Background: and Purpose To clarify the effect of perampanel (PER) on sporadic amyotrophic lateral sclerosis (sALS) progression, the relationship between the changes in Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores and serum PER concentrations was investigated. Methods: 12 patients with sALS from our hospital who agreed to participate and completed the PER for sALS randomized phase 2 study were included. After completing the study, we retrospectively obtained serum PER concentration data from the patients. Based on their mean PER concentrations, we divided the patients who had been taking PER into two groups:four patients with a mean PER concentration of ≥400 ng/mL were assigned to the H group, and three with a mean PER concentration of <400 ng/mL were assigned to the L group. The control group consisted of five patients who had been taking a placebo. We obtained the ALSFRS-R scores of each patient at 36 and 48 weeks after randomization. The differences in ALSFRS-R scores at baseline (0 weeks) and each subsequent week were used in the analysis. Results: At 48 weeks, there were no differences in the degree of deterioration of the bulbar, upper and lower limb, and respiratory ALSFRS-R subscores and total ALSFRS-R score. However, at 36 weeks, the bulbar subscore was significantly lower in the H group than in the control group (p=0.032). Conclusions Because high PER concentrations may exacerbate bulbar symptoms in patients with sALS, serum PER measurements may be beneficial when patients with sALS are taking PER.

Methods: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. Results: TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation. Conclusions Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.

Background: Effect of meteorological factors such as air temperature, humidity, and sunlight exposure on transmission dynamics of novel coronavirus disease 2019 (COVID-19) remains controversial. We investigated the association of these factors on COVID-19 incidence in Japan. Methods: We analyzed data on reverse transcription polymerase chain reaction confirmed COVID-19 cases for each prefecture (total=47) in Japan and incidence rate was defined as the number of all reported cumulative cases from January 15 to March 17, 2020. Independent variables of each prefecture included three climatic variables (mean values of air temperature, relative humidity, and sunlight exposure), population elderly ratio, and the number of inbound travelers from China during February 2020. Multivariable-adjusted Poisson regression model was constructed to estimate COVID-19 incidence rate ratio (IRR) of independent variables. Results: There was a total of 702 cases during the study period in Japan (population=125, 900,000). Mean±standard deviation values of meteorological variables were 7.12°C±2.91°C for air temperature, 67.49%±7.63% for relative humidity, and 46.77±12.55% for sunlight exposure. Poisson regression model adjusted for climate variables showed significant association between the incidence and three climatic variables: IRR for air temperature 0.854 (95% confidence interval [CI], 0.804–0.907; P<0.0001), relative humidity 0.904 (95% CI, 0.864–0.945; P<0.0001), and sunlight exposure 0.973 (95% CI, 0.951–0.997; P=0.026). Conclusion Higher values of air temperature, relative humidity and sunlight exposure were associated with lower incidence of COVID-19. Public health interventions against COVID-19 epidemic in a country should be developed by considering these meteorological factors.

Background: and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca 2+ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS. Methods: Specimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope. Results: This study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ 2 test). Conclusions In sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism.

Objective: Although much is known about acute carbon monoxide (CO) poisoning, little is known about chronic CO poisoning. Chronic CO poisoning is often diagnosed based on the patient’s living environment and medical history. Herein, we report the case of an older patient who presented with repeated unconsciousness due to chronic CO poisoning.Case presentation: A 90-year-old man was brought to the emergency department after being found at home with a disturbance of consciousness. Arterial blood gas measurements in room air revealed a carboxyhemoglobin level of 18.0%. Impaired consciousness was caused by chronic CO poisoning. The patient received high-flow oxygen therapy, which promptly improved his condition. According to his family, briquette kotatsu was the cause of chronic CO poisoning.Conclusion: Although high-flow oxygen therapy has been said to be less effective than hyperbaric oxygen therapy in CO poisoning treatment, recent studies have demonstrated that high-flow oxygen has similar effects and benefits. Thus, in institutions that do not have hyperbaric oxygen, high-flow oxygen may be sufficient to treat patients with CO poisoning, as seen in the present case. It should be noted that briquette kotatsu can lead to CO poisoning. This case highlights the need for clinicians to consider patients’ living conditions.

In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients’ survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.

In dentistry, it is empirically known that the acute exacerbation of periodontal disease often occurs at the time of fatigue, but scientific verification has never been made about the relationship of fatigue and bleeding. In Kampo medicine, there is the concept of spleen failing to control the blood as bleeding at the time of fatigue. Kihito and kamikihito are often used for this condition. Spleen failing to control the blood means that lack of vital energy causes the bleeding. Kamikihito is most often used in the treatment of idiopathic thrombocytopenic purpura. Moreover, there have been some reports on the use of kamikihito in the treatment of gynecological fraud bleeding and aplastic anemia. However, there has been no report on the use of it in the treatment of gingival bleeding. In this case, neither cytopenia nor obvious coagulopathy was recognized. In Kampo medicine, not only spleen failing to control the blood but also blood stasis or blood heat is considered to be the cause of bleeding, but the effectiveness of kamikihito for this case suggested pathophysiology of spleen failing to control the blood. Kamikihito could be a choice to treat gingival bleeding at the time of fatigue.

BACKGROUND: Following the increase in the number of children with food allergies, support systems are now required for school lunches, but a large-scale factual investigation has not been carried out. OBJECTIVE: We evaluated the features of elimination diet due to food allergy and the support system in kindergartens and schools. METHODS: A prefecture-based questionnaire survey regarding measures for food allergies in school lunches of all kindergartens, public elementary schools, and public junior high schools (631 facilities) was conducted in Oita Prefecture, Japan. RESULTS: The recovery rate of the questionnaire was 99.5%, which included 106,008 students in total. A total of 1,562 children (1.5%) required elimination diets. The rate of children on elimination diets in kindergartens and elementary/junior high schools that required medical certification by a physician was 1.2% (324 among 27,761 children), which was significantly lower than the 1.8% of children (1,227 among 68,576 students) on elimination diets at the request of guardians without the need for medical certification (p < 0.0001). A total of 43.9% of the kindergartens and schools said that they would contact guardians if symptoms were observed after accidental ingestion, while a low 8.1% stated that they provided support to children themselves, including the administration of adrenaline auto-injectors. CONCLUSION: Medical certification reduces the number of children requiring elimination diets, but it has not been adequately implemented. Furthermore, waiting to contact guardians after symptoms are observed may lead to the delayed treatment of anaphylaxis. Cooperation between physicians and teachers is desired to avoid the overdiagnosis and undertreatment of children with food allergies.
Anaphylaxis ; Certification ; Child ; Diet ; Eating ; Epinephrine ; Food Hypersensitivity ; Humans ; Japan ; Lunch ; Medical Overuse

　　In recent years, favorable therapeutic outcomes have been reported for arterial injection chemoradiotherapy for tongue cancer. The present case involves an 80-year-old woman in our palliative care department who had high-grade, advanced tongue cancer. Because there was a request for surgery to prevent airway occlusion due to growth of the tumor, she was referred to our department in April 2009. As a treatment policy for controlling tumor growth in high-grade, advanced tongue cancer, arterial injection chemoradiotherapy was carried out through the superficial temporal artery, with a tongue artery catheter in place on both sides. Therapeutic effect was obtained, and it was possible to avoid airway occlusion through tumor regression. Dysphagia and dysphemia were improved, which in turn improved quality of life. In this case, there was an opportunity to carry out multidisciplinary team medicine, including support from the oral care and palliative care teams as part of the process of cancer therapy. Here, we present our findings in this case.