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The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto’s thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1–23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21–1.27), 3.21 (3.13–3.29), 0.53 (0.50–0.58), and 1.38 (1.17–1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08–16.08), 1.76 (1.01–3.07), 1.80 (1.32–2.45), and 1.34 (1.08–1.67) in the age groups 1–7, 8–11, 12–15, and 16–23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Abstract The present study aimed to clarify the characteristics of young evacuees who had missed the Comprehensive Health Check of the Fukushima Health Management Survey (FHMS) after the Great East Japan Earthquake in 2011. The FHMS has been conducted as a prospective cohort study to evaluate the health status of evacuees annually after the great earthquake in 2011. This study focused on the annual participation rate in the Comprehensive Health Check of evacuees aged between 20 and 37 years in 2011 who evacuated due to the Fukushima Daiichi Nuclear Power Plant accident. The characteristics of subjects who did not participate after the second survey year were identified with a multivariate logistic regression model. The participation rate was estimated at 26.6% (9720 among 36,502 residents) and 15.6% (5691 residents) in 2011 and 2012, respectively. The logistic regression model revealed the following characteristics at baseline as independent predictors of non-participation after the second year of the survey: age ≤ 24 years (adjusted odds ratio 2.11, 95% CI 1.84–2.42), 25–29 years of age (1.28, 1.13–1.45), men (1.52, 1.38–1.69), evacuation outside the municipality but within Fukushima prefecture (1.54, 1.40–1.70), evacuation outside the Fukushima prefecture (1.40, 1.21–1.63), anemia (1.23, 1.06–1.43), smoking habit (1.34, 1.21–1.48), and drinking habit (1.20, 1.09–1.32). A medical history of heart disease showed opposite odds ratios, which indicate the association with continuous participation (0.43, 0.26–0.72, respectively). We observed deteriorated participation in the prospective study of the Comprehensive Health Check of the FHMS among evacuees of a younger age group, men, those evacuated outside their municipalities, and those with history of anemia, smoking and drinking habits. Hence, the cohort study may have missed certain population groups with worse health behaviors. Thus, it is necessary to consider various measures to increase the participation rate in the disaster cohort study to understand the long-term health effects of disasters on younger residents in evacuation zones.

Background: The proportion of overweight individuals living in the evacuation zone of Fukushima increased after the Great East Japan Earthquake. However, the change in the prevalence of abdominal obesity has not been reported. Lifestyle habits and changes in these habits after the disaster might have affected the onset of abdominal obesity; however, the association between the two is unclear. Methods: This study evaluated 19,673 Japanese participants of the Fukushima Health Management Survey. We used data from general health check-ups conducted in 13 municipalities between 2008 and 2010. Follow-up examinations were performed from June 2011 to March 2013. Changes in the proportion of individuals with abdominal obesity before and after the disaster were compared. Then, lifestyle habits affecting these changes were assessed. Results: We found that 34.2% and 36.6% of participants (P < 0.001), both evacuees (37.0% and 42.1% [P < 0.001]) and non-evacuees (32.8% and 34.0% [P < 0.001]), had abdominal obesity before and after the disaster, respectively. Abdominal obesity was positively associated with smoking cessation, snacking after dinner, and non-breakfast skipping after the disaster and alcohol drinking before and after the disaster (all P < 0.05). Smoking cessation was positively associated with abdominal obesity in both evacuees and non-evacuees and in both men and women (all P < 0.01). Conclusion: The prevalence of abdominal obesity increased among residents in the area affected by nuclear disaster. It might be associated with not only lifestyle habits before the disaster but also changes in these habits after the disaster, especially smoking cessation.

Background: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia. Methods: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013–2015. Results: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise. Conclusion: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.

Abstract This study aimed to evaluate the sequential changes in the proportion of anemia among young women over eight years after the Great East Japan Earthquake in 2011 using a prospective study of the Fukushima Health Management Survey. This study focused on the women aged between 20 and 44 who lived in the evacuation area of the nuclear power plant accident. The yearly age-adjusted proportion of anemia was accessed with data between July 2011 and March 2019. A total of 9,198 women participated in the health checkup in 2011, albeit the participation was decreased to 1,241 in 2018. The age-adjusted proportion of anemia was 16.7% in 2012 and then declined after 2013 (p with Cochran-Armitage trend test = 0.03). The multivariate regression analysis identified

IntroductionOn March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective.Materials and methodsThis is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women.ResultsDuring a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067).DiscussionEvacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Information regarding the longitudinal effects of natural/environmental disasters on obstetrics outcomes is limited. This study aimed to analyze the longitudinal changes in obstetrics outcomes over 8 years after the Great East Japan Earthquake and the Fukushima power plant accident. We used data from the first 8 years of the Pregnancy and Birth Survey by the Fukushima prefectural government, launched in 2011. We compared data on obstetrics outcomes by year and divided Fukushima Prefecture into six districts based on administrative districts. Longitudinal changes in the occurrence of preterm birth before 37 gestational weeks, low birth weight, and anomalies in newborns were accessed using the Mantel–Haenszel test for trends in all six districts. Overall, 57,537 participants were included. In 8 years, maternal age, conception rate after sterility treatment, and cesarean section delivery incidence increased. Although significant differences were observed in preterm birth and low birth weight occurrence among districts, there was no significant trend in the occurrence of preterm birth, low birth weight, and anomalies in newborns in all six districts of Fukushima Prefecture. The Great East Japan Earthquake and Fukushima power plant accident were associated with increased cesarean section delivery incidence but had no significant adverse effects on obstetrics outcomes.

Abstract Serologic RhD‐negative red cells can cause anti‐D alloimmunization if they carry the Asian‐type DEL or other DEL variants. RHD genotyping is a viable countermeasure if available, but inexpensive alternatives are worthy of consideration. RhD‐negative blood donors in Japan were studied by anti‐D adsorption‐elution and RHD genotyping. We collated published case reports of RhD‐negative red cell transfusions associated with inexplicable anti‐D immunization. Of 2754 serologic RhD‐negative donors, 378 were genotyped D/d. Anti‐D adsorption‐elution revealed 63.5% (240 of 378) to be DEL, of whom 96.7% (232 of 240) had the 1227G > A variant, diagnostic for the Asian‐type DEL. All 240 donors also carried at least one C antigen; none had a cc phenotype. The chance of transfusing DEL red cells to genuinely RhD‐negative Asian patients (based on a three‐unit transfusion) ranges from 16.7% in Korea to 69.4% in Taiwan, versus 0.6% in Germany. Among 22 RhD‐negative recipients of serologic RhD‐negative red cells, who produced new or increased anti‐D antibody titers, all 17 from East Asia were transfused with red cells with a C‐positive phenotype or known to be Asian‐type DEL or both. Serologic RhD‐negative East Asians with a cc phenotype can be red cell donors for RhD‐negative recipients, especially those of childbearing potential.

Background: This study aimed to investigate the effects of maternal exposure to external radiation on perinatal outcomes among women who experienced the Fukushima Daiichi Nuclear Disaster (FDND) using the Fukushima Health Management Survey (FHMS). Methods: Data from the Pregnancy and Birth Survey and Basic Survey in the FHMS were combined to analyze external maternal radiation exposure following the FDND, and the relationship between radiation dose and perinatal outcomes was analyzed using binomial logistic regression analysis. Missing dose data were supplemented using multiple imputation. Results: A total of 6,875 individuals responded to the survey. Congenital anomalies occurred in 2.9% of patients, low birth weight (LBW) in 7.6%, small for gestation age (SGA;

The Great East Japan Earthquake on March 11, 2011, and the subsequent tsunami caused an accident at the Fukushima Daiichi Nuclear Power Plant, in which extensive damage to the nuclear power reactors resulted in massive radioactive contamination. Fukushima Prefecture implemented the Thyroid Ultrasound Examination (TUE) program as part of the Fukushima Health Management Survey project in response to residents’ anxieties about health risks due to radiation exposure for residents aged 0–18 years at the time of the nuclear accident. This program consisted of the primary examination and the confirmatory examination. In the primary examination, thyroid nodules and cysts were examined using portable ultrasound apparatuses. The confirmatory examination was performed to have clinical or cytological diagnosis. As of June 30, 2021, 116, 71, 31, 36, and 9 examinees in the first, second, third, and fourth round of surveys, and the survey at age 25 years, respectively, were determined to have nodules cytologically diagnosed as malignant or suspicious for malignancy. The confirmatory examination of the fourth-round survey and the primary and confirmatory examination of fifth-round survey are currently in progress. Together with the low thyroid absorbed radiation dose estimated in the United Nations Scientific Committee on the Effects of Atomic Radiation 2020 report, our results suggested that the increased incidence of childhood thyroid cancer in Fukushima Prefecture was not caused by radiation exposure, but rather by the highly sensitive detection method. As detailed in this review, there were ongoing challenges in our program, such as actions against the risk of overdiagnosis and psychological support for participants and their families.

Background: Associations have been reported between lifestyle-related diseases and evacuation after the Great East Japan Earthquake (GEJE). However, the relationship between lifestyle-related diseases and the effective radiation dose due to external exposure (EDEE) after the GEJE remains unclear. Methods: From among 72,869 residents of Fukushima Prefecture (31,982 men; 40,887 women) who underwent a comprehensive health check in fiscal year (FY) 2011, the data of 54,087 residents (22,599 men; 31,488 women) aged 16 to 84 years were analyzed. The EDEE data of 25,685 residents with incomplete results from the basic survey, performed to estimate the external radiation exposure dose, were supplemented using multiple imputation. The data were classified into three groups based on EDEE (0 to

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011–2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011–2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008–2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011–2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

There are limited studies on the long-term effects of natural/environmental disasters, especially nuclear disasters, on obstetric outcomes. This study aimed to review the results of perinatal outcomes immediately after the Great East Japan Earthquake (GEJE) and the Fukushima Daiichi Nuclear Power Plant accident, as well as their long-term trends over 8 years, in the Fukushima Health Management Survey. The annual population-based Pregnancy and Birth Survey is conducted as part of the Fukushima Health Management Survey. The Fukushima Prefecture government launched it to assess the health conditions of pregnant women and their neonates after the GEJE. The self-reported questionnaire was sent to 115,976 pregnant women by mail from January 2012, with 58,344 women responding to the questionnaire (50.3% response rate). Pregnancy complications, such as gestational hypertension, respiratory diseases, and mental disorders, increased in some women who were pregnant at the time of the earthquake and immediately after the earthquake. However, the direct effects on newborns, such as preterm birth, low birth weight, and congenital anomalies, were not immediately clear after the earthquake. Although there were significant differences in the occurrence of preterm birth and low birth weight among the districts, there was no change in the occurrences of preterm birth, low birth weight, or anomalies in newborns in Fukushima Prefecture from the fiscal year 2011 to the fiscal year 2018. Therefore, the long-term effects of the post-disaster radiation accident on perinatal outcomes are considered to be very small.

Background: After the first-round (Preliminary Baseline Survey) ultrasound-based examination for thyroid cancer in response to the accident at the Fukushima Daiichi Nuclear Power Plant in 2011, two rounds of surveys (Full-scale Survey) have been carried out in Fukushima Prefecture. Using the data from these surveys, the geographical distribution of thyroid cancer incidence over 6 or 7 years after the disaster was examined. Methods: Children and adolescents who underwent the ultrasound-based examinations in the second- and/or third-round (Full-scale) survey in addition to the first-round survey were included. With a discrete survival model, we computed age, sex, and body mass index standardized incidence ratios (SIRs) for municipalities. Then, we employed spatial statistics to assess geographic clustering tendency in SIRs and Poisson regression to assess the association of SIRs with the municipal average absorbed dose to the thyroid gland at the 59-municipality level. Results: Throughout the second- and third-round surveys, 99 thyroid cancer cases were diagnosed in the study population of 252,502 individuals. Both flexibly shaped spatial scan statistics and maximized excess events test did not detect statistically significant spatial clustering (P = 0.17 and 0.54, respectively). Poisson regression showed no significant dose-response relationship: the estimated relative risks of lowest, middle-low, middle-high, and highest areas were 1.16 (95% confidence interval [CI], 0.52–2.59), 0.55 (95% CI, 0.31–0.97), 1.05 (95% CI, 0.79–1.40), and 1.24 (95% CI, 0.89–1.74). Conclusion: There was no statistical support for geographic clustering or regional association with radiation dose measures of the thyroid cancer incidence in the cohort followed up to the third-round survey (fiscal years 2016–2017) in Fukushima Prefecture.

The Fukushima Health Management Survey (FHMS) was established in response to the Fukushima Daiichi Nuclear Power Plant accident on March 11, 2011. The primary objectives of the study are to monitor residents’ long-term health and promote their future well-being, and to determine the health effects of long-term low-dose radiation exposure. This special issue summarizes the results and current status of the FHMS and discusses the challenges and future directions of the FHMS. The FHMS, a cohort study of all people who were residents in Fukushima Prefecture at the time of the accident, consists of a Basic Survey, Thyroid Ultrasound Examination, Comprehensive Health Check, Mental Health and Lifestyle Survey, and Pregnancy and Birth Survey. The radiation exposure was estimated based on the behavioral records examined using the Basic Survey. Although the response rate was low in the Basic Survey, the representativeness of the radiation exposure data was confirmed using additional surveys. There appears to be no relationship between the radiation exposure and risk of thyroid cancer, although more thyroid cancer cases were detected than initially expected. The ongoing Comprehensive Health Check and Mental Health and Lifestyle Survey have provided evidence of worsening physical and mental health status. The Pregnancy and Birth Survey showed rates of preterm delivery, low birth weight, and congenital abnormalities similar to the national average. Considering the above evidence, the Fukushima Prefectural Government decided to end the Pregnancy and Birth Survey at the end of March 2021, as recommended by the Prefectural Oversight Committee. The framework of the FHMS has not changed, but the FHMS needs to adapt according to the survey results and the changing needs of the eligible residents and municipalities.

Background: One of the components of the Fukushima Health Management Survey (FHMS) is the Basic Survey, which estimates individual external doses for the first 4 months after the 2011 nuclear power plant accident. However, external exposure continues long-term. According to estimations by international organizations, the external dose during the first year accounts for a significant part of the long-term dose. Thus, the present study was intended to estimate the first-year doses by extrapolating the Basic Survey results. Methods: For most municipalities of non-evacuated areas, ambient dose rate had been continuously measured for at least one designated point in each municipality after the accident. In the present study, a municipality-average dose received by residents for a period was assumed to be proportional to the ambient dose measured at the designated point of that municipality during the same period. Based on this assumption, 4-month municipality-average doses calculated from the Basic Survey results were extrapolated to obtain first-year doses. Results: The extrapolated first-year doses for 49 municipalities in the non-evacuated areas had a good correlation with those estimated by UNSCEAR, although the extrapolated doses were generally higher (slope of the regression line: 1.23). The extrapolated municipality-average doses were in reasonable agreement (within 30%) with personal dosimeter measurements, suggesting that the extrapolation was reasonable. Conclusion: The present paper reports the first 4-month average doses for all 59 municipalities of Fukushima Prefecture and the extrapolated first-year doses for 49 municipalities. The extrapolated doses will be the basis for future epidemiological studies related to the FHMS.

A Mental Health and Lifestyle Survey (MHLS) has been conducted yearly as part of the Fukushima Health Management Survey since 2012, in order to monitor different health issues related to long-term evacuation of affected people after the 2011 Fukushima disaster. This survey is a mail-based one of nearly 210,000 affected people living in the evacuation zone at the time of the disaster. Another purpose of the MHLS is to provide efficient interventions by telephone based on the results of the survey. Significant findings contributing to understanding of non-radiological health effects caused by long-term evacuation were obtained from the MHLS, directly connecting to telephone-based interventions for over 3,000 respondents per year. In this article, the mental health outcomes of the MHLS, including depressive symptoms and posttraumatic responses, are reviewed, and the usefulness of telephone-based interventions is discussed. The evidence showed that, despite improvement of core mental health outcomes, the prevalence of respondents at high risk of some psychiatric problems remained high compared to that among the general population in Japan. In particular, several mental health consequences of respondents staying outside of Fukushima Prefecture were higher than those staying inside Fukushima. Along with further efforts to increase the response rate, we need to continue and modify the MHLS to meet the requirements of the affected people and communities.

BackgroundThe burden of psychological distress and post-traumatic stress disorder (PTSD) has been suggested as a factor in developing type 2 diabetes mellitus. However, longitudinal features in psychological distress- and PTSD-related new-onset diabetes mellitus have not been thoroughly evaluated.MethodsThe association between probable depression and probable PTSD and the risk of developing new-onset diabetes mellitus was evaluated in a 7-year prospective cohort of evacuees of the Great East Japan Earthquake in 2011. Probable depression was defined as a Kessler 6 scale (K6) ≥ 13 and probable PTSD as a PTSD Checklist—Stressor-Specific Version (PCL-S) ≥ 44.ResultsThe log-rank test for the Kaplan–Meier curve for new-onset diabetes mellitus was significant between K6 ≥ 13 vs. < 13 and PCL-S ≥ 44 vs. < 44 in men but not in women. In men, both K6 ≥ 13 and PCL-S ≥ 44 remained significant in the Cox proportional hazards model after multivariate adjustment for established risk factors and disaster-related factors, including evacuation, change in work situation, sleep dissatisfaction, and education.ConclusionThe post-disaster psychological burden of probable depression and probable PTSD was related to new-onset diabetes in men but not in women. In post-disaster circumstances, prevention strategies for new-onset diabetes might consider sex differences in terms of psychological burden.

Abstract Background Despite intensive multimodal therapies, the prognosis of relapsed/ refractory Ewing sarcoma family tumors (RR‐ESFTs) is dismal. Some case reports using allogeneic stem cell transplantation (allo SCT) for RR‐ESFTs have been reported, however, the efficacy of allo SCT is yet to be established. Aim The purpose of this study was to evaluate the response and toxicity of T‐cell replete haploidentical SCT (TCR‐haplo‐SCT) in RR‐ESFTs. Methods and results In this study, we retrospectively analyzed six patients with RR‐ESFTs who received TCR‐haplo‐SCT. Four patients had relapsed and two patients had refractory Ewing sarcoma. Before the TCR‐haplo‐SCT, all patients received a reduced intensity‐conditioning regimen containing fludarabine, melphalan, and low‐dose rabbit anti‐thymocyte globulin (2.5 mg/kg), as well as graft‐versus‐host disease (GVHD) prophylaxis, which consisted of tacrolimus, methotrexate, and prednisolone. Primary neutrophil engraftment was achieved in all the patients. Four patients developed acute GVHD (aGVHD) (grade I, 1; grade II, 1; grade III, 2), and two patients developed chronic GVHD (cGVHD). Among the four that developed aGVHD, three survived for 14, 116, and 129 months without relapse, while one died due to a transplant‐related complication. In contrast, the two patients who did not develop aGVHD experienced relapse early after TCR‐haplo‐SCT. Conclusions In this study, three of the six patients with RR‐ESFTs survived for more than one year without relapse, and the treatment toxicity was considered acceptable even for patients who underwent high‐intensity pretreatment. TCR‐haplo‐SCT could be a potential therapeutic option for patients with RR‐ESFTs.

This study examined whether disaster resilience affects the recovery of mental health states and mitigates psychosocial anxiety 10 years later the Fukushima Daiichi nuclear power plant accident. The survey was conducted in Fukushima's evacuation-directed and non-evacuation-directed areas in January 2020. The 695 participants responded to a questionnaire including items on radiation-related anxiety regarding the Fukushima Daiichi accident, an action-oriented approach as a resilience factor, psychological distress, and demographic information. The structural equation modeling showed that the action-oriented approach also eased radiation-related anxiety by mediating with improving mental health states. Moreover, a multi-group model analysis was conducted for evacuation-directed and non-directed areas. In the evacuation-directed area, we found stronger associations among resilience, mental health states, and radiation-related anxiety, and a direct effect of resilience factors on radiation risk anxiety. These findings emphasize the importance of resilience in post-disaster contexts, at least for a decade, where mental health deteriorates and various psychosocial issues become more complex.

Abstract Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth. Red blood cell distribution width (RDW), a measure of the variation red blood cell size, could reflect oxidative stress and chronic inflammation in many diseases such as cardiovascular, pulmonary, and other diseases. The objectives of the present study were to evaluate perinatal factors affecting RDW and to validate whether RDW could be a potential biomarker for BPD. A total of 176 preterm infants born at

Background: After the Fukushima Daiichi Nuclear Power Plant accident, a preliminary ultrasound-based screening for thyroid cancer was conducted to establish a baseline for subsequent evaluations. In this survey, we assessed the relationship between the proportion of non-examinees and characteristics of the target populations. Methods: After summarizing a regional difference of non-examinees among the population of 359,200 (primary evaluation) and 2,246 (confirmatory testing) individuals who were living in Fukushima Prefecture on March 11, 2011, we estimated odds ratios (ORs) for each characteristic, including age, sex, area of residence, and moving after the accident, based on the proportion of non-examinees for the primary examination and the confirmatory testing, using a multivariate logistic regression model. Results: The dataset included 64,117 non-examinees (primary evaluation) and 194 (confirmatory testing). The logistic regression result indicated that girls were not likely to be non-examinees compared to boys, with adjusted OR of 0.80 (95% confidence interval [CI], 0.78–0.81) for the primary evaluation. Odds were lowest for children 6–10 years old (OR 0.26; 95% CI, 0.25–0.27), and higher for those 11–15 years old (OR 1.28; 95% CI, 1.25–1.32) and over 16 years old (OR 5.30; 95% CI, 5.16–5.43) when compared to children 0–5 years old. Individuals residing in the western part of the prefecture showed higher ORs. There was a higher proportion of non-examinees among those who moved after the accident compared to those who did not in the primary evaluation (OR 1.72; 95% CI, 1.64–1.79). Conclusions: In addition to demographic characteristics, a change of residence could be a potential factor that influenced the proportion of non-examinees. Our results will help proper interpretation of reports and prospective management of the survey.

Abstract Background Although disseminated intravascular coagulation (DIC) is a critical disease, there is few gold standard interventions in neonatal medicine. The aim of this study is to reveal factors affecting neonatal DIC at birth and to assess the effectiveness of rTM and FFP for DIC in neonates at birth. Methods We retrospectively evaluated DIC score on the first day of life in neonates with underlying conditions associated with DIC. DIC in neonates was diagnosed according to Japan Society of Obstetrical, Gynecological & Neonatal Hematology 2016 neonatal DIC criteria. Results Comparing neonates with DIC scores of ≥3 (n = 103) to those

Background: The prognosis of refractory/relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains dismal owing to acquired resistance to chemotherapeutic agents. This study aimed to evaluate the efficacy of T-cell replete HLA haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) for pediatric refractory/relapsed BCP-ALL (RR-BCP-ALL).Methods: Nineteen pediatric patients with RR-BCP-ALL underwent TCR-haplo-HSCT between 2010 and 2019 at the Fukushima Medical University Hospital. The disease status at TCR-haplo-HSCT included complete remission (CR) in eight patients and non-CR with active disease in 11 patients. Total body irradiation-based, busulfan-based, and reduced-intensity conditioning regimens were employed in 11, 6, and 2 patients, respectively. Low-dose anti-thymocyte globulin (thymoglobulin, 2.5 mg/kg) was used in all patients. Graft-vs.-host disease (GVHD) prophylaxis was administered with tacrolimus, methotrexate, and prednisolone.Results: All patients received peripheral blood stem cells as the stem cell source. The HLA disparities in graft vs. host directions were 2/8 in one, 3/8 in five, and 4/8 in 13 patients. Among 18 patients who achieved primary engraftment, acute GVHD occurred in all 18 evaluable patients (grade II, 9; grade III, 8; grade IV, 1), and chronic GVHD was observed in 10 out of 15 evaluable patients. Three patients died because of transplant-related mortality. The 3-year overall survival (OS) and leukemia-free survival rates were 57.4 and 42.1%, respectively. Compared to patients older than 10 years in age (N = 10), those younger than 10 years in age (N = 9) showed an excellent OS rate (3-year OS rate: patients < 10 years old, 100%; patients > 10 years old, 20% [95% confidence interval, 3.1–47.5]; p = 0.002).Conclusions: We suggest that TCR haplo-HSCT with low-dose ATG conditioning has the potential to improve the transplantation outcomes in patients with RR-BCP.

Background: Dietary patterns may be linked to the incidence of type 2 diabetes mellitus (T2DM) after disasters. We investigated the association between dietary patterns and new-onset T2DM in evacuees of the Great East Japan Earthquake and the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Methods: Among the 22,740 non-diabetic participants aged 20–89 years who completed the dietary assessment in the Fukushima Health Management Survey between July 2011 and November 2012, the incidence of T2DM was evaluated until 2018. Principal component analysis with varimax rotation was applied to derive dietary patterns based on a validated, short-form food frequency questionnaire. The identified dietary patterns were categorized as typical Japanese, juice, and meat. Results: The cumulative incidence of T2DM was 18.0 and 9.8 per 1000 person-years in men and women, respectively, during the follow-up period. The multiple-adjusted hazard ratio (95% confidence interval) of the highest vs. lowest quartile of the typical Japanese pattern scores for T2DM was 0.80 (0.68, 0.94; P for trend = 0.015) in total, 0.85 (0.68, 1.06; P for trend = 0.181) in men, and 0.76 (0.60, 0.95; P for trend = 0.04) in women. Conclusions: A typical Japanese dietary pattern may be associated with a reduced new-onset T2DM risk in evacuees, especially women, after the Great East Japan Earthquake and the FDNPP accident.

Bronchopulmonary dysplasia (BPD) is a common cause of pulmonary disease in preterm infants. The soluble receptor for advanced glycation end products (sRAGE) is implicated in the development of various pulmonary diseases. The objectives of the current study were to investigate perinatal factors associated with serum sRAGE levels at birth and to establish whether serum sRAGE could be a biomarker for BPD. This retrospective single-center study was conducted at Fukushima Medical University Hospital's Department of Pediatrics Neonatal Intensive Care Unit from April 2014 to September 2020. Mechanically ventilated or oxygenated neonates born at

Aim: The aims of the present study were to develop and validate a psychological resilience scale reflecting the specificity of the Fukushima disaster, and to examine the effects of this scale on mental health.Methods: The Fukushima Resilience Scale was developed based on data obtained from semi-structured interviews with seven people who had lived in the affected area of Fukushima Prefecture at the time of the disaster. The reliability and validity of the scale were then examined in cross-sectional studies conducted on 500 evacuees through an epidemiological mail survey. To examine the effects of the scale and disaster-related factors on the general mental health status of the respondents, a logistic regression analysis was performed using the six-item Kessler psychological distress scale.Results: The newly developed scale consisted of a four-factor structure: “coping with stigma-related issues,” “sharing experiences of the disaster,” “action-oriented approach,” and “sense of support.” Internal consistency coefficients ranged from 0.66 to 0.79. The multivariable logistic regression analysis showed that the only significant association was between “action-oriented approach” (odds ratio = 1.26) and respondents with a K6 score

Background: Platelets participate in many physiological and pathological functions and some platelet parameters predict adult diseases. However, few studies report whether platelet parameters may reflect neonatal disease and mortality in a large cohort.Objective: We aimed to investigate whether platelet parameters could predict bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and NICU mortality.Study Design and Methods: This retrospective cohort study examined records from 2006 to 2017 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. We retrospectively investigated platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on the first day of life in preterm newborns born

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P

Abstract Background Chronic graft-versus-host disease (GVHD) appears several months following allogenic hematopoietic stem cell transplantation (HSCT) and is clinically analogous to autoimmune disorder. Polymyositis is a common neuromuscular disorder in chronic GVHD, but myasthenia gravis (MG) is extremely rare. Hence, its pathophysiology and treatment have not been elucidated. Case presentation A 63-year-old man with a history of chronic GVHD presented with ptosis, dropped head, and dyspnea on exertion, which had worsened over the previous several months. He showed progressive decrement of compound muscle action potential in the deltoid muscle evoked by 3-Hz repetitive nerve stimulation, a positive edrophonium test, and elevated levels of serum anti-acetylcholine receptor antibodies, which suggested a diagnosis of generalized MG. No thymoma was found. Flow cytometric analysis revealed a remarkable depletion of peripheral Tregs (CD4+CD25highFOXP3+ cells, 0.24% of the total lymphocytes). Administration of prednisolone and tacrolimus was insufficient to alleviate his symptoms; however, the use of rituximab successfully improved his condition. Conclusions Myasthenic symptoms appeared in the process of tapering prednisolone for the treatment of chronic GVHD, supporting the diagnosis of MG associated with chronic GVHD. The present case proposes a possibility that reduction of Tregs might contribute to the pathogenesis of MG underlying chronic GVHD. Immunotherapy with rituximab is beneficial for treatment of refractory MG and GVHD.

Abstract Although the incidence of hepatobiliary enzyme abnormality increased immediately after the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident, longer-term trends remain unclear. The aims of this study were to determine longer-term trends in hepatobiliary enzyme abnormality and to elucidate lifestyle factors associated with such changes among residents of a nuclear-disaster-affected area. This longitudinal survey enrolled 20,395 adults living in the vicinity of Fukushima Daiichi Nuclear Power Plant. Data were obtained from the records of annual health checkups of adults aged ≥40 years between 2011 and 2012. Follow-up examinations were conducted from June 2013 to March 2014. Associations were assessed between changes in hepatobiliary enzyme abnormality immediately and 3–4 years after the disaster and lifestyle factors. The overall prevalence of hepatobiliary enzyme abnormality significantly decreased over the study period, from 29.9% to 27.1%. Multivariate logistic regression analysis revealed significant associations between improved hepatobiliary enzyme abnormality and improvements in daily physical activity and frequency of breakfast consumption. The results suggest that improvements in daily physical activity and frequency of breakfast consumption significantly reduced the incidence of hepatobiliary enzyme abnormality 3–4 years after the Great East Japan Earthquake and Fukushima Daiichi Nuclear Power Plant accident.

We previously reported that the lifestyle of evacuees significantly increased the prevalence of polycythemia compared with non-evacuees at an average of 1.6 years (2011–2012) from the previous annual health checkup before the Great East Japan Earthquake (GEJE). Here we analyzed how the prolonged evacuation affected the prevalence of polycythemia an average of 2.5 years (2013–2014) after the previous data. Subjects were individuals aged 40–90 years living in the vicinity of the Fukushima Daiichi Nuclear Power Plant in Fukushima Prefecture who had attended the annual health checkups since 2008. The prevalence of polycythemia and changes in its defining factors of red blood cell count (RBC), hemoglobin (Hb) level, hematocrit (Ht) level were compared between before and after the GEJE in 7713 individuals (3349 men and 4364 women) receiving follow-up examinations both 2011–2012 and 2013–2014. RBC, Hb levels and Ht levels in 2011–2012 were higher among evacuees than non-evacuees in both men and women. However, all levels in 2013–2014 were on the decline from those in 2011–2012. On the other hand, among evacuees, Hb and Ht levels continued to be higher than before the GEJE in both men and women evacuees. The prevalence of polycythemia, which was diagnosed if one of the defining factors was beyond the standard value, was significantly higher among evacuees than non-evacuees regardless of the presence or the absence of overweight/obesity, smoking, and hypertension. Therefore, prolonged evacuation is a cause of polycythemia even 3 to 4 years after the GEJE and regular health management of evacuees is important.

This study examined parental recognition of bullying victimization and associated factors among evacuated children after the 2011 Fukushima Daiichi Nuclear Power Plant accident, using a 3-year follow-up data (wave 1: January 2012; wave 2: January 2013; wave 3: February 2014). The sample included the caregivers of 2,616 children in the first–sixth grades of elementary school, who lived in one of the 13 municipalities that were the target areas of the Mental Health and Lifestyle Survey, conducted as part of the Fukushima Mental Health Management Survey. Across 3 years, around 80% of caregivers responded “not true,” 15% responded “somewhat true,” and 5% responded “certainly true” in response to a question about bullying victimization of their children. Being male was significantly associated with the parental recognition of bullying victimization at wave 1 and wave 3. At wave 1, experiencing the nuclear plant explosion was significantly associated with parental recognition of bullying victimization. Moreover, age at wave 3 was negatively associated with parental recognition of bullying victimization. Our findings will be helpful for establishing community- and school-based mental health care for children, parents, and teachers.

To investigate associations between dietary patterns and the risk of impaired kidney function, we analyzed data from 14,732 participants (40–89 years) who completed the baseline diet questionnaire of The Fukushima Health Management Survey in 2011. The incidence of chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 2 or proteinuria (≥1+ by dipstick test)) and annual changes in eGFR were assessed from 2012 to 2015. Three major dietary patterns were identified. The adjusted cumulative incidence ratio of the highest vs. lowest tertile of a vegetable diet scores was 0.90 (95% confidence interval (CI): 0.82, 1.00) for eGFR < 60 mL/min/1.73 m2, 0.68 (95% CI: 0.52, 0.90) for proteinuria, and 0.88 (95% CI: 0.80, 0.97) for CKD (P for trend = 0.031, 0.007, and 0.005, respectively). The incident risk of CKD in the highest tertile of juice diet scores was 18% higher than the lowest tertile. The odds ratio of the highest vs. lowest tertile of vegetable diet scores was 0.85 (95% CI: 0.75, 0.98) in the rapidly decreasing eGFR group (P for trend = 0.009). We did not observe significant associations for the meat dietary pattern. A Japanese vegetable diet could reduce the risk of developing impaired kidney function and CKD.

Relationships between inflammation and innate immunity in cancer are widely accepted today; however, the precise cell mechanisms mediating these relationships have not yet been elucidated. Interleukin (IL)-17 is a proinflammatory cytokine that has been reported to induce inflammation in patients with autoimmune diseases. Myeloid-derived suppressor cells (MDSC) may contribute to the negative regulation of immune responses during cancer and inflammation. Vascular endothelial growth factor (VEGF) is reported to have multiple biological actions including increasing vascular permeability, neovascularization, and possible inhibition of immune function in malignant diseases. This study investigated the status of systemic inflammation and immune suppression associated with IL-17 and VEGF in patients with breast cancer. IL-17 production and the serum levels of VEGF were also increased in advanced stages of the disease. The production of IL-12, which induces Th1 cells, and the stimulation index (SI), which is a marker of cell-mediated immune function, were both shown to decrease along with disease advancement. Also, the production of IL-17 and the VEGF levels were both positively correlated with the levels of MDSC, the neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and were inversely correlated with IL-12 production and the SI. Nutritional markers, including prealbumin (PA), transferrin (TF), and retinol-binding protein (RBP), were also shown to be significantly lower in patients with high production of IL-17 or high levels of VEGF. These data clearly showed that IL-17 and VEGF, whose levels correlated with each other and with those of MDSC, were significantly associated with disease advancement, systemic inflammation, suppression of cell-mediated immunity including Th1 induction, and malnutrition.

BACKGROUND: CD4+CD25highFOXP3+ regulatory T (Treg) cells, which include thymus-derived and peripherally induced cells, play a central role in immune regulation, and are therefore crucial to prevent graft-versus-host disease (GVHD). The increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with thymus regression, and our case of allo-HSCT shortly after total thymectomy, raised questions about the activity of thymus-derived Treg cells and peripherally induced Treg cells, which are otherwise indistinguishable. RESULTS: We found that despite pre-transplant thymectomy or older age, both naïve and effector Treg cells, as well as naïve and effector conventional T cells, proliferated in allo-HSCT recipients. Higher proportions of total Treg cells 1 month post allo-HSCT, and naïve Treg cells 1 year post allo-HSCT, appeared in patients achieving complete chimera without developing significant chronic GVHD, including our thymectomized patient, compared with patients who developed chronic GVHD. CONCLUSIONS: Treg cells that modulate human allogeneic immunity may arise peripherally as well as in the thymus of allo-HSCT recipients.

This study examined the impact of platelet transfusion (PLT) on the survival of intracerebral hemorrhage (ICH) patients who had been administered anti-platelet agents (APA). This retrospective cohort analysis investigated 432 patients (259 men, 60%) who were newly diagnosed with ICH between January 2006 and June 2011 at the tertiary emergency center of Kitasato University Hospital. Median age on arrival was 67.0 years (range, 40-95 years). ICH was subcortical in 72 patients (16.7%), supratentorial in 233 (53.9%), and infratentorial in 133 (30.8%). PLT was performed in 16 patients (3.7%). Within 90 days after admission to the center, 178 patients (41.2%) had died due to ICH. Before the onset of ICH, 66 patients had been prescribed APA because of atherosclerotic diseases. Multivariate regression analysis indicated APA administration was an independent risk factor for death within 7 days (odds ratio, 5.12; P = 0.006) and within 90 days (hazard ratio, 1.87; P = 0.006) after arrival. Regarding the effect of a PLT in ICH patients with APA, no patient with PLT died. PLT had a survival benefit on patients with ICH, according to our analysis. Further prospective analysis is necessary to confirm the effects of PLT on survival in ICH with APA.

Background Although the AB0 blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of AB0 incompatibility on transplant outcome. This study investigated the effect of AB0 incompatibility in recipients of bone marrow transplants from unrelated donors.Design and Methods We retrospectively analyzed data from 5,549 patients who underwent bone marrow transplantation from unrelated donors in the Japan Marrow Donor Program.Results Overall survival rates in the group with major and minor mismatches were significantly lower than the rate in the AB0-identical group (AB0-identical 63.0%; major mismatch, 56.9%; minor mismatch, 57.1% at 1 year). Treatment-related mortality was higher in the major and minor mismatch groups, but there was no significant difference in the rate of relapse. Cox proportional hazards modeling showed that both major and minor AB0 incompatibility were significant risk factors for transplant-related mortality, independently of disease, patients’ age, and HLA incompatibility. Delayed engraftment of neutrophils, platelets, and erythrocytes was observed in transplants with major incompatibility. There was a high incidence of grade 3 and 4 acute graft-versus-host disease in the groups with major and minor mismatches, which was caused by a high incidence of stage 2 to 4 liver graft-versus-host disease. Interestingly, the risk of grade 2 to 4 graft-versus-host disease in the major mismatch group was higher in patients with early engraftment of erythrocytes. Among the patients receiving reduced-intensity conditioning, the transplant-related mortality was also increased in AB0-incompatible transplants.Conclusions Major and minor AB0 incompatibility have specific effects on transplant-related mortality and acute graft-versus-host disease in recipients of bone marrow transplants from unrelated donors.

Peripheral blood stem cell harvesting (PBSCH) is an established general practice; however, recent medical advances have led to diversification in hematopoietic stem cell transplantation and collection. A questionnaire survey on cell therapy and blood cell apheresis was conducted to understand the current situation and identify issues in Japan. A total of 159 facilities/departments responded to the survey. The annual number of autologous PBSCH was "11-25" in 48% and "1-10" in 37% of the centers, while the annual number of allogeneic PBSCH for related transplantation was "1-10" in 60% of the centers and "1-10" in 50% for unrelated transplantation. Collection sites were in the wards (40%), transfusion department (36%), and dialysis unit (26%). The apheresis system was staffed mainly by clinical engineers (67%) and doctors (23%). Primarily, doctors (96%) performed peripheral vascular punctures and were present at all times during collection in 37% of the centers. The Spectra Optia was the equipment most commonly used for apheresis. To freeze the product, 89% of the centers used "CP-1" without a controlled rate freezer. This survey revealed the diversification of collection methods in Japan, with "task shift" emerging as a significant concern. [ABSTRACT FROM AUTHOR]