Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme

Study of the properties of afterdischarges occurring during cortical stimulation in epilepsy patients and correlation to seizure-onset zones

104 σ.Η διέγερση με ηλεκτρικό ρεύμα περιοχών του φλοιού του εγκεφάλου επιληπτικών ασθενών μπορεί να προκαλέσει μετεκφορτίσεις. Σε πολλούς ασθενείς με επιληψία, η αντιμετώπιση της νόσου γίνεται χειρουργικά. Ο προεγχειρητικός έλεγχος των ασθενών αυτών περιλαμβάνει ενδοκράνιες εγκεφαλικές καταγραφές, οι οποίες γίνονται με πλέγματα ηλεκτροδίων, που τοποθετούνται σε επαφή με τον εγκεφαλικό φλοιό. Από τα ίδια ηλεκτρόδια γίνεται διέγερση του εγκεφαλικού φλοιού με σκοπό τη λειτουργική χαρτογράφησή του. Στόχος της εργασίας είναι η ανάπτυξη μεθοδολογιών για τη μελέτη των μετεκφορτίσεων από τις καταγραφές αυτές και η τοπογραφική συσχέτισή των μετεκφορτίσεων με τη ζώνη έναρξης των επιληπτικών κρίσεων πάνω στο φλοιό. Χρησιμοποιήθηκε ενδοκράνια ηλεκτροεγκεφαλική καταγραφή 3 ασθενών. Οι μεθοδολογίες που χρησιμοποιήθηκαν περιλαμβάνουν χρήση του αλγορίθμου του Κ-Κοντινότερου Γείτονα για τον υπολογισμό της μορφοκλασματικής διάστασης του σήματος, χρήση Διακριτού Μετασχηματισμού Κυματιδίου για τον υπολογισμό των ενεργειών του σήματος ανά ζώνη συχνοτήτων και χρήση μη υπολογιστικών μεγεθών που προέκυψαν από την οπτική επισκόπηση του σήματος. Επιχειρήθηκε συσχέτιση των θέσεων εμφάνισης των μετεκφορτίσεων με τις θέσεις των διεγέρσεων που προκαλούν τις μετεκφορτίσεις με τη ζώνη έναρξης των επιληπτικών κρίσεων. Με τη μέθοδο του Διακριτού Μετασχηματισμού Κυματιδίου διαπιστώθηκε η υψηλή ενέργεια των μετεκφορτίσεων στις ζώνες συχνοτήτων 6.25-12.5Hz και 12.5-25Hz, ενώ με τη μέθοδο του Κ-Κοντινότερου Γείτονα διαπιστώθηκε η μικρή μορφοκλασματική διάσταση των μετεκφορτίσεων. Σε 2 από τους ασθενείς, εντοπίστηκε μία περιοχή ενός μοναδικού ηλεκτροδίου που κατά τη διέγερση του προκαλεί μετεκφορτίσεις με μικρή μορφοκλασματική διάσταση και μεγάλη ενέργεια στις συχνότητες 6.25-25Hz. Κάποια ηλεκτρόδια της ζώνης έναρξης των επιληπτικών κρίσεων σε κάθε ασθενή παρουσίασαν υψηλές τιμές μέσης σχετικής ενέργειας στις ζώνες συχνοτήτων 6.25-12.5Hz και 12.5-25Hz, αλλά δεν κατέστη δυνατό να αποδειχθεί η ύπαρξη θετική συσχέτισης.Electrical stimulation of cortical areas of epilepsy patients can elicit afterdischarges. For many epilepsy patients, surgery is necessary. Presurgical evaluation process includes intracranial electroencephalography using electrode grids placed on the cortex. Through the same electrodes, cortical stimulation can be applied for the purpose of functional cortical mapping. The aim of the current thesis was the development of a methodology for the study of afterdischarges and the correlation of afterdischarge locations to seizure-onset zones. The intracranial electroencephalogram of three patients was studied. The methods used included the k-Nearest-Neighbor algorithm for the evaluation of the fractal dimension of the signal as a measure of its self-similarity, the Discrete Wavelet Transform for the computation of energy component per frequency band and the use of simple values determined through visual inspection. The correlation of both the locations where the afterdischarges occur and the sites of afterdischarge-eliciting stimulation to the seizure onset zones was attempted. With the use of the Discrete Wavelet Transform, it was confirmed that the 6.25-12.5Hz and 12.5-25Hz frequency bands of afterdischarges have high relative energy values, while the use of the k-Nearest-Neighbor algorithm confirmed the low fractal dimension of the afterdischarge signal. In two of the patients, a single electrode area was discovered to elicit afterdischarges of both high energy in the 6.25-25Hz range and low fractal dimension when stimulated. Some electrodes in the seizure-onset zone of each patient were found to have a high mean partial energy component in the 6.25-12.5Hz and 12.5-25Hz frequency bands, but a strong positive correlation could not be established.Θωμάς Β. Καραθάνο

Light-based Approaches to Cardiac Arrhythmia Research: From Basic Science to Translational Applications

Light has long been used to image the heart, but now it can be used to modulate its electrophysiological function. Imaging modalities and techniques have long constituted an indispensable part of arrhythmia research and treatment. Recently, advances in the fields of optogenetics and photodynamic therapy have provided scientists with more effective approaches for probing, studying and potentially devising new treatments for cardiac arrhythmias. This article is a review of research toward the application of these techniques. It contains (a) an overview of advancements in technology and research that have contributed to light-based cardiac applications and (b) a summary of current and potential future applications of light-based control of cardiac cells, including modulation of heart rhythm, manipulation of cardiac action potential morphology, quantitative analysis of arrhythmias, defibrillation and cardiac ablation

Plakophilin-2 is required for transcription of genes that control calcium cycling and cardiac rhythm

Plakophilin-2 (PKP2) is a component of the desmosome and known for its role in cell-cell adhesion. Mutations in human PKP2 associate with a life-threatening arrhythmogenic cardiomyopathy, often of right ventricular predominance. Here, we use a range of state-of-the-art methods and a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout mouse to demonstrate that in addition to its role in cell adhesion, PKP2 is necessary to maintain transcription of genes that control intracellular calcium cycling. Lack of PKP2 reduces expression of Ryr2 (coding for Ryanodine Receptor 2), Ank2 (coding for Ankyrin-B), Cacna1c (coding for CaV1.2) and Trdn (coding for triadin), and protein levels of calsequestrin-2 (Casq2). These factors combined lead to disruption of intracellular calcium homeostasis and isoproterenol-induced arrhythmias that are prevented by flecainide treatment. We propose a previously unrecognized arrhythmogenic mechanism related to PKP2 expression and suggest that mutations in PKP2 in humans may cause life-threatening arrhythmias even in the absence of structural disease

Second asymptomatic carotid surgery trial (ACST-2): a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding: UK Medical Research Council and Health Technology Assessment Programme