Bifidobacterium breve Bif195 ameliorates aspirin-induced gastric mucosal damage: A randomised, double blind, placebo-controlled crossover trial.

BACKGROUND: Gastric and duodenal ulcerations are common during multiple-dosing aspirin treatment, such as for prevention of cardiovascular disease. On capsule endoscopy, oral administration of the bacterial strain Bifidobacterium breve Bif195 (DSM 33360) reduced the risk of aspirin-induced small intestinal damage, without affecting cyclo-oxygenase-2 (COX-2) inhibition. AIM: To evaluate endoscopically the effect of Bif195 on aspirin-induced stomach and duodenal mucosal damage METHODS: Twenty-five healthy volunteers underwent two intervention periods in a randomised, double-blind, placebo-controlled crossover design including four gastroduodenoscopies and 6 weeks washout. Each intervention was a 4-week oral co-treatment of aspirin 300 mg daily and Bif195 (≥1011 colony-forming units daily) or placebo. Primary endpoint was change in Lanza score - ranging from 0 (normal mucosa) to 4 (>10 erosions or ulcer). RESULTS: All 25 participants (56% females); age 27.3 (±4.8) years; BMI 23.2 (±3.4) kg/m2 , completed the trial exhibiting significant increases in Lanza scores during placebo treatment as compared to baseline. Bif195 reduced gastric Lanza score with an odds ratio of 7.2 (95% confidence interval 1.72-30.08, p = 0.009) compared to placebo with no related adverse events. There were no significant changes in Lanza scores in the duodenum. CONCLUSIONS: Bif195 reduces aspirin-induced gastric mucosal damage and may serve as a safe supplement during multiple-dosing aspirin treatment.

Deferasirox causing duodenal ulcer leading to upper gastrointestinal bleed and hemorrhagic shock in a child with beta-thalassemia major.

Iron chelators have significantly reduced the morbidity associated with iron overload and improved the quality of life in children with beta-thalassemia major. A 5-year-old female child with beta-thalassemia major on recurrent transfusions and oral chelation with deferasirox was brought with repeated episodes of frank hematemesis and progressive lethargy. Her evaluation revealed anemia, leukocytosis, and deranged liver function with coagulopathy. She was given red blood cell and plasma transfusions with liver supportive medication and proton-pump inhibitor (PPI) infusion. Her upper gastrointestinal endoscopy revealed multiple ulcers in all three parts of the duodenum, which in the absence of any other likely etiology were attributed to prolonged use of oral deferasirox. The child improved with the above-mentioned measures. Chelation therapy was withheld for 2 weeks and restarted at a lower dose using enteric-coated preparation while PPIs were given for 8 weeks. She showed sustained improvement and remained well on follow-up.

Efficacy and Safety of Keverprazan Compared With Lansoprazole in the Treatment of Duodenal Ulcer: A Phase III, Randomized, Double-Blind, Multicenter Trial.

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.

Duodenal Ulcer Perforation after Activated Charcoal Treatment.

Activated charcoal, having the capacity to absorb substances with its porous surface, has been used in intoxication treatment for nearly 200 years. Although live-saving, occasionally, it can lead to complications. Because of the risk of perforation during activated charcoal therapy, the integrity of the gastrointestinal tract should be checked after the procedure. In this case report, a 27-year patient, who received activated charcoal therapy after diclofenac intoxication developed duodenal ulcer perforation and charcoal peritonitis. The present case constitutes the first report of duodenal ulcer perforation after activated charcoal therapy. It should be remembered that activated charcoal, which is widely used in intoxication treatment, may cause gastrointestinal system perforation, peritonitis, adhesion, abscess formation, organ loss within the abdomen, and prolonged hospitalization. Key Words: Activated charcoal, Intoxication, Duodenal ulcer perforation.

Traditional Chinese Medicine prescription Huang-Qi-Jian-Zhong-Tang ameliorates indomethacin-induced duodenal ulcers in rats by affecting NF-κB and STAT signaling pathways.

Huang-Qi-Jian-Zhong-Tang (HQJZT) is a well-known traditional Chinese herbal formulation. This study aimed to investigate the duodenoprotective properties of HQJZT against Indomethacin (IND)-induced duodenal ulceration in rats, and the mechanisms involved, particularly through NF-κB and STAT signaling pathways. Our results showed that HQJZT completely protected the duodenal mucosa from ulceration caused by IND, as indicated by improved macroscopic and histological appearances. There was a significant decrease in ulcer index and microscopic score, an increase in villus height and crypt depth, and a normalization of the tissue architecture of the duodenum in rats following HQJZT treatment. Blood flow into the duodenal mucosa was significantly increased after HQJZT administration. HQJZT significantly increased PGE2 and NO levels in the duodenal mucosa. A significant reduction in the production of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was observed in the duodenal mucosa under treatment with HQJZT. Mechanistically, the administration of HQJZT significantly lowered the duodenal protein expression of inflammation-related genes, including p-NF-κB and p-IκBß, compared with the ulcer control group. Furthermore, the STAT signaling pathway-related protein markers p-JAK and p-STAT were significantly reduced in the HQJZT (1.30 and 2.60 g/kg) groups. As a result of these findings, HQJZT alleviates duodenal mucosal ulcers caused by IND. A protective effect of HQJZT on duodenal ulcers is attributed to its ability to improve mucosal blood flow, stimulate the production of cytoprotective mediators, minimize proinflammatory cytokines, and block the activation of NF-κB and STAT signaling pathways.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Drug-induced duodenal perforation in the paediatric patient with thalassemia major, an unreported side effect of iron- chelating agent: A case report.

Duodenal ulcer disease is uncommon in paediatric age group. Its perforation is even rarer. However, it should be kept in mind when examining children with acute abdomen especially if there are signs of shock or possibility of upper gastrointestinal bleed. We report a case of a 6 years old female child, a known case of thalassemia major and taking oral Deferasirox since two years of age. She had atypical presentation as there was no previous history of peptic ulcer disease and she only suffered epigastric pain and vomiting for a week but due to lack of proper diagnosis at a local clinic developed duodenal ulcer perforation, which was ultimately diagnosed at a tertiary care hospital and managed with Graham Patch Closure.

Strongly increased risk of gastric and duodenal ulcers among new users of low-dose aspirin: results from two large cohorts with new-user design.

BACKGROUND: Low-dose aspirin is a risk factor for peptic ulcer disease but previous, population-based cohort studies may have underestimated the low-dose aspirin risk because they did not use a new-user design. Gastrointestinal bleeding occurs more frequently early after initiation of low-dose aspirin therapy than in later years. AIM: To assess the associations of low-dose aspirin with gastric and duodenal ulcer incidence in prevalent- and new-user design. METHODS: Multivariate Cox regression models in the German ESTHER study (N = 7737) and the UK Biobank (N = 213,598) with more than 10 years of follow-up. RESULTS: In the prevalent-user design, there was no significant association between low-dose aspirin and gastric ulcer observed in both cohorts. Furthermore, low-dose aspirin was weakly, statistically significantly associated with prevalent duodenal ulcer in the UK Biobank (hazard ratio [95% confidence interval]: 1.27 [1.07-1.51]) but not in the ESTHER study (1.33 [0.54-3.29]). When restricting the exposure to only new users, the hazard ratios for incident gastric and duodenal ulcer disease were 1.82 [1.58-2.11] and 1.66 [1.36-2.04] in the UK Biobank, respectively, and 2.83 [1.40-5.71] and 3.89 [1.46-10.42] in the ESTHER study, respectively. CONCLUSIONS: This study shows that low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers. The associations were not significant or weak in the prevalent-user design and strong and statistically significant in the new-user design in both cohorts. Thus, it is important to weigh risks against benefits when low-dose aspirin treatment shall be initiated and to monitor adverse gastrointestinal symptoms after the start of low-dose aspirin therapy.

Vonoprazan non-inferior to lansoprazole in treating duodenal ulcer and eradicating Helicobacter pylori in Asian patients.

BACKGROUND AND AIM: Duodenal ulcers, especially caused by increasingly drug-resistant Helicobacter pylori, are a concern in Asia. We compared oral vonoprazan versus lansoprazole for efficacy (healing duodenal ulcers) and safety in non-Japanese Asian patients. METHODS: In this phase 3, randomized (1:1), double-blind, double-dummy, parallel-group, non-inferiority study (April 5, 2017, to July 19, 2019), patients with ≥ 1 endoscopically confirmed duodenal ulcer, at 52 hospitals (China, South Korea, and Taiwan), received vonoprazan 20 mg once daily (QD) or lansoprazole 30 mg QD for 6 weeks maximum. Patients with H. pylori received bismuth-containing quadruple therapy including vonoprazan 20 mg twice daily (BID) or lansoprazole 30 mg BID, for 2 weeks, followed by vonoprazan or lansoprazole monotherapy QD (4 weeks maximum). Endpoints were endoscopically confirmed duodenal ulcer healing (Week 4/6; primary) and H. pylori eradication (4 weeks post-treatment; secondary); non-inferiority margins were -6% and -10%, using a two-sided 95% confidence interval (CI). RESULTS: Of 533 enrolled patients, one was lost to follow-up and one withdrew (full analysis set: 531 patients [vonoprazan, n = 263; lansoprazole, n = 268]; 85.4% = H. pylori positive). Vonoprazan was non-inferior to lansoprazole for duodenal ulcer healing (96.9% vs 96.5%; difference 0.4% [95% CI -3.00, 3.79]). H. pylori eradication rates were 91.5% (vonoprazan) and 86.8% (lansoprazole; difference 4.7% [95% CI -1.28, 10.69]). Vonoprazan and lansoprazole were well tolerated, with similar safety profiles, no new safety signals; no deaths occurred. CONCLUSIONS: Vonoprazan was well tolerated and non-inferior to lansoprazole for duodenal ulcer healing and achieved H. pylori eradication above the clinically meaningful threshold (90%), in non-Japanese Asian patients.

The clinical and endoscopic aspects of peptic ulcers secondary to the use of nonsteroidal anti-inflammatory drugs of various origins.

INTRODUCTION: currently, the non-steroid anti-inflammatory drugs constitute a veritable object of auto medication throughout the world. The goal of this study was to evaluate the endoscopic and clinical aspects of gastro-duodenal ulcer secondary to taking of non-steroid anti-inflammatory of various sources. METHODS: this was a cross-sectional study which was conducted between July 2016 and December 2017. All adult patients admitted to hospital for clinical symptoms suggestive of gastroduodenal involvement after taking anti-inflammatory drugs and having undergone upper digestive endoscopy were included in this study. Data analysis was done with Epi-info version 7 Software. RESULTS: a total of 114 patients were included, the mean age was 47.18±26 years with a male predominance (64.9%). Among the patients, only 1.75% had taken a non-steroid anti-inflammatory (NSAIDs) from pharmacy. The NSAIDs used were of different types: diclofenac, aceclofenac, aspirin and non-selective NSAIDs. For each drug used, more than half were derived from the streets. Clinically we noted: the dyspepsia (38.58%), hemorrhages (11.40%), the ulcerous syndrome (77.19%), haematemesis (19.29%), haematemesis associated with melena (37.71%), and the rectorrhagia in 6.14 of cases. The specific endoscopic lesions were bulbar ulcer (45.61%), gastric ulcers (20.17%), antral ulcerations (5.26%) and acute gastritis (9.64%), esophagitis (7.89%), esophageal varices (6.14%), and uncomplicated hiatal hernia in 7.01% of cases. CONCLUSION: the serious gastroduodenal lesions observed in this study and due to use of NSAIDs are mainly attributable to unauthorized molecules due to safety concerns. It would be necessary to conduct sensitization days at the community level and in each health facility.

Obstructive Jaundice Due to Duodenal Ulcer Induced by Lenvatinib Therapy for Hepatocellular Carcinoma.

An 82-year-old man with hepatocellular carcinoma presented with upper abdominal pain, vomiting, and jaundice. He had been taking a standard lenvatinib dose for three months. Although acute cholangitis was suggested, imaging studies failed to detect the biliary obstruction site. An endoscopic examination following discontinuation of lenvatinib and aspirin revealed multiple duodenal ulcers, one of which was formed on the ampulla of Vater and causing cholestasis. Endoscopic biliary drainage and antibiotics improved concomitant Enterobacter cloacae bacteremia. Ulcer healing was confirmed after rabeprazole was replaced with vonoprazan and misoprostol. Our case shows that lenvatinib can induce duodenal ulcers resulting in obstructive jaundice.

Management of Peptic Ulcer Bleeding in Patients Taking Aspirin or Anticoagulant.

Antiplatelet and anticoagulation agents are increasingly prescribed for secondary prophylaxis in patients with cardiovascular and cerebrovascular diseases. These drugs are associated with an increased risk of gastrointestinal bleeding, including peptic ulcer bleeding. It is difficult to decide when to restart the agents after peptic ulcer bleeding in these patients because the risk of rebleeding and thromboembolism should be balanced. The Korean College of Helicobacter and Upper Gastrointestinal Research revised the guidelines for drug-induced peptic ulcers as evidence-based guidelines using a de novo process. This paper introduces new recommendations on the resumption of antiplatelet and anticoagulation agents after peptic ulcer bleeding based on the revised guidelines for drug-induced peptic ulcers.

Lessons of the month 3: Duodenal perforation after polystyrene sulfonate.

Ion-exchange resins, sodium or calcium polystyrene sulfonate, are commonly used medications for management of hyperkalaemia. However, the drug can be associated with serious bowel injury. We report a case of a renal transplant recipient who developed duodenal ulcer perforation secondary to the use of calcium polystyrene sulfonate. Characteristic eosinophilic non-polarisable rhomboid shaped crystals were evident in the affected area of ulceration on histologic examination in addition to features of cytomegalovirus inclusions. We also hypothesised that gastroparesis secondary to autonomic dysfunction could have led to prolonged luminal contact time with polystyrene, further predisposing to bowel injury.

STW 5 is effective against nonsteroidal anti-inflammatory drugs induced gastro-duodenal lesions in rats.

BACKGROUND: Proton pump inhibitors are often used to prevent gastro-intestinal lesions induced by nonsteroidal anti-inflammatory drugs. However, they are not always effective against both gastric and duodenal lesions and their use is not devoid of side effects. AIM: To explore the mechanisms mediating the clinical efficacy of STW 5 in gastro-duodenal lesions induced by nonsteroidal anti-inflammatory drugs (NSAIDs), exemplified here by diclofenac, in a comparison to omeprazole. METHODS: Gastro-duodenal lesions were induced in rats by oral administration of diclofenac (5 mg/kg) for 6 successive days. One group was given concurrently STW 5 (5 mL/kg) while another was given omeprazole (20 mg/kg). A day later, animals were sacrificed, stomach and duodenum excised and divided into 2 segments: One for histological examination and one for measuring inflammatory mediators (tumor necrosis factor α, interleukins-1ß and 10), oxidative stress enzyme (heme oxygenase-1) and apoptosis regulator (B-cell lymphoma 2). RESULTS: Diclofenac caused overt histological damage in both tissues, associated with parallel changes in all parameters measured. STW 5 and omeprazole effectively prevented these changes, but STW 5 superseded omeprazole in protecting against histological damage, particularly in the duodenum. CONCLUSION: The findings support the therapeutic usefulness of STW 5 and its superiority over omeprazole as adjuvant therapy to NSAIDs to protect against their possible gastro-duodenal side effects.