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Background & Aims: Individuals with Barrett's esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to the development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes. Methods: We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle Barrett's Esophagus Study. We calculated homeostatic model assessment scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and the risk of EA using Cox regression models adjusted for known risk factors. Results: Increasing homeostatic model assessment scores were associated with an increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio [HR], 2.45; 95% confidence interval [CI], 1.43–4.1; P trend = .001). Leptin level also was associated significantly with an increased risk of EA within 3 years (HR, 2.51; 95% CI, 1.09–5.81; P trend = .03) and 6 years (HR, 2.07; 95% CI, 1.01–4.26; P trend = .048) of baseline. The level of high-molecular-weight adiponectin had a nonlinear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR, 0.34; 95% CI, 0.14–0.82). Metabolic syndrome was not associated with risk of EA. Conclusions: Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased levels of high-molecular-weight adiponectin is associated inversely with EA. These biomarkers might be used to determine cancer risk among patients with BE. [Copyright &y& Elsevier]

Background: Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective: We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods: We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results: We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ2 1 = 112.0; P < 10−3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion: There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD. [Copyright &y& Elsevier]

Aim To identify the predictive factors for the presence of small bowel lesions in patients with obscure gastrointestinal bleeding ( OGIB). Methods A total of 242 patients with OGIB (overt 149: occult 93) were retrospectively included in the present study. Capsule endoscopy ( CE) was carried out to investigate the small bowel, and detected lesions were classified according to the P0- P2 system. Only P2 lesions were defined as significant lesions. Univariate and multivariate logistic regression analyses were carried out to define the predictive factors for the presence of small bowel lesions. Results In patients with overt OGIB, chronic kidney disease ( CKD) ≥stage 4 (odds ratio [ OR] 4.03; 95% confidence interval [ CI] 1.45-11.1, P = 0.007) was identified as an independent predictor of the presence of vascular lesions, and a history of non-steroidalanti-inflammatory drug ( NSAID) use as that of erosive/ulcerated lesions ( OR 4.73; 95% CI 1.47-15.2, P = 0.009). However, in patients with occult OGIB, no significant predictors of the presence of vascular lesions were identified, whereas a history of low-dose aspirin ( LDA) ( OR 3.57; 95% CI 1.21-10.5, P = 0.02) and proton pump inhibitor ( PPI) use ( OR 3.18; 95% CI 1.02-9.92, P = 0.05) were identified as independent predictors of the presence of erosive/ulcerated lesions. Conclusions Our results indicated that bleeding pattern and clinical characteristics could contribute to predicting the origin of OGIB. [ABSTRACT FROM AUTHOR]

Background & Aims: Many patients with gastroesophageal reflux disease (GERD) have persistent reflux despite treatment with proton pump inhibitors (PPIs). Mixed gas-liquid reflux events are more likely to be perceived as symptomatic. We used esophageal impedance monitoring to investigate whether esophageal gas is processed differently among patients with GERD who do and do not respond to PPI therapy. Methods: We performed a prospective study of 44 patients with typical reflux symptoms with high levels of esophageal acid exposure during a 24-hour period; 18 patients were fully responsive, and 26 did not respond to PPI therapy. Twenty-four–hour pH impedance recordings were analyzed for fasting and prandial air swallows and reflux characteristics, including the presence of gas in the refluxate. Results: PPI-refractory patients had a higher number (83.1 ± 12.7 vs 47.8 ± 7.3, P < .05) and rate (10.5 ± 1.4 vs 5.9 ± 0.8/10 minutes, P < .05) of prandial air swallows than patients who responded to PPI therapy; they also had a higher number (25.5 ± 4.0 vs 16.8 ± 3.3, P < .05) and proportion (70% ± 0.03% vs 54% ± 0.06%, P < .05) of postprandial, mixed gas-liquid reflux. Symptoms of PPI-refractory patients were more often preceded by mixed gas-liquid reflux events than those of PPI responders. Fasting air swallowing and other reflux characteristics did not differ between patients who did and did not respond to PPIs. Conclusions: Some patients with GERD who do not respond to PPI therapy swallow more air at mealtime than those who respond to PPIs and also have more reflux episodes that contain gas. These factors, combined with mucosal sensitization by previous exposure to acid, could affect perception of symptoms. These patients, who can be identified on standard 24-hour pH impedance monitoring, might be given behavioral therapy to reduce mealtime air swallowing. [Copyright &y& Elsevier]

Highlights: [•] Human gastric fluid samples were collected to measure Cr(VI) reduction. [•] Cr(VI) reduction is pH-dependent, mixed second order, and capacity limited. [•] A human PBPK model was developed for Cr with emphasis on the GI tract. [•] The model can be used to support human risk assessment for Cr(VI). [Copyright &y& Elsevier]

Background: Prophylaxis with proton pump inhibitor (PPI) in patients treated with glucocorticoid therapy is a common phenomenon in the general wards of Chinese hospitals. Many of these prescriptions are inappropriate and lead to overuse. Hospital-acquired pneumonia (HAP) is a possible adverse effect for this combination but remains controversial., Methods: We designed a retrospective cohort study using electronic medical record databases from multiple hospitals to investigate whether PPI prophylaxis increases the risk of HAP in hospitalized patients receiving glucocorticoid therapy. The study population was adult patients who were not critical and treated with at least 1 dose of glucocorticoid during hospitalization and the exposure factor was PPIs prophylaxis. The odds ratio of HAP between the exposed and unexposed groups was calculated based on the cohort which was established by propensity score matching. The dose-effect relationship between PPI prophylaxis and HAP was also evaluated., Results: Among the 307,622 admissions eligible for the study, a total of 217,460 (70.7%) admissions had a record of PPI prophylaxis. After reconstructed the cohort by propensity score matching, the exposed and unexposed groups both included 83,786 admissions. The incidence of HAP in the exposed group was higher than that in the unexposed group (2.1% vs. 1.5%, OR: 1.4, 95% CI: 1.3 to 1.5). The risk of HAP increased when the cumulative dose of PPI during hospital was more than 2 defined drug doses. Compared to the unexposed group, the adjusted odds ratio was 1.3 (95% CI: 1.2 to 1.4) in the medium-dose group (2-7 defined drug doses) and 1.9 (95% CI: 1.8 to 2.1) in the high-dose group (>7 defined drug doses)., Conclusions: PPI prophylaxis increased the risk of HAP in hospitalized patients treated with glucocorticoid therapy and the risk of HAP increased as the dose of PPIs accumulated., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1886/coif). Both authors report that the study was funded by Shanghai Municipal Health Commission scientific research project (grant number 201940028). Both authors have no other conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Background & Aims: We performed a prospective cohort study to investigate the effects of gastroprotective agents (such as proton pump inhibitors or histamine-2 receptor antagonists) on long-term clinical outcomes of patients with Helicobacter pylori–negative idiopathic bleeding ulcers. Methods: Patients with H pylori–negative idiopathic bleeding ulcers were recruited from a single center from April 2002 to March 2009 (n = 663). Age- and sex-matched patients with H pylori–positive bleeding ulcers were used as controls (n = 633). After ulcers had healed, 566 patients in the H pylori–negative idiopathic ulcer cohort received gastroprotective agents at clinicians'' discretion, whereas controls received no gastroprotective agent after H pylori eradication therapy. Patients were followed until September 2011 for end points that included recurrent ulcer bleeding and all-cause mortality. Results: During the exposed period of 534 person-years, the incidence rates of recurrent ulcer bleeding and death were 3.8 (95% confidence interval [CI], 2.6–5.4) and 21.8 (95% CI, 18.8–25.3) per 100 person-years among the patients given gastroprotective agents, compared with incidence rates of 2.4 (95% CI, 1.6–3.5; P = .08) and 13.8 (95% CI, 11.9–16.0; P < .001) per 100 person-years, respectively, during the unexposed period of 1588 person-years. Use of gastroprotective agents was not associated with mortality, after adjusting for confounders (hazard ratio, 1.1; 95% CI, 0.6–1.7). Incident rates of recurrent ulcer bleeding and death were significantly higher in patients with H pylori–negative idiopathic ulcers (2.9 and 17.0 per 100 person-years, respectively) than in controls (1.1 and 5.9 per 100 person-years, respectively; P < .001). Conclusions: Gastroprotective agents do not reduce the risk of recurrent bleeding or mortality for patients with H pylori–negative idiopathic bleeding ulcers. [Copyright &y& Elsevier]

Adding proton pump inhibitors (PPIs) to endoscopic therapy has become the mainstay of treatment for peptic ulcer bleeding, with current consensus guidelines recommending high-dose intravenous (IV) PPI therapy (IV bolus followed by continuous therapy). However, whether or not high-dose PPI therapy is more effective than low-dose PPI therapy is still debated. Furthermore, maintaining pH ≥ 4 appears to prevent mucosal bleeding in patients with acute stress ulcers; thus, stress ulcer prophylaxis with acid-suppressing therapy has been increasingly recommended in intensive care units (ICUs). This review evaluates the evidence for the efficacy of IV pantoprazole, a PPI, in preventing ulcer rebleeding after endoscopic hemostasis, and in controlling gastric pH and protecting against upper gastrointestinal (GI) bleeding in high-risk ICU patients. The review concludes that IV pantoprazole provides an effective option in the treatment of upper GI bleeding, the prevention of rebleeding, and for the prophylaxis of acute bleeding stress ulcers. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is useful for treating gastric tumors. Several trials have shown the efficacy of 4 or 8 weeks of proton pump inhibitor (PPI) administration for post-ESD ulcers. However, if the size of the post-ESD ulcer is larger than predicted, PPI administration alone might not be sufficient for the ulcer to heal within 4 weeks. We examined the efficacy of a combination therapy of PPI and rebamipide, a mucosal-protective antiulcer drug, on the acceleration of post-ESD ulcer healing. Patients were randomly assigned to either the PPI and rebamipide therapy or the PPI alone. Sixty-two consecutive patients with gastric tumors gave informed consent for enrolling in the study. In all cases, the estimated size of the post-ESD ulcer was larger than 20 mm. Oral administration of the drug was started on the 2nd day post-ESD and continued to the 28th day. All patients received the assigned pharmaceuticals and adhered well to the treatment regimen for 28 days. The endpoint ulcers reached S1 (scar stage) in 11/31 (36%) patients in the PPI-only group and in 21/31 (68%) in the combination group ( P = 0.010). The combination of PPI plus rebamipide was more effective than the PPI alone for treating ulcers larger than 20 mm within 4 weeks after ESD. [ABSTRACT FROM AUTHOR]

Background: Gastroesophageal reflux disease is thought to be the commonest cause of ‘non-cardiac chest pain’. The use of proton-pump inhibitors resulting in improvement in the chest pain symptom would support this causal association. Objectives: To determine the prevalence of gastroesophageal reflux disease in non-cardiac chest pain and the response of chest pain to proton-pump inhibitor therapy. Methods: Patients with recurrent angina-like chest pain and normal coronary angiogram were recruited. The frequency and severity of chest pain were recorded. All patients underwent esophagogastroduodenoscopy and 48-h Bravo ambulatory pH monitoring before receiving rabeprazole 20 mg bd for 2 weeks. Results: The prevalence of gastroesophageal reflux disease was 66.7% (18/27). The improvement in chest pain score was significantly higher in reflux compared to non-reflux patients ( P = 0.006). The proportion of patients with complete or marked/moderate improvement in chest pain symptoms were significantly higher in patients with reflux (15/18, 83.3%) compared to those without (1/9, 11.1%) ( P < 0.001). Conclusion: The prevalence of gastroesophageal reflux disease in patients with ‘non-cardiac chest pain’ was high. The response to treatment with proton-pump inhibitors in patients with reflux disease, but not in those without, underlined the critical role of acid reflux in a subset of patients with ‘non-cardiac chest pain’. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (HP) eradication therapy is a useful treatment for idiopathic thrombocytopenic purpura (ITP). Some investigators have also reported the effects of proton pump inhibitor (PPI) monotherapy on ITP. We performed a randomized study of HP eradication therapy and PPI monotherapy on ITP. Four of nine patients achieved complete remission (CR), two of nine achieved partial remission (PR) in HP eradication therapy, three of eight achieved CR, and two of eight achieved PR in PPI monotherapy. No significant differences were observed in the CR + PR of these patients between HP eradication therapy and PPI monotherapy. As for cost comparisons, HP eradication therapy is cheaper than PPI monotherapy, but it is less effective. [ABSTRACT FROM AUTHOR]

Background. We studied the effects of a proton pump inhibitor (PPI) and an H2-receptor antagonist (H2- blocker) on angiogenesis during gastric ulcer healing, by examining stromal cell-derived factor (SDF-1) and CXC chemokine receptor 4 (CXCR4) expression in the gastric mucosa. Methods. Patients with gastric ulcers were allocated to an untreated control group, consisting of patients with active ulcers (GA), healing ulcers (GH), and ulcer scars (GS) or a PPI group (P; given rabeprazole at 20mg/day), or an H2-blocker group (H; given nizatidine at 800 mg/day). Frozen sections of biopsy specimens were examined by reverse transcription-polymerase chain reaction (RT-PCR) to analyze SDF-1 and CXCR4 mRNA. Results. CXCR4 mRNA levels were elevated in the control (GH and GS patients) group and the H2-blocker group. CXCR4 was significantly elevated in the P-GA subgroup of the PPI group (P < 0.01), but its level decreased with time. Conclusions. In the PPI group, CXCR4 levels were increased in the early phase of ulcer healing and returned to a level similar to that in the control group during the scar phase. These results suggest that PPIs increase the expression of CXCR4 mRNA and thus promote vessel regeneration and maturation, facilitating ulcer healing. [ABSTRACT FROM AUTHOR]

Background: Laryngopharyngeal reflux (LPR) disease arises from the effects of refluxed gastric contents on the proximal aerodigestive tract. LPR patients are often lumped into the category of “atypical” reflux. LPR symptoms are hoarseness, globus, cough, and pharyngitis. Severe disease is associated with subglottic stenosis and laryngeal cancer. Treatment includes lifestyle modifications and medications. The role of fundoplication for LPR has yet to be defined.Study design: Forty-one patients underwent fundoplication for LPR. They were prospectively followed with three outcomes measures: The Reflux Symptom Index, a laryngoscopic grading scale (Reflux Finding Score), and a reflux-based specific quality-of-life scale.Results: Average early followup was at 4 months and late followup was at 14 months. The Reflux Symptom Index improved by 5.4 early (p < 0.05) and 6.5 late (p < 0.05). Improvement between early and late periods approached significance (p < 0.09). Reflux Finding Score improved 3.8 (p < 0.05) early and 4.4 (p < 0.05) late. The Quality of Life Index improved 0.6 early and 2.3 (p < 0.05) late. By Reflux Symptom Index criteria, 26 patients were improved early versus 35 late (p < 0.05). Factors associated with poor outcomes were structural laryngeal changes in five patients (p < 0.05) and no response to proton pump inhibitors in six patients (p < 0.05).Conclusions: Fundoplication augments treatment of LPR. Improvement of symptoms continues past the first 4 months. Laryngoscopy is critical in patient selection because selected findings are associated with outcomes, diagnosis, and management. [Copyright &y& Elsevier]

No study has reported an association between gastroesophageal reflux disease (GERD) or its therapies and gallbladder function. We compared pre- and postoperative gallbladder function in patients undergoing fundoplication to determine the following: (1) whether patients with chronic GERD have preexisting gallbladder motor dysfunction; (2) whether medical or surgical therapy alters gallbladder function; and (3) whether division of the hepatic branch of the anterior vagus nerve is detrimental to gallbladder motility. Nineteen patients with documented GERD consented to a preoperative cholecystokinin-stimulated technetium hepatobiliary (CCK-HIDA) scan to quantify the gallbladder ejection fraction (GBEF). All patients underwent laparoscopic Nissen fundoplication. One month after fundoplication, 12 patients completed a repeat CCK-HIDA scan for determination of GBEF, with comparison to the preoperative GBEF. Among patients with preoperative GERD, 11 (58%) of 19 met the scintigraphic criteria for gallbladder dysfunction (GBEF <35%), which is a ratio comparable to that in patients undergoing a CCK-HIDA scan for presumed biliary dyskinesia during the same time period (31 [60%] of 53; P = NS, chi-square test) and exceeds the rate of abnormal GBEF reported in healthy volunteers (3%). Six of seven patients with a low preoperative GBEF who underwent repeat evaluation postoperatively had normalization of the GBEF (P < 0.05, paired t-test). In the 12 patients who underwent postoperative CCK-HIDA scanning, there was no association between preservation or division of the hepatic branch of the anterior vagus nerve and postoperative gallbladder dysfunction (P = NS, chi-square test). Unexpectedly, 58% of patients with GERD demonstrated gallbladder motor dysfunction prior to fundoplication, with improvement to normal occurring in most of those studied postoperatively. These data support controlled trials to determine the effect of chronic GERD and antisecretory therapy on gallbladder and global gastrointestinal smooth muscle function. Preservation of the hepatic branch of the anterior vagus nerve during fundoplication offered no clear benefit with regard to early postoperative gallbladder function. ( J Gastrointest Surg 2002;6:806–811.) [Copyright &y& Elsevier]

Non-variceal upper gastrointestinal bleeding (NVUGIB) is defined as bleeding proximal to the ligament of Treitz in the absence of varices. As a common clinical problem, NVUGIB entails a heavy burden on the healthcare system. In addition to endoscopic hemostasis, evaluation and treatment before and after endoscopy are also of critical importance for the clinical management of NVUGIB patients. In recent years, based on the rapid development of endoscopic technology and clinical management of NVUGIB, the research evidence and clinical guidelines have been updated internationally, while some clinical decisions remain controversial. In this article, we mainly reviewed and discussed the current status of NVUGIB patient management before, during, and after endoscopy, aiming to deepen the understanding of the disease for clinicians, and to promote standardized management of patients with NVUGIB., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Gastroesophageal reflux disease has long been implicated as a cause for multiple pediatric symptoms ranging from abdominal pain and regurgitation to cough and dental erosions. Diagnostic testing has evolved greatly over the last 20 years; initial testing with pH-metry to measure esophageal acid reflux burden has evolved into measurement of both acid and non-acid reflux and liquid and gas reflux. However, measuring reflux burden alone only tells a small part of the GERD story and many symptoms originally thought to be reflux related are, in fact, related to other disorder which mimic reflux. The current paradigm which involves empiric treatment of symptoms with acid suppression has been replaced with early testing for not only gastroesophageal reflux but also for other diagnostic masqueraders. The focus for interventions has shifted away from acid suppression toward motility interventions and includes a greater recognition of both functional and motility disorders which present with reflux symptoms., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rosen.)

Introduction: Current treatments of eosinophilic esophagitis (EoE) induce symptomatic and histological remission in a proportion of patients. However, they do not fully meet patients' needs and limitations should be acknowledged. The growing epidemiology of EoE has generated a great interest for research into novel therapeutic approaches., Areas Covered: This article discusses current therapies available for EoE, those under investigation and presents potential additional ones. Established anti-inflammatory treatments for EoE include dietary therapy, proton pump inhibitors, and swallowed topical corticosteroids, which are combined with endoscopic dilation in cases of strictures. Refractoriness, recurrence after treatment-cessation, and need for long-term therapies have encouraged investigation of novel, esophageal-targeted formulas of topical corticosteroids and of new therapeutic approaches directed at blocking the molecular pathways that lead to inflammation in EoE. These include monoclonal antibodies (including mepolizumab, reslizumab, benralizumab, dectrekumab, cendakimab, and dupilumab), JAK-STAT blockers, and S1PR agonists, among others. Some have provided evidence of effectiveness and safeness in the short-term use., Expert Opinion: Therapies under investigation potentially can target multiple Th2-associated diseases that converge in EoE patients. Therapeutic strategies require a personalized and patient-centered approach to reduce the burden of the disease, and cost-effectiveness analysis to position their use in a complex therapeutic landscape.

Abstract Background Gastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce. Methods To elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H2-receptor antagonist (H2RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Student's t-test or Pearson's correlation coefficient, and were further analyzed with multiple linear regression modelling. Results Average FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H2RA users. Among the total population, positively correlated factors and standardized coefficients (β) for FSSG scores are inadequate sleep (β = 0.158), digestive drug users (β = 0.0972 for PPI, β = 0.0903 for H2RA, and β = 0.104 for others), increased body weight in adulthood (β = 0.081), dinner just before bedtime (β = 0.061), the habit of midnight snack (β = 0.055), lower body mass index (β = 0.054), NSAID users (β = 0.051), female gender (β = 0.048), lack of breakfast (β = 0.045), lack of physical exercise (β = 0.035), younger age (β = 0.033), antihyperglycemic agents non-users (β = 0.026), the habit of quick eating (β = 0.025), alcohol drinking (β = 0.025), history of gastrectomy (β = 0.024), history of cardiovascular disease (β = 0.020), and smoking (β = 0.018). Positively correlated factors for PPI users are female gender (β = 0.198), inadequate sleep (β = 0.150), lack of breakfast (β = 0.146), antihypertensive agent non-users (β = 0.134), and dinner just before bedtime (β = 0.129), whereas those for H2RA users are inadequate sleep (β = 0.248), habit of midnight snack (β = 0.160), anticoagulants non-users (β = 0.106), and antihypertensive agents non-users (β = 0.095). Conclusions Among many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H2RA in Japan cannot fully relieve GERD symptoms.

Background: Equine gastric ulcer syndrome (EGUS) is a common and significant cause of morbidity in horses, with a range of clinical signs, including inappetence, colic and poor performance. Hospitalised horses are exposed to factors that may induce EGUS, including fasting and nonsteroidal anti-inflammatory drug (NSAID) administration, and may be at risk for development of squamous (ESGD) and glandular gastric disease (EGGD). Prophylactic anti-ulcer medication is often prescribed for these patients, but drug selection is complicated by different aetiology and response to treatment of ESGD and EGGD., Objectives: To establish the efficacy of sucralfate or omeprazole used prophylactically in horses exposed to a combined feed-fast and NSAID administration EGUS induction protocol. We hypothesised that these drugs would be equally effective for prevention of gastric lesions in the experimental cohort., Study Design: Randomised crossover experimental design., Methods: Horses (n = 14) received either omeprazole (1 mg/kg PO q24h) or sucralfate (20 mg/kg PO q8h) while undergoing the feed-fast/NSAID protocol, allowed an 8-week washout period, and then administered the alternate treatment. Serial gastroscopy, ultrasound and haematology documented treatment effects., Results: ESGD and EGGD score increased over time under both treatments. There was a significant effect of treatment on EGGD scores (P < .001), with post-treatment EGGD scores higher for horses receiving sucralfate (median 3; IQR 2.25,3) than omeprazole (1; 1,1). The effect of treatment on ESGD scores just achieved significance (P = .05), with post-treatment ESGD scores higher for sucralfate (4; 3,4) than omeprazole (2; 2,3)., Main Limitations: This study was performed in healthy horses, and response to treatment may differ in horses with clinical illness. Additional investigation in a larger population may be required to detect significant differences in other clinical parameters., Conclusions: Omeprazole was superior to sucralfate for mitigating gastric lesion severity in healthy horses exposed to a feed-fast/NSAID model., (© 2021 EVJ Ltd.)

• This multi-center RCT will provide evidence for the rational application of PPI in ESD. • Low-dose PPIs were sufficient for prevention post-ESD bleeding and its efficacy level was equivalent to high dose PPIs. • Artificial ulcer healing after ESD in low-dose PPIs was similar to high dose PPIs. Although proton pump inhibitors (PPIs) are widely used in the prevention of gastric bleeding caused by endoscopic submucosal dissection (ESD), there is no consensus on the optimal regimen for these patients. Therefore, we aim to investigate whether intermittent use of low-dose PPI is sufficient to prevent post-ESD bleeding. This multicenter, non-inferiority, randomized controlled trial was conducted at 9 hospitals in China. Consecutive eligible patients with a diagnosis of gastric mucosal lesions after ESD treatment were randomly assigned (1:1) to receive either intermittent low-dose or continuous high-dose PPIs treatment. After three days, all patients administered orally esomeprazole 40 mg once a day for 8 weeks. The primary endpoint was post-ESD bleeding within 7 days. Analysis was done according to the intention-to-treat principle with the non-inferiority margin (Δ) of 5%. 526 consecutive patients were assessed for eligibility from 30 September 2017 to 30 July 2019, of whom 414 were randomly assigned to low-dose (n = 209) or high-dose (n = 205) esomeprazole treatment group without dropouts within7 days. The total post-ESD bleeding is occurred in 13 (6.2 %, 95 % CI 3.3–9.6) of 209 within 7 days in the intermittent low-dose group, and 12 (5.9 %, 95 % CI 2.9–9.3) of 205 in the continuous high-dose group. The absolute risk reduction (ARR) was 0.4 % (−4.2, 4.9). One month after ESD, There are 44 patients (21.1 %, 95 % CI 15.8, 26.8) and 39 patients (19.0 % 95 % CI 13.7, 24.4) in scar stage respectively in low-dose group and high-dose group (P = 0.875).The hospital costs in the low-dose PPI group was lower than high -dose group (P = 0.005). The intermittent use of low-dose PPIs is sufficient to prevent post-ESD bleeding. It might be applied in clinical practice to prevent post-ESD bleeding and reduce the costs related to PPIs. [ABSTRACT FROM AUTHOR]

Aims: The association of acid suppressants use with bone mineral density (BMD) is still unclear, especially in older adult with prolonged use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs). In this study, our aim was to investigate the association between PPI or H2RA use and BMD in general US older adults. Methods: We conducted a cross-sectional study on a sample from National Health and Nutrition Examination Survey. Association between long-term use of PPIs or H2RAs and lumber spine BMD in elderly was evaluated using weighted multivariate linear regression models. Sensitive and subgroup analysis were also performed in this study. Results: Long-term PPI use is correlated with lower lumber spine BMD in our multivariable regression model after adjusting for known confounding factors. Further analysis showed PPI use with a duration over 1 year was negatively associated with lumber spine BMD in male, elderly aged over 70 years, and white elderly. There is no significant association between long-term H2RA use and lumber spine BMD. Conclusions: Our results indicated that the association between long-term use of PPI and lumber spine BMD differed by gender. Long term use of PPIs would reduce lumber spine BMD in older men, while H2RA use is not significantly linked with lumber spine BMD. Patients that are at high risk of bone loss should shortened the duration of PPI use (<1 year) or use H2RAs as alternative if possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Song, Lin, Chen, He, Wei and Li.)

Background: To explore the clinical characteristics of different types of gastric polyps and the relationship between fundic gland polyps, Helicobacter pylori (HP) infection, and proton pump inhibitor (PPI) use., Methods: The clinical data of 186 patients diagnosed with gastric polyps under endoscopy were selected for retrospective analysis, and the clinical data, gastroscopy, polyp histopathology, HP infection, and PPI usage of all subjects were analyzed., Results: Among the 186 patients with gastric polyps, there were significantly more women (131 cases) than men (55 cases), with a ratio of 2.38:1. PPIs were used in 78% of cases for more than 5 years. The pathological types of patients with gastric polyps in this study were fundic gland polyps, hyperplastic polyps, inflammatory fibrous polyps, and adenomatous polyps. Fundic gland polyps were mainly located in the fundus and gastric body, while hyperplastic polyps were mostly located in the gastric body (P<0.05). The positive rate of HP infection in patients with fundic gland polyps was significantly lower than that in patients with other types of polyps (P<0.05). In patients with long-term use of PPIs, the incidence of fundic gland polyps increased significantly (P<0.05)., Conclusions: There were significant differences among the different types of gastric polyps in terms of polyp position, shape, and size. The positive rate of HP infection in patients with fundic gland polyps was low. Long-term use of PPIs (>5 years) increased the incidence of fundic gland polyps to some extent. The mechanisms underlying the relationship between gastric polyps, HP infection, and the use of PPIs remain to be further studied.

Background: Proton pump inhibitors (PPIs) are commonly prescribed for preventing and treating gastrointestinal ulcers. In patients with advanced cancer, it is unclear whether concomitant use of immune checkpoint inhibitors (ICIs) and PPIs could result in poorer outcomes. This study investigates the impact of PPIs on the survival of cancer patients treated with ICIs., Methods: PubMed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from January 1, 1970 to June 2, 2020 for studies reporting the prognoses of cancer patients receiving antitumor therapies including ICIs with or without PPIs. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Hazard ratios (HRs) with a 95% confidence interval (CI) were reported to express the effectiveness of ICIs in PPI users compared to non-PPI users, using a random effects model., Results: Five studies were identified comprising 1,167 cancer patients. Concomitant use of PPIs with ICIs did not result in statistically significant changes in OS (HR 0.996; 95% CI: 0.486-1.447) and PFS (HR 0.858; 95% CI: 0.388-1.328). Statistical testing suggested heterogeneity among studies. Sensitivity analyses confirmed the stability of our results., Conclusions: Concomitant ICI-PPI therapy does not appear to be significantly associated with OS or PFS, and further research on the effect of individual ICIs in different cancer patients is needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7498). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

We herein report a patient with Wernicke-Korsakoff syndrome (WKS) who had neither a history of alcoholism or of history of gastric surgery. A 56-year-old woman was transferred to our hospital because of the loss of consciousness and she was diagnosed to have Wernicke encephalopathy. She showed proton pump inhibitor-induced refractory hypergastrinemia with the subsequent development of hyperemesis and a vitamin B1 deficiency.

Helicobacter pylori can infect the gastric mucosa and cause chronic inflammation, resulting in various diseases, including gastric cancer. Eradication of H. pylori in all infected subjects is recommended; however, the number of H. pylori strains with antibiotic resistance has increased, and the eradication rate has decreased. Vonoprazan, a potassium-competitive acid blocker, produces a stronger acid-inhibitory effect than proton pump inhibitors (PPIs). The H. pylori eradication rate with vonoprazan was found to be higher than that with PPIs. The H. pylori eradication rate with vonoprazan-based triple therapy (vonoprazan, amoxicillin, and clarithromycin) was approximately 90% and had an incidence of adverse events similar to that of PPIs. We review the current situation of H. pylori eradication in Japan, the first country in which vonoprazan was made available.

A 40-year-old man suffered from short bowel syndrome. Since a large amount of intestinal output and watery diarrhea hampered his quality of life, we tried to control the intestinal output by reducing the secretion of gastric acid with lansoprazole. Because the small intestine was only 10 cm in length and effective absorption of oral lansoprazole was doubtful, we monitored his intragastric pH for 24 hours and confirmed that the holding time above pH 3.0 was 14.5 hours (60.4%). He spent his home life eating porridge during the day, and receiving total parenteral nutrition of 1,100 mL/day at night while taking lansoprazole as an oral tablet (30 mg) once a day.

Background: Controversy still exists that whether clopidogrel should add proton pump inhibitors (PPIs) in patients with coronary heart disease after percutaneous coronary intervention (PCI). The aim of this study was to evaluate the efficacy and safety of clopidogrel added proton pump inhibitors (PPIs) vs. clopidogrel for the treatment of patients with coronary heart disease after percutaneous coronary intervention (PCI)., Methods and Results: We systematically searched PubMed, EMBASE, Web of Science, the Chinese Biomedical Medical Literature database, and the Cochrane Library for all clinical trials that were published on this topic through October 2018. We specifically selected the clinical trials that evaluated the efficacy and safety of clopidogrel added proton pump inhibitors vs. clopidogrel in the treatment of patients with coronary heart disease after PCI. RevMan 5.0 software was used for quantitative data analyses.15 randomized controlled trials including 50,366 patients were included. The meta-analysis results showed that compared with the clopidogrel added PPI group, the non-PPI group had significantly less risk of MACE[RR = 0.82,95%CI:0.77-0.88], myocardial infarction recurrence[RR = 0.72,95%CI:0.57-0.90], stent thrombosis[RR = 0.71,95%CI:0.56-0.92], Target vessel revascularization (TVR)[RR = 0.77,95%CI:0.63-0.93] and stroke [RR = 0.72,95%CI:0.67-0.76]. The risks of all cause death [RR = 1.14,95%CI:0.85-1.51], cardiovascular death [RR = 1.14, 95% CI: 0.85-1.52], bleedings events [RR = 1.60,95%CI:0.53-4.81] were similar in the two groups., Conclusions: The patients in the non-PPI group were observed to be associated with less risk of MACE, myocardial infarction recurrence, stent thrombosis, target vessel revascularization (TVR) and stroke. And the two groups had similar all cause death, cardiovascular death, bleedings events.

Introduction: Eosinophilic esophagitis (EoE) is rare but incidence and prevalence is increasing. EoE is characterized by eosinophilic inflammation of the esophagus causing gastrointestinal symptoms such as abdominal pain, vomiting, reflux, dysphagia, and food impactions. If untreated, remodeling and fibrosis of the esophagus can occur and stricture formation may result. Current treatment options are limited to food-restriction diets or medications including proton pump inhibitors (PPIs) or swallowed corticosteroids. Significant progress has been made in understanding the underlying mechanisms of EoE allowing for development of drugs that target specific points in EoE pathways. Investigation of these drugs is early with few controlled studies, but many show promise as future treatments. Areas covered: This review will provide an up to date discussion of current therapies and investigational drugs for EoE. Articles used in this review were retrieved from PubMed. Ongoing or completed clinical trials were obtained through clinicaltrials.gov and review of the PharmaProjects database. Expert Opinion: Multiple therapeutic targets have been identified and several have shown efficacy. Work is needed to define appropriate trial outcome measures. Collaboration between government agencies, patient advocacy groups, and investigator-led consortia is critical for completing new clinical trials which should pave the way for new therapies in clinical practice.

Background: Posttransplantation bone disease is a significant problem, with few well-evidenced therapeutic options. Proton pump inhibitors (PPIs) are associated with hip fracture in the general population and are widely prescribed for kidney transplant recipients., Study Design: A case-control study., Setting & Participants: From the US Renal Data System, we identified from diagnoses and procedures 231 kidney transplant recipients with a first hip fracture. Cases were matched at the hip fracture index date with 15,575 controls on age, sex, race, and transplantation year., Predictor: PPI use., Outcomes: First hip fracture., Results: In the year prior to the index date, a PPI was prescribed to 65.4% of cases and 57.4% of controls. Additionally, in 34.6% of cases and 28.9% of controls, a PPI was prescribed for >80% of the year preceding the index date (higher PPI users). Unadjusted ORs of hip fracture associated with any and higher PPI use were 1.55 (95% CI, 1.18-2.05) and 1.65 (95% CI, 1.2-2.27), respectively. When adjusted for baseline demographic, clinical, and pharmacologic covariables, any and higher PPI use remained associated with hip fracture, with ORs of 1.39 (95% CI, 1.04-1.84) and 1.41 (95% CI, 1.02-1.95), respectively., Limitations: Potential residual confounding through either incorrectly ascertained or unavailable confounders; cohort limited to Medicare beneficiaries receiving low-income subsidy., Conclusions: In summary, PPI use was associated with hip fracture risk in the US kidney transplant population., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims Gastroesophageal reflux disease (GERD) is a common and costly disorder. Symptoms attributed to GERD have a wide spectrum of presentations and complications that have led to complex diagnostic and management algorithms. As such, there is considerable variation in clinical approaches to GERD. In contrast to multiple published guidelines for the management of GERD, there are few validated GERD quality measures. The objective of this study was to use a well-described, formal methodology to develop valid, physician-led quality measures for all aspects of care for patients with GERD. Methods Quality measures were identified from the literature, consensus guidelines, and GERD experts. Eight clinical experts ranked potential measures for validity on the basis of the RAND/University of California, Los Angeles Appropriateness Methodology. Results Of the 52 proposed quality measures, 24 were rated as valid, and 1 new measure was developed. These valid measures were related to initial diagnosis and management (9), monitoring (3), further diagnostic testing (4), proton pump inhibitor refractory symptoms (2), symptoms of chest pain (1), erosive esophagitis (3), esophageal stricture or ring (1), and surgical therapy (2). Fifteen of these measures were ranked with the highest validity. Twenty-seven measures were determined to be equivocal; 89% of these were extracted from guidelines that were based on low or moderate level evidence. Conclusions We used RAND/University of California, Los Angeles Appropriateness Methodology to develop quality measures for GERD care. By examining performance on these valid, formally developed quality measures, clinical practices and individual providers can assess their adherence with them and direct quality improvement efforts accordingly. [ABSTRACT FROM AUTHOR]

The risk for impaired vitamin B 12 status increases with age, as does the use of proton pump inhibitors (PPI). Long-term use of PPIs is associated with several nutritional deficiencies including B 12 . Currently, there are no recommendations for B 12 screening among patients taking PPIs. Data were abstracted on B 12 concentrations, B 12 -containing supplement use, medications, and select hematological values from a retrospective chart review of 658 adults, 391 with serum B 12 concentrations, admitted to 6 different medical units at 2 regional hospitals in Southwestern Ontario between 2010 and 2012. We found no difference between PPI users and nonusers and serum B 12 concentrations (404 ± 224 vs 369 ± 213 pmol/L; P = 0.0690). This may be due to use of B 12 containing multivitamins in 41% of PPI users. Regression modelling found that aging increases the odds of having an impaired B 12 status (<220 pmol/L) by 1.4 times and those using B 12 supplements are almost 4 times more likely to have an impaired status. Mean corpuscular volume was not related to B 12 status. In this population, older PPI users are more likely to be using multivitamins, which may delay nutritional deficiencies. However, the lower B 12 concentrations of PPI users taking only B 12 supplements is a concern and requires further research. Finally, physicians need to be aware that mean corpuscular volume is no longer recommended as an effective biomarker for B 12 screening and updated screening protocols need to be used to reduce the possibility of adverse neurological effects from impaired B 12 status.

Background & Aims: The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Methods: Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of 99mtechnetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. Results: The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7–1.2 vs 4.0; range, 1.6–5.9; P < .001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Conclusions: Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. [Copyright &y& Elsevier]

Background: The incidence of community-acquired Clostridium difficile (CACD) is increasing in the United States. Many CACD infections occur in the elderly, who are predisposed to poor outcomes. We aimed to describe the epidemiology and outcomes of CACD in a nationally representative sample of Medicare beneficiaries. Study Design: We queried a 5% random sample of Medicare beneficiaries (2009−2011 Part A inpatient and Part D prescription drug claims; n = 864,604) for any hospital admission with a primary ICD-9 diagnosis code for C difficile (008.45). We examined patient sociodemographic and clinical characteristics, preadmission exposure to oral antibiotics, earlier treatment with oral vancomycin or metronidazole, inpatient outcomes (eg, colectomy, ICU stay, length of stay, mortality), and subsequent admissions for C difficile. Results: A total of 1,566 (0.18%) patients were admitted with CACD. Of these, 889 (56.8%) received oral antibiotics within 90 days of admission. Few were being treated with oral metronidazole (n = 123 [7.8%]) or vancomycin (n = 13 [0.8%]) at the time of admission. Although 223 (14%) patients required ICU admission, few (n = 15 [1%]) underwent colectomy. Hospital mortality was 9%. Median length of stay among survivors was 5 days (interquartile range 3 to 8 days). One fifth of survivors were readmitted with C difficile, with a median follow-up time of 393 days (interquartile range 129 to 769 days). Conclusions: Nearly half of the Medicare beneficiaries admitted with CACD have no recent antibiotic exposure. High mortality and readmission rates suggest that the burden of C difficile on patients and the health care system will increase as the US population ages. Additional efforts at primary prevention and eradication might be warranted. [ABSTRACT FROM AUTHOR]

Background: Nonvariceal upper GI bleeding (NVUGIB) that occurs in patients already hospitalized for another condition is associated with increased mortality, but outcome predictors have not been consistently identified. Objective: To assess clinical outcomes of NVUGIB and identify predictors of mortality from NVUGIB in patients with in-hospital bleeding compared with outpatients. Design: Secondary analysis of prospectively collected data from 2 nationwide multicenter databases. Descriptive, inferential, and multivariate logistic regression models were carried out in 338 inpatients (68.6 ± 16.4 years of age, 68% male patients) and 1979 outpatients (67.8 ± 17 years of age, 66% male patients). A predictive model was constructed using the risk factors identified at multivariate analysis, weighted according to the contribution of each factor. Settings: A total of 23 Italian community and tertiary care centers. Patients: Consecutive patients admitted for acute NVUGIB. Interventions: Early endoscopy, medical and endoscopic treatment as appropriate. Main Outcome Measurements: Recurrent bleeding, surgery, and 30-day mortality. Results: The mortality rate in patients with in-hospital bleeding was significantly higher than that in outpatients (8.9% vs 3.8%; odds ratio [OR] 2.44; 95% confidence interval [CI], 1.57-3.79; P < .0001). Hemodynamic instability on presentation (OR 7.31; 95% CI, 2.71-19.65) and the presence of severe comorbidity (OR 6.72; 95% CI, 1.87-24.0) were the strongest predictors of death for in-hospital bleeders. Other independent predictors of mortality were a history of peptic ulcer disease and failed endoscopic treatment. Rebleeding was a strong predictor of death only for outpatients (OR 5.22; 95% CI, 2.45-11.10). Risk factors had a different prognostic impact on the 2 populations, resulting in a significantly different prognostic accuracy of the model (area under the receiver-operating characteristic curve = 0.83; 95% CI, 0.77-0-93 vs 0.74; 95% CI, 0.68-0.80; P < .02). Limitations: Study design not experimental, no data on ward specialty, potential referral bias. Conclusions: In-hospital bleeders have a significantly higher risk of death because they are sicker and more often hemodynamically unstable than outpatients. Predictors of death have a different impact in the 2 populations. [Copyright &y& Elsevier]

Background & Aims: Eosinophilic esophagitis (EoE) has become a major cause of upper gastrointestinal morbidity in children and adults. However, there are few data on the nationwide prevalence of EoE. We aimed to estimate the prevalence of EoE in the United States. Methods: We collected health insurance claims from a large database that represented the U.S. commercially insured population. We analyzed data from 2008 to 2011, identifying cases of EoE by using a previously validated definition, and calculated a period prevalence by using data from 2009 to 2011. EoE was defined as any instance of the International Classification of Diseases, 9th revision code 530.13. We calculated the prevalence of the code in the database and standardized the estimate to the U.S. population. Results: Of 35,575,388 individuals in this database, 16,405 had at least 1 code for EoE. The mean age was 33.5 years, 65% were male, 55.8% had dysphagia, and 52.8% had a diagnostic code for at least 1 allergic condition. Among 11,569,217 individuals with continuous insurance coverage between mid-2009 and mid-2011, 6513 had at least 1 code for EoE. When standardized to the U.S. population, the estimated period prevalence of EoE was 56.7/100,000 persons, translating to approximately 152,152 cases in the U.S. Prevalence peaked in men 35–39 years old, with a rate of 114.6/100,000 persons. Conclusions: Despite its relatively recent description, EoE is frequently diagnosed in the United States, with an estimated prevalence of 56.7/100,000 persons. This estimate depends on the accuracy of the International Classification of Diseases, 9th revision code, but it could be an underestimate, because knowledge of the code and recognition of EoE are increasing. [Copyright &y& Elsevier]