Extracolonic involvement of the gastrointestinal tract is extremely uncommon in ulcerative colitis (UC) and rarely found in the upper gastrointestinal tract or in postoperative cases since it typically responds to steroids. Here we report a case of UC complicated by extensive ileal inflammation that was refractory to steroids. A 20-year-old man was diagnosed with UC of typical pancolitis without ileal involvement and started treatment with pH-dependent mesalazine and oral prednisolone. Although his symptoms transiently resolved, the condition flared when the steroid dose was tapered down. Computed tomography revealed marked thickening of the ileal wall, and capsule endoscopy and balloon-assisted enteroscopy found diffuse mucosal inflammation with ulcers in the ileum. On the contrary, the inflammation in the colon and rectum was improving. Since the response to the second steroid course was inadequate, treatment with adalimumab and 6-mercaptopurine was initiated and finally achieved clinical and endoscopic remission. The investigation of small intestinal lesions is necessary in patients with UC whose clinical deterioration cannot be explained by colonic lesions.
6-Mercaptopurine ; Adalimumab* ; Capsule Endoscopy ; Colitis, Ulcerative* ; Colon ; Enteritis* ; Gastrointestinal Tract ; Humans ; Ileum ; Inflammation ; Inflammatory Bowel Diseases ; Mesalamine ; Prednisolone ; Rectum ; Steroids ; Ulcer* ; Upper Gastrointestinal Tract ; Young Adult

BACKGROUND/AIMS: Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. METHODS: UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. RESULTS: A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). CONCLUSIONS: CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.
Colitis, Ulcerative ; Drug Compounding ; Humans ; Medication Adherence ; Mesalamine ; Patient Acceptance of Health Care ; Patient Compliance ; Prospective Studies ; Recurrence ; Tablets ; Ulcer ; Visual Analog Scale

BACKGROUND/AIMS: Fundic gland polyps (FGPs), hyperplastic polyps (HPs), and xanthomas (XTs) are common benign gastric lesions that can be diagnosed by endoscopic appearance alone in most cases. The aim of this study was to evaluate associations between gastric cancer and these benign lesions. METHODS: Two expert endoscopists reviewed a series of gastroscopy images. FGPs, HPs, and XTs were diagnosed by endoscopic appearance, whereas all gastric cancers were confirmed pathologically. RESULTS: Of the 1,227 patients reviewed, 114 (9.3%) had a concurrent or past history of gastric cancer. The overall prevalences of FGPs, HPs and XTs were 9.4%, 6.3% and 14.2%, respectively. HPs and XTs coexisted in 1.6% of patients, whereas other combinations were rarer. XTs were observed in 39.3% and 11.5% of patients with and without gastric cancer, respectively (p<0.001). In contrast, no gastric cancer patients had FGPs, whereas 10.4% of patients without cancer had FGPs (p<0.001). The prevalence of HPs was similar between the two groups (8.8% and 6.0% of patients with and without cancer, respectively, p=0.29). Multivariate and Mantel-Haenszel analyses demonstrated that XTs were positively associated and FGPs were negatively associated with gastric cancer. CONCLUSIONS: XTs and FGPs might be useful as endoscopic risk indicators for monitoring gastric cancer.
Gastroscopy ; Humans ; Polyps ; Prevalence ; Stomach Neoplasms ; Xanthomatosis

Objectives: The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats. Methods: Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points. Results: In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone. Conclusions These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.

Objectives: Chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) is associated with an increased risk of fragility fractures. Etelcalcetide (EC) is a treatment for SHPT that reduces serum parathyroid hormone (PTH) levels. However, the effects of combined treatment with osteoporosis drugs such as teriparatide (TPTD) remain unclear. This study investigates the combined effects of EC and TPTD on bone in CKD model rats. Methods: The CKD model was established in 8-week-old male Wistar rats by feeding them a 0.75% adenine diet for 4 weeks. At 20 weeks of age, the rats were divided into 4 groups (n = 9–10 in each group): CKD group (vehicle administration), TPTD group (30 μg/kg, 3 times/week), EC group (0.6 mg/kg, daily), and Comb group (TPTD and EC combined). EC was injected for 12 weeks starting at 20 weeks of age, and TPTD was injected for 8 weeks starting at 24 weeks of age. After treatment, the followings were evaluated: bone mineral density, bone strength, biochemical tests, bone and fat histomorphometry, and micro-computed tomography. Results: In CKD model rats, the combination of EC and TPTD was more effective in increasing cortical bone thickness and bone strength and inhibiting porosity. In addition, the combined treatment decreased bone marrow adiposity and fibrosis, and it increased bone mass and improved bone microstructure in trabecular bone. Conclusions With the observed benefits such as improved bone mass, bone strength, structural properties, and bone marrow adiposity, combination therapy may be a potential way to improve bone fragility in CKD.

Background: The need for support focused on frailty and quality of life (QoL) in older adults is increasing. The Kihon Checklist (KCL) is a comprehensive and easy-to-use tool to assess frailty in older adults. Previous studies have shown associations between frailty and QoL; however, few studies have investigated the association between frailty using the KCL and QoL. In this study, the quantitative relationship between the KCL and QoL in community-dwelling older adults was investigated. Methods: This cross-sectional study included from participants in the 2017–2019 baseline survey of a cohort study of community-dwelling older adults in Sapporo, Japan. The World Health Organization-Five Well-Being Index (WHO-5) was used to assess QoL. The KCL was used to assess frailty, and the relationship between frailty and QoL was examined using binomial logistic regression analysis and restricted cubic spline models. Results: Four-hundred participants were included in the analysis. Of the participants, 22.5% had a lower QoL and they were more likely to have frailty than healthy participants (p<0.001). The KCL scores were significantly associated with a lower QoL (p<0.001). Furthermore, the association between the KCL score and QoL was linear, and subscales of activities of daily living, and depressive mood were significantly associated with a lower QoL. Conclusion The KCL, a comprehensive frailty questionnaire, was associated with a lower QoL in older adults. To maintain QoL in community-dwelling older adults, it is necessary to provide them with appropriate support from the stage before they are identified as frail by the KCL.

Background: The need for support focused on frailty and quality of life (QoL) in older adults is increasing. The Kihon Checklist (KCL) is a comprehensive and easy-to-use tool to assess frailty in older adults. Previous studies have shown associations between frailty and QoL; however, few studies have investigated the association between frailty using the KCL and QoL. In this study, the quantitative relationship between the KCL and QoL in community-dwelling older adults was investigated. Methods: This cross-sectional study included from participants in the 2017–2019 baseline survey of a cohort study of community-dwelling older adults in Sapporo, Japan. The World Health Organization-Five Well-Being Index (WHO-5) was used to assess QoL. The KCL was used to assess frailty, and the relationship between frailty and QoL was examined using binomial logistic regression analysis and restricted cubic spline models. Results: Four-hundred participants were included in the analysis. Of the participants, 22.5% had a lower QoL and they were more likely to have frailty than healthy participants (p<0.001). The KCL scores were significantly associated with a lower QoL (p<0.001). Furthermore, the association between the KCL score and QoL was linear, and subscales of activities of daily living, and depressive mood were significantly associated with a lower QoL. Conclusion The KCL, a comprehensive frailty questionnaire, was associated with a lower QoL in older adults. To maintain QoL in community-dwelling older adults, it is necessary to provide them with appropriate support from the stage before they are identified as frail by the KCL.

Background: The need for support focused on frailty and quality of life (QoL) in older adults is increasing. The Kihon Checklist (KCL) is a comprehensive and easy-to-use tool to assess frailty in older adults. Previous studies have shown associations between frailty and QoL; however, few studies have investigated the association between frailty using the KCL and QoL. In this study, the quantitative relationship between the KCL and QoL in community-dwelling older adults was investigated. Methods: This cross-sectional study included from participants in the 2017–2019 baseline survey of a cohort study of community-dwelling older adults in Sapporo, Japan. The World Health Organization-Five Well-Being Index (WHO-5) was used to assess QoL. The KCL was used to assess frailty, and the relationship between frailty and QoL was examined using binomial logistic regression analysis and restricted cubic spline models. Results: Four-hundred participants were included in the analysis. Of the participants, 22.5% had a lower QoL and they were more likely to have frailty than healthy participants (p<0.001). The KCL scores were significantly associated with a lower QoL (p<0.001). Furthermore, the association between the KCL score and QoL was linear, and subscales of activities of daily living, and depressive mood were significantly associated with a lower QoL. Conclusion The KCL, a comprehensive frailty questionnaire, was associated with a lower QoL in older adults. To maintain QoL in community-dwelling older adults, it is necessary to provide them with appropriate support from the stage before they are identified as frail by the KCL.

BACKGROUND/AIMS: The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis. METHODS: Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day). RESULTS: The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group. CONCLUSIONS: Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.
Colitis, Ulcerative ; Cytochrome P-450 CYP3A ; Genotype ; Humans ; Pharmacokinetics ; Polymorphism, Single Nucleotide ; Prospective Studies ; Tacrolimus ; Ulcer