each medication type from the models with the best predictive performance. Results: For 3,835 patients meeting inclusion criteria, 70% were prescribed an ACE/ARB, 8% an ARNI, 75% a BB and 40% a MRA. The best-predicting model for each medication type was a random forest. Figure 1 describes the top characteristics associated with each medication type. Conclusions: In this hypothesis generating ML study, we identified additional patient characteristics that may be associated with under-prescribing for HFrEF. These results also align with some patient characteristics that are known barriers to prescribing. Additional research is needed to further elucidate barriers to prescribing for HFrEF.
STEM-21. INHIBITING ADENINE SYNTHESIS ATTENUATES GLIOBLASTOMA CELL STEMNESS AND TEMOZOLOMIDE RESISTANCE
Authors: Simranjit Singh, Landon Hansen, Changzheng Du, Kristen Roso, Rui Yang, Paula Greer, Yiping He
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is a lethal brain cancer that exhibits high levels of drug resistance, a feature partially imparted by tumor cell stemness. Recent work has shown that homozygous MTAP deletion, a frequent genetic alteration in GBM, promotes the stemness of GBM cells. Here, exploiting the MTAP loss-conferred deficiency in adenine salvage, we demonstrated that subtle levels of adenine blockade via treatment with Alanosine, an inhibitor of de novo adenine synthesis, attenuate the stemness of MTAP-null GBM cells. Transcriptomic profiling performed on Alanosine-treated GBM cells revealed a reduction of mitochondrial DNA-encoded gene expression. Furthermore, Seahorse XF analysis showed that Alanosine treatment led to a reduction in mitochondrial respiration and eliminated GBM cells’ spare respiratory capacity, an important metabolic measure of cell fitness that is representative of their ability to respond to oxidative stress. Importantly, long term adenine shortage via treatment with low doses of Alanosine resulted in similarly compromised mitochondria functionality and attenuated GBM cells’ stemness. In further supporting this adenine blockade – compromised mitochondria – reduced stemness cascade, treatment with a mitochondrial respiration inhibitor attenuated the stemness of GBM cells, suggesting the importance of mitochondrial function in maintaining GBM stemness. Finally, in agreement with the diminished stemness and compromised mitochondrial function, we showed that Alanosine sensitized GBM cells to temozolomide (TMZ) in both in vitro cultures and in an orthotopic GBM model. Collectively, these results identify critical roles of adenine supply in maintaining stemness and mitochondrial function in GBM cells, suggest a targeted method of abrogating stemness and chemoresistance in GBMs, and support targeting adenine synthesis as a complementary approach for treating the half of GBMs harboring MTAP deletions.
Abstract 14242: Reverse Remodeling After Catheter Ablation- A Single Center Retrospective Analysis
Authors: Surya K Aedma, pranav mahajan, Raja S Jadav, Anant Naik, Naga Vaishnavi Gadela, Anuj Garg, Abraham G Kocheril
Journal: Circulation (2021)

Introduction: The presence of supraventricular tachyarrhythmia (SVT) causes structural and functional changes over a period. The aim of our study is to assess the changes in structural and functional echocardiographic parameters following cardiac catheter ablation (CA) for SVT to see if correction of arrhythmia and restoration of sinus rhythm using CA leads to reverse remodeling. Methods: A single center retrospective analysis was performed on patients undergoing CA for SVT between January 2019 and April 2020. Pre- and post-ablation left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial volume index (LAVI), left atrial dimension (LAD), left ventricular ejection fraction (LVEF) and left ventricular wall thickness were measured. The cohort was sub-grouped into arrhythmia free (AF) and arrhythmia recurrence (AR) patients. Paired student’s t test was performed to compare mean volumes and differences in pre- and post-ablation parameters amongst AF and AR patients. Results: 51 (67.1%) out of a total of 76 patients were AF and 25 (32.9%) had AR based on electrocardiogram done at or around the time of post- ablation echocardiogram. In AF patients there was a statistically significant decrease in post-ablation LVEDV, LVESV, LAVI, and LAD [LVEDV: Post-117 vs Pre- 124 (p=0.002), LVESV: 59 vs 67 (p=0.002), LAVI: 34 vs 38 (p=0.034), and LAD: 3.9 vs 4 (p=0.006)] and increase in LVEF [51 vs 49 (p=0.004)], whereas AR patients had higher post-ablation volumes [LVEDV: 118 vs 108 (p=0.015) and LVESV: 53 vs 50 (p=0.0001)]. [Figure 1] Conclusions: Our findings were significant for decreases in LVEDV, LVESV and LAVI following successful CA of SVT indicating reversal of cardiac remodeling. Importantly, there was an improvement in LVEF. Our study indicates that CA and restoration of sinus rhythm causes improvement in ejection fraction and is important to consider early CA to treat patients in heart failure from tachyarrhythmias.
A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis
Authors: Maxime Espi, Xavier Charmetant, Thomas Barba, Cyrille Mathieu, Caroline Pelletier, Laetitia Koppe, Elodie Chalencon, Emilie Kalbacher, Virginie Mathias, Anne Ovize, Emmanuelle Cart-Tanneur, Christine Bouz, Laurence Pellegrina, Emmanuel Morelon, Laurent Juillard, Denis Fouque, Cécile Couchoud, Olivier Thaunat, Chantrel François, Reydit Mathilde, Tiple Aurélien, Bechade Clémence, Bemrah Abdelkader, Vigneau Cécile, Sautenent Bénédicte, Kazes Isabelle, Courivaud Cécile, Gabriel Jean-Marc, Edet Stéphane, Mercadal Lucile, Moranne Olivier, Toure Fatouma, Laurain Emmanuelle, Ranlin Alex, Longlune Nathalie, Glowacki François, Tivollier Jean-Michel, Brunet Philippe, Lavainne Fréderic, Berard Etienne, Sarraj Ayman, Bauwens Marc, Testevuide Pascale, Vacher Coponat Henri, Galland Roula, Schauder Nicole, Salmi Louis -Rachid, Cerasuolo Damiano, Tendron-Franzin Anaïs, Bayat Sahar, Halimi Jean Michel, Wolak Aurore, Gentile Stéphanie, Devictor Bénédicte, Monnet Elisabeth, Boucaut Maitre Denis, Nacher Mathieu, Merle Véronique, Jais Jean-Philippe, Daures Jean-Pierre, Vergnenegre Alain, Loos-Ayav Carole, Merle Sylvie, Hazzan Marc, Gervolino Shirley, Nguyen Jean-Michel, Iacobelli Silvia
Journal: Kidney International (2021)
Risk Factors and Prognosis Analysis of Patient-Specific HLA Genomic Loss Relapse Following ATG-Based T-Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation
Authors: Hengwei Wu, Ji Min Shi, Yi Luo, Jian Yu, Xiaoyu Lai, Lizhen Liu, Huarui Fu, Guifang Ouyang, Xiaojun Xu, Xiao Haowen, He Huang, Yanmin Zhao
Journal: Blood (2021)
Abstract 12096: Satellite-Based Urbanization Measures Are Independent Predictors of Metabolic Syndrome
Authors: Mohan Thanikachalam, Kevin Lane, sadagopan thanikachalam
Journal: Circulation (2021)

Introduction: In India, with rapid urbanization, there is a significant increase in the prevalence of cardiovascular diseases at younger ages despite lower rates of obesity. While urbanization has led to nutrition transition, psychosocial stress and behavioral changes, these conventional risk factors do not fully explain the rapid increase in the prevalence. Hypothesis: Urbanization has had a profound impact on the physical environment leading to air pollution, urban heat islands and other effects, which are known to have an impact on metabolic health. Here we assess the impact of built environmental changes on the prevalence of metabolic syndrome (MS) in a rapidly urbanizing population in South India. Methods: Based on census data, a random sample included 8080 participants (20 to 76 years of age; 56% female) from urban, semi-urban, or rural areas spread over 80 x 80 kms. The MODIS satellite land cover data (urban, crops, trees, shrubs and grass land cover) at a 1 km x 1 km resolution was joined to participant's geolocated residential position in ArcGIS. Plus, the distance of the residential location to the urban center was mapped. MS was defined according to the AHA criteria. Multivariable regression models tested the independent association between MS and urban/built environment measures after adjusting for age, sex, physical activity, smoking, alcohol intake, socioeconomic, stress, anxiety, depression, family history of diabetes and hypertension, and energy intake levels. Results: The prevalence was higher in urban (44.6%) and semi-urban communities (35.2%) compared to rural (31.8%). In fully adjusted models, urban participants [OR: 2.11 (1.89, 2.36)], participants in urban land cover [OR: 1.57 (1.38, 1.78)) and those residing within 0 to 20 kms to the urban center [OR: 1.99 (1.7, 2.33)], had significantly higher odds for MS, when compared to rural, participants in crops land cover and those residing 60 to 80 kms from urban center, respectively. Conclusions: There is a significantly higher prevalence of MS in urban regions. After adjusting for traditional risk factors, there is an independent association between urbanization measures and MS suggesting unaccounted factors in the physical or built environment driving the prevalence MS in urban India.
Abstract 13639: The Impact of Income Level on All-Cause and Cardiovascular Mortality Across the Spectrum of Cardiovascular Health & Disease Among Adults in the United States
Authors: Madiha Khan, Isaac Acquah, Zulqarnain Javed, Mohamad Taha, Najah Khan, Miguel Cainzos-Achirica, Kobina Hagan, Safi U Khan, Michael D Shapiro, Michael J Blaha, Ron Blankstein, Salim S Virani, Garima Sharma, Javier Elizondo, Khurram Nasir
Journal: Circulation (2021)

Introduction: There is increasing interest in the role of income level as a social determinant of health for cardiovascular disease (CVD). In this study we examine the interplay of household income...
Abstract 10420: Protective Role of Bariatric Surgery in Prevalence and Risk of Atrial Fibrillation in Obese Patients on Long-Term, with Gradually Waning Effect Over a Decade: A Meta-Analysis
Authors: Rupak Desai, Akhil Jain, Dwayne Wiltshire, Terry R Went, Arashpreet Chhina, Yashwitha Sai Pulakurthi, Vibhor Garg, Praneeth Reddy Keesari, Theresa Allagoa, Muhammad Haisum Maqsood, Sandeep Singh, Abhishek Deshmukh, Gautam Kumar, Rajesh Sachdeva
Journal: Circulation (2021)

Background: Bariatric surgery (BS) has been shown to be beneficial in improving co-morbid conditions in morbidly obese patients. Long-term cardiovascular complications remain undefined and warrant further investigation. We examined the prevalence and risk of atrial fibrillation (AF) in obese patients who underwent BS. Methods: PUBMED/Medline, SCOPUS, EMBASE databases were systematically reviewed using relevant keywords to search prospective and retrospective studies reporting AF with long-term (at least &gt;1-year follow-up) follow-up in patients who had undergone BS. Random effects models were used for meta-analysis and subgroup analysis. I 2 statistics was used to identify substantial (&gt;75%) heterogeneity. Results: Nine studies (3 USA, 2 UK, 4 Sweden) including 24,164 patients who had undergone BS (mean BMI cut off: 35, mean age 42 years) with 29,330 controls were included in the analysis with a median follow-up of 8 years. Pooled prevalence of AF was lower in BS arm (3.0%, 95%CI: 1.4%-5%) as compared to non-BS arm (3.8%, 95% CI: 1.8%-5.0%). The Forest Plot (Fig. 1) depicts significantly reduced odds of having AF in patients who have undergone BS vs controls (OR: 0.74, 95%CI: 0.60-0.91, I 2 =70.2%, p&lt;0.01). Sensitivity analysis using the leave-one-out method did confirm equivalent results. On subgroup analysis, AF prevalence in the BS group was slightly higher in studies with a mean age of ≥50 years (4.8%, 0-12%) as compared to cohorts with mean age &lt;50 (2.0%, 1.4-5.0%). The pooled rate of AF was low on short-term follow-up compared to long-term follow-up after BS: 1.5% (0.9-2.5%) in 1-5 years, 1.9% (0.2-4.5%) in 6-10 years, 5.4% (0-13.9%) ≥10 years of BS. Conclusions: Obese patients undergoing BS had nearly 25% lower risk and lower pooled rate of AF when compared to controls over 8 years of follow-up. The protective effect of BS on reduced risk of AF was seen to gradually wane over longer follow-up which warrants continued efforts to effectively control CVD risk factors.