First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial

Background: Pulsed field ablation (PFA) is a novel form of ablation using electrical fields to ablate cardiac tissue. There are only limited data assessing the feasibility and safety of this type of ablation in humans. Methods: PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; https://www.clinicaltrials.gov ; unique identifier: NCT04198701) is a nonrandomized, prospective, multicenter, global, premarket clinical study. The first-in-human pilot phase evaluated the feasibility and efficacy of pulmonary vein isolation using a novel PFA system delivering bipolar, biphasic electrical fields through a circular multielectrode array catheter (PulseSelect; Medtronic, Inc). Thirty-eight patients with paroxysmal or persistent atrial fibrillation were treated in 6 centers in Australia, Canada, the United States, and the Netherlands. The primary outcomes were ability to achieve acute pulmonary vein isolation intraprocedurally and safety at 30 days. Results: Acute electrical isolation was achieved in 100% of pulmonary veins (n=152) in the 38 patients. Skin-to-skin procedure time was 160±91 minutes, left atrial dwell time was 82±35 minutes, and fluoroscopy time was 28±9 minutes. No serious adverse events related to the PFA system occurred in the 30-day follow-up including phrenic nerve injury, esophageal injury, stroke, or death. Conclusions: In this first-in-human clinical study, 100% pulmonary vein isolation was achieved using only PFA with no PFA system–related serious adverse events.

Influence of electrical stimulation on peripheral nerve regeneration: Protocol for a systematic review

This is a protocol for a systematic review (intervention). Electrical stimulation (ES) is a therapeutic strategy used to improve peripheral nerve regeneration that involves the application of electrical fields of constant or varying frequency. We are going to lead a literature search to identify all published and unpublished randomized controlled trials that describe the use of ES in patients with peripheral nerve injury. We will compare: Electrical stimulation (application of electrical fields of constant or varying frequency) versus sham in patients with peripheral nerve injury; Electrical stimulation versus standard treatment (physiotherapy) in patients with peripheral nerve injury; Electrical stimulation versus no treatment in patients with peripheral nerve injury. Considering the scenario of very numerous strategies and different techniques of ES to stimulate nerve regeneration, decisions to recommend them should consider these uncertainties and should be summarized intended its application in clinical practice. The objective of this review is to assess the influence of electrical stimulation (ES) on nerve regeneration in individuals with peripheral nerve injury.

Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity

Tumor Treating Fields (TTFields) are low intensity, alternating intermediate frequency (200kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells, or interact with TMZ is unclear. Primary cilia are microtubule-based organelles triggered by extracellular ligands, mechanical and electrical field stimulation, and are capable of promoting cancer growth and TMZ chemoresistance. We found in both low and high grade patient glioma cell lines that TTFields ablated cilia within 24 hours. Halting TTFields treatment led to recovered frequencies of elongated cilia. Cilia on normal primary astrocytes, neurons, and multiciliated/ependymal cells were less affected by TTFields. The TTFields-mediated loss of glioma cilia was partially rescued by chloroquine pretreatment, suggesting the effect is in part due to autophagy activation. We also observed death of ciliated cells during TTFields by live imaging. Notably, TMZ-induced stimulation of ciliogenesis in both adherent cells and gliomaspheres was blocked by TTFields. Moreover, the inhibitory effects of TTFields and TMZ on tumor cell recurrence correlated with the relative timing of TMZ exposure to TTFields and ARL13B+ cilia. Finally, TTFields disrupted cilia in patient tumors treated ex vivo. Our findings suggest TTFields efficacy may depend on the degree of tumor ciliogenesis and relative timing of TMZ treatment.

Dark exciton anti-funneling in atomically thin semiconductors

Transport of charge carriers is at the heart of current nanoelectronics. In conventional materials, electronic transport can be controlled by applying electric fields. Atomically thin semiconductors, however, are governed by excitons, which are neutral electron-hole pairs and as such cannot be controlled by electrical fields. Recently, strain engineering has been introduced to manipulate exciton propagation. Strain-induced energy gradients give rise to exciton funneling up to a micrometer range. Here, we combine spatiotemporal photoluminescence measurements with microscopic theory to track the way of excitons in time, space and energy. We find that excitons surprisingly move away from high-strain regions. This anti-funneling behavior can be ascribed to dark excitons which possess an opposite strain-induced energy variation compared to bright excitons. Our findings open new possibilities to control transport in exciton-dominated materials. Overall, our work represents a major advance in understanding exciton transport that is crucial for technological applications of atomically thin materials.

Application of electrical fields to reduce chloride ingress into concrete structures

In the context of a joint research project, a system for monitoring, protection and strengthening of bridges by using a textile reinforced concrete interlayer has been developed which consists of two carbon layers with a spacing of 15 mm and a special mortar. This setup led to the idea to build up an electrical field between the carbon meshes, which suppresses the ingress of chlorides into the concrete. This paper focuses on the question which voltages and electrical field strengths are necessary to prevent critical chloride contents at the reinforcing steel. For this purpose, extensive laboratory tests have been performed, followed by a numerical simulation study. By applying an electrical field, the negatively charged chloride ions are forced to move to the upper carbon mesh that is polarized as an anode. It has been investigated whether the voltages to implement an electrochemical chloride barrier are smaller than they have to be for the common preventive cathodic protection. One advantage of this chloride barrier is that because of the lower current densities the anodic polarisation of the carbon meshes can be reduced. Therefore, different voltages, electrical field strengths, anode materials and anode arrangements were investigated.