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.

[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.

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.).

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.

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.

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.

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.

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.

Perforated Duodenal Ulcer Associated with Deferasirox in a Child with ß-Thalassemia Major.

The oral iron chelator, deferasirox (DFX), is commonly associated with mild gastrointestinal (GI) complaints, but GI hemorrhage and ulcers have occasionally been reported. However, perforated duodenal ulcer (PDU) has been previously reported in only one patient with ß-thalassemia major (ß-TM) on Exjade (DFXE). We hereby report the second case of a 5-year-old Syrian patient, who recently presented with PDU while on DFXE. She was not on any other ulcerogenic medication and was negative for H. pylori and Celiac disease. She had a surgical repair and has done well. She is back on DFX, but with the film-coated tablet, Jadenu or DFXJ. Perforated duodenal ulcer should be suspected in patients with severe GI symptoms, abdominal distension and tenderness while on DFXE, especially at high doses (30+ mg/kg).

[Modern aspects of the complex treatment of perforated gastric and duodenal ulcer]. / Sovremennye aspekty kompleksnogo lecheniya perforativnoi yazvy zheludka i dvenadtsatiperstnoi kishki.

OBJECTIVE: To study the effectiveness of pharmacotherapy for perforated gastric ulcer in a surgical hospital. MATERIAL AND METHODS: A retrospective analysis of the treatment of 693 patients with perforated gastric and duodenal ulcers was carried out. Laparoscopic and open surgeries were performed. Statistical analysis was performed using the Statistica and MS Excel software packages. Student t-test was applied for independent samples and Fisher's F-test was calculated. RESULTS: Combined therapy included surgical treatment (suturing of the ulcer as a rule) and medication with proton pump inhibitors, antibacterial drugs. Over the past 5 years, postoperative quality of life has been significantly improved in patients with perforated ulcers. Stomach resection and vagotomy for perforated ulcers will become historical in the near future. Laparoscopic and open procedures ensure similar periods of ulcer closure. CONCLUSION: Currently, successful treatment of perforated gastric and duodenal ulcers requires an integrated approach at all levels of specialized care and is impossible without modern pharmacotherapy.

Proton pump inhibitors: placing putative adverse effects in proper perspective.

PURPOSE OF REVIEW: This review summarizes the past year's literature, both clinical and basic science, regarding potential adverse effects of proton pump inhibitors (PPIs). RECENT FINDINGS: PPIs are amongst the most widely prescribed and over-prescribed medications worldwide. Although generally considered well tolerated, epidemiologic studies that mine large databases have reported a panoply of putative adverse effects associated with PPIs. It should be emphasized that the quality of the evidence underlying most of these associations is very low and the studies, by design, cannot ascribe cause and effect. These associations continue to be sensationalized in the media and misinterpreted by providers and patients. The unintended consequences are that patients who require PPIs, such as those taking dual antiplatelet agents, are not being prescribed or taking these necessary medications. In addition, physicians are spending an inordinate amount of additional time placing these findings into proper perspective for their patients and reassuring them upon initiating PPI treatment as well as at every follow-up visit. SUMMARY: Most of the recent publicized putative serious adverse effects attributed to PPIs rely on observational data and have not been confirmed in prospective randomized trials. Nevertheless, PPIs should be prescribed for valid indications and when prescribed long-term, they should be used at the lowest effective dose and the need for their use periodically reassessed.

Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control.

AIMS: The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS: Three clinical studies were performed. First, 16 healthy subjects received infusion of ilaprazole 30 mg or esomeprazole 80 mg. Second, 12 healthy subjects received ilaprazole 20 mg followed by 10 mg once daily for 2 days. Finally, 20 patients with duodenal ulcers received ilaprazole 20 mg followed by 10 mg for 2 days or esomeprazole 40 mg twice daily for 3 days. Serial blood samples were collected and intragastric pH was recorded. RESULTS: The mean percentages time of intragastric pH >6 was 63.6 and 51.7% for healthy subjects after receiving ilaprazole 30 mg and esomeprazole 80 mg. Linear pharmacokinetics was observed when the dose was increased to 30 mg but the effect was saturated. Ilaprazole 20 mg followed by 10 mg for 2 days provided higher plasma exposure in healthy subjects than patients, but the effect was comparable. After multiple administrations, ilaprazole provided similar effect to esomeprazole. Ilaprazole infusion was safe and well tolerated without serious adverse events. CONCLUSIONS: Ilaprazole provided comparable effect of pH control to esomeprazole, with lower dose and fewer times of administration. There was no significant difference of ilaprazole between healthy subjects and patients regarding intragastric acid inhibition. A loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days was recommended for Phase 2b/3 studies.

Ilaprazole Compared With Rabeprazole in the Treatment of Duodenal Ulcer: A Randomized, Double-blind, Active-controlled, Multicenter Study.

GOALS: The main goal of this study was to explore the dose-effect relationship of ilaprazole. BACKGROUND: Ilaprazole is a kind of benzimidazole proton-pump inhibitor, which was confirmed efficacious and safe in treatment of duodenal ulcer (DU). However, the dose-effect relationship of ilaprazole was not clear. STUDY: This was a double-blind, parallel, randomized study. Patients aged above 18 years with at least one endoscopically confirmed active nonmalignant DU were treated with rabeprazole 10 mg or ilaprazole 10 mg/5 mg for 4 weeks. Healing of ulcer was determined by its resolution from active to scarring stage. Symptoms relief was evaluated using a graded score. Safety and tolerability were evaluated on basis of clinical assessments. RESULTS: A total of 390 patients completed the study finally. Ulcers were successfully healed in 75.38%, 77.86%, and 83.72% of patients after 4-week treatment with rabeprazole 10 mg, ilaprazole 5 mg, and ilaprazole 10 mg, respectively. The 4-week healing rate difference between rabeprazole 10 mg and ilaprazole 5 mg was 2.48% (95% confidence interval: -7.79% to 12.74%) leading to accept the noninferiority hypothesis. Logistic regression model suggested that ilaprazole 10 mg was superior to ilaprazole 5 mg at week 2 (odds ratio, 1.92; 95% confidence interval: 1.02, 3.59; P=0.04). Most patients (80%) became asymptomatic after treatment. At the dosages administered, the 3 drug groups exhibited similar efficacy and a similar safety profile. CONCLUSIONS: Ilaprazole 5 mg is not inferior to rabeprazole 10 mg in treating DU, and a dose-effect relationship have been revealed between 5 mg and 10 mg of ilaprazole.

[The efficacy of recombinant interleukin-1ß in surgical treatment of acute ulcerative gastroduodenal bleedings.]

There was reported the results of the use of recombinant interleukin-1ß in basic conservative measures in the surgical treatment of acute gastroduodenal ulcer bleeding. Gastric ulcer were in 20 patients, duodenal ulcer in 84 patients and combined ulcers in 16 patients. According to А.А. Шалимов hospitalized patients with mild blood loss were 27, moderate degree - 62 and severe degree - 31 patients. According to J. Forrest, 29 showed active bleeding (F Ia, F Ib), in 67 - unstable hemostasis (F IIa, F IIb, F IIc) and in 24 - F III. Within the framework of differentiated individual-active tactics, patients were operated in emergency (21), urgent (38), delayed (35), and 26 people underwent early planned operations. Patients in the main group (63) after the operation, was included recombinant interleukin-1ß to the basic therapeutic measures additionally, taking into account the degree of blood loss and immune disorders. Patients of comparison group (57) before and after surgery received standard basic therapy without immunocorrection. In a comparative aspect, it has been proved that in postoperative period on the background of standard conservative measures, the use of recombinant interleukin-1ß positively influences elimination of the secondary immunodeficiency and cytokine imbalance significantly improves the results of surgical treatment.

New single capsule of bismuth, metronidazole and tetracycline given with omeprazole versus quadruple therapy consisting of bismuth, omeprazole, amoxicillin and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a Chinese prospective, randomized, multicentre trial.

Objectives: To assess the efficacy and safety of omeprazole given with the new single capsule of bismuth, metronidazole and tetracycline (OBMT) compared with quadruple treatment consisting of omeprazole, bismuth, amoxicillin and clarithromycin (OBAC) for Helicobacter pylori eradication in duodenal ulcer patients. Methods: This single-blind, randomized multicentre trial was conducted in 10 tertiary hospitals in China between January 2013 and April 2014. Patients were randomized to receive 10 days of OBMT therapy or 10 days of OBAC therapy. Our primary outcome was the H. pylori eradication rate, confirmed by negative [13C]urea breath tests 20-25 days after the end of omeprazole maintenance. Antibiotic resistance was determined by Etest. This study is registered with ClinicalTrials.gov, number ChiCTR-TRC-13003143. Results: One hundred and ninety-two patients received OBMT therapy and 192 received OBAC therapy. There was no significant difference between the eradication rates achieved by OBMT and OBAC in either the ITT analysis (86.46% versus 87.50%, P = 0.762) or the PP analysis (94.58% versus 93.06%, P = 0.563). The efficacies of OBMT and OBAC were not affected by metronidazole or clarithromycin resistance. Treatment-emergent adverse events (TEAEs) for both treatments were similar; gastrointestinal and CNS symptoms were the most commonly reported. Conclusions: The new single-capsule OBMT quadruple therapy is as effective and well tolerated as the widely used OBAC therapy for treatment of H. pylori in clinical practice in China. In addition, this OBMT therapy largely overcomes H. pylori metronidazole and clarithromycin resistance.

Stress ulcer prophylaxis in intensive care unit patients receiving enteral nutrition: a systematic review and meta-analysis.

BACKGROUND: Pharmacologic stress ulcer prophylaxis (SUP) is recommended in critically ill patients with high risk of stress-related gastrointestinal (GI) bleeding. However, as to patients receiving enteral feeding, the preventive effect of SUP is not well-known. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP in enterally fed patients on stress-related GI bleeding and other clinical outcomes. METHODS: We searched PubMed, Embase, and the Cochrane database from inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic SUP to either placebo or no prophylaxis in enterally fed patients in the ICU. Results were expressed as risk ratio (RR) and mean difference (MD) with accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored. RESULTS: Seven studies (n = 889 patients) were included. There was no statistically significant difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between groups. This finding was confirmed by further subgroup analyses and sensitivity analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI, 0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25 to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to 0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48 to 0.72, p = 0.50), but was associated with an increased risk of hospital-acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03). CONCLUSIONS: Our results suggested that in patients receiving enteral feeding, pharmacologic SUP is not beneficial and combined interventions may even increase the risk of nosocomial pneumonia.

Therapy with omeprazole modulates regulatory T cell/T helper 17 immune response in children with duodenal ulcers.

The purpose of this study was to determine the effect of omeprazole on the regulatory T cell (Treg) and T helper 17 (Th17)-mediated response in patients with duodenal ulcers (DUs). DU patients were randomly divided into omeprazole and colloid bismuth subcitrate treatment groups. The ratios of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) were measured. Cytokine production and Foxp3+- and RORγt-positive cells were detected. The expressions of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by Western blot. The results showed that DU patients had an imbalanced Treg/Th17 response, as reflected by the higher IL-17 level and Th17 ratio and lower IL-10 level and Treg proportion in serum compared with those in the healthy volunteers. The administration of omeprazole to the patients significantly increased Treg and IL-10 levels and reduced Th17 and IL-17 levels. Omeprazole markedly increased the number of Foxp3-positive cells, decreased the number of RORγt-positive cells and restored the balanced ratio of IL-10/IL-17 in the ulcer tissue. Interestingly, we observed a negative correlation between the ratios of Treg/Th17 and the pathological scores in damaged tissues. Of note, H. pylori-infected PBMCs showed decreased Treg and an increased Th17 proportion, which could be reversed by omeprazole. Finally, omeprazole increased the expression of p-STAT5 and reduced the level of p-STAT3 without any effects on the total expression of STAT5 and STAT3. Our data suggest that omeprazole treatment restores the equilibrium of the Treg/Th17-mediated response in DU patients. Moreover, the modulation of p-STAT3 and p-STAT5 expression by omeprazole induced balanced polarisation of Treg/Th17.