Novel adsorptive type apheresis device Immunopure for ulcerative colitis from clinical perspectives based on clinical trials: Japan and Europe.

Several adsorptive type devices for ulcerative colitis are used for the induction of remission in patients with active severe disease worldwide. In 2020, the novel apheresis device Immunopure for ulcerative colitis was launched in Japan. Immunopure, like the polyethylene terephthalate column, uses polyarylate, a type of polyester resin, as the adsorbent. Similar to the cellulose acetate column, Immunopure is filled with adsorbent beads and expected to provide ease of use, with minimal risk of column clogging. Immunopure adsorbs leukocytes and platelets, especially activated platelets and platelet-leukocyte aggregates. In this article, the capability of Immunopure is evaluated from clinical perspective based on a clinical trial in Japan/Europe. As a result, Immunopure is comparable to other products in clinical effectiveness and indicated for the treatment of patients with refractory moderate ulcerative colitis, making it highly useful in clinical practice.

[Comparison of transabdominal ultrasound with quantitative power Doppler and colonoscopic findings for the evaluation of colonic inflammation in active ulcerative colitis].

BACKGROUND: Transabdominal ultrasound is a promising technique to evaluate inflammatory bowel disease. Several studies have demonstrated a relationship between ultrasound findings and colonic inflammation. However, the applicability of transabdominal ultrasound in patients with ulcerative colitis (UC) has not been elucidated. The aim of this study was to clarify the relationship between the transabdominal ultrasound findings and endoscopic activity in patients with UC. METHODS: Patients with active and underwent transabdominal ultrasound and colonoscopy were enrolled in this retrospective single-center analysis. Blood flow in the bowel wall was evaluated by power Doppler ultrasound. Both the thickness and stratification of the bowel wall were assessed by B-mode ultrasound imaging. The endpoints were the correlations between the ultrasound appearances (i.e., blood flow, thickness, and stratification of the bowel wall) and endoscopic activity (endoscopic Mayo Score). RESULTS: There were 34 lesions in 26 patients evaluated. Blood flow and thickness of the bowel wall were positively significantly correlated with the endoscopic Mayo Scores (r=0.43, p=0.011 and r=0.503, p=0.002, respectively). According to the bowel stratification, the endoscopic Mayo Scores were significantly higher in unclear and diminished bowel wall stratifications than in the clear bowel wall stratifications (p<0.001 and p<0.001, respectively). When focusing on the endoscopic Mayo Scores of three lesions, blood flow was lower in ulcer lesions with a diameter of ≥10mm than in those with a diameter of <10mm. CONCLUSION: All transabdominal ultrasound findings of bowel blood flow, wall thickness, and wall stratification reflected colonic inflammation.

Seven days triple therapy for eradication of Helicobacter pylori does not alter the disease activity of patients with inflammatory bowel disease.

BACKGROUND/AIMS: The influences of Helicobacter pylori eradication therapy on the disease course of inflammatory bowel disease (IBD) are still unclear. We therefore conducted a multicenter, retrospective cohort study to evaluate the safety of H. pylori eradication therapy for IBD patients. METHODS: IBD patients with H. pylori eradication from 2005 to 2015 (eradication group) and control patients (non-eradication group; 2 paired IBD patients without H. pylori eradication matched with each eradicated patient) were included. IBD exacerbation (increased/additional IBD drug or IBD-associated hospitalization/surgery) and disease improvement based on the physicians' global assessment were investigated at baseline, and at 2 and 6 months after eradication or observation. RESULTS: A total of 429 IBD (378 ulcerative colitis, 51 Crohn's disease) patients, comprising 144 patients in the eradication group and 285 patients in the non-eradication group, were enrolled at 25 institutions. IBD exacerbation was comparable between groups (eradication group: 8.3% at 2 months [odds ratio, 1.76; 95% confidence interval, 0.78-3.92; P=0.170], 11.8% at 6 months [odds ratio, 1.60; 95% confidence interval, 0.81-3.11; P=0.172]). Based on the physicians' global assessment at 2 months, none of the patients in the eradication group improved, whereas 3.2% of the patients in the non-eradication group improved (P=0.019). Multivariate analysis revealed that active disease at baseline, but not H. pylori eradication, was an independent factor for IBD exacerbation during 2 months' observation period. The overall eradication rate was 84.0%-comparable to previous reports in non-IBD patients. CONCLUSIONS: H. pylori eradication therapy does not alter the short-term disease activity of IBD.

Changes in Treatment with Granulocyte and Monocyte Adsorptive Apheresis from the Past to Future in Patients with Inflammatory Bowel Disease.

BACKGROUND: Idiopathic acute-on-chronic inflammation in the gastrointestinal tract is an etiology of inflammatory bowel disease (IBD). Granulocyte and monocyte adsorptive apheresis (GMA) is a nonpharmacological treatment tool for patients with IBD. Here, we present a review of the positioning and possibilities of GMA for patients with IBD. SUMMARY: GMA decreases inflammatory cytokines and upregulates regulatory T cells. Intensive GMA is significantly more effective than weekly GMA in patients with IBD. The frequency of GMA sessions per week positively correlates with treatment effects. GMA can be safely used in pregnant women and children because of its low adverse event rates. Maintenance therapy and rescue therapy for loss of response of anti-tumor necrosis factor (TNF)-α antibodies are effective. Optimal patients who responded to combination therapy with infliximab and GMA showed aggravation characteristics against infliximab treatment at week 4. Key Message: Prospective randomized blinded studies using a sham column should be performed for the loss of response against anti-TNF-α antibodies.

Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository.

BACKGROUND: Ulcerative proctitis, one of the disease types of ulcerative colitis, is considered one of the initial manifestations of ulcerative colitis. Prevention of aggravation of ulcerative proctitis is important for improving the prognosis of ulcerative colitis. Here we reviewed the epidemiology, diagnosis, and management of ulcerative proctitis. SUMMARY: The number of patients with ulcerative proctitis is increasing. Disease extension occurs in many patients with ulcerative proctitis. Differential diagnosis from other chronic proctitis is important and should be performed based on the clinical history and endoscopical and histological features. Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis because of its high effectiveness and safety. Topical treatment of ulcerative proctitis, particularly using mesalazine suppository has been underused in clinical practice. Key Messages: Mesalazine suppositories are more effective than dose intensification of oral mesalazine for relapsed patients with maintenance dose of oral mesalazine. However, low adherence to rectal mesalazine has hindered remission in patients with ulcerative proctitis.

[Adherence to oral 5-aminosalicylic acid by patients with quiescent ulcerative colitis: a questionnaire survey].

For patients with ulcerative colitis, adherence to 5-aminosalicylic acid (5-ASA) is generally expected to ensure better maintenance of remission. Over the past 2 years, we have conducted a questionnaire survey in our hospital of 120 outpatients with quiescent ulcerative colitis to assess their adherence to oral 5-ASA. Of them, 112 patients responded. The overall adherence rate was 57%; however, the adherence rate for 5-ASA taken once a day was 95%, which was significantly higher than that for 5-ASA taken twice or three times a day (50%; P=0.00044). Univariate analysis revealed that the factors associated with high adherence included the following: type of 5-ASA derivative, intake of fewer drugs being at a time, and once-daily intake of 5-ASA. However, once-daily intake of 5-ASA was the only factor found to have a statistically significant effect using multivariate analysis. The adherence rate improved from 23% to 100% when the prescription for 5-ASA was changed from two or three times daily to once daily (P=0.000054).

The efficacy of intensive granulocyte and monocyte adsorption apheresis in a patient with Crohn's disease complicated by extensive subcutaneous aseptic neutrophilic abscesses.

BACKGROUND AND AIMS: Subcutaneous aseptic abscess is one phenotype of neutrophilic dermatitis. We were interested to see if a case of steroid refractory Crohn's disease (CD) complicated by subcutaneous aseptic neutrophilic abscesses responds to intensive granulocyte/monocyte adsorptive apheresis (GMA). METHODS: The patient was a 21-year-old male with worsening severe CD while on oral prednisolone (30 mg/day). His symptoms included fever, bloody diarrhoea and multiple painful subcutaneous nodules throughout his body. Skin biopsy showed chronic panniculitis with neutrophilic infiltrates. Further, colonoscopy showed oedematous sigmoid colon, while colonic biopsy showed non-caseous granuloma. Because biologics were feared to increase the risk of bacteraemia as the result of germ culture on his pus was not known at the time, we decided to treat this case with GMA. Five GMA sessions with the Adacolumn over 5 consecutive days (daily GMA) were initiated. RESULTS: On admission, his CD activity index (CDAI) was 355, C-reactive protein (CRP) 11.2 mg/dL. After 5 GMA sessions, CDAI decreased to 170, and CRP fell to 5.0 mg/dL, with no fever. GMA was restarted at 2 sessions/week (total 10 sessions). The patient's CDAI fell to <150, and the skin lesions re-epithelialized. CONCLUSIONS: In this CD case complicated by subcutaneous aseptic neutrophilic abscesses, GMA appeared to be effective. Our impression is that when biopsy reveals neutrophil infiltrate is a major feature of the lesions, GMA should be considered. As GMA appears to have no safety concerns, a frequent GMA protocol, like daily followed by 2 to 3 times/week should be preferred over the routine weekly GMA.

Comparison of adjuvant therapies by an H2-receptor antagonist and a proton pump inhibitor after endoscopic treatment in hemostatic management of bleeding gastroduodenal ulcers.

AIM: Upper gastrointestinal bleeding is often associated with a higher risk of serious blood loss. Both H2-receptor antagonists and proton pump inhibitors are commonly given intravenously for endoscopic hemostatic therapies. We compared the effects of a H2-receptor antagonist (famotidine) and a proton pump inhibitor (omeprazole) injected during the early phase (the first 3 days) on cessation of bleeding and prevention of its recurrence in patients who underwent endoscopic therapy for gastroduodenal ulcer bleeding. METHODS: Consecutive patients who were hospitalized at our clinic with bleeding gastroduodenal ulcers and underwent endoscopic therapy were randomly assigned to receive injections of famotidine, omeprazole, or both. Injection of acid suppressants was switched on the fourth day to the oral administration of omeprazole continued for 8 weeks. RESULTS: Over a 25-month period, 116 patients were enrolled. The overall success rate for endoscopic hemostasis was 115/116 (99.1%). The success rate of hemostasis and prevention of recurrent ulcer bleeding by type of acid suppressant following endoscopic hemostasis was 39/40 (97.5%) for Group 1 (3-day omeprazole administration), 35/37 (94.6%) for Group 2 (3-day famotidine administration), and 38/39 (97.4%) for Group 3 (1-day famotidine and then 2-day omeprazole administration), yielding an overall rate of 112/116 (96.6%). No significant difference in the hemostatic effect was observed among the groups. There were also no differences in the duration of hospital days and the number of fasting days between the three groups. CONCLUSION: Famotidine and omeprazole injected during the early phase of a bleeding ulcer may have similar effects to an adjuvant therapy for preventing rebleeding from endoscopically treated upper gastrointestinal bleeding in Japanese patients.

Treatment of refractory Crohn's disease by intensive granulocyte and monocyte adsorption apheresis: a report on two drug refractory cases.

Granulocyte and monocyte adsorption apheresis (GMA) is one therapeutic option for induction of remission in patients with inflammatory bowel diseases. Recently intensive GMA (2 sessions per week) was reported to be strikingly better than weekly GMA, both in remission rate and time to remission. Here we report two cases of Crohn's disease refractory to weekly GMA who responded to intensive GMA. One patient had not received immunosuppressive therapy while the other had been refractory to combination therapy with infliximab and azathioprine. Intensive GMA induced remission in these 2 patients. Intensive GMA may represent a therapeutic choice for remission induction and maintenance with infliximab.

Double balloon enteroscopy to retrieve an accidentally swallowed dental reamer deep in the jejunum.

Accidentally swallowed foreign objects are not uncommon but difficult to manage without complications. We describe the case of a 68 year old man who accidentally a swallowed sharp-pointed dental reamer that had reached deep in his jejunum. Double balloon enteroscopic retrieval was performed with polypectomy snare but the reamer was entangled in the wire loop of the snare and penetrated the jejunal wall. After releasing the reamer by pushing and pulling the snare for approximately 30 min, the reamer was retrieved with biopsy forceps. This is the first report of double balloon enteroscopic removal of a dental reamer. Furthermore, this is a novel case with regard to decision making in situations when sharp objects are swallowed.

[Change in function of gastric acid secretion by aging].

Until recently, gastric acid secretion has been believed to decrease according to age. Previously the atrophy of gastric mucosa that was the main cause for the decrease in acid secretion was understood as the phenomenon following aging. However, H. pylori was discovered and the infection was indicated to be the main cause for the atrophic change of gastric mucosa. In recent studies, gastric acid secretion has been indicated not to decrease in old people who have no atrophic change of gastric mucosa and the infection. Furthermore, some studies indicated an increase in gastric acid secretion in the old people compared with young people. Consequently the decrease in acid secretion according to aging is now thought to be the result of H. pylori infection and not the result of physiological aging.