tbuckley/cabot-search huggingface dataset:
Abstract 204: Better Volume-Outcome Relationship in the Trauma Centers, but Not in The Regional Hospitals. A Nation-wide Population Based Research in Taiwan
Authors: Dorji Harnod, Chu-Hui Chang, Ray-E Chang, Tomor Harnod
Journal: Circulation (2013)

Background: Survival rates for major trauma patients in different levels of hospitals were analyzed to test for the volume-outcome relationship. Methods: From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2006 to 2008, all of the trauma patients were identified from the database by the ICD-9-CM system. ICD-MAP 90 was used for calculating the Injury Severity Score as the variable controlling the disease severity. The patients of major trauma were defined as ISS more than fifteen. We used patients’ diagnosis one year before trauma admission for calculating Charlson Comorbidity Index. And factors such as age, gender, ICU admission, different hospital levels and the hospital case volumes were adjusted in a logistic regression model for survival analysis. Results: There were 5912, 5611 and 5760 trauma patients admitted from emergency department from 2006 to 2008, and there were 2497 major trauma patients (ISS more then 15). The totally mortality rate was 12.49% (6.98% in the youngest group and 18.19% in the oldest group, P&lt;0.01). After controlling the age, genders, co-morbidity and injury severity, the difference of mortality rates were significant in hospital levels. Compared with the risk in low volume centers, the risk of mortality was 0.65 times in mid-volume trauma centers (P=0.048) and the risk of mortality was 0.43 times in high -volume trauma centers (P=0.014). But in regional hospitals, compared with the risk in low volume hospitals, the risk of mortality was 0.73 times in mid-volume regional hospitals (P=0.253) and the risk of mortality was 0.80 times in high-volume regional hospitals (P=0.354). Conclusions: Our results suggest major trauma patients should be sent to the trauma centers. And, based on the better volume-outcome relationship in trauma centers, we should not have too many trauma centers in metropolitan area. Many trauma centers could lead to the possible dilution effect and lower the survival rates. And, based on our results, the volume-outcome relationship is not prominent in regional hospitals.
Abstract 197: Rapid Pediatric Fluid Resuscitation: A Randomized Controlled Trial Comparing the Efficiency of Two Provider Endorsed Manual Fluid Resuscitation Techniques
Authors: Evan T Cole, Greg Harvey, Sara Urbanski, Gary Foster, Lehana Thabane, Melissa J Parker
Journal: Circulation (2013)

Introduction: Manual syringe techniques are commonly used by Health Care Providers (HCPs) to accomplish fluid resuscitation for children in shock. Objectives: We sought to determine which of two commonly practiced manual fluid resuscitation techniques, Disconnect-Reconnect (DRT) versus Push-Pull (PPT), yielded a higher rate of fluid administration. Hypothesis: We hypothesized that a difference in fluid resuscitation rate would exist between DRT and PPT. Methods: A 16 participant randomized crossover trial was conducted at McMaster Children’s Hospital in Hamilton, Canada. Consenting HCPs were oriented to the experimental setup, which involved a non-clinical model of a 15 kg toddler in decompensated septic shock. The model incorporated a 22-gauge catheter, with administered fluid draining into a 1-litre graduated cylinder. Following randomization, subjects completed a brief standardization procedure and then were asked to rapidly administer 900 mL (60 mL/kg) of 0.9% normal saline to the simulated child. Between DRT and PPT, a 30-minute washout period was enforced. All testing was video recorded, with data extracted from trial videos by two blinded outcome assessors. The primary outcome of a difference in total fluid administration rate was analyzed by paired t-test. Results: Total fluid administration rate (mL/second) significantly differed between the two techniques, with a mean difference of 0.15 [95% CI 0.05; 0.25] (p=0.005). Mean (sd) fluid administration rates were DRT, 1.77 (0.145) and PPT, 1.62 (0.226). A change in fluid administration rate occurred over the intervention for DRT, F(1,15)=2316.36 (p&lt;0.001) and PPT, F(1,15)=806.04 (p&lt;0.001). Pairwise comparisons indicate that DRT Rate 1, 1.63 (0.143) significantly differed from Rate 2, 1.83 (0.176) and Rate 3, 1.88 (0.180); (p&lt;0.001). PPT Rate 1, 1.62 (0.223) and Rate 2, 1.58 (0.237) did not differ, but Rate 2 significantly differed from Rate 3, 1.67 (0.265); (p=0.003). HCPs encountered technical issues more frequently when performing PPT versus DRT. No catheter dislodgements occurred. HCP self reported fatigue did not differ between DRT and PPT (p=0.755). Conclusions: Use of DRT resulted in a faster rate of fluid administration than PPT in a simulated pediatric resuscitation scenario.
Abstract 192: Relationship Between Zolpidem Use and Aortic Dissection Risk: A Taiwanese Population-Based Case-Control Study
Authors: Yen-Nien Lin, Po-Yen Ko, Chih-Ping Chang, Chen-Chia Yang, Jen-Jyh Lin, Kuan-Cheng Chang
Journal: Circulation (2013)

Objective: To evaluate the relationship between the use of zolpidem and risk of subsequent aortic dissection in Taiwanese patients. Method: This case-control study used data obtained from the National Health Insurance Research Database to determine whether the use of zolpidem is associated with an increased risk of aortic dissection. The case group comprised 1314 patients who were newly diagnosed with aortic dissection between January 1, 2003, and December 31, 2010. We also randomly selected a 4-fold greater number of patients without aortic dissection as a control group. Patients were frequency-matched with controls on sex, age, and year of index date. We measured the effect of zolpidem, and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs). Results: We found that exposure to zolpidem was associated with increased risk of aortic dissection (OR=1.59; 95% CI, 1.36-1.86). The risk of aortic dissection increased significantly with increasing exposure to zolpidem; for average exposures of ≦ 40, 41-160, 161-690, and &gt; 690 mg/year, the ORs were 1.45, 1.36, 2.08 and 1.55, respectively; the P value for the trend was &lt;0.001. Regardless of whether people presented with a sleep disorder, the risk of aortic dissection increased with zolpidem exposure; the adjusted OR was 1.70 without sleep disorder and 1.62 with sleep disorder. Conclusions: This population-based study positively associated the use of zolpidem with increased risk of Aortic dissection. Our findings warrant further large-scale and in-depth investigations in this area.
Abstract 190: Groups IIA, IVA and V Phospholipase A <sub>2</sub> in Coronary Thrombus Are Associated With Recurrent Cardiac Events and Development of Atherosclerosis in the Culprit Coronary Artery After Acute Myocardial Infarction
Authors: Soichiro Takahashi, Koji Suzuki, Shun Tamaru, Yosuke Watanabe, Hideto Mishina, Kazuhiro Watanabe, Daisuke Fujioka, Takamitsu Nakamura, Jun-ei Obata, Kenichi Kawabata, Kiyotaka Kugiyama
Journal: Circulation (2013)

Background: The intracoronary thrombus is a source of active lipid mediators including eicosanoids that play critical roles in the pathogenesis of acute myocardial infarction (AMI). Eicosanoids are derived from arachidonic acid generated by phospholipase A 2 (PLA 2 ). This study examined whether PLA 2 were expressed in aspirated coronary thrombi and whether PLA 2 expression in the thrombi may be related to the recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery after AMI. Methods: Intracoronary thrombi were obtained using an aspiration catheter at the emergent PCI from 48 patients with AMI who had successful treatment with PCI. The presence of groups IB, IIA, IID, IIE, IIF, III, IVA, V, VI, VII, X and XIIA PLA 2 was examined using immunohistochemical staining in all of the thrombi obtained. Repeated intravascular ultrasound in the culprit coronary artery was performed at emergent PCI and 6 months later in a subgroup of 20 patients. Results: Each of the 12 subtypes of PLA 2 was detected by its immunoreactivity in 2 - 6% of total nucleated cells and 16 - 39% of platelet area (CD42b-positive area). COX-1, COX-2 and 5-LOX, downstream enzymes for PLA 2 in the arachidonic acid cascade, were co-localized with PLA 2 . During 6 months of follow-up, 11 patients had cardiac events. Percentages of platelet areas immunopositive for groups IIA, IVA and V PLA 2 were significantly higher in patients with cardiac events (n = 11) than without (n = 37) (% of CD42b-positive areas: 36% vs. 14%, 55% vs. 32% and 54% vs. 27%, respectively, p &lt; 0.05 in all). Similarly, percentages of nucleated cells immunopositive for groups IIA, IVA and V PLA 2 were also higher in thrombi from patients with cardiac events than without (p &lt; 0.05 in all). Percentagesby which atheroma volumes and vessel volumes increased in the native coronary segments distal to the culprit coronary lesion were significantly and positively correlated with percentages of nucleated cells immunopositive for groups IIA (r = 0.60 and 0.52, respectively), IVA (r = 0.55 and 0.46) and V PLA 2 (r = 0.45 and 0.48). Conclusion: Groups IIA, IVA and V PLA 2 in coronary thrombi may play a role in recurrence of cardiac events and development of atherosclerosis in the culprit coronary artery in AMI survivors.
Abstract 13974: Loss of Endothelial Primary Cilia Promotes Thrombus Formation in Mice
Authors: Jonathan W Yau, Krishna K Singh, Xi Lei, Adrian Quan, Hwee Teoh, Mohammed Al-Omran, Heyu Ni, Subodh Verma
Journal: Circulation (2016)

Introduction: Recent evidence suggest that endothelial cilia may suppress anti-inflammatory signaling and protect against atherosclerosis. Given that atherosclerosis predisposes to thrombosis, we hypothesized that endothelial cilia may also play a fundamental role in thrombogenesis. Hypothesis: We hypothesize that endothelial cilia is important for protection against thrombosis, and that loss of endothelial cilia promotes thrombus formation in mice. Methods: We focused on the intraflagellar transport 88 (IFT88) gene since endothelial deletion of IFT88 has been associated with decreased atherosclerotic lesions in a murine model of atherosclerosis. Key thrombosis-associated molecules were evaluated in IFT88-silenced human umbilical vein endothelial cells (HUVECs). Thrombi formation were monitored in the laser-injured cremasteric arteries of 8 week old male endothelial cell (EC) specific IFT88 knockout (EC-IFT88 -/- ) mice. Results: Compared to scrambled siRNA-treated HUVECs, those exposed to siIFT88 exhibited lower mRNA and protein levels of tissue factor pathway inhibitor (TFPI) and thrombomodulin, two key regulators of blood coagulation (-27% and -20%, respectively; N=3; p &lt; 0.05). We next examined the effect of IFT88 loss on thrombosis in mice. Upon laser-induced injury, we determined, via mean fluorescence intensity, that although the thrombi formed in the cremasteric arteries of EC-IFT88 -/- mice were similar in size to those produced in the wild type (WT) mice (2.2 ± 0.6 and 2.0 ± 0.3 AU, respectively; x10 6 ; N=32 thrombi; p=0.8), the average rate at which thrombi developed was significantly faster in the EC-IFT88 -/- mice relative to that in WT mice (97 ± 11 and 57 ± 3 AU/s, respectively; N=32 thrombi; p&lt;0.001). Conclusions: Loss of endothelial IFT88 results in decreased TFPI mRNA and protein expression in HUVECs. EC-IFT88 -/- mice exhibited earlier thrombi formation in our laser injury model of thrombosis. These results collectively suggest that endothelial cilia intricately regulates thrombus formation in a TFPI-dependent manner and represents a previously unrecognized target to modulate thrombosis susceptibility.
Abstract 19124: Ca Overload Induced Pathological Cardiac Remodeling Rescued by Na-ca Exchanger Overexpression
Authors: Jing Li, Ying Li, Xiaoying M Zhang, Joseph Cheung, Xiongwen Chen
Journal: Circulation (2013)

Aims: Sarcoplasmic reticulum (SR) Ca2+ overload plays an essential role in pathological cardiac remodeling including hypertrophy, cell death, fibrosis and arrhythmias. Normalization of SR Ca2+ load holds a great promise for the prevention and treatment of heart failure. Here we test this hypothesis by determining if normalization of Ca2+ overload with Na-Ca exchange overexpression in the murine hearts or cultured feline myocytes overexpressing Cav1.2β2a subunit rescues the adverse remodeling and cell death. Results: 1. In vivo, overexpression of β2a for 4 months induced cardiac hypertrophy (HW/BW, Control: 4.16±0.1mg/g, β2a: 4.64±0.24mg/g) accompanied by cell death and fibrosis while these parameters were largely normalized in NCX-coexpression mice (HW/BW, β2a-ncx: 4.24±0.11mg/g). 2. The structural remodeling was supported by ECHO data showing less increases in left ventricular posterior wall and interventricular septal wall thickness and better preserved cardiac function (fractional shortening: β2a: 30.5±9.8%; β2a-ncx: 48.1±7.85); 3. Patch-clamp studies revealed that β2a transgenic myocytes had larger Ca2+ currents (Control: -12.7±2.1 pA/pF; β2a: -17.3±3.4 pA/pF) and co-expression of NCX did not normalize the increased Ica (β2a-ncx: -15.7±1.5 pA/pF). 4. Overexpressing Cav1.2β2a in cultured feline ventricular myocytes increased ICa significantly (control:-2.1±0.3 pA/pF, β2a:-19.4±5.9 pA/pF, β2a-NCX:-16.4±2.3 pA/pF). 5. Overexpression of β2a in feline cells for 48 h resulted in prominent SR Ca2+ overload (caffeine induced Ca2+ transient peak by Fluo-4: F/F0, control:3.2±1.0, β2a:4.8±1.2) while co-expression of NCX prevented it (β2a-NCX: 3.4±1.3). 6. Prominent cell death was also confirmed in β2a-overexpressing feline myocytes (survival rate: Control: 69.9±9.5%, β2a:26.2±6.4%) and cell death was partially protected by the coexpression of NCX (β2a-ncx: 44.6±5.7%). Conclusion: Over-expression of NCX is sufficient for blocking pathological cardiac remodeling as induced by SR Ca2+ overload and may represent a novel therapeutic strategy for heart failure.
Abstract 19105: β2 Integrin-Dependent HuR-Mediated mRNA Stabilization in Macrophages is Required for Lymphatic Vessel Formation in Inflammatory Lymphangiogenesis
Authors: Bryan D Young, Jiange Zhang, Arvind Mohan, Nathaniel D Robinson, Alan R Morrison, Timur O Yarovinsky, Jeffrey R Bender
Journal: Circulation (2013)

Macrophages play a central role in the response to acute and chronic tissue injuries including infection, ischemia, and atherosclerosis, where their effector functions in injured tissue include cytokine, growth factor, and matrix remodeling factor production. β2 integrin engagement promotes stabilization of labile mRNAs bearing adenylate-uridylate-rich elements (AREs) by inducing the rapid nuclear-to-cytoplasmic translocation of the RNA binding protein HuR. The secretory role of macrophages in lymphangiogenesis, together with predicted HuR binding sites in the VEGF-C 3’-UTR, led us to hypothesize that HuR regulates VEGF-C production in macrophages in response to integrin engagement. In bone marrow-derived macrophages from mice harboring a myeloid-specific deletion of HuR, we observed that VEGF-C production is impaired due to an increase in the rate of VEGF-C mRNA decay. A conserved ARE was the degradation target and was necessary to mediate HuR-dependent transcript stability that in turn resulted in increased VEGF-C protein. The HuR knockout mice exhibit an abnormal lymphangiogenic response to intraperitoneal LPS injection despite intact macrophage recruitment. Preliminary data indicates a functional interaction between the mRNA stabilizing effect of HuR and the destabilizing effect of microRNA recognition sequences in the 3’-UTR of VEGF-C and that of other integrin-induced lymphangiogenic gene products including cytokines and matrix remodeling proteins. VEGF-C likely acts in concert with these other factors to help guide vessel formation at sites of tissue injury. In conclusion, β2 integrin signaling through HuR promotes VEGF-C production as a central component of a post-transcriptional gene regulatory program essential for macrophage-directed lymphangiogenesis, a finding with implications for processes including tissue ischemia, wound repair, extracellular fluid trafficking, and atherosclerosis.
Abstract 14714: Association of Plasma Renin and Aldosterone Levels With Future Left Ventricular Structure and Function: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Bharath Ambale Venkatesh, Kihei Yoneyama, Mohammed Ostovaneh, Sirisha Donekal, Venkatesh L Murthy, Ravi V Shah, Pamela Ouyang, Colin O Wu, Matthew Allison, Russell Tracy, David A Bluemke, Joao A C Lima
Journal: Circulation (2015)

Introduction: The renin-angiotensin-aldosterone-system (RAAS) has been implicated in left ventricular (LV) hypertrophy and dysfunction. We explore the association of circulating levels of plasma renin activity (PRA) and aldosterone to subclinical measures of LV structure and function from MRI. Methods: The MESA study enrolled 6814 participants free of cardiovascular disease at baseline (2000-2002). We included MESA participants who had blood assayed for measurement of PRA and aldosterone levels at the second/third follow-up exams (2003-2005) and underwent MRI at the fifth follow-up exam (2010 -2012). We excluded participants on hypertension medication (N=509). Harmonic phase analysis was used to compute circumferential strain and torsion from tagged MRI; LV function and structure measures were obtained from cine images. Linear regression evaluated the relationship between PRA, aldosterone and aldosterone to renin ratio (ARR) with LV structure and function. The models included adjustments for cardiovascular risk factors and demographics at the time of assays (model 1) and at the time of imaging (model 2) separately. Results: At the time of assays, the participants (N=384) were 59±8 years, 53% male, 43% Caucasian, 13% African-American, 17% Chinese, 28% Hispanic, 4% diabetic, with median levels of PRA 0.56 ng/ml (IQR:0.30-0.97), aldosterone 126 pg/ml (IQR:90-176) and ARR 120 ng/ml to pg/ml (IQR:53-234). Higher PRA was associated with lower LV end-diastolic volume index. Higher PRA was associated with higher mass-volume ratio and torsion. Higher ARR was associated with higher LV volume and lower torsion. Conclusions: In individuals not on hypertension medications, higher PRA was associated with concentric remodeling and higher torsion 7 years later but not to LV function. Also, higher ARR was associated with eccentric LV chamber remodeling and lower torsion. In conclusion, RAAS activity may be implicated in future concentric/eccentric LV remodeling.
Abstract 19145: The Effect of Atrial Fibrillation on In-Hospital Mortality in Patients With Acute Myocardial Infarction
Authors: Triston B Smith, Raef Hajjali
Journal: Circulation (2013)

Background: Atrial fibrillation (AF) has been shown in multiple observational studies to be associated with increased long-term mortality. The effect of AF on short-term outcomes in patients with acute myocardial infarction (AMI) is not clearly defined. We sought to investigate the in-hospital mortality among patient with and without AF presenting with acute myocardial infarction. Methods: We queried the Nationwide Inpatient Sample (NIS) database from 2008 to 2010. Using the SPSS data analysis package, we identified 374148 adult patients presenting with AMI, both ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). Among those, 58031 had a diagnosis of AF. Fisher exact test was used to compare mortality amongst patients with and without AF. Logistic regression analysis was performed to adjust for pertinent clinical variables. Results: Patients with AF were older ((x ) - 76.1 yrs. σ 11.8,) compared to those without AF ((x ) - 68.4 yrs. σ 14.5) p&lt;0.001. The proportion of male was higher in the AF group (55.7% vs. 44.3%, p&lt;0.001), as well as the frequency of shock (7.2% vs. 4.9%, p&lt;0.001), CKD (20.3% vs. 12.6%, p&lt;0.001), ESRD (3.8% vs 3.1% p&lt;0.001), Diabetes Mellitus (33.9% vs 33.4% p&lt;0.016), and need for transfusion (11.3% vs 6.9% p&lt;0.001). Patients with AF were less obese (8.7% vs 11.3% p&lt;0.001) and were more likely to be admitted with NSTEMI (74% vs 64.6% p&lt;0.001) and undergo CABG (13.7% vs 7.9% p&lt;0.001). They were less likely to undergo LHC (51.8% vs 67.7%) or be revascularized with PCI (26.7% vs 47% p&lt;0.001) compared to those without AF. Patients with AF and AMI had a longer length of stay (x - 6.4 vs x - 4.6 days). The in-hospital mortality rate for patients with AF and AMI was 8.5%, compared to 4.3% in patients without AF (p&lt;0.001). After adjusting for pertinent clinical and procedural variables using logistic regression analysis, AF remained an independent predictor of higher in-hospital mortality (p&lt;0.001, OR 1.09[1.05-1.13]). Conclusions: In patients presenting with AMI, AF is associated with a higher incidence of NSTEMI, lower rates of revascularization via PCI, longer hospital LOS and higher in-hospital mortality rates than non AF patients.
Abstract 19143: Atrio-Esophageal Fistula After Atrial Fibrillation Ablation: A Pooled Analysis of 33 Cases
Authors: Madhu Y Reddy, Vivek Yarlagadda, Ajay Vallakati, Gopi Manohar Ponnaganti, Pramod Janga, Anand Pillai, Donita Atkins, Dhanunjaya Lakkireddy
Journal: Circulation (2013)

Introduction: Atrio-esophageal fistula (AEF) is one of the most devastating complications of percutaneous atrial fibrillation (AF) ablation. Despite its high case fatality, clinical predictors, presentation and outcomes of the complication are not well studied due to the rarity of the complication. We intended to perform a pooled analysis of all cases of atrio-esophageal fistula reported in the literature. Methods: We reviewed Medline for all cases of AEF as a complication after percutaneous AF ablation. Patient demographics, procedural characteristics, clinical presentation, management and outcomes all these patients were collected and analyzed. Predictors of mortality were assessed using univariate analyses. Results: A total of 33 cases of AEF post-AF ablation were reported in the literature till May of 2013. Mean age of the patients was 54 ± 13 years of which 30 (91%) were males. Majority of them had non-paroxysmal AF (18; 66%). Mean time to presentation after the procedure was 21 ±14 days. Most patients presented with fever (26; 79%). Other common presenting symptoms were chest pain (12; 36%), stroke 8 (26%), seizures (6; 19%) and hematemesis 4 (13%). Of the 33 patients 15 (45%) patients died during the immediate follow-up directly related to the AEF. In 22 (66%) patients surgery was attempted as the primary mode of therapy, 4 (18%) patients had a stent placed and the rest underwent palliative care. In univariate analyses, the only predictor of mortality was age. Patients who died were older than those who survived (61 ±13 vs 49 ±13; p = 0.004). Conclusion: Atrio-esophageal fistula is a devastating complication of AF ablation with a case fatality rate of 45%. Older patients are more likely to die of the complication.