Aichi Medical University

Clinicopathologically, dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) presents as either a non-plaque or plaque type. Here, we report an autopsy case of plaque-type dCJD, supported by genetic and biochemical analyses. A 41-year-old man manifested right-hand paraesthesia. He had received a dural graft in the right parietal region following a traumatic acute subdural haematoma 27 years before symptom onset. The clinical course was slowly progressive. The patient became unable to walk independently 17 months after onset, showed cognitive decline at 22 months, and developed myoclonus and akinetic mutism at 24 months. Periodic sharp-wave complexes were never observed on electroencephalography throughout the disease course. He died 26 months after symptom onset. No mutations were identified in the prion protein (PrP) gene, and the codon 129 polymorphism was homozygous for methionine. Neuropathologically, mild to moderate spongiform changes with fine vacuoles, neuronal loss, and astrogliosis were observed in the brain and spinal cord. Degeneration was relatively severe in the limbic system, striatum, thalamus, and cerebellum, resembling the distribution pattern of VV2 sporadic CJD. Abnormal PrP deposition was broadly distributed consisting of synaptic, perineuronal, and plaque forms. In particular, intense PrP staining was observed throughout the spinal grey matter. Western blotting detected intermediate-type PrP in the brain and cervical cord, but not in systemic organs. Considering the clinical course and PrP staining in the spinal cord, PrP transmission is suggested to occur not directly from the transplanted dura mater to the central nervous system, but rather indirectly via a peripheral route.

Endovascular therapy (EVT) is increasingly used to treat acute limb ischemia (ALI), a condition with high risks of limb loss and mortality. While high hospital volumes are linked with better outcomes in chronic lower extremity arterial disease (LEAD), the impact of hospital volume on ALI outcomes remains unclear. This study evaluated the relationship between hospital volume and procedure failure in ALI. Data from 3437 ALI patients undergoing EVT at 464 hospitals, sourced from the Japanese Endovascular Therapy (J-EVT) registry (2017–2022), were analyzed. Hospital volume was defined as the number of EVTs performed for LEAD at each hospital in the prior year. Propensity score matching (1:1) adjusted the baseline characteristics between low-volume (<53 cases/year) and non-low-volume hospitals. The primary outcome was procedural failure, defined as residual stenosis >30%. Secondary outcomes were perioperative complications. Low-volume hospitals had a significantly higher rate of procedural failure (11.7% vs 8.0%, P  = .008), but perioperative complication rates were similar (6.6% vs 5.4%, P  = .35). Generalized propensity score analysis confirmed a strong inverse correlation between hospital volume and procedural failure. Higher hospital volumes were associated with better EVT procedural outcomes for ALI, highlighting the importance of centralized care in non-low-volume hospitals.

Nanoplastic particles (NPs) derived from common polymers such as polyvinyl chloride and polystyrene (PS) act as persistent environmental reservoirs that facilitate the transport and cellular internalization of dibutyl phthalate (DBP), a ubiquitous plasticizer contaminating air, water, soil, and food through plastic leaching. The platelet-derived growth factor receptor α (PDGFRα) pathway is a well-established regulator of hepatic stellate cell (HSC) activation and fibrogenesis; however, its mechanistic involvement in plastic particle-induced hepatotoxicity and its intersection with DBP-mediated fibrosis remain unclear. Using HSC-hepatic cell cocultures (LX-2-HepG2 or LO2) and transcriptomic profiling, we demonstrate that DBP exposure markedly decreases hepatic cellular viability, elevates proinflammatory cytokines (TNF and IL-6), and induces apoptosis. In parallel, DBP stimulates LX-2 proliferation and upregulates fibrogenic markers (TGFB1, COL1A1, ACTA2) along with enhanced secretion of PDGF-A and PDGF-B, thereby reinforcing hepatic cell injury through paracrine signaling. RNA-seq analysis revealed activation of apoptotic and TNF-related pathways in LO2, whereas LX-2 cells exhibited upregulation of oncogenic and PI3K-Akt signaling, collectively promoting a profibrotic transcriptional landscape. In vivo, both PDGFRα antibody neutralization and pharmacological inhibition with imatinib significantly attenuated DBP-induced hepatic fibrosis and inflammatory gene expression, confirming PDGFRα's central role in DBP toxicity. Polystyrene nanoplastics (PS-NPs) were rapidly internalized by PDGFRα-positive primary HSCs within 24 h, leading to increased PDGFRα and PI3K expression. Co-exposure to PS-NPs and DBP resulted in synergistic hepatotoxicity and exacerbated fibrotic injury, demonstrating compounding effects of mixed environmental pollutants. Collectively, these findings identify PDGFRα as a mechanistic nexus linking DBP and PS-NPs exposure to hepatic fibrosis and highlight its potential as a therapeutic target for environmentally induced liver disease. The results further underscore the importance of co-exposure paradigms in evaluating the health risks of complex contaminant mixtures.