Lichtiger Index Research Articles

P0675 Ultrasonographic assessment of response in hospitalized patients with acute severe ulcerative colitis

Abstract Background Patients admitted with acute severe ulcerative colitis (ASUC) respond to medical therapy in upto two-third cases but monitoring and early detection of non-response is of prime importance to prevent colectomy or mortality, through use of rescue medical therapy. This study evaluates the utility of ultrasonography (USG) in prognostication and decision-making for ASUC patients undergoing standardized treatment protocols. USG offers a non-invasive approach to assess bowel wall thickening and vascularity, pivotal indicators of disease activity. Methods In this prospective study, 45 ASUC patients undergoing intravenous steroid therapy were enrolled, with additional randomization to receive tofacitinib or placebo. USG evaluations of bowel wall thickness (defined as ≥3 mm) and vascularity were conducted at baseline and on day 5, with data available for 41 patients. Clinical responses were assessed using the Lichtiger index. Correlations between USG findings, clinical outcomes, and biochemical markers such as CRP and albumin were analyzed. Results Baseline USG revealed bowel wall thickening in the sigmoid colon in 82.9% (34/41) of patients and in the descending colon in 70% (28/41). (Figure 1) Responders showed a significant reduction in bowel wall thickness in the sigmoid and descending colon (p < 0.05), whereas non-responders exhibited no changes. (Figure 2) There was a moderate correlation between bowel wall thickening across different segments (Spearman’s rho = 0.3–0.5, p < 0.05), but no significant correlation with CRP, albumin, or endoscopic severity. Doppler findings indicated similar rates of increased vascularity (Limberg grade ≥3) in both responders and non-responders at baseline and follow-up. Ancillary findings, such as pericolic fat thickening and free fluid, were associated with poor clinical outcomes, highlighting their prognostic value. Notably, baseline USG identified skip lesions in two patients, later confirmed to have Crohn’s colitis instead of ASUC. The sample size was limited as the trial is ongoing, and the treatment groups (tofacitinib vs. placebo) remain blinded. Conclusion Serial ultrasonography of the left colon provides valuable, non-invasive insights into treatment response in ASUC, correlating well with reductions in clinical activity and bowel wall thickness among responder. Presence of pericolic fat thickening and ascites correlates with poor outcomes, while doppler assessment does not contribute to the assessment. Importantly, baseline USG may aid in differentiating ASUC from Crohn’s colitis in patients with index presentation as acute severe colitis.

Short-Term and Intermediate Efficacy of Tacrolimus for Active Ulcerative Colitis: A Single-Center Retrospective Analysis in Japan.

Background and aim Tacrolimus (tac) is used for induction therapy in refractory and severe ulcerative colitis (UC) cases. The aim of this study was to identify the factors contributing to the induction of remission and to assess the endoscopic or histologic improvement rates following induction of remission by tac. Methods This study examined data from 67 UC patients treated with tac for induction of remission out of 515 patients attending Dokkyo Medical University Hospital. The primary endpoint of the study was the analysis of factors contributing to successful induction of remission treatment with tac. The secondary endpoints were the corticosteroid-free remission rate at 52 weeks after tac induction and the endoscopic and histologic improvement rates following induction of remission. Results Analysis of factors contributing to successful induction of remission by tac showed the Lichtiger index at the beginning of remission induction therapy was 9.5 ± 2.5 for the successful remission group and 11.5 ± 2.4 for the unsuccessful remission group (p = 0.002). The proportions of patients who had used immunomodulators were 13/45 (28.9%) for the successful remission group and 14/22 (63.6%) for the unsuccessful remission group (p = 0.006). The proportions of patients who had used anti-tumor necrosis factor(TNF)α biologics were 4/45 (8.9%) for the successful remission group and 8/22 (36.4%) for the unsuccessful remission group (p = 0.006). Conclusion Patients with UC who are potential candidates for intensification of remission maintenance therapy are good candidates for induction of remission with tac. Moreover, improvement in endoscopic inflammation might be a predictive marker of response to remission induction therapy with tac.

Patients with Inflammatory Bowel Disease who regularly consume fruits and vegetables present lower prevalence of disease activation: A cross-sectional study

BackgroundExclusion diets are common practices among individuals with Inflammatory Bowel Disease (IBD). Reports that certain foods trigger or worsen symptoms are recurrent but lack evidence. The aim of the study was to identify which foods were most frequently avoided by patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) and whether the consumption of any food group was associated with disease activity. MethodsCross-sectional study with adult patients seen at an outpatient clinic in a tertiary public hospital. Dietary intake and eating habits were accessed through questionnaires administered via telephone interview. Disease activity and symptoms were assessed using the Harvey-Bradshaw Index (IHB) for CD and the Lichtiger Index (LI) for UC. Poisson regression with a robust variance estimator was used to estimate prevalence ratios. Analyzes were performed using SPSS - Statistical Package for the Social Sciences. ResultsThe study included 145 patients. Of these, 69.7% avoided certain foods, with citrus fruits and raw vegetables among the most avoided (16.8% and 13.8%, respectively). Regular consumption of fruits (PR= 0.56; CI 95% 0.32 – 0.97; p= 0.042) and vegetables (PR= 0.56; CI 95% 0.32 – 0.98; p= 0.045) was associated with a 44% lower prevalence of the active phase of the disease, compared to those who do not consume these foods, adjusted for age, sex and type of disease. Other food items did not present significant associations in the adjusted model. ConclusionsFruit and vegetable intake appears to have a protective role in the recurrence of IBD. Excluding foods is a common practice, even among patients in remission, and this should be combated as it can lead to nutritional losses. It is important to reinforce with patients the benefits of a varied and less restrictive diet.

Early Sonographic Improvement Predicts Clinical Remission and Mucosal Healing With Molecular-Targeted Drugs in Ulcerative Colitis

Background and AimsPredicting the efficacy of molecular-targeted drugs (MTDs) is an unmet need in the treatment of ulcerative colitis (UC). Intestinal ultrasound (IUS) can be used to safely and repeatedly assess UC activity. MethodsThirty-eight patients who started MTD therapy for active UC and underwent IUS at baseline and 3 months after starting therapy were analyzed. Steroid-free clinical remission (SFCR) and endoscopic improvement (EI) at 6 months were defined as a Lichtiger index of ≤3 and Mayo endoscopic subscore of ≤1 while continuing the MTD without steroid induction or surgery. Sonographically estimated EI (SE-EI) at 3 months was assessed based on a Milan Ultrasound Criterion (MUC) of ≤6.2 and Kyorin Ultrasound Criterion for UC [bowel wall thickness (BWT) of <3.8 mm and submucosa index of <50%]. ResultsThirty-one patients achieved SFCR at 6 months [SFCR(+) group]. The SFCR(+) group demonstrated significantly better improvement in BWT and bowel wall vascularity at 3 months than the SFCR(−) group. The MUC and UC-IUS index also improved significantly more in the SFCR(+) than SFCR(−) group. The areas under the curve of these parameters for predicting SFCR were approximately 0.80. Colonoscopy was performed for 28 patients at 6 months, and 15 patients achieved EI. SE-EI at 3 months was significantly associated with achievement of EI at 6 months. The positive predictive values of SE-EI at 3 months for SFCR and EI at 6 months were 100%. ConclusionsSonographic improvements in 3 months predicted the clinical and endoscopic efficacy of MTD therapy at 6 months, suggesting the longitudinal significance of IUS monitoring for UC treatment.

Machine learning using clinical data at baseline predicts the medium-term efficacy of ustekinumab in patients with ulcerative colitis

Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model.

IDENTIFICATION OF DISEASE SEVERITY DEFINITIONS FOR ULCERATIVE COLITIS AND CROHN’S DISEASE

Abstract BACKGROUND Evidence suggests that, in patients with ulcerative colitis (UC) or Crohn’s disease (CD), those with moderate disease may achieve better outcomes with vedolizumab than those with severe disease. However, no consensus definition of moderate disease exists for UC or CD, as confirmed by a comprehensive literature review published in 2016.1 We aimed to identify definitions of disease severity for UC and CD in studies published since the approval of vedolizumab. METHODS The first stage of the research comprised a systematic literature review (SLR) that complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement and was registered prospectively with PROSPERO (CRD42023427948). Literature searches were conducted in Embase, MEDLINE, and the Cochrane Library databases on May 16, 2023 to identify publications from 2015 onwards. Title and abstract screening, followed by full-text review was undertaken by two blinded reviewers, with discrepancies resolved by a third reviewer. Data on disease severity indices and thresholds used to define mild, moderate, and/or severe disease were extracted from eligible primary publications. RESULTS Data were extracted from 119 eligible publications (Figure 1), of which 109 related to UC only, 7 to CD only, and 3 to both UC and CD. For UC, the most common disease severity index was Truelove and Witts’ criteria (N = 82), followed by Mayo score or one of its derivatives such as partial Mayo score or Mayo sub-score (N = 29), Lichtiger index (N = 9), Montreal classification (N = 4), Rachmilewitz score (N = 3), and Oxford criteria (N = 3). The definitions identified for mild and moderate disease were similar across studies; however, numerical thresholds used to define moderate and severe disease with Mayo score, partial Mayo score, and Lichtiger index overlapped (Figure 2). For CD, the Crohn’s Disease Activity Index (CDAI) (N = 6) was the most commonly used disease severity index, followed by the Harvey–Bradshaw index (HBI) (N = 2). Moderate disease was defined as a CDAI score of 200–450 or 220–450 or a HBI score of 8–16. CONCLUSION For UC, the thresholds used to define moderate disease were similar across studies but overlapped with those used for severe disease in some cases. Too few CD publications were identified to draw robust conclusions, likely due to the exclusion of those describing patients with mild-to-moderate or moderate-to-severe disease without further stratification in the title or abstract. A targeted literature review of publications reporting phase 3 clinical trials of drugs for UC or CD is ongoing; the thresholds of all measurements used to stratify the patient cohorts in these trials will be extracted to further understand the characteristics of patients with moderate disease. 1. Peyrin-Biroulet L, et al. Clin Gastroenterol Hepatol. 2016;14(3):348-354.e17. Figure 1 PRISMA flow diagram. Figure 2 Numerical ranges used to define mild, moderate, and severe disease for UC.

P295 Early sonographic improvement predicts the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis

Abstract Background Today molecular-targeted medications (MTMs) are widely used for ulcerative colitis (UC). Predicting the efficacy of MTMs early after induction remains a crucial clinical challenge. Intestinal ultrasound (IUS) is now considered a non-invasive, promising monitoring tool for UC. It can assess the disease activity of UC in the whole colon safely and repeatedly. Here, we hypothesized that over time IUS assessment can predict the MTM efficacy early, contribute to early clinical decision-making on whether to continue or switch MTMs, and reduce the burden of colonoscopy (CS) recommended to be scheduled at around 6 months after the induction. Methods We analyzed 44 patients who started an MTM for active UC, underwent IUS at baseline and 3 months, and took CS at 6 months after the induction. The clinical disease activity and endoscopic activity at 6 months were assessed with Lichtiger index (LI) and Mayo endoscopic subscore (MES), respectively. Clinical remission was defined as a LI ≤ 3. Endoscopic improvement (EI) was defined as a MES = 0 or 1. In addition to the assessment of sonographic findings, such as bowel wall thickness (BWT), bowel wall stratification including submucosa index (SMI), bowel wall flow with modified Limberg score (mLS), Milan Ultrasound Criteria (MUC), UC-IUS index (UII), Kyorin Ultrasound Criterion for UC (KUC-UC; BWT&amp;lt;3.8mm with SMI&amp;lt;50%) were evaluated. Results Patients who achieved steroid-free clinical remission (SFCR) showed better improvement in BWT, %BWT, and mLS in 3 months compared to those who did not achieve SFCR (p&amp;lt;0.01 for each). The improvement in MUC and UII was also observed in patients who achieved SFCR at 6 months (p&amp;lt;0.001 for both). In ROC analyses, the area under the curve for SFCR at 6 months was 0.80 with BWT, 0.80 with %BWT, 0.81 with mLS, 0.85 with MUC, and 0.85 with UII. Among the 44 patients, 7 patients achieved MUC≤ 6.2, estimating MES=0/1, at 3 months, and 6 out of 7 patients demonstrated EI at 6 months (positive predictive value [PPV]=87.5%). Meanwhile, 4 patients satisfied KUC-UC at 3 months and all of them achieved SFCR and EI at 6 months (PPV=100%). Conclusion Our study suggests that patients who achieved sonographic improvement in 3 months can continue an ongoing MTM therapy and that patients who demonstrated sonographic findings estimating EI at 3 months can postpone CS at 6 months.

Tofacitinib in Acute Severe Ulcerative Colitis (TACOS): A Randomized Controlled Trial.

Intravenous corticosteroids are the mainstay of treatment of patients hospitalized with acute severe ulcerative colitis (ASUC). However, 30%-40% of the patients are refractory to corticosteroids. We investigated whether addition of tofacitinib to corticosteroids improved the treatment responsiveness in patients with ASUC. This single-center, double-blind, placebo-controlled trial randomized adult patients with ASUC (defined by the Truelove Witts severity criteria) to receive either tofacitinib (10 mg thrice daily) or a matching placebo for 7 days while continuing intravenous corticosteroids (hydrocortisone 100 mg every 6 hours). The primary end point was response to treatment (decline in the Lichtiger index by >3 points and an absolute score <10 for 2 consecutive days without the need for rescue therapy) by day 7. The key secondary outcome was the cumulative probability of requiring initiation of infliximab or undergoing colectomy within 90 days following randomization. All analyses were performed in the intention-to-treat population. A total of 104 patients were randomly assigned to a treatment group (53 to tofacitinib and 51 to placebo). At day 7, response to treatment was achieved in 44/53 (83.01%) patients receiving tofacitinib vs 30/51 (58.82%) patients receiving placebo (odds ratio 3.42, 95% confidence interval 1.37-8.48, P = 0.007). The need for rescue therapy by day 7 was lower in the tofacitinib arm (odds ratio 0.27, 95% confidence interval 0.09-0.78, P = 0.01). The cumulative probability of need for rescue therapy at day 90 was 0.13 in patients who received tofacitinib vs 0.38 in patients receiving placebo (log-rank P = 0.003). Most of the treatment-related adverse effects were mild. One patient, receiving tofacitinib, developed dural venous sinus thrombosis. In patients with ASUC, combination of tofacitinib and corticosteroids improved treatment responsiveness and decreased the need for rescue therapy.

The Use of Cannabinoids in the Treatment of Inflammatory Bowel Disease (IBD): A Review of the Literature.

Around the world, about 15 to 40% of individuals with inflammatory bowel disease (IBD) rely on cannabis and cannabinoids to reduce the need for other medications, as well as increase appetite and reduce pain. Whereas more and more patients continue to report benefits accruing from cannabis and cannabinoid usage in IBD, agreement relative to the use of cannabis and its derivatives in IBD remains unclear. This paper reviewed the interplay between cannabinoid use and IBD disease treatment, remission, or symptom relief. The study was conducted from a systematic review perspective. It involved consulting literature from published original research articles, noting outcomes, and performing a meta-analysis to identify trends and draw conclusions. The selected articles were those that had been published in a 10-year period ranging between 2012 and 2022. The motivation was to ensure recency and also relevance to contemporary scientific research and clinical environment practices. Indeed, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework helped in answering the focal question of the investigation, which revolved around whether cannabinoids are beneficial to IBD treatment and to what extent. The aim of using this protocol was to ensure the satisfaction of the article exclusion and inclusion criteria, as well as ensure the utilization of articles directly contributing to the central subject under investigation. In the findings, it was established that on the one hand, cannabinoid usage in IBD treatment comes with promising results as reported in the majority of the selected studies which reported reduced clinical complications which were assessed using Mayo scores, Crohn's Disease Activity Index (CDAI) score, weight gain, enhanced patient health perception, Lichtiger Index and Harvey-Bradshaw Index or general wellbeing. On the other hand, cannabinoid use remains questionable because evidence of high quality is yet to surface vividly, especially in terms of the mode of administration and the appropriate dose. It is also notable that the findings were characterized by a state of high heterogeneity in terms of the study designs of the studies that were selected, disease activity indices, the duration of treatment by different scholarly researchers, the difference in the modes of administration of cannabinoid and cannabis by different researchers, variations in cannabis dosage, differences in the selected studies' inclusion criteria, and variations in their case definitions. The implication is that whereas the efficacy of cannabinoid use in IBD treatment was reported in most studies, outcome generalizability from the review was highly likely to be restricted. In the future, it is recommended that randomized controlled trials center, set universal parameters for IBD treatment using cannabis and cannabinoids to determine intervention safety and effectiveness as well as having homogenous outcomes that can be compared between different studies. In so doing, the appropriate dose and ideal mode of administration of cannabis and its derivatives might be discerned, ensuring relevance based on patient characteristics such as gender and age, as well as the appropriate administration mode and dose as per IBD symptom severity.

P334 Respiratory Manifestations and Association Between Disease Activity in Patients with Inflammatory Bowel Disease in a Reference Center in Salvador, Bahia, Brazil.

Abstract Background Inflammatory bowel diseases (IBD) are chronic diseases that may have a variety of extraintestinal manifestations(EIM), including pulmonary1. Although less frequent than other types of EIM, these alterations have been increasingly. Manifestations present with a wide variety of phenotypes, which can affect different parts of the respiratory system2. As most of these patients are asymptomatic, this type of manifestation is less diagnosed than the other extraintestinal manifestations3,4. Methods Cross-sectional, analytical, single-center study, carried out from April/2021 to October/2022, with the application of a questionnaire and review of medical records of patients from an outpatient clinic specialized in IBD in Salvador/BA, at Hospital Geral Roberto Santos(HGRS). Approved by the HGRS Research Ethics Committee. Inclusion criteria: patients ≥18 years old, diagnosed with IBD and signed the informed consent form. Dyspnea symptoms were evaluated using the Modified Medical Research Council Dyspnea Scale(mMRC), dry or productive cough, chest pain and hemoptysis. The clinical activity of the IBD was evaluated using the Harvey-Bradshaw Index in CD and the Lichtiger Index in UC. To test the association between the presence of respiratory manifestations and the clinical activity of the IBD, the chi-square test was used. Significant associations were considered at p &amp;lt; 0.05. Results Total of 255 patients were included, 47.1% with CD and 52.9% with UC, 44 had respiratory symptoms. Table 1 shows the general and clinical characteristics. Current treatments: mesalazine suppository and oral(63,2%), azathioprine(29.8%), infliximab(17.3%), sulfasalazine(15.7%), adalimumab(8.6%), prednisone(7.5%), ustekinumab(1.6%), methotrexate(1.6%), vedolizumab(0.8%), tacrolimus or cyclosporine(0.4%), tofacitinib(0.4%). Most of these patients(70.6%) were in clinical remission of IBD at the time the questionnaire was collected, while a minority (29.5%) were in clinical activity. In the 44 patients with respiratory symptoms, the majority are female(77.3%). Patients in clinical remission had respiratory symptoms in 12.9%(22/171), while patients in active remission had respiratory symptoms in 26.2%(22/74). Dyspnea was the most frequent symptom. Statistically significant association was found between the presence of respiratory manifestations and clinical activity(p=0.008). No difference in relation to the type of IBD, nor for medication. Table 2 shows association between disease activity and the presence of respiratory symptoms. Conclusion The frequency of respiratory symptoms was high in patients with IBD, with a higher prevalence in patients with active disease. This finding draws attention to a possible mechanism associated with the IBD activity.

P193 Predicting the middle-term efficacy of molecular-targeted medications for Ulcerative Colitis based on the intestinal ultrasound findings

Abstract Background Intestinal ultrasound (IUS) is non-invasive and can assess all segments of the colon even in severe ulcerative colitis (UC). While IUS can estimate the endoscopic findings of UC, in terms of the Treat to Target strategy, it remains a crucial clinical question whether the changes in IUS findings with therapeutic interventions can predict the treatment efficacy and the patient prognosis. Here, we investigated if comparing IUS findings at baseline and 3 months after starting a molecular-targeted medication (MTM) can predict the steroid-free clinical remission (SFCR) of UC at 6 months. Methods Inclusion criteria were (1) patients with UC who started an MTM as the induction therapy by March 2022 in Kyorin University Hospital, (2) IUS was performed at baseline and 3 months after starting the medication, and (3) patients could be tracked until 6 months after starting the medication. SFCR was defined as Lichtiger index &amp;lt;4 without changing the MTM, performing surgery, and using steroids. The bowel wall thickness (BWT, mm), bowel wall flow (BWF, scored with Limberg score), bowel wall stratification (BWS, intact/unclear/loss), increased echoic level of mesenteric fat around the colon (i-fat, yes/no), and haustration (normal/abnormal) were assessed at the most severely affected segment of the colon. The change of each parameter (Δ) was evaluated based on the sonographic findings at baseline and 3 months. The changing rate of BWT (ΔBWT%) was calculated as ΔBWT%=100 X ([BWT at 3 months]-[BWT at the baseline])/(BWT at the baseline). Milan ultrasound criteria (MUC) and UC-IUS index (UII) were scored based on the sonographic findings. This study was approved by the Institutional Review Board of Kyorin University School of Medicine (IRB No. 1668). Results In total 18 cases (ustekinumab: 7, infliximab: 5, vedolizumab: 4, adalimumab: 1, and tofacitinib: 1) were analyzed. IUS was performed at 0 and 88.5 days (median) after starting the molecular-target medications. Fourteen subjects achieved SFCR at 6 months (SFCR+ group). ΔBWT was significantly better in the SFCR+ group (-1.41±2.90) compared to the SFCR- group (1.20±1.31) (p=0.023). The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) of ΔBWT for SFCR at 6 months was 0.875. ΔBWT% showed a similar predicting capacity. Apparent sonographic improvements, (1) BWS became intact, (2) i-fat disappeared, and (3) haustration became normal, were observed only in the SFCR+ group. MUC and UII decreased more in the SFCR+ group compared to the SFCR- group, but not statistically significant in the present analysis. Conclusion Assessing BWT over time at baseline and 3 months can be a promising index to predict the efficacy of the molecular-targeted medications at 6 months.

Tumor Necrosis Factor-α, Fecal Calprotectin, and Disease Activity in Inflammatory Bowel Disease Patients

INTRODUCTION: Inflammatory bowel disease (IBD) has increased incidence and the lack of effective long-term therapeutic options has resulted in mortality from intestinal complications and also significant costs to the country’s health-care system. Evaluation of disease activity in IBD patients is beneficial for establishing clinical judgments, especially in giving therapy and knowing the response of the given therapy. Tumor necrosis factor (TNF)-α, fecal calprotectin (FC), Lichtiger index, and Crohn’s Disease Endoscopic Index of Severity (CDEIS) are useful tools for evaluating disease activity. This study wants to know the relationship between biomarkers with disease activity. METHODS: A cross-sectional retrospective study was conducted on IBD patients. The diagnosis of IBD was based on findings from the gastrointestinal tract during colonoscopy and biopsy that showed features of IBD. TNF-α _was taken from the patient’s serum, while FC was from the patient’s stool sample. Lichtiger index was taken from anamneses, while CDEIS from endoscopy. The data will be analyzed using SPSS 22.0. RESULTS: A total of 35 patients with IBD met the inclusion criteria. This study found a 0.7-fold risk in IBD patients to have moderate-severe activity if they had TNF-α _levels of ≥ 1.14 pg/mL, although it was not significant (p = 0.581; OR:0.68; 95%CI 0.18-2.66). A significant relationship was found in the value of FC with disease activity in IBD patients, with a six-fold risk of having IBD with moderate-to-severe activity if FC levels ≥254 μg/g (p=0,011, OR:6,24, 95%CI 1,44-27,06). CONCLUSION: Fecal calprotectin levels have significant relationship with disease activity in IBD patients, both clinically and endoscopically. Fecal calprotectin is a decent marker for assessing disease activity in IBD patients.

Thiopurine naivety at tacrolimus induction is a predictor of long-term remission in patients with intractable ulcerative colitis who responded to tacrolimus.

The short-term efficacy of tacrolimus (Tac) for steroid-dependent and steroid-resistant refractory ulcerative colitis (UC) has been demonstrated; however, its long-term outcomes have not been well documented. Thus, this study aimed to clarify the long-term outcomes of patients who achieved Tac-induced remission and identify its predictors. This study included patients with moderate-to-severe active UC who started receiving Tac at our hospital between July 2004 and December 2016. Short-term treatment response was assessed using the Lichtiger index 3months after starting Tac, and responding patients were further followed up to assess long-term outcomes. The primary endpoint was the relapse-free survival after Tac-induced remission, and the secondary endpoint was the identification of factors associated with relapse after Tac-induced remission. The cumulative relapse-free survival rate at 10years after Tac-induced remission was 33.2%. Multivariate analysis revealed that being thiopurine naïve at Tac induction was associated with the absence of relapse (hazard ratio: 0.45; 95% confidence interval: 0.22-0.92). Approximately one-third of patients who achieved Tac-induced remission maintained long-term remission. Being thiopurine naïve at Tac induction was a predictor of the absence of relapse.

Evaluation of ulcerative colitis activity using transabdominal ultrasound shear wave elastography.

Transabdominal ultrasound (US) has been reported to be effective in the evaluation of ulcerative colitis (UC). US can measure shear wave elastography (SWE) and shear wave dispersion (SWD), which may be correlated with inflammation and necrosis. We aimed to investigate the relationship between UC activity and SWE and SWD. Patients with UC who underwent US within 2 days before or after a colonoscopy between April 2019 and March 2020 were included. SWE and SWD were measured in the sigmoid colon; the correlations of SWE and SWD with the Lichtiger index and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) were investigated. We also compared SWE and SWD between patients with mucosal healing and those in the active phase according to the UCEIS. Twenty-six UC patients were enrolled. The median Lichtiger index, UCEIS, SWE values, and SWD values were 8 [interquartile range (IQR), 5.3-10.8], 4 (IQR, 3.3-5), 1.69 (IQR, 1.49-2.16) m/s, and 11.9 (IQR, 10.9-13.3) (m/s)/kHz, respectively. The Lichtiger index and UCEIS were negatively correlated with the SWE values (rs=-0.404 and rs=-0.506) but not with the SWD values (rs=0.004 and rs=0.002). The SWE values differed significantly between the mucosal healing and active phase groups [2.40 (IQR, 2.18-3.38) vs. 1.62 (IQR, 1.44-1.95) m/s, P=0.007], whereas the SWD values did not [13.1 (IQR, 7.05-21.6) vs. 11.9 (IQR, 11.1-13.2) (m/s)/kHz, P=0.918]. SWE may be useful for the evaluation of UC activity and could be a noninvasive method of assessing disease severity.

Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis.

Background and AimVedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut‐homing memory T cells into the intestinal submucosa by antagonizing the interaction of α4β7 integrin with MAdCAM‐1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real‐world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy.MethodsThis was a single‐center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty‐two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively.ResultsIn these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab.ConclusionsIn vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24.

Psychological mediators of psychological distress and quality of life in inflammatory bowel disease

Background and aimsUsing the Common Sense Model (CSM), this study aimed to examine the extent to which illness beliefs, coping styles, self-efficacy, and mindfulness mediate this relationship. MethodsTwo hundred and sixty-one adults (198 females; 169 with Crohn's Disease) with IBD participated in this cross-sectional study. Measures used in this study were the short Crohn's Disease Activity Index, Ulcerative Colitis Lichtiger Index, Inflammatory Bowel Disease Questionnaire, New General Self-Efficacy Scale, Carver Brief COPE scale, Mindful Attention Awareness Scale, Brief Illness Perceptions Questionnaire, and the Depression and Anxiety Stress Scales. ResultsUsing structural equation modelling, the final model indicated IBD symptoms had a significant direct influence only on illness perceptions (β = 0.66, p < .001). In turn, illness perceptions had a significant direct influence on depression and anxiety (β = 0.34, p < .001) and QoL (β = −0.67, p < .001), and was also linked to higher maladaptive coping (β = 0.28, p < .001) and lower self-efficacy (β = −0.49, p < .001), but not with mindfulness or adaptive coping (p > .05). Maladaptive coping (β = 0.46, p < .001) and mindfulness (β = 0.23, p < .001) were linked with increased distress. QoL was influenced by distress (β = −0.40, p < .001). ConclusionsConsistent with the predictions of the CSM, the relationships between IBD symptoms and depression and anxiety, and between IBD symptoms and quality of life, are statistically mediated via psychological variables including illness perceptions and maladaptive coping.

Extent of disease affects the usefulness of fecal biomarkers in ulcerative colitis

BackgroundFecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC.MethodsFecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively.ResultsA total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis.ConclusionsFor the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

Cannabis is associated with clinical but not endoscopic remission in ulcerative colitis: A randomized controlled trial.

BackgroundCannabis is often used by patients with ulcerative colitis, but controlled studies are few. We aimed to assess the effect of cannabis in improving clinical and inflammatory outcomes in ulcerative colitis patients.MethodsIn a double-blind, randomized, placebo-controlled trial, patients received either cigarettes containing 0.5 g of dried cannabis flowers with80mgTetrahydrocannabinol (THC)or placebo cigarettes for 8 weeks. Parameters of disease including Lichtiger disease activity index, C reactive protein (CRP), calprotectin, Mayo endoscopic score and quality of life (QOL) were assessed before, during and after treatment.ResultsThe study included 32 patients. Mean age was 30 years, 14 (43%) females. Lichtiger index improved in the cannabis group from 10.9 (IQR 9–14) to5 (IQR 1–7), (p<0.000), and in the placebo group from 11 (IQR 9–13) to 8 (IQR 7–10)(p = 0.15, p between groups 0.001). QOL improved in the cannabis group from 77±4 to 98±20 (p = 0.000) but not in the placebo group (78±3 at week 0 and 78±17 at week 8;p = 0.459; p between groups 0.007). Mayo endoscopic score changed in the cannabis group from 2.13±1 to 1.25±2 (p = 0.015) and in the placebo group from 2.15±1to 1.69±1 (p = 0.367, p between groups 0.17).ConclusionShort term treatment with THC rich cannabis induced clinical remission and improved quality of life in patients with mild to moderately active ulcerative colitis. However, these beneficial clinical effects were not associated with significant anti-inflammatory improvement in the Mayo endoscopic score or laboratory markers for inflammation.(clinicaltrials.gov NCT01040910).

Long-term outcomes of antibiotic combination therapy for ulcerative colitis.

Aims:An antibiotic combination of amoxicillin, tetracycline and metronidazole (ATM) is effective for ulcerative colitis (UC), but this regimen is discontinued in some cases due to adverse events. This study aimed to assess a revised combination, namely, amoxicillin, fosfomycin and metronidazole (AFM), in UC patients with the goal of reducing side effects while maintaining therapeutic efficacy.Methods:A prospective open-label trial was undertaken in 104 adult UC patients. A combination of oral amoxicillin (1500 mg), fosfomycin (3000 mg) and metronidazole (750 mg) was administered to patients daily for 2–4 weeks in addition to their conventional medication. Clinical assessment was performed using the Lichtiger index before treatment and at 0, 3, 6, 9 and 12 months and 2 and 3 years. Endoscopic evaluation was performed using the Mayo score before treatment and at 3 and 12 months.Results:The compliance rate was 99.2%. Response and remission rates were 80.8% and 63.5% at completion, 73.1% and 64.4% at 3 months, and 39.4% for both at 12 months, respectively. Of the 41 patients who were in remission at 12 months, 63.4% maintained that status until the 2-year follow-up. Similarly, 69.2% of those in remission at 2 years remained relapse free at the 3-year follow-up. Side effects were observed in 44.2% of the participants. Fever occurred in one patient (1.0%), which was lower than the rate observed with ATM therapy.Conclusion:These results indicate that AFM therapy induces remission and is appropriate for long-term maintenance of UC while producing fewer and milder adverse events than ATM therapy.Clinical trials:This study was registered in the University Hospital Medical Information Network (No. R000046546).

Efficacy and safety of short-term therapy with indigo naturalis for ulcerative colitis: An investigator-initiated multicenter double-blind clinical trial.

Indigo naturalis (IN) is a blue pigment extracted from Assam indigo and other plants and has been confirmed to be highly effective for ulcerative colitis (UC) treatment in several clinical studies. We conducted a multicenter double-blind study to confirm the efficacy and safety of short-term IN administration. A multicenter, randomized controlled trial was conducted between December 2015 and October 2018 in our facilities. Forty-six patients with mild to moderate active UC (Lichtiger index: 5-10) were randomly assigned to the IN group or the placebo group and received 5 capsules (500 mg) twice a day for 2 weeks. We investigated the efficacy according to blood tests and the Lichtiger index before and after administration, and we also examined adverse events. The analysis included 42 patients (20 males, 22 females) with an average age of 45 years. Nineteen patients were assigned to the placebo group, and 23 were assigned to the IN group. After treatment administration, in the placebo group, no change in the Lichtiger index was observed (7.47 to 6.95, p = 0.359), and hemoglobin was significantly reduced (12.7 to 12.4, p = 0.031), while in the IN group, the Lichtiger index (9.04 to 4.48, p = 0.001) and albumin (4.0 to 4.12, p = 0.022) improved significantly. Mild headaches were observed in 5 patients and 1 patient in the IN and placebo groups, respectively. Short-term administration of IN is highly effective without serious adverse events such as pulmonary hypertension or intussusception and may prevent the occurrence of serious adverse events.