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Rationale: Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis.Objectives: To investigate whether HO-1 can reduce silicosis in mice and humans.Methods and Measurements: Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting.Main Results: Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1.Conclusions: Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression. [ABSTRACT FROM AUTHOR]

Background: The ulcerative colitis intestinal ultrasound (UC-IUS) index (UII) has been reported as a sonographic scoring system correlating with the Mayo endoscopic subscore (MES). Endoscopic improvement (EI) of UC (MES ≤ 1) is a crucial therapeutic target in clinical practice. However, the cutoff value for estimating EI using the UII has not been established., Methods: We established test and validation cohorts comprising patients with UC undergoing IUS and endoscopy within a 15-day interval at our institution. IUS findings (bowel wall thickness, bowel blood flow, bowel wall structure, haustrations, and inflammatory fat) and endoscopic activity (MES) of each colon segment (ascending, transverse, descending, and sigmoid colon) were assessed., Results: In the test cohort (74 segments), UII was correlated with MES (r = 0.645, p < 0.0001). The median UII was 1.0 and 6.0 among participants with MES ≤ 1 and MES ≥ 2, respectively. A UII of 2 was identified as the threshold for estimating MES ≤ 1 with receiver operating characteristic analysis. In the validation cohort (122 segments), UII was correlated with MES (r = 0.675, p < 0.0001) and the estimation ability of UII ≤ 2 for EI had a positive predictive value of 85.4% and negative predictive value of 79.0%. This estimation ability of UII for EI was numerically lower but not statistically different from the previously reported Milan Ultrasound Criteria and Kyorin Ultrasound Criterion for UC., Conclusion: UII ≤ 2 can be a simple, feasible criterion for estimating EI. Correlation with MES is an advantage of the UII compared with other criteria. Proper use of various sonographic criteria is important., Competing Interests: Declarations Conflict of interest Hiromu Morikubo has received grant support from Takeda Pharmaceutical. Minoru Matsuura has received consulting and lecture fees from Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co. Ltd., AbbVie GK, Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co., Ltd., JIMRO Co., Nippon Kayaku Co. Ltd., Mylan EPD G.K., and Aspen Japan Co. Ltd. Jun Miyoshi has received grant support from AbbVie GK, and consulting and lecture fees from EA Pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Jansen Asia Pacific Pte. Ltd., Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, JIMRO Co., Miyarisan Co. Ltd., and Takeda Pharmaceutical Co. Ltd. Tadakazu Hisamatsu has performed Joint Research with Kissei Pharmaceutical Co., Ltd. and EA Pharma Co., Ltd. and received grant support from Mitsubishi Tanabe Pharma Corporation, EA Pharma Co., Ltd., AbbVie GK, JIMRO Co., Ltd., Zeria Pharmaceutical Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Boston Scientific Corporation, and Mochida Pharmaceutical Co., Ltd. as well as consulting and lecture fees from EA Pharma Co., Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co., Ltd., JIMRO Co., Mochida Pharmaceutical Co., Ltd., Bristol Myers Squibb Co., Eli Lilly and Company, Gilead Sciences, Inc., and Takeda Pharmaceutical Co., Ltd. Haruka Komatsu, Yoko Kimura, Chihiro Moue, and Hiromi Yonezawa have no conflicts of interest to declare., (© 2024. Japanese Society of Gastroenterology.)

Introduction: There is a close relationship between the relapse of inflammatory bowel disease (IBD) and lifestyle factors, including concomitant medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, smoking status, and alcohol consumption. However, solid evidence is limited regarding the risk factors at diagnosis and initial disease course. This study aimed to explore the impact of concomitant prescriptions and lifestyle factors in patients with newly diagnosed IBD using a large-scale real-world database., Methods: This is a retrospective inception cohort study using the insurance claims database. Newly diagnosed patients with UC and CD were enrolled between January 2005 and May 2020. Concomitant prescriptions and lifestyle factors were assessed for new biologics use, surgery, and hospitalization during the first year., Results: In total, 6,743 patients with UC and 1,000 patients with CD were enrolled. Proton pump inhibitors, antithrombotics, antibiotics, and NSAIDs were identified as associated factors for both biologics use and hospitalization in UC patients (all p < 0.01), and antithrombotics were identified as associated factors for both biologics use and hospitalization in CD patients (all p < 0.01) in multivariable analyses. Interestingly, smoking was protective against hospitalization in UC patients ( p < 0.01) but not in CD patients ( p = 0.997), analyzed by univariate analysis. Alcohol consumption was protective against hospitalization outcomes in UC patients ( p = 0.02) but not in CD patients ( p = 0.27), analyzed by univariate analysis., Conclusion: Immediate attention should be paid to concomitant medications at diagnosis because they may have impact on the initial course of IBD., Competing Interests: H.M. has received research grants from Japan Foundation for Takeda Pharmaceutical, Applied Enzymology. Under a contract between Kyoto University and Takeda Pharmaceutical Company Limited, fees for consulting with H.Y. were paid to Kyoto University, which are not related to this work. T.K. has received honorariums from AbbVie, Alfresa Pharma, Jansen Pharma, Takeda, Mitsubishi Tanabe Pharma, Phizer, and Mochida, received research grants from Nippon Kayaku and EA Pharma, received scholarship grants from Otsuka Holdings, JIMRO, EA Parma, AbbVie, Zeria, Alfresa Pharma, Mochida Pharmaceutical, Miyarisan Pharmaceutical, and Kyorin Pharmaceutical. These are not related to this work. T.N. and K.N. declare no conflicts of interest associated with this manuscript., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently., Aims: To investigate the association between recent steroid use and relapse risk in UC patients with EH., Methods: This multi-centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non-recent or steroid-naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse., Results: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non-recent/steroid-naïve group (multi-variable-adjusted OR 5.53 [95% CI 2.85-10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid-naïve patients. (p trend  <0.001)., Conclusions: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Predicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity., Methods: Thirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion of ≤6.2 and Kyorin Ultrasound Criterion for UC (bowel wall thickness of <3.8 mm and submucosa index of <50%)., Results: Thirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in bowel wall thickness and bowel wall vascularity at 3 months than the SFCR(-) group. The Milan Ultrasound Criterion and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(-) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%., Conclusion: Sonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment., (© 2024 The Authors.)

Background: Endoscopic improvement (EI; a Mayo endoscopic subscore of 0 or 1) is considered a therapeutic target in ulcerative colitis (UC) treatment. The potential to estimate EI non-invasively is an advantage of intestinal ultrasound (IUS). In a previous study, we developed a new sonographic parameter, the submucosa index (SMI), calculated as the ratio of the submucosal thickness to bowel wall thickness (BWT), and reported that combining BWT and SMI results in a practical and promising criterion for estimating EI without color Doppler assessment. This study aimed to validate the EI estimation ability of our B mode-based criterion, the 'Kyorin Ultrasound Criterion for UC' (KUC-UC; BWT < 3.8 mm and SMI < 50%), using an external cohort., Methods: Patients with UC who underwent IUS and colonoscopy within 15 days without a treatment change between examinations were included. IUS findings, including BWT, SMI, and modified Limberg score for vascularity of the colon, were assessed., Results: Forty-four test pairs of IUS and colonoscopy examinations in a total of 122 colonic segments were analyzed. The KUC-UC showed positive predictive value (PPV) of 94.6% and negative predictive value (NPV) of 80.0% for EI. In comparison, PPV and NPV were 85.4% and 79.0%, respectively, for the common criterion BWT of < 3 mm, and 83.0% and 82.7% for the validated Milan Ultrasound Criteria (a score of ≤ 6.2)., Conclusions: External validation showed that the KUC-UC using only B mode findings without complicated calculations is a feasible and accurate sonographic criterion for estimating the EI of UC., (© 2024. Japanese Society of Gastroenterology.)

Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model., (© 2024. The Author(s).)

Introduction: A large proportion of small bowel lesions in Crohn's disease (CD) may exist beyond the reach of ileocolonoscopy and there is no gold standard imaging modality to screen them, suggesting the need for optimal biomarkers. We aimed to compare the usefulness of C-reactive protein (CRP), faecal calprotectin (FC), and leucine-rich alpha-2 glycoprotein (LRG) in determining small bowel lesions of CD., Methods: This was a cross-sectional observational study. CRP, FC, and LRG were prospectively measured in patients with quiescent CD who underwent imaging examinations (capsule or balloon-assisted endoscopy, magnetic resonance enterography, or intestinal ultrasound) selected by the physician in clinical practice. Mucosal healing (MH) of the small bowel was defined as a lack of ulcers. Patients with a CD activity index >150 and active colonic lesions were excluded., Results: A total of 65 patients (27, MH; 38, small bowel inflammation) were analysed. The area under the curve (AUC) of CRP, FC, and LRG was 0.74 (95% confidence interval: 0.61-0.87), 0.69 (0.52-0.81), and 0.77 (0.59-0.85), respectively. The AUC of FC and LRG in a subgroup of 61 patients with CRP <3 mg/L (26, MH; 32, small bowel inflammation) was 0.68 (0.50-0.81) and 0.74 (0.54-0.84), respectively. The cut-off of 16 μg/mL of LRG showed the highest positive predictive value of 1.00 with specificity of 1.00, while negative predictive value was highest (0.71) with sensitivity of 0.89 at the cut-off of 9 μg/mL., Conclusion: LRG can accurately detect and/or exclude the small bowel lesions with two cut-off values., Competing Interests: K.A. has an endowed chair from AbbVie, JIMRO, Zeria Pharmaceutical, KYORIN Pharmaceutical, Mochida Pharmaceutical, and EA Pharma. T.K. received lecture fees from Takeda Pharmaceutical Co., Ltd. Activaid, Alfresa Pharma Corporation, Zeria Pharmaceutical Co., Ltd., KYORIN Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Pfizer Japan Inc., Janssen Pharmaceutical K.K., Thermo Fisher Diagnostics K.K., and JIMRO Co., Ltd.; received research grants from AbbVie GK, Activaid, Alfresa Pharma Corporation, JMDC Inc., Gilead Sciences, Inc., Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Ferring Pharmaceuticals, and Bristol Myers Squibb; received scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., and Nippon Kayaku Co., Ltd.; belonged to study group sponsorship by Otsuka Holdings, AbbVie GK, EA Pharma Co., Ltd., Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., KYORIN Pharmaceutical Co., Ltd., and Mochida Pharmaceutical Co., Ltd.; received advisory/consultancy fees from Janssen Pharmaceutical K.K., EA Pharma Co., Ltd., KISSEI Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Activaid, Pfizer Japan Inc., Nippon Kayaku Co., Ltd., Alfresa Pharma Corporation, KYORIN Pharmaceutical Co., Ltd., AbbVie GK, Mochida Pharmaceutical Co., Ltd, and Mitsubishi Tanabe Pharma Corporation. MN has served as a speaker or a consultant in Covidien, Mochida Pharmaceutical, Takeda Pharmaceutical, Zeria Pharmaceutical, KYORIN Pharmaceutical, and Nippon Kayaku and received research funding from Mitsubishi Tanabe Pharma and Japanese foundation for research and promotion of endoscopy. SS has served as a speaker for AbbVie, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, and Zeria Pharmaceutical and as an endowed chair for AbbVie, JIMRO, Zeria Pharmaceutical, KYORIN Pharmaceutical, Mochida Pharmaceutical, and EA Pharma. HM has received research grant from Takeda Pharmaceutical. YM has an endowed chair from AbbVie, JIMRO, Zeria Pharmaceutical, KYORIN Pharmaceutical, Mochida Pharmaceutical, and EA Pharma. TF has received research funding from Mitsubishi Tanabe Pharma. TH has received lecture fees from Aspen Japan K.K, AbbVie GK, Ferring, Gilead Sciences, Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Pfizer, and Takeda Pharmaceutical; advisory/consultancy fees from APO PLUS Station, AbbVie GK, Bristol Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Gilead Sciences, Janssen, KYORIN, Mitsubishi Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda Pharmaceutical, Zeria Pharmaceutical and research grants from AbbVie GK, Activaid, Alfresa Pharma Corporation, JMDC Inc., Gilead Sciences, Inc., Nippon Kayaku Co., Ltd., Eli Lilly Japan K.K., Mochida Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Ferring Pharmaceuticals, and Bristol Myers Squibb; received scholarship contributions from Mitsubishi Tanabe Pharma Corporation, Zeria Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd.; and belonged to study group sponsorship by Otsuka Holdings, AbbVie GK, EA Pharma Co., Ltd., Zeria Pharmaceutical Co., Ltd., JIMRO Co., Ltd., KYORIN Pharmaceutical Co., Ltd., and Mochida Pharmaceutical Co., Ltd., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Intestinal ultrasound (IUS) is a promising modality for the management of inflammatory bowel disease (IBD) and has the potential to particularly contribute in monitoring disease activity, an advantage crucial for optimizing the therapeutic strategy. While many IBD physicians appreciate and are interested in the use of IUS for IBD, currently only a limited number of facilities can employ this examination in daily clinical practice. A lack of guidance is one of the major barriers to introducing this procedure. Standardized protocols and assessment criteria are needed such that IUS for IBD can be considered a feasible, reliable examination in clinical practice, and multicenter clinical studies can be conducted for further clinical evidence of the application of IUS in IBD for best patient care. In this article, we provide an overview of how to start IUS for IBD and introduce basic procedures. Furthermore, IUS images from our practice are provided as a color atlas for understanding sonographic findings and scoring systems. We anticipate this "first aid" article will be helpful to promote IUS for IBD in daily practice.

Background and Aim: Crohn's disease (CD) often causes intractable diarrhea after intestinal resection. Anion exchange resins have been reported to be effective in patients with bile acid diarrhea after distal ileectomy; furthermore, bile acid metabolism has been implicated in the pathogenesis of CD. Therefore, we aimed to examine the effectiveness of colestimide in the management of postoperative CD, and to compare its impact between patients with and those without ileocecal resection., Methods: Postoperative CD patients prescribed colestimide for diarrhea between April 2017 and December 2020 were retrospectively evaluated for changes in the total Crohn's disease activity index (CDAI), each CDAI component including diarrhea frequency/week, albumin, and C-reactive protein (CRP) was evaluated before and after the administration of colestimide. Furthermore, comprehensive patient and physician assessments were reviewed from medical records during the first outpatient visit as a global clinical judgment after the initiation of colestimide therapy., Results: A total of 24 patients were included, of whom 17 had a previous history of ileocecal resection. Significant improvement was noted in CDAI and diarrhea frequency only in the ileocecal resection group (CDAI: 114.5 ± 52.7 and 95.4 ± 34.8, P  < 0.05; diarrhea frequency/week 23.8 ± 14.1 and 15.4 ± 11.2, P  < 0.05, respectively). There was no significant improvement in other CDAI components, albumin level, or CRP level in either group. In the global clinical judgment, 13 and 4 patients in the ileocecal and non-ileocecal resection groups, respectively, were judged as "effective," with an overall efficacy rate of 70.8%., Conclusion: Colestimide is effective for diarrhea in patients with postoperative CD, especially after ileocecal resection., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Bowel ultrasonography is a non-invasive imaging tool that can repeatedly monitor ulcerative colitis (UC) activity., Aim: This study aimed to determine whether early transabdominal or transperineal ultrasonography changes can predict subsequent clinical response to induction therapy in patients with UC., Methods: This single-centre prospective study explored ultrasonographic predictors for clinical remission (patient-reported outcome-2 ≤ 1 with no rectal bleeding subscore) at week 8 in patients with active UC who underwent induction therapy, in comparison with faecal calprotectin and C-reactive protein (measured at baseline, week 1 and week 8). Predictive factors were assessed using multivariable regression models and receiver-operating-characteristic curve analysis., Results: A total of 100 patients were analysed, of which 54 achieved remission at week 8. Baseline biomarker and ultrasonographic-parameter values were not predictive of remission. Contrastingly, change from baseline to week 1 in rectal bowel wall thickness measured using transperineal ultrasonography was an independent predictor of remission by week 8 (adjusted odds ratio is associated with a 1-mm decrease: 1.90 [95% confidence interval, 1.22-2.95]). In a subgroup analysis of the patients who did not achieve remission in 1 week, the predictive value of change in rectal bowel wall thickness remained high (AUC = 0.77 [95% confidence interval, 0.61-0.88])., Conclusion: Improvement in rectal bowel wall thickness measured using transperineal ultrasonography at week 1 predicts treatment success and potentially facilitates decision making during the early course of induction therapy in UC., (© 2022 John Wiley & Sons Ltd.)

Background and Aim: The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims-based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims-based algorithm for UC in Japan., Methods: A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims-based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR)., Results: Overall, 1139 claims-defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7-93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7-93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6-46.3) due to incomplete case registration., Conclusions: The claims-based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases., (© 2021 Pfizer Inc. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Mucosal healing is a treatment target for patients with ulcerative colitis. However, the relevance of proactive treatment for residual inflammation limited to the distal colon is unclear., Materials and Methods: Patients with ulcerative colitis who had extensive colitis in clinical remission and underwent colonoscopy were retrospectively enrolled and followed up for 2 years. Patients with complete endoscopic remission (CER; Mayo endoscopic subscore [MES] of 0) and those with short-segment distal inflammation (SS; active inflammation only in the sigmoid colon and/or rectum with a proximal MES of 0) were compared for the incidence of minor (only symptomatic) and major (need for induction treatments or hospitalization) relapses., Results: A total of 91 patients with CER and 54 patients with SS were identified and 63 relapses (47 minor and 16 major) were analyzed. Univariate analysis showed that minor relapses were significantly more frequent in the SS group than in the CER group (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.25-3.97), but major relapses were not more frequent in the SS group than in the CER group (HR, 1.78; 95% CI, 0.65-4.83). Multivariable analysis showed that SS was the only risk factor significantly associated with minor relapse (HR, 2.38; 95% CI, 1.31-4.36). When the SS group was stratified by MES of 1 vs 2/3, minor relapses were significantly more frequent in the subgroup with MES of 2/3 than in the CER group, whereas the incidence of major relapse remained similar., Conclusions: Residual short-segment distal inflammation is not a risk factor for major relapses as long as endoscopic remission is achieved in the proximal colon. Therefore, reactive but not proactive treatment may be appropriate for such lesions., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Real-world big data studies using health insurance claims databases require extraction algorithms to accurately identify target population and outcome. However, no algorithm for Crohn's disease (CD) has yet been validated. In this study we aim to develop an algorithm for identifying CD using the claims data of the insurance system., Methods: A single-center retrospective study to develop a CD extraction algorithm from insurance claims data was conducted. Patients visiting the Kitasato University Kitasato Institute Hospital between January 2015-February 2019 were enrolled, and data were extracted according to inclusion criteria combining the Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis codes with or without prescription or surgical codes. Hundred cases that met each inclusion criterion were randomly sampled and positive predictive values (PPVs) were calculated according to the diagnosis in the medical chart. Of all cases, 20% were reviewed in duplicate, and the inter-observer agreement (Kappa) was also calculated., Results: From the 82,898 enrolled, 255 cases were extracted by diagnosis code alone, 197 by the combination of diagnosis and prescription codes, and 197 by the combination of diagnosis codes and prescription or surgical codes. The PPV for confirmed CD cases was 83% by diagnosis codes alone, but improved to 97% by combining with prescription codes. The inter-observer agreement was 0.9903., Conclusions: Single ICD-code alone was insufficient to define CD; however, the algorithm that combined diagnosis codes with prescription codes indicated a sufficiently high PPV and will enable outcome-based research on CD using the Japanese claims database., Competing Interests: HM has received research grants from Japan Foundation for Applied Enzymology. TK has served as a speaker, a consultant or an advisory board member for Abbvie, Alfresa Pharma, Janssen Pharma, Takeda, Mitsubishi Tanabe Pharma, Pfizer, Mochida, and received research grants from Nippon Kayaku, EA Pharma, Otsuka Holdings, JIMRO, Abbie, Zeria. FT has received research grants from Mitsubishi Tanabe Pharma. TN are employees of JMDC Co. Ltd., holds shares in JMDC Co. Ltd. TaH has served as a speaker, a consultant or an advisory board member for Mitsubishi Tanabe Pharma, AbbVie GK, EA Pharma, Kyorin Pharma, JIMRO, Janssen Pharmaceutical, Mochida Pharmaceutical, Takeda Pharmaceutical, and received research grants from Alfresa Pharma, EA Pharma, Mitsubishi Tanabe Pharma, AbbVie GK, JIMRO, Zeria Pharmaceutical, Daiichi-Sankyo, Kyorin Pharmaceutical, Nippon Kayaku, Astellas Pharma, Takeda Pharmaceutical, Pfizer, Mochida Pharmaceutical. ToH has served as a speaker, a consultant or an advisory board member for Aspen Japan, Abbvie GK, Ferring, Gilead Sciences, Janssen, JIMRO, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical, Zeria, and received research grants from Abbvie, EA Pharma, JIMRO, Otsuka Holdings, Zeria, and received scholarship grants from Zeria. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Aim: Thiopurines are often used in combination with mesalazine for the treatment of ulcerative colitis (UC). Mesalazine formulations are delivered to the digestive tract by various delivery systems and absorbed as 5-aminosalicylic acid (5-ASA). 5-ASA is known to inhibit thiopurine S-methyltransferase (TPMT) activity and to affect thiopurine metabolism. There have been no studies comparing TPMT inhibition by multimatrix mesalazine (MMX) with other formulations. We investigated the difference in TPMT inhibition by different mesalazine formulations and prospectively confirmed the clinical relevance., Methods: Plasma concentrations of 5-ASA, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), and TPMT activities were measured in UC patients receiving various mesalazine formulations (time-dependent or pH-dependent mesalazine or MMX) as monotherapy. Patients already on both time-dependent or pH-dependent mesalazine and thiopurines switched their mesalazine to MMX, examining 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP) 0 and 8 weeks after switching. Clinical relapse after switching was also monitored for 24 weeks., Results: Plasma 5-ASA and N-Ac-5-ASA levels were significantly higher in patients receiving time-dependent mesalazine (n = 12) compared with pH-dependent mesalazine (n = 12) and MMX (n = 15), accompanied by greater TPMT inhibition. Prospective switching from time-dependent mesalazine to MMX decreased 6-TGN levels, increased those of 6-MMP, and increased 6-MMP/6-TGN ratios. Furthermore, this resulted in significantly more relapses than switching from pH-dependent mesalazine to MMX., Conclusions: Time-dependent mesalazine has higher plasma 5-ASA and N-Ac-5-ASA levels and greater TPMT inhibition than MMX. Therefore, switching from time-dependent mesalazine to MMX may lead to an increase of 6-MMP/6-TGN, which may reduce the clinical effectiveness of thiopurines, warranting close monitoring after switch., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The usefulness of second-generation colon capsule endoscopy (CCE2) in ulcerative colitis (UC), especially in clinically inactive patients, has been reported. Capsule Scoring of Ulcerative Colitis (CSUC) was developed as a severity index for UC. We aimed to determine whether CSUC is useful for predicting relapse during clinical remission., Methods: Forty-one UC patients in clinical remission who underwent CCE2 were prospectively registered from April 2016 to August 2019. Patients' CSUC score was obtained; those with subsequent relapse were followed up retrospectively. The correlation of CSUC with white blood cell count, platelet count, albumin, C-reactive protein, fecal calprotectin and fecal lactoferrin levels, and fecal immunochemical test results was evaluated; their predictive values for future relapse were compared., Results: The correlations of CSUC with white blood cell, platelet, albumin, C-reactive protein, fecal calprotectin, fecal immunochemical test, and fecal lactoferrin values were r s  = 0.13, 0.27, -0.25, 0.15, 0.50, 0.43, and 0.50, respectively. CSUC was higher in 12 patients who relapsed within 1 year than in 29 patients who remained in clinical remission (2.83 ± 1.95 vs 0.72 ± 1.00, P < 0.01). Receiver operator characteristic curve analysis showed that CSUC ≥ 1 was a predictor of relapse (area under the curve of 0.82, sensitivity of 83.3%, specificity of 58.6%) and maybe superior to fecal biomarkers. In the univariate analysis, patients with CSUC of 0 had a lower relapse rate than those with CSUC of ≧ 1 (P = 0.03, log-rank test). After analyzing patients who underwent CCE2 within 6 months after the successful induction treatment, results showed that those with CSUC of ≤ 1 remained in clinical remission for a year., Conclusion: CSUC predicts relapse within 1 year in UC patients in clinical remission, especially when used 6 months after induction treatment., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Transabdominal ultrasound is useful to assess inflammation in patients with ulcerative colitis (UC); however, the assessment of the rectum is challenging and a barrier for its widespread use., Aim: To evaluate if transperineal ultrasound is useful for predicting endoscopic and histological findings of the rectum in UC., Methods: Fifty-three consecutive adults with UC who required colonoscopy were included and transperineal ultrasound was performed in combination with transabdominal ultrasound within a week before or after colonoscopy with rectal biopsy. Mayo endoscopic subscore (MES) ≤1 was defined as endoscopic healing and Geboes score <2.1, Robarts histopathology index ≤6, and Nancy index ≤1 were defined as histological healing. Limberg score and bowel wall thickness were recorded with transperineal ultrasound. Faecal calprotectin was also measured., Results: Excellent correlation was confirmed between colonoscopy and transabdominal ultrasound in all segments except for the rectum. Rectal bowel wall thickness and Limberg score in transperineal ultrasound well correlated with rectal MES and histological indices. Bowel wall thickness ≤4 mm predicted endoscopic (Area under the curve [AUC] = 0.90) and histological (AUC = 0.87-0.89) healing. In multivariable logistic regression analysis, only bowel wall thickness in transperineal ultrasound was a significant independent predictor for rectal endoscopic and histologic healing (P < 0.05) and the predictability was better than faecal calprotectin., Conclusions: Transperineal ultrasound predicts endoscopic and histological healing of the rectum. The combination of transperineal ultrasound with transabdominal ultrasound visualises the entire colorectum and is an ideal modality for the treat-to-target strategy. Clinical Trials Registry number UMIN000033611 (https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000038323)., (© 2020 John Wiley & Sons Ltd.)

We report a case of community-acquired fulminant colitis caused by Clostridium difficile in Japan. A 46-year-old woman was diagnosed with severe infectious enterocolitis and was admitted at another hospital. The stool culture was positive for toxigenic C. difficile. Since the patient presented with fulminant C. difficile infection (CDI) with toxic megacolon, respiratory insufficiency, and circulatory failure, she was transferred to Kyorin University Hospital for intensive care. Intubation and antibiotic therapy were performed. The general condition improved with conservative treatment, and she was discharged without sequelae. While the recovered isolate was toxin A and B-positive and binary toxin-positive, it was identified as polymerase chain reaction (PCR) ribotype ts0592 and slpA sequence type ts0592. The isolate was different from PCR ribotype 027 epidemic in Europe and North America. In Japan, binary toxin-producing strains are rare and have not caused an epidemic to date. Furthermore, there are few data on community-acquired CDI in Japan. In this case, a non-elderly woman with no major risk factors such as antibiotic use, administration of proton pump inhibitor and history of gastrointestinal surgery developed community-acquired fulminant CDI caused by the binary toxin-positive strain, and ICU treatment was required. Further studies focusing on the role of binary toxin-positive C. difficile in the severity of community-acquired CDI are necessary.

We herein report a case of simultaneous amebic colitis and cytomegalovirus (CMV) enteritis in an HIV-infected patient. The patient was a 40-year-old man who developed bloody stool and diarrhea. We diagnosed him with severe amebic colitis associated with HIV infection and administered metronidazole. While his symptoms began to improve, the patient then developed CMV enteritis. We administered ganciclovir, and his symptoms improved. However, despite control of the infection, stenosis of the descending colon caused intestinal obstruction, and colostomy was performed. This case shows the importance of considering the possibility of simultaneous infection when gastrointestinal symptoms appear in people infected with HIV.

With advances in cancer chemotherapy, the importance of the new clinical discipline of cardio-oncology, which is concerned with the cardiac effects of chemotherapy, is increasing. Herein we describe the case of a 48-year-old woman with a history of breast cancer who presented with symptoms of heart failure due to chemotherapy-induced cardiomyopathy. Treatment for the patient's breast cancer had included surgery and chemotherapy with anthracyclines and trastuzumab. Echocardiography revealed multiple mobile thrombi in the left ventricle and atrium. In addition, brain magnetic resonance imaging revealed small acute cerebral infarctions due to embolization. Given the high risk of re-embolization, surgical thrombectomy was performed. Thus far, there are no standardized therapeutic guidelines for left-sided cardiac thrombi and the optimal treatment remains contentious. Although this patient was managed successfully with surgical thrombectomy, patients should be managed individually, taking into consideration embolization, bleeding, and surgical risks. With further improvements in cancer chemotherapy, there may be an increase in the incidence of complications such as multiple cardiac thrombi. From the cardio-oncology standpoint, we propose close interactions between cardiologists and oncologists for the optimal care of cancer patients., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Rationale and Objectives: The aims of this study were to assess the influence of slice thickness on the ability of radiologists to detect or not detect nodules and to agree or disagree on the diagnosis and also to investigate the potential dependence of these relations on the sizes, average computed tomographic (CT) values, and locations of the nodules., Materials and Methods: Six radiologists performed qualitative diagnostic readings of multislice CT images with a slice thickness of 2 or 10 mm obtained from 360 subjects. The nodules were diagnosed as nodules for further examination (NFEs), inactive nodules for no further examination (INNFEs), or no abnormality. The results of the diagnoses were cross-tabulated and quantitatively analyzed using the average CT values, sizes, and locations of the nodules with reference to the 2-mm slices. Multivariate logistic regression analyses were used to estimate the significant associations of these parameters with the ability of radiologists to detect or not detect nodules and to agree or disagree on the diagnosis., Results: Totals of 130 NFEs and 403 INNFEs for 2-mm slice thickness and 142 NFEs and 338 INNFEs for 10-mm slice thickness were diagnosed. Nodule classifications were as follows: the same diagnosis on both slice thickness images (67.6%), different diagnoses on two slice thickness images (21%), missed on 10-mm slice thickness images (10.6%), and misinterpreted on 10-mm slice thickness images (0.7%). Regarding detection and nondetection, NFE diagnoses were influenced by size (odds ratio [OR], 132.50; 95% confidence interval [CI], 4.77-4711) and the average CT value (OR, 27.20; 95% CI, 3.21-645.3), and INNFE diagnoses were influenced by size (OR, 16.10; 95% CI, 6.18-55.19) and the average CT value (OR, 7.67; 95% CI, 2.19-30.91). Regarding diagnostic agreement and disagreement, the NFE diagnoses were influenced by size (OR, 3.60; 95% CI, 1.29-11.04), nodule distance from the lung border (OR, 2.85; 95% CI, 1.27-6.65), and nodule location in the right upper lobe (OR, 0.07; 95% CI, 0.003-0.477), while the INNFE diagnoses were influenced by the average CT value (OR, 11.84; 95% CI, 3.33-55.86), size (OR, 0.42; 95% CI, 0.25-0.70), and nodule distance from the lung border (OR, 0.41; 95% CI, 0.25-0.66)., Conclusions: The influence of slice thickness on the ability of radiologists to detect or not detect nodules and to agree or disagree on the diagnosis was quantitatively evaluated. Detection and nondetection of NFEs and INNFEs are influenced by size and average CT value. Agreement and disagreement on NFE and INNFE diagnoses are influenced not only by size and average CT value but also, importantly, by the locations of nodules., (Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of our study was to evaluate serial CT changes from normal or near-normal lungs to honeycomb lungs in dust-exposed patients who developed chronic interstitial pneumonia., Materials and Methods: From the records of the national hospital for pneumoconiosis, we retrospectively identified patients with chronic interstitial pneumonia who were under surveillance between 1986 and 2006. All patients occasionally underwent chest CT for evaluation of silicosis or exclusion of possible complications. Patients were included in this study only if the initial CT examination did not show obvious chronic interstitial pneumonia. Fourteen patients (all men; median age at initial CT, 58 years) were identified as meeting the inclusion criterion. Two independent reviewers randomly reviewed the CT scans of the study patients to score the extent of ground-glass opacity, reticulation, and honeycombing; to provide a summation of all interstitial opacities (fibrosis score); and to assess coarseness., Results: Autopsy findings were available for eight of the 14 patients and confirmed the usual interstitial pneumonia (UIP) pattern seen on CT. The median follow-up period was 15.4 years, and none of the patients experienced acute exacerbation. One hundred two CT scans were reviewed. The earliest CT abnormalities included faint ground-glass opacity limited to the lung bases (n = 13) or only coarse reticular opacity (n = 1). In 13 patients, fibrosis and coarseness progressed linearly, whereas the other opacities did not. The annual increase of the fibrosis score and coarseness ranged from 0.306% to 4.633% and 0.179 to 0.479, respectively. Honeycombing developed in all patients over a median period of 12.1 years (range, 3.7-19.1 years)., Conclusion: The coarseness best represented the progression of chronic interstitial pneumonia in dust-exposed patients. The earliest CT finding of a UIP pattern in dust-exposed patients was indistinguishable from other types of chronic interstitial pneumonia.

Background: Breast cancer screening by mammography is thought to be effective in reducing breast cancer mortality while ultrasonography is not accepted as a population screening modality, although the latter has been suggested to be useful in detection of cancer in the dense breast, relatively more typical for a younger woman., Methods: Mammography with medio-lateral oblique view was offered on trial in 1999-2000 for 3453 female residents in Tochigi prefecture who also underwent clinical breast examination and ultrasonography. The municipalities that provided cancer screening were informed of the final diagnosis for women with positive findings in the screening trial by doctors who performed the diagnostic evaluation. Linkage was also made between the list of participants in the trial and registrations at Tochigi Cancer Registry for breast cancer cases diagnosed during 1999-2001., Results: Thirteen cases with breast cancer were identified during a 2-year follow-up period: 10 were diagnosed subsequent to positive finding in the trial; two were negative in the trial and diagnosed 23 and 24 months after, respectively; and one had a positive finding at the trial but was undiagnosed at first and then diagnosed 18 months after the trial. Among the 11 cases judged as positive in the trial, four were judged only by mammography while three were judged only by ultrasonography. Those mammography alone-detected cases were relatively young, at 36, 40, 47 and 54 years of age, respectively, while the ultrasonography alone-detected cases were aged 50, 55 and 68, respectively., Conclusions: Combined screening with mammography and ultrasonography may be feasible. A larger study is required to evaluate relative performance of mammography and ultrasonography in detail by characteristics of examinees and their breasts.

Purpose: To prospectively evaluate if findings on paired inspiratory and expiratory thin-section computed tomographic (CT) scans in patients with silicosis correlate with pulmonary function test results., Materials and Methods: Institutional review board approval and patient consent were obtained. Thirty-seven men (mean age, 71 years; range, 53-88 years) with silicosis were included. All patients had undergone inspiratory and expiratory thin-section CT and spirometry. Silicotic nodules, large opacity, emphysema, reticular opacities, bronchiectasis, and air trapping were graded subjectively on CT images. Emphysema was quantified on these images with built-in software. CT numbers were correlated with spirometric findings by using Spearman rank correlation analyses. Ten healthy volunteers (three men and seven women; mean age, 58 years) served as control subjects., Results: After exclusion of three patients with inadequate image quality, 34 patients (mean age, 70 years; range, 53-88 years) were enrolled in the study group. Spirometric values did not differ significantly between patients with simple (n = 20) and patients with complicated (n = 14) silicosis but were significantly lower in patients than in control subjects. CT findings included air trapping (n = 33), emphysema (n = 26), nodules (n = 32), bronchiectasis (n = 22), large opacity (n = 19), and reticulation (n = 5). The extent of both air trapping and emphysema correlated negatively with spirometric values; the air trapping score showed the strongest correlation (ratio of forced expiratory volume in 1 second to forced vital capacity [FVC]: rho = -0.632, P < .001; forced expiratory flow at 50% of the FVC: rho = -0.576, P = .001). Silicotic nodule, large opacity, and bronchiectasis scores did not correlate with obstructive functional impairments., Conclusion: In comparison with the spirometric value, the extent of air trapping proved the best CT index in the assessment of obstructive derangement in workers with exposure to silica dust.

Purpose: To retrospectively evaluate pleural disease on images from patients with autopsy-proved silicosis., Materials and Methods: The study had institutional review board approval, and informed consent from relatives of diseased subjects was waived. Lung specimens were obtained at autopsy in 110 men (mean age, 72 years) who had been followed up radiologically for a mean of 14.8 years. Computed tomographic (CT) scans obtained within 2 years before death were examined for presence of pleural thickening; shape, composition, size, and subpleural location of progressive massive fibrosis (PMF); and pleural invagination (bandlike structure between lesion and pleura). Lung specimens were reviewed and compared with CT findings. Serial chest radiographs and CT scans were reviewed for presence of pleural effusion. Association between radiographic findings and pleural invagination was analyzed with chi2 and Student t tests. Multiple logistic regression analysis was used to find predictive variables for pleural invagination., Results: Pleural effusion was found in 12 (11%) patients at chest radiography and CT, and thickening was found in 64 (58%) patients at CT; the latter finding was significantly more frequent with complicated silicosis (P < .001). At CT, 128 PMF lesions were seen, 39 (30%) of which showed pleural invagination; CT scans showed pleural thickening in 36 (92%) of these 39 lesions. In 17 (44%) PMF lesions, CT scans depicted a bandlike structure that was pathologically confirmed to represent invaginated pleura in all cases. Pathologic presence of invagination was significantly associated with pleural thickening (P < .001), ipsilateral pleural effusion (P < .01), interstitial fibrosis (P < .05), and the nearness of PMF to the pleura (P < .005). Multiple logistic regression analysis showed that pleural thickening (odds ratio, 62.51; 95% confidence interval [CI]: 5.564, 70.2) and pleural effusion (odds ratio, 25.865; 95% CI: 1.992, 335.8) were significant CT variables associated with presence of pathologic pleural invagination (P = .001 and .013, respectively). Five PMF lesions had radiographic features of rounded atelectasis., Conclusion: Various pleural abnormalities can occur in silicosis, especially in advanced disease.

We report a case of Caplan syndrome complicated with tuberculosis, which was clinically followed up for 18 years and underwent autopsy. Initial chest radiograph showed 2 large nodules against the background of smaller pneumoconiotic nodules. One of the large nodules showed cavitation during follow-up. Computed tomography (CT) was helpful in identifying calcification in another large nodule. Autopsy confirmed the 2 large nodules as burned-out rheumatoid nodules and revealed additional rheumatoid nodules that were indistinguishable from silicotic nodules by CT.

Modern radiologic technology has to led to increased diagnostic efficacy and accuracy in demonstrating pulmonary changes secondary to occupational dust exposure. This article presents three cases of typical and two cases of atypical silicosis with rounded atelectasis as seen in computed radiographic (CR), computed tomographic (CT), and scintigraphic images and autopsied lung specimens. Chest radiographs revealed both small rounded and small irregular opacities. Small irregular opacities on chest radiographs often proved to be reticular or honeycomb patterns on CT scans. Irregular opacities seen on CR and CT images represented interstitial fibrotic or mixed dust fibrotic changes associated with the accumulation of birefringent particles and emphysematous change, as noted at histologic analysis. CT scans and scintigrams were useful for visualizing parenchymal abnormalities, especially fibrotic change, emphysematous change, and pleural abnormalities.

Computerized morphological analysis of the cell nuclei was performed on 66 cases (2222 nuclei) of aspirated materials from breast tumors: 25 benign cases (302 nuclei), 41 malignant cases (1420 nuclei). Its diagnostic significance and the correlation between nuclear analysis and clinical staging were studied. Nuclear diagram and intranuclear chromatin distribution pattern were evaluated using computer system named 6400. The malignant tumor had larger, more round-shaped nuclei and less uniform chromatin distribution. Under tnm classification, stage IV tumors had larger, more flattened nuclei and more irregular chromatin distribution pattern than the others. Computerized morphological analysis of breast tumors may give a quantitative aspect to classical diagnostic process. Furthermore, this analytical method provides information on clinical stage of breast cancer.