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There have been no systematic epidemiological evaluations of the relationship between thyroid autoimmunity and the clinical background of young patients with thyroid nodules. We aimed to clarify the clinical features associated with thyroglobulin or thyroperoxidase antibodies (thyroid autoantibodies [Tabs]) in children and young adults with nodules. We performed a cross-sectional study using data from 3,018 participants of 3–29 years of age with nodules, including thyroid cancer, from the Fukushima Health Management Survey. After stratification of the data for body mass index (BMI) and the bilateral width and thickness of the area (BWTAR) as indicators of thyroid volume for age, sex, body surface area (BSA), and sex-adjusted standard deviation score (SDS), trend analyses were performed. A logistic regression analysis was performed using tab-positivity as an objective variable. The overall prevalence of tab-positivity is 13.9%. It was high in females (17%), participants with diffuse goiter (DG) (19.2%), and those with papillary thyroid carcinoma (PTC) (12.8%). The age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS, BWTAR-SDS, presence of DG, diagnosis of PTC, and TSH concentrations were 0.962 (0.863–1.073), 1.263 (1.171–1.361), 7.357 (4.816–11.239), 2.787 (1.965–4.014), and 1.403 (1.257–1.564), respectively. Tab positivity was independently associated with a large thyroid, the presence of DG, the presence of PTC, and a high TSH concentration in patients with nodules. Based on the systematic epidemiologic evidence shown in young patients, Tab positivity might complement ultrasonography for the assessment of the thyroid function and identification of malignancy in younger patients with asymptomatic thyroid nodules.

Background & Aims: Hepatitis B virus (HBV)-DNA integration into the host genome contributes to hepatocellular carcinoma (HCC) development. KMT2B is the second most frequent locus of HBV-DNA integration in HCC; however, its role and function remain unclear. We aimed to clarify the impact of HBV-KMT2B integration in HCC development using a human genome-edited induced pluripotent stem cell (iPSCs) model. Methods: Based on the genetic information on HBV-KMT2B integration in HCC, we determined its complete DNA sequence and transcript variants. To exclude the effect of other oncogenic mutations, we reproduced HBV integration in healthy donor iPSCs with an intact genome and analyzed its effects using iPSC-derived hepatic progenitor cells (HPCs) and hepatocytes (iPS-Heps). Results: The reproduced HBV-KMT2B integration significantly upregulated the proliferation of hepatic cells. Comprehensive transcriptional and epigenetic analyses revealed enhanced expression of cell cycle-related genes in hepatic cells with HBV-KMT2B integration based on perturbation of histone 3 lysine 4 tri-methylation (H3K4me3), mimicking that in the original HCC sample. Long-read RNA-sequence detected the common KMT2B transcript variants in the HCC sample and HPCs. Overexpression of the truncated variant significantly enhanced proliferation of hepatic cells, whereas HBV-KMT2B fusion transcripts did not enhance proliferation. HBV-KMT2B-integrated HPCs exhibited replication stress and DNA damage, indicating that our model initiated the process of hepatocarcinogenesis due to abnormally promoted KMT2B function. Conclusions: Our disease model using genetically engineered iPSCs provides the first insight into both the KMT2B function in HCC development and the oncogenic processes by HBV-KMT2B integration. We clarified the novel oncogenic mechanism in HBV-related HCC due to aberrant KMT2B function.

Background: Adults with food-protein-induced enterocolitis syndrome (FPIES) often develop severe abdominal symptoms after eating seafood. However, no investigation of a food elimination strategy for adult FPIES patients has been performed to date. Methods: We conducted a retrospective cohort study of seafood–avoidant adults by telephone interview, based on the diagnostic criteria for adult FPIES reported by González et al. We compared the clinical profiles, abdominal symptoms, and causative seafoods between FPIES and immediate-type food allergy (IgE-mediated FA) patients. We also profiled the detailed intake-status of seafoods in adult FPIES patients. Results: Twenty-two (18.8 %) of 117 adults with seafood-allergy were diagnosed with FPIES. Compared with the IgE-mediated FA patients, FPIES patients had an older age of onset, more pre-existing gastrointestinal and atopic diseases, more episodes, longer latency and duration of symptoms, more nausea, abdominal distention, and severe abdominal pain, and more frequent vomiting and diarrhea. In particular, abdominal distention—reflecting intestinal edema and luminal fluid retention—may be the most distinctive characteristic symptom in adult FPIES (p

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.

Background: Internal carotid artery stenosis is primarily attributed to atherosclerosis in the carotid artery bifurcation. Previous studies have detected oral bacteria in atherosclerotic lesions, suggesting an association between oral bacteria and atherosclerosis. In this study, we compared the bacterial flora of the atherosclerotic plaque in the carotid artery and dental plaque of patients with internal carotid artery stenosis using 16S ribosomal RNA (16S rRNA) metagenomic sequencing. Methods: Fifty-four patients who underwent internal carotid endarterectomy for internal carotid artery stenosis at the Showa University Hospital between April 2016 and February 2018 were included. Polymerase chain reaction targeting the 16S rRNA gene detected bacterial DNA in the carotid plaques of 11 cases, of which only 5 could be further analyzed. Thereafter, DNA extracted from the carotid and oral plaques of these 5 cases were analyzed using metagenomic sequencing targeting 16S rRNA. In addition, their general condition and oral conditions were evaluated. The patients were classified into symptomatic and asymptomatic groups based on the presence or absence of symptoms of transient ischemic attack, and their bacterial flora was evaluated. Results: The results demonstrated that the microflora of carotid plaques (n = 5) contained bacterial species from 55 families and 78 genera. In addition, 86.5% of the bacteria detected in the carotid plaques were also detected in oral plaques. Cariogenic and periodontopathic bacteria accounted for 27.7% and 4.7% of the bacteria in the carotid plaques, respectively. Conclusions: These results suggest that oral bacteria are directly or indirectly involved in the pathogenesis of atherosclerosis. More extensive studies of oral commensal bacteria detected in extra-oral lesions are warranted to comprehensively investigate the role of oral bacteria in the pathogenesis of systemic diseases.

Introduction Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan’s health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients’ mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan.Methods and analysis This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2–3 months after T1) and 4–5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists’ communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors.Ethics and dissemination This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations.Trial status The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026.Trial registration number UMIN000049964.

Abstract The clinical symptoms of an immune checkpoint inhibitor (ICI)‐induced colitis are similar to those of ulcerative colitis. ICI‐induced colitis, like ulcerative colitis, may be complicated by other colitis, such as Clostridioides difficile infection (CDI). A 72‐year‐old man was admitted because of watery and bloody stools 10 times a day after three courses of nivolumab (antibodies against programmed death 1) and ipilimumab (cytotoxic T‐lymphocyte‐associated antigen‐4) for stage IV renal cell carcinoma. Colonoscopy revealed erythema and multiple erosions in the colon. Histopathological examination of colonic mucosa revealed diffuse inflammatory cell infiltration and apoptosis. The initial cytomegalovirus antigen test and C. difficile detection assay results were negative. Based on these findings, we diagnosed the patient with ICI‐induced colitis and discontinued ICI therapy. The symptoms did not improve despite the administration of Prednisolone and infliximab. A repeat colonoscopy revealed a new appearance of pseudomembranes from the sigmoid colon to the rectum one month after the start of these treatments. At this point, the patient tested positive for C. difficile. With treatment with vancomycin for CDI, the abdominal symptoms gradually decreased. Nivolumab alone was cautiously restarted. However, no colitis recurrence and further tumor reduction were observed. Here, we report our experience of a case of refractory ICI‐induced colitis complicated by CDI. ICI‐induced colitis may be complicated by CDI and should be carefully treated with repeated CDI testing if refractory to treatment. We believe that our observation will provide helpful information for determining an appropriate treatment strategy for ICI‐induced colitis.

This study aimed to identify the characteristics and challenges faced by children with disabilities and their families living in rural Thailand, and understand the factors that bring changes in their lives through intervention. In a 2021 online survey on the quality of life of school-aged children with disabilities, approximately half of the respondents indicated that they were not enrolled in school. However, the factors responsible were not identified. Therefore, in 2023, we interviewed three children with disabilities in one of the target areas for the abovementioned survey to explore the correlation between the level of independence in the activities of daily living (ADL) and educational and rehabilitation opportunities. This study did not identify a clear correlation between the two factors. Furthermore, a hypothesis emerged that the changes in their lives are influenced more by environmental factors, especially personal factors such as social group awareness and attitudes, caregivers’ understanding and support, and individual relationships within the community. Further research is needed to develop environmental factor assessment tools for problem-solving in accordance with the regional characteristics of rural areas, assess the degree of functional independence of children with disabilities in daily life, and build regional support models.