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Elkalawy H, Abosena W, Elnagger M, Allison H. Wake up to gastro-oesophageal reflux disease: The interplay between arousal and night-time reflux. J Sleep Res 2024; 33:e14158. [PMID: 38356205 DOI: 10.1111/jsr.14158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 01/15/2024] [Accepted: 01/17/2024] [Indexed: 02/16/2024]
Abstract
This review examines the temporal association between nocturnal gastro-oesophageal reflux and sleep-arousal cycles. Most nocturnal gastro-oesophageal reflux events occur during the awake cycle, and arousals precede most nocturnal gastro-oesophageal reflux events, indicating that arousal from sleep predisposes to nocturnal gastro-oesophageal reflux. This sheds light on the complex relationship between nocturnal gastro-oesophageal reflux and sleep, and has implications for managing nocturnal gastro-oesophageal reflux symptoms. The appearance of symptoms and the pathophysiology of nocturnal gastro-oesophageal reflux are influenced by sleep hygiene, sleep disturbances and the misalignment of circadian rhythms. Nocturnal gastro-oesophageal reflux and its related sleep disorders are prevalent and negatively impact the quality of life. There is conflicting evidence on whether nocturnal gastro-oesophageal reflux and sleep disturbances are causally linked, and whether sleep disturbances drive nocturnal gastro-oesophageal reflux. Poor sleep quality increases oesophageal hypersensitivity and overall acid exposure. The nocturnal gastro-oesophageal reflux is linked to the more severe forms of gastro-oesophageal reflux disease, especially with atypical/extra-oesophageal manifestations and complications of mucosal damage such as oesophagitis and stricture, Barret's oesophagus, and oesophageal adenocarcinoma. This review highlights the role of sleep problems in presenting nocturnal gastro-oesophageal reflux, and the potential benefits of treating sleep disturbances in enhancing patient care and quality of life.
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Affiliation(s)
- Hanan Elkalawy
- Department of Anesthesiology and Perioperative Care, Tufts Medical Center, Boston, Massachusetts, USA
| | - Wael Abosena
- Department of Surgery, Faculty of Medicine, Tanta University, Gharbeya, Egypt
| | - Mohamed Elnagger
- Department of Internal Medicine, Hartford Health Care, Hartford, Connecticut, USA
| | - Harmony Allison
- Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts, USA
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2
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Arabpour E, Khoshdel S, Akhgarzad A, Abdi M, Tabatabaie N, Alijanzadeh D, Abdehagh M. Baclofen as a therapeutic option for gastroesophageal reflux disease: A systematic review of clinical trials. Front Med (Lausanne) 2023; 10:997440. [PMID: 36873860 PMCID: PMC9981648 DOI: 10.3389/fmed.2023.997440] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 02/03/2023] [Indexed: 02/19/2023] Open
Abstract
Background The main components of gastroesophageal reflux disease (GERD) management include a combination of medications and lifestyle modifications; Nevertheless, based on the severity of symptoms and their response to medications, other treatments could be considered. Baclofen has been demonstrated in studies to relieve GERD symptoms. The current study aimed to precisely address the effects of baclofen on the treatment of GERD and its characteristics. Methods A systematic search was carried out in Pubmed/Medline, Cochrane CENTRAL, Scopus, Google Scholar, Web of Science, and clinicaltrials.gov up to December 10, 2021. The search terms included baclofen, GABA agonists, GERD, and reflux. Results We selected 26 papers that matched the inclusion criteria after examining 727 records. Studies were classified into four categories based on the study population and reported outcomes: (1) adults, (2) children, (3) patients with gastroesophageal reflux-induced chronic cough, (4) hiatal hernia patients. The results revealed that baclofen can significantly improve reflux symptoms and pH-monitoring and manometry findings to different degrees in all four mentioned categories; although its effect on pH-monitoring parameters seems less significant than the other parameters. Mild neurological and mental status deterioration were the most reported side effects. However, side effects occurred in a portion of less than 5% of short-term users and nearly 20% of long-term users. Conclusion In PPI-resistant patients, a trial of adding baclofen to the PPI may be helpful. Baclofen therapies may be more beneficial for symptomatic GERD patients who also report concurrent conditions including alcohol use disorder, non-acid reflux, or obesity. Systematic review registration https://clinicaltrials.gov/.
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Affiliation(s)
- Erfan Arabpour
- Department of Gastroenterology and Hepatology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sina Khoshdel
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Akhgarzad
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadamin Abdi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Negin Tabatabaie
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Dorsa Alijanzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdehagh
- Department of Gastroenterology and Hepatology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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3
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Schuitenmaker JM, Kuipers T, Smout AJPM, Fockens P, Bredenoord AJ. Systematic review: Clinical effectiveness of interventions for the treatment of nocturnal gastroesophageal reflux. Neurogastroenterol Motil 2022; 34:e14385. [PMID: 35445777 PMCID: PMC10078437 DOI: 10.1111/nmo.14385] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/28/2022] [Accepted: 04/11/2022] [Indexed: 12/06/2022]
Abstract
BACKGROUND Nocturnal gastroesophageal reflux symptoms have a major impact on sleep quality and are associated with complicated gastroesophageal reflux disease (GERD). We performed a systematic review to assess the data on the effectiveness of the currently available interventions for the treatment of nocturnal reflux symptoms. METHODS We searched PubMed, EMBASE, and the Cochrane Library. All prospective, controlled, and uncontrolled clinical trials in adult patients describing interventions (lifestyle modifications, surgical and pharmacological) for nocturnal gastroesophageal reflux symptoms were assessed for eligibility. A narrative descriptive summary of findings is presented together with summary tables for study characteristics and quality assessment. KEY RESULTS The initial reference search yielded 3067 citations; 66 citations were screened in full text, of which 31 articles were included. Studies on lifestyle modifications include head of bed elevation (n = 5), prolonging dinner-to-bed time (n = 2), and promoting left lateral decubitus position (n = 2). Placebo-controlled clinical trials investigating proton pump inhibitors (PPIs) (n = 11) show success rates ranging from 34.4% to 80.8% in the PPI group versus 10.4%-51.7% in the placebo group. Laparoscopic fundoplication is reserved for severe disease only. There is insufficient evidence for a recommendation on the use of nasal continuous positive airway pressure (nCPAP), hypnotics, baclofen and adding bedtime H2 receptor antagonists for reducing nocturnal reflux. CONCLUSION INFERENCES: A sequential treatment strategy, including head of bed elevation, prolonging dinner-to-bed time, promoting left lateral decubitus position and treatment with acid-suppressive medication is recommended for nocturnal gastroesophageal reflux symptoms. Currently, there is insufficient evidence for the use of nCPAP, hypnotics, baclofen and adding bedtime H2 receptor antagonists.
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Affiliation(s)
- Jeroen M Schuitenmaker
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, The Netherlands
| | - Thijs Kuipers
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, The Netherlands
| | - André J P M Smout
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, The Netherlands
| | - Paul Fockens
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, The Netherlands
| | - Albert J Bredenoord
- Department of Gastroenterology & Hepatology, Amsterdam Gastroenterology and Metabolism, University Medical Centers Amsterdam, Amsterdam, The Netherlands
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4
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Wu J, Ma Y, Chen Y. GERD-related chronic cough: Possible mechanism, diagnosis and treatment. Front Physiol 2022; 13:1005404. [PMID: 36338479 PMCID: PMC9630749 DOI: 10.3389/fphys.2022.1005404] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 10/07/2022] [Indexed: 11/04/2023] Open
Abstract
GERD, or gastroesophageal reflux disease, is a prevalent medical condition that affects millions of individuals throughout the world. Chronic cough is often caused by GERD, and chronic cough caused by GER is defined as GERD-related chronic cough (GERC). It is still unclear what the underlying molecular mechanism behind GERC is. Reflux theory, reflex theory, airway allergies, and the novel mechanism of esophageal motility disorders are all assumed to be linked to GERC. Multichannel intraluminal impedance combined with pH monitoring remains the gold standard for the diagnosis of GERC, but is not well tolerated by patients due to its invasive nature. Recent discoveries of new impedance markers and new techniques (mucosal impedance testing, salivary pepsin, real-time MRI and narrow band imaging) show promises in the diagnosis of GERD, but the role in GERC needs further investigation. Advances in pharmacological treatment include potassium-competitive acid blockers and neuromodulators (such as Baclofen and Gabapentin), prokinetics and herbal medicines, as well as non-pharmacological treatments (such as lifestyle changes and respiratory exercises). More options have been provided for the treatment of GERC other than acid suppression therapy and anti-reflux surgery. In this review, we attempt to review recent advances in GERC mechanism, diagnosis, and subsequent treatment options, so as to provide guidance for management of GERC.
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Affiliation(s)
| | - Yiming Ma
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yan Chen
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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5
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Pauwels A, Raymenants K, Geeraerts A, Boecxstaens V, Masuy I, Broers C, Vanuytsel T, Tack J. Clinical trial: a controlled trial of baclofen add-on therapy in PPI-refractory gastro-oesophageal reflux symptoms. Aliment Pharmacol Ther 2022; 56:231-239. [PMID: 35665521 DOI: 10.1111/apt.17068] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/06/2022] [Accepted: 05/20/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPI) have no effect on non-acid reflux events which can continue to provoke gastro-oesophageal reflux disease (GERD) symptoms. Baclofen, a γ-aminobutyric acid agonist, can decrease non-acid reflux but its symptomatic benefit in refractory GERD symptoms is understudied. AIMS To assess the efficacy of baclofen 10 mg t.i.d. vs placebo as add-on therapy in PPI-refractory GERD symptoms, in a randomised, double-blind, placebo-controlled study. METHODS Patients with persisting typical GERD symptoms on b.i.d. PPI therapy were randomised to 4 weeks of baclofen 10 mg or placebo t.i.d. Before and after treatment, patients underwent 24 h impedance-pH monitoring on-PPI. Throughout the study, patients filled out ReQuest diaries. Data were analysed using mixed models. RESULTS About 60 patients were included (age 47.5 years [range 19-73], 41f/19 m), 31 patients were randomised to baclofen. One patient withdrew consent and five in the baclofen group stopped treatment due to side effects. There was a trend towards a better response for general wellbeing in the baclofen-treated group compared to placebo (p = 0.06). When subdividing patients according to symptom association probability (SAP), only the SAP+ (n = 25) group improved significantly with baclofen (pcorr = 0.02), and worsened with placebo (pcorr = 0.008). The total number of reflux events decreased over time (p = 0.01), mainly due to the baclofen condition (pcorr = 0.1). The number of reflux events with a high proximal extent dropped significantly after baclofen (pcorr = 0.009), but not placebo. CONCLUSION Baclofen decreases several reflux parameters in PPI refractory GERD symptoms, but pH-impedance monitoring is necessary before treatment as only SAP+ patients experience clinical benefit after 4 weeks.
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Affiliation(s)
- Ans Pauwels
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Karlien Raymenants
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Annelies Geeraerts
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Veerle Boecxstaens
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
- Oncological and Vascular Access Surgery, Department of Surgical Oncology, University Hospitals Leuven, Leuven, Belgium
- Department of Oncology, KU Leuven, Leuven, Belgium
| | - Imke Masuy
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Charlotte Broers
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
- Department of Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Rome Foundation, Falls of Neuse, Chapel Hill, North Carolina, USA
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6
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Maselli DB, Camilleri M. Pharmacology, Clinical Effects, and Therapeutic Potential of Cannabinoids for Gastrointestinal and Liver Diseases. Clin Gastroenterol Hepatol 2021; 19:1748-1758.e2. [PMID: 32673642 PMCID: PMC7854774 DOI: 10.1016/j.cgh.2020.04.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 03/30/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023]
Abstract
Cannabis and cannabinoids (such as tetrahydrocannabinol and cannabidiol) are frequently used to relieve gastrointestinal symptoms. Cannabinoids have effects on the immune system and inflammatory responses, as well as neuromuscular and sensory functions of digestive organs, including pancreas and liver. Cannabinoids can cause hyperemesis and cyclic vomiting syndrome, but they might also be used to reduce gastrointestinal, pancreatic, or hepatic inflammation, as well as to treat motility, pain, and functional disorders. Cannabinoids activate cannabinoid receptors, which inhibit release of transmitters from presynaptic neurons and also inhibit diacylglycerol lipase alpha, to prevent synthesis of the endocannabinoid 2-arachidonoyl glycerol. However, randomized trials are needed to clarify their effects in patients; these compounds can have adverse effects on the central nervous system (such as somnolence and psychosis) or the developing fetus, when used for nausea and vomiting during pregnancy. Cannabinoid-based therapies can also hide symptoms and disease processes, such as in patients with inflammatory bowel diseases. It is important for gastroenterologists and hepatologists to understand cannabinoid mechanisms, effects, and risks.
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Affiliation(s)
- Daniel B Maselli
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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7
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Basnayake C, Geeraerts A, Pauwels A, Koek G, Vaezi M, Vanuytsel T, Tack J. Systematic review: duodenogastroesophageal (biliary) reflux prevalence, symptoms, oesophageal lesions and treatment. Aliment Pharmacol Ther 2021; 54:755-778. [PMID: 34313333 DOI: 10.1111/apt.16533] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/20/2021] [Accepted: 07/01/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The prevalence of duodenogastroesophageal reflux (DGER) and its effect on symptoms and oesophageal lesions in gastroesophageal reflux disease (GERD) is unclear. AIMS To conduct a systematic review to determine the prevalence of DGER among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. METHODS We searched Pubmed and MEDLINE for full text, English language articles until October 2020 that evaluated DGER prevalence among patients with GERD, the effect of DGER on symptoms and oesophageal lesions, and the treatment of DGER. RESULTS We identified 3891 reports and included 35 which analysed DGER prevalence in GERD, 15 which evaluated its effect in non-erosive reflux disease (NERD), 17 on erosive oesophagitis, 23 in Barrett's, and 13 which evaluated the treatment of DGER. The prevalence of DGER, when evaluated by Bilitec, among all GERD patients ranged from 10% to 97%, in NERD 10%-63%, in erosive oesophagitis 22%-80% and in Barrett's 50%-100%. There were no differences in the presence or degree of DGER among patients who were asymptomatic or symptomatic on proton pump inhibitors (PPI). The most commonly evaluated treatments for DGER were PPIs and DGER reduced post-PPI therapy in all studies. CONCLUSIONS The prevalence of DGER increased with more advanced oesophageal lesions and did not explain persisting symptoms among patients taking PPI therapy. PPIs appear to be effective in the treatment of DGER. DGER remains an important consideration in patients with GERD and future therapies deserve more study.
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Affiliation(s)
- Chamara Basnayake
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium.,St Vincent's Hospital & University of Melbourne, Melbourne, VIC, Australia
| | - Annelies Geeraerts
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
| | - Ans Pauwels
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
| | - Ger Koek
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Michael Vaezi
- Vanderbilt University Medical Center, Nashville, TN, USA
| | - Tim Vanuytsel
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
| | - Jan Tack
- Department of Chronic Diseases, Metabolism and Ageing (ChroMetA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit Leuven, Leuven, Belgium
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8
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Fass R, Boeckxstaens GE, El-Serag H, Rosen R, Sifrim D, Vaezi MF. Gastro-oesophageal reflux disease. Nat Rev Dis Primers 2021; 7:55. [PMID: 34326345 DOI: 10.1038/s41572-021-00287-w] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2021] [Indexed: 02/07/2023]
Abstract
Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.
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Affiliation(s)
- Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH, USA.
| | - Guy E Boeckxstaens
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Hashem El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Rachel Rosen
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
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9
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Romito JW, Turner ER, Rosener JA, Coldiron L, Udipi A, Nohrn L, Tausiani J, Romito BT. Baclofen therapeutics, toxicity, and withdrawal: A narrative review. SAGE Open Med 2021; 9:20503121211022197. [PMID: 34158937 PMCID: PMC8182184 DOI: 10.1177/20503121211022197] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 05/13/2021] [Indexed: 12/11/2022] Open
Abstract
Baclofen is an effective therapeutic for the treatment of spasticity related to multiple sclerosis, spinal cord injuries, and other spinal cord pathologies. It has been increasingly used off-label for the management of several disorders, including musculoskeletal pain, gastroesophageal reflux disease, and alcohol use disorder. Baclofen therapy is associated with potential complications, including life-threatening toxicity and withdrawal syndrome. These disorders require prompt recognition and a high index of suspicion. While these complications can develop following administration of either oral or intrathecal baclofen, the risk is greater with the intrathecal route. The management of baclofen toxicity is largely supportive while baclofen withdrawal syndrome is most effectively treated with re-initiation or supplementation of baclofen dosing. Administration of other pharmacologic adjuncts may be required to effectively treat associated withdrawal symptoms. This narrative review provides an overview of the historical and emerging uses of baclofen, offers practical dosing recommendations for both oral and intrathecal routes of administration, and reviews the diagnosis and management of both baclofen toxicity and withdrawal.
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Affiliation(s)
- Jia W Romito
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
- Department of Neurological Surgery, The
University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Neurology, The University
of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Emily R Turner
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - John A Rosener
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - Landon Coldiron
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - Ashutosh Udipi
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - Linsey Nohrn
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - Jacob Tausiani
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
| | - Bryan T Romito
- Department of Anesthesiology and Pain
Management, The University of Texas Southwestern Medical Center, Dallas, TX,
USA
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10
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Jeong SO, Lee JS, Lee TH, Hong SJ, Cho YK, Park J, Jeon SR, Kim HG, Kim JO. Characteristics of symptomatic belching in patients with belching disorder and patients who exhibit gastroesophageal reflux disease with belching. J Neurogastroenterol Motil 2021; 27:231-239. [PMID: 33424014 PMCID: PMC8026376 DOI: 10.5056/jnm20114] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 08/02/2020] [Accepted: 08/16/2020] [Indexed: 12/19/2022] Open
Abstract
Background/Aims Belching disorder (BD) is clinically distinct from gastroesophageal reflux disease (GERD) with belching. Supragastric belching (SGB) is closely associated with reflux episodes. This study investigates belch characteristics in association with reflux, compared between patients with BD and those who had GERD with belching. Methods Impedance pH monitoring data from 10 patients with BD and 10 patients with GERD who exhibited belching were retrospectively analyzed. Belches were considered "isolated" or "reflux-related" and acidic/non-acidic. Belch characteristics were compared between patients with BD and those with GERD. Results Symptomatic belches were more frequent in patients with BD than in patients with GERD (median, 160.5 vs 56.0, P < 0.05). SGB was the most common type in both groups; common subtypes comprised "isolated" in patients with BD and "isolated during the reflux period" in patients with GERD. Reflux-related SGB was more common in patients with GERD than in BD (78.3% vs 45.2%, P < 0.005). Both "preceding belching" including the reflux period and acidic SGB were more common in patients with GERD than in BD (31.8% vs 8.6% and 38.1% vs 8.9%, both P < 0.05). Supragastric belch number positively correlated with all reflux episodes in patients with GERD (adjusted R2 = 0.572, P = 0.007). Conclusions BD is characterized by more belching, compared to GERD. SGB is more frequently associated with reflux in GERD than in BD; acidity may be related to GERD. In BD, SGB is typically non-acidic and unrelated to reflux. Distinct SGB characteristics may reflect different pathogenic mechanisms of reflux and associated symptoms.
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Affiliation(s)
- Shin Ok Jeong
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Joon Seong Lee
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Tae Hee Lee
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Su Jin Hong
- Digestive Disease Center and Research Institute, Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Gyeonggi-do, Korea
| | - Young Kyu Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Chungcheongnam-do, Korea
| | - Junseok Park
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Seong Ran Jeon
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Hyun Gun Kim
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jin-Oh Kim
- Institute for Digestive Research, Digestive Disease Center Soonchunhyang University College of Medicine, Seoul, Korea
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11
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Reddy CA, Watts L, Baker JR, Chen JW. Provider Variability in the Management Patterns of Increased Nonacid Reflux. Dig Dis Sci 2021; 66:994-998. [PMID: 32447740 DOI: 10.1007/s10620-020-06348-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/12/2020] [Indexed: 01/24/2023]
Abstract
INTRODUCTION Increased nonacid reflux is diagnosed in a subgroup of patients with gastroesophageal reflux disease who often present with reflux symptoms refractory to proton-pump inhibitor therapy. Despite the prevalence of this condition, the management approach for patients with increased nonacid reflux can often be varied and unclear. AIMS Our primary aim was to investigate physician management patterns for patients who had received a diagnosis of increased nonacid reflux on impedance-pH studies. METHODS Reflux studies in patients with increased nonacid reflux per Lyon Consensus criteria and management approaches were retrospectively reviewed. Reflux symptom survey, manometry findings, reflux symptom association (RSA) on reflux testing, immediate posttesting management information, and managing provider information were assessed. RESULTS A total of 43 subjects in total were analyzed. Management plan after a diagnosis of increased nonacid reflux was decided by a gastroenterologist in over 95% of cases and varied greatly with no changes being the most common. Even among subjects with + RSA on reflux monitoring, no change in management was the most common action, although this occurred much less frequently compared to subjects with - RSA (28.6% vs. 78.6%, p < 0.01). When change in therapy occurred, medical treatment with baclofen was the most common choice (21.4%). Other management changes included medications for visceral hypersensitivity and antireflux surgery, although these changes occurred rarely. CONCLUSIONS Abnormally increased nonacid reflux is frequently encountered on impedance-pH studies; however, management decisions vary significantly among gastroenterologists. When treatment change is implemented, they are variable and can include lifestyle modifications, medication trials, or antireflux surgery. Future development of standardized management algorithms for increased nonacid reflux is needed.
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Affiliation(s)
- Chanakyaram A Reddy
- Division of Gastroenterology, University of Michigan Hospitals-Michigan Medicine, 3912 Taubman Center, 1500 E Medical Center Dr., SPC 5362, Ann Arbor, MI, 48109, USA.
| | - Lydia Watts
- Division of Gastroenterology, University of Michigan Hospitals-Michigan Medicine, 3912 Taubman Center, 1500 E Medical Center Dr., SPC 5362, Ann Arbor, MI, 48109, USA
| | - Jason R Baker
- Division of Gastroenterology, University of Michigan Hospitals-Michigan Medicine, 3912 Taubman Center, 1500 E Medical Center Dr., SPC 5362, Ann Arbor, MI, 48109, USA
| | - Joan W Chen
- Division of Gastroenterology, University of Michigan Hospitals-Michigan Medicine, 3912 Taubman Center, 1500 E Medical Center Dr., SPC 5362, Ann Arbor, MI, 48109, USA
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12
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Laserna-Mendieta EJ, FitzGerald JA, Arias-Gonzalez L, Ollala JM, Bernardo D, Claesson MJ, Lucendo AJ. Esophageal microbiome in active eosinophilic esophagitis and changes induced by different therapies. Sci Rep 2021; 11:7113. [PMID: 33782490 PMCID: PMC8007638 DOI: 10.1038/s41598-021-86464-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Accepted: 03/15/2021] [Indexed: 12/18/2022] Open
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory esophageal disease triggered by food antigens. Cumulative evidence supports the implication of microbiota and the innate immune system in the pathogenesis of EoE. Changes in the esophageal microbiome were investigated by applying 16S rRNA gene sequencing on esophageal biopsies of adult patients with active EoE at baseline (n = 30), and after achieving remission with either proton pump inhibitors (PPI, n = 10), swallowed topical corticosteroids (STC, n = 10) or food-elimination diets (FED, n = 10). Ten non-EoE biopsies were also characterized as controls. Compared to controls, no differences in alpha (intra-sample) diversity were found in EoE microbiota overall. However, it decreased significantly among patients who underwent FED. As for beta (inter-sample) diversity, non-EoE controls separated from EoE baseline samples. Post-treatment samples from patients treated with PPI and FED had a more similar microbiota composition, while those receiving STC were closer to controls. Differential testing of microbial relative abundance displayed significant changes for Filifactor, Parvimonas and Porphyromonas genera. Analysis of predicted functions indicated alterations in metabolic pathways and abundance of sulphur-cytochrome oxidoreductases. Our findings demonstrate changes in microbiota associated with EoE, as well as a treatment effect on the microbiome.
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Affiliation(s)
- E J Laserna-Mendieta
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos, s/n, 13700, Tomelloso, Ciudad Real, Spain. .,Instituto de Investigación Sanitaria de La Princesa, Madrid, Spain. .,Clinical Laboratory, Hospital Universitario de La Princesa, Madrid, Spain.
| | - J A FitzGerald
- School of Microbiology, University College Cork, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - L Arias-Gonzalez
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos, s/n, 13700, Tomelloso, Ciudad Real, Spain.,Instituto de Investigación Sanitaria de La Princesa, Madrid, Spain
| | - J M Ollala
- Department of Pathology, Hospital General La Mancha Centro, Alcázar de San Juan, Spain
| | - D Bernardo
- Mucosal Immunology Lab, Instituto de Biología Y Genética Molecular (IBGM), Universidad de Valladolid-CSIC, Valladolid, Spain.,Centro de Investigación Biomédica en Red Enfermedades Hepáticas Y Digestivas (CIBERehd), Madrid, Spain
| | - M J Claesson
- School of Microbiology, University College Cork, Cork, Ireland.,APC Microbiome Ireland, Cork, Ireland
| | - A J Lucendo
- Department of Gastroenterology, Hospital General de Tomelloso, Vereda de Socuéllamos, s/n, 13700, Tomelloso, Ciudad Real, Spain. .,Instituto de Investigación Sanitaria de La Princesa, Madrid, Spain. .,Centro de Investigación Biomédica en Red Enfermedades Hepáticas Y Digestivas (CIBERehd), Madrid, Spain.
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13
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Xi L, Zhu J, Zhang H, Muktiali M, Li Y, Wu A. The treatment efficacy of adding prokinetics to PPIs for gastroesophageal reflux disease: a meta-analysis. Esophagus 2021; 18:144-151. [PMID: 32519226 DOI: 10.1007/s10388-020-00753-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 05/29/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder. Proton pump inhibitors (PPIs) are first-line drugs for GERD. For those who fail to respond to PPIs, adding prokinetics to PPIs is recommended and several trials have been conducted to evaluate the efficacy of prokinetic-PPI combination therapy. METHODS A systematic literature search was performed using PubMed and the Cochrane Library databases before February 2019 for randomized controlled trials (RCTs), which compared the efficacy of prokinetics plus PPI treatment with that of PPI monotherapy. Relevant studies were examined and data were extracted independently by two investigators. The risk ratios (RRs) with 95% CIs were used to evaluate the responder rate, and standard mean differences (SMDs) or mean differences (MDs) with 95% CIs were used for symptom score changes. Statistical heterogeneity was evaluated by the I2 statistic. Either a fixed-effect or a random-effect model was established for calculating the pooled data. RESULTS A total of 14 studies, comprising 1,437 patients were ultimately included in the meta-analysis. The pooled analysis showed that compared to PPI monotherapy, addition of prokinetics to PPI did not elevate the rate of endoscopic responders (RR = 0.996, 95% CI 0.929 - 1.068, p = 0.917), but improved symptom response (RR = 1.185, 95% CI 1.042 - 1.348, p = 0.010). Additionally, the combined therapy achieved a greater symptom relief than monotherapy both in FSSG and GERD-Q subgroups (MD = - 2.978, 95% CI - 3.319 to - 2.638, p < 0.001; MD = - 0.723, 95% CI - 0.968 to - 0.478, p < 0.001). CONCLUSIONS Adding prokinetics to PPIs achieves symptomatic improvement compared to PPI monotherapy, thus can enhance life quality of GERD patients. However, the combined treatment seems to have no significant effect on mucosal healing.
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Affiliation(s)
- Liting Xi
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Jinzhou Zhu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Huixian Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Merlin Muktiali
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China
| | - Youming Li
- College of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang, China
| | - Airong Wu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
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14
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Belching in Gastroesophageal Reflux Disease: Literature Review. J Clin Med 2020; 9:jcm9103360. [PMID: 33092195 PMCID: PMC7590068 DOI: 10.3390/jcm9103360] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 10/19/2020] [Accepted: 10/19/2020] [Indexed: 12/11/2022] Open
Abstract
Belching is a common phenomenon. However, it becomes bothersome if excessive. Impedance–pH monitoring can classify the belching into two types: gastric belching and supragastric belching (SGB). The former is a physiological mechanism to vent swallowed air from the stomach, whereas the latter is a behavioral disorder. Gastroesophageal reflux disease (GERD) is the most relevant condition in both types of belching. Recent findings have raised awareness that excessive SGB possibly sheds light on the pathogenesis of a part of proton pump inhibitor (PPI) refractoriness in GERD. SGB could cause typical reflux symptoms such as heartburn, regurgitation or chest pain in two ways: SGB-induced gastroesophageal reflux or SGB-induced esophageal distension. In PPI-refractory GERD, it is important to detect hidden SGB as a cause of reflux symptoms since SGB requires psychological treatment instead of high dose PPIs or pain modulators. In the case of PPI-refractory GERD with excessive SGB, recent studies imply that the combination of a psychological approach and conventional treatment can improve treatment outcome.
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15
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O’Hare C, Rahman T, Williams NT. Treatment of Chronic Refractory Cough in Adults: Focus on Neuromodulators and Other Therapeutic Modalities. J Pharm Technol 2020. [DOI: 10.1177/8755122520954866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Objective: To evaluate the literature and educate health care professionals about the different management options for chronic refractory cough (CRC). Data Sources: Searches were performed through MEDLINE (1966 to July 2020) using OVID and EBSCOhost and EMBASE (1947 to July 2020) using OVID. Search terms included chronic cough, neurogenic cough, neuromodulators, chronic cough management, and chronic cough treatment. References of all relevant articles were further used to obtain additional articles. Study Selection and Data Extraction: This review includes articles in the English language and human trial literature. Twenty-three trials explored the use of oral neuromodulators in the management of CRC. Data Synthesis: CRC is a poorly understood disease that may have a complex neuropathic etiology. Oral neuromodulators, such as amitriptyline, baclofen, gabapentin, and pregabalin, continue to be the most commonly used agents for the management of CRC. Alternative pharmacological therapies such as botulinum toxin, anesthetic agents (benzonatate, lidocaine), and narcotic agents have efficacy data, and further research into effective doses and routes of administration is warranted. Alternative nonpharmacologic therapies more commonly used included speech pathology treatment. Conclusion: Several medication and alternative treatment interventions may be effective in managing CRC. Current studies used wide dosing and titration strategies, making it challenging to standardize therapy. No consistent method of assessing cough reflex was used between studies, as well as a lack of consistent randomization and small sample sizes. Additional research is needed to standardize treatment durations, optimum doses, and place in therapy of the available interventions in the management of CRC.
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Affiliation(s)
- Caroline O’Hare
- Southwestern Oklahoma State University, Weatherford, OK, USA
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16
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Zhang M, Zhu Y, Dong R, Qiu Z. Gabapentin versus baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough. J Thorac Dis 2020; 12:5243-5250. [PMID: 33145100 PMCID: PMC7578446 DOI: 10.21037/jtd-2020-icc-002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Refractory gastroesophageal reflux-induced chronic cough (GERC) is a special type of gastroesophageal reflux disease (GERD) with predominant cough resistant to pragmatic standard anti-reflux therapy including antisecretory agents alone or in combination with promotility agents but with a favorable response to intensified anti-reflux treatment. The condition is not rare and is difficult to treat. Neuromodulators such as baclofen and gabapentin are considered potential therapeutic options for refractory GERC. Limited data indicate that gabapentin and baclofen could attenuate the cough symptom in patients with refractory GERC by blockade of gastroesophageal reflux or by direct antitussive effects. However, no study has compared the efficacy of these two drugs in treatment of refractory GERC. In an open-labeled randomized clinical study, we demonstrated that, as add-on therapy, gabapentin and baclofen had a similar prevalence of therapeutic success for suspected refractory GERC but gabapentin may be more preferable because of its fewer central side effects. The efficacy of baclofen and gabapentin was suboptimal, so further studies are needed to select the patients with refractory GERC suitable for precise treatment using these two neuromodulators.
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Affiliation(s)
- Mengru Zhang
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yiqing Zhu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ran Dong
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zhongmin Qiu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
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17
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Scarpignato C, Sloan JA, Wang DH, Hunt RH. Gastrointestinal pharmacology: practical tips for the esophagologist. Ann N Y Acad Sci 2020; 1481:90-107. [PMID: 32822080 DOI: 10.1111/nyas.14447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/19/2020] [Accepted: 07/05/2020] [Indexed: 12/22/2022]
Abstract
Gastroesophageal reflux disease (GERD) is primarily a motor disorder, and its pathogenesis is multifactorial. As a consequence, treatment should be able to address the underlying pathophysiology. Proton pump inhibitors (PPIs) are the mainstay of medical therapy for GERD, but these drugs only provide the control of symptoms and lesions without curing the disease. However, continuous acid suppression with PPIs is recommended for patients with Barrett's esophagus because of their potential chemopreventive effects. In addition to the antisecretory activity, these compounds display several pharmacological properties, often overlooked in clinical practice. PPIs can indeed affect gastric motility, exert a mucosal protective effect, and an antioxidant, anti-inflammatory, and antineoplastic activity, also protecting cancer cells from developing chemo- or radiotherapeutic resistance. Even in the third millennium, current pharmacologic approaches to address GERD are limited. Reflux inhibitors represent a promise unfulfilled, effective and safe prokinetics are lacking, and antidepressants, despite being effective in selected patients, give rise to adverse events in a large proportion of them. While waiting for new drug classes (like potassium-competitive acid blockers), reassessing old drugs (namely alginate-containing formulations), and paving the new avenue of esophageal mucosal protection are, at the present time, the only reliable alternatives to acid suppression.
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Affiliation(s)
- Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta.,Faculty of Medicine, Chinese University of Hong Kong, ShaTin, Hong Kong
| | - Joshua A Sloan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - David H Wang
- Division of Hematology and Oncology, UT Southwestern Medical Center and VA North Texas Health Care System, Dallas, Texas
| | - Richard H Hunt
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
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18
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Nowak K, DiPalma A, Serra S, Quereshy F, Jackson T, Okrainec A, Chetty R. Review of pathological findings in laparoscopic sleeve gastrectomy specimens performed for morbid obesity. J Clin Pathol 2020; 73:618-623. [PMID: 32591353 DOI: 10.1136/jclinpath-2020-206428] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 04/14/2020] [Accepted: 04/16/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Bariatric surgical procedures are employed when there is a failure of lifestyle modification in arresting obesity. Laparoscopic sleeve gastrectomy (LSG) is quickly becoming the bariatric surgical procedure of choice. LSG results in a gastric remnant that is subject to pathological examination. The objective of this paper is to review the literature in regard to histological findings identified in gastric remnants post-LSG and identify the most pertinent histological findings. MATERIALS AND METHODS A literature search was performed to identify relevant case series. Data gathered from relevant case series then underwent statistical analysis. RESULTS The most common histological findings in an LSG specimen were clinically indolent findings such as no pathological abnormalities identified followed by non-specific gastritis. A minority of cases demonstrated clinically actionable findings for which Helicobacter pylori represented the majority of these findings. CONCLUSION There is a broad spectrum of pathological findings in LSG specimens, ranging from clinically indolent to clinically actionable. The most common histological findings are clinically indolent and only a small portion are of clinical significance and, hence, actionable.
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Affiliation(s)
- Klaudia Nowak
- Department of Pathology, University Health Network Laboratory Medicine Program, University of Toronto, Toronto, Ontario, Canada
| | - Adam DiPalma
- Department of General Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Stefano Serra
- Department of Pathology, University Health Network Laboratory Medicine Program, University of Toronto, Toronto, Ontario, Canada
| | - Fayez Quereshy
- Department of General Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Timothy Jackson
- Department of General Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Allan Okrainec
- Department of General Surgery, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Runjan Chetty
- Department of Pathology, University Health Network Laboratory Medicine Program, University of Toronto, Toronto, Ontario, Canada
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19
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Savarino V, Marabotto E, Zentilin P, Furnari M, Bodini G, De Maria C, Tolone S, De Bortoli N, Frazzoni M, Savarino E. Pathophysiology, diagnosis, and pharmacological treatment of gastro-esophageal reflux disease. Expert Rev Clin Pharmacol 2020; 13:437-449. [PMID: 32253948 DOI: 10.1080/17512433.2020.1752664] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic, relapsing disorder, whose knowledge has increased in last years thanks to the advent of new sophisticated techniques, such as 24-h impedance-pH monitoring and high-resolution manometry, for the study of esophageal functions. AREAS COVERED This review provides an overview of our advancements in understanding the complex pathophysiology, improving the diagnosis and defining the modern pharmacological therapeutic approach to GERD. EXPERT OPINION The growing clinical application of impedance-pH testing has allowed us to know the diversity of patients with non-erosive reflux disease (NERD), who nowadays represent about 70% of the whole population with reflux symptoms. We have realized that NERD has to be considered as an umbrella term covering various subgroups with different pathophysiologies. The development of new impedance metrics, in particular mean nocturnal baseline impedance, seems to be promising in the improvement of the diagnostic process of this disease. There are no particularly innovative features in the pharmacological therapy of GERD, unless the interest toward drugs is able to increase the defense properties of esophageal mucosa and/or its protection. These compounds can be of help in combination with proton pump inhibitors in NERD patients with partial response to antisecretory drugs alone.
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Affiliation(s)
| | - Elisa Marabotto
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | | | - Manuele Furnari
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | - Giorgia Bodini
- Department of Internal Medicine, University of Genoa , Genoa, Italy
| | | | - Salvatore Tolone
- Department of Surgery, University of Campania "Luigi Vanvitelli" , Naples, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa, Italy
| | - Marzio Frazzoni
- Department of Gastroenterology, Gastroenterology Digestive Pathophysiology Unit, Baggiovara Hospital , Modena, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua, Italy
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20
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Bagheri Lankarani K, Sivandzadeh GR, Zare M, Nejati M, Niknam R, Taghavi AR, Ejtehadi F, Naini MA, Moini M, Anbardar MH, Peymani P. A preliminary report on the use of Midodrine in treating refractory gastroesophageal disease: Randomized Double-Blind Controlled Trial. ACTA BIO-MEDICA : ATENEI PARMENSIS 2020; 91:70-78. [PMID: 32191657 PMCID: PMC7569571 DOI: 10.23750/abm.v91i1.8486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 02/05/2020] [Indexed: 02/08/2023]
Abstract
Background: Gastroesophageal reflux disease (GERD) is a common disease with various clinical presentations. Acid suppression with proton pump inhibitors and lifestyle modification may not lead to satisfactory response in a substantial portion of patients. We investigated the possible effect of midodrine in patients with refractory GERD. Methods: Patients suffering from GERD and were refractory to one-month course of pantoprazole 40mg twice daily entered the study. This was a pilot, randomized, double-blind, and placebo-controlled study. After randomization, one group received Midodrine 5mg before meals for one month, and the other group received placebo for the same period. Meanwhile, pantoprazole was continued 40mg twice daily in both arms. The severity of symptoms was evaluated by the visual scoring system. Quality of life (QoL) in both groups was measured using a standardized version of Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD). Results: A total of twenty patients were enrolled in this study. There was a significant interaction between the groups and time on all measured scores based on QOLRAD questionnaire. All the markers in the Midodrine group had significant improvement over time, but the placebo group did not show any significant improvement. Both visual severity score and total QoL score in Midodrine arm showed a U shape change during 6 weeks. Conclusions: Midodrine before a meal could be useful in alleviating symptoms and improving QoL in the patients with refractory gastroesophageal disease. (www.actabiomedica.it)
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Affiliation(s)
| | | | - Marziyeh Zare
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences.
| | | | | | | | | | | | | | | | - Payam Peymani
- Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Fars, Iran..
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21
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Zad M, Bredenoord AJ. Chronic Burping and Belching. CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY 2020; 18:33-42. [PMID: 31974815 DOI: 10.1007/s11938-020-00276-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Belching is a physiological event that allows venting of swallowed gastric air. Excessive belching is a common presentation to gastroenterology clinics and could be isolated complains or associated with other gastrointestinal problems. PURPOSE OF THIS REVIEW: It is to describe the presentation, diagnosis, and treatment of belching disorders RECENT FINDINGS: These demonstrate that learned abnormal behaviors in response to unpleasant feeling in the abdomen are the driving causes for excessive belching and addressing these behaviors by speech pathology and cognitive behavior therapy considered as the keystone in its management SUMMARY: The gold standard in the diagnosis of belching is impedance monitoring by which belching is classified into supragastric belching and gastric belching.
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Affiliation(s)
- M Zad
- Department of gastroenterology, Hervey Bay Hospital, Queensland, Australia
| | - A J Bredenoord
- Department of Gastroenterology & Hepatology, Amsterdam UMC, location AMC, Academic Medical Centre, Amsterdam, PO Box 22660, 1100, DD, Amsterdam, the Netherlands.
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22
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Hung JS, Yi CH, Liu TT, Lei WY, Wong MW, Chen CL. Effects of GABA-B agonist baclofen on esophageal motility: Studies using high-resolution manometry. Neurogastroenterol Motil 2019; 31:e13716. [PMID: 31565828 DOI: 10.1111/nmo.13716] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/19/2019] [Accepted: 08/21/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND/AIM Baclofen inhibits transient lower esophageal sphincter (LES) relaxation. This study aimed to investigate the effect of baclofen on esophageal peristaltic function and contraction reserve in healthy adults using high-resolution manometry (HRM). METHODS Fifteen subjects underwent HRM with ten water swallows and five multiple rapid swallows (MRS) 90 minutes after oral intake of either baclofen or placebo on separate days at least 1 week apart. HRM parameters assessed included esophagogastric junction contractile integral (EGJ-CI), resting LES pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, peristaltic breaks, resting upper esophageal sphincter (UES) pressure, and contractile response to MRS. RESULTS Baclofen significantly increased EGJ-CI (P = .007), IRP-4s (P = .003), and LES pressure (P = .004). UES pressure, latency, and DCI were similar between baclofen and placebo (P = .87, P = .84, and P = .54, respectively). There was no difference in contractile response and peristaltic augmentation following MRS between baclofen and placebo (93% vs 100%, P = .30; 53% vs. 73%, P = .26, respectively). CONCLUSIONS Baclofen increases resting LES pressure and EGJ barrier function, but has no effect on primary peristalsis or contraction reserve.
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Affiliation(s)
- Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
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23
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Aktar R, Peiris M, Fikree A, Eaton S, Kritas S, Kentish SJ, Araujo EJA, Bacarin C, Page AJ, Voermans NC, Aziz Q, Blackshaw LA. A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function. J Physiol 2019; 597:1503-1515. [PMID: 30605228 PMCID: PMC6418764 DOI: 10.1113/jp277195] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 12/19/2018] [Indexed: 01/27/2023] Open
Abstract
KEY POINTS Tenascin X (TNX) functions in the extracellular matrix of skin and joints where it maintains correct intercellular connections and tissue architecture TNX is associated exclusively with vagal-afferent endings and some myenteric neurones in mouse and human stomach, respectively. TNX-deficient mice have accelerated gastric emptying and hypersensitivity of gastric vagal mechanoreceptors that can be normalized by an inhibitor of vagal-afferent sensitivity. Cultured nodose ganglion neurones showed no changes in response to capsaicin, cholecystokinin and potassium chloride in TNX-deficient mice. TNX-deficient patients have upper gastric dysfunction consistent with those in a mouse model. Our translational studies suggest that abnormal gastric sensory function may explain the upper gut symptoms present in TNX deficient patients, thus making it important to study gastric physiology. TNX deficiency should be evaluated routinely in patients with connective tissue abnormalities, which will enable a better understanding of its role and allow targeted treatment. For example, inhibitors of vagal afferents-baclofen could be beneficial in patients. These hypotheses need confirmation via targeted clinical trials. ABSTRACT Tenascin-X (TNX) is a glycoprotein that regulates tissue structure via anti-adhesive interactions with collagen in the extracellular matrix. TNX deficiency causes a phenotype similar to hypermobility Ehlers-Danlos syndrome involving joint hypermobility, skin hyperelasticity, pain and gastrointestinal dysfunction. Previously, we have shown that TNX is required for neural control of the bowel by a specific subtype of mainly cholinergic enteric neurones and regulates sprouting and sensitivity of nociceptive sensory endings in mouse colon. These findings correlate with symptoms shown by TNX-deficient patients and mice. We aimed to identify whether TNX is similarly present in neural structures found in mouse and human gastric tissue. We then determined whether TNX has a functional role, specifically in gastric motor and sensory function and nodose ganglia neurones. We report that TNX was present in calretinin-immunoreactive extrinsic nerve endings in mouse and human stomach. TNX deficient mice had accelerated gastric emptying and markedly increased vagal afferent responses to gastric distension that could be rescued with GABAB receptor agonist. There were no changes in nodose ganglia excitability in TNX deficient mice, suggesting that vagal afferent responses are probably the result of altered peripheral mechanosensitivity. In TNXB-deficient patients, significantly greater symptoms of reflux, indigestion and abdominal pain were reported. In the present study, we report the first role for TNX in gastric function. Further studies are required in TNX deficient patients to determine whether symptoms can be relieved using GABAB agonists.
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Affiliation(s)
- Rubina Aktar
- Blizard InstituteQueen Mary University of LondonLondonUK
| | - Madusha Peiris
- Blizard InstituteQueen Mary University of LondonLondonUK
| | - Asma Fikree
- Blizard InstituteQueen Mary University of LondonLondonUK
| | - Simon Eaton
- Institute of Child HealthUniversity College LondonLondonUK
| | - Stamatiki Kritas
- South Australian Health and Medical Research InstituteUniversity of AdelaideAustralia
| | - Stephen J. Kentish
- South Australian Health and Medical Research InstituteUniversity of AdelaideAustralia
| | - Eduardo J. A. Araujo
- Blizard InstituteQueen Mary University of LondonLondonUK
- Department of HistologyCentre for Biological SciencesState University of LondrinaBrazil
| | - Cristiano Bacarin
- Department of HistologyCentre for Biological SciencesState University of LondrinaBrazil
| | - Amanda J. Page
- South Australian Health and Medical Research InstituteUniversity of AdelaideAustralia
| | - Nicol C. Voermans
- Department of NeurologyRadboud University Medical CentreNijmegenNetherlands
| | - Qasim Aziz
- Blizard InstituteQueen Mary University of LondonLondonUK
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Cystic Fibrosis and gastroesophageal reflux disease. J Cyst Fibros 2018; 16 Suppl 2:S2-S13. [PMID: 28986024 DOI: 10.1016/j.jcf.2017.07.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Revised: 07/06/2017] [Accepted: 07/06/2017] [Indexed: 12/19/2022]
Abstract
Gastroesophageal reflux is common in children and adults with cystic fibrosis (CF). Pathological gastroesophageal reflux disease (GERD) is also frequent in patients of all ages with CF. This article reviews the pathophysiology, diagnostic work-up, management options, complications, and future directions in the evaluation and management of GERD - unique to and pertinent for - patients with CF in particular.
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Clarke JO, Fernandez-Becker NQ, Regalia KA, Triadafilopoulos G. Baclofen and gastroesophageal reflux disease: seeing the forest through the trees. Clin Transl Gastroenterol 2018; 9:137. [PMID: 29599487 PMCID: PMC5876385 DOI: 10.1038/s41424-018-0010-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 02/06/2018] [Indexed: 12/19/2022] Open
Abstract
Baclofen has been shown to decrease reflux events and increase lower esophageal sphincter pressure, yet has never established a clear role in the treatment of gastroesophageal reflux disease (GERD). Lei and colleagues have shown in a recent elegant study that baclofen reduces the frequency and initiation of secondary peristalsis and heightens esophageal sensitivity to capsaicin-mediated stimulation. These findings may help explain both the benefit of baclofen in conditions such as rumination and supragastric belching, as well as the apparent lack of benefit of baclofen and other GABAB agonists in long-term treatment of GERD.
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Affiliation(s)
- John O Clarke
- Stanford Multidimensional Program for Innovation and Research in the Esophagus (S-MPIRE) Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
| | - Nielsen Q Fernandez-Becker
- Stanford Multidimensional Program for Innovation and Research in the Esophagus (S-MPIRE) Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - Kirsten A Regalia
- Stanford Multidimensional Program for Innovation and Research in the Esophagus (S-MPIRE) Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA
| | - George Triadafilopoulos
- Stanford Multidimensional Program for Innovation and Research in the Esophagus (S-MPIRE) Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, CA, 94305, USA
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Mermelstein J, Chait Mermelstein A, Chait MM. Proton pump inhibitor-refractory gastroesophageal reflux disease: challenges and solutions. Clin Exp Gastroenterol 2018; 11:119-134. [PMID: 29606884 PMCID: PMC5868737 DOI: 10.2147/ceg.s121056] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
A significant percentage of patients with gastroesophageal reflux disease (GERD) will not respond to proton pump inhibitor (PPI) therapy. The causes of PPI-refractory GERD are numerous and diverse, and include adherence, persistent acid, functional disorders, nonacid reflux, and PPI bioavailability. The evaluation should start with a symptom assessment and may progress to imaging, endoscopy, and monitoring of esophageal pH, impedance, and bilirubin. There are a variety of pharmacologic and procedural interventions that should be selected based on the underlying mechanism of PPI failure. Pharmacologic treatments can include antacids, prokinetics, alginates, bile acid binders, reflux inhibitors, and antidepressants. Procedural options include laparoscopic fundoplication and LINX as well as endoscopic procedures, such as transoral incisionless fundoplication and Stretta. Several alternative and complementary treatments of possible benefit also exist.
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Affiliation(s)
- Joseph Mermelstein
- Gasteroenterology and Nutrition Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alanna Chait Mermelstein
- Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maxwell M Chait
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
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Pauwels A, Broers C, Van Houtte B, Rommel N, Vanuytsel T, Tack J. A Randomized Double-Blind, Placebo-Controlled, Cross-Over Study Using Baclofen in the Treatment of Rumination Syndrome. Am J Gastroenterol 2018; 113:97-104. [PMID: 29206813 DOI: 10.1038/ajg.2017.441] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2017] [Accepted: 09/06/2017] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Both rumination syndrome and supra-gastric belching (SGB) have limited treatment options. We demonstrated (open-label) that baclofen reduces pressure flow events in these patients. We aimed to study the effect of baclofen in a placebo-controlled, double-blind, cross-over study in patients with clinically suspected rumination and/or SGB. METHODS Twenty tertiary-care patients (mean age 42 years (range 18-61), 13f) with clinically suspected rumination and/or SGB were randomized to receive baclofen (10 mg, t.i.d) or placebo for 2 weeks with cross-over to the alternative intervention after a 1 week wash-out period. At the end of each treatment period, patients underwent a solid-state high-resolution impedance manometry measurement, during which they registered symptoms. Patients received a solid meal and recordings continued for 1 h. They scored overall treatment evaluation (OTE) on a -3 to +3 scale. RESULTS Both the number of regurgitation event markers and rumination episodes were significantly decreased after baclofen (6 (0-19) vs. 4 (0-14), P=0.04; 13 (8-22) vs. 8 (3-11), P=0.004). The number of SGB episodes was similar in both groups. Lower esophageal sphincter (LES) pressure was significantly higher and the number of transient LES relaxations was significantly lower after baclofen (17.8 (12.7-22.7) vs. 13.1 (7.2-16.9) mm Hg, P=0.0002; 4(1-8) vs. 7(3-12), P=0.17). The number of reflux events decreased in the baclofen condition (4 (1-9) vs. 3 (0-6), P=0.03). Straining episodes were similar in both arms, but the rumination/straining ratio was significantly lower in the baclofen arm (0.06 (0-0.32) vs. 0.33 (0-0.51), P=0.0012). OTE was superior after baclofen compared to placebo (P=0.03). CONCLUSIONS Baclofen is an effective treatment option for patients with rumination syndrome, probably through its effect on LES pressure.
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Affiliation(s)
- Ans Pauwels
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Charlotte Broers
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Brecht Van Houtte
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium
| | - Nathalie Rommel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium.,ExpORL, Department of Neurosciences, Catholic University of Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium.,Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), Catholic University of Leuven, Leuven, Belgium.,Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium
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Iwakiri K. Treatment Strategy for Standard-Dose Proton Pump Inhibitor-Resistant Reflux Esophagitis. J NIPPON MED SCH 2017; 84:209-214. [PMID: 29142181 DOI: 10.1272/jnms.84.209] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Reflux esophagitis is characterized by excessive esophageal acid exposure. To treat reflux esophagitis, it is necessary to reduce excessive esophageal acid exposure to within the normal range. The first-line drug for the treatment of reflux esophagitis is a standard-dose proton-pump inhibitor (PPI), which is also recommended by the Evidence-based Clinical Practice Guidelines 2015 for gastroesophageal disease of the Japanese Society of Gastroenterology. It has been reported that the response to a standard dose of PPI in patients with mild reflux esophagitis is 90-100%, and that in patients with severe reflux esophagitis is 80-85%. However, PPI-resistant reflux esophagitis has been increasing. When the standard dose of PPI is not effective, modification of the lifestyle with PPI therapy, switching to another PPI, or a change in the administration method (before meals), as well as double-dose PPI (in divided doses), may be effective. In addition, vonoprazan (potassium-competitive acid blocker), which has rapid and potent acid-suppressive effects, became available in February 2015 in Japan. In the clinical trial data, vonoprazan is very effective for reflux esophagitis. However, clinical data on vonoprazan are still insufficient. The establishment of a new treatment for reflux esophagitis taking advantage of the rapid and potent acid-suppressive effects is awaited.
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Affiliation(s)
- Katsuhiko Iwakiri
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine
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29
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Kim S, Koh H, Lee JS. Gastroesophageal Reflux in Neurologically Impaired Children: What Are the Risk Factors? Gut Liver 2017; 11:232-236. [PMID: 27840365 PMCID: PMC5347647 DOI: 10.5009/gnl16150] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 05/13/2016] [Accepted: 06/14/2016] [Indexed: 12/16/2022] Open
Abstract
Background/Aims Neurologically impaired patients frequently suffer from gastrointestinal tract problems, such as gastroesophageal reflux disease (GERD). In this study, we aimed to define the risk factors for GERD in neurologically impaired children. Methods From May 2006 to March 2014, 101 neurologically impaired children who received 24-hour esophageal pH monitoring at Severance Children’s Hospital were enrolled in the study. The esophageal pH finding and the clinical characteristics of the patients were analyzed. Results The reflux index was higher in patients with abnormal electroencephalography (EEG) results than in those with normal EEG results (p=0.027). Mitochondrial disease was associated with a higher reflux index than were epileptic disorders or cerebral palsy (p=0.009). Patient gender, feeding method, scoliosis, tracheostomy, and baclofen use did not lead to statistical differences in reflux index. Age of onset of neurological impairment was inversely correlated with DeMeester score and reflux index. Age at the time of examination, the duration of the disease, and the number of antiepileptic drugs were not correlated with GER severity. Conclusions Early-onset neurological impairment, abnormal EEG results, and mitochondrial disease are risk factors for severe GERD.
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Affiliation(s)
- Seung Kim
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hong Koh
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Joon Soo Lee
- Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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Influence of GABA-B Agonist Baclofen on Capsaicin-Induced Excitation of Secondary Peristalsis in Humans. Clin Transl Gastroenterol 2017; 8:e120. [PMID: 28981081 PMCID: PMC5666117 DOI: 10.1038/ctg.2017.46] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Accepted: 08/15/2017] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVES Esophageal instillation of capsaicin enhances secondary peristalsis, but the γ-aminobutyric acid receptor type B (GABA-B) agonist baclofen inhibits secondary peristalsis. This study aimed to investigate whether baclofen could influence heartburn perception and secondary peristalsis subsequent to capsaicin infusion in healthy adults. METHODS Secondary peristalsis was performed by slow and rapid mid-esophagus air injections in 15 healthy subjects. Two different sessions including esophageal infusion of capsaicin-containing red pepper sauce (0.84 mg) following pre-treatment with placebo or baclofen were randomly performed to test the effects on heartburn perception and secondary peristalsis. RESULTS The intensity of heartburn symptom subsequent to capsaicin infusion was significantly greater after pre-treatment of baclofen as compared with the placebo (P=0.03). Baclofen significantly increased the threshold volume of secondary peristalsis to slow air injections subsequent to esophageal capsaicin infusion (P<0.001). Baclofen significantly increased the threshold volume of secondary peristalsis to rapid air injections subsequent to esophageal capsaicin infusion (P<0.01). The frequency of secondary peristalsis subsequent to capsaicin infusion was significantly decreased with baclofen as compared with the placebo (P<0.002). Baclofen had no effect on any of the peristaltic parameters of secondary peristalsis subsequent to capsaicin infusion. CONCLUSIONS The GABA-B agonist baclofen appears to attenuate the esophagus to capsaicin-induced excitation of secondary peristalsis in healthy adults. Our study suggests the inhibitory modulation for GABA-B receptors on capsaicin-sensitive afferents mediating secondary peristalsis in human esophagus.
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Rouzade-Dominguez ML, Pezous N, David OJ, Tutuian R, Bruley des Varannes S, Tack J, Malfertheiner P, Allescher HD, Ufer M, Rühl A. The selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056) reduces the incidence of reflux episodes in dogs and patients with moderate to severe gastroesophageal reflux disease. Neurogastroenterol Motil 2017; 29. [PMID: 28337838 DOI: 10.1111/nmo.13058] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2016] [Accepted: 02/07/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Transient lower esophageal sphincter relaxations (TLESRs) induced by gastric distension are modulated by the metabotropic glutamate receptor 5 (mGluR5) that influences the vagal reflex loop. We therefore aimed to examine the effects of the selective mGluR5 antagonist mavoglurant (AFQ056) on the number of TLESRs in dogs and reflux episodes in patients with gastroesophageal reflux disease (GERD). METHODS In a dog model, the number of meal-induced TLESRs was determined after intravenous (0.03, 0.1, 0.3, and 1 mg kg-1 ) and oral (1, 3, and 10 mg kg-1 ) doses of mavoglurant with reference to vehicle. In a multicenter, randomized, double-blind, placebo-controlled, three-period crossover study, the incidence of meal-induced reflux episodes was assessed by esophageal impedance monitoring after single, oral doses of mavoglurant (50 and 400 mg) or baclofen (40 mg) in 30 patients with moderate to severe GERD. KEY RESULTS In dogs, mavoglurant reduced the number of TLESRs after intravenous and oral administration. In patients with GERD, the incidence of postprandial reflux episodes was significantly lower at a dose of 400 mg mavoglurant (-37.5% ; 90% confidence interval [CI]: -57.8, -17.2), whereas there was no significant difference at 50 mg of mavoglurant compared to placebo. A significantly lower incidence of reflux episodes was also noted with the active comparator baclofen (-50.3%; 90% CI: -66.2, -34.3), thereby validating this study. CONCLUSIONS AND INFERENCES These data suggest a potential clinical benefit of mGluR5 antagonists such as mavoglurant in patients with GERD, particularly in those with persisting symptoms despite treatment with proton pump inhibitors.
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Affiliation(s)
| | - N Pezous
- Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
| | - O J David
- Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
| | - R Tutuian
- Universitätsspital Zürich, Zürich, Switzerland
| | | | - J Tack
- University Hospitals Leuven, Leuven, Belgium
| | | | - H-D Allescher
- Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Germany
| | - M Ufer
- Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
| | - A Rühl
- Novartis Institutes for Biomedical Research, Novartis Pharma AG, Basel, Switzerland
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Scarpellini E, Pauwels A, Vos R, Rommel N, Tack J. Effect of methylnaltrexone and naloxone on esophageal motor function in man. Neurogastroenterol Motil 2017; 29. [PMID: 28110513 DOI: 10.1111/nmo.12938] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2016] [Accepted: 08/08/2016] [Indexed: 02/08/2023]
Abstract
BACKGROUND Endogenous opioids (EO) acting on μ-opiod receptors in central and enteric nervous system (ENS) control gastrointestinal motility but it is still unclear whether EO in ENS may control esophageal function in man, thus we will study the effects of methylnaltrexone (MNTX), a peripherally selective, and naloxone (NA), a non-selective μ-opiod receptor antagonist, on esophageal motility in healthy subjects. METHODS Fifteen HV (6 M; 34.1 ± 0.6 years; BMI: 22.1 ± 0.1 kg/m2 ) underwent three esophageal high-resolution manometry impedance (HRiM) studies with 10 saline swallows administered every 30 minutes: drug was administered after 30 minutes (MNTX subcutaneously/NA or saline intravenously), a solid meal after 90 minutes; measurements continued for 120 minutes postprandially. KEY RESULTS Methylnaltrexone did not significantly decrease the upper esophageal sphincter (UES) percentage of relaxation preprandially (72.5 ± 5 vs 66.9 ± 4.6 and 73 ± 3.8%, ANOVA between placebo, MNTX and NA, P=NS) and postprandially (60 minutes: 68.2 ± 5.6 vs 61 ± 5.5 and 67.1 ± 5.6%; 120 minutes: 68 ± 5.9 vs 59.3 ± 5.2 and 67.7 ± 4.7%; ANOVA between placebo, MNTX and NA, P=NS). MNTX and NA did not significantly alter preprandial and postprandial LES resting pressures and integrated relaxation pressure (ANOVA between placebo, MNTX and NA, all P=NS). Peak front velocity and distal contractile integral were not altered pre- and postprandially by MNTX and NA (ANOVA between placebo, MNTX and NA, P=NS). Transient lower esophageal sphincter relaxations (TLESRs') number was not altered by MNTX and NA (ANOVA between placebo, MNTX and NA, all P=NS). CONCLUSIONS AND INFERENCES The peripheral selective and non-selective μ-opioid receptor antagonists MNTX and NA, respectively, do not alter TLESRs occurrence and esophageal peristalsis.
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Affiliation(s)
- E Scarpellini
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - A Pauwels
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - R Vos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - N Rommel
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - J Tack
- Division of Gastroenterology, Department of Internal Medicine, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
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Lo WK, Mashimo H. Medical Management of GERD: Algorithms and Outcomes. FAILED ANTI-REFLUX THERAPY 2017:19-23. [DOI: 10.1007/978-3-319-46885-3_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abangah G, Rahmani A, Hafezi-Ahmadi MR, Emami T, Asadollahi K, Jaafari-Haidarlo A, Moradkhani A. Precancerous histopathologic lesions of upper gastrointestinal tract among dyspeptic patients upon endoscopic evaluations. J Gastrointest Cancer 2016; 47:1-7. [PMID: 26454647 DOI: 10.1007/s12029-015-9760-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
PURPOSE Gastric cancer is one of the most important causes of morbidity and mortality worldwide which is influenced by different risk factors. This study aimed to investigate the effects of various factors associated with precancerous lesions among dyspeptic patients. METHODS Among dyspeptic patients admitted to gastrointestinal clinics in Ilam city, west of Iran, 1123 were investigated during 2008 to 2011. All patients were evaluated by endoscopy and their biopsy samples were examined for histological differentiations and their pathology reports were classified according to Sydney criteria. RESULTS One thousand out of 1123 admitted dyspeptic patients were finally analyzed. The mean age of participants was 48 years (ranged 21-84 years), and 64.8% of patients were male. The frequency of patients with atrophy, metaplasia, or both was 14.4%, adenocarcinoma 1.2%, and polyp hyperplasia 0.7%, respectively. The highest frequency was related to those with chronic gastritis accompanied by Helicobacter pylori infection with a figure of 80.8%. The frequency of precancerous lesions among smokers compared to non-smokers was higher significantly (p < 0.03). Though non-significant, BMI was associated with the higher risk of premalignant lesions among dyspeptic patients by an increasing manner. CONCLUSION Chronic gastritis accompanied with H. pylori infection was revealed as the most prevalent variable among dyspeptic patients. Also, higher BMI compared to normal and smokers compared to non-smokers were more involved by precancerous lesions.
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Affiliation(s)
- Ghobad Abangah
- Department of Gastroenterology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Asghar Rahmani
- Student Researches Committee, Ilam University of Medical Sciences, Ilam, Iran
| | | | - Tayebeh Emami
- Student Researches Committee, Ilam University of Medical Sciences, Ilam, Iran
| | - Khairollah Asadollahi
- Department of Social Medicine, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
| | - Ali Jaafari-Haidarlo
- Department of Gastroenterology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | - Atefeh Moradkhani
- Student Researches Committee, Ilam University of Medical Sciences, Ilam, Iran
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Kalinichev M, Girard F, Haddouk H, Rouillier M, Riguet E, Royer-Urios I, Mutel V, Lütjens R, Poli S. The drug candidate, ADX71441, is a novel, potent and selective positive allosteric modulator of the GABA B receptor with a potential for treatment of anxiety, pain and spasticity. Neuropharmacology 2016; 114:34-47. [PMID: 27889489 DOI: 10.1016/j.neuropharm.2016.11.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Revised: 11/13/2016] [Accepted: 11/21/2016] [Indexed: 11/17/2022]
Abstract
Positive allosteric modulation of the GABAB receptor is a promising alternative to direct activation of the receptor as a therapeutic approach for treatment of addiction, chronic pain, anxiety, epilepsy, autism, Fragile X syndrome, and psychosis. Here we describe in vitro and in vivo characterization of a novel, potent and selective GABAB positive allosteric modulator (PAM) N-(5-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)-2-fluorophenyl)acetamide (ADX71441). In vitro, Schild plot and reversibility tests at the target confirmed PAM properties of the compound. In mice and rats ADX71441 is bioavailable after oral administration and is brain penetrant. A single dose of ADX71441 had an anxiolytic-like profile in the mouse marble burying test (minimum effective dose; MED 3 mg/kg) as well as in the elevated plus maze test in mice and rats (both MED 3 mg/kg). Also, in mice, acute administration of ADX71441 reduced visceral pain-associated behaviors in the acetic acid-induced writhing test. ADX71441 dose-dependently reduced time on rotarod in rats (MED 10 mg/kg) indicative of muscle-relaxant qualities. ADX71441 reduced locomotor activity in mice (10 mg/kg) and rats (3 mg/kg) after single dose; however, following sub-chronic administration in mice, 30 mg/kg ADX71441 was associated with normal locomotor activity. While acute administration of ADX71441 reduced body temperature in rats and mice (both MED 10 mg/kg), the effect in the former was transient, rapidly returning to normal levels despite high concentrations of the compound remaining in plasma. Thus, the GABAB PAM ADX71441 represents a valid therapeutic approach for development of novel treatment of anxiety, pain and spasticity.
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Affiliation(s)
- Mikhail Kalinichev
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland.
| | - Françoise Girard
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | - Hasnaà Haddouk
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | - Mélanie Rouillier
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | - Eric Riguet
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | | | - Vincent Mutel
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | - Robert Lütjens
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
| | - Sonia Poli
- Addex Therapeutics SA, Chemin des Mines 9, CH-1202, Geneva, Switzerland
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Scarpellini E, Boecxstaens V, Broers C, Vos R, Pauwels A, Tack J. Effect of baclofen on gastric acid pocket in subjects with gastroesophageal reflux disease symptoms. Dis Esophagus 2016; 29:1054-1063. [PMID: 26541138 DOI: 10.1111/dote.12443] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Postprandial gastroesophageal reflux (PGER) in the distal esophagus (DE) is associated with a gastric juice 'acid pocket' (AP). Baclofen reduces AP extension into the DE in healthy volunteers, in part through increased lower esophageal sphincter (LES) pressure. We aimed to verify whether baclofen also affects postprandial AP location and extent in gastroesophageal reflux disease (GERD) patients. Thirteen treatment-naive heartburn-prevalent GERD patients underwent two AP studies, after pretreatment with baclofen 40 mg or placebo 30 minutes preprandially. We performed pH-probe stepwise pull-throughs (PT) (1 cm/min, LES -10 to +5 cm) before and every 30 minutes from 30 minutes before up to 150 minutes after a test meal. After the meal, both after placebo and baclofen, gastric pH significantly dropped at 30, 60, 90 minutes postprandially (P: nadir pHs of 3.9 ± 0.6, 2.3 ± 0.6, 2.1 ± 0.4; B: nadir pHs of 2.5 ± 0.4, 2.8 ± 0.4, 2.5 ± 0.3; all P < 0.05). After placebo, LES pressure decreased at 60, 90 and 120 minutes postprandially (32.7 ± 6.1 vs. 24.5 ± 3.1, 27.3 ± 5.9, 27.3 ± 6.0 mmHg; analysis of variance [ANOVA], P = 0.037), but this was prevented by baclofen (25.4 ± 3.4 vs. 29.4 ± 2, 32.2 ± 1.4, 35.5 ± 1.7 mmHg, ANOVA, P = not significant (NS)). Baclofen did not significantly decrease the postprandial AP extent above the LES but prevented the postprandial increase in transient lower esophageal sphincter relaxations (TLESRs) (preprandial vs. postprandial, placebo: 1.1 ± 0.3 vs. 3.7 ± 0.7, P < 0.05; baclofen: 1.4 ± 0.4 vs. 2 ± 0.5, P = NS). In GERD patients, baclofen significantly increases postprandial LES pressure, prevents the increase TLESRs but, unlike in healthy volunteers, does not affect AP extension into the DE.
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Affiliation(s)
- E Scarpellini
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
| | - V Boecxstaens
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
| | - C Broers
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
| | - R Vos
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
| | - A Pauwels
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
| | - J Tack
- TARGID (Translational Research Centre for Gastrointestinal Disorders), University of Leuven, Leuven, Belgium
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Abdel Jalil AA, Castell DO. Ineffective Esophageal Motility (IEM): the Old-New Frontier in Esophagology. Curr Gastroenterol Rep 2016; 18:1. [PMID: 26685862 DOI: 10.1007/s11894-015-0472-y] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Ineffective esophageal motility (IEM) is characterized by distal esophageal contraction amplitude of <30 mmHg on conventional manometry (Blonski et al. Am J Gastroenterol. 103(3):699-704, 2008), or a distal contractile integral (DCI) < 450 mmHg*s*cm on high-resolution manometry (HRM) (Kahrilas et al. Neurogastroenterol Motil. 27(2):160-74, 2015) in≥50 % of test swallows. IEM is the most common abnormality on esophageal manometry, with an estimated prevalence of 20-30 % (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004; Conchillo et al. Am J Gastroenterol. 100(12):2624-32, 2005). Non-obstructive dysphagia has been considered to be frequently associated with severe esophageal peristaltic dysfunction. Defective bolus transit (DBT) on multichannel intraluminal impedance testing was found in more than half of IEM patients who presented with dysphagia (Tutuian and Castell Am J Gastroenterol. 99(6):1011-9, 2004), highlighting the functional defect of this manometric finding. Treatment of IEM has been challenging because of lack of promotility agents that have a definite effect on esophageal function.
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Affiliation(s)
- Ala' A Abdel Jalil
- Division of Gastroenterology & Hepatology, University of Missouri-Columbia, One Hospital Dr., CE 405, Columbia, MO, 65212, USA.
| | - Donald O Castell
- Esophageal Disorders Program, Gastroenterology & Hepatology Division, Medical University of South Carolina (MUSC), 114 Doughty St. Suite 249, MSC 702, Charleston, SC, 29425, USA.
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Gastroesophageal reflux disease-related and functional heartburn: pathophysiology and treatment. Curr Opin Gastroenterol 2016; 32:344-52. [PMID: 27206157 DOI: 10.1097/mog.0000000000000282] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn. RECENT FINDINGS The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease. SUMMARY New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.
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Abstract
PURPOSE OF REVIEW Supragastric belching has recently gained recognition as a belching disorder of behavioral origin that can be accurately diagnosed on esophageal impedance monitoring. Its contribution to numerous other gastrointestinal disorders is beginning to be appreciated. Improved knowledge of its pathophysiology has enabled identification of therapeutic goals, some of which have been subject to formal study and demonstrated good outcomes. This review sets out to present and discuss new findings related to the improved understanding of the relationship between supragastric belching and other gastrointestinal disorders, as well as fresh concepts in terms of management. RECENT FINDINGS Supragastric belching is now shown to be associated with globus, as well as reflux symptoms in proton pump inhibitor nonresponders. Patients with supragastric belching experience higher frequency of belching events if they have concurrent esophageal hypomotility. Gum chewing and sleeve gastrectomy have no impact on supragastric belching. Pediatric studies suggest an overlap with aerophagia that is not observed in adults. Successful treatments trialed recently include psychoeducation and behavioral therapy delivered by a health psychologist with expertise in gastroenterology. SUMMARY With the foreseeable increase in recognition and diagnosis of pathological supragastric belching, there is a clear need to better understand its pathophysiology, especially in terms of its emerging importance in relation to other gastrointestinal disorders. Further study is justified to uncover additional therapeutic options for this benign but disabling condition.
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Scarpellini E, Ang D, Pauwels A, De Santis A, Vanuytsel T, Tack J. Management of refractory typical GERD symptoms. Nat Rev Gastroenterol Hepatol 2016; 13:281-94. [PMID: 27075264 DOI: 10.1038/nrgastro.2016.50] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The management of patients with refractory GERD (rGERD) is a major clinical challenge for gastroenterologists. In up to 30% of patients with typical GERD symptoms (heartburn and/or regurgitation), acid-suppressive therapy does not provide clinical benefit. In this Review, we discuss the current management algorithm for GERD and the features and management of patients who do not respond to treatment (such as those individuals with an incorrect diagnosis of GERD, inadequate PPI intake, persisting acid reflux and persisting weakly acidic reflux). Symptom response to existing surgical techniques, novel antireflux procedures, and the value of add-on medical therapies (including prokinetics and reflux inhibitors) for rGERD symptoms are discussed. Pharmaceutical agents targeting oesophageal sensitivity, a condition that can contribute to symptom generation in rGERD, are also discussed. Finally, on the basis of available published data and our expert opinion, we present an outline of a current, usable algorithm for management of patients with rGERD that considers the timing and diagnostic use of pH-impedance monitoring on or off PPI, additional diagnostic tests, the clinical use of baclofen and the use of add-on neuromodulators (tricyclic agents and selective serotonin reuptake inhibitors).
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Affiliation(s)
- Emidio Scarpellini
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.,Division Gastroenterology, Sapienza University of Rome, Viale del Policlinico 155, 00100, Rome, Italy
| | - Daphne Ang
- Division of Gastroenterology, Changi General Hospital, 2 Simei Street 3, Singapore 529889
| | - Ans Pauwels
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
| | - Adriano De Santis
- Division of Gastroenterology, Changi General Hospital, 2 Simei Street 3, Singapore 529889
| | - Tim Vanuytsel
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
| | - Jan Tack
- Translational Research in Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
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Kim JH, Kim BJ, Kim SW, Kim SE, Kim YS, Sung HY, Oh TH, Jeong ID, Park MI. [Current issues on gastroesophageal reflux disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2016; 64:127-32. [PMID: 25252860 DOI: 10.4166/kjg.2014.64.3.127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Gastroesophageal reflux disease (GERD) is one of the most common problems in gastrointestinal disorders. With the increase in our understanding on the pathophysiology of GERD along with the development of proton pump inhibitors, the diagnostic and therapeutic approaches to GERD have changed dramatically over the past decade. However, GERD still poses a problem to many clinicians since the spectrum of the disease has evolved to encompass more challenging presentations such as refractory GERD and extraesophageal manifestations. This has led to significant confusion regarding the optimal approach to these patients. This article aims to discuss current issues on GERD.
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Affiliation(s)
- Jie-Hyun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Seoul, Korea
| | - Beom Jin Kim
- Chung-Ang University College of Medicine, Seoul, Korea
| | - Sang Wook Kim
- Chonbuk National University Medical School, Jeonju, Korea
| | - Sung Eun Kim
- Kosin University College of Medicine, Busan, Korea
| | - Yeon Soo Kim
- Hallym University College of Medicine, Chuncheon, Korea
| | | | - Tae-Hoon Oh
- Inje University College of Medicine, Seoul, Korea
| | - In Du Jeong
- University of Ulsan College of Medicine, Ulsan, Korea
| | - Moo In Park
- Kosin University College of Medicine, Busan, Korea
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Clinical Outcome of Eradication Therapy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma according to H. pylori Infection Status. Gastroenterol Res Pract 2016; 2016:6794848. [PMID: 27034656 PMCID: PMC4789472 DOI: 10.1155/2016/6794848] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 02/07/2016] [Indexed: 12/21/2022] Open
Abstract
Background. To evaluate the long-term outcome of H. pylori eradication therapy for gastric MALT lymphoma according to the presence of H. pylori infection. Methods. We retrospectively reviewed the medical records of patients between January 2001 and June 2014. The clinicopathologic characteristics and clinical outcomes were compared between H. pylori-positive and H. pylori-negative gastric MALT lymphoma groups. Results. Fifty-four patients were enrolled: 12 H. pylori-negative and 42 H. pylori-positive patients. The tumor was located more frequently in both the proximal and distal parts of the stomach (P = 0.001), and the percentage of multiple lesions was significantly greater in the H. pylori-negative group (P = 0.046). Forty-seven patients received initial eradication therapy, and 85% (35/41) of H. pylori-positive patients and 50% (3/6) of H. pylori-negative patients achieved complete remission after eradication therapy. The presence of multiple lesions was a predictive factor for unresponsiveness to H. pylori eradication (P = 0.024). The efficacy of eradication therapy (P = 0.133), complete remission (CR) maintenance period, and relapse after eradication therapy were not significantly different between the two groups. Conclusions. H. pylori eradication therapy could be an effective first-line treatment for localized H. pylori-negative gastric MALT lymphoma, especially for single lesions.
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Xu X, Yu L, Chen Q, Lv H, Qiu Z. Diagnosis and treatment of patients with nonacid gastroesophageal reflux-induced chronic cough. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2016; 20:885-92. [PMID: 26759577 PMCID: PMC4696375 DOI: 10.4103/1735-1995.170625] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Gastroesophageal reflux (GER) is one of the most common causes of chronic cough, and chronic cough due to GER represents a subtype of GER-related diseases. Gastroesophageal reflux-induced chronic cough (GERC) can be divided into two subgroups based on the pH of the GER. Nonacid GERC is less common than acid GERC, and its diagnosis and treatment strategy have not been standardized. However, nonacid GERC usually presents with its unique set of characteristics and features upon diagnosis and treatment in the clinic. Although the underlying molecular mechanism of nonacid GERC is not fully understood, it is considered to be associated with reflux theory, reflex theory and airway hypersensitivity. Multi-channel intraluminal impedance combined with pH monitoring is a promising new technique that can detect both acid and nonacid reflux, and our findings as well as those of others have shown its usefulness in diagnosing nonacid GERC. Development of new diagnostic techniques has led to an increased rate of nonacid GERC diagnosis. We summarize our experience in the diagnosis and treatment of nonacid GERC and provide a guide for future therapeutic approaches.
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Affiliation(s)
- Xianghuai Xu
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Li Yu
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Qiang Chen
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Hanjing Lv
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zhongmin Qiu
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
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45
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Mandaliya R, DiMarino AJ, Cohen S. Survey of findings in patients having persistent heartburn on proton pump inhibitor therapy. Dis Esophagus 2016; 29:27-33. [PMID: 25294046 DOI: 10.1111/dote.12293] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
In patients with refractory heartburn while on proton pump inhibitor (PPI) therapy, changing drugs or increasing treatment to a twice a day (b.i.d.) dose has become a common practice. This study aims to study patients with persistent heartburn while on PPI therapy and to determine if persistent symptom indicates the need for more aggressive or different therapy. A retrospective review of impedance-pH tracings on PPI therapy (q.d. or b.i.d.) for patients with persistent heartburn was performed. DeMeester score, impedance, and symptom sensitive index (SSI) were used as indices. Statistical analyses were performed using chi-squared test with Yates correction and paired t-test. One hundred consecutive patients, (female 50%, male 50%, mean age 54 [range 16-83] years) were studied on q.d. (n = 45) or b.i.d. PPI (n = 55). Only 20% of the patients had abnormal DeMeester score; 41% had an abnormal impedance score and 56% had abnormal SSI; 29% had all indices normal. There was no difference between patients taking q.d. versus b.i.d. PPI for abnormal DeMeester score (22 vs. 18%), impedance (38 vs. 44%) and SSI (53 vs. 58%); P = 0.80, 0.69, and 0.77, respectively. In 56 patients with positive SSI, symptoms were due to acid reflux in 8 (14%) patients, nonacid reflux in 31 (55%) patients, and combined acid and nonacid reflux in 17 (30%) patients. Patients with persistent heartburn on PPI therapy show a variety of disorders: (i) acid reflux (20%); (ii) nonacid reflux (26%); (iii) positive SSI (56%); (iv) all normal indices (29%). These studies indicate that persistent heartburn on PPI therapy is a complex problem that may not respond to simply increasing acid inhibition.
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Affiliation(s)
- R Mandaliya
- Division of Internal Medicine, Abington Memorial Hospital, Abington, Pennsylvania, USA
| | - A J DiMarino
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
| | - S Cohen
- Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, USA
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Warren RL, Davis SM. The Role of Baclofen in the Treatment of Gastroesophageal Reflux Disease. J Pharm Technol 2015; 31:258-261. [PMID: 34860946 PMCID: PMC5990199 DOI: 10.1177/8755122515586835] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/09/2023] Open
Abstract
Objective. To describe the evidence for baclofen in the treatment of gastroesophageal reflux disease (GERD). Data Sources. A search of PubMed and Google Scholar was performed using the terms baclofen, gastroesophageal reflux disease, and treatment. Study Selection and Data Extraction. Publications were reviewed manually for relevance, and studies that addressed the use of baclofen in the treatment of adult symptomatic GERD patients were included. Data Synthesis. Nine studies were evaluated. Baclofen was shown to significantly reduce transient lower esophageal sphincter relaxations (TLESRs), postprandial acid reflux events, and median number of acid-related symptoms in 6 studies evaluating either a single dose of baclofen or short courses of 2 days or less. Three studies followed patients over a slightly longer period of time. These studies confirmed the results of the shorter trials by finding a decrease in supine duodenal reflux episodes, decreased periods when the pH was less than 4, and improvements in symptom scores in patients refractory to proton pump inhibitors. Side effects most frequently reported included drowsiness and dizziness. Conclusions. Baclofen can be considered for the treatment of refractory GERD following diagnostic evaluation. It has been shown to reduce TLESRs, reflux episodes, and reflux-related symptoms with minimal side effects in short-term trials. Future studies demonstrating the long-term efficacy and tolerability of baclofen in the treatment of GERD would help solidify its place in therapy.
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Affiliation(s)
| | - Steven M. Davis
- Campbell University College of Pharmacy
and Health Sciences, Buies Creek, NC, USA
- Wake Forest Baptist Medical Center,
Winston Salem, NC, USA
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Refractory chronic cough due to gastroesophageal reflux: Definition, mechanism and management. World J Methodol 2015; 5:149-56. [PMID: 26413488 PMCID: PMC4572028 DOI: 10.5662/wjm.v5.i3.149] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 07/06/2015] [Accepted: 07/11/2015] [Indexed: 02/06/2023] Open
Abstract
Refractory chronic cough due to gastroesophageal reflux is a troublesome condition unresponsive to the standard medical anti-reflux therapy. Its underlying mechanisms may include incomplete acid suppression, non-acid reflux, transient lower esophageal sphincter relaxations and esophageal hypersensitivity. The diagnosis of this disorder depends on both the findings of multi-channel intraluminal impedance-pH monitoring and the subsequent intensified anti-reflux therapy. The strategies of pharmacological treatment for refractory chronic cough due to reflux include the optimization of proton pump inhibitors and add-on therapies with histamine H2 receptor antagonists, baclofen and gabapentin. However, the further study is needed to satisfy its management.
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Scarpellini E, Boecxstaens V, Farré R, Bisschops R, Dewulf D, Gasbarrini A, Pauwels A, Blondeau K, Tack J. Effect of baclofen on the acid pocket at the gastroesophageal junction. Dis Esophagus 2015; 28:488-95. [PMID: 24758736 DOI: 10.1111/dote.12224] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Previous studies established that a pocket of highly acidic gastric juice is present postprandially at the gastroesophageal junction in man. The GABA-B agonist baclofen inhibits postprandial reflux events through its effects on the lower esophageal sphincter (LES). The aim of the current study was to investigate whether baclofen would affect the location and the extent of the postprandial acid pocket in healthy volunteers. Twelve healthy volunteers underwent acid pocket studies on two different occasions, at least 1 week apart. LES position was determined preprandially with pull-through manometry. Dual pH electrode and manometry probe stepwise pull-through (1 cm/minute, LES-10 to +5 cm) was performed at 30-minute intervals for 150 minutes, with administration of placebo or baclofen 40 mg after the first and ingestion of a liquid meal after the second pull-through. After placebo, a significant drop in intragastric gastric pH was present at the gastroesophageal junction after the meal, reflecting the acid pocket, and this was associated with a drop in LES pressure. Baclofen did not affect the presence of the acid pocket, but prevented the postprandial drop in LES pressure, and the extent of the acid pocket above the upper margin of the manometrically located LES was significantly decreased by baclofen (1.6 ± 0.7 vs. 0.3 ± 0.4 cm at 60 minutes, 2.2 ± 0.6 vs. 0.2 ± 0.6 at 90 minutes, and 1.5 ± 0.5 vs. 0.7 ± 0.7 cm at 120 minutes, all P < 0.05). Baclofen does not alter the intragastric acid pocket, but limits its extension into the distal esophagus, probably through an increase in postprandial LES pressure.
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Affiliation(s)
- E Scarpellini
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - V Boecxstaens
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - R Farré
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - R Bisschops
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - D Dewulf
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - A Gasbarrini
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - A Pauwels
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - K Blondeau
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
| | - J Tack
- Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium
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Abstract
Rumination is a normal and common phenomenon among ruminant animals; but in humans, it is always regarded as symptom indicative of abnormal function of the upper gastrointestinal tract, and understanding of the mechanisms explaining this event are still evolving. Learning-based theories, organic factors such as gastroesophageal reflux disease and psychological disturbances (eg, depression, anxiety) and the role of life stresses have been postulated as potential mechanisms of rumination. In this review, we take the approach that rumination syndrome is a distinct and discrete functional gastroduodenal disorder. We review current concepts of the pathophysiology of this entity and diagnostic approaches, then detail the treatment paradigms that have been pursued in rumination syndrome in adults. Patients with rumination syndrome have a very distinct set of symptoms. It was focused on the immediate postprandial period, but recently, there is an awareness of an expanding spectrum of the clinical presentation. This includes the concept of "conditioned vomiting" occurring in the setting of delayed gastric emptying (gastroparesis). Physicians' awareness of rumination syndrome is essential in the diagnosis and management of this disorder. Stress and psychological aspects in rumination syndrome are invariably in the background and have to be addressed. The crucial steps in the treatment strategy for rumination syndrome rely on reassurance, education and a physiologic explanation to the patient and family that this is not a "disease," followed by behavioral and relaxation programs and addressing stress factors.
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50
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Affiliation(s)
- Prateek Sharma
- Veterans Affairs Medical Center, University of Kansas School of Medicine, Kansas City, Missouri.
| | - Philip Katz
- Albert Einstein Medical Center, Philadelphia, Pennsylvania
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