Results of Definitive (Chemo)radiotherapy Using Computed Tomography-based Brachytherapy for Cervical Cancer.

BACKGROUND/AIM: Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard treatment for locally advanced cervical cancer. Especially, CCRT with magnetic resonance imaging (MRI) or computed tomography-based image-guided brachytherapy (CT-based 3D-IGBT) for cervical cancer has resulted in good LC rates. However, progression-free survival (PFS) and overall survival (OS) rates for locally advanced cervical cancer are still low and could be improved. The aim of the study was to evaluate treatment efficacy and late toxicity of external beam radiotherapy (EBRT) and CT-based IGBT with or without concurrent chemotherapy in patients with squamous cell carcinoma of the uterine cervix and investigate patterns of failure. PATIENTS AND METHODS: We retrospectively analyzed clinical data of cervical squamous cell carcinoma patients treated with definitive radiotherapy with or without concurrent chemotherapy at Saitama Medical University International Medical Center. Local control (LC), PFS, patterns of failure, and late toxicity were the evaluated outcomes. RESULTS: Overall, 290 patients were enrolled in the study. Median follow-up was 51.5 months. During follow-up, 74 patients developed recurrence: 10 patients with intra-pelvic failure only, 45 with extra-pelvic failure only, and 19 with both. The 3-year LC was 100% for T1b-T2a, 96.8% for T2b, 89.5% for T3b, and 88.5% for T4 disease. The 3-year PFS was 100% for stage IB-IIA, 89.0% for stage IIB, 70.7% for stage IIIB, 72.6% for stage IIIC1r, and 40.1% for stage IVA. The incidence of grade 3-4 gastrointestinal and genitourinary toxicities was 3.0% and 1.7%, respectively. CONCLUSION: Combination of EBRT and CT-based IGBT with or without concurrent chemotherapy produced favorable LC with acceptable rates of late toxicities. However, extra-pelvic failures frequently occurred and PFS was less satisfactory in patients with stage III-IVA disease, which indicated the need for additional treatment in these patients.

Workplace Measures Against COVID-19 and Mistreatment in the Workplace Among Japanese Employees: A 1-Year Prospective Cohort Study.

OBJECTIVE: The purpose of this study was to identify the COVID-19 infection prevention measures that are at risk of being perceived by employees as mistreatment in the workplace. METHODS: This study included full-time workers who enrolled as subjects in a nationwide prospective cohort study. Baseline surveys performed during the pandemic were used to identify the workplace measures against COVID-19. A tracing survey was conducted 1 year later to assess workplace mistreatment. RESULTS: Of the 18,170 participants, 276 judged that they had experienced mistreatment by the measures. "Enforcing daily temperature measurement" and "stopping business trips" were associated with mistreatment. Meanwhile, "requesting that employees refrain from going to work when ill" and "restricting work-related social gatherings and entertainment" had the potential to reduce workplace mistreatment. CONCLUSIONS: Certain measures against COVID-19 can reduce or increase the burden on employees.

Prediction of PR interval prolongation after catheter ablation of incisional atrial tachycardia.

A three-dimensional (3D) mapping system is safe and effective for catheter ablation of incisional atrial tachycardia (IAT). Prolongation of the PR interval is occasionally observed after this procedure. Although a first-degree atrioventricular block is typically benign, an excessively prolonged PR interval can indicate a worse prognosis. Currently, a method to predict the PR interval after ablation therapy for IAT is lacking. We report the case of a 70-year-old woman with paroxysmal atrial tachycardia, in which our maneuver using a 3D mapping system and the electrophysiological findings enabled us to preoperatively predict the post-ablation PR interval. We believe that this method is useful for determining treatment strategies for IAT. Learning objective: Three-dimensional (3D) mapping systems can clearly visualize macro-reentrant circuits and enable the creation of precise ablation lines. When creating ablation lines for incisional atrial tachycardia, attention should be paid to the prolongation of the PR interval, because an excessively prolonged PR interval may indicate a worse prognosis. Herein, we have presented a method for predicting the post-ablation PR interval using a 3D mapping system and electrophysiological findings.

Relationship between Effective Refractory Period and Inducibility of Atrial Fibrillation from the Superior Vena Cava after Pulmonary Vein Isolation.

In terms of the pulmonary vein (PV), atrial fibrillation (AF) patients have a shorter effective refractory period (ERP) than those without AF and a large dispersion of the ERP. Although the frequency of AF from the superior vena cava (SVC) was the highest among non-PV foci, the characteristics of the ERP in the SVC (SVC-ERP) were unclear. The purpose of this study was to elucidate the relationship between SVC-ERP and the inducibility of AF after PV isolation (PVI).Consecutive 28 patients who underwent PVI were included. After successful PVI, the SVC-ERP was measured at three positions in SVC. Rapid electrical stimuli were delivered at the shortest SVC-ERP to induce AF. Patients in whom AF was induced were assigned to the SVC-induced group (SIG), and the remaining patients were the non-SVC-induced group (non-SIG). The size of the SVC sleeve was evaluated via three-dimensional electroanatomic mapping.The SIG had a significantly shorter average SVC-ERP (236.0 ± 25.2 versus 294.8 ± 36.8 ms, P < 0.001), whereas SVC-ERP dispersion was not significantly different (30.0 ± 25.4 versus 33.3 ± 20.1 ms, P = 0.56). Although the longer SVC diameter was significantly longer in the SIG (27.4 ± 4.3 versus 22.9 ± 4.6 mm, P = 0.03), the SVC-ERP was significantly associated with pacing inducibility of AF after adjustment for the longer SVC diameter (odds ratio: 0.96 [1 ms increments], P = 0.01).The SIG had a shorter SVC-ERP, whereas the dispersion was not significantly different between the two groups. The SVC-ERP can be one of the mechanisms of arrhythmogenicity for AF originating from the SVC.

Influence of the right ventricular septum/free-wall boundary (hinge) on differentiation of the ventricular lead implantation site.

BACKGROUND: The prognosis associated with right ventricular (RV) free-wall pacing is worse than that of septal pacing. Identification of the pacing site using a 12­lead electrocardiogram (ECG) is controversial and may be influenced by ECG changes within the same septal or free-wall area. The relationship between the diagnostic capabilities of ECG and pacing sites has previously been qualitatively evaluated. However, in this study, this relationship was analyzed quantitatively, and accurate evaluation of the pacing site was determined using computed tomography (CT). METHODS: Of 779 consecutive outpatients, 65 who underwent pacemaker implantation and thoracic CT were prospectively included and classified into the following groups according to the lead tip position: free-wall, septal, or septum/free-wall boundary (hinge) group. The hinge was used as an anatomical marker, and the distance from the hinge to the lead tip was measured. Under RV pacing, a 12­lead ECG was obtained. ECG findings were evaluated using three criteria (including lead I, II, and aVL and precordial leads V5 and V6) previously reported to be useful in differentiating pacing sites. RESULTS: The lead tips were anchored at the free-wall in 10 patients, the septal wall in 19 patients, and the hinge in 32 patients. Paced QRS duration correlated with the distance from the hinge to the lead tip for the free-wall and septum (r = 0.47 and - 0.68, respectively). Estimation of the lead tip implantation site using the ECG algorithm was useful; however, the algorithm's accuracy decreased around the hinge. CONCLUSIONS: ECG is useful in differentiating pacing sites but is less accurate around the hinge, which may be the reason that the identification of the RV pacing site using ECG remains controversial.

Relationship between device displacement distance toward the caudal side during standing and pocket position laterality.

BACKGROUND: The displacement of cardiac implantable electronic devices (CIEDs) toward the caudal side during standing after CIED implantation could cause lead dislodgement. This study investigated the relationship between supine pocket position and standing CIEDs' displacement distance after the implantation. METHODS: After CIED surgeries performed at 2 hospitals between 2012 and 2020, 134 patients underwent postoperative chest x-rays in the supine and standing positions during hospitalization. To measure the displacement distance of CIEDs from the supine to the standing position, we identified the first thoracic vertebrae (Th1) in the supine position using the first rib as an index, drew a horizontal line at the lower edge of the Th1, and calculated the distance from that point to the upper edge of the CIED. The difference between measures for the two positions was compared. At the position of the pocket in the thorax in the supine position, the ratio of the distance between the thorax and the device is defined as the device thorax ratio (DTR). We examined the relationship between DTR and CIED displacement distance. RESULTS: In this study, we included 134 patients (53% men; median age, 79 years, body mass index, 22.3 ± 3.4; pacemaker 93%, left implantation 96%). We found that the more lateral the position of the CIED pocket, the more the CIED fell when standing (confidence interval = 0.34-0.60, P < .001). CONCLUSIONS: The farther the CIED was implanted outside the thorax in the supine position, the more significantly the CIED was displaced in the standing position.

Large discrepancy in optimal atrioventricular delay between sensed and paced atrial events in a pacemaker patient.

A 74-year-old man experienced complete atrioventricular (AV) block 2 days after catheter ablation for right atrial (RA) macroreentrant tachycardia. We performed DDD pacemaker implantation with atrial septal pacing because other sites of pacing threshold were not acceptable. The maximum left ventricular outflow tract velocity time integral was 15.8 cm with sensed AV delay (40 ms) and 15.0 cm with paced AV delay (220 ms); however, this exceeded the pacemaker's maximum difference of 100 ms. We herein report the case of a large discrepancy in optimal AV delay intervals between sensed and paced atrial events, requiring consideration of proper pacemaker settings.

Accessory pathway ablation during atrial fibrillation in Ebstein anomaly.

An 84-year-old woman with type B Wolff-Parkinson-White (WPW) with Ebstein anomaly was admitted with heart failure. She had rapid wide QRS tachycardia due to accessory pathway (AP) conduction associated with atrial fibrillation (AF). Since transesophageal echocardiography before catheter ablation showed a left atrial thrombus, ablation was performed using a 3D mapping system under AF. After marking the functional tricuspid anulus with intra-cardiac echocardiography, 3D intra-cardiac electrogram visualization (ripple map) during AF enabled clear identification of location of the AP. After ablation, there was no complication of cerebral infarction, and the heart failure improved.

Heart failure caused by iatrogenic atrial septal defect after cryoballoon ablation for atrial fibrillation.

An 83-year-old man with no structural heart disease underwent pulmonary vein isolation (PVI) for symptomatic paroxysmal atrial fibrillation (AF). The PVI was successfully performed by cryoballoon ablation with a single transseptal puncture. A 12Fr deflectable sheath and an 8.5Fr long sheath crossed the interatrial septum via the same puncture site. Five months after PVI, the patient was readmitted because of heart failure and recurrence of AF. The echocardiogram showed a large (10.7 × 5.8 mm) iatrogenic atrial septal defect (IASD) at the previous puncture site. Both right-to-left and left-to-right shunts were observed during systole and diastole, respectively. Despite the initiation of optimal medical therapy for heart failure, symptoms were not completely controlled and IASD remained 11 months after PVI. Eventually, he received multiple additional PVI for recurrence of AF and percutaneous transcatheter closure (13 mm disc for 10.9 × 8.9 mm- IASD), then heart failure was controlled with the improvement of the right atrial and ventricular size. Although the induction of heart failure by IASD after PVI is rare, it should be noted as one of the causes, especially after cryoballoon ablation with simultaneous mapping catheter insertion via a single transseptal puncture. .

Incidence of out-of-hospital cardiac arrests and survival rates after 1 month among the Japanese working population: a cohort study.

OBJECTIVES: The prevention and improvement of the prognosis of out-of-hospital cardiac arrests (OHCAs) are important issues especially with respect to their social and economic significance in working populations. The age distribution of the working population in Japan is expected to change continually due to its ageing society and extension of retirement; however, few reports have examined the long-term condition of OHCA in the working population, defined by age. The aim of this study was to determine the incidence of OHCAs and the survival rates after 1 month, among the Japanese working population, defined by age, considering the changing age distribution. DESIGN AND SETTING: We analysed the All-Japan Utstein registry, a prospective, nationwide, population-based, observational registry (2005-2016). PARTICIPANTS: From the registry, 212 961 patients with OHCA from the Japanese working population (defined aged 20-69 years), with only cardiogenic aetiology participated in this study. These patients were further divided into four groups according to the type of citizen bystander (family, friends, work-colleagues and passers-by). PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes were 1-month survival with favourable neurological outcomes. RESULTS: The incidence of OHCAs, in any age group, was almost constant during the 12-year period. The work-colleagues had the best prognosis despite having significantly longer times to initial defibrillations compared with the passers-by (13 vs 12 min, respectively, p<0.001) that was associated independently with 1-month survival with favourable neurological outcomes (adjusted OR: 0.94 (1 min increments), p<0.001). CONCLUSIONS: In the 12-year period, the incidence of OHCAs in any age group remained almost constant, whereas the prognosis improved each year. Reducing the time to initial defibrillation may further improve the prognosis of OHCAs with a work-colleague bystander.

Correction: Water pre-filtration methods to improve environmental DNA detection by real-time PCR and metabarcoding.

[This corrects the article DOI: 10.1371/journal.pone.0250162.].

RR interval variability in the evaluation of ventricular tachycardia and effects of implantable cardioverter defibrillator therapy.

BACKGROUND: An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability. METHODS: We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti-tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated. RESULTS: Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively. CONCLUSIONS: ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible.

Adenosine revives catheter-induced mechanical blocks in radiofrequency ablation.

Adenosine can hyperpolarize the atrial action potential, which helps rapidly re-establish the membrane potential in ablated sites and unmask "dormant conduction." It has been reported that pharmacological agents, including adenosine, were unable to revive traumatized tissues. We present the first case of the catheter-induced mechanical block ("bump" phenomenon) that was unmasked with adenosine administration in the working myocardium of the superior vena cava. This result may be because, unlike before, we could determine the force of contact between the tip of the ablation catheter and the myocardial tissue. This case suggests the clinical usefulness of adenosine for unmasking bumped sites.

Water pre-filtration methods to improve environmental DNA detection by real-time PCR and metabarcoding.

Environmental DNA (eDNA) analysis is a novel approach for biomonitoring and has been mostly used in clear water. It is difficult to detect eDNA in turbid water as filter clogging occurs, and environmental samples contain various substances that inhibit the polymerase chain reaction (PCR) and affect the accuracy of eDNA analysis. Therefore, we applied a pre-filtration method to better detect the fish species (particularly pale chub, Opsariichthys platypus) present in a water body by measuring eDNA in environmental samples containing PCR inhibitors. Upon conducting 12S rRNA metabarcoding analysis (MiFish), we found that pre-filtration did not affect the number or identities of fish species detected in our samples, but pre-filtration through pore sizes resulted in significantly reduced variance among replicate samples. Additionally, PCR amplification was improved by the pre-filtration of environmental samples containing PCR inhibitors such as humic substances. Although this study may appear to be a conservative and ancillary experiment, pre-filtration is a simple technique that can not only improve the physical properties of water, such as turbidity, but also the quality of eDNA biomonitoring.

Rate-dependent pacing failure after pacemaker implantation: Novel insights into the mechanism of using adenosine.

An 82-year-old woman received pacemaker implantation for sick sinus syndrome. Two days after the implantation, electrocardiography showed 2:1 atrial pacing failure, followed by a bradycardia-dependent increase in the atrial pacing threshold during a pacemaker examination. However, transient 1:1 atrial pacing capture recovered by adenosine triphosphate (ATP) administration, which was performed to evaluate the bradycardia-dependent pacing failure mechanism. We considered this phenomenon to be caused by Phase 4 depolarization and avoided replacing this atrial lead. Three weeks later, the atrial pacing threshold had improved. We report the potential role of Phase 4 depolarization in a bradycardia-dependent increase in pacing threshold by using ATP.

Prevention of serious air embolism during cryoballoon ablation; risk assessment of air intrusion into the sheath by catheter selection and change in intrathoracic pressure: An ex vivo study.

INTRODUCTION: One cause of cerebral infarction during cryoballoon ablation is the entry of air into a sheath due to the use of inappropriate catheters. It is known that the left atrial pressure of patients with obstructive sleep apnea syndrome can be negative. However, the effects of catheter selection and negative pressure changes in the sheath on air intrusion are not yet well understood. The aim of this study was to evaluate how catheter selection and negative pressure changes affect air intrusion and to perform countermeasures for air intrusion. METHODS AND RESULTS: This experiment used siphon principle to create negative pressure in the sheath. Noncryoablation catheters (not designed exclusively for cryoballoon ablation) and cryoballoon catheters were investigated. Catheters were inserted into the sheath and then removed. Thereafter, the amount of air in the sheath was measured. For catheters producing significantly larger amounts of air intrusion, the catheters were inserted via a long sheath in the sheath (sheath-in-sheath technique) and the same procedures were repeated. We found that the amount of air intrusion through most of the noncryoablation catheters was significantly larger than that through cryoablation catheters. An increase in the magnitude of negative pressure in the sheath resulted in a proportional increase in air intrusion, but the sheath-in-sheath technique significantly reduced air intrusion. CONCLUSION: The amount of air intrusion increased when using catheters with complicated tip shapes and thin outer diameters and when the magnitude of negative pressure in the sheath increased. The sheath-in-sheath technique may be an effective countermeasure.

Development and Evaluation of Event-Specific Quantitative PCR Method for Genetically Modified Soybean MON87701.

A real-time PCR-based analytical method was developed for the event-specific quantification of a genetically modified (GM) soybean event, MON87701. First, a standard plasmid for MON87701 quantification was constructed. The conversion factor (Cf) required to calculate the amount of genetically modified organism (GMO) was experimentally determined for a real-time PCR instrument. The determined Cf for the real-time PCR instrument was 1.24. For the evaluation of the developed method, a blind test was carried out in an inter-laboratory trial. The trueness and precision were evaluated as the bias and reproducibility of relative standard deviation (RSDr), respectively. The determined biases and the RSDr values were less than 30 and 13%, respectively, at all evaluated concentrations. The limit of quantitation of the method was 0.5%, and the developed method would thus be applicable for practical analyses for the detection and quantification of MON87701.

Elevated Ozone Deteriorates Grain Quality of Japonica Rice cv. Koshihikari, Even if it Does Not Cause Yield Reduction.

BACKGROUND: It is becoming clear that ozone affects not only grain yield but also grain quality in rice. However, the biochemical mechanisms responsible for ozone-induced changes in appearance quality or components are poorly understood. We analyzed appearance quality and starch composition in the rice cultivars "Koshihikari" (japonica) and "Kasalath" (indica) grown under elevated ozone conditions. RESULTS: Elevated ozone significantly increased the proportion of immature (mainly chalky) kernels in "Koshihikari" but not in "Kasalath". Scanning electron microscopy of transverse sections of kernels showed that endosperm starch granules of "Koshihikari" ripened under elevated ozone were loosely packed with large spaces and contained irregular rounded granules. Amylose content was increased in "Koshihikari" kernels with ozone exposure, but was unchanged in "Kasalath" kernels. Distribution analysis of amylopectin chain length showed that ozone induces a decrease of long-side chains and alterations of short side-chains in "Koshihikari" kernels. Furthermore, Starch Synthase (SS) IIIa transcript levels in "Koshihikari" caryopses were decreased by elevated ozone. CONCLUSIONS: The japonica cultivar "Koshihikari" showed significant deterioration in appearance quality of kernels caused by abnormal starch accumulation due to exposure to ozone. The alteration patterns of amylose and amylopectin in ozone-exposed rice kernels are similar to those in rice kernels harvested from SSIIIa-deficient mutants. These findings suggest that the increase of chalky kernels in ozone-treated "Koshihikari" is partly attributable to the repressed expression of SSIIIa involved in amylopectin side-chain elongation with ozone exposure. Elevated ozone reduced appearance quality in "Koshihikari" although it did not impair starch properties contributing to the eating quality of cooked rice.

Ozone-Induced Rice Grain Yield Loss Is Triggered via a Change in Panicle Morphology That Is Controlled by ABERRANT PANICLE ORGANIZATION 1 Gene.

Rice grain yield is predicted to decrease in the future because of an increase in tropospheric ozone concentration. However, the underlying mechanisms are unclear. Here, we investigated the responses to ozone of two rice (Oryza Sativa L.) cultivars, Sasanishiki and Habataki. Sasanishiki showed ozone-induced leaf injury, but no grain yield loss. By contrast, Habataki showed grain yield loss with minimal leaf injury. A QTL associated with grain yield loss caused by ozone was identified in Sasanishiki/Habataki chromosome segment substitution lines and included the ABERRANT PANICLE ORGANIZATION 1 (APO1) gene. The Habataki allele of the APO1 locus in a near-isogenic line also resulted in grain yield loss upon ozone exposure, suggesting APO1 involvement in ozone-induced yield loss. Only a few differences in the APO1 amino acid sequences were detected between the cultivars, but the APO1 transcript level was oppositely regulated by ozone exposure: i.e., it increased in Sasanishiki and decreased in Habataki. Interestingly, the levels of some phytohormones (jasmonic acid, jasmonoyl-L-isoleucine, and abscisic acid) known to be involved in attenuation of ozone-induced leaf injury tended to decrease in Sasanishiki but to increase in Habataki upon ozone exposure. These data indicate that ozone-induced grain yield loss in Habataki is caused by a reduction in the APO1 transcript level through an increase in the levels of phytohormones that reduce leaf damage.