Biomarkers in the cerebrospinal fluid (CSF) are currently regarded as indispensable indicators for accurate differential diagnosis of neurodegenerative disorders. Although high levels of astrocyte-secreted glial fibrillar acidic protein (GFAP) in the CSF of patients with Alzheimer's disease (AD) have been reported, the levels of GFAP in the CSF have not been fully investigated in other neurological disorders that cause dementia, such as dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). In this study, we determined the levels of GFAP in the CSF of healthy control subjects and AD, DLB, and FTLD patients to address two questions: (i) Do the levels of GFAP differ among these disorders? and (ii) Can GFAP be used as a biomarker for the differential diagnosis of these neurodegenerative disorders? The levels of GFAP in AD, DLB, and FTLD patients were significantly higher than those in the healthy control subjects. Although the levels of GFAP were not significantly different between AD and DLB patients, a higher level of GFAP was observed in FTLD patients than in AD and DLB patients. It is concluded that representative neurological disorders causing dementia were associated with higher levels of GFAP in the CSF.

Common bile duct (CBD) stone is a relatively common but potentially life-threatening disease. Endoscopic sphincterotomy (EST) has been performed as standard therapy for CBD stones, but the rate of recurrence of CBD stones is high. Risk factors have been poorly defined, and no effective means for the prevention of the recurrence of CBD stones have been established so far. We aimed to identify significant risk factors for the recurrence of bile duct stones. This study included 477 patients (231 women; mean age, 80.5 years) who underwent EST and cleared CBD stones on cholangiography. A retrospective analysis was performed for the consecutively collected data. During the follow-up period of 6-75 months, the recurrence of CBD stones was observed in 99 patients (20.8%). The median time to the recurrence was 19.0 months (range 4-72 months). Multivariate analysis identified the need for mechanical lithotripsy, which was used for stone fragmentation, as a risk factor. Mechanical lithotripsy caused cholangiography-negative small residua. Notably, saline solution irrigation of the bile duct reduced the recurrence of CBD stones. These results demonstrate that subsequent biliary irrigation after stone removal may prevent the recurrence of CBD stones by clearing small residual fragments.

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Background: Little is known about clinical and genetic factors that predict the long-term response of anti-TNF therapy are limited in Japanese patients with Crohn’s disease (CD). Methods: Association between clinical factors and cumulative clinical relapse-free rates were investigated in 464 patients with CD (373 anti-TNF naïve and 91 anti-TNF switch patients). A genome-wide association study (GWAS) was performed using Cox proportional hazards model. Genotype data of 5,657,947 SNPs from 275 anti-TNF naïve patients were used for GWAS. Results: Lower serum albumin level, perianal disease, and younger age at disease onset were identified as risk factors for earlier clinical relapse in the anti-TNF naïve group (hazard ratio: HR = 1.76, 1.43, and 1.36; P = 0.00029, 0.044, and 0.045, respectively). Previous intestinal resection was associated with clinical relapse in the anti-TNF switch group (HR = 0.42; P = 0.0075). In the GWAS, rs12613485, which is located between RFX8 and MAP4K4, showed the strongest association with relapse (HR = 2.44; P = 3.42E-7). Pathway analysis indicated the association of the TGF-β signaling pathway (P = 3.06E-4). Conclusions: We identified several reasonable clinical factors and candidate genetic factors associated with early relapse during anti-TNF treatments in Japanese CD patients.