tbuckley/cabot-search huggingface dataset:
Abstract 14314: Men Admitted With Takotsubo Syndrome (TTS) Have Increased In-Hospital Morbidity and Mortality: Perspectives From the National Inpatient Sample Database
Authors: Louis T Vincent, Jelani Grant, Bertrand Ebner, Jennifer Maning, Paul Montana, neal olarte, Odunayo P Olorunfemi, Eduardo de Marchena, Rosario A Colombo
Journal: Circulation (2020)

Introduction: Takotsubo Syndrome (TTS), also known as Stress Induced Cardiomyopathy, is characterized by reversible left ventricular dysfunction without obstructive coronary disease, and largely affects post-menopausal women. However, limited data suggest increased mortality risk in men. We sought to compare national in-hospital outcomes between men and women admitted with TTS. Methods: All patients above 18 years who were admitted with primary diagnosis of TTS between 2012-2017 were identified by International Classification of Diseases (ICD)-9 and ICD-10 diagnostic codes in the National Inpatient Sample (NIS) Database. The primary endpoint was in-hospital all-cause mortality. Secondary endpoints included in-hospital complications, total cost, and duration of hospitalization. Results: A total of 8732 patients (90.8% female) were admitted with primary diagnosis of TTS. Women with TTS were older compared to men (66.9±12.4 vs. 63.1±15.7 years, p&lt;0.001). However, men had increased tobacco use (48.8% vs 37.2%), alcohol use (11.6% vs 3.1%), and coronary artery disease (47.0% vs 39.7%, p&lt;0.001 for all). Prevalence of diabetes, hypertension, atrial fibrillation, anemia, and heart failure was similar between groups. Men more frequently developed cardiogenic shock (7.1% vs 4.4%, p&lt;0.001) requiring mechanical circulatory support (2.9% vs 1.7%, p=0.01), and had greater all-cause mortality compared to women (2.5% vs 1.4%, p=0.01). Using a multivariate regression model to adjust for age, race, substance use, and comorbidities, male gender (OR 2.12, 95% CI [1.69-2.68], p&lt;0.001) and cardiogenic shock (OR 15.1, 95% CI [12.6-18.0], p&lt;0.001) were associated with increased all-cause mortality. Lastly, men experienced greater length and cost of stay (4.0±4.2 vs. 3.6±3.6 days, and $56,428 vs. $46,908), fewer routine discharges (74.3% vs. 77.6%), and greater need for skilled nursing facility (11.6% vs. 9.2%, p&lt;0.001 for all). Conclusion: TTS occurs predominantly in women but carries increased risk of in-hospital mortality in men, especially when complicated by cardiogenic shock. Perhaps improved risk stratification and early identification of patients with signs of shock or hemodynamic instability may help to improve outcomes.
The importance of the 2S albumins for allergenicity and cross-reactivity of peanuts, tree nuts, and sesame seeds
Authors: Stephen C. Dreskin, Stef J. Koppelman, Sandra Andorf, Kari C. Nadeau, Anjeli Kalra, Werner Braun, Surendra S. Negi, Xueni Chen, Catherine H. Schein
Journal: Journal of Allergy and Clinical Immunology (2020)
Deep representation learning of electronic health records to unlock patient stratification at scale
Authors: Isotta Landi, Benjamin S. Glicksberg, Hao-Chih Lee, Sarah Cherng, Giulia Landi, Matteo Danieletto, Joel T. Dudley, Cesare Furlanello, Riccardo Miotto
Journal: npj Digital Medicine (2020)

Deriving disease subtypes from electronic health records (EHRs) can guide next-generation personalized medicine. However, challenges in summarizing and representing patient data prevent widespread practice of scalable EHR-based stratification analysis. Here we present an unsupervised framework based on deep learning to process heterogeneous EHRs and derive patient representations that can efficiently and effectively enable patient stratification at scale. We considered EHRs of 1,608,741 patients from a diverse hospital cohort comprising a total of 57,464 clinical concepts. We introduce a representation learning model based on word embeddings, convolutional neural networks, and autoencoders (i.e., ConvAE) to transform patient trajectories into low-dimensional latent vectors. We evaluated these representations as broadly enabling patient stratification by applying hierarchical clustering to different multi-disease and disease-specific patient cohorts. ConvAE significantly outperformed several baselines in a clustering task to identify patients with different complex conditions, with 2.61 entropy and 0.31 purity average scores. When applied to stratify patients within a certain condition, ConvAE led to various clinically relevant subtypes for different disorders, including type 2 diabetes, Parkinson's disease, and Alzheimer's disease, largely related to comorbidities, disease progression, and symptom severity. With these results, we demonstrate that ConvAE can generate patient representations that lead to clinically meaningful insights. This scalable framework can help better understand varying etiologies in heterogeneous sub-populations and unlock patterns for EHR-based research in the realm of personalized medicine.
Abstract 14678: Prevalence Of Sglt2 Inhibitor And Glp-1 Receptor Agonist Prescriptions In Patients With Comorbid Diabetes And Cardiovascular Disease In An Integrated Academic Health System
Authors: Hawkins Gay, Jingzhi Yu, Lucia Petito, Tamara Isakova, Anand Srivastava, Sadiya Khan, Stephen D Persell, Jeffery Linder, Raja K Mutharasan, Mark D Huffman, Sanjiv J Shah, Clyde W Yancy, Faraz S Ahmad
Journal: Circulation (2020)

Introduction: Multiple randomized clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP1) receptor agonists reduce the risk of cardiovascular events and mortality in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD). In order to inform implementation strategies, we sought to describe prescribing trends among patients with T2D in clinical practice. Methods: We developed a clinical T2D cohort using a validated computable phenotype from the electronic data warehouse of a large academic health system among patients receiving care from January 1, 2013 through December 31, 2019. We retrospectively reviewed outpatient prescribing patterns in this cohort, and stratified results by CVD subtype (heart failure [HF] and atherosclerotic CVD [ASCVD]). Results: There were 23,485 patients identified with T2D. Mean (SD) age was 67 years (13), 46% were women, 61% were white, 32% had comorbid CVD (HF or ASCVD), and the mean (SD) hemoglobin A1c was 8.0% (5.7%). The majority of SGLT2 inhibitors and GLP1 receptor agonists were first prescribed by endocrinologists, 52% and 65% respectively. The prescription rate for both medication classes was low, and though SGLT2 inhibitor use increased over time (1% in 2013 to 14% in 2019; p&lt;0.01), GLP1 receptor agonist use did not significantly change (10% in 2013 to 10% in 2019; p=0.93). Among patients with HF, SGLT2 inhibitor and GLP1 receptor agonist use increased annually by 42% and 7%, respectively, while patients with ASCVD experienced year over year growth of 63% and 13% in these categories. See Figure 1 (A and B) for more detail. Conclusions: Prescription rates of SGLT2 inhibitors and GLP1 receptor agonists remains low, especially for patients with T2D and CVD, despite a proven reduction in mortality and cardiovascular events. Strategies to increase the use of these proven medical therapies represent a major opportunity to improve outcomes in this high-risk group.
Abstract 114: Effect of Body Position on Intracranial Pressure and Carotid Blood Flow During Extracorporeal Cardiopulmonary Resuscitation
Authors: Yaël Levy, Rocio Fernandez, Fanny Lidouren, Matthias Kohlhauer, Lionel Lamhaut, Alice Hutin, Pierre-Louis Leger, Guillaume P Debaty, Keith G Lurie, Bijan Ghaleh, Renaud Tissier
Journal: Circulation (2020)

Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) using extracorporeal membrane oxygenation (ECMO) is widely proposed for the treatment of refractory cardiac arrest. Hypothesis: Since cerebral autoregulation is altered in such conditions, body position may modify hemodynamics during ECPR. Our goal was to determine whether a whole body tilt-up challenge (TUC) could lower intracranial pressure (ICP) as previously shown with conventional CPR, without deteriorating cerebral blood flow (CBF). Methods: Pigs were anesthetized and instrumented for the continuous evaluation of CBF, ICP and systemic hemodynamics. After 15 min of untreated ventricular fibrillation they were treated with 30 min of E-CPR followed by sequential defibrillation shocks until resumption of spontaneous circulation (ROSC). ECMO was continued after ROSC to target a mean arterial pressure (MAP) &gt;60 mmHg. Animals were maintained in the flat position (FP) throughout protocol, except during a 2 min TUC of the whole body (+30°) at baseline, during E-CPR and after-ROSC. Results: Four animals received the entire procedure and ROSC was obtained in 3/4. After cardiac arrest, E-CPR was delivered at 29±2 ml/kg/min to maintain a MAP of 57±8 mmHg in the FP. CBF was 28% of baseline and ICP remain stable (12±1 vs 13±1 mmHg during ECPR vs baseline, respectively). Under baseline pre-arrest conditions TUC resulted in a significant decrease in ICP (-63±7%) and CBF (-21±3%) versus the FP, with no significant effect on systemic hemodynamics. During E-CPR and after ROSC, TUC markedly reduced ICP but CBF remained unchanged vs the FP (Figure). Conclusion: During E-CPR whole body TUC reduced ICP without lowering CBF compared with E-CPR flat. Additional investigations with prolonged TUC and selective head and thorax elevation during E-CPR are warranted.
Abstract 334: Evaluating Sedation Regimens and Time to Awakening in Post Cardiac Arrest Patients
Authors: Marissa Levito, Cory McGinnis, Lara Groetzinger, Joseph Durkin, Jonathan Elmer
Journal: Circulation (2020)

Introduction: Guidelines for post-arrest care recommend use of short acting sedation, but there is currently significant practice variation. We tested whether benzodiazepine use was associated with delayed awakening in this population. Methods: We performed a retrospective cohort study at a large academic medical center including comatose patients hospitalized after resuscitation from in- or out-of-hospital cardiac arrest from January 2010 to September 2019. We excluded patients with cardiac arrest secondary to primary neurological event or trauma, those with severe cerebral edema on initial head imaging, those who were awake post-arrest and those with severe shock for whom benzodiazepines might have been chosen for hemodynamic reasons. We extracted all medication information from the electronic medical record and standard clinical and outcome information from a prospective registry maintained at our center. We considered patients to be exposed to benzodiazepines if they received &gt; 10mg midazolam equivalents in the first 72 hours after cardiac arrest and censored cumulative mediation data at awakening for those who awakened before 72 hours. Our primary outcome of interest was days from arrest to awakening, which we defined as following verbal commands. We compared median time to awakening across sedation groups, then performed Cox regression to test the independent association of benzodiazepine exposure with time to awakening after adjusting for age, sex, weight, presenting rhythm, arrest location, initial serum creatinine, initial shock severity, initial neurological examination and presence of epileptiform. Results: Overall, 2,778 patients presented during the study period of which 621 met inclusion criteria for analysis and 209/621 (34%) awakened after a median of 4 [IQR 3 - 7] days. Patients who received benzodiazepines for sedation awakened significantly later than those who did not (5 days vs. 3 days, P=0.004). In adjusted regression, benzodiazepine exposure was independently associated with delayed awakening (adjusted hazard ratio 0.64 (95% CI 0.44 - 0.94)). Conclusion: Benzodiazepine exposure is associated with delayed awakening in comatose survivors of cardiac arrest.
Abstract 129: Gasping During Cardiac Arrest Before Cardiopulmonary Resuscitation Increases Cerebral Oximetry in a Swine Model
Authors: Nelly Rojas-Salvador, Bayert Salverda, Johanna C Moore, Michael Lick, Guillaume P Debaty, Keith G Lurie
Journal: Circulation (2020)

Introduction: Spontaneous gasping (SG) during cardiac arrest is associated with favorable neurological outcomes. SG lowers intrathoracic pressure (ITP), enhancing flow of respiratory gases to the lungs and venous blood to the heart, while simultaneously lowering intracranial pressure (ICP). The impact of SG on regional cerebral oximetry (rSO2) is unknown. Hypothesis: During untreated ventricular fibrillation (VF), SG will increase rSO2 until the gasping effort declines. Methods: Swine (~40 kg) were intubated and anesthetized with isoflurane. After 8 min of untreated VF, conventional mechanical CPR at 100 compressions/min was performed. Intrathoracic pressure (ITP), mean aortic pressure (MAP), ICP, right atrial pressure (RAP) and calculated cerebral perfusion pressure (CerPP) were measured continuously. rSO2 was measured continuously with near-infrared spectroscopy (Equanox 7600, Nonin Medical). These parameters were assessed before and during SG, and during CPR. Data are expressed as mean ± SD. A paired Student’s t- test was used. Results: SG occurred in 19/22 pigs during untreated VF, with 9.2 ± 4.3 gasps/pig. For pigs that gasped, the individual gasp duration was 1.74 ± 0.52 sec and the maximum negative ITP (mmHg) was -3.24 ± 1.93 mmHg. rSO2 increased in 9/19 (47%) pigs from 54.7% ± 4.1 to 57.8% ± 4.8 during SG (p&lt;0.001). Figure 1 shows rSO2 from 2 representative pigs, A) with and B) without SG. SG also decreased ITP (p&lt;0.001), RAP (p=0.02) and ICP (p&lt;0.001), and increased MAP (p&lt;0.001) and CerPP (p&lt;0.001). After 8 min of untreated VF, rSO2 for all 22 pigs was 49.3% ± 3.7. After 30 and 60 sec of CPR, rSO2 values were 54.6% ± 3.8 and 57.8% ± 3.8, respectively. Conclusions: rSO2 values increased in nearly half of animals with SG. This increase in rSO2 with SG was equal to the level of rSO2 achieved after 1 minute of CPR. Further study is warranted to determine potential prognostic and therapeutic implications of SG-induced increases rSO2 during cardiac arrest.
Correction: Kissing scopes: treatment of complete esophageal obstruction using combined antegrade/retrograde approach
Authors: Marina Kim, Daniel Kats, Michel Kahaleh
Journal: Endoscopy (2020)

Correction to: Kissing scopes: treatment of complete esophageal obstruction using combined antegrade/retrograde approachEndoscopy 2021; 53(03): E106-E107DOI: 10.1055/a-1195-1723
Themis regulates metabolic signaling and effector functions in CD4+ T cells by controlling NFAT nuclear translocation
Authors: Mukul Prasad, Joanna Brzostek, Namrata Gautam, Renu Balyan, Vasily Rybakin, Nicholas R. J. Gascoigne
Journal: Cellular and Molecular Immunology (2020)

Themis is a T cell lineage-specific molecule that is involved in TCR signal transduction. The effects of germline Themis deletion on peripheral CD4+ T cell function have not been described before. In this study, we found that Themis-deficient CD4+ T cells had poor proliferative responses, reduced cytokine production in vitro and weaker inflammatory potential, as measured by their ability to cause colitis in vivo. Resting T cells are quiescent, whereas activated T cells have high metabolic demands. Fulfillment of these metabolic demands depends upon nutrient availability and upregulation of nutrient intake channels after efficient TCR signal transduction, which leads to metabolic reprogramming in T cells. We tested whether defects in effector functions were caused by impaired metabolic shifts in Themis-deficient CD4+ T cells due to inefficient TCR signal transduction, in turn caused by the lack of Themis. We found that upon TCR stimulation, Themis-deficient CD4+ T cells were unable to upregulate the expression of insulin receptor (IR), glucose transporter (GLUT1), the neutral amino acid transporter CD98 and the mTOR pathway, as measured by c-Myc and pS6 expression. Mitochondrial analysis of activated Themis-deficient CD4+ T cells showed more oxidative phosphorylation (OXPHOS) than aerobic glycolysis, indicating defective metabolic reprogramming. Furthermore, we found reduced NFAT translocation in Themis-deficient CD4+ T cells upon TCR stimulation. Using previously reported ChIP-seq and RNA-seq data, we found that NFAT nuclear translocation controls IR gene expression. Together, our results describe an internal circuit between TCR signal transduction, NFAT nuclear translocation, and metabolic signaling in CD4+ T cells.
Abstract 15810: Applying an LDL-C Threshold Based Approach to Identify Individuals With Familial Hypercholesterolemia
Authors: Amit Khera, Reena Jasani, Zahid Ahmad, Ruth Schneider, Carol Tujardon, Mujeeb Basit
Journal: Circulation (2020)

Background: Familial hypercholesterolemia (FH) is an inherited disorder associated with increased LDL-C and premature coronary heart disease, which remains significantly underdiagnosed. Screening those with very high LDL-C may help identify those with FH, but the optimal means of applying this approach is unclear. Methods: Individuals from UT Southwestern Medical Center, a large, tertiary academic center, with an LDL-C level ≥ 190 mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C: 190.0 - 219.9, 220.0 - 249.9, 250.0 - 299.9, and ≥ 300.0 mg/dL. One hundred individuals were randomly selected from each category for manual chart review to determine 1) the presence of secondary causes of dyslipidemia (obstructive liver disease, nephrotic syndrome, hypothyroidism, specific medication use, other secondary cause) and 2) diagnosis of possible/definite FH by modified Simon Broome criteria and 3) probable/definite FH by modified Dutch Lipid Clinic Network (DLCN) criteria. Results: Of the 400 individuals with an LDL-C level ≥ 190 mg/dL (mean age 52 years ± 14) in this cohort, the presence of secondary causes increased across each LDL-C category ( p &lt; 0.001) (Figure) with the greatest prevalence in those ≥ 300.0 mg/dL (52%). The prevalence of FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220.0 - 249.9 mg/dL category (52%) and by DLCN criteria in the 250.0 - 299.9 mg/dL category (46%). Conclusions: Amongst those with LDL-C ≥ 190 mg/dL, the prevalence of secondary causes increases with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299 mg/dL) may be the optimal group to prioritize for FH screening using an LDL-C based approach.
Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy
Authors: Bin Zhang, Ping Cheng
Journal: Molecular Cancer (2020)

Abstract As a promising therapeutic strategy, oncolytic virotherapy has shown potent anticancer efficacy in numerous pre-clinical and clinical trials. Oncolytic viruses have the capacity for conditional-replication within carcinoma cells leading to cell death via multiple mechanisms, including direct lysis of neoplasms, induction of immunogenic cell death, and elicitation of innate and adaptive immunity. In addition, these viruses can be engineered to express cytokines or chemokines to alter tumor microenvironments. Combination of oncolytic virotherapy with other antitumor therapeutic modalities, such as chemotherapy and radiation therapy as well as cancer immunotherapy can be used to target a wider range of tumors and promote therapeutic efficacy. In this review, we outline the basic biological characteristics of oncolytic viruses and the underlying mechanisms that support their use as promising antitumor drugs. We also describe the enhanced efficacy attributed to virotherapy combined with other drugs for the treatment of cancer.
Abstract 15053: Vascular Inflammation in Pulmonary Hypertension is Exacerbated by Litaf-dependent Pericyte Signaling
Authors: David Condon, Kian Shamskhou, Abinaya Nathan, Andrew Sweatt, Ananya Chakraborty, Stuti Agarwal, Roham Zamanian, Ke Yuan, Vinicio A De Jesus Perez
Journal: Circulation (2020)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disease which leads to right heart failure and death. Inflammation plays a key role in PAH pathogenesis as evidenced by inflammatory cell infiltrates around pulmonary vascular lesions and elevated patient serum pro-inflammatory cytokine levels. Pericytes are cells that provide mural support, maintain endothelial homeostasis and have immunomodulatory properties as evidenced by their production of cytokines and regulation of endothelial response to injury. Our group has shown that pericytes contribute to vascular remodeling and vessel loss in PAH, but their contribution to perivascular inflammation is unknown. Hypothesis: Lipopolysaccharide induced tumor necrosis factor activating factor (LITAF) positively regulates pericyte production of proinflammatory cytokines in PAH which influence activation of endothelial cells to engage in leukocyte recruitment. Methods: Healthy donor (HD) and PAH lung pericyte RNA-seq and microarray datasets were analyzed to identify candidate inflammatory pathways. Proteomic analysis was performed using Luminex assay followed by supervised machine learning. Quantitative PCR (qPCR) and western blot (WB) studies were conducted on HD and PAH pericytes exposed to serum starvation, hypoxia, LPS, and CoCl 2 (a HIF activator). Results: Network analysis based on RNA-seq, microarray, and Luminex assay data identified LITAF as a potential regulator of inflammatory gene expression. Compared to HD, abundant LITAF expression was visualized in human PAH perivascular lesions. WB of PAH pericytes showed a significant increase in nuclear LITAF compared to HD across all conditions. Pulmonary microvascular endothelial cells (PMVECs) incubated with media from PAH pericytes showed reduced cell-cell junctions and upregulated ICAM and VCAM compared to HD. Incubation of healthy PMVECs with supernatant from LITAF siRNA transfected HD and PAH pericytes showed a decrease in PMVEC proinflammatory cell markers. Conclusions: Our data suggest that LITAF-driven pericyte signaling could play a role in promoting vascular inflammation in PAH. We believe LITAF could serve as a potential new therapeutic target in PAH.