Twice-daily Proton Pump Inhibitor Research Articles

Twice-Daily Proton Pump Inhibitor Induces Higher Remission Rate in Eosinophilic Esophagitis Than Once-Daily Regimen Regardless of Total Daily Dose.

The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.

In adult patients with gastroesophageal reflux disease, is twice-daily proton pump inhibitor dosing more effective than once-daily dosing in relieving symptoms?

In adult patients with gastroesophageal reflux disease, is twice-daily proton pump inhibitor dosing more effective than once-daily dosing in relieving symptoms?

Allergic phenotype identified on allergen testing is associated with proton pump inhibitor nonresponse in eosinophilic esophagitis.

Food/environmental allergens have been associated with eosinophilic esophagitis (EoE); however, the correlation between allergy profiles and disease responsiveness to proton pump inhibitor (PPI) therapy remains unclear. We aimed to assess the association between food/environmental allergies identified on allergen testing and histologic response to PPI in patients with treatment-naive EoE. Adults with newly diagnosed EoE who underwent formal testing for food/environmental allergies at a tertiary center were included. All patients underwent twice-daily PPI for 8weeks with subsequent repeat endoscopy and biopsy to assess histologic response. Patients with <15 eosinophils/hpf on post-PPI mucosal biopsies were classified as responders (PPI-r-EoE), while those with ≥15 eosinophils/hpf were nonresponders (PPI-nr-EoE). Sixty-one patients met inclusion criteria (21 PPI-r-EoE vs 40 PPI-nr-EoE). Demographic, clinical, and endoscopic finding variables were similar between groups. Positive food allergen test was more prevalent among PPI-nr-EoE patients (82.5% vs 42.9%, P=0.003). On multivariable analysis, positive food allergen testing remained an independent predictor for PPI nonresponse (aOR 0.15, CI: 0.04-0.58, P=0.0006). Positive environmental allergen testing was highly prevalent, with no significant differences between groups (77.5% vs 95.2%, P=0.14). However, higher number of positive environmental allergens (23.3% [≥5 allergens] vs 73.3% [<5 allergens], P=0.003) and specific aeroallergens correlated with PPI-nr-EoE. Positive food allergy testing and increased environmental allergens predicted lower likelihood of histologic response to PPI in EoE. Our findings support an allergic phenotype of EoE that may less likely respond to PPI therapy. Formal allergen testing may play a role in therapy selection and tailored management in EoE.

Expert Opinion on the Utilization of Proton Pump Inhibitors for the Treatment of Gastroesophageal Reflux Disease among Indian Patients

Several studies have demonstrated that esomeprazole enhances the management of gastroesophageal reflux disease (GERD) patients by reducing the incidence of heartburn and epigastric pain, as well as relapse rates. But, there was a dearth of data regarding the preference of esomeprazole. So, this study was conducted to gather expert opinions on the routine use of proton pump inhibitors (PPIs) in clinical practice with a focus on the utilization of esomeprazole as a maintenance therapy for GERD in Indian settings. A cross-sectional, questionnaire based study was conducted to collect opinion among physicians involved in managing GERD symptoms across India between June 2022 and December 2022. The study enrolled 972 participants, and 63% of them noted the frequent occurrence of both erosive and non-erosive reflux disease in GERD patients. Approximately 47% of the respondents identified obesity as a significant GERD risk factor, with 32% attributing it to irregular and unhealthy eating habits. The majority of the clinicians preferred PPIs for the treatment of GERD (90%), particularly esomeprazole (87%). The typical duration of PPIs for GERD patients was reported to be 2-4 weeks by approximately 57% of the experts. Most respondents recommended a combination of PPIs and prokinetic drugs for GERD treatment. When dealing with PPI-resistant patients, 56% of physicians preferred maintaining the same PPI therapy twice daily, while 32% advised switching to another PPI. The majority of the respondents (71.81%) recommended making dietary and lifestyle adjustments for managing GERD, including consuming smaller, more frequent meals, refraining from lying down for at least two hours after eating and addressing excess weight around the midsection. It was noted that clinicians recommended PPIs, especially esomeprazole, as the primary approach for GERD management. Experts advise a regimen of twice-daily PPIs for patients who exhibit resistance to the treatment. They also underscore the importance of dietary and lifestyle adjustments in GERD management.

A Prospective Randomized Interventional Study to Establish the Role of Bovine Lactoferrin in Helicobacter Pylori Infection

Helicobacter pylori (H. pylori) are gram-negative spiral bacterium that surrounds itself in the epithelial surface of the stomach. It is found to be the most common bacterial infection affecting the population worldwide approximately 50%. The elimination of H. pylori is not only an important component in the healing of peptic ulcers, but also to decreases their recurrence and reduces the rate of gastric carcinoma. Eradication of H. pylori is currently recommended in numerous guidelines for the treatment of all these associated diseases. In the last two decades, attention has focused on the potential role of bovine lactoferrin (bLf) in the therapy of various gut disorders. bLf, a multifunctional iron-binding glycoprotein that is found in the milk, mucosal secretions (e.g., saliva, tears, bile), pancreatic and seminal fluids, and specific granules of the polymorphonuclear leukocytes in humans. Proton-pumpbased triple therapy (PpTT) is the most commonly accepted H. pylori treatment, which consists of a twice-daily proton pump inhibitor (PPI) such as esomeprazole or pantoprazole or omeprazole; clarithromycin or amoxicillin with tinidazole for 7-14 days. The aim of our study was to evaluate the efficacy of Bovine lactoferrin, administered orally along with triple therapy on H. pylori colonization in humans by a prospective randomized controlled study. 75 Patients with H. pylori positive were recruited and treated as per the protocol for 2 weeks. The subjects were randomized into 2 groups based on inclusion and exclusion criteria, interventional group received bovine lactoferrin at a dose of 100mg twice daily along with triple therapy for 14 days and the control group received, triple therapy for the same period of 14 days. The reduction in symptoms were analyzed by using a set of questionnaire and scored by using Global Overall Symptom Scale (GOS) both prior and post treatment. The eradication of H. pylori was confirmed by (13c) Urea breath test (UBT) that has shown the eradication rate of 76.2% in interventional group and 61.1% in control group. This study results had indicated that the group received bovine lactoferrin had shown significant improvement in the H. pylori eradication. This result can be used to conclude that the role of bovine lactoferrin in the reduction of symptoms and eradication of H. pylori infection by focusing on the relatively high cure rate, good compliance to the treatment and higher quality of life.

Assessment of the clinical and allergy profiles of PPI responsive and non-responsive eosinophilic esophagitis.

A subset of patients with eosinophilic esophagitis (EoE) respond to proton-pump inhibitor (PPI) therapy, however they cannot be distinguished prior to PPI trial and the mechanism of PPI response remains unclear. Improved understanding of the distinct patient phenotypes in PPI-responsive EoE (PPI-r-EoE), PPI-non-responsive EoE (PPI-nr-EoE) and erosive esophagitis (EE) may help guide management. The aim of this paper is to compare the clinical and allergy profiles of PPI-r-EoE versus PPI-nr-EoE and EE. This was a retrospective case-control study of EoE patients (>15 eos/hpf on esophageal biopsies) at a tertiary center. EE controls were identified from the pathology database. EoE patients were classified as PPI-r-EoE or PPI-nr-EoE based on histologic response to twice-daily PPI for ≥8weeks. Patient demographics, comorbidities, symptoms, allergy history and endoscopic findings were recorded. Univariate analyses were performed using the Fisher-exact test or t-test. Multivariable analyses were performed using logistic regression. In all, 104 EoE (57 PPI-r-EoE/47 PPI-nr-EoE) and 80 EE subjects were included. On multivariable analyses, allergic conditions (aOR 20.1, P < 0.0001) and rings (aOR 108.3, P = 0.001) were independent predictors for PPI-r-EoE versus EE, whereas allergic conditions (aOR 4.8, P = 0.03), rings (aOR 27.5, P = 0.002) and furrows (aOR 17.1, P = 0.04) were independent predictors for PPI-nr-EoE versus EE. Esophageal rings was the only significant predictor found in PPI-nr-EoE versus PPI-r-EoE (OR 2.5, P = 0.03). Allergic conditions and esophageal rings are significantly more prevalent in PPI-r-EoE and PPI-nr-EoE compared with EE. PPI-r-EoE appears clinically similar to PPI-nr-EoE and significantly different from EE. Further studies are needed to delineate the underlying pathophysiology of PPI-r-EoE versus PPI-nr-EoE.

S442 Utilization of Diagnostic Testing and Indications for Long-Term Twice-Daily Proton Pump Inhibitor (PPI) Therapy for Gastroesophageal Reflux Disease (GERD) in a Large Healthcare System

Introduction: For symptoms potentially associated with GERD, guidance recommends de-prescribing long-term PPI therapy based on symptoms if possible, particularly in the absence of objective diagnostic findings. We assessed the utilization and yield of diagnostic evaluation (upper endoscopy (EGD) and/or reflux monitoring) among patients with GERD diagnoses receiving long-term twice-daily PPI therapy. Methods: From a healthcare system database, adults with GERD diagnoses (per ICD coding) who received prescriptions for twice-daily PPI for at least 90 days from 2018-2021 were identified. CPT analyses were performed to identify the proportions who underwent EGD and reflux monitoring. Characteristics of patients who underwent diagnostic testing were compared to those who did not. Further, those with objective EGD findings potentially warranting long-term PPI (such as erosive or eosinophilic esophagitis, peptic stricture, Barrett’s esophagus, ulcer) were compared to those without such findings on EGD. Factors significant on univariate analysis were included in multivariate models to identify predictors of A) undergoing diagnostic evaluation, and B) having positive EGD findings. Results: 5565 patients (57.7±0.2 yrs; 67.4% female; BMI 31.3±0.1) met inclusion criteria. 2696 (47.7%) had upper endoscopy, 491 (8.7%) had reflux monitoring, and 2735 (48.4%) had either upper endoscopy or reflux monitoring performed. Factors associated with diagnostic testing included younger age, female gender, and non-white race (Table, Figure A). Among those who underwent EGD, 42.2% had endoscopic findings potentially warranting long-term PPI (37.7% for females vs 52.2% for males; 34.7% for non-white patients vs 47.3% for white patients). Factors associated with the presence of EGD findings included older age, male gender, and white race (Figure B). Conclusion: Among patients receiving prescriptions for long-term, twice-daily PPI for GERD diagnoses, over half did not have procedural diagnostic evaluation documented per CPT analysis, suggesting providers may rely on patient symptom reporting to guide long-term PPI prescriptions. Of those with documented EGD, less than half had objective findings to potentially corroborate the need for long-term, twice-daily PPI. These findings warrant further investigation into potential disparities in care around long-term PPI prescribing patterns based on symptoms and symptom response versus diagnostic evidence.Figure 1.: Forest Plots for Multivariate Analysis of Factors Associated with A) Diagnostic Evaluation (Upper Endoscopy and/or Ambulatory Reflux Monitoring) among Patients with GERD Diagnoses Prescribed Twice-Daily Long-Term PPI Therapy; and B) Objective Endoscopic Findings Potentially Warranting Twice-Daily Long-Term PPI Therapy. Odds Ratios are Depicted with Bars Representing Associated 95% Confidence Intervals; Values Not Crossing the Dashed Line at 1 are Significant. Odds ratios for smoking status variables are in reference to no smoking history. Table 1. - Comparisons Between Patients who Underwent Diagnostic Evaluation (with Upper Endoscopy and/or Ambulatory Reflux Monitoring) and Those Patients Who did Not Undergo Diagnostic Evaluation Evaluated (n=2735) Not Evaluated (n=2920) p Values Age (years) 57.1±0.3 58.3±0.3 0.005* Body Mass Index 31.0±0.1 31.6±0.2 0.006* Gender (female) 1898 (69.4%) 1916 (65.6%) 0.002* Race (data missing = 97) White 1681 (62.4%) 1998 (69.8%) < 0.001* Black 838 (31.1%) 672 (23.5%) Asian 62 (2.3%) 77 (2.7%) Other 115 (4.3%) 115 (4.0%) Ethnicity (data missing =109) Non-Hispanic 2505 (93.1%) 2663 (93.3%) 0.71 Hispanic or Latino 187 (7.0%) 191 (6.7%) Married (data missing =58) Married 1526 (56.2%) 1658 (57.5%) 0.32 Not Married 1189 (43.8%) 1224 (42.5%) Smoking Status (data missing = 5) Current 279 (10.2%) 390 (13.4%) < 0.001* Former 974 (35.6%) 945 (32.4%) Never 1481 (54.2%) 1581 (54.2%)

Transoral incisionless fundoplication is cost-effective for treatment of gastroesophageal reflux disease.

Background and study aims Given the sizable number of patients with symptomatic gastroesophageal reflux disease (GERD) despite proton pump inhibitor (PPI) therapy, non-pharmacologic treatment has become increasingly utilized. The aim of this study was to analyze the cost-effectiveness of medical, endoscopic, and surgical treatment of GERD. Patients and methods A deterministic Markov cohort model was constructed from the US healthcare payer’s perspective to evaluate the cost-effectiveness of three competing strategies: 1) omeprazole 20 mg twice daily; 2) transoral incisionless fundoplication (TIF 2.0); and 3) laparoscopic Nissen fundoplication [LNF]. Cost was reported in US dollars with health outcomes recorded in quality-adjusted life years (QALYs). Ten-year and lifetime time horizons were utilized with 3 % discount rate and half-cycle corrections applied. The main outcome was incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $ 100,000 per QALY. Probabilistic sensitivity analyses were also performed. Results In our base-case analysis, the average cost of TIF 2.0 was $ 13,978.63 versus $ 17,658.47 for LNF and $ 10,931.49 for PPI. Compared to the PPI strategy, TIF 2.0 was cost-effective with an incremental cost of $ 3,047 and incremental effectiveness of 0.29 QALYs, resulting in an ICER of $ 10,423.17 /QALY gained. LNF was strongly dominated by TIF 2.0. Over a lifetime horizon, TIF 2.0 remained the cost-effective strategy for patients with symptoms despite twice-daily 20-mg omeprazole. TIF 2.0 remained cost-effective after varying parameter inputs in deterministic and probabilistic sensitivity analyses and for scenario analyses in multiple age groups. Conclusions Based upon this study, TIF 2.0 was cost-effective for patients with symptomatic GERD despite low-dose, twice-daily PPI.

Value of pH Impedance Monitoring While on Twice-Daily Proton Pump Inhibitor Therapy to Identify Need for Escalation of Reflux Management

Acid exposure time (AET) and reflux episode thresholds from the Lyon Consensus may not apply for pH impedance studies performed while on proton pump inhibitor (PPI) therapy. We aimed to determine metrics from "on PPI" pH impedance studies predicting need for escalation of therapy. De-identified pH impedance studies performed while on twice-daily PPI (Diversatek, Boulder, CO) in healthy volunteers (n= 66, median age 37.5 years, 43.9% female), and patients with proven gastroesophageal reflux disease (GERD) (European heartburn-predominant cohort: n= 43, median age 57.0 years, 55.8% female; North American regurgitation-predominant cohort: n= 42, median age 41.6 years, 42.9% female) were analyzed. Median values and interquartile ranges for pH impedance metrics in healthy volunteers were compared with proven GERD patients with and without 50% symptom improvement on validated measures. Receiver operating characteristic (ROC) analyses identified optimal thresholds predicting symptom response. Both conventional and novel reflux metrics were similar between PPI responders and nonresponders (P ≥ .1 for each) despite differences from healthy volunteers. Combinations of metrics associated with conclusively abnormal reflux burden (AET >4%, >80 reflux episodes) were seen in 32.6% and 40.5% of heartburn and regurgitation-predominant patients, respectively, 57.1% and 82.4% of whom reported nonresponse; and 85% with these metrics improved with invasive GERD management. On ROC analysis, AET threshold of 0.5% modestly predicted nonresponse (sensitivity, 0.62; specificity, 0.51; P= .22), and 40 reflux episodes had better performance characteristics (sensitivity, 0.80; specificity, 0.51; P=.002); 79% with these metrics improved with invasive GERD management. Combinations of abnormal "on PPI" pH impedance metrics are associated with PPI nonresponse in proven GERD patients, and can be targeted for treatment escalation, including surgery, particularly in regurgitation-predominant GERD.

S2133 Amyloidosis-Associated Gastric Ulceration and Submucosal Hematoma

INTRODUCTION: A 77-year-old woman with a history of atrial fibrillation treated with apixaban presented to the hospital after a presyncopal event and hematemesis. Endoscopic evaluation revealed a large submucosal hematoma, which was initially suspicious for an isolated gastric varix, and 2 large gastric ulcers which biopsy later identified as amyloidosis. CASE DESCRIPTION/METHODS: A 77-year-old woman with a history of atrial fibrillation treated with apixaban presented to the hospital after a presyncopal event. Approximately 12 hours after admission, she was noted to have frank hematemesis, requiring IV fluids, blood, and plasma transfusion. EGD demonstrated copious clotted blood in the gastric fundus and a submucosal lesion which appeared to be an isolated varix in the gastric body. The patient was then transferred to a tertiary care center to be evaluated for endoscopic cyanoacrylate therapy. Upon arrival, she was noted to have intermittent episodes of bradycardia, but otherwise remained stable. She experienced no additional episodes of GI bleeding. Repeat EGD demonstrated 2 large, clean-based gastric ulcers with beefy-red margins. Biopsy later identified these as amyloidosis. No interventions were performed on the gastric lesion initially thought to be a gastric varix. This lesion was likely a submucosal hematoma. The patient was discharged to home in stable condition on twice-daily proton-pump inhibitor therapy. DISCUSSION: Amyloidosis is characterized by the pathologic deposition of proteins throughout the body. Within the GI tract, this deposition increases the frailty of blood vessels, hinders intrinsic peristalsis and decreases the compliance of the gut wall, and may present with varying degrees of upper and lower GI bleeding. Cardiac conduction abnormalities are also associated with amyloidosis. The cornerstone of treatment for acquired amyloidosis is the treatment of the underlying disorder causing elevated amyloid precursors. Uniquely, amyloidosis is also associated with submucosal hematoma. The patient in this case presented with massive upper GI bleeding due to amyloid-induced ulcers, and bleeding from these ulcers was exacerbated by apixaban use. Two unique findings suggesting amyloidosis were unexplained bradycardia and a prominent gastric submucosal hematoma (initially thought to be a gastric varix), both of which are highly associated with amyloidosis. Although the patient was discharged in stable condition, she remains at high risk of morbidity and mortality from this systemic disease.Figure 1.: Large gastric body ulcer with prominent beefy-red margins. Biopsies from ulcer margins showed amyloidosis.Figure 2.: Two large amyloidosis-associated gastric ulcers on opposing walls of the gastric body.Figure 3.: This amyloidosis-associated submucosal hematoma was initially mistaken for a gastric varix.

Annals for Educators - 16 June 2020.

Annals for Educators - 16 June 2020.

Management of Laryngopharyngeal Reflux in Asia.

Objectives.This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR).Methods.An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies.Results.Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR.Conclusion.Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.

2734 Immunotherapy-Mediated Hemorrhagic Gastritis After Ipilimumab and Nivolumab Therapy

INTRODUCTION: Combined checkpoint inhibitor immunotherapy with ipilimumab (anti-cytotoxic T-lymphocyte antigen 4 antibody) and nivolumab (anti-programmed cell death receptor 1 antibody) has greatly advanced the treatment of multiple malignancies but is associated with increased immune-related toxicities. Gastrointestinal toxicity is one of the most frequent adverse effects, and while lower GI tract toxicity, such as anti-CTLA-4-mediated colitis, is well known, severe toxicity of the upper GI tract is rare and not well described. We report a case of severe hemorrhagic gastritis in a patient after initiation of ipilimumab and nivolumab therapy for metastatic renal cell carcinoma. CASE DESCRIPTION/METHODS: A 70-year-old man with history of metastatic renal cell carcinoma and recent immune-related myocarditis initially presented with myasthenic weakness after receiving single doses of ipilimumab and nivolumab 5 weeks prior. His presentation was most consistent with seronegative, immune-mediated myasthenia gravis-like syndrome. He was treated with intravenous steroids and plasmapheresis. After 9 days of steroid therapy, he developed large volume melena requiring 4 units of blood despite twice-daily proton pump inhibitor therapy. Endoscopic evaluation revealed diffuse, severe inflammation with hemorrhage characterized by adherent blood and erythematous, friable gastric mucosa in the body, antrum, and prepyloric regions. Hemostatic spray was applied as a temporizing measure to control bleeding. Biopsy specimens demonstrated neutrophilic microabscesses with intraglandular apoptotic bodies, increased lymphocytes and scattered neutrophils in lamina propria, and reactive mucosal features. These findings were compatible with checkpoint inhibitor-induced acute gastritis. Immunohistochemical stains for H. pylori and cytomegalovirus were negative. Despite immunosuppressive therapy with high dose steroids, mycophenalate mofetil, and trial of infliximab, he continued to decline with ongoing anemia and progressive weakness. He was transitioned to comfort measures and died soon afterward. DISCUSSION: To our knowledge, this is the first reported case of severe hemorrhagic, non-infectious gastritis as a rare complication of immunotherapy with ipilimumab and nivolumab. Physicians should be aware that checkpoint inhibitor-induced toxicity of the upper GI tract can occur early after initiation of therapy and have a severe, refractory course. Management includes exclusion of infectious process and immunosuppressive therapy.

Magnetic Sphincter Augmentation Superior to Proton Pump Inhibitors for Regurgitation in a 1-Year Randomized Trial

Regurgitative gastroesophageal reflux disease (GERD) refractive to medical treatment is common and caused by mechanical failure of the anti-reflux barrier. We compared the effects of magnetic sphincter augmentation (MSA) with those of proton-pump inhibitors (PPIs) in a randomized trial. Patients with moderate to severe regurgitation (assessed by the foregut symptom questionnaire) despite once-daily PPI therapy (n= 152) were randomly assigned to groups given twice-daily PPIs (n= 102) or laparoscopic MSA (n= 50) at 20 sites, from July 2015 through February 2017. Patients answered questions from the foregut-specific reflux disease questionnaire and GERD health-related quality of life survey about regurgitation, heartburn, dysphagia, bloating, diarrhea, flatulence, and medication use, at baseline and 6 and 12 months after treatment. Six months after PPI therapy, MSA was offered to patients with persistent moderate to severe regurgitation and excess reflux episodes during impedance or pH testing on medication. Regurgitation, foregut scores, esophageal acid exposure, and adverse events were evaluated at 1 year. Patients in the MSA group and those who crossed over to the MSA group after PPI therapy (n= 75) had similar outcomes. MSA resulted in control of regurgitation in 72/75 patients (96%); regurgitation control was independent of preoperative response to PPIs. Only 8/43 patients receiving PPIs (19%) reported control of regurgitation. Among the 75 patients who received MSA, 61 (81%) had improvements in GERD health-related quality of life improvement scores (greater than 50%) and 68 patients (91%) discontinued daily PPI use. Proportions of patients with dysphagia decreased from 15% to 7% (P <.005), bloating decreased from 55% to 25%, and esophageal acid exposure time decreased from 10.7% to 1.3% (P < .001) from study entry to 1-year after MSA (Combined P<.001). Seventy percent (48/69) of patients had pH normalization at study completion. MSA was not associated with any peri-operative events, device explants, erosions, or migrations. In a prospective study, we found MSA to reduce regurgitation in 95% of patients with moderate to severe regurgitation despite once-daily PPI therapy. MSA is superior to twice-daily PPIs therapy in reducing regurgitation. Relief of regurgitation is sustained over 12 months. ClinicalTrials.gov no: NCT02505945.

Endoscopic management of gastroesophageal reflux disease after sleeve gastrectomy by use of the antireflux mucosectomy procedure.

Endoscopic management of gastroesophageal reflux disease after sleeve gastrectomy by use of the antireflux mucosectomy procedure.

Difficult To Treat Recurrent Esophageal Dysphagia Due To Secondary Esophageal Motility Disorders: A 24 Weeks Follow Up Case Report

Limited data are available on the prevalence of esophageal motility disorders (OMD) with a suggested range of 4-12% in cases with dysphagia. The proposed pathophysiology is either impairment of inhibitory innervation or overactivity of excitatory innervation. The optimal treatment is not defined until now. This case represented one of the secondary OMD in a 70 years year diabetic patient with ischemic cardiomyopathy, who was complaining of recurrent daily intermittent dysphagia to solids and fluids, with a previous vague history of esophageal dilatation without available documentation. After endoscopy with multiple biopsies and barium imaging, the picture of the corkscrew esophagus was revealed. The patient, who was already on nitrates, failed to respond to twice-daily proton pump inhibitor for two months with a prokinetic drug, calcium channel blocker, and the first session of endoscopic esophageal dilatation. After the second session of dilatation, we add sodium alginate with the substitution of nitrates with sildenafil, and the patient reported a gradual improvement of dysphagia especially to fluids with decreasing in daily attacks. We learn from this case that there is a different patient-to-patient response, which necessitates the use of different treatment modalities even just switching between nitric oxide scavengers for each patient. Keywords: Case Report; Dysphagia; esophageal Motility Disorders.

ARE THE PERSISTENT SYMPTOMS TO PROTON PUMP INHIBITOR THERAPY DUE TO REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE OR TO OTHER DISORDERS?

Gastroesophageal reflux disease (GERD) is a clinical condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. Transient lower esophageal sphincter relaxation is the main pathophysiological mechanism of GERD. Symptoms and complications can be related to the reflux of gastric contents into the esophagus, oral cavity, larynx and/or the lung. Symptoms and other possible manifestations of GERD are heartburn, regurgitation, dysphagia, non-cardiac chest pain, chronic cough, chronic laryngitis, asthma and dental erosions. The proton pump inhibitor (PPI) is the first-choice drug and the most commonly medication used for the treatment of GERD. The most widespread definition of Refractory GERD is the clinical condition that presents symptoms with partial or absent response to twice-daily PPI therapy. Persistence of symptoms occurs in 25% to 42% of patients who use PPI once-daily and in 10% to 20% who use PPI twice-daily. The objective is to describe a review of the current literature, highlighting the causes, diagnostic aspects and therapeutic approach of the cases with suspected reflux symptoms and unresponsive to PPI. Initially, the management of PPI refractoriness consists in correcting low adherence to PPI therapy, adjusting the PPI dosage and emphasizing the recommendations on lifestyle modification change, avoiding food and activities that trigger symptoms. PPI decreases the number of episodes of acid reflux; however, the number of "non-acid" reflux increases and the patient continues to have reflux despite PPI. In this way, it is possible to greatly reduce greatly the occurrence of symptoms, especially those dependent on the acidity of the refluxed material. Response to PPI therapy can be evaluated through clinical, endoscopic, and reflux monitoring parameters. In the persistence of the symptoms and/or complications, other causes of Refractory GERD should be suspected. Then, diagnostic investigation must be initiated, which is supported by clinical parameters and complementary exams such as upper digestive endoscopy, esophageal manometry and ambulatory reflux monitoring (esophageal pH monitoring or esophageal impedance-pH monitoring). Causes of refractoriness to PPI therapy may be due to the true Refractory GERD, or even to other non-reflux diseases, which can generate symptoms similar to GERD. There are several causes contributing to PPI refractoriness, such as inappropriate use of the drug (lack of patient adherence to PPI therapy, inadequate dosage of PPI), residual acid reflux due to inadequate acid suppression, nocturnal acid escape, "non-acid" reflux, rapid metabolism of PPI, slow gastric emptying, and misdiagnosis of GERD. This is a common cause of failure of the clinical treatment and, in this case, the problem is not the treatment but the diagnosis. Causes of misdiagnosis of GERD are functional heartburn, achalasia, megaesophagus, eosinophilic esophagitis, other types of esophagitis, and other causes. The diagnosis and treatment are specific to each of these causes of refractoriness to clinical therapy with PPI.

Laparoscopic magnetic sphincter augmentation versus double-dose proton pump inhibitors for management of moderate-to-severe regurgitation in GERD: a randomized controlled trial

GERD patients frequently complain of regurgitation of gastric contents. Medical therapy with proton-pump inhibitors (PPIs) is frequently ineffective in alleviating regurgitation symptoms, because PPIs do nothing to restore a weak lower esophageal sphincter. Our aim was to compare effectiveness of increased PPI dosing with laparoscopic magnetic sphincter augmentation (MSA) in patients with moderate-to-severe regurgitation despite once-daily PPI therapy. One hundred fifty-two patients with GERD, aged≥21 years with moderate-to-severe regurgitation despite 8 weeks of once-daily PPI therapy, were prospectively enrolled at 21 U.S. sites. Participants were randomized 2:1 to treatment with twice-daily (BID) PPIs (N= 102) or to laparoscopic MSA (N= 50). Standardized foregut symptom questionnaires and ambulatory esophageal reflux monitoring were performed at baseline and at 6 months. Relief of regurgitation, improvement in foregut questionnaire scores, decrease in esophageal acid exposure and reflux events, discontinuation of PPIs, and adverse events were the measures of efficacy. Per protocol, 89% (42/47) of treated patients with MSA reported relief of regurgitation compared with 10% (10/101) of the BID PPI group (P< .001) at the 6-month primary endpoint. By intention-to-treat analysis, 84% (42/50) of patients in the MSA group and 10% (10/102) in the BID PPI group met this primary endpoint (P< .001). Eighty-one percent (38/47) of patients with MSA versus 8% (7/87) of patients with BID PPI had ≥50% improvement in GERD-health-related quality of life scores (P< .001), and 91% (43/47) remained off of PPI therapy. A normal number of reflux episodes and acid exposures was observed in 91% (40/44) and 89% (39/44) of MSA patients, respectively, compared with 58% (46/79) (P< .001) and 75% (59/79) (P= .065) of BID PPI patients at 6 months. No significant safety issues were observed. In MSA patients, 28% reported transient dysphagia; 4% reported ongoing dysphagia. Patients with GERD with moderate-to-severe regurgitation, especially despite once-daily PPI treatment, should be considered for minimally invasive treatment with MSA rather than increased PPI therapy. (Clinical trial registration number: NCT02505945.).

Once Versus Twice-Daily Oral Proton Pump Inhibitor Therapy for Prevention of Peptic Ulcer Rebleeding: A Propensity Score-Matched Analysis.

BackgroundAfter inpatient management of upper gastrointestinal bleeding (GIB) due to peptic ulcer disease (PUD), oral proton pump inhibitor (PPI) therapy is recommended at discharge to decrease rebleeding risk and improve ulcer healing. Our aim is to determine whether once-daily oral PPI dosing at hospital discharge is associated with inferior 30-day rebleeding outcomes as compared to twice-daily dosing.MethodsWe retrospectively identified 233 patients admitted with signs and symptoms of upper GIB found to be due to PUD on upper endoscopy. After inpatient management, patients discharged on once-daily oral PPI were compared to those discharged on twice-daily therapy. We utilized propensity score matching based on Rockall scores to ensure the two groups were closely matched in terms of their baseline rebleeding risk. Primary outcome was the incidence of rebleeding within 30 days. Secondary outcomes were all-cause mortality, blood transfusion requirement, requirement for interventional radiology or surgery.ResultsOverall, 49 patients were discharged on once-daily and 184 on twice-daily PPI. Recurrent bleeding occurred in 18 patients (7.7%) within 30 days. There was no statistically significant difference in recurrent bleeding rates between once-daily (n = 7, 14.3%) as compared to twice-daily PPI (n = 11, 6%) (P = 0.053). In a 1:1 propensity score matched analysis, there was no statistically significant difference in 30-day recurrent bleeding rate between groups (14% once-daily vs. 4% twice-daily, P = 0.159). There were no differences in secondary outcomes.ConclusionsOnce-daily oral PPI dosing at hospital discharge was not associated with inferior outcomes compared to twice-daily dosing in patients hospitalized for upper GIB due to PUD.

Abnormal esophageal acid exposure on high-dose proton pump inhibitor therapy is common in systemic sclerosis patients.

Esophageal dysfunction and gastro-esophageal reflux disease (GERD) are common among patients with systemic sclerosis (SSc). Although high-dose proton pump inhibitors (PPIs) typically normalize esophageal acid exposure, the effectiveness of PPI therapy has not been systematically studied in SSc patients. The aim of this study was to characterize reflux in SSc patients on high-dose PPI using esophageal pH-impedance testing. In this case-controlled retrospective analysis, 38 patients fulfilling 2013 American College of Rheumatology SSc criteria who underwent esophageal pH-impedance testing on twice-daily PPI between January 2014 and March 2017 at a tertiary referral center were compared with a control-cohort of 38 non-SSc patients matched for PPI formulation and dose, hiatal hernia size, age, and gender. Patient clinical characteristics, including endoscopy and high-resolution manometry findings, were assessed via chart review. On pH-impedance, SSc patients had higher acid exposure times (AETs) than controls. Sixty-one percent of the SSc patients and 18% of the control patients had a total AET ≥4.5% (P<.001). Systemic sclerosis patients also had significantly longer AETs, longer median bolus clearance, and lower nocturnal impedance values. Abnormal esophageal acid exposure despite high-dose PPI therapy was common among patients with SSc. The lack of increased reflux episodes in the SSc patients, and longer bolus clearance times and lower nocturnal impedance, supports ineffective clearance as the potential mechanism. Systemic sclerosis patients may require adjunctive therapies to PPIs to control acid reflux.