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We present the discovery of highly-collimated radio jets spanning a total of 355 kpc around the nearby elliptical galaxy NGC 2663, and the possible first detection of recollimation on kiloparsec scales. The small distance to the galaxy (~28.5 Mpc) allows us to resolve portions of the jets to examine their structure. We combine multiwavelength data: radio observations by the Murchison Widefield Array (MWA), the Australian Square Kilometre Array Pathfinder (ASKAP) and the Australia Telescope Compact Array (ATCA), and X-ray data from Chandra, Swift and SRG/eROSITA. We present intensity, rotation measure, polarisation, spectral index and X-ray environment maps. Regions of the southern jet show simultaneous narrowing and brightening, which can be interpreted as a signature of the recollimation of the jet by external, environmental pressure, though it is also consistent with an intermittent Active Galactic Nuclei (AGN) or complex internal jet structure. X-ray data suggest that the environment is extremely poor; if the jet is indeed recollimating, the large recollimation scale (40 kpc) is consistent with a slow jet in a low-density environment., 16 pages, 14 figures, Accepted for publication in MNRAS

Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thromboembolic events. CKD concomitantly contributes to several pathophysiological changes predisposing towards a pro-haemorrhagic state. Purpose To evaluate the impact of kidney function on peri-procedural complications and clinical outcomes in AF patients undergoing left atrial appendage occlusion (LAAO) with a Watchman device. Methods 2124 consecutive AF patients undergoing Watchman implantation at 8 different centers were categorized into CKD stage 1+2 (n=1089), CKD stage 3 (n=796), CKD stage 4 (n=170), CKD stage 5 (n=69) based on the estimated glomerular filtration rate at baseline. The primary efficacy endpoint included a composite of cardiovascular (CV) mortality, stroke, transient ischemic attack, peripheral thromboembolism (TE), and major bleeding. Results A non-significant higher incidence of major peri-procedural adverse events (1.7% vs. 2.3% vs. 4.1% vs. 4.3%) was observed with worsening baseline kidney function (p=0.14). The mean follow-up period was 13 ± 7 months [2226 patient-years (PY)]. In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank p-value= 0.04), CKD stage 4 (log-rank p-value= 0.01), and CKD stage 5 (log-rank p-value= 0.001) (Fig.1A). A non-significant increase in event rates for stroke/TIA and clinically relevant bleeding was observed among the four groups. LAAO led to a TE risk reduction of 72%, 66%, 62%, and 41% in each group (Fig.1B). The relative risk reduction in the incidence of major bleeding was 58%, 44%, 51%, and 52%, respectively (Fig.1C). Conclusion Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. However, the relative risk reduction in the incidence of TE and major bleeding was consistent across CKD groups, irrespective of the very different risk profiles at baseline.

Funding Acknowledgements Type of funding sources: None. Background Acute kidney injury (AKI) is a serious complication after invasive cardiac procedures and has been associated with a higher incidence of periprocedural complications and increased mortality. Data on the occurrence of AKI associated with left atrial appendage occlusion (LAAO) are very limited. Purpose To report the incidence, predictors, and clinical implications of AKI following percutaneous LAAO. Methods This multicenter registry included 2124 patients with successful Watchman implantation. AKI was defined according to the AKI Network criteria as an increase in serum creatinine of ≥0.3 mg/dL or of ≥50% over the course of 48 hours post-procedure. Patients meeting this definition were further categorized in three stages: stage 1, increase in serum creatinine ≥ 0.3 mg/dl (≥ 26.4 μmol/l) or of 1.5 to 2 times compared to baseline; stage 2, increase in serum creatinine of 2 to 3 times compared to baseline; stage 3, increase in serum creatinine of > 3 times compared to baseline or serum creatinine ≥ 4.0 mg/dl [≥ 354 μmol/l] with an acute increase of at least 0.5 mg/dl [44 μmol/l]. Results Post-procedural AKI was documented in 68 (5.5%) of 1234 patients with creatinine determination between 24 and 48 hours post-LAAO. Among them, 63 (92.6%) patients had AKI stage 1, 4 (5.9%) had AKI stage 2, and 1 (1.5%) had AKI stage 3. AKI was associated with higher CHA2DS2-VASc (5.3 ± 1.4 vs. 4.8 ± 1.4; p=0.001) and HAS-BLED (3.8 ± 0.9 vs. 3.5 ± 1.0; p=0.01) scores at baseline, as well as a higher prevalence of diabetes mellitus (p=0.04) and CHF (p At multivariate analysis (Table 1), independent predictors of AKI were CKD stage 4/5 (OR: 1.998; 95% CI: 1.018 – 3.923; p=0.04), and CHF (OR: 2.286; 95% CI: 1.328 – 3.934; p=0.01). The average follow-up was 13 ± 7 months. The annualized rates of cardiovascular mortality were 5.5% in AKI and 1.0% in non-AKI patients (p=0.01). The annualized rates of overall mortality were 15.1% in AKI and 3.4% in non-AKI patients (p Conclusion AKI was an infrequent complication following percutaneous LAAO and a powerful predictor of cardiovascular and overall mortality during follow-up.

Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Institute of Health Research St George's, University of London Background SCN5A-E1784K (c.5350G>A) is the most common variant associated with the LQT3 long QT syndrome (LQTS) and Brugada syndrome (BrS). It exhibits incomplete penetrance and can manifest variably as a mixed clinical phenotype of LQTS, BrS and/or conduction disorders (1-4). This presents a challenge for risk stratification and optimal management. We aimed to describe the clinical characteristics and risk markers in a large, well characterised international cohort of SCN5A-E1784K subjects and identify demographic and/or ECG parameters associated with event free survival. Methods Comprehensive clinical data, including initial presentation and follow-up data, were collected from SCN5A-E1784K subjects. Outcome ‘events’ included sudden death, aborted cardiac arrest, and documented VF or VT or arrhythmic syncope. ‘Lethal events’ included sudden death, aborted cardiac arrest or documented VF or VT. Associations between clinical characteristics and event free survival were investigated using Cox proportional hazard regression models. Results SCN5A-E1784K subjects (n=231) were recruited from 16 centres. Median follow up was 24.9 years (15.2 - 43.3) and 45 individuals (19%) experienced an event. Lethal events were observed in 14 subjects (6%). Figure 1 shows event (A) and lethal event (B) free survival in SCN5A-E1784K subjects. Higher QRS duration (corrected for age) was associated with shorter event-free interval. QRS duration was the only characteristic associated with increased risk with a hazard ratio (HR) of 1.04 or 1.05 per ms for events and lethal events, respectively. The observed survival for events and lethal events for QRS tertiles are shown in Figure 2. Discussion Ventricular myocardial conduction, as evidenced by QRS duration, appears to play a role in the risk of arrhythmic events in patients with SCN5A-E1784K. Corrected QT interval and BrS phenotype were, however, not associated with risk. This provides an important opportunity for the personalisation of risk stratification of these patients, whose management can otherwise be very challenging. Figures

Bimodal cochlear implant (CI) listeners have difficulty utilizing spatial cues to segregate competing speech, possibly due to tonotopic mismatch between the acoustic input frequency and electrode place of stimulation. The present study investigated the effects of tonotopic mismatch in the context of residual acoustic hearing in the non-CI ear or residual hearing in both ears. Speech recognition thresholds (SRTs) were measured with two co-located or spatially separated speech maskers in normal-hearing adults listening to acoustic simulations of CIs; low frequency acoustic information was available in the non-CI ear (bimodal listening) or in both ears. Bimodal SRTs were significantly better with tonotopically matched than mismatched electric hearing for both co-located and spatially separated speech maskers. When there was no tonotopic mismatch, residual acoustic hearing in both ears provided a significant benefit when maskers were spatially separated, but not when co-located. The simulation data suggest that hearing preservation in the implanted ear for bimodal CI listeners may significantly benefit utilization of spatial cues to segregate competing speech, especially when the residual acoustic hearing is comparable across two ears. Also, the benefits of bilateral residual acoustic hearing may be best ascertained for spatially separated maskers.

International audience; Sonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker® microbubbles (MBs; VisualSonics—Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 108 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.

The auditory brainstem implant (ABI) can provide hearing sensation to individuals where the auditory nerve is damaged. However, patient outcomes with the ABI are typically much poorer than those for cochlear implant recipients. A major limitation to ABI outcomes is the number of implanted electrodes that can produce auditory responses to electric stimulation. One of the greatest challenges in ABI surgery is the intraoperative positioning of the electrode paddle, which must fit snugly within the cochlear nucleus complex. While there presently is no optimal procedure for intraoperative electrode positioning, intraoperative assessments may provide useful information regarding viable electrodes that may be included in patients’ clinical speech processors. Currently, there is limited knowledge regarding the relationship between intraoperative data and post-operative outcomes. Furthermore, the relationship between initial ABI stimulation with and long-term perceptual outcomes is unknown. In this retrospective study, we reviewed intraoperative electrophysiological data from 24 ABI patients (16 adults and 8 children) obtained with two stimulation approaches that differed in terms of neural recruitment. The interoperative electrophysiological recordings were used to estimate the number of viable electrodes and were compared to the number of activated electrodes at initial clinical fitting. Regardless of the stimulation approach, the intraoperative estimate of viable electrodes greatly overestimated the number of active electrodes in the clinical map. The number of active electrodes was associated with long-term perceptual outcomes. Among patients with 10-year follow-up, at least 11/21 active electrodes were needed to support good word detection and closed-set recognition and 14/21 electrodes to support good open-set word and sentence recognition. Perceptual outcomes were better for children than for adults, despite a lower number of active electrodes.