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Previous studies have identified noninvasive methods for predicting atrial fibrillation (AF) recurrence after catheter ablation (CA). We assessed the association between AF recurrence and atrial late potentials (ALPs), which were measured using P‐wave signal‐averaged electrocardiography (P‐SAECG). Consecutive patients with paroxysmal AF who underwent their first CA at our institution between August 2015 and August 2019 were enrolled. P‐SAECG was performed before CA. Two ALP parameters were evaluated: the root‐mean‐square voltage during the terminal 20 ms (RMS20) and the P‐wave duration (PWD). Positive ALPs were defined as an RMS20<2.2 μV and/or a PWD >115 ms. Patients were allocated to either the recurrence or nonrecurrence group based on the presence of AF recurrence at the 1‐year follow‐up post‐CA. Of the 190 patients (age: 65 ± 11 years, 37% women) enrolled in this study, 21 (11%) had AF recurrence. The positive ALP rate was significantly higher in the recurrence group than in the nonrecurrence group (86% vs. 64%, p= .04), despite the absence of differences in other baseline characteristics between the two groups. In the multivariate analysis, positive ALP was an independent predictor of AF recurrence (odds ratio: 3.83, 95% confidence interval: 1.05–14.1, p= .04). Positive ALP on pre‐CA P‐SAECG is associated with AF recurrence after CA. P‐wave signal‐averaged electrocardiography (P‐SAECG) findings could indicate atrial fibrosis, i.e., an arrhythmogenic substrate in patients with AF. We evaluated the association between AF recurrence after catheter ablation (CA) and atrial late potentials (ALPs), which were measured using P‐SAECG. The positive ALP rate was significantly higher in the Recurrence group than in the non‐Recurrence group (86% vs. 64%, p= .04). In the multivariate analysis, positive ALP was an independent predictor of AF recurrence (odds ratio: 3.83, 95% confidence interval: 1.05–14.1, p= .04).

IL-26 is a Th17 cytokine, with its gene being absent in rodents. To characterize the in vivo immunological effects of IL-26 in chronic systemic inflammation, we used human IL26transgenic (hIL-26Tg) mice and human umbilical cord blood mononuclear cells (hCBMC) in mouse allogeneic-graft-versus-host disease (GVHD) and chronic xenogeneic-GVHD model, respectively. Transfer of bone marrow and spleen T cells from hIL-26Tg mice into B10.BR mice resulted in GVHD progression, with clinical signs of tissue damage in multiple organs. IL-26 markedly increased neutrophil levels both in the GVHD-target tissues and peripheral blood. Expression levels of Th17 cytokines in hIL-26Tg mice-derived donor CD4 T cells were significantly increased, whereas IL-26 did not affect cytotoxic function of donor CD8 T cells. In addition, granulocyte-colony stimulating factor, IL-1β, and IL-6 levels were particularly enhanced in hIL-26Tg mice. We also developed a humanized neutralizing anti-IL-26 monoclonal antibody (mAb) for therapeutic use, and its administration after onset of chronic xenogeneic-GVHD mitigated weight loss and prolonged survival, with preservation of graft-versus-leukemia effect. Taken together, our data elucidate the in vivo immunological effects of IL-26 in chronic GVHD models and suggest that a humanized anti-IL-26 mAb may be a potential therapeutic agent for the treatment of chronic GVHD.

IL‐26 is a Th17 cytokine, with its gene being absent in rodents. To characterize the in vivo immunological effects of IL‐26 in chronic systemic inflammation, we used human IL26transgenic (hIL‐26Tg) mice and human umbilical cord blood mononuclear cells (hCBMC) in mouse allogeneic‐graft‐versus‐host disease (GVHD) and chronic xenogeneic‐GVHD model, respectively. Transfer of bone marrow and spleen T cells from hIL‐26Tg mice into B10.BR mice resulted in GVHD progression, with clinical signs of tissue damage in multiple organs. IL‐26 markedly increased neutrophil levels both in the GVHD‐target tissues and peripheral blood. Expression levels of Th17 cytokines in hIL‐26Tg mice‐derived donor CD4 T cells were significantly increased, whereas IL‐26 did not affect cytotoxic function of donor CD8 T cells. In addition, granulocyte‐colony stimulating factor, IL‐1β, and IL‐6 levels were particularly enhanced in hIL‐26Tg mice. We also developed a humanized neutralizing anti‐IL‐26 monoclonal antibody (mAb) for therapeutic use, and its administration after onset of chronic xenogeneic‐GVHD mitigated weight loss and prolonged survival, with preservation of graft‐versus‐leukemia effect. Taken together, our data elucidate the in vivo immunological effects of IL‐26 in chronic GVHD models and suggest that a humanized anti‐IL‐26 mAb may be a potential therapeutic agent for the treatment of chronic GVHD. In an allogeneic graft‐versus host disease (GVHD) mouse model, IL‐26 markedly increases neutrophil levels and augments T helper 17 responses while in a xenogeneic model, humanized neutralizing anti‐IL‐26 monoclonal antibody impedes the development of chronic GVHD with preservation of graft‐versus‐leukemia effect.

Although the lesion size index (LSI) has been well established, it is sometimes difficult to achieve first‐pass pulmonary vein isolation (PVI) and to avoid acute pulmonary vein reconnections, even with LSI‐guided procedures. The purpose of this study was to assess the predictive accuracy of a novel parameter, the optimized lesion size index (o‐LSI), to perform PVI. The voltage maps created by the Advisor™ high‐density (HD) grid catheter before PVI in 35 atrial fibrillation (AF) patients were examined for an association between the voltage amplitude and insufficient ablation sites (IAS), which were defined as either (i) spontaneous reconnection sites, (ii) dormant PV conduction sites unmasked with 20 mg of adenosine triphosphate disodium hydrate (ATP) injection, or (iii) PV‐LA gap sites after the initial PVI. IAS was observed in 25/1417 of the total ablation sites. IAS was significantly associated with higher bipolar voltage areas (4.20 ± 2.68 vs 2.43 ± 1.93 mV, P< .0001) but not with LSI. A novel index, o‐LSI (defined as LSI/bipolar voltage), was significantly lower in IAS than in others (1.14 [0.82, 1.81] vs 2.35 [1.31, 4.80] LSI/mV). By receiver operating characteristic analysis, an o‐LSI of 2.04 was the best cutoff value for the prediction of IAS (88% sensitivity and 55% specificity, P< .0001, areas under the curve: 0.742). Low o‐LSI was strongly associated with IAS, potentially providing a novel index to improve first‐pass PV isolation. To achieve first‐pass pulmonary vein isolation (PVI) and to avoid the acute pulmonary vein reconnections is sometimes difficult even with the lesion size index (LSI)‐guided radiofrequency ablation. We focused on the relationship between the optimized ‐LSI (o‐LSI) (LSI/bipolar voltage within the PV‐encircling lines, which were defined by the Advisor™ HD Grid catheter) and the sufficient ablation sites and found that was strongly associated with acute PV reconnection. The o‐LSI may potentially be novel strategies for durable PVI.

Right ventricular (RV) pacing causes left ventricular (LV) dyssynchrony sometimes resulting in pacing‐induced cardiomyopathy. However, RV pacing for hypertrophic obstructive cardiomyopathy is one of the treatment options. LV flow energy loss (EL) using vector flow mapping (VFM) is a novel hemodynamic index for assessing cardiac function. Our study aimed to elucidate the impact of RV pacing on EL in normal LV function and hypertrophic cardiomyopathy (HCM) patients. A total of 36 patients with dual‐chamber pacemakers for sick sinus syndrome or implantable cardioverter defibrillators for fatal ventricular tachyarrhythmias were enrolled. All patients were divided into two groups: 16 patients with HCM (HCM group) and others (non‐HCM group). The absolute changes in EL under AAI (without RV pacing) and DDD (with RV pacing) modes were assessed using VFM on color Doppler echocardiography. In the non‐HCM group, the mean systolic EL significantly increased from the AAI to DDD modes (14.0 ± 7.7 to 17.0 ± 8.6 mW/m, P= .003), whereas the mean diastolic EL did not change (19.0 ± 12.3 to 17.0 ± 14.8 mW/m, P= .231). In the HCM group, the mean systolic EL significantly decreased from the AAI to DDD modes (26.7 ± 14.2 to 21.6 ± 11.9 mW/m, P< .001), whereas the mean diastolic EL did not change (28.7 ± 16.4 to 23.9 ± 19.7 mW/m, P= .130). RV pacing increased the mean systolic EL in patients without HCM. Conversely, RV pacing decreased the mean systolic EL in patients with HCM. In non‐HCM patients, the RV pacing decreased the vortex area and the circulation and in HCM patients, it increased the vortex area and the circulation. The RV pacing significantly increased systolic energy loss in the non‐HCM group (P= .003), but it significantly decreased in the HCM group (P< .001). The effects of RV pacing on intraventricular blood flow were significantly different between non‐HCM and HCM patients.

We performed cavotricuspid isthmus (CTI) linear ablation for atrial flutter; however, the tachycardia cycle length was not changed at all. In such cases, repeated or broad line ablation is usually performed. We presented that high‐density three‐dimensional mapping after the first CTI linear ablation, which revealed the complex tachycardia circuit with the epicardial and endocardial breakthrough.

Plasma irradiation of cancer is expected to activate a cancer-specific immune response; however, its long-term systemic effect in animal models has not been sufficiently investigated. In this paper, the long-term systemic effect induced by plasma irradiation was examined using C57BL/6 mice inoculated with B16F10 melanoma. Melanoma tumors on the right hind legs of the mice were resected after treatment with nanosecond pulsed streamer discharge. The results showed that plasma treatment delayed the growth of recurrent tumors at the site of resection. In addition, plasma treatment delayed the growth of tumors reinoculated at the nonirradiated site on the left leg of the mice after resection. Histological and single-cell analyses revealed that plasma had no direct effect on primary tumors, whereas it enhanced cytotoxic T cell infiltration into reinoculated tumors. These results suggest that plasma treatment induces cancer-specific long-term immune memory in mice.

We isolated a cold sensitive virescent1(csv1) mutant from a rice (Oryza sativaL.) population mutagenized by carbon ion irradiation. The mutant exhibited chlorotic leaves during the early growth stages, and produced normal green leaves as it grew. The growth of csv1plants displayed sensitivity to low temperatures. In addition, the mutant plants that were transferred to low temperatures at the fifth leaf stage produced chlorotic leaves subsequently. Genetic and molecular analyses revealed translocation of a 13-kb genomic fragment that disrupted the causative gene (CSV1; LOC_Os05g34040). CSV1encodes a plastid-targeted oxidoreductase-like protein conserved among land plants, green algae, and cyanobacteria. Furthermore, CSV1transcripts were more abundant in immature than in mature leaves, and they did not markedly increase or decrease with temperature. Taken together, our results indicate that CSV1supports chloroplast development under cold stress conditions, in both the early growth and tillering stages in rice.

A 57‐year‐old man was admitted to our hospital due to syncopal attack. He was diagnosed with Brugada syndrome due to which a subcutaneous implantable cardiac defibrillator (S‐ICD) was inserted using the standard technique. Two hours after the implantation, he experienced inappropriate shock while conscious. Device interrogation revealed a contentious baseline shift and frequent oversensing of low‐amplitude signals, which was followed by a shock. Lateral chest X‐ray revealed subcutaneous air surrounding the proximal electrode. Another inappropriate shock could be avoided by changing the sensing vector. The subcutaneous air was completely resolved 7 days after implantation.

► We analyzed germline mutations induced by 290-keVμm−1heavy-ion beams in Arabidopsis. ► Ar- and C-ion beams induced large deletions (100bp) and rearrangements. ► The proportion of large deletions increased with increasing LET.

Aim:Ablation index (AI) is a useful tool of CARTO? system to make effective lesions during a pulmonary vein isolation (PVI) for atrial fibrillation (AF) ablation. However, the optimal distance between neighboring ablation points (inter-lesion distance; ILD) during AI-guided PVI is still unclear. Here, we evaluated the effective ILD in AI-guided PVI.Methods:Forty-seven AF patients who underwent AI guided-PVI in our institute from July 2018 to March 2019 were retrospectively enrolled in this study. Target AI was set at 550 in anterior wall and 400 in posterior wall based on the previous report, and we compared the ILD with and without electrical gaps after a first encircling PVI.Results:In the right PV (RPV), the ILDs with electrical gaps were longer compared with that without electrical gaps (anterior wall: 5.3?2.0 vs. 4.3?1.2 mm, p<0.0001, posterior wall: 5.8?2.0 vs. 4.9?1.6, p<0.0001). Similarly, in the left PV (LPV), the ILD with electrical gaps was also longer than that without electrical gaps (anterior: 5.8?1.9 vs. 4.2?1.5 mm, p<0.0001, posterior: 6.5?2.4 vs. 5.2?1.9 mm, p<0.05). The best cutoff values of ILD to detect the electrical gaps using ROC curve were 5.4 mm (AUC 0.67, sensitivity 0.42, specificity 0.83, p<0.001) for the RPV anterior wall, and 4.4 mm (AUC 0.67, sensitivity 0.91, specificity 0.40, p<0.001) for the RPV posterior wall. Similarly, in the LPV, the best cutoff value of ILD was 5.5 mm (AUC 0.74, sensitivity 0.65, specificity 0.82, p<0.0001) for the LPV anterior wall, and 5.1 mm (AUC 0.67, sensitivity 0.79, specificity 0.52, p<0.05) for the LPV posterior wall.Conclusion:Shorter than 5.4/4.4 mm (anterior/posterior wall) in the RPV, and 5.5/5.1 mm (anterior/posterior wall) in the LPV were cutoff values of the inter-lesion distance to reduce the electrical gaps under AI-guided PVI.

Background:Recurrence of atrial fibrillation (AF) after catheter ablation (CA) during blanking period (BP) is associated with the long-term recurrence of AF. However, the predictors of the AF recurrence during BP and whether the prophylactic administration of anti-arrhythmic drug (AAD) during BP suppress the long-term recurrence of AF remain unclear. Here, we sought to elucidate the predictors of AF recurrence during BP (Study 1), and the effect of AAD during BP for the long-term recurrence of AF (Study 2).Methods:Study 1: The study population consisted of 729 patients who were treated with CA for AF during 2014 to 2019. We determined the factors of recurrence AF during BP by the logistic regression analysis, and constructed a scoring system using these factors. Study 2: In the high risk patients extracted by our scoring system, we retrospectively evaluated the long-term AF recurrence with or without prophylactic AAD during BP (AAD or non-AAD groups). AAD was started on the same day after CA. The primary endpoint was the recurrence of AF or other atrial tachy-arrhythmia after the 90-day blanking period. Observational period was set at 1 year after the index ablation.Result:Study 1: In the logistic regression and the ROC curve, higher age (> 66 year-old), persistent or long-standing persistent AF, radiofrequency CA (not cryoballoon CA), performed mitral isthmus ablation, concomitance with congestive heart failure, larger left atrial dimension (> 41 mm), and higher BNP (> 78 pg/ml) were determined as the factors of recurrence AF during BP and assigned 1 point for each parameter (minimum 0, maximum 7). When we set the threshold as 4 points for prediction of the recurrence, it achieved 72% sensitivity and 57% specificity (p< 0.0001, AUC = 0.67). Study 2: In the next study, 157 patients were classified as the high risk (score 4-7 points) of AF recurrence during the BP. In those patients, of the long-term AF recurrence occurred in 43 (27%). The AAD group (n=45) showed significantly lower recurrence rate than the non-AAD group (p= 0.04, HR 2.26; 95%CI 1.072 to 5.554).Conclusions:In the patients with high risk of AF recurrence during BP, prophylactic AAD during BP was effective for the suppression of long-term AF recurrence.

Background:Gastric hypoperistalsis (GH) is possible complication of catheter ablation (CA) for atrial fibrillation (AF). Usefulness of esophagus temperature monitoring to avoid esophageal injuries has been controversial, however, the relationship between GH and this system remains unclear. Here, we sought to elucidate the relationship between esophagus temperature and asymptomatic GH evaluated by gastrointestinal endoscopy.Methods:The study population consisted of 254 patients who were treated with CA for AF during November 2017 to October 2018. We excluded the patients who underwent cryoballoon ablation, lack of data of esophagus temperature. Temperature alarm was set at 40 degree Celsius, and patients without the esophagus temperature alarm were also excluded because of the lack of temperature data. Finally, 102 patients were enrolled in this study. Patients underwent gastrointestinal endoscopy the day after the index CA with at least 12 hours of fasting. GH was defined as a food stagnation in the stomach despite of an inanition. We evaluated clinical background and ablation procedure including esophagus temperature by dividing into GH group and non-GH group.Results:The median age was 66 (59 - 75) years old with 30% of females. The GH were observed in 25% of the patients performed CA in this study, which was significantly more frequent than the incidence of GH in general populations (1.7%). The highest esophagus temperature showed higher in the GH group than that in the non-GH group (42.6?C vs. 41.8?C, p= 0.027). When we determined the esophageal temperature detected GH using ROC curve, 42.4?C of esophagus temperature was the best value with 64% sensitivity and 64% specificity (p= 0.0214, area under curve 0.65).Conclusion:Esophagus temperature monitoring is useful for the prediction of the asymptomatic gastric hypoperistalsis after radiofrequency catheter ablation for atrial fibrillation.

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