Proton pump inhibitor effect on esophageal protein signature of eosinophilic esophagitis, prediction, and evaluation of treatment response.

BACKGROUND: Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response. METHODS: We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8-week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non-responders (non-responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways. RESULTS: Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder-PrePPI, non-responder-PrePPI, and non-responder-PostPPI) and without inflammation (controls and responder-PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder-PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder-PrePPI and non-responder-PrePPI EoE patients before treatment. CONCLUSION: These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE.

Proton Pump Inhibitor Induced Hypomagnesemia Causing Seizures: A Rare Adverse Effect of a Commonly Used Medication.

Hypomagnesemia is defined as serum magnesium levels less than 0.7mmol/L and can result in a plethora of symptoms ranging from mild gastrointestinal symptoms to serious conditions such as cardiac arrhythmias and neurological complications. When considering the etiological factors, drug-induced hypomagnesemia is highlighted because commonly used medications such as proton pump inhibitors (PPIs), aminoglycoside antibiotics, and loop and thiazide diuretics can cause low magnesium levels. A 49-year-old male presented to the emergency department with severe vomiting worsening over three days complicated with generalized tonic-clonic seizures. He was an averagely built male, a non-smoker, and a non-alcoholic with no significant co-morbidities. He had a history of chronic over-the-counter pantoprazole intake over the last one year, and apart from that, his medication history was unremarkable. Initial investigations revealed severe hypomagnesemia (with serum magnesium level of 0.1mmol/L), with marginal hypokalemia, hypophosphatemia, and hypocalcemia. Following the initial resuscitation and magnesium supplementation, the patient's clinical condition significantly improved. Due to the lack of proper knowledge, the patient continued to take omeprazole 20mg tablets after discharge, and up until proper education and total cessation of PPIs, marginal hypomagnesemia, with serum magnesium level of 0.5mmol/L, persisted without any significant overt clinical manifestations. In this case report, we intend to highlight the importance of assessing for all possible electrolyte abnormalities in a patient presenting with neurological symptoms, relevance of taking a thorough drug history including all undocumented over-the-counter medications, and importance of patient education in the prevention of further episodes.

A network meta-analysis: evaluating the efficacy and safety of concurrent proton pump inhibitors and clopidogrel therapy in post-PCI patients.

Introduction: The objective of this research was to evaluate the risk of major adverse cardiovascular events (MACEs) associated with the use of various proton pump inhibitors (PPIs) in combination with clopidogrel in patients who underwent percutaneous coronary intervention (PCI). Methods: To accomplish this, we analyzed data from randomized controlled trials and retrospective cohort studies sourced from key electronic databases. These studies specifically examined the effects of different PPIs, such as lansoprazole, esomeprazole, omeprazole, rabeprazole, and pantoprazole, when used in conjunction with clopidogrel on MACEs. The primary focus was on the differential impact of these PPIs, while the secondary focus was on the comparison of gastrointestinal (GI) bleeding events in groups receiving different PPIs with clopidogrel vs. a placebo group. This study's protocol was officially registered with INPLASY (INPLASY2024-2-0009). Results: We conducted a network meta-analysis involving 16 studies with a total of 145,999 patients. Our findings indicated that rabeprazole when combined with clopidogrel, had the lowest increase in MACE risk (effect size, 1.05, 95% CI: 0.66-1.66), while lansoprazole was associated with the highest risk increase (effect size, 1.48, 95% CI: 1.22-1.80). Esomeprazole (effect size, 1.28, 95% CI: 1.09-1.51), omeprazole (effect size, 1.23, 95% CI: 1.07-1.43), and pantoprazole (effect size, 1.38, 95% CI: 1.18-1.60) also significantly increased MACE risk. For the secondary outcome, esomeprazole (effect size, 0.30, 95% CI: 0.09-0.94), omeprazole (effect size, 0.34, 95% CI: 0.14-0.81), and pantoprazole (effect size, 0.33, 95% CI: 0.13-0.84) demonstrated an increased potential for GI bleeding prevention. Conclusions: In conclusion, the combination of lansoprazole and clopidogrel was found to significantly elevate the risk of MACEs without offering GI protection in post-PCI patients. This study is the first network meta-analysis to identify the most effective regimen for the concurrent use of clopidogrel with individual PPIs. Systematic Review Registration: https://inplasy.com/inplasy-2024-2-0009/, identifier (INPLASY2024-2-0009).

Prescriptions of anti-reflux drugs in neonatology and neonatal intensive care units: A large multicentre observational study (2014-2022).

AIMS: Gastro-oesophageal reflux is common in newborns, especially in premature infants. Treatment by medication is controversial as the drugs prescribed have not been consistently proven to be effective and are known to have adverse effects. This study sought to identify trends in the prescription of anti-reflux medication in a large group of French neonatal units. METHODS: Data on prescriptions of anti-reflux treatments-proton pump inhibitors (PPIs), antacids, histamine-2 receptor antagonists (H2RAs), and prokinetics-from 2014 to 2022 for infants with a corrected gestational age <45 weeks, were extracted from a prescription database (Logipren®) used by 63 French neonatal units, and then analysed. RESULTS: Of all infants recorded in the database during the study period (n = 152 743), 10.2% (n = 15 650) were prescribed anti-reflux medication (95% confidence interval [CI] 10.0-10.4%), mainly as monotherapy (77.5%). The rate was higher in the subgroup of preterm infants born before 28 weeks of gestation (n = 9493) (20.6%, 95% CI 19.8-21.4%; n = 1956). PPIs were the most commonly prescribed anti-reflux medications (6.9% of infants, 95% CI 6.8-7.0), followed by antacids (5.2%, 95% CI 5.1-5.3%), while H2RAs and prokinetics were rarely prescribed. Over the period, the prescription rate remained stable for PPIs, decreased for H2RAs (τ = -0.86, P = .02), and, among preterm infants born at gestational ages of 28-31 or 32-36 weeks, increased for antacids. CONCLUSIONS: Anti-reflux medications were frequently prescribed by neonatal units, especially for extremely premature infants. Most of these prescriptions were for PPIs and antacids.

Vonoprazan-associated Clostridioides difficile infection: an analysis of the Japanese Adverse Drug Event Report and the FDA Adverse Event Reporting System.

Background: Prolonged or excessive use of acid suppressants may increase the risk of Clostridioides difficile infection (CDI) by altering the intestinal microecosystem. Vonoprazan, a novel potassium-competitive acid blocker, exhibits a faster and more sustained acid-suppressive effect than proton pump inhibitors (PPIs). Therefore, vonoprazan may have a greater impact on the gut microbiota, potentially resulting in CDI. Objectives: This study aimed to explore the potential relationship between acid suppressants and CDI by the Japan Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) databases. Design: A retrospective analysis of the JADER and FAERS databases was examined by disproportionality analysis. Methods: We performed signal detection analyses of CDI induced by vonoprazan and PPIs using the JADER and FAERS databases. The association between acid suppressants and CDI was calculated using the reporting odds ratio (ROR) and corresponding 95% confidence interval (95% CI). When the lower limit of the 95% CI is exceeded by 1, the association is considered statistically significant. Results: In the JADER database, the ROR (95% CI) for vonoprazan and PPIs based on suspect drug reports was 15.84 (12.23-20.50) and 2.51 (1.92-3.28), respectively. In the FAERS database, the ROR (95% CI) for vonoprazan and PPIs based on primary and secondary suspect drug reports was 11.50 (6.36-20.82) and 1.42 (1.34-1.51), respectively. Subgroup analysis showed that elderly patients aged 60 years and older were more strongly associated with CDI. The ROR (95% CI) for vonoprazan and PPIs in patients aged 60 years and older in the JADER database was 15.35 (11.59-20.33) and 1.65 (1.14-2.39), respectively. Similarly, the ROR (95% CI) for vonoprazan and PPIs in the FAERS database was 12.56 (6.26-25.20) and 1.43 (1.31-1.57), respectively. Excluding the effect of Helicobacter pylori (H. pylori) infection, the use of acid suppressants was still associated with CDI. Conclusion: While signal detection analysis based on the JADER and FAERS databases could not establish causality, our study demonstrated that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan showed a stronger association with CDI in both databases.

Introduction: Vonoprazan is a new type of acid suppressant, which has a stronger effect on acid inhibition than traditional proton pump inhibitors (PPIs). Vonoprazan may have a greater impact on the gut microbiota, which may increase the risk of Clostridioides difficile infection (CDI). The FDA created the FDA Adverse Event Reporting System (FAERS) database to support the post-market surveillance program. The PMDA created the Japan Adverse Drug Reaction Event Report (JADER) database to specifically collect adverse reaction reports in Japan. To further understand the potential relationship between acid suppressants and CDI, this study was analyzed using the JADER and FAERS databases. Methods: This study analyzed cases of CDI reported after the use of acid suppressants in the JADER and FAERS databases. Results: The analysis revealed that vonoprazan and PPIs are significantly associated with CDI in both databases. Notably, vonoprazan exhibited a stronger association compared to PPIs. Subgroup analysis indicated that this association was more pronounced in elderly patients aged 60 years and older. Additionally, excluding the influence of Helicobacter pylori (H. pylori) did not diminish the association between acid suppressants and CDI. Conclusion: Although signal detection analysis based on the JADER and FAERS databases could not establish causality, the results showed that both vonoprazan and PPIs were significantly associated with CDI. Vonoprazan was also more strongly associated with CDI than PPIs, which could be a potential safety concern, and further clinical studies are needed to confirm this finding.

Vonoprazan and Clostridioides difficile infection risk.

Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast.

OBJECTIVES: The objective of this investigation was to assess the impact of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer (mBC) who received palbociclib as first-line or successives therapy. MATERIALS AND METHODS: A retrospective observational study was conducted, enrolling patients diagnosed with estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, and eligible for palbociclib treatment. Patients were categorized as "concurrent PPIs" if they received PPIs for at least two-thirds of the palbociclib therapy duration, and as "no concurrent PPIs" if they did not receive PPIs during the course of palbociclib treatment. RESULTS: A total of 165 patients were included in the study. Among first-line patients treated with palbociclib, those using concurrent PPIs exhibited a PFS of 8.88 months, while patients using palbociclib without concurrent PPIs had a PFS of 67.81 months (p < 0.0001). In second-line or subsequent treatments, patients on palbociclib with concurrent PPIs had a PFS of 7.46 months, whereas those using palbociclib without concurrent PPIs had a PFS of 17.29 months (p = 0.122). CONCLUSION: This study demonstrates that the concurrent use of PPIs in mBC patients receiving palbociclib negatively affects PFS, particularly in the first-line setting. Nevertheless, further investigation is warranted to explore the impact of PPIs on cycle-dependent kinase 4/6 inhibitors.

Absorption, Metabolism, and Excretion of [14C]-Labeled Anaprazole: A New Proton Pump Inhibitor, After a Single Oral Administration in Healthy Chinese Male Subjects.

Anaprazole is a proton pump inhibitor. This study aims to elucidate absorption, metabolism, and excretion pathways of anaprazole sodium in the human body. A total of 4 healthy Chinese male subjects were administered a single oral dose of 20 mg/100 µCi of [14C]-anaprazole sodium enteric-coated capsules. The whole blood, plasma, and excreta were analyzed for a total radioactivity (TRA) and metabolite profile. The cumulative radioactivity excretion rate was 93.2%, with 53.3% and 39.9% of the radioactive dose excreted in urine and feces, respectively, and 91.6% of dose recovered within 96 hours after dosing. The parent drug, anaprazole, showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism. Overall, 35 metabolites were identified in plasma, urine, and fecal samples. Anaprazole was the most abundant component in plasma followed by the thioether M8-1, accounting for 28.3% and 16.6%, respectively, of the plasma TRA. Thioether carboxylic acid XZP-3409 (26.3% of urine TRA) and XZP-3409 oxidation and dehydrogenation product M417a (15.1% of fecal TRA) were the major metabolites present in urine and feces, respectively. Anaprazole was undetectable in urine, while fecal samples showed traces (0.07% dose). Blood/plasma ratios of the radioactivity (approximately 0.60) remained consistent over time. Anaprazole showed good absorption and was extensively metabolized majorly to thioether M8-1 via nonenzymatic metabolism, and cytochrome P450 3A4 also contributed to its metabolism in healthy individuals.

Association between proton pump inhibitors use and the severity of periodontal disease and peri-implantitis: a systematic review.

This systematic review investigates the probable effect of proton pump inhibitor (PPI) use on the severity of periodontal disease and peri-implantitis and implant survival. We conducted a literature search in PubMed, Scopus, and Cochrane Central Library up to April 2024. Two review authors independently screened the title and abstracts and then the full texts of retrieved studies. Observational and clinical trial studies that assessed the association between PPIs use and periodontal disease severity and peri-implantitis or implant survival were included. Data extraction from the included studies was done by two reviews independently. Of 940 studies initially retrieved from online searching, 7 research met the inclusion criteria. Three studies examined periodontitis, while four focused on peri-implantitis and implant longevity. On the contrary, evidence regarding the impact of PPIs use on peri-implantits and implant survival is conflicting. Therefore, more well-designed RCTs are warranted to come to a definite conclusion. Since proton pump inhibitors alter the gut microbiome, and affect bone, plus the pathogenesis and etiology of periodontal disease are affected by bacteria within the periodontal pocket, it is hypothesized that they may affect periodontal pathogenesis.

A Comprehensive Review on the Efficacy and Safety of Vonoprazan in the Management of Gastric Acid-Related Diseases.

Gastric acid-related diseases, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and Helicobacter pylori (H. pylori) infection, present significant clinical challenges due to their prevalence and potential for severe complications. Effective management of these conditions is essential for symptom relief, mucosal healing, and prevention of complications. This review aims to evaluate the efficacy and safety of vonoprazan, a novel potassium-competitive acid blocker (P-CAB), in the treatment of gastric acid-related diseases and to compare it with traditional proton pump inhibitors (PPIs). A comprehensive analysis of clinical trials and studies was conducted to assess the effectiveness of vonoprazan in managing GERD, PUD, and H. pylori infection. The safety profile of vonoprazan was also reviewed, and comparisons were made to PPIs and other gastric acid suppressants. Vonoprazan demonstrates superior and more consistent acid suppression than PPIs, resulting in rapid and sustained symptom relief and mucosal healing. Clinical trials have shown its efficacy in treating GERD, PUD, and H. pylori infection, with higher eradication rates for H. pylori when used in combination therapies. The safety profile of vonoprazan is favorable, with fewer adverse effects and drug interactions compared to PPIs. Vonoprazan offers a promising alternative to traditional PPIs for the management of gastric acid-related diseases. Its unique mechanism of action and superior efficacy make it a valuable option for patients requiring effective and reliable acid suppression. Further research is warranted to explore its potential in broader clinical applications and to establish long-term safety data.

Prevalence of Helicobacter pylori infection among patients with esophageal carcinoma.

BACKGROUND: Helicobacter pylori (H. pylori) is a widespread microorganism related to gastric adenocarcinoma (AC). In contrast, it has been reported that an inverse association exists between H. pylori infection and esophageal carcinoma. The mechanisms underlying this supposedly protective effect remain controversial. AIM: To determine the prevalence of H. pylori infection in esophageal carcinoma patients, we performed a retrospective observational study of esophageal tumors diagnosed in our hospital. METHODS: We retrospectively reviewed the prevalence of H. pylori infection in a cohort of patients diagnosed with esophageal carcinoma. Concomitant or previous proton pump inhibitor (PPI) usage was also recorded. RESULTS: A total of 89 patients with esophageal carcinoma (69 males, 77.5%), with a mean age of 66 years (range, 26-93 years) were included. AC was the most frequent pathological variant (n = 47, 52.8%), followed by squamous cell carcinoma (n = 37, 41.6%). Fourteen ACs (29.8%) originated in the gastroesophageal junction and 33 (70.2%) in the esophageal body. Overall, 54 patients (60.7%) presented at stages III and IV. Previous H. pylori infection occurred only in 4 patients (4.5%), 3 with AC (6.3% of all ACs) and 1 with squamous cell carcinoma (2.7% of all squamous cell tumors). All patients with previous H. pylori infection had stage III-IV. Only one patient had received prior H. pylori eradication therapy, whereas 86 (96.6%) had received previous or concomitant PPI treatment. CONCLUSION: In our cohort of patients, and after histologic evaluation of paraffin-embedded primary tumors, we found a very low prevalence of previous H. pylori infection. We also reviewed the medical history of the patients, concluding that the majority had received or were on PPI treatment. The minimal prevalence of H. pylori infection found in this cohort of patients with esophageal carcinoma suggests a protective role.

Experimental drugs for erosive esophagitis: what is in the clinical development pipeline?

INTRODUCTION: Proton pump inhibitor (PPI) has revolutionized the treatment of erosive esophagitis (EE) in the past few decades. However, roughly 30-40% of patients, especially with severe EE (Los Angeles Grade C/D), remain poorly responsive to this medication. Novel drugs have been formulated and/or repurposed to address this problem. AREAS COVERED: This review highlights novel drugs that have been investigated for use in EE, such as mucosal protectants, prokinetics, transient lower esophageal sphincter relaxation (TLESR) reducers, novel PPIs, and the new potassium-competitive acid blocker (PCAB). Studies have demonstrated that PCAB has promising results (efficacy and safety) compared to PPI for the healing of EE, especially in severe diseases. EXPERT OPINION: PCAB has gained interest in recent years, with pharmacokinetics and pharmacodynamics properties surpassing PPI. Although recent data on PCABs, which comprised mainly of Vonoprazan, have shown promising results, more randomized controlled trials for other PCAB drugs are needed to elucidate and confirm the superiority of this drug class to PPI, the current first-line treatment of EE.

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study.

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280-6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

The Impact of a Twice-daily vs Once-daily Proton Pump Inhibitor Dosing Regimen on Laryngopharyngeal Reflux Symptoms: A Prospective Randomized Controlled Trial.

Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19-79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from the baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16-week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups. Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions: Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Short-term usage of proton pump inhibitors during admission was associated with increased risk of rehospitalization in critically ill patients with myocardial infarction: a cohort study.

PURPOSE: Previous studies showed that long-term use of proton pump inhibitors (PPIs) was associated with cardiovascular events. However, the impact of short-term PPI exposure on intensive care unit (ICU) patients with myocardial infarction (MI) remains largely unknown. This study aims to determine the precise correlation between short-term PPI usage during hospitalization and prognostic outcomes of ICU-admitted MI patients using Medical Information Mart for Intensive Care IV database (MIMIC-IV). METHODS: Propensity score matching (PSM) was applied to adjust confounding factors. The primary study outcome was rehospitalization with mortality and length of stay as secondary outcomes. Binary logistic, multivariable Cox, and linear regression analyses were employed to estimate the impact of short-term PPI exposure on ICU-admitted MI patients. RESULTS: A total of 7249 patients were included, involving 3628 PPI users and 3621 non-PPI users. After PSM, 2687 pairs of patients were matched. The results demonstrated a significant association between PPI exposure and increased risk of rehospitalization for MI in both univariate and multivariate [odds ratio (OR) = 1.157, 95% confidence interval (CI) 1.020-1.313] analyses through logistic regression after PSM. Furthermore, this risk was also observed in patients using PPIs > 7 days, despite decreased risk of all-cause mortality among these patients. It was also found that pantoprazole increased the risk of rehospitalization, whereas omeprazole did not. CONCLUSION: Short-term PPI usage during hospitalization was still associated with higher risk of rehospitalization for MI in ICU-admitted MI patients. Furthermore, omeprazole might be superior to pantoprazole regarding the risk of rehospitalization in ICU-admitted MI patients.

Intragastric bacterial infection and endoscopic findings in Helicobacter pylori-negative patients.

In the present study, the authors examined the association between gastric bacterial infection and gastric endoscopic findings in Helicobacter pylori (H. pylori)-negative patients. The subjects were 105 H. pylori-negative patients. The mean age was 72.8 ±â€…9.1 years. Endoscopy and gastric juice culture were performed. The presence or absence of endoscopic findings was checked according to the Kyoto classification of gastritis. Culture was positive in 69 patients (65.7%), with Streptococcus α-hemolytic being the most common (51 patients), followed by Neisseria sp. (43 patients). According to the univariate analysis, there was a significant difference between the results of culture and background factors in the use of gastric antisecretory drugs and between the results of culture and various endoscopic findings in atrophic gastritis, intestinal metaplasia, regular arrangement of collecting venule, mucosal swelling, sticky mucus, hyperplastic polyps, hematin, and gastric cobblestone-like lesions. Furthermore, multivariate analysis revealed significant differences in background factors such as the use of gastric antisecretory drugs and endoscopic findings only in patients with mucosal swelling. Endoscopic findings of non-H. pylori bacteria-positive gastritis differed from endoscopic findings of H. pylori-infected gastritis in several respects. In conclusion, our results suggest that non-H. pylori bacteria may infect the stomach and cause gastric inflammation, especially in patients who long term use gastric antisecretory drugs.

Gastric Polyps in Long-Term Proton Pump Inhibitor Use: Identification of Risks and Characteristics.

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Adverse cardiovascular outcomes associated with proton pump inhibitor use after percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for gastroprotection in patients undergoing percutaneous coronary intervention (PCI), who are at increased risk of gastrointestinal bleeding due to antiplatelet therapy. However, emerging evidence suggests that PPIs may adversely impact cardiovascular outcomes. This systematic review and meta-analysis sought to assess the relationship between using PPIs and cardiovascular outcomes in patients following PCI. METHODS: We searched various databases up to March 15, 2024, for observational studies and randomized controlled trials (RCTs) assessing the cardiovascular effects of PPIs in PCI patients. Data were extracted on study characteristics, patient demographics, PPI use, and cardiovascular outcomes. The Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool 2 assessed study quality. Meta-analyses were conducted using a random-effects model using R software version 4.3. RESULTS: A total of 21 studies involving diverse populations and study designs were included. Observational studies suggested a moderate increase in risk for composite cardiovascular diseases (CVD), myocardial infarction (MI), and major adverse cardiac events (MACE) associated with PPI use, with pooled hazard ratios (HRs) of 1.20 (95% CI: 1.093-1.308) for CVD, 1.186 (95% CI: 1.069-1.303) for MI, and 1.155 (95% CI: 1.001-1.309) for MACE. However, RCTs showed no significant link between PPI therapy and negative cardiovascular events (Relative Risk: 1.016, 95% CI: 0.878-1.175). Substantial heterogeneity was observed among observational studies but not RCTs. CONCLUSION: The findings indicate that while observational studies suggest a potential risk of adverse cardiovascular events with post-PCI use of PPI, RCTs do not support this association. Further large-scale, high-quality studies are required to understand the cardiovascular implications of individual PPIs better and optimize patient management post-PCI. This analysis shows the complexity of PPI use in patients with coronary artery diseases and the necessity to balance gastroprotective benefits against potential cardiovascular risks.

The silent epidemic: Inappropriate use of proton pump inhibitors among hospitalized patients.

BACKGROUND AND STUDY AIMS: There is an increasing trend to inappropriately prescribe proton pump inhibitors (PPIs) in different clinical settings despite the reported adverse outcomes. This study aimed to assess (1) the prevalence of potentially inappropriate use of PPIs and its associated risk factors among hospitalized patients, at pre-admission and discharge and (2) the prevalence of valid indications of PPIs use without prescription. PATIENTS AND METHODS: A retrospective observational study was performed at a single center, examining the records of patients aged ≥18 years who were admitted to the Family Medicine inpatient service over a one-year period. The appropriateness of PPIs use was assessed against a set of pre-approved indications. RESULTS: A total of 289 patients were included in the analysis. Of these, 34.67 % were taking PPIs upon admission, increasing to 43.67 % at discharge (p < 0.001). Inappropriate PPI use was identified in 51.92 % at pre-admission and 57.25 % at discharge. Multivariate analysis identified significant factors contributing to inappropriate PPI use: polypharmacy at both admission and discharge (OR = 4.587, p = 0.031), and the presence of two or more comorbidities at discharge (OR = 5.421, p = 0.011; OR = 13.005, p = 0.037). Age ≤65 was associated with increased inappropriate use only at discharge (p < 0.003). Conversely, appropriate prescribing was noted in patients over 65 and those on antiplatelet therapy, aligning with clinical guidelines. CONCLUSIONS: This study reveals a high prevalence of inappropriate PPI use among hospitalized patients, notably increasing from admission to discharge. Key contributors to inappropriate PPI usage included polypharmacy and high comorbidity scores at discharge, particularly in patients under 65. This emphasizes the need for targeted interventions to optimize PPI prescribing practices in clinical settings.

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.