Teikyo University

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by pruritus, barrier dysfunction, and complex immune dysregulation. Phototherapy with narrow-band ultraviolet B (NB-UVB) or 308 nm excimer devices is clinically effective for AD, but the underlying mechanisms remain incompletely understood. In this study, we investigated the therapeutic effects of a 308-nm excimer lamp using a murine model of AD induced by topical application of the vitamin D3 analog MC903. C57BL/6 mice were treated with MC903 for 13 consecutive days, with or without irradiation by a 308-nm excimer lamp at 100 mJ/cm2 every other day. Clinical severity was assessed daily, and histological, immunohistochemical, and molecular analyses were performed on lesional skin. Excimer irradiation significantly alleviated MC903-induced dermatitis from days 4 to 12, with reduced clinical severity scores, epidermal thickness, and acanthosis compared with non-irradiated controls. Immunohistochemical analysis revealed a significant decrease in intraepidermal PGP9.5-positive nerve fibers in irradiated mice, suggesting that excimer therapy attenuates pruritus through neuroimmune modulation. Furthermore, excimer irradiation increased dermal infiltration of Foxp3-positive regulatory T cells and decreased plasma IgE levels, although no significant upregulation of IL-10 mRNA was detected. Importantly, quantitative PCR demonstrated that excimer irradiation reduced thymic stromal lymphopoietin (TSLP) expression in lesional skin, while levels of other Th2-related cytokines such as IL-4 and IL-13 remained unchanged. These findings indicate that 308-nm excimer lamp therapy ameliorates AD-like dermatitis through dual mechanisms: suppression of intraepidermal nerve fibers and downregulation of epithelial-derived TSLP, together with enhanced regulatory T-cell infiltration. This study provides new mechanistic insights into the immunological and neurocutaneous effects of excimer phototherapy, supporting its clinical use in AD and potentially other inflammatory skin diseases.

Since comprehensive data on the pathogenic variants of ABCG5 and ABCG8 and clinical features in sitosterolemia remain limited, we aimed to compile a catalog through an extensive literature search of case reports from 2002 to 2024, as well as an evaluation of variants reported in review articles. We compiled 155 cases of sitosterolemia from 133 families with nonsynonymous variants in ABCG5 and ABCG8, along with data on clinical information from case reports. Pathogenic variants were defined either as 1) protein-truncating variants, 2) classified as pathogenic or likely pathogenic variants according to the ACMG guidelines, or 3) serum sitosterol level of the case was measured at ≥ 1 mg/dL. Xanthoma was observed in 69.2% of patients, ischemic heart disease in 14.2%, and hematologic abnormalities in 57.9%. Fifty-three variants in ABCG5 and 52 in ABCG8 were evaluated for their pathogenicity, in which 33 in ABCG5 and 29 in ABCG8 were protein-truncating variants. Additionally, based on the ACMG criteria and serum sitosterol levels, 50 variants in ABCG5 and 51 variants in ABCG8 were finally classified as pathogenic. Among them, the frequently observed R446X and R389H in ABCG5 were highly prevalent in East Asians, while W361X and S107X in ABCG8 were predominantly found in Europeans. We provided the largest catalog of clinical features and pathogenic variants of ABCG5 and ABCG8 in the world. This study may help clarify the pathogenicity of variants in ABCG5 and ABCG8 and provide a valuable reference for the genetic diagnosis of sitosterolemia.

BackgroundThis study aimed to evaluate the prevalence and potential associations among lateral ankle sprains (LAS), recurrent LAS, chronic ankle instability (CAI), and CAI by criteria for clinical practice (CAI-C). Chronic ankle instability by criteria for clinical practice is a condition that meets CAI inclusion criteria but also falls under the exclusion criteria defined by the International Ankle Consortium (IAC). Chronic ankle instability by criteria for clinical practice represents a broader clinical definition of CAI.MethodsThis study was a descriptive epidemiological study of the prevalence of LAS, recurrent LAS, CAI, and CAI-C in sports disciplines. A total of 2,175 athletes (1,522 males and 653 females) from 12 sports were surveyed using a structured questionnaire incorporating the Japanese version of the Identification of Functional Ankle Instability. Classification was based on criteria from the IAC.ResultsThe results showed that 52.9% of the participants experienced LAS, and 36.2% had a recurrence. Among those with LAS history, 68.5% had recurrent episodes. Chronic ankle instability was observed in 17.9% of athletes, and CAI-C was present in 32.6%, nearly 1.8 times more prevalent than typical CAI. In particular, the prevalence of CAI-C was more than twice that of CAI in rugby football, cheerleading, and soccer. Furthermore, 90.0% of recurrent LAS cases progressed to CAI-C. Chronic ankle instability was most prevalent in basketball and handball, whereas CAI-C was prevalent not only in these sports but also in soccer and judo, based on adjusted residuals ≥1.96.ConclusionsWe found that the number of participants with CAI-C differed from that of participants with CAI. This finding suggests that CAI may not reflect the entire clinical population with CAI conditions. Therefore, it has been suggested that it is also necessary to identify CAI-C in clinical practice. These findings underscore and support the need to consider tailored prevention programs and clinical attention to at-risk sports to reduce the long-term impact of ankle instability in athletes.Levels of Evidence:Prognostic, Level IV: case series.

Abstract Drug-induced liver injury (DILI) is an acute inflammatory liver disease caused not only by prescription and over-the-counter medications but also by health foods and dietary supplements. Typically, DILI patients recover once the causative substance is identified and discontinued. In contrast, autoimmune hepatitis (AIH) results from the immune-mediated destruction of hepatocytes due to a breakdown of self-tolerance mechanisms. Patients presenting with acute-onset AIH often lack characteristic clinical features, such as autoantibodies, and require prompt steroid treatment to prevent progression to liver failure. Liver biopsy currently remains the gold standard to differentiate acute DILI from AIH; however, general pathologists face significant diagnostic challenges due to overlapping histopathological features. This study integrates pathology expertise with deep learning-based artificial intelligence (AI) to differentiate DILI from AIH using histopathological images. Our AI model demonstrates promising classification accuracy (Accuracy 74%, AUC 0.81). This paper presents a detailed pathological analysis alongside AI methods, discusses the current model performance and limitations, and proposes directions for future improvements.

Hyalinizing clear cell carcinoma of lung is rare. In recent years, the increased numbers of case reports and its inclusion in the WHO 2021 classification have led to growing recognition of this tumor. However, it remains unclear whether there are associated underlying conditions, as histological observation around the tumor have not been documented in previous reports. We report a case of a bronchial hyalinizing clear cell carcinoma under suspicion of allergic bronchopulmonary aspergillosis (ABPA). At the distal side of tumor, we found eosinophil-rich mucoid impaction and eosinophilic pneumonia, and also a lesion with intermediate morphology between hyalinizing clear cell carcinoma and basal cells within bronchial inflammatory polyp-like tissue.

Central venous access is essential in perioperative management of major abdominal surgery. While centrally inserted central venous catheters (CVCs) are widely used, insertion-related mechanical complications remain a concern. Peripherally inserted central catheters (PICCs) may represent an alternative strategy, particularly when integrated into nurse-led task-sharing workflows. This study evaluated the feasibility and procedural outcomes of ultrasound-guided PICC placement during general anesthesia. This single-center retrospective observational study included 86 adult patients undergoing gastrointestinal surgery under general anesthesia who required central venous access between January 2023 and December 2025. Patients were divided into a PICC group (n = 41) and a CVC group (n = 45). The primary outcome was catheter placement time (minutes). Secondary outcomes included catheter dwell time (days), catheter-related bloodstream infection (CRBSI), and catheter occlusion with intraluminal thrombus. CRBSI was assessed in accordance with CDC guidance, and patients were followed until catheter removal. Baseline characteristics were comparable between groups. Catheter placement time was significantly shorter in the PICC group than in the CVC group (5.5 ± 3.1 vs. 7.0 ± 2.3 minutes, p = 0.013). Catheter dwell time was longer in the PICC group (7.1 ± 3.1 vs. 3.3 ± 1.7 days, p < 0.001). CRBSI incidence did not significantly differ between groups (2.4% vs. 8.9%, p = 0.363). Catheter occlusion with intraluminal thrombus occurred in one patient (2.4%) in the PICC group and in none in the CVC group. All catheter placements were successful (100% in both groups). Ultrasound-guided PICC placement during general anesthesia was associated with shorter catheter placement time and longer catheter duration than CVC placement in this retrospective cohort. Catheter-related complications were infrequent; however, definitive conclusions regarding comparative safety are limited by the observational design and low event counts. These findings support the feasibility of perioperative PICC use and suggest potential workflow implications within structured nurse-led task-sharing models. Further prospective multicenter studies incorporating direct operating room workflow metrics and catheter-day-based outcomes are warranted.

The role of transcatheter aortic valve replacement (TAVR) in nonagenarians remains uncertain, especially regarding long-term outcomes and prognostic factors. This study aimed to evaluate long-term outcomes of TAVR in nonagenarians, focusing on cause-specific mortality and the prognostic influence of frailty and malnutrition. We analyzed 4,623 patients who underwent transfemoral TAVR in a multicenter Japanese registry, including 700 aged ≥90 years. Outcomes were followed for 5 years. We analyzed all-cause mortality, cause-specific mortality, and the prognostic impact of the Clinical Frailty Scale and Geriatric Nutritional Risk Index. At 5 years, all-cause mortality was higher in patients aged ≥90 years than in those <90 years (53.2% vs37.0%, P < 0.001), primarily due to noncardiovascular deaths such as senility and infections (32.5% vs 19.9%; P < 0.001). Cardiovascular mortality was similar (20.3% vs 17.0%; P = 0.198). Multivariable analysis showed that age ≥90 years was not an independent predictor; frailty and malnutrition were the strongest prognostic factors. A Clinical Frailty Scale-Geriatric Nutritional Risk Index heatmap revealed marked heterogeneity, identifying subgroups of nonagenarians with preserved nutrition and low frailty who achieved favorable long-term survival. In this large multicenter registry, excess mortality in nonagenarians after TAVR was driven mainly by noncardiovascular causes. Frailty and malnutrition, rather than chronological age, were central determinants of long-term outcomes. These findings emphasize that TAVR candidacy in nonagenarians should be guided on geriatric assessment of frailty and nutrition to identify patients most likely to achieve meaningful survival while avoiding futile interventions.