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Objective: The high prevalence of diabetes in non-Caucasian populations is reported not only for Native Hawaiians who suffer from high rates of obesity, but also for Japanese with a relatively low body weight. The objectives of this study were to estimate the prevalence of diabetes among participants of the Multiethnic Cohort (MEC) and to examine the association of body mass index (BMI) with self-reported diabetes by ethnicity.Design: Cross-sectional analysis of baseline questionnaire at cohort entry.Participants: 187,439 MEC subjects in Hawaii and California from five ethnic groups.Main Outcome Measures: Participants completed a 26-page, self-administered survey with questions concerning anthropometrics, demographic, medical, lifestyle, and food consumption behavior. Age-adjusted prevalence of diabetes was calculated by sex and ethnicity and stratified by BMI. Prevalence ratios were determined using logistic regression while adjusting for variables that are known to be related to diabetes. The c statistic was computed to compare models with different confounders.Results: The prevalence of self-reported diabetes in the MEC was 11.6%. The age-adjusted diabetes prevalence ranged from 6.3% in Caucasians to 10.2% in Japanese, 16.1% in Native Hawaiians, 15.0% in African Americans, and 15.8% in Latinos. After adjustment for known risk factors, the prevalence ratio by ethnicity ranged between 2.1 (African American and Latino), 2.8 (Japanese), and 3.0 (Native Hawaiian) as compared to Caucasians. These differences were observed among all BMI categories.Conclusions: Ethnic differences in the prevalence of diabetes persisted after stratification by BMI. The prevalence of diabetes was at least two-fold higher in all ethnic groups than among Caucasians. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop a prediction model for intestinal perforation from meconium ileus (MI) based on findings from plain X-ray images., Methods: Very low birth weight (VLBW) infants with MI hospitalized in two tertiary centers between 2011 and 2022 were included in this study. We retrospectively reviewed clinical parameters and assessed plain X-ray images from 0 to 5 days of age. The standardized transverse diameter of intestinal gas (STDI) was calculated by dividing the largest diameter of the intestinal gas by the distance from the upper edge of L1 to the lower edge of L4. We then compared the STDI of patients with and without intestinal perforation., Results: Among 81 VLBW infants with MI, intestinal perforation occurred in 6 (7 %). Among known risk factors, significant differences were observed between the two groups regarding pregnancy-induced hypertension (p = 0.03), weeks of gestation (p < 0.01), birthweight (p = 0.02), and indomethacin administration (p < 0.01). The mortality rate was higher in the perforation group (33 %) than in the non-perforation group (3 %) (p = 0.021). There were significant differences between the perforated and non-perforated groups regarding STDI except at 0 days of age. The positive and negative predictive cut-off values of STDI were respectively 0.08 and 0.93 on day 0, 0.30 and 1.00 on day 1, 0.33 and 0.97 on day 2, 0.33 and 1.00 on day 3, 0.29 and 1.00 on day 4, and 0.33 and 0.98 on day 5, respectively., Conclusions: Our novel prediction model, using STDI, predicted intestinal perforation in VLBW infants with MI., Levels of Evidence: Level Ⅲ., Competing Interests: Conflicts of interest The authors have no financial conflicts of interest to disclose concerning the study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bipolar voltage amplitude is capable of helping determine the ideal lesion size index (LSI) setting during radiofrequency ablation for atrial fibrillation (AF)., Objective: We aimed to determine whether voltage-guided pulmonary vein isolation (PVI) is noninferior to conventional LSI-guided PVI in patients with nonvalvular AF., Methods: This was a multicenter randomized trial conducted during a period of 12 months. The primary efficacy end points of the study were AF recurrence, atrial flutter, and atrial tachycardia, and the noninferiority margin was set at a hazard ratio of 1.4. The primary safety end point was a composite of procedure-related complications., Results: A total of 370 patients underwent randomization; 189 and 181 were assigned to the voltage (underwent voltage-guided PVI) and control (underwent conventional LSI-guided PVI) groups, respectively. The primary efficacy end point occurred in 22 patients (12.0%) in the voltage group and 23 patients (12.9%) in the control group (1-year Kaplan-Meier event-free rate estimates, 88.0% and 87.1%, respectively; hazard ratio, 1.00; 95% confidence interval, 0.80-1.25). The primary safety end points were 4.8% in the voltage group and 6.6% in the control group (P = .2791). PVI time was significantly shorter in the voltage group (35.7 ± 14.5 minutes vs 39.7 ± 14.7 minutes; P < .001)., Conclusion: Voltage-guided PVI was noninferior to conventional LSI-guided PVI with respect to efficacy in the treatment of patients with AF, and its use significantly reduced procedure time. UMIN Clinical Trials Registry: UMIN000042325., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The lesion size index (LSI) predicts radiofrequency (RF) ablation lesion size and is an established parameter for pulmonary vein isolation. However, the effectiveness and safety of LSI for cavotricuspid isthmus (CTI) linear ablation remain unclear., Methods: This single-center retrospective study included 50 of patients (67 ± 10 years, 68% male) who underwent de novo CTI linear ablation between July 2020 and December 2020. The LSI target was set at 5.0 and 4.0 for the anterior 2/3 and posterior 1/3 segments, respectively. Acute procedural parameters of ablation were evaluated., Results: Acute bidirectional CTI block was achieved in all patients with an RF application time of 4.0 min (3.1-5.0 min), RF application number of 15 ± 7, and length of CTI of 36.9 ± 9.3 mm. First-pass bidirectional conduction block of the CTI was achieved in 39/50 (78%) patients. No major complications were observed. The contact force (CF) per application was significantly lower in the gap tag group than in the non-gap tag group (7 g [7-8 g] vs. 10 g [7-12 g], P = 0.0284)., Conclusions: LSI-guided CTI linear ablation is an effective and safe treatment approach. CF affects gap formation, even when the target LSI is the same., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The mechanical properties of the myocardium in the left ventricle and right atrium were estimated by simultaneously measuring the local impedance (LI) and contact force (CF) using an ablation catheter. Radiofrequency catheter ablation (RFCA) is a well-established arrhythmia treatment. Monitoring the RF power, CF and properties of myocardium during RFCA are necessary to estimate the effect of ablation. Indices, such as CF, lesion size index and ablation index, do not include the myocardium mechanical properties. Therefore, there is the risk of side effects, such as cardiac tamponade, by excessive catheter indentation into vulnerable areas. We propose the simultaneous measurement of LI and CF for estimating the myocardial mechanical properties to reduce the side effects. In this study, an in vitro experimental system was constructed to measure LI and CF via the catheter. The relationship between the porcine myocardial tissue thickness and CF-LI curve was investigated using the left ventricle and right atrium. Power function coefficients approximating the CF-LI curve increased with thicker left ventricle. The thickness of the myocardium can be estimated by simultaneously measuring LI and CF. Intraoperative measurement of the myocardial mechanical properties can be used to determine the ablation conditions at each site.

Purpose: Although the impairment of regulatory T-cells (Tregs) has been shown in the liver or portal area of biliary atresia (BA) the frequency and function of circulating Tregs in BA patients is poorly understood. We aimed to investigate the frequency and function of circulating Tregs in BA patients., Methods: Peripheral blood mononuclear cells were collected from 25 BA patients and 24 controls. Treg frequency was measured by flow cytometry; function was determined by T-cell proliferation assay. We also assessed the association between Treg frequency/function and clinical parameters in BA cases., Results: There was no significant difference between the two groups in both frequency (BA: 3.4%; control: 3.2%; p = 0.97) and function (BA: 22.0%; control: 7.5%; p = 0.23) of Tregs. We further focused on 13 preoperative BA patients and 14 age-matched controls. Neither Treg frequency nor function were significantly different (frequency: BA: 4.6%; control: 3.4%; p = 0.38, function: BA: 2.7%; control: 7.6%; p = 0.89). There was no association between Treg frequency/function and clinical parameters., Conclusion: Neither the frequency nor function of circulating Tregs was affected in BA patients, suggesting the negative role of circulating Tregs in the pathogenesis of BA. Further investigation of local Treg profiles is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: 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)., Methods: 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 (RMS 20 ) and the P-wave duration (PWD). Positive ALPs were defined as an RMS 20 <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., Results: 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)., Conclusions: Positive ALP on pre-CA P-SAECG is associated with AF recurrence after CA., Competing Interests: The authors declare no conflict of interests for this article., (© 2022 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Introduction: Direct comparison studies about the incidence of esophagogastric complications between radiofrequency (RF) and cryoballoon (CB) catheter ablation (CA) for atrial fibrillation (AF) have been scarce. We sought to elucidate the relationship between the pulmonary vein isolation (PVI) modalities and esophagogastric complications., Methods: The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 160 patients were enrolled and divided into the RF and CB groups. Esophageal ulcers, gastric hypomotility, and exfoliative esophagitis detected by esophagogastroduodenoscopy were defined as esophagogastric complications in this study., Results: The median age was 68 years old, with 34% being females. Esophagogastric complications were observed in 42.5% of patients who underwent CA. According to the detailed esophagogastric complications, the RF group had a higher prevalence of esophageal ulcers than the CB group (19% vs. 0%, p < .0001). There was no significant difference between the two groups regarding gastric hypomotility and exfoliative esophagitis (18% vs. 28%; p = .15 and 16% vs. 21%; p = .42, respectively)., Conclusion: Asymptomatic esophagogastric complications were common in CA for AF. The incidence of esophageal ulcers was higher in the RF group than in the CB group, whereas the other esophagogastric complications did not significantly differ., (© 2022 Wiley Periodicals LLC.)

The recurrence of atrial fibrillation (AF) after catheter ablation (CA) is still an unsolved issue. Although structural remodeling is relatively well defined, the method to assess electrical remodeling of the atrium is not well established. In this study, we evaluated the relationship between atrial conduction properties and recurrence after CA for AF. One hundred six consecutive patients (66 ± 11 years old, male: 68%) who underwent CA for AF with a CARTO system from July 2016 to July 2019 were enrolled in this study. An activation map of both atria was constructed to precisely evaluate the total conduction time, distance, and conduction velocity between the earliest and latest activation sites during sinus rhythm. All parameters were compared between the patients with or without AF recurrence. Of the patients, 27 had an AF recurrence (Rec group). The left atrial (LA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (101.2 ± 17.9 vs. 116.9 ± 18.0 cm/s, P < 0.01). Likewise, the right atrial (RA) conduction velocity was significantly slower in the Rec group than in the non-Rec group (81.1 ± 17.5 vs. 103.6 ± 25.4 cm/s, P < 0.01). A multivariate logistic analysis demonstrated that the LA and RA conduction velocities were independent predictors of AF recurrence, with adjusted odds ratios of 0.95 (95% confidential interval: 0.91-0.98, P < 0.01) and 0.94 (0.89-0.98, P < 0.01), respectively. In conclusion, slower conduction velocity of the atrium was associated with AF recurrence after pulmonary vein isolation., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: Local impedance (LI) can indirectly measure catheter contact and tissue temperature during radiofrequency catheter ablation (RFCA). However, data on the effects of catheter contact angle on LI parameters are scarce. This study aimed to evaluate the influence of catheter contact angle on LI changes and lesion size with two different LI-sensing catheters in a porcine experimental study., Methods: Lesions were created by the INTELLANAV MiFi™ OI (MiFi) and the INTELLANAV STABLEPOINT™ (STABLEPOINT). RFCA was performed with 30 W and a duration of 30 s. The contact force (CF) (0, 5, 10, 20, and 30 g) and catheter contact angle (30°, 45°, and 90°) were changed in each set (n = 8 each). The LI rise, LI drop, and lesion size were evaluated., Results: The LI rise increased as CF increased. There was no angular dependence with the LI rise under all CFs in the MiFi. On the other hand, the LI rise at 90° was lower than at 30° under 5 and 10 g of CF in STABLEPOINT. The LI drop increased as CF increased. Regarding the difference in catheter contact angles, the LI drop at 90° was lower than that at 30° for both catheters. The maximum lesion widths and surface widths were smaller at 90° than at 30°, whereas there were no differences in lesion depths., Conclusion: The LI drop and lesion widths at 90° were significantly smaller than those at 30°, although the lesion depths were not different among the 3 angles for the MiFi and STABLEPOINT., (© 2022 Wiley Periodicals LLC.)

The clinical features and risk factors of acute appendicitis in infants are unclear. Our aim was to evaluate the association between anthropometrics and the occurrence of infantile appendicitis. This was a retrospective study of infants (<6 years of age) and school-age children (6-10 years of age) of Asian ethnicity who required hospitalization for appendicitis at our two participating institutions between 2004 and 2018. The Z-score for height, body weight, and body mass index (BMI) was compared between the two groups, as well as between patients presenting with perforated and non-perforated appendicitis. The analysis included data from 73 infants and 362 school-age children. Z-scores were greater in infants than in school-age children for height (0.37 versus -0.03, p = 0.003) and body weight (0.12 versus -0.36, p = 0.023), with no between-group difference for the Z-score of BMI. There was no difference in Z-scores for height, weight, and BMI between the perforated and non-perforated appendicitis infant groups. Infants presenting with acute appendicitis were characterized by a larger physique but with normal proportion. This trend was not observed in school-age children. Therefore, larger infants presenting with abdominal pain should be screened for appendicitis.

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., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Purpose: Ablation index (AI) is a useful tool of the CARTO® system to make effective lesions during pulmonary vein isolation (PVI) for atrial fibrillation (AF). However, the optimal distance between neighboring ablation points (interlesion distance (ILD)) is still unclear. Here, we evaluated the optimal ILDs in the AI-guided PVI., Methods: Forty-nine 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 500 and 400 for anterior and posterior walls, respectively, and we compared the ILDs with and without electrical gaps after a first encircling PVI., Results: In both PV, the ILDs with electrical gaps were longer than those without electrical gaps. The best cutoff values of ILD to detect the electrical gaps using the ROC curve were 5.4 mm for the RPV anterior wall (AUC, 0.67; sensitivity, 0.42; specificity, 0.84, P < 0.01) and 4.4 mm for the RPV posterior wall (AUC, 0.68; sensitivity, 0.91; specificity, 0.39, P < 0.01). Similarly, the best cutoff values of ILD were 5.5 mm for the LPV anterior wall (AUC, 0.74; sensitivity, 0.65; specificity, 0.82, P < 0.01) and 5.1 mm for the LPV posterior wall (AUC, 0.67; sensitivity, 0.79; specificity, 0.53, P =0.03)., Conclusion: The optimal interlesion distances for PVI were different in each PV segment. To achieve the first-pass isolation, less than 5.4/4.4 mm for the RPV anterior/posterior and 5.5/5.1 mm for the LPV anterior/posterior walls of interlesion distances were the best cutoff values in the patients with AF., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The incidence of new-onset atrial high-rate episode (AHRE) is higher among patients with cardiac implantable electronic devices (CIEDs) than in the general population. We sought to elucidate the clinical factors associated with AHRE in CIED patients, including P-wave dispersion (PWD) in sinus rhythm. Methods and Results: In all, 101 patients with CIEDs newly implanted between 2010 and 2014 were included in the study. PWD was measured at the time of device implantation via a body-surface electrocardiogram. AHRE was defined as any episode of sustained atrial tachyarrhythmia (>170 beats/min) recorded in the device's memory. Patients were divided into an AHRE (n=34) and non-AHRE (n=67) group based on the presence or absence of AHRE within 1 year of device implantation and compared. Mean (±SD) patient age was 75±11 years. A greater incidence of sick sinus syndrome (P=0.05) and longer PWD (62.6±13.1 vs. 38.2±13.9 ms; P<0.0001) were apparent in the AHRE than non-AHRE group. Multivariate analysis revealed that PWD was an independent predictor of new-onset AHRE (odds ratio 1.11; 95% confidence interval 1.06-1.17; P<0.0001). In logistic regression analysis, receiver-operating characteristic curve analysis (area under the curve 0.90; P<0.001) suggested the best cut-off value for PWD was 48 mm (sensitivity 73.8%, specificity 77.9%). Conclusions: PWD is a simple but feasible predictor of new-onset AHRE in patients with CIEDs., Competing Interests: J.A. is a member of Circulation Reports’ Editorial Team. The authors declare there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported herein., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Background: 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., Methods: 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., Results: 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)., Conclusion: Low o-LSI was strongly associated with IAS, potentially providing a novel index to improve first-pass PV isolation., Competing Interests: This study received no financial support from commercial sources, and the authors have no conflicts of interest to declare., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Background: Gastric hypomotility (GH) is a possible complication of catheter ablation (CA) for atrial fibrillation (AF). However, it is unclear which factors are associated with GH. We sought to elucidate the relationship between the CA procedure and GH., Methods: The study population consisted of 254 patients who underwent CA for AF from November 2017 to October 2018. Finally, 119 patients were enrolled and divided into two groups: with or without GH (GH or non-GH groups). To evaluate the association with GH, the clinical backgrounds and procedure characteristics of the radiofrequency CA (RFCA) were compared between the two groups., Results: The median age was 69 years old with 34% of female. GH were observed in 27.7% of patients who underwent RFCA, which was significantly higher than that in the cohort of patients who underwent esophago-gastro-duodenoscopy during the same time period (1.9%: 151 in 8063 patients, p < 0.0001). According to the detailed RFCA procedure, additional posterior wall isolation with pulmonary vein isolation (PVI) had a higher prevalence of GH than that with only PVI (54.8% vs. 18.2%; odds ratio 5.46, 95%CI 2.24-13.32, p = 0.0002). After an adjustment using a multivariate logistic analysis, a posterior wall isolation with the PVI was identified as the only independent predictor for GH (odds ratio 5.01, 95%CI 1.94-13.43, p = 0.0009)., Conclusions: Additional posterior wall isolation with PVI was associated with gastric hypomotility., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Recent clinical trials have demonstrated the possible pleiotropic effects of SGLT2 (sodium-glucose cotransporter 2) inhibitors in clinical cardiovascular diseases. Atrial electrical and structural remodeling is important as an atrial fibrillation (AF) substrate. Methods and Results The present study assessed the effect of canagliflozin (CAN), an SGLT2 inhibitor, on atrial remodeling in a canine AF model. The study included 12 beagle dogs, with 10 receiving continuous rapid atrial pacing and 2 acting as the nonpacing group. The 10 dogs that received continuous rapid atrial pacing for 3 weeks were subdivided as follows: pacing control group (n=5) and pacing+CAN (3 mg/kg per day) group (n=5). The atrial effective refractory period, conduction velocity, and AF inducibility were evaluated weekly through atrial epicardial wires. After the protocol, atrial tissues were sampled for histological examination. The degree of reactive oxygen species expression was evaluated by dihydroethidium staining. The atrial effective refractory period reduction was smaller ( P =0.06) and the degree of conduction velocity decrease was smaller in the pacing+CAN group compared with the pacing control group ( P =0.009). The AF inducibility gradually increased in the pacing control group, but such an increase was suppressed in the pacing+CAN group ( P =0.011). The pacing control group exhibited interstitial fibrosis and enhanced oxidative stress, which were suppressed in the pacing+CAN group. Conclusions CAN and possibly other SGLT2 inhibitors might be useful for preventing AF and suppressing the promotion of atrial remodeling as an AF substrate.

Background: 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., Methods: 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., Results: 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)., Conclusions: RV pacing increased the mean systolic EL in patients without HCM. Conversely, RV pacing decreased the mean systolic EL in patients with HCM., Competing Interests: The authors declares that there are no conflicts of interest related to this study., (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

We prospectively collected device and heart rate data through remote monitoring (RM) of patients with an implantable cardioverter defibrillator (ICD). The objective was to identify the predictors of lethal arrhythmic events (VT/VF).Thirty-three patients (mean age: 50 years) with ICDs [with functionality of heart rate variability (HRV) analysis] were divided into two groups [VT/VF (+), VT/VF (-) ]. Clinical, device (ventricular lead impedance; amplitude of ventricular electrogram), and HRV data were compared between the two groups. The NN interval-index (SDNNi) was calculated for every 5 minutes, and the mean, maximum, minimum, and standard deviation of SDNNi during the 24-hour period were used.During the observation period of 13 ± 10 months, 10 patients experienced VT/VF events. Total mean, max, and min SDNNi were higher in the VT/VF (+) than the VT/VF (-) group (132.9 ± 9.3 versus 93.5 ± 6.1, P = 0.0013; 214.6 ± 10.6 versus 167.0 ± 7.0, P = 0.0007; 71.2 ± 7.5 versus 43.9 ± 4.9, P = 0.0047). On logistic regression analysis, a total mean SDNNi of 100.1, max SDNNi of 185.0 and min SDNNi of 52.0 as cut-off values for prediction of a VT/VF event demonstrated significant receiver operating characteristic (ROC) curves (AUC = 0.86, P = 0.0007; AUC = 0.84, P = 0.0005; AUC = 0.78, P = 0.0030). The max ΔSDNNi, i.e., difference from baseline SDNNi, and min ΔSDNNi in 7 and 28 days preceding VT/VF events were significant predictors of VT/VF events.Time-domain HRV analysis through a RM system may help identify patients at high risk of lethal arrhythmic events; in addition, it may help predict the occurrence of lethal arrhythmic events in specific cases.

Complex atrial tachycardias (ATs) after catheter ablation or a MAZE procedure is sometimes difficult to determine the circuits of the tachycardia. A high-density, grid-shapes mapping catheter has been launched, which can be useful for detecting the detail circuits of tachycardias on three-dimensional mapping systems. The signal quality is also important for performing electrophysiological studies (EPSs), such as entrainment mapping, to identify the circuit. This unique mapping catheter has 1 mm electrodes on 2.5 Fr shafts, which improve the signal quality. The high-quality intracardiac electrograms facilitate differentiating small critical potentials, which allows us to perform detailed entrainment mapping in targeted narrow areas. Here, we describe a patient with a perimetral AT with epi-endocardium breakthrough after a MAZE surgery and catheter ablation, which was treated successfully along with detailed entrainment mapping using the HD Grid. This catheter with high-quality signals could be a significant diagnostic tool for a classic EPS as well as for the construction of 3D mapping.

Background: The wearable cardioverter defibrillator (WCD) has been available since 2014 in Japan, and its benefit in the in-hospital acute phase at high risk of ventricular tachyarrhythmia (VTA) has been established, but its clinical use in the outpatient setting remains unclear, especially in Japan. Methods and Results: The subjects consisted of 43 consecutive patients with WCD use in the outpatient setting from April 2014 to October 2019 at the present institute. Event alerts and wearing compliance were checked via the remote monitoring system, and a dedicated WCD training team contacted the patients if necessary. The median observation period was 51 days (IQR, 37-68 days) and the median daily wearing time was 23.1 h/day (IQR, 22.0-23.6 h/day). WCD was prescribed for primary prevention of VTA in 7 patients (16%), and for secondary prevention in 36 (84%). The common reason for WCD use was preventive therapy and/or clinical observation. Two appropriate and one inappropriate shock were observed. Eleven patients were not indicated for ICD because of successful catheter ablation optimal medical therapy, VTA in early onset of heart disease and refusal. The remaining 32 patients, however, underwent ICD implantation. Conclusions: In the present real-world study, the WCD wearing compliance was well-maintained in the outpatient setting. WCD is useful for patients at high risk of VTA., Competing Interests: A.H., J.K., S.N., D.S., G.M., T.S., Y.S., S.K., Y.A., R.N., H.N., N.I., J.O., and A.S. declare no conflicts of interest. H.F. received lecture fees from Boehringer Ingelheim and Daiichi-Sankyo. J.A. received research funding from Bristol Meyers, Pfizer, Boehringer Ingelheim, Bayer, Daiichi-Sankyo, and lecture fees from Sanofi, Bristol-Meyers, Pfizer, Boehringer Ingelheim, Bayer, and Daiichi-Sankyo. J.A. is a member of Circulation Reports’ Editorial Team., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

Background: The relationship between atrial high-rate episode (AHRE) burden (i.e., the frequency of atrial tachyarrhythmia) and heart failure (HF) risk is unclear. We hypothesized that new-onset and higher burden of AHRE are associated with HF., Methods and results: We included 104 consecutive patients with cardiac implantable electronic devices (CIEDs) capable of continuous atrial rhythm monitoring. Patients with AF history were excluded. To stratify patients, AHREs were evaluated only during the initial 1 year after CIED implantation. The primary endpoint was all-cause death or new-onset or worsening HF that required unplanned hospitalization or readjustment of HF drug therapy. At 1 year after CIED implantation, 34/104 patients (33%) exhibited AHREs. No difference in basal clinical characteristics except for left ventricular ejection fraction between patients with and without new-onset AHREs was found. AHRE groups had more HF events than the non-AHRE group. All patients were divided into 3 groups based on AHRE burden: none, low, and high. Worsening HF was observed in 12 patients (12%). Cox hazard analysis revealed that AHRE and higher AHRE burden were independent predictive factors for worsening HF. The high group showed a higher risk for HF than the non-AHRE groups, but no significant difference was found between the low- and non-AHRE groups., Conclusions: New-onset higher AHRE burden was associated with subsequent risk for HF in patients with CIEDs.

Purpose: Fatality resulting from respiratory collapse (RC) during general anesthesia (GA) induction in children with mediastinal tumors has been reported. We explored potentially useful parameters for predicting the risk of RC based on objective imaging results., Methods: We retrospectively reviewed the records of 31 patients (median age: 4years; range: 4months-15years) with mediastinal tumors treated between 2000 and 2015. Comparing those with RC under GA induction to those without (RC group vs. non-RC group), we analyzed a variety of factors that might predict respiratory obstruction during GA induction, including our new parameter, the standardized tumor volume (STV), which is adapted from the formula for the volume of an ellipsoid., Results: All eight patients in the RC group had large tumors in the anterior mediastinum, including lymphoma, teratoma, and germ cell tumor. The mean STV value of the RC group was significantly larger than that of the non-RC group (3.6±1.4 vs. 1.4±1.0, p=0.006). Using an STV cut-off value of 2.5, the sensitivity and specificity for predicting RC under GA induction were both 0.86, making STV more useful than previously reported risk factors., Conclusion: Anterior mediastinal tumors in children can often cause airway obstruction under GA induction. Measuring STV can help predict the respiratory risk during GA among pediatric patients with anterior mediastinal tumors., Level of Evidence: III., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The incidence of delayed bleeding after endoscopic submucosal dissection (ESD) for gastric neoplasms is reported to be approximately 5 %. We examined whether postprocedural combined treatment using the coagulation plus artery-selective clipping (2C) method is a useful measure for preventing delayed bleeding after ESD., Methods: A total of 234 gastric epithelial neoplasms were treated from June 2007 to May 2012. Post-ESD coagulation (PEC) and clipping for part of the vessels was performed for 154 lesions from June 2007 to June 2010. A total of 80 lesions were treated using the 2C method from July 2010 to May 2012. During ESD, the locations of the arteries were recorded on a schematic diagram of the lesion. Arteries were defined as regions of arterial bleeding that required coagulation or apparent arteries in which preventive coagulation was performed. When ESD was completed, soft coagulation was performed for arteries in the resection area using hemostatic forceps, followed by arterial clipping for additional strength. Coagulation also was performed continuously for visible vessels in the resection area. This was a retrospective study. The incidence rates of delayed bleeding after ESD, as evidenced by hematemesis or melena, or the presence of anemia (decline in Hb >2 g/dl) that required emergency endoscopy were recorded., Results: Delayed bleeding occurred in 7 (4.5 %) of the 154 cases treated using PEC and in 1 (1.3 %) of the 80 cases treated using the 2C method. The mean time required for the 2C method was 15.0 ± 7.0 min (range, 5-44 min). The mean number of clippings per lesion was 3.8 ± 2.8 (range, 0-13). Almost all clips fell off within 2 months of the procedure., Conclusions: Coagulation plus artery-selective clipping (the 2C method) of post-ESD ulcers might effectively reduce the incidence of delayed bleeding after ESD for gastric neoplasms.

The 2012 American College of Clinical Pharmacy (ACCP) Certification Affairs Committee was charged with developing guidelines for the desired professional development pathways for clinical pharmacists. This document summarizes recommendations for postgraduate education and training for graduates of U.S. schools and colleges of pharmacy and describes the preferred pathways for achieving, demonstrating, and maintaining competence as clinical pharmacists. After initial licensure within the state or jurisdiction in which the pharmacist intends to practice, completion of an accredited PGY1 pharmacy residency is recommended to further develop the knowledge and skills needed to optimize medication therapy outcomes. An accredited PGY2 pharmacy residency should be completed if a pharmacist wishes to seek employment in a specific therapeutic area or practice setting, if such a residency exists. Clinical pharmacists intending to conduct advanced research that is competitive for federal funding are encouraged to complete a fellowship or graduate education. Initial certification by the Board of Pharmacy Specialties (BPS) or other appropriate sponsoring organizations should be completed in the desired primary therapeutic area or practice setting within 2 years after accepting a position within the desired specific therapeutic area or practice setting. Clinical pharmacists subsequently will need to meet the requirements to maintain pharmacist licensure and board certification. Traineeships, practice-based activities, and certificate programs can be used to obtain additional knowledge and skills that support professional growth. Pharmacists are strongly encouraged to adopt a lifelong, systematic process for professional development and work with ACCP and other professional organizations to facilitate the development and implementation of innovative strategies to assess core practice competencies., (© 2013 Pharmacotherapy Publications, Inc.)

Background: Standard choledochal cyst (CC) operations involve dilated extrahepatic bile duct excision followed by biloenterostomy. However, biliary variants and associated intrahepatic bile duct (IHBD) stenoses or dilatations triggering postoperative sequelae require additional procedures. The usefulness of preoperative 3-dimensional magnetic resonance cholangiopancreatography (3D MRCP) and virtual cholangioscopy (VES) for observing biliary morphology and pancreaticobiliary maljunction (PBM) was evaluated., Methods: In 16 pediatric CC patients (age range, 4 months to 9 years; median, 3 years), visualization of PBM and aberrant bile duct anatomy and IHBD morphology at the hepatic hilum (HH), umbilical portion (UP), and posterior branch (POST) were compared between 3D-MRCP and intraoperative cholangiography (IOC). VES and intraoperative cholangioscopy (IOS) findings were compared., Results: HH, UP, and POST visualization rates were 100%, 94%, and 94%, respectively, by 3D-MRCP, and 100%, 69%, and 69%, respectively, by IOC. IHBD stenosis detection rates at each region were 38%, 13%, and 13%, respectively, by 3D-MRCP, and 25%, 0%, and 9%, respectively, by IOC. IHBD dilatation detection rates at each part were 75%, 47%, and 60%, respectively, by 3D-MRCP, and 88%, 82%, and 91%, respectively, by IOC. PBM was confirmed in 56% and 93% of cases on 3D-MRCP and IOC, respectively. Both 3D-MRCP and IOC showed biliary variants in 5 cases (31%). VES showed membranous strictures at HH, UP, and POST in 6, 2, and 2 cases, respectively, whereas IOS did so at HH in 4 cases and POST in 2., Conclusion: Preoperative 3D-MRCP and VES accurately depict biliary morphology, allowing concrete operative planning in pediatric CC patients, complementing IOC and IOS., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background/aims: To evaluate the usefulness of multi-detector row computed tomography (MDCT) in the postoperative long-term follow-up of biliary atresia (BA) patients for detection of esophagogastric varices due to portal hypertension and intrahepatic bile duct (IHBD) dilatations. Well-developed esophagogastric varices can cause unexpected life-threatening rupture and contribute to the progression of hepatopulmonary vascular diseases. Dilated IHBDs can trigger cholangitis., Methods: After corrective surgery, 29 BA patients (median age 14 years, range 6 months to 27 years) with suspected long-term sequelae underwent 16-slice MDCT. Esophagogastric varices and IHBD dilatations were evaluated using reconstructed images. Detection rates for esophagogastric varices were compared between MDCT and endoscopic findings. Differences in detection rates for IHBD dilatations between MDCT and ultrasonography (US) were also investigated., Results: Detection rates for esophageal varices did not differ significantly between MDCT and endoscopy, while three cases positive only on MDCT, including one with hepatopulmonary syndrome, showed conspicuous peri-esophageal varices deep in the esophageal wall. MDCT showed a significantly higher detection rate than endoscopy (p = 0.03) for gastric fundal varices. MDCT with the maximum intensity projection disclosed IHBD dilatations in 17 postoperative BA cases, 15 out of which had past history of cholangitis, while US detected them in 6 cases (p = 0.003). In addition, MDCT was more advantageous for detecting IHBD dilatations, particularly those located in the posterior lobe., Conclusions: Among postoperative BA patients, compared to endoscopy, MDCT had comparable and superior detection rates for esophageal and gastric fundal varices, respectively. MDCT also precisely demonstrated the location and extent of IHBD dilatations. In long-term follow-up of BA patients, MDCT can help determine follow-up strategies.

Purpose: Neuroblastoma (NB) is one of the most common extracranial solid tumors in children and is known for its clinical and biological heterogeneity. The aim of this study is to reveal the functional role of src family kinases in the biological behavior of NB by inhibiting their kinase activities with a specific inhibitor, PP2 (4-amino-5-(4-chloro-phenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine)., Methods: NB cell lines (SH-SY5Y, IMR32, RT-BM-1, CHP134, NLF, and LA-N-5) were treated with 0.1-10 µM of PP2. Morphological changes, cell growth, and cell death were assessed, as well as all-trans retinoic acid (ATRA)-induced neuronal differentiation and epidermal growth factor (EGF)-induced proliferation., Results: At 24 h after PP2 treatment, NB cell lines showed drastic cell aggregation. PP2 also inhibited cell growth of NB in a dose-dependent manner. Apoptosis was detected in these cells. ATRA-induced neuronal differentiation of RT-BM-1 was not affected by PP2. PP2 reduced the proliferative effect of EGF. EGF-induced rapid activation of Akt, which was not blocked by PP2 treatment, suggesting that the cellular events triggered by PP2 were independent to PI3 kinase/Akt signaling pathway., Conclusion: Our data suggests that src family kinases promote cell survival/proliferation and reduces cell aggregation of NBs. Src family kinase inhibitors may be good candidates for a novel molecular target therapy.

Subtilase cytotoxin (SubAB) is an AB(5) cytotoxin produced by some strains of Shiga-toxigenic Escherichia coli. The A subunit is a subtilase-like serine protease and cleaves an endoplasmic reticulum chaperone, BiP, leading to transient inhibition of protein synthesis and cell cycle arrest at G(1) phase. Here we show that SubAB, but not the catalytically inactive mutant SubAB(S272A), induced apoptosis in Vero cells, as detected by DNA fragmentation and annexin V binding. SubAB induced activation of caspase-3, -7, and -8. Caspase-3 appeared earlier than caspase-8, and by use of specific caspase inhibitors, it was determined that caspase-3 may be upstream of caspase-8. A general caspase inhibitor blocked SubAB-induced apoptosis, detected by annexin V binding. SubAB also stimulated cytochrome c release from mitochondria, which was not suppressed by caspase inhibitors. In HeLa cells, Apaf-1 small interfering RNA inhibited caspase-3 activation, suggesting that cytochrome c might form an apoptosome, leading to activation of caspase-3. These data suggested that SubAB induced caspase-dependent apoptosis in Vero cells through mitochondrial membrane damage.

We report herein a case of prenatally detected neonatal adrenocortical tumor (ACT). The patient was an otherwise healthy newborn girl. No signs of Beckwith-Wiedemann syndrome were identified, and her family medical history did not suggest predisposition to cancer. Computed tomography and ultrasonography after birth revealed a round solid tumor 40 mm in diameter in the right suprarenal area. The precise diagnosis of ACT was unexpectedly obtained based on results from the Japanese neonatal mass screening program. Blood 17-hydroxyprogesterone is routinely measured as a part of this program for early detection of congenital adrenal hyperplasia in Japan. Abnormally elevated level of 17-hydroxyprogesterone was reported in the patient and, thus, led to the diagnosis of ACT. Surgical resection was safely performed with perioperative steroid replacement. Adrenocortical tumors are extremely rare in childhood, particularly in the neonatal period. Some of these tumors secrete abnormally high levels of cortisol, suppressing function of the contralateral adrenal gland and, thus, leading to life-threatening postoperative adrenal insufficiency. Scheduled steroid replacement enables safe perioperative management in such cases. Adrenocortical tumor should always be considered among the differential diagnoses for neonatal suprarenal mass because precise diagnosis will enable the physician to develop appropriate treatment strategies.

A rare case of gastric duplication of childhood is reported. A 1-month-old boy underwent pyloromyotomy for infantile hypertrophic pyloric stenosis. At laparotomy, a protruding lesion was identified in the anterior wall of the pylorus. The pylorus was hypertrophic as indicated preoperatively, and a normal pyloromyotomy was performed. Wedge biopsy of the protruding lesion revealed an intestinal structure, and gastric duplication was diagnosed. The child remained asymptomatic thereafter, but considering the risk of the duplication becoming symptomatic, a second laparotomy was performed at 1 year of age. The duplication cyst shared part of the wall with the pylorus, and the cyst was removed by cystectomy, leaving the pyloric muscle intact. The cyst was found to be communicating with the pancreatic duct. The child is doing well without any symptoms as of 18 months after second laparotomy. To the best of our knowledge, this is the youngest case of gastroduodenal duplication with pancreatic duct communication yet reported.

Subtilase cytotoxin (SubAB) is a AB(5) type toxin produced by Shiga-toxigenic Escherichia coli, which exhibits cytotoxicity to Vero cells. SubAB B subunit binds to toxin receptors on the cell surface, whereas the A subunit is a subtilase-like serine protease that specifically cleaves chaperone BiP/Grp78. As noted previously, SubAB caused inhibition of protein synthesis. We now show that the inhibition of protein synthesis was transient and occurred as a result of ER stress induced by cleavage of BiP; it was closely associated with phosphorylation of double-stranded RNA-activated protein kinase-like ER kinase (PERK) and eukaryotic initiation factor-2alpha (eIF2alpha). The phosphorylation of PERK and eIF2alpha was maximal at 30-60 min and then returned to the control level. Protein synthesis after treatment of cells with SubAB was suppressed for 2 h and recovered, followed by induction of stress-inducible C/EBP-homologous protein (CHOP). BiP degradation continued, however, even after protein synthesis recovered. SubAB-treated cells showed cell cycle arrest in G1 phase, which may result from cyclin D1 downregulation caused by both SubAB-induced translational inhibition and continuous prolonged proteasomal degradation.

Subtilase cytotoxin (SubAB) is a recently identified AB5 subunit toxin produced by Shiga-toxigenic Escherichia coli. The A subunit is thought to be a subtilase-like, serine protease, whereas the B subunit binds to the toxin receptor on the cell surface. We cloned the genes from a clinical isolate; the toxin was produced as His-tagged proteins. SubAB induced vacuolation at concentrations greater than 1 microg/ml after 8 h, in addition to the reported cytotoxicity induced at a ng/ml level after 48 h. Vacuolation was induced with the B, but not the A, subunit and was dependent on V-type ATPase. The cytotoxicity of SubAB at low concentrations was associated with the inhibition of protein synthesis; the 50% inhibitory dose was approximately 1 ng/ml. The A subunit, containing serine 272, which is thought to be a part of the catalytic triad of a subtilase-like serine protease, plus the B subunit was necessary for this activity, both in vivo and in vitro. SubAB did not cleave azocasein, bovine serum albumin, ovalbumin, or synthetic peptides. These data suggest that SubAB is a unique AB toxin: first, the B subunit alone can induce vacuolation; second, the A subunit containing serine 272 plus the B subunit inhibited protein synthesis, both in vivo and in vitro; and third, the A subunit proteolytic activity may have a strict range of substrate specificity.

Some shiga toxin-producing Escherichia coli secrete a novel AB5 cytotoxin, named subtilase cytotoxin (SubAB), which induces vacuole formation in addition to cytotoxicity in susceptible cells. By immunoprecipitation with SubAB from Vero cells, we discovered proteins of 100 kDa, 135 kDa and 155 kDa as potential candidates for its receptor. These proteins were N-glycosylated in their extracellular domains, a modification that was necessary for interaction with SubAB. Biotinylated receptors were partially purified by Datura stramonium agglutinin affinity chromatography and avidin-agarose and analysed by TOF mass spectroscopy. The peptide sequences of p135 were identical to beta1 integrin, and its identification was confirmed with anti-integrin beta1 antibody. The p155 protein was identified as alpha2 integrin using anti-integrin alpha2 antibody. In addition, treatment of Vero cells with beta1 integrin RNAi before exposure to SubAB prevented vacuolating activity. These results suggested that SubAB recognizes alpha2beta1 integrin as a functional receptor; this first interaction may be an important key step leading to the SubAB-induced morphological changes in Vero cells.