Objective: The effectiveness of clozapine is clearly superior to other antipsychotics in the treatment of refractory schizophrenia. Clozapine leads to various side effects, and therefore many patients are forced to discontinue. In this study, we analyzed the registry database of all cases in Japan to identify risk factors for discontinuation of clozapine. Methods: The Clozaril patient monitoring service® (CPMS) database from July 31, 2009 to January 26, 2020 was acquired. We defined the following exclusion criteria: patients who had ever taken clozapine by a non-CPMS method, such as an individual import or clinical trial, patients who did not receive clozapine after being enrolled in CPMS, and patients with initial doses other than 12.5 mg (outside the current protocol). Therefore, all patients in this study are new users. Multivariate Cox regression analysis was used to investigate independent risk factors associated with time to discontinuation of clozapine. Results: We identified 8,263 patients as the study population. Clozapine discontinuation was significantly associated with age 40 and older [hazard ratio (HR)=1.66, p<0.001], intolerance to olanzapine (HR=1.31, p=0.018), previous treatment with clozapine (HR=1.30, p=0.001), and leukocyte counts <6,000/mm3 (HR=1.24, p<0.001). The Kaplan-Meier curves for clozapine discontinuation by age group revealed that older age at the time of clozapine introduction tended to have lower continuation rates. Conclusion Careful administration is important because patients with these factors have a high risk of discontinuation. In addition, the initiation of clozapine during the younger period was more effective and more tolerated.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients’ outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10−4 ) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10−4 ) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10−3 ). Conclusion Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Background: Currently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP).We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously. Materials and Methods: Healthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gramstained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared. Results: Measuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood. Conclusion Calculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate.

Background: Currently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP).We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously. Materials and Methods: Healthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gramstained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared. Results: Measuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood. Conclusion Calculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate.

A laser endoscopy system was developed in 2012. The system allows blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization. Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology was released in 2016 to 2017 in some areas in which laser endoscopes have not been approved for use, including the United States and Europe. This system enables blue light imaging (this is also known as BLI) and LCI with an LED light source instead of a laser light source. Several reports have shown that these modes have improved tumor detection. In this paper, we review the efficacy of BLI and LCI with laser and LED endoscopes in tumor detection and characterization.
Colorectal Neoplasms ; Endoscopes ; Endoscopy ; Europe ; United States

OBJECTIVES: Cholesteatoma is a nonneoplastic destructive lesion of the temporal bone with debated pathogenesis and bone resorptive mechanism. Both molecular and cellular events chiefly master its activity. Continued research is necessary to clarify factors related to its aggressiveness. We aimed to investigate the expression of Ki-67, cytokeratin 13 (CK13) and cytokeratin 17 (CK17) in acquired nonrecurrent human cholesteatoma and correlate them with its bone destructive capacity. METHODS: A prospective quantitative immunohistochemical study was carried out using fresh acquired cholesteatoma tissues (n=19), collected during cholesteatoma surgery. Deep meatal skin tissues from the same patients were used as control (n=8). Cholesteatoma patients were divided into 2 groups and compared (invasive and noninvasive) according to a grading score for bone resorption based upon clinical, radiologic and intraoperative findings. To our knowledge, the role of CK17 in cholesteatoma aggressiveness was first investigated in this paper. RESULTS: Both Ki-67 and CK17 were significantly overexpressed in cholesteatoma than control tissues (P < 0.001 for both Ki-67 and CK17). In addition, Ki-67 and CK17 were significantly higher in the invasive group than noninvasive group of cholesteatoma (P=0.029, P=0.033, respectively). Furthermore, Ki-67 and CK17 showed a moderate positive correlation with bone erosion scores (r=0.547, P=0.015 and r=0.588, P=0.008, respectively). In terms of CK13, no significant difference was found between cholesteatoma and skin (P=0.766). CONCLUSION: Both Ki-67 and CK17 were overexpressed in cholesteatoma tissue and positively correlated with bone resorption activity. The concept that Ki-67 can be a predictor for aggressiveness of cholesteatoma was supported. In addition, this is the first study demonstrating CK17 as a favoring marker in the aggressiveness of acquired cholesteatoma.
Bone Resorption ; Cholesteatoma* ; Ear, Middle ; Humans* ; Keratin-13* ; Keratin-17* ; Keratins* ; Ki-67 Antigen ; Prospective Studies ; Skin ; Temporal Bone