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Abstract Background The continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties. Methods Our investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure. Results Multivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%. Conclusions Our findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.

Abstract Aims A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.

Abstract Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Abstract Objective This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon‐assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow‐up in high‐risk patients.

Abstract Intestinal intraepithelial lymphocytes (IELs) reside in the gut epithelial layer, where they help in maintaining intestinal homeostasis. Peripheral CD4+ T cells can develop into CD4+CD8αα+ IELs upon arrival at the gut epithelium via the lamina propria (LP). Although this specific differentiation of T cells is well established, the mechanisms preventing it from occurring in the LP remain unclear. Here, we show that chemokine receptor 9 (CCR9) expression is low in epithelial CD4+CD8αα+ IELs, but CCR9 deficiency results in CD4+CD8αα+ over-differentiation in both the epithelium and the LP. Single-cell RNA sequencing shows an enriched precursor cell cluster for CD4+CD8αα+ IELs in Ccr9 −/− mice. CD4+ T cells isolated from the epithelium of Ccr9 −/− mice also display increased expression of Cbfβ2, and the genomic occupancy modification of Cbfβ2 expression reveals its important function in CD4+CD8αα+ differentiation. These results implicate a link between CCR9 downregulation and Cbfb2 splicing upregulation to enhance CD4+CD8αα+ IEL differentiation.

Background/Aims Thromboprophylaxis is recommended for hospitalized patients with inflammatory bowel disease (IBD) in Western countries, although it is selectively administered to high-risk patients in East Asia. A central venous catheter (CVC) is commonly placed in patients with IBD. Although CVC placement is considered a risk factor for venous thromboembolism (VTE), the degree of increased risk in patients with IBD is uncertain. This study aimed to identify the risk of VTE with CVC placement in hospitalized Japanese patients with IBD without thromboprophylaxis. Methods This retrospective cohort study included patients with ulcerative colitis or Crohn’s disease who were admitted for disease flares at Keio University Hospital between January 2016 and December 2020. Patients who already had thrombosis or were administered any antithrombotic treatment on admission were excluded. VTE development during the hospitalization was surveyed, and VTE risk associated with CVC indwelling was estimated using propensity score matching and inverse probability of treatment weighting analyses. Results Altogether, 497 hospitalized patients with IBD (ulcerative colitis, 327; Crohn’s disease, 170) were enrolled. VTE developed in 9.30% (12/129) of catheterized patients and in 0.82% (3/368) of non-catheterized patients. The propensity score matching yielded 127 matched pairs of patients. The catheterized group demonstrated higher odds for VTE than the non-catheterized group (odds ratio, 13.15; 95% confidence interval, 1.68–102.70). A similar result was obtained in the inverse probability of treatment weighting analysis (odds ratio, 11.02; 95% confidence interval, 2.64–46.10). Conclusions CVC placement is a major risk factor for VTE among hospitalized Japanese patients with IBD without thromboprophylaxis.

Background & Aims: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. Methods: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. Results: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. Conclusions: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.

Background/Aims Complementary and alternative medicine (CAM) is prevalent in East Asia. However, information on CAM in East Asian patients with inflammatory bowel disease (IBD) is scarce. We aimed to profile the prevalence and pattern of CAM use among East Asian IBD patients and to identify factors associated with CAM use. We also compared physicians’ perspectives on CAM. Methods Patients with IBD from China, Japan, and South Korea were invited to complete questionnaires on CAM use. Patient demographic and clinical data were collected. Logistic regression analysis was applied for predictors of CAM use. Physicians from each country were asked about their opinion on CAM services or products. Results Overall, 905 patients with IBD participated in this study (China 232, Japan 255, and South Korea 418). Approximately 8.6% of patients with IBD used CAM services for their disease, while 29.7% of patients sought at least 1 kind of CAM product. Current active disease and Chinese or South Korean nationality over Japanese were independent predictors of CAM use. Chinese doctors were more likely to consider CAM helpful for patients with IBD than were Japanese and South Korean doctors. Conclusions In 8.6% and 29.7% of East Asian patients with IBD used CAM services and products, respectively, which does not differ from the prevalence in their Western counterparts. There is a significant gap regarding CAM usage among different Asian countries, not only from the patients’ perspective but also from the physicians’ point of view.

Background/Aims Adalimumab has been shown to induce and maintain clinical remission in patients with moderate to severe ulcerative colitis (UC). However, no large-scale population-based studies have been performed in Japan. This study was conducted to evaluate the safety and effectiveness of adalimumab in clinical practice in Japanese patients with UC. Methods In this 52-week, prospective, multicenter, single-cohort, noninterventional, observational, postmarketing surveillance study, patients with moderate to severe UC received an initial subcutaneous injection of adalimumab 160 mg, followed by 80 mg at 2 weeks, and then 40 mg every other week. Safety assessments were the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness assessments were clinical remission, corticosteroid-free remission, mucosal healing, and change in C-reactive protein (CRP) levels from baseline. Results Of 1,593 registered patients, 1,523 (male, 57.6%; mean age, 41.8 years) and 1,241 patients were included in the safety and effectiveness populations, respectively. ADRs were reported in 18.1% and serious ADRs in 4.9% of patients. Clinical remission was achieved in 49.7% of patients at week 4, increasing to 74.4% at week 52. Corticosteroid-free remission rates increased over time, from 10.4% at week 4 to 53.1% at week 52. More than 60% of patients demonstrated mucosal healing at weeks 24 and 52. Mean CRP levels (mg/dL) decreased from 1.2 at baseline to 0.6 at week 4 and 0.3 at week 52. Conclusions This large real-world study confirmed the safety and effectiveness of adalimumab in patients with UC in Japan. No new safety concerns were identified.

Background/Aims Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings. Methods This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI). Results The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks. Conclusions Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.

Cytotoxic CD4+ T cells (CD4-CTLs) show the presence of cytolytic granules, which include the enzymes granzyme and perforin. The cells have a pathogenic and protective role in various diseases, including cancer, viral infection, and autoimmune disease. In mice, cytotoxic CD4+ T cells express CD8αα+ and reside in the intestine (mouse CD4+CTLs; mCD4-CTLs). The population of cytotoxic CD4+ T cells in the human intestine is currently unknown. Moreover, it is unclear how cytotoxic CD4 T cells change in patients with inflammatory bowel disease (IBD). Here, we aimed to identify cytotoxic CD4+ T cells in the human intestine and analyze the characteristics of the population in patients with IBD using single-cell RNA-seq (scRNA-seq). In CD4+ T cells, granzyme and perforin expression was high in humanMAIT (hMAIT) cells and hCD4+CD8A+ T cell cluster. Both CD4 and CD8A were expressed in hTreg, hMAIT, and hCD4+CD8A+ T cell clusters. Next we performed fast gene set enrichment analysis to identify cell populations that showed homology to mCD4CTLs. The analysis identified the hCD4+CD8A+ T cell cluster (hCTL-like population; hCD4-CTL) similar to mouse CTLs. The percentage of CD4+CD8A+ T cells among the total CD4+ T cells in the inflamed intestine of the patients with Crohn’s disease was significantly reduced compared with that in the noninflamed intestine of the patients. In summary, we identified cytotoxic CD4+CD8+ T cells in the small intestine of humans. The integration of the mouse and human sc-RNA-seq data analysis highlight an approach to identify human cell populations related to mouse cell populations, which may help determine the functional properties of several human cell populations in mice.

Group 2 innate lymphoid cells (ILC2s) serve as frontline defenses against parasites. However, excluding helminth infections, it is poorly understood how ILC2s function in intestinal inflammation, including inflammatory bowel disease. Here, we analyzed the global gene expression of ILC2s in healthy and colitic conditions and revealed that type I interferon (T1IFN)-stimulated genes were up-regulated in ILC2s in dextran sodium sulfate (DSS)-induced colitis. The enhancement of T1IFN signaling in ILC2s in DSS-induced colitis was correlated with the downregulation of cytokine production by ILC2s, such as interleukin-5. Blocking T1IFN signaling during colitis resulted in exaggeration of colitis in both wild-type and Rag2-deficient mice. The exacerbation of colitis induced by neutralization of T1IFN signaling was accompanied by reduction of amphiregulin (AREG) in ILC2s and was partially rescued by exogenous AREG treatment. Collectively, these findings show the potential roles of T1IFN in ILC2s that contribute to colitis manifestation.

Abstract Background and Aim Preoperative histological evaluation of pancreatic neoplasms is important for guiding the resection strategy and preventing postoperative adverse events. However, conventional endoscopic methods have technical limitations that reduce the accuracy of the histopathological examination. Probe electrospray ionization mass spectrometry (PESI‐MS) may be a useful technique for rapidly evaluating small specimens. Methods This single‐center prospective study included patients with pancreatic neoplasms between October 2018 and December 2019. Pancreatic ductal adenocarcinoma (PDAC) specimens were obtained via endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) and non‐neoplastic tissue was obtained via surgery. Specimens were subjected to PESI‐MS and the mass spectra were analyzed using partial least squares regression‐discriminant analysis. Results The study included 40 patients with 20 nonneoplastic specimens and 19 PDAC specimens (1 case of neuroendocrine carcinoma was omitted). All nonneoplastic specimens were sufficient for PESI‐MS analysis, although only 7 of 19 PDAC specimens were sufficient for PESI‐MS analysis because of poor sample quality or insufficient quantity (

Abstract Background and Aim Percutaneous endoscopic gastrostomy (PEG) has been used in patients with dysphagia and inadequate food intake via an oral route. Despite being a procedure with a high success rate, complications and death have been reported. The aim was to identify the factors related to major complications and mortality, as well as PEG removal prognostic factors due to improvement of their general condition. Methods Patient characteristics, comorbidities, laboratory data, concomitant medication, sedation, and indication for PEG placement were collected. Major complications, mortality, and PEG removal factors were assessed. Results A total of 388 patients were enrolled. There were 15 (3.9%) cases of major complications, with major bleeding being the most frequent in 6 (1.5%) patients. Corticosteroids were the independent variable associated with major complications (odds ratio [OR] 5.85; 95% confidence interval [CI] 1.71–20; P =

A 77-year-old female who had an acute severe abdominal pain was taken to the emergency room in the previous hospital. CT scans showed jejunum and ileum wall thickening and fatty deposits around the small intestinal tract, and gastrointestinal perforation could not be ruled out. By using single anal and oral balloon endoscopy, we observed mild edema with petechial erythema, shallow erosions with edematous mucosa and ulcers with surrounded disrupted villous structures at the jejunum and ileum. Histological analysis revealed atypical lymphocytes infiltrating the small intestinal mucosa demonstrating intraepithelial lymphocytosis. Immunohistochemical staining revealed that CD3, CD7, and CD56 staining was positive, and CD4, CD5, and CD8 staining was negative in infiltrated lymphocytes. We made the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with the combination of HE staining and IHC. PET-CT showed abnormal uptake in irregular wall thickening of the small intestine, lymph nodes, ribs, spine and pelvic bone. She was treated with chemotherapy (etoposide, prednisolone, oncovin, cyclophosphamide, hydroxydaunorubicin) and is still alive 1 year after the diagnosis. We reported the various endoscopic findings in the same MEITL patient by using single balloon endoscopy. We also summarized endoscopic characteristics of MEITL patients.

AbstractBackground and Aim In patients with Crohn’s disease (CD) and small bowel stenosis, endoscopic balloon dilation (EBD) is considered to be useful in improving stenotic symptoms and avoiding surgery. However, it carries risks such as bleeding and perforation. The aim of this study was to identify the indications for endoscopic intervention in patients with CD and small bowel stenosis.Methods From November 2007 to March 2020, 143 CD patients with small bowel stenosis were enrolled in this study. We identified the factors associated with not requiring endoscopic intervention during long-term follow-up of these patients.Results Forty of the 143 patients had abdominal symptoms of stenosis and had undergone EBD, whereas the remaining 103 were asymptomatic and had not undergone endoscopic intervention. During long-term follow-up, 95 of those 103 patients never required endoscopic or surgical intervention. Multivariate logistic regression analysis revealed that not consuming an elemental diet (OR 3.18, 95% CI 1.48–6.82; p

Summary: Intestinal intraepithelial lymphocytes (IELs), the first line of defense against microbial and dietary antigens, are classified as natural or induced based on their origin and receptor expression. Induced CD4+CD8αα+TCRβ+ T cells (double positive, DPIELs) originated from CD4+CD8α−TCRβ+ T cells (single positive, SPIELs) increase with aging. However, the metabolic requirements and the metabolic-related genes in IEL development remain unclear. We determined that the intraepithelial compartment is hypoxic in the presence of microbes and DPIELs increased more than natural IELs in this location. Moreover, DPIELs consumed less oxygen and glucose and exhibited unique alterations in mitochondria. Using inhibitors and genetically modified mice, we revealed that DPIELs adapt to their surrounding oxygen-deprived environment in peripheral tissues by modulating specific genes, including hypoxia-inducible factor, mammalian target of rapamycin complexes (mTORC), phosphorylated ribosomal protein S6 (pS6), and other glycolytic factors. Our findings provide valuable insight into the metabolic properties of IELs.

Abstract Since its introduction into clinical practice in 2000, capsule endoscopy (CE) has become an important procedure for many pathologies of small bowel (SB) diseases, including inflammatory bowel disease (IBD). Currently, the most commonly used capsule procedures are small bowel capsule endoscopy (SBCE), colon CE (CCE), and the recently developed pan‐enteric CE that evaluates the SB and colon in patients with Crohn's disease (CD). SBCE has a higher diagnostic performance compared to other radiological and conventional endoscopic modalities in patients with suspected CD. Additionally, CE plays an important role in monitoring the activity of CD in SB. It can also be used in evaluating response to anti‐inflammatory treatment and detecting recurrence in postsurgical patients with CD who underwent bowel resection. Due to its increasing use, different scoring systems have been developed specifically for IBD. The main target with CCE is ulcerative colitis (UC). The second‐generation colon capsule has shown high performance for the assessment of inflammation in patients with UC. CCE allows noninvasive evaluation of mucosal inflammation with a reduced volume of preparation for patients with UC.

Background/Aims: The evaluation of small bowel lesions of Crohn’s disease (CD) using balloon-assisted enteroscopy (BAE) is crucial because mucosal healing is associated with a good prognosis. However, BAE procedures are invasive, requiring sedation or analgesia to reduce the patient’s pain. This study evaluated the clinical usefulness of a novel ultrathin single-balloon enteroscopy (SBE) procedure for CD. Methods: This single-center retrospective study included 102 CD patients who underwent trans-anal SBE between January 2012 and May 2018. Of these patients, 82 underwent enteroscopy using conventional SBE, while 20 underwent ultrathin SBE. Patients were analyzed using propensity score matching, with 20 patients per group. The median duration of the examination, terminal ileum intubation rate, median cecum intubation time, median insertion depth, adverse events, and sedated dose in each group were compared. Results: Before propensity score matching, the conventional SBE group had a larger number of surgical history patients than the ultrathin SBE group (p=0.05). After matching, the two groups did not significantly differ clinically. There were no significant differences in the mean duration of the examination, cecum intubation time, or terminal ileal intubation rate between ultrathin SBE and conventional SBE. The mean insertion depth of ultrathin SBE tended to be deeper than that of conventional SBE (p=0.09). The use of ultrathin SBE also reduced the sedative dose during needed for enteroscopy compared with conventional SBE (p=0.005). Conclusions: Novel ultrathin SBE may be less painful for CD patients than conventional SBE.

Colon capsule endoscopy was initially introduced in 2006. Since the results of a prospective study to evaluate first-generation colon capsule endoscopy efficacy for the detection of colonic neoplasia were unsatisfactory, second-generation colon capsule endoscopy was developed and reported in 2009. In this review article, we provide an overview of the current state of colon capsule endoscopy for evaluation of inflammatory bowel disease in a clinical setting and describe our clinical experience with this technology and its application. Among the various types of inflammatory bowel diseases, ulcerative colitis is the primary target for application of colon capsule endoscopy. Nevertheless, the initial results of studies using first-generation colon capsule endoscopy to evaluate inflammation were unclear. More recently, second-generation colon capsule endoscopy has provided higher accuracy for assessment of inflammation in patients with ulcerative colitis. Colon capsule endoscopy enables noninvasive observation (with reduced volume preparation) of mucosal inflammation severity in patients with ulcerative colitis.

Background and Aim. Direct oral anticoagulant- (DOAC-) induced small-bowel lesions have not been described. We evaluated small-bowel lesions related to DOAC using video capsule endoscopy (VCE). Methods. This study was a prospective, open-label, nonblinded, multicenter, and observational study. From September 2013 to March 2017, patients taking DOACs were enrolled. Patients underwent VCE. The type and location of small-bowel lesions were registered. Also, (1) the proportion of lesions detected between types of DOAC was evaluated and (2) the hemoglobin (Hb) and serum ferritin levels were compared between patients with and without small-bowel lesions. Results. 33 patients were enrolled, but 4 patients withdrew their consent, and VCE was performed on 29 patients. Eight, 13, and 8 patients received dabigatran, rivaroxaban, and apixaban, respectively. Small-bowel transit was complete in 27 of 29 patients (93.1%). Small-bowel lesions were detected in 23 (79.3%), redness in 12 (41.4%), erosions in 14 (48.3%), and angioectasia in 3 (10.3%) patients, and 6 patients (20.7%) had no abnormalities. Redness and erosions were detected in the upper, middle, or lower portions, but erosions tended to be less frequent in the middle portion (p=0.25, 0.06). Angioectasia was not detected in the lower portion. No patients had active bleeding. The findings did not differ according to the drug. The relationships between the endoscopic findings and the Hb and serum ferritin levels were not significant. Conclusion. Many patients taking DOACs had small-bowel lesions; however, most lesions were relatively mild. Observing small-bowel lesions over longer periods may be necessary in patients taking DOACs. This trial is registered with UMIN000011527.

Ulcerative colitis (UC) is one of the major clinical phenotypes of inflammatory bowel diseases. Although 5-aminosalicylic acid (5-ASA) is widely used for UC and its efficacy and safety have been demonstrated, a few patients paradoxically develop a severe exacerbation of colitis by 5-ASA administration. It is crucial to know clinical features including endoscopic findings in this condition for making a correct diagnosis and a prompt decision to withdraw the medication. Here, we report case series with UC exacerbated by 5-ASA. Medical records of 8 UC patients experiencing an exacerbation of colitis after induction of 5-ASA that was improved by the withdrawal of 5-ASA but also re-aggravated by dose increase or re-administration of 5-ASA were reviewed. The patients were newly diagnosed with UC, started 5-ASA and developed an exacerbation in approximately 2 to 3 weeks. They did not appear to have systemic allergic reactions. Seven of the 8 patients had a high fever. Three of 5 patients who undertook total colonoscopy showed right-side-dominant colitis. These findings suggest clinical characteristics in this condition. Further assessment of clinical and endoscopic features in more cases is necessary for establishing diagnostic criteria and understanding underlying mechanisms in those cases where 5-ASA aggravates the colitis.

Background/AimsThis study compared the efficacy of multimatrix mesalazine 2.4 g/day and 4.8 g/day with controlled-release mesalazine 2.25 g/day.MethodsIn this multicenter, randomized, double-blind study, 251 patients with mildly to moderately active ulcerative colitis received multimatrix mesalazine 2.4 g/day once daily (Multimatrix-2.4), 4.8 g/day once daily (Multimatrix-4.8), or controlled-release (time-dependent) mesalazine 2.25 g/day 3 times daily (Time-2.25) for 8 weeks. The primary efficacy endpoint was the change in the ulcerative colitis-disease activity index (UC-DAI) score.ResultsThe mean change in the UC-DAI score and standard deviation in the per protocol set was −1.9±2.5 for Multimatrix-2.4 and −2.4±2.8 for Time-2.25. The difference between Multimatrix-2.4 and Time-2.25 was 0.3 (two-sided 95% confidence interval [CI], −0.5 to 1.1), thus non-inferiority was not demonstrated based on the pre-defined non-inferiority margin (1.0). In the full analysis set, the difference between Multimatrix-4.8 and Time-2.25 was −1.2 (two-sided 95% CI, −2.0 to −0.5), and the mean change in UC-DAI score in the FAS was −3.3 (two-sided 95% CI, −3.9 to −2.8) for Multimatrix-4.8 and −1.9 (two-sided 95% CI, −2.5 to −1.3) for Multimatrix-2.4, indicating that Multimatrix-4.8 was more effective than Time-2.25 and Multimatrix-2.4. There was no difference among the treatment groups in terms of safety.ConclusionsThis study showed that the efficacy of multimatrix mesalazine 2.4 g/day was comparable to controlled release mesalazine 2.25 g/day, although non-inferiority was not demonstrated. Importantly, this was the first study to indicate that multimatrix mesalazine 4.8 g/day was more effective than 2.4g/day with no associated safety concerns.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Background/Aims: This study compared the efficacy of once-daily administration of multimatrix mesalazine 2.4 g/day with multiple-dose mesalazine for the maintenance of remission.Methods: In this multicenter, randomized, double-blind study, 203 patients with ulcerative colitis in remission received multimatrix mesalazine 2.4 g/day once-daily or time-dependent (controlled-release) mesalazine 2.25 g/day 3 times-daily for 48 weeks. The primary efficacy endpoint was the proportion of patients without rectal bleeding.Results: The proportion of patients without rectal bleeding during the 48-week treatment period in the per protocol set was 84.8% (84/99) in the multimatrix mesalazine 2.4 g/day group and 78.0% (78/100) in the controlled-release mesalazine 2.25 g/day group. The difference between the 2 treatment groups was 6.8% (two-sided 95% confidence interval, −3.9% to 17.6%). The noninferiority margin of −10% was met in the comparison of multimatrix mesalazine 2.4 g/day once-daily with controlled-release mesalazine 2.25 g/day. Multimatrix mesalazine 2.4 g/day once-daily demonstrated consistent efficacy in all subgroups. There was no difference between the 2 treatment groups with regard to safety.Conclusions: A once-daily dose of 2 multimatrix mesalazine tablets (2.4 g) was not inferior to controlled-release mesalazine 2.25 g/day 3 times-daily in maintaining absence of rectal bleeding in ulcerative colitis.

Background/Aims: This study assessed the efficacy and safety of high-dose multimatrix mesalazine once-daily (QD) compared to another form of high-dose mesalazine.Methods: In this multicenter, randomized, double-blind study, 280 patients with mildly to moderately active ulcerative colitis (UC) received multimatrix mesalazine 4.8 g/day QD or pH-dependent-release mesalazine 3.6 g/day three times daily for 8 weeks. The primary endpoint was the change in the UC-Disease Activity Index (UC-DAI) at the end of the treatment period.Results: The change in the UC-DAI (mean±standard deviation) in the per-protocol set was −2.6±2.47 in the multimatrix mesalazine 4.8 g/day group (n=134) and −1.8±2.64 in the pH-dependent-release mesalazine 3.6 g/day group (n=129). The difference in the mean change between the 2 groups was −0.7 (two-sided 95% confidence interval, −1.3 to −0.1). The noninferiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was verified within the noninferiority margin (1.1). The superiority of multimatrix mesalazine 4.8 g/day to pH-dependent-release mesalazine 3.6 g/day was also investigated and confirmed in the full analysis set, according to the study protocol. In subgroup analyses, the effectiveness of multimatrix mesalazine 4.8 g/day was consistent in all subgroups. There was no difference in safety between the 2 treatment groups.Conclusions: Multimatrix mesalazine 4.8 g/day has higher efficacy and shows no difference in safety in mildly to moderately active UC, in comparison with pH-dependent-release mesalazine 3.6 g/day.

Background and study aims Endoscopic papillectomy (EP) is a minimally invasive treatment for ampullary neoplasms and is recognized as an alternative treatment to surgical resection; however, there are few reports on a suitable pancreatic stent (PS) after EP for preventing pancreatitis. The aim of this study was to evaluate the efficacy of a long PS after EP. Patients and methods In this retrospective single-center study, 39 patients with pathologically proven ampullary neoplasms who underwent EP between March 2012 and August 2018 were enrolled. The study participants were divided into two subgroups according to the PS length: those with a PS shorter than 5 cm (short PS group, n = 17) and those with a PS of 7 cm (long PS group, n = 22). The incidence of adverse events and risk factors for pancreatitis were evaluated. Results The diameter of all PSs was 5 Fr. Post-EP pancreatitis occurred in nine patients (23.1 %), with two cases of severe pancreatitis (5.1 %). Pancreatitis occurred more frequently in the short PS group (7/17, 41.2 %) than in the long PS group (2/22, 9.1 %) (P = 0.026). There were no significant differences between the two groups in terms of other adverse events. Univariate and multivariate analyses showed that a long PS was the only factor associated with a decreased incidence of post-EP pancreatitis (P = 0.042; odds ratio, 0.16; 95 % confidence interval, 0.027–0.94). Conclusion A long (7 cm) PS significantly decreased incidence of pancreatitis after EP. Prospective randomized studies with a larger number of patients and wider range of PS lengths are required.

Background and aimsThere is a need to safely achieve conscious sedation during endoscopic retrograde cholangiopancreatography (ERCP). We evaluated the safety and feasibility of a mainstream capnometer system to monitor apnoea during ERCP under CO2 insufflation.MethodsNon-intubated adult patients undergoing ERCP-related procedures with intravenous sedation were enrolled. End-tidal CO2 (EtCO2) was continuously monitored during the procedure under CO2 insufflation using a mainstream capnometer system, comprising a capnometer and a specially designed bite block for upper gastrointestinal endoscopy and ERCP. Oxygen saturation (SpO2) was also monitored continuously during the procedure. In this study, we evaluated the safety and feasibility of the capnometer system.ResultsEleven patients were enrolled. Measurement of EtCO2 concentration was possible from the beginning to the end of the procedure in all 11 cases. There was no measurement failure, dislocation of the bite block, or adverse event related to the bite block. Apnoea linked to hypoxaemia occurred five times (mean duration, 174.4 s).ConclusionThis study confirmed that apnoea was detected earlier than when using a percutaneous oxygen monitor. Measurement of EtCO2 concentration using the newly developed mainstream capnometer system was feasible and safe even under CO2 insufflation.

[This corrects the article DOI: 10.1371/journal.pone.0212989.].

BackgroundVedolizumab safety and efficacy have been established in many populations all over the world, but have never been studied in Japan. We report results from a Phase 3, randomized, double-blind, placebo-controlled study of vedolizumab in Japanese patients with active ulcerative colitis (UC).MethodsPatients with moderate-to-severe UC were enrolled into Cohort 1 (double-blinded) or Cohort 2 (open-label) in the induction phase. Cohort 1 was randomized 2:1 to receive 300 mg vedolizumab or placebo, while Cohort 2 received vedolizumab 300 mg only, at Weeks 0, 2, and 6. Patients from Cohorts 1 and 2 showing a clinical response to vedolizumab at Week 10 were randomized 1:1 to receive vedolizumab or placebo (double-blinded) at Week 14 and then every 8 weeks up to Week 54 as the maintenance phase. The primary endpoint was clinical response at Week 10, for the induction phase, and clinical remission at Week 60, for the maintenance phase.ResultsA total of 292 patients were enrolled into the induction phase (246 in Cohort 1, 46 in Cohort 2); 83 patients achieved response to vedolizumab and were subsequently enrolled into the maintenance phase. Clinical response rates at Week 10 were 39.6% (65/164) and 32.9% (27/82) in the vedolizumab and placebo groups in Cohort 1, respectively (adjusted odds ratio [AOR] = 1.37, 95% CI 0.779-2.399; p = 0.2722). In the maintenance phase, clinical remission rate at Week 60 was significantly higher in the vedolizumab group, at 56.1% (23/41), versus 31.0% (13/42) for placebo (AOR = 2.88, 95% CI 1.168-7.108; p = 0.0210). Most adverse events were mild to moderate in intensity, and no deaths occurred during the study period.ConclusionsVedolizumab showed numerically greater efficacy compared with placebo as induction therapy, but the difference was not statistically significant. Vedolizumab was significantly superior to placebo as maintenance therapy in Japanese patients with UC. Vedolizumab has favourable safety and tolerability in these patients.Trial registrationClinicalTrials.gov: NCT02039505.

Background: Corticosteroids may be temporarily effective for ulcerative colitis (UC), but long-term use increases the risk of adverse drug reactions. Objective: The goal of the study was to examine steroid use in remission induction therapy after diagnosis of UC. Study Design: A retrospective observational study using the Japan Medical Data Center (JMDC) Claims Database from January 2008 to December 2014. Setting: Clinics, university hospitals, and national/public hospitals. Intervention: Initiation of steroids after diagnosis of UC. Main outcome measures: Start time and annual rate of steroid use, and use during the first 6 months of remission induction therapy. Results: The subjects were 399 patients were newly diagnosed with UC in the study period. The rate of steroid use after diagnosis was 58.4% in 2009, and showed a significant decreasing trend yearly after 2010 (p ≤ 0.0001). Regarding the start time, 52.2% of patients began steroids within 60 days after diagnosis of UC. At 6 months after initiation, 23.7% continued to use steroids and 73.9% of these patients used high-dose steroids. Conclusion: In treatment of UC after diagnosis, many patients continue to use steroids for >6 months after initiation. Reduced use of steroids based on clinical practice guidelines for UC should be promoted.

Endoscopy plays a significant role in the diagnosis, management, and surveillance of colorectal cancer (CRC) and inflammatory bowel diseases (IBDs). Moreover, magnifying endoscopy and image-enhanced endoscopy has a crucial role in the clinical setting. Recently, a super-magnifying endoscope has been developed, and two devices, confocal laser endomicroscopy (CLE) and an endocytoscopy system (ECS), which allow in vivo microscopic inspection of the microstructural mucosal features of the gastrointestinal tract, are currently available. Studies on the use of ECS in CRC were reported by a Japanese group. Additionally, a few studies on the use of ECS in IBD have been reported. CLE has been shown to be reliable in assessing the activity of the disease in IBDs in both ulcerative colitis and Crohn’s disease. Various published studies evaluated the use of CLE during colonoscopy to distinguish colorectal polyp pathology and neoplasia. However, these studies are heterogeneous, and further evidence is necessary to confirm the efficacy of CLE.

Background and study aims We report the effectiveness of a newly developed plastic stent for preventing bile leakage after endoscopic ultrasonography (EUS)-guided antegrade stenting. This treatment was performed on a 59-year-old woman with malignant obstructive jaundice caused by peritoneal metastasis. First, we attempted transpapillary drainage using short-type single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography, but we could not achieve it. We then attempted EUS-guided antegrade stenting through the intrahepatic bile duct from the esophagojejunal anastomosis. We successfully inserted uncovered metallic stents for common bile duct and a newly plastic stent for hepaticojejunostomy from the antegrade approach. There were no adverse events after the treatment.

Background and study aims Traversing the ileocecal valve (ICV) is technically challenging with a retrograde approach to single-balloon enteroscopy (SBE). A novel technique called responsive insertion technology (RIT) colonoscopy was developed to obtain a higher cecal intubation rate in this setting. A prototype long SBE equipped with RIT (P-SBE) was developed to obtain superior insertability. The aim of this study was to compare the insertability of a standard single-balloon enteroscope (S-SBE) versus a P-SBE. Patients and methods This study was a multicenter, randomized, non-blinded, trial of 62 patients with small bowel pathologies. All procedures were performed with SBE via the trans-anal route. Procedure success was defined as stable intubation of the terminal ileum (TI) 20 cm beyond the ICV. The primary variable was time to reach stable TI intubation 20 cm beyond the ICV (TSTII). If stable TI intubation was not achieved within 10 minutes, the initial SBE was removed through the indwelling overtube and replaced with another SBE. Results Sixty patients were examined with two patients excluded from this study. TSTII using P-SBE was significantly decreased compared to S-SBE (mean P-SBE vs S-SBE: 98.3 vs 169.4 second, P = 0.006). The completion rates for stable intubation within 10 minutes of using P-SBE and S-SBE were 96.8 % and 86.2 %, respectively (P = 0.19). On endoscope replacement, all patients had achieved stable TI intubation. Conclusions SBE with RIT improves insertability when traversing the ileocecal valve in retrograde SBE.

Background and study aims In Japan, the elderly population has been increasing annually. The number of elderly patients for whom esophagogastroduodenoscopy (EGD) and colonoscopy (CS) is indicated also has been rising. The aim of this study was to evaluate the safety and efficacy of routine endoscopy in a cohort of octogenarians aged 85 years and older – defined by the World Health Organization as the very elderly. Patients and methods A total of 5,586 patients underwent EGDs, and 2,484 patients underwent CSs performed at the Keio University Hospital from January to September 2014. One hundred eighty-five EGDs and 70 of the CS were performed in the very elderly. Six hundred nine EGDs and 262 CS were performed on younger patients (aged forties). Statistical analysis was performed by univariate and multivariate analyses. Results On univariate analysis, the rate of adverse events (AEs) in the very elderly was significantly higher compared to the younger group (6.3 % vs. 1.1 %; P

Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.

The guidelines for colonoscopy present withdrawal time (WT) and adenoma detection rate (ADR) as the quality indicator. The purpose of this retrospective study is to analyze the predicting factors with polyp detection rate (PDR) as a surrogate for ADR by using comprehensive health checkup data, and assess the correlation between PDR per each colonic segment and WT, and factors influencing WT.One thousand and thirty six consecutive health checkup cases from April 2015 to March 2016 were enrolled in this study, and 880 subjects who undertook colonoscopy without polyp removal or biopsy were divided into the two groups (polyp not detected group vs polyp detected group). The two groups were compared by subjects and clinical characteristics with univariate analysis followed by multivariate analysis. Colonoscopies with longer WT (≥ 6 min) and those with shorter WT (< 6 min) were compared by PDR per each colonic segment, and also by subjects and clinical characteristics.A total of 1009 subjects included two incomplete colonoscopies (CIR, 99.9%) and overall PDR was 35.8%. A multiple logistic regression model demonstrated that age, gender, and WT were significantly related factors for polyp detection (odds ratio, 1.036; 1.771; 1.217). PDR showed a linear increase as WT increased from 3 min to 9 min (r = 0.989, p = 0.000) and PDR with long WT group was higher than that with short WT group per each colonic segment, significantly in transverse (2.3 times, p = 0.004) and sigmoid colon (2.1 times, p = 0.001). Not only bowel preparation quality but also insertion difficulty evaluated by endoscopist were significant factors relating with WT (odds ratio, 3.811; 1.679).This study suggests that endoscopists should be recommended to take more time up to 9 min of WT to observe transverse and sigmoid colon, especially when they feel no difficulty during scope insertion.

Background and study aims Colonoscopies can predict long-term prognoses in patients with ulcerative colitis (UC). Recently, a new imaging technology has been developed that uses 3 types of illumination with center wavelengths of 540 nm, 600 nm, and 630 nm. The use of both the 600-nm and 630-nm lights (Dual red imaging; DRI) is critical for identifying blood vessels in deeper tissue. The aim of this study was to evaluate the usefulness of DRI for assessing the severity of inflammation in patients with UC. Patients and methods A total of 43 UC patients were retrospectively enrolled to evaluate the endoscopic severity of 112 colon segments, and Mayo endoscopic scores, DRI scores and the severity of inflammation on a visual analogue scale (VAS) were compared. The Mayo endoscopic scores, DRI scores, and histologic scores were evaluated, and the interobserver agreement on DRI scores among 5 investigators was also assessed. The usefulness of DRI scores for predicting prognoses was also assessed in patients with clinical remission. Results The DRI scores were closely correlated with the VAS for the severity of colonic inflammation (r = 0.96) and the histologic scores (r = 0.72 – 0.8). The DRI scores had a higher rate of interobserver agreement (κ values = 0.63 – 0.88) than the Mayo endoscopic scores (κ values = 0.44 – 0.59). Inter-observer agreement between 4 non-experts was also excellent (mean κ value = 0.76, range 0.63 – 0.82). The expected time until recurrence was significantly longer in patients with lower DRI scores (P

5-Aminosalicylic acids (5-ASA) are effective for ulcerative colitis (UC) as a maintenance therapy. It is not clear when and how to reduce a dose of 5-ASA after inducing remission. We aimed to investigate the clinical characteristics and evaluate the risk factors of relapse for UC patients receiving 5-ASA.The medical records of prospectively registered UC patients who received oral 5-ASA as maintenance therapy between January and December 31, 2014, were investigated. The patients' clinical characteristics in a 2-year follow-up were compared between a relapse group and a remission group.Of 527 UC patients receiving only oral 5-ASA, 390 (74.0%) maintained remission and 137 (26.0%) relapsed during the follow-up period. Multivariable analysis indicated that a shorter duration of disease remission (p < 0.001, OR: 1.24, 95% CI: 1.12-1.38) was statistically significant for each comparison between the remission and relapse groups among all the patients. Risk factors for clinical relapse were a shorter duration of disease remission (p

There have been many reports about a variety of factors associated with incomplete colonoscopy or difficult colonoscopy with long cecal intubation time (CIT). The aim of this retrospective study was to analyze the factors related to difficult colonoscopy under conscious sedation and demonstrate the clinical utility of a small-caliber scope as rescue by using the data from a large number of subjects who underwent health check-ups.Consecutive 1036 cases over a 12-month period (April 2015 to March 2016) were enrolled and 619 subjects were divided into two groups: Easy colonoscopy (CS) Group (CIT ≤ 10 min); Difficult CS Group (CIT > 10 min or incomplete colonoscopy by a standard scope). The two groups were compared by subjects and colonoscopy characteristics with univariate analysis followed by multivariate logistic regression analysis. Reasons for incomplete colonoscopy were also assessed.Cecal intubation rate increased from 97.9% to 99.9% (1007/1008) by the rescue scope. Main reasons for incomplete colonoscopy were tortuosity in the left hemicolon (38%), redundancy in the right hemicolon (29%), pain (19%) and fixation (14%). Moreover, 95% (20/21) of rescue colonoscopies were completed without additional sedation. Higher BMI (21 kg/m2 ≤ BMI) and intermediate visceral adipose tissue (VAT) (75 cm2 ≤ VAT < 150 cm2) were significantly associated with easy CS (80.7% vs 19.3%, P = 0.004; 56.3% vs 43.7%, P = 0.001) by univariate analysis. Age, gender, and VAT, not BMI, were independently associated with difficult colonoscopy by multivariate analysis (OR (95% CI), P: 0.964 (0.942, 0.985), 0.001; 1.845 (1.101, 3.091), 0.020; 2.347 (1.395, 3.951), 0.001). Subgroup analysis by gender also showed VAT as the best predictor for both genders.Difficult colonoscopy was significantly associated with advancing age, female gender and, lower (< 75 cm2) or higher (150 cm2 ≤) VAT. These subjects may benefit from having complete and more comfortable colonoscopy examinations by using the small-caliber scope rather than the standard scope.

Background and study aims: Olympus recently developed a new algorithm called Omni mode that discards redundant video capsule endoscopy (VCE) images. The current study aimed to demonstrate the non-inferiority of the Omni mode in terms of true positives (TPs) and the superiority of the Omni mode with regard to reading time against a control (ordinary ES-10 system). Patients and methods: This multicenter prospective study included 40 patients with various small bowel diseases. VCE images were evaluated by 7 readers and 3 judging committee members. Two randomly allocated readers assessed the VCE images obtained using the 2 modalities for each patient. The order of the modalities was switched between the 2 readers and the interval between readings by the same reader was 2 weeks. The judging committee predefined clinically relevant lesions as major lesions and irrelevant lesions as minor lesions. The number of TPs for major and minor lesions and the reading times were compared between the modalities. The predefined non-inferiority margin for the TP ratio of the Omni mode compared with the control was 0.9. Results: The estimated TP ratios and 95 % confidence intervals for total, major, and minor lesions were 0.87 (0.80 – 0.95), 0.93 (0.83 – 1.04), and 0.83 (0.74 – 0.94), respectively. Although non-inferiority was not demonstrated, the rate of detection of major lesions was not significantly different between the modalities. The reading time was significantly lower when using the Omni mode than when using the control. Conclusions: The Omni mode may be only appropriate for the assessment of major lesions.

Background and study aims: Small intestinal pathology in hemodialysis (HD) patients has been studied in only a small number of retrospective case series. One method for noninvasively surveying small intestinal disorders is video capsule endoscopy (VCE). The primary aim of this study was to investigate the prevalence of small intestinal abnormalities among asymptomatic maintenance HD outpatients using VCE. The secondary aim was to assess the clinical impact of these abnormalities. Patients and methods: This study consisted of two phases. In phase I, a cross-sectional study, a cohort of patients who received maintenance HD three times weekly at an outpatient hemodialysis clinic were studied using VCE. Phase II was a prospective cohort study with follow up for 1 year after VCE. Results: Fifty-six patients were enrolled in this study, and two were excluded from analysis due to capsule retention in the stomach. The prevalence of small bowel abnormalities in HD patients was 64.8 % (35/54) (95 % confidential interval 52.1 % – 77.6 %). Of 54 patients, 21 (38.9 %) had mucosal lesions, 10 (18.5 %) had vascular lesions, and 4 (7.4 %) had both lesion types. During the 1-year follow-up period, events occurred in four patients. A small bowel-associated event was observed in one patient, who underwent laparoscopy-assisted small intestinal partial resection 3 months after diagnosis by VCE. All patients in whom events were seen had small bowel abnormalities; no events were observed in the VCE-negative group. Conclusions: Although asymptomatic maintenance HD patients had a high prevalence of small bowel abnormalities (64.8 %), they did not have a high incidence of small bowel-associated events during the 1-year follow-up.

Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS).

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41-4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). METHODOLOGY AND PRINCIPAL FINDINGS: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898-0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r(s) = 0.592, 95%CI: 0.385-0.742, p