Tomomi Yukawa

Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis

Objectives Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn’s disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Materials and Methods Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Results Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20–12.4, P = 0.023). Conclusions Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab.

Efficacy of a concomitant elemental diet to reduce the loss of response to adalimumab in patients with intractable Crohn's disease

Secondary loss of response to adalimumab (ADA‐LOR) commonly occurs in patients with Crohns disease (CD) treated with adalimumab (ADA). We evaluated the efficacy of concomitant elemental diet (ED) therapy to reduce ADA‐LOR in adult CD patients.

A comparison of short-term therapeutic efficacy between infliximab and tacrolimus for moderate to severe ulcerative colitis.

Abstract Introduction. Both infliximab (IFX) and tacrolimus (Tac) are effective for inducing clinical remission in patients with ulcerative colitis (UC). However, no randomized study has addressed the relative efficacies of IFX and Tac for patients with moderate to severe UC. This study aimed to conduct a retrospective study on the relative efficacy of IFX and Tac in patients with moderate to severe UC, using an inverse probability of treatment weighting (IPTW) technique to adjust background factors statistically. Methods. Between July 2009 and March 2016, data obtained from 122 patients with moderate to severe UC who were treated with either IFX (n = 58) or Tac (n = 64) were analyzed retrospectively. We compared the short-term therapeutic efficacy between the IFX group and Tac group using IPTW technique. Results. The clinical remission rate at 14 weeks after treatment was 37.9% (22/58) in the IFX group and 50% (32/64) in the Tac group, respectively. The efficacy of IFX and Tac for clinical remission rate was not different according to univariate (Odds ratio [OR] 1.64, 95% confidence interval [CI] 0.80-3.37 P = 0.18) and multivariate analyses (OR 2.19, 95% CI 0.85-5.61, P = 0.10). After the background and confounders factors were adjusted by using IPTW based on propensity score, the efficacy of IFX and Tac for clinical remission rate was not differed statistically (OR, 1.483; 95% CI, 0.581-3.785; P = 0.409) Conclusion. IFX and Tac have equivalent short-term efficacies for induction in patients with moderate to severe UC.

Sepsis Markers Soluble IL-2 Receptor and Soluble CD14 Subtype as Potential Biomarkers for Complete Mucosal Healing in Patients With Inflammatory Bowel Disease

Background and Aims Novel noninvasive biomarkers with high diagnostic accuracy are required to assess mucosal healing, which is associated with sustained clinical remission, in inflammatory bowel disease. This study aimed to explore sepsis markers as potential biomarkers for mucosal healing. Methods Patients with ulcerative colitis [UC] or Crohns disease [CD], who underwent blood tests for C-reactive protein [CRP], serum procalcitonin [PCT], soluble interleukin-2 receptor [sIL-2R], and plasma soluble CD14 subtype [sCD14-ST] within 2 weeks of endoscopy, were retrospectively recruited; and we assessed the relationship between marker levels and clinical features. Complete mucosal healing [cMH] was defined as a Mayo endoscopic subscore [MES] of 0 for UC and a simple endoscopic score for Crohns disease [SES-CD] of 0 for CD. Results In all, 68 UC patients and 33 CD patients were included in this study. In patients with UC, the sIL-2R level was significantly higher in patients without cMH than in those with cMH. The sIL-2R level had the highest diagnostic value for identifying cMH in UC. In patients with CD, CRP and sCD14-ST levels were significantly higher in patients without cMH than in those with cMH, and both CRP and sCD14-ST had good diagnostic values for identifying cMH. The sCD14-ST level had a high diagnostic value for identifying cMH even among CD patients with complete clinical remission, defined as a Harvey-Bradshaw index of 0. Conclusions The sIL-2R and sCD14-ST levels in patients with UC and CD, respectively, can be useful surrogate markers for identifying mucosal healing in inflammatory bowel disease.

Analysis of the Risk Factors of Surgery after Endoscopic Balloon Dilation for Small Intestinal Strictures in Crohn's Disease Using Double-balloon Endoscopy

Objective Balloon-assisted endoscopy enables access to and treatment of strictures in the small intestine using endoscopic balloon dilation (EBD); however, the long-term outcomes of EBD have not been sufficiently evaluated. This study evaluated the long-term outcomes of EBD in Crohns disease to identify the risk factors associated with the need for subsequent surgical intervention. Methods We retrospectively analyzed patients with Crohns disease who had undergone EBD with double-balloon endoscopy (DBE) for small intestinal strictures at a single center between 2006 and 2015. The long-term outcomes were assessed based on the cumulative surgery-free rate following initial EBD. Results Seventy-two EBD with DBE sessions and 112 procedures were performed for 37 patients during this period. Eighteen patients (48.6%) required surgery during follow-up. Significant factors associated with the need for surgery in a multivariate analysis were multiple strictures (adjusted hazard ratio, 14.94; 95% confidence interval, 1.91-117.12; p=0.010). One patient (6.7%) required surgery among 15 who had single strictures compared to 17 (77.3%) among 22 patients with multiple strictures. Conclusion In a multivariate analysis, the presence of multiple strictures was a significant risk factor associated with the need for surgery; therefore, a single stricture might be a good indication for EBD using DBE for small intestinal strictures in Crohns disease patients.

Serum interleukin-6 level is associated with response to infliximab in ulcerative colitis

Abstract Objectives: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection. Materials and method: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period. Results: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p = .012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio = 0.72; 95% confidence interval, 0.54–0.96; p = .027) was independently associated with response to infliximab. Conclusions: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.

The Efficacies and Issues for Endoscopic Assessment of Mucosal Healing in Patients with Crohn’s Disease

Mucosal healing has been a focus of attention as an emerging ideal treatment goal of Crohn’s disease. Endoscopy is the gold standard for evaluating mucosal lesion. Objective precise monitoring, especially for the small bowel, is important for stratifying the treatment strategy. Some limitations and issues for definition of mucosal healing, accessibility of stricture or adhesion, feasible endoscopic score still remain. It is important in clinical practice to identify the appropriate time for intensifying the CD treatment for small ulcerative lesion endoscopically. There are characters for each imaging modality, for instance assessment of intestinal tract wall and extrawall information. The combination with other complementary imaging modalities or biomarkers is useful in optimizing the CD treatment strategy. An appropriate accelerated step-up treatment strategy combined with stratified precise monitoring of the SB should provide optimal prognosis in patients with CD. Endoscopic prediction of long-term prognosis or efficacy of treatment is an important subject for investigation.

Combined Infection of Human Herpes Viruses: A Risk Factor for Subsequent Colectomy in Ulcerative Colitis

Background Little is known about the prevalence and pathogenicity of human herpes viruses except for cytomegalovirus (CMV) in patients with inflammatory bowel disease (IBD). The aim of this study was to determine the prevalence of human herpes viruses on colonic mucosa in patients with IBD and assess the long-term outcomes in these patients. Methods We examined the colonic mucosal specimens from 66 patients with ulcerative colitis (UC), 54 patients with Crohns disease (CD), and 29 healthy patients to identify the 6 most common types of human herpes virus, using multiplex polymerase chain reaction (PCR) technique. Results Herpes simplex virus (HSV)-1/2 and varicella-zoster virus (VZV) were not detected in any of the groups. There was a higher prevalence of Epstein-Barr virus (EBV) (21.2%) and CMV (15.1%) in patients with UC than in patients with CD (EBV 9.3%, CMV 0%) and patents in the healthy control group (EBV 0%, CMV 3.4%). The prevalence of human herpes virus (HHV)-6A/B and HHV-7 was not statistically different among the groups. Five UC patients with inflammation had coexisting CMV and EBV or HHV-6. The combined infection of CMV with EBV or HHV-6 was a significant and independent prognostic factor for subsequent colectomy in patients with UC. Conclusions The increased prevalence of CMV coexisting with EBV/HHV-6 infection was associated with the clinical course in patients with UC. 10.1093/ibd/izy005_video1izy005_Video_15786489376001.