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.

     

Therapeutic effects of dl-3-n-butylphthalide in a transgenic mouse model of amyotrophic lateral sclerosis

Background  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of the upper and lower motor neurons. Transgenic mice over-expressing a mutant form of the human SOD1 gene develop an ALS-like phenotype. Currently, there is no effective treatment or drug for the fatal disease. Previous studies reported potent efficacy of dl-3-n-butylphthalide (DL-NBP) for several neurodegenerative disorders and cerebral ischemia. SOD1-G93A mice are a mouse model of ALS. In this study, we investigated the efficacy of DL-NBP on this ALS mouse model.

Methods  Sixty SOD1-G93A female mice were divided into four groups. The vehicle control group received 0 mg∙kg^-1∙d^-1 DL-NBP. The experimental groups received DL-NBP with doses of 30, 60 or 120 mg∙kg^-1∙d^-1, respectively. For measurement of motor activity, the hanging wire test and rotarod test were performed. Survival statistics were analyzed by Kaplan-Meier survival curves. The body weight of each mouse was recorded twice per week. The statistical motor unit number estimation (MUNE) technique was used to estimate the number of functioning motor units in gastrocnemius muscle. Muscle morphology was evaluated by hematoxylin and eosin staining. Motor neuron quantitation was performed by Nissl staining and microglia activation was observed by immunohistochemistry.

Results  Oral administration of 60 mg∙kg^-1∙d^-1 DL-NBP significantly prolonged survival ((164.78±16.67) days) of SOD1-G93A mice compared with vehicle control ((140.00±16.89) days). Treating mice with DL-NBP (60 mg∙kg^-1∙d^-1) significantly decreased the progression rate of motor deficits and suppressed body weight reduction. Furthermore, we found that treating SOD1-G93A mice with DL-NBP (60 mg∙kg^-1∙d^-1) slowed the rate of MUNE reduction (P <0.01). Motor neurons were remarkably preserved in the anterior horns in mice treated with DL-NBP (60 mg∙kg^-1∙d^-1) at the stage of 19 weeks (P <0.01). Treating mice with DL-NBP (60 mg∙kg^-1∙d^-1) significantly reduced CD11b immunoreactivity compared with vehicle control mice (P <0.05). No significant effect was observed in mice treated with DL-NBP of 30 or 120 mg∙kg^-1∙d^-1.

Conclusions  The post-disease-onset administration of DL-NBP significantly prolonged survival and improved motor performance in SOD1-G93A mice. DL-NBP may be a potential therapeutic agent for ALS.

     

Effect of high-dose rosuvastatin loading before percutaneous coronary intervention in female patients with non-ST-segment elevation acute coronary syndrome

Background  Early loading statin therapy before percutaneous coronary intervention (PCI) is associated with reduced mortality and periprocedural myocardial injury. The aim of this study was to study the effect of rosuvastatin loading therapy before PCI in female patients with non-ST-segment elevation acute coronary syndrome (NSTEACS).

Methods  Consecutive 117 female patients with NSTEACS were randomly assigned to either the group of rosuvastatin loading before PCI (20 mg 12 hours before angioplasty procedure, with a further 10 mg dose 2 hours before procedure, the loading dose group, n=59) or the no rosuvastatin treatment group before PCI (control group, n=58). Periprocedural myocardial injury, periprocedural changes of high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-a in serum and the incidence of major adverse cardiac events (MACE) 3 months and 6 months later were assessed.

Results  The incidence of periprocedural myocardial injury was higher in control group than loading dose group (CKMB: 10.17% vs. 25.86% , P=0.027; Troponin I: 11.86% vs. 29.31%, P=0.019). MACE occurred in 1.69% of patients in loading dose group and 12.07% of those in control group 3 months after procedure (P=0.026), 3.39% vs. 17.24% at 6 months (P=0.014). The levels of hs-CRP, IL-1, IL-6, and TNF-a in serum were not significantly different between the two groups before PCI, but after PCI they were significantly higher in control group.

Conclusions  High-dose rosuvastatin loading before PCI significantly reduced periprocedural myocardial injury and periprocedural inflammation cytokines release and improved 3-month and 6-month clinical outcomes in female patients with NSTEACS who underwent PCI.     

Effect of glucose-insulin-potassium infusion on mortality in patients with acute ST-segment elevation myocardial infarction: the CREATE-ECLA randomized controlled trial

Context  Glucose-insulin-potassium (GIK) infusion is a widely applicable, low-cost therapy that has been postulated to improve mortality in patients with acute ST-segment elevation myocardial infarction (STEMI). Given the potential global importance of GIK infusion, a large, adequately powered randomized trial is required to determine the effect of GIK on mortality in patients with STEMI. Objective  To determine the effect of high-dose GIK infusion on mortality in patients with STEMI. Design, Setting, and Participants  Randomized controlled trial conducted in 470 centers worldwide among 20 201 patients with STEMI who presented within 12 hours of symptom onset. The mean age of patients was 58.6 years, and evidence-based therapies were commonly used. Intervention  Patients were randomly assigned to receive GIK intravenous infusion for 24 hours plus usual care (n = 10 091) or to receive usual care alone (controls; n = 10 110). Main Outcome Measures  Mortality, cardiac arrest, cardiogenic shock, and reinfarction at 30 days after randomization. Results  At 30 days, 976 control patients (9.7%) and 1004 GIK infusion patients (10.0%) died (hazard ratio [HR], 1.03; 95% confidence interval [CI], 0.95-1.13; P = .45). There were no significant differences in the rates of cardiac arrest (1.5% [151/10 107] in control and 1.4% [139/10 088] in GIK infusion; HR, 0.93; 95% CI, 0.74-1.17; P = .51), cardiogenic shock (6.3% [640/10 107] vs 6.6% [667/10 088]; HR, 1.05; 95% CI, 0.94-1.17; P = .38), or reinfarction (2.4% [246/10 107] vs 2.3% [236/10 088]; HR, 0.98; 95% CI, 0.82-1.17; P = .81). The rates of heart failure at 7 days after randomization were also similar between the groups (16.9% [1711/10 107] vs 17.1% [1721/10 088]; HR, 1.01; 95% CI, 0.95-1.08; P = .72). The lack of benefit of GIK infusion on mortality was consistent in prespecified subgroups, including in those with and without diabetes, in those presenting with and without heart failure, in those presenting early and later after symptom onset, and in those receiving and not receiving reperfusion therapy (thrombolysis or primary percutaneous coronary intervention). Conclusion  In this large, international randomized trial, high-dose GIK infusion had a neutral effect on mortality, cardiac arrest, and cardiogenic shock in patients with acute STEMI.      

Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials

Context  The benefits of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) are still a matter of debate. Objective  To combine data from all randomized trials conducted with abciximab in STEMI. Data Sources  Formal searches of electronic databases (MEDLINE, PubMed) from from January 1990 to December 2004. Study Selection  We examined all completed, published, randomized trials of abciximab in STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, facilitated angioplasty, stenting, fibrinolysis, IIb-IIIa inhibitors, and abciximab. Data Extraction  Information on study design, type and dosage of drugs, inclusion and exclusion criteria, number of patients, and clinical outcome was extracted by 2 investigators. Disagreements were resolved by consensus. Data Synthesis  Eleven trials were analyzed, involving 27115 patients (12 602 [46.5%] in the abciximab group, 14 513 [53.5%] in the control group). When compared with the control group, abciximab was associated with a significant reduction in short-term (30 days) mortality (2.4% vs 3.4%, P = .047) and long-term (6-12 months) mortality (4.4% vs 6.2%, P = .01) in patients undergoing primary angioplasty but not in those treated with fibrinolysis or in all trials combined. Abciximab was associated with a significant reduction in 30-day reinfarction, both in all trials combined (2.1% vs 3.3%, P<.001), in primary angioplasty (1.0% vs 1.9%, P = .03), and in fibrinolysis trials (2.3% vs 3.6%, P<.001). Abciximab did not result in an increased risk of intracranial bleeding (0.61% vs 0.62%, P = .62) but was associated with an increased risk of major bleeding complications when combined with fibrinolysis (5.2% vs 3.1%, P<.001) but not with primary angioplasty (4.7% vs 4.1%, P = .36). Conclusions  This meta-analysis shows that, when compared with the control group, adjunctive abciximab for STEMI is associated with a significant reduction in 30-day and long-term mortality in patients treated with primary angioplasty but not in those receiving fibrinolysis. The 30-day reinfarction rate is significantly reduced in patients treated with either fibrinolysis or primary angioplasty. A higher risk of major bleeding complications is observed with abciximab in association with fibrinolysis.      

Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial

Context  Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective  To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. Design, Setting, and Participants  Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main Outcome Measures  Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). Results  Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days. Conclusion  In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. Trial Registration  ClinicalTrials.gov Identifier NCT00064428      

Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial

Context  Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents. Objective  To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI. Design, Setting, and Patients  Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004. Intervention  Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88). Main Outcome Measures  The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR). Results  Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002). Conclusion  Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.      

Ultrasound facilitates identification of combined spinal-epidural puncture in obese parturients

Background  The palpation method is widely used in clinical practice to identify the puncture site of combined spinal-epidural (CSE) blocks, but it is usually difficult to accurately locate the puncture site in obese parturients. Accurate identification of the puncture site is crucial for successful CSE block. The objective of this study was to evaluate the impact of ultrasound imaging on the success rate of CSE puncture in obese parturients.

Methods  Sixty obese parturients with a body mass index ³30 kg/m² who were scheduled for caesarean section were randomized into two equal-sized groups for location of the puncture site: an ultrasound group and a palpation group. The success rate of puncture at the first puncture site, the number of puncture attempts, duration of CSE procedure, time taken to determine the puncture site, and the depth of the epidural space were compared between groups. The frequencies of complications such as puncture site hemorrhage, neurological damage, and inadvertent dural puncture were also studied.

Results  There were no differences in age, body weight, height, body mass index, or gestational age between the two groups. The success rate of puncture at the first puncture site was significantly higher in the ultrasound group than the palpation group (100.00% vs. 70.00%, P=0.004). The number of puncture attempts was significantly lower in the ultrasound group than the palpation group (c²=6.708, P=0.035). The time taken for determining the puncture site was (0.30±0.12) minutes in the palpation group and (2.60±0.61) minutes in the ultrasound group (P <0.001). The duration of CSE procedure was (7.67±1.52) minutes in the palpation group and (9.37±1.35) minutes in the ultrasound group (P <0.001). The depth of the epidural space was similar in both groups (P=0.586). Puncture site hemorrhage was observed in 6 (20.00%) patients in the palpation group and 2 (6.67%) patients in the ultrasound group (P=0.255).

Conclusions  Ultrasound imaging improves the rate of successful puncture at the first puncture site and decreases the number of puncture attempts. It facilitates CSE puncture in obese parturients.

     

Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction

Context  The clinical benefit of glucose-insulin-potassium (GIK) infusion in patients with ST-segment elevation myocardial infarction (STEMI) is unclear. While some smaller trials suggest benefit, in the CREATE-ECLA trial, GIK infusion had no effect on 30-day mortality in 20 201 patients. Objectives  To determine the association between GIK infusion therapy and 30-day and 6-month outcomes in patients with STEMI. Design, Setting, and Participants  Primary analysis of the OASIS-6 GIK randomized controlled trial of 2748 patients with acute STEMI; prespecified analyses of the combined trial data from the OASIS-6 GIK and CREATE-ECLA GIK trial populations of 22 943 patients with acute STEMI; subgroup analysis on the timing of initiation of GIK infusion therapy and outcomes; and post hoc analyses exploring whether GIK infusion may cause early harm by increasing glucose and potassium levels and net fluid gain. Intervention  High-dose GIK solution consisting of 25% glucose, 50 U/L of regular insulin, and 80 mEq/L of potassium infused at 1.5 mL/kg per hour for 24 hours. Main Outcome Measures  Mortality rates at 30 days and 6 months in the OASIS-6 GIK trial and rates of death, heart failure, and the composite of death or heart failure at 3 and 30 days in the combined OASIS-6 GIK and CREATE-ECLA GIK trial populations. Results  At 6 months, 148 (10.8%) GIK infusion patients and 143 (10.4%) control patients died in the OASIS-6 trial (hazard ratio [HR], 1.04; 95% CI, 0.83-1.31; P = .72); 153 (11.1%) GIK patients and 185 (13.5%) control patients had heart failure (HR, 0.83; 95% CI, 0.67-1.02; P = .08); and 240 (17.5%) GIK patients and 264 (19.2%) control patients had a composite of death or heart failure (HR, 0.91; 95% CI, 0.76-1.08; P = .27). In the prespecified analyses of the combined trial data, there were 712 deaths (6.2%) in the GIK group and 632 deaths (5.5%) in the control group at 3 days (HR, 1.13; 95% CI, 1.02-1.26; P = .03). This difference disappeared by 30 days, with 1108 deaths (9.7%) in the GIK group and 1068 (9.3%) in the control group (HR, 1.04; 95% CI, 0.96-1.13; P = .33). GIK therapy increased levels of glucose, potassium, and net fluid gain postinfusion, all 3 of which predicted death after adjusting for multiple confounders. Adjusting for glucose, potassium, and net fluid gain eliminated the apparent increase in mortality at 3 days observed with GIK infusion, suggesting a direct association with these factors. Administration of GIK infusion within 4 hours of symptom onset yielded no benefit compared with later initiation. Conclusions  Infusion of GIK provided no benefit and may cause early harm following STEMI. Avoidance of infusion-related hyperglycemia, hyperkalemia, and net fluid gain may be advisable in future studies of metabolic modulation in patients with STEMI. Trial Registration  clinicaltrials.gov Identifier: NCT00064428      

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects naïve to antiretroviral therapy

Background  The frequencies of regulatory T cells (Tregs) increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs.

Methods  Tregs were defined as CD4⁺CD25⁺CD127^lo/- T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer.

Results  Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4⁺CD25⁺CD127^lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads (r=0.3163, P=0.004) and negatively with CD4 T-cell counts (r=−0.4153, P <0.0001). In addition, significant associations between HLA-DR expression on CD4⁺CD25⁺CD127^lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4⁺ and CD8⁺ T cells were also identified.

Conclusion  HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

     

Early changes of CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation

Background  Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4⁺CD25⁺Foxp3⁺ Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation.

Methods  A rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Th1, Th2, Tc1 and Tc2 cells in the samples.

Results  In the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P=0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08±8.98)% to (23.91±15.36)%, and from (40.40±21.56)% to (65.48±23.88)%, respectively.

Conclusions  At an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Th1 and Tc1 dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.     

Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial

Context  No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. Objective  To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. Design, Setting, and Patients  International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset. Interventions  Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183). Main Outcome Measures  The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days. Results  The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was –6.8% (95% confidence interval [CI], –10.2% to –3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37). Conclusion  An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.      

Effects of reviparin, a low-molecular-weight heparin, on mortality, reinfarction, and strokes in patients with acute myocardial infarction presenting with ST-segment elevation

Context  Although reperfusion therapy, aspirin, -blockers, and angiotensin-converting enzyme inhibitors reduce mortality when used early in patients with acute myocardial infarction (MI), mortality and morbidity remain high. No antithrombotic or newer antiplatelet drug has been shown to reduce mortality in acute MI. Objective  To evaluate the effects of reviparin, a low-molecular-weight heparin, when initiated early and given for 7 days in addition to usual therapy on the primary composite outcome of death, myocardial reinfarction, or strokes at 7 and 30 days. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation [CREATE]) of 15 570 patients with ST-segment elevation or new left bundle-branch block, presenting within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004. Intervention  Reviparin or placebo subcutaneously twice daily for 7 days. Main Outcome Measure  Primary composite outcome of death, myocardial reinfarction, or stroke at 7 and 30 days. Results  The primary composite outcome was significantly reduced from 854 (11.0%) of 7790 patients in the placebo group to 745 (9.6%) of 7780 in the reviparin group (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .005). These benefits persisted at 30 days (1056 [13.6%] vs 921 [11.8%] patients; HR, 0.87; 95% CI, 0.79-0.95; P = .001) with significant reductions in 30-day mortality (877 [11.3%] vs 766 [9.8%]; HR, 0.87; 95% CI, 0.79-0.96; P = .005) and reinfarction (199 [2.6%] vs 154 [2.0%]; HR, 0.77; 95% CI, 0.62-0.95; P = .01), and no significant differences in strokes (64 [0.8%] vs 80 [1.0%]; P = .19). Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days (<2 hours: HR, 0.70; 95% CI, 0.52-0.96; P = .03; 30/1000 events prevented; 2 to <4 hours: HR, 0.81; 95% CI, 0.67-0.98; P = .03; 21/1000 events prevented; 4 to <8 hours: HR, 0.85; 95% CI, 0.73-0.99; P = .05; 16/1000 events prevented; and 8 hours: HR, 1.06; 95% CI, 0.86-1.30; P = .58; P = .04 for trend). There was an increase in life-threatening bleeding at 7 days with reviparin and placebo (17 [0.2%] vs 7 [0.1%], respectively; P = .07), but the absolute excess was small (1 more per 1000) vs reductions in the primary outcome (18 fewer per 1000) or mortality (15 fewer per 1000). Conclusions  In patients with acute ST-segment elevation or new left bundle-branch block MI, reviparin reduces mortality and reinfarction, without a substantive increase in overall stroke rates. There is a small absolute excess of life-threatening bleeding but the benefits outweigh the risks.      

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.

     

Outcome of in vitro fertilization in endometriosis-associated infertility: a 5-year database cohort study

Background  Endometriosis affects natural fertility through various approaches, and in vitro fertilization (IVF) is a good treatment. But the IVF result of endometriosis patients is still under debate. We investigated the effect of endometriosis on IVF by analyzing the data from a single reproductive center.

Methods  A retrospective, database-searched cohort study was performed. Relevant information was collected from the electronic records of women who underwent IVF/intracytoplasmic sperm injection between January 2006 and December 2010 in the Assisted Reproductive Unit of Sir Run Run Shaw Hospital. Patients with endometriosis were enrolled the study group. The rest of the women formed the control group. The main outcome was the clinical pregnancy rate. Secondary outcomes were oocytes retrieved number, fertilization rate, high-quality embryo rate, number of high-quality embryo for embryo transplantation, and implantation embryo/high-quality embryo ratio (IE/HQE ratio). Comparisons were performed by the  c²-test and independent t-test.

Results  The endometriosis group (n=177) had a markedly lower oocytes retrieved number, fertilization rate, implantation rate, and clinical pregnancy rate (7.6±5.1, 63.6%, 27.7%, and 45.2%, respectively) compared with the non-endometriosis group (n=4267; 11.8±7.3, 68.4%, 36.2%, and 55.2%, respectively).  Stratified analysis showed that this difference was found in the subgroup younger than 35-years old, while only fertilization rate and implantation rate were different in the elder subgroup. The ratio of high-quality embryos transferred is lower in endometriosis group (53.7% vs. 71.8%, P <0.05), but there is no difference in IE/HQE ratio between two groups. There is no significant difference in fertilization rate, implantation rate, and clinical pregnancy rate between mild and severe endometriosis patients.

Conclusions  Endometriosis patients suffer a decreasing IVF pregnancy rates mainly caused by reducing oocytes number and fertilization rate, regardless of the severity of the disease. Appropriate intracytoplasmic sperm injection manipulation might improve the outcomes of IVF.

     

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.

     

Transesophageal echocardiography guided cannulation for peripheral cardiopulmonary bypass during robotic cardiac surgery

Background  Minimally invasive cardiac surgery and closed chest cardiopulmonary bypass (CPB) techniques continue to evolve. Previous reports have demonstrated the benefits of fluoroscopy guided cannulation for endovascular CPB during port access cardiac surgery. However, few data are available on the role of transesophageal echocardiography (TEE) guided cannulation for peripheral CPB during robotic cardiac surgery. The purpose of this study was to evaluate TEE guided cannulation for peripheral CPB during robotic cardiac surgery.

Methods  We performed a retrospective analysis of intraoperative data of 129 consecutive patients underwent robotic cardiac surgical procedures requiring peripheral CPB from September 2007 to August 2011, which was established using femoral arterial inflow and kinetic venous drainage by way of the femoral vein and right internal jugular vein and a transthoracic aortic cross clamp. TEE was used to guide cannulation of the inferior vena cava (IVC), superior vena cava (SVC), and ascending aorta (AAO). The success rate and the complication rate of TEE guided cannulation for peripheral CPB were evaluated and compared with the results of fluoroscopy guided cannulation in a historical control group.

Results  One hundred and twenty-nine consecutive patients underwent robotic cardiac surgical procedures requiring peripheral CPB. There were 67 female (51.9%) and 62 male (48.1%) patients, ranging in age from 13 to 70 years (mean (43.94 ± 13.82) years) and body surface area 1.32 to 2.39 m² (mean (1.71 ± 0.20) m²). Some 61 (47.3%) patients underwent mitral valve repair, 27 (20.9%) mitral valve replacement, 27 (20.9%) left atrial myxoma removal, and 14 (10.9%) ventricular septal defect repair. Of the 129 patients, TEE guided cannulation of the IVC or SVC was successful in all patients (100%), and no puncture related complications occurred in all patients. Of the 129 patients, successful cannulation of the AAO was achieved in all patients (100%), and aortic perforation occurred in 1 patient (0.78%) under TEE guidance. Of the 42 patients in the historical control group, successful cannulation occured in 39 patients (92.86%), and major complications occurred in 3 patients (7.14%) under fluoroscopy guidance. TEE guided cannulation of the AAO significantly improved success rate (100% vs. 92.86%, P=0.014) and decreased complication rate (0.78% vs. 7.14%, P=0.046).

Conclusion  TEE may be useful in guiding successful placement of the cannulae in the IVC, SVC, and AAO in the establishment of peripheral CPB during robotic cardiac surgery.

     

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial

Context  Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective  To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients  This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions  Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures  The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results  No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). Conclusion  In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. Trial Registration  clinicaltrials.gov Identifier: NCT00091637      

Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis

Background  The heme oxygenase/carbon monoxide (HO/CO) system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin (COHb) level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis (HBC) complicated by hepatic encephalopathy (HE), and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC.

Methods  According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group (group N) consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen (PaO₂) and oxygen saturation (SaO₂) were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome (HRS), upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis (SBP) in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades (I, II, III, and IV), PaO₂, SaO₂ and hypoxemia were analyzed.

Results  The COHb level in group P-H ((1.672±0.761)%) was significantly higher than that in group N ((0.983±0.231)%) (P <0.01), and the level in group H ((2.102±1.021)%) was significantly higher than groups P-H and N (P <0.01). A positive correlation was observed between the COHb concentration and the grade of HE (r_s=0.357, P=0.004). There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices ((2.302±1.072)% vs. (1.802±1.041)%, P >0.05) or the occurrence of SBP ((2.960±0.561)% vs. (2.030±1.021)%, P >0.05). Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS ((2.502±1.073)% vs. (1.981±1.020)%, P=0.029). The COHb level had a negative correlation with PaO₂ (r=−0.335, P=0.007) while no statistically significant relationship was found with SaO₂ (r=−0.071, P >0.05). However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased ((2.621±0.880)% vs. (1.910±0.931)%, P=0.011).

Conclusions  COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.

     

Distal microcirculatory protection during percutaneous coronary intervention in acute ST-segment elevation myocardial infarction: a randomized controlled trial

Context  Atheromatous and thrombotic embolization during percutaneous coronary intervention (PCI) in acute myocardial infarction is common and may result in microcirculatory dysfunction, the prevention of which may improve reperfusion success, reduce infarct size, and enhance event-free survival. Objective  To determine whether protection of the distal microcirculation from thromboembolic debris liberated during primary PCI results in improved reperfusion and decreased infarct size. Design, Setting, and Patients  Prospective randomized controlled trial at 38 academic and community-based institutions in 7 countries enrolling 501 patients aged 18 years or older with ST-segment elevation myocardial infarction (STEMI) presenting within 6 hours of symptom onset and undergoing primary PCI or rescue intervention after failed thrombolysis. Interventions  Patients were randomized between May 20, 2002, and November 21, 2003, to receive PCI with a balloon occlusion and aspiration distal microcirculatory protection system vs angioplasty without distal protection. Main Outcome Measures  Coprimary end points were ST-segment resolution (STR) measured 30 minutes after PCI by continuous Holter monitoring and infarct size measured by technetium Tc 99m sestamibi imaging between days 5 and 14. Secondary end points included major adverse cardiac events. Results  Among 252 patients assigned to distal protection, aspiration was performed in 97% (242/251), all angioplasty balloon inflations were fully protected in 79% (193/245), and visible debris was retrieved from 73% (182/250). Complete STR was achieved in a similar proportion reperfused with vs without distal protection (63.3% [152/240] vs 61.9% [148/239], respectively; absolute difference, 1.4% [95% confidence interval, –7.7% to 10.5%; P = .78]), and left ventricular infarct size was similar in both groups (median, 12.0% [n = 229] vs 9.5% [n = 208], respectively; P = .15). Major adverse cardiac events at 6 months occurred with similar frequency in the distal protection and control groups (10.0% vs 11.0%, respectively; P = .66). Conclusions  A distal balloon occlusion and aspiration system effectively retrieves embolic debris in most patients with acute STEMI undergoing emergent PCI. Nonetheless, distal embolic protection did not result in improved microvascular flow, greater reperfusion success, reduced infarct size, or enhanced event-free survival.