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Background: The mortality and risk factors of severe disease and death due to arterial and venous thromboembolism (ATE and VTE, respectively) in patients with inflammatory bowel disease (IBD) remain unclear, especially in Asia. Aims: This study aimed to reveal the mortality and risk factors of TE in IBD patients in Japan. Methods: In the primary surveillance, responses to questionnaires regarding the number of cases of severe TE and TE-associated death in IBD patients in a span of over the past 10 years were obtained from 32 institutions in Japan. In the secondary surveillance, detailed data about IBD patients with TE were collected. The characteristics, laboratory data, therapy status, and situation at the time of TE development were retrospectively collected, and the data were compared between the patients with and without severe TE and TE-associated death. Results: The incidence of TE was 1.89% among 31,940 IBD patients. The frequencies of severe TE and TE-associated mortality were 10.7% and 1.0% among the total IBD and TE with IBD patients, respectively. The only risk factor for severe ATE and ATE-associated death was ischemic heart disease. The independent risk factors for severe VTE and VTE-associated death were age (≤ 45 years old), the site of VTE, and disease severity, with anti-TNF therapy as a potential negative risk factor. Patients with severe VTE had a high risk of developing persistent VTE and sequelae. Conclusion: Unlike ATE, the incidence of VTE was comparable in Asian and Western countries. Therapeutic and prophylactic strategies for managing IBD-associated TE in Asia are urgently needed. [ABSTRACT FROM AUTHOR]

Also, an Appendix listing iCREST-CD Study Group collaborators is included in this correction. Appendix: iCREST-CD Study Group Collaborators Masakazu Nagahori: Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University; Tatsu Yukawa: Inflammatory Bowel Disease Center Yokohama City University Medical Center; Daisuke Saito: Department of Gastroenterology and Hepatology, Kyorin University School of Medicine; Mikio Kawai: Department of Intestinal Inflammation Research, Hyogo College of Medicine; Atsushi Masamune: Division of Gastroenterology, Tohoku University Graduate School of Medicine; Mitsuo Nagasaka: Department of Gastroenterology, Fujita Health University School of Medicine; Tomoe Kazama: Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine. [Extracted from the article]

Background and aims: Although serum albumin levels are associated with mortality in non-institutionalized elderly people under 80 years old, as well as in the institutionalized very elderly, little is known about the relationship in community-dwelling very elderly people. We, therefore, examined the association in a Japanese population of 80-year-old community residents. Methods: Serum albumin levels were measured in 672 (267 men, 405 women) out of 1282 80-year-old individuals. Over the following 4 years, the dates and causes of death were recorded from resident registration cards and official death certificates. Results: Of the above individuals, 107 subjects died (58 men, 49 women: 27 due to cancer, 27 cardiovascular disease, and 22 pneumonia). Survival rates were compared among 4 groups (highest >45 g/L, higher than 43-44 g/L, lower than 41-42 g/L, lowest <40 g/L). After adjustment for confounding factors, total death or cardiovascular death in the lowest albumin group was 3.1 times and 10.7 times more incident than in the highest albumin group, but there were no differences among groups as regards deaths due to cancer or pneumonia. Conclusion: Serum albumin levels are an independent predictor of mortality due to all-cause or cardiovascular disease, but not of mortality due to cancer or pneumonia in very elderly Japanese community residents. [ABSTRACT FROM AUTHOR]

Background: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan., Methods: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum., Results: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA., Conclusions: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis., (© 2024. The Author(s).)

Purpose: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA., Methods: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests., Results: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively., Conclusion: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

Purpose: Therapeutic efficacy of ustekinumab in the real-world data is limited in patients with refractory Crohn's disease (CD). In addition, factors predictive of better therapeutic efficacy of ustekinumab remains unsolved in CD. We aimed to evaluate therapeutic efficacy of ustekinumab in patients with refractory CD and to identify the factors associated with the efficacy of ustekinumab., Methods: We retrospectively analyzed the clinical data of 72 patients treated with ustekinumab for refractory CD. Therapeutic efficacy was assessed at weeks 8, 26, 52, and 104 on the basis of dual remission, defined as the combination of Crohn's Disease Activity Index < 150 and CRP < 0.3 mg/dL, and factors predictive of the induction and maintenance of dual remission were investigated. The cumulative continuation rates and safety of ustekinumab were assessed., Results: The dual remission rates at weeks 8, 26, 52, and 104 were 31.9%, 37.9%, 47.5%, and 42.6%, respectively. A short disease duration (≤ 2 years) and higher baseline serum albumin levels (≥ 3.1 g/dL) were positively associated with dual remission at weeks 8 and 52. Meanwhile, higher serum CRP levels (≥ 1.19 mg/dL) were negatively associated with dual remission at week 8. The cumulative ustekinumab continuation rate was favorable, and no severe adverse events were found., Conclusion: A short disease duration and higher baseline serum albumin levels might be predictive of favorable therapeutic efficacy of ustekinumab in refractory CD. Induction efficacy appears to be lower in patients with higher serum CRP levels., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported., Methods: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded., Results: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively., Conclusions: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients., (© 2022. Japanese Society of Gastroenterology.)

Background: Although combining thiopurine with infliximab (IFX) is considered to improve the clinical efficacy of IFX when treating Crohn's disease (CD), it also increases the risk of adverse events (AEs). We compared the efficacy and safety of delayed thiopurine addition after loss of response (LOR) to IFX with the efficacy and safety of an earlier combination of thiopurine and IFX., Methods: This retrospective study analyzed patients with CD who started IFX as a first-line biologic at Kyushu University Hospital between June 2002 and July 2018. Patients were assigned to either the early-combination (EC) group, who started IFX and thiopurine simultaneously, or the late-combination (LC) group, who were treated with IFX alone until they developed LOR. We compared the cumulative IFX continuation rates and AE incidence between the two groups., Results: One hundred seventy-six patients were enrolled in this study; 49 were enrolled in the EC group, and 127 were enrolled in the LC group. Disease activity at baseline did not significantly differ between the groups, nor did the cumulative IFX continuation rates differ between the groups (P = 0.30); however, the AE rate was significantly higher in the EC group than in the LC group (38.7% vs. 21.2%; P = 0.02). The severe AE rate was also higher in the EC group than in the LC group (18.3% vs 3.1%; P = 0.001)., Conclusion: Considering the risk-benefit balance, delayed addition of thiopurine after LOR to IFX might be an alternative strategy when using IFX to treat CD., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array., Methods: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction., Results: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02)., Conclusions: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.

Background: Findings from several studies suggest associations between tooth loss and health outcomes, including malnutrition, poor quality of life, and mortality, in older individuals. However, limited information is available regarding whether those associations remain true in very elderly subjects after adequately considering confounding factors such as sex and smoking status. Herein, we determined whether the number of teeth in 80-year-old subjects is an independent predictor of mortality., Methods: We initially contacted 1282 80-year-old community-dwelling individuals born in 1917, of whom 697 responded and participated in a baseline study, with follow-up examinations conducted 4 and 5.5 years later. Data from interviews and medical and oral examinations were obtained, and oral health was determined according to the number of teeth remaining in the oral cavity., Results: A total of 108 and 157 subjects died in 4 years and 5.5 years, respectively, after the baseline study. Tooth loss was significantly associated with mortality at age 85.5, but not at age 84, after adjusting for potential confounders. When the analysis was stratified by sex, we found a stronger association in females in follow-up examinations conducted at both 4- and 5.5 years. On the other hand, the effect of tooth loss on mortality was not significantly different between smokers and non-smokers., Conclusion: Tooth loss is a significant predictor of mortality independent of health factors, socio-economic status, and lifestyle in octogenarians, with a stronger association in females.

Since little is known about the very elderly population aged 80 years and older, we evaluated the association of quality of life (QoL) in an 85-year-old population with physical fitness measurements assessed at age 80 and 85 years. Two hundred seven individuals (90 males, 117 females) aged 85 years underwent the Short Form-36 (SF-36) questionnaires for QoL assessment and physical fitness measurements (handgrip strength, leg-extensor strength, one-leg standing time, stepping rate of legs, walking speed). In 85-year-olds, significant associations were found, by multiple regression analysis or logistic regression analysis, with adjustment for various influencing factors in QoL assessed by SF-36 with physical fitness measurements examined at the age of 85 and 80 years. Physical scales and scores in SF-36, such as physical functioning (PF), limitation in role functioning for physical reasons (role physical; RP), bodily pain (BP), and the physical component score (PCS) tended to be more tightly associated with fitness measurements than mental scales and scores such as limitation in role functioning for emotional reasons (role emotional; RE), and emotional well-being (mental health; MH), and mental component score (MCS). Three scales the general health perceptions (GH), the vitality (VT), and the social functioning (SF) consisting of both physical and mental components were associated with fitness, the extent being intermediate between physical scales and mental scales. Of the several physical fitness measurements, leg-extensor strength and the walking speed of 85-year-olds, and the stepping rate of 80-year-olds were most closely associated with QoL. In a very elderly population of 85- and 80-year-olds, significant associations were found between QoL by SF-36 and physical fitness measurements, suggesting that increases in the levels of physical fitness, even in the very elderly, can contribute to improvements in QoL., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Hypertension is one of the greatest risk factors for cardiovascular disease, but its contribution to cardiovascular mortality weakens with aging. We have previously demonstrated that at the age of 80, higher systolic blood pressure (SBP) is not correlated with increased mortality in Japan. However, we did not examine in detail whether diastolic blood pressure (DBP) independently affects mortality. In the present study, 639 participants, who were 80 years old in 1997, were enrolled. The subjects were divided by their DBP [below 70 mmHg (group 1, n = 136), from 70 mmHg to 80 mmHg (group 2, n = 200), from 80 mmHg to 90 mmHg (group 3, n = 194), over 90 mmHg (group 4, n = 109)]. During the 4-year follow-up period, 90 individuals died. Cox multivariate regression analysis revealed that group 1 showed a significantly higher mortality rate than group 4 [relative risk (RR) 2.47, confidence interval (CI) 1.07-5.70, p = 0.03)]. The relative risks of deaths from cardiovascular diseases, pneumonia, and cancer tended to be higher in group 1 than in group 4, but the difference did not reach statistical significance. These results suggest that decreased DBP is associated with higher mortality in the Japanese elderly.

Aim: Helicobacter pylori (HP) has been implicated as a risk factor for cardiovascular and atherosclerotic diseases. Arterial stiffness determined by pulse wave velocity (PWV) or the cardio-ankle vascular index (CAVI) has been shown to be higher in HP-positive subjects than in HP-negative subjects; however, this result has been observed only in young subjects. The aim of the study was to investigate the possible correlation between HP infection and PWV or CAVI in middle-aged subjects., Methods: We measured brachial-ankle PWV (baPWV), CAVI, metabolism markers, pepsinogens (PGs) and IgG antibody to HP in 343 individuals aged either 60 or 65 year old. Atrophic gastritis (AG) was diagnosed based on the values of PGs., Results: baPWV and CAVI were significantly higher in the AG-positive group than in the AG-negative group even after adjusting for possible confounding factors (baPWVc; 16.63+/-3.50 vs. 15.59+/-3.47 p=0.010, CAVIc; 8.59+/-1.20 vs. 8.27+/-1.19 p=0.022). baPWV and CAVI values tended to be higher in the HP-positive group than in the HP-negative group. High-density lipoprotein (HDL) cholesterol level and the adiponectin level were lower in the AG-positive group than in the AG-negative group., Conclusion: There may be an association between atrophic gastritis and atherosclerosis in middle-aged subjects.

Background: Immunoglobulin levels are elevated in the older people. However, it is unknown whether these levels are related to mortality., Object: To evaluate the association between immunoglobulin levels and mortality., Methods: The study population included 697 individuals (277 males and 420 females) of 1,282 eighty-year-old individuals residing in the Fukuoka prefecture, Japan. The participants were followed for 4 years after the baseline examination., Results: The hyper-IgA group, defined as a serum IgA level >400 mg/dl, had high mortality using Kaplan-Meier analysis (log rank, p=0.037). Multivariate Cox regression analyses revealed a high risk of mortality (hazard rate=1.233, 95% confidence interval 1.109-1.491, p=0.031) after adjusting for covariates. The high risk of mortality in the hyper-IgA group was significant in males, but not in females. Moreover, Kaplan-Meier analysis revealed that IgA was related to cancer mortality in males (log rank, p=0.031), but not to pneumonia or cardiovascular disease. IgM and IgG levels were not related to high risk of mortality., Conclusion: Serum IgA levels appear to be a predictor of mortality, especially cancer mortality in males., (Copyright 2008 S. Karger AG, Basel.)

Objectives: To evaluate the association between high-level functional capacity and chewing in a middle-old community-based population., Background: Although basic and instrumental activities of daily living are known to be associated with chewing ability in the elderly, an association between higher levels of competence and chewing ability has not been evaluated in the elderly., Materials and Methods: The association between chewing ability using a number of different foods and high-level functional capacity by the Tokyo Metropolitan Institute of Gerontology was evaluated in 694, 80-year-old people residing in Fukuoka Prefecture, Japan., Results: A significant correlation was found, using multiple regression or logistic regression analyses adjusted for various confounding factors, between the number of total chewable foods, hard foods or moderately hard foods, and total functional capacity, instrumental activity, intellectual activity or social role ability. In contrast, the number of slightly hard foods, easily chewable foods and remaining teeth were only partly related to total functional capacity and intellectual activity., Conclusion: High-level functional capacity including intellectual activity and social role in middle-old elderly was associated with the ability to chew hard foods than to chew easily chewable foods. Maintenance of chewing ability in elderly might result in better intellectual activity and social role.

Background: The relationship between Helicobacter pylori (HP) infection and body mass index (BMI) is controversial. Several reports have indicated that eradication of HP infection induces an increase in BMI. In contrast, epidemiological case-control studies have failed to show an association between HP infection and BMI. Therefore, we investigated whether HP and atrophic gastritis (AG) were associated with BMI., Methods: A total of 617 individuals were recruited for the measurements of BMI, serum leptin, pepsinogens (PGs) I and II, and IgG antibody to HP (HP-IgG). BMI and leptin of the subjects were compared when the subjects were stratified by HP-IgG and PGs., Results: The subjects were divided into AG-positive and AG-negative groups according to PGs (AG-positive: PG I < or = 70 ng/ml and PG I/II ratio < or =3.0). BMI after adjusting for sex and age was significantly lower in the AG-positive group than in the AG-negative group (23.47 +/- 3.05 vs. 24.18 +/- 3.25, P = 0.010). When the subjects were divided into two groups according to HP-IgG, BMI tended to be lower in the HP-IgG-positive group, though the difference was not large. When the subjects were divided into four groups for different combinations of AG and HP-IgG, BMI was the lowest in the AG-positive and HP-IgG-negative group., Conclusions: BMI was associated with AG, as diagnosed by PGs, but not with HP infection status. These results mean that HP infection affects BMI via atrophic gastritis.