The albumin to globulin ratio is associated with clinical outcome in Japanese patients with ulcerative colitis.

PURPOSE: The albumin to globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC. METHODS: The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day). RESULTS: The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52-14.18 and adjusted OR, 4.97; 95% CI, 2.14-12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56-11.51 and adjusted OR, 5.22; 95% CI, 1.97-14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06-21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found. CONCLUSION: Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.

Effect of disease duration on the association between C-reactive protein-albumin ratio and endoscopic activity in ulcerative colitis.

BACKGROUND: A simple serum biomarker for clinical outcome in patients with ulcerative colitis (UC) remains an unmet need. Some studies have shown an association between C-reactive protein (CRP)-albumin ratio (CAR) and prognosis in patients with inflammatory bowel disease (IBD), but evidence regarding the association between CAR and UC remains limited. We evaluated the association between CAR and clinical outcome in Japanese patients with UC. METHODS: Subjects were 273 Japanese patients with UC. Clinical remission was defined as absence of both abnormally high stool frequency (< 3 per day) and rectal bleeding. Mucosal healing (MH) was defined as Mayo endoscopic subscore (MES) 0. Moderate to severe endoscopic activity was defined as MES 2-3. Subjects were divided according to CAR into tertiles (low, moderate, and high). RESULTS: The proportions of patients with clinical remission, MH, and moderate to severe endoscopic activity were 57.9%, 26.0%, and 37.0%, respectively. High CAR was significantly positively associated with moderate to severe endoscopic activity but not MH or clinical remission after adjustment (adjusted odds ratio [OR] 2.18 [95% confidence interval (CI) (1.11-4.35)], p for trend 0.023), but only in patients with long disease duration (> 7 years) (adjusted OR 2.95 [95% CI (1.06-8.79)], p for trend 0.023). CAR was not associated with clinical remission or MH. CONCLUSIONS: CAR may be significantly positively associated with moderate to severe endoscopic activity but not clinical remission or MH in Japanese patients with UC. In patients with long UC duration, CAR might be a useful serum marker for disease activity.

Serum Globulin Is Associated with Endoscopic Findings and Mucosal Healing in Japanese Patients with Ulcerative Colitis.

BACKGROUND: Serum globulin is an inflammation marker. To date, no evidence regarding the association between serum globulin and disease activity in patients with ulcerative colitis has been reported. AIMS: We evaluated the association between serum globulin and endoscopic activity in patients with ulcerative colitis. METHODS: Serum globulin was divided into tertiles based on the distribution of study subjects (low globulin, ≤ 2.7 g/dl (reference); moderate globulin, 2.7-3.1 g/dl; and high globulin, > 3.1 g/dl). A single endoscopic specialist evaluated the endoscopic findings, and mucosal healing was based on Mayo endoscopic subscore. RESULTS: A total of 277 patients with ulcerative colitis were included in the study. Serum globulin was independently positively associated with diminished or absent vascular markings [moderate: adjusted odds ratio (OR) 3.70 (95% confidence interval, CI: 1.82-7.88) and high: adjusted OR 2.40 (95%CI: 1.20-4.94), p for trend = 0.005]. A similar positive association between globulin and erosion was found [high: adjusted OR 2.00 (95%CI: 1.05-3.86)]. Serum globulin was independently inversely associated with mucosal healing [moderate: adjusted OR 0.37 (95%CI: 0.18-0.73) and high: adjusted OR 0.31 (95%CI: 0.14-0.64), p for trend = 0.001] and adjusted partial mucosal healing [moderate: OR 0.51 (95%CI: 0.26-0.98), p for trend = 0.048]. The inverse association between globulin and mucosal healing was significant in the low but not the high C-reactive protein group. CONCLUSIONS: In patients with ulcerative colitis, serum globulin was significantly positively associated with endoscopic activity, and was significantly inversely associated with mucosal healing, especially in the low C-reactive protein group.

Association Between Peripheral Blood Monocyte Count and Mucosal Healing in Japanese Patients With Ulcerative Colitis.

INTRODUCTION: Monocytes play an important role in innate immunity. Some epidemiological evidence indicates an association between peripheral blood monocytes and ulcerative colitis (UC). The association between peripheral blood monocytes and mucosal healing (MH), however, remains unclear. We evaluated this issue in patients with UC. METHODS: Study subjects consisted of 272 Japanese patients with UC. Monocyte counts were taken in the morning after overnight fasting. Monocyte count was divided into tertiles based on the distribution of values among all study subjects. Information on clinical remission was obtained from medical records. MH was assessed using the Mayo endoscopic subscore. RESULTS: The mean monocyte count was 360.1 ± 155.3/mm3. Rates of clinical remission, MH, and complete MH were 61.0%, 66.2%, and 27.9%, respectively. High monocyte count was significantly inversely associated with clinical remission, MH, and complete MH (adjusted odds ratio [OR] 0.45 [95% confidence interval [CI]: 0.23-0.89], OR 0.45 [95% CI: 0.23-0.89], and OR 0.48 [95% CI: 0.23-0.97], respectively). Patients were also classified according to C-reactive protein (CRP) levels; in the low CRP group (<0.1 mg/dL), high monocyte count was independently inversely associated with complete MH but not with clinical remission or MH (OR 0.33 [95% CI: 0.10-0.92], P for trend = 0.027). In the high CRP group, there was no association between monocyte count and clinical outcomes. DISCUSSION: Our findings suggest that peripheral blood monocyte count can be used as a serum supplemental marker for MH in UC patients with low CRP levels.

Time spent per day in strenuous activity and total physical activity are inversely associated with mucosal healing but not with clinical remission in patients with ulcerative colitis.

BACKGROUND: Epidemiological evidence on the association between physical activity (PA) and ulcerative colitis (UC) is limited, and the effect of PA on the prognosis of UC is currently unknown. We evaluated the association between PA and clinical outcomes, including clinical remission and mucosal healing (MH), in Japanese patients with UC. METHODS: The study subjects were 327 Japanese patients with UC. Subjects were asked about the average time spent per day on 4 types of PA (sedentary, standing, walking, and strenuous activity) and metabolic equivalents (METs) using a validated questionnaire. Clinical outcomes were complete MH, MH, and clinical remission. The association between PA, including hours spent on each type of PA and average daily METs, and clinical outcomes was assessed by multivariate logistic regression. RESULTS: Plentiful strenuous activity was significantly inversely associated with MH and complete MH after adjustment (MH: adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.23-0.89; complete MH: adjusted OR 0.24, 95%CI 0.07-0.62; P for trend=0.008). A very high daily MET total was significantly inversely associated with complete MH after adjustment (adjusted OR 0.37, 95%CI 0.16-0.80; P for trend=0.010). In contrast, no association between PA and clinical remission was found (plentiful strenuous activity: adjusted OR 1.10, 95%CI 0.55-2.23; very high daily total METs: adjusted OR 0.74, 95%CI 0.37-1.46). CONCLUSION: In Japanese patients with UC, time spent per day on strenuous activity and total PA per day may be significantly inversely associated with complete MH, but not with clinical remission.

Effect of disease duration on the association between serum albumin and mucosal healing in patients with ulcerative colitis.

OBJECTIVE: Serum albumin is used as a marker of acute inflammation. Several studies have addressed the association between serum albumin and clinical outcome in patients with ulcerative colitis (UC). While mucosal healing (MH) has been indicated as the therapeutic goal for UC, the association between serum albumin and MH remains unclear. We evaluated this issue in patients with UC overall and explored whether duration of UC affected this association. DESIGN: This cross-sectional study recruited consecutive patients with UC. Study subjects consisted of 273 Japanese patients with UC. Serum albumin was divided into tertiles based on its distribution in all study subjects. One endoscopy specialist was responsible for measuring partial MH and MH, which were defined as a Mayo endoscopic subscore of 0-1 and 0, respectively. The association between serum albumin and clinical outcomes was assessed by multivariate logistic regression. RESULTS: Rates of clinical remission, partial MH and MH were 57.9%, 63% and 26%, respectively. Only high serum albumin (>4.4 mg/dL) was significantly positively associated with MH (OR 2.29 (95% CI: 1.03 to 5.29), p for trend=0.043). In patients with short UC duration (<7 years) only, high serum albumin was significantly positively associated with MH and clinical remission. In patients with long UC duration (≥7 years), in contrast, no association between serum albumin and clinical outcomes was found. CONCLUSION: In Japanese patients with UC, serum albumin was significantly positively associated with MH. In patients with short UC duration, serum albumin might be a useful complementary marker for MH.

Association between serum bilirubin and mucosal healing among Japanese patients with ulcerative colitis: a cross-sectional study.

PURPOSE: Bilirubin is known to have antioxidant effects. Several pieces of evidence regarding association between serum bilirubin and UC exist. Three studies found that serum bilirubin was inversely associated with severity of ulcerative colitis (UC), but no evidence regarding an association between serum bilirubin and mucosal healing (MH) has yet been shown. Thus, we evaluated this issue among Japanese patients with UC. METHODS: The study subjects consisted of 304 Japanese patients with UC. Serum total bilirubin and indirect bilirubin were divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH, which was defined as a Mayo endoscopic subscore of 0. The information on clinical remission was collected using medical records. RESULTS: The mean age was 49.9 years, the percentage of male patients was 59.2%, and the percentage of MH was 29.3%. High serum total bilirubin was independently positively associated with MH (OR 2.26 [95%CI 1.13-4.61]. However, after adjustment for confounding factors, the association between total bilirubin and MH disappeared. Very high serum indirect bilirubin was independently positively associated with MH (OR 2.31 [95%CI 1.10-5.00], p for trend = 0.026). No association between bilirubin and clinical remission was found. CONCLUSIONS: Among Japanese patients with UC, serum indirect bilirubin, but not total bilirubin, was significantly positively associated with MH but not clinical remission.

Association between platelet count and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study.

BACKGROUND: Mucosal healing (MH) has been indicated as the therapeutic goal for ulcerative colitis (UC). Platelet count is known as an inflammation evaluation. However, the association between platelet count and MH among patients with UC is still scarce. We therefore assessed this issue among Japanese patients with UC. METHODS: The study subjects consisted of 345 Japanese patients with UC. Platelet count was divided into quartiles on the basis of the distribution of all study subjects (low, moderate, high, and very high). Several endoscope specialists were responsible for evaluating MH and partial MH, which was defined as a Mayo endoscopic subscore of 0 and 0-1, respectively. Estimations of crude odds ratios (ORs) and their 95% confidence intervals (CIs) for partial MH and MH in relation to platelet count were performed using logistic regression analysis. Age, sex, CRP, steroid use, and anti-Tumor necrosis factor α (TNFα) preparation were selected a priori as potential confounding factors. RESULTS: The percentage of partial MH and MH were 63.2 and 26.1%, respectively. Moderate and very high was independently inversely associated with partial MH (moderate: OR 0.40 [95%CI 0.19-0.810], very high: OR 0.37 [95%CI 0.17-0.77], p for trend = 0.034). Similarly, moderate, high, and very high were independently inversely associated with MH (moderate: OR 0.37 [95% CI 0.18-0.73], high: OR 0.41 [95% CI 0.19-0.83], and very high: OR 0.45 [95% CI 0.21-0.94], p for trend = 0.033) after adjustment for confounding factors. CONCLUSIONS: Among patients with UC, platelet count was independently inversely associated with MH.

Carbonic Anhydrate I Epitope Peptide Improves Inflammation in a Murine Model of Inflammatory Bowel Disease.

BACKGROUND: Carbonic anhydrase I (CA I), a major cecal bacterial antigen, improves inflammatory bowel disease (IBD) symptoms in a murine model. The aim of this study was to identify the responsible epitope region within the CA I protein and evaluate its effect on inflammation using a murine IBD model. METHODS: Candidate peptides within the CA I protein sequence that interact with major histocompatibility complex class II were chosen and their immune responses were evaluated using mesentery lymph nodes (MLNs) from a CD4CD25 T-cell transfer murine colitis model. Mice were treated with regulatory dendritic cells (Reg-DCs)-pulsed CA I peptide. We assessed their clinical signs, histopathology, induction of cytokines and transcription factors, and generation of CD103CD11c dendritic cells and regulatory T cells (Tregs). RESULTS: We identified 4 candidate epitope peptides of CA I. Among these, Reg-DCs pulsed with CA I 58-73 peptide (Reg-DCsCA I 58-73) alone ameliorated colitis. Reg-DCsCA I 58-73-treated mice showed higher mRNA expression levels of forkhead box protein 3, aldehyde dehydrogenase family 1a2, transforming growth factor-ß, and interleukin (Il)10, when compared with lower mRNA expression of retinoic acid-related orphan receptor gamma and Il17a in MLNs. Compared with control mice, these mice also showed higher numbers of Foxp3CD4CD25 Tregs and CD103CD11c dendritic cells in MLNs and colon. Administration of Reg-DCsCA I 58-73 induced antigen-specific Tregs in MLNs of colitic mice. CONCLUSIONS: CA I 58-73 peptide induces antigen-specific therapeutic effect in a murine IBD model using Reg-DCs, indicating that CA I 58-73 is a candidate epitope for IBD immunotherapy.

Oral administration of carbonic anhydrase I ameliorates murine experimental colitis induced by Foxp3-CD4+CD25- T cells.

IBDs are thought to involve uncontrolled innate and adaptive immunity against intestinal self-antigens and bacterial antigens. Mouse CA I is a major cecal bacterial antigen in fecal extracts and is implicated in the pathogenesis of IBD. We show here that oral tolerization to CA I induced antigen-specific protection from intestinal inflammation in a murine model. Oral administration of CA I but not irrelevant antigen (KLH) ameliorated CD4(+)CD25(-) T cell transfer murine colitis and DSS-induced murine colitis. Next, we investigated the mechanisms involved in the therapeutic effects of oral administration, such as induction of ALDH1a2, transcription factors, cytokines, CD103(+)CD11c(+) DCs, and generation of Tregs. Oral administration of CA I induced ALDH1a2 mRNA expression in the MLN and colon. When compared with PBS-treated mice, CA I-treated mice had higher Foxp3(+)CD4(+)CD25(+) Treg and CD103(+)CD11c(+) DC numbers in the MLN and colon; had higher TGF-ß production in the MLN and colon; had lower RORγt mRNA expression in the MLN and colon; and had lower IL-17 mRNA expression and production in the MLN. These results demonstrate that oral administration of CA I induced antigen-specific immune tolerance by generating Foxp3(+)CD4(+)CD25(+) Tregs and inhibiting Th17 cells in a murine colitis model, thus suggesting that oral tolerization with CA I is an effective therapeutic strategy for IBD regulation.

[Evaluation of bronchial arterial infusion (BAI) for lung cancer with carcinomatous pleuritis].

MATERIALS AND METHODS: Six high-risk patients of lung cancer with carcinomatous pleuritis to which BAI was done were examined. BAI was performed using CDDP (40-50 mg/m2) + CPT-11 (40-50 mg/m2). The therapeutic effects, side effects, a reduction of the symptoms and prognosis were examined. RESULTS: All cases were revealed as stable disease according to the rule of the RECIST. The side effect of appetite loss for over grade 2 was found in one case. The reduction of respiratory symptoms (cough, dyspnea at the movement in 3, chest pain in 1 and loss of the movement in 1) was recognized by four out of five cases. Five patients died in three to seven months after the treatment of BAI. The causes of death were the recurrence of carcinomatous pleuritis and the primary lesion or the metastasis lesion of the lung in 4 cases and the recurrence of the primary lesion in 1 case. The recurrence of the malignant pleural effusion was recognized in 1 case without intra-thoracic infusion. COMMENT: BAI was effective as a reduction of the respiratory symptoms in the high-risk patients of lung cancer with carcinomatous pleuritis. It appeared that a long-term survival was probable with the combination of BAI, intra-thoracic infusion and systemic chemotherapy.