ObjectivesThis is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer’s disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients.Patients and methodsThis was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10–25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined.ResultsThe tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions.ConclusionThe modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).

Altered peripheral carbonyl stress markers, high levels of serum pentosidine, which accumulates following carbonyl stress, and low levels of pyridoxal (vitamin B6), which detoxifies reactive carbonyl compounds, have been reported in a cross-sectional study of chronic schizophrenia. However, changes in the levels of these compounds in patients with schizophrenia have not been investigated in a longitudinal study. To clarify whether these markers may be biological markers that reflect the clinical course of the disease, the serum levels of these compounds were investigated in a cross-sectional and a longitudinal study. One hundred and thirty-seven acute-stage Japanese patients were enrolled. Among these, 53 patients were followed from the acute stage to remission. A portion of patients in the acute stage (14 cases, 10.2%) showed extremely high pentosidine levels. These levels were not associated with the severity of symptoms but were associated with antipsychotic dose amounts. Pyridoxal levels were lower in schizophrenia and increased according to the clinical course of the illness. Furthermore, 18 patients with decreased pyridoxal levels according to the clinical course showed that the greater the decrease in pyridoxal levels, the lesser the improvement in symptoms. Thus, extremely high pentosidine levels in a portion of patients may be caused by higher daily antipsychotic doses, whereas pyridoxal levels were lower in schizophrenia and increased according to the clinical course. Patients with decreasing pyridoxal levels during the clinical course showed less improvement in symptoms. Carbonyl stress markers may also be therapeutic biological markers in some patients with schizophrenia.

Introduction Several studies have demonstrated that non-small cell lung cancer patients (NSCLCs) harboring epidermal growth factor receptor (EGFR) mutations have poor clinical outcomes in response to treatment with programmed death-1 (PD-1) inhibitors. However, it remains unclear whether EGFR-mutated NSCLCs with a high programmed death-ligand-1 (PD-L1) expression (tumor proportion score ≥ 50%) respond to PD-1 inhibitors. Methods We retrospectively investigated the NSCLCs who had received PD-1 inhibitors between January 2016 and December 2018 to assess the efficacy of PD-1 inhibitors in patients with an EGFR mutation and high PD-L1 expression. Results There were 153 patients with a high PD-L1 expression level, and the median progression-free survival (mPFS) was 5.3 months [95% confidence interval (CI) 1.3-12.4 months] in the patients with EGFR mutations (n = 17) and 8.3 months (95% CI 6.0-11.7 months) in those with wild-type EGFR (n = 136; hazard ratio (HR) 1.62; 95% CI 0.83-2.87). Among the 110 patients in the low PD-L1 expression group, the mPFS was 1.6 months (95% CI 1.3-5.9 months) in the patients with EGFR mutations (n = 18) and 3.8 months (95% CI 2.5-5.9 months) in those with wild-type EGFR (n = 92; HR 2.59; 95% CI 1.48-4.31). The HR for PFS in the group with EGFR mutations and high PD-L1 expression was 0.97 (95% CI 0.56-1.59) compared to the group with wild-type EGFR and low PD-L1 expression. Conclusions PD-1 inhibitors can serve as one of the treatment options for NSCLCs with an EGFR mutation and high PD-L1 expression.

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