Insights into the Structure of Sucralfate by Advanced Solid- and Liquid-State NMR.

Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by 27Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.

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.

Decision-Utility Analysis of Empiric Treatment Versus Test and Treat Strategies for Helicobacter pylori in Patients With Duodenal Ulcer.

OBJECTIVES: The optimal strategy of Helicobacter pylori eradication in patients with duodenal ulcer is unclear. In this study, we aimed to compare the utility and the ulcer recurrence rate using the empiric treatment versus the test and treat strategies in patients with uncomplicated duodenal ulcer. METHODS: A decision-utility analysis was performed using a decision tree. The empiric treatment strategy was compared with the test and treat strategy. The probabilities of recurrent ulcers were determined and utilities of the 2 strategies were compared using the quality-adjusted life-year (QALY). Sensitivity analysis was performed to evaluate for model robustness. RESULTS: The probability of recurrent ulcer with the empiric strategy was 10.5%. The probabilities of recurrent ulcer with the test and treat strategy were 12.6%, 14.7%, 16.8%, and 17.9% based on 95%, 90%, 85%, and 80% sensitivity for histopathology, respectively. At the 95% estimate for the sensitivity of histopathology, the empiric strategy was associated with greater QALY compared with the test and treat strategy, 0.9875 versus 0.9853. The empiric treatment strategy was associated with greater QALY at extreme values for the estimates in our model. CONCLUSIONS: The empiric treatment strategy is associated with 2.1% to 7.4% lower recurrence rate for a range of test sensitivity between 95% and 80%, and results in greater QALY compared with the test and treat strategy.

[A case of duodenal ulcer as prominent manifestation of IgG4-related disease].

A case of IgG4-related disease presented with a duodenal ulcer to improve the understan-ding of IgG4-related diseases was reported. A 70-year-old male presented with cutaneous pruritus and abdominal pain for four years and blackened stools for two months. Four years ago, the patient went to hospital for cutaneous pruritus and abdominal pain. Serum IgG4 was 3.09 g/L (reference value 0-1.35 g/L), alanine aminotransferase 554 U/L (reference value 9-40 U/L), aspartate aminotransferase 288 U/L (reference value 5-40 U/L), total bilirubin 54.16 µmol/L (reference value 2-21 µmol/L), and direct bilirubin 29.64 µmol/L (reference value 1.7-8.1 µmol/L) were all elevated. The abdominal CT scan and magnetic resonance cholangiopancreatography indicated pancreatic swelling, common bile duct stenosis, and secondary obstructive dilation of the biliary system. The patient was diagnosed with IgG4-related disease and treated with prednisone at 40 mg daily. As jaundice and abdominal pain improved, prednisone was gradually reduced to medication discontinuation. Two months ago, the patient developed melena, whose blood routine test showed severe anemia, and gastrointestinal bleeding was diagnosed. The patient came to the emergency department of Beijing Hospital with no improvement after treatment in other hospitals. Gastroscopy revealed a 1.5 cm firm duodenal bulb ulcer. After treatment with omeprazole, the fecal occult blood was still positive. The PET-CT examination was performed, and it revealed no abnormality in the metabolic activity of the duodenal wall, and no neoplastic lesions were found. IgG4-related disease was considered, and the patient was admitted to the Department of Rheumatology and Immunology of Beijing Hospital for further diagnosis and treatment. The patient had a right submandibular gland mass resection history and diabetes mellitus. After the patient was admitted to the hospital, the blood test was reevaluated. The serum IgG4 was elevated at 5.44 g/L (reference value 0.03-2.01 g/L). Enhanced CT of the abdomen showed that the pancreas was mild swelling and was abnormally strengthened, with intrahepatic and extrahepatic bile duct dilation and soft tissue around the superior mesenteric vessels. We pathologically reevaluated and stained biopsy specimens of duodenal bulbs for IgG and IgG4. Immunohistochemical staining revealed remarkable infiltration of IgG4-positive plasma cells into duodenal tissue, the number of IgG4-positive cells was 20-30 cells per high-powered field, and the ratio of IgG4/IgG-positive plasma cells was more than 40%. The patient was treated with intravenous methylprednisolone at 40 mg daily dosage and cyclophosphamide, and then the duodenal ulcer was healed. IgG4 related disease is an immune-medicated rare disease characterized by chronic inflammation and fibrosis. It is a systemic disease that affects nearly every anatomic site of the body, usually involving multiple organs and diverse clinical manifestations. The digestive system manifestations of IgG4-related disease are mostly acute pancreatitis and cholangitis and rarely manifest as gastrointestinal ulcers. This case confirms that IgG4-related disease can present as a duodenal ulcer and is one of the rare causes of duodenal ulcers.

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.

Hidróxido de alumínio em suspensão de 60 mg/mL para o tratamento de gastrite, úlceras gástricas e duodenais e esofagite de refluxo / Aluminum hydroxide in suspension of 60 mg/mL for the treatment of gastritis, gastric and duodenal ulcers and reflux esophagitis

INTRODUÇÃO: Há um grupo de doenças cuja patogênese está relacionada ao ácido gástrico, tanto em função de distúrbios na secreção, quanto da ação direta desse composto na mucosa do trato gastrintestinal. A hipersecreção gástrica está diretamente relacionada à patogênese de úlceras duodenais, e a magnitude da supressão ácida é diretamente proporcional à taxa de recuperação dessas lesões. Já nas úlceras gástricas, enquanto a secreção gástrica se mantém em níveis normais, a inibição da secreção por tempo e em magnitude adequados está associada a melhoria nas taxas de recuperação e cura. O mesmo ocorre para doença do refluxo gastroesofágico. A utilização de antiácidos como o hidróxido de alumínio é preconizada nos casos com sintomas leves a moderados e infrequentes em associação ao tratamento com anti-secretores. Faz-se nesse relatório uma revisão rápida da literatura sobre a utilização de hidróxido de alumínio no tratamento dessas doenças. PERGUNTAS: Hidróxido de alumínio em suspensão é eficaz e seguro para o tratamento de gastrite, úlceras gástricas e duodenais e doença do refluxo esofágico? EVIDÊNCIAS CLÍNICAS: Em gastrite a utilizaçã de hidróxido alumínio ou desse em associação a hidróxido de magnésio em adultos em suspensão entre 6 a 7 vezes ao dia por 4 a 8 semanas foi mais eficaz que placebo e igualmente eficaz a misoprostol, antagonistas dos receptores H2, sucralfato e hidróxido de magnésio no alívio completo ou redução da severidade de sintomas relacionados à gastrite tais como dor abdominal; pirose; regurgitação; náusea; êmese. No tratamento de úlceras pépticas em adultos (gástrica e duodenal) a utilização de hidróxido de alumínio isolado ou em associação com hidróxido de magnésio em doses de 10 a 30 mL entre uma e 8 vezes ao dia por 4 a 8 semanas foi igualmente ou mais eficaz que placebo na diminuição dos episódios e severidade da dor e do tempo com dor. A utilização de ranitidina em associação a antiácido a base de hidróxido de alumínio não foi diferente do antiácido isolado na diminuição da intensidade de dor. Da mesma forma não se identificaram diferenças entre o antiácido e cimetidina de 800 a 1.200 mg por dia por 4 a 8 semanas na redução de dor dispepsia e pirose; ou entre o antiácido isolado e a associação com oxetacaína. No tratamento de doença do refluxo gastresofágico em adultos a utilização de hidróxido de alumínio e magnésio (1,5 g (15 mL) uma vez ao dia por 12 semanas) foi mais eficaz que placebo na redução dos episódios de refluxo, do número de episódios de refluxo com mais de cinco minutos e do tempo médio dos episódios. O número de pacientes com pH esofágico menor do que 4 diminuiu mais no grupo que recebeu o antiácido. Não houve diferença estatisticamente significativa quando se compararam tratamentos com ranitidina na dose de 300 mg ao dia e antiácido a base de hidróxido de magnésio e alumínio (10 mL sete vezes ao dia por 6 semanas). ANÁLISE DE IMPACTO ORÇAMENTÁRIO: O impacto orçamentário relacionado à aquisição da suspensão de 60 mg/mL é de cerca de 1,5 milhões por ano para o período de 2023 a 2027. O impacto total para o período foi de 7,6 milhões. CONSIDERAÇÕES FINAIS: Segundo as especificações da Farmacopeia brasileira é permitida uma variação de 10% para mais ou para menos na quantidade de alumínio na suspensão. Entende-se que entre as suspensões com concentrações de 6,15% e 6,00% há uma variação de 2,5% da quantidade de hidróxido de alumínio para menos, o que está dentro da faixa de variação permitida mínima para o produto segundo os critérios da farmacopeia. Segundo esses critérios espera-se que esses produtos apresentem a mesma eficácia em termos de capacidade de neutralização ácida. Segundo a evidência constante em estudos controlados randomizados, tratamentos em adultos com hidróxido de alumínio em suspensão isolado ou em associação ao hidróxido de magnésio são mais eficazes que placebo e não diferentes de antagonistas do receptor H2 na redução ou resolução de sintomas relacionados à gastrite, úlcera duodenal e doença do refluxo gastresofágico. Na população pediátrica há pouca ou nenhuma evidência que suporte o uso dessa medicação. Esse medicamento pode ser utilizado como alternativa, em adultos intolerantes aos tratamentos com medicamentos anti-secretores ácidos. Entretanto, esses estudos, em sua maioria, foram publicados nas décadas de 70 e 80 e estão relacionados a um alto risco de viés. PERSPECTIVA DO PACIENTE: Foi aberta chamada pública para inscrição de participantes na perspectiva do paciente para discussão deste tema, entre os dias 10/03/2023 e 20/03/2023. Duas pessoas se inscreveram, contudo, não deram seguimento ao processo preparatório. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Medicamentos presentes na 117ª Reunião Ordinária da Conitec, realizada no dia 28 de março de 2023, deliberaram por unanimidade recomendar a incorporação da suspensão oral de hidróxido de alumínio na concentração de 60,0 mg/mL. CONSULTA PÚBLICA: A Consulta Pública nº 10/2023 foi realizada entre os dias 19/04/2023 e 08/05/2023. Foi recebida uma contribuição pelo formulário para contribuições técnico-científicas, mas nenhuma pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Na contribuição recebida identificou-se posicionamento favorável à recomendação preliminar do Comitê de Medicamentos, apesar da manifestação desfavorável constante no formulário. Dessa forma, declarou-se que o hidróxido de alumínio é um medicamento eficaz para o tratamento de gastrite, úlceras gástricas e duodenais e esofagite de refluxo. Disse também que a única razão para a exclusão desse medicamento do SUS fora a caducidade do registro sanitário, complementando que a nova formulação discutida neste relatório fora aprovada pela Agência Nacional de Vigilância Sanitária (Anvisa) para comercialização. Sobre o impacto orçamentário não houve contribuições recebidas por meio de consulta pública, entretanto, na apreciação inicial do tema o Comitê solicitou que se refizesse a projeção de impacto orçamentário incluindo a estimativa do quantitativo de pacientes que, devido à exclusão da ranitidina do SUS, passariam a utilizar, como substituto terapêutico, o hidróxido de alumínio. Dessa forma elaborou-se nova análise de impacto orçamentário. Pela nova projeção haveria um aumento médio de R$ 100.000,00 (8%) pela absorção da demanda criada pela exclusão da ranitidina do SUS (novos valores no compêndio econômico). RECOMENDAÇÃO FINAL DA CONITEC: O Comitê de Medicamentos da Conitec, em sua 119ª Reunião Ordinária, no dia 31 de maio de 2023, deliberou por unanimidade recomendar a incorporação da suspensão oral de hidróxido de alumínio na concentração de 60,0 mg/mL no SUS. Os membros do Comitê de Medicamentos consideraram que não houve novas evidências que pudessem alterar a recomendação preliminar. Por fim, foi assinado o Registro de Deliberação nº 830/2023. DECISÃO: Incorporar, no âmbito do Sistema Único de Saúde - SUS, a suspensão oral de hidróxido de alumínio na concentração de 60 mg/mL, publicada no Diário Oficial da União nº 140, seção 1, página 125, em 25 de julho de 2023.

Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study.

BACKGROUND: The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole. METHODS: In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. RESULTS: The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). CONCLUSIONS: The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. REGISTRATION: ClinicalTrials.gov, NCT04215653.

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.).

Úlcera duodenal perforada: tratamiento endoscópico-conservador / Perforated duodenal ulcer: Endoscopic-conservative management

No disponible

Proton Pump Inhibitor to Treat an Eosinophilic Duodenal Ulcer with Esophageal Involvement: A Pediatric Case.

Eosinophilic gastrointestinal disorders are diseases that cause inflammation and dysfunction due to infiltration of eosinophils into various regions of the gastrointestinal tract. Symptoms and treatment vary depending on lesion severity. We describe the first pediatric case of an eosinophilic duodenal ulcer with esophageal involvement that was effectively treated using proton pump inhibitor monotherapy. A 12-year-old boy with no relevant family or medical history presented with a one-month history of epigastric pain. Laboratory test results were as follows: white blood cell count, 4,700/µL; eosinophil count, 150/µL (3.2%); and total IgE, 151.6 IU/L; and IgG antibodies for Helicobacter pylori were absent. Esophagogastroduodenoscopy revealed longitudinal linear furrows in the esophagus, indicating eosinophilic esophagitis with an A1 ulcer from the duodenal bulb to the descending duodenum. The patient was diagnosed with an eosinophilic duodenal ulcer with esophageal involvement based on pathological findings. Esomeprazole, a common proton pump inhibitor, was orally administered, after which the symptoms promptly improved. After two months, the esophagogastroduodenoscopy and pathological examination results showed improvement in both the esophagus and duodenum. There have been no previous reports of an eosinophilic duodenal ulcer with esophageal involvement without post-duodenal involvement at the time of diagnosis. The possibility of eosinophilic gastrointestinal disorders should be investigated in patients with duodenal ulcers by means of active biopsy, and patients should be investigated for other types of gastrointestinal lesions. Proton pump inhibitor monotherapy may be considered a first-line treatment for eosinophilic duodenal ulcers with esophageal involvement, depending on lesion severity.

Eosinophilic Duodenal Ulcer Exacerbation after Helicobacter pylori Eradication in a 14-Year-Old Boy.

Eosinophilic gastrointestinal disorders (EGIDs) cause various gastrointestinal symptoms due to infiltration of eosinophils into the gastrointestinal tract. Helicobacter pylori (H. pylori) is a microorganism that is associated with various diseases such as autoimmune diseases. In recent years, H. pylori is considered protective in inflammatory bowel diseases and gastrointestinal autoimmune disorders but is not known to be protective in EGIDs. A 14-year-old boy presented with epigastric pain and nausea, without diarrhea. His symptoms were not associated with meals. Blood examination showed an eosinophil count of 1,666 cells/µL (17.0%) and an interleukin-5 (IL-5) level of less than 3.9 pg/mL. Esophagogastroduodenoscopy showed chronic gastritis and duodenal ulcers. Capsule endoscopy and colonoscopy showed no abnormal findings. The patient was diagnosed with chronic gastritis due to H. pylori infection and eosinophilic duodenal ulcers. H. pylori eradication was performed. However, the abdominal pain worsened with elevated peripheral eosinophil count [2,314/µL (26%)] and serum IL-5 level (8.0 pg/mL). Montelukast administration improved the symptoms and laboratory findings [peripheral eosinophil count, 330/µL (5.9%); IL-5, < 3.9 pg/mL]. EGIDs should be considered as a cause of duodenal ulcers. H. pylori may be protective in EGIDs. Montelukast monotherapy may be considered as a first line treatment for eosinophilic duodenal lesions.

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.

IMPROVEMENT OF ERADICATION THERAPY IN CHILDREN WITH DUODENAL ULCER ASSOCIATED WITH HELICOBACTER PYLORI.

OBJECTIVE: The aim: To evaluate the efficacy of the drug VitD children with H.pylori-associated duodenal ulcer. PATIENTS AND METHODS: Materials and methods: Two treatment groups of children with DU were formed: I - 60 children with H. pylori-associated DU, who received the optimal scheme of anti- Helicobacter therapy (AHBT) for Chernivtsi region; II - 62 children with H. pylori-associated DU who received a modified treatment regimen: AGBT + VitD at a dose of 2000 IU / day for 1 month. The effectiveness of the treatment was evaluated taking into account the Relative Risk Reduction (RRR) of the adverse event and Number Needed to Treat (NNT). RESULTS: Results: All children with DU and a positive H. pylori infection test showed changes in serum VitD levels: 81.9% deficiency and 18.1% insufficiency. Successful eradication was achieved in 77.1% of children, in particular in the first group 73.3%, in the second - 82.2%. Predictors of successful eradication are the duration of infection, H. pylori CagA (+), VitD level. When using the VitD treatment regimen in children with DU associated with CagA (+) strain H.pylori, RRR was observed 2.29 times (χ2 = 6.34, pφ<0.05) with NNT 1.59. CONCLUSION: Conclusions: Due to the reduced level of serum VitD in children with H. pylori-associated DU, it is advisable to include in the treatment regimen the adjuvant component of AHBT in the form of VitD. Predictors of effective eradication of H. pylori are CagA (+) strain of H. pylori, duration of infection and VitD level.

Antibiotic Resistance of Helicobacter pylori in Patients with Peptic Ulcer.

Background and Objectives: To determine the antibiotic resistance rate of H. pylori among patients with peptic ulcer. Materials and Methods: A cross-sectional monocentric study was conducted from January to December 2021 among patients aged from 16 years with gastrointestinal symptoms and esophagogastroduodenoscopy. Gastric mucosa biopsies were collected at the edges of the ulcer or at lesion sites for H. pylori culture. Five antibiotics (amoxicillin (AMX), clarithromycin (CLR), metronidazole (MTZ), levofloxacin (LEV), and tetracycline (TET)) were selected for antibiotic susceptibility testing. Results: One hundred and twenty-five patients were included, and the sex ratio was 0.6. Their mean age was 47.3 ± 14.2 years. All of the participants had gastritis, and 24.0% had duodenitis. A total of 21.6% of patients had a duodenal ulcer, and 12.8% had an antral ulcer. A total of 40 specimens have grown in H. pylori culture. The proportion of resistance to AMX, CLR, MTZ, LEV, and TET was 27.5%, 50%, 67.5%, 35%, and 5%, respectively. The proportion of multidrug resistance was 22.5%. The proportion of double resistance to AMX + CLR was 20.0%, AMX + MTZ was 15.0%, AMX + LEV was 2.5%, CLR + MTZ was 32.5%, and TET + MTZ was 5.0%. Conclusions: Our research results show that the treatment with MTX-TET or LVX-AMOX has the highest sensitivity rate. Therefore, practitioners should refer to these regimes to eradicate H. pylori in patients with gastric and duodenal ulcers. The reports on H. pylori eradication from different geographic areas show heterogeneous results. Therefore, continuous monitoring of antibiotic resistance of H. pylori in each population is very important. Having evidence helps clinicians to treat patients most effectively, reduce treatment costs, and limit the rate of antibiotic resistance.

Indications for the Use of Proton Pump Inhibitors for Stress Ulcer Prophylaxis and Peptic Ulcer Bleeding in Hospitalized Patients.

Proton pump inhibitors are widely used throughout the world for the treatment of gastrointestinal disorders that are related to acid secretion, such as peptic ulcer disease and dyspepsia. Another common indication for proton pump inhibitors is stress ulcer prophylaxis. Proton pump inhibitors have proven efficacy for the treatment of acid-related gastrointestinal disorders, but there is concern that their use may be associated with the development of significant complications, such as fractures, Clostridium difficile infection, acute kidney injury, chronic kidney disease, and hypomagnesemia. Proton pump inhibitors are overused in the hospital setting, both for stress ulcer prophylaxis and gastrointestinal bleeding, and then they are often inappropriately continued after discharge from the hospital. This narrative review article outlines the evidence surrounding appropriate proton pump inhibitor use for stress ulcer prophylaxis and peptic ulcer bleeding.

Ulcerative colitis relapse after Helicobacter pylori eradication in a 12-year-old boy with duodenal ulcer.

BACKGROUND: Helicobacter pylori (H. pylori) prevalence is lower in patients with inflammatory bowel disease (IBD) than in those without IBD, suggesting that H. pylori plays a protective role in IBD. It has been reported that IBD may occur due to H. pylori eradication; however, it is unclear whether H. pylori eradication increases the incidence of IBD. Moreover, the effect of H. pylori eradication on IBD activity is unclear. CASE PRESENTATION: An 11-year-old boy diagnosed with ulcerative colitis (UC) was in clinical remission, with treatment involving 5-aminosalicylic acid. Fecal calprotectin (FC) level had decreased to 33.2 mg/kg, indicating mucosal healing. At age 12, he experienced epigastric pain on an empty stomach, which was relieved with dietary intake. His FC level was elevated without UC symptoms, such as diarrhea and bloody stools. He was diagnosed with H. pylori duodenal ulcer. H. pylori eradication (clarithromycin and amoxicillin for 7 days and a proton-pump inhibitor) led to symptom improvement the day after treatment initiation. However, he developed diarrhea and his FC level remained high despite improvement in duodenal ulcer symptoms and endoscopic findings of H. pylori eradication. Colonoscopy results indicated UC relapse. CONCLUSIONS: H. pylori eradication may worsen UC activity. However, further studies are required as this case report involved only one pediatric patient with increased UC activity after H. pylori eradication.