Altered gut microbiota in patients with small intestinal bacterial overgrowth.

BACKGROUND AND AIM: Small intestinal bacterial overgrowth (SIBO) is diagnosed by using quantitative culture of duodenal aspirates and/or a hydrogen breath test. However, few studies have analyzed bacterial microbiota in Japanese patients with SIBO. METHODS: Twenty-four patients with any abdominal symptoms and suspected SIBO were enrolled. Quantitative culture of duodenal aspirates and a glucose hydrogen breath test were performed on the same day. SIBO was diagnosed based on a bacterial count ≥ 103  CFU/mL or a rise in the hydrogen breath level of ≥ 20 ppm. The composition of the duodenal microbiota was analyzed by 16S rRNA gene sequencing. RESULTS: Small intestinal bacterial overgrowth was diagnosed in 17 of the 24 patients (71%). The positive rates for the hydrogen breath test and quantitative culture of duodenal aspirates were 50% and 62%, respectively. Patients with SIBO showed significantly reduced α-diversity compared with non-SIBO patients, and analysis of ß-diversity revealed significantly different distributions between SIBO and non-SIBO patients. In addition, the intestinal microbiome in SIBO patients was characterized by increased relative abundance of Streptococcus and decreased relative abundance of Bacteroides compared with non-SIBO patients. CONCLUSIONS: Duodenal dysbiosis was identified in patients with SIBO and may play a role in the pathophysiology of SIBO.

Clinical effect of home enteral tube feeding supplementation on nutritional status after esophagectomy with retrosternal gastric tube reconstruction.

Body weight loss and poor nutritional status are frequently observed after esophageal cancer surgery. The aim of this study was to pilot an investigation on the impact of home enteral tube feeding supplementation (HES) for up to 3 months after esophageal cancer surgery. We retrospectively reviewed consecutive 67 esophageal cancer patients who underwent esophagectomy with gastric tube reconstruction. We started HES from April 2017. The patients were divided into 2 groups. Among 67 patients, 40 patients underwent HES between April 2017 and November 2020 (HES group). Other 27 patients who underwent esophagectomy between January 2012 and March 2017 were not administered HES (C group). Thereafter, multiple factors concerning patient nutritional status at long-term follow-up were evaluated. The baseline characteristics were balanced between the two groups. There were no significant differences in nutritional status scores before esophagectomy. The percentage weight loss was less in the HES group compared with the C group both at 3 months and 1 year after surgery: 7.3% (-7.6 to 15.2), 7.7% (-4 to 13.9) in the HES group and 10.6% (-3.6 to 29.1), 10.8% (-5.8 to 20.0) in C group (P < 0.05, P < 0.05). In the patients with anastomotic stenosis, the percentage weight loss was less in the HES group compared with the C group: 7.2% (2.0-14.9) and 14.6% (6.2-29.1), P < 0.05. HES may improve early weight loss in postesophagectomy patients.

Effect of the Gastrojejunostomy Position on the Postoperative Amount of Oral Intake in Pancreaticoduodenectomy.

INTRODUCTION: We investigated the effect of the gastrojejunostomy position on the postoperative oral intake in patients who have undergone pancreaticoduodenectomy (PD). METHODS: We investigated 119 patients who underwent PD between June 2013 and December 2019 and examined the effect of the horizontal and vertical distance rates of the gastrojejunostomy position on the postoperative oral intake. The patients were categorized as having poor or good oral intake based on whether their intake was up to half the required calorie intake. RESULTS: There were significant differences in the number of cases with grade B or C postoperative pancreatic fistula (good, 20.3% vs. poor, 60.0%; p < 0.001), horizontal distance rate (good, 0.57 vs. poor, 0.48; p = 0.02), and postoperative hospitalization period (good, 15 vs. poor, 35 days; p < 0.001). However, there was no significant difference in the vertical distance rate (good, 0.67 vs. poor, 0.71; p = 0.22). The horizontal distance rate was the independent risk factor for postoperative poor oral intake at 2-3 weeks (risk ratio, 3.69; 95% CI: 1.48-9.20). DISCUSSION: The oral intake was greater in patients whose gastrojejunostomy position in PD was farther from the median, suggesting the necessity of intraoperative placement of the gastrojejunostomy position as far from the median as possible.

Ustekinumab trough levels predicting laboratory and endoscopic remission in patients with Crohn's disease.

BACKGROUNDS: Optimal concentration of ustekinumab (UST) predicting endoscopic remission has not been fully investigated in Crohn's disease (CD). We aimed to identify the optimal UST trough levels predicting clinical, laboratory and endoscopic remission in CD patients. METHODS: Twenty-eight patients with CD were enrolled and investigated (27 patients by enteroscopy and 1 by colonoscopy). The endoscopic activity was assessed using the scoring system that applied the Rutgeerts score to observed intestine. Serum UST trough levels and anti-UST antibodies (AUAs) levels were determined by in-house immunoassays. RESULTS: Endoscopic activity was negatively correlated with serum UST trough levels (Spearman's rank correlation coefficient (ρ) = - 0.66, P = 0.0001) and serum albumin levels (ρ = - 0.60, P = 0.0007). The endoscopic activity was positively and significantly correlated with CRP (ρ = 0.59, P = 0.0009) and ESR (ρ = 0.44, P = 0.033). There was no significant association between the endoscopic score and AUA levels and/or Crohn's disease activity index (CDAI). Serum UST trough levels and albumin levels were significantly higher in the endoscopic remission group (scores of 0 and 1) than in the non-endoscopic remission group (UST trough, mean 3.3 vs. 1.8 µg/mL). No significant difference was observed in AUAs between the endoscopic remission and non-remission groups. Receiver operation curve (ROC) analysis revealed that the optimal cutoff value of UST trough levels predicting normal CRP and serum albumin levels was 1.7 µg/mL for each, and the optimal cutoff value predicting endoscopic remission was 2.0 µg/mL (AUC: 0.80, 95% CI 0.64-0.96). CONCLUSION: Achievement of endoscopic remission requires higher UST trough levels than required for normalization of CRP and serum albumin levels.

Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures (supplement to the Clinical Practice Guidelines for Enteroscopy).

Balloon-assisted enteroscopy allows endoscopic treatments in the deeper segments of the small bowel. Endoscopic balloon dilation has become a popular minimally invasive alternative for the treatment of Crohn's disease-associated small intestinal strictures. As a supplement to the Clinical Practice Guidelines for Enteroscopy, the Japan Gastroenterological Endoscopy Society's Working Committee has developed the present "Guidelines for endoscopic balloon dilation in treating Crohn's disease-associated small intestinal strictures," based on new scientific techniques and evidence. The guidelines cover standard procedures for the insertion route of the balloon endoscope, bowel preparation, indications, procedure-related complications, efficacy, target diameter and duration, management of multiple strictures, and the current state of combined and alternative treatments. Unresolved future research questions are also listed in this guideline.

[Fecal microbiota transplantation for refractory Clostridioides difficile infection with Crohn's disease in an allogeneic bone marrow transplant recipient].

We report a case of a 15-year-old girl who developed refractory Clostridioides difficile infection (CDI) after allogeneic bone marrow transplantation (BMT). She was treated successfully with fecal microbiota transplantation (FMT). The patient who had aplastic anemia underwent allogeneic BMT from an HLA 1-locus-mismatched unrelated donor. Four months later, she developed gastrointestinal graft-versus-host disease (GVHD), and immunosuppressive treatment improved the GVHD. However, she developed CDI 5 months after BMT and experienced recurrence after that. Fifteen months after transplant, CDI relapsed despite discontinuation of immunosuppressive treatment; thus, she underwent FMT. Colonoscopy at the time of FMT revealed round aphthae, mainly in the ileocecum, and colonic biopsy revealed inflammatory cell infiltration and noncaseating epithelioid granuloma, which fulfilled the diagnostic criteria for Crohn's disease. Following FMT for CDI, she was treated with enteric budesonide and intravenous methotrexate for Crohn's disease. These interventions resulted in a marked improvement in both CDI and Crohn's disease. Twenty-eight months after FMT, both CDI and Crohn's disease remained in remission with oral mesalamine monotherapy.

[A case of obstructive jaundice due to the movement of pancreatic calculi].

A 44-year-old man with a history of chronic alcoholic pancreatitis and Crohn's disease presented with abdominal pain. Computed tomography revealed pancreatic calculi in the head of the pancreas and a dilated pancreatic duct. The patient was diagnosed with an acute exacerbation of chronic pancreatitis due to the impact of pancreatic calculi on the main pancreatic duct. During the clinical course, the movement of pancreatic calculi to the major papilla was confirmed, leading to obstructive jaundice. Endoscopic treatment with sphincterotomy of the pancreatic duct was successful. Herein, we report the case of an unusual clinical course involving obstructive jaundice caused by the movement of pancreatic calculi.

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Factors Affecting Energy Metabolism and Prognosis in Patients with Amyotrophic Lateral Sclerosis.

BACKGROUND/AIMS: Nutritional status is a factor affecting prognosis in patients with amyotrophic lateral sclerosis (ALS). Here, we aimed to clarify the factors associated with hypermetabolism and the prognosticators of ALS. METHODS: Forty-two inpatients (22 men, 20 women) diagnosed with ALS according to the revised El-Escorial criteria were investigated. The following data were retrospectively analyzed: anthropometric measurements, blood biochemistry, disease severity, basal energy expenditure (BEE), resting energy expenditure (REE) measured by indirect calorimetry, spirometry, and bioelectrical impedance analysis. Single and multiple regression analysis was performed to examine factors affecting REE and metabolic changes (defined as the ratio of REE to fat-free mass [FFM]). The Kaplan-Meier method was used to examine factors associated with the occurrence of cumulative events (death or tracheostomy). RESULTS: Among the 42 inpatients, REE was significantly higher than BEE, indicating hypermetabolism in ALS. Multiple regression analysis revealed that REE/FFM is strongly associated with the skeletal muscle index (-3.746 to -1.532, p < 0.0001) and percent forced vital capacity (%FVC) (-0.172 to -0.021, p = 0.013). Moreover, both the skeletal muscle index and %FVC were significant prognosticators associated with the occurrence of cumulative events. CONCLUSIONS: Energy metabolism was elevated in ALS, and respiratory status and muscle mass were associated with the hypermetabolism and poor prognosis. Adequate nutritional support may improve outcomes in ALS by preventing deterioration of respiratory status and reduction in muscle mass.

Vonoprazan vs lansoprazole for the treatment of artificial gastric ulcer after endoscopic submucosal dissection: a prospective randomized comparative study.

Vonoprazan is a potent inhibitor of gastric acid secretion and may have better response than proton pump inhibitors (PPIs) in the treatment of endoscopic submucosal dissection induced artificial ulcers. However, reported outcomes remain controversial. In this study, we conducted a prospective, randomized comparative trial to evaluate healing effects of vonoprazan and lansoprazole on endoscopic submucosal dissection (ESD)-induced ulcers. We enrolled 216 patients who underwent endoscopic submucosal dissection for early gastric neoplasms. They were randomly divided into vonoprazan (20 mg/day) and lansoprazole (30 mg/day) groups. The primary endpoint was the reduction rate of ulcer and complete healing (scar) ratio of ESD-induced ulcers at 4 and 8 weeks. Finally, 101 patients of the vonoprazan group and 95 patients of the lansoprazole group were included in the analysis. There were no significant differences in the reduction rate between the vonoprazan and lansoprazole groups at either timepoint (4 weeks, 94.0 vs 93.4%; 8 weeks, 99.8 vs 99.9%, respectively). The complete healing ratio at 4 and 8 weeks did not differ significantly between the vonoprazan and lansoprazole groups (4 weeks, 11.9 vs 12.6%; 8 weeks, 87.1 vs 86.3%, respectively). In the anti-H. pylori-antibody negative or positive patients, there were no significant differences in the reduction rate and complete healing ratio between the vonoprazan and lansoprazole groups. Regardless of treatment choice, the overall complete healing ratio at 8 weeks was significantly higher in the anti-H. pylori-antibody negative patients than the positive patients (p = 0.006). The healing effects of vonoprazan on ESD-induced ulcers were comparative to those of lansoprazole.

Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease.

BACKGROUND AND AIM: Ustekinumab is a human monoclonal antibody to the p40 subunit of human IL-12/IL-23. The purpose of this report is to verify the newly developed immunoassays for serum ustekinumab and anti-ustekinumab antibody (AUA) concentrations and assess their clinical utility. METHODS: Serum ustekinumab trough levels and AUA levels were measured using new immunoassays in 38 patients with Crohn's disease under ustekinumab maintenance injection. RESULTS: Mean ustekinumab trough levels were 2.54 ± 2.1 µg/mL, and 3 of 38 patients (7.9%) were positive for AUAs. There was no association between ustekinumab trough levels and AUA levels. The optimal trough level of ustekinumab to maintain negative C-reactive protein levels (≤ 0.3 mg/dL) was 1.67 µg/mL determined by receiver operating characteristic curve analysis. Ustekinumab trough level negatively but significantly correlated with C-reactive protein, erythrocyte sedimentation rate, and Crohn's disease activity index and positively and significantly correlated with serum albumin levels. Ustekinumab trough levels were significantly higher in biologics-naïve patients than in biologics-experienced patients, although there was no difference in AUA levels. CONCLUSIONS: We developed new assays for serum ustekinumab trough and AUA levels. These assays might provide new insights into therapeutic drug monitoring-based management of Crohn's disease patients under ustekinumab therapy.

Energy Metabolism and Nutritional Status in Hospitalized Patients with Chronic Heart Failure.

INTRODUCTION: Malnutrition is a factor that defines vital prognosis in chronic heart failure. OBJECTIVE: This study investigated nutritional and metabolic disorders in patients with heart failure by examining the association of severity of heart failure with inflammatory cytokines, appetite-regulating hormones, and energy metabolism. METHODS: Subjects were 50 patients with heart failure. On admission, nutritional status was assessed, and biochemical blood tests were performed, including for serum tumor necrosis factor-α, interleukin-6, ghrelin, and leptin levels. Resting energy expenditure (REE) was also measured by indirect calorimetry to examine its association with severity of heart failure and levels of inflammatory cytokines and appetite-regulating hormones. RESULTS: There were significant associations between serum brain natriuretic peptide (BNP) level and nutrition indices, indicating that nutritional status was worse when heart failure was more severe. Inflammatory cytokine levels showed significant positive correlations with BNP level. Measured REE/bodyweight was not associated with severity of heart failure, but was negatively correlated with body fat percentage and leptin levels. CONCLUSIONS: Energy metabolism was not associated with serum BNP level among patients with heart failure with New York Heart Association functional class up to III. Body fat percentage and leptin levels may be a good predictor of energy metabolism in patients with heart failure.

The effect of preoperative synbiotic treatment to prevent surgical-site infection in hepatic resection.

We aimed to clarify the influence of preoperative synbiotic therapy on surgical-site infections (SSIs) after hepatic resection. Between January 2011 and December 2017, 284 patients who underwent hepatic resection without biliary tract reconstruction and resection of other organs were included. We prospectively administered Clostridium butyricum and partially hydrolyzed guar gum before hepatic resection between April 2016 and December 2017 (synbiotic group). One-hundred-fifteen patients of the synbiotic group and 169 patients (conventional group) treated between January 2011 and the end of March 2016 were compared using propensity score matching. The frequency of laparoscopic resection was significantly larger in the synbiotic group (conventional group; 28% vs synbiotic group; 55%, p<0.001) and the amount of intraoperative bleeding was significantly smaller in the synbiotic group (median; conventional group, 700 ml vs synbiotic group, 200 ml; p<0.001). The postoperative SSI was significantly lower in the synbiotic group of six patients (5.2%) than in the conventional group of 30 patients (17.8%) (p = 0.002). Sixty patients in each group remained after propensity score matching. There was no significant difference in the incidence of SSI between the groups (conventional group, 15% vs synbiotic group, 6.7%; p = 0.239). In conclusion, preoperative synbiotic treatment did not reduce SSIs after hepatic resection.

pH-Dependent 5-Aminosalicylates Releasing Preparations Do Not Affect Thiopurine Metabolism.

BACKGROUND/AIMS: Thiopurines are key drugs in maintenance therapy for treating inflammatory bowel disease (IBD). Time-dependent 5-aminosalicylates (5-ASA) releasing preparations (time-dependent 5-ASA) increase 6-thioguanine nucleotide (6-TGN), an active metabolite of thiopurines. However, the effects of pH-dependent 5-ASA releasing preparations (pH-dependent 5-ASA) on thiopurine metabolism were not reported. METHODS: We conducted a retrospective study of 134 IBD patients who received thiopurine treatment. The 6-methylmercaptopurine (6-MMP)/6-TGN values after taking the same dose of thiopurine preparations for at least 28 days were included. RESULTS: There was a significant decrease in the 6-MMP/6-TGN ratio in time-dependent 5-ASA compared with group without 5-ASA preparations and the pH-dependent 5-ASA group (p = 0.008 and < 0.001 respectively). Spearman's rank correlation coefficient indicated a negative relationship between the daily oral dose of time-dependent 5-ASA and the 6-MMP/6-TGN ratio (r = -0.362, p = 0.003). Multivariate logistic regression analysis was performed in the groups with 6-MMP/6-TGN ratios of 1 or more and less than 1. The use of time-dependent 5-ASA and concomitant allopurinol negatively affected the independent 6-MMP/6-TGN ratio (p = 0.006 and 0.007 respectively). CONCLUSION: Our study revealed that time-dependent but not pH-dependent 5-ASA decreases the 6-MMP/6-TGN ratio. We also confirmed that concomitant allopurinol results in a low 6-MMP/6TGN ratio.

Elemental diet induces alterations of the gut microbial community in mice.

The aim of the present study was to investigate elemental diet (ED)-induced alteration of the fecal and mucosal microbiome in mice. The control group was fed a normal chow and the ED group was fed normal chow containing 50% w/w Elental® (EA Pharma, Tokyo, Japan) for 28 days. Fecal and mucosal microbiome were analyzed using 16S rRNA gene sequencing. In the fecal samples, the observed species, an index for microbial richness, was significantly decreased in the ED group. Principal coordinate analysis revealed that there were significant compositional differences between the control and ED groups (PERMANOVA p = 0.0007 for unweighted and p = 0.002 for weighted UniFrac distance, respectively). In contrast, there was no significant difference in the overall structure of mucosal microbiome between the control and ED groups. In the fecal samples, abundance of the genera Adlercreutzia, Akkermansia, Streptococcus, Helicobacter, Coprobacillus and Coprococcus was significantly reduced in the ED group compared to the control group. Abundance of the genera Lactobacillus and Staphylococcus was significantly increased in the ED group. In a functional analysis using PICRUSt software, ED altered various pathways involved in amino acid metabolism of the gut microbiome. In conclusion, ED caused a reduction in bacterial diversity and altered metabolic functions.

Astaxanthin, a xanthophyll carotenoid, prevents development of dextran sulphate sodium-induced murine colitis.

Astaxanthin is a xanthophyll carotenoid, which possesses strong scavenging effect on reactive oxygen species. In this study, we examined the effect of astaxanthin on dextran sulfate sodium (DSS)-induced colitis in mice. Experimental colitis was induced by the oral administration of 4% w/v DSS in tap water in C57BL/6J mice. Astaxanthin was mixed with a normal rodent diet (0.02 or 0.04%). Astaxanthin significantly ameliorated DSS-induced body weight loss and reduced the disease activity index. The ameliorating effects was observed in a dose-dependent manner. Immunochemical analyses showed that astaxanthin markedly suppressed DSS-induced histological inflammatory changes (inflammatory cell infiltration, edematous changes and goblet cell depletion). Plasma levels of malondialdehyde and 8-hydroxy-2-deoxyguanosine were significantly reduced by the administration of 0.04% astaxanthin. Astaxanthin significantly suppressed the mucosal mRNA expression of IL-1ß, IL-6, TNF-α, IL-36α and IL-36γ. Astaxanthin blocked the DSS-induced translocation of NF-κB p65 and AP-1 (c-Jun) into the nucleus of mucosal epithelial cells, and also suppressed DSS-induced mucosal activation of MAPKs (ERK1/2, p38 and JNK). In conclusion, astaxanthin prevented the development of DSS-induced colitis via the direct suppression of NF-κB, AP-1 and MAPK activation. These findings suggest that astaxanthin is a novel candidate as a therapeutic option for the treatment of inflammatory bowel disease.

Successful Helicobacter pylori eradication therapy improves symptoms of chronic constipation.

BACKGROUNDS AND AIMS: Constipation is one of the most common gastrointestinal functional disorders. Recently, the gut microbiota has been implicated in the development of constipation. Helicobacter pylori infection is considered to be a possible factor influencing the gut microbiota profile. Here, we investigated the effect of H. pylori eradication therapy on symptoms of chronic constipation. METHODS: We recruited 166 H pylori-positive patients who underwent eradication therapy after endoscopy. We evaluated the severity of symptoms of chronic constipation before eradication therapy and 2 months post-therapy using two questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Izumo scale. In addition, we evaluated association with constipation and H. pylori infection in patients with constipation-related symptoms in not only all patients, but also patients with the constipation-related symptoms in relation to eradication outcome, the severity of constipation-related symptoms, and the severity of endoscopic gastric mucosal atrophy. RESULTS: Mean GSRS scores were 5.10 ± 2.67 in all patients and 6.15 ± 2.91 in constipation patients which were significantly lower than that before eradication (5.78 ± 3.27, P < 0.01 and 8.19 ± 3.09, P < 0.01, respectively). Constipation-related scores of the GSRS questionnaire in the successful eradication group were significantly improved after eradication from 5.63 ± 3.06 in all patients and 8.00 ± 2.85 in constipation patients to 5.11 ± 2.71 (P = 0.02) and 6.16 ± 2.96 (P < 0.01), while scores in the failed eradication group before and after eradication were similar. Constipation-related scores in patients with mild gastric atrophy (Kimura-Takemoto classification, C-I to O-I) were significantly decreased after eradication, but were not decreased in patients with severe atrophy (O-II and O-III). CONCLUSIONS: Successful eradication therapy for H. pylori infection may confer additional benefits in H. pylori-positive patients with symptoms of chronic constipation, especially in patients with mild gastric atrophy.

Dexmedetomidine is safe and reduces the additional dose of midazolam for sedation during endoscopic retrograde cholangiopancreatography in very elderly patients.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) often requires deep sedation. Dexmedetomidine, a highly selective α2-adrenoceptor agonist with sedative activity and minimal effects on respiration, has recently been widely used among patients in the intensive care unit. However, its use in endoscopic procedures in very elderly patients is unclear. In this study, we retrospectively investigated the safety and efficacy of dexmedetomidine sedation during ERCP. METHODS: The study included 62 very elderly patients (aged over 80 years) who underwent ERCP from January 2014, with sedation involving dexmedetomidine (i.v. infusion at 3.0 µg/kg/h over 10 min followed by continuous infusion at 0.4 µg/kg/h) along with midazolam. For comparison, the study included 78 patients who underwent ERCP before January 2014, with midazolam alone. We considered additional administration of midazolam as needed to maintain a sedation level of 3-4, according to the Ramsay sedation scale. The outcome measures were amount of midazolam, adverse events associated with sedation, and hemodynamics. RESULTS: The incidence of decreased SpO2 and median dose of additional midazolam were significantly lower in the dexmedetomidine group than in the conventional group. The minimum systolic blood pressure and minimum heart rate during and after examination was significantly lower in the dexmedetomidine group than in the conventional group. However, serious acute heart failure or arrhythmia was not noted. CONCLUSIONS: Dexmedetomidine can decrease the incidence of respiratory complications and the total dose of other sedative agents. It can be used as an alternative to conventional methods with midazolam for adequate sedation during ERCP in very elderly patients.

Long-term retention of adalimumab treatment and associated prognostic factors for 1189 patients with Crohn's disease.

BACKGROUND AND AIM: There are few studies on the long-term efficacy of adalimumab treatment for patients with Crohn's disease. We have conducted a large, multicenter, retrospective cohort study to evaluate the long-term retention rate and prognostic factors associated with the discontinuation of adalimumab treatment in patients with Crohn's disease. METHODS: Data were collected from all patients with Crohn's disease who had received at least one induction dose of 160 mg of adalimumab between October 2010 and December 2013 at 41 institutions. The cumulative retention rates of adalimumab treatment following the first administration were estimated using the Kaplan-Meier method. Prognostic factors related to the cumulative retention rates were evaluated by log-rank tests and multivariate Cox regression analysis. RESULTS: A total of 1189 patients were included in the study. The 1-, 2-, 3-, and 4-year cumulative retention rates of adalimumab were 81%, 72%, 65%, and 62%, respectively. The multivariate Cox regression analysis confirmed female sex, previous infliximab use, perianal disease, concomitant treatment with prednisolone at baseline, higher C-reactive protein levels, and lower albumin levels as significant independent predictors of poor retention rate of adalimumab treatment. Significantly, more female patients than male patients discontinued adalimumab because of adverse events, especially skin reactions, infections, and arthralgia. CONCLUSIONS: Our data demonstrated a good retention rate of adalimumab in patients with Crohn's disease over a 4-year period. Female sex, perianal disease, concomitant treatment with prednisolone at baseline, previous infliximab use, higher C-reactive protein levels, and lower albumin levels were associated with poor retention of adalimumab treatment.

Ameliorating effects of bortezomib, a proteasome inhibitor, on development of dextran sulfate sodium-induced murine colitis.

We examined the effect of bortezomib, a proteasome inhibitor, on the development of dextran sulfate sodium (DSS)-induced colitis in mice. DSS-colitis was induced by the administration of 3% DSS in water in C57BL/6J mice. Bortezomib was intraperitoneally administered daily for 9 days from the start of DSS. Ubiquitination of IκBα was evaluated by immunoblot. Bortezomib significantly ameliorated DSS-induced body weight loss and reduced the disease activity. The translocation of NF-κBp65 into the nucleus was markedly suppressed in the DSS + bortezomib group compared to the DSS group, but this difference was not detected in submucosal tissue. Ubiquitinated IκBα in the cytoplasm of colon epithelial cells was increased in the DSS + bortezomib group compared to the DSS group. In HT-29 cells, bortezomib blocked tumor necrosis factor-α (TNF-α)-induced nuclear translocation of NF-κB and this was accompanied by an increase in ubiquitinated IκBα in the cytoplasm. The mRNA expression of inflammatory mediators in colonic epithelial cells was significantly reduced by the treatment of bortezomib. Bortezomib inhibited the nuclear translocation of NF-κB in colonic epithelial cells by suppressing the degradation of IκBα and contributed to an improvement in DSS colitis. Our study suggests that bortezomib may be a new treatment option for IBD.