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Nowadays, it has become very common to find in Japan that nitrate nitrogen concentrations are very high in spring water and in well water where the land use of a watershed is agricultural. We have often observed around 50 mg/L of nitrate nitrogen in the spring water where we live. Crops produced in those fields are mainly vegetables such as celery, cabbage, lettuce, carrots, and so on. Green tea is also popular in Japan. In order to produce good quality green tea, farmers apply a great amount of nitrogen fertilizer. This amount can reach up to 1,000 kg/ha in some areas, although the average application amounts to 628 kg/ha in Japan. As a result, ground water that is rich in nitrate flows into the river, which results in a high nitrogen concentration in river water and ground water. Further, this causes a low pH in river water in some tributary rivers in Japan, though this kind of case is very rare. We knew from field tests that if water contained a high nitrogen concentration and was introduced into paddy fields, high nitrogen removal would be performed. This paper presents the outline and results of a system on how to remove nitrogen using paddy fields (wetlands). Further, this paper presents the evaluated results of the removal quantity at the watershed level. [ABSTRACT FROM AUTHOR]

The dry and wet depositions of atmospheric ammonia (NH 3) is one of the important pathways of nitrogen loads to aquatic ecosystems and should be managed to mitigate lake eutrophication. Crop and livestock agriculture, one of the largest emitters of NH 3 in Asian countries, are known to cause high spatial and seasonal variation of NH 3 and influence the surrounding lake basin areas via its dry and wet deposition. However, the spatial characteristics of the NH 3 concentration in basin scale are not completely understood for regulation in NH 3 emission because a paucity of monitoring network is currently available for NH 3 in many Asian countries. Here we aim to clarify dominant factors of spatial and seasonal variations of the NH 3 concentration in a shallow eutrophic lake basin (Lake Kasumigaura basin) surrounded by agricultural areas in eastern Japan. Passive sampling over various land use categories in the basin was conducted at 36 sites in total from October 10, 2018 to January 14, 2020. Mean NH 3 concentration in the observational period was in the order of farmland (6.6 ppbv), lake (5.9 ppbv), rural (3.5 ppbv), and forest (2.6 ppbv). Interestingly, the observed NH 3 concentration near the livestock houses were higher in winter than summer, which was inconsistent with knowledge of seasonal changes of current NH 3 emission inventory based on temperature-driven volatilization process. Comparing monthly NH 3 concentrations at farmland and lake sites with various meteorological factors, we suggested the importance of seasonal advection of NH 3 from high emission sources to which has been rarely paid attention by the previous past studies. Consequently, a higher nitrogen input by dry deposition of NH 3 was preliminarily estimated over the lake than that of wet deposition of total nitrogen. Our finding of a role of seasonal advection in NH 3 spatial pattens should be considered for lake ecosystem management since its deposition is known to be closely related to the ecological processes such as phytoplankton blooming. • Passive sampling of NH 3 was made at 36 sites in a lake basin for 16 months. •High NH 3 concentration in winter was observed around emission source areas. •A role of advection was suggested in a lake basin under a monsoon circulation. •Estimated dry deposition of NH 3 was higher than wet deposition over the lake. •Advection of NH 3 should be considered in lake ecosystem management. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the prognostic value of the geriatric nutritional risk index (GNRI) in patients undergoing curative gastrectomy for remnant gastric cancer (RGC)., Methods: This multicenter retrospective study included 105 patients with RGC of ≥ 65 years of age who underwent curative gastrectomy at 10 institutions in Japan between January 2000 and December 2016. Postoperative complications, overall survival (OS), and disease-specific survival (DSS) were analyzed., Results: Receiver operating curve analyses indicated that the optimal cutoff value of the GNRI for OS was 95.4. Patients were categorized into high and low GNRI groups based on the optimal GNRI cutoff value. The GNRI was significantly correlated with body mass index (p < 0.001), amount of bleeding (p = 0.021), Clavien-Dindo grade 5 postoperative complications (p = 0.040), death caused by primary disease (p = 0.010), and death caused by other diseases (p = 0.002). The OS and DSS were significantly worse in the low GNRI group. A low GNRI and T3 or deeper tumor invasion were independent prognostic factors for OS and DSS., Conclusions: The GNRI is a promising predictor of both short- and long-term outcomes in older patients with RGC., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study., (© 2024. The Author(s).)

Background: The real-world data evidences how establishment of neuromyelitis optica (NMO) disease concept and development disease modifying therapy affect the patients with multiple sclerosis (MS) and NMO are lacking. The aim of this study is to clarify the diachronic trend of the severity and admissions of patients with MS and NMO., Methods: We retrospectively investigated the trends in admissions, treatments, and disabilities in the patients with MS and NMO using the Japanese administrative data between 2012 and 2017., Results: We analyzed acute stage 9545 and 2035 admissions in each 6100 MS and 1555 NMO patients. The annual number of admission in MS significantly decreased in 6 years; however, those in NMO consistently increased. The patient proportion with lower disability was significantly increased in MS and NMO. These trends were especially observed in patients admitted to centralized hospitals with more active treatments, such as second-line disease modifying therapy for MS and plasmapheresis for NMO. Patients with NMO using DMT for MS diminished in 6 years., Conclusion: A gradual improvement of disability in patients with MS and NMO was observed, probably due to advanced treatments, increased NMO awareness, and decreased misdiagnosis, which seems to be the key for better prognosis in MS and NMO., Competing Interests: Declaration of Competing Interest Y. Matsumoto and K. Tarasawa report no disclosure. T. Misu received speaker honoraria from Tanabe Mitsubishi Pharma, Novartis Pharma., Alexion Pharma., Teijin Pharma., Viela Bio, and Biogen Idec Japan, and received research support from Cosmic Corporation, and Medical and Biological Laboratories Co.; and received Grant-in-Aid for scientific research from Ministry of Education, Culture, Sports, Science, and Technology. C. Namatame and Y. Takai and H. Kuroda report no disclosure. K. Fujihara serves on the advisory boards for Bayer Schering Pharma, Biogen Idec, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Alexion Pharmaceuticals, and Medimmune; has received travel funding and speaker honoraria from Bayer Schering Pharma, Biogen Idec, Eisai Inc, Mitsubishi Tanabe Pharma Corporation, Novartis Pharma, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Asahi Kasei Medical Co., Daiichi Sankyo, and Nihon Pharmaceutical; is on the editorial board for Clinical and Experimental Neuroimmunology; is an advisory board member for Sri Lanka Journal of Neurology; and received research support from Bayer Schering Pharma, Biogen Idec Japan, Asahi Kasei Medical, The Chemo-Sero-Therapeutic Research Institute, Teva Pharmaceutical, Mitsubishi Tanabe Pharma, Teijin Pharma, Chugai Pharmaceutical, Ono Pharmaceutical, Nihon Pharmaceutical, Genzyme Japan, Ministry of Education, Science and Technology of Japan, and Ministry of Health, Welfare and Labor of Japan. K. Fushimi and K. Fujimori report no disclosures. M. Aoki received research support from the Japanese Ministry of Health Labor and Welfare, and the Japanese Ministry of Education, Culture, Sports, Science, and Technology., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The impact of the COVID-19 pandemic on dental anesthesiologists has not been examined. This study aimed to determine how the COVID-19 pandemic affected Japanese dental anesthesiologists' professional lives., Methods: An online questionnaire related to the effects of COVID-19 on dental anesthesiologists' professional lives was emailed to 351 board-certified dental anesthesiology specialists from the Japanese Dental Society of Anesthesiology. The endpoints of this study were changes in income and job satisfaction as a dental anesthesiologist from 2019 prior to the COVID-19 pandemic., Results: A total of 141 dental anesthesiologists participated in the survey. Most respondents reported no change in income relative to 2019 for 2020 or 2021. Significantly more dental anesthesiologists reported income decreases relative to 2019 for 2020 (39%) vs 2021 (21.3%; P = .001). Very few dental anesthesiologists reported income increases relative to 2019 for 2020 (2.1%) vs 2021 (15.6%; P < .001). Job satisfaction as a dental anesthesiologist remained unchanged for all 3 years., Conclusion: Even though many Japanese dental anesthesiologist specialists lost income because of COVID-19, they maintained their job satisfaction., (© 2023 by the American Dental Society of Anesthesiology.)

Background: A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression., Methods: We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Participants were assigned to receive an extended-release formulation of aceneuramic acid (SA-ER) or placebo. Changes in muscle strength and function over 48 weeks were compared between treatment groups using change in the upper extremity composite (UEC) score from baseline to Week 48 as the primary endpoint and the investigator-assessed efficacy rate as the key secondary endpoint. For safety, adverse events, vital signs, body weight, electrocardiogram, and clinical laboratory results were monitored., Results: A total of 14 patients were enrolled and given SA-ER (n = 10) or placebo (n = 4) tablets orally. Decrease in least square mean (LSM) change in UEC score at Week 48 with SA-ER (- 0.115 kg) was numerically smaller as compared with placebo (- 2.625 kg), with LSM difference (95% confidence interval) of 2.510 (- 1.720 to 6.740) kg. In addition, efficacy was higher with SA-ER as compared with placebo. No clinically significant adverse events or other safety concerns were observed., Conclusions: The present study reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy., Trial Registration Number: ClinicalTrials.gov (NCT04671472)., (© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).)

The distribution of floating plastic debris around the Kuroshio Current which transports plastics from the coastal waters of Asian countries to North Pacific subtropical gyre, was investigated in 2014. The mean abundance and weight of plastic debris on the sea surface were 100,376 counts/km 2 and 446.16 g/km 2 , respectively. Intensive plastic accumulation was observed in the frontal area between the northern edge of the Kuroshio and coastal waters off Shikoku, while a relatively higher abundance in the south of Kuroshio was generally associated with anticyclonic mesoscale eddies. Such an accumulation resulted from the eddy-Kuroshio interactions which are specifically associated with the offshore non-large meandering Kuroshio path. Overall, white, fragmented, small-sized (≤1 mm) particles with polyethylene and polypropylene polymers were dominant. In the southern area of Kuroshio, the contribution of polystyrene and larger-sized plastic was higher, suggesting a rapid influx of fresh particles from western Japan to offshore by the northwest monsoon., Competing Interests: Declaration of competing interest The authors declare no competing interests regarding the work described in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully., Methods: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated., Results: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis., Conclusion: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered a potential conflict of interest., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: GNE myopathy is an ultra-rare muscle disease characterized by a reduction in the synthesis of sialic acid derived from pathogenic variants in the GNE gene. No treatment has been established so far., Objective: We evaluated the safety and efficacy of oral supplementation of aceneuramic acid in patients with GNE myopathy., Methods: This multicenter, placebo-controlled, double-blind study comprised genetically confirmed GNE myopathy patients in Japan who were randomly assigned into treatment groups of sialic acid-extended release (SA-ER) tablets (6 g/day for 48 weeks) or placebo groups (4:1). The primary endpoint of effectiveness was set as the change in total upper limb muscle strength (upper extremity composite [UEC] score) from the start of administration to the final evaluation time point., Results: Among the 20 enrolled patients (SA-ER group, 16; placebo group, 4), 19 completed this 48-week study. The mean value of change in UEC score (95% confidence interval [CI]) at 48 weeks was -0.1 kg (-2.1 to 2.0) in the SA-ER group and -5.1 kg (-10.4 to 0.3) in the placebo group. The least squares mean difference (95% CI) between the groups in the covariance analysis was 4.8 kg (-0.3 to 9.9; P = 0.0635). The change in UEC score at 48 weeks was significantly higher in the SA-ER group compared with the placebo group (P = 0.0013) in the generalized estimating equation test repeated measurement analysis. In one patient in the SA-ER group, who was found to be pregnant 2 weeks after drug administration fetal death with tangled umbilical cord occurred at 13 weeks after the discontinuation of treatment. No other serious adverse effects were observed., Conclusions: The present study indicates that oral administration of SA-ER tablets is effective and safe in patients with GNE myopathy in Japan.

Background: Several studies investigated the utility of inflammation and nutritional markers in predicting the prognosis in patients with gastric cancer; however, the markers with the best predictive ability remain unclear. This retrospective study aimed to determine inflammation and nutritional markers that predicted prognosis in elderly patients over 75 years of age undergoing curative gastrectomy for gastric cancer., Methods: Between January 2005 and December 2015, 497 consecutive elderly gastric cancer patients aged over 75 years underwent curative gastrectomy in 12 institutions. The geriatric nutritional risk index (GNRI), prognostic nutritional index, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and C-reactive protein/albumin ratio were examined as prognostic markers for overall survival (OS) and disease-specific survival (DSS) using area under the curve (AUC) using receiver operating characteristic (ROC) curve analysis., Results: The GNRI had the highest AUC and predictive value for both OS (0.637, p < 0.001) and DSS (AUC 0.645, p < 0.001). The study cohort was categorized into the high and low GNRI groups based on the optimal GNRI cut-off values for OS (97.0) and DSS (95.8) determined with the ROC analysis. For both OS and DSS, there was a significant correlation between the GNRI and several clinicopathological factors including age, body mass index, albumin, American Society of Anesthesiologists physical status score, depth of tumor invasion, lymph node metastasis, lymphatic invasion, pathological stage, operation duration, bleeding, procedure, approach, death due to primary disease, and death due to other disease. The GNRI remained a crucial independent prognostic factor for both OS (Hazard ratio [HR] = 1.905, p < 0.001) and DSS in multivariate analysis (HR = 1.780, p = 0.043)., Conclusions: Among a panel of inflammation and nutritional markers, the GNRI exhibited the best performance as a prognostic factor after curative gastrectomy in elderly patients with gastric cancer, indicating its utility as a simple and promising index for predicting OS and DSS in these patients., (© 2022. The Author(s).)

Sarcopenia is associated with poor prognosis of patients with hepatocellular carcinoma (HCC). We investigated the association of skeletal muscle volume (SMV) and its change in HCC patients taking lenvatinib. In 130 HCC patients, psoas mass index (PMI) was calculated as the left-right sum of the major × minor axis of psoas muscle at the third lumbar vertebra, divided by height squared. Patients were classified into two groups (low and normal PMI) based on indices of < 6.0 cm 2 /m 2 for man and < 3.4 cm 2 /m 2 for women. Change in PMI per month during the lenvatinib administration period (ΔPMI/m) was calculated; and patients were classified into two groups (severe and mild atrophy) based on the ΔPMI/m rate, as ≥ 1% or < 1%, respectively. There was no significant difference in Overall survival (OS) between the low and normal PMI groups at the start of lenvatinib administration. OS was significantly lower in the severe atrophy group than in the mild atrophy group (median; 15.2 vs. 25.6 months, P = 0.005). Multivariate analysis revealed a significant association of severe atrophy with OS (hazard ratio 1.927, P = 0.031). Progressive loss of SMV is a strong predictor of poor prognosis in HCC patients taking lenvatinib., (© 2022. The Author(s).)

Background: Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income., Methods: We utilised prospective birth cohort from the Japan Environment and Children's Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income., Results: Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%)., Conclusions: This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions., (© 2022. The Author(s).)

Abstract: We conducted a study to estimate the seroprevalence of coronavirus disease 2019 (COVID-19) in Kobe, Japan with positive immunoglobulin G (IgG) rate of 3.3% (95% confidence interval [CI] 2.3%-4.6%) in April 2020. Because there were large concerns about the spread of COVID-19 among citizens thereafter, we conduct a follow-up cross-sectional study to estimate the seroprevalence, and we also added a validation study using a different assay.We conducted cross-sectional serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody using 1000 samples from patients at outpatient settings who visited the clinic from May 26 to June 7, 2020, stratified by the decade of age and sex. We used both Kurabo and Abbott serology assays to identify IgG against SARS-CoV-2.There were 18 and 2 positive IgG among 1000 serum samples using Kurabo and Abbott serology assays, respectively (1.8%, 95% CI 1.1%-2.8%, and 0.2%, 95% CI 0.02%-0.7% respectively). By applying the latter figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG is 3038 (95% CI: 304-10,632) while a total of 285 patients were identified by polymerase chain reaction (PCR) testing at the end of the study period. Assuming Abbott assay as the reference, Kurabo assay had calculated sensitivity and specificity of 100% and 98.4% respectively. Age and sex adjusted prevalence of positivity was calculated to be 0.17%.We found a lower seroprevalence than 2 months before in Kobe city although the figures were still higher than those detected by PCR. Kurabo assay showed more false positives than true positives despite reasonable sensitivity and specificity, due to low prevalence in Kobe., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Acute liver failure (ALF) is a rare but dramatic clinical syndrome characterized by massive hepatic necrosis leading to multiorgan failure. It is difficult to predict the outcomes in patients with ALF using existing prognostic models. We aimed to analyze hepatic perfusion using contrast-enhanced ultrasound and Doppler ultrasound in patients with ALF and investigate its utility as a prognostic biomarker., Approach and Results: In this prospective observational study, 208 patients with acute liver injury/ALF were enrolled from 2015 to 2019. We evaluated 50 consecutive patients with ALF with Doppler ultrasound and contrast-enhanced ultrasound performed on admission. The cases were divided into the following two groups: survivors (recovered without surgical intervention) and nonsurvivors (died of ALF or underwent liver transplantation). The time to peak and peak intensity of hepatic artery, portal vein, hepatic vein, and liver parenchyma were calculated using the time-intensity curve analysis. The hepatic artery (HA) resistive index was calculated using the fast Fourier transform analysis of Doppler ultrasound. The time interval (TI) between the time to peak of HA and liver parenchyma (LP) was significantly shorter in the nonsurvivors than in the survivors (P < 0.0001). The area under the receiver operating curve values for TI (HA, LP), Japanese scoring system, HE prediction model, Model for End-Stage Liver Disease score, and King's College Hospital criteria for the prediction of poor prognosis were 0.953, 0.914, 0.861, 0.816, and 0.731, respectively. The most appropriate cutoff value of TI (HA, LP) was 6.897 seconds; the sensitivity, specificity, positive and negative predictive values were 94.4%, 90.6%, 85.0%, and 96.7%, respectively., Conclusions: TI (HA, LP) accurately predicts the outcome in patients with ALF and may be useful in clinical decision making., (© 2020 The Authors. HEPATOLOGY published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Metformin plus a dipeptidyl peptidase-4 inhibitor (DPP-4i) is the most common therapy for Japanese patients with type 2 diabetes. This 24-week, multicentre, open-label, parallel-group trial randomized patients on dual therapy to add-on tofogliflozin (20 mg/day, n = 33) or glimepiride (0.5 mg/day, n = 31). The primary outcome was change in body fat percentage. The secondary outcomes included changes in HbA1c, fat mass, fat-free mass, liver function variables and uric acid. Tofogliflozin and glimepiride reduced HbA1c to a similar extent. Body fat percentage did not change from baseline in either group. Fat mass was reduced by tofogliflozin but was increased by glimepiride (by -2.0 ± 1.7 kg and +1.6 ± 1.6 kg, P = .002). Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by -1.3 ± 1.3 kg and +0.9 ± 2.0 kg, P < .001). Alanine aminotransferase and uric acid levels were reduced by tofogliflozin (P = .006 and P < .001, respectively). These data provide novel information useful for selecting the third oral agent for patients whose diabetes is inadequately controlled with metformin plus DPP-4i dual therapy., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This study aimed to describe undergraduate nursing students' perceived eHealth literacy and learning experiences of eHealth literacy in Japan and to clarify the relationship between these factors. We conducted a self-administered online questionnaire survey using a convenience sample of 353 Japanese undergraduate nursing students selected from three universities. Participants completed the eHealth Literacy Scale and questionnaires on learning experiences of eHealth literacy and some demographic factors. Participants had moderate perceived eHealth (mean [SD], 24.52 [5.20]). More than half the participants responded that they had no learning experiences of health or science literacy. We observed a positive correlation between the total mean eHealth literacy and learning experiences scores. Undergraduate nursing students in Japan had slightly lower perceived eHealth literacy than nursing students in other countries, hospital nurses, and even patients. Of the 353 participants in this study, 69.4% did not know "where to find helpful health resources on the Internet," 80.2% of those lacked the skills "to evaluate health resources," and 68.9% could not "differentiate the quality of health resources on the Internet"; few of the participants perceived themselves as having any experience in learning the six domains of eHealth literacy. Very few reported learning about health (43.3%) and scientific (21.8%) literacy. The low perceived eHealth literacy among participants might reflect lack of knowledge and confidence in eHealth literacy as well as their own low level of health-promoting behaviors; this might influence the quality of health education of clients and their families. Nursing educators should address the lack of eHealth literacy among undergraduate nursing students.

Purpose: The improvement of physical activity in patients with COPD is an important issue. However, no standard for the recommended number of steps for patients with COPD has been determined. We conducted a retrospective observational study to create a simple standard equation for the daily step count, which makes it easier to determine whether each subject is attaining his/her predicted value or not., Patients and Methods: Stable outpatients diagnosed with COPD whose physical activities had been measured using a triaxial accelerometer for more than 2 weeks were recruited from 5 institutes in Japan. Factors associated with the step count were detected by multivariate regression analysis. After the data were transformed to a normalized distribution, a multivariate linear regression equation was created using stepwise regression., Results: One hundred sixty-two patients aged 72.3 (7.2) years and of FEV1 %pred 59.2 (22.8) % were recruited. Among the parameters, age, mMRC dyspnea scale and inspiratory capacity (IC) were detected by the stepwise method. The created standard equation was "Step count = (-0.079×[age]-1.595×[mMRC]+2.078×[IC]+18.149) 3 ". The correlations between the calculated values and the measured values were observed, and fixed, and proportional biases between them were also observed. When patients with <6500 steps/day were selected, no systematic bias between them could be detected., Conclusion: A simple standard equation for Japanese patients with COPD was created using age, mMRC and IC, and could provide an individual-predicted value, especially for patients with <6500 steps/day., Competing Interests: YM received lecturer fee from Nippon Boehringer Ingelheim. The authors report no other conflicts of interest in this work., (© 2019 Nakanishi et al.)

In recent years, blooms of toxic Alexandrium ostenfeldii strains have been reported from around the world. In 2013, the species formed a red tide in a shallow lagoon in western Japan, which was the first report of the species in the area. To investigate the genetic relatedness of Japanese A. ostenfeldii and global isolates, the full-length SSU, ITS and LSU sequences were determined, and phylogenetic analyses were conducted for isolates from western and northern Japan and from the Baltic Sea. Genotyping and microsatellite sequence comparison were performed to estimate the divergence and connectivity between the populations from western Japan and the Baltic Sea. In all phylogenetic analyses, the isolates from western Japan grouped together with global isolates from shallow and low saline areas, such as the Baltic Sea, estuaries on the east coast of U.S.A. and from the Bohai Sea, China. In contrast, the isolates from northern Japan formed a well-supported separate group in the ITS and LSU phylogenies, indicating differentiation between the Japanese populations. This was further supported by the notable differentiation between the sequences of western and northern Japanese isolates, whereas the lowest differentiation was found between the western Japanese and Chinese isolates. Microsatellite genotyping revealed low genetic diversity in the western Japanese population, possibly explained by a recent introduction to the lagoon from where it was detected. The red tide recorded in the shallow lagoon followed notable changes in the salinity of the waterbody and phytoplankton composition, potentially facilitating the bloom of A. ostenfeldii., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Treatment-free remission (TFR), the ability to maintain a molecular response (MR), occurs in approximately 50% of patients with chronic myelogenous leukemia (CML) treated with tyrosine kinase inhibitors (TKIs)., Methods: A multicenter phase 2 trial (Delightedly Overcome CML Expert Stop TKI Trial: DOMEST Trial) was conducted to test the safety and efficacy of discontinuing imatinib. Patients with CML with a sustained MR of 4.0 or MR4.0-equivalent for at least 2 years and confirmed MR4.0 at the beginning of the study were enrolled. In the TFR phase, the international scale (IS) was regularly monitored by IS-PCR testing. Molecular recurrence was defined as the loss of MR4.0. Recurrent patients were immediately treated with dasatinib or other TKIs including imatinib., Results: Of 110 enrolled patients, 99 were evaluable. The median time from diagnosis to discontinuation of imatinib was 103 months, and the median duration of imatinib therapy was 100 months. Molecular recurrence-free survival rates were 69.6%, 68.6% and 64.3% at 6, 12, and 24 months, respectively. After discontinuation of imatinib therapy, 26 patients showed molecular recurrence, and 25 re-achieved deep MR after dasatinib treatment. Molecular response MR4.0 was achieved in 23 patients within 6 months and 25 patients within 12 months. Multivariate analysis revealed that a longer time from diagnosis to discontinuation of imatinib therapy (p = 0.0002) and long duration of imatinib therapy (p = 0.0029) predicted a favorable prognosis., Conclusions: This DOMEST Trial showed the feasibility of TKI discontinuation in a Japanese clinical setting.

Objectives: Transcatheter arterial chemoembolization (TACE) is the standard therapy for patients with intermediate-stage hepatocellular carcinoma (HCC). This study aimed to determine whether combination therapy with radiofrequency ablation (RFA) and TACE was superior to TACE monotherapy for intermediate-stage HCC and identify cases in which this technique was the most effective., Materials and Methods: We selected patients with intermediate HCC who met the following eligibility criteria: (1) ≥ 20 years of age, (2) receiving initial therapy, (3) ≤7 tumors, and (4) maximum tumor diameter <5 cm. We performed propensity score matching (PSM) using potential confounding factors. We retrospectively compared the cumulative overall survival rate and recurrence-free survival rate between the TACE + RFA and TACE groups. Additionally, a sub-group analysis was performed for preoperative factors., Results: Among the 103 patients, 92 were selected using PSM. The cumulative overall survival rates at 1, 3, and 5 years for the TACE + RFA group were 97.4%, 70.4%, and 60.4%, respectively, which were significantly higher than those for the TACE group (92.7%, 55.7%, and 22.8%, respectively, p = .045). The recurrence-free survival rates at 0.5, 1, and 2 years for the TACE + RFA group were 80.0%, 58.6%, and 33.3%, respectively, which were significantly higher than those for the TACE group (34.5%, 8.8%, and 2.9%, respectively, p < .01). For the sub-group with α-fetoprotein (AFP) <100 ng/mL, the TACE + RFA group demonstrated a significantly improved prognosis than the TACE group (p = .036)., Conclusions: The addition of RFA to TACE improved cumulative overall and recurrence-free survival in patients with intermediate-stage HCC, especially in patients with AFP <100.

Aim: To evaluate the usefulness of frozen section diagnosis (FSD) of bile duct margins during surgery for extrahepatic cholangiocarcinoma (CCA)., Methods: We retrospectively analyzed 74 consecutive patients who underwent surgery for extrahepatic CCA from 2012 to 2017, during which FSD of bile duct margins was performed. They consisted of 40 distant and 34 perihilar CCAs (45 and 55 bile duct margins, respectively). The diagnosis was classified into three categories: negative, borderline (biliary intraepithelial neoplasia-1 and 2, and indefinite for neoplasia), or positive. FSD in the epithelial layer, subepithelial layer, and total layer was compared with corresponding permanent section diagnosis (PSD) postoperatively. Then, association between FSD and local recurrence was analyzed with special reference to borderline., Results: Analysis of 100 duct margins revealed that concordance rate between FSD and PSD was 68.0% in the total layer, 69.0% in the epithelial layer, and 98.0% in the subepithelial layer. The extent of remaining biliary epithelium was comparable between FSD and PSD, and more than half of the margins lost > 50% of the entire epithelium, suggesting low quality of the samples. In FSD, the rate of negative margins decreased and that of borderline and positive margins increased according to the extent of the remaining epithelium. Diagnostic discordance between FSD and PSD was observed in 31 epithelial layers and two subepithelial layers. Alteration from borderline to negative was the most frequent (20 of the 31 epithelial layers). Patients with positive margin in the total and epithelial layers by FSD demonstrated a significantly worse local recurrence-free survival (RFS) compared with patients with borderline and negative margins, which revealed comparable local RFS. Patients with borderline and negative margins in the epithelial layer by PSD also revealed comparable local RFS. These results suggested that epithelial borderline might be regarded substantially as negative. When classifying the status of the epithelial layer either as negative or positive, concordance rates between FSD and PSD in the total, epithelial, and subepithelial layers were 95.0%, 93.0%, and 98.0%, respectively., Conclusion: During intraoperative assessment of bile duct margin, borderline in the epithelial layer can be substantially regarded as negative, under which condition FSD is comparable to PSD., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests related to this study.

Introduction: Delayed neurologic sequelae (DNS) after carbon monoxide (CO) poisoning manifest as a relapse of neurologic deficits. However, the long-term outcome of DNS has not been fully clarified. Myelin basic protein (MBP) levels in the cerebrospinal fluid (CSF) have been reported to be elevated in DNS. However, the precise timing and clinical value of the CSF examination have not been fully evaluated. We aimed to clarify the long-term outcome and the factors predicting the outcome of DNS and to evaluate the utility of CSF-MBP for predicting the development and severity of DNS., Methods: This work was designed as a single-center, prospective, observational study. We graded DNS severity as Grade 1 (consistent independence), Grade 2 (temporary dependence), or Grade 3 (persistent dependence). We analyzed the percentage categorized in each grade and the parameters associated with outcome., Results: Of 100 patients experiencing acute CO poisoning (median age: 46 years; 69% male), 20 (20%) developed DNS, including six Grade 1 (30%), ten Grade 2 (50%), and four Grade 3 (20%) cases. The Grade 3 patients [median: 77 years; interquartile range (IQR): 76-82] were older than the Grade 1 patients [42; 30-46] (P<0.01); the DNS onset of the Grade 1 patients [median interval after poisoning: 35 days; IQR: 32-56] occurred later than that of the Grade 3 patients [10; 9-13] P<0.001) and the Grade 2 patients [25; 23-27] (P<0.05). The CSF-MBP levels of the DNS patients were higher than those of the non-DNS patients (P<0.0001). The 1-month CSF-MBP levels of the Grade 3 patients were higher than those of the Grade 1 patients (P<0.05); the MBP index, defined as [(Age)×(1-month CSF-MBP)], was higher in the Grade 3 patients than in the Grade 1 patients (P<0.01). Severe DNS were associated with advanced age (>72.5 years), earlier onset (<18 days), higher 1-month CSF-MBP (>252 pg/ml), and higher MBP index (>20.9 year × ng/ml)., Conclusions: Poor DNS outcomes were associated with advanced age and earlier onset. CSF-MBP can serve as a sensitive predictor of both the development and outcomes of DNS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: It is well known that people with Down's syndrome (DS) frequently complicate with congenital heart diseases (CHDs). Patients with heart diseases often have sleep-disordered breathing as a co-morbidity (SDB) which worsens the heart diseases. However, the relationship between SDB and CHDs in DS people has not yet been fully elucidated. The aim of this study was to establish the association between SDB and CHDs in DS people using data from a large nationwide questionnaire survey in Japan., Methods: We conducted a cross-sectional questionnaire survey of a randomly selected sample of 2,000 DS people and their caregivers throughout Japan to examine the associations between observed signs of SDB and CHDs in DS people. The questionnaire included the presence of SDB symptoms (snoring, apnea, arousal, nocturia, and napping) and CHDs (the presence and types of CHDs)., Results: Of the 1,222 replies received from the caregivers, 650 reported complications of some type of CHDs. The observed apnea tended to be higher among DS people with CHDs than those without CHDs (OR=1.28, 95% CI=0.97-1.70, p=0.09). DS people with tetralogy of Fallot reported significantly more frequent apnea than those without CHDs (OR=3.10, 95% CI=1.36-7.05, p<0.01)., Conclusion: SDB prevailed among DS people with severe CHDs, such as tetralogy of Fallot. Careful attention to the signs of SDB in such patients may lead to earlier clinical intervention removing the vicious cycle between SDB and CHDs.

Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) are immune-mediated peripheral neuropathies, and most of these cases were known to be associated with a preceding infection. Recent reports evidenced an increase in the number of infectious disease cases after the earthquake. The aim of this report is to investigate the incidence and clinical features of GBS and FS after the Great East Japan Earthquake. We found GBS and FS patients had markedly increased in 2011, the year of the earthquake. In regard to an antecedent illness, gastrointestinal infection was significantly increased in GBS patients after the earthquake. These results suggest environmental factors including infectious agents and stress caused by the earthquake might have been involved in the outbreak of the diseases.

We investigated the molecular characteristics of ESBL-producing Escherichia coli in Japan. A total of 101 clinical isolates of ESBL-positive E. coli collected in Japan between June 2008 and November 2009 were studied. Among the 101 strains, 97 were positive for CTX-M, while 47 and two were positive for TEM and SHV, respectively. Sequencing revealed that CTX-M-14 was most common (49/101), followed by CTX-M-27 (22/101) and CTX-M-15 (8/101). Based on MLST data, seven of eight CTX-M-15 producers belonged to ST131. This is the first report about clinical isolates of E. coli ST131 possessing CTX-M-15 in Japan., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Reports of non-anaplastic peripheral T-cell lymphoma (PTCL) in paediatric patients, especially results of stem cell transplantation (SCT), are relatively rare. We herein report the results of SCT using the Transplant Registry Unified Management Program system of the Japanese Society of Stem Cell Transplantation in paediatric patients with non-anaplastic PTCL. We analysed 26 patients (13 females and 13 males) aged ≤18 years with non-anaplastic PTCL who underwent a total of 28 SCT. Median age at transplantation was 13·5 years (range: 0-18 years). PTCL not otherwise specified was diagnosed in 17 patients; extranodal Natural Killer (NK)/T cell lymphoma, nasal type in nine; and subcutaneous panniculitis-like T-cell lymphoma in two. Transplantation was with syngeneic donor in one, related donor in 10; unrelated donor in 10; and auto transplantation in 7. Five-year overall survival rate and event-free survival rate was 62·96% and 55·56%, respectively. Male gender, chronic graft-versus-host disease (GVHD), and reduced intensity conditioning were good prognostic factors in all patients. In 20 patients with refractory or relapsed disease, male gender and chronic GVHD were also good prognostic factors. This study is the first report concerning transplantation in children with non-anaplastic PTCL, although the number of patients was small. Larger studies are needed to confirm these findings., (© 2012 Blackwell Publishing Ltd.)

An anammox assay involving a ¹⁵N tracer and gas chromatography-mass spectrometry revealed that the potential anammox activity accounted for 1 to 5% of total N₂ production in a ravine paddy field, Japan. Among four 4-cm-deep layers, the top layer showed the highest activity. Clone libraries showed that the DNA in the top layer contained sequences related to those of Candidatus 'Brocadia fulgida', Ca. 'B. anammoxidans', and Ca. 'Kuenenia stuttgartiensis'. These results suggest that a specific population of anammox bacteria was present in paddy soils, although a small part of dinitrogen gas was emitted from the soil via anammox.

Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation., (Copyright 2008 Wiley-Liss, Inc.)

Severe sensorineural hearing loss (bilateral >80 dB) was diagnosed in a case of familial hemophagocytic lymphohistiocytosis (FHL). The female patient developed HLH at 3 months of age and underwent allogeneic cord blood transplantation at 11 months of age following 7 months of immuno-chemotherapy. The type 2 FHL patient had a homozygous perforin gene mutation of 1090-1091delCT, and was noted to have hearing loss at 3.5 years of age. Retrospective evaluation did not clarify the exact causes of hearing loss. Reports on Kawasaki disease, suggesting a correlation between severe inflammatory status in infancy and the development of sensorineural hearing loss, may shed some light on this rare complication in this case of FHL. Considering the markedly improved prognosis of FHL due to recent advances made in the molecular diagnosis and in the management including allogeneic hematopoietic stem cell transplantation, auditor by screening might be warranted for surviving FHL patients.

Objectives: Several clinical features, such as the spontaneous regression of some renal cell carcinoma (RCC) metastases after nephrectomy, suggest immune involvement in tumor destruction., Patients and Methods: We investigated the role of genetic variation at the HLA class II loci in RCC by analyzing the HLA-DR antigen and HLA-DRB1, DRB3, DRB4 and DRB5 alleles in 55 patients using the polymerase chain rection., Results: No statistically significant differences were observed in the frequency of the HLA-DR antigen or HLA-DRB3, DRB4, or DRB5 genes between the patients and a healthy control group. On the other hand, the HLA-DRB1*0403 and *1202 alleles were significantly more frequent in the patients than in the controls (p < 0.001 and p < 0.01, respectively)., Conclusion: RCC might be linked to these two alleles in Japanese patients., (Copyright 2000 S. Karger AG, Basel)

Purpose: Nonoperative management for blunt pancreatic injury in children was performed between 1977 and 1998. The efficiency and safety of nonoperative management was examined., Methods: Pancreatic injury was diagnosed in 20 children. The surgical indication was determined by hemodynamic instability and the management of associated injuries. Children without surgical indications were treated initially by nonoperative management., Results: Nineteen of 20 children were treated initially nonoperatively, and 18 of the 19 survived. Surgical exploration was performed in only 1 child with perforation of the duodenum and bile duct. One child died of complications of total parenteral nutrition. Ultrasound scan and computed tomography scan showed pancreatic contusion in 9, laceration in 6, and injury of the main pancreatic duct (MPD) in 5. Pseudocysts were detected in 10 (5 laceration and 5 MPD injury). Pseudocysts smaller than 10 cm disappeared after nonoperative management, and those larger than 10 cm required operative management. Rupture of pseudocysts occurred in 2 children by rotating the upper torso., Conclusions: Nonoperative management of pancreatic injuries is effective in children, although careful management is required to avoid complications. Pseudocysts smaller than 10 cm were treated successfully by nonoperative management, and those larger than 10 cm required surgical management.

A comparative study of ofloxacin (OFLX), a new oral quinolone, was carried out at the Department of Urology, Osaka University Hospital and its eighteen affiliated hospitals to evaluate the clinical efficacy and safety of daily dose of 300 mg, given either once daily dose (SID group), or in three divided doses (TID group), in the treatment of acute uncomplicated cystitis in women. Clinical efficacy was evaluated in 42 cases from the SID group, and 43 cases from TID group, respectively, according to the criteria by the Japanese UTI Committee. In the SID group, the clinical efficacy was evaluated as excellent in 29 cases, moderate in 12 and poor in 1, with an overall clinical effectiveness rate of 98%. In the TID group, it was evaluated as excellent in 25 cases, moderate in 17 and poor in 1, with an overall clinical effectiveness rate of 98%. Safety was monitored only by subjective complaints. In the SID group, no subjective side effects appeared (0%). In the TID group, one of the 43 women (2.3%) complained of borborygmus. These findings suggest that there was no significant difference between the two groups in the safety and efficacy of ofloxacin.

A statistical observation was made on operations at our department from April, 1967 to March, 1989. The total number of operations was 4469. Operation methods and operation numbers about each organ are shown and discussed briefly.

A total of 1799 swine sera collected in Toyama prefecture in the central part of Japan during the years 1978-82 were tested for antibody against swine influenza virus (SIV), A/New Jersey/8/76 (H1N1). A high prevalence of antibody was observed in the years after the severe epizootic of SI, 34.5% in 1979 and 51.7% in 1982. In other years, the percentages of positive sera were low and ranged from 1.7 to 12.4%. Regional variations were seen in relation to a small scale epizootic. No antibody to SIV was detected in any of the sera collected during the warm season. In the following dry and cold winter, however, a severe epizootic occurred among the swine populations.