Effectiveness and Factors Associated with Response to Golimumab in Japanese Patients with Ulcerative Colitis in Real Clinical Practice: The Phoenix Study.

Introduction: There have been limited reports on the clinical efficacy of golimumab (GLM) in Japanese patients with ulcerative colitis (UC) in real clinical practice. This study aimed to explore the real-life effectiveness and factors associated with response to GLM in Japanese patients with UC. Methods: This observational, retrospective, multicenter study was conducted in hospitals with expertise in inflammatory bowel disease treatment. Sixty-three patients treated with GLM and active UC were included in the analysis. Clinical remission (CR) (partial Mayo (pMayo) score ≤2) in the induction and maintenance phases after GLM treatment and associated factors were evaluated. Results: The proportion of patients achieving CR in the induction and maintenance phases was 41.3% (26/63) and 46.0% (29/63, the last observation carried forward method was used for patients who discontinued treatment for reasons other than inadequate response), respectively. The median pMayo score was 5 (interquartile range (IQR): 4-6) at baseline, 3 (IQR: 1-5) in the induction phase, and 1 (IQR: 0-3) in the maintenance phase. Hemoglobin, platelet, and C-reactive protein levels changed, consistent with the pMayo score. Multivariate logistic analysis revealed that biologic-naive status was an independent factor associated with CR in the induction (p = 0.0200) and maintenance (p = 0.0459) phases, and a disease duration of >60 months until GLM initiation was associated with CR in the induction phase (p = 0.0427). Conclusions: The effectiveness of GLM in daily clinical practice has been confirmed in Japanese patients with active UC. Biologic-naive patients responded more to GLM in the induction and maintenance phases, and patients with disease duration of >60 months until initiation of GLM were more responsive in the induction phase.

Monitoring of leucine-rich alpha-2-glycoprotein and assessment by small bowel capsule endoscopy are prognostic for Crohn's disease patients.

Background and Aim: Endoscopy is important to determine the effectiveness of treatment for Crohn's disease (CD), but searching the entire small intestine is difficult. Thus, we investigated the usefulness of leucine-rich alpha-2 glycoprotein (LRG), a new biomarker for predicting mucosal activity, in evaluating the activity of CD small intestinal lesions. This will further determine whether the results of small bowel capsule endoscopy (SBCE) affect the prognosis of patients with CD. Methods: A total of 114 patients with CD who underwent SBCE were included. We analyzed the correlation between LRG and Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). The cutoff value of LRG to achieve mucosal healing was calculated using the receiver operating characteristic curve. Then, we compared the presence or absence of intervention and the relapse rate of patients who could not achieve mucosal healing. Results: The CECDAI correlated with LRG. The calculated LRG value for achieving mucosal healing was ≤11.9. Ninety-one patients were in clinical remission at the time of SBCE. During the follow-up period, 17 patients relapsed. As a result of SBCE, when no treatment intervention was performed in the case of CECDAI ≥3.5, the relapse rate was significantly higher than when CECDAI <3.5 or intervention was performed in the case of CECDAI ≥3.5. Conclusions: The results reveal that LRG correlates with the activity of the entire small intestine and that SBCE assessment and therapeutic intervention can influence patient prognosis.

Distinct effects of TU-100 (daikenchuto) on long-lasting dysbiosis in the small intestine in patients with colorectal cancer and inflammatory bowel disease.

The profile of the human small intestinal microbiota remains to be uncovered primarily due to sampling difficulties. Ileostomy provides the intestinal luminal contents as ileostomy effluents (IE) that offer opportunity for performing extensive analyses of nutrients, gastrointestinal fluids, metabolites, and microbiome. In the present study, we evaluated changes in the microbiome, pH, and bacterial short-chain fatty acids (SCFAs) in IE obtained from patients who had undergone ileostomy following surgical resection of colon cancer and inflammatory bowel disease (IBD). We enrolled 11 patients who varied in the duration of ileostomy from 3 days to >5 years after surgery and had no inflammation in the small intestine. The analyses suggested that IE from patients previously having IBD had less diversity and greater intraday and interday fluctuations, and increased pH and decreased levels of propionic acid and acetic acid than those in IE from patients previously having cancer. Furthermore, correlation analysis suggested a possible effect of the intestinal microbiome on luminal pH, presumably via SCFA production. The present study suggested that inflammation in the colon may induce long-term dysbiosis in the small intestine even after removal of diseased parts of the colon. Moreover, pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) was found to have beneficial effects on postoperative bowel dysfunction and the human small intestinal microbiota. Taken together, these results suggest the necessity of a direct remedy for dysbiosis and the treatment of gastrointestinal lesions to achieve favorable outcomes for chronic gastrointestinal disorders.

Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency. METHODS: IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this 2-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn's Disease Activity Index [CDAI]) before and after ZAH administration were analyzed. RESULTS: Fifty-one patients with Crohn's disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5-91.0 µg/dL, P< 0.001; 171.5-129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0-81.0 µg/dL, P< 0.001; 177-148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 µg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea. CONCLUSIONS: ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.

Levels of major and trace metals in the scalp hair of Crohn's disease patients: correlations among transition metals.

Concentrations of 16 metals in the scalp hair of male Crohn's disease (CD) patients (n = 28) were compared to those of male control subjects (n = 25). The majority of patients (n = 20) took an anti-inflammatory agent (mesalazine), and several patients underwent colectomy. A low concentration of serum ferritin was observed in approximately 50% of CD patients due to Fe-deficiency anemia. The concentrations of Fe, Cr, and Co in the hair of CD patients were significantly higher than those of control subjects, and particularly high concentrations were found in CD patients with low serum ferritin. Significant correlations were found among the concentrations of Fe, Cr, and Co in the hair of CD patients, but not in control subjects. In agreement with previous reports, a significant negative correlation was found between ferritin and transferrin concentrations in serum, although the available data in this study was limited (n = 8). Transferrin not only binds to Fe3+ but also to Cr3+ and Co3+, and the amount of transferrin is increased in Fe-deficiency anemia. Thus, the majority of the Fe3+, Cr3+, and Co3+ in the serum of CD patients is likely to bind to transferrin, which may be associated with the higher concentrations of those metals, as well as the significant correlations among those metals in the scalp hair of CD patients. In addition, colectomy may alter the intestinal absorption rate of some metals, while mesalazine may increase the concentrations of Mn and some metals in the scalp hair by chelate formation.

Stable isotope ratios of carbon, nitrogen and selenium concentration in the scalp hair of Crohn's disease patients who ingested the elemental diet Elental®.

RATIONALE: Elental® is an elemental diet widely used as a nutritional supplement for Crohn's disease (CD) patients in Japan. Elental® contains amino acids as nitrogen sources and does not contain selenium (Se), and the δ13 C and δ15 N values of Elental® are markedly higher and lower, respectively, than those of a normal diet. METHODS: We compared the δ13 C and δ15 N values and Se concentration in the scalp hair of CD patients with those of control subjects who ate a regular diet, and estimated the amount of Elental® ingested as a supplement. The δ13 C and δ15 N values and the Se concentrations were quantified using isotope ratio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. RESULTS: An increase in Elental® ingestion increased the δ13 C value in the hair of CD patients (p <0.05), while it reduced the δ15 N value (p <0.05) and tended to reduce the Se concentration in female patients. CONCLUSIONS: The amount of Elental® ingested could be estimated by the δ13 C and δ15 N values in the hair of CD patients. Furthermore, the Se deficiency in female patients may be predicted from the δ13 C and δ15 N values.

Anal Canal Adenocarcinoma in a Patient with Longstanding Crohn's Disease Arising From Rectal Mucosa that Migrated From a Previously Treated Rectovaginal Fistula.

BACKGROUND This study reports the pathogenesis of anal canal adenocarcinoma in a patient with longstanding Crohn's disease (CD). CASE REPORT A 50-year-old woman with a 33-year history of CD presented with perianal pain of several months' duration. She had been treated surgically for a rectovaginal fistula 26 years earlier and had been treated with infliximab (IFX) for the previous 4 years. A biopsy under anesthesia revealed an anal canal adenocarcinoma, which was removed by abdominoperineal resection. Pathological examination showed that a large part of the tumor consisted of mucinous adenocarcinoma at the same location as the rectovaginal fistula had been removed 26 years earlier. There was no evidence of recurrent rectovaginal fistula, but thick fibers surrounded the tumor, likely representing part of the previous rectovaginal fistula. Immunohistochemical analysis using antibodies against cytokeratins (CK20 and CK7) revealed that the adenocarcinoma arose from the rectal mucosa, not the anal glands. CONCLUSIONS Mucinous adenocarcinoma can arise in patients with CD, even in the absence of longstanding perianal disease, and may be associated with adenomatous transformation of the epithelial lining in a former fistula tract.

Decrease of peripheral and intestinal NKG2A-positive T cells in patients with ulcerative colitis.

To investigate the role of inhibitory natural killer receptors (iNKRs) in inflammatory bowel disease (IBD), we analyzed the expression of NKG2A, one of the iNKRs, on T cells in a mouse colitis model and human IBD. During the active phase of dextran sulfate sodium (DSS)-induced mouse colitis, the frequency of NKG2A+ T cells was significantly decreased in the peripheral blood, and increased in the intestine, suggesting the mobilization of this T cell subset to the sites of inflammation. Administration of anti-NKG2A antibody increased the number of inflammatory foci in DSS-induced colitis, suggesting the involvement of NKG2A+ T cells in this colitis model. In ulcerative colitis (UC) patients, the frequency of peripheral blood NKG2A+ T cells was significantly decreased, compared with Crohn's disease (CD) patients and healthy controls, regardless of clinical conditions such as treatment modalities and disease activity. Notably, in sharp contrast to the DSS-induced mouse colitis model, the frequency of NKG2A+ cells among intestinal T cells was also decreased in UC patients. These results suggest that inadequate local infiltration of NKG2A+ T cells may be involved in the pathogenesis of UC.

[Immunological rapid urease test].

Immunological rapid urease test for detection of Helicobacter pylori infection, composed of a solid-phase tip coated with monoclonal antibody against H. pylori's urease and ion-sensitive field transistor (ISFT)-based pH sensor system, was developed. The monoclonal antibody against H. pylori's urease was useful to avoid the contamination of urease activity in other bacteria. Because ISFTT had high ability to detect pH change, the sensitivity and specificity of immunological rapid urease test was significantly improved comparing with that of conventional rapid urease test. The utility of immunological rapid urease test was evaluated in some clinical studies.