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Percutaneous cardiovascular interventions have changed dramatically in recent years, and the impetus given by the rapid implementation of novel techniques and devices have been mirrored by a refinement of antithrombotic strategies for secondary prevention, which have been supported by a significant burden of evidence from clinical studies. In the current manuscript, we aim to provide a comprehensive, yet pragmatic, revision of the current available evidence regarding antithrombotic strategies in the domain of percutaneous cardiovascular interventions. We revise the evidence regarding antithrombotic therapy for secondary prevention in coronary artery disease and stent implantation, the complex interrelation between antiplatelet and anticoagulant therapy in patients undergoing percutaneous coronary intervention with concomitant atrial fibrillation, and finally focus on the novel developments in the secondary prevention after structural heart disease intervention. A special focus on treatment individualization is included to emphasize risk and benefits of each therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: The present study investigated the effectiveness of stimulation applied at cervical levels on pain and Parkinson's disease (PD) symptoms using either tonic or burst stimulation mode. Methods: Tonic high cervical spinal cord stimulation (T-HCSCS) was applied on six PD patients suffering from low back pain and failed back surgery syndrome, while burst HCSCS (B-HCSCS) was applied in twelve PD patients to treat primarily motor deficits. Stimulation was applied percutaneously with quadripolar or octapolar electrodes. Clinical evaluation was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr (H&Y) scale. Pain was evaluated by a visual analog scale. Evaluations of gait and of performance in a cognitive motor task were performed in some patients subjected to B-HCSCS. One patient who also suffered from severe autonomic cardiovascular dysfunction was investigated to evaluate the effectiveness of B-HCSCS on autonomic functions. Results: B-HCSCS was more effective and had more consistent effects than T-HCSCS in reducing pain. In addition, B-HCSCS improved UPDRS scores, including motor sub-items and tremor and H&Y score. Motor benefits appeared quickly after the beginning of B-HCSCS, in contrast to long latency improvements induced by T-HCSCS. A slight decrease of effectiveness was observed 12 months after implantation. B-HCSCS also improved gait and ability of patients to correctly perform a cognitive–motor task requiring inhibition of a prepared movement. Finally, B-HCSCS ameliorated autonomic control in the investigated patient. Conclusions: The results support a better usefulness of B-HCSCS compared to T-HCSCS in controlling pain and specific aspects of PD motor and non-motor deficits for at least one year. [ABSTRACT FROM AUTHOR]

The recent introduction of frameless devices has enabled stereotactic neurosurgery to reach a level of accuracy that is comparable to traditional frame-based methodologies. Among frameless devices, the Nexframe appears to be very useful in implanting electrodes into the subthalamic nucleus or other structures for deep brain stimulation in Parkinson’s disease. However, frameless devices, including the Nexframe, limit the possibility of intraoperative visual control of the placement of electrodes in the brain. Utilizing intraoperative O-arm Computed tomography (CT) scan or high-field Magnetic Resonance Imaging (MRI) could overcome this limitation, but their high cost restricts their use. Thus, in this paper we propose an innovation in Nexframe surgical planning that allows the intraoperative use of a C-arm X-ray apparatus to establish: (1) the progression of the electrode guide tube and the electrode in the brain; (2) the accuracy of the electrode trajectory; and (3) the correct attainment of the target. The proposed frameless technique using the Nexframe has been developed and successfully applied in our practice. It was shown to be helpful in overcoming the major issues that are usually encountered when electrodes are placed in the brain with frameless neurosurgery and reduced the risk of having to re-operate on patients to reposition the electrodes. [ABSTRACT FROM AUTHOR]

Background: Recent studies on the medical treatment of Parkinson's disease (PD) led to the introduction of the so called Deep Brain Stimulation (DBS) technique. This particular therapy allows to contrast actively the pathological activity of various Deep Brain structures, responsible for the well known PD symptoms. This technique, frequently joined to dopaminergic drugs administration, replaces the surgical interventions implemented to contrast the activity of specific brain nuclei, called Basal Ganglia (BG). This clinical protocol gave the possibility to analyse and inspect signals measured from the electrodes implanted into the deep brain regions. The analysis of these signals led to the possibility to study the PD as a specific case of dynamical synchronization in biological neural networks, with the advantage to apply the theoretical analysis developed in such scientific field to find efficient treatments to face with this important disease. Experimental results in fact show that the PD neurological diseases are characterized by a pathological signal synchronization in BG. Parkinsonian tremor, for example, is ascribed to be caused by neuron populations of the Thalamic and Striatal structures that undergo an abnormal synchronization. On the contrary, in normal conditions, the activity of the same neuron populations do not appear to be correlated and synchronized. Results: To study in details the effect of the stimulation signal on a pathological neural medium, efficient models of these neural structures were built, which are able to show, without any external input, the intrinsic properties of a pathological neural tissue, mimicking the BG synchronized dynamics. We start considering a model already introduced in the literature to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. This model used Morris Lecar type neurons. This neuron model, although having a high level of biological plausibility, requires a large computational effort to simulate large scale networks. For this reason we considered a reduced order model, the Izhikevich one, which is computationally much lighter. The comparison between neural lattices built using both neuron models provided comparable results, both without traditional stimulation and in presence of all the stimulation protocols. This was a first result toward the study and simulation of the large scale neural networks involved in pathological dynamics. Using the reduced order model an inspection on the activity of two neural lattices was also carried out at the aim to analyze how the stimulation in one area could affect the dynamics in another area, like the usual medical treatment protocols require. The study of population dynamics that was carried out allowed us to investigate, through simulations, the positive effects of the stimulation signals in terms of desynchronization of the neural dynamics. Conclusions: The results obtained constitute a significant added value to the analysis of synchronization and desynchronization effects due to neural stimulation. This work gives the opportunity to more efficiently study the effect of stimulation in large scale yet computationally efficient neural networks. Results were compared both with the other mathematical models, using Morris Lecar and Izhikevich neurons, and with simulated Local Field Potentials (LFP). [ABSTRACT FROM AUTHOR]

Background: Contemporary definitions of bleeding endpoints are restricted mostly to clinically overt events. Whether hemoglobin drop per se, with or without overt bleeding, adversely affects the prognosis of patients with acute coronary syndrome (ACS) remains unclear.Objectives: The aim of this study was to examine in the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial the incidence, predictors, and prognostic implications of in-hospital hemoglobin drop in patients with ACS managed invasively stratified by the presence of in-hospital bleeding.Methods: Patients were categorized by the presence and amount of in-hospital hemoglobin drop on the basis of baseline and nadir hemoglobin values and further stratified by the occurrence of adjudicated in-hospital bleeding. Hemoglobin drop was defined as minimal (<3 g/dl), minor (≥3 and <5 g/dl), or major (≥5 g/dl). Using multivariate Cox regression, we modeled the association between hemoglobin drop and mortality in patients with and without overt bleeding.Results: Among 7,781 patients alive 24 h after randomization with available hemoglobin data, 6,504 patients (83.6%) had hemoglobin drop, of whom 5,756 (88.5%) did not have overt bleeding and 748 (11.5%) had overt bleeding. Among patients without overt bleeding, minor (hazard ratio [HR]: 2.37; 95% confidence interval [CI]: 1.32 to 4.24; p = 0.004) and major (HR: 2.58; 95% CI: 0.98 to 6.78; p = 0.054) hemoglobin drop were independently associated with higher 1-year mortality. Among patients with overt bleeding, the association of minor and major hemoglobin drop with 1-year mortality was directionally similar but had wider CIs (minor: HR: 3.53 [95% CI: 1.06 to 11.79]; major: HR: 13.32 [95% CI: 3.01 to 58.98]).Conclusions: Among patients with ACS managed invasively, in-hospital hemoglobin drop ≥3 g/dl, even in the absence of overt bleeding, is common and is independently associated with increased risk for 1-year mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox; NCT01433627). [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is an inherited X-linked neuromuscular disorder. A number of questionnaires are available to assess quality of life in DMD, but there are concerns about their validity. This systematic review aimed to appraise critically the content and structural validity of quality of life instruments for DMD. Five databases (EMBASE, MEDLINE, CINAHL, PsycINFO, and Cochrane Library) were searched, with supplementary searches in Google Scholar. We included articles with evidence on the content and/or structural validity of quality of life instruments in DMD, and/or instrument development. Evidence was evaluated against the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Fifty five articles featured a questionnaire assessing quality of life in DMD. Forty instruments were extracted and 26 underwent assessment. Forty-one articles contained evidence on content or structural validity (including 37 development papers). Most instruments demonstrated low quality evidence and unsatisfactory or inconsistent validity in DMD, with the majority not featuring direct validation studies in this population. Only KIDSCREEN received an adequate rating for instrument design and a satisfactory result for content validity based on its development, yet, like the majority of PROMs, the measure has not been directly validated for use in DMD. Further research is needed on the validity of quality of life instruments in DMD, including content and structural validity studies in this population. [ABSTRACT FROM AUTHOR]

Cardiogenic shock is a dreadful complication of myocardial infarction. Despite widespread use and availability, intra‐aortic balloon pump (IABP) does not reduce mortality nor improves outcomes. Advanced mechanical circulatory support with IMPELLA system can substantially support hemodynamics and improve short‐term prognosis in patients with myocardial infarction and cardiogenic shock. [ABSTRACT FROM AUTHOR]

How does a single brain region participate in multiple behaviors? Here we argue that two separate interneuron circuits in the primary motor cortex (M1) contribute differently to two varieties of physiological and behavioral plasticity. To test this in human brain noninvasively, we used transcranial magnetic stimulation (TMS) of M1 hand area to activate two independent sets of synaptic inputs to corticospinal neurons by changing the direction of current induced in the brain: posterior-to-anterior current (PA inputs) and anteriorto-posterior current (AP inputs). We demonstrate that excitability changes produced by repetitive activation of AP inputs depend on cerebellar activity and selectively alter model-based motor learning. In contrast, the changes observed with repetitive stimulation of PA inputs are independent of cerebellar activity and specifically modulate model-free motor learning. Thefindings are highly suggestivethat separate circuits in M1 subserve different forms of motor learning. [ABSTRACT FROM AUTHOR]

Key points Repetitively pairing peripheral nerve stimulation with transcranial magnetic stimulation of the corresponding contralateral motor cortex at 10 ms (paired associative stimulation; PAS10) leads to centre-depressant effects on corticospinal excitability in a short time window., PAS10-induced centre-depressant effects are due to weakening of excitatory synapses between principal cortical neurons, but not those located on corticospinal neurons, or inhibitory synapses., Inhibitory interneurons are gate-keepers to producing centre-depressant PAS effects. The same mechanisms appear to govern PAS10-induced surround-facilitatory effects., We propose a model specifying the composition and laminar location of the involved microcircuit of PAS-induced plasticity that may enhance its utility as a model of spike-timing- dependent plasticity in humans., Abstract Synaptic weight changes induced by temporal correlations between the spikes of pre- and postsynaptic neurons are referred to as spike-timing-dependent plasticity (STDP). Transcranial magnetic stimulation (TMS) induces long-lasting effects on corticospinal excitability, if it is repetitively paired with stimulation of afferents from a corresponding contralateral hand region at short intervals (paired associative stimulation, PAS). PAS-induced plasticity has been linked with synaptic STDP. We aimed to investigate which elements of the cortical microcircuitry sustain and govern PAS-induced depression of corticospinal excitability in the target muscle representation (and enhancement of excitability in its functional surround). We show that the time window during which the interaction between both stimulus-induced cortical events leads to immediate post-interventional depression is short (<4.5 ms). The depressant PAS effects at the target representation were completely blocked by applying a subthreshold magnetic pulse 3 ms before the principal TMS pulse, even when the strength of the latter was adjusted to generate a motor-evoked potential of similar amplitude to that with the unconditioned magnetic pulse. Epidural recordings from the cervical cord of a patient showed that under this condition late TMS-evoked I-waves remain suppressed. When the intensity of the TMS component during PAS was lowered - sufficient to allow activation of inhibitory neurons, but insufficient to activate corticospinal neurons - excitability of short-latency intracortical inhibition remained unchanged. PAS-induced facilitation in the functional surround followed the same pattern as the centre-depressant effects. These findings may suggest that excitability-depressant PAS-induced effects are due to weakening of excitatory synapses between upper cortical layer principal neurons, but not those located on the corticospinal neuron, or inhibitory synapses. Inhibitory interneurons involved in short-latency intracortical inhibition are gate-keepers to producing centre-depressant/surround-facilitatory PAS effects. Based on these and earlier findings we propose a model specifying the composition and laminar location of the involved microcircuit of PAS-induced plasticity that may enhance its utility as a model of STDP in humans. [ABSTRACT FROM AUTHOR]

The article presents a reprint of the article "Transcranial direct current stimulation effects on I-wave activity in humans" by M.A. Nitsche and colleagues that was published in the March 23, 2011 issue of the periodical. The authors investigated the physiological mechanisms and effects of anodal transcranial direct current stimulation (tDCS) of the human cerebral cortex. They concluded that anodal tDCS develops its facilitatory effects on motor evoked potential amplitudes.

Gait disturbances and akinesia are extremely disabling in advanced Parkinson's disease. It has been suggested that modulation of the activity of the pedunculopontine nucleus (PPN) may be beneficial in the treatment of these symptoms. We report the clinical affects of deep brain stimulation (DBS) in the PPN and subthalamic nucleus (STN). Six patients with unsatisfactory pharmacological control of axial signs such as gait and postural stability underwent bilateral implantation of DBS electrodes in the STN and PPN. Clinical effects were evaluated 2-6 months after surgery in the OFF- and ON-medication state, with both STN and PPN stimulation ON or OFF, or with only one target being stimulated. Bilateral PPN-DBS at 25 Hz in OFF-medication produced an immediate 45% amelioration of the motor Unified Parkinson's Disease Rating Scale (UPDRS) subscale score, followed by a decline to give a final improvement of 32% in the score after 3-6 months. In contrast, bilateral STN-DBS at 130-185 Hz led to about 54% improvement. PPN-DBS was particularly effective on gait and postural items. In ON-medication state, the association of STN and PPN-DBS provided a significant further improvement when compared to the specific benefit mediated by the activation of either single target. Moreover, the combined DBS of both targets promoted a substantial amelioration in the performance of daily living activities. These findings indicate that, in patients with advanced Parkinson's disease, PPN-DBS associated with standard STN-DBS may be useful in improving gait and in optimizing the dopamine-mediated ON-state, particularly in those whose response to STN only DBS has deteriorated over time. This combination of targets may also prove useful in extra-pyramidal disorders, such as progressive supranuclear palsy, for which treatments are currently elusive. [ABSTRACT FROM AUTHOR]