AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclu...AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area(immunohistochemistry and PCR analysis).Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase.Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed.The p H values were assessed in the aerosolized environment of the oropharynx(Dxp H Catheter) and compared to a subsequently applied combined p H/MII measurement.RESULTS:Twenty patients with LPR symptoms were included.In only one patient,the laryngeal H+K+-ATPase was verified by immunohistochemical staining.In another patient,real-time RT-PCR for each H+K+-ATPase subunit was positive.Fourteen out of twenty patients had pathological results in Dxp H,and 6/20 patients had pathological results in p H/MII.Four patients had pathological results in both functional tests.Nine out of twenty patients responded to PPIs.CONCLUSION:The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms.Alternative hypotheses for the pathomechanism are needed.The role of pharyngeal p H-metry remains unclearand its use can only be recommended for patients in a research study setting.展开更多
The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its c...The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.展开更多
AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.The...AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.展开更多
AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web o...AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.展开更多
BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopat...BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.展开更多
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 i...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.展开更多
文摘AIM:To determine the laryngeal H+K+-ATPase and pharyngeal p H in patients with laryngopharyngeal reflux(LPR)-symptoms as well as to assess the symptom scores during PPI therapy.METHODS:Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area(immunohistochemistry and PCR analysis).Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase.Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed.The p H values were assessed in the aerosolized environment of the oropharynx(Dxp H Catheter) and compared to a subsequently applied combined p H/MII measurement.RESULTS:Twenty patients with LPR symptoms were included.In only one patient,the laryngeal H+K+-ATPase was verified by immunohistochemical staining.In another patient,real-time RT-PCR for each H+K+-ATPase subunit was positive.Fourteen out of twenty patients had pathological results in Dxp H,and 6/20 patients had pathological results in p H/MII.Four patients had pathological results in both functional tests.Nine out of twenty patients responded to PPIs.CONCLUSION:The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms.Alternative hypotheses for the pathomechanism are needed.The role of pharyngeal p H-metry remains unclearand its use can only be recommended for patients in a research study setting.
文摘The survival and replication cycle of Helicobacter pylori(H.pylori)is strictly dependant on intragastric pH,since H.pylori enters replicative phase at an almost neutral pH(6-7),while at acid pH(3-6)it turns into its coccoid form,which is resistant to antibiotics.On these bases,it is crucial to increase intragastric pH by proton pump inhibitors(PPIs)when an antibiotic-based eradicating therapy needs to be administered.Therefore,several tricks need to be used to optimize eradication rate of different regimens.The administration of the highest dose as possible of PPI,by doubling or increasing the number of pills/day,has shown to be able to improve therapeutic outcome and has often proposed in rescue therapies,even if specific trials have not been performed.A pre-treatment with PPI before starting antibiotics does not seem to be effective,therefore it is discouraged.However,the choice of PPI molecule could have a certain weight,since second-generation substances(esomeprazole,rabeprazole)are likely more effective than those of first generation(omeprazole,lansoprazole).A possible explanation is due to their metabolism,which has been proven to be less dependent on cytochrome P450(CYP)2C19 genetic variables.Finally,vonoprazan,a competitive inhibitor of H+/K+-ATPase present on luminal membrane of gastric parietal cells has shown the highest efficacy,due to both its highest acid inhibition power and rapid pharmacologic effect.However current data come only from Eastern Asia,therefore its strong power needs to be confirmed outside this geographic area in Western countries as well as related to the local different antibiotic resistance rates.
文摘AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.
基金Supported by National Natural Science Foundation of China,No.31171106,No.81070302 and No.81270463
文摘AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.
文摘BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.
基金Supported by First Affiliated Hospital,Guangxi Medical University
文摘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.
