Aichi Medical University

Neuronal intranuclear inclusion disease (NIID) is an autosomal dominant inherited neurodegenerative disease caused by NOTCH2NLC GGC repeat expansions. A high-intensity signal in the corticomedullary junction (CMJ) on magnetic resonance (MR) diffusion-weighted imaging (DWI) is a well-known characteristic of NIID. However, because of its diverse clinical symptoms and frequent presence of cerebral white matter hyperintensity (WMH) lesions on MRI, patients with NIID may be suspected of having other leukoencephalopathies. The aim of the present study was to identify patients with NOTCH2NLC GGC repeat expansions among those with undiagnosed leukoencephalopathies, recruited from NOTCH3-negative cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)-suspected and GFAP-negative Alexander disease (AxD)-suspected patients. Among 459 NOTCH3-negative CADASIL-suspected patients, 18 (3.9%) showed NOTCH2NLC GGC repeat expansions; however, among 40 GFAP-negative AxD-suspected patients, none exhibited such repeat expansions. On comparing 17 patients with GGC repeat expansions, whose clinical information was available, with 179 CADASIL probands previously reported by us, the former showed significantly higher frequencies of seizure (23.5 vs. 6.9%, respectively), WMH in the corpus callosum (92.9 vs. 9.2%, respectively), paravermis (21.4 vs. 2.7%, respectively), and middle cerebellar peduncle (21.4 vs. 3.4%, respectively), and DWI high-intensity signals in CMJ (61.5 vs. 1.4%, respectively). In conclusion, not only DWI high-intensity signals in CMJ, but also the WMH distribution, particularly a high frequency in the corpus callosum, and presence of seizures are useful for detecting NIID in patients with undiagnosed leukoencephalopathies.

ABSTRACT A 59‐year‐old man presented with left upper abdominal pain. Contrast‐enhanced computed tomography suggested a duodenal intussusception and a mass with mixed fat and soft‐tissue density extending from the duodenal bulb to the descending duodenum. Esophagogastroduodenoscopy identified a giant pedunculated lesion originating from the posterior wall of the duodenal bulb with a focal depressed area and marked redness. Narrow‐band imaging showed no obvious epithelial neoplastic changes. An upper gastrointestinal series demonstrated an elevated lesion approximately 5 cm in size. Based on these findings, we suspected giant duodenal Brunner's gland hyperplasia. Endoscopic resection was performed under general anesthesia due to the risk of intussusception and potential malignant transformation. En bloc resection was achieved using a scissor‐type endoscopic device with traction, and the specimen was safely retrieved under laparoscopic assistance with gentle compression. Histopathological examination revealed lobulated proliferation of Brunner's glands with fibrous septa and adipose tissue in the submucosa, confirming duodenal Brunner's gland hyperplasia.

Background: Candidemia remains a life-threatening infection with high mortality despite advances in antifungal therapy. Malnutrition has been suggested as an important contributor to poor outcomes; however, the prognostic value of different nutritional assessment tools in candidemia has not been fully clarified. This study aimed to evaluate the impact of nutritional status on prognosis in patients with candidemia and to identify the most reliable nutritional assessment tool. Method: We conducted a retrospective cohort study of adult patients diagnosed with candidemia at a tertiary teaching hospital in Japan between 2014 and 2024. A total of 170 patients were included, with a mean age of 73 years. Nutritional status was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria and Controlling Nutritional Status (CONUT) score. The primary outcome was 30-day mortality. Results: According to the GLIM criteria, 72% of patients were classified as malnourished. The 30-day and in-hospital mortality rates were 35% and 44%, respectively. The CONUT score demonstrated good prognostic performance for 30-day mortality (Area under the Receiver operating characteristic 0.723, p < 0.001), with an optimal cut-off value of 12. Patients with higher CONUT scores had significantly shorter overall survival (Log-rank test p < 0.001). In multivariate analysis, a CONUT score ≥ 12, SOFA score ≥ 5, and the European Confederation of Medical Mycology Quality of Clinical Candidemia Management (EQUAL) Candida score ≥ 10 were independent predictors of 30-day mortality, whereas malnutrition defined by the GLIM criteria was not. Conclusions: The CONUT score is a useful prognostic indicator for short-term mortality in patients with candidemia, outperforming the GLIM criteria.

We aimed to examine the psychometric properties of the second version of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD-V2.0) and its correspondence with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity scale (CGI-S) scores. This cross-sectional study was conducted at 18 institutes in Japan. We performed correlational analyses to test the convergent and divergent validity of the BE-PSD-V2.0. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). The equipercentile equating method was employed to examine the linking of the BE-PSD-V2.0 with the PANSS and the CGI-S. A total of 353 patients with schizophrenia spectrum disorders were included. Spearman's rank correlation coefficients between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores ranged from 0.64 to 0.86, indicating sufficient convergent validity. These specific correlation coefficients were consistently the highest among all item-to-factor comparisons, indicating sufficient divergent validity. In 34 patients, ICCs for the BE-PSD-V2.0 itemand total scores ranged from 0.60 to 0.94, showing sufficient inter-rater reliability. Conversion tables were established between the BE-PSD-V2.0 total score and the PANSS total score, between the BE-PSD-V2.0 total score and the CGI-S score, and between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores. A correspondence between symptomatic remission criteria using the PANSS and BE-PSD-V2.0 was confirmed. The BE-PSD-V2.0 possesses sufficient psychometric properties and corresponds to the PANSS and CGI-S. It is a sound and reliable brief rating scale for assessing symptoms in schizophrenia spectrum disorders, and its established conversion correspondences facilitate score interpretation within existing clinical paradigms for both clinical practice and research.

Pleural mesothelioma (PM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with PM. This study aims to identify a novel molecular target inhibitor to develop more effective therapeutics for PM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective antiproliferative properties against NF2/CDKN2A(p16)-deficient PM cells, surpassing the effects of C75, cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient PM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact PM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient PM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of PM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for PM.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT) proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018 and updated in 2022 (Ozaki et al. in Cardiovasc Interv Ther 33:178-203, 2018), (Ozaki et al. in Cardiovasc Interv Ther 37:1-34, 2022). Following the publication of the 2023 European Society of Cardiology (ESC) Guidelines for the management of acute coronary syndromes, the CVIT Task Force released another revised version in 2024 (Ozaki et al. in Cardiovasc Interv Ther 39:335-375, 2024). In light of new clinical evidence and technological advances that have emerged since then, the Task Force now proposes an updated expert consensus document for the management of ACS focusing on procedural aspects of primary PCI in 2026 version.