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Background: Laparoscopic colectomy for malignant disease technically is feasible but not widely accepted because there are no large-series studies or data on long-term outcomes. A retrospective, multicenter study investigating a large series of patients was conducted in Japan to evaluate preliminary long-term results of laparoscopic surgery for colorectal cancer.Methods: The study group comprised 2,036 patients who underwent laparoscopic colorectal resection April 1993 to August 2002 in 12 participating surgical units (Japanese Laparoscopic Surgery Study Group).Results: Of the 1,495 patients with colon cancer, 781 (59%) had International Union Against Cancer (UICC) stage I, 248 (19%) had stage II, and 284 (22%) had stage III disease. Cancer recurred for 61 (4.1%) of 1,367 curatively treated patients (median follow-up period, 32 months; range, 6-125 months). The 5-year survival rate was 96.7% for stage I, 94.8% for stage II, and 79.6% for stage III disease. Of the 541 patients with rectal cancer, 220 (56%) had stage I, 62 had (16%) stage II, and 108 (28%) had stage III disease. Cancer recurred for 30 (5.6%) of 476 curatively treated patients (median follow-up period, 25 months; range 6-102 months). The 5-year survival rate was 95.2% for stage I, 85.2% for stage II, and 80.8% for stage III disease.Conclusions: The findings indicate that laparoscopic surgery for colorectal cancer yields an oncological outcome as good as that reported for conventional open surgery in the Japanese Registry for all disease stages. [ABSTRACT FROM AUTHOR]

Colorectal cancer incidence in relation to body size, smoking, and alcohol consumption was studied in a cohort of 29 051 city residents of Japan. In 1992, each participant completed a self-administered questionnaire on sociodemographic characteristics, drinking, cigarette smoking, diet, exercise, and reproductive and medical histories. The response rate was 92%. From 1993 to 2000, 161 men and 134 women were diagnosed with colorectal cancer at two major hospitals in the city. Relative risks and 95% confidence intervals were calculated by using Cox proportional hazard models. A positive relation between height and colorectal cancer was seen in both sexes, controlling for age, body mass index (BMI), smoking and drinking habits, and years of education. The findings were statistically significant only for men (relative risk 2.13 for the tallest compared with the shortest height tertile; 95% confidence interval=1.26-3.58). Body mass index was also associated positively with colon cancer risk for men, whereas the pattern for women was not clear. There was a positive association between pack-years of cigarette smoking and the risk of rectal cancer in men. A positive dose-response relation between alcohol consumption and colon cancer risk was observed for men and women. [ABSTRACT FROM AUTHOR]

Two major types of mafic granulite layers occur within the Horoman peridotite, an 8 km * 10 km * 3 km orogenic lherzolite exposed in the high-T and low-P Hidaka metamorphic belt of Hokkaido, Japan. The mineral assemblages and textures of these layers reflect subsolidus reactions occurring during uplift from the upper mantle to the crust. Nevertheless, their whole-rock compositions can be used to infer the primary mineralogy of these layers, and a genetic relationship to melts geochemically similar to mid-ocean ridge basalts (MORB). The intralayer compositional variation of Type I layers (Al-Ti augite type mafic granulites) shows that the centers formed as garnet clinopyroxenites in equilibrium with an incompatible element depleted melt that crystallized to form the margins. In contrast, the Type II layers (Cr-diopside type mafic granulites) formed at relatively shallow depths and are much older, ~830 Ma, than the Type I garnet pyroxenites, which formed at ~80 Ma. The temporal sequence supports the hypothesis that the Horoman peridotite represents shallow MORB-related oceanic mantle that had subsided to deeper mantle depths before crustal emplacement. [ABSTRACT FROM PUBLISHER]

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Objectives: In the phase 3 JAVELIN Renal 101 trial in patients with advanced renal cell carcinoma (aRCC), objective response rate (ORR) and progression-free survival (PFS) were significantly improved in patients treated with first-line avelumab plus axitinib vs sunitinib. Here we evaluate real-world outcomes with first-line avelumab plus axitinib in Japanese patients with aRCC., Methods: In this multicenter, noninterventional, retrospective study, clinical data from patients with aRCC treated with first-line avelumab plus axitinib between December 2019 and December 2020 in Japan were reviewed. Endpoints included ORR and PFS per investigator assessment, and time to treatment discontinuation (TTD)., Results: Data from 48 patients (median age, 69 years) from 12 sites were analyzed. Median follow-up was 10.4 months (range, 2.6-16.5), and median duration of treatment was 7.4 months (range, 0.5-16.5). International Metastatic RCC Database Consortium risk category was favorable, intermediate, or poor in 16.7%, 54.2%, and 29.2% of patients, respectively. The ORR was 48.8% (95% CI, 33.3%-64.5%), including complete response in 3/43 patients (7.0%). Thirteen patients (27.1%) had disease progression or died, and median PFS was 15.3 months (95% CI, 9.7 months - not estimable). At data cutoff, 24 patients (50.0%) were still receiving avelumab plus axitinib, and median TTD was 15.2 months (95% CI, 7.4 months - not estimable). Three patients (6.3%) received high-dose corticosteroid treatment for immune-related adverse events, and 8 (16.7%) received treatment for infusion-related reactions., Conclusions: We report the first real-world evidence of the effectiveness and tolerability of first-line avelumab plus axitinib in Japanese patients with aRCC. Results were comparable with the JAVELIN Renal 101 trial., (© 2023 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Medaka Oryzias latipes is a small freshwater fish widely distributed in Japan. It is a popular ornamental fish and now has been recognized as an important model organism in many areas of biological research. Here we report microsporidian infections for the first time in medaka, from 2 research facilities and a wild population. Infected medaka exhibited abnormal appearance with whitish trunk muscle, and microsporidian spores were detected from the affected tissue. The size of spores was similar in all the three cases: 7.0 μm in length and 3.7-4.2 μm in width. In the histological observation, numerous sporophorous vesicles containing spores or other developmental stages were observed within the myocytes of the trunk muscle. Nucleotide sequence of the ribosomal RNA gene was determined and it was identical among all three cases. A BLAST search revealed it shared 99.5-99.6% identity with Pleistophora hyphessobryconis, a microsporidian known to infect >20 freshwater fish species. Light microscopic observation of spores and histological features also indicated the microsporidian infection in medaka is caused by P. hyphessobryconis. This is the first record of the microsporidian species from medaka and from Japan., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Worldwide, children, newborns, and pregnant or postpartum women are vulnerable to disasters and emergency situations, and providing support to this population is of great concern. Japan is located in a disaster-prone area, so disaster response and risk reduction strategies are important priorities., Methods: We introduce a system called the Disaster Liaison for Pediatric and Perinatal Medicine (DLPPM). This was created with a specific focus on perinatal children and pregnant women in Japan. We report the details of its activities, discuss its challenges, and draw on lessons learned for the further development of perinatal support systems, particularly for children., Results: The lessons learned from the activities of the DLPPM include the following: (1) establish a support system for emergency specialists beyond those with pediatric and perinatal specialties; (2) mitigate the risk of indirect damage caused by primary disasters; and (3) establish a networking function linked to existing pediatric and perinatal medicine facilities., Conclusions: By establishing similar systems, we believe that it will be feasible to address pediatric and perinatal care needs in disaster response contexts in other countries and regions around the world., (© 2024 Japan Pediatric Society.)

Background: Participating in groups with diverse members is associated with improved health among older adults. The study examined the relationship between diversity of group members and needed support or long-term care., Methods: We conducted a longitudinal study for the Japan Gerontological Evaluation Study with 61,281 participants aged ≥ 65 years who were surveyed in 2013 and followed-up for six years. We assessed three dimensions of the diversity of the participating members (sex, age, and region of residence). We then graded the diversity level into four categories: level 0 (not in any group), level 1 (in a group without diversity or in a group with diversity in one of the three factors), level 2 (in a group with diversity in two of the three factors), or level 3 (in a group with diversity across all factors). We adjusted for 12 covariates using Cox hazard survival analysis models with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated for the association between group members' diversity levels and needed support or long-term care. The same study was conducted when stratified by employment status at baseline., Results: Participants in social participation groups with more diverse group members had a lower incidence of needed support or long-term care as compared to their counterparts. Compared to those with no participation group, HR decreased by 14% to 24% with increasing levels of diversity. The HR for the level of care needed for participants in the social participation group with high residential diversity was 0.89 (95% CI: 0.84-0.94). For participants who were currently unemployed, HR reductions ranged from 16%-28% with increasing levels of diversity compared to the non-participating group. No association was found for employed participants., Conclusions: The reason the HRs of Japanese elderly people certified as needing support or care are lower when the diversity of participating groups is higher could be owing to the presence of a variety of people and the diversification of social networks, which facilitates the building of bridging social relational capital. Public health policies that encourage participation in diverse organizations will be important in the future., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The clinical features of coronavirus disease 2019 (COVID-19) in children have been changing because of the emergence and rapid spread of variants of concern (VOC). The increase in cases infected with VOC has brought concern with persistent symptoms after COVID-19 in children. This survey aimed to analyze the clinical manifestations and persistent symptoms of pediatric COVID-19 cases in Japan., Methods: We analyzed the clinical manifestations of pediatric COVID-19 cases reported between February 2020 and April 2022 in Japan, using a dedicated database updated voluntarily by the members of the Japan Pediatric Society. Using the same database, we also analyzed persistent symptoms after COVID-19 in children who were diagnosed between February 2020 and November 2021., Results: A total of 5411 and 1697 pediatric COVID-19 cases were included for analyzing clinical manifestations and persistent symptoms, respectively. During the Omicron variant predominant period, the percentage of patients with seizures increased to 13.4% and 7.4% in patient groups 1-4 and 5-11 years of age, respectively, compared with the pre-Delta (1.3%, 0.4%) or Delta period (3.1%, 0.0%). Persistent and present symptoms after 28 days of COVID-19 onset were reported in 55 (3.2%)., Conclusions: Our survey showed that the rate of symptomatic pediatric COVID-19 cases increased gradually, especially during the Omicron variant predominant period, and a certain percentage of pediatric cases had persistent symptoms. Certain percentages of pediatric COVID-19 patients had severe complications or prolonged symptoms. Further studies are needed to follow such patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Regenerative medicine products using allogeneic cells, such as allogeneic cultured epidermis (allo-CE), have become a more critical therapeutic method for the treatment of burns. However, there are no clinically available allo-CE products in Japan. Therefore, establishing a quality-controlled cell bank is mandatory to create regenerative medical products using allogeneic cells. In this study, we selected ten patients from the Department of Plastic Surgery of Kyoto University Hospital to become cell donors. We performed medical interviews and blood sampling for the donor to ensure virus safety. We examined the tissues and isolated cells by performing a nucleic acid test (NAT). To establish a master cell bank, quality evaluation was performed according to the International Conference of Harmonization (ICH) Q5A. Serological tests of the blood samples from the ten donors showed that two of them were ineligible. The cells registered in the cell bank were found to be compatible after virus testing was performed, and a master cell bank was constructed. Hence, we established a keratinocyte and fibroblast bank of clinically usable human cultured cells in Japan for the first time., (© 2022. The Japanese Society for Artificial Organs.)

With the increasing availability of the COVID-19 vaccines, vaccination has been rapidly promoted globally as a countermeasure against the spread of COVID-19. In Japan, vaccination was first introduced in February 2021. However, the amount of concern towards vaccination differs between individuals, and topics of concern include adverse reactions and side effects. This study investigated attitudes toward vaccines or vaccination during the COVID-19 pandemic across different Japanese prefectures, using Yahoo! JAPAN search queries. We first defined a vaccine concern index (VCI) by aggregating the search counts of vaccine-related queries from Yahoo! JAPAN users before examining VCI across all Japanese prefectures, accounting for gender and age. Our results demonstrated that VCI tended to be lower in more populated areas, and VCI was higher in their 20s to 40s than older people, especially in female users. Furthermore, there was a significant positive correlation (Spearman's Rank correlation coefficient [Formula: see text] = 0.60, [Formula: see text]) between VCI and prefectural vaccination rate, suggesting that web searching of adverse vaccine reactions may precede actual vaccination. This could reflect the information-seeking behavior of individuals who are accepting of vaccinations., (© 2022. The Author(s).)

Laboratory tests, especially point-of-care testing (POCT), and related health information exchange (HIE) are necessary for patient management in the home care setting, where clinic-hospital cooperation and interprofessional collaboration are important. We raised the issues ahead of HIE in relation to POCT in home care in Japan, including issues in electronic medical record use, localized interprofessional collaboration networks with information and communication technology, personal health record use and open connectivity. HIE system may depend on the initiatives of expert communities with non-expert partnership, as well as national healthcare policies. We promote future challenges in this growing area., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has affected the lives of people of all ages. Most reports on pediatric cases suggest that children experience fewer and milder symptoms than do adults. This is the first nationwide study in Japan focusing on pediatric cases reported by pediatricians, including cases with no or mild symptoms., Methods: We analyzed the epidemiological and clinical characteristics and transmission patterns of 840 pediatric (<16 years old) COVID-19 cases reported between February and December 2020 in Japan, using a dedicated database which was maintained voluntarily by members of the Japan Pediatric Society., Results: Almost half of the patients (47.7%) were asymptomatic, while most of the others presented mild symptoms. At the time of admission or first outpatient clinic visit, 84.0% of the cases were afebrile (<37.5°C). In total, 609 cases (72.5%) were exposed to COVID-19-positive household members. We analyzed the influence of nationwide school closures that were introduced in March 2020 on COVID-19 transmission routes among children in Japan. Transmission within households occurred most frequently, with no significant difference between the periods before and after declaring nationwide school closures (70.9% and 74.5%, respectively)., Conclusions: COVID-19 symptoms in children are less severe than those in adults. School closure appeared to have a limited effect on transmission. Controlling household transmission from adult family members is the most important measure for prevention of COVID-19 among children., (© 2021 Japan Pediatric Society.)

Background: COVID-19 has disrupted lives and livelihoods and caused widespread panic worldwide. Emerging reports suggest that people living in rural areas in some countries are more susceptible to COVID-19. However, there is a lack of quantitative evidence that can shed light on whether residents of rural areas are more concerned about COVID-19 than residents of urban areas., Objective: This infodemiology study investigated attitudes toward COVID-19 in different Japanese prefectures by aggregating and analyzing Yahoo! JAPAN search queries., Methods: We measured COVID-19 concerns in each Japanese prefecture by aggregating search counts of COVID-19-related queries of Yahoo! JAPAN users and data related to COVID-19 cases. We then defined two indices-the localized concern index (LCI) and localized concern index by patient percentage (LCIPP)-to quantitatively represent the degree of concern. To investigate the impact of emergency declarations on people's concerns, we divided our study period into three phases according to the timing of the state of emergency in Japan: before, during, and after. In addition, we evaluated the relationship between the LCI and LCIPP in different prefectures by correlating them with prefecture-level indicators of urbanization., Results: Our results demonstrated that the concerns about COVID-19 in the prefectures changed in accordance with the declaration of the state of emergency. The correlation analyses also indicated that the differentiated types of public concern measured by the LCI and LCIPP reflect the prefectures' level of urbanization to a certain extent (ie, the LCI appears to be more suitable for quantifying COVID-19 concern in urban areas, while the LCIPP seems to be more appropriate for rural areas)., Conclusions: We quantitatively defined Japanese Yahoo users' concerns about COVID-19 by using the search counts of COVID-19-related search queries. Our results also showed that the LCI and LCIPP have external validity., (©Zhiwei Gao, Sumio Fujita, Nobuyuki Shimizu, Kongmeng Liew, Taichi Murayama, Shuntaro Yada, Shoko Wakamiya, Eiji Aramaki. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 20.07.2021.)

Obtaining an accurate prediction of the number of influenza patients in specific areas is a crucial task undertaken by medical institutions. Infections (such as influenza) spread from person to person, and people are rarely confined to a single area. Therefore, creating a regional influenza prediction model should consider the flow of people between different areas. Although various regional flu prediction models have previously been proposed, they do not consider the flow of people among areas. In this study, we propose a method that can predict the geographical distribution of influenza patients using commuting data to represent the flow of people. To elucidate the complex spatial dependence relations, our model uses an extension of the graph convolutional network (GCN). Additionally, a prediction interval for medical institutions is proposed, which is suitable for cyclic time series. Subsequently, we used the weekly data of flu patients from health authorities as the ground-truth to evaluate the prediction interval and performance of influenza patient prediction in each prefecture in Japan. The results indicate that our GCN-based model, which used commuting data, considerably improved the predictive accuracy over baseline values both temporally and spatially to provide an appropriate prediction interval. The proposed model is vital in practical settings, such as in the decision making of public health authorities and addressing growth in vaccine demand and workload. This paper primarily presents a GCN as a useful means for predicting the spread of an epidemic., Competing Interests: The authors have declared that funding from a commercial source, Yahoo Japan Corporation, does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cancer Information and Support Centers (CISCs), which are set up at designated cancer care hospitals (DCCHs) according to the national cancer control programs in Japan, are expected to provide cancer patients and their families with information and counseling, but their public recognition remains low. Therefore, it is necessary to evaluate the publicity activities of CISCs., Methods: In this study, we evaluated two types of activities for publicizing CISCs conducted inside and outside one of the DCCHs ('Inside Activity' and 'Outside Activity', respectively) by multi-attribute utility technology (MAUT). Seven types of stakeholders, including physicians (n = 5), nurses (n = 4), CISC cancer counselors (n = 5), executives (n = 5), office department staff (n = 5), and licensed social insurance consultants in the hospital (n = 5), as well as patients and citizens (n = 19) were involved in the evaluation., Results: Eight goals of the program for publicizing CISCs were determined. The utility score for each goal was separately calculated for Inside Activity and Outside Activity, and those of the eight goals were summed up to obtain an overall utility score for each activity. Finally, no substantial difference in overall utility score was found between the activity types (Inside Activity = 82.00 vs. Outside Activity = 81.18)., Conclusions: It is implied that omitting or reducing either activity should be avoided in streamlining publicity activities at the CISCs. Despite the limited external validity of the finding, the methodology presented in this study is widely applicable to evaluate other multifaceted programs under an increasingly tight budget in the oncology setting. As the MAUT approach enables us to obtain numerical data for priority settings, it will contribute to rationalized healthcare management, especially in the oncology setting in which objective evaluations of the national cancer-related control programs are lacking and a broad range of stakeholders is involved., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: In patients with severe obesity, albuminuria can be improved by both conventional medical therapy and bariatric surgery. The purpose of this study was to compare the impact of weight loss achieved through conventional medical therapy or laparoscopic sleeve gastrectomy (LSG) on albuminuria in Japanese subjects with severe obesity and identify the factors involved., Methods: We retrospectively evaluated the clinical characteristics including the urinary albumin/creatinine ratio (UACR) of 340 consecutive subjects with a body mass index ≥35 who received LSG (n = 242) or medical therapy (n = 98) between 2010 and 2018 and were followed for at least 12 months., Results: The baseline of the UACR was not different between the 2 groups. At the 12-month follow-up, total weight loss (TWL) and decreases in glycosylated hemoglobin (HbA1c) and loge UACR were greater in the LSG group than in the medical therapy group (body weight; -35.7 kg vs. -8.0 kg, p < 0.001, HbA1c; -1.4% vs. -0.7%, p < 0.001, loge UACR; -0.3 vs. 0.9, p < 0.001). The rate of complete remission of diabetes was significantly higher in the LSG group than in the medical therapy group. At 12 and 36 months (n = 111 in the medical therapy group, n = 56 in the LSG group at 36 months), loge UACR increased in the medical therapy group, while it remained unchanged or decreased in the LSG group. In subjects with microalbuminuria and macroalbuminuria, changes in the loge UACR correlated with percent total body weight loss (%TWL) in both groups at 12 months. Percent TWL contributed independently to the change in the loge UACR, irrespective of whether LSG was performed. In receiver-operating characteristic analysis, a weight loss of 7.8% predicted a decrease in the UACR (∆UACR <0 at 12 months)., Conclusion: Our analysis suggests that albuminuria may increase over time if only medical therapy is continued. To improve albuminuria, weight loss may be more important than whether LSG is performed., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Background: Because of the overabundance of vaccination information on the internet, in the media, and on social media, providing clear and correct information on immunization is critical for parental decision-making. In 2018, the Japan Pediatric Society created and distributed a Vaccine Information Statement (VIS) to provide appropriate immunization information to caregivers. The objectives of the present study were to evaluate the effect of the VIS on immunization rates, adherence to schedule, and parental understanding of immunization in Japan., Methods: This cross-sectional study was conducted at 18 centers in 2 prefectures in Japan. Caregivers were assigned to an intervention group, which received the VIS and a questionnaire when their child reached the age of 1 month, and a control group, which received only the questionnaire. Using the self-reported questionnaires, we evaluated vaccination rates and schedule adherence at age 2 months, and parental knowledge, attitudes, and beliefs regarding immunization. Three months later, the questionnaires were returned, and the findings were compared between the 2 groups., Results: We contacted 422 and 428 persons in the intervention and control groups, respectively, and 111/422 (26.3%) and 119/428 (27.8%) returned the surveys. Vaccination rates and adherence rates for the first dose of 4 recommended vaccines did not differ significantly (P > 0.25); however, there were some positive effects on items related to vaccine knowledge (P = 0.03), perceived benefits (P = 0.02), perceived barriers (P < 0.001), and perceived behavioral control (P = 0.01)., Conclusion: The VIS improved parent comprehension of infant immunization. Future studies should examine if the effects of such an intervention persist and affect vaccine uptake throughout childhood., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Background: More than 100 COVID-19 vaccine candidates are in development since the SARS-CoV-2 genetic sequence was published in January 2020. The uptake of a COVID-19 vaccine among children will be instrumental in limiting the spread of the disease as herd immunity may require vaccine coverage of up to 80% of the population. Prior history of pandemic vaccine coverage was as low as 40% among children in the United States during the 2009 H1N1 influenza pandemic., Purpose: To investigate predictors associated with global caregivers' intent to vaccinate their children against COVID-19, when the vaccine becomes available., Method: An international cross sectional survey of 1541 caregivers arriving with their children to 16 pediatric Emergency Departments (ED) across six countries from March 26 to May 31, 2020., Results: 65% (n = 1005) of caregivers reported that they intend to vaccinate their child against COVID-19, once a vaccine is available. A univariate and subsequent multivariate analysis found that increased intended uptake was associated with children that were older, children with no chronic illness, when fathers completed the survey, children up-to-date on their vaccination schedule, recent history of vaccination against influenza, and caregivers concerned their child had COVID-19 at the time of survey completion in the ED. The most common reason reported by caregivers intending to vaccinate was to protect their child (62%), and the most common reason reported by caregivers refusing vaccination was the vaccine's novelty (52%)., Conclusions: The majority of caregivers intend to vaccinate their children against COVID-19, though uptake will likely be associated with specific factors such as child and caregiver demographics and vaccination history. Public health strategies need to address barriers to uptake by providing evidence about an upcoming COVID-19 vaccine's safety and efficacy, highlighting the risks and consequences of infection in children, and educating caregivers on the role of vaccination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Backgrounds: Since the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients., Methods: Patients and doctors were recruited to complete a web-based questionnaire survey by the Japan Lung Cancer Society., Results: About 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that "there was no discussion" about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that "there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held." About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were "poor physical condition due to side effects of treatment or illness" and "concern about causing problems in the workplace." To assist in balancing work and pharmacotherapy, patients desired "increased opportunities to consult about work" (36.9%) and "provision of treatment options with few adverse events" (28.9%)., Conclusion: This study highlights the importance of doctor-initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work-related topics with their patients., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cell therapy is a promising treatment. One of the key aspects of cell processing products is ensuring sterility of cell-processing facilities (CPFs). The objective of this study was to assess the environmental risk factors inside and outside CPFs. We monitored the temperature, humidity, particle number, colony number of microorganisms, bacteria, fungi, and harmful insects in and around our CPF monthly over one year. The temperature in the CPF was constant but the humidity fluctuated depending on the humidity outside. The particle number correlated with the number of entries to the room. Except for winter, colonies of microorganisms and harmful insects were detected depending on the cleanliness of the room. Seven bacterial and two fungal species were identified by PCR analyses. Psocoptera and Acari each accounted for 41% of the total trapped insects. These results provide useful data for taking the appropriate steps to keep entire CPFs clean., Competing Interests: The authors have declared that no competing interests exist.

Background: Cor a 9 and Cor a 14 are effective markers for predicting hazelnut allergy. However, there have been no reports on the component-resolved diagnostics (CRD) of hazelnut allergy using an oral food challenge (OFC) for diagnosis in Asia. We hypothesized that CRD would improve the accuracy of diagnosing hazelnut allergies in Japanese children., Methods: We recruited 91 subjects (median age: 7.3 years) who were sensitized to hazelnuts and had performed a hazelnut OFC at the National Hospital Organization Sagamihara National Hospital between 2006 and 2017. All subjects were classified as allergic or asymptomatic to 3 g of hazelnuts. The sIgE levels (hazelnut/Cor a 1/Cor a 8/Cor a 9/Cor a 14/alder pollen) were measured using ImmunoCAP. We aimed to determine the predictive factors of hazelnut allergy., Results: Nine subjects (10%) were allergic to ≤3 g of hazelnuts. Levels of sIgE for Cor a 9 in hazelnut-allergic subjects were significantly higher than those in asymptomatic subjects (4.47 vs. 0.76 kU A /L, p = 0.039). Levels of sIgE to alder pollen and Cor a 1 in hazelnut-allergic subjects were significantly lower than those in asymptomatic subjects (<0.10 vs 13.0 kU A /L, p = 0.004; <0.10 vs 5.03 kU A /L, p = 0.025). The area under the receiver operating characteristics curve for hazelnut/alder/Cor a 1/Cor a 9 was 0.55/0.78/0.72/0.71, respectively, with p = 0.651/0.006/0.029/0.040, respectively., Conclusions: The findings of a high sIgE level for Cor a 9 and a low sIgE level for Cor a 1 can improve the diagnostic accuracy to better identify Japanese children sensitized to hazelnuts., (Copyright © 2019 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other organs. This disease should be considered any individual with liver abnormality except infant, any patient older than teenage with neurological (especially for extra pyramidal signs) or neuropsychiatric disorder with or without liver disease and sibling of Wilson disease patient. Typically, a combination of low serum ceruloplasmine levels and high levels of urinary copper contents is sufficient to establish a diagnosis. As other diagnostic tests, measurement of hepatic copper content and ATP7B gene analysis are available. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents, such as D-penicillamine or Trientine, and/or zinc acetate. The author recommend zinc acetate monotherapy for mild to moderate hepatic disorder, Trientine mono therapy for mild to moderate neurologic disorder and combination therapy of Trientine and zinc acetate for sever hepatic or neurologic disorder.

Background: Outbreaks of enterovirus D68 (EV-D68) respiratory infections in children were reported globally in 2014. In Japan, there was an EV-D68 outbreak in the autumn of 2015 (September-October). The aim of this study was to compare EV-D68-specific polymerase chain reaction (PCR)-positive and EV-D68-specific PCR-negative patients., Methods: Pediatric patients admitted for any respiratory symptoms between September and October 2015 were enrolled. Nasopharyngeal swabs were tested for multiplex respiratory virus PCR and EV-D68-specific reverse transcription-PCR. EV-D68-specific PCR-positive and -negative patients were compared regarding demographic data and clinical information., Results: A nasopharyngeal swab was obtained from 76 of 165 patients admitted with respiratory symptoms during the study period. EV-D68 was detected in 40 samples (52.6%). Median age in the EV-D68-specific PCR-positive and -negative groups was 3.0 years (IQR, 5.5 years) and 3.0 years (IQR, 4.0 years), respectively. The rates of coinfection in the two groups were 32.5% and 47.2%, respectively. There was no significant difference in the history of asthma or recurrent wheezing, length of hospitalization, or pediatric intensive care unit admission rate between the groups. The median days between symptom onset and admission was significantly lower for the EV-D68-positive group (3.0 days vs 5.0 days, P = 0.001). EV-D68 was identified as clade B on phylogenetic analysis. No cases of acute flaccid myelitis were encountered., Conclusions: More than half of the samples from the children admitted with respiratory symptoms were positive for EV-D68-specific PCR during the outbreak. Asthma history was not associated with the risk of developing severe respiratory infection., (© 2019 Japan Pediatric Society.)

Aim: To evaluate volume-outcome relationship in paediatric out-of-hospital cardiac arrest (OHCA)., Methods: This post hoc analysis of the SOS-KANTO 2012 study included data of paediatric OHCA patients <18 years old who were transported to the 53 emergency hospitals in the Kanto region of Japan between January 2012 and March 2013. Based on the paediatric OHCA case volume, the higher one-third of institutions (more than 10 paediatric OHCA cases during the study period) were defined as high-volume centres, the middle one-third institutions (6-10 cases) were defined as middle-volume centres and the lower one-third of institutions (less than 6 cases) were defined as low-volume centres. The primary outcome measurement was survival at 1 month after cardiac arrest. Multivariate logistic regression analysis for 1-month survival and paediatric OHCA case volume were performed after adjusting for multiple propensity scores. To estimate the multiple propensity score, we fitted a multinomial logistic regression model, which fell into one of the three groups as patient demographics and prehospital factors., Results: Among the eligible 282 children, 112, 82 and 88 patients were transported to the low-volume (36 institutions), middle-volume (11 institutions) and high-volume (6 institutions) centres, respectively. Transport to a high-volume centre was significantly associated with a better 1-month survival after adjusting for multiple propensity score (adjusted odds ratio, 2.55; 95% confidence interval, 1.05-6.17)., Conclusion: There may be a relationship between institutional case volume and survival outcomes in paediatric OHCA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims/introduction: To assess the associations of working conditions, eating habits and glycemic control among young Japanese workers with type 2 diabetes., Materials and Methods: This hospital- and clinic-based prospective study included 352 male and 126 female working patients with diabetes aged 20-40 years. Data were obtained from June to July 2012 and June to July 2013. Logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for suboptimal glycemic control (glycosylated hemoglobin level of ≥7%) obtained from June to July 2013., Results: Multivariable logistic regression analysis showed that disease duration of ≥10 years (OR 2.43, 95% CI 1.02-5.80), glycosylated hemoglobin level of ≥7% in 2012 (OR 8.50, 95% CI 4.90-14.80), skipping breakfast and late evening meals (OR 2.50, 95% CI 1.25-5.00) and working ≥60 h/week (OR 2.92, 95% CI 1.16-7.40) were predictive of suboptimal glycemic control in male workers, whereas a glycosylated hemoglobin level of ≥7% in 2012 (OR 17.96, 95% CI 5.93-54.4), oral hyperglycemic agent therapy (OR 12.49, 95% CI 2.75-56.86) and insulin therapy (OR 11.60, 95% CI 2.35-57.63) were predictive of suboptimal glycemic control in female workers., Conclusions: Working ≥60 h/week and habitual skipping breakfast concomitant with late evening meals might affect the ability of young male workers with type 2 diabetes to achieve and maintain glycemic control., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Cardiac arrest, particularly in children, often has a poor outcome and international guidelines highlight significant gaps in the evidence base for effective resuscitation. Whilst randomised controlled trials for some interventions can be justified, they are not appropriate for many aspects of resuscitation. Therefore, guidelines must use other sources of data such as epidemiological evidence from cardiac arrest registries, to improve the efficacy of resuscitation. The aim of our study was to identify existing national cardiac arrest registries and document key information about the registries, including whether they contain data on paediatric arrests., Methods: Key bibliographic databases were searched for papers about or using data from cardiac arrest registries. Two reviewers independently screened the search results for relevant papers. A list of registers named in the papers was compiled and information obtained from the papers and the websites of registers where possible., Results: Twenty three active national or large regional cardiac arrest registries were identified. These included five international collaborations and 10 registries that cover a population of at least 10 million people. Twelve registries are based in Europe, five in North America, four in Asia and two in Australasia. The registries vary in their organisation, but the majority (20) defer to the Utstein reporting guidelines for cardiac arrest. Registries covered populations between 0.4 and 174.5 million and contained between 100 and 605,505 records. Sixteen collected data on out-of-hospital arrests only; three in-hospital arrests only; and four included both. For ten registers the number of paediatric arrests was available and ranged from 56 to 3900., Conclusions: To our knowledge this report contains the most complete list of active national and large regional cardiac arrest registries. Register data support current guidelines on effective resuscitation however, even the largest registries include relatively small numbers, particularly of paediatric events. A less fragmented approach has the potential to improve the utility of registration data for the benefit of patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

[Objective] To contribute to countermeasures against pulmonary tuberculosis in patients with HIV infection through analyzing and evaluating its treatment outcomes and patient management. [Methods] The 'subjects were pulmonary tuberculosis patients newly registered between 2008 and 2014 in whom concomitant HIV infection was detected. For the control, sex- and generation-matched pulmonary tuberculosis patients newly registered in Osaka City -between 2012 and 2014 were adopted. On analysis, the X² test and Fisher's exact test were used, and a significance level below 5% was regarded as significant. [Results] 1) There were 25 pulmonary tuberculosis patients complicated by HIV. All were male -and the mean age was 43.2 years old. 2) The sputum smear positivity rate was 76.0% in the pulmonary tuberculosis patients complicated by HIV and 50.8 % in 250 control pulmonary tuberculosis patients, showing a significantly higher rate in the former. 3) Risk factors for the discontinuation of medication for tuberculosis: In the patients complicated by HIV, the follow- ing risks of the discontinuation of medication were noted in the order of a decreasing frequency: 'Lack of medication helpers' in 68.0%, 'Side effects' in 48.0%, 'Financial prob- lems' in 32.0%, and 'Liver damage' in 28.0%. Those in the control pulmonary tuberculosis patients were 33.2%, 22.8 %, 16.0%, and 11.6%, respectively, showing a significant difference in each factor. 4) The DOTS executing rates were 68.0% and 94.8% in the patients complicated by HIV and control patients, respectively, showing that it was significantly lower in the patients complicated by HIV. On comparison of the treatment outcomes excluding died, on treatment, transferred out, not evaluated, treatment succeeded in 72.7% in the patients complicated by HIV and 92.9% in the control patients, showing a significantly lower success rate in the patients complicated by HIV. The numbers of risk factors of discon- tinuation in. 16 and 6 patients complicated by HIV in whom treatment succeeded and treatment failed/defaulted were 3.8 and 2.8, respectively, showing that the number was higher in patients with successful treatment, and the DOTS execution rates were 75.0% and 33.3%, respectively, showing a higher rate in the successful treatment cases. [Conclusion] The treatment outcome was significantly poorer in pulmonary tuberculosis patients complicated by HIV than in the control pulmonary tuberculosis patients. More risk factors for the discontinuation of medication were observed and the DOTS execution rate was lower in the patients complicated by HIV, suggesting that risk assess- fient for the discontinuation of medication should be appro- priately performed, and support for medication should be strengthened.

[Purpose] To improve the treatment outcomes by analyzing/evaluating the association between DOTS and treatment outcomes in patients with extra-pulmonary tuber- culosis. [Methods] The subjects were patients with extra-pulmonary tuberculosis newly registered in Osaka City between 2012 and 2014. As controls, patients with pulmonary tuberculosis during this period were enrolled. Patients in whom compli- ance was confirmed once a month or more were regarded as completing DOTS. [Results] There were 434 patients with extra-pulmonary tuberculosis. Treatment was completed in 73.3% of these patients. Defaulted rates accounted for 9.4%. The mortality rate was 13.4%. Treatment is being conducted in 2.8%. Furthermore, 0.7% was transferred out. The results were unclear in 0.5%. We investigated changes in the DOTS and defaulted rates, excluding patients who died, those who were referred to other hospitals, those receiving treatment, and those whose results were unclear. The DOTS rates in 2012, 2013, and 2014 were 85.5, 87.5, and 91.2%, respectively, showing a slight increase. The defaulted rates were 14.5, 10.7, and 7.8%, respectively, showing a decrease. When compar- ing the results between the extra-pulmonary and pulmonary tuberculosis patients, the defaulted rates were 11.4 and 6.2 %, respectively; the percentage was significantly higher in the extra-pulmonary tuberculosis patients. The DOTS rates were 87.7 and 97.2%, respectively; the percentage was sig- nificantly lower in the extra-pulmonary tuberculosis patients. There were 41 defaulted cases. The reasons were "side effects" in 41.5%, "physicians' instructions" in 24.4%, "self- discontinuation/refusal" in 22.0%, and "preferential treatment for other diseases" in 12.2%. In the extra-pulmonary tuberculosis patients, the proportion of those in whom "side effects" led to defaulted was higher than in the pulmonary tubercu- losis patients, and that of those "self-discontinuation/refusal" was significantly lower. [Conclusion] Although the defaulted rate has decreased with an increase in the DOTS rate in patients with extra- pulmonary tuberculosis, both the DOTS and defaulted rates were less favorable than in patients with pulmonary tuber- culosis. In the future, it may be necessary to decrease the defaulted rate by intensifying DOTS. Of the reasons for defaulted, "side effects" and "physicians' instructions" account- ed for a high percentage. Therefore, it may be important to provide medical institutions with information.

Purpose: To evaluate the efficacy and safety of imidafenacin (IM), a novel short half-life anticholinergic, as add-on therapy for male LUTS with nocturia and nocturnal polyuria., Materials and Methods: This multicenter, prospective, randomized, open-labelled study was conducted and involved men who had frequency, urgency, and nocturia despite receiving a stable dose of α1-blocker for ≥1 month. Subjects were randomised to control (α1-blocker alone), IM twice/day (α1-blocker +0.1 mg imidafenacin twice daily), or IM nightly (α1-blocker plus 0.1 mg imidafenacin nightly) group; the treatment period was 8 weeks. Primary endpoints included improvements in night-time frequency and Nocturia Quality of Life Questionnaire (N-QOL) scores. Secondary endpoints included changes from the baseline in frequency volume chart variables, and post-void residual volume., Results and Limitations: Compared with the controls, IM twice/day and IM nightly patients had a significantly lower night-time frequency (changes from baseline: 0.1 ± 0.8 in control, -0.6 ± 0.9 in IM twice/day, and -0.4 ± 1.0 in IM nightly, p = 0.5227, 0.0006 and 0.0143, respectively). The hours of undisturbed sleep and N-QOL score were significantly improved in IM twice/day group, though not IM nightly group. Nocturnal urine volume was significantly reduced in IM nightly group, although total urine volume remained unchanged., Conclusions: A short half-life anticholinergic is suggested to be safe and effective as an add-on therapy for residual nocturia in patients with male LUTS receiving α1-blocker treatment. Anticholinergic administration nightly could reduce the nocturnal urine volume.

As mouth breathing is associated with asthma and otitis media, it may be associated with other diseases. Therefore, this population-based cross-sectional study evaluated the association of mouth breathing with the prevalences of various diseases in children. Preschool children older than 2 years were included. A questionnaire was given to parents/guardians at 13 nurseries in Tokushima City. There were 468 valid responses (45.2%). We defined a subject as a mouth breather in daytime (MBD) if they had 2 or more positive items among the 3 following items: "breathes with mouth ordinarily," "mouth is open ordinarily," and "mouth is open when chewing." We defined subjects as mouth breathers during sleep (MBS) if they had 2 or more positive items among the following 3 items: "snoring," "mouth is open during sleeping," and "mouth is dry when your child gets up." The prevalences of MBD and MBS were 35.5% and 45.9%, respectively. There were significant associations between MBD and atopic dermatitis (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.4-4.2), MBS and atopic dermatitis (OR: 2.4, 95% CI: 1.3-4.2), and MBD and asthma (OR: 2.2, 95% CI: 1.2-4.0). After adjusting for history of asthma and allergic rhinitis; family history of atopic dermatitis, asthma, and allergic rhinitis; and nasal congestion; both MBD (OR: 2.6, 95% CI: 1.3-5.4) and MBS (OR: 4.1, 95% CI: 1.8-9.2) were significantly associated with atopic dermatitis. In preschool children older than 2 years, both MBD and MBS may be associated with the onset or development of atopic dermatitis.

Objective: This study was designed to evaluate efficacy and safety of aripiprazole once-monthly (AOM) by verifying non-inferiority of AOM to oral aripiprazole in Asian patients with schizophrenia., Method: The study consisted of a screening phase and three phases: an oral conversion phase (≤12weeks), an oral stabilization phase (≤12weeks) and a 52-week double-blind phase. Patients meeting stabilization criteria for 4weeks during the oral stabilization phase were randomly assigned (1:1) to AOM (400mg) or oral aripiprazole (6-24mg/day). The primary endpoint was Kaplan-Meier estimated rate of non-exacerbation of psychotic symptoms/non-relapse at Week 26., Results: A total of 724 patients were screened, and 502 patients entered the oral stabilization phase. Of 455 patients randomized in the double-blind phase, 228 received AOM and 227 received oral aripiprazole. The non-exacerbation of psychotic symptoms/non-relapse rates at Week 26 were 95.0% (AOM) and 94.7% (oral aripiprazole) and the difference was 0.3% (95% CI: -3.9,4.5), thus non-inferiority of AOM compared to oral aripiprazole with respect to non-exacerbation of psychotic symptoms/non-relapse rate was shown with a margin of -3.9% which is well above the pre-defined non-inferiority limit (-15%). The proportions of patients meeting exacerbation of psychotic symptoms/relapse criteria and stabilization of psychotic symptoms/maintenance criteria were 6.6% and 92.5% in both groups. Discontinuation rates due to all reasons were 25.9% (AOM) and 33.5% (oral aripiprazole). AOM was well tolerated as well as oral aripiprazole., Conclusions: Non-inferiority of AOM to oral aripiprazole was established. AOM is efficacious in maintenance treatment of stabilized schizophrenia, with comparable efficacy and tolerability to oral aripiprazole., Clinical Trials Registration: JapicCTI-101175., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Conclusion: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is considered to be a distinct entity in Japan. The combination of both HPV-DNA sequencing analysis and immunohistochemistry (IHC) for p16(INK4A) is useful to discriminate the OPSCC patients with a better prognosis from other cases, especially in the advanced stage. Surgical treatment is recommended for HPV-negative advanced cancer., Objective: The number of HPV-related OPSCCs has been increasing worldwide. However, the incidence and prognostic significance of this cancer in Japan have not yet been fully elucidated., Methods: Seventy-seven Japanese patients with OPSCC were enrolled in this study. The prevalence of HPV-DNA was assessed by PCR and sequencing. The expression of p16(INK4A) and p53 was examined by IHC. The clinicopathological parameters and disease-specific survival were analyzed for HPV-positive and -negative patients., Results: HPV-DNA was detected in 32 patients. Thirty-four patients were p16(INK4A)-positive by IHC. The patients who were positive for HPV infection were significantly younger. Furthermore, in the stage III or IV cases, the 3-year disease-specific survival of the HPV infection-positive group was significantly better than that of the HPV-negative group. Surgical treatment was demonstrated to lead to a good prognosis for the patients with HPV-negative advanced cancer.

Background: Filaggrin (FLG) is a major protein component of the stratum corneum (SC) layer, and FLG loss-of-function mutations are a predisposing factor for atopic dermatitis (AD). Previous cohort studies of children from northern and western Europe have reported FLG loss-of-function mutation frequencies of 15.1-20.9% and 5.8-13.0% in AD and non-AD groups, respectively., Objective: To elucidate the association between AD prevalence of FLG loss-of-function mutation carriers and climate conditions, we determined the AD prevalence and FLG loss-of-function mutation frequencies in a cohort of children from Ishigaki Island. Ishigaki Island has a subtropical climate with high humidity (monthly average, 60.8-78.7%) and high temperature (monthly average, 18.5-29.4°C) throughout the year., Methods: We diagnosed AD prevalence and analyzed eight FLG loss-of-function mutations in the Japanese population against a cohort of 721 children from the Kyushu University Ishigaki Atopic Dermatitis Study (KIDS) cohort. Parents gave consent for the mutation analysis during their medical examinations from 2001 to 2006., Results: Average AD prevalence was 7.3% per year, and a total of 127 children (17.6%) were diagnosed with AD at least once between 2001 and 2006. The average total serum IgE level differed significantly between the AD and non-AD groups (199.0 and 69.0IU/ml, respectively). Although five kinds of FLG loss-of-function mutations isolated in previous Japanese FLG mutation studies were identified, the FLG loss-of-function mutation frequency in children of the KIDS cohort was not significantly different between the AD and non-AD groups (7.9% and 6.1%, respectively; P=0.174)., Conclusion: The FLG loss-of-function mutation frequency was not significantly different between the AD and non-AD groups in a cohort of children from Ishigaki Island, which has a subtropical climate, suggesting that FLG loss-of-function mutations are not always a predisposing factor for AD prevalence., (Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Epstein-Barr virus (EBV) infection is usually asymptomatic and persists lifelong. Although EBV-infected B cells have the potential for unlimited proliferation, they are effectively removed by the virus-specific cytotoxic T cells, and EBV-associated lymphoproliferative disease develops only in immunocompromised hosts. Rarely, however, individuals without apparent immunodeficiency develop chronic EBV infection with persistent infectious mononucleosis-like symptoms. These patients have high EBV-DNA load in the peripheral blood and systemic clonal expansion of EBV-infected T cells or natural killer (NK) cells. Their prognosis is poor with life-threatening complications including hemophagocytic lymphohistiocytosis, organ failure, and malignant lymphomas. The term "chronic active EBV infection" (CAEBV) is now generally used for this disease. The geographical distribution of CAEBV is markedly uneven and most cases have been reported from Japan and other East Asian countries. Here we summarize the current understanding of CAEBV and describe the recent progress of CAEBV research in Japan., (© 2014 Japan Pediatric Society.)

Purpose: To assess the incidence, background, outcome and risk factors for death of severe sepsis in Japanese paediatric intensive care units (PICUs)., Methods: A data analysis of a prospective, multicentre, 3-year case registry from nine medical-surgical Japanese PICUs. Children with severe sepsis, aged 0-15 years, who were consecutively admitted to the participating PICUs from 1 January 2007 to 31 December 2009 were enrolled. The incidence, background, causative pathogens or infective foci, outcome and risk factors for death caused by severe sepsis were analysed., Results: One hundred forty-one cases were registered. After the exclusion of 14 patients because of incomplete data or inappropriate entry, 127 patients were eligible for the analysis. There were 60 boys and 67 girls, aged 23 [5-68] (median [IQR]) months and weighed 10 [5.5-16.5] kg. The incidence was 1.4 % of total PICU admissions. Sepsis was community-acquired in 35 %, PICU-acquired in 37 % and acquired in hospital general wards in 28 %. Methicillin-resistant Staphylococcus aureus was the most frequent pathogen. The crude 28-day mortality was 18.9 %, comparable to the mean PIM-2 predicted mortality (17.7 %). The mortality rate in patients with shock was significantly increased to 28 % compared to those without shock (5 %). The presences of existing haematological disorders (OR 8.97, 95 % CI, 1.56-51.60) and shock (OR 5.35, 1.04-27.44) were significant factors associated with mortality by multivariate analysis., Conclusions: The mortality from severe sepsis/septic shock in Japanese PICUs was ~19 %. Haematological disorders and presence of shock were associated with death.

Objective: We assessed out-of-hospital cardiac arrests (OHCAs) for various pediatric age groups., Methods: This prospective, population-based, observational study included all emergency medical service-treated OHCAs in Osaka, Japan, between 1999 and 2006 (excluding 2004). Patients were grouped as adults (>17 years), infants (<1 year), younger children (1-4 years), older children (5-12 years), and adolescents (13-17 years). The primary outcome measure was 1-month survival with favorable neurologic outcome., Results: Of 950 pediatric OHCAs, resuscitations were attempted for 875 patients (92%; 347 infants, 203 younger children, 135 older children, and 190 adolescents). The overall incidence of nontraumatic pediatric OHCAs was 7.3 cases per 100 000 person-years, compared with 64.7 cases per 100 000 person-years for adults and 65.5 cases per 100 000 person-years for infants. Most infant OHCAs occurred in homes (93%) and were not witnessed (90%). Adolescent OHCAs often occurred outside the home (45%), were witnessed by bystanders (37%), and had shockable rhythms (18%). One-month survival was more common after nontraumatic pediatric OHCAs than adult OHCAs (8% [56 of 740 patients] vs 5% [1677 of 33 091 patients]; adjusted odds ratio: 2.26 [95% confidence interval: 1.63-3.13]). One-month survival with favorable neurologic outcome was more common among children than adults (3% [21 of 740 patients] vs 2% [648 of 33 091 patients]; adjusted odds ratio: 2.46 [95% confidence interval: 1.45-4.18]). Rates of 1-month survival with favorable neurologic outcome were 1% for infants, 2% for younger children, 2% for older children, and 11% for adolescents., Conclusion: Survival and favorable neurologic outcome at 1 month were more common after pediatric OHCAs than adult OHCAs.

Background: In-hospital cardiopulmonary arrest (CPA) is an important issue, but data in Japan are limited., Methods and Results: To investigate in-hospital CPA, we conducted a prospective multicenter observational registry of in-hospital CPA and resuscitation in Japan (J-RCPR). During January 2008 to December 2009, patients were registered from 12 participating hospitals. All patients, visitors and employees within the facility campus who experience a cardiopulmonary resuscitation event defined as either a pulseless or a pulse with inadequate perfusion requiring chest compressions and/or defibrillation of ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) were registered. Data were collected in 6 major categories of variables: facility data, patient demographic data, pre-event data, event data, outcome data, and quality improvement data. Data for 491 adults were analyzed. The prevalence of pulseless VT/VF as first documented rhythm was 28.1%, asystole was 29.5% and pulseless electrical activity was 41.1%. Immediate causes of event were arrhythmia 30.6%, acute respiratory insufficiency 26.7%, and hypotension 15.7%. Return of spontaneous circulation was 64.7%; the proportion of survival 24h after CPA was 49.8%, the proportion of survival to hospital discharge was 27.8% and proportion of favorable neurological outcome at 30 days was 21.4%., Conclusions: This is the first report of the registry for in-hospital CPA in Japan and shows that the registry provides important observational data., (All rights are reserved to the Japanese Circulation Society.)

Wilson disease is an autosomal recessive disorder with copper metabolism. In Japan, the standard treatment is the administration of copper chelating agents, such as D-penicillamine and trientine. In this study, the authors used zinc acetate to treat Japanese patients with Wilson disease and investigated its efficacy. The 37 patients that comprise this study were found to have Wilson disease using clinical and biochemical tests and were administrated zinc acetate for 48 weeks. The authors followed the clinical symptoms and laboratory findings of the patients by assessing their complete blood counts, biochemical findings, as well as the results of urinalysis and special laboratory tests for copper and zinc metabolism. We also examined side effects of the treatment. Zinc acetate did not aggravate the hepatic or neurological symptoms of any of the patients. Blood biochemical analysis also did not reveal elevation of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltranspeptidase levels. Zinc treatment did not aggravate the patients' clinical signs and/or laboratory findings. However, it did improve some clinical symptoms of the Wilson disease patients. Although this agent had some side effects, none of them were severe. The authors measured spot urinary copper excretion, which gave an indication of the efficacy of treatment and of the sufficient dosage of zinc. We recommend maintaining a spot urinary copper excretion less than 0.075-μg/mg creatinine. The authors conclude that zinc acetate is an effective and safe treatment for Japanese patients with Wilson disease., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Periodontitis is a chronic inflammatory disease caused by the infection of periodontopathic bacteria in dental plaque. However, an individual's susceptibility to this disease appears to be associated with multiple genetic factors, as seen in the case of leprosy. In order to gain a better understanding of the pathophysiology of periodontal disease in subjects with leprosy, we investigated the clinical features of periodontitis and the immunological responses against periodontopathic bacteria in 382 subjects with a history of leprosy and 451 age-matched control subjects. The prevalence of periodontitis and the degree of periodontal pocket depth were found to be significantly higher in leprosy patients than in age-matched controls. Furthermore, a comparison of the clinical parameters of lepromatous leprosy (L-lep) and tuberculoid leprosy (T-lep) patients showed that the probing pocket depth of L-lep patients with periodontal disease was significantly higher than that for T-lep patients. In contrast, serum IgG titers against Porphyromonas gingivalis in L-lep patients were significantly lower than in T-lep patients. These results imply that L-lep patients show more severe periodontal disease than T-lep patients or age-matched control subjects, and that low humoral immunity against P. gingivalis might be one of the genetic factors determining periodontal disease susceptibility in leprosy patients.

Background: Recent reports indicated that nonsense mutations in filaggrin (FLG) found in ichthyosis vulgaris (IV) patients are predisposing factors for atopic dermatitis (AD) with asthma. The exon 3 of FLG contains tandemly repeated, highly homologous, 11-13 sequence units of 972 or 975 bp, each of which corresponds to the coding sequence of the processed filaggrin with slight sequence difference. This unique gene structure has hampered the precise DNA sequence determination., Objective: We developed a novel DNA sequencing method "FLG-shotgun" to directly characterize the mutations in Japanese AD patients., Methods: We examined 24 Japanese AD patients with "FLG-shotgun" method., Results: Multiple units of FLG were amplified by PCR using several sets of common primers for the conserved regions, and DNA sequences of each cloned PCR product were determined. Multiple reads of DNA sequences in both alleles were aligned and re-constructed to cover the entire coding regions. We found three major genotypes (A, B, and C) which represent different numbers (11-13) of homologous sequence units. Furthermore, we found two novel nonsense mutations; one mutation 8666-8667CC>GA on the unit 9 of allele B that causes a nonsense mutation S2899X in two patients and the other mutation 9887C>A on the unit 10 of allele B that causes a nonsense mutation S3296X in two patients., Conclusion: We found two novel FLG mutations by directly analyzing Japanese patients with AD. FLG-shotgun will provide a valuable tool to further define the nature of the AD phenotype associated with FLG mutations.

Wilson's disease (WND) is an autosomal recessive disorder of copper (Cu) accumulation leading to liver and/or brain damage. Oral chelating agents and diet are effective in treating WND. However, once irreversible damage has occurred, the effect of treatment is diminished and the patient's quality of life is compromised. For these reasons an effective method for screening has been needed for early detection of presymptomatic patients. We conducted an early and presymptomatic detection of WND using a novel automated assay of ceruloplasmin (Cp) concentration in urine and selected the mandatory medical health care examination for 3-year-old children in Hokkaido Prefecture (the largest administrative division in Japan) as a sampling point. We measured urinary Cp concentrations in 11,362 children using an immunological latex agglutination assay kit developed by us. Among these children we identified a positive case with markedly reduced urinary Cp concentration. Detailed medical examination provided no clinical manifestations to support the diagnosis of WND, although serum Cp and Cu levels were remarkably low in this case. Therefore, we analyzed the WND gene in order to confirm the diagnosis. Sequence analysis revealed that the case was compound heterozygous for the WND gene mutations 2871del.C and D1296N. According to the Ferenci scoring system for WND diagnosis, the case was established as a WND patient at the presymptomatic stage. Consequently, the patient has maintained a good quality of life under medical treatment with polaprezinc administration to date. Our investigation suggests that the screening system for WND using the automated urinary assay at the mandatory medical health care examination for 3-year-old children is a noninvasive and efficient method for the early and presymptomatic diagnosis of WND.

Objective: Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program., Methods: Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) 2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of '%PSADT > 2y' was expected to be >80%., Results: One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT > 2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired., Conclusions: The primary endpoint, '%PSADT > 2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.

Background: The efficacy of individual chemotherapy based on chemosensitivity has scarcely been studied., Methods: We examined the chemosensitivites for four anticancer agents - 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3 (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), carboplatin, cisplatin, and etoposide - of 43 malignant astrocytic tumors (21 anaplastic astrocytomas and 22 glioblastomas) by using a collagen gel matrix assay, and we also determined the survival periods of the tumor-bearing patients. The chemosensitivity was evaluated in terms of the growth inhibition rate, using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) method., Results: For the anaplastic astrocytomas, the mean growth inhibitory rate was 33.2% with cisplatin, 37.2% with carboplatin, 28.0% with ACNU, and 24.8% with etoposide. For the glioblastomas, these rates were 36.9%, 42.3%, 23.2%, and 34.8%, respectively. The median overall and progression-free survivals of anaplastic astrocytoma-bearing patients who had undergone chemotherapy with two anticancer drugs, both of which showed significant anticancer activity (growth inhibitory rate >30%) were significantly longer than those of the patients who had been treated with two drugs, one or both of which did not show significant anticancer activity. On the other hand, there was no significant difference in the overall or the progression-free survivals in the two corresponding groups of glioblastoma-bearing patients., Conclusion: The collagen gel matrix assay is clinically useful to determine in vitro chemosensitivity that reflects in vivo chemosensitivity. Individual chemotherapy for malignant astrocytic tumors, based on chemosensitivity data, could contribute to longer survival, particularly in anaplastic astrocytoma-bearing patients.

The risk of the development of colon cancer in relation to a western diet was studied in a community-based cohort in Japan. From 1992 to 2000, 13,894 men and 16,327 women were followed. In men, high consumption of processed meat increased the risk in comparison with low consumption (adjusted RR=1.98, 95% CI: 1.24-3.16). In women, daily coffee drinkers had a reduced risk in comparison with individuals who never or rarely drank coffee (adjusted RR=0.43, 95% CI: 0.22-0.85). The findings suggest the possible linkage between a western diet and risk of colon cancer.