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Extramammary Paget's disease (EMPD) is a rare adenocarcinoma that arises in apocrine gland-bearing skin and is associated with increased risk of underlying or distant malignancies. The average time between EMPD and malignancies that preceded EMPD diagnosis was 5.5 ± 6.7 years, and an average of 3.3 ± 3.9 years for malignancies diagnosed after EMPD. Increased incidence of secondary malignancies, particularly of colorectal and genitourinary cancers, in EMPD patients should prompt clinicians to conduct age-appropriate and other relevant and frequent cancer screening. [Extracted from the article]

Langerhans cell histiocytosis (LCH) that is refractory to conventional chemotherapy has a poor outcome. Hematopoietic stem cell transplanta tion (SCT) is a promising approach for refractory LCH because of its immunomodulatory effect. In this study, the outcomes of children with refractory LCH undergoing SCT in Japan were analyzed. Between November 1995 and March 2007, 15 children younger than 15 years (9 males, 6 females) with refractory LCH underwent SCT. The patients’ median age at diagnosis was 8 months (range, 28 days to 28 months), and all had failed conventional chemotherapy. The median age at SCT was 23 months (range, 13–178 months). Nine had risk organ involvement at diagnosis, including liver (n=6), spleen (n=5), lung (n=5), and/or hematopoietic system (n=4). For SCT, a myeloablative regimen was used for 10 patients, and a reduced-intensity conditioning regimen (RIC) was used for five. The donor source varied among the patients, but allogeneic cord blood was primarily used (n=10). Subsequently, 11 of 15 patients have survived with no evidence of disease, with a 10-year overall survival (OS) rate (median±standard error) of 73.3±11.4%. The 10-year OS rate of nine patients with risk organ involvement at diagnosis was 55.6±16.6%, whereas six without risk organ involvement have all survived with no evidence of disease (P=0.07). These results indicate that SCT is promising as a salvage approach for children with refractory LCH. [ABSTRACT FROM AUTHOR]

Aims: To investigate the prevalence of integrons and antimicrobial resistance genes in Salmonella recovered from animals in Japan. Methods and Results: Forty-eight out of ninety-four (51·1%) Salmonella isolates showed multidrug resistance phenotypes and harboured at least one antimicrobial resistance gene. Twenty-two out of forty-seven (46·8%) Salmonella enterica serovar Typhimurium that were multidrug-resistant were of definitive phage type DT104. Class 1 integrons were identified in 34/94 isolates (36·2%): 21 isolates containing two gene cassettes, aadA2 and blaPSE–1, and 13 containing one gene cassette, aadA1, aadA2 or blaPSE–1. Class 2 integrons containing estX- sat2- aadA1 gene cassettes were only identified in Salmonella Enteritidis. The β-lactamase-encoding gene, blaTEM, was only detected in S. Typhimurium. The plasmid-mediated quinolone resistance gene, qnrS1, was identified in S. Typhimurium and Salmonella Thompson. Conclusions: Our results characterized integrons and antimicrobial resistance genes in Salmonella of animal origin. To the best of our knowledge, this is the first report of qnrS in Salmonella from Japan and also the first report of qnrS in S. Thompson. Significance and Impact of the Study: Little is known about the molecular basis of antimicrobial resistance in Salmonella isolated from animals. This study provides useful data on the incidence of integrons and resistance genes in Salmonella of animal origin. [ABSTRACT FROM AUTHOR]

Study design:Case series.Objectives:To investigate the effects of wheelchair basketball game on plasma interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and blood cell counts in persons with spinal cord injury (SCI).Setting:The 2009 Mei-shin League of Wheelchair Basketball Games held at Wakayama, Japan.Participants:Five wheelchair basketball players with SCI voluntarily participated in this study.Interventions:Blood samples were taken approximately 1 h before the player warm-up for the game and immediately after the game.Main outcome measures:IL-6, TNF-α, CRP and blood cell count were measured.Results:Plasma IL-6 level and number of monocytes were significantly increased after the game, compared with pre-game measurements (P<0.05). No changes were observed in other measurements. There was a significant relationship between increased IL-6 levels and accumulated play duration.Conclusion:The lack of change in TNF-α and CRP levels suggested that the exercise-induced rise in IL-6 was not related to exercise-induced inflammatory response. Furthermore, the associated increase in the number of monocytes did not correlate with exercise-induced IL-6 changes, negating monocytes as the source of IL-6. [ABSTRACT FROM AUTHOR]

Introduction: Buccal midazolam (buc MDL) is the first buccal mucosal delivery formulation applied for status epilepticus in Japan. Herein, we aimed to investigate the effectiveness and adverse events of buc MDL as a pre-hospital treatment for epileptic seizures in real-world clinical practice., Methods: This study involved a retrospective review based on medical records. We included children who received buc MDL as pre-hospital treatment for epileptic seizures and were subsequently transported to the emergency department between April 2021 and November 2023., Results: This study included 26 patients (136 episodes). The overall efficacy rate, which was defined as seizure cessation within 10 min after buc MDL administration with no recurrence within 30 min, was 43 %. Moreover, 70 % of the episodes did not require additional medications. None of the episodes required bag-mask ventilation or intubation following seizure cessation with buc MDL alone. The efficacy was decreased when buc MDL was administered longer than 15 min from seizure onset. Furthermore, the efficacy did not decrease as long as it was within 0.2-0.5 mg/kg, even if the dose was smaller than the appropriate dose for the specific age., Conclusions: The response rate was significantly higher in episodes where buc MDL was administered within 15 min. Additionally, there was no concern regarding respiratory depression with buc MDL alone., 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 © 2024. Published by Elsevier B.V.)

Background: Adaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations., Methods: BAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models., Results: Of the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis., Conclusions: Our results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci., (© 2024. The Author(s).)

Background: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the β-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding β-ARs and BAT activity in human adults., Methods: Single nucleotide polymorphisms (SNPs) in β1-, β2-, and β3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIR TRS ) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber., Results: We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIR TRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits., Conclusions: The present study supports the importance of β2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function., (© 2024. The Author(s).)

Background: The association of the combination of body mass index (BMI) and weight change at admission with prognoses in patients with heart failure (HF) is unclear. Therefore, we investigated whether BMI and weight changes at admission affect mortality in patients with HF., Methods: This retrospective cohort study lasted 99 months, starting in April 2014, and included 4,862 patients with HF from a Japanese real-world database. Cubic and thin-plate smoothing spline analyses were performed to investigate the association of BMI and weight changes with mortality. The percentage weight change was calculated every 6 months. The study outcome was the presence or absence of death., Results: The patients' mean age was 81.5±9.6 years, and 1,239 (25.5%) patients died. Cubic spline analysis revealed a negative correlation of BMI with mortality hazard ratio (HR) (BMI of 18.5 kg/m2 and 25 kg/m2; HR=1.3 [1.2-1.4] and 0.8 [0.7-0.9], respectively). Cubic spline analysis of weight change showed that weight loss tended to increase the mortality HR (each 6% decrease in weight change rate was associated with a 1.1 times higher mortality risk (95% CI [1.0-1.2]) Thin-plate smoothing spline analysis showed that the odds ratio (OR) negatively correlated with BMI (1-year mortality: BMI of 18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.5, 1.0, and 0.7, respectively; 2-year mortality: BMI=18.5 kg/m2, 22 kg/m2, and 25 kg/m2; OR at 0% weight change=1.4, 0.9, and 0.7, respectively)., Conclusion: A low BMI in patients with HF was associated with a higher risk of mortality. Weight loss in patients, regardless of BMI, was associated with a higher OR for mortality.

Purpose: Adolescent and young adult cancer patients (AYAs) often experience profound psychological distress, with various unmet supportive care needs that can be alleviated with appropriate screening and attention by healthcare workers. The Distress Thermometer and Problem List-Japanese version (DTPL-J) is our previously developed screening tool to facilitate individual support of AYAs. This study evaluated the feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs in clinical practice., Methods: This multicenter, retrospective, observational study included 19 of 126 wards and 9 of 75 outpatient clinics at 8 institutions in Japan. Over 200 patients were expected to participate during the eligibility period. Patients participated in a support program at least once, and approximately once a month based on the DTPL-J results. The program was evaluated using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation framework., Results: The screening rate of the 361 participants was 90.3%, suggesting high feasibility. Distress Thermometer scores, the number of supportive care needs, and the rates of AYAs with high distress were significantly reduced 1 month after screening (p < 0.05), suggesting the preliminary effectiveness of the program. The program was continued at the 8 institutions as part of routine care after the study., Conclusion: Analysis using the RE-AIM suggested the sufficient feasibility and preliminary effectiveness of a psychosocial support program based on the DTPL-J for AYAs., Trial Registration: University Hospital Medical Information Network (UMIN CTR) UMIN000042857. Registered 25 December 2020-Retrospectively registered., (© 2023. The Author(s).)

Background: Preventing infection and managing febrile neutropenia (FN) is mandatory for children with cancer undergoing chemotherapy. However, the current situation in Japan is unknown., Methods: We conducted a nationwide web-based questionnaire survey in 153 institutions treating childhood cancer in Japan. We asked about the type prophylaxis used to prevent infectious disease and manage FN. If patients with childhood cancer were managed by both pediatricians and surgeons at the same institution, we asked both to reply., Results: We received replies from 117 departments at 111 centers: of these, 108 were from pediatricians. Laminar air flow for neutropenic patients, and frequent hand sanitization with ethanol, were widespread. Twenty-eight percent and forty percent of departments performed active surveillance by taking cultures from patients and the environment, respectively, before initiation of chemotherapy. Forty-four percent of departments administered prophylactic intravenous antibiotics according to patient status. Many departments measured serum (1,3)-β-D glucan, procalcitonin, and aspergillus galactomannan at the onset of FN. Twenty-eight percent of departments used carbapenem as empirical therapy for FN. Some departments used prophylactic granulocyte-colony stimulating factor for acute leukemia. Seventy-two percent of departments used prophylactic immunoglobulin for hypogammaglobinemia caused by chemotherapy. Palivizumab was administered widely for respiratory syncytial virus prophylaxis in immunocompromised infants., Conclusion: As a whole, intensive care for infectious prophylaxis or FN is applied in Japan; however, the methods vary among centers, and some are excessive or inadequate. Therefore, it is desirable to conduct clinical trials and establish adequate care protocols for infection in children with cancer in Japan., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

We conducted a cross-sectional study using a questionnaire to explore the late effects in survivors of allogenic hematopoietic stem cell transplantation (HSCT) for juvenile myelomonocytic leukemia (JMML). The attending pediatric hematologists/oncologists completed the questionnaires. Of the 30 survivors, approximately 83% showed more than one late effect. The identified late effects included endocrine, dental, skin, ophthalmologic, musculoskeletal, pulmonary, neurocognitive, and cardiovascular dysfunction. The prevalence of short stature, pulmonary, cardiovascular, and nephrological complications was significantly elevated among survivors who were 12 years or more lapsed after HSCT. Therefore, a multidisciplinary follow-up system for survivors of JMML is crucial., (© 2022 Wiley Periodicals LLC.)

Background: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused., Methods: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized., Results: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values., Conclusion: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS., (© 2023. The Author(s).)

Background: The PRAETORIAN score was developed to evaluate the implant position and predict defibrillation success in patients implanted with a subcutaneous implantable cardioverter-defibrillator (S-ICD). However, usefulness of the PRAETORIAN score for Japanese patients is unknown., Methods: We evaluated usefulness of this score, which was determined by width of sub-coil fat, sub-generator fat, and anterior positioning of the S-ICD generator by post-operative chest X-ray, in consecutive 100 Japanese S-ICD implanted patients [78 men, median age 59 (IQR 46.5-67.0) years, median body mass index (BMI) 24.2 (21.3-27.2) kg/m 2 ]., Results: The median PRAETORIAN score was 30 (30-45) and 93 patients were classified as a low risk of conversion failure. The remaining seven were at an intermediate risk. Almost all patients were classified as an optimal pulse-generator position in the second and third steps of the PRAETORIAN score. The only difference observed was in the width of sub-coil fat in the first step. To further evaluate its significance, patients were divided into the Thicker group (sub-coil fat >1 coil width, n = 19) and the Thinner group (sub-coil fat ≤1 coil width, n = 81). BMI and post-shock impedance were both higher in the Thicker group than in the Thinner group [27.1 (25.6-31.6) versus 23.1 (20.9-25.7) kg/m 2 , p < 0.001, and 75 (68-88) versus 63 (55-74) Ω, p = 0.003, respectively]. During the median follow-up periods of 888 (523-1418) days, 7 patients experienced appropriate shock therapy for spontaneous ventricular tachyarrhythmias, who were all at a low risk. No conversion failure was observed. Inappropriate shock (IAS) occurred in 11 patients, and there was no difference in IAS rate between the Thicker group (n = 2) and the Thinner group (n = 9) (p = 0.747 by log-rank test)., Conclusions: Most Japanese patients were classified as at low risk of conversion failure. The PRAETORIAN score may be useful for the evaluation of conversion failure in Japanese S-ICD implanted patients., Competing Interests: Disclosures Drs Shingo Sasaki and Hirofumi Tomita have received research grant supports from Medtronic Japan Co., Ltd. and Fukuda Denshi Kita-tohoku Hanbai Co., Ltd. and BIOTRONIK Japan Co., Ltd. Drs Shingo Sasaki and Hirofumi Tomita have received scholarship grants from Japan Lifeline Co., Ltd. and Boston Scientific Japan Co., Ltd. Dr. Yuji Ishida is an assistant professor of the department of Cardiac Remote Management System, which is an endowment department supported by BIOTRONIK Japan Co., Ltd. Dr. Masaomi Kimura is an associate professor and Dr. Taihei Itoh is an assistant professor of the department of Advanced Management of Cardiac Arrhythmias, which is an endowment department supported by Medtronic Japan Co., Ltd. and Fukuda Denshi Kita-tohoku Hanbai Co., Ltd. The rest of authors have no relevant disclosures., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We measured the concentrations of cesium isotopes ( 133 Cs, 134 Cs, and 137 Cs) in zooplankton samples collected in waters off the east coast of Japan from May 2015 to June 2020. By combining these data with those obtained previously from May 2012 to February 2015, we evaluated the long-term impacts of the Fukushima Dai-ichi Nuclear Power Plant accident on marine zooplankton. Relatively high 137 Cs concentrations in zooplankton, exceeding 10 Bq/kg-dry weight, were sporadically observed until June 2016, regardless of year or station. After May-June 2017, 137 Cs concentrations decreased to below 1 Bq/kg-dry at most stations, and by May 2020, concentrations were below 0.5 Bq/kg-dry except those off Fukushima Prefecture. Since the accident, the 137 Cs/ 133 Cs atom ratios of zooplankton samples were higher than those of ambient seawater until 2019, but in May-June 2020 the ratios matched those of seawater except off Fukushima Prefecture. Highly radioactive particles were not detected in zooplankton samples by autoradiography using imaging plates after May-June 2017, although they were before. Therefore, the persistence of elevated 137 Cs/ 133 Cs ratios in zooplankton relative to seawater for nine years after the accident was probably due to the incorporation of highly radioactive particles (cesium-bearing particles or clay-mineral aggregates with highly adsorbed radiocesium) onto/into zooplankton for several years after the accident. However, since at least May-June 2017, these elevated ratios have likely been caused by small highly radioactive particles (or larger particles disaggregated into small pieces) entering the ocean from land via rivers or directly discharged from the Fukushima Nuclear Power Plant. Microplastics enriched with radiocesium with higher 137 Cs/ 133 Cs ratios than seawater may have also contributed 137 Cs to the zooplankton., 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 © 2022 Elsevier Ltd. All rights reserved.)

There is no standard birth weight curve for twins in Japan other than a prototype curve based on 1988-1991. Twins have a high perinatal mortality rate than singletons; therefore, we developed a new standard curve for twin birth weight using data from the 1995-2016 Vital Statistics and compared it with previous reports. We used 469,064 cases for analysis, excluding stillbirths and cases with missing values, and created a standard curve using LMS (statistical methods to vary the distribution by using skewness, median, and coefficient of variation) method. In comparison with previous reports, the mean birth weight decreased by 100-200 g. The groups with the lowest neonatal death rates (NDRs) and infant death rates (IDRs) were those with a birth weight of 1,500-2,499 g (NDR: 0.3%, IDR: 0.6%) and those born at 34-36 weeks (NDR: 0.2%, IDR: 0.4%). Compared to these, the IDR was significantly higher in the 2,500-3,999 g group and the 37-39 weeks group (incidence rate ratio (IRR): 1.1 in the 2,500-3,999 g group, IRR: 1.3 in the 37w0d-39w6d group). In particular, the risks of neonatal mortality and infant mortality were higher in infants born at a birth weight above 3,500 g. Infants born at a birth weight above 3,500 g may include recipients of twin-to-twin transfusion syndrome. The most common causes of infant mortality are accidental death and sudden infant death syndrome (SIDS). We considered the possibility that infants treated as healthy newborns and whose mothers were discharged from the hospital without adequate twin care guidance may be more likely to experience unintentional accidents and SIDS at home. The present study suggested that creating a new twin birth weight standard curve and guidance on managing twins at home for full-term and normal birth weight infants may lead to a reduction in infant deaths., Competing Interests: The authors have declared that no competing interests exist.

Aim: We investigated the influence of weight change on concurrent changes in predicted cardiovascular disease (CVD) risk and individual CVD risk factors over time., Methods: A total of 2,140 community-dwellers aged 40-74 years participated in both 2002 and 2007 health examinations. Obesity was defined as body mass index ≥ 25 kg/m 2 . Weight trajectories were classified as: "stable obese" (obese at both examinations), "obese to nonobese" (obese in 2002 but nonobese in 2007), "nonobese to obese" (nonobese in 2002 but obese in 2007), or "stable nonobese" (nonobese at both examinations). We compared changes in the model-predicted risk for CVD and individual CVD risk factors across weight-change categories., Results: The predicted risk for CVD increased during 5 years in all groups; the increment in the predicted risk for CVD was smallest in the obese to nonobese participants and steepest in the nonobese to obese subjects. Compared with the stable obese participants, the obese to nonobese participants had greater favorable changes in waist circumferences, blood pressure, fasting plasma glucose, serum high-density lipoprotein cholesterol, serum triglycerides, and liver enzymes. For all these parameters, opposite trends were observed when comparing the nonobese to obese participants with the stable nonobese group., Conclusions: We demonstrated the favorable association of losing weight in obese people and avoiding excessive weight gain in nonobese people with global risk of future CVD and individual CVD risk factors in a real-world setting. The findings could improve behavioral lifestyle interventions that provide information on the health consequences of weight change at health checkups.

The Japan Society of Clinical Oncology (JSCO) published the "JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients" in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer., (© 2021. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive)., (© 2021. The Author(s).)

Importance: Although the suicide rate in Japan increased during the COVID-19 pandemic, the reasons for suicide have yet to be comprehensively investigated., Objective: To assess which reasons for suicide had rates that exceeded the expected number of suicide deaths for that reason during the COVID-19 pandemic., Design, Setting, and Participants: This national, population-based cross-sectional study of data on suicides gathered by the Ministry of Health, Labor, and Welfare from January 2020 to May 2021 used a times-series analysis on the numbers of reason-identified suicides. Data of decedents were recorded by the National Police Agency and compiled by the Ministry of Health, Labor, and Welfare., Exposure: For category analysis, we compared data from January 2020 to May 2021 with data from December 2014 to June 2020. For subcategory analysis, data from January 2020 to May 2021 were compared with data from January 2019 to June 2020., Main Outcomes and Measures: The main outcome was the monthly excess suicide rate, ie, the difference between the observed number of monthly suicide deaths and the upper bound of the 1-sided 95% CI for the expected number of suicide deaths in that month. Reasons for suicide were categorized into family, health, economy, work, relationships, school, and others, which were further divided into 52 subcategories. A quasi-Poisson regression model was used to estimate the expected number of monthly suicides. Individual regression models were used for each of the 7 categories, 52 subcategories, men, women, and both genders., Results: From the 29 938 suicides (9984 [33.3%] women; 1093 [3.7%] aged <20 years; 3147 [10.5%] aged >80 years), there were 21 027 reason-identified suicides (7415 [35.3%] women). For both genders, all categories indicated monthly excess suicide rates, except for school in men. October 2020 had the highest excess suicide rates for all cases (observed, 1577; upper bound of 95% CI for expected number of suicides, 1254; 25.8% greater). In men, the highest monthly excess suicide rate was 24.3% for the other category in August 2020 (observed, 87; upper bound of 95% CI for expected number, 70); in women, it was 85.7% for school in August 2020 (observed, 26; upper bound of 95% CI for expected number, 14)., Conclusions and Relevance: In this study, observed suicides corresponding to all 7 categories of reasons exceeded the monthly estimates (based on data from before or during the COVID-19 pandemic), except for school-related reasons in men. This study can be used as a basis for developing intervention programs for suicide prevention.

Background: Robotic gastrectomy (RG) for gastric cancer (GC) has gradually gained nationwide prominence following 2011 guidelines from the Japan Society for Endoscopic Surgery (JSES), including the surgeons' criteria and the proctor system. In this retrospective study, we examined the short-term outcomes of the initial series of RGs performed by second-generation operating surgeons trained within our institute., Methods: Between January 2017 and April 2020, five surgeons each performed RG in 20 patients with clinical stage III or lower GC in accordance with the JSES guidelines. We evaluated both the rate of Clavien-Dindo grade II or higher morbidities and the console time required to reach the learning plateau via cumulative summation (CUSUM) analysis., Results: We observed no mortality and 3% of morbidity following RG. Both the operative time (430 vs 387.5 min, P = 0.019) and console time (380 vs . 331.5 min, P = 0.009) were significantly shorter in the second 10 cases than in the initial 10 cases. We observed a remarkable trend in cases of distal gastrectomy (DG), in which the total operative time and console time were significantly shorter in the later cases. Our CUSUM analysis revealed that seven cases were required to achieve a learning plateau in RG when confined to DG., Conclusions: Non-expert RG surgeons meeting the operating surgeon's criteria from the JSES who had trained under an expert RG surgeon safely performed RG in an initial 20 cases., (© 2021 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

A nationwide cross-sectional survey was conducted in long-term survivors of allogeneic hematopoietic stem cell transplantation (HSCT) in childhood to investigate the effect of chronic graft-versus-host disease (cGVHD) on quality of life (QOL) and differences in QOL assessments between raters. QOL was evaluated by a visual analogue scale (VAS). Assessments were compared between the survivor, guardian, and attending pediatrician for those aged 15 years or younger, and between the survivor and attending pediatrician for those aged 16 years or older. For cGVHD, severity scores were obtained by organ and their association with the VAS score was analyzed. The average pediatrician-rated VAS score was higher than that of other raters for both patient age groups (< 15 years and > 16 years). By organ, involvement of the skin, digestive organs, and joints in GVHD affected the VAS scores. A high joint score was associated with a low VAS score, and conversely, a high lung score was associated with a low pediatrician-rated VAS score. Our results indicate that differences between raters must be considered when evaluating QOL of HSCT survivors, because patients appeared to experience grater inconvenience and difficulties due to joint GVHD than their pediatricians perceived., (© 2021. Japanese Society of Hematology.)

This cross-sectional study aimed to examine the oral hygiene behaviors in the general population and identify factors affecting oral hygiene behaviors and plaque removal efficacy. A survey was distributed to patients through 11 dental practices in Japan, and each patient's plaque index score (PIS) was recorded. In total, 1184 patients participated (521 women and 660 men), with 84.04% using manual toothbrushes (MTBs) and 15.96% using electric toothbrushes (ETBs). ETB users had a significantly lower PIS compared to MTB users ( p = 0.0017). In addition, a statistically significant difference in the PIS was detected in relation to the frequency of brushing per day (≥2 times) and time spent on brushing (≥1 min). Some MTB users spent less than 1 min brushing, while all ETB users spent at least 1 min brushing, and extended brushing periods significantly improved the PIS for the MTB users. MTB users tend to replace brush heads more frequently than ETB users, and the frequency of replacement affected the PIS significantly ( p < 0.01) for the MTB users. The status of dental treatment (first visit, in treatment versus recall) also significantly affected the PIS ( p < 0.01). The ETB was more effective than the MTB in terms of better plaque removal and reduced frequency of brush head replacement.

Japan is surrounded by the sea and is also a mountainous country with many rivers. Japan has the second- highest rate of deaths caused by drowning in the world. Pleural effusion (PE) is one of the major findings at autopsy. It is found in approximately 80% of drowning mortalities and is observable for a relatively long postmortem interval (PMI). We focused on the amount of pleural fluid in drowning cases, discussed the relationship of PE with the drowning environment, water temperature, and postmortem interval, and established more simple and practical criteria for the diagnosis of drowning. We measured the weight of the lungs, PE, and their sum as the intrathoracic (IT) weight (total weight of lungs + pleural effusion), and calculated the PE ratio [(PE weight/IT weight) × 100]. A total of 130 drowning deaths diagnosed through forensic autopsies were investigated in this study. The cases were classified by drowning environment (freshwater, brackish water, and seawater), water temperature (under 20 °C, more than 20 °C), and postmortem interval (less than 1 day, 1-3 days, more than 3 days). The present study demonstrated that the PE ratio may be more effective for the diagnosis of drowning. Moreover, the accumulation of PE is affected by drowning environment, water temperature, and PMI. Collectively, it is important to assess the PE ratio and consider these factors in autopsy cases of victims found in water., (© 2021. The Author(s).)

Introduction: Data on the risk factors for symptomatic radiation pneumonitis (RP) in non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors., Materials and Methods: This multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP., Results: In the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007)., Conclusion: The incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning., (Copyright © 2021. Published by Elsevier Inc.)

This cross-sectional study aimed to examine the accuracy of the Simplified Nutritional Appetite Questionnaire (SNAQ) and the SNAQ for Japanese Elderly (SNAQ-JE) for the Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition and sarcopenia screening in older persons. We included 380 inpatients aged ≥65 years (mean age, 79.3 ± 7.9; 60.0% women) and admitted to rehabilitation units. Undernutrition and sarcopenia were diagnosed based on GLIM criteria and the Asian Working Group for Sarcopenia, respectively, using bioimpedance analysis. Poor appetite was defined as an SNAQ score of <14 points and an SNAQ-JE score of ≤14 points. The sensitivity, specificity, and accuracy of these tools for detecting poor appetite for GLIM-defined malnutrition and sarcopenia were assessed. The rates of GLIM-defined malnutrition and sarcopenia were 56.8% and 59.2%, respectively. The number of patients with poor appetite was 94 (24.7%) for the SNAQ and 234 (61.6%) for the SNAQ-JE. The sensitivity and specificity of the SNAQ measured against GLIM-defined malnutrition were 32.9% and 73.1%, respectively, and against sarcopenia were 29.8% and 70.2%, respectively. The sensitivity and specificity of the SNAQ-JE measured against GLIM-defined malnutrition were 82.6% and 51.0%, respectively, and against sarcopenia were 86.0% and 53.7%, respectively. The SNAQ-JE showed fair accuracy for GLIM-defined malnutrition and sarcopenia in older patients admitted to rehabilitation units.

Abstract: Steroid pulse therapy is widely used to treat virus-associated acute encephalopathy, especially the cytokine storm type; however, its effectiveness remains unknown. We sought to investigate the effectiveness of early steroid pulse therapy for suspected acute encephalopathy in the presence of elevated aspartate aminotransferase (AST) levels.We enrolled children admitted to Hyogo Children's Hospital between 2003 and 2017 with convulsions or impaired consciousness accompanied by fever (temperature >38°C). The inclusion criteria were: refractory status epilepticus or prolonged neurological abnormality or hemiplegia at 6 hours from onset, and AST elevation >90 IU/L within 6 hours of onset. We excluded patients with a neurological history. We compared the prognosis between the groups with or without steroid pulse therapy within 24 hours. A good prognosis was defined as a Pediatric Cerebral Performance Category Scale (PCPC) score of 1-2 at the last evaluation, within 30 months of onset. Moreover, we analyzed the relationship between prognosis and time from onset to steroid pulse therapy.Fifteen patients with acute encephalopathy and 5 patients with febrile seizures were included in this study. Thirteen patients received steroid pulse therapy within 24 hours. There was no between-group difference in the proportion with a good prognosis. There was no significant correlation between PCPC and timing of steroid pulse therapy (rs = 0.253, P = .405). Even after excluding 2 patients with brainstem lesions, no significant correlation between PCPC and steroid pulse therapy timing (rs = 0.583, P = .060) was noted. However, the prognosis tended to be better in patients who received steroid pulse therapy earlier.Steroid pulse therapy within 24 hours did not improve the prognosis in children with suspected acute encephalopathy associated with elevated AST. Still, even earlier administration of treatment could prevent the possible neurological sequelae of this condition., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Inappropriate antimicrobial therapy for surgical site infections (SSIs) can lead to poor outcomes and an increased risk of antibiotic resistance. A nationwide survey was conducted in Japan from 2018 to 2019 to investigate the antimicrobial susceptibility of pathogens isolated from SSIs. The data were compared with those obtained in 2010 and 2014-2015 surveillance studies. Although the rate of detection of extended-spectrum β-lactamase producing strains of Escherichia coli was increased from 9.5% in 2010 to 23% in 2014-2015, the incidence decreased to 8.7% in 2018-2019. Although high susceptibility rates were detected to piperacillin/tazobactam (TAZ), the geometric mean MICs were substantially higher than to meropenem (2.67 vs 0.08 μg/mL). By contrast, relatively low geometric mean MICs (0.397 μg/mL) were demonstrated for ceftolozane/TAZ. Although the MRSA incidence rate decreased from 72% in the first surveillance to 53% in the second, no further decrease was detected in 2018-2019. For the Bacteroides fragilis group species, low levels of susceptibility were observed for moxifloxacin (65.3%), cefoxitin (65.3%), and clindamycin (CLDM) (38.9%). In particular, low susceptibility against cefoxitin was demonstrated in non-fragilis Bacteroides, especially B. thetaiotaomicron. By contrast, low susceptibility rates against CLDM were demonstrated in both B. fragilis and non-fragilis Bacteroides species, and a steady decrease in susceptibility throughout was observed (59.3% in 2010, 46.9% in 2014-2015, and 38.9% in 2018-2019). In conclusion, Japanese surveillance data revealed no significant lowering of antibiotic susceptibility over the past decade in organisms commonly associated from SSIs, with the exception of the B. fragilis group., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.

Hip fracture is a common injury in elderly patients. In Japan, the number of super-old patients-age >90 years-with hip fractures has increased drastically over time. Available strategies for anaesthetic management for hip fracture surgery include general anaesthesia, neuraxial anaesthesia and peripheral nerve block. However, general and neuraxial anaesthesia are often avoided for various reasons, particularly in elderly patients. In recent years, peripheral nerve block has proven effective in various surgical procedures. Additionally, dexmedetomidine exhibits neuroprotective effects and has been used safely in super-old patients. Herein, we demonstrate successful anaesthetic management with peripheral nerve block under dexmedetomidine sedation for open reduction and internal fixation of a femoral neck fracture in a 97-year-old patient., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We conducted a cross-sectional observational study investigating socioeconomic status among Japanese survivors of pediatric hematopoietic stem cell transplantation (HCT) and the impact of chronic graft-versus-host disease (cGVHD) on socioeconomic outcomes, which are topics not well explored in the previous research. We collected data on socioeconomic outcomes from 442 HCT survivors through a questionnaire and obtained demographic and clinical information from their attending physicians and a national database between February 2013 and November 2014. We used logistic regression analysis to examine the relationship between cGVHD and socioeconomic outcomes in allogeneic HCT (allo-HCT) survivors. Most survivors did not experience socioeconomic problems. Nevertheless, allo-HCT survivors with cGVHD aged 8-15 years had poorer economic status (p = 0.013), and allo-HCT survivors with cGVHD aged ≥ 16 years were more likely to have never married (p = 0.034) and less likely to have more than a high school education (p = 0.023), compared with allo-HCT survivors without cGVHD. Thus, cGVHD in Japanese allo-HCT survivors was a risk factor for economic difficulties for those aged 8-15 years, and for never marrying and low educational achievement in those aged ≥ 16 years.

Cognitive health is subject to decline with increasing numbers of lost teeth which impacts mastication. This study is a descriptive data analysis of the association between masticatory and cognitive conditions using a large database. We obtained the dental and medical records from Japan's universal healthcare system (UHCS) from the national database in 2017. The data from 94% of the Japanese population aged 65 and over is included. It is inclusive of diagnostic codes for various types of cognitive impairment, as well as dental treatment records from 2012 to 2017. The cognitive impairment group was compared to those without a diagnosis of cognitive impairment. Crude odds ratio between loss of mastication with natural teeth (exposure) and cognitive impairments (outcome) were compared. Patients who have lost masticatory function are likely to have cognitive impairment with an odds ratio of 1.89 (p<0.0001) for early elderly (aged 65-75) and 1.33 (p<0.0001) for advanced elderly (over 75). Patients who are edentulous and function with complete dentures are likely to have cognitive impairment with an odds ratio of 2.38 (p<0.0001) and 1.38 (p<0.0001), respectively. The data shows a convincing and significant result of an association between cognitive health and oral health, related to masticatory conditions.

Few studies have examined the association between the accumulation of unhealthy eating habits and the likelihood of obesity or central obesity in a general Japanese population. We examined this association in a sample of 1906 community-dwelling Japanese subjects (age: 40-74 years) who participated in a health check-up in 2014. A face-to-face questionnaire interview was conducted to collect information about three unhealthy eating habits, i.e., snacking, eating quickly, and eating late-evening meals. Obesity was defined as body mass index ≥25 kg/m 2 and central obesity was defined as waist circumference ≥90 cm in men and ≥80 cm in women. The odds ratios (OR) were estimated by using a logistic regression analysis. Subjects with any one of the three eating habits had a significantly higher likelihood of obesity than those without that habit after adjusting for confounding factors. The multivariable-adjusted OR for obesity increased linearly with an increase in the number of accumulated unhealthy eating habits ( p for trend < 0.001). Similar associations were observed for central obesity. Our findings suggest that modifying each unhealthy eating habit and avoiding an accumulation of multiple unhealthy eating habits might be important to reduce the likelihood of obesity.

Objective: To investigate the prevalence of seizures/febrile seizures in children up to 3 years of age and examine the effects of gestational age at birth on the risk for febrile seizures., Design: Retrospective longitudinal population-based cohort study., Setting: Kobe City public health center, Kobe, Japan, from 2010 to 2018., Participants: Children who underwent a medical check-up at 3 years of age., Methods: Information regarding seizures was collected from the parents of 96 014 children. We identified the occurrence of seizure/febrile seizure in 74 017 children, whose gestational ages at birth were noted. We conducted a multivariate analysis with the parameter, gestational age at birth, to analyse the risk of seizure. We also stratified the samples by sex and birth weight (<2500 g or not) and compared the prevalence of seizure between those with the term and late preterm births., Results: The prevalence of seizure was 12.1% (11.8%-12.3%), 13.2% (12.2%-14.4%), 14.6% (12.4%-17.7%) and 15.7% (10.5%-22.8%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. The prevalence of febrile seizures was 9.0% (8.8%-9.2%), 10.5% (9.5%-11.5%), 11.8% (9.7%-14.5%) and 11.2% (6.9%-17.7%) in children born at 37-41, 34-36, 28-33 and 22-27 gestational weeks, respectively. Male was an independent risk factor for seizures (OR: 1.15, 95% CI 1.09 to 1.20; absolute risk increase 0.014, 95% CI 0.010 to 0.019) and febrile seizures (OR: 1.21, 95% CI 1.15 to 1.28; absolute risk increase 0.016, 95% CI 0.012 to 0.020), respectively. Late preterm birth was not associated with an increased risk of seizure/febrile seizure., Conclusions: Although very preterm birth may increase the risk of seizure/febrile seizure, the risk associated with late preterm birth is considerably small and less than that associated with male., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown., Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer., Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020., Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group)., Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated., Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009)., Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

Background: Migraines are a broad spectrum of disorders classified by the type of aura with some requiring attentive treatment. Vasoconstrictors, including triptans, should be avoided in the acute phase of migraines with brainstem aura, in hemiplegic migraine, and in retinal migraine. This study investigated the characteristics and burden of these migraines., Methods: Medical charts of 278 Japanese pediatric patients with migraines were retrospectively reviewed. Migraine burden of migraines with brainstem aura, hemiplegic migraines, and retinal migraine was assessed using the Headache Impact Test-6™ (HIT-6) and the Pediatric Migraine Disability Assessment scale (PedMIDAS)., Results: Of 278 patients screened, 12 (4.3%) patients with migraines with brainstem aura (n = 5), hemiplegic migraines (n = 2), and retinal migraine (n = 5) were enrolled in the study. All patients had migraine with/without typical aura, whereas some patients had coexisting migraine with another type of headache (chronic tension-type headache in 3 patients, and 1 each with frequent episodic tension-type headache, headache owing to medication overuse, and chronic migraine). Migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients with coexisting headaches had higher HIT-6 or PedMIDAS scores, whereas migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients without coexisting headache did not show high HIT-6 or PedMIDAS scores., Conclusion: All migraines with brainstem aura, hemiplegic migraines, and retinal migraine patients experienced migraine with or without typical aura, and some patients having other coexisting headaches also had high PedMIDAS and HIT-6 scores. PedMIDAS and HIT-6 should not be considered diagnostic indicators of migraines with brainstem aura, hemiplegic migraines, or retinal migraine. In clinical practice for headaches in children, careful history taking and proactive assessment of the aura are needed for accurate diagnosis of migraines with brainstem aura, hemiplegic migraines, and retinal migraine.

Aim: The Geriatric Nutritional Risk Index (GNRI) can predict nutritional risk. However, just a few studies have validated the optimal cut-off value of GNRI for nutrition screening in older patients. Hence, this study aimed to determine the optimal value of GNRI to screen the risk of malnutrition among older patients., Methods: This retrospective cross-sectional study was carried out with 5867 consecutive older adult patients who were admitted to an academic hospital in Japan. Receiver operating characteristic curve analyses were carried out to obtain the optimal cut-off value of GNRI, and the results were compared against the Mini Nutritional Assessment - Short Form and Malnutrition Universal Screening Tool. The validation of the obtained cut-off value was examined on the concordance rate of malnutrition diagnosis based on the European Society of Clinical Nutrition and Metabolism criteria., Results: The mean age of the patients was 76.0 ± 7.0 years. The optimal cut-off value of GNRI for Mini Nutritional Assessment - Short Form ≤11 points was 95.92 (area under the curve 0.827 [0.817-0.838], P < 0.001), and that for Malnutrition Universal Screening Tool ≥1 point was 95.95 (area under the curve 0.788 [0.776-0.799], P < 0.001). By adapting GNRI <96 points as an initial screening cut-off in the European Society of Clinical Nutrition and Metabolism-defined malnutrition process, the concordance rates of comparisons were 98.5% and 98.5% for Mini Nutritional Assessment - Short Form-based and MUST-based diagnosis, respectively., Conclusions: The study showed GNRI <96 points as the optimal cut-off value for nutritional screening. GNRI might be one of the easy-to-use tools for nutritional screening and for diagnosing malnutrition in older adults. Geriatr Gerontol Int 2020; 20: 811-816., (© 2020 Japan Geriatrics Society.)

Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is recommended for moderately emetogenic chemotherapy in several guidelines to prevent chemotherapy-induced nausea and vomiting. There is a lack of information about the efficacy and safety of antiemetic therapy with aprepitant, palonosetron, and dexamethasone in patients treated with oxaliplatin in Japan. We recruited patients with untreated colorectal cancer who underwent oxaliplatin-based chemotherapy. All patients were treated with aprepitant, palonosetron, and dexamethasone. The complete response and complete protection rates were analyzed. A total of 52 patients were enrolled in this clinical trial. The complete response rate overall, and in the acute and delayed phases was 92.3%, 98.1%, and 92.3%, respectively. The complete protection rate overall and in the acute and delayed phases was 73.1%, 86.5%, and 73.1%, respectively. Grade 3-4 non-hematological toxicity did not occur. Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is effective and safe in patients treated with oxaliplatin.

Objective: The study aims to examine the association between overtime-working environment (OWE) and individual psychological distress among Japanese workers., Methods: Data of 7786 workers from 101 companies in Japan were analyzed. Psychological distress was assessed through a 29-item questionnaire. The OWE was evaluated by calculating the proportion of workers whose monthly overtime was 45 hours or more in a workplace. Multilevel logistic regression was used., Results: As 10% increase in the OWE was associated with a 16% higher risk of individual psychological distress after adjustment of individual covariates, including overtime working hours. Cross-level interaction showed that the risk was varied depending on individual overtime working hours., Conclusions: OWE was associated with the psychological distress of workers. It is necessary to create a non-OWE at workplaces to prevent psychological distress for workers.

Purpose: To evaluate barbiturate anaesthetic therapy using thiamylal for febrile refractory status epilepticus (fRSE) in children., Methods: This was a review of a prospectively-collected database between April 2012-March 2016 for fRSE cases treated with thiamylal anaesthetic therapy in a single paediatric hospital in Japan. The sample comprised 23 children (median age, 23 months) with fRSE that underwent thiamylal anaesthetic therapy for convulsive seizures lasting longer than 60 min, sustained after intravenous administration of benzodiazepine and non-benzodiazepine anticonvulsants. The intervention comprised protocol-based thiamylal anaesthetic therapy with bolus administration. We measured the dose and time required to achieve the burst suppression pattern (BSP) on electroencephalography, seizure recurrence, death, neurological sequelae, and complications., Results: All patients except one reached the BSP. The thiamylal median dose until reaching the BSP was 27.5 mg/kg, and the median time from thiamylal administration to reaching the BSP was 109.5 min. There was one case of immediate treatment failure and one of withdrawal seizure, but no breakthrough seizure. No deaths occurred during treatment, and neurological sequelae occurred in four cases (17%). Vasopressors were administered in all cases. Other complications included 11 cases of pneumonia and one of enterocolitis., Conclusion: We revealed the time and dose required to reach the BSP with thiamylal anaesthetic therapy using bolus administration in children. Our results suggested that reaching the BSP with bolus administration requires markedly less time than without bolus administration, rarely causes seizure recurrence in paediatric fRSE, and causes haemodynamic dysfunction and infections as often as observed without bolus administration., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: To clarify the dissemination status of cognitive behavioural therapy (CBT) in Japan under the national health insurance scheme., Design: Retrospective observational study., Setting: National Database of Health Insurance Claims and Specific Health Checkups of Japan., Participants: Patients who received CBT under the national health insurance scheme from fiscal years (FY) 2010 to 2015., Primary and Secondary Outcome Measures: We estimated the change rate and the standardised claim ratio (SCR) for the number of patients receiving CBT and analysed the association between the CBT status and several regional factors., Results: We found that (a) a total of 60 304 patients received CBT during the study period; (b) the number of patients receiving CBT was highest in the first year (-1.8% from FY2010 to FY2015); (c) the number of patients who received CBT per 100 000 population decreased (or remained at zero) in most prefectures (32 out of 47); (d) there was a maximum 424.7-fold difference between prefectures in the standardised claim ratio for CBT and (e) the number of registered CBT institutions was significantly associated with the number of patients who received CBT., Conclusions: The provision of CBT did not increase in the first 6 years (FY2010-2015) after its coverage in Japan's national health insurance scheme. Further studies including a questionnaire survey of registered CBT institutions are required to get more detailed information on the dissemination of CBT in Japan., Competing Interests: Competing interests: NY has received a speaking honorarium from Gakken Medical Support, and writing honoraria from Igaku Shoin, Nihon-Hyouronsha, Sogensha, and Medical Friend. The other authors declare that they have no conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives : The dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin is indicated for type 2 diabetes mellitus (T2DM). However, the long-term safety, effectiveness, and clinical relationship with cardiovascular events of vildagliptin have not been evaluated in Japan. Methods : The authors conducted post-marketing surveillance (PMS) to evaluate the safety and effectiveness of vildagliptin in more than 3000 Japanese T2DM patients for up to 3 years. Main assessments included demographics, major adverse cardiovascular events (MACE), adverse events (AEs), adverse drug reactions (ADRs), and glycated hemoglobin (HbA1c). Results : In this PMS, 3831 patients (775 sites) were registered in April 2010 - April 2012. The safety analysis population comprised 3769 patients; 2085 patients were aged ≥65 years, and 240, 411, and 114 had renal impairment, hepatic impairment, and heart failure, respectively. The median treatment duration was 2.7 years. The incidence of MACE was 6.04 cases/1000 person-years, mostly attributable to cerebrovascular events (4.27 cases/1000 person-years). The AE and ADR incidences were 26.0% and 5.3%, respectively. The incidence of hypoglycemia was 0.6%. No significant changes in body weight occurred and mean change in HbA1c from baseline at final assessment was -0.74 ± 1.41% ( p < 0.0001). Conclusions : In real-world clinical settings, vildagliptin was well tolerated, with similar profiles as previously reported.

Background: Patients with childhood cancer and their families frequently experience psychosocial distress associated with cancer and its treatment. We thus examined the reliability and validity of a Japanese version of the Psychosocial Assessment Tool, which was designed to screen for psychosocial risk factors among families of children with cancer., Methods: Forward-backward translation was used to develop the Japanese version of the Psychosocial Assessment Tool. We conducted a cross-sectional study. Mothers (N = 117), who were the primary caregivers of children with cancer, completed the Japanese version of the Psychosocial Assessment Tool and other measures to establish validity. The internal consistency and 2-week test-retest reliability of the Japanese version of the Psychosocial Assessment Tool were also examined., Results: The internal consistency of the Japanese version of the Psychosocial Assessment Tool total score was sufficient (Kuder-Richardson 20 coefficient = 0.84); however, the subscales 'structure and resources,' 'stress reactions' and 'family beliefs' were less than optimal (Kuder-Richardson 20 coefficients = 0.03, 0.49 and 0.49, respectively). The test-retest reliability for the Japanese version of the Psychosocial Assessment Tool total score was sufficient (intraclass correlation coefficient = 0.92). Significant correlations with the criteria measures indicated the validity of the Japanese version of the Psychosocial Assessment Tool total score. The optimal cut-off score for screening mothers with high psychosocial risk was 0.9/1.0, which was associated with 92% sensitivity and 63% specificity., Conclusions: This study indicated that the Japanese version of the Psychosocial Assessment Tool is a valid and reliable tool to screen mothers for elevated distress., (© Crown copyright 2019.)

Purpose: To investigate the risk factors, onset timing, and progression of epiretinal membrane (ERM) after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD)., Design: Retrospective, comparative case series., Participants: The study included 322 eyes of 322 patients who underwent primary PPV for RRD from January 2014 through December 2016., Methods: Patients underwent OCT before and 1, 3, 6, and 12 months after surgery. Patients showing hyperreflective lines above the inner retinal surface and deformation of the foveal pit were defined as ERM cases. Those with loss of the foveal pit were defined as advanced ERM cases. A multivariate logistic regression model was used to evaluate the risk factors of postoperative ERM. The onset timing of ERM and progression to advanced ERM after PPV for RRD were also investigated based on the OCT findings., Main Outcome Measures: Risk factors, onset timing, and progression of ERM after PPV for RRD., Results: In the multivariate analysis, the incidence of postoperative ERM was significantly higher in eyes with preoperative vitreous hemorrhage (VH; P = 0.011) and without internal limiting membrane (ILM) peeling (P < 0.001). Among the patients who underwent ILM peeling, none demonstrated postoperative ERM. Postoperative ERM was observed in 39 of the 322 eyes (12.1%) within 1 year after surgery; in 30 of these eyes (76.9%), ERM occurred within 3 months after surgery. Advanced ERM was observed in 12 eyes (12/39 eyes [30.8%]). Among these, 9 eyes (9/12 eyes [75%]) showed progression within 3 months after surgery., Conclusions: Preoperative VH can increase the occurrence of postoperative ERM. In most patients with ERM, the occurrence and progression were detected relatively early after surgery; therefore, in high-risk patients, careful follow-up is encouraged until 3 months after surgery., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single-center study called "High-tech Omics-based Patient Evaluation" or "Project HOPE" conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole-exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed "Shizuoka Multi-omics Analysis Protocol" developed in-house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non-cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

In June 2015, Japanese diagnostic reference levels (Japan DRLs 2015) was released by Japan Network for Research and Information on Medical Exposures (J-RIME). After six months the release of Japan DRLs 2015, we have conducted a questionnaire and received 222 responses from hospital staff regarding their perception level, and implementation on Japan DRLs 2015 at their facilities. 131 people (59.0%) were familiar with Japan DRLs 2015, of which 56 people (29.2%) were not currently implementation of them. A total of 66 people (30.1%) understood how to implement Japan DRLs 2015. There were 35 people (18.2%) who heard of diagnostic reference levels (DRLs) for the first time through this survey. Those are the levels of perception and implementation on Japan DRLs 2015 became clear. It is necessary to compare the dose levels used at each facility with Japan DRLs 2015 to optimize patient protection during medical exposure. It is essential to continue to grow the medical community's understanding of DRLs with the expanded perception and implementation of this survey as an opinion poll across Japan.

Immune checkpoint inhibitors have improved the prognosis of advanced melanoma. Although anti-programmed death ligand-1 (PD-L1) is a well-studied biomarker for response to anti-programmed death-1 PD-1 therapy in melanoma, its clinical relevance remains unclear. It has been established that the high expression of indoleamine 2,3-dioxygenase (IDO) is correlated to a response to anti-CTLA-4 treatment in melanoma. However, it is still unknown whether the IDO expression is associated with response to anti-PD-1 therapy in advanced melanoma. In addition, acral and mucosal melanomas, which comprise a great proportion of all melanomas in Asians, are genetically different subtypes from cutaneous melanomas; however, they have not been independently analyzed due to their low frequency in Western countries. To evaluate the association of IDO and PD-L1 expression with response to anti-PD-1 antibody in acral and mucosal melanoma patients, we analyzed 32 Japanese patients with acral and mucosal melanomas treated with anti-PD-1 antibody from the perspective of IDO and PD-L1 expression levels by immunohistochemistry (IHC). Multivariate Cox regression models showed that the low expression of IDO in tumors was associated with poor progression-free survival (HR = 0.33, 95% CI = 0.13-0.81, P = 0.016), whereas PD-L1 expression on tumors was not associated with progression-free survival. Significantly lower expression of IDO in tumors was found in non-responders compared to responders. Assessment of the IDO expression could be useful for the identification of suitable candidates for anti-PD-1 therapy among acral and mucosal melanomas patients. Further validation study is needed to estimate the clinical utility of our findings., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: Japanese teachers are not only responsible for students but also for tasks outside the classroom, including engagement with parents and the community, and maintaining safety. They work longer hours and have lower self-efficacy than teachers in other countries. Thus, we aimed to develop an assessment scale for job stress in teachers and to evaluate its psychometric properties., Methods: We developed the "School Teachers Job Stressor Scale (STJSS) Draft" comprising 45 items, based on previous anonymous self-report questionnaires collected from 98 teachers in four elementary and middle schools in Miyazaki City, Japan. Subsequently, the scale draft and the previously validated Brief Job Stress Questionnaire (23-item abridged version) were distributed to 2276 teachers from 73 elementary and middle schools in Miyazaki City. Finally, we analyzed data from 1300 participants. After excluding inappropriate data based on ceiling and floor effect analysis, we carried out a good-poor, item-total correlation, and exploratory factor analyses. We then verified construct validity, criterion-related validity, and reliability using correlation analysis, confirmatory factor analysis, and Cronbach's alpha, respectively., Results: After item-total correlation analysis, five items were excluded. Exploratory factor analysis extracted five factors: "Time spent outside of work," "Self-assessment of one's ability as a teacher," "Relationship with other teachers," "Social interactions outside of teaching," and "Duties outside of teaching." The final version of the STJSS comprised 23 items and five factors., Conclusion: The 23-item STJSS developed to measure specific stressors in Japanese teachers to improve their mental health care could provide an accurate assessment tool with adequate reliability and validity., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)