tbuckley/cabot-search huggingface dataset:
Abstract 13631: Improving Cardiac Rehabilitation Attendance Through an Appointment-based Approach
Authors: Catherine Xie, Sean Fournier, Susan Hiller, Joyce Oen Hsiao, Rachel P Dreyer
Journal: Circulation (2020)

Introduction: Cardiac rehabilitation (CR) is the pillar of secondary prevention for patients with cardiovascular disease (CVD). Despite its effectiveness, there remain systemic issues with adherence to in-clinic CR sessions, with the median number of CR sessions completed nationwide being 26 (out of a total of 36 sessions). We evaluated pre-post health outcomes for patients participating in a patient-driven appointment-based CR program, reasons for discharge, as well as predictors of total CR sessions attended. Methods: We utilized data from the Yale New-Haven Health (YNHH) CR program over a 6-year period (2012-2017). Data was collected on patient demographics, socio-economic status, and clinical characteristics. We evaluated CR outcomes with paired T-tests and conducted logistic regression analysis to determine predictors of CR adherence and completion. Results: A total of 2,135 patients were enrolled in CR from 2012 to 2017 (27.9% women, mean age 65±12 years). Patients completed a median of 30 sessions out of a total of 36. The primary reason for discharge was completion of all 36 sessions of CR (46.4%). The appointment-based CR program resulted in significant improvements in physical health outcomes (Table) , with matched-subject improvements of 1.42 METs increase, 0.32 kg/m 2 decrease in BMI and a 1.88% decrease in body fat percentage (P&lt;0.001). Patients also demonstrated improvements in blood pressure control, lipid profiles and diabetes management. Logistic regression modeling found that patient-specific medical factors, such as self-reported levels of stress and physical activity were predictive of CR completion. Conclusion: We demonstrated that an appointment-based CR program led to an increase in the median number of CR sessions completed versus the nationwide average, and produced significant improvements in health outcomes. Appointment-based CR could aid in optimizing the dose-response benefit of CR for patients with CVD.
Abstract 17294: Outcomes of ECMO Use in Cardiogenic Shock: Analysis From the Nationwide Readmissions Database
Authors: Prakash Acharya, Abdulelah nuqali, Sagar Ranka, Zubair Shah, Kamal gupta
Journal: Circulation (2020)

Introduction: Extracorporeal membrane oxygenation (ECMO) is being increasingly used for acute support in patients with cardiogenic shock (CS). Data regarding the indications, outcomes, and readmissions in these patients from a nationally representative sample is lacking. Methods: A secondary analysis of the Nationwide Readmission Database for years 2016-2017 was performed. Patients who were admitted with a primary diagnosis of CS were identified using ICD-10, Clinical Modification codes and were sub-grouped into those with acute coronary syndrome (ACS) and without ACS (non-ACS). Any readmission within 30 days of discharge was considered for analysis. Results: A total of 6,126 patients with CS received ECMO support, among which 35% had concurrent acute coronary syndrome (ACS). Patients on ECMO who had ACS were significantly older (60.5±11 vs 45.1±11 years, p&lt;0.001) compared to non-ACS patients. Time to ECMO placement was also significantly shorter in ACS patients (3.4±5 vs 6.9±15 days, p&lt;0.001). There was no difference in complications during index admission including vascular complications and stroke among the two groups. The length of index hospitalization was longer in the non-ACS group (32.8±36 vs 19.6±22.9 days, p&lt;0.001) whereas mortality was significantly higher in patients with ACS (58.21 vs 49.55%, p&lt;0.001). Every decade increase in the age above 50 years significantly increased odds of mortality in the non-ACS group whereas in the ACS group, mortality increased significantly only when the age is over 70 years [HR 2.32, CI(1.35-3.99), p=0.002]. The rate of readmission among patients who survived to discharge was 18.2% (17.3% in ACS group vs 18.9% in non-ACS group, p=0.35). The most common primary causes of readmission were local complications from ECMO placement (7.65%), CHF, (6.5%), sepsis (6.5%), critical illness poly-myopathy/neuropathy (2.9%) and stroke (1.46%). The mortality during readmission was 8.2%. Conclusions: Only 1 in every 2 patients with CS on ECMO survives to discharge. Survival to discharge in these patients differs significantly according to the presence or absence of ACS. Among the patients who survive to discharge, 18% of patients are readmitted within 30 days.
Abstract 15336: Higher Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios Are Associated With Postoperative Atrial Fibrillation Following Transcatheter Aortic Valve Insertion
Authors: David Jin, Arul Baradi, Rohan Navani, Sarah Brazel, Robert Whitbourn, Arthur Nasis, Andrew M Wilson, Sonny Palmer
Journal: Circulation (2019)

Introduction: Postoperative atrial fibrillation (POAF) is a known complication following transcatheter aortic valve insertion (TAVI) and is associated with worse postoperative outcome. Both neutrop...
Hollow silica reinforced magnesium nanocomposites with enhanced mechanical and biological properties with computational modeling analysis for mandibular reconstruction
Authors: Somasundaram Prasadh, Vyasaraj Manakari, Gururaj Parande, Raymond Chung Wen Wong, Manoj Gupta
Journal: International Journal of Oral Science (2020)

Abstract The present study investigates Mg-SiO 2 nanocomposites as biodegradable implants for orthopedic and maxillofacial applications. The effect of presence and progressive addition of hollow silica nanoparticles (0.5, 1, and 1.5) vol.% on the microstructural, mechanical, degradation, and biocompatibility response of pure Mg were investigated. Results suggest that the increased addition of hollow silica nanoparticles resulted in a progressive increase in yield strength and ultimate compressive strength with Mg-1.5 vol.% SiO 2 exhibiting superior enhancement. The response of Mg-SiO 2 nanocomposites under the influence of Hanks’ balanced salt solution revealed that the synthesized composites revealed lower corrosion rates, indicating rapid dynamic passivation when compared with pure Mg. Furthermore, cell adhesion and proliferation of osteoblast cells were noticeably higher than pure Mg with the addition of 1 vol.% SiO 2 nanoparticle. The biocompatibility and the in vitro biodegradation of the Mg-SiO 2 nanocomposites were influenced by the SiO 2 content in pure Mg with Mg-0.5 vol.% SiO 2 nanocomposite exhibiting the best corrosion resistance and biocompatibility when compared with other nanocomposites. Enhancement in mechanical, corrosion, and biocompatibility characteristics of Mg-SiO 2 nanocomposites developed in this study are also compared with properties of other metallic biomaterials used in alloplastic mandibular reconstruction in a computational model.
Abstract 14421: Association Between Meeting Daily Step Count Goals With Ambulatory Function and Quality of Life in Patients With Claudication
Authors: Andrew W Gardner, Polly Montgomery, Ming Wang, Biyi Shen
Journal: Circulation (2020)

Introduction: The aims were to determine (a) whether patients with peripheral artery disease (PAD) who walked at least 7,000 and 10,000 steps/day had better ambulatory function and health-related quality of life (HRQoL) than patients who walked less than 7,000 steps/day, and (b) whether these group differences persisted after adjusting for covariates. Hypothesis: Patients who walk at least 7,000 steps/day have significantly better ambulatory function, as measured by greater 6-minute walk distance (6MWD), and better HRQoL, as measured by a higher distance score on the Walking Impairment Questionnaire (WIQ), than patients who walked less than 7,000 steps/day, and that patients who walked more than 10,000 steps/day would have the best values. Furthermore, group differences in the primary outcomes would persist after adjustment for covariates. Methods: Two hundred forty-eight patients were assessed on their daily activity for one week with a step activity monitor, and were grouped according to daily step counts as follows: Group 1 (&lt;7,000 steps/day; n=153), Group 2 (7,000-9,999 steps/day; n=57), Group 3 (&gt;10,000 steps/day; n=38). Primary outcomes were 6MWD and WIQ distance score, which is a disease-specific measurement of HRQoL. Results: Groups were different (p&lt;0.05) on ankle/brachial index, and on prevalence of hypertension, diabetes, abdominal obesity, arthritis, and chronic obstructive pulmonary disease. Thus, these variables served as covariates in adjusted analyses, along with age, weight, and sex. 6MWD (mean±SD) was significantly different among the groups in unadjusted (p&lt;0.01) and adjusted (p&lt;0.01) analyses (Group 1=313±90 m, Group 2=378±84 m, Group 3=414±77 m), with Groups 2 and 3 having higher 6MWD than Group 1 (p&lt;0.01). Similar results were found for the WIQ distance score (Group 1=30±30%, Group 2=45±35%, Group 3=47±34%; p&lt;0.01). Conclusions: PAD patients who walked more than 7,000 and 10,000 steps/day had greater ambulatory function and HRQoL than patients who walked fewer than 7,000 steps/day, and this finding persisted after adjusting for covariates. The clinical significance is that PAD patients should be encouraged to walk more than 7,000 steps/day because this target is associated with greater ambulatory function and HRQoL
Abstract 12718: Ethnic Disparities in Outcomes After Left Ventricular Assist Device Implantation: An Analysis of National Inpatient Sample
Authors: Hiroki Ueyama, Aaqib H Malik, Toshiki Kuno, Yujiro Yokoyama, Suchith Shetty, Alexandros BRIASOULIS
Journal: Circulation (2020)

Introduction: Previous studies of patients undergoing various cardiac surgeries demonstrated worse outcomes among African American (AA) patients. It remains unclear if race is a predictor of outcomes among Left Ventricular Assist Device (LVAD) recipients. Methods: Patients who underwent LVAD implantation between 2010 and 2017 were identified using the national inpatient sample (NIS). Race was classified as Caucasians vs. AA vs. Hispanics, and endpoints were in-hospital outcomes, length of stay and cost. Procedure-related complications were identified via ICD-9 and ICD-10 coding and analysis was performed via mixed effect models. Results: A total of 27,132 adults (5,114 unweighted) underwent LVAD implantation in the U.S. between 2010 and 2017, including Caucasians (63.8%), AA (23.8%) and Hispanics (6%). The number of LVAD implantations increased in both Caucasians and AA during the study period. AA LVAD recipients were younger, with higher rates of females and most of the comorbidities, but lower rates of coronary artery disease and coronary artery bypass grafting compared to Caucasians and Hispanics. Medicaid and median income at the lowest quartile were more frequent among AA LVAD recipients. We did not identify differences in in-hospital mortality, stroke, bleeding complications, infectious complications, and acute kidney injury requiring hemodialysis among racial groups (Table). AA LVAD recipients had lower rates of routine discharge than Caucasians and Hispanics, longer length of stay than Caucasians but similar cost of hospitalization. After adjustment with age gender and clinical comorbidities, race was not a predictor of in-hospital mortality. Conclusions: We identified differences in clinical characteristics but not in in-hospital complications among LVAD recipients of different race.
Abstract PO-006: Single cell transcriptomic analysis of primary head and neck cancer stem cells
Authors: Molly E. Heft Neal, Stephanie The, John Henry J. Owen, Clifford Chang, Mark E.P. Prince, Arvind Rao, Steven B. Chinn
Journal: Cancer Research (2020)

Abstract Despite advances in treatment modalities for head and neck squamous cell carcinoma (HNSCC) survival rates remain unchanged. Tumor heterogeneity within HNSCC as well as within the tumor microenvironment (TME) has been shown to be a major driver of treatment failure and poor outcomes. A key component of the TME and a potential key to deciphering tumor heterogeneity are cancer stem cells. While numerous studies have demonstrated the tumorigenicity and malignant potential of these cells, few studies have investigated their expression profiles. The aim of this study is to leverage single cell technology to investigate the expression profile of primary HNSCC cancer stem cells. We performed single cell sequencing of five primary HPV-negative head and neck cancers and two HNSCC cell lines that were presorted into the CSC (CD44high/ALDH+) and non-CSC (CD44low/ALDH-) phenotype. We are able to characterize an expression profile of the CSC TME niche and a novel CSC expression profile (DCN, C110rf96, KLF4, MEG3 and NR4A1) relative to non-CSC. We confirm this CSC profile is conserved across all five primary tumors. Together these data provide some of the first insights into CSC transcriptome, further define the CSC-TME niche, and identify conserved targets within HNSCC CSC as a means to decipher the challenges inherent to tumor heterogeneity. Citation Format: Molly E. Heft Neal, Stephanie The, John Henry J. Owen, Clifford Chang, Mark E.P. Prince, Arvind Rao, Steven B. Chinn. Single cell transcriptomic analysis of primary head and neck cancer stem cells [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-006.
Abstract 17220: Functional Roles and Molecular Mechanisms of Calcium Release Signaling in Hypoxic Cellular Responses in Pulmonary Artery Smooth Muscle Cells
Authors: Yong-xiao Wang, Yun-Min Zheng
Journal: Circulation (2020)

Introduction: Hypoxia causes contractile and proliferative responses in pulmonary arterial smooth muscle cells (PASMCs), but not systemic artery SMCs, thereby leading to pulmonary hypertension (PH), but not systemic hypertension. However, the underlying mechanisms remain unclear. Hypothesis: Ca 2+ release signaling in PASMCs may mediate hypoxic pulmonary artery vasoconstriction, remodeling and hypertension. Methods: Single cell RT-PCR and Western blot analysis, FRET and immunoprecipitation, tissue contraction assay, immunohistochemistry staining and pressure-volume loop analysis, and genetic and pharmacological approaches, were, respectively, used to determine targeted molecular expression, interaction and function. Results: All ryanodine receptor (RyR1, RyR2 and RyR3) Ca 2+ release channels are expressed in mouse PASMCs. RyR1 or RyR3 knockout (KO) partially inhibits, while RyR2 KO completely blocks, hypoxic cellular responses. SMC-specific RyR2 KO restores abolishes hypoxic pulmonary artery vasoconstriction, remodeling and hypertension in mice. RyR2 KO also inhibits hypoxic nuclear factor (NF)-κB and downstream cyclin D1 activation. FK506 binding protein 12.6 (FKBP12.6) is an endogenous RyR2 inhibitor; its KO or FK506 treatment enhances, and treatment of S107 (a specific RyR2/FKBP12.6 stabilizer) inhibits hypoxic PH. Lentiviral shRNA-mediated SMC-specific Rieske iron-sulfur protein (RISP) knockdown diminishes mitochondrial reactive oxygen species (ROS) generation, RyR2/FKBP12.6 complex dissociation, and RyR2 activation, thereby blocking hypoxic PH. Conclusions: RyR1, RyR2 and RyR3 are all involved in hypoxic contractile and proliferative responses in PASMCs, but RyR2 is a most important player. RISP-dependent mitochondrial ROS - FKBP12.6/RyR2 complex dissociation - RyR2 hyperfunction signaling mediate PA vasoconstriction. RyR2 hyperfunction also activates Ca2+-dependent NF-κB/cyclinD1 pathway to provoke PA remodeling; PA vasoconstriction and remodeling together cause PH. Furthermore, RISP-mediated ROS inhibition, RyR2/FKBP12.6 complex stabilization and Ca2+ release blockade may be novel and effective options for the treatment of PH.
Driver Mutation Acquisition <i>in Utero</i> and Childhood Followed By Lifelong Clonal Evolution Underlie Myeloproliferative Neoplasms
Authors: Nicholas Williams, Joe Lee, Luiza Moore, Joanna E Baxter, James Hewinson, Kevin J Dawson, Andrew Menzies, Anna L Godfrey, Anthony R Green, Peter J Campbell, Jyoti Nangalia
Journal: Blood (2020)
Abstract PO-099: SOX2 delineates a mouse lung adenocarcinoma subtype vulnerable to targeted therapy
Authors: Jonathan E. Cooper, Anneleen Daemen, Dorothee Nickles, Szymon Myrta, Oded Foreman, Jeff Eastham, Melissa R. Junttila, Heinrich Jasper
Journal: Cancer Research (2020)

Abstract Lung adenocarcinomas comprise the largest fraction of non-small cell lung cancer, which is the leading cause of cancer deaths. 75% of adenocarcinomas lack targeted therapies due to scarcity of druggable drivers. We leveraged transcriptional data from &amp;gt;800 early-stage and advanced patients to classify tumors based on signaling similarities and discover subgroups within this unmet patient population. The subtypes capture heterogeneity even amongst tumors lacking known oncogenic drivers. Paired multi-regional intratumoral biopsies demonstrate unified subtypes despite divergently evolved pro-oncogenic mutations, indicating subtype stability during selective pressure. We identified differential subtype response to MEK inhibition across multiple preclinical model systems and a clinical trial, supporting prognostic utility of transcriptional subtyping. Differential subtype dependency on MEK signaling reproduced in a mouse model of KRAS-mutant lung adenocarcinoma, where a MEK-dependent adenocarcinoma subtype is driven by a SOX2 cellular state. Our findings support forward translational relevance of transcriptional subtypes and reveal that naturally evolved yet ectopic expression of a pioneer transcription factor may modulate tumor subtype and response. Citation Format: Jonathan E. Cooper, Anneleen Daemen, Dorothee Nickles, Szymon Myrta, Oded Foreman, Jeff Eastham, Melissa R. Junttila, Heinrich Jasper. SOX2 delineates a mouse lung adenocarcinoma subtype vulnerable to targeted therapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-099.
Covid-19: Government buried negative data on its favoured antibody test
Authors: Stephen Armstrong
Journal: BMJ (2020)

The UK government delayed the findings of a Public Health England (PHE) study that question the accuracy of a leading covid antibody test just as it was about to announce that it had spent £75m (€84.3m; $99.4m) on buying one million of the tests.

The study,1 published online this week at bmj.com, is the first independent assessment of the test and finds it to be significantly less accurate than a manufacturer funded study has claimed. If the test is used in the community as intended, and assuming that 10% of recipients have previously been infected, around one in five positive AbC-19 tests would be a false positive, the findings suggest.

The AbC-19 Rapid Test uses a drop of blood from a finger prick to see whether someone has previously been infected with SARS-CoV-2. It gives …
Abstract IA-15: Metabolic networks in the pancreatic tumor microenvironment
Authors: Costas A. Lyssiotis
Journal: Cancer Research (2020)

Abstract Pancreatic tumors are dynamic pseudo-organs that contain numerous cell types interacting to create unique physiology. A typical pancreatic tumor is made up largely of stromal fibroblasts and immune cell populations, rather than cancer cells. These non-malignant cells act collaboratively to create a dense fibrotic matrix that blocks cancer cells from accessing nutrients and oxygen by inhibiting vascularization. The cancer cells are thus in a state of near-starvation and must employ unorthodox methods to obtain nutrients to support their bioenergetic and biosynthetic needs. Our group has provided foundational work describing the cell autonomous reprogramming of metabolic processes in the cancer cells to facilitate survival and growth under these challenging circumstances. Beyond cell intrinsic metabolic alterations, pancreatic cancer cells also work cooperatively with non-cancer cells in the tumor microenvironment through the exchange of growth factors, signaling molecules and metabolites. In this seminar, I will describe new work illuminating pathways of metabolic crosstalk among pancreatic cancer-associated fibroblasts, tumor associated macrophages, and malignant pancreatic cancer cells in maintenance of tumor growth, survival and therapeutic resistance. Citation Format: Costas A. Lyssiotis. Metabolic networks in the pancreatic tumor microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-15.
Abstract 13719: Long Qt Associated Ventricular Tachycardia Caused by Sex Hormone Therapy
Authors: Bina Kviatkovsky, mohammad abureesh, Samer Saouma, Michael P Cinelli, Philippe Akhrass, Rina Shah, Marcin Kowalski, Soad Bekheit
Journal: Circulation (2020)

Introduction: Increasing number of patients are currently receiving hormonal therapies for a variety of conditions. Modulation of cardiac repolarization by sex hormones resulting in VT remains controversial. Anastrozole is an aromatase inhibitor (ANI), used as an anti-estrogen medication in women with breast cancer or as replacement therapy for hypogonadism. Arrhythmias associated with ANI are extremely rare and hence ANI is considered relatively safe to use. Case Presentation: We report two cases receiving ANI who presented with VT and long QT (LQT). Case 1, 71 year old female with breast cancer on ANI recently started on levofloxacin 750 mg qd, presented with monomorphic VT. Post-conversion ECG showed sinus rhythm (SR) QT 0.48s/QTc 0.56s. Case 2, 50 year old male with hypogonadism on ANI and clomiphene (CL) presented with monomorphic VT, post conversion ECG showed SR with QT 0.65s/QTc 0.59s. Both patients had normal electrolytes and coronaries. Discussion: Studies have shown that levofloxacin is not associated with significant LQT, however, a relationship between its concentration and the extent of LQT has been demonstrated. LQT in our first case can be explained by an increase in levofloxacin level resulting from inhibition of CYP by ANI. CL is a HERG inhibitor however has not been shown to prolong QT. ANI lower the estradiol level which blocks the membrane trafficking of KCNH2 channels, potentially lengthening the QT. LQT in the second case can be explained by the additive effect of both HERG and KCNH2 inhibition. Conclusion: Although reported as safe, ANI hormone therapy can be arrhythmogenic if combined with agents that potentially affect potassium currents. We recommend QT monitoring in such patients to prevent lethal arrhythmias.
Relationships Between Academic Medicine Leaders and Industry—Time for Another Look?
Authors: Carolyn Becker
Journal: JAMA (2020)

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