Uji Hospital

Moyamoya disease (MMD) has a strong genetic basis, with the rare RNF213 p.Arg4810Lys variant (rs112735431) representing a major risk factor, while the broader genetic architecture and disease-relevant vascular cell types remain incompletely understood. We conducted a genome-wide association study in Japanese individuals (n=47 656; 401 MMD cases and 47 255 controls). Population-level features at MMD risk loci were examined by regional allele frequency and haplotype analyses. We performed single-nucleus RNA-seq of superficial temporal arteries from patients with MMD (n=3). Cell type-specific enrichment of genome-wide association study signals was assessed using the Single-Cell Disease Relevance Score. Endothelial signatures were validated by integration with publicly available single-cell data sets from controls (n=5) and immunohistochemistry for candidate markers (n=1). Beyond rs112735431, we identified a genome-wide significant signal in the HDAC9-TWIST1 region (rs12530920; P=3.3×10-14; odds ratio, 1.77). Conditional analysis on rs112735431 revealed a protective RNF213 missense variant, p.Asp1331Gly (rs8074015; P=3.7×10-9; odds ratio, 0.53), whose minor allele was mutually exclusive with rs112735431-A on haplotypes. Population analysis revealed geographic variation and extended haplotype structure of the rs112735431-A allele in Japan. Single-nucleus RNA-seq identified a mesenchymal-like endothelial cell (MEC) population with selective FN1 expression. Genome-wide association study-prioritized disease genes were strongly enriched in MECs. MECs showed mesenchymal pathway activation with a regulatory program distinct from canonical endothelial states. The proportion of MECs was markedly increased in MMD (72% versus 28% in controls), and fibronectin 1 (FN1) expression in endothelial regions was confirmed by immunohistochemistry. Our findings identify a protective RNF213 p.Asp1331Gly variant (rs8074015) that is mutually exclusive with the known rs112735431-A allele. Genetic risk converges on an MEC state markedly expanded in MMD.

Esophageal squamous cell carcinoma (ESCC) remains a leading cause of cancer-related mortality, with early detection being challenging. Although endoscopic screening can aid in diagnosis, its invasiveness and cost limit widespread compliance. To address this, we developed and validated a non-invasive diagnostic panel based on urinary exosomal microRNAs (miRNAs) for early ESCC detection. Urine samples were prospectively collected from ESCC patients and healthy controls across five institutions, and exosomal miRNA profiles were obtained using small RNA sequencing. A diagnostic panel was constructed using machine learning with recursive feature elimination in a proof-of-concept (POC) cohort comprising 99 ESCC and 93 control samples, and its performance was evaluated by five-fold cross-validation. This panel was subsequently tested in a blinded validation cohort of 50 ESCC and 61 control samples. In the POC cohort, the multi-miRNA panel achieved an area under the curve (AUC) of 0.90. In the validation cohort, the AUC was 0.85 (95% CI: 0.77-0.92), with 84% sensitivity and 66% specificity. The panel showed high sensitivity across disease stages-100% for Stage 0, 91% for Stage I, and 73% for Stages II-IV-and its performance was not significantly affected by sex, body mass index, alcohol use, or smoking. Furthermore, in early-stage cases, the diagnostic score significantly declined after treatment (p = 0.026). These findings suggest that the urinary exosomal miRNA panel may offer a practical screening approach for the early detection of ESCC.

The Paris System for Reporting Urinary Cytology (TPS) has clearly and simply identified the criteria for the accurate diagnosis of high-grade urothelial carcinoma (HGUC); however, the urine cytological findings of secondary tumours have not been fully assessed. Therefore, we evaluated the urine cytological features of colorectal adenocarcinoma cells that invaded the urinary tract. Thirty urine cytology specimens with cells considered colorectal adenocarcinoma were retrieved by clinicopathological review, subject to the following criteria: no urothelial carcinoma history, diagnosed as HGUC by TPS and supported by CDX-2 immunocytochemistry. Cases were morphologically re-evaluated. CDX-2 immunostaining, performed in four available cases, showed nuclear positivity in all cases. Tall columnar carcinoma cells were identified in 12/30 cases, tumour cells with pale or vacuolated cytoplasm in 4/30, large and eosinophilic nucleoli in most atypical cells in 4/30, large cells simulating HGUC cells in 27/30 and small cells with irregularly shaped or crescentic nuclei in 27/30. A histological review of transurethral or colorectal resection specimens revealed morphologically identical small cells on the surface of all well-to-moderately differentiated adenocarcinomas, demonstrating desquamated and degenerated adenocarcinoma cells. One cytological specimen from a poorly differentiated adenocarcinoma showed dispersed isolated tumour cells with uniform and round nuclei containing finely granular chromatin and prominent nucleoli. Colorectal adenocarcinoma cells in the urine may not only be large and tall columnar or vacuolated, but can also simulate HGUC cells or have small round or crescentic nuclei. Recognising this morphological diversity is important for accurate diagnosis.

Introduction: With the growth of the aging population, we need to ensure that elderly people can live the rest of their lives with a satisfactory quality of life. However, the occurrence of psychosis in the elderly, especially at a later age, is a risk for decreased quality of life and a high risk of morbidity and mortality. The first episode of psychosis in age 60 or over is called very late-onset schizophrenia-like psychosis (VLOSLP) and needs to be distinguished from secondary psychosis such as Alzheimer’s Disease (AD) with psychotic symptoms. Case: A 77-year-old woman was brought by her family to the geriatric psychiatry clinic due to strange behavior such as hearing voices and obeying the voices’ commands since the last 6 months that worsened in the last month. In the last month, the patient also had sleeping difficulty, pacing at night, and accusing family of trying to harm her. After one month of therapy with Risperidone, the patient was showing improvement in the reduction of the voices. Discussion: The patient was assessed as VLOSLP with the first episode of psychosis with schizophrenia spectrum core symptoms such as paranoid delusion and auditory-verbal hallucination. Conclusion: In this case, clinicians work with insufficient additional examination data, and that could also apply to clinicians in the remote area with no access to more comprehensive modalities to differentiate early stages of AD with psychosis and VLOSLP from clinical symptoms. However, more data is needed to establish clinical criteria regarding VLOSLP.

Introduction : Strangulated common peroneal neuropathy is a well-known cause of foot drop. However, it can also present solely with pain and numbness in the area of the common peroneal nerve, necessitating differentiation from lumbar degenerative diseases. Additionally, it has also been reported to occur after lumbar spinal surgery and may cause failed back surgery syndrome (FBSS). We treated four patients diagnosed with common peroneal neuropathy due to residual or new symptoms in the lower leg following posterior lumbar decompression surgery. All patients underwent common peroneal nerve neurolysis (CPNN) under local anesthesia. Herein, we report our experience with these cases.

Anticoagulation therapy for atrial fibrillation (AF) has undergone major changes following the introduction of direct oral anticoagulants (DOAC) in 2011. However, the transition of anticoagulation therapy for AF patients with severe renal dysfunction remains to be elucidated. Follow-up data, including creatinine clearance (CrCl), were available for 3,706 patients in the Fushimi AF Registry. We divided patients into 3 groups based on CrCl as follows: (1) CrCl ≥50 mL/min; (2) 50 mL/min>CrCl≥30 mL/min; and (3) CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50>CrCl≥30 mL/min, prescription of oral anticoagulants increased year-by-year from 2011 to 2021 with a growing proportion of DOAC; however, the prescription of oral anticoagulants remained almost unchanged in those with CrCl <30 mL/min. In patients with CrCl ≥50 mL/min and 50 mL/min>CrCl≥30 mL/min, the incidence of adverse events, including stroke/systemic embolism and major bleeding, was lower among patients enrolled after 2014 than before 2013. However, these trends were not seen in patients with CrCl <30 mL/min. Despite the increased use of DOAC in patients with AF since 2011, anticoagulation therapy for AF patients with severe renal dysfunction has largely remained unchanged, and a reduction in adverse events in those patients has not been observed.

Some patients with postoperative hip fractures (HF) experience persistent severe pain. In this longitudinal study, we examined the characteristics of patients with persistent pain after HF surgery, and the factors influencing pain intensity. We conducted an 8-week prospective study in patients with postsurgical HF. Verbal rating scale (VRS), and multifaceted outcomes, including pressure pain threshold (PPT) (affected site and biceps), were evaluated at 2, 4, and 8 weeks postoperatively. Patients were divided into mild (VRS ≤1) and severe (VRS ≥2) groups according to pain intensity at 8 weeks postoperatively. Statistical analyses were performed using two-way ANOVA and decision-tree analysis. VRS, PPT at the affected site and biceps, and physical activity (PA) time were significantly lower in the severe group than in the mild group 2 weeks postoperatively. VRS, PPT at the affected site, pain catastrophizing (PCS)-13, and the Tampa Scale for Kineshiophobia (TSK)-11 did not show significant improvements in the severe group. Decision tree analysis revealed that the VRS and PCS-13 at 4 weeks, PA time at 2 weeks, and TSK-11 change between 4 weeks and 2 weeks were factors influencing severe pain intensity at 8 weeks after HF surgery. Persistent severe pain after HF surgery was characterised by high peripheral and central sensitisation, pain catastrophizing, and reduced PA at 2 weeks after HF surgery. In addition, early pain intensity, pain catastrophizing, and PA may be hierarchically influential factors for persistent pain 8 weeks after HF surgery.