tbuckley/cabot-search huggingface dataset:
Abstract 16741: A Comparison of High versus Conventional Power Radiofrequency Catheter Ablation for Pulmonary Vein Isolation: A Systematic Review and Meta-Analysis
Authors: Mustapha Amin, Tarek Nayfeh, Ahmad Nanaa, Samer Mohir Saadi, Ammar M Killu, Malini Madhavan, Suraj Kapa, Christopher V Desimone, Siva K Mulpuru, Abhishek Deshmukh
Journal: Circulation (2020)

Objectives: We sought to evaluate the procedural safety and outcomes of high power (HP) versus conventional power (CP) radiofrequency (RF) ablation during pulmonary vein isolation (PVI). Methods: A systematic search was used via MEDLINE, EMBASE, and Cochrane databases between 01/1998 and 05/2020 for studies comparing the safety and efficacy between HP and CP during RF ablation for PVI using contact-force catheters (ThermocoolSmartTouch or TactiCath). The search terms used were “AF” AND “catheter ablation” OR “radiofrequency ablation”. Results: From eight comparative observational studies, we developed a cohort of 992 patients (478 in the HP and 514 in the CP group). The median maximum energy output used in the HP group was 50W vs 35W in the CP group. There was a statistically significant difference noted in acute pulmonary vein reconnection (APVR) in the HP group compared to the CP groups at16% vs 32.6%, respectively (RR: 0.53, 95% CI: 0.33 - 0.86, P = 0.01). Freedom from arrhythmia at 12 months follow-up was also significant and found to be 87.8% of cases in the HP group versus75.2% of cases in the CP group (RR: 0.46, 95%CI: 0.32 - 0.65, P &lt;0.01). The mean RF ablation time was 20.1 minutes in the HP group vs 39.6 minutes in the CP group (P &lt;0.01). The mean total procedural time was 103.5 minutes in the HP group compared to 135 minutes in the CP group (P &lt;0.01). Two patients in the CP group experienced severe adverse events (1 cardiac tamponade and 1 myocardial infarction). No serious AEs were found in the HP group. Non-serious AEs (groin complications, pericardial effusion, and phrenic nerve injury) were reported in 0.35% and 0.51% of cases in the HP and CP group, respectively. Conclusion: This study suggests that HP PVI ablation can be associated with better ablation outcomes by reducing the rate of acute and late PV reconnection and atrial arrhythmia recurrence, with similar safety profiles, and shorter procedural times. These findings merit evaluation in a randomized controlled trial.
Abstract 15499: Repression of Age-Determined Vascular Calcification by Ectonucleotidase CD73
Authors: Nadia R Sutton, Judy Kim, Rachel Kroll, Jun Chen, David J Pinsky
Journal: Circulation (2019)

Introduction: Vascular aging leads to vascular calcification, reduced vascular compliance, and ultimately, cardiovascular disease. The ectonucleotidase CD73 is a transmembrane enzyme which cataboli...
Contemporary Management of Heart Failure in Patients With Diabetes
Authors: James A. Shaw, Mark E. Cooper
Journal: Diabetes Care (2020)

Both heart failure and diabetes are increasing in prevalence in Western communities. The interrelationship between these two conditions is well known, with conventional heart failure therapies including several newer drug classes providing benefit to subjects with diabetes. Furthermore, several of the more recently introduced medications for type 2 diabetes have resulted in significant cardiovascular morbidity and mortality benefits with a marked improvement in heart failure symptoms and hospital presentations as well as deaths. This review outlines current therapies used to treat patients with or at risk for heart failure and their particular role in subjects with diabetes. Newer therapies, including certain glucose-lowering medications and their benefits in treating heart failure patients with and without diabetes, are also discussed. Finally, heart failure is also observed in long-duration, aging patients with type 1 diabetes, but this clinical issue has not been as extensively explored as in patients with type 2 diabetes and warrants further clinical investigation.
Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary T-Helper Cell Type 17 Response that Mitigates Susceptibility to <i>Streptococcus pneumoniae</i>
Authors: Benjamin G. Wu, Imran Sulaiman, Jun-Chieh J. Tsay, Luisanny Perez, Brendan Franca, Yonghua Li, Jing Wang, Amber N. Gonzalez, Mariam El-Ashmawy, Joseph Carpenito, Evan Olsen, Maya Sauthoff, Kevin Yie, Xiuxiu Liu, Nan Shen, Jose C. Clemente, Bianca Kapoor, Tonia Zangari, Valeria Mezzano, Cynthia Loomis, Michael D. Weiden, Sergei B. Koralov, Jeanine D’Armiento, Sunil K. Ahuja, Xue-Ru Wu, Jeffrey N. Weiser, Leopoldo N. Segal
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with an increased T-helper cell type 17 (Th17) inflammatory phenotype.Objectives: In this study, we evaluated the microbial and host immune-response dynamics after aspiration with oral commensals using a preclinical mouse model.Methods: Aspiration with a mixture of human oral commensals (MOC; Prevotella melaninogenica, Veillonella parvula, and Streptococcus mitis) was modeled in mice followed by variable time of killing. The genetic backgrounds of mice included wild-type, MyD88-knockout, and STAT3C backgrounds.Measurements and Main Results: 16S-rRNA gene sequencing characterized changes in microbiota. Flow cytometry, cytokine measurement via Luminex and RNA host-transcriptome sequencing was used to characterize the host immune phenotype. Although MOC aspiration correlated with lower-airway dysbiosis that resolved within 5 days, it induced an extended inflammatory response associated with IL-17-producing T cells lasting at least 14 days. MyD88 expression was required for the IL-17 response to MOC aspiration, but not for T-cell activation or IFN-γ expression. MOC aspiration before a respiratory challenge with S. pneumoniae led to a decrease in hosts' susceptibility to this pathogen.Conclusions: Thus, in otherwise healthy mice, a single aspiration event with oral commensals is rapidly cleared from the lower airways but induces a prolonged Th17 response that secondarily decreases susceptibility to S. pneumoniae. Translationally, these data implicate an immunoprotective role of episodic microaspiration of oral microbes in the regulation of the lung immune phenotype and mitigation of host susceptibility to infection with lower-airway pathogens.
COVID-19 Infection—Preventing Clinical Deterioration
Authors: Christopher W. Seymour, Howard Bauchner, Robert M. Golub
Journal: JAMA (2020)

Eric J. Lenze, MD; Caline Mattar, MD; Charles F. Zorumski, MD; Angela Stevens, BA; Julie Schweiger; Ginger E. Nicol, MD; J. Philip Miller, AB; Lei Yang, MPH, MSIS; Michael Yingling, MS; Michael S. Avidan, MBBCh; Angela M. Reiersen, MD, MPE
Abstract 12871: Comparison of Risk Scores at Predicting Mortality and Morbidities After Isolated Tricuspid Valve Surgery
Authors: Tom Kai Ming Wang, Kevser Akyuz, Alejandro Duran Crane, Samantha Xu, Bo Xu, A Gillinov, Gosta B Pettersson, Brian P Griffin, Milind Y Desai
Journal: Circulation (2020)

Background: Risk models play important roles in stratification and decision-making towards cardiac surgery. Isolated tricuspid valve surgery (TVR) is a high risk but increasingly performed operation, however the performance of surgical risk models, including the recently developed Society of Thoracic Surgeon’s (STS) TVR score, have not been externally evaluated in these patients. We compared the prognostic utility of contemporary risk scores for isolated TVR. Methods: Consecutive patients undergoing isolated TVR at Cleveland Clinic during 2004-2018 were evaluated. EuroSCORE II and STS-TVR score were retrospectively calculated, and their performance for predicting 30-day mortality, post-operative complications and mortality during follow-up were assessed. Results: Amongst 207 patients studied, mean age was 54.1±17.9 years, 116 (56.0%) were female, 92 (44.4%) had secondary tricuspid regurgitation, and 151 (72.9%) had surgical repair. Mean EuroSCORE II and STS-TVR scores were 6.3±6.6% and 5.5±6.2% respectively. Operative mortality occurred in 10 (4.9%). C-statistics (95% confidence intervals) for 30-day mortality were 0.83 (0.74-0.93) for EuroSCORE II and 0.60 (0.45-0.75) for STS-TVR score (Table), and observed/expected ratios were 0.78 and 0.89 respectively. EuroSCORE II also had higher c-statistics for composite and most post-operative complications. In univariable Cox regression for mortality during follow-up, hazards ratios (95% confidence intervals) were 1.08 (1.05-1.11) for EuroSCORE II and 1.06 (1.02-1.11) for STS-TVR score. Conclusion: EuroSCORE II was superior to STS-TVR score at predicting adverse outcomes after isolated TVR. Although risk scores traditionally under-estimated 30-day mortality after isolated TVR, our excellent surgical results meant that calibration of both scores were satisfactory for our cohort, and provides a benchmark for future studies of isolated surgical and transcatheter tricuspid valve procedures.
Abstract 136: Disparities in Out of Hospital Cardiac Arrest Care and Outcomes in Texas
Authors: Ryan Huebinger, Henry Wang, Jeff Jarvis, Cameron Decker, Robert Dickson, Lesley Osborn, Mark Escott, Lynn White, Normandy Villa, Micah Panczyk, Bentley Bobrow
Journal: Circulation (2020)

Background: Minorities and impoverished persons experience disparities in access to healthcare. Large inequalities in out-of-hospital cardiac arrest (OHCA) care have been described. We sought to characterize racial and socioeconomic disparities in OHCA care and outcomes in Texas. Hypothesis: There are census tract level disparities in OHCA care and outcomes in Texas. Methods: We analyzed Texas-Cardiac Arrest Registry to Enhance Survival (CARES) data from 13 EMS agencies providing care in 15 counties to roughly 30% of the state population. We included all adult (&gt;=18 year) OHCA from 1/1/14 through 12/31/18 with complete data. Using census tract data, we stratified census tracts into racial/ethnic categories: &gt;50% non-Hispanic/Latino white, &gt;50% black, and &gt;50% Hispanic/Latino. We also stratified census tracts into neighborhoods above and below the median for socioeconomic characteristics: household income, employment rate, and high school graduation. We defined outcomes as bystander CPR rates, public bystander AED use, and survival to hospital discharge. Using mixed models, we analyzed the associations between outcomes and neighborhood (1) racial/ethnic categories and (2) socioeconomic categories. Results: We included data on 18,487 OHCAs from 1,727 census tracts. Relative to white neighborhoods, black neighborhoods had a significantly lower rate of bystander AED use (OR 0.3, CI 0.1-0.9), and Latino neighborhoods had a lower rate of bystander CPR (OR 0.7, CI 0.6-0.8), bystander AED use (OR 0.4, CI 0.3-0.6) and survival to hospital discharge (OR 0.9, CI 0.8-0.98). Lower income was associated with a lower rate of bystander CPR (OR 0.8, CI 0.7-0.8), bystander AED use (OR 0.5, 0.4-0.8), and survival to hospital discharge (OR 0.6, CI 0.5-0.9). Lower high school graduation was associated with a lower rate of bystander CPR (OR 0.8, CI 0.7-0.9) and bystander AED use (OR 0.6, CI 0.4-0.9). High unemployment was associated with lower rates of bystander CPR (OR 0.9, CI 0.8-0.94) and bystander AED use (OR 0.7, CI 0.5-0.99). Conclusion: Minority and poor neighborhoods in Texas experience large and unacceptable disparities in OHCA bystander response and outcomes. These data present an important opportunity for targeted resuscitation training and quality improvement.
Abstract PO-062: EMT-induced gemcitabine resistance in pancreatic cancer involves the functional loss of equilibrative nucleoside transporter 1
Authors: Brenna Weadick, Debasis Nayak, Avinash K. Persaud, Sau Wai Hung, Radhika Raj, Wei Chen, Junan Li, Terence M. Williams, Rajgopal Govindarajan
Journal: Cancer Research (2020)

Abstract Epithelial-mesenchymal transition (EMT) in cancer cells drives cancer chemoresistance, yet the molecular events of EMT that underpin the acquisition of chemoresistance are poorly understood. Here, we demonstrate a significant loss of gemcitabine chemosensitivity facilitated by human equilibrative nucleoside transporter 1 (ENT1) during EMT in pancreatic cancer and identify that cadherin switching from the epithelial (E) to neuronal (N) type, a hallmark of EMT, contributes to this loss. Our findings demonstrate that N-cadherin decreases ENT1 expression, basolateral membrane localization and gemcitabine transport, while E-cadherin augments each of these. Besides E- and N-cadherin, another epithelial cell adhesion molecule, EpCAM, played a more prominent role in determining ENT1 membrane localization. Forced expression of EpCAM opposed cadherin switching with restored ENT1 expression, basolateral localization and gemcitabine transport in EMT-committed pancreatic cancer cells. In gemcitabine-treated mice, EpCAM positive tumors had high ENT1 expression and reduced metastasis, whereas tumors with N-cadherin expression resisted gemcitabine treatment and formed extensive secondary metastatic nodules. Tissue microarray profiling and multiplexed immunohistochemical analysis of pancreatic cancer patient-derived primary tumors revealed EpCAM and ENT1 cell surface co-expression is favored, and ENT1 plasma membrane expression positively predicted median overall survival times in patients treated with adjuvant gemcitabine. Together, our findings identify ENT1 as an inadvertent target of EMT signaling mediated by cadherin switching and provide a mechanism by which mesenchymal pancreatic cancer cells evade gemcitabine therapy during EMT. Citation Format: Brenna Weadick, Debasis Nayak, Avinash K. Persaud, Sau Wai Hung, Radhika Raj, Wei Chen, Junan Li, Terence M. Williams, Rajgopal Govindarajan. EMT-induced gemcitabine resistance in pancreatic cancer involves the functional loss of equilibrative nucleoside transporter 1 [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 PO-062.
Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Jennifer Ramsay, John McClure, Colin Berry
Journal: Circulation (2020)

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.
Abstract 13557: Regulation of PBEF Release by NAD Glycohydrolase CD38
Authors: Xiangdong Zhu, Angelo Meliton, Jing Li, Youhua Wang, Mengqi Zhu, Alan R Leff, Terry L Vanden Hoek
Journal: Circulation (2015)

Introduction: Our previous work suggests that PBEF is an early blood marker inversely related to hypothermia protection and resuscitation survival in a mouse model of hemorrhagic shock. Given that neutrophils are a potential high-concentration source of blood PBEF, we studied mechanisms of PBEF release from isolated human neutrophils that could help design novel resuscitation strategies. Methods: Human blood neutrophils were isolated by Percoll density gradient. PBEF secretion into neutrophil supernatant was measured by ELISA. Results: Non-stimulated neutrophils (i.e. exposed to serum-starved conditions) released PBEF. PBEF in supernatant was observed at 5 min and plateaued after 30 min at 37oC. This release was not due to cell injury since LDH was unchanged, nor was it blocked by the classical secretion inhibitors, brefeldin A (blocks ER-Golgi transport) or nocodazole (blocks microtubule polymerization). As PBEF product NAD+ is consumed by multiple intra- and ecto-NADases, we determined whether inhibition of NADase activity impairs PBEF release. Nicotinamide, a global inhibitor of all NADases, blocked PBEF secretion by 73%, suggesting NADases promote PBEF secretion. To identify the specific NADase in PBEF secretion, neutrophils were treated with inhibitors for PARP, sirtuin, CD38 or mono-ADP-ribosyltransferase. We found that inhibition of CD38 by tannic acid or apigenin was able to block PBEF secretion in neutrophils (10.2 ± 2.8 ng/ml for control vs 1.8 ± 0.2 ng/ml for tannic acid at 100 μM, P &lt; 0.01), but not by inhibitors of the other NADases. This observation indicated that CD38 glycohydroase activity is required for PBEF secretion. To further support the role of tannic acid in CD38 inhibition, tannic acid was shown to inhibit ε-ADP ribose production when neutrophils were treated with ε-NAD+. Finally, PBEF secretion was significantly enhanced by oxidative stress using H2O2 exposure. Conclusions: PBEF is constitutively released from neutrophils and this release is regulated by CD38 NAD glycohydrolase activity. Changes in human neutrophil microenvironment, especially oxidative stress, result in significant PBEF release within a timeframe that could account for the blood changes seen during mouse cardiovascular resuscitation.
Time to blood culture positivity in Staphylococcus aureus bacteraemia to determine risk of infective endocarditis
Authors: Fredrik Kahn, Fredrik Resman, Sissela Bergmark, Peter Filiptsev, Bo Nilson, Patrik Gilje, Magnus Rasmussen
Journal: Clinical Microbiology and Infection (2020)

Patients with Staphylococcus aureus bacteraemia (SAB) at risk for infective endocarditis (IE) need to be identified because they should undergo echocardiography. We validated previous scoring systems for IE risk determination and evaluated whether time to blood culture positivity (TTP) could improve scoring systems.This retrospective population-based study included adults with SAB in 2016 in a derivation cohort and those from 2017 in a validation cohort. TTP was compared between patients with and without IE. A new score including TTP was constructed using a least absolute shrinkage selection operator. The new POSITIVE score was compared to the previously described PREDICT and VIRSTA scores.A total of 465 episodes with SAB were included in the derivation cohort, of which 38 (8.2%) represented IE. Median (interquartile range) TTP was significantly shorter in episodes with IE, at 8.7 (7.7-10.6) hours compared to those without, at 13.3 (10.5-16.5) hours. When using a cutoff at 13 hours, TTP had a sensitivity of 100% (95% confidence interval (CI), 91-100) and specificity of 52% (95% CI, 47-57) for IE. The POSITIVE score included TTP, intravenous drug use, embolizations and presence of preexisting heart conditions. It had a sensitivity of 93% (95% CI, 76-99) and a specificity of 70% (95% CI, 66-74) in the validation cohort. The performance of POSITIVE was superior to PREDICT, and the specificity was higher than that of VIRSTA.TTP, either by itself or as part of the POSITIVE score, can be used to identify patients with SAB at low risk for IE. Further validation is needed because TTP is sensitive to several external factors.
Primary care networks: More effort is needed to engage with general practices, says report
Authors: Adrian O’Dowd
Journal: BMJ (2020)

The networks set up to improve primary care services for patients in England have good potential but have been held back in their first year by a lack of engagement from GP surgeries and deficiency in management capacity, a report has found.1

In July 2019 NHS England invited groups of general practices to join together as primary care networks (PCNs) and use new funding to offer extra services for improving patient health, including pharmacists based within general practices, additional GP and nursing support for care homes, and social prescribing.

A new evaluation study of PCNs, carried out by a team from the University of Birmingham’s Health Services Management Centre and the research institute …
Abstract 15055: Quantitative Echocardiography of the Left Atrium: Traditional Measurement by Manual Planimetry Can be Replaced by Automated Four-dimensional Imaging That is More Efficient and Provides Additional Information
Authors: Thuy Nguyen, Jonathan Wong, Christiane Abouzeid, Dwight Bibby, Qizhi Fang, Dai-Yin Lu, Nelson B Schiller
Journal: Circulation (2020)

Background: Manual volume measurement of the left atrium (LA) using two-dimensional (2D) imaging is time consuming and mainly produces volumetric information. Hypothesis: LA chamber quantification by semi-automated four-dimensional (4D) imaging may be more efficient and produces both volume and comprehensive functional analysis. Methods: Fifty subjects from the Healthy eHeart cohort of normal echocardiograms studied at the Research Cardiac Physiology Laboratory were selected by representative LA volumes. Studies were performed on a GE Vivid E95. Plainimetry was done on LA 2D images from apical 2 and 4 chamber views. Biplane LA maximal volume index (LAVImax) and minimal volume index (LAVImin) were calculated by method of discs. LA 4D images were obtained from an apical 4 chamber view. LA volume was calculated using a commercially available 4D Auto LAQ package. All 2D and 4D measurements were repeated at random by a sonographer. Analysis times for each LA volume quantitation were recorded. Intra-observer reproducibility was analyzed by coefficient of variation (CV). Results: Mean age of subjects was 51 ± 17 years (60% male). On 2D analysis, mean LAVImax was 26.7 ± 9.5 ml/m2 and mean LAVImin was 10.9 ± 4.4 ml/m2. Intra-observer reproducibility showed a CV of 9.1% for LAVImax and 8% for LAVImin. On 4D analysis, mean LAVImax was 27.2 ± 8.9 ml/m2 and mean LAVImin was 11.8 ± 3.9 ml/m2. Intra-observer reproducibility showed a CV of 4.0% for LAVImax and 5.0% for LAVImin. Time for LA volume quantification was 74 ± 15 seconds for 4D vs. 195 ± 30 seconds for 2D, p &lt; 0.001. The 4D analysis offered a LA volume curve, LA global longitudinal strain, and a real time 4D LA image that 2D did not. Conclusion: Acquisition and analysis of LA volume by 4D echocardiogram using a 4D Auto LAQ package requires less time than 2D analysis while producing a more comprehensive and reproducible result. It is worth considering advancing 4D LA quantification to a first-line method in clinically quantitating LA function.