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Abstract The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04–1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04–1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding.

Abstract In addition to testosterone, various endocrine hormones, such as dehydroepiandrosterone sulfate (DHEA-S) and estradiol, may be involved in erectile function. However, the role of these sex hormones in the erectile function of men without hypoandrogenism remains unclear. This cross-sectional study included 398 community-dwelling men without hypoandrogenism. The participants were categorized into the non-ED and ED groups. Multivariable logistic regression analyses were performed to investigate the relationship between ED and serum sex hormone levels, including total testosterone, DHEA-S, estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin. Among the 398 men, 66 (17%) and 332 (83%) were categorized into the non-ED and ED groups, respectively. In the multivariable analyses, serum DHEA-S and estradiol levels were significantly associated with ED (odds ratio [OR]: 0.996, P = 0.030; OR: 1.082, P = 0.002; respectively), whereas serum total testosterone, LH, FSH, and prolactin levels did not demonstrate significant association. After adjusting for age, none of neutrophil-to-lymphocyte ratio, serum plasminogen activator inhibitor-1 levels, and skin advanced glycation end-products levels demonstrated significant correlation with serum DHEA-S and estradiol levels. In conclusion, lower testosterone levels did not affect ED in men with normal testosterone levels, whereas serum DHEA-S and estradiol levels were significantly associated with ED.

Abstract In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer’s disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76–1.43), 1.68 (95%CI 1.08–2.61), and 1.51 (95%CI 1.08–2.11) for 1.0–1.9 mg/L, 2.0–2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to

Abstract The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P

The purpose of this study is to facilitate knowledge discovery about the relationship between driving and health among the elderly. In the Iwaki Health Promotion Project that is an annual project conducted by Hirosaki University, we have included a survey on driving for the first time in 2019. After linking the data obtained from the survey with four years of health data for 2016–2019, we have utilized PLSA as a machine learning method to cluster those data in an integrated manner. As a result, we have found latent classes broadly classified according to whether the health level has been generally high or low. Also, when we have focused on a specific health item, for example, cognitive function, we have found some people with higher and lower maintenance of cognitive function over four years, even if they have belonged to a same latent class. To characterize these differences in detail, we have utilized t-SNE as a machine learning method. As a result, we have found that “I like driving” as a factor related to the Kansei (sensitivity) may characterize the high maintenance of cognitive function. For those who like driving, it is considered that the high maintenance of cognitive function may be occurred because they enjoy driving, have a wider range of activities, and increase the possibility of multitasking.

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults. Methods: This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P

Abstract Objectives This study aimed to clarify the disinfectant efficacy of the 222‐nm far ultraviolet‐C (UV‐C) during esophagogastroduodenoscopy using bacterial cultures. Methods The endoscopists performed esophagogastroduodenoscopy wearing a gown with a tryptic soy agar medium plate on their epigastric region and were divided into two groups: 222‐nm far UV‐C irradiation (UV group) and non‐UV irradiation (non‐UV group). As a control group, tryptic soy agar medium plates were placed about 110 cm above the floor. The incidence of bacterial contamination was determined by positive bacterial culture. The cultured bacteria were identified by 16S rRNA sequencing. Additionally, the actual UV exposure dose was measured using the UV‐indicator card which changed colors upon exposure to 222 nm far UV‐C. Results The bacterial culture positivity in the UV group (5.03%) was significantly lower than that in the non‐UV group (25.76%), p < 0.0001. Most of the bacteria identified in the UV and non‐UV groups were normal constituents of the oral flora, including Streptococcus salivarius and Staphylococci. Conversely, pathogenic microbes were found in the control group. The actual exposure doses of 222‐nm far UV‐C at the endoscopists’ face, neck, and epigastric region were 2.09 ± 0.29, 5.89 ± 0.49, and 7.36 ± 0.58 mJ/cm2, respectively. Conclusions The 222‐nm far UV‐C irradiation reduced bacterial contamination for endoscopists. It can be used with conventional physical coverings to provide more effective infection control.

Abstract Objectives The whole picture of the disturbance in endoscopy performance caused by the coronavirus disease 2019 (COVID‐19) pandemic in Japan remains to be clarified. Therefore, the Japan Gastroenterological Endoscopy Society‐Tohoku conducted this questionnaire survey in Tohoku region of Japan. Methods A questionnaire on the number of diagnostic endoscopy procedures and resulting diagnosed cancers in 2019 and 2020 was sent to all guidance/guidance cooperation hospitals in the Japan Gastroenterological Endoscopy Society who worked in the Tohoku region. The percentage change was calculated by comparing the numbers in 2020 with those in 2019 (the pre‐COVID‐19 period). Results Among the applicable 89 guidance/guidance cooperation hospitals, 83 (94%) returned the questionnaire. The number of endoscopy procedures promptly decreased to the nadir in April and May 2020 (during the first state of emergency in Japan); however, it recovered relatively quickly, within a few months after the state of emergency was lifted. Consequently, the annual reduction in the number of endoscopy procedures in 2020 (in comparison to 2019) was 10.1% for esophagogastroduodenoscopy and 7.9% for colonoscopy. The reduction in the number of diagnostic endoscopy procedures led to a 5.5% reduction in esophagogastric cancer and 2.7% in colorectal cancer. Conclusions This is the most comprehensive survey on the impact of the COVID‐19 pandemic on the performance of endoscopy and the resulting diagnosis of cancer in Japan. Understanding the magnitude of the decline in endoscopic examinations and cancer detection due to the pandemic is critical to understanding how many people will ultimately be affected and establishing a strategy for providing endoscopy during national emergencies.

Abstract Background Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. Materials and methods A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten’s classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. Results Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. Conclusion The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. Level of evidence Level III, retrospective case–control study.

This study aimed to investigate the effect of Japanese dietary patterns on metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis. After excluding factors affecting the diagnosis of hepatic steatosis, 727 adults were analyzed as part of the Health Promotion Project. The dietary patterns of the participants were classified into rice, vegetable, seafood, and sweet based on their daily food intake. Liver stiffness measurements and controlled attenuation parameters were performed using FibroScan. Energy and nutrient intake were calculated using the Brief-type Self-administered Diet History Questionnaire. Univariate and multivariate analyses were used to identify the risk factors for liver fibrosis within the MASLD population. The vegetable group had significantly lower liver fibrosis indicators in the MASLD population than the rice group. The multivariate analysis identified a body mass index ≥ 25 kg/m2 (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.01–1.83; p = 0.047) and HOMA-IR ≥ 1.6 (OR, 3.18; 95% CI, 1.74–5.78; p < 0.001) as risk factors for liver fibrosis, and vegetable group membership was a significant low-risk factor (OR, 0.38; 95% CI, 0.16–0.88; p = 0.023). The multivariate analysis of nutrients in low-risk foods revealed high intake of α-tocopherol (OR, 0.74; 95% CI, 0.56–0.99; p = 0.039) as a significant low-risk factor for liver fibrosis. This study suggests that a vegetable-based Japanese dietary pattern, through the antioxidant effects of α-tocopherol, may help prevent liver fibrosis in MASLD and the development of MASLD.

Abstract Although altered networks inside the hippocampus (hippocampal intra-networks) have been observed in dementia, the evaluation of hippocampal intra-networks using magnetic resonance imaging (MRI) is challenging. We employed conventional structural imaging and incident component analysis (ICA) to investigate the structural covariance of the hippocampal intra-networks. We aimed to assess altered hippocampal intra-networks in patients with mild cognitive impairment (MCI). A cross-sectional study of 2122 participants with 3T MRI (median age 69 years, 60.9% female) were divided into 218 patients with MCI and 1904 cognitively normal older adults (CNOA). By employing 3D T1-weighted imaging, voxels within the hippocampus were entered into the ICA analysis to extract the structural covariance intra-networks within the hippocampus. The ICA extracted 16 intra-networks from the hippocampal structural images, which were divided into two bilateral networks and 14 ipsilateral networks. Of the 16 intra-networks, two (one bilateral network and one ipsilateral networks) were significant predictors of MCI from the CNOA after adjusting for age, sex, education, disease history, and hippocampal volume/total intracranial volume ratio. In conclusion, we found that the relationship between hippocampal intra-networks and MCI was independent from the hippocampal volume. Our results suggest that altered hippocampal intra-networks may reflect a different pathology in MCI from that of brain atrophy.

Abstract Background and Aim While short and long attachment caps are available for colonoscopy, it is unclear which type is more appropriate for stigmata of recent hemorrhage (SRH) identification in acute hematochezia. This study aimed to compare the performance of short versus long caps in acute hematochezia diagnoses and outcomes. Methods We selected 6460 patients who underwent colonoscopy with attachment caps from 10 342 acute hematochezia cases in the CODE BLUE‐J study. We performed propensity score matching (PSM) to balance baseline characteristics between short and long cap users. Then, the proportion of definitive or presumptive bleeding etiologies found on the initial colonoscopy and SRH identification rates were compared. We also evaluated rates of blood transfusions, interventional radiology, or surgery, as well as the rate of rebleeding and mortality within 30 days after the initial colonoscopy. Results A total of 3098 patients with acute hematochezia (1549 short cap and 1549 long cap users) were selected for PSM. The rate of colonic diverticular bleeding (CDB) diagnosis was significantly higher in long cap users (P = 0.006). While the two groups had similar rates of the other bleeding etiologies, the frequency of unknown etiologies was significantly lower in long cap users (P

Purpose: To investigate the association between skin advanced glycation end-products (AGEs) levels, blood antioxidative vitamin and carotenoid concentrations, and severe erectile dysfunction (ED) in community-dwelling men. Materials and Methods: This cross-sectional study used the 5-Item International Index of Erectile Function to identify 335 community- dwelling men with ED. The accumulation of skin AGEs was assessed noninvasively by measuring skin autofluorescence. Background-adjusted multivariable logistic regression analyses using the inverse probability of treatment weighting method were performed to evaluate the effects of AGEs, vitamins, and carotenoids on severe ED. Moreover, multiple linear regression analyses were performed to assess the association between skin AGEs levels and serum carotenoid concentrations. Results: The median age of study participants was 57 years. Of the 335 men, 289 (86.3%) and 46 (13.7%) were classified into the mild/moderate and severe ED groups, respectively. Multivariable analyses revealed that skin AGEs levels, blood vitamins C and E, lutein, zeaxanthin, β-cryptoxanthin, α-carotene, β-carotene, total lycopene, and cis-lycopenes concentrations were significantly associated with severe ED, whereas all-trans lycopene concentrations were not. In the multiple linear regression analyses, serum zeaxanthin concentrations were negatively and significantly correlated with skin AGEs levels. Conclusions: Higher skin AGEs levels and lower blood antioxidative vitamin and carotenoid concentrations were significantly associated with severe ED. Serum zeaxanthin levels were negatively and significantly correlated with skin AGEs levels, suggesting the possible effects of zeaxanthin on ED by decreasing tissue AGEs levels.

Abstract Aims/Introduction Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non‐producers and type 2 diabetes. Materials and Methods The participants included 147 patients with type diabetes mellitus aged 70–89 years, and 147 age‐ and sex‐matched controls. To ascertain the equol producers or non‐producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut‐off value −1.75). Results The urinary equol concentration was significantly lower in the diabetes group compared with the non‐diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non‐diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non‐diabetes group (52.8%; P

Background: Decreased gut microbiota diversity is associated with gut dysbiosis and causes various diseases, including allergic diseases. We investigated the relationship between gut microbial diversity and sensitization to major inhaled allergens. Furthermore, the relationship of allergic symptom onset with bacterial composition in sensitized individuals was investigated. Methods: This study included 1092 local residents who had participated in the Iwaki Health Promotion Project in 2016. Blood samples were analyzed to ascertain specific IgE levels against major inhaled allergens (JCP, HD1, Grass-mix, Weed-mix). Nasal symptoms were estimated by questionnaires. Fecal samples were analyzed for bacterial 16S rRNA using next generation sequencing. The diversity index (α-diversity, β-diversity) and the composition of gut microbes in phylum/order levels were compared between patients sensitized or unsensitized to allergen, and symptomatic and asymptomatic groups. Results: Some α-diversity metrics were significantly decreased in patients who were sensitized to any/all four allergens compared with the unsensitized group. β-diversity differed significantly between those unsensitized and sensitized to all allergens (aged 20–49 years), and between those unsensitized and sensitized to any/all four allergens (aged ≥50 years). The relative abundance of Bacteroidales was significantly lower in the unsensitized than in the sensitized group. The composition and diversity of gut microbiota were similar between the symptomatic and asymptomatic groups. Conclusions: Our results suggest that lack of diversity in gut microbiota has an effect on sensitization to allergens. Bacteroidales in order level may affect sensitization; however, the onset of allergy symptoms was not significantly associated with bacterial composition and diversity.

The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men (n = 442) and women (n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: β = 0.18, CI: 0.04–0.31, p = 0.009; women: β = 0.07, CI: 0.00–0.12, p = 0.028). Blautia, Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman’s correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella, coupled with a decrease in Faecalibacterium, may contribute to muscle strengthening or the suppression of muscle weakness.

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.

Abstract Objectives We surveyed and reported low protective equipment usage and insufficient knowledge among endoscopy‐fluoroscopy departments in Japan in 2020. Two years later, we conducted a follow‐up survey of doctors, nurses, and technologists in Japan. Methods We conducted a questionnaire survey on radiation protection from May to June 2022. The participants were medical staff, including doctors, nurses, and radiological and endoscopy technicians in endoscopy‐fluoroscopy departments. The questionnaire included 17 multiple‐choice questions divided into three parts: background, equipment, and knowledge. Results We surveyed 464 subjects from 34 institutions. There were 267 doctors (58%), 153 nurses (33%), and 44 technologists (9%). The rate of wearing a lead apron was 98% in this study. The rates of wearing a thyroid collar, lead glasses, and radiation dosimeter were 27%, 35%, and 74%, respectively. The trend of the protective equipment rate was similar to that of our previous study; however, radiation dosimetry among doctors was still low at 58%. The percentage of subjects who knew the radiation exposure (REX) dose of each procedure was low at 18%. Seventy‐six percent of the subjects attended lectures on radiation protection, and 73% knew about the three principles of radiation protection; however, the concept of diagnostic reference levels was not well known (18%). Approximately 60% of the subjects knew about the exposure dose increasing cancer mortality (63%) and the 5‐year lens REX limit (56%). Conclusions There was some improvement in radiation protection equipment or education, but relatively little compared to the 2020 survey of endoscopy departments.

Abstract Objectives Gastrointestinal endoscopy increases the risk of bacterial exposure to endoscopists. However, before 2019, most endoscopists did not pay attention to microorganism transmission from patients. This study aimed to investigate the incidence of bacterial exposure to endoscopists’ faces during gastrointestinal endoscopic procedures using the bacterial culture method. Methods This was a single‐centered, retrospective study including endoscopists who performed various gastrointestinal endoscopy procedures at the Division of Endoscopy, Hirosaki University Hospital between August 31 and October 6, 2020. Endoscopists wore surgical masks and affixed pre‐sterilized films over them. Following the gastrointestinal endoscopic procedures, attached microbes were collected from the endoscopists’ surface films using sterilized swabs. Collected microorganisms were cultured on tryptic soy agar and 5% sheep blood agar, and the incidence of bacterial exposure was determined by bacterial culture positivity. Cultured bacteria were identified by gram staining and 16S rRNA gene sequencing. Results Bacterial culture positivity was 12.6%, and it was significantly higher in therapeutic than in diagnostic endoscopy. Notably, therapeutic endoscopy increased bacterial culture positivity in colonoscopy, but not in esophagogastroduodenoscopy. Staphylococci, including Staphylococcus epidermidis and Staphylococcus capitis, were the most commonly found bacteria in samples identified through 16S rRNA gene sequencing. Conclusions The risk of bacterial exposure to the endoscopist's face was increased in colonoscopy treatment procedures. Therefore, endoscopists should be aware of the significant risk of microbial infection from scattering fluid that comes from the endoscopy's working channel.

Surgery avoidance is an important goal in Crohn’s disease (CD) treatment and predicting the risk of subsequent surgery is important to determine adequate therapeutic strength for patients with newly diagnosed CD. Herein, we aimed to construct a prediction model for the risk of subsequent surgery based on disease characteristics at the patients’ initial visit. We retrospectively collected disease characteristic data from 93 patients with newly diagnosed CD. A logistic regression model with a brute force method was used to maximize the area under the receiver operating characteristic curve (auROC) by employing a combination of potential predictors from 14 covariates (16,383). The auROC remained almost constant when one to 12 covariates were considered, reaching a peak of 0.89 at four covariates (small-bowel patency, extensive small-bowel lesions, main lesions, and the number of poor prognostic factors), and it decreased with increasing covariate size. The most significant predictors were small-bowel patency, extensive small-bowel lesions, and age or major lesions. Therefore, this prediction model using covariates may be helpful in determining the likelihood that a patient with newly diagnosed CD will require surgery, which can aid in appropriate treatment selection for high-risk patients.

Abstract Relationships between the neutrophil–lymphocyte ratio (NLR) and/or the platelet-lymphocyte ratio (PLR) and neuroinflammatory diseases have been reported. Depression is also associated with neuroinflammation. Here, we determined the association between the NLR, PLR, and depressive symptoms. This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2017. We analyzed the characteristics and laboratory data of 1,015 Japanese subjects (597 females, 408 males) including their NLR and PLR values. We assigned the subjects with a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 to the depressive symptoms group. We performed a multivariate logistic regression analysis to determine whether the NLR and/or PLR were associated with depressive symptoms (CES-D ≥ 16). Two hundred subjects (19.7%; 122 [20.4%] females, 78 [19.1%] males) were assigned to the depressive symptoms group. There were significant differences between the non-depressive symptoms and depressive symptoms groups in the NLR [median (25th to 75th percentile): 1.54 (1.24, 1.97) vs. 1.76 (1.32, 2.37), P = 0.005] and the PLR [median (25th to 75th percentile): 123.7 (102.0, 153.9) vs. 136.8 (107.0, 166.5), P = 0.047] in males, but not in females. The multivariate logistic regression analysis demonstrated that the NLR was significantly associated with depressive symptoms in males (adjusted odds ratio: per 1 increase, 1.570; 95% confidence interval: 1.120–2.220; P = 0.009). In conclusion, our findings indicate that higher NLR may be associated with depressive symptoms in males.

Abstract Amylase genes reside in a structurally complex locus, and their copy numbers vary greatly, and several studies have reported their association with obesity. The mechanism of this effect was partially explained by changes in the oral and gut microbiome compositions; however, a detailed mechanism has been unclarified. In this study, we showed their association with diabetes in addition to obesity, and further discovered a plausible mechanism of this association based on the function of commensal bacteria. First, we confirmed that the amylase copy number in the population tends to be larger than that reported in other studies and that there is a positive association between obesity and diabetes (p = 1.89E–2 and 8.63E–3). Second, we identified that relative abundance of some genus level microbiome, Capnocytophaga, Dialister, and previously reported bacteria, were significantly associated with amylase copy numbers. Finally, through functional gene-set analysis using shotgun sequencing, we observed that the abundance of genes in the Acarbose pathway in the gut microbiome was significantly decreased with an increase in the amylase copy number (p-value = 5.80E–4). Our findings can partly explain the mechanism underlying obesity and diabetes in populations with high amylase copy numbers.

Rationale & Objective: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Study Design: Population-based cross-sectional study. Setting & Participants: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. Exposures: UACR and eGFR levels. Outcomes: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). Analytical Approach: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Results: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and

Abstract In this study, we investigated the impact of single nucleotide polymorphisms in solute carrier (SLC) transporters, that is, SLC22A7 c.1586 + 206A > G, SLC22A2 c.808G > T, SLC22A3 c.1233G > A, SLC47A1 c.922‐158G > A, and SLC47A2 c.‐130G > A, on serum creatinine (SCr) concentrations. This cross‐sectional study included residents who participated as volunteers in a health promotion study. Lifestyle data, blood chemical analysis data, and SLC gene polymorphism information were collected from each participant. Univariate analyses were carried out to determine differences between groups and correlations in SCr. Stepwise multiple regression analysis was performed to confirm the independence of factors that were significantly different in the univariate analyses. In multiple regression analyses, muscle mass, serum cystatin C concentrations, body fat percentage, serum albumin concentrations, and SLC47A2 c.‐130G/G had the highest contribution to SCr concentrations, in that order (standardized regression coefficients = .505, .332, −.234, .123, and .084, respectively). The final model explained 72.2% of the variability in SCr concentrations. The SLC47A2 c.‐130G > A polymorphism may affect creatinine dynamics in the proximal tubules. Further studies are needed to determine the effects of SLC transporter gene polymorphisms on SCr concentrations in patients with various diseases in real‐world clinical settings.

ObjectivesImproving the lifestyle of occupational workers is essential for extending healthy life expectancy. We investigated various lifestyle-related items in a rural Japanese population and compared them between agricultural and non-agricultural workers.MethodsThis cross-sectional study was conducted as a part of the "Iwaki Health Promotion Project." Lifestyle-related items such as sleep, work hours, nutrition, health-related quality of life, and proportion of time spent performing each daily activity were compared between agricultural and non-agricultural workers in the ≥60 years (n = 251) and ResultsAgricultural workers had significantly lower Pittsburgh Sleep Quality Index total scores than non-agricultural workers in the ConclusionsAgricultural workers have better sleep habits but work longer than non-agricultural workers, with some differences in energy intake and proportion of time spent on each daily activity. These differences should be considered when planning lifestyle intervention programs for agricultural workers.

Abstract Gut microbiomics is based on analysis of both live and dead cells in the stool. However, to understand the ecology of gut microbiota and their symbiotic relationships with hosts, spatial distribution of live bacteria must be examined. Here, we analyzed the live composition of luminal microbiota (LM) and mucosa-associated microbiota (MAM) in the ascending and descending colons and the rectums of 10 healthy adults and compared it with the total composition. The abundance of Lachnospiraceae in live LM decreased along the gut length and was significantly lower than that in total LM. Contrastingly, the abundance of Bacteroidaceae and Bifidobacteriaceae in live LM was higher than that in total LM, suggesting differences in death rate during gut migration. Live Enterobacteriaceae levels in MAM were significantly higher in rectum than in the ascending and descending colons and in LM. High-performance liquid chromatographic analysis of luminal bile acids revealed that 7α-dehydroxylation occurred towards the rectum. In live LM where a bile acid-inducible gene could be detected, 7α-dehydroxylation rates were higher than those in the group without the gene. Overall, we showed differences in live bacteria composition among three gut sites and between LM and MAM, highlighting the importance of understanding their spatial distribution.

Background/Aims Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C > T) has been shown to be associated with thiopurine-induced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype. Methods A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records. Results Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19–0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104–298) pmol/8 × 108 red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P = 0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P = 0.339 and P = 0.422, respectively). Conclusions Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype.

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera’s regression coefficients (Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, Holdemania, Lactobacillus, Mitsuokella, and Oscillibacter) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.

A novel treatment method for achalasia of the esophagus and related disorders is known as peroral endoscopic myotomy (POEM). This study aimed to calculate the resting energy expenditure (REE) and evaluated the degree of physical invasiveness based on metabolic changes during the perioperative period of POEM. Fifty-eight patients who underwent POEM were prospectively enrolled; REE, body weight (BW), and basal energy expenditure were measured on the day of POEM, postoperative day 1 (POD 1), and three days after POEM (POD 3). The median REE/BW increased from 19.6 kcal/kg on the day of POEM to 24.5 kcal/kg on POD 1. On POD 3, it remained elevated at 20.9 kcal/kg. The stress factor on POD 1 was 1.20. Among the factors, including the Eckardt score, operation time, and the length of myotomy, the length of myotomy was associated with changes in REE/BW. During the perioperative period of POEM, the level of variation in energy expenditure was lower than that of esophageal cancer surgeries performed under general anesthesia. However, because the length of myotomy is a factor affecting changes in energy expenditure, careful perioperative management is desirable for patients with longer myotomy lengths.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan–asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

Abstract Outcomes of acute lower gastrointestinal bleeding have not been compared according to hospital capacity. We aimed to perform a propensity score-matched cohort study with path and mediation analyses for acute hematochezia patients. Hospitals were divided into high- versus low-volume hospitals for emergency medical services. Rebleeding and death within 30 days were compared. Computed tomography, early colonoscopy (colonoscopy performed within 24 h), and endoscopic therapies were included as mediators. A total of 2644 matched pairs were yielded. The rebleeding rate within 30 days was not significant between high- and low-volume hospitals (16% vs. 17%, P = 0.44). The mortality rate within 30 days was significantly higher in the high-volume cohort than in the low-volume cohort (1.7% vs. 0.8%, P = 0.003). Treatment at high-volume hospitals was not a significant factor for rebleeding (odds ratio [OR] = 0.91; 95% confidence interval [CI], 0.79–1.06; P = 0.23), but was significant for death within 30 days (OR = 2.03; 95% CI, 1.17–3.52; P = 0.012) on multivariate logistic regression after adjusting for patients’ characteristics. Mediation effects were not observed, except for rebleeding within 30 days in high-volume hospitals through early colonoscopy. However, the direct effect of high-volume hospitals on rebleeding was not significant. High-volume hospitals did not improve the outcomes of acute hematochezia patients.

Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes. Nevertheless, the association between SFN and the microbiota has not been clarified. A total of 1056 individuals were recruited in the 2018 Iwaki Health Promotion Project. Pain sensation was evaluated based on the pain threshold from intraepidermal electrical stimulation (PINT). Patients with PINT scores

Daily dietary habits directly or indirectly influence the intestinal microbiota, and the resulting changes in its composition and metabolic activity alter the health conditions of the host. Although many studies have analyzed the association between individual nutrients/food items and intestinal microbiota, the assessment of the diet and intestinal microbiota from a macroscopic perspective has not yet been performed in Japan. Therefore, we focused on vegetables and fruits and aimed to identify dietary patterns of high intake of these foods and to examine their relationship with the intestinal microbiota. This cross-sectional study included 1019 healthy individuals aged ≥20 years in a rural area in northern Japan. Six dietary patterns were detected by factor analysis using the brief-type self-administered diet history questionnaire (BDHQ) data to identify the “vege pattern”, which was the dietary pattern rich in vegetables and fruits. Permutational multivariate analysis of variance revealed changes in β-diversity according to dietary patterns. In multivariable-adjusted models, the adherence to the vege pattern was positively correlated with α-diversity. This is the first study to reveal a correlation between intestinal microbiota and dietary habits rich in vegetables and fruits in a rural area of Japan.

Abstract Objectives Cancer patients treated with immune checkpoint inhibitors occasionally show persistent diarrhea accompanied by endoscopic features of ulcerative colitis. The endoscopic mucosal inflammation may appear mild in some patients compared to the clinical severity, which can make choosing a treatment challenging. In this study, we evaluated the factors that support the continuation of chemotherapy by assessing the endoscopic and histopathological characteristics of patients who experienced diarrhea after immune checkpoint inhibitor administration. Methods This study included eight patients who were diagnosed with collagenous colitis based on pathological assessments. We retrospectively investigated these patients’ backgrounds, laboratory data, and computed tomography images that were extracted from their medical records. We also summarized their endoscopic and pathologic findings. Results All eight patients were being treated with anti‐programmed cell death‐1/programmed cell death‐ligand 1 therapeutic agents and had a recent history of oral proton pump inhibitor therapy. The anti‐programmed cell death‐1‐related collagenous colitis in these cases was characterized by endoscopically mild mucosal inflammation, high fecal calprotectin levels, and a lower frequency of intestinal wall thickening on computed tomography. Histological assessments showed CD8+ lymphocytes predominantly infiltrating the lamina propria and crypts of the colonic mucosa. Suspending the proton pump inhibitor therapy relieved the patients’ symptoms and allowed the continuation of the anti‐programmed cell death‐1/programmed cell death‐ligand 1 therapy. Conclusions Anti‐programmed cell death‐1‐related collagenous colitis is reversible; appropriate diagnosis of adverse events is crucial for the continuation of immune checkpoint inhibitor therapy.

Recently, the importance of achieving clinical and deep remissions with mucosal healing (MH) has been demonstrated as a therapeutic goal to avoid Crohn’s disease (CD) surgical operations. Although ileocolonoscopy (CS) is considered the gold standard, there are increasing reports on the benefits of capsule endoscopy (CE) and serum leucine-rich α2-glycoprotein (LRG) for evaluating small-bowel lesions in CD. We evaluated the data of 20 patients with CD who underwent CE in our department between July 2020 and June 2021 and whose serum LRG level was measured within 2 months. Concerning the mean LRG value, there was no significant difference between the CS-MH and CS-non-MH groups. Conversely, the mean LRG level was 10.0 μg/mL in seven patients in the CE-MH group and 15.2 μg/mL in 11 patients in the CE-non-MH group with a significant difference between the two groups (p = 0.0025). This study’s findings show that CE can sufficiently determine total MH in most cases, and LRG is useful for evaluating CD small-bowel MH because of its correlation with CE-MH. Furthermore, satisfying CS-MH criteria and a cut-off value of 13.4 μg/mL for LRG suggests its usefulness as a CD small-bowel MH marker, which could be incorporated into the treat-to-target strategy.

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms’ muscle mass [β = −0.02, −0.03]), renal (plasma renin activity [β = 0.27], urine albumin creatinine ratio [β = 0.50]), adrenal cortical (cortisol [β = 0.14]), and thyroid function (free thyroxine [β = 0.05]), iron metabolism (serum iron [β = −0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all βs ≤ −0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (β = 0.32), Megamonas (β = 0.56), and Streptococcus (β = 0.65); and negatively correlated with Roseburia (β = −0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all βs ≥ 0.07) or negatively (all βs ≤ −0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.

Probiotic products have been shown to have beneficial effects on human hosts, but what happens in the gastrointestinal tract after its ingestion remains unclear. Our aim was to investigate the changes within the small intestines after a single intake of a fermented milk product containing a probiotic. We have periodically collected the small-intestinal fluids from the terminal ileum of seven healthy subjects for up to 7 h after ingestion by small-intestinal fluid perfusion using an endoscopic retrograde bowel insertion technique. The bacterial composition of the terminal ileum clearly revealed that the ingested probiotics (Lactobacillus casei strain Shirota: LcS and Bifidobacterium breve strain Yakult: BbrY) occupied the ileal microbiota for several hours, temporarily representing over 90% of the ileal microbiota in several subjects. Cultivation of ileal fluids showed that under a dramatic pH changes before reaching the terminal ileum, a certain number of the ingested bacteria survived (8.2 ± 6.4% of LcS, 7.8 ± 11.0% of BbrY). This means that more than 1 billion LcS and BbrY cells reached the terminal ileum with their colony-forming ability intact. These results indicate that there is adequate opportunity for the ingested probiotics to continuously stimulate the host cells in the small intestines. Our data suggest that probiotic fermented milk intake affects intestinal microbes and the host, explaining part of the process from the intake of probiotics to the exertion of their beneficial effects on the host.

ObjectiveWe evaluated the clinical characteristics of metabolic dysfunction-associated fatty liver disease (MAFLD) to evaluate the usefulness of the MAFLD diagnostic criteria in a resident health survey.MethodsIn 1056 participants of a health survey, we compared obesity, diabetes, metabolic dysregulation, FibroScan-aspartate aminotransferase (FAST) score, dietary habits, and gut microbiota between healthy individuals and participants with MAFLD and Nonalcoholic fatty liver disease (NAFLD).ResultsThe proportion of participants with MAFLD in the fatty liver was higher than that with NAFLD (88.1% vs. 75.5%, respectively). Of 36 participants with a FAST score > 0.35, 29 (80.6%) participants had MAFLD and 23 (63.9%) participants had NAFLD. Of 29 patients with liver fibrosis, 26 (89.7%) participants had obesity and metabolic dysregulation. In the evaluation of diet, the total energy, protein, dietary fiber, and salt intake were significantly higher in participants with MAFLD than those in participants without fatty liver. In the microbiota analysis, the results of the linear discriminant analysis effect size analysis revealed nine bacterial genera that were significantly different in participants with MAFLD in comparison with participants without fatty liver. Of these genera, the relative abundance of Blautia was especially low in participants with MAFLD.ConclusionIn a resident health survey, participants with MAFLD had a higher proportion of fatty liver than those with NAFLD. MAFLD criteria could help in improved screening of participants with liver fibrosis. Therefore, the MAFLD criteria could be a useful diagnostic tool for aggressively identifying participants with a high risk of fatty liver. Additionally, Blautia might be involved in the development of MAFLD.

Capsule endoscopy has been widely used as a non-invasive diagnostic tool for small or large intestinal lesions. In recent years, automated lesion detection systems using machine learning have been devised. This study aimed to develop an automated system for capsule endoscopic severity in patients with ulcerative colitis along the entire length of the colon using ResNet50. Capsule endoscopy videos from patients with ulcerative colitis were collected prospectively. Each single examination video file was partitioned into four segments: the cecum and ascending colon, transverse colon, descending and sigmoid colon, and rectum. Fifty still pictures (576 × 576 pixels) were extracted from each partitioned video. A patch (128 × 128 pixels) was trimmed from the still picture at every 32-pixel-strides. A total of 739,021 patch images were manually classified into six categories: 0) Mayo endoscopic subscore (MES) 0, 1) MES1, 2) MES2, 3) MES3, 4) inadequate quality for evaluation, and 5) ileal mucosa. ResNet50, a deep learning framework, was trained using 483,644 datasets and validated using 255,377 independent datasets. In total, 31 capsule endoscopy videos from 22 patients were collected. The accuracy rates of the training and validation datasets were 0.992 and 0.973, respectively. An automated evaluation system for the capsule endoscopic severity of ulcerative colitis was developed. This could be a useful tool for assessing topographic disease activity, thus decreasing the burden of image interpretation on endoscopists.

Myelodysplastic syndromes (MDSs) are a group of myeloid neoplasms characterized by blood cell deformation and dysfunction, and MDS with trisomy 8 is closely linked with intestinal Behçet’s-like diseases. Intestinal Behçet’s-like disease is refractory to conventional therapies, including prednisolone, immunomodulators, and anti-tumor necrosis factor α agents. Here, we describe a 56-year-old woman with intestinal Behçet’s-like disease ascribed to MDS with trisomy 8 who had multiple intractable intestinal ulcers. She presented with periodic fever and abdominal pain. The genetic analysis showed a heterozygous E148Q mutation in the Mediterranean fever gene. The patient did not tolerate treatment with colchicine because of diarrhea; therefore, azacitidine therapy was initiated. One cycle of azacitidine therapy improved the multiple intestinal ulcers, and the periodic fever and abdominal pain gradually disappeared. After eight cycles of azacitidine therapy, ileocolonoscopy, histological assessment and capsule endoscopy revealed mucosal healing. Azacitidine therapy was continued, and mucosal healing was maintained for more than 2 years. This case suggests that azacitidine therapy which has immunoregulatory effects and epigenetic modulations, might control intestinal Behçet’s-like disease associated with MDS involving trisomy 8.

Fever of unknown origin (FUO) is caused by various diseases, making differential diagnosis difficult. This study aimed to determine the clinical features of patients with FUO for use in daily medical practice. Medical records of patients who first visited our department for FUO between January 2008 and December 2017 were reviewed. We classified the diagnostic categories as infection, non-infectious inflammation, neoplasm, others, and unidentified through definitive diagnosis and compared the clinical characteristics of patients who fulfilled the criteria of classical FUO and those who did not. The most prevalent diseases in patients who fulfilled the criteria were adult-onset Still’s disease, Behçet’s disease (BD), and polymyalgia rheumatica, which do not have any specific image inspection or specific serological markers. BD and familial Mediterranean fever were most prevalent in patients who did not fulfill the criteria. All neoplasms fulfilled the criteria of classical FUO. The most useful diagnostic procedure was determined according to the criteria of each disease. The key factor that did not fulfill the criteria was periodic fever continuing for less than 3 weeks. When examining patients with FUO, we should strictly diagnose in accordance with the criteria of each disease and consider diseases that cause periodic fever.

Water-soluble dietary fiber is primarily a substrate for degradation of short chain fatty acids (SCFAs), particularly butyric acid, by gut microbiota. SCFAs have beneficial effects on the whole body. However, epidemiological studies on the association between water-soluble dietary fiber from daily food intake and butyric acid-producing bacteria are inconsistent. The purpose of this study was to determine the association between levels of water-soluble dietary fiber from daily food intake and gut microbiota, particularly butyric acid producers, in middle-aged and older adults in a rural area in Japan. We examined the effects of water-soluble dietary fiber intake on gut microbiota after adjusting for confounding factors. After propensity score matching, 520 subjects (260 in the low-intake group and 260 in the high-intake group) were selected. One year later after a follow-up survey, we re-classified the participants and again compared low- and high-intake groups. As a result, people with a high intake had a higher relative abundance of butyric acid-producing bacteria. It was also revealed that butyric acid-producing bacteria remained high in the group that maintained high intake the next year. We concluded that continuous intake of water-soluble dietary fiber from daily food is necessary to maintain sufficient amounts of butyric acid-producing bacteria.

The gut microbiota has become a significant factor associated with health and disease. Although many studies have reported the implications of changes in the gut microbiota on cardiovascular diseases, there are no reports on the relationship between heart rate variability (HRV) and the gut microbiota. Therefore, we investigated the association between gut microbiota abundance and HRV parameters in this cross-sectional study of the general Japanese population. This study included 950 participants of the Iwaki Health Promotion Project who underwent a medical examination in 2019 that included HRV and gut microbiota measurements. At the genus level, multivariate regression analysis showed that higher gut microbial diversity was associated with a higher standard deviation of RR intervals (SDNN). Moreover, a higher SDNN was associated with a higher relative count of Lachnospiraceae incertae sedis. L. incertae sedis abundance was associated with higher HRV parameters such as SDNN, coefficient of variation of RR intervals, low-frequency component power (LF)/high-frequency component power, and LF. In the general Japanese population, higher gut microbial diversity and L. incertae sedis abundance were associated with higher HRV parameters.

Abstract Background and aims It is essential for endoscopists, technologists, and nurses to understand radiation protection. However, protective equipment usage is still low, and there is little awareness of radiation protection in practice. Methods We conducted a questionnaire survey on radiation protection from January to February 2020. The participants were medical staff, including medical doctors, nurses, and radiological and endoscopy technician in endoscopy‐fluoroscopy departments. The questionnaire included 14 multiple‐choice questions divided among three parts: background, equipment, and knowledge. Results We surveyed a total of 282 subjects from 26 institutions. There were 168 medical doctors (60%), 90 nurses (32%), and 24 technologists (9%). Although almost all staff members (99%) always wore a lead apron, only a few wore a thyroid collar (32%) and lead glasses (21%). The rate of wearing a radiation dosimeter was insufficient (69%), especially among doctors (52%). A few subjects knew the radiation exposure dose of each procedure (15%), and slightly over half had attended lectures on radiation protection (64%) and knew about the three principles of radiation protection (59%). Protection adherence did not differ by years of experience, knowledge of fluoroscopy, awareness of radiation exposure doses, or attendance at basic lectures on radiation protection. However, medical doctors who were aware of the radiation exposure dose of each procedure were significantly more likely to wear dosimeters than those who were not (p = 0.0008). Conclusion Medical staff in endoscopy departments in Japan do not have enough radiation protection equipment or education.

A 45-year-old Japanese male patient who was diagnosed with celiac disease (CeD) developed type I enteropathy-associated T-cell lymphoma (EATL). In 2013, the patient was admitted to our hospital with worsening of diarrhea and weight loss. Pathological examination of biopsy specimens from the duodenum and ileum led to a diagnosis of suspected EATL. A previous total colonoscopy (TCS) indicated villous atrophy in the terminal ileum. The patient was changed to a gluten-free diet, and the nutritional status gradually improved. In September 2014, he experienced acute right lower abdominal pain. He underwent urgent surgery, and a perforation was identified in the ileum. A diagnosis of type I EATL was made following histopathological examination. After eight courses of CHOP therapy, the patient entered complete remission. TCS and esophagogastroduodenoscopy with magnifying narrow-band imaging performed in 2015 identified villous regrowth in the distal ileum and duodenum. Capsule endoscopy also found villous regrowth in the entire small intestine. To our knowledge, this is the first case of type I EATL following CeD with villous atrophy before EATL occurrence in a Japanese HLA-DQ2 carrier. The possibility of type I EATL occurring after CeD should be recognized, although CeD is quite rare in Japan.

Currently, the number of patients treated with immune-checkpoint inhibitor involving nivolumab is increasing. Nevertheless, it causes various immune-related adverse events (irAEs). Here, we report the case of a patient who underwent long-term follow-up after suffering from nivolumab-associated colitis. The patient was a 57-year-old man who underwent resection of a bladder tumor. Following surgery, lymph node metastasis was detected, and he was treated by nivolumab. Two months after treatment with nivolumab, the patient complained of bloody diarrhea. Colonoscopy revealed pancolitis with erosions, loss of vascular pattern and erythema. Pathological findings indicated a disease state of pan-ulcerative colitis. As an irAE by nivolumab, the patient was started with 30 mg of prednisolone. Prednisolone treatment successfully induced clinical remission and mucosal healing. Nevertheless, eight months after stopping the steroid treatment, the colitis relapsed with diarrhea following elevation of fecal immunochemical test (FIT) and fecal calprotectin (CPT). The relapsed colitis was treated by mesalazine, and then diarrhea was improved. Nivolumab-associated colitis relapsed following mucosal healing suggesting that it is necessary to consider maintenance therapy as well as remission induction for long-term survivor. The present case also demonstrates that the FIT and CPT would be effective biomarker to assess the disease activity of nivolumab-associated colitis.

Esophageal endoscopic submucosal dissection (ESD) is considered to be more complex than gastric ESD. This study aimed to assess the physical invasiveness of esophageal ESD during perioperative periods by measuring resting energy expenditure (REE). The factors affecting REE that could be used to identify patients requiring perioperative management were also investigated. Overall, 75 patients who had undergone esophageal ESD were prospectively enrolled. REE, body weight, and basal energy expenditure were measured on the day of and the day following ESD. The mean REE/body weight was 20.2 kcal/kg/day on the day of ESD and significantly increased to 23.0 kcal/kg/day one day after ESD. The stress factor on the day after ESD was 1.11. White blood cell, neutrophil, and C-reactive protein levels increased on the day after ESD and correlated with the changes in REE. Among the factors including age, body mass index, total resection area, operation time, and sarcopenia, only the total resection area was associated with changes in REE. In conclusion, energy metabolism increases during the perioperative period for esophageal ESD. The increase in the stress factor for esophageal ESD was higher than that in gastric and colorectal ESD. Furthermore, patients with large resection areas require greater attention in perioperative management.

Abstract Background The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes. Methods This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%. Discussion This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients. Trial registration UMIN-CTR Identifier, UMIN000021129. Registered on 21 February 2016; ClinicalTrials.gov Identifier, NCT03098173. Registered on 24 March 2017.

Visceral fat accumulation is an independent risk factor for cardiovascular disease and mortality. Visceral fat is a causal risk factor for hypertension and type 2 diabetes, which was reported as one of the risk factors for dementia. Visceral fat areas (VFA) might be clinically important to prevent dementia; however, the association between VFA and cognitive function in the elderly remains unknown. We aimed to evaluate the association between brain structural abnormalities using magnetic resonance imaging (MRI) and VFA, and the association between cognitive function and VFA, in the elderly. A total of 2364 healthy individuals were enrolled, and we excluded those diagnosed with dementia. Participants were divided into a high-VFA and a low-VFA group based on median VFA. The high-VFA group had significantly lower cognitive function than the low-VFA group (p = 0.025), after adjustment for related factors using a linear regression model. Regarding brain structure in MRI, VFA remained significantly associated with white matter lesions (odds ratio (OR), 1.90; 95% confidence interval (1.33–2.70); adjusted p < 0.001) and perivascular space (OR, 1.28; 95% confidence interval (1.02–1.61); adjusted p = 0.033). Further follow-up studies are needed, but reducing visceral fat might be important, not only to prevent cardiovascular disease but also to prevent dementia.