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Polymorphisms in the nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) gene are associated with thiopurine-induced leukopenia in patients with inflammatory bowel disease (IBD). NUDT15-associated subcellular thiopurine metabolism has not been investigated in primary lymphocytes. We hypothesized that NUDT15 mutation increases DNA-incorporated deoxythioguanosine (dTG) and induces apoptosis in lymphocytes. DNA-incorporated dTG in peripheral blood mononuclear cells (PBMCs) and 6-thioguanine nucleotides (6-TGN) in red blood cells were measured in patients with IBD undergoing thiopurine treatment. The association of a single nucleotide polymorphism for NUDT15 (rs116855232) with dTGPBMC was examined. The pro-apoptotic effect of DNA-incorporated dTG was examined ex vivo in association with NUDT15 genotypes by co-culturing patient-derived peripheral CD4+ T lymphocytes with 6-thioguanine (6-TG). dTGPBMC was significantly higher in NUDT15 variants than in non-variants. dTGPBMC, but not 6-TGNRBC, negatively correlated with peripheral lymphocyte counts (r = – 0.31 and – 0.12, p = 0.012 and 0.173, respectively). DNA-incorporated dTG significantly accumulated to a greater extent in lymphocytes from NUDT15 variants when co-cultured with 6-TG ex vivo than in those from non-variants and was associated with decreased proliferation and increased apoptosis. Increased DNA-incorporated dTG may be responsible for thiopurine-induced leukocytopenia through cell apoptosis in IBD patients with NUDT15 mutation.

BACKGROUND: Crohn's disease (CD) is a disease with an impaired immune response characterized by chronic, relapsing‐remitting, and progressive inflammation mainly affecting the gastrointestinal tract. Certolizumab pegol (CZP) is a biological agent that regulates the impaired immune response by controlling tumour necrosis factor‐α (TNFα). However, the efficacy and safety of long‐term administration of CZP for people with CD with inflammation under control are not well understood. OBJECTIVES: To assess the efficacy and safety of CZP for maintenance of remission in people with CD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, and conference abstracts from inception to 23 March 2022. We contacted pharmaceutical companies involved with the production of CZP for further relevant information. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing CZP with placebo in adults with CD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. The main outcomes were failure to maintain clinical remission at week 26, failure to maintain clinical response at week 26, and serious adverse events. We planned to perform meta‐analyses including all available studies if similar enough for pooling to be appropriate and calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes. We analyzed the number needed to treat for an additional beneficial outcome (NNTB) and the number needed to treat for an additional harmful outcome (NNTH) to indicate the magnitude of treatment effects. The same two review authors independently evaluated the risk of bias by using the Cochrane RoB 2 tool and evaluated the certainty of evidence using the GRADE framework. MAIN RESULTS: We identified one study meeting our prespecified eligibility criteria. The included study enrolled 428 adults with CD who responded to induction therapy with CZP 400 mg at weeks 0, 2, and 4. The study evaluated long‐term efficacy and safety of CZP administered subcutaneously every four weeks compared with placebo. The proportion of participants who failed to maintain clinical remission at week 26 was 52.3% (113/216) in the CZP group compared to 71.7% (152/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical remission at week 26 (RR 0.73, 95% CI 0.63 to 0.85). The NNTB was 5 (95% CI 4 to 9). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who failed to maintain clinical response at week 26 was 37.5% (81/216) in the CZP group compared to 64.2% (136/212) in the placebo group. Treatment of CZP probably results in a large reduction in failure to maintain clinical response at week 26 (RR 0.58, 95% CI 0.48 to 0.71). The NNTB was 4 (95% CI 3 to 5). We judged this outcome at low risk of bias. Using the GRADE assessment, we judged the certainty of evidence as moderate due to the low number of events occurred. The proportion of participants who developed serious adverse events was 5.6% (12/216) in the CZP group compared to 6.6% (14/212) in the placebo group. Treatment of CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment (RR 0.84, 95% CI 0.40 to 1.78). The NNTB was 95 (95% CI NNTH 19 to NNTB 25). We evaluated the risk of bias for this outcome as low. We evaluated the certainty of evidence as low due to the low number of events occurred and the CIs were not sufficiently narrow. AUTHORS' CONCLUSIONS: CZP probably results in a large reduction in failure to maintain clinical remission and response at week 26 in people with CD. The evidence suggests that CZP may lead to no difference in serious adverse events compared to placebo when used as a remission maintenance treatment. However, the current studies are limited to 26 weeks of follow‐up and only included adults. Therefore, these conclusions cannot be used to guide longer term treatment or for treatment in children at present.

Ulcerative colitis and Crohn's disease, the most common types of inflammatory bowel disease, are idiopathic, intractable disease characterized by chronic inflammation in the intestine. In recent years, studies elucidating the clinical characteristics of these diseases and basic researches have suggested that the diseases are induced by the immunological abnormalities through the involvement of environmental factors with their predisposition. In Japan, significant progress of basic and epidemiological researches has been developed for these diseases and the clinical guidelines have been established. However, no fundamental treatment for these diseases has been established yet. The current number of patients in Japan continues to increase, with at least 180,000 patients suffering from ulcerative colitis and 40,000 suffering from Crohn's disease. Thus, further studies are required to understand these diseases and improve medical treatments.

Background/aims The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis. Methods Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day). Results The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group. Conclusions Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.

We performed this study to provide the latest evidence of the diagnostic accuracy of all Aspergillus antibodies for chronic pulmonary aspergillosis (CPA). In this meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and other databases, until 19 March 2020, for studies that examined the diagnostic accuracy of each Aspergillus-specific antibody for CPA and assessed the risk of bias using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. We integrated the results using a hierarchical summary receiver operating characteristic (HSROC) model and calculated the point estimates of specificity with sensitivity fixed at 0.90 using the HSROC curve. We identified 32 published and one unpublished studies, including 75 studies on five antibody test types: 18 of precipitin test (2810 participants), 46 of IgG (8197), three of IgA (283), six of IgM (733) and two of combined IgG and IgM (IgG + IgM) (920). The results of specificity with sensitivity fixed at 0.90 were as follows: precipitin test, 0.93 (95% credible intervals: 0.86, 1.00); IgG, 0.90 (0.86, 0.95); IgA, 0.74 (0.00, 1.00); IgM, 0.50 (0.37, 0.53); IgG + IgM, 0.47 (0.00, 1.00). However, the precipitin test showed imprecision and instability in the sensitivity analysis. Most studies had a high risk of bias due to the case-control design. Although there is lack of applicability for malignancy or immunosuppressive patients, our study suggests a preference for IgG over other antibody tests in CPA screening. Particularly, IgG should be used as an adjunct when ruling out CPA.

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.

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.

Background/aims Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. Methods UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. Results A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). Conclusions CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.

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 rs = 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

Background and aims The current goal of treatment for ulcerative colitis [UC] is endoscopic and ultimately histological mucosal healing. However, there is no consensus on the definition of histological mucosal healing. We evaluated histological risk factors for clinical relapse in UC patients with endoscopically normal mucosa to focus on the importance of histological evaluation. Methods Patients with UC who underwent colonoscopy confirming Mayo endoscopic subscore [MES] ≤ 1 with biopsies were enrolled into this retrospective cohort. Three expert pathologists evaluated the presence or absence of chronic inflammatory cell infiltrate, breaches in the surface epithelium, crypt abscesses, mucin depletion, crypt architectural irregularities and basal plasmacytosis. Clinical relapse was defined as partial Mayo score ≥ 3 or modification of induction treatment. Prediction models of clinical relapse were generated, especially in patients with MES 0. Results A total of 194 UC patients were enrolled. Histological abnormalities existed more frequently in patients with MES 1 than those with MES 0, while the vast majority of patients still possessed at least one abnormality. There was no significant difference in time to relapse between MES 0 and 1. Crypt architectural irregularities and mucin depletion were associated with time to relapse in patients with MES ≤ 1. In patients with MES 0, the presence of mucin depletion was the only factor significantly and independently associated with the risk of relapse (hazard ratio, 2.18 [1.16-5.82]; p = 0.03). Conclusions Mucin depletion was shown to be a histological risk factor for clinical relapse in UC patients with MES 0.

Background Second-generation colon capsule endoscopy (CCE-2) has been reported as a potential tool for monitoring ulcerative colitis (UC). However, its excretion rate is still unsatisfactory, and the bowel preparation regimen is not well tolerated. Furthermore, a standard bowel preparation regimen validated for UC has not been established. The aim of this study was to develop a simple 1-day CCE-2 procedure while evaluating its excretion rate and acceptability in UC. Factors associated with the colonic transit time and acceptability of CCE-2 were evaluated. Methods Thirty-three patients were prospectively evaluated. Five hundred milliliters of hypertonic polyethylene glycol solution, followed by 250 mL of water, was ingested 2.5 hours before, then 1, 3, and 6 hours after capsule ingestion until its excretion, with castor oil added to the second ingestion. Mayo endoscopic subscore (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were graded, and their correlations with fecal calprotectin (FC) were assessed. A questionnaire comparing CCE-2 with previous colonoscopy (CS) was conducted. Results The excretion rate was 93.9% (31/33). The acceptability of CCE-2 was superior to CS (CCE-2 42.4% vs CS 27.3%). The median colonic transit time was 119 minutes and showed a positive correlation with MES (P = 0.010), UCEIS (P = 0.010), and FC (P = 0.041). CCE-2 was not favored by patients whose colonic transit times were longer. Conclusions A novel bowel preparation regimen of CCE-2 was well tolerated, with a high excretion rate, by UC patients. Patients with active disease required longer colonic transit time, which may have resulted in the lower acceptability of CCE-2.

Background: Inflammatory bowel disease (IBD), though historically common in the West, is now increasingly prevalent in industrializing countries. A simultaneous dramatic increase in IBD drug options has enabled most patients to achieve remission. Nevertheless, worldwide disparities in the approval of IBD drugs, or “drug lag”, remain problematic. Summary: Drug lag for major IBD drugs before March 31, 2018 (12 for Crohn’s disease [CD] and 13 for ulcerative colitis [UC]) was compared between that of the United States (US), European Union (EU), and Asia (Japan, China, South Korea, Taiwan, and the Philippines) to assess current trends. In the US, unapproved IBD drugs accounted for 16.7% (2/12) for CD and 23.1% (3/13) for UC; approval lag was 3.8 (0–80.5) months for CD and 3.6 (0–88) months for UC. In the EU, unapproved drugs accounted for 16.7% (2/12) for CD and 15.4% (2/13) for UC; approval lag was 0.03 (0–13.9) months for CD and 0 (0–13.9) months for UC. This demonstrates the short drug lag in both regions, although one drug developed in a joint US/EU clinical trial had around a 350-day approval lag. In Asia, the proportion of unapproved IBD drugs was the lowest in Japan at 33.3% (4/12) for CD and 23.1% (3/13) for UC; South Korea had the shortest lag for CD at 13.2 (0–133.1) months and the Philippines had the shortest lag for UC at 9.9 (0.6–176.2) months, but these countries still had longer lag periods than the West. However, a proportion of unapproved drugs and approval lag has decreased considerably in Asia since the start of the biologics era. Key Messages: Despite the recent shortening drug lag between different countries and regions, this study shows that disparities persist. With globalization, eliminating these disparate drug lags is necessary to manage IBD and may require efforts toward international adoption of a more standardized approval process.

Background A novel thiopurine metabolizing enzyme, nucleotide diphosphate-linked moiety X-type motif 15 (NUDT15) was associated with drug-induced leukopenia in patients with non-synonymous genetic polymorphisms. Thiopurine-induced leukopenia in Japanese patients with genetic variance in NUDT15 (c.415C>T) appears to be independent of the 6-thioguanine nucleotide concentration in red blood cells. However, detailed molecular mechanism how NUDT15 variance causes thiopurine-induced leukopenia remains unclear and NUDT15-associated subcellular thiopurine metabolism has not been investigated in patients with inflammatory bowel diseases (IBD). Methods DNA-incorporated deoxythioguanosine (dTG) was measured in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with IBD under thiopurine treatment. Association of a single-nucleotide polymorphism for NUDT15 (c.415C>T) with dTG in PBMCs (dTGPBMC) was examined. Peripheral blood T lymphocytes were cultured in vitro with 6-thioguanine (6-TG) to examine the Impact of NUDT15 genotypes on incorporation into DNA, cell proliferation and apoptosis. Results NUDT15 variants had significantly higher dTGPBMC per thiopurine dosage than non-variants (homozygous variants (TT) vs. heterozygous variants (CT) vs. non-variants (CC), 4418.0 vs. 663.0 vs. 295.3 dTG mol/106 moles dA per mg/kg/day of 6-MP (Figure A)). dTGPBMC and peripheral lymphocyte counts showed a negative correlation (r = −0.30, p = 0.015) (Figure B). Peripheral blood lymphocytes from patients with NUDT15 variance showed a higher DNA-incorporated dTG associated with increased apoptosis (increase of Annexin V+ PI+ CD4+ lymphocytes; TT vs. CT vs. CC, 158.5 % vs. 80.1 % vs. 57.9 % (p = 0.0427)) (Figure C) and decreased proliferation (decrease of proliferative CD4+ lymphocytes, TT vs. CT vs. CC, 49.0 % vs. 25.0 % vs. 19.1 % (p = 0.0098)) (Figure D) when cultured with 6-thioguanine in vitro. Conclusion DNA-incorporated dTG affected by NUDT15 genotypes induces T lymphocyte apoptosis in patients with IBD.

Background Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. Objectives The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. Search methods We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. Selection criteria We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. Data collection and analysis We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). Main results Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. Authors' conclusions Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

Background & Aims The accuracy of ultrasound for evaluation of individual colorectal segments in patients with inflammatory bowel diseases (IBD) has not been evaluated in a systematic review. We evaluated the diagnostic accuracy of ultrasound in different colorectal segments of patients with IBD. Methods We searched publication databases from inception through March 2019 for studies that assessed the accuracy of ultrasound in detection of inflammation in right, transverse, and left colon and in rectum in patients with IBD, using findings from colonoscopy as the reference standard. Subgroup analyses were performed including IBD type, patient age, body mass index, and study design. The risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Nineteen studies (1101 patients) were included in the qualitative synthesis. After we assessed the risk of bias, 7 studies (comprising 84 patients with Crohn’s disease and 420 patients with ulcerative colitis) were included in the meta-analysis. Bowel wall thickness ≥ 3 mm identified colorectal segments with inflammation with 86.4% pooled sensitivity (95% CI, 76.1%–92.7%) and 88.3% pooled specificity (95% CI, 58.1%–97.6%). In rectum only, bowel wall thickness ≥ 3 mm identified inflammation with 74.5% sensitivity (95% CI, 53.0%–88.3%) and 69.5% specificity (95% CI, 33.6%–91.1%). Diagnostic accuracy was comparable among subgroups. Increased bowel wall flow and loss of stratification had higher true-positive odds ratios. Conclusions Based on meta-analysis of patient-level data, ultrasound has higher diagnostic accuracy for detecting inflammation in colon than rectum in patients with IBD. Studies are needed to increase the accuracy of ultrasound detection of inflammation in rectum.

Anti-tumor necrosis factor-α (TNF-α) is a principal treatment for Crohn's disease (CD). However, it increases the susceptibility to tuberculosis (TB) infection, and therefore, screening examination prior to treatment initiation is crucial. Here, we report the case of a patient with CD who developed pulmonary TB following anti-TNF-α therapy, despite negative screening. A 19-year-old female who had no history of TB or had traveled to TB-endemic regions was diagnosed with CD. After negative TB screening with chest X-ray and interferon-gamma release assay, the patient was initiated on oral prednisolone and pH-dependent mesalazine. The treatment was changed to infliximab (IFX) because of the inadequate response observed to prednisolone;however, she developed pulmonary TB only 10 weeks after the initiation of IFX. The standard short-course anti-TB regimen was initiated to treat pulmonary TB, whereas IFX was discontinued and replaced with budesonide. Our case suggests that the risk of developing TB should not be excluded, despite the initial negative TB screening, particularly when a patient develops respiratory symptoms during anti-TNF-α therapy.

Background Fecal calprotectin (FC) is well accepted as a non-invasive biomarker which objectively reflects colonic inflammation in ulcerative colitis (UC). However, its value as a marker of response during the early phase of remission induction treatment has not been well studied. The aim of this study is to evaluate the significance of FC for predicting the short-term outcomes of remission induction treatment in patients with UC. Methods A prospective observational study was conducted among 31 patients with active UC. FC was monitored with two-item patient-reported outcome (PRO2), partial Mayo score (PMS), and Lichtiger clinical activity index (CAI) during the first 4 weeks of remission induction treatment. Clinical response was defined as a decrease in CAI of 3 or more points below baseline. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0 or 1. Within-day and within-stool variability of FC were assessed during the first week of treatment. Results In week 4-clinical responders, PRO2, PMS, and CAI significantly decreased from day 3, however, FC did not show significant reduction until week 2. Among all markers, the decrease in PRO2 at week 4 most accurately predicted MH at week 12. Within-day variability of FC was remarkably wide even at the first week in clinical responders. Within-stool variability was extremely small. Conclusions PRO2 predicted the short-term outcomes of remission induction treatment earlier than FC possibly because of the wide within-day variability of FC in active UC.