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Hypofunction of the N-methyl-d-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1-90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63-80 Hz) in occipital regions and upregulated low frequency (5-28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.

Background: In the randomised TATORT-NSTEMI trial routine thrombus aspiration in comparison with standard percutaneous coronary intervention (PCI) did not reduce the primary endpoint of microvascular obstruction assessed by cardiac magnetic resonance imaging in patients with non-ST-elevation myocardial infarction (NSTEMI). So far, no data on long-term outcome of head-to-head comparisons between both treatment strategies in NSTEMI patients have been reported., Methods: The prospective, controlled, multicentre, randomised, open-label TATORT-NSTEMI trial assigned patients with NSTEMI and thrombus-containing lesions to aspiration thrombectomy plus PCI ( n=221) or standard PCI only ( n=219). The primary endpoint of the current analysis was the occurrence of major adverse cardiac events defined as the composite of death, myocardial reinfarction, target vessel revascularisation, and new congestive heart failure at 12-month follow-up. In addition, functional outcome and quality of life were assessed., Results: At one year, major adverse cardiac events occurred in 19 patients in the thrombectomy arm and 29 patients in the standard PCI group (8.7% vs. 13.4%, relative risk 0.63, 95% confidence interval 0.35-1.12, p=0.11). The individual components of the combined endpoint such as death ( p=0.20), myocardial reinfarction ( p=0.73), target vessel revascularisation ( p=0.42), and congestive heart failure ( p=0.18) were similar in both groups. Functional outcome and quality of life did not differ significantly between both groups (Canadian Cardiovascular Society class: p=0.68, New York Heart Association class: p=0.70 and EuroQol5D score: p=0.96). Post-hoc analyses revealed consistent results with regard to the occurrence of major adverse cardiac events across a wide range of subgroups (all p>0.05)., Conclusions: In this first randomised trial on thrombectomy in NSTEMI patients, routine thrombus aspiration before PCI did not improve clinical outcome at 12-month follow-up.

Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006 mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13-30 Hz) and gamma (30-90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30-90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: High serum phosphate is linked to cardiovascular morbidity and mortality in the general population. Fibroblast growth factor 23 (FGF-23) is a critical phosphate regulating hormone, potentially reflecting phosphate load better than a single serum phosphate measurement. Recent pioneering echocardiographic studies associated FGF-23 with left-ventricular morphology. However, the association between FGF-23 and left-ventricular function is unknown, prompting us to investigate this relationship in our HOM SWEET HOMe study., Methods and Results: We studied the association between C-terminal FGF-23, coronary artery disease, and left-ventricular function in 885 subjects undergoing elective coronary angiography. Left-ventricular function was assessed with ventriculography. More, pro-brain natriuretic peptide (pro-BNP) plasma levels were measured. The presence of left-ventricular hypertrophy and atrial fibrillation was assessed by electrocardiography. Patients with an ejection fraction <40% had significantly higher FGF-23 levels compared with patients with the ejection fraction >40% (P< 0.001). In multivariable regression analysis, the observed relationship between FGF-23 and left-ventricular function remained significant after adjustment for estimated glomerular filtration rate, presence of left-ventricular hypertrophy, and other confounding variables. In accordance, FGF-23 significantly correlated with pro-BNP plasma levels (r = 0.31; P< 0.001). Prevalent atrial fibrillation was associated with elevated FGF-23 levels, while the presence of coronary artery disease was not., Conclusions: Fibroblast growth factor 23 levels are associated with left-ventricular function and atrial fibrillation even in the absence of renal function impairment. Of note, these cross-sectional data cannot prove causality; therefore, future studies will have to discern whether FGF-23 exerts a direct untoward effect on the myocardium, or rather represents an 'innocent bystander' which reflects a high phosphate burden.

Aims: Multiple trials in patients with ST-segment elevation myocardial infarction (STEMI) compared early routine percutaneous coronary intervention (PCI) after successful fibrinolysis vs. standard therapy limiting PCI only to patients without evidence of reperfusion (rescue PCI). These trials suggest that all patients receiving fibrinolysis should receive mechanical revascularization within 24 h from initial hospitalization. However, individual trials could not demonstrate a significant reduction in 'hard' endpoints such as death and reinfarction. We performed a meta-analysis of randomized controlled trials to define the benefits of early PCI after fibrinolysis over standard therapy on clinical and safety endpoints in STEMI., Methods and Results: We identified seven eligible trials, enrolling a total of 2961 patients. No difference was found in the incidence of death at 30 days between the two strategies. Early PCI after successful fibrinolysis reduced the rate of reinfarction (OR: 0.55, 95% CI: 0.36-0.82; P = 0.003), the combined endpoint death/reinfarction (OR: 0.65, 95% CI: 0.49-0.88; P = 0.004) and recurrent ischaemia (OR: 0.25, 95% CI: 0.13-0.49; P < 0.001) at 30-day follow-up. These advantages were achieved without a significant increase in major bleeding (OR: 0.93, 96% CI: 0.67-1.34; P = 0.70) or stroke (OR: 0.63, 95% CI: 0.31-1.26; P = 0.21). The benefits of a routine invasive strategy over standard therapy were maintained at 6-12 months, with persistent significant reduction in the endpoints reinfarction (OR: 0.64, 95% CI: 0.40-0.98; P = 0.01) and combined death/reinfarction (OR: 0.71, 95% CI: 0.52-0.97; P = 0.03)., Conclusion: Early routine PCI after fibrinolysis in STEMI patients significantly reduced reinfarction and recurrent ischaemia at 1 month, with no significant increase in adverse bleeding events compared to standard therapy. Benefits of early PCI persist at 6-12 month follow-up.

Background: Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting., Methods and Results: In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area., Conclusions: First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.

Aims: Current data concerning the influence of X-ray contrast media on the incidence of thrombotic complications in interventional cardiology are controversial. The effect of ionic contrast media on acute (< or =72 h) and subacute (< or =30 days) stent thrombosis has not been investigated., Methods: Three thousand, nine hundred and ninety consecutive patients underwent coronary stent placement. Group I (n=1808) received non-ionic contrast media while group II (n=2182) was given the ionic Ioxaglate. All patients were treated with a standard regimen of aspirin and ticlopidine for 4 weeks post intervention., Results: Both acute and subacute stent occlusion occurred more frequently in patients receiving non-ionic contrast media compared to ionic contrast media (acute stent occlusion: 1.3% in group I vs 0.3% in group II, P=0.001; subacute stent occlusion: 2.4% in group I vs 0.7% in group II, P=0.001). The incidence of the combined clinical end-point of coronary artery bypass grafting, target lesion revascularization, and overall mortality within 12 months was significantly reduced by the use of Ioxaglate (22.9% vs 16.3%, P=0.001)., Conclusions: Based upon these data, we recommend the use of Ioxaglate in coronary interventions when stent placement is anticipated., (Copyright 2001 The European Society of Cardiology.)