Background/Objectives: The cause of ulcerative colitis (UC) may be related to commensal bacteria in genetically susceptible patients. We previously demonstrated that triple antibiotic combination therapy induces remission in patients with active UC in randomized controlled trials (RCTs). Now, we investigate changes in the gut microbiota of patients who responded to the antibiotic combination therapy. Methods: Thirty-one patients with UC given ATM/AFM (amoxicillin, metronidazole, and tetracycline or fosfomycin) therapy for two weeks were enrolled in this study. The clinical conditions of these UC patients were evaluated by the partial Mayo score. The gut microbiota was compared via the metagenomic shot gun analysis of fecal samples. Results: Of the 31 patients, 16 and 8 experienced complete and partial remission, respectively, over three months in response to ATM/AFM therapy, whereas ATM/AFM showed no efficacy in 7 patients. The dysbiosis before treatment in the active stage could be associated with increased populations of Bacteroides, Parabacteroides, Rickenella, Clostridium, Flavonifractor, Pelagibacter, Bordetella, Massilia, and Piscrickettsia species. Metagenomic analysis revealed dramatic changes in the gut microbiota at an early stage, that is, just two weeks after starting ATM/AFM therapy. After treatment in the responder group, the populations of bifidobacterium and lactobacilli species were significantly increased, while the population of bacteroides decreased. Conclusions: These results suggest that metagenomic analysis demonstrated a marked change in the gut microbiota after antibiotic combination treatment. In the triple antibiotic combination therapy, remission was associated with an increase in bifidobacterium and lactobacilli species.

Celiac disease is a systemic autoimmune disorder leading to manifestations of malabsorption syndrome. A 47-year-old Japanese man developed severe diarrhea after surgery for gastric cancer. The diarrhea persisted for seven months, leading to a state of malabsorption. Celiac disease was suspected based on small bowel capsule endoscopy findings. The duodenal findings observed during gastric cancer surgery were reassessed, and Marsh-Oberhuber classification type 3c celiac disease was diagnosed. The anti-tissue glutaminase antibody test results were positive. The patient was started on a gluten-free diet, following which the diarrhea resolved, and the nutritional status improved. Adjuvant therapy after gastric cancer surgery was initiated.

Background: Influence of Helicobacter pylori infection and sex difference on leukocyte differentials was insufficiently understood. We therefore conducted the current study to evaluate influence of H. pylori and sex on peripheral leukocyte differentials as well as influence of Helicobacter pylori eradication. Methods: Dyspeptic patients and persons asked to examine gastroduodenal lesions at medical check were included. Total leukocytes, differentials, and anti- H.pylori IgG antibody were measured. Those change after eradication was also measured. H. pylori infection was assessed by anti- H. pylori IgG antibody, rapid urease test, and pathologic findings. H. pylori -uninfected patients and non-dyspeptic/seronegative persons were regarded as negative controls. Results: Totally 374 patients and 299 controls were evaluated, and 167 patients were successfully eradicated. Peripheral counts of neutrophil and monocyte elevated with H. pylori infection: 3221.7+/-1108.7 vs. 2911.9+/-1027.3/μL and 307.5+/-130.5 vs. 281.5+/-106.4/μL, (p­=.0002 and .0054). Compared to females, males manifested elevated counts of every leukocyte, but the difference was insignificant in basophil (p=.0089, 0.0316, <.0001, and .0384 for neutrophil, lymphocyte, monocyte, and eosinophil, respectively). After eradication, counts of neutrophil, lymphocyte, and monocyte declined: 3111.0+/-966.8 to 2785.1+/997.2/μL, 1905.9+/-603.2 to 1831.6+/-613.5/μL, and 293.1+/-113.3 to 264.3+/-93.6/μL by 2 months (p=<.0001, .0189, and .0004). In contrast, eosinophil counts elevated from 123.2+/-97.0 to 139.8+/-115.4 by 2 months, and to 159.6+/-132.8/μL by 6 months (p=.0349 and <.0001). Conclusions: We confirmed increases in neutrophils and monocytes in H. pylori -infected patients. Successful eradication reduced peripheral counts of neutrophil, lymphocyte, and monocyte, whereas it increased eosinophil counts. Males manifested elevated counts of every leukocyte, comparing to females. H. pylori infection influences systemic immune response and may not predispose to allergic disorders. Trial registration: The study protocol was registered on UMIN (University hospital Medical Information Network system) in Japan (R000017345) in 2014.

The timed up and go (TUG) test assesses balance and mobility performance. This study aims to investigate the association between TUG time and mortality in Japanese older persons and to clarify possible moderation effects on mortality and TUG time. In all, 874 participants who were ≥ 65 years of age completed the TUG test and had their anthropometric parameters and physical functions measured. We investigated the association between all-cause mortality and TUG using a Cox regression model that included confounders, and explored the time associated with mortality using a restricted cubic spline. We also performed subgroup analyses to explore whether age, sex, and body mass index (BMI) affected the relationship between TUG time and mortality. The median age and mean follow-up period were 74 and 8.5 years, respectively. Median TUG time was 7.4 s and the prevalence of mortality was 25.7%. TUG time in one second was positively associated with an increased risk of total mortality [hazard ratio (HR): 1.054 (1.016–1.093); P = 0.005] in the Cox regression model. The positive association of mortality and TUG time was present when the TUG was over 10.5 s in the restricted cubic spline curve. Older age (75 years or older) moderated the relationship between TUG time and mortality [Pinteraction = 0.096]. This study demonstrates that TUG time is associated with all-cause mortality in Japanese older adults.

Background Immune checkpoint inhibitors (ICIs) have been used to treat many cancers, but ICIs are rarely administered for malignant tumours coexisting with inflammatory bowel disease. Methods and results We report a 77-year-old man experiencing an ulcerative colitis (UC) flare-up after receiving nivolumab as third-line therapy for multiple metastases of renal cell carcinoma. Mild UC (proctitis form) had been diagnosed at age 59 years and remission was maintained for 17 years with only a low dose of 5-ASA. After nivolumab treatment, the patient developed diarrhoea, bloody stools and was hospitalised. Computed tomography revealed inflammation involving the entire colon and endoscopy revealed severe UC exacerbation. Histological analysis showed UC findings and also increased crypt apoptosis which is unusual for inflammatory bowel diseases, while being typical of ICI-induced colitis. As with ICI-induced colitis, this exacerbation was strongly suggested to have been caused by nivolumab, although remission was achieved by increasing the 5-ASA dose to 4000 mg without prednisolone. Conclusion The administration of ICI for UC is not as yet sufficiently safe and further research is required.

Background Crohn's disease is intractable and is frequently diagnosed in younger people. No clear policies exist regarding medical treatment for seniors with this disease, and its diagnosis and treatment are often hindered by difficulties attributable to comorbidities, complex differential diagnoses, and polypharmacy. We describe an elderly-onset Crohn's disease patient showing a marked remission-maintaining effect with no adverse events after administration of ustekinumab. Methods and results A 75-year-old patient with Crohn's disease and a history of pulmonary tuberculosis had first presented to our hospital at age 64 years and was hospitalized. Based on physical examinations, colonoscopy, and blood test results, Crohn's disease was diagnosed. The patient experienced secondary losses of responsiveness to two tumor necrosis factor (TNF)-alpha inhibitors, and after repeated hospital admissions, she was administered ustekinumab. The patient's symptoms, endoscopic findings, Crohn's Disease Activity Index, serum albumin, and physical activity levels improved markedly, and disease remission has been maintained for 2 years to date. Conclusion Ustekinumab is an effective treatment option for elderly patients with intractable Crohn's disease when TNF-alpha inhibitors are ineffective.

Disability is an important health problem among older individuals, prompting the need for long-term care. Age-related disability is usually associated with mobility; however, little is known about the association between mobility and long-term care. Therefore, this study aimed to clarify the association between the timed up and go (TUG) test measuring mobility and long-term care eligibility. We analyzed follow-up data of 489 community-dwelling healthy older adults (≥ 65 years) who participated in a prospective observational study. They were divided into certified (59 participants) and uncertified (430 participants) groups based on long-term care eligibility. Anthropometric and physical functioning measures included the TUG test and hand grip strength (HGS), among others. These measures were compared between groups and a multivariate logistic regression analysis evaluated the association between the TUG test times and long-term care eligibility. Participants’ minimum follow-up period was 4 years. TUG times were significantly slower (median time: 7.4 vs. 8.3 s, p < 0.001) and HGS and knee-extension strength significantly lower in the certified group than in the uncertified group. The logistic regression analysis showed that TUG times were significantly associated with long-term care eligibility after adjusting for potential covariates. In addition, mediation analysis showed that 53.1% of the association between HGS and long-term care eligibility was mediated through TUG times. The TUG test was associated with long-term care eligibility among healthy older adults, implying that the test may be helpful as a predictor for the early determination of dependence in old age.

Serum adiponectin levels are associated with frailty and cardiovascular diseases. Longitudinal changes in adiponectin levels might enhance our understanding of age-related conditions and diseases.

Edwardsiella tarda is commonly isolated from aquatic environments and a variety of animals. We present the first case of E. tarda bacteremia with psoas and epidural abscess. The patient was a 65-year-old woman with recurrent gastric cancer who had frequently consumed raw fish and grilled eel. She was successfully treated with antimicrobials and surgery. We also review reports published in English regarding E. tarda bacteremia in Japan and the experience at our hospital. On the basis of this review, we conclude that the major underlying disease leading to E. tarda bacteremia is malignancy and that the gastrointestinal tract is the most commonly affected organ. The overall mortality rate due to E. tarda bacteremia in our review was 38.1% (8/21). Although E. tarda bacteremia is rare, clinicians should be aware of this fatal food-borne infection.

We report herein on a rare case of deep-soft tissue infection due to invasive pneumococcal disease (IPD). A 77-year-old woman was admitted to our hospital with progressive pain in the right upper arm and the distal leg associated with swelling. We diagnosed the condition as multiple instances of cellulitis that were initially treated with ceftriaxone and clindamycin. Penicillin-susceptible Streptococcus pneumoniae (PSSP) was isolated from blood cultures on admission. Although inflammatory marker levels improved following susceptive antibiotic therapy (ampicillin), multiple abscesses, septic arthritis and osteomyelitis were detected with image testing. The antibiotic was then changed to meropenem and arthroscopic surgery was performed for the right shoulder; the patient's clinical symptoms improved. Since pneumococcal infection including skin and soft tissue infection (SSTI) often causes blood stream invasion or metastatic suppurative complications, metastatic lesions or multiple abscesses should be taken care of.

SummaryBackgroundWe previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission.AimTo assess whether antibiotic combination therapy is effective for active UC refractory to or dependent on steroids in a multicentre, open‐label trial.MethodsWe enrolled 30 patients with steroid‐refractory and 64 with steroid‐dependent active UC. These patients received three‐times‐daily by mouth amoxicillin 500 mg, tetracycline 500 mg and metronidazole 250 mg, for two weeks, as well as conventional treatment. Symptom assessment and colonoscopic evaluation were performed before enrolment and at 3 and 12 months after treatment completion. Clinical response was defined as a Lichtiger symptom score decrease in ≥3 points and clinical remission as a score ≤4.ResultsNineteen of the 30 steroid‐refractory (63.3%) and 47 of the 64 steroid‐dependent (73.4%) patients showed a clinical response within 2 weeks. At 3 and 12 months, 60% and 66.6% of steroid‐refractory patients, and 56.3% and 51.6% of steroid‐dependent patients, respectively, achieved clinical remission. In the steroid‐dependent group, 39 of the 64 patients (60.9%) were able to stop steroid therapy and remained in remission for 3 months. Three (10%) steroid‐refractory and four (6.3%) steroid‐dependent patients underwent colectomy.ConclusionsThis multicentre, long‐term follow‐up study suggests 2 week antibiotic combination therapy to be effective and safe in patients with active UC refractory to or dependent on steroids.

Despite promising results of fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI), this form of therapy has not gained much acceptance among physicians. Treatment with vancomycin and fidoximicin in addition to being expensive is also associated with high risk of relapse. The objective of this study was to assess physician perceptions and their willingness to consider FMT as a treatment option for their patients with recurrent CDI. MethodsA survey-based study collecting information from practicing gastroenterologists and infectious disease specialists was conducted. was designed using an online tool Survey Monkey and comprised of 10 questions related to FMT. Print forms of the survey were also utilized to obtain data via facsimile. ResultsA total of 72 completed responses (of over 250 surveys) were obtained. About 69% of respondents were gastroenterologists and 31% were Infectious disease specialists. The respondents comprised of 70% males and 30% females, 62% practicing in academic center and 38% in private practice. 83% of respondents would consider FMT for their patients with recurrent CDI while as 14% of respondents would not consider FMT for their patients. 3% responded never thinking about this treatment. Among those respondents who would not consider FMT, 58% did not know how to perform the procedure, 33% were skeptical about the safety of the procedure, 33% did not think there is enough evidence to support the therapy. 16% thought that the procedure was tiresome, and 16% were skeptical about patient acceptance of the therapy. Majority of the respondents who would not consider FMT (67%) were willing to accept if training workshops were provided and 42% would accept if published guidelines from GI societies or more scientific evidence supporting its use was available. Conclusion: Physicians are generally receptive of FMT as a therapeutic option for treating recurrent CDI. Majority of those reluctant to use FMT would consider such treatment if training workshops were provided and clinical practice guidelines by the GI Societies were available.

Primary gastric plasmacytoma is a rare disease with malignant potential. We previously described in Gastrointestinal Endoscopy a 60-year-old man with primary gastric plasmacytoma (IgM, γ type) (Fig. 1A, C, D), in which endoscopic regression of the tumor was observed after the eradication of Helicobacter pylori.1Kato K. Sugitani M. Nagata T. et al.A case of gastric plasmacytoma associated with Helicobacter pylori infection: improvement of abnormal endoscopic and ultrasonographic findings after eradication of Helicobacter pylori.Gastrointest Endosc. 2001; 53: 352-355PubMed Scopus (18) Google Scholar However, atypical plasma cells persisted at the histological level and contained monoclonal cytoplasmic IgM γ in this case. Three cases have since been reported with complete regression of primary gastric plasmacytoma after H pylori eradication.2Papadaki H.A. Skordilis P. Minadakis G. et al.Complete regression of primary gastric plasmacytoma following Helicobacter pylori eradication.Ann Hematol. 2003; 82: 589-592Crossref PubMed Scopus (22) Google Scholar, 3Shapiro M. Kimchi N.A. Herbert M. et al.Gastric plasmacytoma and Helicobacter pylori infection.J Clin Gastroenterol. 2005; 39: 56-57PubMed Google Scholar, 4Stasi R. Evangelista M.L. Brunetti M. et al.Primary gastric plasmacytoma and Helicobacter pylori.Infect J Clin Oncol. 2009; 27: 150-153Crossref PubMed Scopus (18) Google Scholar We followed up our case for 12 years after H pylori eradication without other therapy. During this follow-up period, the negative status of the H pylori infection and the macroscopic disappearance of gastric lesions have been maintained. We documented complete histological regression of gastric plasmacytoma 6 years after H pylori eradication (ie, tumor regression lasted for another 6 years. Endoscopic findings indicated no abnormalities in the gastric mucosa, and the absence of relapse was verified histologically with no detectable Ig rearrangement (Fig. 1B, E). Furthermore, IgM monoclonal protein and Bence Jones proteins were undetectable in serum and urine. To our knowledge, this is the first report of very-long-term follow-up of gastric plasmacytoma after H pylori eradication. Our case and others showing complete regression suggest that H pylori eradication, together with treatment strategies aimed at pathological and genetic factors, might be a potential first-line therapy for patients with primary gastric plasmacytoma associated with H pylori infection. However, our case also suggests long-term endoscopic and clinical follow-up after H pylori eradication to be essential for confirming efficacy. However, another reported case resistant to H pylori eradication may suggest heterogeneity in the response to treatments, including H pylori eradication.5Lu H.S. Xu Y.F. Gan M.F. Primary gastric plasmacytoma associated with Helicobacter pylori infection: a report of two cases with different prognosis.Int J Hematol. 2010; 92: 174-178Crossref PubMed Scopus (8) Google Scholar Further extensive case studies are required. Primary gastric plasmacytoma is a rare disease with malignant potential. We previously described in Gastrointestinal Endoscopy a 60-year-old man with primary gastric plasmacytoma (IgM, γ type) (Fig. 1A, C, D), in which endoscopic regression of the tumor was observed after the eradication of Helicobacter pylori.1Kato K. Sugitani M. Nagata T. et al.A case of gastric plasmacytoma associated with Helicobacter pylori infection: improvement of abnormal endoscopic and ultrasonographic findings after eradication of Helicobacter pylori.Gastrointest Endosc. 2001; 53: 352-355PubMed Scopus (18) Google Scholar However, atypical plasma cells persisted at the histological level and contained monoclonal cytoplasmic IgM γ in this case. Three cases have since been reported with complete regression of primary gastric plasmacytoma after H pylori eradication.2Papadaki H.A. Skordilis P. Minadakis G. et al.Complete regression of primary gastric plasmacytoma following Helicobacter pylori eradication.Ann Hematol. 2003; 82: 589-592Crossref PubMed Scopus (22) Google Scholar, 3Shapiro M. Kimchi N.A. Herbert M. et al.Gastric plasmacytoma and Helicobacter pylori infection.J Clin Gastroenterol. 2005; 39: 56-57PubMed Google Scholar, 4Stasi R. Evangelista M.L. Brunetti M. et al.Primary gastric plasmacytoma and Helicobacter pylori.Infect J Clin Oncol. 2009; 27: 150-153Crossref PubMed Scopus (18) Google Scholar We followed up our case for 12 years after H pylori eradication without other therapy. During this follow-up period, the negative status of the H pylori infection and the macroscopic disappearance of gastric lesions have been maintained. We documented complete histological regression of gastric plasmacytoma 6 years after H pylori eradication (ie, tumor regression lasted for another 6 years. Endoscopic findings indicated no abnormalities in the gastric mucosa, and the absence of relapse was verified histologically with no detectable Ig rearrangement (Fig. 1B, E). Furthermore, IgM monoclonal protein and Bence Jones proteins were undetectable in serum and urine. To our knowledge, this is the first report of very-long-term follow-up of gastric plasmacytoma after H pylori eradication. Our case and others showing complete regression suggest that H pylori eradication, together with treatment strategies aimed at pathological and genetic factors, might be a potential first-line therapy for patients with primary gastric plasmacytoma associated with H pylori infection. However, our case also suggests long-term endoscopic and clinical follow-up after H pylori eradication to be essential for confirming efficacy. However, another reported case resistant to H pylori eradication may suggest heterogeneity in the response to treatments, including H pylori eradication.5Lu H.S. Xu Y.F. Gan M.F. Primary gastric plasmacytoma associated with Helicobacter pylori infection: a report of two cases with different prognosis.Int J Hematol. 2010; 92: 174-178Crossref PubMed Scopus (8) Google Scholar Further extensive case studies are required. ErratumGastrointestinal EndoscopyVol. 77Issue 6PreviewIn “Long-term gastric plasmacytoma follow-up after helicobacter pylori eradication” (Gastrointest Endosc 2013;77:674-5) by Kimitoshi Kato et al, the 2 gamma signs should have been lambda signs: Full-Text PDF

The etiology of Cronkhite-Canada syndrome (CCS) remains unknown and many cases are refractory to treatment. Therefore, new therapies are urgently needed. Furthermore, a number of CCS cases with gastrointestinal carcinoma have been reported. Our patient had rapid onset of CCS and early development of colon carcinoma associated with adenomas. High anterior resection of the sigmoid colon and ileostomy were performed, and her symptoms and endoscopic and histological findings improved. Helicobacter pylori eradication was carried out 2 years later, surgical closure of an ileal fistula the following year. After 4 months, upper gastrointestinal endoscopy and colonoscopy showed that the CCS lesions had completely disappeared, and biopsies confirmed a normal stomach, duodenum, ileum and colon histologically. The patient has maintained remission for 2 years. The clinical course of this case, showing complete regression of CCS lesions following abdominal colectomy and H. pylori eradication, suggests the significance of H. pylori infection in the treatment of CCS.