Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction

Background  The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). 

Methods  Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1:1:1 ratio to receive either adenosine 50 µg∙kg^-1∙min^-1 (low-dose group, n=31), or 70 µg∙kg^-1∙min^-1 (high-dose group, n=32), or saline 1 ml/min (control group, n=27) for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade (TFG) and TIMI myocardial perfusion grade (TMPG), and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram (ECG) and their ratio (STsum-post/STsum-pre) were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure.

Results  A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 (35.5%) patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group (both P=0.001). STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group (low-dose group vs. control group, P=0.003 and high-dose group vs. control group, P=0.001), without a dose-dependent pattern (P=0.238). The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group (P=0.024). Compared to the left ventricular ejection fraction (LVEF) in control group, LVEF in the low-dose group increased by 5.8% at 24 hours (P=0.012) and by 10.9% at 6 months (P=0.007), LVEF in the high-dose group increased by 9.5% at 24 hours (P=0.001) and by 10.0% at 6 months (P=0.001), respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups (P=0.008). There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly (P=0.013, P=0.016).

Conclusion  Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.

     

Effect of short-term high-dose atorvastatin on systemic inflammatory response and myocardial ischemic injury in patients with unstable angina pectoris undergoing percutaneous coronary intervention

Background Percutaneous coronary intervention （PCI） could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property.The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.Methods From March 2012 to May 2014,one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital,were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group （HD group,n=56） or 20 mg/d as normal dose group （ND group,n=57） or an additional single high loading dose （80 mg） followed 6-day atorvastatin 20 mg/d as loading dose group （LD group,n=52）.Plasma C-reactive protein （CRP） and interleukin-6 （IL-6） levels were determined before intervention and at 5 minutes,24 hours,48 hours,72 hours,and 7 days after intervention.Creatine kinase-myocardial isoenzyme （CK-MB） and cardiac troponin I （cTnl） were measured at baseline and then 24 hours following PCI.Results Plasma CRP and IL-6 levels increased from baseline after PCI in all groups.CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI.Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group （（9.14±3.02） mg/L） than in the LD group （（11.06±3.06） mg/L） and ND group （（12.36±3.08） mg/L,P ＜0.01）; this effect persisted for 72 hours.IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group （（16.19±5.39） ng/L and （14.26±4.12） ng/L,respectively）） than in the LD group （（19.26±6.34） ng/L and （16.03±4.08） ng/L,respectively,both P ＜0.05） and ND group （（22.24±6.98） ng/L and （17.24±4.84） ng/L,respectively）.IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups.Although PCI cau     

Clinical relevance of angiographic coronary collaterals during primary coronary intervention for acute ST-elevation myocardial infarction

Background Collaterals to occluded infarct-related coronary arteries （IRA） have been observed after the onset of acute ST-elevation myocardial infarction （STEMI）.We sought to investigate the impact of early coronary collateralization,as evidenced by angiography,on myocardial reperfusion and outcomes after primary percutaneous coronary intervention （PCI）.Methods Acute procedural results,ST-segment resolution （STR）,enzymatic infarct size,echocardiographic left ventricular function,and major adverse cardiac events （MACE） at 6-month follow-up were assessed in 389 patients with STEMI undergoing primary PCI for occluded IRA （TIMI flow grade 0 or 1） within 12 hours of symptom-onset.Angiographic coronary collateralization to the occluded IRA at first contrast injection was graded according to the Rentrop scoring system.Results Low （Rentrop score of 0 or 1） and high （Rentrop score of 2 or 3） coronary collateralization was detected in 329 and 60 patients,respectively.Patients with high collateralization more commonly had prior stable angina and right coronary artery occlusion,but less often had left anterior descending artery occlusion.At baseline,these patients presented with less extent of ST-segment elevation and lower serum levels of creatine kinase myocardial band （CK-MB） and cardiac troponin Ⅰ （cTnl）.Procedural success rate,STR,corrected TIMI flame count,and area under the curve of CK-MB and cTnl measurements after the procedure were similar between patients with high collateralization and those with low collateralization （for all comparisons P＞0.05）.There were no differences in left ventricular ejection fraction and rates of MACE at 6 months according to baseline angiographic collaterals to occluded IRA.Conclusions In patients with acute STEMI undergoing primary PCI within 12 hours of symptom-onset,coronary collateralization to the occluded IRA was influenced by clinical and angiographic features.Early recruitment of collaterals limits infarct size at baseline,but has no significant impact on myocardial reperfusion after the procedure and subsequent left ventricular function and clinical outcomes.     

High volume practice proved the safety of off-pump coronary artery bypass surgery in left main coronary artery lesions: a two-year single center experience

Background  Left main coronary artery (LMCA) stenosis has been recognized as a risk factor for early death among patients undergoing coronary artery bypass grafting (CABG). This study aimed to assess if LMCA lesions pose an additional risk of early or mid-term mortality and/or a major adverse cardiac and cerebrovascular event (MACCE) after off-pump coronary artery bypass grafting (OPCABG), compared with non-left main coronary artery stenosis (non-mainstem disease).

Methods  From January 1, 2009 to December 31, 2010, 4869 patients had a primary isolated OPCABG procedure at Beijing Anzhen Hospital. According to the pathology of LMCA lesions, they were retrospectively classified as a non-mainstem disease group (n=3933) or a LMCA group (n=936). Propensity scores were used to match the two groups, patients from the non-mainstem disease group (n=831) were also randomly selected to match patients from the LMCA group (n=831). Freedom from MACCE in the two groups was calculated using the Kaplan-Meier method.

Results  The difference in the mortality and the rate of MACCE during the first 30 days between the non-mainstem disease group and the LMCA group did not reach statistical significance (P=0.429, P=0.127 respectively). With a mean follow-up of (12.8±7.5) months and a cumulative follow-up of 1769.6 patient-years, the difference in the freedom from MACCEs between the two groups, calculated through Kaplan-Meier method, did not reach statistical significance (P=0.831).

Conclusion  Analysis of a high volume of OPCABG procedures proved that LMCA lesions do not pose additional early and mid-term risk to OPCABG. Therefore, a LMCA lesion is as safe as non-mainstem disease lesion during the OPCABG procedure.

     

Safety and feasibility of repeated percutaneous transradial coronary intervention in the same route

Background  The radial approach has been increasingly used as an alternative to femoral access. And more procedures using repeated transradial coronary intervention (r-TRI) are performed. However, few data about r-TRI has been obtained. Therefore, we investigated the safety and feasibility of r-TRI using the same route.

Methods  A total of 423 consecutive eligible patients undergoing r-TRI were enrolled in the r-TRI group, and 846 patients with initial TRI (i-TRI) were assigned to the i-TRI group in a 2:1 matching ratio compared to r-TRI group. The primary endpoint included the success rate of the procedure and the incidence of vascular related complications.

Results  The baseline clinical characteristics in the two groups were comparable. The success rate of procedures in the r-TRI and i-TRI was similar (96.0% vs. 97.5%, P=0.130). In subgroup analysis (coronary angiography only or angiography with pecutaneous coronary intervention), similar results were also observed. The puncture numbers and incidence of radial artery spasm in the r-TRI group were significantly higher than in the i-TRI group (P=0.024 and P <0.001, respectively). The other procedural outcomes in the two groups were identical. With respect to the incidence of overall vascular related complication and independent events, there were no significant differences in spite of a higher incidence of radial artery occlusion (RAO) in the r-TRI group (RAO: 1.2% vs. 0.7%, P=0.521). The patients in the i-TRI group had more comfortable feeling than patients in the r-TRI group (P=0.001).

Conclusions  R-TRI produces a comparable procedure success rate and incidence of vascular complication when compared to i-TRI. It should be considered as an acceptable and safe procedure.

     

Investigation of long-term implantation of BuMA stent in a porcine coronary model

Background  Stent-based delivery of sirolimus has been shown to reduce neointimal hyperplasia significantly. However, the long-term effect of the polymer is thought to initiate and sustain an inflammatory response and contribute to the occurrence of late complications. Our study aimed to evaluate the efficacy and safety of the BuMA biodegradable drug-coated sirolimus-eluting stent (BSES) for inhibiting neointimal hyperplasia in a porcine coronary model.

Methods  Four types of stents were implanted at random in different coronary arteries of the same pig: BSES (n=24), bare metal stent (BMS) (n=24), biodegradable polymer coated stent without drug (PCS) (n=24) and only poly (n-butyl methacrylate) base layer coated stent (EGS) (n=23). In total, 26 animals underwent successful random placement of 95 oversized stents in the coronary arteries. Coronary angiography was performed after 28 days, 90 days and 240 days of stent implantation. After 14 days, 28 days, 90 days and 240 days, 6 animals at each timepoint were sacrificed for histomorphologic analysis.

Results  The 28-day, 90-day and 240-day results of quantitative coronary angiography (QCA) showed reduction in luminal loss (LL) in the BSES group when compared with the BMS group;  (0.20±0.35) mm vs. (0.82±0.51) mm (P=0.035), (0.20±0.30) mm vs. (0.93±0.51) mm (P=0.013), and (0.18±0.16) mm vs. (0.19±0.24) mm (P=0.889), respectively. By 28-day, 90-day and 240-day histomorphomeric analysis results, there was also a corresponding significant reduction in neointimal tissue proliferation with similar injury scores of BSES compared with the BMS control; average neointimal area (0.90±0.49) mm² vs. (2.16±1.29) mm² (P=0.049), (1.53±0.84) mm² vs. (3.41±1.55) mm² (P=0.026), and (2.43±0.95) mm² vs. (3.12±1.16) mm² (P=0.228), respectively. High magnification histomorphologic examination revealed similar inflammation scores and endothelialization scores in both the BSES and BMS groups.

Conclusions  The BuMA biodegradable drug-coated sirolimus-eluting stents can significantly reduce neointimal hyperplasia and in-stent restenosis. Re-endothelialization of the BuMA stent is as good as that of the BMS in the porcine coronary model due to the reduced inflammation response to the BuMA stent.

     

Impact of primary percutaneous coronary intervention on blood perfusion in nonculprit artery in patients with anterior ST elevation myocardial infarction

Background Recent studies have demonstrated that epicardial flow in nonculprit arteries,which has been assumed to be normal,was slowed in the setting of ST-elevation myocardial infarction (STEMI).Howev...     

Impact of different termination modes on atrial fibrillation termination in catheter ablation of persistent atrial fibrillation

Background  The optimal endpoint for catheter ablation of persistent atrial fibrillation (AF) remains ambiguous. This study investigated the impact of AF termination as a procedural endpoint and the termination mode on long-term clinical outcome.

Methods  Two hundred and ninety-three patients who underwent stepwise ablation for persistent AF were categorized into the AF termination by ablation group and into the electrical cardioversion (CV) group. Subgroups were also analyzed based on different termination modes. Follow-up assessment included early recurrence and sinus rhythm (SR) maintenance.

Results  During initial ablation, 33 patients (11.3%) were directly converted to SR, 166 patients (56.7%) were converted to atrial tachycardia (AT) that subsequently restored SR with further ablation in 98 patients (33.4%), and a total of 162 patients (55.3%) underwent cardioversion due to persistent atrial arrhythmias. Comparison between termination by ablation and termination by cardioversion in patients exhibiting AF or AT revealed that no significant difference was observed in early recurrence (38.2% vs. 43.8%, P=0.328) and SR maintenance (67.2% vs. 59.8%, P=0.198) during the (23±7) months follow-up. Even after repeat ablation, the SR maintenance continued to exhibit no statistical difference in above two groups (72.5% vs. 70.4%, P=0.686). Further analysis of subgroups, however, demonstrated that patients with AF terminated directly to SR experienced better clinical outcomes than other subgroups (P <0.05). Furthermore, atrial arrhythmias present during ablation have been implicated in prediction of recurrence mode: AF or AT (P <0.05).

Conclusions  Termination as a procedural endpoint is not associated with favorable long-term SR maintenance in persistent AF. AF methods that convert arrhythmia directly to SR have, however, been linked with improved clinical outcomes, although conversions to AT may not be correlated. Atrial arrhythmias observed during the ablation may be used to predict the recurrence mode.

     

Detection of atherosclerotic plaque progression in the abdominal aorta of rabbits with 3T magnetic resonance imaging

Background  With features of high tissue contrast, MRI can be used for the qualitative and quantitative evaluation of atherosclerosis plaques. In this study we investigated the development of atherosclerosis plaque with high resolution 3T MRI in a rabbit model and compared the findings with the histopathological results.

Method  Twenty male New Zealand white rabbits were randomly allocated into an experimental group (n=16) and a control group (n=4). Atherosclerotic lesions were induced in the abdominal aorta by balloon injury and cholesterol feeding. Multiple sequences MRI examination (ToF, T1WI, T2WI, and CE T1WI) were performed at the 2nd, 3rd, and 4th months after aortic denudation. Vessel wall thickness, total vessel area, lumen area, and vessel wall area were recorded. Plaque components were analyzed using histological results as a standard reference.

Results  Seventeen rabbits (14 in the experimental group and 3 in the control group) received all three MR examinations. Gradually, from 2 months to 4 months, vessel wall thickness and area in the experimental group increased significantly compared with the control group (P <0.01). In the lumen area progressive stenosis was not found, even a slight dilation had developed in the experimental group. Lipid, fibrotic and calcified plaques can be differentiated by MR image. According to histological results, MRI had good performance in detection of lipid plaque.

Conclusion  MRI can be used to monitor progression of atherosclerosis and differentiate plaque components.

     

Randomized study on the safety and efficacy of dual-axis rotational versus standard coronary angiography in

Background  Dual-axis rotational coronary angiography (DARCA) was developed as an innovative adaptation of rotational angiography (RA), but it requires a longer coronary injection compared to standard coronary angiography (SA). As the body of the average Chinese patient is smaller than that of most western patients, with the same contrast injection time, the risk of complications from the contrast agent is increased in this population. The purpose of this study was to assess the clinical safety and efficacy of DARCA in the diagnosis of coronary artery disease (CAD) in the Chinese population by directly comparing it to SA.

Methods  Two hundred Chinese patients were randomized to either the SA group (n=100) or DARCA group (n=100). Contrast utilization, radiation exposure and procedure time were recorded for each modalities. Blood pressure (BP), heart rate (HR) pre and post injection symptoms and any arrhythmias were recorded.

Results  Compared to the SA group, there was a 42% reduction in contrast utilization, 55% reduction in radiation exposure and a 31% shorter procedure time in the DARCA group. In both groups, there were slight declines in the systolic BP values in the left coronary artery (LCA) post injection (P <0.01). Moreover, post injection HRs for the LCA were also reduced in the DARCA group (P <0.01). But all of these changes were small, transient and without clinical importance. Only one patient (1%) in the DARCA group had an attack of ventricular tachycardia immediately post injection and it resolved by itself during LCA angiography. No arrhythmias occurred in the SA group.

Conclusion  DARCA is a safe, efficient, and clinically comparable alternative to SA in the diagnosis of coronary artery disease in the Chinese population with less contrast utilized, which is less radiation exposure and a shorter procedure time than SA.

     

Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

Background  In response to the injury of the central nervous system (CNS), the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP), which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.

Methods  We generated ephrin-B2 knockout mice specifically in CNS astrocytes. Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates. In both groups, a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury. Twenty-eight days after the injury, Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups. All the data were analyzed by t-test for between-group comparison.

Results  We successfully set up the conditional ephrin-B2 knockout mice strain, which was confirmed by genotyping and ephrin-B2/GFAP double staining. These mice developed normally without apparent abnormality in general appearance. Twenty-eight days following brain injury, histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups. Compared with wild-type group, the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P=0.005) and hippocampus (P=0.027). Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P=0.008).

Conclusions  The establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes. Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury, which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

     

Effect of in-hospital medical complications on case fatality post-acute ischemic stroke: data from the China National Stroke Registry

Background  In-hospital medical complications are associated with poorer clinical outcomes for stroke patients after disease onset. However, few studies from China have reported the effect of these complications on the mortality of patients with acute ischemic stroke. In this prospective work, the China National Stroke Registry Study, we investigated the effect of medical complications on the case fatality of patients with acute ischemic stroke.   

Methods  From September 2007 to August 2008, we prospectively obtained the data of patients with acute stroke from 132 clinical centers in China. Medical complications, case fatality and other information recorded at baseline, during hospitalisation, and at 3, 6, and 12 months after stroke onset. Multivariable Logistic regression was performed to analyze the effect of medical complications on the case fatality of patients with acute ischemic stroke.

Results  There were 39 741 patients screened, 14 526 patients with acute ischemic stroke recruited, and 11 560 ischemic stroke patients without missing data identified during the 12-month follow-up. Of the 11 560 ischemic patients, 15.8% (1826) had in-hospital medical complications. The most common complication was pneumonia (1373; 11.9% of patients), followed by urinary tract infection and gastrointestinal bleeding. In comparison with patients without complications, stroke patients with complications had a significantly higher risk of death during their hospitalization, and at 3, 6 and 12 months post-stroke. Having any one in-hospital medical complication was an independent risk factor for death in patients with acute ischemic stroke during hospital period (adjusted OR=6.946; 95% CI 5.181 to 9.314), at 3 months (adjusted OR=3.843; 95% CI 3.221 to 4.584), 6 months (adjusted OR=3.492; 95% CI 2.970 to 4.106), and 12 months (adjusted OR= 3.511; 95% CI 3.021 to 4.080). Having multiple complications strongly increased the death risk of patients.

Conclusion  Short-term and long-term outcomes of acute stroke patients are affected by in-hospital medical complications.     

Protective effect of low potassium dextran solution on acute kidney injury following acute lung injury induced by oleic acid in piglets

Background  Low potassium dextran (LPD) solution can attenuate acute lung injury (ALI). However, LPD solution for treating acute kidney injury secondary to ALI has not been reported. The present study was performed to examine the renoprotective effect of LPD solution in ALI induced by oleic acid (OA) in piglets.

Methods  Twelve animals that suffered an ALI induced by administration of OA into the right atrium were divided into two groups: the placebo group (n=6) pretreated with normal saline and the LPD group (n=6), pretreated with LPD solution. LPD solution was injected intravenously at a dose of 12.5 ml/kg via the auricular vein 1 hour before OA injection.

Results  All animals survived the experiments with mild histopathological injury to the kidney. There were no significant differences in mean arterial pressure (MAP), creatinin and renal damage scores between the two groups. Compared with the placebo group, the LPD group had better gas exchange parameters at most of the observation points ((347.0±12.6) mmHg vs. (284.3±11.3) mmHg at 6 hours after ALI, P <0.01). After 6 hours of treatment with OA, the plasma concentrations of NGAL and interleukin (IL)-6 in both groups increased dramatically compared to baseline ((6.0±0.6) and (2.50±0.08) folds in placebo group; and (2.5±0.5) and (1.40±0.05) folds in LPD group), but the change of both parameters in the LPD group was significantly lower (P <0.01) than in the placebo group. And 6 hours after ALI the kidney tissue concentration of IL-6 in the LPD group ((165.7 ± 22.5) pg∙ml^-1∙g^-1 protein) was significantly lower (P <0.01) than that in placebo group ((67.2± 25.3) pg∙ml^-1∙g^-1 protein).

Conclusion  These findings suggest that pretreatment with LPD solution via systemic administration might attenuate acute kidney injury and the cytokine response of IL-6 in the ALI piglet model induced by OA injection.

     

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial

Context  Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. Objectives  To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. Design, Setting, and Participants  The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. Interventions  Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. Main Outcome Measures  One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. Results  At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P = .02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P = .23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P = .051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P = .07). Conclusions  Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.      

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Significance of Aspergillus spp. isolation from lower respiratory tract samples for the diagnosis and prognosis of invasive pulmonary aspergillosis in chronic obstructive pulmonary disease

Background  Chronic obstructive pulmonary diseases (COPD) is an emerging population at risk for invasive infection of Aspergillus. Isolation of Aspergillus from lower respiratory tract (LRT) samples is important for the diagnosis of invasive pulmonary aspergillosis (IPA). The purpose of this study was to investigate the value of Aspergillus isolation from LRT samples for the diagnosis and prognosis of IPA in COPD population.

Methods  Clinical record with Aspergillus spp. isolation in COPD and immunocompromised patients was reviewed in a retrospective study. Patients were categorized and compared according to their severity of illness (admitted to general ward or ICU) and immunological function (COPD or immunocompromised).

Results  Multivariate statistical analysis showed that, combined with Aspergillus spp. isolation, APACHE II scores >18, high cumulative doses of corticosteroids (>350 mg prednisone or equivalent dose) and more than four kinds of broad-spectrum antibiotics received in hospital may be predictors of IPA in COPD (OR=9.076, P=0.001; OR=4.073, P=0.026; OR=4.448, P=0.021, respectively). The incidence of IPA, overall mortality, mortality of patients with IPA and mortality of patients with Aspergillus spp. colonization were higher in COPD patients in ICU than in general ward, but were similar between COPD and immunocompromised patients.

Conclusions  Aspergillus spp. isolation from LRT in COPD may be of similar importance as in immunocompromised patients, and may indicate an increased diagnosis possibility of IPA and worse prognosis when these patients received corticosteroids, antibiotics, and need to admit to ICU. Aspergillus spp. isolation from LRT samples combined with certain risk factors may be useful in differentiating colonization from IPA and evaluating the prognosis of IPA in COPD patients.

     

Characteristics of pulmonary inflammation in combined pulmonary fibrosis and emphysema

Background  The condition of concomitant upper lobe emphysema and lower lobe fibrosis as identified by computer tomography is known as combined pulmonary fibrosis and emphysema (CPFE). CPFE has distinct clinical characteristics compared with emphysema alone (EA) and idiopathic pulmonary fibrosis (IPF) without emphysema. However, the pulmonary inflammation characteristics of CPFE are not well known, and the differences between CPFE and the other two diseases with regards to pulmonary inflammation need to be explored. The pulmonary inflammatory characteristics were investigated in CPFE patients and compared with EA and IPF.

Methods  Fraction exhaled nitric oxide (Fe,NO) and differential cell counts, the concentrations of monokine induced by interferon gamma (MIG/CXCL9), interferon-inducible protein 10 (IP-10/CXCL10), and interferon-inducible T cell alpha chemoattractant (I-TAC/CXCL11) were measured in induced sputum obtained from subjects with CPFE (n=22), EA (n=22), IPF (n=14), and healthy volunteers (HV, n=12). In addition, immunohistochemistry was used to quantify the expression of nitric oxide synthases in alveolar macrophages in 23 lung tissues from patients and control subjects.

Results  The CPFE group had higher alveolar NO than subjects in the EA and HV groups (P=0.009, P=0.001, respectively) but not than the IPF group (P >0.05). Numbers of sputum eosinophils were significantly elevated in CPFE and IPF groups compared with the HV group (P=0.001, P=0.008). In contrast, eosinophil counts in EA group did not differ from those in the HV group. Compared with the EA and HV groups, the CPFE group had a lower concentration of I-TAC/CXCL11 in sputum supernatants (P=0.003, P=0.004). Immunoreactivity for inducible nitric oxide synthase (iNOS) was higher in the CPFE group than in the EA group (P=0.018).

Conclusions  The pulmonary inflammation of CPFE group is more similar to IPF group, while the distal airway inflammation is more significant in CPFE and IPF groups than in EA group. Lung eosinophil cell infiltration and high NOS expression in alveolar macrophage might participate in this pathogenesis.

     

Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

Background  Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures. In this study, we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.

Methods  Three groups of rats were used: (1) a stimulation group (n=12), (2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA), and (3) a control group (n=12) with sham surgery. Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT. High-frequency stimulation was performed in each group except the sham stimulation group. Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in the stimulation group. The concentrations of glucose, lactate, and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.

Results  The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020, P=0.001; respectively). However, no significant difference in the concentration of glucose and pyruvate was found between these groups (P >0.05). Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05), but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).

Conclusions  This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation. These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

     

Predictive factors improving survival after gastric and hepatic surgical treatment in gastric cancer patients with synchronous liver metastases

Background  The prognosis for patients with gastric cancer and synchronous liver metastases is very poor. However, a standard therapeutic strategy has not been well established. The clinical benefit and prognostic factors after hepatic surgical treatment for liver metastases from gastric cancer remain controversial.

Methods  Records of 105 patients who underwent gastrectomy regardless of hepatic surgical treatment for gastric cancer with synchronous liver-only metastases in our center between 1995 and 2010 were retrospectively reviewed.

Results  The overall survival rate for the 105 patients was 42.1%, 17.2%, and 10.6% at 1, 2, and 3 years, respectively, with a median survival time of 11 months. Multivariate survival analysis revealed that the extent of lymphadenectomy (D) (P <0.001), lymph node metastases (P <0.001), extent of liver metastases (H) (P=0.008), and lymphovascular invasion (P=0.002) were significant independent prognostic factors for survival. Among patients who underwent D2 lymphadenectomy, those who underwent hepatic surgical treatment had a significantly improved survival compared with those who underwent gastrectomy alone (median survival, 24 vs. 12 months; P <0.001). However, hepatic surgical treatment was not a prognostic factor for patients who underwent D1 lymphadenectomy (median survival, 8 vs. 8 months; P=0.495). For the 35 patients who underwent gastrectomy plus hepatic surgical treatment, D2 lymphadenectomy (P <0.001), lymph node metastases (P=0.015), and extent of liver metastases (H1 vs. H2 and H3) (P=0.017) were independent significant prognostic factors for survival.

Conclusions  D2 lymphadenectomy plus hepatic surgical treatment may provide hope for long-term survival of judiciously selected patients with hepatic metastases from gastric cancer. Patients with a low degree of lymph node metastases and H1 liver metastases would make the most appropriate candidates. However, if D2 dissection cannot be achieved, hepatic surgical treatment is not recommended.