Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:Delphi consensus study

BACKGROUND Gastro-esophageal reflux disease(GERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by GERD.Antacids,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for GERD.Nevertheless,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse effects.An effective and safe alternative pharmacological tool for GERD is needed.After the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus process.AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method.METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD.The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:Gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)GERD disease;and(2)GERD treatment.Statements for each of these topics were then formulated and validated.The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform.RESULTS According to their routinary GERD practice and current clinical evidence,the panel members provided feedback to each questionnaire statement.The experts evaluated 15 statements and reached consensus on all 15.The statements regarding the GERD disease showed high levels of agreement,with consensus ranging from 70%to 92%.The statements regarding the GERD treatment also showed very high levels of agreement,with consensus ranging from 90%to 100%.This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management,such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel.The consensus was unanimous among the physicians with different specializations,underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management.The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable(reducing PPIs administration to as-needed use),should be considered.CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

Effects of proton pump inhibitors on inflammatory bowel disease:An updated review

Inflammatory bowel disease(IBD)is believed to be caused by various factors,including abnormalities in disease susceptibility genes,environmental factors,immune factors,and intestinal bacteria.Proton pump inhibitors(PPIs)are the primary drugs used to treat acid-related diseases.They are also commonly prescribed to patients with IBD.Recent studies have suggested a potential association between the use of certain medications,such as PPIs,and the occurrence and progression of IBD.In this review,we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms.Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Exposure to proton pump inhibitors and risk of diabetes:A systematic review and meta-analysis

BACKGROUND Exposure to proton pump inhibitors(PPIs)has been reported to have a potential role in the development of diabetes.AIM To determine the association between PPIs and diabetes.METHODS This meta-analysis is registered on PROSPERO(CRD42022352704).In August 2022,eligible studies were identified through a comprehensive literature search.In this study,odds ratios were combined with 95%confidence intervals using a random-effects model.The source of heterogeneity was assessed using sensitivity analysis and subgroup analysis.The publication bias was evaluated using Egger’s test and Begg’s test.RESULTS The meta-analysis included 9 studies with a total of 867185 participants.Results showed that the use of PPIs increased the risk of diabetes(odds ratio=1.23,95%confidence interval:1.05-1.43,n=9,I2=96.3%).Subgroup analysis showed that geographic location and study type had significant effects on the overall results.Both Egger’s and Begg’s tests showed no publication bias(P>0.05).Sensitivity analysis also confirmed the stability of the results.CONCLUSION The results of this study indicated that the use of PPIs was related to an increased risk of diabetes.However,more well-designed studies are needed to verify these results in the future.

Proton pump inhibitors and gastroprotection in patients treated with antithrombotic drugs: A cardiologic point of view

Aspirin,other antiplatelet agents,and anticoagulant drugs are used across a wide spectrum of cardiovascular and cerebrovascular diseases.A concomitant proton pump inhibitor(PPI)treatment is often prescribed in these patients,as gastrointestinal complications are relatively frequent.On the other hand,a potential increased risk of cardiovascular events has been suggested in patients treated with PPIs;in particular,it has been discussed whether these drugs may reduce the cardiovascular protection of clopidogrel,due to pharmacodynamic and pharmacokinetic interactions through hepatic metabolism.Previously,the concomitant use of clopidogrel and omeprazole or esomeprazole has been discouraged.In contrast,it remains less known whether PPI use may affect the clinical efficacy of ticagrelor and prasugrel,new P2Y12 receptor antagonists.Current guidelines recommend PPI use in combination with antiplatelet treatment in patients with risk factors for gastrointestinal bleeding,including advanced age,concurrent use of anticoagulants,steroids,or non-steroidal anti-inflammatory drugs,and Helicobacter pylori(H.pylori)infection.In patients taking oral anticoagulant with risk factors for gastrointestinal bleeding,PPIs could be recommended,even if their usefulness deserves further data.H.pylori infection should always be investigated and treated in patients with a history of peptic ulcer disease(with or without complication)treated with antithrombotic drugs.The present review summarizes the current knowledge regarding the widespread combined use of platelet inhibitors,anticoagulants,and PPIs,discussing consequent clinical implications.

Effects of postoperative use of proton pump inhibitors on gastrointestinal bleeding after endoscopic variceal treatment during hospitalization

BACKGROUND Endoscopic variceal treatment(EVT)is recommended as the mainstay choice for the management of high-risk gastroesophageal varices and acute variceal bleeding in liver cirrhosis.Proton pump inhibitors(PPIs)are widely used for various gastric acid-related diseases.However,the effects of PPIs on the development of post-EVT complications,especially gastrointestinal bleeding(GIB),remain controversial.AIM To evaluate the effects of postoperative use of PPIs on post-EVT complications in patients with liver cirrhosis during hospitalization.METHODS Patients with a diagnosis of liver cirrhosis who were admitted to the Department of Gastroenterology of the General Hospital of Northern Theater Command,treated by an attending physician between January 2016 and June 2020 and underwent EVT during their hospitalization were included.Logistic regression analyses were performed to explore the effects of postoperative use of PPIs on the development of post-EVT complications during hospitalization.Odds ratios(ORs)with 95%confidence intervals(CIs)were calculated.RESULTS A total of 143 patients were included.The incidence of post-EVT GIB and other post-EVT complications was 4.90%and 46.85%,respectively.In the overall analyses,postoperative use of PPIs did not significantly reduce the risk of post-EVT GIB(OR=0.525,95%CI=0.113-2.438,P=0.411)or other post-EVT complications(OR=0.804,95%CI=0.413-1.565,P=0.522).In the subgroup analyses according to the enrollment period,type and route of PPIs after the index EVT,use of PPIs before the index EVT,use of vasoactive drugs after the index EVT,indication of EVT(prophylactic and therapeutic),and presence of portal venous system thrombosis,ascites,and hepatocellular carcinoma,the effects of postoperative use of PPIs on the risk of post-EVT GIB or other post-EVT complications remain not statistically significant.CONCLUSION Routine use of PPIs after EVT should not be recommended in patients with liver cirrhosis for the prevention of post-EVT complications during hospitalization.

Progress in the Study of Vonoprazan Fumarate vs. Proton Pump Inhibitors in the Treatment of Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

High-dose vs low-dose proton pump inhibitors for upper gastrointestinal bleeding:A meta-analysis

AIM:To evaluate the efficacy of high-dose proton pump inhibitors(PPIs)vs low-dose PPIs for patients with upper gastrointestinal bleeding.METHODS:PubMed,Embase,the Cochrane Library,and Web of Science were searched to identify relevant randomized controlled trials(RCTs).Eligible trials were RCTs that compared high-dose PPI with low-dose PPI following endoscopic hemostasis.The primary endpoint was rebleeding;secondary endpoints were patient numbers that needed surgery,and mortality.The meta-analysis was performed with a fixed effects model or random effects model.RESULTS:Nine eligible RCTs including 1342 patients were retrieved.The results showed that high-dose intravenous PPI was not superior to low-dose intra-venous PPI in reducing rebleeding[odds ratio(OR)= 1.091,95%confidential interval(CI):0.777-1.532],need for surgery(OR=1.522,95%CI:0.643-3.605) and mortality(OR=1.022,95%CI:0.476-2.196).Subgroup analysis according to different region revealed no difference in rebleeding rate between Asian patients(OR=0.831,95%CI,0.467-1.480)and European patients(OR=1.263,95%CI:0.827-1.929).CONCLUSION:Low-dose intravenous PPI can achieve the same efficacy as high-dose PPI following endoscopic hemostasis.

Proton pump inhibitors as a risk factor for recurrence of Clostridium-difficile-associated diarrhea

AIM:To investigate the risk factors for Clostridiumdifficile-associated diarrhea(CDAD)recurrence,and its relationship with proton pump inhibitors(PPIs). METHODS:Retrospective data of 125 consecutive hospitalized patients diagnosed with CDAD between January 2006 and December 2007 were collected by medical chart review.Collected data included patient characteristics at baseline,underlying medical disease, antibiotic history before receiving a diagnosis of CDAD, duration of hospital stay,severity of CDAD,concurrenttreatment with PPIs,laboratory parameters,response to CDAD therapy,and recurrence of disease within 90 d of successful treatment.Various clinical and laboratory parameters were compared in patients in whom CDAD did or did not recur. RESULTS:Of the 125 patients(mean age,67.6± 13.9 years)that developed CDAD,98(78.4%)did not experience recurrence(non-recurrent group)and 27 (21.6%)experienced one or more recurrences(recurrent group).Prior to the development of CDAD,96% of the 125 patients were prescribed antibiotics,and 56(44.8%)of the patients received PPIs.Age older than 65 years(P=0.021),feeding via nasogastric tube(NGT)(P=0.045),low serum albumin level(P =0.025),and concurrent use of PPIs(P=0.014) were found to be risk factors for CDAD recurrence by univariate analysis.However,sex,length of hospital stay,duration and type of antibiotics used,severity of disease,leukocyte count and C-reactive protein(CRP) were not associated with risk of CDAD recurrence.On multivariate analysis,the important risk factors were advanced age(>65 years,adjusted OR:1.32,95% CI:1.12-3.87,P=0.031),low serum albumin level(< 2.5 g/dL,adjusted OR:1.85,95%CI:1.35-4.91,P= 0.028),and concurrent use of PPIs(adjusted OR:3.48, 95%CI:1.64-7.69,P=0.016). CONCLUSION:Advanced age,serum albumin level< 2.5 g/dL,and concomitant use of PPIs were found to be significant risk factors for CDAD recurrence.

Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors

AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.

Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis

AIM To investigate whether the use of proton pump inhibitors(PPIs) increases the incidence of spontaneous bacterial peritonitis(SBP) in patients with cirrhosis and ascites.METHODS An historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm3 without evidence of an intraabdominal, surgically treatable source of infection.RESULTS Of 738 cirrhotic patients, 582(58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection(36.2%) and alcohol abuse(25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299(51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP(22.5%). Among 107 non-users of PPIs, 23 developed SBP(21.5%)(HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh(CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo(Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP(58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP(P = 0.34). CONCLUSION In conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

Impact of Drug-Drug Interaction between CDK4/6 Inhibitors and Proton Pump Inhibitors on Survival Outcomes in the Treatment of Metastatic Breast Cancer—Real World Data from a Portuguese Center

Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.

Nissen fundoplication vs proton pump inhibitors for laryngopharyngeal reflux based on p H-monitoring and symptom-scale

AIM To compare the outcomes between laparoscopic Nissen fundoplication(LNF)and proton pump inhibitors(PPIs)therapy in patients with laryngopharyngeal reflux(LPR)and typeⅠhiatal hernia diagnosed by oropharyngeal p H-monitoring and symptom-scale assessment.METHODS From February 2014 to January 2015,70 patients who were diagnosed with LPR and type I hiatal hernia and referred for symptomatic assessment,oropharyngeal p H-monitoring,manometry,and gastrointestinal endoscopy were enrolled in this study.All of the patients met the inclusion criteria.All of the patients underwent LNF or PPIs administration,and completed a2-year follow-up.Patients’baseline characteristics and primary outcome measures,including comprehensive and single symptoms of LPR,PPIs independence,and satisfaction,and postoperative complications were assessed.The outcomes of LNF and PPIs therapy were analyzed and compared. RESULTS There were 31 patients in the LNF group and 39patients in the PPI group.Fifty-three patients(25 in the LNF group and 28 in the PPI group)completed reviews and follow-up.Oropharyngeal p H-monitoring parameters were all abnormal with high acid exposure,a large amount of reflux,and a high Ryan score,associated reflux symptom index(RSI)score.There was a significant improvement in the RSI and LPR symptom scores after the 2-year follow-up in both groups(P<0.05),as well as typical symptoms of gastroesophageal reflux disease.Improvement in the RSI(P<0.005)and symptom scores of cough(P=0.032),mucus(P=0.011),and throat clearing(P=0.022)was significantly superior in the LNF group to that in the PPI group.After LNF and PPIs therapy,13 and 53 patients achieved independence from PPIs therapy(LNF:44.0%vs PPI:7.14%,P<0.001)during follow-up,respectively.Patients in the LNF group were more satisfied with their quality of life than those in the PPI group(LNF:62.49±28.68 vs PPI:44.36±32.77,P=0.004).Body mass index was significantly lower in the LNF group than in the PPI group(LNF:22.2±3.1kg/m^2 vs PPI:25.1±2.9 kg/m^2,P=0.001).CONCLUSION Diagnosis of LPR should be assessed with oropharyngeal p H-monitoring,manometry,and the symptom-scale.LNF achieves better improvement than PPIs for LPR with type I hiatal hernia.

Proton pump inhibitors and colorectal cancer:A systematic review

BACKGROUND The use of proton pump inhibitors(PPI)is common worldwide,with reports suggesting that they may be overused.Several studies have found that PPI may affect colorectal cancer(CRC)risk.AIM To summarize current knowledge on the relationship between PPI and CRC from basic research,epidemiological and clinical studies.METHODS This systematic review was based on the patients,interventions,comparisons,outcome models and performed according to PRISMA guidelines.MEDLINE,EMBASE,Scopus,and Web of Science databases were searched from inception until May 17,2021.The initial search returned 2591 articles,of which,28 studies met the inclusion criteria for this review.The studies were categorized as basic research studies(n=12),epidemiological studies(n=11),and CRC treatment studies(n=5).The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.RESULTS Data from basic research indicates that PPI do not stimulate CRC development via the trophic effect of gastrin but instead may paradoxically inhibit it.These studies also suggest that PPI may have properties beneficial for CRC treatment.PPI appear to have anti-tumor properties(omeprazole,pantoprazole),and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors(pantoprazole,ilaprazole),and chemosensitizing agents(pantoprazole).However,these mechanisms have not been confirmed in human trials.Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk.Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes,while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil,leucovorin,oxaliplatin(FOLFOX)regimen.CONCLUSION An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted.This review identifies that different PPI agents may have differential effects on CRC treatment,with practical implications.Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.

Endoscopic full-thickness plication along with argon plasma coagulation for treatment of proton pump inhibitor dependent gastroesophageal reflux disease

BACKGROUND Most endoscopic anti-reflux interventions for gastroesophageal reflux disease(GERD)management are technically challenging to practice with inadequate data to support it utility.Therefore,this study was carried to evaluate the effectiveness and safety newer endoscopic full-thickness fundoplication(EFTP)device along with Argon Plasma Coagulation to treat individuals with GERD.AIM To evaluate the effectiveness and safety newer EFTP device along with Argon Plasma Coagulation to treat individuals with GERD.METHODS This study was a single-center comparative analysis conducted on patients treated at a Noble Institute of Gastroenterology,Ahmedabad,hospital between 2020 and 2022.The research aimed to retrospectively analyze patient data on GERD symptoms and proton pump inhibitor(PPI)dependence who underwent EFTP using the GERD-X system along with argon plasma coagulation(APC).The primary endpoint was the mean change in the total gastroesophageal reflux disease health-related quality of life(GERD-HRQL)score compared to the baseline measurement at the 3-month follow-up.Secondary endpoints encompassed enhancements in the overall GERD-HRQL score,improvements in GERD symptom scores at the 3 and changes in PPI usage at the 3 and 12-month time points.RESULTS In this study,patients most were in Hill Class II,and over half had ineffective esophageal motility.Following the EFTP procedure,there were significant improvements in heartburn and regurgitation scores,as well as GERDHRQL scores(P<0.001).PPI use significantly decreased,with 82.6%not needing PPIs or prokinetics at end of 1 year.No significant adverse events related to the procedures were observed in either group.CONCLUSION The EFTP along with APC procedure shows promise in addressing GERD symptoms and improving patients'quality of life,particularly for suitable candidates.Moreover,the application of a lone clip with APC yielded superior outcomes and exhibited greater cost-effectiveness.

Sporadic fundic gland polyps are not associated with proton pump inhibitors therapy but negatively correlate with Helicobacter pylori infection in China

Background Sporadic fundic gland polyps （FGPs） are common gastric polyps.Some studies reported that FGPs dramatically increased due to proton pump inhibitors （PPIs） use and a decreased prevalence of Helicobacter pylori （H.pylon） infection in Western countries.However,data are still controversial.This study aimed to identify the relationships between these two factors and FGPs in China.Methods Consecutive patients with FGPs detected were retrospectively analyzed.Data including patients＇ age,sex,symptoms,H.pylori infection,history of PPIs use,and the polyps were documented.Each patient was compared with two randomly selected age-and sex-matched controls with similar symptoms in the same period.Results During the period from March 2011 to March 2012,a total of 328 patients were diagnosed as FGPs in 23 047 patients who underwent routine esophagogastroduodenoscopy and 656 patients without FGPs as controls.The mean age was （55.12±12.61） years,and 75.91％ were women.The prevalence of H.pylori in patients with FGPs was significantly lower than in those without FGPs （22.30％ （64/287） vs.42.26％ （224/530）,P ＜0.001,OR 0.392,95％ Cl 0.283-0.544）.Overall,a total of 54 patients with FGPs （54/328,16.46％） and 136 patients without FGPs （136/656,20.73％） received PPIs therapy （P=0.110）.According to the different duration of PPIs use,no significant differences of PPIs use were found between the cases and controls among all subgroups.Moreover,the PPIs use was also similar,regardless of age,sex,H.pylori infection,and the number of polyps.Conclusion Sporadic FGPs may not be induced by PPIs therapy but negatively correlate with H.pylori infection in China,which is not the same with the data in Western countries.

Hypomagnesaemia associated with long-term use of proton pump inhibitors

Hypomagnesaemia and associated hypocalcaemia and hypoparathyroidism have been increasingly recognised as rare longterm side-effects of proton pump inhibitors(PPIs).The PPIs may inhibit active magnesium(Mg)absorption by interfering with transcellular transient receptor potential melastatin-6 and-7(TRPM 6 and 7)channels.More recent cell culture studies have suggested concomitant inhibition of passive Mg absorption by omeprazole.After being treated with a range of PPIs,the four patients in our case series developed hypomagnesaemia,which responded to withdrawal of therapy and initiation of Mg replacement.Their clinical course and management demonstrate key aspects of hypomagnesaemia associated with long-term use of PPIs.

Efficacy and Safety of Direct-acting Antivirals in Hepatitis C Virus-infected Patients Taking Proton Pump Inhibitors

Background and Aims:Direct-acting antiviral(DAA)therapy is the cornerstone of the treatment of chronic hepatitis C virus(HCV)infection.Eradication of HCV,predicted by the attainment of a sustained virologic response(SVR)12 weeks following DAA therapy,is the goal of this treatment.Interestingly,recent studies have reported the possible association between HCV-infected patients with DAA therapy concomitant use of proton pump inhibitors(PPIs)and lower odds of achieving SVR.This meta-analysis was conducted to summarize all available data and to estimate this potential association.Methods:Comprehensive literature review was conducted by first searching the Medline and Embase databases through March 2017 to identify all studies that investigated the safety and efficacy of DAAs in patients with HCV infection taking PPIs versus those without PPIs.Adjusted point estimates from each study were combined by the generic inverse variance method of DerSimonian and Laird.Results:Nine cohort studies with 32,684 participants met the eligibility criteria and were included in the meta-analysis.The use of PPIs concomitant with DAAs among HCV-infected patients was associated with lower odds of achieving SVR compared with non-PPI users(pooled odds ratio(OR):0.74,95%confidence interval(CI):0.63-0.88,I2=24%).Subgroup analysis addressed the association between PPIs use and SVR12 demonstrated the association of PPI users showing lower odds of achieving SVR12 compared with those with no use of PPIs(pooled OR:0.68,95%CI:0.51-0.9,I2=33%).Conclusions:This study demonstrated a significantly increased risk of failure to achieve SVR in HCV-infected patients taking DAA with PPIs compared to non-PPI users.Providers should consider whether PPI therapy is indicated for patients and withdraw of PPI therapy in the absence of indications,especially while on DAA therapy.

Impact of concomitant use of proton pump inhibitors on anti-platelet therapy of clopidogrel in patients undergoing percutaneous coronary intervention

Background In clopidogrel-treated patients undergoing percutaneous coronary intervention （PCI）, the effect of concomitant use of PPIs on prognosis remains unclear. Methods From July 2010 to June 2012, 600 patients after implantation of drug-eluting stent （DES） were assigned to 3 groups according to the medical therapy： group 1 （n = 200） received dural antiplatelet therapy （DAPT） alone （aspirine 100 mg daily plus clopidogrel 75 mg daily）, group 2（n = 199） received DAFT plus pantoprazole 20 mg daily while group 3（n = 201） received DAFT plus omeprazole 20 mg daily for 1 year. The primary outcome was major adverse cardiovascular events （MACEs） which compose of death, nonfatal myocardial infarction （MI）, nonfatal stroke, target vessel revascularization （TVR） or stent thrombosis （ST） at 1 year. Platelet reactivity was evaluated for all patients before PCI and 1 year after PCI. Results There was no significant difference in the platelet reactivity among the 3 groups at 1-year follow-up（27.3% versus 29.9% versus 29.3%, respectively, P = 0.339）. Neither was there significant difference in the incidence of 1-year MACEs （13% versus 14.6% versus 12.4%, respectively, P = 0.809）. Conclusions Concomitant use of pantoprazole or omeprazole did not influence platelet reactivity or clinical events in patients receiving DAPT after implantation of DES.