Functional gastrointestinal disorders (FGID) and gastroesophageal reflux (GERD) disease affect a large global population and incur substantial health care costs. Impairment in gut-brain communication is one of the main causes of these disorders. The central nervous system (CNS) provides its inputs to the enteric nervous system (ENS) by modulating the autonomic nervous system (ANS) to control the gastrointestinal functions. Therefore, GERD and FGID's might be associated with autonomic dysfunction, which can be identified via heart rate variability (HRV). FGIDs may be treated by restoring the autonomic dysfunction via neuromodulation. This article reviews the roles of HRV in the assessment of autonomic function and dysfunction in (i) gastroesophageal reflux (GERD), and the following FGIDs: (ii) functional dyspepsia (FD) and gastroparesis, (iii) irritable bowel syndrome (IBS) and (iv) constipation. The roles of HRV in the assessment of autonomic responses to various interventions were also reviewed. We used PUBMED, Web of Science, Elsevier/Science direct and Scopus to search the eligible studies for each disorder, which also included the keyword 'heart rate variability'. The retrieved studies were screened and filtered to identify the most suitable studies using HRV parameters to associate the autonomic function with any of the above disorders. Studies involving both human and animal models were included. Based on analyses of HRV, GERD as well as the FGIDs were found to be associated with decreased parasympathetic activity and increased sympathetic nervous system activity with the autonomic balance shifted towards the sympathetic nervous system. In addition, the HRV methods were also reported to be able to assess the autonomic responses to various interventions (mostly neuromodulation), typically the enhancement of parasympathetic activity. In summary, GERD and FGIDs are associated with impaired autonomic dysfunction, mainly due to suppressed vagal and overactive sympathetic tone, which can be assessed noninvasively using HRV.

Background: Patients with end-stage renal disease (ESRD) complain of many gastrointestinal (GI) problems. The goal of the current study was to compare the prevalence of GI disorders in a relatively large group of patients with ESRD with healthy participants. Methods: In a matched case-control study, 597 patients undergoing hemodialysis and 740 healthy participants were investigated. All subjects were asked to complete Rome III questionnaire, including five modules to evaluate GI disorders. The Hospital Anxiety and Depression questionnaire, as well as the 12-general health questionnaire for psychological disorders assessment, were used. Results: Our results showed that in patients undergoing hemodialysis, the prevalence of irritable bowel syndrome (IBS) (OR=1.75), gastroesophageal reflux disease (GERD) (OR=1.55), and dyspepsia (OR=3.39) was significantly higher than in healthy control participants, while no significant difference was found in terms of constipation (OR=0.88). The association remained significant for dyspepsia and IBS even after controlling for psychological disorders as important potential confounding variables. On the other hand, adjustment for psychological disorders led to an insignificant association between hemodialysis and GERD. Surprisingly a significant relationship was observed between constipation and hemodialysis after adjustment for mentioned psychological factors. Conclusion: Our results showed that there was a significant relationship between hemodialysis and some GI complaints such as IBS, dyspepsia, GERD, and bloating. Psychological disorders only influence GERD prevalence in patients undergoing hemodialysis.

Reflux hypersensitivity (RH) is one of the phenotypes of gastroesophageal reflux disease. The latest Rome IV defines RH as a condition with typical reflux symptoms and positive reflux-symptom association despite normal acid exposure. Subsequently, the Lyon consensus proposed detailed cutoff values for the criteria on the basis of experts' consensus. Rome IV brought a clear-cut perspective into the pathophysiology of gastroesophageal reflux disease and the importance of esophageal hypersensitivity. This perspective can be supported by the fact that other functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia often overlap with RH. Although several possible pathophysiological mechanisms of esophageal hypersensitivity have been identified, there is still unmet medical needs in terms of treatment for this condition. This review summarizes the current knowledge regarding RH.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Barium studies are essential to the diagnostic work-up, especially in dysphagia, heartburn (dyspepsia), or gastroesophageal reflux (GERD). The barium swallow test, or esophagram, is essential in investigating patients with abnormalities within the esophagus. The barium sulfate used is inert to the gastrointestinal tract and causes no harm. However, problems begin when the contrast agent enters the trachea and then into the lungs. The author herein presents a case of barium aspiration in a 60 years old Indian male being investigated for the cause of dysphagia. In this case, the paradox was the radiograph's contradictory features and the patient's clinical features. The large aspiration on the radiograph alerted the clinicians. However, the patient was relatively asymptomatic, and thus a clinical and radiographic paradox should always be kept in the minds of the treating physicians, especially post barium aspiration.

Autoimmune gastritis is characterized by atrophy of acid secreting parietal cells resulting in achlorhydria. Upper gastrointestinal symptoms are common in autoimmune gastritis and frequently result in prescriptions for acid suppressant medications despite the inability of the stomach to secrete acid. Evidence-based recommendations for management of gastrointestinal symptoms in autoimmune gastritis are lacking.

Chronic atrophic gastritis (CAG) is a common chronically digestive disease which is notoriously characterized by atrophy of the epithelium and glands of the gastric mucosa, reduced number, thinning of the gastric mucosa, thickening of the mucosal base, or pyloric glandular hyperplasia and intestinal glandular hyperplasia, or with atypical hyperplasia. Banxia Xiexin decoction (BXD) has been applied for two thousand years and is considered an effective therapy for functional dyspepsia, gastroesophageal reflux disease and colon cancer. In this current study, to probe into the underlying mechanism of BXD on CAG, network pharmacology was conducted to collect druggable ingredients and predicted targets of BXD and the CAG-associated targets were harvested to take intersection with druggable ingredients from BXD predicted targets to obtain potential critical action targets. Subsequently, GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted to elucidate the underlying mechanisms and roles from the perspective of overall pathways and cellular functions. Eventually, molecular docking integrated with molecular dynamics simulations was conducted to further investigate the mechanism of action of BXD active ingredients on CAG from drug molecule-target interactions and to provide a theoretical basis for BXD drug development.

Dietary interventions may alleviate symptoms related to functional gastrointestinal disorders, now termed disorders of gut-brain interaction. We reviewed which interventions have high-quality data to support their use in gastroesophageal reflux disease (GERD), functional dyspepsia (FD), irritable bowel syndrome, and chronic idiopathic constipation.

Cinitapride is a gastrointestinal prokinetic drug, prescribed for the treatment of functional dyspepsia, and as an adjuvant therapy for gastroesophageal reflux disease. In this study, we aimed to explore the impact of relevant variants in CYP3A4 and CYP2C8 and other pharmacogenes, along with demographic characteristics, on cinitapride pharmacokinetics and safety; and to evaluate the impact of CYP2C8 alleles on the enzyme's function. Twenty-five healthy volunteers participating in a bioequivalence clinical trial consented to participate in the study. Participants were genotyped for 56 variants in 19 genes, including cytochrome P450 (CYP) enzymes (e.g., CYP2C8 or CYP3A4) or transporters (e.g., SLC or ABC), among others. CYP2C8*3 carriers showed a reduction in AUC of 42% and Cmax of 35% compared to *1/*1 subjects (p = 0.003 and p = 0.011, respectively). *4 allele carriers showed a 45% increase in AUC and 63% in Cmax compared to *1/*1 subjects, although these differences did not reach statistical significance. CYP2C8*3 and *4 alleles may be used to infer the following pharmacogenetic phenotypes: ultrarapid (UM) (*3/*3), rapid (RM) (*1/*3), normal (NM) (*1/*1), intermediate (IM) (*1/*4), and poor (PM) metabolizers (*4/*4). In this study, we properly characterized RMs, NMs, and IMs; however, additional studies are required to properly characterize UMs and PMs. These findings should be relevant with respect to cinitapride, but also to numerous CYP2C8 substrates such as imatinib, loperamide, montelukast, ibuprofen, paclitaxel, pioglitazone, repaglinide, or rosiglitazone.

The prevalence of Helicobacter pylori (H. pylori) infection has exceeded 50% worldwide, and it is considered a high-risk factor for chronic gastritis, peptic ulcer, gastric adenocarcinoma, gastroesophageal reflux disease and functional dyspepsia. H. pylori drug resistance is a common problem worldwide. In recent years, the relationship between H. pylori infection and gastrointestinal microecology has received much attention. H. pylori infection changes the structure and composition of gastrointestinal microflora by regulating the gastrointestinal microecological environment, local pH value, cytokines and antimicrobial peptides, and immune response and then plays a crucial role in the occurrence and development of digestive system tumors, liver metabolism and extragastrointestinal diseases. The quadruple strategy of H. pylori eradication can also aggravate gastrointestinal microflora disorder. However, probiotics can reduce intestinal flora changes and imbalances through different mechanisms, thus enhancing the efficacy of H. pylori eradication therapy and reducing adverse reactions caused by eradication therapy. Therefore, this paper reviews the relationship between H. pylori infection and gastrointestinal microecology and its clinical application, providing a basis for clinical treatment.

Non-erosive reflux disease (NERD) is classified into grade N (no minimal change) and grade M (minimal change) based on the Los Angeles classification. However, few reports have described the clinical characteristics of grade M. This study was performed to clarify the clinical characteristics of grade M. Among 290 consecutive patients with gastroesophageal reflux disease (GERD), 45 patients with grade M, 62 patients with grade N, and 94 patients with grade A were compared with respect to clinical differences. The degree of symptom improvement after 4 weeks of proton pump inhibitor administration was also prospectively compared among the three groups. Grades N and M showed no or little difference in the patients' backgrounds (including sex and body mass index), GERD/functional dyspepsia symptom scores, life dissatisfaction (diet, sleep, work, and mood), Short Form-8 (mental component summary) scores, and symptom improvement. In contrast, significant differences were present between grades M and A as well as between grades N and A. The overall results of our study suggest that the distinction between grade M and grade N is of little clinical significance from the viewpoint of clinical characteristics.

Background and aim Increasing the appropriateness of upper gastrointestinal endoscopy (UGIE) improves the quality of care while containing costs. The aim of this study was to improve the appropriateness of UGIE through a process involving evaluation of prescriptions and the use of a non-invasive alternative. Materials and methods A senior endoscopist evaluated the appropriateness of all outpatient referrals for UGIE and established the proper timing. Referrals were either accepted and programmed, canceled, or substituted by a non-invasive evaluation of gastric function, determining serum levels of gastrin-17 (G17), Pepsinogen I (PGI) and II (PGII), and antibodies against Helicobacter pylori. Results A total of 5102 requests for UGIE examinations were evaluated; 540 (10.4%) were inappropriate and had been prescribed for: gastroesophageal reflux disease (n=307), surveillance with erroneous timing (n=113), dyspepsia (n=66), other indications (n=20), and absence of written indication (n=34). Gastric function was evaluated in 282/540 patients; findings included normal values in 94 patients without proton-pump inhibitor therapy (PPI) and in 48 on PPI, active H pylori infection in 56, previous H pylori infection in 30, GERD in n=50, and atrophic gastritis in n=4. UGIE was performed in the latter 4 cases. Within 2 years (range 1-22 months) of the initial refusal, 105/504 patients underwent UGIE, with normal endoscopic findings in 71/105 (67.5%), and with no cases of cancer. Conclusions This strategy, based on a strict control of prescriptions, is effective to increase the appropriateness while containing public health costs. The use of gastric function testing improves patient selection for UGIE endoscopy.

(1) Background: Heartburn and reflux discomfort are frequent reasons for consultation at the community pharmacy. To facilitate the assistance work of the community pharmacist and its coordination between different levels of care, a group of experts in Community Pharmacy, Primary Care, and Gastroenterology have recently worked on an algorithm to manage these symptoms in the community pharmacy (Professional Pharmaceutical Service). The objective of this study is to analyze the clinical and sociodemographic characteristics of patients with heartburn and/or reflux-like symptoms who go to a community pharmacy, and to evaluate the clinical and humanistic results after the implementation of a Professional Pharmaceutical Service. (2) Methods: A pre-post study will be carried out to evaluate clinical and humanistic results after the implementation of a Professional Pharmaceutical Service. We will include 1200 patients who ask for advice or get a non-prescription medication due to acid and/or reflux symptoms in 240 Spanish pharmacies. Clinical data will be collected at baseline and 15 days after the pharmaceutical intervention. The GERD Impact Scale (GIS) questionnaire will be applied to assess changes in heartburn/reflux-like symptoms and quality of life after the intervention.

Aluminum hydroxide is a medication used in the management and treatment of acid indigestion. It is in the antacid class of drugs. This activity outlines the indications, action, and contraindications for aluminum hydroxide as a valuable agent in the management of acid indigestion or topical burns. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions) pertinent for members of the healthcare team in the treatment of patients with acid reflux and related conditions.

Definition of gastritis has its basis in histological features of the gastric mucosa. It is not erythema observed during gastroscopy, and there are no specific clinical presentations or symptoms defining it. The current classification of gastritis centers on time course (acute versus chronic), histological features, anatomic distribution, and underlying pathological mechanisms. Acute gastritis will evolve to chronic, if not treated. Helicobacter pylori (H. pylori) is the most common cause of gastritis worldwide. However, 60 to 70% of H. pylori-negative subjects with functional dyspepsia or non-erosive gastroesophageal reflux were also found to have gastritis. H. pylori-negative gastritis is a consideration when an individual fulfill all four of these criteria (i) A negative triple staining of gastric mucosal biopsies (hematoxylin and eosin, Alcian blue stain and a modified silver stain), (ii) A negative H pylori culture, (iii) A negative IgG H. pylori serology, and (iv) No self-reported history of H. pylori treatment. In these patients, the cause of gastritis may relate to tobacco smoking, consumption of alcohol, and/or the use of non-steroidal anti-inflammatory drugs (NSAIDs) or steroids. Other causes of gastritis include: 1. Autoimmune gastritis associated with serum anti-parietal and anti-intrinsic factor antibodies; characterized by chronic atrophic gastritis limited to the corpus and fundus of the stomach that is causing marked diffuse atrophy of parietal and chief cells. 2. Gastritis causes include organisms other than H. pylori such as Mycobacterium avium intracellulare, Herpes simplex, and Cytomegalovirus. 3. Gastritis caused by acid reflux. Rare causes of gastritis include collagenous gastritis, sarcoidosis, eosinophilic gastritis, and lymphocytic gastritis. Clinical presentation, laboratory investigations, gastroscopy, as well as the histological and microbiological examination of tissue biopsies are essential for the diagnosis of gastritis and its causes. Treatment of H. pylori-associated gastritis results in the rapid disappearance of polymorphonuclear infiltration and a reduction of chronic inflammatory infiltrate with the gradual normalization of the mucosa. Mucosal atrophy and metaplastic changes may resolve shortly, but it is not necessarily the outcome of treatment of H. pylori in all treated patients. Other types of gastritis should be treated based on their causative etiology. 

Neurogastroenterology and motility is a rapidly evolving subspecialty that encompasses over 33% of gastroenterological disorders, and up to 50% of referrals to gastroenterology practice. It includes common problems such as dysphagia, gastroesophageal reflux disease, irritable bowel syndrome, chronic constipation, gastroparesis, functional dyspepsia, gas/bloating, small intestinal bacterial overgrowth, food intolerance and fecal incontinence Standard diagnostic tests such as endoscopy or imaging are normal in these conditions. To define the underlying mechanism(s)/etiology of these disorders, diagnostic motility tests are often required. These are best performed by well-trained personnel in a dedicated motility laboratory. Our purpose is to provide an up-to-date overview on how to organize and develop a motility laboratory based on our collective experiences in setting up such facilities in academia and community practice.