Gut microbial carbohydrate metabolism contributes to insulin resistance.

Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes1,2. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance3-9. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host's overall energy extraction10, thereby playing a role in the pathogenesis of obesity and prediabetes3,4,6. Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.

Precancerous nature of intestinal metaplasia with increased chance of conversion and accelerated DNA methylation.

OBJECTIVE: The presence of intestinal metaplasia (IM) is a risk factor for gastric cancer. However, it is still controversial whether IM itself is precancerous or paracancerous. Here, we aimed to explore the precancerous nature of IM by analysing epigenetic alterations. DESIGN: Genome-wide DNA methylation analysis was conducted by EPIC BeadArray using IM crypts isolated by Alcian blue staining. Chromatin immunoprecipitation sequencing for H3K27ac and single-cell assay for transposase-accessible chromatin by sequencing were conducted using IM mucosa. NOS2 was induced using Tet-on gene expression system in normal cells. RESULTS: IM crypts had a methylation profile unique from non-IM crypts, showing extensive DNA hypermethylation in promoter CpG islands, including those of tumour-suppressor genes. Also, the IM-specific methylation profile, namely epigenetic footprint, was present in a fraction of gastric cancers with a higher frequency than expected, and suggested to be associated with good overall survival. IM organoids had remarkably high NOS2 expression, and NOS2 induction in normal cells led to accelerated induction of aberrant DNA methylation, namely epigenetic instability, by increasing DNA methyltransferase activity. IM mucosa showed dynamic enhancer reprogramming, including the regions involved in higher NOS2 expression. NOS2 had open chromatin in IM cells but not in gastric cells, and IM cells had frequent closed chromatin of tumour-suppressor genes, indicating their methylation-silencing. NOS2 expression in IM-derived organoids was upregulated by interleukin-17A, a cytokine secreted by extracellular bacterial infection. CONCLUSIONS: IM cells were considered to have a precancerous nature potentially with an increased chance of converting into cancer cells, and an accelerated DNA methylation induction due to abnormal NOS2 expression.

Feasibility of Colorectal Endoscopic Submucosal Dissection in Elderly Patients: The Impact of Sarcopenia.

INTRODUCTION: Colorectal cancer is a public health concern associated with high incidence rates. Sarcopenia is a known risk factor for postoperative complications, although an association between increased complications after colorectal endoscopic submucosal dissection (ESD) and sarcopenia remains undocumented. Herein, we aimed to explore the feasibility of colorectal ESD in patients with sarcopenia. METHODS: This retrospective study included 499 patients (69 with and 430 without sarcopenia). We evaluated the short- and long-term outcomes of colorectal ESD. RESULTS: There were no significant differences between the two groups regarding en bloc, R0, or curative resection rates. However, poor bowel preparation was significantly more common in the sarcopenia group. Moreover, patients with sarcopenia exhibited a significant increase in complications (37.7% vs. 10.5%). Multivariate analysis revealed that sarcopenia (odds ratio [OR]: 3.78, 95% confidence interval [Cl]: 1.85-7.73, p < 0.001), anticoagulation therapy (OR: 3.59, 95% Cl: 1.86-6.92, p < 0.001), procedure time (OR: 1.28, 95% Cl: 1.11-1.47, p < 0.001), and resection size (OR: 1.25, 95% Cl: 1.03-1.52, p = 0.02) were significantly correlated with the Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 2. The correlation between sarcopenia and CTCAE ≥ grade 2 was maintained after matching, resulting in more extended hospital stays in patients with sarcopenia. However, we detected no association between sarcopenia and overall survival and ESD-related death. CONCLUSION: Sarcopenia is a risk factor for complications in colorectal ESD, suggesting that colorectal ESD could be performed for patients with sarcopenia, although much caution should be taken.

Transcriptome analysis reveals the essential role of NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) in gastric adenocarcinoma of fundic-gland type.

BACKGROUND: Gastric adenocarcinoma of fundic-gland type (GA-FG) is a gastric malignancy with little relation to Helicobacter pylori. Clinical characteristics of GA-FG have been established, but molecular mechanisms leading to tumorigenesis have not yet been elucidated. METHODS: We subjected three GA-FG tumors-normal mucosa pairs to microarray analysis. Network analysis was performed for the top 30 up-regulated gene transcripts, followed by immunohistochemical staining to confirm the gene expression analysis results. AGS and NUGC4 cells were transfected with the gene-encoding NK2 homeobox 1/thyroid transcription factor 1 (NKX2-1/TTF-1) to evaluate transcriptional changes in its target genes. RESULTS: Comprehensive gene expression analysis identified 1410 up-regulated and 1395 down-regulated gene probes with ≥ two-fold difference in expression. Among the top 30 up-regulated genes in GA-FG, we identified transcription factor NKX2-1/TTF-1, a master regulator of lung/thyroid differentiation, together with surfactant protein B (SFTPB), SFTPC, and secretoglobin family 3A member 2(SCGB3A2), which are regulated by NKX2-1/TTF-1. Immunohistochemical analysis of 16 GA-FG specimens demonstrated significantly higher NKX2-1/TTF-1 and SFTPB levels, as compared to that in adjacent normal mucosa (P < 0.05), while SCGB3A2 levels did not differ (P = 0.341). Transduction of NKX2-1/TTF-1 into AGS and NUGC4 cells induced transactivation of SFTPB and SFTPC, indicating that NKX2-1/TTF-1 can function as normally in gastric cells as it can in the lung cells. CONCLUSIONS: Our first transcriptome analysis of GA-FG indicates significant expression of NKX2-1/TTF1 in GA-FG. Immunohistochemistry and cell biology show ectopic expression and normal transactivation ability of NKX2-1/TTF-1, suggesting that it plays an essential role in GA-FG development.

Reduced DEFA5 Expression and STAT3 Activation Underlie the Submucosal Invasion of Early Gastric Cancers.

INTRODUCTION: Submucosal invasion is a core hallmark of early gastric cancer (EGC) with poor prognosis. However, the molecular mechanism of the progression from intramucosal gastric cancer (IMGC) to early submucosal-invasive gastric cancer (SMGC) is not fully understood. The objective of this study was to identify genes and pathways involved in the submucosal invasion in EGC using comprehensive gene expression analysis. METHODS: Gene expression profiling was performed for eight cases of IMGC and eight cases of early SMGC with submucosal invasion ≥500 µm. To validate the findings of gene expression analysis and to examine the gene expression pattern in tissues, immunohistochemical (IHC) staining was performed for 50 cases of IMGC and SMGC each. RESULTS: Gene expression analysis demonstrated that the expression levels of small intestine-specific genes were significantly decreased in SMGC. Among them, defensin alpha 5 (DEFA5) was the most downregulated gene in SMGC, which was further validated in SMGC tissues by IHC staining. Gene set enrichment analysis showed a strong association between SMGC, the JAK-STAT signaling pathway, and the upregulation of STAT3-activating cytokines. The expression of phosphorylated STAT3 was significant in the nucleus of tumor cells in SMGC tissues but not in areas expressing DEFA5. CONCLUSION: The results of this study strongly suggest that the downregulation of DEFA5 and the activation of STAT3 play a significant role in the submucosal invasion of EGC.

Risk factors for gastric cancer in Japan in the 2010s: a large, long-term observational study.

BACKGROUND: The numbers of Helicobacter pylori (HP)-infected individuals and deaths due to gastric cancer are decreasing in Japan. We aimed to determine whether the serological test for chronic gastritis (the ABC method) is still useful for gastric cancer risk stratification in the 2010s and to analyze risk factors for developing gastric cancer in Japan. METHODS: In this prospective study, we monitored 20773 individuals for the incidence of gastric cancer from 2010 to 2019. The relationships between blood sampling results, physical examination, and lifestyle in 2010 and the cumulative incidence of gastric cancer were analyzed. RESULTS: A total of 19343 participants who met the study criteria were analyzed. Overall, 0.08% of participants in group A (9/11717), 0.63% in group B (28/4452), 2.05% in group C (43/2098), 1.52% in group D (1/66), and 0.30% in group E (3/1010) developed gastric cancer. Cox hazard analysis showed that age ≥ 50 years; groups B, C, and D according to the ABC method; and current smoking habits were independent risk factors for gastric cancer. The hazard ratios (HRs) of the incidence of gastric cancer were 6.7 in group B and 21.7 in groups C and D, while the HRs of group E was 2.8, which was not significantly different from that of group A. The incidence of gastric cancer was not statistically significantly different between those with and without successful HP eradication in groups B, C, and D during follow-up. CONCLUSIONS: The ABC method was still useful for gastric cancer risk stratification in the 2010s.

Analysis of Barrett's Esophagus and Its Risk Factors: A Cross-Sectional Study of 10,122 Subjects at a Japanese Health Examination Center.

INTRODUCTION: Helicobacter pylori eradication is expected to significantly change the prevalence of Barrett's esophagus (BE). However, few reports on this relationship exist. We analyzed the risk factors of BE using the current consensus on length of BE considering H. pylori infection status. METHODS: We analyzed 10,122 individuals (5,962 men; mean age = 52.9 ± 9.9 years) who had undergone esophagogastroduodenoscopy as part of a medical checkup. Correlations among factors including H. pylori infectious status, endoscopic findings, and BE ≥1 cm were analyzed. RESULTS: Prevalence of BE, long-segment BE, and esophageal adenocarcinoma was 22.5%, 0.014%, and 0%, respectively. Logistic regression analysis showed that the risk factors for BE were hiatal hernia (odds ratio [OR]: 2.89 [2.59-3.24]), female sex (OR: 0.52 [0.46-0.59]), social drinking (OR:0.77 [0.68-0.87]), H. pylori eradication therapy (OR: 1.34 [1.19-1.51]), proton pump inhibitor (PPI) use (OR: 1.52 [1.18-1.96]), bile reflux (OR: 1.18 [1.04-1.33]), age ≥50 years (OR: 1.13 [1.02-1.26]), and nonsteroidal anti-inflammatory drug (NSAID) use (OR: 1.29 [1.02-1.62]). Although reflux esophagitis (RE) was more common in H. pylori-negative patients (17.2%) than in those after H. pylori eradication therapy (11.8%, p < 0.00001), the latter was correlated with BE, disputing RE as a strong risk factor for BE. Therefore, we conducted a subgroup analysis; most of the risk factors except for PPI use (p = 0.75), H2-receptor antagonist use (p = 0.078), and atrophic gastritis absence (p = 0.72) were positively correlated with BE after H. pylori eradication therapy compared with H. pylori-negative status. CONCLUSIONS: H. pylori eradication, bile reflux, PPI use, and NSAID use were risk factors for BE along with hiatal hernia, male sex, and older age.

The impact of sarcopenia on adverse events associated with gastric endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) is one of the main methods of treatments for early gastric cancer. Sarcopenia is a known risk factor for postoperative adverse events; however, the effect of sarcopenia on gastric ESD is unclear. We investigated the impact of sarcopenia on short-term prognosis after gastric ESD. METHODS: This was a retrospective cohort study. We reviewed 832 patients who underwent gastric ESD between January 2015 and December 2019 and classified them into two groups: sarcopenia and non-sarcopenia groups. The curative resection rate, adverse events, and lengths of hospital stay were evaluated. We also evaluated risk factors associated with adverse events. RESULTS: 700 patients were analyzed (239 in the sarcopenia group and 461 in the non-sarcopenia group). The curative resection rates were similar in both groups. Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 2 (17% vs. 10%) were significantly more common, and the length of hospital stay was longer (8 vs. 7 days) in the sarcopenia group. Univariate analysis identified age ≥ 75 years, antithrombotic medication, history of gastric surgery, submucosal (SM) invasion, and sarcopenia as risk factors for CTCAE grade ≥ 2. Multivariate analysis showed that sarcopenia [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-2.89, p = 0.016], history of gastric surgery (OR 9.32, 95% CI 1.97-44.05, p = 0.005), and SM invasion (OR 2.14, 95% CI 1.24-3.70, p = 0.006) were significant independent risk factors. CONCLUSIONS: Sarcopenia significantly affected short-term prognosis and is a novel risk factor for gastric ESD.

Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers?

BACKGROUND AND AIMS: Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes. CONCLUSIONS: Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Possible Gender Difference in the Association Between Abdominal Obesity, Chronic Inflammation, and Preclinical Atherosclerosis in the General Population.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.

Impact of clinical characteristics of colonic diverticular bleeding in extremely elderly patients treated with direct oral anti-coagulant drugs: a retrospective multi-center study.

Since there were no available data about colonic diverticular bleeding in extremely elderly patients (>80 years old) treated with direct oral anticoagulants (DOACs), we tried to determine clinical characteristics in those with colonic diverticular bleeding taking DOACs and to compare clinical outcomes of those in DOAC-treated to those in warfarin-treated . We enrolled DOAC-treated (n = 20) and warfarin-treated (n = 23) extremely elderly patients with diverticular bleeding diagnosed by colonoscopy. We performed a retrospective review of patients' medical charts and endoscopic findings. We classified colonic diverticular bleeding based on endoscopic features due to modified previous study following three groups, type A (active bleeding), type B (non-active bleeding) and type C (bleeding suspected). Clinical outcomes such as number of recurrent bleeding, thrombotic events and mortality were estimated. There were no differences in endoscopical features and clinical characteristics between patients treated with DOAC and warfarin therapy. However, the number of recurrent bleeding, frequency of required blood transfusions and units of blood transfusion in warfarin-treated patients were significantly higher (p<0.05) compared to those in DOAC-treated groups. In addition, mortality and thrombotic events did not differ between DOAC- and warfarin-treated patients. Clinical outcomes suggest that DOACs can be recommended for extremely elderly patients with colonic diverticular disease.

Steroid injection and polyglycolic acid shielding to prevent stricture after esophageal endoscopic submucosal dissection: a retrospective comparative analysis (with video).

BACKGROUND AND AIMS: Postoperative stricture after expansive esophageal endoscopic submucosal dissection (ESD) is a severe adverse event. Previous single-arm reports have suggested that polyglycolic acid (PGA) shielding may prevent stricture. This study was performed to assess the efficacy of this method through a comparative analysis. METHODS: This is a retrospective analysis of 500 consecutive cases of esophageal ESD performed between 2002 and 2018 at the University of Tokyo Hospital. After 2013, patients with a diagnosis of superficial esophageal carcinoma covering more than half of the esophageal circumference underwent preventive treatment with either PGA shielding or steroid injection + PGA shielding after ESD. The efficacy of these methods for preventing post-ESD stricture was assessed through multivariable logistic regression analysis. RESULTS: The risk of postoperative stricture was especially high in the cervical esophagus (odds ratio [OR], 4.60; 95% confidence interval [CI], 0.65-61.09) and after total circumferential resection (OR, 3.58×103; lower bound of 95% CI, >185). Steroid injection + PGA shielding was the only method significantly effective in preventing stricture (OR, 0.30; 95% CI, 0.10-0.78; P = .009). In the relatively low-risk subgroup (excluding cervical esophageal cancer and complete circumferential resection), the postoperative stricture rates for steroid injection + PGA shielding versus PGA shielding versus control were 18.9% versus 41.4% versus 51.7%, respectively (P = .015). However, the efficacy of this was limited in extremely high-risk cases. CONCLUSION: The combination of steroid injection and PGA shielding is effective for preventing post-ESD stricture. There is a need for even more effective methods for cervical esophageal cancer and complete circumferential resection.

Highly accurate artificial intelligence systems to predict the invasion depth of gastric cancer: efficacy of conventional white-light imaging, nonmagnifying narrow-band imaging, and indigo-carmine dye contrast imaging.

BACKGROUND AND AIMS: Diagnosing the invasion depth of gastric cancer (GC) is necessary to determine the optimal method of treatment. Although the efficacy of evaluating macroscopic features and EUS has been reported, there is a need for more accurate and objective methods. The primary aim of this study was to test the efficacy of novel artificial intelligence (AI) systems in predicting the invasion depth of GC. METHODS: A total of 16,557 images from 1084 cases of GC for which endoscopic resection or surgery was performed between January 2013 and June 2019 were extracted. Cases were randomly assigned to training and test datasets at a ratio of 4:1. Through transfer learning leveraging a convolutional neural network architecture, ResNet50, 3 independent AI systems were developed. Each system was trained to predict the invasion depth of GC using conventional white-light imaging (WLI), nonmagnifying narrow-band imaging (NBI), and indigo-carmine dye contrast imaging (Indigo). RESULTS: The area under the curve of the WLI AI system was .9590. The lesion-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the WLI AI system were 84.4%, 99.4%, 94.5%, 98.5%, and 92.9%, respectively. The lesion-based accuracies of the WLI, NBI, and Indigo AI systems were 94.5%, 94.3%, and 95.5%, respectively, with no significant difference. CONCLUSIONS: These new AI systems trained with multiple images from different angles and distances could predict the invasion depth of GC with high accuracy. The lesion-based accuracy of the WLI, NBI, and Indigo AI systems was not significantly different.

Nuclear staining of claudin-18 is a new immunohistochemical marker for diagnosing intramucosal well-differentiated gastric adenocarcinoma.

Diagnosis of gastric adenocarcinoma using small biopsy samples is occasionally difficult. Various markers have been employed for improving the diagnostic accuracy, but there remains room for improvement. A total of 129 endoscopically biopsied samples were studied, consisting of 104 intramucosal tubular adenocarcinomas, 24 non-cancerous lesions and one cancer sample originally suspected of non-cancer but revised as cancer after immunostaining. We evaluated the association between histopathology and immunohistochemical expression of MUC1, HER2, p53, CEA, E-cadherin, ß-catenin and claudin-18. Regarding ß-catenin and claudin-18, not only membranous expression (ß-catenin(M) and claudin-18(M)) but also nuclear expression (ß-catenin(N) and claudin-18(N)) were analyzed. When subtyped with mucin core protein expression, the gastric-type cancers dominantly expressed claudin-18(M), while claudin-18(N) was significantly encountered in intestinal- and mixed-types. Expression of MUC1 (P = 0.0010), HER2 (P = 0.0173), p53 (P = 0.0002), CEA (P = 0.0019) and claudin-18(N) (P < 0.0001) revealed significant correlation with gastric cancers. Negative correlation of claudin-18(M) (P = 0.0125) was also noted. MUC1 and p53 were negative in non-cancer lesions. The non-cancer group exceptionally expressed HER2 and ß-catenin(N). Membranous expression of E-cadherin was consistent in both groups. Logistic regression analysis showed that MUC1 (P = 0.0086), p53 (P = 0.0031), claudin-18(M) (P = 0.0158) and claudin-18(N) (P = 0.0190) were independently associated with gastric cancers. Nuclear expression of claudin-18 should be the novel diagnostic marker for gastric cancer.

Effect of cigarette smoking on carotid artery atherosclerosis: a community-based cohort study.

Cigarette smoking is closely associated with the development of cardiovascular diseases. However, the relationship between cigarette smoking and subclinical atherosclerosis has not been fully studied. We sought to clarify the association between cigarette smoking and carotid intima-media thickness (cIMT) in a general Japanese population. Among 1,209 participants who received a medical check-up with cardiovascular examination at our institution, 450 participants (37.2%) were smokers (including both past and current smokers). We evaluated cIMT as a marker of subclinical atherosclerosis. The value of cIMT and rate of carotid plaque defined as IMT ≥ 1.1 mm did not differ between smokers and never smokers. However, the rate of carotid high-risk atheroma, defined as carotid artery atheroma including hypoechoic dominant and ulceration, was significantly higher among smokers than never smokers (30.4%, vs 23.6%, p = 0.009). Even after adjustment for covariates, cigarette smoking was independently associated with high-risk atheroma formation (odds ratio 1.384, 95% CI 1.019-1.880; p = 0.038). The value of cIMT and the rate of high-risk atheroma were significantly higher in smokers than never smokers in the subgroup of participants aged ≥ 60 years, whereas the rate of high-risk atheroma only was higher in smokers than never smokers in the subgroup of participants aged < 60 years. In conclusion, the development of high-risk carotid artery atheroma may precede the thickening of cIMT in cigarette smokers, which suggests the novel insight for the pathological mechanism underlying cardiovascular events and cigarette smoking.

Association Between Waist Circumference and Carotid Intima-Media Thickness in the General Population.

Waist circumference (WC) is measured for the assessment of abdominal obesity, whereas carotid intima-media thickness (IMT) is a marker of preclinical atherosclerosis. The relationship between WC and carotid IMT in the general population is not fully understood. In this study, we examined 1,182 subjects (658 men and 524 women, 62.3 ± 11.7 years on average) who underwent voluntary health check-ups and sought to determine the optimal cut-off value of WC for predicting carotid IMT thickness. Receiver operating characteristic curve analysis of WC was utilized to predict high carotid IMT (defined as carotid IMT ≥ 1.1 mm). We determined that the appropriate WC cut-off value was a WC ≥ 79 cm for men and women. There was a statistically significant difference in the prevalence of high carotid IMT between WC ≥ 79 cm and WC < 79 cm in both men and women. However, multivariable logistic regression analysis demonstrated that the WC category was independently associated with high carotid IMT in men, but not in women. Our study indicates that the optimal cut-off value of WC to identify preclinical atherosclerosis may be lower than the current Japanese diagnostic criteria for metabolic syndrome (MetS) in both men and women. Compared to women, the association between WC and preclinical atherosclerosis may be more pronounced in men.

Association Between Changes in Body Weight and Fat Weight in Middle Age General Population.

Body weight gain in middle age is thought to be mainly attributable to body fat gain. However, the association between the change in body weight and change in fat weight is not fully understood. In this study, we aimed to clarify the association between the changes in body weight and fat weight in a middle-aged general population using a community-based cohort. We studied 3,193 subjects who underwent health check-ups. Fat weight was measured using a TANITA DC-270A body composition analyzer (Tanita Corporation, Tokyo). Good correlation was observed between the changes in body weight and fat weight (Pearson r = 0.88, P < 0.001). Among the study subjects, 408 (13%) were categorized in the weight loss group (weight loss ≥ 5%), 2,442 (76%) in the weight stable group, and 343 (11%) in the weight gain group (weight gain ≥ 5%). The percentage of change in fat weight in relation to the change in body weight was 65% on average in subjects with body weight loss, and 70% on average in those with body weight gain. Good correlation between changes in body weight and fat weight was observed regardless of age, gender, and baseline body mass index. A change in body weight was closely correlated with a change in fat weight among the middle-aged general population. Body weight change in the middle-age population appears to be mainly attributable to the change in fat weight.

Endoscopic tissue shielding to prevent bleeding after endoscopic submucosal dissection: a prospective multicenter randomized controlled trial.

BACKGROUND: Bleeding after endoscopic submucosal dissection (ESD) is a severe adverse event. Recent reports have described the efficacy of the endoscopic shielding method with polyglycolic acid (PGA) sheets and fibrin glue for the prevention of adverse events after ESD. The aim of the present study was to investigate whether the PGA shielding method provides additional benefit in preventing post-ESD bleeding compared with standard care. METHODS: This was a prospective, multicenter, randomized controlled trial. Patients at high risk of post-ESD bleeding were enrolled in the study. Before ESD, patients were randomized to either the PGA group or the control group. After completing ESD in the PGA group, PGA sheets were placed onto the ulcer floor and adhered with fibrin glue. The primary end point was the post-ESD bleeding rate. RESULTS: 140 eligible patients were enrolled from September 2014 to September 2016, and 137 were included in the intention-to-treat analysis (67 in the PGA group and 70 in the control group). Post-ESD bleeding occurred in three patients (4.5 %) in the PGA group and in four patients (5.7 %) in the control group; there was no significant difference between the two groups (P > 0.99). Post-ESD bleeding tended to occur later in the control group than in the PGA group (median 12.5 days [range 8 - 14] vs. 2 days [range 0 - 7], respectively). CONCLUSION: The PGA shielding method did not demonstrate a significant effect on the prevention of post-ESD bleeding.

Effect of Body Weight Change on Blood Pressure in a Japanese General Population with a Body Mass Index ≥ 22 kg/m2.

The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m2 who underwent health check-ups. Among the study subjects, 175 (15%) were categorized in the weight loss group (weight loss ≥ 5%), 869 (74%) in the weight stable group, and 126 (11%) in the weight gain group (weight gain ≥ 5%). There were no significant differences in baseline BP between the 3 groups. In the weight loss group, systolic and diastolic BP, and the rates of stage 2 (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) and stage 1 hypertension (130 mmHg≤ systolic BP < 140 mmHg or 80 mmHg≤ diastolic BP < 90 mmHg) decreased. In contrast, in the weight gain group, systolic and diastolic BP and the rate of stage 2 hypertension increased. Subgroup analysis showed that the correlation between change in body weight and BP was seen in each subgroup according to age, sex, and BMI. The results of the present study suggest the significance of body weight control for BP control in subjects with BMI ≥ 22 kg/m2.