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Pathophysiology and treatment options for gastroesophageal reflux disease: looking beyond acid.
Sharma, P, Yadlapati, R
Annals of the New York Academy of Sciences. 2021;(1):3-14
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Abstract
Gastroesophageal reflux disease (GERD) is a disorder due to the retrograde flow of refluxate into the esophagus. Although GERD is a common clinical diagnosis, its pathogenesis is quite complex. As a result of its multifactorial development, many patients continue to experience adverse symptoms due to GERD despite prolonged acid suppression with proton pump inhibitor therapy. The pathogenesis of GERD involves an interplay of chemical, mechanical, psychologic, and neurologic mechanisms, which contribute to symptom presentation, diagnosis, and treatment. As such, GERD should be approached as a disorder beyond acid. This review will investigate the major factors that contribute to the development of GERD, including factors related to the refluxate, esophageal defenses, and factors that promote pathologic reflux into the esophagus. In reviewing GERD pathogenesis, this paper will highlight therapeutic advances, with mention of future opportunities of study when approaching GERD.
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The pharmacotherapeutic management of gastroesophageal reflux disease (GERD).
Chapelle, N, Ben Ghezala, I, Barkun, A, Bardou, M
Expert opinion on pharmacotherapy. 2021;(2):219-227
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a very common worldwide condition, affecting about 15-20% of the whole population, and representing a major burden for health-care systems. Because of its frequency, health physicians - family doctors as well as specialists - should be aware of the different pharmacotherapeutic approaches in managing GERD, according to disease severity. AREAS COVERED Authors summarize the pharmacological management of GERD in adults, present the different pharmaceutical classes, and review the evidence on efficacy for each treatment according to the most common clinical scenarios: non-erosive gastroesophageal reflux disease (NERD), erosive esophagitis (EE), and proton-pump inhibitor (PPI) refractory GERD. They also provide an overview of treatments under development. EXPERT OPINION To date, PPIs remain the most effective treatment option for both NERD and EE. However, Potassium-Competitive Acid blockers (PCAB) may be considered, with at least similar efficacy in Asian populations. Preliminary data suggest that PCABs could be superior to classic PPIs in patients with severe EE, and may also be of particular interest in the management of PPI-refractory GERD patients. Their definitive role in GERD management, however, still remains to be determined based on properly designed and conducted randomized clinical trials.
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Eosinophilic Esophagitis: Etiology and Therapy.
Patel, RV, Hirano, I, Gonsalves, N
Annual review of medicine. 2021;:183-197
Abstract
Eosinophilic esophagitis (EoE) is a relatively recently identified but now frequently encountered antigen/immune-mediated disease which places significant burden on patients and the healthcare system. With its growing prevalence and recognition by healthcare providers in multiple disciplines, substantial progress has been made regarding the diagnostic criteria, clinical evaluation, tools for disease assessment, and immune pathways related to pathogenesis. Current treatment goals focus on the amelioration of inflammation and prevention of remodeling consequences using proton pump inhibitors, swallowed topical steroids, elimination diets, and esophageal dilation. Ongoing research holds promise for more efficacious and targeted therapies as well as a personalized approach to the care of patients with EoE.
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Eosinophilic Esophagitis: Update on Diagnosis and Treatment in Pediatric Patients.
Rossetti, D, Isoldi, S, Oliva, S
Paediatric drugs. 2020;(4):343-356
Abstract
Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder characterized by symptomatic esophageal dysfunction and an eosinophil-predominant inflammation of the esophagus. EoE arises from interaction between genetic and environmental factors. In pediatric patients, clinical manifestations vary depending on age, from a gastroesophageal reflux disease (GERD)-like condition to severe dysphagic symptoms. Upper endoscopy is considered the gold standard for diagnosis and monitoring of EoE; however, significant efforts are underway to identify noninvasive diagnostic tools and biomarkers to avoid repetitive invasive procedures. Therapeutic first-line options currently available for EoE are elimination diets, proton pump inhibitors (PPIs), and steroids. The aim of treatment is to improve clinical symptoms while obtaining mucosal healing and avoiding long-term complications. Dietary treatment options comprise different empiric diets or an exclusively amino acid formula. Despite the efficacy of diets, compliance is often challenging. PPIs and topical steroids represent the main pharmacological options for EoE, and both can induce and maintain remission. Topical steroids have been reported as more effective, but data on long-term safety remain insufficient for both these and PPIs. Endoscopic dilations are currently reserved for severe untreated fibrostenotic disease unresponsive to medical therapies. Several biologic agents are available but not yet approved for EoE.
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PPIs and Beyond: A Framework for Managing Anticoagulation-Related Gastrointestinal Bleeding in the Era of COVID-19.
Patel, P, Sengupta, N
Digestive diseases and sciences. 2020;(8):2181-2186
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Abstract
Coronavirus disease of 2019 (COVID-19) can be associated with high morbidity and mortality; patients with severe clinical manifestations may develop significant coagulopathy as well as unexpected thromboembolic complications. In response, centers are increasingly treating selected patients with intermediate-dose prophylactic or even therapeutic dose anticoagulation in order to prevent potentially catastrophic thrombotic complications. With this changing practice, the authors suspect that inpatient gastrointestinal consult teams across the country will be frequently managing COVID-19 patients with gastrointestinal bleeding (GIB). In order to reduce potentially avoidable hospital readmissions for GIB while improving patient outcomes, it is imperative to appropriately risk-stratify patients prior to initiation of anticoagulation. In this review, we discuss how to appropriately identify high-risk patients for GIB and how to mitigate GIB risk with proton-pump inhibitor co-therapy, medication reconciliation, and Helicobacter pylori testing and treating in this complex and morbid population.
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Update on quinolone-containing rescue therapies for Helicobacter pylori infection.
Mori, H, Suzuki, H
World journal of gastroenterology. 2020;(15):1733-1744
Abstract
Third generation of quinolones, such as levofloxacin and moxifloxacin, -containing regimens are often used in second-line or rescue treatment of Helicobacter pylori infection. However, the increasing antibiotic resistance to quinolones affects the efficacies of quinolones-containing therapies in recent years. Therefore, there is a need to enhance the effectiveness of quinolones-containing therapies. Sitafloxacin, a fourth-generation quinolone, and vonoprazan, a novel potassium-competitive acid blocker, are now available as more effective treatment options. The aim of this paper is to summarize the current evidence of quinolone-containing therapies in rescue treatments, and to discuss the importance of drug sensitivity tests or analysis of gyrA mutation before treatments.
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Proton Pump Inhibitors and the Kidney: Implications of Current Evidence for Clinical Practice and When and How to Deprescribe.
Al-Aly, Z, Maddukuri, G, Xie, Y
American journal of kidney diseases : the official journal of the National Kidney Foundation. 2020;(4):497-507
Abstract
Proton pump inhibitors (PPIs), long thought to be safe, are associated with a number of nonkidney adverse health outcomes and several untoward kidney outcomes, including hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, kidney failure, and increased risk for all-cause mortality and mortality due to chronic kidney disease. PPIs are abundantly prescribed, rarely deprescribed, and frequently purchased over the counter. They are frequently used without medical indication, and when medically indicated, they are often used for much longer than needed. In this In Practice review, we summarize evidence linking PPI use with adverse events in general and adverse kidney outcomes in particular. We review the literature on the association of PPI use and risk for hypomagnesemia, acute kidney injury, acute interstitial nephritis, incident chronic kidney disease, kidney disease progression, end-stage kidney disease, and death. We provide an assessment of how this evidence should inform clinical practice. We review the impact of this evidence on patients' perception of risk, synthesize PPI deprescription literature, and provide our recommendations on how to approach PPI use and deprescription.
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Diagnosis and treatment of eosinophilic esophagitis.
Gonsalves, NP, Aceves, SS
The Journal of allergy and clinical immunology. 2020;(1):1-7
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Abstract
Eosinophilic esophagitis (EoE) is an eosinophil-rich, TH2 antigen-mediated disease of increasing pediatric and adult worldwide prevalence. Diagnosis requires greater than or equal to 15 eosinophils per high-power field on light microscopy. Symptoms reflect esophageal dysfunction, and typical endoscopic features include linear furrows, white plaques, and concentric rings. Progressive disease leads to pathologic tissue remodeling, with ensuing esophageal rigidity and loss of luminal diameter caused by strictures. Therapies include proton pump inhibitors, elimination diets, and topical corticosteroids. Effective treatment can reverse tissue fibrosis in some patients, as well as decrease the rate of food impactions. Esophageal dilation might be required to increase luminal patency. The chronic nature of EoE necessitates long-term therapy to avoid disease recurrence and complications. This review serves the function of providing the current state-of-the-art diagnostic criteria and disease management for adult and pediatric EoE.
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Pathophysiology of Drug-Induced Hypomagnesaemia.
Katopodis, P, Karteris, E, Katopodis, KP
Drug safety. 2020;(9):867-880
Abstract
Magnesium (Mg2+) is the second most abundant intracellular and fourth extracellular cation found in the body and is involved in a wide range of functions in the human cell and human physiology. Its role in most of the enzyme processes (ATP-ases)-stabilisation of nucleic acids (DNA, RNA), regulation of calcium and potassium ion channels, proliferation, glucose metabolism and apoptosis-make it one of the most important cations in the cell. Three pathogenetic mechanisms are mainly implicated in the development of hypomagnesaemia: reduced food intake, decreased intestinal absorption and increased renal excretion of Mg2+. This review presents the function of Mg2+, how it is handled in the kidney and the drugs that cause hypomagnesaemia. The frequency and the number of drugs like diuretics and proton-pump inhibitors (PPIs) that are used daily in medical practice are discussed in order to prevent and treat adverse effects by providing an insight into Mg2+ homeostasis.
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Management of Eosinophilic Esophagitis: Dietary and Nondietary Approaches.
Chen, JW
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2020;(5):835-847
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Abstract
Eosinophilic esophagitis (EoE) is an allergen-driven chronic inflammatory condition, characterized by symptoms related to esophageal dysfunction and confirmed histologically by esophageal mucosal eosinophilia. Since its first description in the 1990s, the incidence and prevalence of EoE have been on the rise. It is known to affect all ages of various ethnic backgrounds and both sexes; however, it is most seen in White males. Children with EoE often present with abdominal pain, nausea, vomiting, and failure to thrive, whereas adults with EoE typically present with dysphagia and food impaction. Diagnosis of EoE requires histologic confirmation of elevated esophageal eosinophils in a symptomatic patient, and only after secondary causes have been excluded. Because EoE is a chronic and progressively fibrostenotic disease, treatment goals include resolution of symptoms, induction and maintenance of disease remission, and prevention and possibly reversal of fibrostenotic complications, while minimizing treatment-related adverse effects and improving quality of life. Treatment strategies include the "3 D's"-drugs, diet, and dilation. Standard drug therapies include proton-pump inhibitors and topical corticosteroids. Dietary therapies include elemental diet, allergy testing-directed elimination diet, and empiric elimination diets. Endoscopic esophageal dilation for EoE strictures can alleviate esophageal symptoms but has no effect on mucosal inflammation. Recent progress in EoE research has made possible evidence-based clinical guidelines. Ongoing pharmacologic trials show promise for novel biologic agents in the treatment of refractory EoE.