In patients with refractory colorectal cancer, TAS-102, as compared with placebo, was associated with a significant improvement in overall survival. (Funded by Taiho Oncology-Taiho Pharmaceutical; RECOURSE ClinicalTrials.gov number, NCT01607957.).

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).

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Objective: It has been reported that neonatal bone abnormalities occur as a result of long-term intravenous magnesium administration (MgSO₄) to pregnant women. The purpose of this retrospective study was to evaluate the frequency of such abnormalities and the clinical background of both mothers and neonates. PatientsandMethods: We reviewed maternal (114 cases) and neonatal (139 cases) charts from all pregnant women who received intravenous MgSO₄ administration for preterm labor and preeclampsia between June 1 1992, and May 31,1994. All chest X-ray films were obtained within 48 h after birth and reviewed by a doctor who was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the proximal humerus were considered as abnormal. The subjects were divided into affected (group 1 and la) and unaffected (group 2 and 2a) groups. Neonates born to pregnant women given no MgSO₄ at the same period, were considered as control. Results: The total number of bone abnormalities in the offspring of mothers receiving MgSO₄ amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2 of 101 cases. In the control group bone abnormalities were not observed (p < 0.05). Significant differences were found between groups 1 and 2 in the gestational ages at the start of MgSO₄ administration and at delivery, and in the total duration of administration and doses of MgSO₄. Also, cases of multiple pregnancy and pregnancy complicated with impaired glucose tolerance were more prevalent in group 1. According to the results obtained from 139 neonates, cases showing low Apgar and high magnesium score and those receiving respiratory support were more noticeable in group 1 a (15 cases). Conclusions: The gestational ages and the total doses of MgSO₄ in pregnant women were the main factors related to the onset of neonatal bone abnormalities, but other factors also have a possible bearing on the condition. In addition, the cases with onset of bone abnormality seemed to be associated with symptoms attributable to hypermagnesemia of neonates.

Electroconvulsive therapy (ECT) is known as a successful treatment for severe depression. Despite great efforts, the biological mechanisms underlying the beneficial effects of ECT remain largely unclear. In this study, animals received a single, 10, or 20 applications of electroconvulsive seizure (ECS), and then cell proliferation and apoptosis were investigated in the subgranular zone (SGZ) of the dentate gyrus. We analyzed whether a series of ECSs could induce changes in the dentate gyrus in a dose-response fashion. A single-ECS seizure significantly increased cell proliferation in the SGZ by ∼2.3-fold compared to sham treatment. After 10 ECSs, a significant increase in cell proliferation was observed in the SGZ by ∼2.4-fold compared to sham treatment. Moreover, 10 ECSs induced a significant increase in cell proliferation by 1.3-fold compared to a single-ECS group. However, cell proliferation did not differ between the group with 20 ECSs and sham group. In addition, a significant increase in the number of apoptotic cells was found in the group with 10 ECSs, whereas no significant change in it was found in either a single ECS or 20 ECSs group compared to sham treatment. These findings indicate that the optimal number of treatments and duration of stimulation requires investigation. Further studies are needed to elucidate the intracellular mechanisms underlying both effective and excessive ECT.

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Multiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21, n = 10 first and second cohorts, respectively), Parkinson’s disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson’s disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson’s disease patients. Our results shed light on alterations to brain microstructure in MSA.