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During rest and sleep, memory traces replay in the brain. The dialogue between brain regions during replay is thought to stabilize labile memory traces for long-term storage. However, because replay is an internally-driven, spontaneous phenomenon, it does not have a ground truth - an external reference that can validate whether a memory has truly been replayed. Instead, replay detection is based on the similarity between the sequential neural activity comprising the replay event and the corresponding template of neural activity generated during active locomotion. If the statistical likelihood of observing such a match by chance is sufficiently low, the candidate replay event is inferred to be replaying that specific memory. However, without the ability to evaluate whether replay detection methods are successfully detecting true events and correctly rejecting non-events, the evaluation and comparison of different replay methods is challenging. To circumvent this problem, we present a new framework for evaluating replay, tested using hippocampal neural recordings from rats exploring two novel linear tracks. Using this two-track paradigm, our framework selects replay events based on their temporal fidelity (sequence-based detection), and evaluates the detection performance using each event's track discriminability, where sequenceless decoding across both tracks is used to quantify whether the track replaying is also the most likely track being reactivated., Competing Interests: MT, MH, MT, DB The authors declare that no competing interests exist., (© 2024, Takigawa et al.)

Background: Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes., Objectives: This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis., Methods: In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA)., Results: SV-origin extra-PV AF triggers occurred in 20.3% (n = 622) of patients, whereas PA-origin triggers occurred in 11.9% (n = 365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2, and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95% CI: 1.34-2.29; P < 0.001) and SV-AF (HR: 1.31; 95% CI: 1.19-1.45; P < 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups., Conclusions: SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers., Competing Interests: Funding Support and Author Disclosures This research received financial support from the Tailor-made Medical Treatment Program (grant number 1K157), Grant-in-Aid (Grant No. 26293052) bestowed by the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, and the Practical Research Project for Life-Style Related Diseases Including Cardiovascular Diseases and Diabetes Mellitus, courtesy of the Japan Agency for Medical and Development (AMED) under Project Code 15656344. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Very high-power short-duration (vHPSD) ablation creates shallower lesions, potentially reducing efficacy. This study aims to identify factors leading to insufficient lesions during pulmonary vein antral isolation (PVAI) with vHPSD-ablation and to develop an optimized PVAI strategy using this technology., Methods: PVAI was performed on 41 atrial fibrillation patients using vHPSD-ablation (90 W/4 s). Lesion parameters were recorded and analyzed to identify predictors of insufficient lesions. An optimized PVAI strategy, based on these predictors, was tested in subsequent 42 patients., Results: In total, 3099 RF-applications, including 103(3.3%) insufficient lesions, were analyzed. First-pass PVAI was achieved in 19/40(47.5%) right PVs and 24/41(58.5%) left PVs. Multivariate analysis identified significant predictors of insufficient lesions: local largest bipolar voltage (Bi-V), average contact force, baseline impedance, impedance drop, temperature rise, inter-lesion distance (ILD), and anatomical location (carina or not). An ILD:4-6 mm increased the risk of insufficient lesions 2.2-fold, and lesions at the carina increased it 3.6-fold for both ILD < 4 mm and ILD:4-6 mm. Local largest Bi-V was the strongest predictor for insufficient lesions. The optimized PVAI approach, utilizing vHPSD-ablation with an ILD < 4 mm in non-carinal areas with Bi-V < 4 mV, and high-power ablation-index guided ablation (HPAI, 50 W, ablation-index:450-550) in remaining areas, achieved first-pass PVAI in 92.7% of right PVs and 88.1% of left PVs, using vHPSD-ablation in approximately 65% of total RF-applications. The optimized PVAI achieved significantly higher first-pass PVI rate (p < .0001) with shorter ablation time (p = .04)., Conclusion: Appropriate use of vHPSD and HPAI, based on local largest Bi-V and anatomical information, may achieve high first-pass PVAI rates in shorter ablation time with minimal energy delivery., (© 2024 Wiley Periodicals LLC.)

Introduction: The novel cryoballoon with 28 mm or 31 mm adjustable diameters, aims to achieve a wide antral pulmonary vein isolation (PVI). However, the distribution of antral lesions and their variations based on left atrial (LA) remodeling require further clarification., Methods: We evaluated 22 patients (67 [59.5-74.8] years, 19 males) who underwent PVI of atrial fibrillation (AF) (13 paroxysmal AF [PAF] and 9 non-PAF) using size-adjustable cryoballoons. LA electro-anatomical mapping was performed post-PVI with three-dimensional mapping systems. We assessed the shapes of the LA and pulmonary veins (PVs) and the distribution of isolated areas (IAs), comparing the results between PAF and non-PAF patients., Results: In the left PVs (LPVs), the distance between the PV orifice and IA edge (PVos-IA) was larger on the roof and posterior segments (~15 mm) but relatively smaller on the anterior segment near the PV ridge (<10 mm). For the right PVs (RPVs), it was more extensive in the posterior segment (10-15 mm). Comparing PAF and non-PAF, there were no significant differences in the PVos-IA except for the right posterior-carina segment, antrum IA (LPVs: 5.9 ± 1.6 vs. 5.8 ± 0.8 cm², p = .81; RPVs: 4.8 ± 2.3 vs. 4.8 ± 1.2 cm², p = .81), distances between the right and left IAs on the LA posterior wall (LAPW), and un-isolated LAPW area (9.0 ± 4.9 vs. 9.9 ± 2.5 cm², p = .62). No individual PVIs were observed in either group. Two patients exhibited overlapping IAs on the roof, and one patient who underwent 31 mm balloon applications for all PVs exhibited an LAPW isolation., Conclusion: The size-adjustable cryoballoon achieved a wide antral PVI even in non-PAF patients., (© 2024 Wiley Periodicals LLC.)

Background: Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited., Objectives: We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation., Methods: A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed., Results: In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01)., Conclusions: The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice., (© 2024 Wiley Periodicals LLC.)

Background: Japan lacks an established framework for routine seasonal influenza vaccine effectiveness (SIVE) assessment at the national and municipal levels. This study aimed to estimate SIVE among older adults using an innovative population-based administrative database linking medical fee claims data with vaccination records, while also exploring its potential bias., Methods: In this retrospective population-based cohort study, we assessed SIVE against medically attended influenza during the 2017/18 season among older adults aged ≥65 years in a Japanese city. A Cox proportional hazards model was used to estimate hazard rate ratios, treating vaccination status as time-dependent. To explore potential biases, multivariate logistic regression analysis was used to investigate the association between vaccination status and acute respiratory infection (ARI) diagnosis and trauma/injury during the non-influenza season., Results: This study included 82 % (n = 110,892) of the city's older adult population, with 39.7 % vaccination coverage. The estimated SIVE was 2.9 % (95 % confidence interval: -6.2-11.2), showing no statistical significance. Similarly, subgroup analyses by age and comorbidities revealed no significant protective effect of SIVE. In the non-season analysis, adjusted odds ratios of vaccination were significantly higher for ARI [1.3 (1.3-1.4)] and trauma/injury [1.2 (1.1-1.2)]. However, no significance was observed for hospitalizations with these diagnoses, which include severe conditions less associated with healthcare-seeking behaviors [0.9 (0.8-1.1) and 0.8 (0.6-1.0), respectively]., Conclusions: No significant SIVE was observed during the 2017/18 season. Our real-world observational study, based on medical fee claims data, indicates a potential underestimation of SIVE owing to bias related to healthcare-seeking behaviors., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Very high power and short duration (vHPSD) ablation is recently used for pulmonary vein isolation. However, low first-pass isolation rates have been reported, possibly because of shallow lesion formation, necessitating deeper lesions to improve treatment outcomes., Objective: This study aimed to confirm the safety and efficacy of double radiofrequency applications of vHPSD ablation in an in vivo beating swine heart model., Methods: Eighteen swine were anesthetized and underwent vHPSD ablation using the QDOT-MICRO catheter at 90 W for 4 seconds, targeting a contact force of 10 g. Radiofrequency applications were performed as single application (SA) and double applications (DA) with 4-8 seconds rest intervals. Lesion surface area and volume were measured postablation., Results: A total of 337 atrial lesions and 74 ventricular lesions were created. Both 4-6 seconds DA and 7-8 seconds DA produced significantly larger and deeper lesions than did SA, with atrial surface lengths averaging 9.0 mm for 4-6 seconds DA, 9.2 mm for 7-8 seconds DA, and 8.0 mm for SA. Transmurality was observed at 100% for 4-6 seconds and 7-8 seconds DAs, while it was 94% for SA (P = .002). Ventricular lesion metrics followed similar trends. Except for 1 event of tiny char formation during 4 seconds DA in the ventricle, neither steam pops nor char formation was observed in either the atrium or the ventricle., Conclusion: In an in vivo swine heart model, DA with 4-6 seconds and 7-8 seconds intervals create deeper and wider lesions than does SA, suggesting its potential for clinical application in areas with thicker myocardial walls. However, DA with very short intervals may still pose a risk of excessive tissue heating., Competing Interests: Disclosures Drs Goto, Takigawa, and Miyazaki received endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, and Win International. No other authors have conflict of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the regional amplitude and phase of dissolved 129 Xe red blood cell (RBC) signal oscillations in the lung vasculature with keyhole spectroscopic imaging and to compare with previous methodology, which does not account for oscillation phase., Methods: 129 Xe gas transfer was measured with a four-echo 3D radial spectroscopic imaging sequence. Keyhole reconstruction-based RBC signal oscillation amplitude mapping was applied retrospectively to data acquired from 28 healthy volunteers, 4 chronic thromboembolic pulmonary hypertension (CTEPH) patients, and 5 patients who were hospitalized due to COVID-19 pneumonia and had residual lung abnormalities. Using a sliding window keyhole reconstruction, maps of RBC oscillation amplitude were corrected for regional phase difference. Repeatability of the phase-adjusted oscillation amplitude was assessed in 8 healthy volunteers across three scans., Results: With sliding window keyhole reconstruction, regional phase differences were observed in the RBC signal oscillations: mean phase = (0.27 ± 0.19) rad in healthy volunteers, (0.24 ± 0.13) rad in CTEPH patients, and (0.33 ± 0.19) rad in patients with post-COVID-19 residual lung abnormality. The oscillation amplitude and phase maps were more heterogeneous (i.e., they showed increased coefficient of variation) for the CTEPH patients. The RBC oscillation amplitude was repeatable, and the mean three-scan coefficient of variation was smaller when the phase adjustment was made (0.07 ± 0.04 compared with 0.16 ± 0.05)., Conclusion: Sliding window keyhole reconstruction of radial dissolved 129 Xe imaging reveals regional phase differences in the RBC oscillations, which are not captured when performing two phase keyhole reconstruction. This regional phase information may reflect the hemodynamic effect of the cardiac pulse wave in the pulmonary microvasculature., (© 2024 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Pulsed field ablation (PFA), a novel treatment for atrial fibrillation (AF), has yet to be evaluated in a Japanese cohort., Methods: In this sub-analysis of the PULSED AF trial, 12-month outcomes of paroxysmal AF (PAF) and persistent AF (PsAF) patients treated with PFA in four Japan centers were assessed. After a 90-day blanking period, primary efficacy was determined via freedom from a composite endpoint of acute procedural failure, arrhythmia recurrence, or antiarrhythmic drug escalation over 1 year. Patient improvement was evaluated via two quality of life (QoL) surveys (AFEQT and EQ-5D) at baseline and 12 months., Results: The analysis included 32 patients, 16 PAF and 16 PsAF, with PAF patients averaging 61.1 ± 10.6 years and PsAF patients averaging 62.8 ± 11.5 years of age. Females made up 31% of PAF and 25% of PsAF cohorts. Acute pulmonary vein isolation was achieved in 100% of both cohorts. The primary efficacy success rate at 12 months was 75.0% for PAF and 56.3% for PsAF patients. No primary safety events occurred. The mean AFEQT score significantly increased for both PAF (25.9 points, p < 0.0001) and PsAF (13.2 points, p = 0.0002) patients, while the EQ-5D-5L score improved significantly for PAF (0.12 points, p = 0.048) patients but not for PsAF (0.04 points, p = 0.08) patients., Conclusions: Similar to outcomes in the global cohort, ablation with the PulseSelect™ PFA catheter was efficient, effective, and safe in a Japanese population, resulting in improved QoL for PAF and PsAF patients., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT04198701., (© 2024. The Author(s).)

Purpose: Radiofrequency (RF) ablation with half-normal saline (HNS) irrigation is reported to potentially enlarge local lesion compared to normal saline (NS) in power-controlled ablation (PC-Abl). However, the effect of HNS-irrigation in temperature-flow-controlled ablation (TFC-Abl) on lesion characteristics is unknown. We compared this between TFC-Abl with QDOT-Micro™ catheter and PC-Abl with Thermocool SmartTouch SF™ catheter (STSF)., Methods: RF-application with NS (n = 480) and HNS (n = 480) irrigation were performed on swine myocardium placed in a circulating saline bath. Lesion characteristics without steam-pops under various conditions (target AI, 400/550; ablation power, 30/50 W; contact force, 10/20/30 g; catheter orientation, perpendicular/parallel) were assessed and compared between two irrigants., Results: After matching, 343 lesions without steam-pops in each group were evaluated. In PC-Abl, lesion size did not differ between two groups (NS, 188 ± 97 vs. HNS, 200 ± 95 mm 3 , p = 0.28 in volume; 33.9 ± 7.3 vs. 34.8 ± 9.5 mm 2 , p = 0.34 in surface area; and 4.0 ± 1.0 vs. 4.0 ± 1.0 mm, p = 0.81 in depth), but steam-pops were more frequently observed with HNS-irrigation (23.8% vs. 37.9%, p = 0.001). Contrary, in TFC-Abl, HNS-irrigation produced significantly larger (214 ± 106 vs. 243 ± 128 mm 3 , p = 0.017) and deeper (4.0 ± 1.0 vs. 4.3 ± 1.1 mm, p = 0.002) lesions without increasing the risk of steam-pops (15.0% vs 15.0%, p = 0.99). Automatic temperature-guided titration was more frequently observed in HNS-irrigation (54.8% vs. 78.5%, p < 0.001)., Conclusions: TFC-Abl with QDOT-Micro™ catheter utilizing HNS-irrigation might increase volume and depth of local lesion without increasing the risk of stem-pops compared to NS-irrigation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives : The predicted serum concentrations of vancomycin are determined using population pharmacokinetic parameters. However, the accuracy of predicting vancomycin serum concentrations in the older population remains unclear. Therefore, this study aimed to investigate the accuracy of predicting vancomycin serum concentrations and identifying elements that diminish the prediction accuracy in older people. Materials and Methods : A total of 144 patients aged 75 years or older were included. The serum vancomycin concentrations in the patients were predicted based on population pharmacokinetic parameters common in Japan. We examined the accuracy of serum vancomycin concentration prediction in elderly individuals by comparing the predicted and measured serum vancomycin concentrations in each patient. The prediction accuracy was evaluated using the mean prediction error (ME) and mean absolute error of prediction (MAE) calculated from the measured and predicted serum vancomycin concentrations in each patient. Results : The ME for all patients was 0.27, and the 95% CI included 0, indicating that the predicted values were not significantly biased compared to the measured values. However, the predicted serum concentrations in the <50 kg body weight and serum creatinine (Scr) < 0.6 mg/dL groups were significantly biased compared to the measured values. The group with a history of intensive care unit (ICU) admission showed the largest values for the ME and MAE. Conclusions : Our prediction accuracy was satisfactory but tended to be lower in underweight patients, those with low creatinine levels, and patients admitted to the ICU. Patients with multiple of these factors may experience a greater degree of decreased predictive accuracy.

Background: Unipolar electrograms (uni-EGMs) are an essential part of intracardiac mapping. Although Wilson central terminal (WCT) is conventionally used as a reference for signals, avoidance of contamination by far-field and nonphysiologic signals is challenging., Objective: The aim of the study was to explore the impact of an intracardiac indifferent reference electrode close to the recording electrodes, in lieu of WCT, on electrograms., Methods: Sinus node activation was mapped in patients undergoing catheter ablation by a multielectrode array with a close indifferent electrode (CIE) embedded in the distal end of the catheter shaft. An equal number of points was sequentially acquired at each site with use of CIE as a reference first and subsequently with WCT. Uni-EGMs, bipolar EGMs, and the earliest activation area (defined as the area activated in the first 10 ms of the beat) were compared between CIE- and WCT-based activation maps., Results: Seventeen patients (61 ± 18 years; 76% male) were studied. Uni-EGM voltages acquired with CIE were significantly larger than (n = 11) or comparable to (n = 4) those acquired with WCT. When points from the entire cohort were analyzed altogether, unipolar voltages and their maximum negative dV/dT and bipolar voltages recorded with CIE were significantly larger than those recorded with WCT (2.36 [1.42-3.79] mV vs 1.96 [1.25-3.03] mV, P < .0001; 0.40 [0.18-0.77] mV/s vs 0.35 [0.15-0.71] mV/s, P < .0001; and 1.46 [0.66-2.81] mV vs 1.33 [0.54-2.64] mV, P < .0001, respectively). The earliest activation area was significantly smaller in CIE-based activation maps than in WCT-based ones (0.3 [0.7-1.4] cm 2 vs 0.6 [1.0-1.8] cm 2 , P = .01)., Conclusion: CIE-based maps were associated with an approximately 20% increase in unipolar voltage and may highlight the origin of a focal activation more clearly than WCT-based ones., Competing Interests: Disclosures Drs Goto, Takigawa, and Miyazaki belong to the division that receives endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, APEX, and WIN International. No other authors have conflict of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The ligament of Marshall is an epicardial structure characterized by its composition of fat, fibrous tissue, blood vessels, muscle bundles, nerve fibers, and ganglia. Its intricate network forms muscular connections with the coronary sinus and left atrium, alongside adjacent autonomic nerves and ganglion cells. This complexity plays a pivotal role in initiating focal electrical activities and sustaining micro- and macro-reentrant circuits, thereby contributing to the onset of atrial fibrillation and atrial tachycardia. However, endocardial ablation in this area may encounter challenges due to anatomical variations and insulation by fibrofatty tissue. Combining ethanol infusion into the vein of Marshall with radiofrequency ablation presents a promising strategy for effectively and safely eliminating this arrhythmogenic structure and terminating associated tachycardias.

Background: The innovative peak frequency mapping facilitates the quantification of electrogram sharpness. However, reference values for normal atrial tissue are currently undefined. In this study, we explored the distribution of peak frequency and omnipolar peak-to-peak voltage (V-max) in a normal heart., Methods: Twenty-two patients with structurally normal heart were included. Either the right atrium (RA) and superior vena cava (SVC) or the left atrium (LA) and pulmonary veins (PVs) were mapped during sinus rhythm., Results: In total, 13,654 points in the RA and 4143 points in the SVC from 15 patients and 4662 points in the LA and 2761 points in PVs from 7 patients were analyzed. The correlation between peak frequency and V-max was weak (R = 0.223). The median peak frequency was larger in the SVC than in the RA (441 [358-524] Hz vs. 358 [291-441] Hz, P < 0.0001) and in PVs than in the LA (346 [253-441] Hz vs. 323 [262-397] Hz, P < 0.0001). Conversely, the median V-max was smaller in the SVC than in the RA (1.96 [0.77-3.75] mV vs. 4.11 [2.10-6.83] mV, P < 0.0001) and in PVs than in the LA (1.16 [0.33-3.17] mV vs. 4.42 [2.63-6.84] mV, P < 0.0001). More than 95% of peak frequencies were > 174 Hz in the RA and > 185 Hz in the LA, and > 95% of V-maxes were > 0.52 and > 1.07 mV in the RA and LA, respectively., Conclusion: Given the limited correlation between peak frequency and V-max, and recognizing their potential to provide distinct information, they can be used complementarily. Employing these parameters to extract varied insights can provide comprehensive understandings of tissue characteristics., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The safety of hyperbaric oxygen treatment (HBO 2 ) in patients with cardiovascular implanted electronic devices (CIED) remains unclear., Methods: We conducted a retrospective analysis of seven CIED patients (median age 79 [73-83] years, five males [71.4%]), including five with pacemakers and two with implantable cardioverter defibrillators (ICD), who underwent HBO 2 between June 2013 and April 2023. During the initial session, electrocardiogram monitoring was conducted, and CIED checks were performed before and after the treatment. In addition, the medical records were scrutinized to identify any abnormal CIED operations., Results: All seven CIED patients underwent HBO 2 within the safety pressure range specified by the CIED manufacturers or general pressure test by the International Organization for Standardization (2.5 [2.5-2.5] atmosphere absolute × 18 [5-20] sessions). When comparing the CIED parameters before and after HBO 2 , no significant changes were observed in the waveform amplitudes, pacing thresholds, lead impedance of the atrial and ventricular leads, or battery levels. All seven patients, including two with the rate response function activated, exhibited no significant changes in the pacing rate or pacing failure. Two ICD patients did not deactivate the therapy, including the defibrillation; however, they did not experience any arrhythmia or inappropriate ICD therapy during the HBO 2 ., Conclusion: CIED patients who underwent HBO 2 within the safety pressure range exhibited no significant changes in the parameters immediately after the HBO 2 and had no observable abnormal CIED operations during the treatment. The safety of defibrillation by an ICD during HBO 2 should be clarified., Competing Interests: Dr. Goto, Dr. Takigawa, and Dr. Miyazaki belong to the endowed departments of Medtronic and Boston Scientific. Dr. Miyazaki received speaker honoraria from Medtronic., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Background/aim: Pharmacovigilance data and clinical studies have indicated a risk of acute kidney injury (AKI) associated with concomitant administration of vancomycin and piperacillin-tazobactam. However, no pharmacovigilance studies have evaluated time-to-onset and outcomes of AKI related to this combination. Therefore, this study used a pharmacovigilance database to investigate the incidence, time-to-onset, and outcomes of AKI in patients treated with intravenous vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics., Patients and Methods: From data in the Japanese Adverse Drug Event Report (JADER) database, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs), time-to-onset, and outcomes of AKI following intravenous administration of vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics and with other vancomycin regimens, including monotherapy., Results: The JADER database contained 4,471 reports of intravenous vancomycin treatment, including 517 reports of AKI. The adjusted RORs (95%CIs) of AKI in cases with co-administration of intravenous vancomycin and piperacillin-tazobactam was 2.58 (2.06-3.24). The median time-to-onset for AKI in vancomycin plus piperacillin-tazobactam was 6.0 (interquartile range=3.0-10.3). Weibull shape parameter analysis showed that the pattern of onset of AKI in vancomycin plus piperacillin-tazobactam represented a wear out failure, predicting an increasing hazard with time. For the outcome of AKI, there was no significant difference between all vancomycin regimen and the piperacillin-tazobactam combination groups., Conclusion: Concomitant use of intravenous vancomycin and piperacillin-tazobactam may increase the incidence of AKI but may not affect the outcome. This combination does not necessarily have to be avoided, but long-term use is not advisable., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We explore an optimized approach for increasing lesion size using a novel ablation catheter with a surface thermocouple and efficient irrigation in a temperature-control setting., Methods: We conducted radiofrequency applications at various power levels (35 W, 40 W, and 45 W), contact forces (CFs, 10 g/20 g), and durations (60 s/120 s/180 s) in perpendicular/parallel catheter orientations, with normal saline irrigation (NS-irrigation) and Half NS-irrigation (HNS-irrigation) in an ex-vivo model (Step 1). In addition, we performed applications (35 W/40 W/45 W for 60 s/120 s/180 s in NS-irrigation and 35 W/40 W for 60 s/120 s/180 s in HNS-irrigation) in four swine (Step 2), evaluating lesion characteristics and the occurrence of steam pops., Results: In Step 1, out of 288 lesions, we observed 47 (16.3%) steam pops, with 13 in NS-irrigation and 34 in HNS-irrigation ( p  = .001). Although steam pops were mostly observed with the most aggressive setting (45 W/180 s, 54%) with NS-irrigation, they happened in less aggressive settings with HNS irrigation. Lesion size significantly increased with longer-duration ablation but not with HNS-irrigation. The optimal %impedance-drop cutoff to predict steam pops was 20% with a negative-predictive-value (NPV) = 95.1% including NS- and HNS-irrigation groups, and 22% with an NPV = 96.1% in NS-irrigation group. In Step 2, similar to the ex-vivo model, lesion size significantly increased with longer-duration ablation but not with HNS-irrigation. Steam pops were absent with NS-irrigation (0/35) even with the largest %impedance-drop reaching 31% at 45 W/180 s. All steam pops were observed with HNS-irrigation (6/21, 29%). The optimal %impedance-drop cutoff predicting steam pops was 24% with an NPV = 96.3% including both NS- and HNS-irrigation groups., Conclusions: Rather than using HNS-irrigation, very long-duration of radiofrequency applications up to 45 W/180 s may be recommended to safely and effectively increase lesion dimensions using this catheter with NS-irrigation., Competing Interests: Drs. Goto, Takigawa, and Miyazaki belong to the division which receives research endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, APEX, and WIN international. Dr. Takigawa received a lecture fee from Abbott Medical Japan, LIS. Dr. Ohuchi received a joint research fund from Abbott Medical Japan, LIS. No other authors have conflict of interest to declare., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

The Ligament of Marshall (LOM) is a remnant of the embryonic sinus venosus and the left cardinal vein, containing a combination of fat, fibrous tissue, blood vessels, muscle bundles, nerve fibers, and ganglia. Various muscular connections exist between the LOM and the left atrium (LA) and the coronary sinus (CS). The LOM is richly innervated by autonomic nerves, with ganglion cells distributed around it. The unique characteristics of the LOM are responsible for generating focal electrical activities and enable it to serve as a substrate for micro- and macro-reentrant circuits. This, in turn, leads to the initiation and perpetuation of atrial fibrillation (AF) and atrial tachycardia (AT). Endocardial ablation in this region does not consistently succeed due to anatomical constraints within the left lateral LA, including the presence of a thicker and longer mitral isthmus (MI), anatomical variations between the MI and epicardial structures such as the CS and vein of Marshall (VOM) and circumflex artery, and the presence of fibrofatty tissue insulating the LOM. Furthermore, epicardial ablation is challenging for inexperienced institutions because of its invasive nature. Ethanol infusion into the VOM (EI-VOM) represents an effective and safe approach that can be employed in conjunction with radiofrequency ablation to eliminate this arrhythmogenic structure., Competing Interests: Drs Jais̈ and Martin received lecture fees from Biosense Webster. Drs Jais̈ and Takigawa has received speaking honoraria from Abbott. Drs Jais̈ and Martin received speaking honoraria and consulting fees from Boston Scientific., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Pharmacists are expected to demonstrate their expertise in clinical practice and conduct research activities to generate new evidence. However, the factors promoting research activities among pharmacists remain unclear. Therefore, we investigated the research activities of Japanese pharmacists through a questionnaire survey and examined the factors contributing to the promotion of research activities. A web-based questionnaire using Google Forms was disseminated across pharmacists working in community pharmacies, drugstores, hospitals, and clinics. The questionnaire included respondents' backgrounds, research activities, and research environments. Logistic regression analysis was used to examine the factors promoting pharmacists' research activities, with experience in research paper acceptance as the objective variable. In total, 401 responses were included in the analysis. Of the respondents, 54.1% were hospital pharmacists, and 77.1% were pharmacists with > 5 years of pharmacist experience. Furthermore, 50.4% of the pharmacists had presented at conferences, and 22.2% had experience in research paper acceptance. The influential factors were "master's degree or higher," "number of affiliated academic societies," "acquisition of specialists/certified pharmacists," and "daily availability of a consultant for writing research papers." This study revealed the factors contributing to the promotion of research activities among pharmacists. We believe that our findings will help promote research among pharmacists., (© 2024. The Author(s).)

Background: Lesion size is reported to become larger as contact force (CF) increases. However, this has not been systematically evaluated in temperature-guided very high-power short-duration (vHPSD) ablation, which was therefore the purpose of this study., Methods: Radiofrequency applications (90 W/4 s, temperature-control mode) were performed in excised porcine myocardium with four different CFs of 5, 15, 25, and 35 g using QDOT-MICRO™ catheter. Ten lesions for each combination of settings were created, and lesion metrics and steam-pops were compared., Results: A total of 320 lesions were analyzed. Lesion depth, surface area, and volume were smallest for CF of 5 g than for 15, 25, and 35 g (depth: 2.7 mm vs. 2.9 mm, 3.0 mm, 3.15 mm, p  < .01; surface area: 38.4 mm 2 vs. 41.8 mm 2 , 43.3 mm 2 , 41.5 mm 2 , p  < .05; volume: 98.2 mm 3 vs. 133.3 mm 3 , 129.4 mm 3 , 126.8 mm 3 , p  < .01 for all pairs of groups compared to CF = 5 g). However, no significant differences were observed between CFs of 15-35 g. Average power was highest for CF of 5 g, followed by 15, 25, and 35 g (83.2 W vs. 82.1 W vs. 77.1 W vs. 66.1 W, p  < .01 for all pairs), reflecting the higher incidence of temperature-guided power titration with greater CFs (5 g:8.8% vs. 15 g:52.5% vs. 25 g:77.5% vs. 35 g:91.2%, p  < .01 for all pairs except for 25 g vs. 35 g). The incidence of steam-pops did not significantly differ between four groups (5 g:3.8% vs. 15 g:10% vs. 25 g:6.2% vs. 35 g:2.5%, not significant for all pairs)., Conclusions: For vHPSD ablation, lesion size does not become large once the CF reaches 15 g, and the risk of steam-pops may be mitigated through power titration even in high CFs., Competing Interests: Drs. Goto, Takigawa, and Miyazaki received endowments from Medtronic Japan, Boston Scientific, Japan Lifeline, and WIN international. Dr. Martin has received honoraria and speaker fees from Medtronic, Boston Scientific, and Biosense Webster. No other authors have conflict of interest to declare., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Burow's solution is a 13% aluminum acetate solution used for treating chronic suppurative otitis media. However, multiple formulations for Burow's and neo-Burow's solutions are used as in-hospital preparations. Each formulation uses different types and amounts of reagents, and takes a different time to prepare. Thus, the ions, including aluminum ion (Al 3+ ), and other molecules in the prepared Burow's and neo-Burow's solutions are not identical, and the pH also differs. Furthermore, details about the antibacterial activity of these preparations are unknown. This study evaluated the stability and antibacterial activity of four Burow's and two neo-Burow's solutions prepared using different methods. Preparation times ranged from 20 min to 3 d, and the pH ranged from 2.2 to 4, meaning some solutions were more acidic or more basic than the pH 3 devised by Burow. In addition, the Al 3+ concentrations ranged from 0.05 to 1.51 mol/L, meaning some solutions were more concentrated or diluted than 13% aluminum acetate (0.64 mol/L). One of the Burow's solutions we prepared produced a white residue after 14 d, making it difficult to ensure stability. In addition, confirming the antibacterial activity of another Burow's solution against the test bacteria was problematic. Despite the differences in pH and Al 3+ concentrations between the various Burow's and neo-Burow's solutions, the antibacterial activity was equivalent. It was considered necessary to use the basic data obtained in this study to select a formulation for each hospital. Evaluation of the antibacterial activity of each formulation in clinical settings will be a subject for future study.

Recently, a novel size-adjustable cryoballoon has been introduced in clinical practice, which can be inflated to two different diameters (28 and 31 mm). The 31 mm cryoballoon is specifically designed to achieve better contact with remodeled pulmonary veins (PVs) that have wider ostia while avoiding deep cannulation, thereby potentially reducing the risk of phrenic nerve injury (PNI) associated with deep balloon cannulation. However, we encountered two cases of PNI during cryoballoon ablation using the novel system among our initial 25 consecutive case series. Herein, we present two cases that exhibited PNI during freezing of the right superior PV with a size-adjustable balloon. While larger balloons are expected to create a larger area of isolation, the safety of this novel balloon system needs to be evaluated in a large-scale clinical study., (© 2023 Wiley Periodicals LLC.)

Background: A left atrial posterior wall isolation (LAPWI) is one of the atrial fibrillation (AF) ablation strategies., Hypothesis: We hypothesized that an additional empirical LAPWI would increase the freedom from recurrent atrial arrhythmias as compared to standard AF ablation in persistent AF patients., Methods: The CORNERSTONE AF study is a prospective, randomized, multicenter study investigating patients with AF persisting for >7 days and <3 years undergoing first-time AF ablation. They will be randomized to pulmonary vein isolation (PVI) or PVI + LAPWI in a 1:1 manner. Although PVI can be performed with either radiofrequency catheters or cryoballoons, only radiofrequency catheters will be permitted to achieve LAPWIs. Additional focal ablation targeting non-pulmonary vein triggers will be allowed. A total of 516 patients will be enrolled in 17 centers between August 2022 and February 2024 based on the calculation with 80% power, considering the assumption that 65% and 75% of the PVI and PVI + LAPWI group patients will be free from atrial arrhythmia recurrence 18-months postprocedure (10% of dropout). The primary endpoint is freedom from documented atrial arrhythmias 18 months postsingle procedures. Clinical follow-up will include 7-day ambulatory electrocardiograms and routine outpatient consultations by electrophysiologists at 1, 3, 6, 9, 12, and 18 months postprocedure., Results: As of August 2023, a total of 331 patients (68 ± 9 years, 270 men, 43 longstanding persistent AF) have been enrolled., Conclusions: The CORNERSTONE AF study is a prospective, randomized, multicenter trial designed to evaluate the efficacy and safety of an adjunctive empirical LAPWI following standard AF ablation in persistent AF patients., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Aims: The usefulness of coronary venous system mapping has been reported for assessing intramural and epicardial substrates in patients with scar-related ventricular tachycardia (VT). However, there has been little data on mapping from coronary arteries. We investigated the safety and utility of mapping from coronary arteries with a novel over-the-wire multielectrode catheter in scar-related VT patients., Methods and Results: Ten consecutive scar-related VT patients with non-ischaemic cardiomyopathy who underwent mapping from a coronary artery were analysed. Six patients underwent simultaneous coronary venous mapping. High-density maps were created by combining the left ventricular endocardium and coronary vessels. Substrate maps were created during the baseline rhythm with 2438 points (IQR 2136-3490 points), including 329 (IQR 59-508 points) in coronary arteries. Abnormal bipolar electrograms were successfully recorded within coronary arteries close to the endocardial substrate in seven patients. During VT, isthmus components were recorded within the coronary vessels in three patients with no discernible isthmus components on endocardial mapping. The ablation terminated the VT from an endocardial site opposite the earliest site in the coronary arteries in five patients., Conclusion: The transcoronary mapping with an over-the-wire multielectrode catheter can safely record abnormal bipolar electrograms within coronary arteries. Additional mapping data from the coronary vessels have the potential to assess three-dimensional ventricular substrates and circuit structures in scar-related VT patients., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

During sleep, recent memories are replayed by the hippocampus, leading to their consolidation, with a higher priority given to salient experiences. To examine the role of replay in the selective strengthening of memories, we recorded large ensembles of hippocampal place cells while male rats ran repeated spatial trajectories on two linear tracks, differing in either their familiarity or number of laps run. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the animal. In contrast, the rate of sleep replay events decreased if the animal was more familiar with the track. Furthermore, we find that the cumulative number of awake replay events occurring during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, providing a more parsimonious neural correlate for the selective strengthening of memories., (© 2023. Crown.)

The acquisition of motility via epithelial-mesenchymal transition (EMT) and osteoclast induction are essential for the invasion and metastasis of oral squamous cell carcinoma (OSCC) to bone. However, the molecule suppressing both EMT and osteoclastogenesis is still unknown. In this study, we found that cellular communication network factor 6 (CCN6) was less produced in a human OSCC cell line, HSC-3 with mesenchymal phenotype, than in HSC-2 cells without it. Notably, CCN6 interacted with bone morphogenetic protein 2 (BMP2) and suppressed the cell migration of HSC-3 cells stimulated by BMP2. Moreover, knockdown of CCN6 in HSC-2 cells led to the promotion of EMT and enhanced the effect of transforming growth factor-β (TGF-β) on the promotion of EMT. Furthermore, CCN6 combined with BMP2 suppressed EMT. These results suggest that CCN6 strongly suppresses EMT in cooperation with BMP2 and TGF-β. Interestingly, CCN6 combined with BMP2 increased the gene expression of receptor activator of nuclear factor-κB ligand (RANKL) in HSC-2 and HSC-3 cells. Additionally, CCN6 interacted with RANKL, and CCN6 combined with RANKL suppressed RANKL-induced osteoclast formation. In metastatic lesions, increasing BMP2 due to the bone destruction led to interference with binding of CCN6 to RANKL, which results in the promotion of bone metastasis of OSCC cells due to continuous osteoclastogenesis. These findings suggest that CCN6 plays dual roles in the suppression of EMT and in the promotion of bone destruction of OSCC in primary and metastatic lesions, respectively, through cooperation with BMP2 and interference with RANKL., (© The Author(s) 2023. Published by Oxford University Press.)

Cellular communication network factor 2 (CCN2) molecules promote endochondral ossification and articular cartilage regeneration, and circular RNAs (circRNAs), which arise from various genes and regulate gene expression by adsorbing miRNAs, are known to be synthesized from CCN2 in human vascular endothelial cells and other types of cells. However, in chondrocytes, not only the function but also the presence of CCN2-derived circRNA remains completely unknown. In the present study, we investigated the expression and function of CCN2-derived circRNAs in chondrocytes. Amplicons smaller than those from known CCN2-derived circRNAs were observed using RT-PCR analysis that could specifically amplify CCN2-derived circRNAs in human chondrocytic HCS-2/8 cells. The nucleotide sequences of the PCR products indicated novel circRNAs in the HCS-2/8 cells that were different from known CCN2-derived circRNAs. Moreover, the expression of several Ccn2-derived circRNAs in murine chondroblastic ATDC5 cells was confirmed and observed to change alongside chondrocytic differentiation. Next, one of these circRNAs was knocked down in HCS-2/8 cells to investigate the function of the human CCN2-derived circRNA. As a result, CCN2-derived circRNA knockdown significantly reduced the expression of aggrecan mRNA and proteoglycan synthesis. Our data suggest that CCN2-derived circRNAs are expressed in chondrocytes and play a role in chondrogenic differentiation. Production and role of CCN2-derived RNAs in chondrocytes., (© 2023. The Author(s).)

Background and Aims: The safety evaluation of TactiFlex, a novel contact-force sensing catheter with a flexible 4-mm tip irrigated through laser-cut kerfs, has been ongoing. This study aimed to verify the safety of this type of catheter., Methods: Study 1: Radiofrequency (RF) applications at a range of powers (30-50 W), contact forces (10-20 g), and durations (10-60 s) using perpendicular/parallel catheter orientation with half-normal (HNS) or normal saline irrigation were compared between TactiFlex (4-mm tip) and TactiCath (3.5-mm tip) with temperature-controlled mode in excised porcine hearts. Study 2: The relation between RF applications using TactiFlex and the incidence of steam-pops in the real clinical cases were examined., Results: Study-1: 576 RF lesions were examined. TactiFlex demonstrated a significantly lower risk of steam-pops (5[1.7%] vs. 59[20.5%], p < .0001). Compared to 3.5-mm-tip catheter (TactiCath), 4-mm-tip catheter (TactiFlex) produced smaller lesion volume at perpendicular (193[98-554]mm 3 vs. 263[139-436]mm 3 , p < .0001), but relatively similar lesion volume at parallel contact (243[105-443]mm 3 vs. 278[180-440]mm 3 , p = .06). HNS-irrigation tended to increase the lesion volume in both catheters and to increase the incidence of steam-pops with TactiCath, but not with TactiFlex. The cut-off value of %impedance-drop ( = absolute impedance-drop/initial impedance) of 20% predicted steam-pops with a sensitivity = 100% and specificity = 89.6% in TactiFlex. Study-2: 5496 RF applications in 84 patients (51AFs/8ATs/3AVNRTs/4AVRTs/17PVCs/4VTs) using TactiFlex were analyzed. Four steam-pops (0.07%) in three patients with pericardial effusion were observed (%impedance-drop = 24%/26%/29%/35%, respectively). The cut-off value of %impedance-drop = 20%, derived from ex-vivo study, showed sensitivity = 100% and specificity = 90.1% in detecting steam-pops., Conclusion: TactiFlex reduced the risk of steam-pops than TactiCath. %impedance-drop ≤ 20% may be reasonable for safely use with a sufficient safety margin. For 4-mm-tip catheter, parallel-contact may be recommended for larger lesion creation., (© 2023 Wiley Periodicals LLC.)

Background: For lesion size prediction, each input parameter, including ablation energy (AE), and output parameter, such as impedance, is individually used. We hypothesize that using both parameters simultaneously may be more optimal., Methods and results: Radiofrequency applications at a range of power (30-50 W), contact force (10 g and 20 g), duration (10-60 s), and catheter orientation with normal saline (NS)- or half-normal saline (HNS)-irrigation were performed in excised porcine hearts. The correlations, with lesion size of AE, absolute impedance drop (∆Imp-drop), relative impedance drop (%Imp-drop), and AE*%Imp-drop were examined. Lesion size was analyzed in 283 of 288 lesions (NS-irrigation, n=142; HNS-irrigation, n=141) without steam pops. AE*%Imp-drop consistently showed the strongest correlations with lesion maximum depth (NS-irrigation, ρ=0.91; HNS-irrigation, ρ=0.94), surface area (NS-irrigation, ρ=0.87; HNS-irrigation, ρ=0.86), and volume (NS-irrigation, ρ=0.94; HNS-irrigation, ρ=0.94) compared with the other parameters. Moreover, compared with AE alone, AE*%Imp-drop significantly improved the strength of correlation with lesion maximum depth (AE vs. AE*%Imp-drop, ρ=0.83 vs. 0.91, P<0.01), surface area (ρ=0.73 vs. 0.87, P<0.01), and volume (ρ=0.84 vs. 0.94, P<0.01) with NS-irrigation. This tendency was also observed with HNS-irrigation. Parallel catheter orientation showed a better correlation with lesion depth and volume using ∆Imp-drop, %Imp-drop, and AE*%Imp-drop than perpendicular orientation., Conclusions: The combination of input and output parameters is more optimal than each single parameter for lesion prediction.

Background: Substrate abnormalities can alter atrial activation during atrial tachycardias (ATs) thereby influencing AT-wave morphology on the surface electrocardiogram., Objectives: This study sought to identify determinants of isoelectric intervals during ATs with complex atrial activation patterns., Methods: High-density activation maps of 126 ATs were studied. To assess the impact of the activated atrial surface on the presence of isoelectric intervals, this study measured the minimum activated area throughout the AT cycle, defined as the smallest activated area within a 50-millisecond period, by using signal processing algorithms (LUMIPOINT)., Results: ATs with isoelectric intervals (P-wave ATs) included 23 macro-re-entrant ATs (40%), 26 localized-re-entrant ATs (46%), and 8 focal ATs (14%), whereas those without included 46 macro-re-entrant ATs (67%), 21 localized-re-entrant ATs (30%), and 2 focal ATs (3%). Multivariable regression identified smaller minimum activated area and larger very low voltage area as independent predictors of P-wave ATs (OR: 0.732; 95% CI: 0.644-0.831; P < 0.001; and OR: 1.042; 95% CI: 1.006-1.080; P = 0.023, respectively). The minimum activated area with the cutoff value of 10 cm 2 provided the highest predictive accuracy for P-wave ATs with sensitivity, specificity, and positive and negative predictive values of 96%, 97%, 97%, and 95%, respectively. In re-entrant ATs, smaller minimum activated area was associated with lower minimum conduction velocity within the circuit and fewer areas of delayed conduction outside of the circuit (standardized β: 0.524; 95% CI: 0.373-0.675; P < 0.001; and standardized β: 0.353; 95% CI: 0.198-0.508; P < 0.001, respectively)., Conclusions: Reduced atrial activation area and voltage were associated with isoelectric intervals during ATs., Competing Interests: Funding Support and Author Disclosures This research was partly funded by a grant from Investissement d’avenir: IHU LIRYC ANR-10-IAHU-04. Ms Carapezzi is an employee of Boston Scientific. Dr Jaïs has received speaking honoraria and consulting fees from Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Abnormal atrial potentials (AAPs) recorded during sinus rhythm/atrial pacing may indicate areas of slow conduction capable of supporting reentrant atrial tachycardia (AT). Therefore, we sought to examine the relationship between AAPs and AT circuits., Methods: One hundred twenty-three reentrant ATs in 104 patients were analyzed. AAPs, consisting of fragmented potentials and split potentials, were assessed using the Rhythmia LUMIPOINT algorithm., Results: There was 93±13% overlap between areas with AAPs during sinus rhythm/atrial pacing and areas of slow conduction along the reentry circuit during AT. The cumulative area of AAPs was smaller in patients with localized-reentrant ATs compared with anatomic macro-reentrant ATs (20.0 [14.6-30.5] versus 28.9 [21.8-35.6] cm 2 ; P =0.021). Patients with perimitral ATs had larger areas of AAPs on the lateral wall whereas patients with roof-dependent ATs had larger areas of AAPs on the roof and posterior wall ( P ≤0.018 for all comparisons). The patchy scar that was associated with localized-reentrant AT exhibited a larger area of AAPs at its periphery than the scar that did not participate in localized-reentrant AT (3.1 [2.4-4.5] versus 1.0 [0.7-1.6] cm 2 ; P <0.001)., Conclusions: AAPs recorded during sinus rhythm/atrial pacing are associated with areas of slow conduction during reentrant AT. The burden and distribution of AAPs may provide actionable insights into AT circuit features, including in cases in which ATs are difficult to map., Competing Interests: Disclosures Dr Jaïs received speaking honoraria, lecture fees, and consulting fees from Boston Scientific. Drs Derval and Sacher have received lecture fees from Boston Scientific. A. Carapezzi is an employee of Boston Scientific. The other authors report no conflicts.

Exposure to particulate matter less than 2.5 µm in diameter (PM 2.5 ) is a cause of concern in cities and major emission regions of northern India. An intensive field campaign involving the states of Punjab, Haryana and Delhi national capital region (NCR) was conducted in 2022 using 29 Compact and Useful PM 2.5 Instrument with Gas sensors (CUPI-Gs). Continuous observations show that the PM 2.5 in the region increased gradually from < 60 µg m -3 in 6-10 October to up to 500 µg m -3 on 5-9 November, which subsequently decreased to about 100 µg m -3 in 20-30 November. Two distinct plumes of PM 2.5 over 500 µg m -3 are tracked from crop residue burning in Punjab to Delhi NCR on 2-3 November and 10-11 November with delays of 1 and 3 days, respectively. Experimental campaign demonstrates the advantages of source region observations to link agricultural waste burning and air pollution at local to regional scales., (© 2023. Springer Nature Limited.)

Aims: Although the mechanism of an atrial tachycardia (AT) can usually be elucidated using modern high-resolution mapping systems, it would be helpful if the AT mechanism and circuit could be predicted before initiating mapping., Objective: We examined if the information gathered from the cycle length (CL) of the tachycardia can help predict the AT-mechanism and its localization., Methods: One hundred and thirty-eight activation maps of ATs including eight focal-ATs, 94 macroreentrant-ATs, and 36 localized-ATs in 95 patients were retrospectively reviewed. Maximal CL (MCL) and minimal CL (mCL) over a minute period were measured via a decapolar catheter in the coronary sinus. CL-variation and beat-by-beat CL-alternation were examined. Additionally, the CL-respiration correlation was analysed by the RhythmiaTM system. : Both MCL and mCL were significantly shorter in macroreentrant-ATs [MCL = 288 (253-348) ms, P = 0.0001; mCL = 283 (243-341) ms, P = 0.0012], and also shorter in localized-ATs [MCL = 314 (261-349) ms, P = 0.0016; mCL = 295 (248-340) ms, P = 0.0047] compared to focal-ATs [MCL = 506 (421-555) ms, mCL = 427 (347-508) ms]. An absolute CL-variation (MCL-mCL) < 24 ms significantly differentiated re-entrant ATs from focal-ATs with a sensitivity = 96.9%, specificity = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 66.7%. The beat-by-beat CL-alternation was observed in 10/138 (7.2%), all of which showed the re-entrant mechanism, meaning that beat-by-beat CL-alternation was the strong sign of re-entrant mechanism (PPV = 100%). Although the CL-respiration correlation was observed in 28/138 (20.3%) of ATs, this was predominantly in right-atrium (RA)-ATs (24/41, 85.7%), rather than left atrium (LA)-ATs (4/97, 4.1%). A positive CL-respiration correlation highly predicted RA-ATs (PPV = 85.7%), and negative CL-respiration correlation probably suggested LA-ATs (NPV = 84.5%)., Conclusion: Detailed analysis of the tachycardia CL helps predict the AT-mechanism and the active AT chamber before an initial mapping., Competing Interests: Conflict of interest: Drs Haïssaguerre, Hocini, Jaïs, Martin, and Sacher have received lecture fees from Biosense Webster. Drs Haïssaguerre, Hocini, Jaïs, and Sacher have received lecture fees and Takigawa has received speaking honoraria from Abbott. Drs Derval, Jaïs, Martin, and Sacher have received speaking honoraria and consulting fees from Boston Scientific. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Little is known about the impact of blood-pool local impedance (LI) on lesion characteristics and the incidence of steam pops., Methods: Radiofrequency applications at a range of powers (30, 40, and 50 W), contact forces (CF) (5, 15, and 25 g), and durations (15, 30, 45, and 120 s) using perpendicular/parallel catheter orientation were performed in 40 excised porcine preparations, using a catheter capable of monitoring LI (StablePoint©, Boston Scientific). To simulate the variability in blood-pool impedance, the saline-pool LI was modulated by calibrating saline concentrations. Lesion characteristics were compared under three values of saline-pool LI: 120, 160, and 200 Ω., Results: Of 648 lesions created, steam pops occurred in 175 (27.0%). When power, CF, time, and catheter orientation were adjusted, ablation at a saline-pool impedance of 160 or 200 Ω more than doubled the risk of steam pops compared with a saline-pool impedance of 120 Ω (Odds ratio = 2.31; p = .0002). Lesions in a saline-pool impedance of 120 Ω were significantly larger in surface area (50 [38-62], 45 [34-56], and 41 [34-60] mm 2 for 120, 160, and 200 Ω, p < .05), but shallower in depth (4.0 [3-5], 4.4 [3.2-5.3], and 4.5 [3.8-5.5] mmfor 120, 160, and 200 Ω, respectively, p < .05) compared with the other two settings. The correlation between the absolute LI-drop and lesion size weakened as the saline-pool LI became higher (e.g., 120 Ω group (r 2  = .30, r 2  = .18, and r 2  = .16, respectively for 120, 160, and 200 Ω), but the usage of %LI-drop (= absolute LI-drop/initial LI) instead of absolute LI-drop may minimize this effect., Conclusions: In an experimental model, baseline saline-pool impedance significantly affects the lesion metrics and the risk of steam pops., (© 2023 Wiley Periodicals LLC.)

Background: The impact of filtering on bipolar electrograms (EGMs) has not been systematically examined. We tried to clarify the optimal filter configuration for ventricular tachycardia (VT) ablation., Methods: Fifteen patients with VT were included. Eight different filter configurations were prospectively created for the distal bipoles of the ablation catheter: 1.0-250, 10-250, 100-250, 30-50, 30-100, 30-250, 30-500, and 30-1000 Hz. Pre-ablation stable EGMs with good contact (contact force > 10 g) were analyzed. Baseline fluctuation, baseline noise, bipolar peak-to-peak voltage, and presence of local abnormal ventricular activity (LAVA) were compared between different filter configurations., Results: In total, 2276 EGMs with multiple bipolar configurations in 246 sites in scar and border areas were analyzed. Baseline fluctuation was only observed in the high-pass filter of (HPF) ≤ 10 Hz (p < .001). Noise level was lowest at 30-50 Hz (0.018 [0.012-0.029] mV), increased as the low-pass filter (LPF) extended, and was highest at 30-1000 Hz (0.047 [0.041-0.061] mV) (p < .001). Conversely, the HPF did not affect the noise level at ≤30 Hz. As the HPF extended to 100 Hz, bipolar voltages significantly decreased (p < .001), but were not affected when the LPF was extended to ≥100 Hz. LAVAs were most frequently detected at 30-250 Hz (207/246; 84.2%) and 30-500 Hz (208/246; 84.6%), followed by 30-1000 Hz (205/246; 83.3%), but frequently missed at LPF ≤ 100 Hz or HPF ≤ 10 Hz (p < .001). A 50-Hz notch-filter reduced the bipolar voltage by 43.9% and LAVA-detection by 34.5% (p < .0001)., Conclusion: Bipolar EGMs are strongly affected by filter settings in scar/border areas. In all, 30-250 or 30-500 Hz may be the best configuration, minimizing the baseline fluctuation, baseline noise, and detecting LAVAs. Not applying the 50-Hz notch filter may be beneficial to avoid missing VT substrate., (© 2023 Wiley Periodicals LLC.)

Global lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) led to air pollutant emission reductions. While the COVID-19 lockdown impacts on both trace gas and total particulate pollutants have been widely investigated, secondary aerosol formation from trace gases remains unclear. To that end, we quantify the COVID-19 lockdown impacts on NO x and SO 2 emissions and sulfate-nitrate-ammonium aerosols using multiconstituent satellite data assimilation and model simulations. We find that anthropogenic emissions over major polluted regions were reduced by 19 to 25% for NO x and 14 to 20% for SO 2 during April 2020. These emission reductions led to 8 to 21% decreases in sulfate and nitrate aerosols over highly polluted areas, corresponding to >34% of the observed aerosol optical depth declines and a global aerosol radiative forcing of +0.14 watts per square meter relative to business-as-usual scenario. These results point to the critical importance of secondary aerosol pollutants in quantifying climate impacts of future mitigation measures.

The development of new anti-HIV drugs and advances in antiretroviral therapy (ART) regimens have enabled longer and more effective treatments in people living with HIV (PLWH). However, the aging of PLWHs is another issue that needs to be addressed. In addition to ART, many PLWHs frequently receive medications for various comorbidities. However, real-world data on the occurrence of adverse events in PLWHs and their causative drugs are rare. Therefore, this study aimed to clarify the characteristics of adverse event reports among PLWHs in Japan. PLWH cases with adverse events were comprehensively searched and analyzed using the Japanese Adverse Drug Event Report database (JADER). Despite changes in guideline-recommended ART regimens, anti-HIV drugs were the main cause of adverse events in PLWHs throughout the study period. However, considerable variations have been observed in the reporting rate of anti-HIV drug classes registered as causative drugs in JADER, especially for anchor drugs. In other words, the reporting rate of integrase strand transfer inhibitors has increased in recent years, while that of protease inhibitors and non-nucleoside reverse transcriptase inhibitors has decreased. Immune reconstitution inflammatory syndrome was the most reported adverse event and was frequently noticed by healthcare providers managing patients with HIV infections. The trends in adverse event reports for female and older patients differed from those for the overall population. This study may provide insights that can help in the establishment of optimal management strategies for PLWHs.

The central venous port has been widely used for patients who require long-term intravenous treatments, and the number of palcement has been increasing. The Japanese Society of Interventional Radiology developed a guideline for central venous port placement and management to provide evidence-based recommendations to support healthcare providers in the decision-making process regarding the central venous port. The guideline consisted of two parts: (i) a comprehensive review of topics including preoperative preparation, techniques for placement or removal, complications, and maintenance methods and (ii) recommendations for the six clinical questions regarding blood vessels for central venous port placement, port implantation site, prophylactic antibiotic therapy, imaging guidance for puncture, disinfectant prior to accessing the central venous port, and the optimal procedure at the end of drug administration via the central venous port, generated on the basis of the rating quality of evidence by systematic review., Competing Interests: Hidefumi Mimura received grants from Terumo Corporation and Toray Medical Co., Ltd. Shunsuke Sugawara received honorarium from Becton, Dickinson and Company (Medicon). Tomoaki Yamanishi received honorarium from Terumo Corporation and Stryker Corporation., (© 2023 Japanese Society of Interventional Radiology.)

Cellular communication network factor (CCN) 3, which is one of the founding members of the CCN family, displays diverse functions. However, this protein generally represses the proliferation of a variety of cells. Along with skeletal development, CCN3 is produced in cartilaginous anlagen, growth plate cartilage and epiphysial cartilage. Interestingly, CCN3 is drastically induced in the growth plates of mice lacking CCN2, which promotes endochondral ossification. Notably, chondrocytes in these mutant mice with elevated CCN3 production also suffer from impaired glycolysis and energy metabolism, suggesting a critical role of CCN3 in cartilage metabolism. Recently, CCN3 was found to be strongly induced by impaired glycolysis, and in our study, we located an enhancer that mediated CCN3 regulation via starvation. Subsequent investigations specified regulatory factor binding to the X-box 1 (RFX1) as a transcription factor mediating this CCN3 regulation. Impaired glycolysis is a serious problem, resulting in an energy shortage in cartilage without vasculature. CCN3 produced under such starved conditions restricts energy consumption by repressing cell proliferation, leading chondrocytes to quiescence and survival. This CCN3 regulatory system is indicated to play an important role in articular cartilage maintenance, as well as in skeletal development. Furthermore, CCN3 continues to regulate cartilage metabolism even during the aging process, probably utilizing this regulatory system. Altogether, CCN3 seems to prevent "overwork" by chondrocytes to ensure their sustainable life in cartilage by sensing energy metabolism. Similar roles are suspected to exist in relation to systemic metabolism, since CCN3 is found in the bloodstream., (© 2023. The International CCN Society.)

Background: The FlexAbility™ SE catheter has a laser-cut 8Fr 4-mm flexible tip irrigated through laser-cut kerfs with a thermocouple 0.3 mm from the distal end. The TactiCath™ SE catheter has an 8Fr 3.5-mm tip and 6-irrigation port with a thermocouple 2.67 mm proximal to the tip. We investigated the impact of these differences on the efficacy and safety of radiofrequency (RF) applications., Methods: RF applications at a range of powers (20 W, 30 W, and 40 W), contact forces (5 g, 15 g, and 25 g), and durations (10-60 s) using perpendicular/parallel catheter orientation were performed in excised porcine hearts. Lesion characteristics and incidence of steam pops were compared., Results: A total of 540 lesions were examined. The FlexAbility™ SE catheter produced smaller lesion depths (4.0 mm vs. 4.4 mm, p = 0.014 at 20 W; 4.6 mm vs. 5.6 mm, p = 0.015 at 30 W), surface areas (22.7mm 2 vs. 29.2mm 2 at 20 W, p = 0.005; 23.2mm 2 vs. 28.7mm 2 , p = 0.009 at 30 W), and volumes (126.1mm 3 vs. 175.1mm 3 , p = 0.018 at 20 W; 183.2mm 3 vs. 304.3mm 3 , p = 0.002 at 30 W) with perpendicular catheter placement. However, no differences were observed with parallel catheter placement. Steam-pops were significantly less frequently observed with the FlexAbility™ SE catheter (4% vs. 22%, p < 0.001) irrespective of catheter direction to the tissue. Multivariate analysis showed that use of the TactiCath™ SE catheter, power ≥ 40 W, contact force ≥ 25 g, RF duration > 30 s, parallel angle, and impedance drop ≥ 20Ω were significantly associated with occurrence of steam-pops., Conclusions: The FlexAbility™ SE catheter reduced the risk of steam-pops but produced smaller lesions with perpendicular catheter placement compared to the TactiCath™ SE catheter., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.