Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis.

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, p = 2 × 10-9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.

Plasmablastic Lymphoma of the Small Intestine in an HIV- and EBV-negative Patient.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.

Vonoprazan-based triple therapy is effective for Helicobacter pylori eradication irrespective of clarithromycin susceptibility.

BACKGROUND: Helicobacter pylori causes peptic ulcers and accounts for over 90% of gastric cancers; however, eradication rates have been declining due to antimicrobial resistance. Vonoprazan (VPZ), a potassium-competitive acid blocker, produces rapid and profound gastric acid suppression and has shown promising effects in the improvement of H. pylori eradication rates. The efficacy and safety of VPZ-based triple therapy as a first-line regimen for H. pylori eradication and its relationship with clarithromycin (CAM) susceptibility were evaluated. METHODS: From May 2015 to September 2017, H. pylori-infected patients who underwent esophagogastroduodenoscopy with CAM susceptibility testing were prospectively enrolled. Patients received a 7-day triple therapy regimen (VAC) of VPZ (20 mg), amoxicillin (750 mg), and CAM (200 mg) twice daily. Eradication rates, demographics, CAM susceptibility, and safety profiles were assessed. RESULTS: VAC was administered to 146 patients (median age: 63, range: 22-85 years) (60% of whom were females) who underwent CAM susceptibility testing, and 131 patients underwent 13C-urea breath testing to evaluate eradication success. The prevalence of CAM resistance was 34.2%. The overall eradication rates of VAC in per protocol (PP) and "intention to treat" (ITT) analyses were 90.8% (n = 131) and 81.5% (n = 146), respectively. In PP analysis for CAM susceptibility, the eradication rates of VAC were comparable between CAM-sensitive (91.6%, n = 83) and CAM-resistant (89.4%, n = 47) strains. The corresponding rates from the ITT analysis were 80.0% (n = 95) and 84.0% (n = 50), respectively. No adverse events requiring discontinuation of VAC were observed. CONCLUSIONS: CAM-resistant H. pylori was prevalent in one-third of patients in the Tokyo metropolitan area. VPZ-based triple therapy was highly effective and well-tolerated irrespective of CAM susceptibility. Therefore, it could be a valuable first-line treatment regimen for H. pylori infection.

Effectiveness of Cytapheresis for Ulcerative Colitis in Special Situations: Delayed Onset of Optimum Efficacy in Elderly Patients.

BACKGROUND: Cytapheresis is a non-pharmacologic treatment option in which depleting elevated/activated leucocytes is known to exacerbate and perpetuate ulcerative colitis (UC) by releasing inflammatory cytokines. Therefore, it is a relevant treatment for elderly patients who wish to avoid pharmacologicals. METHODS: The efficacy of Cytapheresis for remission induction in 72 patients who received Cytapheresis for active UC at our hospital was retrospectively evaluated. Patients included 11 elderly cases, patients on steroids, biologics, calcineurin inhibitor, and 13 with extra-intestinal complications. Lichtiger's UC clinical activity index ≤4 meant remission was assessed at the end of therapy and then 1 month later. The efficacy on extra-intestinal manifestations meant improvement of the main morbidity. RESULTS: At the end of Cytapheresis therapy, the remission rate in the elderly was 36.4%, and 54.2% in the non-elderly patients. One-month post Cytapheresis, the remission rate in the elderly had increased to 72.7% (p = 0.042), but to 58.3% in the non-elderly, suggesting a delayed response phenomenon in the elderly. The efficacy of Cytapheresis in 4 cases with loss of response to biologics was 75%, and 84.6% in the 13 patients with extra-intestinal complications, indicating a dramatic efficacy on dermatitis and arthralgia. CONCLUSIONS: Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.

PCR detection of human herpesviruses in colonic mucosa of individuals with inflammatory bowel disease: Comparison with individuals with immunocompetency and HIV infection.

BACKGROUND: Detection of human herpesviruses (HHVs) other than cytomegalovirus (CMV) in colonic mucosa of individuals with inflammatory bowel disease (IBD) remains unknown. This study identified eight HHVs in the colonic mucosa of individuals with IBD and compared the results with immunocompetent and human immunodeficiency virus (HIV)-infected individuals. METHODS: A total of 89 individuals who had colorectal ulcer on colonoscopy were enrolled: 26 with immunocompetency (n = 26), 41 with IBD, and 22 with HIV infection. We examined the colonic ulcers for the presence of eight HHVs-herpes simplex virus (HSV)-1/2, varicella zoster virus (VZV), CMV, Epstein-Barr virus (EBV), HHV-6, HHV-7, and HHV-8-using mucosal PCR. RESULTS: The IBD group had positivity rates of 0%, 0%, 0%, 53.7%, 24.4%, 39%, 39%, and 0% for HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8, respectively. The positivity rates of EBV and CMV in colonic mucosa increased significantly in the order of the immunocompetent, IBD, and HIV groups (EBV: 23.1%, 53.7%, 72.7%, P for trend = 0.0005; CMV, 7.7%, 24.4%, 54.5%, P for trend = 0.0003, respectively), but no increase was found in the other HHVs. Median mucosal EBV DNA values in the immunocompetent, IBD, and HIV groups were 0, 76, and 287 copies/µg DNA, respectively (P for trend = 0.002). Corresponding median mucosal CMV DNA values were 0, 0, and 17 copies/µg DNA (P for trend = 0.0001). There was no significant difference in the positivity rates of the eight HHVs between ulcerative colitis and Crohn's disease. CONCLUSION: The HHVs of EBV, CMV, HHV-6, and HHV-7, but not of HSV-1, HSV-2, VZV, or HHV-8, were identified in the colonic mucosa of IBD individuals. EBV and CMV in colonic mucosa was correlated with host immune status in increasing order of immunocompetent, IBD, and HIV-infected individuals.

Colonic cytomegalovirus detection by mucosal PCR and antiviral therapy in ulcerative colitis.

BACKGROUND: We aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases. METHODS: We retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral load. RESULTS: At baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA- patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA- patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000-36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157-5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA- cases and CMV-DNA+ cases with low viral loads. CONCLUSIONS: Aging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.