Sae Kyung Chang

The effect of a multispecies probiotic mixture on the symptoms and fecal microbiota in diarrhea-dominant irritable bowel syndrome: a randomized, double-blind, placebo-controlled trial.

Background: The clinical effect of probiotics on irritable bowel syndrome (IBS) is still controversial. Aims: We aimed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS (D-IBS). Methods: Fifty patients with D-IBS were randomized into placebo or probiotic mixture (Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium lactis, Bifidobacterium longum, and Streptococcus thermophilus 1.0×1010 CFU) groups. Treatment was taken daily for 8 weeks. The primary outcome was adequate relief (AR) of overall IBS symptoms, which was assessed weekly for 10 weeks. A responder was defined as a patient who experienced AR for at least half of the 10-week study period. Secondary outcomes included the effects on individual symptoms, stool parameters, and IBS quality of life. The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis (DGGE). Results: The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period (P<0.05). The proportion of responders was significantly higher in the probiotics group than in the placebo group (48% vs. 12%, P=0.01). Stool consistency improved significantly in the probiotics group compared with the placebo group. Percent changes in individual symptom scores were similar in the 2 groups, but IBS quality of life improvement tended to be higher in the probiotics group. Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group (69.5% vs. 56.5%, P=0.005). Conclusions: The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients, although it had no significant effect on individual symptoms. The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota.

Clinical features of active tuberculosis that developed during anti-tumor necrosis factor therapy in patients with inflammatory bowel disease

Background/Aims Anti-tumor necrosis factor (TNF) therapy for active ulcerative colitis (UC) and Crohns disease (CD) is associated with increased risks of tuberculosis (TB) infection. We analyzed the incidence and clinical features of Korean patients with inflammatory bowel disease (IBD) who developed active TB during anti-TNF therapy. Methods Ten cases of active TB developed in patients treated with infliximab (n=592) or adalimumab (n=229) for UC (n=160) or CD (n=661) were reviewed. We analyzed demographics, interval between start of anti-TNF therapy and active TB development, tests for latent TB infection (LTBI), concomitant medications, and the details of diagnosis and treatments for TB. Results The incidence of active TB was 1.2% (10/821): 1.5% (9/592) and 0.4% (1/229) in patients receiving infliximab and adalimumab, respectively. The median time to the development of active TB after initiation of anti-TNF therapy was three months (range: 2–36). Three patients had past histories of treatment for TB. Positive findings in a TB skin test (TST) and/or interferon gamma releasing assay (IGRA) were observed in three patients, and two of them received anti-TB prophylaxis. Two patients were negative by both TST and IGRA. The most common site of active TB was the lungs, and the active TB was cured in all patients. Conclusions Active TB can develop during anti-TNF therapy in IBD patients without LTBI, and even in those with histories of TB treatment or LTBI prophylaxis. Physicians should be aware of the potential for TB development during anti-TNF therapy, especially in countries with a high prevalence of TB.

Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma

Dermatomyositis is an idiopathic inflammatory myopathy with typical cutaneous manifestations. It has been proposed that dermatomyositis may be caused by autoimmune responses to viral infections. Previous studies have shown an association between dermatomyositis and malignant tumors such as ovarian cancer, lung cancer, and colorectal cancer. However, a chronic hepatitis B virus (HBV) infection associated with dermatomyositis and hepatocellular carcinoma (HCC) has been very rarely reported. Here, we report a rare case of dermatomyositis coinciding with HBV-associated HCC. A 55-year-old male was confirmed to have HCC and dermatomyositis based on proximal muscle weakness, typical skin manifestations, elevated muscle enzyme levels, and muscle biopsy findings. This case suggests that HCC and/or a chronic HBV infection may be factors in the pathogenesis of dermatomyositis through a paraneoplastic mechanism.

Efficacy and Safety of Infliximab Therapy and Predictors of Response in Korean Patients with Crohn's Disease: A Nationwide, Multicenter Study

Purpose Infliximab is currently used for the treatment of active Crohns disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD. Materials and Methods A total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated. Results In patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis. Conclusion Infliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events.

A Case of Acute Myocarditis as the Initial Presentation of Crohn's Disease

We experienced a case of acute myocarditis as the initial presentation of Crohns disease. A 19-year-old woman was admitted with impaired consciousness, shock, and respiratory failure. She had suffered from frequent diarrhea and abdominal pain for several years. Cardiac troponin I and creatine kinase-MB fraction levels were elevated to 5.32 and 16.66 ng/mL, respectively. A 12-lead electrocardiogram showed sinus tachycardia, and a chest radiograph revealed interstitial pulmonary edema. An echocardiogram showed dilated ventricles with akinesia of the basal to apical inferoseptal, anteroseptal, anterior, and inferior left ventricular walls and severely impaired systolic function. Intensive care with inotropic support was effective, and her clinical condition gradually improved. Two weeks later, a colonoscopy revealed ulceration with stenosis in the terminal ileum and multiple aphthous ulcers in the rectum. A biopsy of the rectum revealed non-caseating granulomatous inflammation. She was diagnosed with Crohns disease presenting with acute myocarditis.

Efficacy of ramosetron in male patients with irritable bowel syndrome with diarrhea (neurogastroenterol motil 2011;23:1098-1104).

Serotonin (5-Hydroxytryptamine [5-HT]) plays an important role in gastrointestinal (GI) motility and sensation, and abnormal levels have been shown in patients with irritable bowel syndrome (IBS).1,2 Drugs acting on 5-HT receptors have the potential to reduce the smooth muscle spasm, abdominal pain, and changes in bowel habit in IBS. Recently, Lee et al3 assessed the efficacy and safety of ramosetron, a 5-HT3 receptor antagonist, compared with mebeverine in male patients with diarrhea-predominant IBS (IBS-D). This study was performed in a multicenter, randomized, open-label, parallel-group, non-inferiority comparative design. A total of 343 male patients with IBS-D were randomized to either ramosetron 5 µg once daily or mebeverine 135 mg 3 times daily for 4 weeks. The weekly responder rates for global IBS symptoms, abdominal pain/discomfort and abnormal bowel habits in the ramosteron and mebeverine groups significantly increased during the treatment period (P < 0.001). The severity scores of abdominal pain/discomfort and urgency, the stool form scores and the stool frequency recorded daily were reduced significantly in both treatment arms, compared with the baselines (P < 0.001). There were no significant differences in the weekly responder rates (37% vs 38% at 4-week) and in the adverse event profiles between the ramosetron and mebeverine groups. Neither severe constipation nor ischemic colitis was reported. The authors concluded that the ramosetron 5 µg once daily was as effective as mebeverine 3 times daily in male patients with IBS-D.

S1314 The Effect of Probiotic Mixture on the Symptoms and Fecal Microbiota in Diarrhea-Dominant Irritable Bowel Syndrome: Randomized, Double-Blind, Placebo-Controlled Trial

Background & Aims: Some reports suggest that probiotics are helpful for treatment of Irritable bowel syndrome (IBS). The aim of this study was to evaluate the effects of probiotic mixture compared with placebo on the symptoms and the compositions of fecal microbiota in patients with diarrhea-dominant IBS (D-IBS). Methods: Forty-seven patients with D-IBS consented by ROME III were randomized in a parallel group, double-blind design to placebo or seven probiotics mixture 7x1011 CFU (Streptococcus thermophous, Lactobacillus plantarum, Lactobacillus acidophilus, Lactobacillus rhamnosus, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium breve) daily for 8 weeks after 1-week run-in period. The primary outcome was the adequate relief (AR) for overall IBS symptoms; secondary outcomes included the individual IBS symptoms, and the IBS quality of life (IBS-QOL). The AR was weekly checked by questionnaire for 10 weeks (8 weeks of treatment phase, 2 weeks of post-treatment phase). The IBS symptom diary based on visual analogue scale (VAS for abdominal pain, abdominal discomfort, diarrhea, urgency, mucus in stool, bloating, passage of gas) and stool parameters (hardness and frequency) were recorded on a daily basis and assessed each week for 11 weeks. IBS-QOL assessment and stool sampling for evaluating the composition of fecal microbiota by denaturing gradient gel electrophoresis (DGGE) were performed at the beginning and at the end of the treatment phase. Results: For all weeks, the proportions of AR was higher in probiotics group than placebo (p<0.05). The proportion of the patients who reported “yes” to adequate relief on half of the weeks (5 weeks) in the treatment trial was significantly higher in probiotics group than placebo (50% vs. 13%, p= 0.01). However, the improvements of the individual symptom scores and stool parameters were not superior in probiotics group. In IBS-QOL, the changing rates of overall scores for probiotics group tended to be higher than those for placebo (21.3±21.6% vs. 9.0±21.5%, p=0.073). The improvements of all 8 domains of IBS-QOL were consistently superior in probiotics group. In the comparison for DGGE profiles of fecal bacteria, there was no difference in the similarities of their bacterial compositions between the two groups. The concordance rates of bacterial compositions from the two time-points were 66.2±13.4% in probiotics and 69.1±11.8% in placebo group (p=0.519). Conclusion: The probiotic mixture is effective in providing adequate relief of overall IBS symptoms, and has a tendency to improve of IBS-QOL in D-IBS. But, the effect of probiotics is not related with the compositional changes of fecal microbiota.