Celiac Disease Diagnosed after Gastrectomy for Gastric Cancer.

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.

Mobility performance impacts mortality risk in community-dwelling healthy older adults in Japan: a prospective observational study.

BACKGROUND: The timed up and go (TUG) test assesses balance and mobility performance. AIM: 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. METHODS: 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. RESULTS: 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]. CONCLUSION: This study demonstrates that TUG time is associated with all-cause mortality in Japanese older adults.

Remission of ulcerative colitis flare-up induced by nivolumab.

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.

Mobility performance among healthy older adults eligible for long-term care in Japan: a prospective observational study.

BACKGROUND AND AIM: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Elderly-onset Crohn's disease remarkably responsive to ustekinumab: a case report.

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.

Edwardsiella tarda Bacteremia with Psoas and Epidural Abscess as a Food-borne Infection: A Case Report and Literature Review.

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.

High-molecular-weight adiponectin levels in healthy, community-dwelling, elderly Japanese volunteers: a 5-year prospective observational study.

BACKGROUND: 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. AIMS: This prospective observational study aimed to: (1) elucidate age-related changes in high-molecular-weight (HMW) adiponectin levels; and (2) identify variables predictive of elevated HMW adiponectin levels and the association with well-known adiponectin single-nucleotide polymorphisms (SNPs) in healthy, elderly Japanese participants. METHODS: Healthy elderly volunteers (n = 196; 55 men and 141 women; median age 72.0 years; range 69.0-75.0 years) underwent anthropometric and physical function measurements, as well as laboratory tests at baseline and the 5-year follow-up. RESULTS: HMW adiponectin levels were significantly higher in women than in men (8.4, 5.3-11.9 vs. 5.7, 3.1-9.0 µg/mL; p < 0.001) at baseline and decreased significantly at follow-up in women (7.7, 4.8-11.2 µg/mL; p < 0.001), but not in men. In the multiple regression analysis, high-density lipoprotein cholesterol levels and body weight were independent predictors of HMW adiponectin levels. The rate of change in HMW adiponectin levels was inversely correlated with the rates of change in body weight, body mass index, and knee leg extension strengths, and positively correlated with rates of change in high-density lipoprotein cholesterol and one-leg standing time. There were no significant differences in HMW adiponectin levels among SNPs. DISCUSSION: Decreasing HMW adiponectin levels might lead to an increased risk of cardiovascular diseases in elderly women. CONCLUSION: HMW adiponectin levels significantly decreased over a 5-year period in community-dwelling elderly Japanese women.

Synthesis of carbon fibers with branched nanographene sheets for electrochemical double layer capacitor application.

We demonstrate a one step technique to synthesis the carbon fibers (CNFs) with branched nanographene sheets by the pulsed discharge (PD) plasma chemical vapor deposition (CVD) process. Highly crystalline branched nanographene sheets were directly grown from the surface of the carbon fibers to obtain a three dimensional (3D) nanostructure. The growth process can be explained from the catalyst support growth of the CNFs, and subsequently nucleation and growth of the nanographene sheets from the crystalline surface of the CNF. The deposited nanostructured films with different pulse discharge were used as an electrode for electrochemical double-layer capacitors (EDLC). It is observed that the capacitance is dependent on the morphology of the electrode materials and an optimum capacitance is obtained with the branched nanographene on CNFs.

[Invasive pneumococcal disease of serotype 6C with skin and soft tissue infections in an immunocompetent adult].

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.

Spontaneous Regression of Polyposis following Abdominal Colectomy and Helicobacter pylori Eradication for Cronkhite-Canada Syndrome.

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.

Helicobacter pylori upregulates peripheral platelet counts mainly in female patients.

To evaluate the influence of Helicobacter pylori and sex difference on peripheral platelet counts, dyspeptic patients without immunohaematologic disorders were evaluated. H. pylori infection was verified with the rapid urease test and serum anti-H. pylori IgG antibody. Platelet counts were analysed with a reference to H. pylori infection and sex difference. Among H. pylori-eradicated patients, changes in platelet counts were separately evaluated. Totally, 655 patients were enrolled: 340 patients were infected with H. pylori and 178 patients received eradication therapy, with a success rate of 88.2% (157/178). Females with H. pylori infection definitely manifested elevated platelet counts (infected vs. uninfected 244 ± 57 vs. 219 ± 54 × 10(9)/l; p < 0.0001). H. pylori eradication reduced peripheral platelets by 8 weeks, 5-6 months, 1, 2 and ≥3 years after eradication in females from 248 ± 54 to 237 ± 49, 237 ± 54, 229 ± 48, 238 ± 61 and 232 ± 50 × 10(9)/l (p = 0.0003, 0.0182, 0.0041, 0.0398 and 0.0289), respectively. In males, the reduction was verified by 8 weeks, 1 year and ≥3 years from 226 ± 52 to 217 ± 47, 214 ± 44 and 200 ± 49 × 10(9)/l (p = 0.0464, 0.0164 and 0.0016), respectively. In conclusion, H. pylori infection upregulates platelet counts mainly in females, and eradication reduced peripheral platelets in both sexes. Females appeared more susceptible to H. pylori infection than males with regard to upregulation of platelet counts.

Antibiotic combination therapy for steroid withdrawal in steroid-dependent ulcerative colitis.

BACKGROUND AND AIM: Immunosuppressive drugs are recommended for use as replacements of steroid therapy in sustaining remission of steroid-dependent ulcerative colitis (UC). However, discontinuation of these therapeutic agents leads to a high relapse, and their long-term administration has not been proven safe. A newly introduced antibiotic combination therapy led to improvement and remission of active UC. The aim of this study is to examine whether this new therapy can replace immunosuppressive agents and allow discontinuation of steroids in steroid-dependent UC remission. METHODS: 48 patients with steroid-dependent UC were recruited for a 2-week treatment with amoxicillin, tetracycline, and metronidazole (ATM). Examination of clinical symptoms, endoscopy, and histological evaluation were performed before and 6 and 12 months after treatment. RESULTS: The proportion of patients who showed clinical improvement at 6 and 12 months after treatment was 54.2% (26/48) and 75.0% (36/48), respectively. The rate of clinical remission at 6 and 12 months was 31.3% (15/48) and 37.5% (18/48), respectively. Steroid withdrawal was attained in 64.6% (31/48) and 70.8% (34/48) of patients at 6 and 12 months, respectively. Endoscopic improvement was detected in 56.3% (27/48), and histological improvement was detected in 52.1% (25/48) at the final observation point for each patient. CONCLUSION: The triple antibiotic therapy resulted in improvement, remission, and steroid withdrawal in steroid-dependent UC patients.

Long term changes in platelet counts after H. pylori eradication in non-ITP patients.

Helicobacter pylori eradication is becoming a first-line therapy against idiopathic thrombocytopenic purpura (ITP) and its long term efficacy has already been reported. In contrast, eradication therapy reduced peripheral platelets in non-ITP patients 8 weeks later. To confirm the long term efficacy of Helicobacter eradication on platelet counts in non-ITP patients, we evaluated changes in peripheral platelet counts in endoscopically diagnosed patients with Helicobacter infection. Endoscopically diagnosed patients with Helicobacter infection received eradication therapy using amoxicillin (1500 mg/day), clarithromycin (400 mg/day) and lansoprazole (60 mg/day). The changes in platelet counts after Helicobacter eradication were serially evaluated for as long as 3 years or more. In total, 294 patients were enrolled: 243 patients successfully received eradication therapy and 51 were unsuccessfully treated. As a whole, peripheral platelet counts significantly decreased after Helicobacter eradication, being reduced by more than 1.0 × 109/l by 5-6 months, 1 year, 2 years and 3 years or more (from 24.2+/-5.6 to 23.1+/-5.0, 23.0+/-5.0, 22.1+/-4.5, 22.4+/-5.6, and 21.6+/-5.3 × 109/l: p = <0.0001, <0.0001, 0.0001, 0.0052, and <0.0001, respectively). Helicobacter pylori eradication finally reduced peripheral platelet counts around 2.0 × 109/l in non-ITP patients. There was a definite difference in platelet regulation by Helicobacter pylori between ITP and non-ITP patients. These bivalent effects, upregulation and downregulation, on the peripheral platelet induced by Helicibacter pylori infection appeared to originate from quite different mechanisms.

Efficacy of antibiotic combination therapy in patients with active ulcerative colitis, including refractory or steroid-dependent cases.

BACKGROUND AND AIMS: We previously demonstrated that antibiotic combination therapy is effective for induction and maintenance of ulcerative colitis (UC) remission. Herein, we assessed whether antibiotic combination therapy is effective for active UC, including cases with steroid refractory or dependent disease. METHODS: We enrolled 25 patients with active UC including 17 steroid-dependent or refractory cases. These patients received amoxicillin 500 mg t.i.d., tetracycline 500 mg t.i.d. and metronidazole 250 mg t.i.d. for 2 weeks as well as conventional treatment. Seven colonic segments from the appendiceal region to the rectum were scored for endoscopic activity and histology. Clinical activity indexes (CAI) were also determined. RESULTS: At 3 and 12 months after antibiotic treatment, CAI and endoscopic score were significantly decreased as compared to those before treatment (P < 0.001 and P < 0.05, P < 0.01, respectively). Histological scores were also significantly decreased at 12 months as compared to before treatment (P < 0.01). The clinical response rates in steroid-dependent patients were 60% and 73.3% at 3 and 12 months, respectively, while being 50% at 12 months in steroid-refractory patients. Among the 17 steroid-dependent or refractory patients, 12 (70.6%) were able to discontinue steroid therapy at 12 months. No serious drug-related toxicities were observed during the trial. CONCLUSION: This long-term follow-up study suggests 2-week antibiotic combination therapy to be effective and safe in patients with active UC including those with steroid-refractory or dependent disease.

Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial.

OBJECTIVES: Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC. METHODS: Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred. CONCLUSIONS: The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Anti-inflammatory activity of probiotic Bifidobacterium: enhancement of IL-10 production in peripheral blood mononuclear cells from ulcerative colitis patients and inhibition of IL-8 secretion in HT-29 cells.

AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS: Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted. RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-alpha, whereas no such effect was observed with heat-killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IkappaB-zeta mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM. CONCLUSION: Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.

Usefulness of rectally administering [1-(13)C]-butyrate for breath test in patients with active and quiescent ulcerative colitis.

OBJECTIVE: Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. MATERIAL AND METHODS: Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. RESULTS: The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. CONCLUSIONS: Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.