Proton Pump Inhibitor Treatment Research Articles

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors

The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Proton pump inhibitor use associated with an increased risk of gout: A population-based case-control study.

In previous reports, proton pump inhibitor (PPI) use increased the risk of gout. However, there is no epidemiological study investigating this association. We aimed to examine the potential impact of PPI treatment on the risk of developing gout. A population-based case-control study was performed using a Longitudinal Health Insurance Database 2000 from Taiwan (population 23 million). We identified gout cases and non-gout controls through propensity score matching at 1:1, which was matched by sex and age. We used a conditional logistic regression model to estimate an odds ratio and 95% confidence intervals (CI) for gout population versus controls. Esomeprazole increased the risk of gout after adjusting confounding variables (adjusted odds ratio [aOR] 1.3; 95% CI 1.0-1.6). The risk of gout was highest within 30 days of PPI treatment (aOR 1.7; 95% CI 1.4-1.9) and attenuated thereafter. The risk of gout was increased among female users of PPI compared with male users (aOR 2.2; 95% CI 1.7-2.8). The aOR of gout in people with PPI use was higher in middle-aged individuals (41-60 years: aOR 2.1; 95% CI 1.7-2.7) than in the older group (≥60 years: aOR 1.8; 95% CI 1.5-2.2). Our findings provide population-level evidence for the hypothesis that PPI treatment is positively associated with the risk of developing gout. Further research on the mechanism underlying this association is warranted.

Is There a Potential Link between Gastroesophageal Reflux Disease and Recurrent Respiratory Tract Infections in Children?

Background: The implications of gastroesophageal reflux disease in respiratory tract infections have been investigated over time. The aim of our study was to evaluate the relationship between these two pathologic entities and the outcome after proper antireflux treatment. Methods: A group of 53 children with recurrent respiratory tract infections admitted in the gastroenterology clinic of a children’s hospital in North-East Romania was investigated for gastroesophageal reflux disease through 24 h pH-metry. Those with a Boix-Ochoa score higher than 11.99 received proton pump inhibitor treatment and were reevaluated after 2 months. Results: A total of 41 children were found with a positive Boix-Ochoa score. After 2 months of antireflux therapy, eight patients still had a positive Boix-Ochoa score. Conclusions: Recurrent respiratory tract infections with symptoms resistant to treatment should be considered a reason to investigate for gastroesophageal reflux, because the symptoms may be due to micro- or macro-aspiration of the gastric refluxate or to an esophageal-bronchial reflex mediated through the vagal nerve.

Proton pump inhibitor treatment is associated with acute-on-chronic liver failure in patients with advanced cirrhosis.

Acute-on-chronic liver failure (ACLF) is a fatal complication of cirrhosis. Hence, identification of risk factors for ACLF is crucial. Previous studies have linked proton pump inhibitor (PPI) treatment to complications of cirrhosis, however, a possible effect of PPI treatment on the risk of ACLF has not been investigated yet. Therefore, the present study aimed to characterize the impact of PPI treatment on ACLF development. A total of 642 patients hospitalized due to complications of cirrhosis were retrospectively identified, and PPI treatment during an observation period of 3 years following the hospitalization was reviewed. Subsequently, 74 patients with newly initiated PPI treatment at the time of hospitalization (PPI group) were 1:1 propensity score matched to 74 patients who received no PPI treatment (no-PPI group). Primary end point was the development of ACLF during the observation period, and secondary endpoints were mortality and upper gastrointestinal bleeding. PPI and no-PPI groups had comparably severe chronic liver disease at baseline. Nevertheless, the cumulative incidence of ACLF in the presence of death as competing risk was markedly higher in the PPI group compared with the no-PPI group. ACLF-related deaths contributed significantly to a higher 3-year mortality in the PPI group. Uni and multivariable competing risk regression models confirmed that PPI treatment was an independent predictor of ACLF in the study collective (subdistribution HR: 1.892, 95% CI: 1.092-3.281, p = 0.023). The impact of PPI treatment on ACLF development was particularly strong in patients with a model for end-stage liver disease score >12. Upper gastrointestinal bleeding was slightly less frequent in the PPI group. The present results indicate that PPI treatment could be a risk factor for ACLF in patients with advanced cirrhosis.

Randomized Controlled Trial of Anti-reflux Mucosectomy Versus Radiofrequency Energy Delivery for Proton Pump Inhibitor-refractory Gastroesophageal Reflux Disease.

The efficacy and safety of anti-reflux mucosectomy (ARMS) or radiofrequency energy delivery in the treatment of gastroesophageal reflux disease (GERD) have been reported, but the difference between the 2 remains unclear. This was a single center, randomized, comparative clinical study. Patients with symptoms of heartburn and/or regurgitation despite proton pump inhibitor treatment were randomly assigned to either ARMS group (n = 20) or radiofrequency group (n = 20). Primary outcome was the standardized GERD questionnaire (GERDQ) at 2 years after the procedures. Secondary outcomes were the proportions of patients with complete proton pump inhibitor (PPI) cessation and patients satisfied with the treatment. A total of 18 patients randomized to ARMS and 16 to radiofrequency were analyzed in this study. The operation success rate of the 2 groups was 100%. In both ARMS and radiofrequency groups, GERDQ scores at 2 years after the procedures were significantly lower than that before operation (P = 0.044 and P = 0.046). At 2 years postoperatively, the scores of GERDQ did not differ between the 2 groups (P = 0.755). There was no significant difference in the rate of discontinuation of PPIs and patient satisfaction in the ARMS and radiofrequency groups (P = 0.642 and P = 0.934). The clinical efficacy of ARMS and radiofrequency for the PPI-refractory GERD is equivalent. ARMS, the efficacy of which could be maintained for at least 2 years, is promising endoscopic management for the treatment of refractory GERD.

A single-center retrospective study on epidemiological and Traditional Chinese Medicine syndrome characteristics of 21010 patients with reflux/heartburn symptoms.

To provide a basis for the clinical identification of true and false reflux, integrated traditional Chinese and Western medicine, and psychosomatic treatment, we conducted a retrospective study of the etiology and epidemiological and Traditional Chinese Medicine (TCM) syndrome characteristics of patients with reflux/heartburn symptoms. The 210 10 patients with reflux/heartburn treated at Tianjin Nankai Hospital from January 1, 2016, to December 31, 2019, were divided into four groups according to their pathogenesis. Sex, age, course of disease, incidence rate, gastroscopy, 24-h pH-impedance, esophageal manometry, Hamilton Anxiety Scale (HAMA) / Hamilton Depression Scale (HAMD) score, 8-week proton pump inhibitor (PPI) treatment effect, and TCM syndrome characteristics were statistically analyzed. A total of 21010 patients (8864 men and 12146 women), with reflux/heartburn symptoms were screened, including 6284 (29.9%) patients with reflux esophagitis (RE), 10427 (49.6%) patients with non-erosive reflux esophagitis (NERD), 2430 (11.6%) patients with reflux hypersensitivity (RH), and 1870 (8.9%) patients with functional heartburn (FH). The incidence of the disease was higher in women than in men (0.0001). The ranking of the incidence of anxiety and depression in these four groups was FH>RH>NERD>RE ( 0.0001). There were more women than men in the groups with anxiety and more men than women in the groups with depression ( 0.0001), and there was no significant difference in the distribution of anxiety and depression between men and women ( 0.5689). There were significant differences in TCM syndrome characteristics between NERD, RE, and functional esophageal diseases ( 0.01). The highest proportion of functional esophageal disease TCM symptoms was stagnation and phlegm obstruction syndrome (36.16%), and there was no significant difference between RH and FH. The effective rates of PPI treatment at 8 weeks in patients in the RE, NERD, RH, and FH groups were 89%, 72%, 54%, and 0%, respectively. RE was classified into grades A, B, C, and D according to the Los Angeles grading system. The ranking of the incidence of these four grades was A>B>C>D ( 0.0001). The effective rates of PPI treatment at 8 weeks were 91%, 81%, 69%, and 63% in patients with grade A, B, C, and D RE, respectively ( 0.0001). The highest proportion of TCM syndrome types of NERD and RE was the stagnated heat syndrome in the liver and stomach syndrome, 38.99% and 33.90%, respectively. Reflux/heartburn symptoms are relatively common in middle-aged women, and NERD is the most common etiology, followed by RE, RH, and FH. The most common TCM syndrome characteristics in NERD and RE were stagnated heat syndrome in the liver and stomach syndrome, and stagnation and phlegm obstruction syndrome in functional esophageal diseases. Most patients with reflux/heartburn symptoms also experienced anxiety and depression.

Pediatric Gastroesophageal Reflux Disease (GERD): A Literature Review

Background: Gastroesophageal reflux disease (GERD) is a condition where stomach contents reflux into the esophagus, causing discomfort and complications. It is most prevalent in infants (26.9%) and lesser in children under 10 (3.2%) and over 10 years old (10.1%). Discussion: GERD is caused by frequent relaxations of the lower esophageal sphincter (LES), allowing stomach contents to escape into the esophagus. Symptoms vary with age, with infants experiencing regurgitation and irritability, while older children may have heartburn and nausea. Diagnosis requires differentiating GERD from similar conditions and may involve various tests, though their primary use lacks sufficient evidence. Nonpharmacological treatments include thickened feeding, reducing feeding volume but increasing frequency and possibly eliminating cow's milk protein. Pharmacological treatments include Proton Pump Inhibitors (PPIs), and Histamine Receptor Antagonists (H2RAs), though their efficacy varies. Prokinetics are generally not recommended due to lack of evidence. If all these treatments fail, anti-reflux surgery such as fundoplication can be considered. Conclusion: The hallmark of GERD is the presence of esophagitis during endoscopy. However, Barrett’s esophagus is rare in pediatric GERD patients. Factors indicating a worse prognosis include early onset age, an initial GERD diagnosis, and the need for PPI or combination of H2RA and PPI treatment.

A PhysioMechanical Model of Esophageal Function in Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is characterized by eosinophilic inflammation, but also heterogeneous presentations involving fibrostenotic esophageal remodeling and esophageal dysmotility. We aimed to define and evaluate phenotypes of EoE using functional lumen imaging probe (FLIP) panometry (ie, a PhysioMechanical classification of EoE). Patients with EoE who completed FLIP during endoscopy were included in a cross-sectional study. FLIP studies were analyzed for distensibility plateau and compliance of the esophageal body, maximum esophagogastric junction diameter, and contractile response pattern. These FLIP features were then applied to define PhysioMechanical classifications. A total of 215 patients with EoE (mean [standard deviation] age 38 [12] years; 31% female) were included. Seven PhysioMechanical classifications were identified that differed by various clinical characteristics, including symptom duration (P < .001) and Endoscopic EoE Reference Scores (EREFS) (P < .001). In particular, patients with "nonreactive fibrostenosis" (n= 14), had greater symptom duration (median [interquartile range] 20 [10-30] years) and more frequently had EREFS grade 2 or 3 ring scores (14 of 14 patients) than patients with a "normal" PhysioMechanical classification (symptom duration: 3 [1-8] years; 4 of 50 [8%] had EREFS grade 2 or 3 rings). In addition, among patients off treatment at cross-sectional evaluation (n= 46), there was a difference between PhysioMechanical classifications in future proton pump inhibitor (PPI) response rates (ie, achieving peak mucosal eosinophil count <15 per high-powered field after PPI treatment); P= .009. PPI response ranged from 87% (13 of 15 patients) with "isolated esophagogastric junction outflow obstruction" to 11% (1 of 9 patients) with "spastic-reactive fibrostenosis." Classifying PhysioMechanical esophageal function in EoE based on FLIP panometry features may facilitate defining disease severity and directing management in EoE.

Mid-term outcomes after single anastomosis sleeve ileal (SASI) bypass in treatment of morbid obesity

BackgroundAccording to several short-term studies, single-anastomosis sleeve ileal (SASI) bypass offers similar weight loss to Roux-en-Y Gastric Bypass (RYGB) with fewer complication and better comorbidity reduction/resolution. Long-term data on this operation is lacking in the literature. The purpose of this study was to analyze the outcomes of SASI bypass up to 4 years.MethodsThis study is a retrospective cohort analysis of 366 patients with morbid obesity who underwent primary SASI bypass from January 2018 to February 2022.ResultsThe mean age and preoperative body mass index (BMI) were 41 years (range 22–71 years) and 43.9 ± 6.5 kg/m2, respectively. Follow-up was available for 229 patients at 1-year (89%), 112 patients at 2-year (75%), 61 patients at 3-year (75%), and 35 patients at 4-year (71%). The intraoperative, short-term, and long-term complication rates were 0%, 2.5%, 4.6%, respectively. After 4 years, mean percentage excess weight loss (%EWL) was 93.3% and total weight loss (%TWL) was 41.2%. Remission of comorbidities was 93% for type 2 diabetes mellitus, 73% for hypertension, 83% for hyperlipidemia, 79% for sleep apnea, and 25% for gastroesophageal reflux disease (GERD). Biliary gastritis and ulcers are seldom. Eight patients developed de novo GERD symptoms requiring proton pump inhibitor treatment. None of the patients in our study had hypoalbuminemia or malabsorption that did not respond to increased protein intake and vitamin or mineral supplementation.ConclusionSASI bypass appears to be safe, and one of the most effective bariatric procedures regarding weight loss and obesity related comorbidities. The double-outlet created in this procedure seemingly minimizes nutritional complications.Graphical abstract

Urea Breath Testing to Detect Helicobacter pylori in Patients with Peptic Ulcer Bleeding During Proton Pump Inhibitor Treatment.

This was a descriptive study carried out from January to December 2021, at Quanzhou First Hospital, an affiliated hospital of Fujian Medical University, to investigate the efficacy of the urea breath test in detecting Helicobacter pylori infection in patients with peptic ulcer bleeding affected with proton pump inhibitors. A total of 77 patients with peptic ulcer bleeding, who underwent urea breath testing after active bleeding, were divided into two groups. The Helicobacter pylori infection positivity rate in patients with peptic ulcer bleeding was 66.2%. The time from bleeding to detection and from admission to detection was not significantly different between the Helicobacter pylori-positive and -negative groups (p=0.840 and 0.285, respectively). Even with high-dose proton pump inhibitor treatment, a urea breath test can be performed after peptic ulcer bleeding ceases and results in an acceptable positivity rate. There was no significant difference in the accuracy of Helicobacter pylori detection between the time from bleeding to testing and from admission to testing. Key Words: Peptic ulcer, Helicobacter pylori, Upper gastrointestinal bleeding, Urea breath test, Proton pump inhibitor.

243P Concomitant administration of palbociclib and proton pump inhibitors affects clinical outcomes in metastatic breast cancer patients

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are usually combined with fulvestrant or aromatase inhibitors for the treatment of patients with metastatic breast cancer (mBC). Drug-drug interactions may affect absorption by different mechanims, for instance, modification of digestive pH. Proton pump inhibitors (PPIs) are known to reduce the oral bioavailability of some anticancer drugs. Palbociclib is a weak base with pH-dependent solubility, therefore variations in gastric pH could affect its absorption. The objective of this study was to evaluate the interaction between PPIs and palbociclib by analizing progression-free survival (PFS) in patients with mBC. This is a retrospective study approved by the local Ethics Committee. Patients had received palbociclib between January 2016 and December 2021. The following variables were collected: age, menopausal status, performance status, hormonal treatment (fulvestrant or aromatase inhibitors), visceral or non-visceral disease, first-line vs second-line treatment, ki67, and concomitant use of PPIs. PFS was defined as the time from starting treatment to progression of the disease. Survival was estimated with the Kaplan-Meier method, whereas Cox Regression models were used to estimate hazard ratios and the chi-square test for categorical variables. A total of 169 patients were enrolled in the study: 80 received a PPI and 86 did not, without significant differences in clinical characteristics in both groups. The median PFS was 17.3 months (95% CI: 13.83-20.76), 36 months in first-line and 13 months in second and subsequent lines. Patients taking PPIs had a shorter median PFS (14.30 versus 42.6 months, p<0.001; HR 4.18: 95% CI 2.57-6.80; p<0.0001). Median PFS was 44 vs. 14 months in first-line ans 17 vs 9 months in second or subsequent lines. The line of treatment (first vs second or beyond) and ki67 had a significant influence on DFS, whereas the remaining clinical variables did not. Patients with mBC treated with hormonal therapy plus palbociclib had poor PFS when receving a concomitant PPI. Although further studies are needed in the field, caution is recommended with the long-term use of PPIs in this population.

Association of proton pump inhibitor and antibiotic use with the clinical outcomes of hepatocellular carcinoma patients receiving atezolizumab and bevacizumab: A multicenter analysis.

This retrospective study aimed to investigate the impact of proton pump inhibitor treatment (PPI) and antibiotic treatment on the therapeutic outcomes of hepatocellular carcinoma (HCC) patients receiving atezolizumab and bevacizumab (Atez/Bev). The present study included a total of 441 HCC patients who were treated with Atez/Bev in 20 Japanese institutions from September 2020 to April 2022. We adopted the inverse probability of treatment weight to adjust for imbalance in the baseline characteristics of patients with and without PPI treatment as well as patients with and without antibiotic treatment. The progression-free survival (PFS) and overall survival (OS) of patients with and without PPI treatment did not differ to a statistically significant extent. In the weighted cohort, the difference in PFS and OS between the patients with and without PPI did not reach statistical significance (median PFS, 7.0 vs. 6.5months, p=0.07; 1-year survival rate 66.3% and 73.8%, p=0.9). The PFS and OS in patients with antibiotic treatment were worse in comparison to patients without antibiotic treatment (median PFS, 3.8 vs. 7.0months, p=0.007; 1-year survival rate 58.8% and 70.3%, p=0.01). In the weighted cohort, the PFS and OS of the two groups did not differ to a statistically significant extent (median PFS, 3.8 vs. 6.7months, p=0.2; 1-year survival rate, 61.8% and 71.0%, p=0.6). The therapeutic outcomes of Atez/Bev in HCC patients did not differ between patients with and without PPI treatment or between patients with and without antibiotic treatment.

Increased Sensitivity of Cough Reflex is Not the Mechanism of Cough Attributed to Laryngopharyngeal Reflux

In laryngopharyngeal reflux (LPR) patients acid reaches laryngopharyngeal area and stimulates/sensitizes respiratory nerve terminals mediating cough. We addressed several hypothesis: if stimulation of respiratory nerves is responsible for coughing then acidic LPR should correlate with coughing and proton pump inhibitor (PPI) treatment should reduce both LPR and coughing. If sensitization of respiratory nerves is responsible for coughing then cough sensitivity should correlate with coughing and PPI should reduce both coughing and cough sensitivity. In this prospective single center study, patients with positive reflux symptom index (RSI > 13) and/or reflux finding score (RFS > 7) and ≥1 LPR episode/24 hours were enrolled. We evaluated LPR by dual channel 24-hour pH/impedance. We determined number of LPR events with pH drop at levels 6.0, 5.5, 5.0, 4.5, and 4.0. Cough reflex sensitivity was determined as lowest capsaicin concentration causing at least 2/5 coughs (C2/C5) by single breath capsaicin inhalation challenge. For statistical analysis C2/C5 values were -log transformed. Troublesome coughing was evaluated on the scale 0-5. We enrolled 27 LPR patients. The number of LPR events with pH 6.0, 5.5, 5.0, 4.5, and 4.0 was 14[8-23],4[2-6],1[1-3],1[0-2] and 0[0-1], respectively. There was no correlation between number of LPR episodes at any pH level and coughing (Pearson range -0.34 to 0.21, P = NS). There was no correlation between cough reflex sensitivity C2/C5 and coughing (R = -0.29 to 0.34, P = NS). Of patients that completed PPI treatment, 11 had RSI normalized (18.36 ± 2.75 vs. 7 ± 1.35, P < 0.01). There was no change in cough reflex sensitivity in PPI-responders. C2 threshold was 1.41 ± 0.19 vs. 1.2 ± 0.19 (P = 0.11) before and after PPI. No correlation between cough sensitivity and coughing and no change in cough sensitivity despite improvement of coughing by PPI argue that an increased cough reflex sensitivity is not mechanism of cough in LPR. We identified no simple relationship between LPR and coughing suggesting that this relationship is more complex.

Proton pump inhibitor prophylaxis after Roux-en-Y gastric bypass: A national survey of surgeon practices.

Proton pump inhibitors (PPIs) are frequently used after Roux-en-Y gastric bypass (RYGB) to prevent marginal ulceration. The optimal duration of PPI treatment after surgery to minimize ulcer development is unclear. Assess bariatric surgeon practice variability regarding postoperative PPI prophylaxis. Survey of medical directors of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited centers. Members of the American Society for Metabolic and Bariatric Surgery research committee developed and administered a web-based anonymous survey in November 2021 to bariatric surgeons of Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program-accredited programs detailing questions related to surgeons' use of PPI after RYGB including patient selection, medication, dosage, and treatment duration. The survey was completed by 112 surgeons (response rate: 52.6%). PPIs were prescribed by 85.4% of surgeons for all patients during their hospitalization, 3.9% for selective patients, and 10.7% not at all. After discharge, 90.3% prescribed PPIs. Pantoprazole was most often used during hospitalization (38.5%), while omeprazole was most prescribed (61.7%) after discharge. The duration of postoperative PPI administration varied; it was 3 months in 43.6%, 1 month in 20.2%, and 6 months in 18.6% of patients. Finally, surgeons' practice setting and case volume were not associated with the duration of prophylactic PPI administration after RYGB. PPI administration practices vary widely among surgeons after RYGB, which may be related to the limited comparative evidence and guidelines on best duration of PPI administration. Large prospective clinical trials with objective outcome measures are needed to define optimal practices for PPI prophylaxis after RYGB to maximize clinical benefit.

Effect of Proton Pump Inhibitor Treatment in "PPI Non-responsive" Patients with Eosinophilic Esophagitis.

Some eosinophilic esophagitis (EoE) patients can have a decline in eosinophil count after proton pump inhibitor (PPI) treatment without achieving histologic response, but little is known about this group. We aimed to determine the effect of PPIs on reducing esophageal eosinophilia in patients deemed non-responsive to PPI therapy. We analyzed prospectively collected cohort data from newly diagnosed adults with EoE who were histologic non-responders (≥15 eos/hpf) to PPI-only therapy. Symptoms, endoscopic histologic features were assessed before and after PPI. Pre- and post-PPI treatment esophageal biopsies were read by pathologists to determine peak eosinophil counts and other histologic findings. Of 125 patients, peak eosinophil counts were 102.1 ± 69.8 and 102.9 ± 101.1 (p=0.93) before and after PPI treatment, respectively, but lamina propria fibrosis decreased from 97% to 41% (p<0.001). Heartburn frequency also decreased (19% to 11%; p=0.006), though endoscopic findings did not change. There were 75 patients (60%) who had some decrease in eosinophil counts, with 30 patients (24%) having ≥50% decrease in counts. When comparing the ≥50% and <50% decrease groups, differences in endoscopic features were identified, but the ≥50% group had improvement in eosinophil degranulation, microabscesses, spongiosis, and basal cell hyperplasia. Peak eosinophil counts did not decrease overall after PPI treatment, but symptoms of heartburn improved. Approximately a quarter had ≥50% decrease in eosinophil counts, with associated decreases in other histologic findings. Further research may consider what role PPIs have in this subset of non-responders or in combination therapies.

Laparoscopic antireflux surgery for refractory gastroesophageal reflux disease: long-term clinical outcomes

Persistent symptoms despite adequate Proton Pump Inhibitors (PPI) treatment are described in up to 40% of patients with Gastroesophageal Reflux Disease (GERD). The efficacy of Laparoscopic Antireflux Surgery (LARS) in PPI non-responder patients is still unclear. This observational study aims to report the long-term clinical outcomes and predictors of dissatisfaction in a cohort of refractory GERD patients submitted to LARS. Patients with preoperative refractory symptoms and objective GERD evidence submitted to LARS between 2008 and 2016 were included in the study. Primary endpoint was overall satisfaction with the procedure, secondary endpoints were long-term GERD symptom relief and endoscopic findings. Univariate and multivariate analyses were performed to compare satisfied and dissatisfied patients, in order to identify preoperative predictors of dissatisfaction. A total of 73 refractory GERD patients who underwent LARS were included in the study. At a mean follow-up of 91.2 ± 30.5 months, the satisfaction rate was 86.3%, with a statistically significant reduction in typical and atypical GERD symptoms. Causes of dissatisfaction were severe heartburn (6.8%), gas bloat syndrome (2.8%), and persistent dysphagia (4.1%). Multivariate analysis showed that a number of Total Distal Reflux Episodes (TDRE) > 75 was a predictive factor of long-term dissatisfaction after LARS while a partial response to PPI was a protective factor against dissatisfaction. LARS guarantees a high level of long-term satisfaction for selected refractory GERD patients. An abnormal TDRE at 24 h-multichannel intraluminal impedance-pH monitoring and the lack of response to preoperative PPI were predictors of long-term dissatisfaction.

Effects of prolonged proton pump inhibitor treatment on nutritional status and respiratory infection risk in cystic fibrosis: A matched cohort study.

Evidence on the effectiveness of proton pump inhibitors (PPI) as adjuvant therapy to improve maldigestion in people with cystic fibrosis (pwCF) is limited and there is increasing concern on possible side effects. We conducted a matched cohort study based on paediatric and adult pwCF who received PPI for ≥3 months. Treated patients were matched to a group of patients who never received PPI using a nearest neighbour propensity score matching based on sex, year of birth, CFTR genotype and pancreatic insufficiency. The study included 160 pwCF: 80 treated and 80 untreated patients. Over a median follow-up of 2 years, no significant differences in changes in BMI z-score were detected between groups (adjusted mean difference: 0.06, 95% CI: -0.17-0.30). At baseline 25% (n=20) of the treated patients and 22.5% (n=18) of the untreated patients had a positive culture for P. aeruginosa (Pa). At follow-up percentages of Pa positive cultures increased to 47.5% (n=38) in the treated group and to 26.3% (n=21) in the untreated group (adjusted mean difference: 23.1%, 95% CI: 10.8-35.3). Prolonged PPI therapy should be used cautiously in pwCF since it may increase the risk of respiratory infection by Pa. In addition, such treatment does not seem to improve nutritional status.

Assessment of small intestinal bacterial overgrowth and methane production in patients on chronic proton-pump inhibitor treatment: prevalence and role of rifaximin in its management in primary care.

Although proton pump inhibitor (PPI) drugs have considered able to induce small intestinal bacterial overgrowth (SIBO), no data are so far available from primary care (PC). We assessed the prevalence of SIBO and methane (CH<inf>4</inf>) production consequent to chronic PPI therapy using Lactulose Breath Test (LBT). Secondary aim was to explore the possible role of rifaximin in treating PPI-induced SIBO patients. One hundred twenty-five gastroesophageal reflux disease patients, constantly treated with PPI for at least 6 months and undergoing to LBT, were retrospectively assessed. An age-matched control population (control) of 100 patients, which had not used PPI in the last 6 months, was also enrolled. In the PPI group, SIBO positive patients and CH<inf>4</inf> producers were treated with rifaximin 1200 mg/daily for 14 days and re-checked with LBT one month after the end of treatment. The area under the curve (AUC) before and after treatment was also calculated for both SIBO positive patients and CH<inf>4</inf> producers. In the PPI group, SIBO prevalence was significantly higher vs. controls (38/125 [30.4%] vs. 27/100 [27%], P<0.05). 77/125 (61.6%) PPI patients were found to be CH<inf>4</inf> producers vs. 21/100 (21%) controls (P<0.05). Among SIBO patients in the PPI group, 34 (89.4%) were also CH<inf>4</inf> producers vs. 17/27 (63%) controls (P<0.05). After treatment, LBT resulted negative in 15/22 SIBO patients (68.1%) (P<0.05) and in 18/34 CH<inf>4</inf> producers (52.9%) (P<0.05). At the AUC analysis, an overall reduction of 54.2% for H<inf>2</inf> in SIBO patients and of 47.7% for CH<inf>4</inf> was assessed after rifaximin treatment (P<0.05). Our data showed that chronic use of PPI could be able to increase the prevalence of SIBO and to shift the intestinal microbial composition towards a CH4-producing flora. rifaximin could represent a useful therapeutical option for PPI-induced SIBO and for modulating CH4-producing flora.

No evidence for the benefit of PPIs in the treatment of acute pancreatitis: a systematic review and meta-analysis

Although current guidelines do not recommend the use of proton pump inhibitors (PPIs) in the standard of care of acute pancreatitis (AP), they are often prescribed in clinical practice, mainly for ulcer stress prophylaxis. In this systematic review and meta-analysis we evaluated the association between the use of PPIs in the management of AP and various clinical outcomes. We conducted the systematic research in six databases without restrictions on January 24th, 2022. We investigated adult patient with AP, who were treated with PPI compared to conventional therapy. The pooled odds ratios, mean differences, and corresponding 95% confidence intervals were calculated with random effect model. We included six RCTs and three cohort studies, consisting of 28,834 patients. We found a significant decrease in the rate of pancreatic pseudocyst formation in patients who received PPI treatment. PPI use was associated with a higher risk of GI bleeding, however this finding could be due to the patients’ comorbid conditions. We found no significant difference in the rates of 7-day mortality, length of hospital stay, and acute respiratory distress syndrome between the groups. The available data on this topic are limited; therefore, further well designed RCTs are needed to evaluate the potential benefits and adverse effects of PPIs in AP.