tbuckley/cabot-search huggingface dataset:
Abstract 18814: Autologous CD133+ Immunoselected Cells for the Treatment of "no-option" Critical Limb Ischemia: A Pilot Monocentric Study
Authors: Massimiliano Gnecchi, Vittorio Arici, Antonio Bozzani, Fabrizio Calliada, Elisabetta Cervio, Marila Cervio, Giuseppe Malpasso, Francesco Alessandrino, Claudia Del Fante, Gianluca Viarengo, Cesare Perotti
Journal: Circulation (2012)

Background: critical limb ischemia (CLI) is characterized by chronic ischemic rest pain, ulcers or gangren. CLI results in major amputation in about 50% of patients. Recently, it has been shown that bone marrow-derived (BM) CD34+/CD133+ circulating cells promote new vessel growth in experimental models of CLI. Accordingly, we investigated the feasibility and safety of local intramuscular administration of autologous immunoselected CD133+ (AI-CD133+) cells in “no-option” patients. Methods: the protocol was approved by the ethical committee of our hospital and 10 “no-option” patients suffering CLI were enrolled. BM-derived mononuclear cells were mobilized by G-CSF administration and collected by leukapheresis. CD133+ cells were selected with Clini-MACS (Miltenyi Biotec). AI-CD133+ cells were administered intramuscularly by direct injection. FACS analysis and Hill assay (CFU-Hill colonies) were performed both before and after G-CSF administration. Clinical examination, pain assessment, Ankle Brachial Index (ABI) and transcutaneous oxygen tension (TcPO2) measurements were performed before the treatment and 3, 6 and 12 months thereafter. At the same time points, patients underwent Contrast Enhanced UltraSound (CEUS) to assess muscle perfusion. Results: mobilization of CD34+/CD133+ cells was successful in 8 out of 10 patients. Of relevance, 6 out of 8 treated patients showed relevant clinical improvements. In particular, the treatment drastically ameliorated local pain and favored the healing of the ulcers (figure). The 2 non-responders, both diabetics, underwent major amputation. An overall increase in ABI rate was documented by CEUS (ABI at 12 months increased from 91,45 to 136,82; p&lt;0.05). TcPO2 increased by 45.5±34.1% after 1 year (p&lt;0.05). The number of CFU-Hill colonies was significantly lower (p&lt;0.05) in CLI patients compared with healthy donors; after G-CSF stimulation, the number of CFU colonies significantly increased, except in those patients who did not respond to the treatment. Conclusions: our results demonstrate the feasibility and safety of G-CSF mobilized AI-CD133+ cell injection in end stage CLI patients. Clinical and instrumental data suggest a dramatic effect of CD133+ treatment, except in diabetic patients.
Abstract 18851: Effect of Diabetes Mellitus Treatment Type in Patients Undergoing Percutaneous Coronary Intervention
Authors: Rani Y Upahyay, Guillermo A Cortes, Han Tun, Nazila Z Rad, Anilkumar Mehra, David M. M Shavelle, Ray V Matthews, Leonardo C Clavijo
Journal: Circulation (2012)

Background: Patients with type 2 diabetes mellitus have a higher risk of cardiovascular events than those without diabetes. The effect of specific oral treatment type for diabetes on cardiovascular events remains unclear. Objective: The goal of this study is to investigate baseline risk factors, angiographic characteristics, interventional procedural information, and hospital outcomes in non-diabetic and diabetic patients who undergo percutaneous coronary intervention (PCI). Diabetic patients were divided into insulin treated diabetics and oral medication treated patients. Oral medication treated patients were subdivided according to oral medication drug class. Methods: We performed a retrospective analysis of 1,381 patients treated with PCI at the Los Angeles County Hospital + USC Medical Center and Keck Medical Center of USC between January 2008 and June 2011. Patients were divided into two groups: non-diabetic (ND, n= 645) and type-2 diabetes mellitus (DM, n= 704). Diabetic patients were further divided into those treated with insulin (IDM, n= 414) or oral medication (ODM, n= 290). Additional comparisons of ODM patients according to medication class were performed between sulphonyurea, biguanide and thiazolidinediones. Results: IDM patients were more likely than ODM patients to present with an acute coronary syndrome (56.2% vs. 43.8%) and suffer in hospital mortality (1.01% vs. 0%, p=0.03). Acute renal failure (6.10% vs. 1.99% vs. 1.37%, p&lt;0.000), intra-aortic balloon pump-IABP (12.53% vs. 6.01% vs. 6.27%, p=0.0008), and MACE (13.77% vs. 8.39% vs. 8.99%, p=0.02) rates were higher in IDM than ODM and ND. Among ODM, biguanide treated patients compared to sulphonylurea and thiazolidinediones were more likely to present with an ACS (77.3% vs. 19.3% vs. 3.4%). There were no differences between groups on infract size and post-procedure success rate or TIMI flow. Conclusion: Insulin and biguanide treated diabetic patients are more likely to present with an acute coronary syndromes than non-diabetic and other orally treated diabetic patients. The outcome of insulin treated diabetic patients after PCI is worse than any other group with higher mortality, renal failure, IABP use and MACE.
Abstract 18996: Comparison of Clinical Outcomes After Stent Implantation for Left Main Trunk Disease Between First- and Second-generation Drug-eluting Stent Eras
Authors: Yusuke Hyodo, Kazushige Kadota, Yasushi Fuku, Naoki Saito, Hideaki Otsuji, Suguru Otsuru, Daiji Hasegawa, Yoshikazu Shigemoto, Seiji Habara, Takeshi Tada, Hiroyuki Tanaka, Tsuyosih Goto, Kazuaki Mitsudo
Journal: Circulation (2012)

Purpose: In Japan, zotarolimus-eluting stent (ZES) became available from May 2009 and everolimus-eluting stent (EES) from January 2010 in addition to the first-generation drug-eluting stents (DES). The aim of this study was to clarify the impact of second-generation drug-eluting stent (DES) on clinical outcomes in left main trunk disease (LMTD). Methods: A total of 238 patients (174 men, 64 women, mean age 70.8±10.1 years) who had undergone DES implantation for LMTD were classified into two groups: group A (first-generation DES era, 168 patients, March 2003 to April 2009, median follow-up period 1489 days, interquartile range [IQR] 1165-1967) and group B (second-generation DES era, 70 patients, May 2009 to December 2010, median follow-up period 608 days, IQR 450-721), and long-term clinical outcomes were assessed. Patients who had undergone percutaneous coronary intervention in the past were excluded. Results: In group A, SES was deployed in 142 patients and PES in 3. In group B, ZES was deployed in 35 patients and EES in 18. Bifurcation lesion was significantly higher in group B (A, 75.6% vs. B, 88.6%, p=0.038). Syntax score showed no significant difference between groups (26.6±9.6 vs. 27.2±11.4, p=0.70). Stent strategy, either single- or two-stent, showed no significant difference (two-stent strategy: 30.4% vs. 28.6%, p=0.92). The Kaplan-Meier method revealed that the event-free survival rate of target vessel failure, defined as a composite of cardiac death, myocardial infarction, and target vessel revascularization, was significantly higher in group B (p=0.029). Conclusion: Our data indicate that the outcomes of DES implantation for LMTD are more preferable in the second-generation DES era than in the first-generation DES era.
Abstract 17485: Novel Role of NADPH Oxidase Subunit p67 <sup>phox</sup> C-terminus Region in Mediation of α <sub>1</sub> -Adrenergic Receptor-Induced Cardiac Hypertrophy
Authors: Guiqing Zhao, Chongxu Zhang, Xianyao Xu, Qiong Zhao, J. D Lambeth, Lei Xiao
Journal: Circulation (2011)

We previously reported that α 1 -adrenergic receptor (α 1 AR)-induced hypertrophy in adult rat ventricular myocytes (ARVM) was mediated via activation of MEK1/2-ERK1/2 cascade. The hypertrophy was attenuated by NADPH oxidase (NOX) inhibitors and a dominant-negative (DN) mutant (V204A) of NOX subunit p67 phox that completely inhibits NOX activity of reactive oxygen species (ROS) generation, suggesting the roles of NOX and ROS in α 1 AR signaling. We also showed that cardiac-specific overexpression of this V204A mutant attenuated chronic pressure-overload-induced hypertrophy in transgenic mouse heart. In this study, we further tested the potential ROS-independent role of p67 phox in α 1 AR signaling using a truncated mutant (1-235) of p67 phox , which lacks the p67 phox C-terminus region and is known not affecting NOX activity of ROS generation. Adenoviral constructs containing β-galactosidase (AdLacZ) or p67 phox mutant 1-235 (Ad235) were expressed in ARVM, and their effects on α 1 AR stimulation (1 μM norepinephrine + 2 μM propranolol)-induced hypertrophy and activation of MEK-ERK cascade was studied. Overexpression of Ad235 significantly attenuated α 1 AR -induced activation of MEK1/2 (58±7% ↓) and ERK1/2 (65±8% ↓) vs. AdLacZ as measured by Western blots. Furthermore, α 1 AR-induced hypertrophy (48 hr) was also prevented by Ad235 as measured by 3 H-leucine incorporation (71±5% ↓) and fetal gene ANF mRNA expression (54±11% ↓) using qRT-PCR. These data confirmed that p67 phox mediates α 1 AR-induced hypertrophy and MEK1/2-ERK1/2 activation, also suggested an interesting notion that the reported non-ROS generating region of p67 phox C-terminus may also contribute to α 1 AR-induced hypertrophic signaling in ARVM. In addition, immunoprecipitation of ARVM lysates with anti-p67 phox antibody followed by Western blotting with anti-ERK or anti-MEK antibodies showed the co-localization of p67 phox with ERK and MEK kinases, suggesting the direct interaction between MEK-ERK cascade and p67 phox in ARVM. Taken together, our data showed that the non-ROS generating region of p67 phox C-terminus mediates α 1 AR-induced hypertrophy in ARVM, suggesting a novel role of p67 phox as a signaling molecule in α 1 AR-induced hypertrophy via a potential ROS-independent mechanism.
Abstract 8142: By Virtue of Its Interaction with the β <sub>2</sub> -adrenergic Receptor, CXCR4 Plays a Role in the Regulation of β <sub>2</sub> -adrenergic Receptor Signaling Pathway Affecting Calcium and Contractility in Cardiac Myocytes
Authors: Thomas LaRocca, Hunter Champion, Georges Haddad, Roger Hajjar, Lakshmi Devi, Alison Schecter, Sima T Tarzami
Journal: Circulation (2011)

Chemokines are small secreted proteins with chemoattractant properties that play a key role in inflammation, metastasis, and embryonic development. We previously demonstrated a nonchemotactic role for one such chemokine pair, stromal cell-derived factor-1α (SDF-1α) and its G-protein coupled receptor, CXCR4. SDF-1 α /CXCR4 are expressed on cardiac myocytes and have direct consequences on cardiac myocyte physiology by inhibiting contractility in response to the nonselective β-adrenergic receptor (βAR) agonist, isoproterenol. As a result of the importance of β-adrenergic signaling in heart failure pathophysiology, we investigated the underlying mechanism involved in CXCR4 modulation of βAR signaling. We hypothesis that β 2 adrenergic receptor in the heart is negatively modulated by interactions with CXCR4 chemokine receptor. For this we have used biophysical techniques such as bioluminescence resonance energy transfer assay and biochemical techniques such as immunoprecipitation and signaling assays to identify the CXCR4-β2AR interaction and determine the physiological significance of this interaction. Our studies demonstrate activation of CXCR4 by SDF-1 leads to a decrease in βAR-induced PKA activity as assessed by cAMP accumulation and PKA-dependent phosphorylation of phospholamban, an inhibitor of SERCA2a. We determined CXCR4 regulation of βAR downstream targets is β2AR-dependent. In conclusion, we demonstrated a physical interaction between CXCR4 and β2AR as determined by coimmunoprecipitation, confocal microscopy, and BRET techniques. The CXCR4-β2AR interaction leads to G-protein signal switching from Gαs to Gαi-mediated pathway and suggests the interaction is a novel mechanism for regulating cardiac myocyte calcium handling and subsequent contractility. Chemokines are physiologically and developmentally relevant to myocardial biology and represent a novel receptor class of cardiac modulators. The CXCR4- β2AR complex could represent a hitherto unknown target for therapeutic intervention.
Abstract 18899: Distribution of Low CT Number Area is Dominant and Wide in Vessel Containing Vulnerable Plaque - Vessel-wide Cross-sectional Scannning by Multi-detector Row Computed Tomography
Authors: Sei Komatsu, Atsuko Imai, Mitsuhiko Takewa, Hitoshi Minamiguchi, Tomoki Ohara, Kazuhisa Kodama
Journal: Circulation (2012)

Introduction. Lipid-rich plaque is shown to be dominant in the culprit by intravascular ultrasound and multidetector row computed tomography in acute coronary syndrome (ACS) than in stable angina pectoris (SAP). However, there were few reports compared the disposition of lipid-rich plaque in vessel-wide. Hypothesis We assessed the hypothesis that lipid-rich plaque is dominantly located in ACS patients by our original vessel-wide cross-sectional scanning. Methods One hundred eight patients (32 acute coronary syndrome (ACS), 38 stable angina pectoris (SAP), and 38 patients without plaque) underwent 64-slice computed tomography angiography. Cross-sectional images for 1mm-intervals were analyzed containing culprit lesion from the ostium. Areas and ratio of 0-50, 50-100, 100-150, 150-200, 200-250, 250-300, 300-350, 350-400, 400-450, &gt;450HU surrounding vessel were calculated for each cross-sectional images and continuously demonstrated as a graph (see figure). Results Analyzed cross-sectional images were averaged 52±18 images for 76 vessels. Fifty cross-sectional images for 38 vessels in patients without plaque were analyzed as control. The ratios of 0-50, 50-100 HU were statistically dominant in ACS patients compared to SAP patients or without plaque (34.7±14.4% vs. 19.6±4.1% vs. 14.8±3.6%, P&lt;0.0001; 22.3±5.5% vs.15.4±3.4% vs. 14.6±2.0%; P&lt;0.0001). The number of slices in which 0-50HU were dominant were higher in ACS than SAP (18±6 vs 12±4 slices, p&lt;0.01). The number of positive remodeling in the vessel was higher ACS than SAP (3.6±0.9 vs. 1.5±0.8, p&lt;0.001). The slices of 64 culprits (91%) were not the most distributed by 0-50HU in the vessels. Conclusions. In ACS patients, lipid-rich component, demonstrated as the area 0-50HU, distributed dominantly and wide on the vessel including the culprit.
Abstract 9904: The Impact of Energy Loss on Cardiac Function in Fontan Circulation
Authors: Takashi Honda, Keiichi Itatani, Atsushi Kitagawa, Hisashi Ando, Yayoi Nakahata, Norihiko Oka, Kagami Miyaji, Masahiro Ishii
Journal: Circulation (2012)

Background: There have been several numerical studies discussing the flow energy loss (EL) at Fontan anastomosis that reflects flow efficiencies and which would lead to increase the cardiac workload. However, in-vivo clinical measurements of EL have never been reported. In this study, we measured EL in Fontan patients with simultaneous measurements of pressure and velocity, and revealed its influence to the cardiac functions of the single ventricles. Methods: Catheter exams measuring pressure and velocity simultaneously were performed 1 year after the Fontan procedure in 9 patients (mean age 27.4 ± 3.2 months). EL was calculated using the averaged pressure and velocity data of 20 cardiac cycles in the superior and inferior vena cava and the bilateral pulmonary arteries. Systolic functions were evaluated with max dp/dt during the isovolumic systolic phase (Sdpdt), ejection fraction (EF), and cardiac output (CO); whereas diastolic functions were evaluated with max -dp/dt (Ddpdt) and time constant tau in the isovolumic diastolic phase. The ratio of Ddpdt/Sdpdt was examined to detect heart failure with preserved systolic function. Tei index was also examined. Results: EL significantly correlated with Sdpdt (r=0.842), but not with EF or CO (r=0.472 and -0.199, respectively), indicating that high EL reflected afterload increase. EL significantly correlated with Ddpdt and tau (r=-0.574 and 0.795, respectively). EL strongly correlated with Ddpdt/Sdpdt and Tei index (r=0.889 and 0.757, respectively), indicating that diastolic function was impaired when EL increased, while systolic function was preserved. Conclusions: EL is a novel and sensitive parameter detecting early heart failure with preserved systolic function with increased afterload and impaired diastolic function, and could be an index to decide the indication of medication therapy with vasodilator such as angiotensin-converting enzyme inhibitor for heart failure after Fontan procedure.
Abstract 8706: Impact of Small Dense Low-Density Lipoproteins Cholesterol on Cardiovascular Disease in an Urban Japanese Cohort: The Suita Study
Authors: Hidenori Arai, Yoshihiro Kokubo, Makoto Watanabe, Tatsuya Sawamura, Tomonori Okamura, Yoshihiro Miyamato
Journal: Circulation (2011)

Aim: Increased plasma low-density lipoprotein cholesterol (LDL-C) concentrations have been shown to be one of the major risk factors for cardiovascular disease (CVD). Clinical evidence also indicates that small dense LDL (sd-LDL) particles are more atherogenic than large buoyant LDL particles. Because there was no easy assay to measure the amount of sd-LDL-C, few studies have addressed the association between sd-LDL-C and CVD. In this study, we hypothesized that higher sd-LDL-C is associated with increased risk for CVD. To this end, we examined the association between sd-LDL-C and CVD in Japanese by using a new kit to measure sd-LDL-C. Methods: We studied 2034 Japanese individuals (30 to 79 years old without stroke or coronary heart disease (CHD)) in the Suita Study, who completed measurement of direct LDL-C and sd-LDL-C by a kit based on the precipitation method with filtration, and then followed for 11.7 years on average. We calculated the Cox proportional adjusted hazard ratios (HRs) of LDL-C, sd-LDL-C, and sd-LDL-C/LDL-C ratio quartiles for incident CAD, stroke, and CVD (CHD + stroke) adjusting for age, sex, body mass index, diabetes, blood pressure category (defined on the basis of the ESH-ESC 2007 criteria), smoking and drinking at baseline. Results: The mean age of this cohort was 59.3 years old and 52.4% was women. The HR of the 4th quartile of sd-LDL-C for the development of CAD was 3.35 (95% confidence intervals: 1.38 to 8.13), which was higher than that in the analysis using LDL-C quartiles. In multivariable adjustment, the HR of the 4th quartile was almost similar. When we used the quartiles of sd-LDL/LDL ratio, increased sd-LDL/LDL ratio was associated with the incidence of CVD, CAD, and stroke. Sex-specific analysis showed that the association of sd-LDL-C with CAD and CVD was statistically significant in men, but not in women. Conclusions: We demonstrated that increased levels of sd-LDL-C are significantly associated with the development of CVD. Our data indicate that sd-LDL-C is a better risk factor for CVD than LDL-C for risk assessment.
Abstract 329: Is Procalcitonin the Prognostic Marker in Septic Shock Patients Caused by Methicillin-Resistant Staphylococcus aureus?
Authors: Takumi Taniguchi, Masaki Okajima
Journal: Circulation (2012)

Background : Procalcitonin (PCT) has emerged as the most specific biomarker for bacterial infection. Recently, several investigations showed that PCT not only has diagnostic value as a marker for sepsis, especially among critically ill patients, but also may have prognostic value as well. However, there are few studies whether PCT is the prognostic marker on septic shock patients caused by methicillin-resistant Staphylococcus aureus (MRSA), or not. The present study evaluated the PCT value and the change of PCT value as the prognostic marker on septic shock patients caused by MRSA in intensive care unit (ICU). Hypothesis : We hypothesis that the PCT value and the change of PCT value are the prognostic marker on septic shock patients caused by MRSA. Methods : Eleven patients (M/F 8/3, mean age 61 years) with septic shock induced by MRSA were measured PCT value at the time of ICU admission and 1, 2, 3 days after ICU admission Primary outcome was the correlation between PCT and severity (mortality and SOFA score), and secondary outcomes were the correlations between PCT and inflammatory responses after ICU admission. Results : The PCT level was 1.8 ± 3.3 ng/mL at the time of ICU admission and was 1.5 ± 1.0 ng/mL 3days after ICU admission. There is not significant correlation between PCT level and SOFA scores (r=0.21, p=0.289) at the time of ICU admission. There is not significant correlation between PCT level at the time of ICU admission and mortality (r=0.14, p=0.414), and not correlation between the change of PCT level and mortality (r=0.18, p=0.301). Moreover, PCT did not significantly correlate with WBC counts (r=0.04) and CRP level (r=0.25). The change of PCT level did not significantly correlate with the changes of WBC counts and CRP level. Conclusion : The PCT value and the change of PCT value are not the prognostic marker on septic shock patients caused by MRSA.
Abstract 35: A Validation of the Association Between a Quantitative CT Scan Measure of Cerebral Edema and Outcomes Post Cardiac Arrest
Authors: Cristal Cristia, Mai-Lan Ho, Sean Levy, Tyler Giberson, Justin Salciccoli, Michael N Cocchi, Michael W Donnino
Journal: Circulation (2012)

Introduction: The presence of cerebral edema post cardiac arrest (CA) may indicate widespread neurologic injury. Previous studies have examined the association between a quantitative measure of brain edema on CT scan and outcome. A calculated gray matter to white matter attenuation ratio (GWR) of &lt;1.2 was associated with near 100% non-survivable injury post CA. These findings have yet to be validated in a separate population. Objective: To validate whether a GWR &lt;1.2 reliably indicates poor survival post arrest. We also sought to determine the inter-relater reliability among reviewers and develop a novel GWR that may be simpler to use in practice. Methods: We performed a retrospective analysis of post CA patients admitted to a single center from 2008 to 2012. Inclusion criteria were age &gt;18years, non traumatic arrest, and a brain CTscan within 24 hours of ROSC. Three independent physician reviewers measured attenuation in pre-specified areas. Results: We evaluated 300 patients, of whom 91 met inclusion criteria and 79 had a technically adequate CT for evaluation. Mean age was 64 years (SD +/- 17); 69% were male. In-hospital mortality was 63%. Approximately 59% of patients received therapeutic hypothermia. For the validation measurement, the interclass correlation coefficient was 0.70. Results of GWR &lt;1.2 are shown in Table. Adjusting the cut-off value to &lt;1.1, no survivors were noted by reviewers 2 and 3 (0/19) and 89% did not survive as judged by reviewer 1 (1/8). Conclusion: A GWR &lt;1.2 on CT imaging within 24 hours post CA was associated with a high degree of mortality and poor neurologic outcome, however this was not invariably true. Similarly, our experimental model did not perform well enough to be used for prognostication. We caution against implementation based on previous investigations until reasons for these disparate findings are elucidated. A threshold &lt;1.1 may be a safer cut-off to identify patients with low chance of neurological survival.