At the beginning of 2000, the National Cancer Center had little involvement in cancer statistics. In addition, cancer incidence data were collected by regional cancer registries (approximately 30 prefectures have on-site registries), but the problems were that (1) the completeness of the registration was low, (2) the registration method was not standardized, and (3) usage was limited. In the Third Comprehensive Strategic Cancer Research Project (2004-2013), Field 7, "Research on Developing Cancer Surveillance System and Disseminating Cancer Information," was added, and we could build a system to aggregate the latest cancer statistical data from Japan and provide it as content for cancer information services. In addition, within the Regional Cancer Registry Research Group, we promoted the standardization of population-based cancer registry methods through "formulation and dissemination of standard registration forms" and "development and dissemination of standard registry systems." We believe that these factors served as the basis for the smooth transfer to the National Cancer Registry under the Cancer Registry Promotion Act, which was enacted in 2013.

In contrast, to take over the function of Hisamichi's "Evaluation of the Effectiveness of New Cancer Screening Methods" report published in 2001, the Ministry of Health, Labour and Welfare Cancer Research Grant "Research on the Establishment of Appropriate Methods for Cancer Screening and Evaluation Methods" group, which started in 2003, formulated the guideline development procedure and updated the guidelines, and the work of updating the guidelines was subsequently taken over by the National Cancer Center. This remains an important mechanism to ensure that cancer screening methods that do not have a scientifically confirmed balance between benefits and harms are not introduced into policy.

For several decades, the counterfactual model and the sufficient cause model have shaped our understanding of causation in biomedical science and, more recently, the link between these two models has enabled us to obtain a deeper understanding of causality. In this article, I provide a brief overview of these fundamental causal models using a simple example. The counterfactual model focuses on one particular cause or intervention and gives an account of the various effects of that cause. By contrast, the sufficient cause model considers sets of actions, events, or states of nature which together inevitably bring about the outcome under consideration. In other words, the counterfactual framework addresses the question "what if?" while the sufficient cause framework addresses the question "why does it happen?" Although these two models are distinct and address different causal questions, they are closely related and used to elucidate the same cause-effect relationships. Importantly, the sufficient cause model makes clear that causation is a multifactorial phenomenon, and it is a "finer" model than the counterfactual model; an individual is of one and only one response type in the counterfactual framework, whereas an individual may be at risk of none, one, or several sufficient causes. Understanding the link between the two causal models can provide greater insight into causality and can facilitate the use of each model in appropriate contexts, highlighting their respective strengths. I will briefly present three topics of interest from our research: the relationship between the concepts of confounding and of covariate balance; distinctions between attributable fractions and etiologic fractions; and the identification of operating mediation and mechanism. It is important to scrutinize observed associations in a complementary manner, using both the counterfactual model and the sufficient cause model, employing both inductive and deductive reasoning. This holistic approach will better help us to unravel causality.

T cell receptors (TCRs) have a highly diverse sequence pattern resulting from the random recombination of gene components in the thymus. This diversity enables TCRs to distinguish between a wide range of self and non-self-antigens, thereby shaping the reactivity of the acquired immune system. Self-responsiveness arising from impaired TCR-based self-discrimination is a crucial trigger for the development of autoimmune diseases. The immunological importance of TCR research is evident, yet traditional experimental and analytical techniques have not fully captured the vast information contained within the TCR repertoire. However, recent advancements in massive parallel sequencing, efficient library preparation pipelines, single-cell experiment platforms, and genome engineering are poised to transform our understanding of TCR diversity, sparking interest in the field. These advancements have made it possible to "read through" the entire TCR repertoire and partially identify their cognate antigens. In parallel, methods for efficiently analyzing large datasets of comprehensive TCR sequences have also progressed. These innovations in experimental and analytical techniques are leading TCR research in new directions, such as using TCR as a real-time biomarker, exploring the link between TCR and T cell differentiation, and investigating TCR genetic regulation. This review will cover recent updates on big data science related to TCR-mediated immune regulation.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of mature T-cell neoplasms with different clinical, biological, and molecular features. These include PTCL, not otherwise specified, nodal T follicular helper cell lymphomas (nTFHLs), anaplastic large cell lymphoma (ALCL), extranodal natural killer (NK) /T-cell lymphoma (ENKTL), and adult T-cell leukemia/lymphoma (ATLL). Over the past decade, several genetic studies using targeted, whole-exome, and more recently whole-genome sequencing have identified numerous driver alterations in PTCLs. These alterations include mutations, copy number alterations, and structural variations (SVs) involving T-cell receptor/NF-κB (such as PLCG1, VAV1, and CD28) and JAK/STAT (JAK3 and STAT3) pathway components, epigenetic regulators (TET2, DNMT3A, and ARID1A), immune-associated molecules (HLA-A/B, CD58, and PD-L1), and tumor suppressors (TP53 and CDKN2A), which are shared among various PTCL subtypes. Conversely, subtype-specific alterations, such as RHOA G17V and IDH2 R172 mutations in nTFHLs; ALK fusions in ALCL; DDX3X and MSN mutations in ENKTL; and PRKCB, CIC, and CCR4 mutations in ATLL. Regarding the clinical relevance of genetic alterations, combining genetic information with clinical factors has been reported to improve prognostic stratification in several subtypes of PTCLs, such as ENKTL and ATLL. Additionally, several genetic alterations may have the potential to predict a response to a specific molecularly targeted agent, such as ALK fusions for ALK inhibitors, PD-L1 SVs for immune checkpoint inhibitors (including anti-PD-1 antibodies), and mutations in epigenetic regulators for histone deacetylase inhibitors and hypomethylating agents. In this study, we summarize the current understanding of somatic alterations in various subtypes of PTCLs and highlight their clinical utility.

The evolution of innovative artificial intelligence (AI) systems in pediatric hospitals in Japan promises benefits for patients and healthcare providers. We actively contribute to advancements in groundbreaking medical treatments by leveraging deep learning technology and using vast medical datasets. Our team of data scientists closely collaborates with departments within the hospital. Our research themes based on deep learning are wide-ranging, including acceleration of pathological diagnosis using image data, distinguishing of bacterial species, early detection of eye diseases, and prediction of genetic disorders from physical features. Furthermore, we implement Information and Communication Technology to diagnose pediatric cancer. Moreover, we predict immune responses based on genomic data and diagnose autism by quantifying behavior and communication. Our expertise extends beyond research to provide comprehensive AI development services, including data collection, annotation, high-speed computing, utilization of machine learning frameworks, design of web services, and containerization. In addition, as active members of medical AI platform collaboration partnerships, we provide unique data and analytical technologies to facilitate the development of AI development platforms. Furthermore, we address the challenges of securing medical data in the cloud to ensure compliance with stringent confidentiality standards. We will discuss AI's advancements in pediatric hospitals and their challenges.

DNA methylation is an epigenetic modification implicated in psychiatric disorders influenced by both genetic and environmental factors. Methylation risk scores (MRSs) have emerged as a tool for quantifying accumulated epigenetic modifications and assessing the predisposed risk for certain common disorders. This narrative review introduces the MRS application in psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), social anxiety disorder (SAD), and panic disorder (PD), while also discussing the current limitations and ethical considerations in psychiatric research. MRSs are calculated from epigenome-wide association studies (EWASs) for psychiatric disorders in various tissues from blood and brain and reflect methylation patterns associated with the psychiatric disorder risk. MRSs provide a perspective of how the cumulative methylation patterns at specific CpG sites may contribute to the onset of psychiatric disorders. In SCZ and BD, MRSs derived from both blood and brain tissues have shown distinct methylation profiles that differentiate these disorders, particularly in patients with a high genetic SCZ risk. MRSs are also used to assess the impact of environmental factors, such as early-life adversity and chronic stress, on psychiatric outcomes. In SAD and PD, where epigenetic studies are relatively limited, MRSs revealed both shared and distinct epigenetic features between anxiety disorders, with specific methylation changes associated with social avoidance in SAD patients. MRSs can serve as biomarkers, providing a valuable understanding of both genetic predispositions and environmental influences on gene regulation. However, the lack of large-scale EWAS datasets and standardized summary statistics remains as a limitation. To address this issue, this review provides a list of publicly available raw intensity data (IDAT) files from psychiatric epigenetic studies that can help facilitate future research by providing the raw data necessary for conducting independent EWASs and MRS calculations. As the field advances, careful consideration must be given to the ethical implications of MRS applications, particularly in clinical intervention and prevention. While MRSs hold promise for future personalized medicine applications, informing treatment decisions based on an individual's methylation profile, caution is warranted regarding their predictive utility and effect size limitations. This review emphasizes the importance of MRSs in advancing psychiatric research, bridging the gap between genetic risk and environmental factors.

Chronic epipharyngitis is associated with a wide variety of symptoms, including local symptoms such as postnasal drip, sore throat, lump sensation of the pharynx, headache, chronic cough, nasal obstruction, tinnitus/ear fullness, chronic phlegm and dysphonia due to inflammation of the epipharynx, functional somatic symptoms such as chronic fatigue, dizziness, insomnia, brain fog, abdominal discomfort, and depression caused by dysfunction of the hypothalamus-limbic system via disturbances of vagal response and cerebrospinal fluid outflow, and distant organ symptoms such as immunoglobulin A nephropathy and palmoplantar pustulosis caused by the epipharyngeal lymphoid tissue as an etiologic organ. In the past, chronic inflammation in the epipharynx was difficult to prove by gross findings, now, direct observation of the epipharyngeal inflammation by endoscopy has become easier for the diagnosis. For the treatment of chronic epipharyngitis, epipharyngeal abrasive therapy (EAT), epipharyngeal application of a 1% zinc chloride solution intranasally or orally was popular since the 1960s, recently, endoscopic EAT (E-EAT), in which epipharynx is safely and accurately observed and abraded under clear vision using an endoscope, has been developed. The mechanisms of EAT effects can be classified into anti-inflammatory/antiviral effect, bloodletting effect, and vagus nerve stimulation effect. Recently, the effectiveness of EAT for post-acute sequelae of coronavirus disease 2019 (COVID-19), known as long COVID, has come into the limelight, and the number of patients for whom EAT is expected to increase. In 2019, the Japan Society of Stomato-pharyngology established the EAT Review Committee to accumulate evidence on the efficacy of EAT and to establish indications and techniques for its use. In this article, the EAT Review Committee outlines its symptoms, pathogenesis, and diagnosis of chronic epipharyngitis, technique of E-EAT, mechanisms of EAT effects, past reports for the efficacy of EAT, and a multicenter prospective study.

The Japan Agency for Medical Research and Development (AMED) was established in April 2015 as a funding agency for medical research and development. AMED has been striving to ensure the provision of state-of-the-art medical services and the advancement of a society characterized by health and longevity. Furthermore, AMED facilitates the seamless integration of research projects, spanning the spectrum from basic to applied research and practical applications. The current article presents an overview of the trends observed in awarded projects related to psychiatric disorders. Consequently, there was a considerable rise in the number of projects pertaining to medical devices, particularly within the domain of digital mental health. It is anticipated that an increased number of social implementation studies will obtain regulatory approval under the Pharmaceutical and Medical Device Act.

Background: The recommendation to limit dietary saturated fat intake is primarily drawn from observational studies rather than randomized controlled trials of cardiovascular disease prevention. Thus, we aimed to investigate the efficacy of saturated fat reduction in preventing mortality and cardiovascular diseases.

Methods: In this systematic review and meta-analysis of randomized controlled trials, Cochrane CENTRAL, PubMed, and Ichu-shi databases were searched for articles up to April 2023. Randomized controlled trials on saturated fat reduction to prevent cardiovascular diseases were selected. Cardiovascular and all-cause mortality and cardiovascular outcomes were evaluated. Changes in electrocardiography or coronary angiography findings were excluded because they could be evaluated arbitrarily. Two or more reviewers independently extracted and assessed the data. A random-effects meta-analysis was performed.

Results: Nine eligible trials with 13,532 participants were identified (2 were primary and 7 were secondary prevention studies).No significant differences in cardiovascular mortality (relative risk [RR] = 0.94, 95% confidence interval [CI]: 0.75-1.19), all-cause mortality (RR = 1.01, 95% CI: 0.89-1.14), myocardial infarction (RR = 0.85, 95% CI: 0.71-1.02), and coronary artery events (RR = 0.85, 95% CI: 0.65-1.11) were observed between the intervention and control groups. However, owing to limited reported cases, the impact of stroke could not be evaluated.

Conclusions: The findings indicate that a reduction in saturated fats cannot be recommended at present to prevent cardiovascular diseases and mortality. Clinical trials are needed to evaluate the effects of saturated fat reduction under the best possible medical care, including statin administration.

Systematic review registration number: This systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (CRD42023428498).

Introduction: Administrative claims data are used in clinical studies. However, individuals insured by different insurance systems have different backgrounds, ages, and disease prevalences. This study aimed to examine the crude and adjusted prevalence of diseases between employee and nonemployee health insurance in Japan.

Methods: We conducted a cross-sectional study using the DeSC database, an administrative claims database covering multiple insurers. We calculated the prevalence of 10 disease categories and 6 specific cancers with and without adjustments for age and sex and compared them between the employee (Kempo) and nonemployee (Kokuho) insurance systems.

Results: We identified 740,217 and 3,312,042 individuals covered by Kempo and Kokuho, respectively. The Kokuho group showed a higher crude prevalence of malignancies, endocrinological diseases, mental disorders, neurological diseases, cardiovascular diseases, and kidney or genitourinary diseases. The adjusted prevalence differed in mental disorders (7.2% vs. 10.6%), neurological diseases (10.5% vs. 14.0%), and gastrointestinal diseases (50.1% vs. 34.1%) between the Kempo and Kokuho groups.

Conclusions: While using administrative claims data, researchers should consider differences in patient backgrounds and disease prevalence among insurance providers.

Introduction: Acute ischemic stroke (AIS) can lead to sequelae or death if not treated promptly. Patients residing in areas with limited acute care access may not receive prompt treatment; however, the association between accessibility to acute care and discharge outcomes in patients with AIS remains controversial. This study aimed to clarify the association between acute care density index (ACDI) and home-to-hospital distance and in-hospital mortality in patients with AIS.

Methods: Using the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination database, we examined 525,689 patients (from April 2015 to March 2020). Hospital accessibility was assessed using ACDI and home-to-hospital distance. The patient residences were classified as urban, rural, or depopulated.

Results: In urban areas, ACDI was associated with in-hospital mortality, with adjusted odds ratios for Q2, Q3, and Q4 compared with Q1 of 1.16 (95% confidence interval: 1.02-1.31), 1.23 (1.10-1.39), and 1.35 (1.19-1.53), respectively. Similar trends were observed in rural areas. In depopulated areas, home-to-hospital distance exceeding the median was associated with a reduction in in-hospital mortality, with adjusted odds ratios for Q3 and Q4 compared with Q1 of 0.84 (0.74-0.95) and 0.78 (0.68-0.89), respectively.

Conclusions: A lower ACDI was associated with higher in-hospital mortality in both urban and rural areas, whereas longer home-to-hospital distance was not necessarily associated with higher in-hospital mortality.

Introduction: Chagas disease is one of the most critical of the neglected tropical diseases in Latin America where it poses a serious public health issue. However, the current burden of vectorial transmission from natural reservoirs to humans is unclear. This study aimed to clarify the active mode of transmission to humans disentangled from the feeding pattern of Triatoma dimidiata (T. dimidiata) infected by Trypanosoma cruzi (T. cruzi).

Methods: A total of 1,376 T. dimidiata specimens were collected across the 14 departments of El Salvador. From these specimens, 135 midgut samples from 37 households in eight departments were positive for T. cruzi (n = 135/1,376; 9.8% [95% confidential interval (CI): 8.35%-11.5%]). Using a universal vertebrate primer, vertebrate blood sources were positively identified by next-generation sequence analysis of deoxyribonucleic acid (DNA) extracted from the midgut contents of T. dimidiata.

Results: A total of 13 vertebrates were detected as blood sources; humans, and five domestic, three synanthropic, and four sylvatic species. Triatomines identified as having fed on human blood accounted for approximately 67% (n = 90/135 [95% CI: 58.3%-74.1%]) of the samples analyzed.

Conclusions: In this study, a holistic understanding of the feeding patterns of T. cruzi-positive T. dimidiata in El Salvador is dated. The detection of human DNA in the midgut contents of T. dimidiata indicated the possibility of active vectorial transmission to humans.

Introduction: Loneliness is a major factor hindering the health of migrants. There is concern that social changes due to the COVID-19 pandemic, in addition to the acculturation gap with their host country, exacerbated loneliness among Vietnamese migrants in Japan. Therefore, this study aimed to clarify the prevalence of loneliness and to evaluate the relationship with depressive and anxiety symptoms among Vietnamese migrants in Japan.

Methods: We used a cross-sectional study design with a self-administered questionnaire. The data were collected from May 2 to June 6, 2022. The target population for this study was Vietnamese migrants living in Japan, 213 of whom were included in the analysis. The questionnaire consisted of items regarding participants' characteristics, socioeconomic status, social support, Patient Health Questionnaire-9 scores, Generalized Anxiety Disorder-7 scores, and University of California Los Angeles 3-Item Loneliness Scale scores. Logistic regression analysis was performed with depressive and anxiety symptoms as dependent variables and loneliness and other socioeconomic factors as independent variables.

Results: The mean age of the participants was 26.8 ± 4.4 years. The study included 112 men (52.6%) and 101 women (47.4%). Their mean years of residence in Japan was 4.4 ± 2.5 years. The mean score on the University of California Los Angeles 3-Item Loneliness Scale was 7.2 ± 2.4. Multivariate logistic regression analysis revealed that depressive symptoms were associated with loneliness (odds ratio [OR]: 1.797; 95% confidence interval [CI]: 1.434-2.251). Similarly, factors associated with anxiety disorders included loneliness (OR: 2.051; 95% CI: 0.204-1.750).

Conclusions: Loneliness is a significant factor contributing to depressive and anxiety symptoms among Vietnamese migrants in Japan. Therefore, reducing loneliness is essential to improving the mental health and overall well-being of the rapidly growing Vietnamese migrant population.

Introduction: Obesity affects over 2.5 billion adults globally in 2022, posing a significant public health challenge. In Japan, obesity, defined as a body mass index ≥25 kg/m², impacted 33.0% of men and 22.3% of women in 2020. Despite this, over 25% of Japanese adults report no intention to improve health habits.

The Health Interest Scale (HIS) assesses health-related attitudes across three dimensions: health consciousness, health motivation, and health value. Although overall HIS scores are associated with health outcomes, the specific roles of these dimensions in obesity risk are unclear. This study examines the associations between each HIS dimension and obesity risk among Japanese corporate employees, supporting targeted interventions for sedentary, working-age populations.

Methods: This cross-sectional study analyzed data from 2,260 employees of information technology-related companies in Japan, collected via health checkups and self-administered surveys in 2023. HIS scores (range: 0-36) were used as continuous variables. Logistic regression assessed associations between HIS subscale scores and obesity status, adjusting for demographic, occupational, and lifestyle factors and obesity-related diseases.

Results: Higher scores on each HIS dimension were associated with lower obesity odds. Adjusted odds ratios per one-point increase were: health consciousness, 0.84 (95% confidence interval: 0.81-0.88); health value, 0.85 (0.81-0.89); and health motivation, 0.91 (0.87-0.95). Male sex, short sleep (<7 hours), and sedentary occupations were associated with increased obesity odds (all p < 0.001). The associations remained significant after adjustment for obesity-related diseases. Additionally, stronger associations were observed among participants with obesity-related diseases in univariate analysis.

Conclusions: This study identified significant associations between the three HIS dimensions and obesity risk, which remained robust after adjusting for obesity-related diseases. Stronger associations were observed across all HIS dimensions in participants with obesity-related diseases. These findings underscore the importance of tailored interventions targeting HIS dimensions, particularly health consciousness and health value, to reduce obesity risk in sedentary, working-age populations.

Introduction: As artificial intelligence (AI) continues to proliferate, it becomes imperative that medical students are not only instructed in the use of AI but also afforded regular opportunities to interact with it throughout their medical education. In 2023 and 2024, an art-based reflective reports assignment was implemented among new-entry students of the medical program at a university in Japan. The assignment required students to use generative AI within their submissions. The objective of this study was to assess the perceptions of these students regarding the use of generative AI in their reflective reports over the course of two academic years.

Methods: First-year medical students were tasked with submitting an art-based reflective report about their experiences during the community-based inquiry learning session. The assignment was a component of their reflective competencies assessment. We conducted a survey of the 2023 and 2024 student cohorts and examined their perceptions of using generative AI using a five-point Likert scale. We compared the survey responses of the two cohorts using the t-test.

Results: The participants exhibited a notably higher mean score for positive perceptions toward generative AI in 2024 compared with 2023 (3.8 versus 2.9 points; p < 0.01). In addition, the proportion of participants who expressed a preference for using generative AI was significantly higher in 2024 than in 2023 (32.0% versus 17.4%; p = 0.02).

Conclusions: A substantial and rapid increase has been observed in the proportion of medical students indicating a preference for using generative AI. The joint adoption of generative AI by medical students and faculties signifies a significant and urgently required development in AI use within medical education.

Introduction: The Japanese Society of Gout, Uric, and Nucleic Acid developed the Japanese Guideline for Management of Hyperuricemia and Gout (JGMHG) third edition, which contains seven clinical questions (CQs) and corresponding recommendations. Questionnaire surveys were conducted to clarify how recommendations regarding CQs influence decision-making in clinical practice.

Methods: The surveillances were conducted twice in 2018, just after the publication of JGMHG, and in 2020, 2 years later. The participants were members of the Japanese Society of Gout, Uric, and Nucleic Acid. While the 2018 surveys contained questionnaires on the recommendations of seven CQs as well as three questionnaires on the status of their use, the 2020 surveys contained those regarding their recommendations of seven CQs and seven questionnaires on the status of their use. The answers from 74 (response rate: 16%) and 61 (response rate: 14%) participants in 2018 and 2020, respectively, were analyzed using the chi-square test or Fisher's exact test.

Results: The proportion of respondents in 2020 who agreed to reduce serum uric acid levels below 6 mg/dL in gout patients with tophi significantly increased compared to 2018. The agreement in 2020 with the long-term use of colchicine to reduce the recurrence of gout flares when initiating urate-lowering agents (ULAs) significantly increased compared to 2018. There were no significant differences between 2018 and 2020 in clinicians' attitudes toward support for the third JGMHG in daily practice, support for the use of recommendations toward each CQ, or support for finding themes for research or important clinical issues.

Conclusions: The third JGMHG plays an important role in popularizing recommendations for serum uric acid levels in patients with tophi and the long-term use of colchicine for prophylaxis of gout flares when initiating ULA, although it did not influence the distribution of responses regarding clinicians' attitudes toward its support.

Introduction: Although the importance of home blood pressure (BP) management has been widely reported, the achievement rate of home BP targets remains low in Japan. Sacubitril/valsartan is a novel antihypertensive agent with potent antihypertensive effects. Despite its theoretical advantages, the real-world clinical application of sacubitril/valsartan in optimizing home BP management remains underexplored. The aim of this study was to evaluate the effect of switching from azilsartan treatment to sacubitril/valsartan treatment on the achievement of home BP targets and to refine hypertension management strategies in practical clinical settings.

Methods: A cohort of 55 patients, with a mean morning home systolic BP of 135 mmHg or more was enrolled for an 8-week treatment phase with azilsartan and calcium-channel blockers. Morning BP, pulse rate (PR), estimated glomerular filtration rate, and B-type natriuretic peptide, serum potassium, serum uric acid (UA), and hemoglobin A1c levels were assessed at baseline and then at 8, 24, and 48 weeks after switching from 20 mg azilsartan to 200 mg sacubitril/valsartan.

Results: At 48 weeks after switching to sacubitril/valsartan, there was a 60% increase in the rate of attainment of home systolic BP targets. Sacubitril/valsartan significantly reduced the mean systolic BP (from 143.6 ± 7.0 mmHg to 131.4 ± 8.7 mmHg), diastolic BP (from 86.9 ± 12.3 mmHg to 80.2 ± 10.7 mmHg), PR (from 74.8 ± 11.0 bpm to 72.1 ± 10.1 bpm), and serum UA (from 5.9 ± 1.1 mg/dL to 5.5 ± 0.9 mg/dL) within the first 8 weeks (all p < 0.01). These effects were maintained for 48 weeks.

Conclusions: The switch from azilsartan to sacubitril/valsartan treatment resulted in a significant improvement in the achievement of home BP targets, which is consistent with our goal of refining hypertension management strategies in practical clinical settings.

Introduction: Luminal breast cancer is the most common breast cancer subtype. Although its prognosis can be good, this type of breast cancer is characterized by a high incidence of late recurrence. However, to the best of our knowledge, there are no publications showing prognostic value regarding the invasive-disease-free survival (IDFS) and distant relapse-free survival in this group in clinical practice. Therefore, this study examined the clinical data and prognosis of patients participating in the MonarchE trial.

Methods: This study included patients who underwent surgery at Tokyo Metropolitan Komagome Hospital and whose corresponding prognosis to the Monarch E trial could be followed up.

Results: The total number of participants was 152, of whom 104 (68%) were treated with chemotherapy. Seventy-five patients (49%) were postmenopausal. The IDFS after 5 years was 85.0%. Although IDFS did not differ in terms of the menstrual status, premenopausal patients tended to receive a higher proportion of tamoxifen, and there was a greater number of patients treated with chemotherapy. However, neither chemotherapy nor menstrual statuses were found to affect the IDFS incidence.

Conclusions: Real clinical data applicable to the MonarchE study were examined. Our univariate analysis revealed that there were no factors affecting IDFS.

Introduction: Lifestyle factors such as physical and cognitively stimulating activities may protect against various diseases. However, only a few simple and validated questionnaires assess the lifestyle factors in Japan. Thus, we aimed to create Japanese versions of such questionnaires for assessing physical and cognitively stimulating activities. This study examined their inter-rater reliability and test-retest reproducibility.

Methods: We developed a Japanese version of questionnaires by translating the English questionnaire that assesses the frequency of several physical and cognitively stimulating activities. Additionally, the Japanese version assesses the duration of engagement in physical activities, and we have added mental activities such as meditation and Zen practice. The inter-rater reliability and test-retest reproducibility of evaluating the frequency, duration, frequency × duration of each physical activity, and frequency of each cognitively stimulating activity were tested in healthy volunteers.

Results: The study included 48 participants aged 25-67 years. We observed good inter-rater reliability and test-retest reproducibility for the physical and cognitively stimulating activity questionnaires. As a pilot approach, we calculated the Total Physical Activity Score (metabolic equivalents·min/week) with an intraclass correlation coefficient (ICC) (2,1) of 0.818 (95% confidence interval, 0.698-0.894), indicating good test-retest reproducibility.

Conclusions: The Japanese versions of questionnaires used to assess the frequency and duration of physical and cognitively stimulating activities generally have good inter-rater reliability and test-retest reproducibility. While introducing the duration of engagement might enable the estimation of the Total Physical Activity Score, further validation using objective measures of activities and other self-reported physical activity questionnaires is necessary, which is a limitation of this study.

Introduction: Because regional physician maldistribution is considered a potential contributor to disparities in healthcare outcomes, several countries regulate the number of physicians and specialists per region to ameliorate health disparities. However, the association between regional physician maldistribution and specific outcomes, such as out-of-hospital cardiac arrest (OHCA) at the regional level, remains unclear. This study aims to evaluate the association between regional physician and specialist maldistribution and OHCA outcomes.

Methods: This ecological study used 12 years of longitudinal public open datasets in Japan. We examined the disparity trends of indices of physician and specialist (emergency physicians, cardiologists, and cardiac surgeons) distribution using the Gini index. We also examined the physician uneven distribution index, a newly introduced policy index incorporating local demand and supply of medical services. Next, we analyzed the association between these distributions and OHCA-related outcomes (30-day survival rate and 30-day favorable neurological outcome).

Results: The overall number of physicians and each specialist steadily increased throughout all regions and the observation period, but the trends in the regional distribution of specialists for each region were not always synchronized with the distribution of overall physicians. Although the disparity within each index has gradually decreased, the disparity of specialists remained high compared with overall physicians. Moreover, regional physician distributions, which showed the lowest level of disparity across regions, were consistently associated with OHCA-related outcomes, whereas the regional disparity of specialists, which consistently exhibited a higher level of disparity, was not associated with the outcomes.

Conclusions: Paradoxically, the unevenly distributed specialist distribution indices did not reflect their relevant outcomes, despite their direct involvement in the specific outcomes. Therefore, our findings call into question the validity of policies aimed at correcting the total number of physicians without considering the impact of specialists on healthcare outcomes.

Introduction: Sarcopenic obesity substantially affects the recovery of physical function in patients with stroke. However, few studies have investigated the relationship between changes in skeletal muscle mass (SMM) and skeletal muscle quality (SMQ) and sarcopenic obesity diagnosed using the Japanese Working Group on Sarcopenic Obesity (JWGS) diagnostic criteria in patients with stroke who undergo rehabilitation. Therefore, this study aimed to investigate the relationship between sarcopenic obesity and changes in SMM and SMQ in patients with stroke who undergo rehabilitation.

Methods: Patients with stroke admitted to a rehabilitation ward in a single center in Japan were enrolled in this retrospective cohort study. The inclusion criteria were age 40-75 years and hospitalization for rehabilitation therapy due to stroke. The exclusion criteria were length of hospital stay <14 days and missing clinical data. Data were collected from medical records. Classification of sarcopenic obesity was based on the JWGS diagnostic criteria. The outcomes were the change in SMM and phase angle (PhA) from admission to discharge. Multiple regression analysis was used to investigate the relationship between sarcopenic obesity and changes in SMM and PhA after adjustment for confounding factors.

Results: A total of 173 patients were analyzed. 8 patients (3 male and 5 female) were diagnosed with sarcopenic obesity using the JWGS criteria. Multiple regression analysis revealed that sarcopenic obesity was negatively associated with changes in SMM (β: −0.281, 95% confidence interval [CI]: −0.449 to −0.113, p < 0.001) and PhA (β: −0.189, 95% CI: −0.367 to −0.010, p = 0.038).

Conclusions: Sarcopenic obesity is negatively associated with changes in SMM and SMQ in patients with stroke who undergo rehabilitation, highlighting the importance of evaluating sarcopenic obesity in patients with stroke from an early stage.

Introduction: We examined the clinical factors associated with a decrease in weight induced by weekly semaglutide in patients with type 2 diabetes mellitus (T2DM).

Methods: Patients with T2DM who visited the Diabetes Care Center of Jinnouchi Hospital between June 2020 and October 2023 and were treated with semaglutide, 1.0 mg weekly, in addition to their ongoing medications were retrospectively registered. We measured body weight both before weekly administration of 1.0 mg semaglutide and 180 days after treatment and calculated the change in weight.

Results: A total of 96 patients with T2DM were enrolled, with a mean body weight of 87.2 ± 17.1 kg and mean HbA1c of 7.3 ± 1.7% at baseline. The greater response group, defined as having 1.0 mg weekly semaglutide treatment-related weight reduction of more than 7.0%, comprised 23 patients (24.0%). Weekly 1.0 mg semaglutide treatment for 180 days significantly reduced body weight (−3.1 ± 4.8 kg, p < 0.001) and glycated hemoglobin (−0.39% ± 1.23%, p = 0.003). Multivariable logistic regression analysis found that pretreatment high-density lipoprotein (HDL) -cholesterol levels per 1.0 mg/dL (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.01-1.09, p = 0.02) were independently and significantly associated with greater weight reduction after weekly 1.0 mg semaglutide treatment, while a switch from other glucagon-like peptide-1 receptor agonists (OR 0.31; 95% CI 0.11-0.87; p = 0.03) was independently and significantly associated with lesser weight reduction after weekly 1.0 mg semaglutide treatment. In receiver-operator characteristic analysis, the cutoff value of pretreatment HDL-cholesterol levels for the presence of greater response in weight reduction was 46 mg/dL (sensitivity 61%, specificity 62%; p = 0.03).

Conclusions: Pretreatment HDL-cholesterol levels serve as important information for weekly treatment with 1.0 mg semaglutide in patients with T2DM and expectation of weight reduction.

Introduction: To increase the coverage rate and effectiveness, universal newborn hearing screening (NHS) should be financed by public funding rather than individuals. This study investigated the impact of the publicly-funded NHS program on the detection rate and the time to diagnosis and initiation of intervention for children with congenital hearing loss.

Methods: We compared two groups: one group included newborns born between April 2011 and March 2016 who either did not pass NHS or were referred due to high risk (Group 1); the other group included newborns born between April 2017 and March 2022 who met the same criteria (Group 2). The screening costs of Group 1 were covered by the guardians' payments, whereas those of Group 2 were covered by public funding. The NHS program in Group 2 exhibited improved screening methods, course, and timing of diagnostic hearing tests for referred newborns. The number of detected newborns with hearing impairment, the period between birth and the initial visit to a diagnostic institution, and the time to intervention were evaluated.

Results: Group 2 had more newborns with hearing loss (n = 51) than Group 1 (n = 32), representing a significant difference (p = 0.005). Group 2 had more children with bilateral hearing loss (n = 29) than Group 1 (n = 21), but the difference was not significant. The duration until the diagnostic test was significantly reduced in Group 2 (58 days in Group 1 vs. 35 days in Group 2). The duration of intervention also was significantly reduced in Group 2 (147 days vs. 99 days).

Conclusions: The improved program based on public funding achieved an increased number of detected infants with hearing loss. Additionally, it shortened the durations until the first diagnostic test to an institution and intervention. The new NHS program funded by local governments achieved improved effectiveness by unifying the screening method, the course of diagnostic hearing examination, and the follow-up.

Introduction: Many treatments for patients with metabolic dysfunction-associated steatohepatitis (MASH) have been proposed; however, most studies showed the results for a single medication and a short duration of treatment. The long-term outcomes of the multidrug therapies remain indeterminate. We conducted a study to investigate the usefulness of multidrug combination therapy for every kind of MASH patient and the differences between treatment-sensitive and treatment-resistant patients.

Methods: Fifty-one patients (middle-aged, in their 40s to 60s, metabolic generation) with MASH-determined fibrosis staging were enrolled. Primary treatment (weight control and medication of vitamin E and sodium-glucose cotransporter 2 inhibitor (SGLT2i) ) was done and then pemafibrate treatment was added.

Results: Regarding responses to the step-by-step multidrug therapy, patients with MASH were divided into 3 groups, with use of 3 markers-alanine aminotransferase (ALT) (hepatitis), elasticity value (E value, liver stiffness measurement) (hepatitis/fibrosis), and type IV collagen (fibrosis); group 1: sensitive to primary treatment (n = 35), group 2: resistant to primary treatment and sensitive to pemafibrate treatment (n = 11), and group 3: resistant to both treatments (n = 5).

To determine the parameters related to treatment resistance, the baseline levels of parameters_-obesity (body mass index), metabolic factor (visceral fat, controlled attenuation parameter), diabetes mellitus (DM) (glycated hemoglobulin (HbA1_c), fasting immunoreactive insulin), lipid metabolism (triglyceride), and hepatitis (ALT) -were compared between treatment-sensitive group 1+group 2 and treatment-resistant group 3. However, none of them had differences statistically. The same analysis showed that type IV collagen, E value, FIB-4 index (age (year) x AST (IU/L) /platelet count (10⁴/L) x ALT (IU/L) ^1/2), and MASH fibrosis had differences statistically.

Conclusions: The most effective treatment for patients with MASH could not be determined, according to the baseline levels of characteristics; however, weight control and step-by-step multidrug therapies made it possible to stabilize more than 90% of patient conditions and to solve MASH without worsening fibrosis. Since high levels of liver fibrosis-related markers affected the treatment resistance, MASH treatments should be started in an early stage while the levels of each marker are still low; type IV collagen <5.3 ng/mL, E value <13.7 kPa, FIB-4 index <1.89 and MASH fibrosis stage 2 or less.

Introduction: Skeletal muscle mass and function are crucial for assessing physical frailty, sarcopenia, and cachexia, which significantly impact the prognosis of geriatric patients with heart failure (HF). Ultrasound-based assessment of skeletal muscles offers a non-invasive, real-time alternative to traditional methods. The compariSON of various methods In evaluatIon of sarCopenia in patients with Heart Failure study (SONIC-HF) aimed to evaluate the feasibility and prognostic impact of ultrasound-based muscle assessment in geriatric patients with HF.

Methods: This multicenter, prospective cohort study enrolled patients with HF aged ≥65 years who could ambulate independently at discharge. Certified observers assessed muscle thickness (biceps, quadriceps, rectus femoris, and diaphragm) using ultrasound at rest and during contraction. The primary endpoint was all-cause mortality. Secondary endpoints included HF hospitalization, unplanned hospital visits, and cardiovascular and non-cardiovascular mortality.

Results: Of the 692 enrolled patients (median age 81 [interquartile range 74-86] years, 57.6% women, left ventricular ejection fraction 45% [32%-60%]), ultrasound-based muscle assessments were completed in 606 patients. Interobserver reliability was excellent (intraclass correlation coefficient 0.84-0.99). Median muscle thicknesses at rest and during contraction were: diaphragm 1.9 (1.6-2.3) mm and 2.9 (2.3-3.8) mm; biceps 19.6 (15.9-23.1) mm and 25.3 (21.3-29.5) mm; quadriceps 19.0 (15.0-23.5) mm and 24.8 (19.9-29.5) mm; rectus femoris 9.7 (7.1-12.3) mm and 12.1 (9.6-15.0) mm. The median follow-up time was 733.5 (438-882) days.

Conclusions: The SONIC-HF registry will provide valuable insights into the feasibility and prognostic implications of ultrasound-based muscle assessment in geriatric patients with HF.

Introduction: Bloodstream infections (BSIs) are a major concern in pediatric patients with cancer, especially during episodes of febrile neutropenia (FN). In this study, we aimed to evaluate the incidence of BSI across various pediatric malignancies and identify cancer subtypes associated with a heightened risk of BSI.

Methods: This single-center, retrospective cohort study analyzed the electronic medical records of pediatric patients with cancer treated between April 2012 and March 2023. Eligible patients included those diagnosed with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), lymphoma, brain tumors, and solid tumors. For each chemotherapy course, we assessed BSI incidence and FN episodes.

Results: This study included 152 pediatric patients who underwent 829 chemotherapy courses. The cohort comprised 21 patients with AML, 52 with ALL, 10 with lymphoma, 26 with brain tumors, and 43 with solid tumors. Compared to other cancer types, the AML group exhibited the highest proportion of BSI across all chemotherapy courses (17% vs. 4%-7%). During FN episodes, the AML cohort had a significantly higher BSI incidence (22%) than other groups (7%-13%). Notably, chemotherapy courses involving high-dose cytarabine (HD-CA) had a substantially higher BSI incidence (30%) among the patients with AML than courses without HD-CA (2%).

Conclusions: Patients with AML have the highest risk of BSIs in pediatric malignancies, particularly during FN episodes. In addition, our findings highlight an association between BSIs and HD-CA use in patients with AML.

Introduction: Utilizing a nationwide inpatient database in Japan, we aimed to develop a novel comorbidity score for pediatric patients to predict in-hospital mortality-the Children Comorbidity Score (CCS) -based on the International Classification of Diseases, 10th Revision (ICD-10) codes.

Methods: We retrospectively analyzed pediatric patients hospitalized between 2010 and 2017 using the Japanese Diagnosis Procedure Combination database. Eighty percent of the data was used as a training set, where we applied Lasso regression to a model with 56 candidate comorbidity categories to predict in-hospital mortality. We employed the 1-standard-error rule in Lasso regression to derive a parsimonious model and forced the entry of 12 categories of pediatric Complex Chronic Conditions (CCC). Thus, we developed the CCS, an integer-based comorbidity score using the selected variables with nonzero coefficients. The remaining 20% of the data was used as the test set, where we evaluated the CCS's predictive performance using C-statistics, calibration, and decision curve analysis, comparing it with two other scores: a CCC-based score using ICD-10 codes and the Charlson Comorbidity Index (CCI).

Results: Among 1,968,960 pediatric patients, we observed 6,492 (0.33%) in-hospital mortalities. The developed integer-based CCS, utilizing 10 comorbidity categories via variable selection by Lasso regression, had better discrimination ability (C-statistics, 0.720 [95% confidence intervals (CI), 0.707-0.734]) than the CCC (0.649 [0.636-0.662]) and CCI (0.544 [0.533-0.555]). The superior discrimination of the CCS was consistent across all age categories, sexes, and body mass index categories. The CCS showed good calibration, with a calibration slope of 1.027 (95% CI, 0.981-1.073). Decision curve analysis indicated that the CCS provided the highest net benefit compared to either of the reference models.

Conclusions: The ICD-10-based CCS outperformed conventional comorbidity scores in predicting in-hospital mortality and would be useful in comorbidity assessment among pediatric inpatients.

The COVID-19 pandemic has profoundly transformed medical education, shaping students' career aspirations and impacting their mental well-being. A global survey among medical students conducted in 2023 revealed that over half of medical and nursing students are inclined toward nonclinical careers, while a substantial majority express concerns regarding their mental health. These insights underscore the urgent need to broaden educational trajectories beyond direct patient care and prioritize the psychosocial welfare of students.

We explore the implications of these shifts, emphasizing the rising interest in public health and research as viable alternative career paths. Medical schools in Japan are increasingly introducing healthcare policy and administration courses, offering students opportunities to assume public health and research roles. Moreover, medical education must adapt to mitigate the pressures associated with future workloads and extensive academic demands by integrating digital technologies, such as artificial intelligence and virtual reality, into the curriculum.

Furthermore, enhancing career guidance and expanding international exchange programs will cultivate a more versatile talent pool and equip students for diverse career trajectories in healthcare. By accommodating clinical and nonclinical interests and addressing student mental health, the future of medical education can elevate healthcare quality and advancing public health outcomes. Ultimately, a holistic and multifaceted approach to medical education is crucial for nurturing professionals adept at confronting the challenges of future pandemics and pioneering innovations in healthcare.

Although Japan recorded the world's highest rate of COVID-19 messenger ribonucleic acid (mRNA) vaccination doses per capita, COVID-19 cases and deaths exploded after the emergence of the Omicron variant, followed by a significant increase in excess deaths in 2022 and 2023. Although several hypotheses have been proposed to explain these phenomena, the truth remains to be established because sufficient studies and data disclosures have not been conducted to adequately investigate the possible contribution of mRNA vaccines. The causes of the excess deaths from not only COVID-19 but also other factors after repeated mRNA vaccinations must be elucidated, given this could provide valuable information to help combat future infectious disease outbreaks.

Kaposi's sarcoma (KS) is a chronic, multifocal lymphoangioproliferative tumor that occurs mainly in older individuals in the Mediterranean region. KS is often observed as a malignant tumor in patients with acquired immunodeficiency syndrome, and classic KS is rare. An 82-year-old man was referred to our department with bilateral lower-leg edema with purpura and small nodules. When the patient was in his mid-50s, edema with purpura appeared in his lower extremities without any specific trigger. Eight years earlier (in his mid-70s), the purpura lesions gradually turned nodular. A similar skin rash appeared on the forearms and back of the hands two years earlier. Physical examination revealed diffuse brown pitting edema over the entirety of the lower extremities and extending from the dorsum of the bilateral hands to the elbows. Multiple purple-red, elastic, hard nodules ranging from a few millimeters to about 1 cm were localized and fused over the edema. Histological examination of the forearm nodule revealed proliferation of collagen fibers and cellular infiltration in the dermis. The intricately proliferating cells in the dermis were spindle-shaped with round nuclei. Immunohistochemical staining revealed spindle-shaped cells positive for CD31, CD34, and D2-40. These cells were positive for human herpesvirus (HHV) -8 and negative for human immunodeficiency virus (HIV) antigens and antibodies. He was diagnosed with classic KS. We proposed chemotherapy, but he refused to receive any treatment. Our patient did not receive any immunosuppressive therapy, and the HIV test result was negative. Therefore, immunosuppressive status may not be involved in the development of KS in our patient. He had opportunities to consult dermatologists but was never diagnosed with KS. A skin biopsy helps diagnose KS; thus it should be considered when a patient experiences long-standing, slowly progressive, unexplained leg edema accompanied by a skin rash.

Superior mesenteric vein thrombosis (SMVT) is a rare condition characterized by thrombus formation in the superior mesenteric vein. SMVT is generally caused by abnormal blood coagulation, inflammation, or surgical interventions. This condition can lead to intestinal ischemia and necrosis due to blood flow stasis.

We report the case of a man in his 60s who presented with abdominal pain and vomiting. Abdominal contrast-enhanced computed tomography shows a thrombus in the portal and superior mesenteric veins, and reduced contrast in the small intestine. Approximately 1.5 m of the necrotic jejunum was resected, an open management approach was undertaken, and anticoagulation with continuous intravenous heparin was initiated. On the fourth day of treatment, a thrombus was retrieved from the superior mesenteric vein within the main trunk of the portal vein using a stent clot retrieval device. The patient's bowel edema improved soon thereafter.

This case of SMVT was successfully managed using a hybrid approach of bowel resection and transcatheter thrombus retrieval.

Porencephalic cysts are very rare in adults. Herein, we present a case of an 88-year-old man with a symptomatic expanding porencephalic cyst after intracerebral hematoma evacuation. He was admitted because of disturbed consciousness and right hemiparesis. A computed tomography (CT) showed a large subcortical hematoma in the left parietal lobe. Hematoma evacuation was performed, his consciousness level improved but gradually deteriorated. Follow-up CT revealed a new cystic lesion with perifocal edema at the hematoma site, with progressive expansion of the cyst. Cyst drainage and -peritoneal shunt placement were performed on postoperative day 14; consequently, his symptoms improved. Considerably, a porencephalic cyst have developed because the cerebrospinal fluid flowed into the closed hematoma cavity from the ventricle owing to the osmotic pressure difference between the ventricle and the hematoma cavity.