Clinical Activity Index Score Research Articles

Fuzapladib in a randomized controlled multicenter masked study in dogs with presumptive acute onset pancreatitis.

Currently, no specific treatment is available for acute onset pancreatitis (AP), and management relies on symptomatic and supportive standard of care (SOC). Fuzapladib is a novel leukocyte function-associated antigen type-1 (LFA-1) activation inhibitor, blocking activation and subsequent adhesion and migration of neutrophils, potentially decreasing the risk of pancreatitis progression and systemic inflammation. Evaluate the safety and clinical response of dogs with AP after 3 days of administration of fuzapladib. Sixty-one client-owned dogs with presumptive AP. Randomized, masked, and placebo controlled multicenter study. Sixty-one dogs with AP were included for safety assessment, whereas 35 evaluable cases (fuzapladib, n = 16; placebo, n = 19) were included for clinical evaluation. Clinical improvement was assessed based on the change in the modified clinical activity index (MCAI) score on Day 3 compared to Day 0. Secondary variables included canine acute pancreatitis clinical severity index (CAPCSI) scores and serum concentrations of canine pancreatic lipase immunoreactivity, cytokines, and C-reactive protein. Fuzapladib was well tolerated by all treated dogs. Mean change in MCAI scores was significantly higher in the fuzapladib-treated (-7.75) than the placebo group (-5.68; P = .02, 95% confidence interval [CI] for the difference, -4.33, -0.35), suggesting clinical improvement in fuzapladib-treated dogs. No significant difference was found in any of the secondary variables between groups. Administration of fuzapladib to dogs was safe, and a favorable response was detected in 2 clinical activity scores. Effects of fuzapladib on survival and duration of hospitalization were not studied.

Prospective Evaluation of Low-Fat Diet Monotherapy in Dogs with Presumptive Protein-Losing Enteropathy.

For dogs with protein-losing enteropathy (PLE) and evidence of lymphangiectasia, the efficacy of low-fat diet as monotherapy or combined with prednisone remains poorly characterized. In this prospective, observational cohort study of 14 dogs with presumptive PLE and ultrasonographic evidence of lymphangiectasia, subjects were placed on various low-fat diets as monotherapy and prednisone was added if response was deemed inadequate. Dogs were assessed and scored at four recheck examinations across a 6 mo study period, including a final recheck ultrasound. Clinical and clinicopathologic variables were collected and dogs were divided into three outcome groups: clinical remission on dietary monotherapy (LOF); clinical remission on dietary therapy plus immunosuppressive prednisone (LOP); and treatment failure (TXF). Eleven of 14 dogs were in clinical remission at the study end date (6 mo after enrollment): 6 LOF dogs and 5 LOP dogs. LOF dogs achieved a significant reduction in Canine Chronic Enteropathy Clinical Activity Index score and a significant increase in serum albumin within 2 wk of beginning dietary monotherapy. Four of 11 dogs in remission also had ultrasonographic evidence of resolution of linear striations. Low-fat diet appears to be an effective monotherapy in some dogs with presumptive PLE and ultrasonographic evidence of lymphangiectasia.

Positive zinc intake and a Japanese diet rich in n-3 fatty acids induces clinical remission in patients with mild active ulcerative colitis: a randomized interventional pilot study.

Zinc intake has reduced hospitalizations in patients with ulcerative colitis (UC), highlighting the need to maintain blood zinc levels. This prospective study investigated whether the promotion of zinc intake and a Japanese diet (high in n-3 fatty acids) could induce clinical remission in patients with mild active UC. Patients with mild active UC were randomly assigned to either (1) continue an unrestricted diet or (2) receive nutritional guidance promoting zinc intake and a Japanese diet. The primary endpoint was clinical remission at 24 weeks. Secondary endpoints were the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores, Clinical Activity Index (CAI), Geboes Histopathology Score (GHS), and biomarkers, including zinc levels, measured at 12 and 24 weeks. Nutritional assessments were performed using the Food Frequency Questionnaire. The CAI, UCEIS, and GHS scores were significantly lower in the intervention group than in the control group, with a significantly higher proportion of patients achieving clinical remission. Furthermore, the intervention group exhibited weight gain and significantly increased blood zinc levels. The combination of promoting dietary zinc intake and a Japanese diet rich in n-3 fatty acids can induce clinical remission in patients with mild active UC.

S112 Optimal Timing and Donor-Patient Matching of Fecal Microbiota Transplantation for Ulcerative Colitis

Background: In recent years, rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. As several ongoing trials are exploring the possibility of using FMT to treat UC, discerning factors associated the long-term efficacy of FMT treatment becomes important. Our present study explored the factors related to the efficacy of FMT combined with triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); (A-FMT)] in patients with UC. Methods: Patients aged 16 years or older suffering from active UC with a Lichtiger’s clinical activity index (CAI) score ≥4 or Mayo endoscopic score (MES) ≥1 participated in the clinical study between March 2014 and October 2019. After rigorous screening, we selected relatives aged 20 years or older, or other volunteer donors. After 2 weeks of oral administration of 3 antibacterial agents, about 200ml of fresh or frozen stool solution of donor stool dissolved in saline solution was obtained by colonoscopy. CAI score at 4 weeks after treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points, "remission" if the CAI further improved to ≤3 points, and "relapse" if the CAI increased or treatment was intensified at 48 weeks after treatment in the effective group. Results: Ninety-seven patients (68 males, 29 females, age 39.2 ± 12.9 years, disease duration 8.5 ± 8.0 years, CAI 10.7 ± 3.0, Mayo endoscopic subscore (MES) 1.8 ± 0.7) and 62 donors were included. 93 patients completed A-FMT, with an efficacy rate of 63.9% (ITT) at 4 weeks of treatment and a remission induction rate of 36.1%. The short-term efficacy was associated with pre-treatment Mayo endoscopic score (response P = 0.001, remission P < 0.001), history of corticosteroid treatment (response P = 0.04, remission P = 0.01), and history of tacrolimus treatment (response P = 0.04, remission P = 0.14). The cumulative non-relapse rate was significantly higher in the sibling donor group than in the parent-child donor group (P = 0.001). The age difference between patients and donors also affected the cumulative non-relapse rate (P = 0.01). Conclusion: In our study, the optimal timing for patients to receive A-FMT is before corticosteroid and tacrolimus treatments, and early-stage patients receive fecal transplants from siblings with the best clinical outcomes. While the short-term efficacy of A-FMT was related to the patient's own characteristics, the long-term efficacy was related to patient-donor matching.

Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis: 24-week data from the SIMPACT study.

ObjectivesThe aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients.MethodsSIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored.ResultsThree hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P = 0.0001) and CDAI (P = 0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs.ConclusionReal-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old.Trial registrationClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686.

Prospective evaluation of a change in dietary therapy in dogs with steroid‐resistant protein‐losing enteropathy

To describe the clinical effect of dietary alteration as a sole change to therapy in dogs with steroid-resistant protein-losing enteropathy. Prospective study. Eligible enrolled dogs received dietary alteration as sole change to their therapeutic plan. Canine Chronic Enteropathy Clinical Activity Index and serum albumin were monitored for the 3-month study period. Long-term follow-up data were also available for some of the study participants. Fifteen dogs were eligible for enrollment over the study period. Twelve were enrolled, 10 remained in the study at 30 days, nine completed the 3-month study period. Following dietary alteration, eight of 10 dogs achieved complete remission, one dog achieved partial remission and one dog had no response. Seven of eight dogs achieving complete remission have remained in remission up to 4 years following study. In dogs with complete remission, median Canine Chronic Enteropathy Clinical Activity Index score was 11.5 and 4, and median serum albumin concentration was 15 g/L and 26 g/L at 0 and 14-28 days, respectively. Dogs with protein-losing enteropathy with previous lack of response to a combination of dietary therapies, glucocorticoids and immunosuppressive medications can achieve remission following a dietary change. Improvement is likely to be seen within 14 to 30 days. A change in dietary approach may be an alternative to further immunosuppression or anti-inflammatory strategies in some dogs with difficult to treat protein-losing enteropathy.

Cytapheresis re-induces high-rate steroid-free remission in patients with steroid-dependent and steroid-refractory ulcerative colitis.

BACKGROUNDIt is a crucial issue for patients with refractory ulcerative colitis (UC), including steroid-dependent and steroid-refractory patients, to achieve and maintain steroid-free remission. However, clinical studies focused on the achievement of steroid-free remission in refractory UC patients are insufficient. Cytapheresis (CAP) is a non-pharmacological extracorporeal therapy that is effective for active UC with fewer adverse effects. This study comprised UC patients treated with CAP and suggested the efficacy of CAP for refractory UC patients.AIMTo clarify the efficacy of CAP in achieving steroid-free remission in refractory UC patients.METHODSWe retrospectively reviewed the collected data from 55 patients with refractory UC treated with CAP. We analyzed the following points: (1) Efficacy of the first course of CAP; (2) Efficacy of the second, third, and fourth courses of CAP in patients who experienced relapses during the observation period; (3) Efficacy of CAP in colonic mucosa; and (4) Long-term efficacy of CAP. Clinical efficacy was evaluated using Lichtiger’s clinical activity index or Sutherland index (disease activity index). Mucosal healing was evaluated using Mayo endoscopic subscore. The primary and secondary endpoints were the rate of achievement of steroid-free remission and the rate of sustained steroid-free remission, respectively. Statistical analysis was performed using the paired t-test and chi-squared test.RESULTSThe rates of clinical remission, steroid-free remission, and poor effectiveness after CAP were 69.1%, 45.5%, and 30.9%, respectively. There were no significant differences in rate of steroid-free remission between patients with steroid-dependent and steroid-refractory UC. The mean disease activity index and Lichtiger’s clinical activity index scores were significantly decreased after CAP (P < 0.0001). The rates of steroid-free remission after the second, third, and fourth courses of CAP in patients who achieved steroid-free remission after the first course of CAP were 83.3%, 83.3%, and 60%, respectively. Mucosal healing was observed in all patients who achieved steroid-free remission after the first course of CAP. The rates of sustained steroid-free remission were 68.0%, 60.0%, and 56.0% at 12, 24, and 36 mo after the CAP. Nine patients (36%) had maintained steroid-free remission throughout the observation period.CONCLUSIONOur results suggest that CAP effectively induces and maintains steroid-free remission in refractory UC and re-induces steroid-free remission in patients achieving steroid-free remission after the first course of CAP.

Gastric mucosal pathology in Belgian Shepherd dogs with and without clinical signs of gastric disease

BackgroundGastric carcinoma (GC) is uncommon in dogs, except in predisposed breeds such as Belgian Shepherd dogs (BSD) of the Tervuren and Groenendael varieties. When GC is diagnosed in dogs it is often late in the disease, resulting in a poorer prognosis. The aim of this prospective clinical study was to investigate possible associations of gastric mucosal pathologies with clinical signs, laboratory test results and GC in BSD. An online survey gathered epidemiological data to generate potential risk factors for vomiting as the predominant gastric clinical sign, and supported patient recruitment for endoscopy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) score and signs of gastroesophageal reflux (GER) were used to allocate BSD older than five years to either Group A, with signs of gastric disease, or Group B, without signs. Findings in the clinical history, laboratory tests and gastric histopathology of endoscopic biopsies were statistically analysed in search of associations.ResultsThe online survey included 232 responses. Logistic regression analysis recognized an association of vomiting with gagging, poor appetite and change in attitude. Recruitment for endoscopy included 16 BSD in Group A (mean age 9.1 ± 1.8 years, mean CCECAI = 3.1 ± 2.2 and signs of GER); and 11 in Group B (mean age 9.8 ± 1.4 years, CCECAI = 0, no signs of GER). Seven (25.9%) of the 27 BSD (Group A 4/16, Group B 3/11) had leukopenia. Serum C-reactive protein tended to be increased with more advanced GC (P = 0.063). Frequency of GC, mucosal atrophy, mucous metaplasia, or glandular dysplasia did not differ between groups. GC was frequently diagnosed (6/27), even without clinical signs (2/11). The odds ratio for vomiting (OR = 9.9; P = 0.016) was increased only when glandular dysplasia was present. GC was associated with mucous metaplasia (P = 0.024) and glandular dysplasia (P = 0.006), but not with mucosal atrophy (P = 1).ConclusionsGC can develop as an occult disease, associated with metaplasia and dysplasia of the gastric mucosa. Suggestive clinical signs, notably vomiting, should warrant timely endoscopy in BSD. Extensive endoscopic screening of asymptomatic dogs remains, however, unrealistic. Therefore, biomarkers of mucosal pathology preceding clinical illness are needed to support an indication for endoscopy and enable early diagnosis of GC.

Platelet abnormalities and platelet-to-lymphocyte ratios in canine immunosuppressant-responsive and non-responsive enteropathy: A retrospective study in 41 dogs.

Few studies have examined platelet alterations in dogs with chronic enteropathy. Our aim was to investigate platelet count (PLT), mean platelet volume (MPV), and platelet-to-lymphocyte ratio (PLR) in dogs diagnosed with immunosuppressant-responsive enteropathy (IRE). In this retrospective study of 41 dogs, data regarding signalment, canine chronic enteropathy clinical activity index (CCECAI), endoscopic and histopathological scores, PLT, MPV, PLR, total serum protein concentrations, albumin, and iron were collected. Clinical response and relapse were assessed with the evaluation of CCECAI over time. One month after starting therapy, dogs with >25% CCECAI reduction were considered responders. During a three-month CCECAI evaluation as part of a twelve-month follow-up, a CCECAI >3 together with a ≥2 unit increase in responder dogs was considered a relapse. PLT and PLR displayed significant negative correlation with MPV. MPV was positively correlated with total protein and albumin levels and negatively correlated with CCECAI. Three dogs were classified as non-responders, and 14 relapsed within 12 months. No differences were observed in PLT, MPV, or PLR between responding/non-responding and relapsing/non-relapsing groups. PLT, MPV, and PLR correlated with total protein, albumin, and CCECAI, confirming PLT as a potential marker, and suggesting MPV as a new marker of clinical efficacy against canine IRE.

Predicting a rapid response to adalimumab treatment and favorable short-term outcomes through the high platelet count in patients with ulcerative colitis: A multicenter retrospective cohort study.

This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 109/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.

Efficacy and safety of adsorptive granulomonocytapheresis in Chinese patients with ulcerative colitis: A retrospective analysis of 50 cases with focus on factors impacting clinical efficacy.

BackgroundMyeloid‐derived leucocytes, a major source of inflammatory cytokines, play an important role in the exacerbation of ulcerative colitis (UC). Selective depletion of myeloid leucocytes by adsorptive granulomonocytapheresis (GMA) with an Adacolumn should alleviate inflammation and promote remission. However, there are discrepancies among the reported efficacy outcomes. This study aimed to evaluate the efficacy and safety of GMA in UC patients with a focus on factors affecting clinical efficacy.MethodsThis was a retrospective analysis of 50 patients with active UC who had received GMA therapy. GMA efficacy was evaluated based on the Rachmilewitz's clinical activity index (CAI) and Mayo endoscopic score for mucosal healing. Laboratory findings were analyzed to demonstrate any relationship with the GMA‐responder or nonresponder feature. Adverse events were recorded during and after GMA therapy.ResultsThe overall clinical remission rate (CAI ≤4) was 79.2%, and among these, the mucosal healing rate was 59.2%. The clinical remission rate was 69.2% in patients who received 5 GMA sessions and 82.3% in patients who received 10 sessions. Significantly higher baseline CAIs and lower albumin and hemoglobin levels were observed in nonremission cases compared with those who achieved remission. Four patients (8%) experienced transient adverse events, but none were severe.ConclusionsGMA was favored by patients because of its safety and nonpharmacological treatment options. Accordingly, UC patients were spared from pharmaceuticals after applying GMA therapy.

Rapid Resolution of Large Bowel Diarrhea after the Administration of a Combination of a High-Fiber Diet and a Probiotic Mixture in 30 Dogs.

Canine fiber responsive diarrhea is a form of chronic colitis that improves clinically after adding fiber to the diet. In the present study, we investigated the effect of a combination of a high-fiber, highly digestible, hypoallergenic diet with a probiotic mixture in 30 dogs with chronic colitis that were unresponsive to various dietary and/or pharmacological interventions. Fecal scores, canine chronic enteropathy clinical activity index (CCECAI) scores, the dysbiosis index (DI), and histologic images of colonic biopsies were evaluated. At baseline (day 0; T0) and after 30 days of treatment (T1), all variables evaluated in our patients (i.e., fecal and CCECAI scores and histopathology) improved significantly at T1, with the exception of DI. However, there was a numerical shift from a state of dysbiosis to one of normobiosis. The combination of the diet and the probiotic used in the present study induced the resolution of clinical signs in a mean of 8.5 days (maximum 15 days) and did not necessitate any other treatments or the further addition of alimentary fiber.

P044 HIGH STRESS REACTIVITY AND SYMPTOM FLARES IN ULCERATIVE COLITIS PATIENTS

Abstract Psychological stress has long been implicated as a cause of symptom relapse in IBD. Whether psychological stress is associated with alterations in the brain-gut-microbiome (BGM) axis and intestinal inflammation requires further investigation. Aims: We hypothesize that stress-induced changes in BGM interactions play a role in the development of symptomatic flares in patients with ulcerative colitis (UC). We aimed to test this hypothesis in a prospective study of 100 UC patients in clinical remission to identify gut microbiome, brain network connectivity, and stress-associated biomarkers of UC patients at baseline that can predict the risk of future symptomatic flares. Methods: Ninety-four subjects in clinical remission (Mayo score ≤ 1 AND Simple Colitis Clinical Activity Index (SCCAI) score &amp;lt; 5) underwent comprehensive phenotyping, including clinical and behavioral assessments, brain imaging, and autonomic testing for heart rate variability (HRV) and electrodermal activity (EDA) before, during, and after a 3 minute arithmetic stress test at baseline, with longitudinal follow-up every 3 months and at time of flare. Clinical flares (SCCAI &amp;gt;5) and subjective flares (“Do you think you are in a flare?”) were assessed. Fecal calprotectin has been collected at baseline and every 3 months and at time of flare. Results: To date, there have been 18 clinical flares (19%) and 8 symptomatic flares (8.5%) in 94 patients over a mean follow-up time of 8.1 months. Baseline measurements have identified two clusters of patients (low stress reactivity in cluster 1, high stress reactivity in cluster 2), based on trait anxiety (International Personality Item Pool [IPIP]-Neuroticism), and perceived stress (Cohen’s Perceived Stress Scale) measured at baseline. These groups differed in the frequency of clinical flares (9.3% vs. 27.4%, p=0.03) and subjective flares (3.6% vs. 11.8%, p=0.28), respectively. There were no cluster differences in heart rate variability, but there was overall greater EDA noted in the high stress reactivity group (EDA: 3.99 (SE: 0.27) vs. 5.02 (SE: 0.25); p=0.007). Conclusions: Based on our current results, the frequency of symptomatic flares in UC patients in clinical remission is predicted by measures of perceived stress and trait anxiety and by heightened sympathetic arousal as measured by electrodermal activity. We expect that gut microbiome profiles and brain imaging networks will further delineate the stress-responsive subset of UC patients with heightened flare risk and that fecal calprotectin levels collected will confirm whether the stress-responsive subset of UC patients experiences biochemical flare with increase in symptoms.

Endoscopic score vs blood cell indices for determining timing of immunomodulator withdrawal in quiescent ulcerative colitis

While immunomodulators (IMs) are used as key drugs in remission maintenance treatment for ulcerative colitis (UC), there has been no evidence to date for determining monitoring methods and drug withdrawal. Therefore, we examined if a decrease in white blood cell count (WBC) and an elevation in mean cell volume (MCV) could be used as optimization indices and if mucosal healing (MH) could be a rationale for determining the time of IM withdrawal. Subjects were 89 UC patients who were using IMs and for whom clinical remission had been maintained. Those with a Rachmilewitz Clinical Activity Index score of 4 or lower and those with a Mayo endoscopic subscore (MES) of 0 or 1 were defined as MH. The remission maintenance rates of the following comparative groups were examined: an IM continuation group and an IM withdrawal group; an IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and an IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower; an IM continuation group of patients for whom MH had been achieved and an IM continuation group of patients for whom MH had not been achieved; and an IM withdrawal group with a MES of 0 and an IM withdrawal group with a MES of 1. A significantly higher remission maintenance rate was observed in the IM continuation group compared to the withdrawal group (p < 0.01). No significant difference was observed between the IM continuation group with a WBC of less than 3000 or a MCV of 100 or greater and the IM continuation group with a WBC of 3000 or greater and a MCV of 99 or lower (p = 0.08). Higher remission maintenance rates were observed in the IM continuation group of patients for whom MH had been achieved compared to the IM continuation group of patients for whom MH had not been achieved (p = 0.03). No significant difference was observed between the IM withdrawal group with MES 0 and the IM withdrawal group with MES 1. (p = 0.48). This retrospective study showed that remission maintenance could be firmly obtained by continuing IM administration in case of endoscopic MH; however, MH was not an indicator of IM withdrawal.

P052 Combination therapy of fresh fecal microbial transplantation and triple-antibiotic therapy for ulcerative colitis

BACKGROUND: Fecal microbiota transplantation (FMT) has proved its efficacy for treating recurrent Clostridium difficile infection, but an effective FMT protocol is still yet to be found for treating ulcerative colitis (UC). We previously demonstrated that fresh fecal-microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] induced dramatic changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Furthermore, we also reported that A-FMT combination therapy contributed to the microbiological improvement of intestinal dysbiosis in UC patients via successful transplantation of live Bacteroidetes cells from donors. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment may promote the entry of living Bacteroidetes cells, thereby improving the dysbiosis of intestinal microbiota induced by UC. Here, we evaluated the efficacy of A-FMT compared to AFM monotherapy and examined factors correlated with clinical response. METHODS: This was an open label, non-randomized, prospective control study of the use of FMT in treating UC, following AFM pre-treatment. This clinical study included participants above 20 years of age. These patients were diagnosed with active UC, with a Lichtiger's Clinical Activity Index (CAI) of 5 or more, or with an endoscopic Mayo clinic score of 1 or more, between July 2014 and March 2017. Patients' spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient's colon via colonoscopy within 6 h. The clinical features of UC were judged using CAI scores before treatment and 4 weeks after treatment. Clinical responses were defined as a CAI of less than 10 points and a decrease of 3 or more points, and clinical remission was defined as a CAI of 3 points or less. RESULTS: Patients with mild-to-severe active UC (n = 55 A-FMT group; n = 37 AFM monotherapy group) were included in this assessment. Seventy-nine patients completed this assessment (n = 47 A-FMT group; n = 32 AFM monotherapy group). Although the Mayo score was slightly higher in the A-FMT group, no significant difference was observed between the 2 treatment groups. No serious adverse events were observed during the study. At 4 weeks after treatment with FMT, the clinical responses were observed in 31 patients {Per Protocol Set (PPS): 66.0%) in the A-FMT group, resulting higher than of the AFM monotherapy group (PPS: 56.3%). In A-FMT group, the clinical remission rate was observed to be significantly higher than AFM monotherapy (A-FMT group 40.4%, AFM monotherapy 18.6%; P = 0.04). The endoscopic sum score was associated with clinical responses (Responders 7.5 ± 3.2, Non-responders 5.1 ± 3.6; P = 0.03) in A-FMT. CONCLUSION(S): A-FMT combination therapy exhibited reassuring clinical outcomes in comparison to AFM monotherapy. Further follow-up studies are required to evaluate the long-term efficacy of this FMT protocol, and it is possible that this protocol may become a useful strategy for the management of patients with UC.

Platelet indices as biomarkers for characterization and determination of severity in canine chronic enteropathy

Human studies have shown an association between certain platelet indices and active inflammatory bowel disease when compared to healthy controls. The objectives of this retrospective study were to determine if any platelet indices differ between dogs with chronic enteropathies and healthy age- and sex-matched control dogs and are predictive of the severity of chronic enteropathy based on canine chronic enteropathy clinical activity index (CCECAI) scores. Medical records for 22 chronic enteropathy-positive dogs and 22 healthy control dogs were reviewed for historical and physical examination findings, platelet indices, and histologic diagnoses of chronic enteropathy. Platelet indices were compared between the groups, and an association between platelet indices and CCECAI scores in dogs with chronic enteropathy was investigated.Chronic diarrhea and weight loss were common clinical signs associated with chronic enteropathy. Lymphoplasmacytic enteritis was the most common histologic diagnosis. Only one platelet index, platelet component distribution width (P = 0.045), was found to be significantly different between the groups. For predicting severity of disease, determined by CCECAI score, statistically significant differences in indices associated with higher scores were platelet count (P = 0.024) and platelet dry mass distribution width (P = 0.036). Only platelet component distribution width showed potential in characterizing dogs with chronic enteropathy compared to normal dogs. Elevated platelet count and decreased platelet dry mass distribution width had a significant effect on total CCECAI scores. These findings suggest further investigation into the utility of platelet indices as predictors of disease presence and severity in dogs with chronic enteropathy is warranted.

P160 EFFICACY OF COMBINATION OF FRESH FECAL MICROBIOTA TRANSPLANTATION AND TRIPLE-ANTIBIOTIC THERAPY FOR ULCERATIVE COLITIS

Fecal microbiota transplantation (FMT) has proved its efficacy for treating recurrent Clostridium difficile infection, but an effective FMT protocol is still yet to be found for treating ulcerative colitis (UC). We previously demonstrated that fresh fecal-microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] induced dramatic changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Furthermore, we also reported that A-FMT combination therapy contributed to the microbiological improvement of intestinal dysbiosis in UC patients via successful transplantation of live Bacteroidetes cells from donors. Here, we evaluated the efficacy of A-FMT compared to AFM monotherapy and examined factors correlated with clinical response. This was an open label, non-randomized, prospective control study of the use of FMT in treating UC, following AFM pre-treatment. This clinical study included participants above 20 years of age. These patients were diagnosed with active UC, with a Lichtiger’s Clinical Activity Index (CAI) of 5 or more, or with an endoscopic Mayo clinic score of 1 or more, between July 2014 and March 2017. Patients’ spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient’s colon via colonoscopy within 6 h. The clinical features of UC were judged using CAI scores before treatment and 4 weeks after treatment. Clinical responses were defined as a CAI of less than 10 points and a decrease of 3 or more points, and clinical remission was defined as a CAI of 3 points or less. Patients with mild-to-severe active UC (n = 55 A-FMT group; n = 37 AFM monotherapy group) were included in this assessment. Seventy-nine patients completed this assessment (n = 47 A-FMT group; n = 32 AFM monotherapy group). Although the Mayo score was slightly higher in the A-FMT group, no significant difference was observed between the 2 treatment groups. No serious adverse events were observed during the study. At 4 weeks after treatment with FMT, clinical responses were observed in 31 patients (66.0%) in A-FMT group, which higher than in AFM monotherapy group (56.3%), but not significantly. In A-FMT group, the clinical remission rate was observed to be significantly higher than AFM monotherapy (A-FMT group 40.4%, AFM monotherapy18.6%; p = 0.04). The endoscopic sum score was associated with clinical responses (Responders 7.5 ± 3.2, Non-responders 5.1 ± 3.6; p = 0.03) in A-FMT. A-FMT combination therapy exhibited reassuring clinical outcomes in comparison to AFM monotherapy. Further follow-up studies are required to evaluate the long-term efficacy of this FMT protocol, and it is possible that this protocol may become a useful strategy for the management of patients with UC.

P160 EFFICACY OF COMBINATION OF FRESH FECAL MICROBIOTA TRANSPLANTATION AND TRIPLE-ANTIBIOTIC THERAPY FOR ULCERATIVE COLITIS

Fecal microbiota transplantation (FMT) has proved its efficacy for treating recurrent Clostridium difficile infection, but an effective FMT protocol is still yet to be found for treating ulcerative colitis (UC). We previously demonstrated that fresh fecal-microbiota transplantation (FMT) following triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); A-FMT] induced dramatic changes in the phylum Bacteroidetes, which constitutes a critical factor correlated with clinical responses. Furthermore, we also reported that A-FMT combination therapy contributed to the microbiological improvement of intestinal dysbiosis in UC patients via successful transplantation of live Bacteroidetes cells from donors. Here, we evaluated the efficacy of A-FMT compared to AFM monotherapy and examined factors correlated with clinical response. This was an open label, non-randomized, prospective control study of the use of FMT in treating UC, following AFM pre-treatment. This clinical study included participants above 20 years of age. These patients were diagnosed with active UC, with a Lichtiger’s Clinical Activity Index (CAI) of 5 or more, or with an endoscopic Mayo clinic score of 1 or more, between July 2014 and March 2017. Patients’ spouses or relatives were selected as donor candidates. Donor fecal samples were collected on the day of administration and transferred into the patient’s colon via colonoscopy within 6 h. The clinical features of UC were judged using CAI scores before treatment and 4 weeks after treatment. Clinical responses were defined as a CAI of less than 10 points and a decrease of 3 or more points, and clinical remission was defined as a CAI of 3 points or less. Patients with mild-to-severe active UC (n = 55 A-FMT group; n = 37 AFM monotherapy group) were included in this assessment. Seventy-nine patients completed this assessment (n = 47 A-FMT group; n = 32 AFM monotherapy group). Although the Mayo score was slightly higher in the A-FMT group, no significant difference was observed between the 2 treatment groups. No serious adverse events were observed during the study. At 4 weeks after treatment with FMT, clinical responses were observed in 31 patients (66.0%) in A-FMT group, which higher than in AFM monotherapy group (56.3%), but not significantly. In A-FMT group, the clinical remission rate was observed to be significantly higher than AFM monotherapy (A-FMT group 40.4%, AFM monotherapy18.6%; p = 0.04). The endoscopic sum score was associated with clinical responses (Responders 7.5 ± 3.2, Non-responders 5.1 ± 3.6; p = 0.03) in A-FMT. A-FMT combination therapy exhibited reassuring clinical outcomes in comparison to AFM monotherapy. Further follow-up studies are required to evaluate the long-term efficacy of this FMT protocol, and it is possible that this protocol may become a useful strategy for the management of patients with UC.

P048 SHORT- AND LONG-TERM OUTCOME OF PATIENTS TREATED WITH INDIGO NATURALIS FOR INFLAMMATORY BOWEL DISEASE: A SINGLE CENTER RETROSPECTIVE STUDY

Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective for inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for inducing and maintaining remission in patients with inflammatory bowel disease (IBD). Data were collected from electric medical records of IBD patients who had been started IN between March 2015 and April 2017 at Kyushu University hospital. Cumulative IN continuing rates at 8, 52, and 104 weeks were estimated using the Kaplan-Meier method. Among patients who could sustain IN treatment, clinical remission (clinical activity index (CAI) ≤4, Crohn’s disease (CD) activity index (CDAI) ≤150) rate at each point was also assessed. In addition, overall adverse events (AEs) during the treatment of IN were analyzed. Seventeen UC patients and eight CD patients were enrolled. The median CAI score in UC was 8 (range; 5-13), and the median CDAI in CD was 227 (range; 158-291). The cumulative IN continuing rates at 8, 52, and 104 weeks were 88%, 76%, and 71% in UC patients, and 75%, 38%, and 38% in CD patients, respectively. Among patients who could sustain IN treatment, clinical remission rates at 8, 52 and 104 weeks were 94%, 100%, and 100% in UC patients and 33%, 67%, and 67% in CD patients, respectively. A total of 10 patients (40%) experienced AEs during follow-up. Mild AEs including headache, liver dysfunction and renal dysfunction were observed in 9 patients. However, serious AEs were identified in three patients; one patient developed ileocecal intussusception requiring surgery and two patients developed acute colitis requiring hospitalization. IN showed good short- and long-term therapeutic efficacy for UC, however, therapeutic efficacy for CD seemed to be modest. While not so common, possible risk of serious adverse events should be kept in mind when using IN.

Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza and Upper Respiratory Infection in Patients With Inflammatory Bowel Disease.

BackgroundWe evaluated whether oral vitamin D supplementation during the winter and early spring reduces the incidence of influenza and upper respiratory infections in patients with inflammatory bowel disease (IBD).MethodsA randomized, double-blind, controlled trial was conducted to compare the effects of vitamin D supplementation (500 IU/day) and a placebo. The primary outcome was the incidence of influenza; the secondary outcome was the incidence of upper respiratory infection. Prespecified subgroup analyses were performed according to 25-hydroxyvitamin D (25-OHD) levels (low <20 ng/mL or high ≥20 ng/mL) and whether ulcerative colitis (UC) or Crohn’s disease (CD) was present. We also used the Lichtiger clinical activity index for patients with UC and the Crohn’s Disease Activity Index (CDAI) for patients with CD before and after interventions.ResultsWe included 223 patients with IBD and randomized them into 2 groups: vitamin D supplementation (n = 108) and placebo (n = 115). The incidence of influenza did not differ between the groups. However, the incidence of upper respiratory infection was significantly lower in the vitamin D group (relative risk [RR], 0.59; 95% confidence interval (CI), 0.35–0.98; P = 0.042). This effect was enhanced in the low 25-OHD level subgroup (RR, 0.36; 95% CI, 0.14–0.90; P = 0.02). With respect to adverse events, the Lichtiger clinical activity index score was significantly worse in the vitamin D group (P = 0.002) and remained significant only in the high 25-OHD level subgroup.ConclusionsVitamin D supplementation may have a preventative effect against upper respiratory infection in patients with IBD but may worsen the symptoms of UC.