Treatment of cryptogenic new-onset refractory status epilepticus (C-NORSE) with tocilizumab: A case report.

A 35-year-old woman with no prior history of epilepsy developed status epilepticus (SE), which was highly resistant to multiple antiseizure medications and sedatives. The etiology of SE was not identified despite extensive investigation, and the patient was diagnosed with cryptogenic new-onset refractory status epilepticus (C-NORSE). Although first-line immunotherapies such as high-dose corticosteroids and plasma exchange were ineffective, the patient manifested a resolution of SE after the administration of tocilizumab, which inhibits interleukin-6. Non-antibody-mediated inflammation has been hypothesized to be a probable pathophysiology of C-NORSE in recent studies, and tocilizumab may be a plausible second-line treatment.

Recovery after Prolonged Disturbance of Consciousness and Repeated Cerebral Perfusion Changes in Neuronal Intranuclear Inclusion Disease.

Encephalitic episodes are a clinical manifestation of neuronal intranuclear inclusion disease (NIID) and often show transient disturbance of consciousness. We herein report a genetically confirmed patient with NIID who initially presented progressive dementia and showed prolonged disturbance of consciousness preceded by an acute-onset headache. During that time, we performed N-isopropyl-p-[123I] iodoamphetamine single-photon-emission computed tomography twice and found that the blood flow increased in different regions. Prolonged disturbance of consciousness following an encephalitic episode may be associated with repeated hyperperfusion in various regions resulting from mitochondrial dysfunction. NIID patients presenting with encephalitic episodes can recover gradually and spontaneously even after prolonged disturbances of consciousness.

Athlete Sleep Behavior Questionnaire in Japanese (ASBQ-J): An Adaptation and Validation Study.

Purpose: The Athlete Sleep Behavior Questionnaire (ASBQ) is an 18-item self-reported questionnaire that can be used to screen for sleep disorders in athletes and assess environmental, behavioral, and sports-related factors along with sleep disorders. This study aimed to analyze the reliability and validity of the ASBQ translated into Japanese (ASBQ-J). Patients and Methods: 111 female collegiate athletes completed both the initial test and retest. Independent variables were what kind of sports they perform, level as an athlete, grade (freshman, sophomore, junior, senior), and age. The reliability of the survey was assessed using Cronbach's alpha and intraclass correlation, and Pearson's correlation coefficient was calculated to determine the correlation between the total ASBQ scores and three components which were routine/environmental, behavioral, and sports factors. Results: A total of 37.8% of athletes had ASBQ scores equal or less than 36 indicating good sleep. However, 19.8% of athletes scored more than 42, indicating poor sleep. Cronbach alpha was 0.62 and 0.65 for test and retest, respectively. Intraclass correlation was 0.78 (P < 0.01), indicating sufficient internal consistency and test-retest validity. Mean ASBQ scores were 38.5 ± 5.0 and 37.0 ± 6.5 for test and retest, respectively, and it was not significantly different between the two groups (P = 0.37). The correlation coefficients between the ASBQ-J and component scores were all statistically significant (all P < 0.01). Conclusion: ASBQ-J is a reliable questionnaire for assessing sleep disorders in athletes whose primary language is Japanese.

Perioperative Use of Intravenous Levodopa as an Anti-Parkinsonian Drug: A Propensity Score Analysis.

Background: Perioperative discontinuation of oral anti-parkinsonian medication can negatively impact the prognosis of abdominal surgery in patients with Parkinson's disease. Although intravenous levodopa may be an alternative, its efficacy has not yet been investigated. Objectives: To determine the efficacy of intravenous levodopa as an alternative to oral anti-Parkinsonian drugs during gastric or colorectal cancer surgery. Methods: We identified patients with Parkinson's disease who underwent surgery for gastric or colorectal cancer between April 2010 and March 2020, using the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan. Patients were divided into two groups: those who received intravenous levodopa during the perioperative period and those who did not. We compared in-hospital mortalities, major complications, and postoperative length of stay between the groups after adjusting for background characteristics with overlap weights based on propensity scores. Results: We identified 648 patients who received intravenous levodopa and 1207 who did not receive levodopa during the perioperative period. In the adjusted cohort, the mean postoperative length of stay was 24.7 and 29.0 days (percent difference, -7.7%; 95% confidence interval, -13.1 to -1.5); in-hospital death was 3.2% and 3.3% (adjusted odds ratio, 0.95; 95% CI: 0.54-1.67); and incidence of major complications were 21.4% and 19.3% (adjusted odds ratio, 0.89; 95% confidence interval, 0.70-1.13) in those with and without intravenous levodopa, respectively. Conclusions: Intravenous levodopa was associated with a shorter postoperative length of stay, but not with mortality or morbidity. Intravenous levodopa may improve perioperative care in patients with Parkinson's disease.

Ethical Challenges of the COVID-19 Pandemic: A Japanese Perspective.

This article focuses on how Japan experienced the COVID-19 pandemic. It delineates the various challenges the country faced and the measures the national government took to stop the spread of the infection. The article begins with the author's personal experience of COVID-19. The second section explains how the Japanese government lacked the legal sanctions to enforce a state of emergency. The third section deals with the current pandemic response as characterized by the increased use of digital technologies to control the spread of the virus. I argue that the lack of effective governance hampered Japan's timely use of digital technologies. The fourth section will touch on the issues created by the rapid spread of the infection and an increase in the hospitalization rate, focusing on intensive care unit triage and the ethical debates that ensued in Japan. The fifth section discusses the pandemic from the perspective of disaster preparedness and management, exploring the ways the pandemic responses share ethical challenges with responses to other disasters such as earthquakes and typhoons.

One-Step Pharmaceutical Preparation of PEG-Modified Exosomes Encapsulating Anti-Cancer Drugs by a High-Pressure Homogenization Technique.

The use of exosomes encapsulating therapeutic agents for the treatment of diseases is of increasing interest. However, some concerns such as limited efficiency and scalability of conventional drug encapsulation methods to exosomes have still remained; thus, a new approach that enables encapsulation of therapeutic agents with superior efficiency and scalability is required. Herein, we used RAW264 macrophage cell-derived exosomes (RAW-Exos) and demonstrated that high-pressure homogenization (HPH) using a microfluidizer decreased their particle size without changing their morphology, the amount of exosomal marker proteins, and cellular uptake efficiency into RAW264 and colon-26 cancer cells. Moreover, HPH allowed for modification of polyethylene glycol (PEG)-conjugated lipids onto RAW-Exos, as well as encapsulation of the anti-cancer agent doxorubicin. Importantly, the doxorubicin encapsulation efficiency became higher upon increasing the process pressure and simultaneous HPH with PEG-lipids. Moreover, treatment with PEG-modified RAW-Exos encapsulating doxorubicin significantly suppressed tumor growth in colon-26-bearing mice. Taken together, these results suggest that HPH using a microfluidizer could be useful to prepare PEG-modified Exos encapsulating anti-cancer drugs via a one-step pharmaceutical process, and that the prepared functional Exos could be applied for the treatment of cancer in vivo.

Impact of COVID-19 pandemic on epilepsy care in Japan: A national-level multicenter retrospective cohort study.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on epilepsy care across Japan was investigated by conducting a multicenter retrospective cohort study. METHODS: This study included monthly data on the frequency of (1) visits by outpatients with epilepsy, (2) outpatient electroencephalography (EEG) studies, (3) telemedicine for epilepsy, (4) admissions for epilepsy, (5) EEG monitoring, and (6) epilepsy surgery in epilepsy centers and clinics across Japan between January 2019 and December 2020. We defined the primary outcome as epilepsy-center-specific monthly data divided by the 12-month average in 2019 for each facility. We determined whether the COVID-19 pandemic-related factors (such as year [2019 or 2020], COVID-19 cases in each prefecture in the previous month, and the state of emergency) were independently associated with these outcomes. RESULTS: In 2020, the frequency of outpatient EEG studies (-10.7%, p<0.001) and cases with telemedicine (+2,608%, p=0.031) were affected. The number of COVID-19 cases was an independent associated factor for epilepsy admission (-3.75*10-3 % per case, p<0.001) and EEG monitoring (-3.81*10-3 % per case, p = 0.004). Further, the state of emergency was an independent factor associated with outpatient with epilepsy (-11.9%, p<0.001), outpatient EEG (-32.3%, p<0.001), telemedicine for epilepsy (+12,915%, p<0.001), epilepsy admissions (-35.3%; p<0.001), EEG monitoring (-24.7%: p<0.001), and epilepsy surgery (-50.3%, p<0.001). SIGNIFICANCE: We demonstrated the significant impact that the COVID-19 pandemic had on epilepsy care. These results support those of previous studies and clarify the effect size of each pandemic-related factor on epilepsy care.

Outcomes of gastrointestinal cancer surgeries in Parkinson's disease patients: A nationwide study.

BACKGROUND: Parkinson's disease (PD) patients with comorbid cancers are increasing in aging populations. However, little is known about the impact of PD on the outcomes of surgeries to resect these cancers. We sought to clarify the association between PD and discharge status of patients who underwent surgery for gastrointestinal cancers, as the most prevalent malignant neoplasms worldwide. METHODS: We identified patients who underwent surgery for gastric and colorectal cancers between April 01, 2014 and March 31, 2018 using the Diagnosis Procedure Combination database, a nationwide administrative inpatient database in Japan. We then collected data on their sex, age, smoking status, body mass index, activities of daily living, cancer stage, and comorbidities. Multivariable Cox regression analyses were conducted to determine factors that influenced discharge to home. RESULTS: Compared with non-PD patients (n = 272,668), PD patients (n = 1341) were significantly older and less likely to receive laparoscopic surgery, and had lower body mass index, more advanced cancer stage, and lower activities of daily living. The proportions of PD and non-PD patients discharged to home were 80.3% and 96.2%, respectively. The adjusted hazard ratio for discharge to home for PD patients was 0.68 (95% confidence interval, 0.64-0.73; P < 0.001). CONCLUSIONS: Compared with non-PD patients, PD patients were less likely to be discharged to home after surgery for gastrointestinal cancers. The present results may indicate a necessity to improve perioperative care for patients with PD.

Barriers to telemedicine among physicians in epilepsy care during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: This study aimed to investigate the factors affecting the unwillingness of physicians involved in epilepsy care to continue telemedicine during the coronavirus disease 2019 (COVID-19) pandemic in Japan. METHOD: This was a national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan) which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES). We asked physicians who conducted telemedicine in patients with epilepsy (PWE) during the COVID-19 pandemic at four clinics and 21 hospitals specializing in epilepsy care in Japan from March 1 to April 30, 2021. The following data were collected: (1) participant profile, (2) characteristics of PWE treated by telemedicine, and (3) contents and environmental factors of telemedicine. Statistically significant variables (p < 0.05) in the univariate analysis were analyzed in a multivariate binary logistic regression model to detect the independently associated factors with the unwillingness to continue telemedicine. RESULT: Among the 115 respondents (response rate: 64%), 89 were included in the final analysis. Of them, 60 (67.4%) were willing to continue telemedicine, and 29 (32.6%) were unwilling. In the univariate binary logistic regression analysis, age (Odds ratio [OR] = 1.84, 95% confidence interval [CI] 1.10-3.09, p = 0.02), psychiatrist (OR = 5.88, 95% CI 2.15-16.08, p = 0.001), hospital (OR = 0.10, 95% CI 0.01-0.94, p = 0.04), the number of COVID-19 risk factors in the participant (OR = 2.88, 95% CI 1.46-5.69, p = 0.002), the number of COVID-19 risk factors in the cohabitants (OR = 2.52, 95% CI 1.05-6.01, p = 0.04), COVID-19 epidemic area (OR = 4.37, 95% CI 1.18-16.20, p = 0.03), consultation time during telemedicine (OR = 2.51, 95% CI 1.32-4.76, p = 0.005), workload due to telemedicine (OR = 4.17, 95% CI 2.11-8.24, p < 0.001) were statistically significant. In the multivariate binary logistic regression analysis, workload due to telemedicine (OR = 4.93, 95% CI 1.96-12.35) was independently associated with the unwillingness to continue telemedicine. CONCLUSION: This national-level cross-sectional survey found that workload due to telemedicine among physicians involved in epilepsy care was independently associated with the unwillingness to continue telemedicine.

Risk factors for psychological distress in electroencephalography technicians during the COVID-19 pandemic: A national-level cross-sectional survey in Japan.

OBJECTIVE: To identify the risk factors for psychological distress in electroencephalography (EEG) technicians during the coronavirus disease 2019 (COVID-19) pandemic. METHOD: In this national-level cross-sectional survey initiated by Japan Young Epilepsy Section (YES-Japan), which is a national chapter of The Young Epilepsy Section of the International League Against Epilepsy (ILAE-YES), a questionnaire was administered to 173 technicians engaged in EEG at four clinics specializing in epilepsy care and 20 hospitals accredited as (quasi-) epilepsy centers or epilepsy training facilities in Japan from March 1 to April 30, 2021. We collected data on participants' profiles, information about work, and psychological distress outcome measurements, such as the K-6 and Tokyo Metropolitan Distress Scale for Pandemic (TMDP). Linear regression analysis was used to identify the risk factors for psychological distress. Factors that were significantly associated with psychological distress in the univariate analysis were subjected to multivariate analysis. RESULTS: Among the 142 respondents (response rate: 82%), 128 were included in the final analysis. As many as 35.2% of EEG technicians have been under psychological distress. In multivariate linear regression analysis for K-6, female sex, examination for patients (suspected) with COVID-19, and change in salary or bonus were independent associated factors for psychological distress. Contrastingly, in multivariate linear regression analysis for TMDP, female sex, presence of cohabitants who had to be separated from the respondent due to this pandemic, and change in salary or bonus were independent associated factors for psychological distress. CONCLUSION: We successfully identified the risk factors associated with psychological distress in EEG technicians during the COVID-19 pandemic. Our results may help in understanding the psychological stress in EEG technicians during the COVID-19 pandemic and improving the work environment, which is necessary to maintain the mental health of EEG technicians.

Preparation of Metal Nitride Particles Using Arc Discharge in Liquid Nitrogen.

A simple process to synthesize metal nitride particles was proposed using submerged arc discharge plasma in liquid nitrogen. Gibbs standard free energy was considered for the selection of the nitride-forming materials. In this study, titanium (Ti) and aluminum (Al) electrodes were used as raw materials for nitride particle preparation. Liquid nitrogen acted as a dielectric medium as well as a nitridation source in this process. A copper electrode was also used as a non-reactive material for comparison with the reactive Ti and Al electrodes. As the operating conditions of the experiments, the arc discharge current was varied from 5 A (low-power mode) to 30 A (high-power mode). The formation of titanium nitride (TiN) and aluminum nitride (AlN) was confirmed in the particles prepared in all experimental conditions by X-ray powder diffraction (XRD). The observation using a field emission scanning electron microscope (FE-SEM) and a field emission transmission electron microscope (FE-TEM) indicated that the synthesized TiN particles showed a cubic morphology, whereas AlN particles containing unreacted Al showed a spherical morphology. The experiments using different metal electrode configurations showed that the anode generated most of the particles in this process. Based on the obtained results, a particle formation mechanism was proposed.

Clozapine Prolongs Cortical Silent Period in Patients with Treatment-Resistant Schizophrenia.

Objectives: Although clozapine exhibited high efficacy for treating the symptoms of patients with treatment-resistant schizophrenia (TRS), its precise action mechanisms have not been fully understood. Recently, accumulating evidence has suggested the presence of abnormalities in the gamma-aminobutyric acid (GABA) systems in patients with schizophrenia, and the potential effects of clozapine on GABA receptors have gained a great deal of attention. Experimental Designs: In the present study, the cortical silent period (CSP), an electrophysiological parameter of GABA function via GABAB receptors, was measured using with the transcranial magnetic stimulation in patients with schizophrenia and healthy control subjects. Then the CSP of patients treated with clozapine (N = 12) was compared with that of patients treated with other antipsychotics (N = 25) and with that of healthy controls (N = 27). Principal Observations: The CSP of the patients treated with clozapine was significantly longer compared to those of the other two groups. The CSP of patients treated with other antipsychotics was similar to that of healthy subjects. There was a positive correlation between CSP and global assessment of function (GAF) in patients with TRS. Conclusions: The present study indicated that CSP was prolonged in patients receiving clozapine, and suggested that clozapine enhances the transmission signal via GABAB receptors.

Forgoing life-sustaining treatment - a comparative analysis of regulations in Japan, Korea, Taiwan, and England.

BACKGROUND: Regulations on forgoing life-sustaining treatment (LST) have developed in Asian countries including Japan, Korea and Taiwan. However, other countries are relatively unaware of these due to the language barrier. This article aims to describe and compare the relevant regulatory frameworks, using the (more familiar) situation in England as a point of reference. We undertook literature reviews to ascertain the legal and regulatory positions on forgoing LST in Japan, Korea, Taiwan, and England. MAIN TEXT: Findings from a literature review are first presented to describe the development of the regulatory frameworks surrounding the option of forgoing LST in each country. Based on the findings from the four countries, we suggest five ethically important points, reflection on which should help to inform the further development of regulatory frameworks concerning end-of-life care in these countries and beyond. There should be reflection on: (1) the definition of - and reasons for defining - the 'terminal stage' and associated criteria for making such judgements; Korea and Taiwan limit forgoing LST to patients in this stage, but there are risks associated with defining this too narrowly or broadly; (2) foregoing LST for patients who are not in this stage, as is allowed in Japan and England, because here too there are areas of controversy, including (in England) whether the law in this area does enough to respect the autonomy of (now) incapacitated patients; (3) whether 'foregoing' LST should encompass withholding and withdrawing treatment; this is also an ethically disputed area, particularly in the Asian countries we examine; (4) the family's role in end-of-life decision-making, particularly as, compared with England, the three Asian countries traditionally place a greater emphasis on families and communities than on individuals; and (5) decision-making with and for those incapacitated patients who lack families, surrogate decision-makers or ADs. CONCLUSION: Comparison of, and reflection on, the different legal positions that obtain in Japan, Korea, Taiwan, and England should prove informative and we particularly invite reflection on five areas, in the hope the ensuing discussions will help to establish better end-of-life regulatory frameworks in these countries and elsewhere.

Ethical Issues Around the Withdrawal of Dialysis Treatment in Japan.

In Japan, terminating life-sustaining treatment (LST) in non-terminal patients is legally and ethically problematic given the lack of legal regulations regarding the termination of LST, including dialysis treatment. This article describes an ethically problematic case that happened at a hospital in Tokyo in March 2019, in which a patient died after a physician withdrew kidney dialysis upon the patient's request. Most national newspapers in Japan reported the case extensively and raised the question of ethical and legal permissibility of withdrawing dialysis treatment from non-terminal patients. In this article, we first examine the case within the current policy framework in Japan and then discuss how Japan can improve its end-of-life practice, focusing specifically on the patient's right to self-determination and treatment refusal. We recommend that policymakers consider legalizing the termination of LST and the patient's right to refuse treatment based on the principle of respect for autonomy.