JMA journal最新文献

Atherosclerosis, the leading cause of coronary artery disease, stroke, and peripheral arterial disease, is now recognized as a lipid-driven disease complicated by an immune response that plays a major role in its pathogenesis. The response-to-injury hypothesis proposed by Ross et al. laid the foundation for understanding atherosclerosis as a chronic inflammatory process, in which endothelial injury and lipid insudation trigger immune activation, smooth muscle cell proliferation, and plaque formation. Traditional approaches, such as immunohistochemistry, flow cytometry, and bulk RNA sequencing, have identified macrophages and T cells as the key immune players in plaques. However, these methods lack the resolution to differentiate among diverse immune cell states or to detect rare but functionally significant populations. Recent advances in single-cell and spatial transcriptomic technologies have revolutionized our understanding of atherosclerotic plaques. These methods have generated detailed cellular atlases in murine models and human atherosclerotic tissues, revealing previously unrecognized immune cell subsets and novel pathogenic pathways. Single-cell analyses have identified a heterogeneous spectrum of macrophages, including resident-like, inflammatory, and TREM2^high foamy subsets, in addition to a CD163⁺ macrophage subset, including the hemoglobin-stimulated macrophage [M(Hb)] phenotype. In parallel, functionally diverse T-cell subsets with specialized pro- and anti-inflammatory roles have also been characterized. Spatial transcriptomics has provided further insights into the anatomical organization of these immune populations within plaques, highlighting region-specific inflammatory niches and fibrous-cap dynamics. Furthermore, single-cell T-cell receptor sequencing has identified antigen-specific T-cell expansions, supporting the hypothesis that atherosclerosis exhibits autoimmune-like characteristics. These findings have major therapeutic implications. The selective targeting of specific types of pro-inflammatory macrophages and tailored immunomodulation of T-cell subsets may provide new strategies to stabilize plaques and other novel and targeted immunomodulatory approaches to prevent cardiovascular events. As single-cell and spatial technologies continue to evolve, they will further refine our ability to design precision immunotherapies for atherosclerosis by integrating classical inflammatory models with high-resolution molecular insights.

Introduction: Most rheumatic diseases are caused by a complex interplay of genetic, physical, and environmental factors. Large-scale disasters affect all of these factors; however, their impact on rheumatic diseases is unknown. We aimed to investigate changes in antirheumatic drug prescriptions among victims and non-victims after the 2018 Japan Flood: the second largest water-related disaster in Japan.

Methods: In this retrospective cohort study, we used data from the Japanese National Database of Health Insurance Claims, which included information on all drugs prescribed by physicians. We included all cases of prescription at medical institutions in disaster-stricken areas between July 2017 and June 2019. The newly initiated prescription of methotrexate (MTX, 2-mg tablets or capsules), which has been exclusively approved for rheumatoid arthritis, juvenile idiopathic arthritis, or psoriatic arthritis/psoriasis in Japan, and other antirheumatic drugs within the first year after the disaster were evaluated for government-certified disaster victims and non-victims. Baseline characteristics and MTX prescription status in the pre-disaster period were also assessed to compare the groups.

Results: In the pre-disaster period, no significant association was found between victim status and MTX prescription. The number of individuals who had not been prescribed MTX before the disaster was 4,973,401, including 31,006 victims. Among them, 14,908 (including 110 victims) had a history of MTX prescription after the disaster. In the MTX-naive group, new MTX prescriptions within one year after the disaster were significantly more frequent in victims than in non-victims (age- and sex-adjusted hazard ratio: 1.83; 95% confidence interval: 1.37-2.46). Similarly, a non-significant increase in prescriptions for conventional synthetic/biological disease-modifying antirheumatic drugs was observed.

Conclusions: Victims of the 2018 Japan Flood were more likely to be prescribed MTX for the first time.

This report highlights the successful integration of behavioral science-based interventions in the treatment of an 8-year-old girl with atopic dermatitis (AD) and behavioral problems, including tantrums. The patient, who had a history of poorly managed AD, presented with worsened eczema and sleep disturbances, in addition to increased tantrums, scratching, and reluctance to attend school. She was admitted for inpatient treatment, which included standard AD management and multidisciplinary care, focusing on proper skin care, diet, and lifestyle changes. Despite relief of her eczema, her problematic behaviors persisted, which worsened her condition. To address this, behavioral interventions were implemented. Anger management techniques were introduced, whereby the patient assessed her anger levels and used relaxation methods. She was taught alternative behaviors to manage the itching, such as applying topical treatments or interacting with her favorite stuffed animal. Her parents also received guidance on managing her behavior. Over her three-month hospitalization, her tantrums and problematic behaviors resolved, and her AD went into remission. Post-discharge, her eczema remained well controlled, and her behavior improved, with no recurrence of tantrums or other issues. This case illustrates the importance of combining pharmacological treatments with behavioral interventions in managing AD and associated psychosocial challenges. Behavioral science-based approaches can play a crucial role in alleviating behavioral issues linked to AD, such as anger and scratching, which can further exacerbate the condition. In this case, behavioral therapy effectively alleviated the patient's behavior problems and improved eczema control, underscoring the need for clinicians to be equipped to address both the physical and behavioral aspects of AD.

Introduction: Statins can treat dyslipidemia, but even if low-density lipoprotein decreases to target levels, high triglyceride (TG) levels may represent a residual risk. Therefore, we performed a crossover study comparing pemafibrate and omega-3-acid ethyl esters docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in patients with untreated hypertriglyceridemia.

Methods: Patients were randomized by the envelope method to pemafibrate or DHA+EPA for 6 months and then switched to the other medication for 6 months. The primary endpoint was TG level, and secondary endpoints were lipid markers, fatty acid 4-fractionation, kidney and liver markers, and the Fibrosis-4 index.

Results: In the 36 analyzed patients, pemafibrate showed a significantly greater decrease in TG (p < 0.001) and remnant-like particles cholesterol (p = 0.001) and a significantly greater increase in high-density lipoprotein (p < 0.001), but DHA+EPA showed a significantly greater improvement in fatty acid 4-fractionation (p < 0.001).

Conclusions: When combined with a statin, pemafibrate appears to have a stronger effect in lowering TG and remnant-like particles cholesterol but DHA+EPA appears to be more effective in terms of fatty acids. Pemafibrate may be an effective first choice for hypertriglyceridemia, and add-on DHA+EPA may be beneficial when pemafibrate is not sufficiently effective. Findings need to be confirmed in larger studies.

Introduction: This study aimed to examine the predictive factors and timing of delirium onset in hospitalized patients with heart failure, focusing on the impact of total anticholinergic load and other contributing variables.

Methods: The single-site retrospective cohort study included 694 patients hospitalized for heart failure and receiving treatment for hyperpolypharmacy between January 2015 and March 2023. The patients were categorized into delirium and non-delirium groups, with the delirium group further subdivided into early-onset (within 6 days) and late-onset (day 7 or later) subgroups. Logistic regression analyses were performed to identify significant factors associated with delirium onset.

Results: Compared with the non-delirium group, the delirium group (n = 54) showed a higher total anticholinergic load, malnutrition prevalence, and elevated N-terminal pro-brain natriuretic peptide levels. Early-onset delirium was associated with a higher total anticholinergic load and C-reactive protein levels, whereas late-onset delirium correlated with malnutrition. Hyperactive delirium was predominant in the early-onset group and the hypoactive or mixed subtypes in the late-onset.

Conclusions: Elevated anticholinergic loads and the presence of infection were primary contributors to early-onset delirium; malnutrition and the body mass index were critical for late-onset delirium. These findings emphasize the need for targeted preventive strategies based on delirium onset timing.

Introduction: Near-infrared photoimmunotherapy (NIR-PIT) has emerged as a promising treatment for unresectable locally advanced or recurrent head and neck cancer. This study aimed to identify potential predictors of NIR-PIT efficacy before treatment by focusing on blood biomarkers in addition to pathological findings, including epidermal growth factor receptor (EGFR) expression in tumors.

Methods: A retrospective analysis of the medical records of 10 patients with head and neck cancer, who exhibited confirmed EGFR expression and underwent NIR-PIT treatment at Akita University Hospital from December 2021 to April 2024, was conducted (13 cycles of NIR-PIT). EGFR expression, cluster of differentiation (CD)4/CD8 ratio, regulatory T cell (Treg) frequency, serum albumin, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-eosinophil ratio (NER) were calculated from the tumor tissue and blood collected immediately before treatment. Correlations of these factors with tumor response to NIR-PIT were determined.

Results: The objective response rate (ORR) was 61.5% and the disease control rate (DCR) was 100%. A statistically significant association was observed between the EGFR index and tumor response. No statistically significant correlation was found between other biomarkers (CD4/CD8 ratio, Treg frequency, serum albumin, NLR, NER) and tumor response.

Conclusions: These findings underscore the important role of EGFR expression in predicting the efficacy of NIR-PIT in the management of head and neck cancer, and highlight the significance of incorporating EGFR assessment in patient selection and optimized treatment strategies. Further studies are needed to elucidate the role that these other potential predictors, including tumor immune response markers, play in NIR-PIT outcomes.

Generative artificial intelligence (GenAI) is now widely used in medicine, including medical writing. Its merits and demerits have been discussed; however, such discussion has not been based on evidence-based medicine (EBM). Here, I focus primarily on GenAI use in medical writing, illustrating how it has already spread before its safety-especially long-term safety-has been confirmed by EBM. I therefore make several modest proposals. Assuming GenAI is a new drug, its use has not yet cleared even the first step of a phase I trial. Assuming it is a new procedure, it remains at the "experience" or "case report" phase. EBM requires the completion of phase I-III trials and randomized controlled trials or meta-analyses before any drug or procedure is confirmed safe and effective. Emergency evacuation can be applied for life-threatening medical conditions; however, it does not apply to "writing." Nevertheless, the current publication world has already gone far beyond: GenAI use is already considerable in medical publication. Thus, three propositions have been made. First, we must recognize that the use of GenAI for writing operates outside the usual EBM framework. Second, we should conduct trials, even if they are difficult and time-consuming, to evaluate the safety and effectiveness of GenAI in writing. Third, we should use GenAI in writing only modestly until safety is confirmed. What is true becomes evident long after, and thus, I believe that we should take a cautious stance toward GenAI use in writing. How cautious should be discussed widely. This viewpoint may contribute to the discussion of GenAI use more generally, beyond medical writing.

Introduction: Hearing loss is a public concern, considering its high prevalence and negative effects on older adults. Limited data on hearing loss are available from Japan, which has a high aging rate. Hearing loss generally begins bilaterally at high frequencies with age. This study aimed to describe the prevalence, age-standardized prevalence, and incidence rates of bilateral high-frequency hearing loss (HFHL), using data from Japan.

Methods: This descriptive study utilized Ningen Dock and regular health check-up examination data obtained from the Seirei Health Care Division from 2014 to 2020. The outcome was bilateral inaudibility of 40 dB at 4 kHz (bilateral HFHL). The prevalence in each age group in 2020, age-standardized prevalence from 2014 to 2020 using the direct method, and incidence rates (per 1,000 person-years) were calculated by sex.

Results: Most participants (60% male) underwent Ningen Dock. Each year, the number of participants was 55,000-62,500. The mean age of participants was in the early 50s. Both the prevalence and incidence rates of bilateral HFHL increased sharply from the 60s and were higher in males than in females across generations; the prevalence was < 4% in the early 50s, reaching 46.5% and 20.2% in males and females, respectively, in their 70s. Incidence rates were 10.8 and 2.1, respectively, in the 50s, increasing to 106.7 and 43.5, respectively, in the 80s. Age-standardized prevalence slightly decreased from 2014 to 2020 in both sexes.

Conclusions: Both the prevalence and incidence rates of bilateral HFHL increased dramatically from the 60s and were higher in males than in females across generations. Age-standardized prevalence slightly decreased during the study period. This study is valuable because of the limited number of studies on hearing loss in Japan. However, most participants were considered to have high socioeconomic status, and further research targeting Japanese individuals is warranted.