High-dose Proton Pump Inhibitor Therapy Research Articles

Comparison of Vonoprazan versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding after Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial

High-dose proton pump inhibitor (PPI) therapy has been recommended to prevent rebleeding of high-risk peptic ulcer (PU) after hemostasis. Vonoprazan has been proven to be noninferior to PPIs in various acid-related diseases. This study aims to compare the efficacy of vonoprazan versus PPI for preventing high-risk PU rebleeding after hemostasis. A multicenter, randomized, noninferiority study was conducted in 6 centers. Pre-endoscopic and endoscopic therapy were performed according to standard protocol. After successful hemostasis, patients with high-risk PU bleeding (Forrest class Ia/Ib, IIa/IIb) were randomized into 1:1 to receive vonoprazan (20-mg BID for 3 days, then 20-mg OD for 28 days) or high-dose PPI (pantoprazole intravenous infusion 8 mg/hour for 3 days, then omeprazole 20-mg BID for 28 days). The primary outcome was a 30-day rebleeding rate. Secondary outcomes included 3-and 7-day rebleeding rate, all-cause and bleeding-related mortality, rate of rescue therapy, blood transfusion, length of hospital stay, and safety. Of 194 patients, baseline characteristics, severity of bleeding, and stage of ulcers were comparable among the two groups. The 30-day rebleeding rate in vonoprazan and PPI groups were 7.1% (7/98) and 10.4% (10/96), respectively; noninferiority (within 10% margin) of vonoprazan to PPI was confirmed (%risk difference= -3.3; 95% confidence interval = -11.2, 4.7; P<0.001). The 3-day and 7-day rebleeding rates in vonoprazan group remained noninferior to PPI (P< 0.001 by Farrington and Manning test). All secondary outcomes were also comparable between the two groups. In patients with high-risk PU bleeding, the efficacy of vonoprazan in preventing 30-day rebleeding was noninferior to intravenous PPI.

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video)

Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P= .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P= .023). No adverse events from TXA were recorded. The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

Comprehensive Review: Acute Esophageal Necrosis in the Setting of Gastric Volvulus.

Acute esophageal necrosis (AEN) in the setting of gastric volvulus is a rare condition with only a handful of cases reported. Volvulus may contribute to AEN by limiting tissue perfusion and promoting massive reflux of gastric contents on compromised esophageal mucosa. We reviewed 225 original articles, literature reviews, case series, brief reports, case reports, and discuss six total cases of co-occurring esophageal necrosis and gastric volvulus. We present the first comprehensive analysis of all reported cases in the literature to date and formulate management strategies for the co-occurrence of AEN and volvulus. Management of AEN should be directed at correcting underlying medical conditions, providing hemodynamic support, initiating nil-per-os restriction, and administering high-dose proton pump inhibitor therapy. Surgical intervention is typically reserved for cases of esophageal perforation with mediastinitis and abscess formation.

S709 Proton-Pump Inhibitor Infusion Misuse in the Community Hospital Setting

Introduction: Proton pump inhibitors (PPIs) are the most potent acid suppressants available. Several studies have shown that in hospitalized patients with acute upper gastrointestinal (GI) bleeding from peptic ulcer disease, high-dose PPI therapy via continuous infusion reduces the rate of high-risk bleeding lesions (active bleeding, visible vessel, adherent clot) on initial endoscopy. While the benefits of PPI infusions have been clearly described for these specific indications, they are often over-prescribed to inpatients. Our study aim was to determine the rate of misuse in a tertiary care community hospital setting. Methods: A retrospective cohort study was conducted at Lankenau Medical Center, a 370 bed community hospital. The usage of pantoprazole infusion was determined among hospitalized patients between March 1, 2018 and March 1, 2021 through review of the EPIC electronic medical record system. Appropriate candidates for pantoprazole infusion were defined as patients with hematemesis, melena, coffee-ground emesis, or hematochezia with hemodynamic instability. All other indications were categorized as inappropriate. Variables including age, sex, race, serum hemoglobin at the time of PPI infusion initiation, and antiplatelet use were collected. The rate of PPI infusion misuse was determined. Factors which significantly affected utilization of PPI infusion were determined through multivariate analysis. Results: A total of 348 pre-endoscopic PPI infusions were ordered during the three-year period. Approximately 35% of these prescriptions were ordered without an appropriate indication. The mean age of patients who were prescribed PPI infusions was 68.8 years. 48.6% were on an antiplatelet agent. The only significant variable between patients who were given a PPI infusion for an appropriate versus inappropriate indication was age, where the mean patient age was 68.8 compared to 71.1 years (p=0.04). Patient sex, race, antiplatelet use, and hemoglobin value did not significantly affect PPI infusion use. (Table) Conclusion: Pre-endoscopic PPI infusion was prescribed inappropriately in 34.8% of patients in a community hospital setting. Misuse of this drug leads to unnecessary healthcare costs and reflects poor understanding among prescribers of its appropriate clinically indicated uses. While PPIs are generally regarded as safe, misuse can increase the risk of adverse side effects. A follow-up study looking at a quality improvement intervention will follow this study. Table 1. - Characteristics and Multivariate Analysis of PPI Infusion Misuse Inappropriate PPI Infusion No Yes Total p-value n = 227 n = 121 n = 348 Age (Mean/SD) 67.6 (14.8) 71.1 (15.1) 68.8 (15.0) 0.04 Sex 0.571 Male 131 (57.7%) 66 (54.6%) 197 (56.6%) Female 96 (42.3%) 55 (45.5%) 151 (43.4%) Race 0.705 White 104 (46.0%) 59 (48.8%) 163 (47.0%) Black 112 (49.6%) 55 (45.5%) 167 (48.1%) Other 10 (4.4%) 7 (5.8%) 17 (4.9%) Ethnicity 0.12 Not Hispanic 225 (99.6%) 116 (97.5%) 341 (98.8%) Hispanic 1 (0.4%) 3 (2.5%) 4 (1.2%) Total Number of Antiplatelets 0.629 0 121 (53.3%) 58 (47.9%) 179 (51.4%) 1 70 (30.8%) 41 (33.9%) 111 (31.9%) 2 36 (15.9%) 22 (18.2%) 58 (16.7%) Antiplatelet Type (n = 169 Yes Only) Aspirin 103 (45.4%) 61 (50.4%) 164 (47.1%) 0.37 Clopidogrel 36 (15.9%) 23 (19.0%) 59 (17.0%) 0.456 Ticagrelor 4 (1.8%) 4 (3.3%) 8 (2.3%) 0.456 Prasugrel 1 (0.4%) 0 1 (0.3%) 1 Last Hemoglobin (Mean/SD, g/dl) 8.9 (2.6) 8.6 (2.9) 8.8 (2.7) 0.344 Missing Hemoglobin 19 8 27 Transfusion Units (median/IQR) 2 (0-6) 2 (0-4) 2 (0-5) 0.478

S3666 Severe Hemorrhagic Gastritis in a Patient Receiving PD-1 Inhibitor Treated With High Dose Proton Pump Inhibitor

Introduction: The programmed death 1 (PD-1) immune checkpoint is a negative regulator of T-cell function. Pembrolizumab is a monoclonal antibody which inhibits PD-1 receptor and is commonly used to treat many types of malignancies. While this therapy allows for an enhanced immune response against tumor cells, it can also cause immune-mediated adverse events with the gastrointestinal (GI) tract being the most commonly affected. Systemic corticosteroids are frequently used in patients who develop these side effects. We present a rare case of a patient with clear cell renal cell carcinoma (ccRCC) presenting with hemorrhagic gastritis while on Pembrolizumab, successfully treated with high dose proton pump inhibitor (PPI). Case Description/Methods: A 61-year-old man with metastatic ccRCC treated with Pembrolizumab, presented to the hospital with intractable vomiting and significant weight loss secondary to poor oral intake. Upper endoscopy showed diffusely friable gastric mucosa with oozing of blood (Image 1a). Biopsy revealed mucosa with regenerative changes and active non-specific inflammation with ulcerated granular tissue, negative for CMV, H. pylori, atypical infiltrating cells, or malignancy (Image 1b). These findings were compatible with Pembrolizumab induced autoimmune gastritis. He was started on pantoprazole 40 mg BID with significant clinical improvement; thus, steroid therapy was not initiated. Repeat endoscopy a month later showed resolution of prior endoscopic findings (Image 1c). Pembrolizumab was restarted two months later while on PPI therapy without recurrence of symptoms. Discussion: Gastrointestinal side effects from immunotherapy are common. However, isolated PD-1 blockage-associated gastritis is rare and hemorrhagic gastritis is even more with only a few cases reported in literature. The management of this condition is not well established although systemic steroids are usually used to suppress the immune response. In our case, high dose PPI therapy alone led to resolution of symptoms and mucosal healing. No clinical or histological signs of hemorrhagic gastritis were noted after resuming Pembrolizumab. Whether PPI therapy has a role in preventing or minimizing this immune-induced gastritis is still unknown and more studies are needed to establish this therapy as standard.Figure 1.: (a) Initial endoscopy showing hemorrhagic gastritis. (b) H&E stain at 20× showing inflammatory infiltrate. (c) Repeat endoscopy showing healing mucosa.

S2451 Acute Esophageal Necrosis: A Rarely Encountered Clinical Entity

Introduction: Acute Esophageal Necrosis (AEN), otherwise known as black esophagus for its remarkable appearance during endoscopy, is a rather rare entity in the gastroenterology field. Case Description/Methods: A 51-year-old male with a past medical history of diabetes complicated by peripheral neuropathy presented to the hospital with left lower extremity swelling and pain after a fall. On admission he underwent lower extremity x-ray with subcutaneous air concerning for necrotizing fasciitis. He was taken emergently to the operating room where he underwent 3 compartment exploration with irrigation and drain placement. On day 7 of hospitalization he developed persistent nausea and vomiting for which we were consulted. The following morning he was taken to the endoscopy suite. He was noted to have circumferential black appearance of the esophagus from 28 to 40 cm with abrupt transition to normal-appearing gastric mucosa at the GE junction. This was endoscopically consistent with acute esophageal necrosis He was placed on high-dose intravenous proton pump inhibitor (PPI) therapy as well as sucralfate suspension. Transfer was facilitated to a tertiary care center where repeat endoscopy confirmed the diagnosis. He had a gastrostomy tube placed and ultimately underwent repeat endoscopy 8 weeks later at the same tertiary care center which revealed severe benign appearing esophageal stricturing with inability to pass adult endoscope. It was recommended to continue on PPI therapy with repeat endoscopic evaluation with possible dilation the following month. Unfortunately, in the meantime the patient expired due to unknown causes (Figure). Discussion: AEN is defined by a circumferential, necrotic appearance that almost always affects the distal esophagus with abrupt cessation of the black contour at the GE junction. Incidence is 0.28%, affects men over 4 times more often than women with a mortality near 32%. AEN is usually multifactorial and affects people with many comorbidities. Presenting symptoms varied greatly, with the most prevalent being hematemesis (34%). Injury is related to esophageal ischemia and topical injury. AEN is almost always diagnosed by endoscopy. Biopsy can rule out other similarly appearing pathologies. Management of AEN typically involves treating the underlying cause. Empirical treatment includes IV fluids, PPI, sucralfate, NPO, and TPN in patients with poor nutritional status after 24 hours.Figure 1.: Multiple images showing diffuse esophageal necrosis with abrupt transition to normal mucosa at the GE junction.

Proton Pump Inhibitors in Allergy: Benefits and Risks

Proton pump inhibitors (PPIs) are widely prescribed and are indicated for the treatment of several gastrointestinal disorders. Allergists may prescribe PPIs as a result of the coincidence of gastroesophageal reflux disease with asthma or rhinitis, or when gastroesophageal reflux disease presents as chronic cough. Furthermore, long-term, high-dose PPI therapy is a recommended option for managing eosinophilic esophagitis, resulting in histologic remission in approximately 40% of patients. Here, we discuss current recommendations for PPI use, its deescalation, and its side effect profile. We review evidence supporting the epidemiologic link between the use of acid-suppressant medication and the subsequent development of allergic disorders.

Management of Dysplastic Barrett's Esophagus and Early Esophageal Adenocarcinoma.

While patients with Barrett's esophagus without dysplasia may benefit from endoscopic surveillance, those with low-grade dysplasia may be managed with either endoscopic surveillance or endoscopic eradication. Patients with Barrett's esophagus with high-grade dysplasia and/or intramucosal adenocarcinoma will generally require endoscopic eradication therapy. The management of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma is predominantly endoscopic, with multiple effective methods available for the resection of raised neoplasia and ablation of flat neoplasia. High-dose proton-pump inhibitor therapy is advised during the treatment of Barrett's esophagus with dysplasia and early esophageal adenocarcinoma. After the endoscopic eradication of Barrett's esophagus and associated neoplasia, surveillance is required for the diagnosis and retreatment of recurrence or progression.

Esophageal Stricture: Not Your Usual Culprit?

Question: A 60-year-old woman with past medical history of ATTR amyloidosis and status post heart and liver transplantation presented with complaints of progressive esophageal dysphagia to solids and liquids. She was on tacrolimus, mycophenolate mofetil (MMF), and prednisone. Other pertinent medications included trimethoprim sulfamethoxazole and valganciclovir for infection prophylaxis. Physical examination and laboratory data were unremarkable. Esophagogastroduodenoscopy (EGD) with histopathologic examination of biopsies from the middle third of the esophagus showed the findings presented in Figure A and B. Despite high-dose proton pump inhibitor therapy and repeated dilations, symptoms were unchanged and little progress was made in maintaining an increase in luminal diameter. What is the most likely diagnosis? Look on page 400 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The EGD demonstrates a long, benign-appearing, intrinsic moderate stenosis with extensive fibrotic stricturing in the middle one-third of the esophagus (8 mm inner diameter × 4 cm in length) (Figure A). The stenosis was dilated with a through the scope dilator to 11 mm. Esophageal biopsies demonstrated extensive ulceration with fibrinopurulent exudate and inflamed granulation tissue (Figure B). No fungal or viral infection or malignancy was seen. The patient underwent placement of a percutaneous gastrostomy tube. Over the next year, despite continuous high-dose proton pump inhibitor therapy, she continued to experience dysphagia and required monthly dilations. After ruling out an infectious etiology, MMF was suspected as the possible culprit. Immediately upon withdrawal of MMF, the patient reported significant clinical improvement. A follow-up EGD 4 months later showed a widely patent esophageal lumen with only mild mucosal variance characterized by flattening and scarring in the mid esophagus. MMF has well-known gastrointestinal (GI) adverse effects, including nausea, vomiting and diarrhea. Although the entire GI tract is susceptible to MMF-related toxicity, the colon and, less commonly, the small bowel are the most affected areas.1Nguyen T. Park J.Y. Scudiere J.R. Montgomery E. Mycophenolic acid (CellCept and Myofortic) induced injury of the upper GI tract.Am J Surg Pathol. 2009; 33: 1355-1363Crossref PubMed Scopus (59) Google Scholar A variety of mucosal changes can be seen in the lower GI tract, ranging from inflammatory bowel disease–like changes to features akin to graft-versus-host disease. Upper GI tract toxicities of MMF have included features ranging from those compatible with nonsteroidal anti-inflammatory drug use with topical irritation and damage to ulcerative esophagitis, reactive gastropathy, and duodenal ulceration.2Panarelli N.C. Drug-induced injury in the gastrointestinal tract.Semin Diagn Pathol. 2014; 31: 165-175Crossref PubMed Scopus (24) Google Scholar MMF-related esophageal strictures are rare.3Kim J.J. Mulki R.H. Sebastian K.M. Recalcitrant esophageal stricture secondary to mycophenolate mofetil.Case Rep Gastrointest Med. 2020; 2020: 8817801PubMed Google Scholar This case highlights an uncommon cause of a refractory esophageal stricture that should be considered as a potential etiology for dysphagia, especially in a transplant recipient, when more common etiologies have been excluded or when esophagitis is refractory to proton pump inhibitor therapy.

Effectiveness of PPI treatment and guideline adherence in 236 patients with eosinophilic oesophagitis-Results from the population-based DanEoE cohort shows a low complication rate.

BackgroundProton pump inhibitors (PPIs) are often the first drug of choice in the treatment of eosinophilic oesophagitis (EoE), and in Denmark 8 weeks of high‐dose PPI therapy is recommended as first‐line treatment followed by rebiopsying, reflecting international recommendations.AimsTo assess the population‐based effectiveness of PPIs in the treatment of EoE and evaluate whether patients were treated and followed according to the regional guideline.MethodsThis is a retrospective, registry‐based, DanEoE cohort study of 236 adult EoE patients diagnosed between 2007 and 2017 in the North Denmark Region. After patient file revision, the EoE diagnosis was defined according to the AGREE 2 consensus. Symptomatic PPI response was defined as complete symptom resolution and histological remission (<15 eosinophils per high‐power field).ResultsPPI treatment was initiated in 92% of the EoE patients. High‐ and low‐dose PPIs were prescribed in 55% and 45% of the cases, respectively. When treated with high‐dose PPIs, 68% of the patients were completely symptom‐free, and 49% were in histological remission. In 39% of high‐dose PPI‐treated patients, the symptomatic and histological responses were conflicting. While treated with PPIs, complications were rare, with <5% strictures in responders and <10% in non‐responders. Rebiopsying was done in 67% of the EoE patients started on PPIs.ConclusionsHigh‐dose PPI treatment was effective in half of the EoE patients started on PPIs, but conflicting symptomatic and histological PPI responses were common. Complications were rare when PPIs were started. One‐third of the patients were not rebiopsied as recommended.

ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding.

We performed systematic reviews addressing predefined clinical questions to develop recommendations with the GRADE approach regarding management of patients with overt upper gastrointestinal bleeding. We suggest risk assessment in the emergency department to identify very-low-risk patients (e.g., Glasgow-Blatchford score = 0-1) who may be discharged with outpatient follow-up. For patients hospitalized with upper gastrointestinal bleeding, we suggest red blood cell transfusion at a threshold of 7 g/dL. Erythromycin infusion is suggested before endoscopy, and endoscopy is suggested within 24 hours after presentation. Endoscopic therapy is recommended for ulcers with active spurting or oozing and for nonbleeding visible vessels. Endoscopic therapy with bipolar electrocoagulation, heater probe, and absolute ethanol injection is recommended, and low- to very-low-quality evidence also supports clips, argon plasma coagulation, and soft monopolar electrocoagulation; hemostatic powder spray TC-325 is suggested for actively bleeding ulcers and over-the-scope clips for recurrent ulcer bleeding after previous successful hemostasis. After endoscopic hemostasis, high-dose proton pump inhibitor therapy is recommended continuously or intermittently for 3 days, followed by twice-daily oral proton pump inhibitor for the first 2 weeks of therapy after endoscopy. Repeat endoscopy is suggested for recurrent bleeding, and if endoscopic therapy fails, transcatheter embolization is suggested.

1809 Gurvits Syndrome: A Rare Cause of Upper Gastrointestinal Bleed

INTRODUCTION: Acute Esophageal Necrosis (AEN), also known as Black Esophagus or Gurvit’s syndrome, is a rare disorder that can present as an acute gastrointestinal (GI) bleed. Given the high risk of perforation and mortality, a GI bleed in the correct clinical context should put AEN on the differential. We discuss clinical, endoscopic and management of AEN. CASE DESCRIPTION/METHODS: 57-year-old female with hypertension and gastroesophageal reflux disease presented after a pre-syncopal event. She was admitted for septic shock secondary to urinary tract infection. She was hypothermic with a blood pressure of 76/48 mm Hg on arrival to the ICU. She was started on broad spectrum antimicrobials, in addition to, norepinephrine and vasopressin to maintain mean atrial pressures above 60 mmHg. On ICU day two, she had multiple episodes of coffee-ground emesis and was intubated for airway protection. Her hemoglobin acutely dropped from 8 g/dl to 6.8 g/dl over 12 hours. EGD revealed circumferential ulceration of the lower esophagus with areas of necrosis. Patient was started on high-dose intravenous proton pump inhibitor and supportive therapy with treatment of septic shock. Three days later an endoscopic nasojejunal tube was placed for enteral feeding which revealed increasing amounts of viable mucosa with a decrease in the area of necrosis. There were no further GI bleed and patient was discharged 30 days later. DISCUSSION: AEN is multifactorial with a combination of an ischemic insult, corrosive injury to the mucosa from gastric contents and impaired reparative mechanism in setting of acute illness. Risk factors include male sex, older age and multiple chronic medical conditions. Men are four times more commonly affected than women. Diagnosis is made via direct visualization with findings of circumferential black discoloration of the distal esophagus that abruptly ends at the gastroesophageal junction. With comparatively less dense vasculature, the distal esophagus is the water-shed area of the esophagus. Treatment of AEN focuses on aggressive treatment of underlying disease, supportive therapy, and acid suppression. Complications of AEN include esophageal perforation, mediastinitis, and abscess formation. Long term complications include stricture formation and stenosis. Insertion of nasogastric tube should be avoided given the high risk of perforation secondary to the friability of the esophageal mucosa. In our patient, endoscopically placed nasojejunal tube was a safer alternative to restoring enteral feeding.

CYP2C19 and STAT6 Variants Influence the Outcome of Proton Pump Inhibitor Therapy in Pediatric Eosinophilic Esophagitis.

Proton pump inhibitors (PPIs) are an effective treatment for eosinophilic esophagitis (EoE); however, only 30% to 60% of patients respond. Common genetic variants in CYP2C19 and STAT6 associate with PPI plasma concentration and magnitude of inflammatory response, respectively. Our objective was to determine if genetic variation in the genes for CYP2C19 and STAT6 influence differentiation between PPI responsive esophageal eosinophilia versus PPI nonresponsive EoE (PPI-REE, PPI-nonresponsive EoE). Genomic DNA was isolated from 92 esophageal tissue biopsies collected from participants of a prospective clinical trial of high-dose PPI therapy for esophageal eosinophilia in children. Of the 92 patients examined, 57 (62%) were PPI-REE and 35 (38%) were PPI-nonresponsive EoE. Forty-six of the 92 patients were further characterized by pH probe monitoring; there was no association between reflux index and carriage of CYP2C1917 (P = 0.35). In children who received a PPI dose between ≥1.54 and ≤2.05 mg/kg/day, binary logistic regression modeling showed that carriage of CYP2C1917 associated with PPI-nonresponsive EoE (odds ratio (OR) [95% confidence interval (CI)] = 7.71 [1.21, 49.11], P = 0.031). Carriage of STAT6 allelic variant rs1059513 predicts PPI-REE (OR [95% CI] = 6.16 [1.44, 26.4], P = 0.028), whereas carriage of STAT6 rs324011 synergizes with CYP2C1917 to predict PPI-nonresponsive EoE (rs324011 OR [95% CI] = 5.56 [1.33, 20.72], P = 0.022; CYP2C1917 OR [95% CI] = 8.19[1.42, 50.57], P = 0.023). Common variants in CYP2C19 and STAT6 associate with a PPI-nonresponsive EoE outcome of PPI therapy for esophageal eosinophilia suggesting that response rates may be improved by adopting a genotype-guided approach to PPI dosing.

Reconciliation of Recent Helicobacter pylori Treatment Guidelines in a Time of Increasing Resistance to Antibiotics.

Increasing resistance to antibiotics worldwide has adverse effects on the effectiveness of standard therapies to eradicate Helicobacter pylori infection. We reviewed guidelines developed by expert groups in Europe, Canada, and the United States for the treatment of H pylori infection. We compared the recommendations of these guidelines, reconciled them, and addressed the increasing resistance of H pylori to antibiotic therapy regimens. The guidelines recommend bismuth quadruple therapy for first-line treatment, replacing clarithromycin-based triple therapy. There is consensus for concomitant 4-drug therapy as an alternative, especially when bismuth is not available. When therapy is unsuccessful, it is likely due to resistance to clarithromycin, levofloxacin, and/or metronidazole; these drugs, if used previously, should be avoided in subsequent eradication attempts. Second-line therapies should be bismuth quadruple therapy or levofloxacin triple therapy, depending on suspected resistance, reserving rifabutin-based triple and high-dose dual amoxicillin proton pump inhibitor therapy for subsequent treatment attempts. The increasing resistance of H pylori to antibiotic therapy necessitates local availability of susceptibility tests for individuals, and establishment of regional and national monitoring programs to develop evidence-based locally relevant eradication strategies. Further studies into the development of more easily accessible methods of resistance testing, such as biomarker analysis of stool samples, are required. Options under investigation include substituting vonoprazan for proton pump inhibitors, adding probiotics, and vaccine development. Narrow-spectrum antibiotics and new therapeutic targets could be identified based on genomic, proteomic, and metabolomic analyses of H pylori.

GASTROESOPHAGEAL REFLUX (GERD): A MAJOR FACTOR IN HIGHLY LABILE STEROID-DEPENDENT ASTHMA

Introduction In the setting of severe asthma with difficult to control symptoms, it is crucial to evaluate for other diagnoses and comorbidities in order to optimize management. In the case presented, sub-optimally treated GERD was identified as the driving force causing severe asthma symptoms. Case Description A 13-year-old female was evaluated for systemic steroid-dependent asthma. She reported frequent sudden-onset nocturnal dyspnea that was partially responsive to bronchodilators. She had one ICU admission and two near-syncopal events due to severe respiratory distress in the past year. Episodes persisted despite taking 2 mg/kg of prednisone, daily. Bronchoscopy and high-resolution chest CT were unremarkable. A 24-hour pH / impedance probe study identified excessive acid and nonacid reflux reaching the proximal portion of the esophagus and pooling of fluid in the esophagus. High-dose proton pump inhibitor therapy was initiated, and prednisone was tapered without worsening of her asthma. Discussion As in the case presented, ongoing reflux can manifest as highly labile difficult to control asthma even in the absence of typical reflux symptoms. It is important to consider an impedance study to assess for ongoing GERD in patients with difficult to control asthma. If present, optimizing GERD management with acid suppression therapy and, in some cases, surgically with fundoplication, may be necessary to control severe asthma symptoms.

Dual pH Probes Without Proximal Esophageal and Pharyngeal Impedance May Be Deficient in Diagnosing LPR

Laryngopharyngeal reflux (LPR) is commonly treated with empiric acid suppression. More evidence points to pepsin in the pathophysiology of LPR. Previous studies have evaluated esophageal impedance in patients who had previously failed high dose proton pump inhibitor (PPI) using older catheters without proximal esophageal (just under the upper esophageal sphincter) and pharyngeal impedance sensors. The aim of this study was to compare what traditional diagnostic tools, used for esophageal reflux, would detect and diagnose compared with what a combined hypopharyngeal-esophageal MII catheter with dual pH (HEMII-pH) can detect in the esophagus and pharynx in patients with suspected LPR. Forty-two subjects with presumed LPR were referred for HEMII-pH testing. The number of distal and proximal esophageal impedance events, number of pharyngeal impedance events, symptom correlation, and event acidity were recorded. Previous normative values (>1 pharyngeal impedance events every 24 hours) were used to designate what was pathological LPR on HEMII-pH. Forty-two total subjects had pharyngeal impedance sensor data recorded. Twelve (28.6%) of the subjects were tested while taking high-dose PPI therapy. The mean number of proximal esophageal events was 23.3. The mean number of pharyngeal impedance events was 10. Thirty-four subjects (81%) tested positive for pharyngeal reflux. All patients who tested positive using traditional proximal impedance criteria also tested positive using pharyngeal criteria. Of patients who tested negative using traditional criteria, 72% were positive based on pharyngeal criteria. HEMII-pH catheters should be considered in patients with LPR symptoms. Traditional criteria used for diagnosing esophageal reflux may not translate into LPR.

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.

O-16 Lean body weight based dosing achieves comparable systemic pantoprazole exposures for normal-weight and overweight/obese children

Background We previously reported increased AUCtot and decreased CL/F for the commonly prescribed pro-ton pump inhibitor (PPI) and CYP2C19 substrate, pan-toprazole, in obese vs. non-obese children. In light of increasing concerns regarding adverse events associated with high systemic exposure to PPIs in children (e.g., os-teopenia, infection, micronutrient deficiencies), we aimed to identify a pantoprazole dosing strategy appropriate for overweight/obese children, who are six times more likely to suffer from gastroesophageal reflux disease and require PPI therapy than normal weight peers. Given that most physiologic metabolic processes occur in lean body tissues, lean body weight (LBW) based doing was imple-mented in this prospective paediatric pharmacokinetic investigation. Methods 62 children (6–17 years of age; 39% Female), genotyped for CYP2C19 *2, *3, *4, *17 alleles (TaqMan), re-ceived a single oral dose of pantoprazole (1.2 mg/kg lean body weight). LBW was calculated via the Janmahasatian equation. Plasma pantoprazole and metabolite concen-trations were measured (HPLC-UV) at 10 time-points, over 8 hours, and pharmacokinetic parameters (PK) generat-ed via non-compartmental techniques (Kinetica 5.0). For children with at least one wild-type CYP2C19 allele (*1), select pantoprazole PK were compared in normal-weight (Body Mass Index (BMI) 10-84th% for age; n=29) and over-weight/obese (BMI ≥85th% for age; n=30) children, using independent student t-test (SPSS v23; α=0.05). Results No statistically significant differences were observed for pantoprazole AUCtot in normal-weight (13.9±32.2 µMolar*h) vs. overweight/obese (14.68±31.03 µMolar*h) children (p=0.9). No statistically significant dif-ferences in pantoprazole CL/F (23.9±16.6 vs. 19.8±25.8 L/h; p=0.5) or Cmax (5.66±3.8 vs. 7.76±4.4 uMolar; p=0.06) were observed between normal-weight and overweight/obese children. Conclusion LBW, rather than total body weight, based dosing is most appropriate to achieve comparable sys-temic exposures to pantoprazole for normal-weight and overweight/obese children. This dosing strategy appears to eliminate the systemic pantoprazole overexposure previously observed in obese children and will likely min-imize their risk for adverse events associated with high-dose PPI therapy. Future pharmacokinetic-pharmacody-namic studies of PPIs may be warranted for overweight and obese children.

Little Cost Difference Among PPI Therapies for Bleeding Peptic Ulcers

Evidence strongly indicates that high-dose intravenous proton-pump inhibitor (PPI) therapy improves clinical outcomes in patients with bleeding peptic

Transoral Incisionless Fundoplication for Refractory Gastroesophageal Reflux Disease: Where Do We Stand?

Gastroesophageal reflux disease (GERD) is a chronic, progressive, and costly medical condition affecting a substantial proportion of the world population, predominantly the Western population. The available treatment options for patients with refractory GERD symptoms are limited to either laparoscopic surgery with significant sequelae or potentially lifelong, high-dose proton pump inhibitor therapy. The restoration of the antireflux competence of the gastroesophageal junction at the anatomic and physiologic levels is critical for the effective long-term treatment of GERD. Transoral incisionless fundoplication (TIF) surgery is a safe, well-tolerated, and effective treatment that has yielded significant symptomatic improvement in patients with medically refractory GERD symptoms. In this review article, we have summarized case series and reports describing the role of TIF for patients with gastroesophageal reflux symptoms. The reported indications, techniques, complications, and success rates are also discussed.