Effect of Serum Perampanel Concentration on Sporadic Amyotrophic Lateral Sclerosis Progression

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.

Switching to systemic therapy after locoregionaltreatment failure: Definition and best timing

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.

High Infant Mortality Presumably Due to Thiamine Deficiency in Lao PDR / 国際保健医療

<b>Introduction</b><br> During the course of primary health care activities in Khammouane province of Lao PDR by non- profit organization, international support and partnership for health, an exceedingly high infant mortality rate was recognized in some villages. As thiamine deficiency was strongly suspected for the main cause of the high mortality, the household survey with an emphasis on nutritional aspect and the measurement of thiamine level in the blood of mothers as well as their breast-milk were carried out for the confirmation.<br><b>Methods</b><br> The survey was conducted at Sibounhouane sub-district (Group 1) with the highest infant mortality and Hatkhamhieng sub-district (Group 2) with the lowest mortality. Fifty families of the two groups, each consisting of randomly selected 25 families with less than one year old infant(s) were interviewed by using prepared questionnaire. The body weight of both mother and infant was measured and blood and milk were taken from the mother.<br><b>Results</b><br> The ethnic minorities of the group 1 consisted of Lao Lum (44%) and Lao Theung (56%), whereas only Lao Lum in the group 2. The economical indicators and the mother's educational level in the group 1 were inferior to those in the group 2. There was no significant difference in the methods of preparing staple glutinous rice, likely to flux thiamine and intake of thiaminases between the two groups. High infant mortality rate was documented in the group 1 whose clinical symptoms were mostly consistent with those of infantile beriberi. The concentration of thiamine in the blood and milk of mothers in both groups were considerably lower and significant reduction of thiamine level was observed in the group 1 than the group 2. Nevertheless, both groups of those infants tended to be inadequately fed with the foods except for breast-milk during their early infantile phase.<br><b>Conclusions</b><br> The low concentration of thiamine in the blood and milk of mothers was strongly suggestive that infantile beriberi due to thiamine deficiency was the principal cause of the infant mortality in the study region. We hereby surmise that thiamine deficiency could be extensively prevalent in Lao PDR than the currently studied areas because of their traditional preparing methods of staple dietary rice, postpartum food taboos and intake of thiaminases. For the prevention of infant death due to severe thiamine deficiency, necessary measures including the exchange of information among the institutions concerned, adequate thiamine supplementation and nutritional counseling have to be urgently adopted.