tbuckley/cabot-search huggingface dataset:
Abstract 18681: Molecular Imaging of Angiogenesis in Atherosclerosis Using a Caspase 3 Targeted PET Tracer <sup>18</sup> F-CP18
Authors: Balaji K Tamarappoo, Helen Su, Natalia Gorodny, Janna Arteaga, Luis Felipe Gomez, Umesh Gangadarmath, Fanrong Mu, Joseph Walsh, Katrin A Szardenings, Hartmuth Kolb
Journal: Circulation (2012)

Background: Rupture of unstable coronary artery plaque results in luminal thrombosis and myocardial infarction. Smooth muscle migration, neovascularization and apoptosis are believed to constitute key steps that precede plaque rupture. Identification of plaque with enhanced apoptosis may therefore allow differentation of stable from high-risk plaque. We have developed [ 18 F]CP18, a PET tracer that is cleaved by caspase 3, a terminal enzyme in the apoptosis cascade. We sought to test the ability of this tracer to detect plaque apoptosis in an ApoE double knockout mouse model of atherosclerosis. Methods: ApoE knockout mice (n=6) were fed a high fat western diet for 30 weeks at the end of which 250µCi of 18 F-CP18 was injected intravenously. Mice were sacrificed 60 min post-injection and the aorta was excised. Ex-vivo autoradiography was performed using either whole aorta or 10 µm-thick transverse sections of the aorta mounted on glass slides. Apoptotic activity and plaque inflammation in tissue sections from similar locations in the aorta were visually assessed using TUNEL staining and CD68 antibody staining respectively. Lipid deposition was visualized by oil red O staining with an H&amp;E counterstain. Results: In the ApoE KO mice fed a high fat diet, atherosclerotic plaque visualized by Oil Red O was present in the aortic root and aortic arch. Qualitative analysis of ex-vivo autoradiography of the aorta showed preferential uptake of 18 F-CP18 by aortic plaque at these same locations. Tunel staining and CD68 staining co-localized with plaques that exhibited increased 18 F-CP18 uptake. In contrast, in ApoE mice fed a regular diet and in wild-type mice fed the high-fat diet, there were fewer plaques in the aorta, with minimal tracer uptake and negligible histochemical evidence of macrophage influx and apoptotic activity. Conclusion: We were able to label a caspase 3 substrate CP18 with 18 F by click chemistry. Preliminary studies demonstrate that uptake of this tracer in aortic plaque strongly correlates with high levels of apoptotic activity by TUNEL staining and macrophage entry detected by CD68 staining. 18 F-CP18 may be a valuable imaging agent to detect plaque apoptosis and may allow early detection of hig-risk plaque.
Abstract 19141: Comparison of Long-term Clinical Outcome Between Chronic Kidney Disease stage3a and stage3b in Patients with Acute Coronary Syndrome
Authors: Yusuke Iwasaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Masato Kawasaki, Atsushi Kikuchi, Takashi Naito, Tadao Fujimoto, Kentaro Ozu, Takumi Kondo, Kaoruko Sengoku, Hironori Yamamoto, Masatake Fukinami
Journal: Circulation (2012)

Backgruond: Chronic kidney disease (CKD) is highly prevalent and associated with an increase of risk to major adverse cardiac and events (MACE) in patients with acute coronary syndrome (ACS). However, there is little information available on the prognostic significance of the difference between whether CKD stage 3a (mild to moderate stage; estimated glomerular filtration rate (eGFR): 45-59 ml/min/1.73m 2 ) and CKD stage 3b (moderate stage; eGFR: 30-44 ml/min/1.73m 2 ) in patients with ACS. Therefore, we assessed to whether the CKD stage might affect the prognosis in patients with ACS. Methods and Results: We followed up 209 patients (72.7% men, mean age 70±11 yrs) with ACS. Patients were classified into 4 groups according to eGFR [groupA: CKD stages 1 and 2, eGFR ≧ 60 ml/min/1.73m 2 (n=82); group B: CKD stage 3a (n=53); group C: CKD stage 3b (n=30); group D: CKD stages 4 and 5, eGFR &lt; 30 ml/min/1.73m 2 (n=44)]. There were no significant differences in baseline clinical characteristic among the four groups. During the follow up period (550±359days), MACE including all-cause mortality, myocardial infarction, and target vessel revascularization were compared among each group. Kaplan-Meier analysis revealed that patients in group C had a significantly higher risk of MACE than those in group B (46% vs 21%, p=0.024). Hazard ratio (HR) for MACE was 5.81(95%CI, 2.59 to 13.31) in group D, 3.95(95%CI, 1.57 to 9.71) in group C and 1.22(95%CI, 0.48 to 2.79) in group B, compared to group A. Notably, patients with group C had a significantly higher risk of MACE than those in group B (HR 3.34; 95%CI,1.25 to 8.87). Conclusion: Patients with moderate CKD (stage 3b) had a higher risk of MACE than those with mild to moderate CKD (stage3a). Thus, we should sub-divide CKD stage 3 into early (3a) and late (3b) components at the evaluation of the subsequent risk of MACE in patients with ACS.
Abstract 19194: Cardiac MRI and Electrophysiology Study Can Risk Stratify Patients with Ventricular Tachycardia and Structurally Normal Heart
Authors: Nilesh Mathuria, Yoav Michowitz, John Moriarty, Roderick Tung, Eric Buch, Jason Bradfield, Osamu Fujimura, Noel Boyle, Ravi Mandapati, J. Paul Finn, Jie Cheng, Kalyanam Shivkumar
Journal: Circulation (2012)

Introduction The role of MR imaging in risk stratification of patients with ventricular tachycardia (VT) and structurally normal heart is not well defined. Methods From 2005-2010, patients who presented with sustained VT or frequent nonsustained VT without echocardiographic evidence of structural heart disease were reviewed. All patients had a normal ejection fraction and no angiographic evidence of coronary artery disease. Patients received cardiac MRI and electrophysiology study (EPS) as part of their evaluation and long term outcomes were assessed. Results Thirty-two pts were evaluated for VT or nonsustained VT despite structurally normal hearts and underwent cardiac MRI with delayed gadolinium hyperenhancement (DHE) protocol to assess for scar prior to EPS. Fifteen had outflow tract VT (OTVT) morphology and eighteen presented with “non idiopathic” VT (not compatible with OTVT or fascicular VT). All 15 patients with OTVT morphology had a normal MRI and only the clinical VT was induced during EPS. Of the 18 patients with “non idiopathic” VT morphology, four patients had evidence of delayed enhancement on MRI (3 basal inferior/inferolateral LV, 1 basal to mid anterior LV). 3/4 with DHE had multiple VT (mean 2.25) induced during EPS. One patient had normal MRI yet multiple VT induced during EPS. All other patients had a negative MRI and EPS. During mean followup of 32+/-29 months, 2/4 patients (50%) with DHE on MRI, had recurrent VT requiring either ICD therapy or cardioversion. Additionally, the patient with multiple VT induced during EPS and normal MRI, also had recurrent VT at 7 months requiring cardioversion. The remaining 13 patients with non idiopathic VT morphology but normal MRI and EPS have not had recurrence. No deaths have occurred in any patient. All patients with outflow tract VT had normal MRI and have been managed medically or with ablation without reccurrence. Conclusions Cardiac MRI and EPS can help risk stratify patients with “non idiopathic” VT and structurally normal heart. Abnormal findings on MRI and EPS may identify a subgroup of patients who may be at higher risk for recurrent arrhythmic events.
Abstract 7: The Impact of Time to Target Temperature on Survival to Hospital Discharge for Patients Undergoing a Comprehensive Postresuscitation Program Following Out-of-Hospital Cardiac Arrest
Authors: Kelly N Sawyer, Michael C Kurz, Michelle Gossip, Charlotte Roberts, Harinder Dhindsa, Renee Reid, Joseph P Ornato, Mary Ann Peberdy
Journal: Circulation (2011)

Objectives: A comprehensive post-resuscitation program (CPRP) of care including therapeutic hypothermia (TH) is recommended by the 2010 AHA guidelines to improve survival from out-of-hospital cardiac arrest (OOH-CA). We sought to determine the influence of time to target temperature (T2T) on survival. Methods: Adult, non-traumatic, OOH-CA patients surviving to hospital admission and enrolled in our CPRP between January 2008 and January 2011 were included. Structured data including all relevant interval times from OOH-CA to target temperature were collected retrospectively. T2T was measured from ROSC, and TH duration began after reaching target temperature. Data were analyzed using descriptive statistics and logistic regression (significance α = 0.05). Results: Of 169 patients enrolled, 56 (33%) were female, 103 (61%) were African American, and mean age was 58.1 years (95% CI 55.83, 60.37). Overall, 84 patients (49.7%) survived to hospital discharge. The odds of survival for VF patients were 6.53 times greater than the PEA patients (95% CI 3.28 to 13.01), so separate analyses were performed. For VF, average T2T was 321.4 ± 180.58 minutes (95% CI 285.41, 357.44), and a longer T2T was a significant predictor for survival (P 0.026). For PEA, the average T2T was 321.7 ± 174.24 minutes (95% CI 279.16, 364.16). There was a trend for a longer T2T to be associated with improved survival in the PEA group (P 0.165). Conclusions: A longer T2T is associated with survival in patients treated with therapeutic hypothermia after OOH-CA. Patients with longer T2T have a longer total hypothermic treatment time, which may be an important and unique variable in the application of CPRP.
Abstract 19221: Rates of Arterial Revascularization in Patients Treated with Vorapaxar vs. Placebo in the TRA 2°P-TIMI 50 Trial
Authors: Erin A Bohula May, Marc P Bonaca, Benjamin M Scirica, Joao Morais, Markku Nieminen, Sabina A Murphy, Eugene Braunwald, David A Morrow
Journal: Circulation (2012)

Vorapaxar is a selective antagonist of protease-activated receptor (PAR)-1 that potently blocks platelet activation by thrombin. Thrombin signaling also influences vascular endothelial and smooth muscle function via PAR-1. Antagonism of PAR-1 reduces restenosis in animal models, suggesting the potential for vorapaxar to influence atherosclerotic disease progression. METHODS: The TRA2°P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5mg daily in 26,449 patients with stable atherosclerotic vascular disease, including prior myocardial infarction, stroke or peripheral arterial disease. Eligible patients had either an MI or ischemic stroke within the prior 2 weeks to 12 months or claudication with an ABI less than 0.85 or prior limb revascularization. We evaluated the rates of arterial revascularization in all patients included in the trial. RESULTS: Patients treated with vorapaxar had significantly lower rates of any arterial revascularization over 3 years as compared to placebo (13.6% versus 15.5%, HR 0.89; 95% CI 0.83-0.95, p&lt;0.001). Specifically, the rates of revascularization were significantly lower with vorapaxar for both peripheral (3.9% versus 5.2%, p&lt;0.001) and coronary vascular beds (9.7% versus 10.4%, p = 0.044), including a reduced rate of coronary artery bypass grafting (CABG) (1.7% versus 2.0%, p = 0.038). Moreover, elective revascularizations were reduced with vorapaxar (8.4% vs. 9.4%, p = 0.041). CONCLUSIONS: In this secondary analysis from a large randomized placebo-controlled trial, vorapaxar significantly reduced all arterial revascularizations suggesting possible clinical relevance of antagonism of PAR-1 mediated effects on endothelial or smooth muscle cells, as well as platelets.
Abstract 206: Distribution of ETCO <sub>2</sub> Values in Out-of-Hospital Cardiac Arrest Patients
Authors: Ahamed H Idris, Saeed Babaeizadeh, Mohamud Daya, Dana Edelson, Reza Firoozabadi, Eric Helfenbein, Sophia Zhou
Journal: Circulation (2011)

Background The American Heart Association 2010 guidelines recommend that capnography be used to verify tracheal tube placement and monitor CPR quality as well as detect ROSC during resuscitation. Capnography has been rapidly adopted by EMS in out-of-hospital CPR. Though capnography has been well understood in hospital patient care, the EtCO2 distribution in the population of interest has not been well studied. Objective Determine the distribution of EtCO2 levels during CPR in out-of-hospital cardiac arrest (OHCA) patients. Methods Recordings from 107 OHCA patients with capnogram waveforms were collected from 2008 to 2010 in two EMS agencies based in Oregon and Texas. Experts manually annotated all the recordings for breathing cycles and EtCO2 values. The histogram was generated using only the segments with active chest compression (total of 33 hours, 19,444 breath cycles). Each patient had chest compressions for an average of 19.8 ± 14.2 minutes. Chest compressions had an average rate of 108 ± 12 compressions-per-minute and average depth of 3.7 ± 0.7 centimeters. Results The figure below shows the distribution of the EtCO2 values in the OHCA patients. EtCO2 values varied from 0.5 to 99 mmHg, had a median value of 26 mmHg, and had an average value of 29 ± 18 mmHg. Conclusion In OHCA populations, EtCO2 values during CPR vary widely. EtCO2 values below 10 mmHg occurred in 13% of breaths and almost 60% of values were below 30 mmHg. Recommendations that make use of EtCO2 values in OHCA should consider this distribution.
Abstract 18374: Secretoneurin Gene Therapy Improves Hindlimb and Cardiac Ischemia in Apo E -/- mice Without Influencing Systemic Atherosclerosis
Authors: Markus Theurl, Karin Albrecht-Schgoer, Wilfried Schgoer, Daniela Lener, Egon Demetz, Otmar Pachinger, Ivan Tancevski, Rudolf Kirchmair
Journal: Circulation (2012)

Background: Hypercholesterolemia (HC) is a major risk factor for the development of cardiovascular diseases and associated with reduced neovascularization in response to ischemia. Recent studies showed up-regulation of secretoneurin (SN) by hypoxia and reported induction of angio-, arterio- and vasculogenesis in the hindlimb ischemia (HLI) model. The aim of this study is to evaluate the therapeutic effect of SN in a condition associated with impaired vascular response. Methods/Results: SN stimulated capillary tube formation, proliferation and activation of ERK1/2 and Akt in umbilical vein endothelial and coronary artery endothelial cells (CAEC) in the presence of 50 microg/ml oxidized LDL (oxLDL) comparable to VEGF (rel. capillary tube formation CAEC: SN 1.56±0.05 vs. VEGF 1.63±0.09, n=4, P&lt;0.01 vs ctr). To assess a therapeutic effect of SN in-vivo Apo E -/- mice set on western diet underwent HLI by ligation of the femoral artery or myocardial infarction (MI) by ligation of the left anterior descending artery. SN-plasmid (p-SN) or control-plasmid (p-ctr) was injected in the ischemic adductor muscle or the infarct border zone. In the HLI-model SN-therapy increased capillary (capillaries/HPF 200x: p-SN 354.6±14 vs. p-ctr 204.8±8.6; P&lt;0.001) and arteriole (arterioles/HPF 200x: p-SN 5.6±0.52 vs. p-ctr 3.1±0.24; P&lt;0.001) density and improved limb perfusion, assessed by laser Doppler perfusion imaging (rel. LDPI ratio ischemic/non ischemic limb day 28: p-SN 0.78±0.04 vs. p-ctr 0.64±0.02; n=10; P&lt;0.05). Interestingly, SN didn’t induce recruitment of endothelial progenitor cells to ischemic muscle in Apo E -/- mice (% lin - sca + flk + c-kit + cells: p-SN 1.72±0.3 vs. p-ctr 1.65±0.3, n=5, n.s.) In the MI-model cardiac parameters were significantly improved by SN-therapy (ejection fraction % 49.2±4.3 vs. 34.1±2.8, P&lt;0.01; left ventricular end diastolic diameter mm 3.2±0.2 vs. 3.8±0.3, P&lt;0.05; n=13). Aortic plaque area wasn’t affected by SN (Sudan IV staining % plaque area: p-SN 15.6±0.8 vs. p-ctr 15.2±2, n=5, n.s.) Conclusion: SN-therapy induces angiogenesis in-vitro and in-vivo without affecting vasculogenesis or atherosclerosis in HC and therefore represents a promising therapeutic strategy to reduce tissue ischemia in atherosclerotic diseases.
Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy
Authors: Hanchen Shen, Hongbin Wang, Jianlan Mo, Jianyu Zhang, Changhuo Xu, Feiyi Sun, Xinwen Ou, Xinyan Zhu, Lidong Du, Huaqiang Ju, Ruquan Ye, Guangfu Shi, Ryan T.K. Kwok, Jacky W.Y. Lam, Jianwei Sun, Tianfu Zhang, Shipeng Ning, Ben Zhong Tang
Journal: Bioactive Materials (2024)

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.
Abstract 18645: Axial Integrity of Coronary Stents: Evaluation Using Intravascular Ultrasound
Authors: Danny Dvir, Hironori Kitabata, Israel M Barbash, Joshua Loh, Rebecca Torguson, Salem Badr, Lowell F Sattler, Augusto D Pichard, Ron Waksman
Journal: Circulation (2012)

Background: Longitudinal stent deformation (i.e. the axial shortening or lengthening of a stent after implantation) is increasingly reported. However, the axial integrity of stents has not been systematically studied using intravascular ultrasound (IVUS). Methods: Consecutive coronary artery disease patients who underwent IVUS analysis after drug-eluting stent implantation for de-novo lesions were evaluated. Stent length was studied using automatic pullback of an IVUS catheter (Boston Scientific Corp/SCIMED) and was further analyzed for change in length (IVUS - label) (mm), the absolute change in length [|IVUS - label|] (mm), and the absolute value of the relative change in length [|(IVUS -label)|/label] (%). Results: A total of 183 stents were included: 38.3% sirolimus-eluting stents (SES); 27.9% zotarolimus-eluting stents (ZES); 20.2% Co-Ch everolimus-eluting stents (Cc-EES); 7.1% Pl-Ch everolimus-eluting stents (Pc-EES) - the Element platform and 6.6% paclitaxel-eluting stents (PES). The change in stent length (mm) and the relative change in length (%) differed between groups: SES 0.3 ± 1.2; ZES 1.0 ± 1.3; Cc-EES 0.6 ± 1.0; Pc-EES 0.4 ± 1.1; PES -0.1 ± 1.4 (p=0.008) and SES 1.7 ± 6.0; ZES 5.7 ± 6.7; Cc-EES 3.5 ± 5.8; Pc-EES 2.3 ± 6.0; PES -2.2 ± 8.1 (p&lt;0.001), respectively. The relative change in stent length was higher in the ZES group in comparison with SES and PES groups, (p&lt;0.001 for both). There were no statistical differences between the Pc-EES (Element) and any other stent types. The absolute relative change in stent length (&gt;5%) was lower in the SES group compared to the other groups: SES 34%; ZES 63%; Cc-EES 54%; Pc-EES 46%; and PES 67% (p=0.02). Significant (&gt;15%) absolute value of the relative change in stent length was rare (3.8%) and did not differ between groups (p=0.54). Long stents (≥20 mm, n=62) had a higher absolute change in stent length when compared to other stent groups (18 mm, n=50 and ≤16 mm, n=71): 1.3 ± 1.0 vs. 1.0 ± 0.6 vs. 1.0 ± 0.6, respectively (p=0.02). Conclusion: IVUS analysis revealed that significant change in stent length after implantation was rare in all stent types. Stent axial integrity was influenced by stent length; longer stents displayed a higher absolute change in length than did shorter stents.
Abstract 18386: The Association Between Tissue Characteristics Evaluated with Optical Coherence Tomography and Mid-term Results after Paclitaxel-eluting Balloon Dilatation for In-stent Restenosis Lesions: a Comparison with Plain Old Balloon Angioplasty
Authors: Takeshi Tada, Kazushige Kadota, Shunsuke Kubo, Masatomo Ozaki, Yusuke Hyoudou, Koshi Miyake, Yuki Hayakawa, Naoki Saito, Hideaki Otsuji, Suguru Otsuru, Daiji Hasegawa, Yoshikazu Shigemoto, Seiji Habara, Hiroyuki Tanaka, Yasushi Fuku, Naoki Oka, Harumi Kato, Hiroyuki Yamamoto, Tsuyoshi Goto, Kazuaki Mitsudo
Journal: Circulation (2012)

Background: The morphological assessment of neointimal tissue using optical coherence tomography (OCT) is highly significant to clarify the pathophysiology of in-stent restenosis (ISR) lesions. These OCT findings may be related to recurrence of ISR. Meanwhile, the effectiveness of paclitaxel-eluting balloon (PEB) dilatation for ISR lesions was reported recently. The aim of this study was to define the impact of OCT findings on recurrence of ISR after PEB dilatation compared with plain old balloon angioplasty (POBA). Methods: Between July 2008 and November 2011, we performed percutaneous coronary intervention for 165 ISR lesions in 141 patients using PEB (109 lesions, PEB group) or POBA (56 lesions, POBA group). The morphological assessment of neointimal tissue at the minimum lumen area site using OCT, including restenotic tissue structure (homogeneous, heterogeneous, or layered type), restenotic tissue backscatter (high or low), visible microvessels, lumen shape, red or white thrombus, lipid-rich plaque (lipid arc more than 90 degrees) was performed. We examined the association between lesion morphologies and mid-term (6-8 months) results including ISR and target lesion revascularization (TLR) rates. Results: The patients were 114 men and 27 women, and the mean age was 68.9 ± 9.6 years. The association of tissue structure with ISR and TLR in both PEB and POBA groups are shown in the figure. The ISR rate of lesions with high backscatter was significantly lower in the PEB group than in the POBA group (17.2% vs. 40.0%, p&lt;0.05). Both ISR and TLR rates of lesions without lipid-rich plaque were significantly lower in the PEB group than in the POBA group (ISR: 22.7% vs. 58.3%, p&lt;0.01; TLR: 15.9% vs. 41.6%, p&lt;0.05). There was no significant difference in other factors between two groups. Conclusions: The morphological assessment of ISR tissue using OCT might be useful to identify ISR lesions favorable for PEB dilatation.
Abstract 8453: 2D Speckle Tracking Strain for Functional Characterization of Right Ventricular Wall Motion
Authors: Muhammad Ashraf, Edward Hickey, Ling Hui, David J Sahn
Journal: Circulation (2011)

Background: Left ventricular (LV) twist appears to play an important role in effective ejection fraction (EF). MRI based tagging methods are limited for tracking right ventricular (RV) free wall motion, especially for the normal thin free wall. We used a new motion analysis program based on tracking speckles in B-mode echo images to study RV motion. Methods: For our study, 6 small (2-3kg) piglets were intubated and anesthetized; median sternotomy was done to expose the heart. We used a 10MHz sector probe and a 13MHz linear probe to acquire 2D and tissue Doppler images of the RV from the surface of the heart, using liver as a standoff to improve extent and clarity of the RV free wall images. Short axis views were acquired on a GE Vivid 7 Dimension ultrasound system at frame rates &gt;100/sec. The study was conducted at 3 hemodynamic states of baseline and after 10% and 20% volume loading. Data was later analyzed offline in EchoPac using 2D speckle tracking. Results: There was a minimal component of rotation in the free wall of the RV (1°-2°) but more in the septum (5°-8°), which was similar to the rotation of the LV free wall for that level. Strain values were similar in both free wall and the RV side of the septum. With volume loading, there was an increase in the septum (mean 2° ± 1°) amplitude of twist and a decrease in time to peak twist, but the RV free wall showed no significant change. Conclusions: These findings are consistent with observations that the septum plays an important role in RV dynamic function.