Ustekinumab effectiveness in Crohn's disease with lesions in the intestines.

Ustekinumab is prescribed for the treatment of patients with steroid-resistant moderate to severe Crohn's disease. We investigated its clinical outcome in patients with small and large intestinal lesions. Patients who were newly administered ustekinumab between March 2014 and December 2020 at Hamamatsu University Hospital were included in the study. The primary endpoint was Crohn's disease activity index score at baseline and weeks 8, 24, and 48 after the initiation of treatment, and secondary endpoints were albumin, hemoglobin, and C-reactive protein at these time points. Ustekinumab treatment retention was examined in both groups; the 2 groups were compared using the Friedman test, Mann-Whitney U test, or Fisher exact test. Overall, Crohn's disease activity index scores improved between baseline and 48 weeks, but the difference was not significant. However, there was a significant improvement between baseline and 48 weeks in patients with lesions in the small intestine only. Overall, patients showed significant improvement in albumin levels between baseline and 48 weeks but not in C-reactive protein or hemoglobin levels. When limited to patients with lesions in the small intestine, albumin and hemoglobin levels showed significant improvement. Both types showed high rates of treatment retention, although there was no significant difference. Ustekinumab appears to be a safe and effective treatment option that may be particularly effective in patients with lesions in the small intestine only.

Albumin change predicts failure in ulcerative colitis treated with adalimumab.

Anti-tumor necrosis factor (TNF) -α antibodies, including infliximab (IFX), adalimumab (ADA), and golimumab, which were the first biologic therapeutic agents, have a crucial position in advanced therapy for ulcerative colitis (UC). We aimed to investigate serum albumin (Alb) change as a prognostic factor for the therapeutic effect of ADA in UC. Thirty-four patients with UC treated with ADA were enrolled in this study and were divided into failure and non-failure groups. Biological data, such as Alb were compared between the two groups. Thirteen patients showed failure within six months. Examination of the biological data showed a significant difference between the two groups only in the week 2/week 0 Alb ratio. In receiver-operating characteristic (ROC) curve analysis to predict failure, the cut-off value of week 2/week 0 Alb ratio was 1.00, and the area under the curve was 0.868 (95% confidence interval: 0.738-0.999). In addition, in the sub-group analysis of only clinically active patients, the week 2/week 0 Alb ratio of the non-failure group was significantly higher than that of the failure group, and the cut-off-value in ROC analysis was 1.00. Week 2/week 0 Alb ratio ≤ 1 predicts failure within six months of ADA for UC.

Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports.

BACKGROUND: Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis. CASE SUMMARY: We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively. CONCLUSION: Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.

Comparison of fecal calprotectin levels and endoscopic scores for predicting relapse in patients with ulcerative colitis in remission.

BACKGROUND: Although the usefulness of endoscopic scores, such as the Mayo Endoscopic Subscore (MES), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS), and biomarkers such as fecal calprotectin (FC) for predicting relapse in ulcerative colitis (UC) has been reported, few studies have included endoscopic scores for evaluating the entire colon. AIM: To compare the usefulness of FC value and MES, UCEIS, and UCCIS for predicting relapse in patients with UC in clinical remission. METHODS: In total, 75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled. The diagnosis of UC was confirmed based on the clinical presentation, endoscopic findings, and histology, according to the current established criteria for UC. Fecal samples were collected the day before or after the colonoscopy for measurement of FC. Endoscopic evaluations were performed using MES, UCEIS, and UCCIS. The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES, UCEIS, UCCIS, and FC. The secondary outcome was the comparison between endoscopic scores and biomarkers in enrolled patients with UC with mucosal healing. RESULTS: FC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively). Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve of UCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patients experienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of the remission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The area under the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significant difference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was 86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES. CONCLUSION: The three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEIS may be the most useful in terms of ease of evaluation and accuracy.

Importance of eosinophilic infiltration of the colonic mucosa in ulcerative colitis patients who are refractory to maintenance therapy: A prospective, single-center study.

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely understood. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to the clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for the clinical background when starting steroid treatment. The clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of the clinical activity index, the Mayo endoscopic subscore, and the UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All scores improved significantly after steroid use (P = .042, P = .002, P = .002, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistance to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.

Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study.

BACKGROUND: Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS: One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS: In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS: Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Lymphocyte to monocyte ratio and serum albumin changes predict tacrolimus therapy outcomes in patients with ulcerative colitis.

Tacrolimus therapy for ulcerative colitis is ineffective in certain patients; these patients require biologics or colectomy. We examined the ability of serum albumin levels and leukocyte subtypes to predict the therapeutic efficacy of tacrolimus. Patients with ulcerative colitis treated with tacrolimus were divided into non-failure and failure (required colectomy or switch to biologics or systemic steroids) groups. Serum albumin levels and leukocyte subtypes at induction, week 1, and week 2 after reaching high trough levels were retrospectively examined. Tacrolimus therapy failed in 18/45 patients within 3 months. The week 2/week 1 albumin ratio was significantly different between the failure and non-failure groups (P < 0.001). The receiver operating characteristic curve analysis revealed optimal cut-off value of the week 2/week 1 albumin ratio was 1.06, and area under the curve was 0.815. Analysis of leukocyte subtypes revealed significant between-group difference in the week 1 lymphocyte to monocyte ratio (P < 0.001). Multivariate analysis showed week 2/week 1 albumin ratio ≤ 1.06 and week 1 lymphocyte to monocyte ratio ≤ 3.86. Therefore, a low week 2/week 1 albumin and low week 1 lymphocyte to monocyte ratio predicted failure within 3 months of tacrolimus induction; a combination of these markers could accurately predict failure.

Modified method of patency judgement using patency capsule prior to capsule endoscopy in clinical practice.

In 2012, Japan approved the use of a tag-less patency capsule (PC), which evaluates gastrointestinal patency before small-bowel capsule endoscopy (SBCE). This study aimed to evaluate the validity of our modification on the passage criteria for this PC in clinical practice. We retrospectively enrolled 326 consecutive patients who underwent PC examination before SBCE. If X-ray could not reveal the PC in the body during the judgement time (30-33 h after ingestion), we defined it as 'estimated patency' and performed SBCE. We employed plain computed tomography (CT) for the second judgement, as needed. The overall patency rate was 95.1%. By X-ray, 41 (12.6%) patients were judged to have 'estimated patency', and SBCE could be safely performed. Plain CT judgement was necessary in 106 patients (32.5%). One PC case had a residual coating film associated with stenosis in a patient with Crohn's disease (CD), and one (0.3%) SBCE case had capsule retention resulting from false CT judgement. Multivariate analysis revealed that established CD and inpatient were factors related to no-patency. In conclusion, PC is useful for examining gastrointestinal patency, keeping in mind CT misjudgement. If PC was not found in the body via X-ray, performing SBCE as 'estimated patency' seemed appropriate.

Lymphocyte-to-monocyte ratio is a short-term predictive marker of ulcerative colitis after induction of advanced therapy.

Advanced therapies for patients with mild-to-severe ulcerative colitis (UC) may result in treatment failure. We examined whether the lymphocyte-to-monocyte ratio (L/M ratio) could predict the failure of advanced therapies. This retrospective, observational, cohort study included 73 patients who were treated with advanced therapies at the Hamamatsu University School of Medicine (Shizuoka, Japan) between February 2011 and November 2020. The patients were divided into the non-failure and failure groups, and their leukocyte counts and ratios before induction were examined. Univariate and multivariate analyses were performed to identify the prognostic factors. Advanced therapies failed within 3 months in 15 (20.5%) patients. Only the L/M ratio was significantly lower in the failure group than in the non-failure group (P = 0.004). Receiver-operating characteristic (ROC) curve analysis revealed that an L/M ratio of ≤3.417 was predictive of treatment failure; the area under the curve (AUC) was 0.747 (95% CI, 0.620-0.874). Kaplan-Meier analysis revealed that the failure-free rate was significantly lower in the group with an L/M ratio of ≤3.417 than in the group with an L/M ratio of >3.417 (log-rank test P = 0.002). Cox proportional hazard regression analysis identified an L/M ratio of ≤3.417 as an independent risk factor for failure within 3 months after the induction of advanced therapies. Furthermore, ROC analysis of patients who did not receive immunomodulators also revealed that the cut-off L/M ratio was 3.417 and the AUC was 0.796 (95% CI, 0.666-0.925). In patients receiving advanced therapies for active UC, the L/M ratio can predict treatment failure within 3 months. L/M ratios could facilitate the transition from advanced therapies to subsequent treatments.

Predicting Ulcerative Colitis Relapse in Clinical Remission With Fecal Immunochemical Occult Blood Test or Prostaglandin E-Major Urinary Metabolite.

INTRODUCTION: The fecal immunochemical occult blood test (FIT) and prostaglandin E-major urinary metabolite (PGE-MUM) have been reported to predict the relapse of ulcerative colitis (UC) during remission. In this study, we directly compared FIT and PGE-MUM in predicting relapse and examined the effect of disease duration on these biomarkers. METHODS: Measurements of 2 biomarkers and endoscopic examination were performed in 73 patients with UC in remission. The patients were followed up for 12 months, and clinical relapse was evaluated. In addition, we divided the patients into long-term disease duration and short-term disease duration groups for analysis. RESULTS: Twenty-one patients (28.8%) relapsed within 12 months. FIT and PGE-MUM levels were significantly higher in the relapsed group than in the remission group. Cutoff values of FIT and PGE-MUM for predicting relapse using receiver operating characteristic analysis were 65.0 ng/mL (area under the curve [AUC]: 0.723) and 25.2 µg/g·Cr (AUC: 0.701), respectively. Patients with FIT ≥ 65.0 ng/mL and PGE-MUM ≥ 25.2 µg/g·Cr had a higher risk of clinical relapse. In the short-term disease duration group, the AUCs of FIT were larger than those of PGE-MUM using receiver operating characteristic analysis, in most instances. By contrast, the AUCs of PGE-MUM were larger than those of FIT in most cases in the long-term disease groups. DISCUSSION: FIT and PEG-MUM were highly accurate in predicting clinical relapse in UC patients with short and long disease durations in remission, respectively.

Real-World Efficacy and Safety Monitoring for Predicting Continuation of Tofacitinib Therapy in Patients with Ulcerative Colitis.

BACKGROUND: Although the clinical efficacy of tofacitinib in patients with ulcerative colitis (UC) has been assessed in the OCTAVE trial, there is a lack of adequate data on its efficacy in real-world clinical settings. AIMS: To analyze the efficacy of tofacitinib and the predictors of its continuation. METHODS: Changes in clinical activity index (CAI), blood test results (C-reactive protein [CRP], albumin [Alb], and hemoglobin), and endoscopic scores (Mayo endoscopic subscore [MES], ulcerative colitis endoscopic index of severity [UCEIS]) were evaluated, and we investigated the factors that affect the rate and continuity of tofacitinib. RESULTS: Twenty-two patients with UC who were treated with tofacitinib were enrolled. Tofacitinib was continued in 16/22 (72.7%) patients. CAI significantly improved 4 weeks after tofacitinib induction (P < 0.01). In the blood tests, only Alb level improved significantly at week 2 compared with baseline (P = 0.03). In the non-failure group, serum Alb and CRP levels improved significantly from week 0 to week 24; however, similar changes were not observed in the failure group. After 6 months, the overall MES and UCEIS had significantly improved (P = 0.03 and P = 0.02, respectively). Kaplan-Meier analysis demonstrated that those with baseline UCEIS ≥ 5 had significantly lower tofacitinib continuation rate than those with baseline UCEIS ≤ 4, suggesting that baseline UCEIS may be a predictor of tofacitinib continuation (log-rank test: P < 0.01). CONCLUSIONS: Tofacitinib is a promising therapeutic agent for the induction and maintenance therapy in UC. Baseline UCEIS may predict its therapeutic effects.

Comparison between Prostaglandin E-major urinary metabolite and C-reactive protein levels to reflect endoscopic scores in patients with ulcerative colitis.

Prostaglandin E-major urinary metabolite (PGE-MUM) and C-reactive protein (CRP) are useful biomarkers in patients with ulcerative colitis. However, whether changes in endoscopic scores over time are reflected in the values of these biomarkers has not been verified. This prospective observational study aimed to assess the relationship between changes in biomarker levels and endoscopic scores in patients with ulcerative colitis. A total of 100 colonoscopy intervals of patients with ulcerative colitis were enrolled. The relationship between variations in the Mayo endoscopic subscore over time and the accompanying changes in biomarker values were investigated. PGE-MUM levels showed a significant rise in the increased endoscopic score group (P = 0.007) and a decrease with reduced endoscopic score group (P = 0.023). CRP levels showed a significant decline with lower endoscopic values (P < 0.001); however, there was no corresponding increase with higher endoscopic scores (P = 0.141). Biomarker levels remained unchanged with stable endoscopic scores (P = 0.090 and P = 0.705). PGE-MUM levels varied significantly, and corresponded to the mucosal healing state (P = 0.019 and P = 0.009). The correlation between changes in PGE-MUM and the endoscopic score was stronger than that for CRP (r = 0.518, P < 0.001 vs. r = 0.444, P < 0.001, respectively). PGE-MUM reflected changes in endoscopic scores more accurately than CRP.

Usefulness of the capsule endoscopy Crohn's disease activity index in assessing the necessity of early additional treatment in patients with Crohn's disease in clinical remission.

ABSTRACT: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI) was recently reported as a new scoring system to evaluate the mucosal lesions of patients with Crohn's disease (CD). We investigated whether CECDAI is useful for assessing the necessity of early additional treatment in patients with CD in clinical remission.Twenty-one patients with small intestinal CD in clinical remission underwent capsule endoscopy (CE). The CECDAI and Lewis score (LS) were used to evaluate the intestinal lesions. We analyzed the correlations between several biomarkers and CECDAI or LS and examined the changes in therapeutic regimens based on the CECDAI.CE identified intestinal abnormalities in most CD patients in clinical remission: 81.0% and 85.7%, as assessed using CECDAI and LS, respectively. A significant positive correlation was observed between the CDAI and LS (P = .025), as well as between CDAI and CECDAI (P = .014) in these cases. Compared to LS, CECDAI scores were more evenly distributed. No significant correlations were observed between endoscopic scores and serum markers, including CRP, hemoglobin, and albumin levels. Additional treatment was performed significantly more often in patients with moderate-severe disease activity (CECDAI ≥5.8) (P = .012) than in those with normal (CECDAI <3.5) and mild (3.5≤CECDAI<5.8) disease activity. Resection of the small intestine did not affect the small bowel transit time or CE score.CECDAI is useful in evaluating mucosal lesions in small bowel CD patients in clinical remission and helps in assessing the requirement for additional treatment for these patients, including those who undergo intestinal resection.

Further research on the clinical relevance of the ulcerative colitis colonoscopic index of severity for predicting 5-year relapse.

PURPOSE: The ulcerative colitis colonoscopic index of severity (UCCIS) evaluates the state of the entire colonic mucosa in ulcerative colitis. However, no cut-off values of scores for predicting clinical relapse in patients with ulcerative colitis have been established. This study aimed to determine the cut-off values for predicting clinical relapse in patients with ulcerative colitis. METHODS: The endoscopic scores (sum of Mayo endoscopic subscores (S-MES) and UCCIS) of 157 patients with ulcerative colitis experiencing clinical remission and their subsequent clinical course were retrospectively reviewed. The optimal cut-off values for predicting relapse and relapse-free rates were analyzed by receiver operating characteristic analysis. RESULTS: Forty patients with ulcerative colitis experienced relapse within 24 months. The median UCCIS for these patients at the time of study enrollment was significantly higher than that for patients with clinical remission (P < 0.001). The cut-off value of the UCCIS for predicting relapse was 9.8. The relapse-free rate was significantly lower in patients with UCCIS ≥ 9.8 than in those with UCCIS < 9.8 (log-rank test P < 0.001). For patients who experienced relapse within 5 years, the optimal cut-off values for the UCCIS and S-MES were 10.2 and 1, respectively (P = 0.004). CONCLUSIONS: The data from this study indicate that the USSIC is a more relevant score than the S-MES for predicting the time to relapse in patients with ulcerative colitis in remission.

Prevalence of UL97 gene mutations and polymorphisms in cytomegalovirus infection in the colon associated with or without ulcerative colitis.

Cytomegalovirus (CMV) reactivation in the colon is common in patients with severe ulcerative colitis (UC). Ganciclovir (GCV) resistance conferring CMV UL97 gene mutations have been reported in recent years. However, the prevalence of UL97 gene mutations in GCV-naive CMV infection in the colon remains unknown. We investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. Twenty-two GCV-naive patients with colonic CMV infection, 15 with UC and 7 with other diseases, were enrolled. Frozen biopsy samples or formalin-fixed paraffin-embedded samples were used for nested polymerase chain reaction (PCR) amplification of the UL97 gene. Sanger DNA sequencing was performed. In comparison with AD169 reference strain, natural polymorphisms were frequently detected in codons N68D (100%), I244V (100%), and D605E (86.4%). Seven polymorphisms were detected infrequently (< 10%) outside the kinase domain. However, no known GCV resistance mutations were found. There seemed to be no difference between the ratio of polymorphisms in patients with and without UC. In conclusions, we did not detect UL97 gene mutations associated with GCV resistance in GCV-naive patients with or without UC. Consistent with previous reports, D605E polymorphism may be used as a genetic marker for CMV in East Asian countries.

Therapeutic monitoring of adalimumab at non-trough levels in patients with inflammatory bowel disease.

Adalimumab (ADA) trough level and anti-ADA antibody (AAA) positivity influence mucosal healing and loss of response in patients with inflammatory bowel disease (IBD). In this study, we clarified the correlation between ADA monitoring, including non-trough level, and real-world IBD clinical outcomes. This retrospective, observational, single-center study involved patients with ulcerative colitis (19) and Crohn's disease (33) treated with ADA from January 2007 to August 2018. Serum ADA and AAA levels were measured 4‒14 days after ADA administration. The AAA positivity rate was 23.1% (12/52). ADA continuity was higher in AAA-negative patients than in AAA-positive patients (P = 0.223). Receiver operating characteristic (ROC) analysis revealed that a serum AAA cut-off of 9.2 µg/mL was associated with ADA continuity. The ADA level was significantly higher in the endoscopic remission group than in the non-remission group (P = 0.02). Based on the ROC curve analysis results of serum ADA level and endoscopic remission, the cut-off value of the serum ADA level was set to 11.1 µg/mL. Under the combined use of ADA with immunomodulators and AAA positivity, ADA continuity was significantly higher when the serum AAA level at 4-14 days after ADA administration was ≥9.2 µg/mL. Furthermore, endoscopic remission can be expected with a serum ADA level of ≥11.1 µg/mL. Overall, to predict clinical outcomes, it would be useful to measure the blood level of ADA regardless of the timing of the trough.

C-reactive protein is superior to fecal biomarkers for evaluating colon-wide active inflammation in ulcerative colitis.

We evaluated the association between endoscopic scores of colonic inflammation and fecal calprotectin (FC), fecal immunochemical occult blood test (FIT), and C-reactive protein (CRP) in patients with ulcerative colitis (UC). Endoscopic scores reflecting the most severe lesion [maximum Mayo Endoscopic Subscore (M-MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS)] and those reflecting the inflammation of the entire colon [sum of MES (S-MES) and Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)] were evaluated. FC, FIT, and CRP were measured, and their association with the four endoscopic scores was evaluated. Endoscopic scores of 78 complete colonoscopies (66 UC patients) were evaluated using the three biomarkers. FC and CRP tended to correlate more strongly with S-MES and UCCIS than with M-MES and UCEIS. In the M-MES 0, 1 group, compared to CRP, FC and FIT showed stronger correlations with S-MES and UCCIS. Conversely, in the M-MES 2, 3 group, only CRP was significantly correlated with each descriptor. CRP more strongly reflects colon-wide mucosal inflammation than FC and allows reliable assessment of inflammation throughout the colon in active UC.

Early serum albumin changes in patients with ulcerative colitis treated with tacrolimus will predict clinical outcome.

BACKGROUND: Oral tacrolimus is a therapeutic agent for moderate to severe steroid-dependent or resistant ulcerative colitis (UC), but remission induction is difficult, and it is necessary to treat the patient while considering the next treatment. AIM: To examine serum albumin (Alb) level as a prognostic factor for the therapeutic effect of tacrolimus in clinical practice. METHODS: Forty-seven patients with UC treated with tacrolimus at our institution were divided into remission and failure groups (colectomy or switch to biologics), and the biological data at the start of observation and at weeks 1 and 2 were retrospectively examined. Kaplan-Meier and multivariate analyses were performed using Alb as a prognostic factor in UC treatment. RESULTS: During the three months observed, 17 (36.2%) patients failed treatment with tacrolimus. A comparison between the failure and remission groups showed a significant difference only in Alb in week 2, and in the week 2/week 0 Alb ratio, which showed the rate of change in Alb. The cut-off value of the week 2/week 0 Alb ratio that predicted failure was 1, and its area under the curve was 0.751 (95%CI: 0.604-0.898). In the Kaplan-Meier analysis, a week 2/week 0 Alb ratio ≤ 1 had a significantly higher failure rate than that of > 1; Cox proportional hazard regression analysis also showed that a week 2/week 0 Alb ratio ≤ 1 was an independent prognostic factor for failure within 3 mo after the start of tacrolimus treatment. CONCLUSION: A week 2/week 0 Alb ratio ≤ 1 predicts failure within 3 mo of tacrolimus administration for UC. High failure risk exists with week 2 Alb values ≤ 1 on admission.

Serum N-terminal telopeptide of type I collagen as a biomarker for predicting bone density loss in patients with Crohn disease.

BACKGROUND: The serum N-terminal telopeptide of type I collagen (NTx) is significantly higher in patients with Crohn disease (CD) than in healthy individuals and patients with ulcerative colitis. This study aimed to investigate whether an elevated serum NTx level is a risk predictor of osteoporosis in patients with CD. METHODS: Based on whether the femoral Z-score decreased over a 2-year period, 41 CD patients were divided into the ΔZ-score <0 group (Z-score decreased) and the ΔZ-score ≥0 group (Z-score did not decrease). The risk predictors of a femoral Z-score decrease were examined. Furthermore, we investigated the correlations between the ΔZ-score (which represents the change in the Z-score over a 2-year period) and the mean levels of biomarkers, including the Crohn Disease Activity Index (CDAI), serum albumin, C-reactive protein, and bone metabolism markers (including NTx) measured initially (i.e., in our previous study) and 2 years later (present study). The relationships between anti-tumor necrosis factor α (anti-TNF-α) therapy and serum NTx levels were also examined. RESULTS: Although there was no correlation between the mean CDAI and the ΔZ-score, the mean serum NTx and albumin levels were significantly correlated with the ΔZ-score (P<0.01 and P = 0.02, respectively). Furthermore, the femoral Z-score tended to be lower in the anti-TNF-α administration group than in the non-administration group. CONCLUSIONS: These observations indicated that an elevated serum NTx could be a useful marker for predicting a decrease in the femoral bone mineral density in CD patients. Anti-TNF-α therapy maintained an elevated serum NTx level, suggesting that treatment with anti-TNF-α may help control increased bone resorption in CD patients.