Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Integrated Distress Activity Score (IDAS) was developed in order to evaluate both positive and negative aspects of patient’s conditions throughout hospitalization. IDAS were evaluated by nurses everyday and when patients continued to have IDAS less than or equal to zero, we used this tool for determining continuous deep sedation. From 2013-2017, 1306 patients were enrolled in the study. The average rate of continuous deep sedation in the PCU was 1.2%(16 patients). Dyspnea was the most common condition (62.5%, 10 patients), followed by delirium (37.5%, 6 patients).The average days that took to decide for sedation (from the day when IDAS was less than or equal to zero), was 3.7 days. This study suggested that IDAS could be a useful tool for determining continuous deep sedation.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.
Asian Continental Ancestry Group ; Colectomy ; Colitis, Ulcerative ; Colorectal Neoplasms ; Consensus ; Crohn Disease ; Disease Management* ; Disease Progression ; Early Intervention (Education) ; Epidemiology ; Expert Testimony ; Gastrointestinal Tract ; Hospitalization ; Humans ; Inflammatory Bowel Diseases* ; Japan* ; Prevalence ; Prognosis

Objective: Spinal cord compression symptoms are complications that greatly reduce the quality of life of cancer patients. We report a retrospective study on the efficacy of and adverse reactions to high-dose dexamethasone therapy for patients with concomitant spinal cord compression symptoms. Subjects: This study included 8 patients with concomitant spinal cord compression symptoms who received high-dose dexamethasone therapy at our hospital between May 2009 and September 2011. Results: Only high-dose dexamethasone therapy was performed in 8 patients who could not undergo radiotherapy or surgery in combination. Among them, the results of manual muscle testing were improved in 4 patients (50.0%), and grades according to the modified Frankel Classification showed improvement in 5 patients (62.5%). Out of 7 non-ambulatory patients, one (14.3%) regained independent ambulation with highdose dexamethasone therapy alone and was discharged home. No serious adverse reactions were observed in any of the 8 patients. Discussion: This study suggested high-dose dexamethasone therapy to possibly be a useful option for relieving neurological symptoms in patients with spinal cord compression who cannot undergo radiotherapy or surgery in combination.

Purpose: Evaluation of the efficacy and safety of sublingual drug administration in palliative care patients lacking the ability to swallow as well as other drug administration routes. Methods: Buprenorphine, 0.1∼0.2mg/dose (n=15) and fentanyl, 0.05∼0.2mg/dose (n=26) were administered sublingually for cancer pain, and midazolam, 0.1mg/kg (n=16) for insomnia respectively. Results: The three drugs were all rapidly absorbed by the oral cavity and showed efficacy in about 90% of patients. No adverse events were observed other than drowsiness, nausea and over production of sputum in patients suffering from dysphagia. Conclusion: Sublingual administration is a viable alternative for maintaining the quality of life of patients not accessible through conventional administration routes in the palliative setting. Palliat Care Res 2010; 5(1): 201-205

Pancreatic duct cells secrete HCO3(-) ions into a HCO3(-)-rich luminal fluid (~140 mmol/L in human) against at least a 6-fold concentration gradient. Candidate mechanisms for HCO3(-) transport across the apical membrane include Cl(-)-HCO3(-)exchange by an SLC26 anion transporter and diffusion via the HCO3(-) conductance of cystic fibrosis transmembrane conductance regulator (CFTR). Members of the SLC26 family are known to mediate Cl(-)-HCO3(-) exchange across the apical membrane of other epithelia and both SLC26A6 and SLC26A3 have been detected in pancreatic ducts. Co-expression studies have also revealed that murine slc26a6 and slc26a3 physically interact with CFTR through the STAS domain of slc26 and the R domain of CFTR, resulting in mutually enhanced activity. Other studies have indicated that these exchangers are electrogenic: slc26a6 mediating 1Cl(-)-2HCO3(-) exchange and slc26a3 mediating 2Cl(-)-1HCO3(-) exchange. Recent experiments using isolated pancreatic ducts from slc26a6(-)/(-) mice suggest that slc26a6 mediates most of the Cl(-)-dependent secretion of HCO3(-) across the apical membrane in the mouse and the data are consistent with the reported electrogenicity of slc26a6. However, the role of SLC26A6 in human pancreatic HCO3(-) secretion is less clear because human ducts are capable of secreting much higher concentrations of HCO3(-). The role of SLC26A6 must now be evaluated in a species such as the guinea pig which, like the human, is capable of secreting HCO3(-) at a concentration of ~140 mmol/L. From existing guinea pig data we calculate that a 1Cl(-)-2HCO3(-) exchanger such as slc26a6 would be unable to secrete HCO3(-) against such a steep gradient. On the other hand, the HCO3(-) conductance of CFTR could theoretically support secretion of HCO3(-) to a much higher concentrations. CFTR may therefore play a more important role than SLC26A6 in HCO3(-) secretion by the guinea pig and human pancreas.
Animals ; Bicarbonates ; metabolism ; Chloride-Bicarbonate Antiporters ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; physiology ; Guinea Pigs ; Humans ; Membrane Transport Proteins ; physiology ; Mice ; Pancreatic Ducts ; cytology ; secretion

1. 5-HT inhibits spontaneous fluid secretion as well as stimulated secretion with secretin (cAMP mediated) or ACh (Ca2+ mediated) in the isolated guinea pig pancreatic ducts. 2. The inhibitory effect of 5-HT is reversible and is dependent on the concentration in the range 0.01-0.1 microM, which is much lower than those that affect intestinal motility and secretion. 3. The 5-HT3 receptor in duct cells appears to mediate the inhibitory effect of 5-HT. 4. [Ca2+]i is unlikely to mediate the inhibitory effect of 5-HT.
5-Methoxytryptamine/pharmacology ; Acetylcholine/pharmacology ; Animal ; Calcium/metabolism ; Guinea Pigs ; Pancreatic Ducts/metabolism* ; Pancreatic Ducts/drug effects ; Secretin/pharmacology ; Serotonin/pharmacology ; Serotonin/metabolism* ; Serotonin/analogs & derivatives* ; Vasodilator Agents/pharmacology

No abstract available.
Animal ; Bicarbonates/metabolism* ; Biological Transport/physiology ; Pancreatic Ducts/metabolism* ; Perfusion