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Objective Although colorectal polyps (CPs) can be observed with colon capsule endoscopy (CCE), it is difficult to determine the type of polyp using CCE. The objective of this study was to differentiate adenomatous polyps (APs) from hyperplastic polyps (HPs) with CCE. Methods In this single-center retrospective study, an analysis was conducted on the same CPs with both CCE and colonoscopy (CS) and histopathologically diagnosed as AP or HP. The color difference (ΔE) between the polyp surface and the surrounding mucosa was calculated using the CIE1976 L*a*b* color space method on white light (WL), flexible spectral imaging color enhancement (FICE), and blue mode (BM) CP images. We investigated the ability of the ratio of the color differences (ΔE') to differentiate between APs and HPs. Results The size of all 51 polyps (34 APs, 17 HPs) was 7.5±4.6 mm with CCE and 7.3±4.2 mm with CS, and this difference was not significant (p=0.28). The FICEΔE' of APs was 3.3±1.8, which was significantly higher than the FICEΔE' of HPs (1.3±0.6; p

Low-dose aspirin (LDA) administration prevents cerebral infarction and myocardial infarction, but many studies found an association with mucosal injury. Proton-pump inhibitors (PPIs) can prevent gastric and duodenal mucosal damage, but they may exacerbate small-intestinal mucosal injury by altering the microbiota. We aimed to assess the effect of PPIs on the intestinal flora of LDA users. Thirty-two recruited patients, who received LDA (100 mg/day) but did not take PPIs, were divided into 15 patients additionally receiving esomeprazole (20 mg/day) and 17 patients additionally receiving vonoprazan (10 mg/day). On days 0, 30, 90, and 180, the microbiota of each patient was examined by terminal restriction fragment length polymorphism analysis, and the serum gastrin, hemoglobin, and hematocrit levels were measured. Additional PPI administration increased the proportion of Lactobacillales in the microbiota of LDA users. This trend was more prevalent in the vonoprazan group (p

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet‐leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

The elderly people are characterized by multiple comorbidities, dementia, and are at risk of developing sarcopenia and frailty. Sarcopenia is defined by loss of muscle mass and muscle strength or physical decline. Sarcopenia is a main component of physical frailty. Screening tools for sarcopenia that can be easily determined in daily practice are useful and include the SARC-F screening tool. SARC-F is a questionnaire consisting of five questions: Strength (S), Assistance walking (A), Rising from a chair (R), Climbing stairs (C), and Falls (F) on a scale of 0 to 2. The recommended cutoff value is ≥4 points. The SARC-F has been shown to correlate well with clinical outcomes in the elderly and various underlying diseases, while it is also true that the SARC-F has its shortcomings such as low sensitivity for sarcopenia. In this review, we mainly outline the SARC-F and mention other screening tools for sarcopenia.

Reversible post-translational modification of serine and threonine residues by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation has been indicated to regulate the activities of a number of different proteins. Augmented O-GlcNAcylation contributes to the etiologies of type 2 diabetes mellitus (T2DM) and cancer. Moreover, diabetic conditions increase the risk of colorectal cancer. However, the effect of O-GlcNAcylation in patients with colorectal cancer and concurrent T2DM has not been elucidated. The current study evaluated the level of O-GlcNAcylation in patients with colorectal cancer with or without T2DM. Notably, O-GlcNAcylation levels were significantly higher in tissues from patients with T2DM compared with those in patients without T2DM, and higher in cancer tissues compared with corresponding adjacent tissues. O-GlcNAcylation and cancer stage were more strongly correlated in cancer tissues from patients with T2DM compared with those from patients without T2DM. Additionally, distant metastasis was significantly correlated with O-GlcNAcylation in cancer tissues from patients with T2DM. β-catenin levels in colorectal cancer tissues were the highest in patients with advanced-stage cancer and concurrent T2DM. In SW480 human colon cancer cells, thiamet G (TMG) treatment and OGA silencing, which increased O-GlcNAcylation, significantly increased β-catenin and SNAIL in high-glucose, but not during normal-glucose conditions. These data suggest that O-GlcNAcylation is closely associated with distant metastasis, most likely through upregulation of the β-catenin/SNAIL signaling pathway in colorectal cancer patients with T2DM.

The interleukin (IL)-23/Th17 pathway plays a critical role in ulcerative colitis (UC). The IL-12p40 subunit, which is shared by IL-23 and IL-12, is encoded by the IL12B gene. The current case-control study investigated the association between IL12B SNP rs6887695 and the UC risk.There were 384 cases within 4 years of UC diagnosis and 661 controls who were enrolled. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, and body mass index.Subjects with the GG IL12B SNP rs6887695 genotype had a significantly increased risk of UC compared with those with the CC genotype (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.08-2.36). This positive association was also significant using the additive and recessive models (AOR, 1.25; 95% CI, 1.03-1.52; AOR, 1.50; 95% CI, 1.08-2.09, respectively). An independent inverse relationship was observed between ever alcohol consumption and the UC risk in those with the CC genotype while no significant association was found in those with at least one G allele (P for interaction = 0.0008).IL12B SNP rs6887695 was significantly associated with UC. The influence of alcohol consumption might rely on rs6887695.

We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.

Simple Summary There have been few reports with regard to the relevance between the SARC-F score and the prognosis in patients with gastrointestinal advanced cancers, and we aimed to elucidate these issues (n = 421, median age = 73 years). During the follow-up period, 145 patients (34.4%) died. The 1-year cumulative overall survival rate in patients with SARC-F ≥ 4 (recommended cutoff point, n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the overall survival, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score 1 (p = 0.0147) and 2 (p < 0.0001), ECOG-PS 2 (p < 0.0001), and 3 (p < 0.0001) and 4 (p < 0.0001) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and the best cutoff point of the SARC-F score was two. The SARC-F score appears to be useful in patients with gastrointestinal advanced malignancies. Abstract We sought to elucidate the prognostic impact of the SARC-F score among patients with gastrointestinal advanced malignancies (n = 421). A SARC-F score ≥ 4 was judged to have a strong suspicion for sarcopenia. In patients with ECOG-PS 4 (n = 43), 3 (n = 61), and 0–2 (n = 317), 42 (97.7%), 53 (86.9%) and 8 (2.5%) had the SARC-F score ≥ 4. During the follow-up period, 145 patients (34.4%) died. All deaths were cancer-related. The 1-year cumulative overall survival (OS) rate in patients with SARC-F ≥ 4 (n = 103) and SARC-F < 4 (n = 318) was 33.9% and 61.6% (p < 0.0001). In the multivariate analysis for the OS, total lymphocyte count ≥ 1081/μL (p = 0.0014), the SARC-F score ≥ 4 (p = 0.0096), Glasgow prognostic score (GPS) 1 (p = 0.0147, GPS 0 as a standard), GPS 2 (p < 0.0001, GPS 0 as a standard), ECOG-PS 2 (p < 0.0001, ECOG-PS 0 as a standard), ECOG-PS 3 (p < 0.0001, ECOG-PS 0 as a standard), and ECOG-PS 4 (p < 0.0001, ECOG-PS 0 as a standard) were independent predictors. In the receiver operating characteristic curve analysis on the prognostic value of the SARC-F score, the sensitivity/specificity was 0.59/0.70, and best cutoff point of the SARC-F score was two. In conclusion, the SARC-F score is useful in patients with gastrointestinal advanced malignancies.

Background and Aims: A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes. Methods: Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54. Results: The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3–1.6] μg/mL vs. 0.9 [0.6–1.3] μg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 μg/mL as the target threshold for achieving clinical remission at week 54. Conclusion: Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

Background and Aims: The calcineurin inhibitor tacrolimus is reportedly effective for moderate/severe ulcerative colitis (UC); however, it is also reportedly associated with nephrotoxicity. We investigated the risk factors for tacrolimus-induced nephrotoxicity and whether renal impairment adversely affected the outcomes of tacrolimus treatment in patients with UC. Methods: We conducted a retrospective study of 93 patients with UC who were administered tacrolimus leading to high trough levels (10–15 ng/mL) for 2 weeks and low trough levels (5–10 ng/mL) for 3 months. Results: Acute kidney injury (AKI) occurred in 44 patients (47.3%) during tacrolimus treatment. Of these patients, 34 (36.6%) developed AKI during the high trough phase and 17 (18.3%) developed AKI when the trough value exceeded the original target value of 15 ng/mL. Multivariate logistic regression analysis revealed that the male sex was significantly associated with AKI (p = 0.002, AOR = 4.38, 95% CI [1.69–11.3]). Clinical remission rate after 4, 8, 12, and 24 weeks of tacrolimus treatment in patients with AKI was lower than that in patients without AKI. Six patients (6.5%) had chronic kidney disease (CKD) after tacrolimus treatment completion, and all patients with CKD developed AKI during treatment. The median duration of treatment with no improvement in AKI was significantly longer in patients with CKD than in those without CKD (p = 0.016). Conclusion: We revealed the risk factors for tacrolimus-induced nephrotoxicity. Renal impairment occurrence adversely affected the tacrolimus treatment outcome; therefore, it is important to carefully administer tacrolimus to prevent renal impairment.

Background and aim Although an inverse relationship between current smoking and the development of ulcerative colitis (UC) has been shown in North America and Europe, evidence is limited in Asian countries, where the incidence of UC is rapidly increasing. This Japanese case-control study examined the association between active and passive smoking and risk of UC. Methods A self-administered questionnaire was used to obtain information on smoking and potential confounding factors in 384 cases with a diagnosis of UC within the past four years and 665 controls. Results Compared with having never smoked, having ever smoked was associated with an increased risk of UC (adjusted odds ratio [OR] = 1.70, 95% confidence interval [CI]: 1.23-2.37). No association was observed between current smoking and risk of UC, but former smokers had a significant elevation in risk (adjusted OR = 2.40, 95% CI: 1.67-3.45). There was a positive dose-response relationship with pack-years smoked (P for trend = 0.006). Among never smokers, passive smoking exposure at home was significantly associated with an increased risk of UC (adjusted OR = 1.90, 95% CI: 1.30-2.79). A significant dose-response gradient was also observed between pack-years of passive smoking at home and risk of UC (P for trend = 0.0003). Conclusions We confirmed that former smoking elevated the risk of UC, whereas an inverse association between current smoking and the risk of UC did not reach a statistically significant level. Passive smoking may be associated with an increased risk of UC.

Malnutrition is a major contributor to muscle loss and muscle dysfunction, known as sarcopenia. Malnutrition is common in patients with inflammatory bowel disease (IBD). IBD includes ulcerative colitis (UC) and Crohn’s disease (CD). The number of patients with IBD has recently been increasing. More severe malnutrition is often seen in CD compared to UC, probably due to CD affecting the main site of nutrient absorption, extensive mucosal lesions, fistulas, short bowel syndrome after resection, or obstruction of the gastrointestinal tract. A recent meta-analysis showed the high prevalence of sarcopenia in patients with IBD, and thus sarcopenia is a very important problem for IBD. Although IBD is more common in younger patients, sarcopenia can develop through a variety of mechanisms, including malnutrition, chronic inflammation, increased inflammatory status in adipose tissue, vitamin deficiency, and imbalance of the muscle–gut axis. In addition, sarcopenia has a negative impact on postoperative complications and hospital stay in patients with IBD. Appropriate intervention for sarcopenia may be important, in addition to clinical remission and endoscopic mucosal healing in patients with IBD. Much more attention will thus be paid to sarcopenia in patients with IBD. In this review, we outline IBD and sarcopenia, based on the current evidence.

We sought to clarify the relevance in the neutrophil to lymphocyte ratio (NLR) and the SARC-F score in patients with gastrointestinal diseases (G-Ds, n = 672, median age = 73 years). Univariate and multivariate analysis for the SARC-F score were performed. Advanced malignancy was identified in 162 patients (24.1%). The median of NLR for all cases was 2.65. The median of NLR in ECOG-PS 0 (n = 436), 1 (n = 128), 2 (n = 49) and 3 or 4 (n = 59) was 2.26, 2.97, 4.41 and 5.99 (overall p < 0.0001). NLR had a significant correlation with the SARC-F score (r = 0.54, p < 0.0001). The median of NLR in the SARC-F score ≥4 (recommended value for sarcopenia, n = 84) and

Recently, a hazard analysis technique STAMP/STPA has been widely accepted since it is recognized as being suitable for software-intensive systems. Using STAMP/STPA, we can find hazardous scenarios of the target system that cannot be obtained by other traditional hazard analysis methods and those scenarios can be used for validation testing. However, generally the number of obtained scenarios can be huge and the validation testing involves a considerable cost. In this study, we propose a method to prioritize hazardous scenarios identified by STAMP/STPA with the help of a statistical model-checking technique. We give a procedure for systematically transforming the model defined by STAMP/STPA to a formal model for a statistical model-checking tool. We also show the usefulness of the proposed method using an example of train gate control system.

Background Endoscopic removal of colorectal adenoma is considered an effective treatment for reducing the mortality rates associated with colorectal cancer. Warfarin, a type of anticoagulant, is widely used for the treatment and prevention of thromboembolism; however, bleeding may increase with its administration after polypectomy. In recent times, a high incidence of bleeding after endoscopic polypectomy has been reported in patients receiving heparin bridge therapy. However, previous studies have not compared the bleeding rate after endoscopic colorectal polypectomy between patients who continued with anticoagulant therapy and those who received heparin bridge therapy. We hypothesised that endoscopic colorectal polypectomy under the novel treatment with continuous warfarin is not inferior to endoscopic colorectal polypectomy under standard treatment with heparin bridge therapy with respect to the rate of postoperative bleeding. This study aims to compare the efficacy of endoscopic colorectal polypectomy with continuous warfarin administration and endoscopic colorectal polypectomy with heparin bridge therapy with respect to the rate of postoperative bleeding. Methods We will conduct a prospective multicentre randomised controlled non-inferiority trial of two parallel groups. We will compare patients scheduled to undergo colorectal polypectomy under anticoagulant therapy with warfarin. There will be 2 groups, namely, a standard treatment group (heparin bridge therapy) and the experimental treatment group (continued anticoagulant therapy). The primary outcome measure is the rate of postoperative bleeding. On the contrary, the secondary outcomes include the rate of cumulative bleeding, rate of overt haemorrhage (that does not qualify for the definition of haemorrhage after endoscopic polypectomy), incidence of haemorrhage requiring haemostasis during endoscopic polypectomy, intraoperative bleeding during endoscopic colorectal polypectomy requiring angiography, abdominal surgery and/or blood transfusion, total rate of bleeding, risk factors for postoperative bleeding, length of hospital stay, incidence of thromboembolism, prothrombin time-international ratio (PT-INR) 28 days after the surgery, and incidence of serious adverse events. Discussion The results of this randomised controlled trial will provide valuable information for the standardisation of management of anticoagulants in patients scheduled to undergo colorectal polypectomy. Trial registration UMIN-CTR UMIN000023720. Registered on 22 August 2016

Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid., Lay Summary EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.

Background: During the COVID-19 pandemic, safe treatment of inflammatory bowel disease is required. Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC) with few adverse events. Therefore, elucidating the effectiveness of GMA without steroids is important in the current situation. The aim of this study was to investigate the effectiveness of GMA in active UC patients who are not receiving steroids. Methods: A single-arm, open-label, and multicenter prospective clinical trial was conducted at ten facilities in Japan.UC patients who had insufficient responses to 5-aminosalicylic acid without steroids received GMA twice a week for five consecutive weeks. The primary and secondary endpoints were the induction of a response and endoscopic mucosal healing in the patients who achieved a response. Findings: A total of 67 patients were enrolled. The response rate of all patients who received GMA ten times was 58·2%. Of the 39 patients who achieved a response, 74·4% achieved endoscopically confirmed mucosal healing. Both the median Mayo score and ulcerative colitis endoscopic index of severity score were significantly decreased in the patients who achieved a response. The response rate of the patients who were suffering from their first episode was significantly higher than that of those with relapse-remitting UC (80·0% [16/20] vs. 48·9% [23/47], p=0·029). Undergoing the first episode of UC (odds ratio [OR]: 4·952, 95% confidence interval [CI]: 1·292-18·981, p>0.001) was defined as an independent predictor of a response. Interpretation: This study strongly suggest that GMA shows promising effectiveness in inducing remission in active UC patients who are not receiving steroid treatment. We expect that GMA can be made available during the COVID-19 pandemic. Trial Registration: UMIN registration No. 000013702 Funding Statement: Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan (Investigation and Research for intractable Inflammatory Bowel Disease to HN). Declaration of Interests: MM reports personal fees from Janssen Pharmaceutical K.K., and commercial research funding from AbbVie GK. and Nippon Kayaku Co., Ltd. SN reports receiving personal fees from EA Pharma Co., Ltd., AbbVie GK., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd. KH reports receiving research funding from EA Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co., Ltd. HN reports receiving personal fees from AbbVie GK., Kissei Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co., Ltd., Pfizer Lnc., Cell gene Corporation., EA Pharma Co., Ltd., Zeria Pharmaceutical CO., Ltd., Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Daiichi Sankyo Company, Limited., JIMRO Co., Ltd., as well as grants for commissioned/joint research from Hoya Group Pentax Medical, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. All other authors declare no competing interests. Ethics Approval Statement: The protocol of the clinical trial was approved by the IRB at each institution. Informed consent to participate in the study was obtained from each participant before inclusion.

We sought to examine the relationship between the SARC-F score and the Controlling Nutritional Status (CONUT) score in patients with gastrointestinal diseases (GDs, n = 735, median age = 71 years, and 188 advanced cancer cases). The SARC-F score ≥ 4 (highly suspicious of sarcopenia) was found in 93 cases (12.7%). Mild malnutritional condition was seen in 310 cases (42.2%), moderate in 127 (17.3%) and severe in 27 (3.7%). The median SARC-F scores in categories of normal, mild, moderate and severe malnutritional condition were 0, 0, 1 and 1 (overall p < 0.0001). The percentage of SARC-F score ≥ 4 in categories of normal, mild, moderate and severe malnutritional condition were 4.4%, 12.9%, 26.8% and 25.9% (overall p < 0.0001). The SARC-F score was an independent factor for both the CONUT score ≥ 2 (mild, moderate or severe malnutrition) and ≥5 (moderate or severe malnutrition). In the receiver operating characteristic (ROC) curve analysis for the CONUT score ≥ 2, C reactive protein (CRP) had the highest area under the ROC (AUC = 0.70), followed by the SARC-F score (AUC = 0.60). In the ROC analysis for the CONUT score ≥ 5, CRP had the highest AUC (AUC = 0.79), followed by the SARC-F score (AUC = 0.63). In conclusion, the SARC-F score in patients with GDs can reflect malnutritional status.

Background/aims The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. Methods IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians' global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. Results A total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians' global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months' observation period. The overall eradication rate was 84.0%-comparable to previous reports in non-IBD patients. Conclusions H. pylori eradication therapy does not alter the short-term disease activity of IBD.

We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.

Although low-dose aspirin (LDA) is known to induce small intestinal mucosal injury, the effect of dual antiplatelet therapy (DAPT; LDA + clopidogrel) on small intestinal mucosa in patients after percutaneous coronary intervention (PCI) for coronary stenosis is unknown. Fifty-one patients with a history of PCI and LDA use were enrolled, and 45 eligible patients were analyzed. Patients were grouped based on DAPT (DAPT: n = 10 and non-DAPT: n = 35) and proton pump inhibitor (PPI) use (PPI user: n = 22 and PPI-free patients: n = 23) to compare small intestinal endoscopic findings. The relationship between LDA-use period and small intestinal endoscopic findings was also examined. Multivariate analysis was performed to identify risk factors for LDA-induced mucosal injury using age, sex, DAPT, PPI, gastric mucoprotective drug, and LDA-use period. The rate of small intestinal mucosal injury incidence did not significantly differ between DAPT and non-DAPT patients (50% vs 51.1%, respectively; p = 0.94), or PPI users and PPI-free patients (50% vs 52.2%, respectively; p = 0.88). Additionally, LDA-use period of ≤24 months (n = 15) yielded a significantly higher rate of small intestinal mucosal injury incidence than LDA-use period >24 months (n = 30) (80% vs 36.7%, respectively; p = 0.006). Multivariate analysis revealed that a LDA-use period of ≤24 months was a significant risk factor for small intestinal mucosal injury (odds ratio: 19.5, 95% confidence interval: 2.48-154.00, p = 0.005). Following PCI for coronary stenosis, neither DAPT nor PPI affected LDA-induced small intestinal mucosal injury. Moreover, patients who used LDA within the last 24 months were at a greater risk of small intestinal mucosal injury.

We provide an operational scenario-based assurance method for assuring the safety of a software product. Software safety is usually demonstrated by assessing the software development process in what is called a process-based approach. Because the process-based approach indirectly explains safety of software product, it cannot explicate safety boundary: Software product is safe or unsafe in what context of use. In this paper, we focus on operational scenario and unusual events which can occur in the scenario. The proposed method provides an operational scenario-based safety case which explains tolerable and not-tolerable abnormal scenarios including unusual events as the boundary. The method promotes domain experts identifying unusual events from a normal scenario. Furthermore, it constructs scenario-based safety case by using Event Sequence Diagram. To evaluate the method, we applied it to a ground system for artificial satellite, and engine control system of the rocket system. As a result, we conclude that the method can construct a valid operational scenario-based safety case.

We investigated the risk factors of and appropriate treatment for cytomegalovirus colitis in patients with ulcerative colitis, using quantitative polymerase chain reaction analysis to detect cytomegalovirus in the colonic mucosa. Between February 2013 and January 2017, patients with exacerbated ulcerative colitis who were admitted to our hospital were consecutively enrolled in this retrospective, single-center study. Patients were evaluated for cytomegalovirus using serology (antigenemia) and quantitative polymerase chain reaction analyses of the colonic mucosa, which were sampled during colonoscopy. Of 86 patients, 26 (30.2%) had positive quantitative polymerase chain reaction results for cytomegalovirus; only 4 were also positive for antigenemia. The ages of the cytomegalovirus DNA-positive patients were significantly higher than those of negative patients (p = 0.002). The mean endoscopic score of cytomegalovirus DNA-positive patients was significantly higher than that of cytomegalovirus DNA-negative patients. Treatment with combined immunosuppressants was associated with an increased risk of cytomegalovirus. Fourteen of 15 (93.3%) cytomegalovirus DNA-positive patients who were negative for antigenemia showed a clinical response to treatment with additional oral tacrolimus, without ganciclovir. cytomegalovirus reactivation in active ulcerative colitis is associated with age and combined immunosuppressant therapy. Because additional treatment with tacrolimus was effective, patients who are negative for antigenemia and cytomegalovirus DNA-positive colonic mucosa may recover without antiviral therapy.