Attitudes toward using “Simple simulator for calculating nutritional food stocks in preparation for large-scale disasters” among local governmental personnel and public health dietitians in Japan: An explanatory mixed methods study

The Japanese Ministry of Health, Labour and Welfare compiled an Excel sheet — “Simple simulator for calculating nutritional food stocks in preparation for large-scale disasters” (Simulator). We examined the level of recognition and use of the Simulator by local governments and identified the points for its improvement. In stage 1, we surveyed local government personnel who participated in the “Workshop for nutrition assistance during large-scale disasters” held in November 2020 (n = 458; 313 responded) with an online questionnaire on the use of the Simulator and associated issues. Stage 2 involved group interviews with 15 public health dietitians who had been involved in food assistance during past natural disasters to identify points for improving the Simulator and the problems with food assistance during natural disasters. In stage 1, 233 responders (74.4%) confirmed their awareness of the existence of the Simulator. While 85 individuals (36.6%) used the Simulator, 63 individuals (74.1%) confirmed that they would use it in the future to plan and evaluate local government stocks. In stage 2, multiple comments regarding the Simulator''s applicability and improvement in a realistic situation were collected. In order for the administrative staff in charge of disaster management to understand the nutritional importance of stockpiling main/side dishes, it was suggested that specific combinations of foods that meet the required amounts should be shown and that visualization using food products and the number of people covered by stockpiled foods may be easier to understand than pure nutritional values.     

Epipericardial Fat Necrosis: A Retrospective Analysis in Japan

Objective Epipericardial fat necrosis (EFN) has been considered to be a rare cause of acute chest pain, and especially important for emergency physicians. Chest computed tomography (CT) is often used for the diagnosis of EFN after excluding life-threatening states, such as acute coronary syndrome and pulmonary embolism. While the proportion of EFN patients who underwent chest CT in emergency departments is being clarified, little is still known about other departments in Japan. To investigate the proportion of EFN patients who underwent chest CT for acute chest pain in various departments. Methods Chest CT performed from January 2015 to July 2020 in Asahikawa Medical University Hospital in Japan was retrospectively analyzed in this study. All images were reviewed by two radiologists. Results There were 373 outpatients identified by a search using the word ‘chest pain’ who underwent chest CT. Eight patients satisfying the imaging criteria were diagnosed with EFN. The proportions of patients diagnosed with EFN were 10.7%, 4.8%, 2.8%, 0.9% and 0% in the departments of general medicine, cardiovascular surgery, emergency medicine, cardiovascular internal medicine and respiratory medicine, respectively. Only 12.5% of the patients were correctly diagnosed with EFN, and the other patients were treated for musculoskeletal symptoms, acute pericarditis or hypochondriasis. Conclusion EFN is not rare and is often overlooked in various departments. All physicians as well as emergency physicians should consider the possibility of EFN as the cause of pleuritic chest pain.     

Spinocerebellar Ataxia Type 31 Exacerbated by Anti-amino Terminal of Alpha-enolase Autoantibodies

We herein report a 61-year-old woman who was genetically diagnosed with spinocerebellar ataxia type 31 whose symptoms were modified by anti-amino terminal of alpha-enolase (NAE) antibodies, known as a biomarker of Hashimoto''s encephalopathy (HE), and ultimately responded to immunotherapy. The relative titers of anti-NAE antibodies increased when her cerebellar ataxia showed acute deterioration and decreased after immunotherapy. This is the first report of cerebellar ataxia associated with genetic spinocerebellar ataxia with concomitant cerebellar type HE. Physicians should be mindful of measuring anti-NAE antibodies to prevent overlooking patients with genetic spinocerebellar ataxia with treatable simultaneous ataxic diseases.     

Effect of canagliflozin on the decline of estimated glomerular filtration rate in chronic kidney disease patients with type 2 diabetes mellitus: A multicenter,randomized, double‐blind,placebo‐controlled,parallel‐group,phase III study in Japan

Aims/IntroductionThe Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial has shown the effects of canagliflozin on preventing clinically important kidney outcomes in patients with type 2 diabetes mellitus and chronic kidney disease; however, not many Japanese patients were included in the trial. The present study evaluated the efficacy and safety of canagliflozin in Japanese chronic kidney disease patients with type 2 diabetes mellitus.Materials and MethodsIn this multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, chronic kidney disease patients with type 2 diabetes mellitus were randomly assigned to receive either 100 mg canagliflozin or a matching placebo once daily for 104 weeks. The primary efficacy end‐point was the incidence of a 30% decline in estimated glomerular filtration rate.ResultsOverall, 308 patients were randomized to the canagliflozin (n = 154) and placebo (n = 154) groups. The incidence of a 30% decline in estimated glomerular filtration rate at week 104 was 18.2% and 29.5%, respectively, and the point estimate of the intergroup difference (placebo − canagliflozin) was 11.3% (95% confidence interval 1.2–21.5, P = 0.029), which was significant. The overall incidence of adverse events was similar in the two groups.ConclusionsThis study suggests that canagliflozin safely reduces the risk of end‐stage renal disease in Japanese chronic kidney disease patients with type 2 diabetes mellitus.     

SARC-F scores can predict health status and daily activity in patients with idiopathic pulmonary fibrosis

BackgroundThe strength, assistance in walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) is widely used for screening sarcopenia. We aimed to examine the association of SARC-F scores with the measurements of quality of life and activity in patients with idiopathic pulmonary fibrosis (IPF).MethodsThis cross-sectional pilot study prospectively enrolled 54 patients with IPF who completed pulmonary function tests, the 6-min walk test, the chronic obstructive pulmonary disease assessment test (CAT), St. George’s Respiratory Questionnaire (SGRQ), the Hospital Anxiety and Depression Scale, and a daily step count. The daily step count was measured continuously for 7 consecutive days using a tri-axis accelerometer device.ResultsThe mean age was 73.6±7.9 years and the mean percent predicted forced vital capacity was 80.4%±15.6%. The median [interquartile range] SARC-F score, SGRQ total scores, and CAT scores were 2 [1–3.25], 28.8 [14.4–46.9], and 13 [7–22], respectively. SARC-F scores were correlated with the percent predicted forced vital capacity (r=−0.51, P<0.001), CAT score (r=0.57, P<0.001), SGRQ total score (r=0.77, P<0.001), Hospital Anxiety and Depression Scale anxiety score (r=0.31, P=0.025), and Hospital Anxiety and Depression Scale depression score (r=0.28, P=0.041). Linear regression analyses revealed that the 6-minute walk test (6MWT) (standardized β=0.33, P=0.011) and SARC-F score (standardized β=−0.39, P=0.005), but not the CAT score and SGRQ total score, were significant predictors for daily step count.ConclusionsSARC-F scores were correlated with health status and daily activity in patients with IPF. Further studies are warranted to validate the utility of the SARC-F in patients with IPF.     

Effect Estimate of Time-varying Social Support and Trust on the Physical and Mental Health of Mothers at 2.5 Years Postpartum: The Japan Environment and Children’s Study (JECS)

BackgroundMany epidemiological studies have reported the association between various social factors and health status in mothers during and after pregnancy. However, little is known about their joint and longitudinal impact. We examined the association of lack of social support and trust during pregnancy and at 2.5 years postpartum with health status in mothers.MethodsTo adequately address time-varying exposure, marginal structural models were fitted to a pseudopopulation constructed using inverse probability weighting. The model included records of 90,071 mothers participating in the Japan Environment and Children’s Study. Social support and trust were measured using a 9-item questionnaire (Q1–9). Mental and physical health were measured using Mental and Physical Component Summary scores from the 8-item Short-Form Health Survey.ResultsFor the Mental Component Summary, the magnitude of the effect estimate was largest when participants lacked close friends/neighbors (Q4) at only 2.5 years postpartum (effect estimate, −6.23), followed by a lack in emotional support (Q2) at the same time point (effect estimate, −4.94). For the Physical Component Summary, effect estimates were negligible. The magnitude of the effect estimates of lack of social support and trust tended to be larger when there was a lack at only 2.5 years postpartum than at both time points.ConclusionThese findings suggest that, after childbirth, a loss in social support, particularly in an emotional aspect, carries high risk, especially for mental health. Our results highlight the importance of supporting mothers for more than a few years after pregnancy.Key words: SF-8, emotional support, inverse probability of treatment weighting, causal association, pregnant women     

Downregulation of microRNA‐100/microRNA‐125b is associated with lymph node metastasis in early colorectal cancer with submucosal invasion

A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation, despite a very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR‐100 and miR‐125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real‐time PCR in a larger set of clinical samples. The transfection of a miR‐100 or miR‐125b inhibitor into colon cancer HCT116 cells significantly increased cell invasion, migration, and MMP activity. Conversely, overexpression of miR‐100 or miR‐125b mimics significantly attenuated all these activities but did not affect cell growth. To identify target mRNAs, we undertook a gene expression array analysis of miR‐100‐silenced HCT116 cells as well as negative control cells. The Ingenuity Pathway Analysis, TargetScan software analyses, and subsequent verification of mRNA expression by real‐time PCR identified mammalian target of rapamycin (mTOR) and insulin‐like growth factor 1 receptor (IGF1R) as direct, and Fas and X‐linked inhibitor‐of‐apoptosis protein (XIAP) as indirect candidate targets for miR‐100 involved in lymph node metastasis. Knockdown of each gene by siRNA significantly reduced the invasiveness of HCT116 cells. These data clearly show that downregulation of miR‐100 and miR‐125b is closely associated with lymph node metastasis in submucosal CRC through enhancement of invasion, motility, and MMP activity. In particular, miR‐100 may promote metastasis by upregulating mTOR, IGF1R, Fas, and XIAP as targets. Thus, miR‐100 and miR‐125b may be novel biomarkers for lymph node metastasis of early CRCs with submucosal invasion.     

Comparison of advanced adenocarcinomas of esophagogastric junction and distal stomach in Japanese patients

Background

There have been no reports on the incidence, characteristics, treatment outcomes, and prognosis of inoperably advanced or recurrent adenocarcinoma of the esophagogastric junction (AEGJ) in Japan.

Methods

We investigated the clinicopathological characteristics, treatment outcomes, and prognosis for 816 patients with esophagogastric junctional and gastric adenocarcinoma who received first-line chemotherapy between 2004 and 2009.

Results

Of 816 patients, 82 (10 %) had AEGJ. The patients with AEGJ had significantly more lung and lymph node metastasis, but less peritoneal metastasis, than those with gastric adenocarcinoma (GAC). The objective response rate to first-line chemotherapy was 23.3 % for patients with AEGJ and 22.6 % in patients with GAC (p = 0.90). The median survival was 13.0 months in AEGJ and 11.8 months in GAC (p = 0.445). In no patient was tumor site a significant prognostic factor (p = 0.472). In patients with AEGJ, ECOG PS ≥ 2, presence of liver metastasis, and absence of lung metastasis were significantly associated with poor prognosis.

Conclusions

No significant differences were observed in treatment outcomes between advanced AEGJ and GAC. Therefore, the same chemotherapy regimen can be given as a treatment arm in future Japanese clinical trials to both patients with inoperably advanced or recurrent AEGJ and those with GAC.     

Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers

Accumulating evidence suggests that post‐diagnostic insulin levels may influence colorectal cancer (CRC) survival. Yet, no previous study has examined CRC survival in relation to a post‐diagnostic diet rich in foods that increase post‐prandial insulin levels. We hypothesized that glycemic and insulin scores (index or load; derived from food frequency questionnaire data) may be associated with survival from specific CRC subtypes sensitive to the insulin signaling pathway. We prospectively followed 1,160 CRC patients from the Nurses' Health Study (1980–2012) and Health Professionals Follow‐Up Study (1986–2012), resulting in 266 CRC deaths in 10,235 person‐years. CRC subtypes were defined by seven tumor biomarkers (KRAS, BRAF, PIK3CA mutations, and IRS1, IRS2, FASN and CTNNB1 expression) implicated in the insulin signaling pathway. For overall CRC and each subtype, hazard ratio (HR) and 95% confidence interval (95% CI) for an increase of one standard deviation in each of glycemic and insulin scores were estimated using time‐dependent Cox proportional hazards model. We found that insulin scores, but not glycemic scores, were positively associated with CRC mortality (HR = 1.19, 95% CI = 1.02–1.38 for index; HR = 1.23, 95% CI = 1.04–1.47 for load). The significant positive associations appeared more pronounced among PIK3CA wild‐type cases and FASN‐negative cases, with HR ranging from 1.36 to 1.60 across insulin scores. However, we did not observe statistically significant interactions of insulin scores with PIK3CA, FASN, or any other tumor marker (p interaction > 0.12). While additional studies are needed for definitive evidence, a high‐insulinogenic diet after CRC diagnosis may contribute to worse CRC survival.