tbuckley/cabot-search huggingface dataset:
Abstract 19134: Elevated Troponin T is Associated with Adverse Outcomes After Aortic Valve Replacement
Authors: AshwatDhillon, KanhaiyaPoddar, MuratTuzcu, EricRoselli, LarsSvensson, SamirKapadia
Journal: Circulation (2014)

Background: Data regarding association of elevated cardiac enzymes and adverse outcomes in patients who undergo aortic valve replacement (AVR) has been inconclusive. Role of coronary revascularization prior to AVR remains uncertain. We sought to understand prognostic implication of post procedure troponin T (TnT) elevation in patients undergoing AVR. Hypothesis: We hypothesized that patients with significantly elevated TnT after AVR will have worse outcomes representing important coronary circulation which is not revascularized. Methods: We retrospectively studied 4648 consecutive patients who underwent AVR at a single tertiary care center between January 2007 and December 2013. These were divided into surgical AVR (SAVR) and transcatheter AVR (TAVR). Median post procedure peak TnT was identified in the SAVR and TAVR groups. Patients were divided into quartiles based on median TnT level. Results: Of 4648 patients who underwent AVR, 4200 (66% male) were SAVR and 448 (59% male) were TAVR. Median post proced...
Abstract 12387: Comparison of Brain Injury and Quantitative Eeg Measures After Ventricular Fibrillation and Asphyxial Cardiac Arrest
Authors: Yongqin Li, Pei Wang, Bihua Chen, Mi He
Journal: Circulation (2015)

Introduction: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest. However, different mechanisms of cardiac arrest cause different morphologic patterns of brain injury. In the present study, we compared postresuscitation brain injury and characteristics of EEG between animals resuscitated from cardiac arrest induced by ventricular fibrillation (VF) and asphyxiation (AS). Methods: Thirty-two healthy adult Sprague-Dawley rats of both sexes were randomized to either VF or AS. For animals assigned to VF, cardiac arrest was induced through high frequency transesophageal cardiac pacing and untreated for 5 mins. After 2 mins of cardiopulmonary resuscitation (CPR), a 2-J biphasic defibrillation shock was delivered. For AS, cardiac arrest was induced by airway obstruction, and CPR was initiated after pulselessness was maintained for 5 mins. Serum level of S100B were measured at baseline, 2 and 4 hrs postresuscitation. EEG were continuously measured for 4 hrs and was quantified by information quantity entropy (IQE). Results: There were no significant difference in body weight, baseline heart rate, mean arterial pressure and ejection fraction measurement. All of the animals were successfully resuscitated. However, duration of CPR (72±28 s vs. 200±59 s, p&lt;0.001) was significantly shorter in AS group. Figure 1 shows the S100B (A) and IQE (B) measurement before and after resuscitation. Brain injuries were severe while EEG measures were lower in the AS group during the postresuscitation period. This was associated with considerably lower 96 hrs survival rate (25.0% vs. 87.5%, p&lt;0.001) compared with VF. Conclusion: In this rat model, both VF and AS cardiac arrests caused brain injuries. Compared with VF, AS caused more severe brain injury and associated with lower survival rate. Quantitative EEG analysis was prognostic for neurological outcome when mechanisms of cardiac arrest was different.
Abstract 4685: Phenotypic difference of CD103+ tissue-resident memory T cells in various cancers
Authors: Hye Seon Park, Young-Ae Kim, Won Seon Bang, Heejae Lee, Miseon Lee, In Ah Park, In Hye Song, Sun-Hee Heo, Hyeonjin Lee, Hee Jin Lee, Gyungyub Gong
Journal: Cancer Research (2018)

Abstract Background: The presence and clinical importance of tissue-resident memory T cells (TRM) have been recently described in human lung, liver, and bladder cancer. However, the frequency and phenotypic characteristics of TRM in other tumors are largely unknown. Methods: We analyzed single-cell populations of renal cell carcinoma (n=20), breast (n=16), colorectal (n=20), and stomach cancer (n=15) by dissociation of tumor tissue with collagenase/hyaluronidase. We investigated population of memory T cells and TRM using anti-CD45RO or anti-CD103 antibodies by flow cytometry. Results: Colorectal cancer had higher level of CD4+ T cells (70.1%) among CD3+ T cells than other tumors (stomach cancer, 59.6%; renal cell carcinoma, 49.4%; breast cancer, 49.0%; p=0.001). In CD4+ T cells, the percentage of CD45RO+ memory T cells was higher in renal cell carcinoma (75.7%) and breast cancer (85.4%) than colorectal (36.9%) and stomach cancer (38.1%, p&amp;lt;0.001). About 4% of CD4+ T cells in renal cell carcinoma, colorectal and stomach cancer were TRM, while 14.3% of CD4+ T cells were TRM in breast cancer (p&amp;lt;0.001). The percentage of CD45RO+ memory T cells among CD4+ TRM was about 60% in all tumors (p=0.164). In CD8+ T cells, the percentage of CD45RO+ memory T cells was higher in renal cell carcinoma (73.5%), breast (66.4%) and stomach cancer (54.4%) than colorectal cancer (33.0%, p&amp;lt;0.001). Stomach cancer had higher level of TRM (74.3%) among CD8+ T cells than other tumors (colorectal cancer, 19.6%; renal cell carcinoma, 20.1%; breast cancer, 30.6%; p&amp;lt;0.001). The percentage of CD45RO+ TRM in renal cell carcinoma (89.3%) and breast cancer (89.5%) was higher than colorectal (43.0%) and stomach cancer (51.5%, p&amp;lt;0.001). Conclusions: The frequency and phenotypic characteristics of TRM in renal cell carcinoma, colorectal, stomach, and breast cancer were different. Further studies regarding functional difference and clinical significance of TRM in various tumors are warranted.Acknowledgement: This study was supported by Basic Science Research Programs through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT &amp; Future Planning, Republic of Korea (NRF-2017R1D1A1B03033104). Citation Format: Hye Seon Park, Young-Ae Kim, Won Seon Bang, Heejae Lee, Miseon Lee, In Ah Park, In Hye Song, Sun-Hee Heo, Hyeonjin Lee, Hee Jin Lee, Gyungyub Gong. Phenotypic difference of CD103+ tissue-resident memory T cells in various cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4685.
Abstract 18811: Improving the Practicality of Echocardiographic Screening for Rheumatic Heart Disease: Performance of Non-expert Users Following Completion of a Standardized Computer-based Training Curriculum
Authors: Andrea Beaton, Bruno R Nascimento, Adriana C Diamantino, Gabriel T Pereira, Eduardo L Lopes, Cassio O Miri, Kaciane K Bruno, Graziela Chequer, Camila G Ferreira, Luciana C Lafeta, Hedda Richards, Lindsay Perlman, Catherine Webb, Antonio L Ribeiro, Craig Sable, Maria do Carmo P Nunes
Journal: Circulation (2015)

Background: Echocardiography (echo) is the most sensitive tool for rheumatic heart disease (RHD) detection. However, widespread screening programs are non-existent due to lack of financial and expert human resources in endemic areas. Task-shifting to non-experts to perform RHD screening is promising; however, investigations into workforce composition and replicable training schemes are needed. Objective: Test non-experts’ ability to conduct RHD screening following a brief, standardized, computer-based training course. Methods: Six non-experts with a variety of backgrounds (nurses, health technicians, medical students) and echo experience (6 wks-1 yr) completed a 3-module computer-based curriculum focusing on simplified criteria for RHD screening (mitral regurgitation (MR) ≥1.5cm and/or any aortic regurgitation). Following training, two teams of 3 non-experts were placed in school screening environments. Gold-standard diagnoses of RHD (2012, World Heart Federation criteria) were made by cardiologists using standard portable echo equipment. Children diagnosed with RHD and 25% of the general screening population was blindly evaluated by each non-expert using the simplified criteria with handheld echo. Results: Screening was performed in 1,381 children, with 397 (47 borderline RHD, 6 definite RHD, 336 normal &amp; 8 other) referred for handheld echo (209 Team 1 &amp; 188 Team 2). Age ranged from 5-18 years (mean 13.6); 59% were female. Overall sensitivity of the simplified approach was 90.8% (95% CI 85.4-94.6%; range 75-100%), with an overall specificity of 82.4% (95% CI 79.9-84.7%; range 75-89%). The most common reasons for false-negative screens (n=16) were missed MR (44%) and MR ≤1.5cm (29%), and for false-positive screens (n=179) included identification of erroneous color jets (25%), incorrect MR measurement (24%), and appropriate application of simplified guidelines (MR between 1.5 and 2.0 cm, 39.4%). Conclusions: A short, computer-based curriculum can be successfully used to train a heterogeneous group of non-experts to preform large-scale RHD screening. This simplified approach addresses prohibitive financial and workforce barriers to widespread RHD screening and holds the potential to significantly reduce the global burden of RHD.
Abstract 19129: Does System Modification “Really” Modify Survival in Patients With High Defibrillation Threshold? Probably Not
Authors: Najmul Siddiqi, Salim Ahmed, Rohan Bhojwani, Mohammed Kanj, Patrick Tchou, Niraj Varma
Journal: Circulation (2014)

Introduction: Defibrillation threshold (DFT) testing is a routine part of implantable cardiac defibrillator (ICD) placement at most centers. If a patient is found to have a high DFT, many physicians perform system modification by adding subcutaneous or transvenous shocking coil to the ICD in an attempt to lower DFT. It is not clear how patients with system modification fare compared to patients without such modification. Hypothesis: System modification should have an effect of reducing mortality in patients high DFT when compared with those who don’t undergo it. Methods: We retrospectively reviewed demographic and procedural data from 6520 patients who underwent ICD implant at the Cleveland Clinic, between August 1996 and November 2010. The Social Security Death Index was queried to obtain mortality data. High DFT was defined as DFT greater than 25 joules. Among patients with high DFT, survival was compared between those who underwent system modification versus those who did not, using the log-rank test. Results: 191 patients had a high DFT (mean DFT 30.6+/- 3.4J). The types of ICDs were single chamber 64 (33.5%); dual chamber 72 (37.7%) and cardiac resynchronization or CRT-D 55 (28.8%). 120 patients underwent a system modification (mean DFT after modification was 24.3+/- 5.6J). The commonest system modification was subcutaneous coil (70 patients; Medtronic 6996SQ-58). Median follow-up was 1788 days. Kaplan-Meier survival curves of these two groups exhibited no significant difference in mortality between patients with and without system modification (Mantel-Cox Log-rank, p = 0.731). Conclusions: Patients with high DFT at ICD implant managed by system modification have mortality similar to patients without it. This questions the practice of system modification &amp; calls for further analysis.
Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery
Authors: Sergey E. Borisov, Lia D'Ambrosio, Rosella Centis, Simon Tiberi, Keertan Dheda, Jan-Willem Alffenaar, Rohit Amale, Evgeny Belilowski, Judith Bruchfeld, Barbara Canneto, Justin Denholm, Raquel Duarte, Aliasgar Esmail, Alex Filippov, Lina Davies Forsman, Mina Gaga, Shashank Ganatra, Gaida Anastasia Igorevna, Barbara Lazaro Mastrapa, Vinicio Manfrin, Selene Manga, Andrey Maryandyshev, Gilbert Massard, Pablo González Montaner, Jai Mullerpattan, Domingo Juan Palmero, Agostina Pontarelli, Apostolos Papavasileiou, Emanuele Pontali, Rodolfo Romero Leyet, Antonio Spanevello, Zarir Farokh Udwadia, Pietro Viggiani, Dina Visca, Giovanni Sotgiu, Giovanni Battista Migliori
Journal: Journal of Infection (2018)
Endothelin-1 Inhibits Endothelin-Converting Enzyme-1 Expression in Cultured Rat Pulmonary Endothelial Cells
Authors: ShojiroNaomi, TaisukeIwaoka, TumbaDisashi, JunnosukeInoue, YoshieKanesaka, HiroshiTokunaga, KimioTomita
Journal: Circulation (1998)

Background—The lung expresses large amounts of endothelin-converting enzyme-1 (ECE-1), which catalyzes a step in the biosynthesis of potent vasoactive endothelin-1 (ET-1) from the inactive intermediate big ET-1. Because there has been no report concerning a possible relationship between ET-1 and ECE-1, we investigated the effects of ET-1 on ECE-1 expression in cultured rat pulmonary endothelial cells. Methods and Results—ECE-1 messenger RNA (mRNA) and protein expression in cultured endothelial cells were assayed by Northern and Western blotting, respectively. Incubation with ET-1 for 6 hours caused a significant decrease in ECE-1 mRNA expression. The action of ET-1 on ECE-1 mRNA expression was antagonized by pretreatment with BQ788, a specific ETB receptor antagonist, but not by pretreatment with BQ123, a specific ETA receptor antagonist. The expression of ECE-1 protein was also inhibited at 6 hours after incubation with ET-1. The effects of ET-1 on ECE-1 mRNA and protein expression were shown to be mimic...
Alteration in Energetics in Patients With Left Ventricular Dysfunction After Myocardial Infarction
Authors: YoshihikoHayashi, MotoshiTakeuchi, HideyukiTakaoka, KatsuyaHata, MasukiMori, MitsuhiroYokoyama
Journal: Circulation (1996)

Background Although the use of inotropic agents to treat congestive heart failure (CHF) in patients with coronary artery disease has yielded short-term hemodynamic improvement, long-term mortality has shown less improvement. The loss of cardiac muscle as a result of infarction not only decreases the pumping ability of the heart but also leads to some dramatic changes in myocardial energetics. However, little is known about the mechanoenergetics of the heart in patients with left ventricular (LV) dysfunction after myocardial infarction. Methods and Results The present study was designed to compare, by means of the Vo2-pressure-volume area relation (PVA, a measure of total mechanical energy) and Emax (LV contractility index), the incremental oxygen cost of contractility measured as nonmechanical energy per unit increment in contractility in patients with various kinds of LV dysfunction. We assessed Emax, Vo2, and PVA using conductance and Webster catheters under control conditions and during different rat...
Abstract 97: Induction of Hexosamine Biosynthetic Pathway Promotes Cardiac Hypertrophy through Activation of O-GlcNAcylation
Authors: Diem H Tran, Jianping Li, Xiaoding Wang, Herman I May, Gabriele G Schiattarella, Thomas G Gillette, Zhao V Wang
Journal: Circulation Research (2017)

Background &amp; significance: Heart failure affects approximately 6 million Americans, with 5-year survival of 50%, which is responsible for a huge burden on the US economy and healthcare system. The relevance and significance of the metabolic alteration to the pathogenesis of pressure overload-induced cardiac hypertrophy and heart failure are largely unknown. The hexosamine biosynthetic pathway (HBP) that is linked to metabolism of glucose, fatty acids and amino acids, has been implicated in the pathophysiology of heart diseases. Methods &amp; results: Thoracic aortic constriction (TAC) was performed to induce heart failure by pressure overload in mice. At the in vitro levels, treatment of phenylephrine (PE, 50 μM) was used to induce cellular hypertrophy in neonatal rat ventricular myocytes (NRVM). Our data revealed that all the enzymes of the HBP were upregulated while induction of hypertrophy at both in vivo and in vitro levels. Consistently, the intermediate product of the HBP was elevated in heart by afterload stress, as measured by metabolomics analyses. In the transgenic mice model for Gfat1, the rate-limiting enzyme of the HBP, we found more profound cardiac hypertrophy and cardiac remodeling in response to pressure overload. The increase of O-GlcNAc was also observed. In addition, the regulation of O-GlcNAcylation by specific targeting of two enzymes of the HBP (1 mM Alloxan, an inhibitor of OGT and 10 μM PUGNAc, an inhibitor of OGA) in NRVM suggested an involvement of the mTOR signaling in the activation of O-GlcNAc levels and the hypertrophy response. Targeting of the HBP by either specific siRNA or Gfat1 inhibitor (Azaserine, 5 μM) led to decrease in cellular hypertrophic response. Conclusions: Together, our data strongly suggest that the HBP participates in cardiac hypertrophic growth and pharmacologic targeting of the HBP may represent a novel approach to ameliorate pathological remodeling.
Abstract 333: USP1 is required for replication fork stability in BRCA1-deficient tumors
Authors: Kah Suan Lim, Heng Li, Emma A. Roberts, Emily F. Gaudiano, Connor Clairmont, Karthikeyan Ponnienselvan, Jessica C. Liu, Kalindi Parmar, Ning Zheng, Alan D'Andrea
Journal: Cancer Research (2018)

Abstract Homologous-recombination (HR) deficient tumors with BRCA1 and BRCA2 mutations exhibit replication fork stability defects. To date, PARP inhibitors are the only targeted therapy available in the clinic against HR deficient tumors, and alternative therapies are needed. In this study, we found a deubiquitinase, USP1, to be significantly upregulated in tumors with mutations in BRCA1. SiRNA mediated silencing or small molecule inhibition of USP1 activity resulted in replication fork destabilization and decreased viability of BRCA1 deficient cells, revealing a synthetic lethal relationship between USP1 and BRCA1. The cofactor of USP1, UAF1, had previously been shown to have DNA-binding activity. We observed that USP1 independently binds to and is stimulated by fork DNA. It is therefore the first known deubiquitinase (DUB) to be directly regulated by DNA binding. A truncated form of USP1, lacking its DNA binding region, was not stimulated by DNA and failed to localize and protect the replication fork. Persistence of monoubiquitinated PCNA at the replication fork was the mechanism of fork destabilization and cell death in the absence of USP1. Loss of monoubiquitinated PCNA, resulting from RAD18 knockdown, rescued the sensitivity and replication fork instability induced by USP1 inhibition. USP1 therefore is the first DUB enzyme exhibiting DNA-mediated activation at the replication fork, and is required for fork protection in BRCA1 deficient cells. We propose small molecule inhibitors against USP1 as a therapeutic option for BRCA1 deficient cancers. Citation Format: Kah Suan Lim, Heng Li, Emma A. Roberts, Emily F. Gaudiano, Connor Clairmont, Karthikeyan Ponnienselvan, Jessica C. Liu, Kalindi Parmar, Ning Zheng, Alan D'Andrea. USP1 is required for replication fork stability in BRCA1-deficient tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 333.
Comparisons of Baseline Demographics, Clinical Presentation, and Long-Term Outcome Among Patients With Early, Late, and Very Late Stent Thrombosis of Sirolimus-Eluting Stents
Authors: TakeshiKimura, TakeshiMorimoto, KenKozuma, YasuhiroHonda, TeruyoshiKume, TadanoriAizawa, KazuakiMitsudo, ShunichiMiyazaki, TetsuYamaguchi, EmiHiyoshi, EizoNishimura, TakaakiIsshiki
Journal: Circulation (2010)

Background— Stent thrombosis (ST) after sirolimus-eluting stent implantation has not yet been adequately characterized, mainly because of its low incidence. Methods and Results— The Registry of Stent Thrombosis for Review and Reevaluation (RESTART) is a Japanese nationwide registry of sirolimus-eluting stent–associated ST comprising 611 patients with definite ST (early [within 30 days; EST], 322 patients; late [between 31 and 365 days; LST], 105 patients; and very late [>1 year; VLST], 184 patients). Baseline demographics, clinical presentation, and long-term outcome of sirolimus-eluting stent–associated ST were compared among patients with EST, LST, and VLST. Baseline demographics were significantly different according to the timing of ST. Characteristic demographic factors for LST/VLST versus EST identified by multivariable model were hemodialysis, end-stage renal disease not on hemodialysis, absence of circumflex target, target of chronic total occlusion, prior percutaneous coronary intervention, and a...
Abstract 14189: Does the Presence of Microvascular Obstruction on Cardiac MRI Following Myocardial Infarction Create a More Favorable Target for Intracoronary Stem Cell Delivery
Authors: Sarah J Davidson, Timothy D Henry, Atul R Chugh, Phillip C Yang, Jay H Traverse
Journal: Circulation (2017)

Background: Microvascular obstruction (MVO) is associated with greater infarct size, adverse left-ventricular (LV) remodeling and reduced ejection fraction following ST-elevation myocardial infarct...
Abstract 12641: Endothelial Cell Hspa12B Plays a Cardioprotective Role in Sepsis Induced Cardiac Dysfunction via the Release of MicroRNA Containing Exosomes
Authors: XiaZhang, XiaohuiWang, TuanzhuHa, LiLiu, RaceKao, JohnKalbfleisch, DavidWilliams, ChuanfuLi
Journal: Circulation (2014)

Heat shock protein A12B (HSPA12B) is predominately expressed in endothelial cells and has been reported to contribute to angiogenesis. We hypothesized that HSPA12B plays a protective role in sepsis-induced cardiac dysfunction. Endothelial HSPA12B-/- (n=6) and wild type (WT, n=6) mice were subjected to cecal ligation and puncture (CLP)-induced sepsis. Sham surgical operation served as sham control (n=6). Cardiac function was examined by echocardiography before and 6 hour after CLP. In WT septic mice, ejection fraction (EF%) and fractional shortening (%FS) were significantly reduced by 34.8% and 43.1% (p<0.05), compared with control. HSPA12B-/- septic mice showed even greater decrements in EF% and FS% values (19.9% and 22.5%), when compared with WT septic mice. Serum levels of TNFα and IL-6 were higher in HSPA12B-/- septic mice than in WT septic mice. The expression of ICAM1 and VCAM1 in the myocardium of HSPA12B-/- septic mice was greater than in WT septic mice. Exosomes play an important role in cell-cell...