Prokinetics-safety and efficacy: The European Society of Neurogastroenterology and Motility/The American Neurogastroenterology and Motility Society expert review.

BACKGROUND: Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high-quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects. PURPOSE: Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.

Virtual Reality Improves Symptoms of Functional Dyspepsia: Results of a Randomized, Double-Blind, Sham-Controlled, Pilot Study.

INTRODUCTION: We investigated the efficacy and safety of virtual reality (VR) for functional dyspepsia. METHODS: Patients were randomized 2:1 between active vs sham VR. Symptoms were assessed using the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) over 2-week. RESULTS: Patients in the active VR group had greater numerical improvement in PAGI-SYM scores (mean difference -0.7; P < 0.001) compared with sham VR (mean difference -0.4; P = 0.032). Active VR led to significant improvements for all PAGI-SYM subscales, except lower abdominal pain, whereas sham only improved heartburn/regurgitation and nausea/vomiting. Half of the total patients reported nonserious adverse effects, although only 1 patient withdrew from the study because of adverse effects. DISCUSSION: VR is safe and results in significant symptom improvement in functional dyspepsia. Larger trials are warranted.

Irritable bowel syndrome - less irritable, or better treatments?

PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a chronic, often bothersome disorder of gut-brain interaction (DGBI) characterized by abdominal pain associated with a change in stool frequency and/or caliber. Recent advancements have improved our understanding of the underlying pathophysiology, thus opening new avenues for therapeutic intervention. The purpose of this review is to summarize the current literature regarding treatment modalities for IBS. RECENT FINDINGS: Altering the gut microbiome via probiotic and antibiotic administration, avoiding dietary triggers, and modulating the gut-brain axis have all proven efficacious for the management of IBS symptoms. Several gut-specific pharmacotherapies are approved for the treatment of IBS, many of which primarily address either diarrhea or constipation, although many patients remain symptomatic despite appropriate use. Brain-gut behavioral therapies (BGBTs) are increasingly used to treat symptoms of IBS, particularly in those who do not respond to traditional therapies. Virtual reality represents an exciting new approach to treating DGBIs, like IBS, though data are limited. SUMMARY: As our understanding of IBS continues to evolve, so should our therapeutic approach. Individualizing the therapeutic approach is of utmost importance.

Gastroparesis: time for a paradigm change.

PURPOSE OF REVIEW: Gastroparesis (GP) is a syndrome defined by symptoms and delayed gastric emptying in the absence of mechanical obstruction. Typical symptoms include nausea, vomiting, abdominal pain, and early satiety. Only one medication is currently FDA-approved for the treatment of GP. This review highlights recent research findings pertaining to GP and provides evidence to support a change in the current GP diagnostic and treatment paradigm. RECENT FINDINGS: An analysis of GP trials over the past four decades demonstrates the power of placebo and the need to perform longer studies with clearly defined patient populations. Two studies highlight the need to evaluate patients with suspected GP carefully and to perform gastric emptying studies properly. The misdiagnosis of GP symptoms is reviewed, preceded by a discussion of whether GP should be considered a disorder of gut-brain interaction. Finally, new data on therapies that target the pylorus are highlighted. SUMMARY: Gastroparesis is frequently over-diagnosed and incorrectly diagnosed. Performing a proper gastric emptying study which adheres to standard protocol, and accurately interpreting the results in the context of the individual patient, are critical to making an accurate diagnosis of GP. The treatment paradigm needs to shift from simply aiming to accelerate gastric emptying to treating global symptoms of a chronic syndrome that may represent gut-brain dysfunction in many patients.

Gastroparesis: Myths, Misconceptions, and Management.

Gastroparesis (GP), a historically vexing disorder characterized by symptoms of nausea, vomiting, abdominal pain, early satiety, and/or bloating, in the setting of an objective delay in gastric emptying, is often difficult to treat and carries a tremendous burden on the quality of patients' lives, as well as the healthcare system in general. Though the etiology of GP has been fairly well defined, much work has been done recently to better understand the pathophysiology of GP, as well as to identify novel effective and safe treatment options. As our understanding of GP has evolved, many myths and misconceptions still abound in this rapidly changing field. The goal of this review is to identify myths and misconceptions regarding the etiology, pathophysiology, diagnosis, and treatment of GP, in the context of the latest research findings which have shaped our current understanding of GP. Recognition and dispelling of such myths and misconceptions is critical to moving the field forward and ultimately advancing the clinical management of what will hopefully become a better understood and more manageable disorder in the future.

Virtual Reality: A New Treatment Paradigm for Disorders of Gut-Brain Interaction?

Disorders of gut-brain interaction (DGBIs), previously called functional bowel disorders, are prevalent, reduce patients' quality of life, and impose a significant negative economic impact on the health care system. Functional dyspepsia and irritable bowel syndrome (IBS) are 2 of the most common DGBIs. An overlying, and in many cases unifying, symptom for many of these disorders is the presence of abdominal pain. Chronic abdominal pain can be difficult to treat, as many antinociceptive agents are associated with side effects that limit their use and other agents may only partially improve, but not completely relieve, all aspects of the pain. Novel therapies to alleviate chronic pain and the other symptoms that characterize DGBIs are thus needed. Virtual reality (VR), a technology that immerses patients in a multisensory experience, has been shown to relieve pain in burn victims and other instances of somatic pain. Two recent novel studies have demonstrated that VR has the potential to play an important role in the treatment of functional dyspepsia and IBS. This article examines the development of VR, its role in the treatment of somatic and visceral pain, and its potential position in the treatment of DGBIs.

The treatment of functional dyspepsia: present and future.

INTRODUCTION: Functional dyspepsia (FD) is a prevalent, but frequently overlooked and/or under diagnosed disorder of gut-brain interaction (DGBI). Functional dyspepsia frequently co-exists with other DGBIs, and persistent symptoms have a significant impact on patients' quality of life. A variety of therapies (e.g. diet, probiotics, antibiotics, acid suppressants, neuromodulators, prokinetics) are employed to treat the multiple symptoms of FD, although none are uniformly effective. AREAS COVERED: This review covers currently available therapies for the treatment of FD in addition to novel and emerging therapies that may change the treatment paradigm in the near future. PubMed, Embase and the Cochrane data bank were searched from 1990 to October 2022 for relevant articles. EXPERT OPINION: Dietary intervention, eradication of H. pylori, and/or a trial of acid suppression are reasonable initial treatment options for patients with FD. Neuromodulators and fundic accommodation agents are underemployed and should be used more routinely by healthcare providers, especially for patients with moderate-severe symptoms. Alternative therapies, such as cognitive behavioral therapy and hypnotherapy, are gaining recognition as safe and effective treatments for FD and can be used alone or in combination with medications. Virtual reality has the potential to significantly improve global FD symptoms.

Updates in functional dyspepsia and bloating.

PURPOSE OF REVIEW: Functional dyspepsia and bloating are common gastrointestinal conditions that frequently lead to gastroenterology referral. Both disorders have a significant negative impact on patients' quality of life and the healthcare system. The purpose of this review is to highlight important new findings in the cause, pathophysiology and treatment of these two disorders. RECENT FINDINGS: Confocal laser endomicroscopy identified changes in epithelial barrier structure and function, providing important insights into the development of functional dyspepsia symptoms when combined with new observations of localized duodenal inflammation. Changes in the gut microbiome may be responsible for functional dyspepsia symptoms in some patients and may respond to gut-selective antibiotics. New data from the NIH-sponsored Gastroparesis Consortium confirmed that functional dyspepsia and gastroparesis are not distinct disorders but rather exist on a spectrum. Virtual reality may be a new therapeutic option for the treatment of functional dyspepsia. A novel questionnaire was developed and validated to assess symptoms, prevalence and impact in patients with bloating and distension. A meta-analysis identified medications to treat symptoms of bloating in patients with irritable bowel syndrome and constipation. SUMMARY: Advances in our understanding of the pathophysiology of functional dyspepsia and bloating are leading to important changes in medical therapies.

A Practical Approach to the Diagnosis and Treatment of Abdominal Bloating and Distension.

Abdominal bloating and distension are highly prevalent symptoms that can negatively impact quality of life and lead to medical consultation. Despite their prevalence, symptoms of bloating and distension pose a unique diagnostic and therapeutic challenge, as they are inherently nonspecific symptoms with a complex etiology, and no uniform diagnostic or treatment algorithm currently exists. Additionally, bloating is common among disorders of gut-brain interaction, which can be difficult to treat. This article offers a practical approach for evaluating and treating symptoms of bloating and distension through discussion of 5 common etiologies: diet, small intestinal bacterial over-growth, constipation, visceral hypersensitivity, and abdomino-phrenic dyssynergia. An effective personalized evaluation and treatment plan can be established to address symptoms of bloating and distension through consideration of these etiologies in the context of the patient's individual characteristics and presentation.

Impact of Artificial Intelligence on Miss Rate of Colorectal Neoplasia.

BACKGROUND & AIMS: Artificial intelligence (AI) may detect colorectal polyps that have been missed due to perceptual pitfalls. By reducing such miss rate, AI may increase the detection of colorectal neoplasia leading to a higher degree of colorectal cancer (CRC) prevention. METHODS: Patients undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa. Adenoma miss rate (AMR) was calculated as the number of histologically verified lesions detected at second colonoscopy divided by the total number of lesions detected at first and second colonoscopy. Mean number of lesions detected in the second colonoscopy and proportion of false negative subjects (no lesion at first colonoscopy and at least 1 at second) were calculated. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted by endoscopist, age, sex, and indication for colonoscopy. Adverse events were also measured. RESULTS: A total of 230 subjects (116 AI first, 114 standard colonoscopy first) were included in the study analysis. AMR was 15.5% (38 of 246) and 32.4% (80 of 247) in the arm with AI and non-AI colonoscopy first, respectively (adjusted OR, 0.38; 95% CI, 0.23-0.62). In detail, AMR was lower for AI first for the ≤5 mm (15.9% vs 35.8%; OR, 0.34; 95% CI, 0.21-0.55) and nonpolypoid lesions (16.8% vs 45.8%; OR, 0.24; 95% CI, 0.13-0.43), and it was lower both in the proximal (18.3% vs 32.5%; OR, 0.46; 95% CI, 0.26-0.78) and distal colon (10.8% vs 32.1%; OR, 0.25; 95% CI, 0.11-0.57). Mean number of adenomas at second colonoscopy was lower in the AI-first group as compared with non-AI colonoscopy first (0.33 ± 0.63 vs 0.70 ± 0.97, P < .001). False negative rates were 6.8% (3 of 44 patients) and 29.6% (13 of 44) in the AI and non-AI first arms, respectively (OR, 0.17; 95% CI, 0.05-0.67). No difference in the rate of adverse events was found between the 2 groups. CONCLUSIONS: AI resulted in an approximately 2-fold reduction in miss rate of colorectal neoplasia, supporting AI-benefit in reducing perceptual errors for small and subtle lesions at standard colonoscopy. CLINICALTRIALS: gov, Number: NCT03954548.

Development and validation of a novel scoring system for bloating and distension: The Mayo Bloating Questionnaire.

BACKGROUND: Abdominal bloating and distension are prevalent gastrointestinal symptoms. Our aim was to design and validate a questionnaire to reliably measure the multiple symptom components of bloating and distension in the outpatient setting. METHODS: A 45-item questionnaire was developed after an extensive literature review. Face and content validity were established through expert review and a focus group. Validation was achieved by administering an identical questionnaire 1 week apart. Data were assessed using standard methods. KEY RESULTS: Forty one patients returned both questionnaires (85% women; mean age = 44 years). Respondents reported a variety of diagnoses, including irritable bowel syndrome (63%), gastroesophageal reflux disease (54%), functional dyspepsia (27%), small intestinal bacterial overgrowth (22%), and gastroparesis (17%). Test-retest reliability revealed excellent agreement (k ≥ 0.81) and substantial agreement (0.61 ≤ k < 0.81) for 29% and 43% of categorical questions, respectively. Alternate-parallel form reliability was supported by association between responses for questions that evaluated missing school/work and questions that evaluated symptom impact on daily activities (p < 0.05). Patients who missed school/work due to bloating symptoms were more likely to report a severe impact on their ability to enjoy life (p < 0.05) and their overall well-being (p < 0.01). Contingency analyses revealed an association between overall 7-day symptom severity and impact on daily activities (p < 0.001), enjoying life (p < 0.001), and overall well-being (p < 0.001). CONCLUSIONS AND INFERENCES: This novel questionnaire demonstrated good validity and reliability in patients with symptoms of bloating and distension. The questionnaire was easy to use and score, making it a potentially useful tool for both research studies and clinical purposes.

Delayed Gastric Emptying in Prelung Transplant Patients Is Associated With Posttransplant Acute Cellular Rejection Independent of Reflux.

GOAL: The goal of this study was to evaluate the relationship between pretransplant delayed gastric emptying (DGE) and posttransplant acute cellular rejection (ACR) in lung transplant recipients. BACKGROUND: DGE is very prevalent (23% to 91%) after lung transplantation but pretransplant prevalence has not been well studied. DGE may lead to poor posttransplant outcomes by predisposing to microaspiration. Pretransplant testing for DGE may help identify patients at risk for negative posttransplant outcomes including ACR. MATERIALS AND METHODS: A retrospective review of a prospectively collected database of consecutive patients undergoing prelung transplant evaluation at a tertiary referral center from 2010 to 2015 was performed. Patients with pretransplant gastric emptying scintigraphy were included in the study. ACR diagnosis was made using International Society for Heart and Lung Transplantation (ISHLT) histologic criteria. Typical gastroparesis symptoms at the time of gastric emptying scintigraphy and pretransplant 24-hour pH impedance monitoring (MII-pH) data was collected. Logistic regression was used for multivariate analysis. Subgroup analyses were performed to account for gastroesophageal reflux (GER). RESULTS: A total of 83 subjects (18 with DGE, 51.8% male, mean age: 53.6 y) met the criteria for inclusion. Patients with DGE were more likely to have typical symptoms of gastroparesis, though 61.1% of DGE patients were asymptomatic. ACR was more prevalent in patients with DGE (33.3% vs. 12.3%, P=0.04). This correlation was independent of GER as measured by MII-pH on subgroup analysis (75% vs. 14.3%, n=0.02). DISCUSSION: Lung transplant recipients with pretransplant DGE have a higher incidence of ACR, independent of GER. Routine pretransplant testing for DGE may help identify patients at greater risk for adverse posttransplant outcomes as the majority of patients with DGE are asymptomatic.

Gastroparesis.

PURPOSE OF REVIEW: This review highlights recent research advances regarding the pathophysiology and treatment of gastroparesis. RECENT FINDINGS: Differences in brain activity have been identified on functional MRI imaging in gastroparesis patients with nausea. Abdominal pain is common in patients with gastroparesis and does not correlate with the severity of gastric emptying delay, though may be associated with depression and anxiety. Autonomic dysfunction may play an important role in the pathophysiology of gastroparesis. There is increasing sentiment that gastroparesis should be considered a part of the same spectrum of gastric neuromuscular disorders. The risk of tardive dyskinesia with metoclopramide has likely been significantly overestimated historically. Endoscopic BoTox injection of the pylorus and gastric electrical stimulation remain controversial treatments for gastroparesis. New, highly selective 5-hydroxytryptamine 4 (5-HT4) agonists appear safe and may be effective in improving symptoms of gastric emptying. Long-term data assessing the use of gastric peroral endoscopic myotomy (G-POEM) for the treatment of refractory gastroparesis suggest durable clinical improvement. SUMMARY: Altered central processing and autonomic dysfunction may be important factors in the pathogenesis of gastroparesis. While the risk of tardive dyskinesia appears much lower than historically advertised, there is increasing hope for novel therapeutics with the advent of new 5-HT4 agonists, neurokinin-1 receptor (N1KR) antagonists, and G-POEM.