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Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

Background Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. Methods Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. Results A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. Conclusions For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

Background and Aim Vedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut‐homing memory T cells into the intestinal submucosa by antagonizing the interaction of α4β7 integrin with MAdCAM‐1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real‐world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy. Methods This was a single‐center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty‐two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively. Results In these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab. Conclusions In vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24. Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis with moderate to severe activity.

A 19-year-old man with a history of Peutz-Jeghers syndrome (PJS) and two previous partial small bowel resections because of intussusception presented with lower abdominal pain. Computed tomography (CT) showed concentric multilayer and cord-like structures in the transverse colon. Colo-colonic intussusception was suspected and he was hospitalized. After two therapeutic enemas were unsuccessful, a colonoscopy was performed. The intussusception was reduced and a 40-mm transverse colon polyp with a thick stalk was resected. After the procedure, his abdominal pain was relieved and he was discharged on the sixth hospital day. This case and several previous reports suggest that PJS polyps with tumor diameter exceeding 30 mm and location in the transverse or sigmoid colon can cause intussusception. Endoscopic treatment should be considered for these lesions.

Background and Aim. Half-elemental diet (ED) (900 kcal/day of ED) has clinical efficacy to treat Crohn’s disease (CD). However, the underlying mechanisms of how the ED exerts its efficacy remain unclear. Alterations of the gut microbiota, known as dysbiosis, have been reported to play a role in CD pathogenesis. Many variables including diet affect the gut microbiota. We hypothesized that half-ED has the potential to change the gut microbiota composition and functions leading to anti-inflammatory actions. Given that inflammation can be a confounding factor affecting the intestinal microbiota, we aimed to test our hypothesis among healthy individuals in this pilot study. Methods. This prospective study included four healthy volunteers. The subjects continued their dietary habits for 2 weeks after the registration of the study and then started half-ED replacing 900 kcal of the regular diet with ED (time point 1, T1). The subjects continued half-ED for 2 weeks (T2). After the withdrawal of ED, subjects resumed their original dietary habits for 2 weeks (T3). Fecal samples were collected from all subjects at all time points, T1-3. Fecal DNA and metabolites were extracted from the samples. We performed 16S rRNA gene amplicon sequencing and metabolomic analysis to examine the bacterial compositions and intestinal metabolites. Results. There were differences in the gut bacterial compositions and metabolites at each time point as well as overtime changing patterns between subjects. Several bacteria and metabolites including short-chain fatty acids and bile acids altered significantly across the subjects. The bacterial membership and intestinal metabolites at T3 were different from T1 in all subjects. Conclusions. Half-ED shifts the gut bacterial compositions and metabolites. The changes varied with each individual, while some microbes and metabolites change commonly across individuals. The impact of half-ED may persist even after the withdrawal. This trial is registered with UMIN ID: 000031920.

Inflammatory bowel diseases include Crohn's disease (CD) and ulcerative colitis (UC), both of which require endoscopic evaluation of mucosal surfaces. Capsule endoscopy has been used in clinical practice since 2000 as a minimally invasive means of mucosal evaluation. In Japan, there is an innovative algorithm that incorporates capsule endoscopy into the diagnostic algorithm for CD. However, capsule retention is a potential complication, and intestinal patency must be evaluated using a patency capsule or other means before capsule ingestion. In addition, the pathophysiology of CD is a combination of inflammation and stenosis, so the interpretation of score values remains an issue to be addressed. Colon capsule endoscopy for UC is useful in understanding the localization and severity of colorectal inflammation. However, capsule endoscopy is not appropriate for cancer surveillance in patients with UC, and further improvements in bowel preparation are needed. Despite these issues, capsule endoscopy, which allows noninvasive observation of mucosal surfaces, is attractive, and further development is expected.

The effect of the addition volume of Ni on the microstructures and tensile and fatigue properties of Sn-6.4Sb-3.9Ag (mass%) was investigated using micro-size specimens. The addition of Ni into Sn-6.4Sb-3.9Ag tends to increase the number of grains formed in the solidification process and produce a high-angle grain boundary. An amount of 0.1% proof stress of Sn-6.4Sb-3.9Ag decreases with an increase in the Ni addition volume at a strain rate of 2.0 × 10−1 s−1. The effect of the addition of Ni into Sn-6.4Sb-3.9Ag on tensile strength is negligible at both 25 °C and 175 °C. The elongation of Sn-6.4Sb-3.9Ag decreases with an increase in the Ni addition volume at 25 °C according to the fracture mode change from ductile chisel point fracture to shear fracture. The effect of the addition of Ni into Sn-6.4Sb-3.9Ag on the elongation is negligible at 175 °C. The low cycle fatigue test result shows that the fatigue life does not degrade even at 175 °C in all alloys investigated. The fatigue life of Sn-6.4Sb-3.9Ag-0.4Ni (mass%) is superior to those of Sn-6.4Sb-3.9Ag and Sn-6.4Sb-3.9Ag-0.03Ni (mass%) in the high cycle fatigue area. The electron back scattering diffraction (EBSD) analysis result shows that fine recrystallized grains are generated at the cracked area in Sn-6.4Sb-3.9Ag-0.4Ni in the fatigue test at 175 °C, and the crack progresses in a complex manner at the grain boundaries.

Dysregulation of circadian rhythm can cause nocturia. Levels of fatty acid metabolites, such as palmitoylethanolamide (PEA), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), and 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid (4-HDoHE), are higher in the serum of patients with nocturia; however, the reason remains unknown. Here, we investigated the circadian rhythm of fatty acid metabolites and their effect on voiding in mice. WT and Clock mutant ( Clock Δ19/Δ19 ) mice, a model for nocturia with circadian rhythm disorder, were used. Levels of serum PEA, 9-HODE, and 4-HDoHEl were measured every 8 h using LC/MS. Voiding pattern was recorded using metabolic cages after administration of PEA, 9-HODE, and 4-HDoHE to WT mice. Levels of serum PEA and 9-HODE fluctuated with circadian rhythm in WT mice, which were lower during the light phase. In contrast, circadian PEA and 9-HODE level deteriorated or retreated in Clock Δ19/Δ19 mice. Levels of serum PEA, 9-HODE, and 4-HDoHE were higher in Clock Δ19/Δ19 than in WT mice. Voiding frequency increased in PEA- and 4-HDoHE-administered mice. Bladder capacity decreased in PEA-administered mice. The changes of these bladder functions in mice were similar to those in elderly humans with nocturia. These findings highlighted the novel effect of lipids on the pathology of nocturia. These may be used for development of biomarkers and better therapies for nocturia.