Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Background: This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Methods: Data from 600 older adults (mean age, 74.1±6.4 years; women, 62.0%) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS; maximum 30 points) by assessing the 1-week consumption frequencies of ten foods. An FFS of ≤16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: “Do you engage in moderate levels of physical exercise or sports aimed at health?” and “Do you engage in low levels of physical exercise aimed at health?” Participants who responded “No” to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. Results: The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio=2.80, 95% confidence interval 1.22–6.28). Conclusion The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Background: This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Methods: Data from 600 older adults (mean age, 74.1±6.4 years; women, 62.0%) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS; maximum 30 points) by assessing the 1-week consumption frequencies of ten foods. An FFS of ≤16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: “Do you engage in moderate levels of physical exercise or sports aimed at health?” and “Do you engage in low levels of physical exercise aimed at health?” Participants who responded “No” to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. Results: The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio=2.80, 95% confidence interval 1.22–6.28). Conclusion The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Background: This study aimed to investigate the potential association between the combination of low physical activity and low dietary diversity with mild cognitive impairment (MCI) in older Japanese adults. Methods: Data from 600 older adults (mean age, 74.1±6.4 years; women, 62.0%) were analyzed. We evaluated dietary variety based on the Food Frequency Score (FFS; maximum 30 points) by assessing the 1-week consumption frequencies of ten foods. An FFS of ≤16 indicated low dietary diversity. We assessed MCI using the National Center for Geriatrics and Gerontology Functional Assessment Tool. Physical activity levels was determined based on participant responses to two questions: “Do you engage in moderate levels of physical exercise or sports aimed at health?” and “Do you engage in low levels of physical exercise aimed at health?” Participants who responded “No” to both questions were classified as having low physical activity levels. We classified the participants into robust, low-dietary diversity, low-physical activity, and coexistence groups. Results: The overall prevalence of MCI was 20.7%, with rates in the robust, low dietary diversity, low physical activity, and coexistence groups of 17.7%, 24.7%, 25.0%, and 41.9%, respectively. Multiple logistic regression analysis revealed that low dietary diversity and physical activity were associated with MCI in older adults (odds ratio=2.80, 95% confidence interval 1.22–6.28). Conclusion The results of the present study demonstrated the association of the co-occurrence of low dietary diversity and low physical activity with MCI. Older adults with both risk factors may require early detection, as well as physical activity and dietary interventions.

Background: Dementia is a critical late-life health issue that occurs among members of aging societies. This study examined the relationships between eating out, dietary diversity, and mild cognitive impairment (MCI) among community-dwelling older adults. Methods: We analyzed data from 597 older adults (median age 73.0 years, interquartile range 69.0–78.0 years; 62.6% females). We applied the food frequency score to evaluate diet variety and the weekly consumption frequencies of ten food items were determined. The National Center for Geriatrics and Gerontology Functional Assessment Tool (NCGG-FAT) was used to evaluate MCI. Finally, we asked the participants how often they ate out each month; those who replied "none" were categorized into the "non-eating out" group. Results: The overall prevalence of MCI was 122 (20.4%), with a higher prevalence in the low dietary diversity group than in the high dietary diversity group (28.6% vs. 18.6%). After adjusting for covariates, the participants who self-described as not eating out were independently associated with low dietary diversity (odds ratio [OR]=1.97, 95% confidence interval [CI] 1.20–3.20), while low dietary diversity was associated with MCI (OR=1.72; 95% CI 1.02–2.87). Structural equation models revealed that not eating out had no direct effect on MCI but was associated with MCI via low dietary diversity (root mean square error of approximation=0.030, goodness-of-fit index=0.999, and adjusted goodness-of-fit index=0.984). Conclusions Although non-eating out may not have a direct effect on MCI, an indirect relationship may exist between eating-out habits and MCI via dietary diversity status.

Complex anatomical restrictions can lead to further interventions after the emergence of a postoperative aneurysm enlargement in thoracic endovascular aortic repair (TEVAR) for a thoracoabdominal aortic aneurysm (TAAA). A 75-year-old male underwent a TEVAR for a Crawford extent I TAAA. The main device and the distal extension were placed using a fenestrated technique, outside of the instructions for use. The aneurysm expanded because of an endoleak and stent graft migration; and was surgically repaired by fully salvaging the previous endografts 38 months after the first TEVAR. However, the distal extension, which was the proximal anastomosis site with a prosthetic graft, became completely dislocated from the main device eight months after the open surgical conversion, resulting again in the enlargement of the aneurysm. An additional TEVAR was successfully performed to correct the dislocated stent graft. An appropriate treatment strategy is crucial to prevent multiple reinterventions for TAAA with complex anatomical restrictions.

Neoadjuvant chemotherapyeoadjuvant chemoradiotherapy (NAC/NACRT) can be performed in patients with pancreatic cancer to improve survival. We aimed to clarify the clinical outcomes of biliary drainage with a metal stent (MS) or a plastic stent (PS) during NAC/NACRT. Between October 2013 and April 2016, 96 patients with pancreatic cancer were registered for NAC/NACRT. Of these, 29 patients who underwent biliary drainage with MS or PS before NAC/NACRT and a subsequent pancreatoduodenectomy were retrospectively analyzed with regard to patient characteristics, preoperative recurrent biliary obstruction rate, NAC/NACRT delay or discontinuation rate, and operative characteristics. The median age of the patients was 67 years. NAC and NACRT were performed in 14 and 15 patients, respectively, and MS and PS were used in 17 and 12 patients, respectively. Recurrent biliary obstruction occurred in 6% and 83% of the patients in the MS and PS groups, respectively (p<0.001). NAC/NACRT delay was observed in 35% and 50% of the patients in the MS and PS groups, respectively (p=0.680). NAC/NACRT discontinuation was observed in 12% and 17% of the patients in the MS and PS groups, respectively (p=1.000). The operative time in the MS group tended to be longer than that in the PS group (625 minutes vs 497 minutes, p=0.051), and the operative blood loss volumes and postoperative adverse event rates were not different between the two groups. MS was better than PS from the viewpoint of preventing recurrent biliary obstruction, although MS was similar to PS with regards to perioperative outcomes.

BACKGROUND/AIMS: Although studies using conventional animal models have shown that specific stressors cause irritable bowel syndrome (IBS), it is unclear whether depression itself causes IBS. Our aim was to establish a rat model to determine if depression itself promotes the onset of IBS and to elucidate the role of gut microbiota in brain-gut axis pathogenesis during coincident depression and IBS. METHODS: Rat models of depression were induced using our shuttle box method of learned helplessness. Visceral hypersensitivity was evaluated by colorectal distension (CRD) to diagnose IBS. Gut microbiota compositions were analyzed using high-throughput sequencing. In the subanalysis of rats without depression-like symptoms, rats with posttraumatic stress disorder (PTSD) were also examined. RESULTS: The threshold value of CRD in depressed rats was significantly lower than that in control rats. Microbial community analysis of cecal microbiota showed that the relative abundance of Clostridiales incertae sedis, the most prevalent microbe, was significantly lower in depressed rats than in control rats. The distribution pattern of the microbiota clearly differed between depressed rats and control rats. Neither visceral hypersensitivity nor the composition of gut microbiota was altered in rats with PTSD-like phenotypes. CONCLUSIONS: Our rat model of depression is useful for clarifying the effect of depression on IBS and suggests that depression itself, rather than specific stressors, promotes the onset of IBS. Further, we provided evidence that various psychiatric diseases, viz., depression and PTSD, are associated with unique gut microbiota profiles, which could differentially affect the onset and progression of coincident IBS.
Animals ; Clostridiales ; Depression ; Dysbiosis ; Gastrointestinal Microbiome ; Helplessness, Learned ; Hypersensitivity ; Irritable Bowel Syndrome ; Methods ; Microbiota ; Models, Animal ; Phenotype ; Rats ; Stress Disorders, Post-Traumatic

A 69-year-old woman complained of general malaise. Chest X-ray film revealed massive left-sided pleural effusion and CT detected a giant aneurysm of the aortic arch. A diagnosis of ruptured aortic arch aneurysm was made and she underwent total arch replacement as emergency surgery. The intraoperative diagnosis was not a ruptured arch aneurysm but an arch aneurysm penetrating into the left pulmonary artery. The postoperative course was uneventful and the patient was discharged home on the 16th postoperative day.