Background and aims:Lenvatinib(LEN)is a newly developed tyrosine kinase inhibitor,and is approved as a first-line treatment for advanced hepatocellular carcinoma(HCC)in Japan.This retrospective multi-center study investigated the effect of the relative dose intensity(RDI)of LEN on response rate,progression-free survival(PFS),and overall survival(OS). Methods:This retrospective study enrolled 123 patients with advanced HCC who were treated with LEN at six hospitals in Japan between March 2018 and December 2019.These patients were divided into two groups:RDI ≥70％(RDI 70 group,N=70)or RDI＜70％(control group,N=53)in the first 30 days.The following data were compared between groups:patient backgrounds,adverse events,treatment out-comes,PFS,and OS.PFS and OS were analyzed using the Kaplan-Meier method,followed by the log-rank test.To identify significant factors that contributed to response,PFS,and OS,multivariate analysis was performed using factors for which P-values were ＜0.10 in univariate analysis. Results:The proportion of patients with Child-Pugh class 5A was significantly greater in the RDI 70 group than that in the control group(64.3％ vs. 28.3％,P＜0.01).Dose interruption due to adverse events was significantly more common in the control group.The response rate was significantly higher in the RDI 70 group than that in the control group(35.7％ vs. 11.3％,P＜0.01).Median PFS was significantly longer in the RDI 70 group(9.4 vs.4.7 months,P＜0.01).Multivariate analysis showed that RDI ≥70％(hazard ratio(HR)=0.55,P=0.025),hypertension grade ≥2(HR=0.47,P=0.019),and response(HR=0.52,P=0.033)were independently associated with improved PFS.Median OS was also significantly longer in the RDI 70 group(20.0 vs.13.3 months,P=0.045).Multivariate analysis showed that female sex(HR=0.33,P=0.034)and disease control(HR=0.31,P＜0.01)were independently associated with improved OS.RDI ≥70％ was not statistically significant in multivariate analysis. Conclusions:Our study revealed the importance of achieving RDI ≥70％ in the first 30 days of treatment to maximize the effects of LEN.

Before the introduction of high density barium for contrast studies of the upper gastrointestinal tract, we conducted a survey concerning the adverse reactions to a swallow of barium and barium concentration.
The incidence of side effects rose as the density of barium increased but the effects were transient. There were no cases requiring medical treatment.
Furthermore, the constipation group and the normal group were examined separately.
The ratio of adverse reactions was high in the constipation group even when the barium density was low. In this group stool hardening and delayed excertion were also noticed.
The constancy of barium stool excretion was basically normal, and the barium density had little effect.
The effects of a laxative on the excretion consistency were investigated. The administration of a laxative did not always have a positive affect on excretion. The timing of the administration of the laxative and the amount of water intake should be examined in the future.
We also investigated how the patients feel when they are swallowing barium. We found that whether feel uncomfortable or not depended on the properties of barium rather than its density.
From these results it appears that appropriate guidance is necessary about the use of high density barium, in order to supress the occurrence of side effects, especially in the constipation group.

  Aquatic walking, which is influenced by the physical characteristics of water such as buoyancy, resistance, water pressure, and water temperature, is known to be effective for reducing stress on joints and increasing muscular strength. However, there is no consensus on its influence on blood pressure changes in elderly people. To address this uncertainty, we researched the effects of aquatic walking on the blood pressure of elderly people. Study participants were 48 females enrolled in a class to prevent the need for nursing care. In accordance with the diagnostic criteria for hypertension, participants were divided into two groups based on initial blood pressure measurements: a “high blood pressure group” with 27 people and a control group with 21 people. Both groups did the following program once a week for five weeks: 10 minute warmup, 15 minutes of aquatic walking (forward, backward, and sideways walking), 10 minute break, and additional 10 minutes of aquatic walking. Systolic blood pressure, diastolic blood pressure, heart rate, and average blood pressure of the participants were recorded. Results showed that the high blood pressure group showed significant decreases in systolic blood pressure after one week, and significant decreases in both diastolic blood pressure and average blood pressure from three weeks onward. No significant change was evident in the control group. However, comparing values measured immediately before and after aquatic walking showed that the control group had a significant post-aquatic walking increase in both systolic and diastolic blood pressures as well as a significant decrease in heart rate. Similar significant post-aquatic walking increases in systolic and diastolic blood pressures as well as a significant decrease in heart rate was also evident in the high blood pressure group from five weeks onward, once their measured values had improved. These results suggest that continuing an aquatic walking program will lower the blood pressure of elderly individuals meeting the diagnostic criteria for hypertension, but it is necessary to be attentive to physical condition because blood pressure increases immediately after aquatic walking in non-hypertensive individuals.

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

Objective：The purpose of this study was to evaluate the effectiveness of a four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration (SCD), using the Scale for the Assessment and Rating of Ataxia (SARA) total score and sub-score.Methods：This study included 23 SCD patients；we considered those with a SARA gait score of＜3 points. Our program included a one-hour training session with individualized instructions and a one-hour self-balance training session. Additionally, occupational or speech-language-hearing therapy was performed for one hour daily. Our program was conducted five days weekly for four weeks. We assessed the SARA total score and sub-score findings immediately, before the first and after the last interventions.Results：The SARA total, gait, stance, and heel-shin scores showed more significant improvement after intervention than before intervention (p＜0.05). The other SARA sub-scores were not significantly different between “before and after” interventions.Conclusion：The four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration improved the SARA total score and ataxia of the trunk and lower limbs.

Objective：The purpose of this study was to evaluate the effectiveness of a four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration (SCD), using the Scale for the Assessment and Rating of Ataxia (SARA) total score and sub-score.Methods：This study included 23 SCD patients；we considered those with a SARA gait score of＜3 points. Our program included a one-hour training session with individualized instructions and a one-hour self-balance training session. Additionally, occupational or speech-language-hearing therapy was performed for one hour daily. Our program was conducted five days weekly for four weeks. We assessed the SARA total score and sub-score findings immediately, before the first and after the last interventions.Results：The SARA total, gait, stance, and heel-shin scores showed more significant improvement after intervention than before intervention (p＜0.05). The other SARA sub-scores were not significantly different between “before and after” interventions.Conclusion：The four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration improved the SARA total score and ataxia of the trunk and lower limbs.

BACKGROUND: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/μL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/μL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted β of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.
Aged ; Antigens, CD34 ; blood ; Biomarkers ; blood ; Carotid Intima-Media Thickness ; Cross-Sectional Studies ; Hepatocyte Growth Factor ; metabolism ; Humans ; Japan ; Male ; Middle Aged