Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation. METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the Nine Item ARFID Screen (NIAS) and the Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Gastric retention and fundic accommodation (for Gp and FD) were determined from gastric emptying scintigraphy. KEY RESULTS: At baseline, the proportion of children screening positive for ARFID on the NIAS versus PARDI-AR-Q was Gp: 48.5% versus 63.6%, FD: 66.7% versus 65.2%, HC: 15.3% versus 9.7%, respectively; p < 0.0001 across groups. Of children who screened positive at baseline and participated in the follow-up, 71.9% and 53.3% were positive 2 months later (NIAS versus PARDI-AR-Q, respectively). A positive ARFID screen in Gp or FD was not related to the presence/absence of delayed gastric retention or abnormal fundic accommodation. CONCLUSIONS & INFERENCES: ARFID detected from screening questionnaires is highly prevalent among children with Gp and FD and persists for at least 2 months in a substantial proportion of children. Children with these disorders should be screened for ARFID.

Epidemiology of functional dyspepsia and gastroparesis as diagnosed in Flemish-Belgian primary care: A registry-based study from the Intego database.

BACKGROUND: Dyspepsia is a prevalent condition in the general population. Besides organic causes, the differential diagnosis of dyspepsia includes functional dyspepsia (FD) and gastroparesis (GP) which share similar pathophysiological mechanisms and clinical presentation. So far, no study investigated the prevalence of FD and GP in a primary care in Belgium. METHODS: Data were obtained from Intego, a Flemish-Belgian general practice-based morbidity registration network. From 586,164 patients between 2000 and 2021, we selected patients with ICD-10 code for FD and GP. Patients with organic gastrointestinal diseases were excluded. We determined demographics and comorbidities of FD/GP. For prevalence and incidence calculation, we included those who consulted their general practitioners at least once in the given year. Pair-wise comparison was conducted to access the impact of comorbidities on risk of FD/GP. KEY RESULTS: Between 2011 and 2021, the prevalence of FD/GP ranged from 1.03% to 1.21%. The incidence of FD/GP ranged from 109 to 142 per 100,000 adults. In total 5242 cases of FD/GP were identified. These cases shared commonly coexisting diagnoses of gastroesophageal reflux disease (18.8%), irritable bowel syndrome (17.1%), and chronic constipation (18.7%). Patients with somatization/anxiety/depression had significantly higher risk of FD/GP, compared to the control (OR 1.38, 95% CI 1.19-1.61, p < 0.01). CONCLUSIONS AND INFERENCES: The prevalence (1.03%-1.21%) and incidence (109-142/100,000) of FD/GP in primary care over last decade appear to conflict with epidemiological research in the general population. The discrepancies suggest a potential lack of awareness of FD and GP among physicians and/or patients in Flemish-Belgium.

Gastroparesis.

Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.

The High-Resolution Three-Dimensional Magnetic Detector System 3D-Magma Accurately Measures Gastric and Small Bowel Motility in People with Type 2 Diabetes with Neuropathy.

Gastroparesis is an important complication of diabetes. Motility disorders are underdiagnosed and can lead to unexplained hypoglycemia. Currently diagnostic options are limited. All established methods harbor certain disadvantages. The 3D-MAGMA system is capable of reliably measuring gastric and small intestinal motility. The aim of the current study was to determine if 3D-MAGMA is able to detect changes in intestinal motility in people with type 2 diabetes. 18 healthy volunteers and 19 people with type 2 diabetes underwent motility testing by 3D-MAGMA. In the control group the retention time in the stomach was 33.0 [min] compared to 75.3 [min] in the diabetes group. The median time in the duodenum was 12.7 [min] compared to 8.1 [min]. The time for the first 50 cm of the jejunum was 29.9 [min] compared to 28.2 [min]. Discussion and conclusion: 3D-MAGMA is able to detect changes in intestinal motility. Its clinical value might be useful in patients with fluctuating blood glucose levels and unexplained hypoglycemic episodes.

Effects of Spinal Cord Stimulation in Patients with Chronic Nausea, Vomiting, and Refractory Abdominal Pain.

BACKGROUND: Patients with chronic nausea and vomiting often also have chronic abdominal pain. Spinal cord stimulation (SCS) may provide pain control, but scarce data are available regarding the effect of SCS on chronic nausea and vomiting. AIMS: We aimed to determine the effect of SCS in patients with chronic nausea, vomiting, and refractory abdominal pain. METHODS: Retrospective chart review of 26 consecutive patients who underwent SCS trial for a primary diagnosis of nausea, vomiting and refractory abdominal pain. RESULTS: 26 patients underwent SCS trial, with an average age of 48 years. Twenty-three patients (88.5%) reported > 50% pain relief during the temporary SCS trial and then underwent permanent implantation. Patients were then followed for 41 (22-62) months. At baseline, 20 of the 23 patients (87.0%) reported daily nausea, but at 6 months and the most recent follow-up, only 8 (34.8%) and 7 (30.4%) patients, respectively, had daily nausea (p < 0.001). Days of nausea decreased from 26.3 days/month at baseline to 12.8 and 11.7 days/month at 6 months and at the most recent visit, respectively. Vomiting episodes decreased by 50%. Abdominal pain scores improved from 8.7 to 3.0 and 3.2 at 6 months and the most recent visit, respectively (both p < 0.001). Opioid use decreased from 57.7 mg MSO4 equivalents to 24.3 mg at 6 months and to 28.0 mg at the latest patient visit (both p < 0.05). CONCLUSIONS: SCS may be an effective therapy for long-term treatment of symptoms for those patients afflicted with chronic nausea, vomiting, and refractory abdominal pain.

Epidemiology, Etiology, and Treatment of Gastroparesis: Real-World Evidence From a Large US National Claims Database.

BACKGROUND & AIMS: Although gastroparesis carries a considerable health care and patient burden, associated epidemiological data are limited. To provide new real-world evidence for gastroparesis, we estimated disease prevalence, and investigated patient demographics and disease etiology in a large US claims database. METHODS: This retrospective, cross-sectional analysis used de-identified, longitudinal patient-level enrollment and billing data for adults from the Optum Clinformatics Data Mart database, a large US national administrative health insurance claims database. Prevalence was age-, sex-, and geographical region-standardized using the 2018 US census. Descriptive analyses of demographic and clinical variables and underlying disease etiologies were performed. RESULTS: The overall standardized prevalence of gastroparesis was 267.7 (95% confidence interval [CI] 264.8-270.7) per 100,000 US adults, whereas prevalence of "definite" gastroparesis (individuals diagnosed within 3 months of gastric emptying scintigraphy testing with persistent symptoms for more than 3 months) was 21.5 (95% CI 20.6-22.4) per 100,000 persons. Patients with gastroparesis had an overall Charlson Comorbidity Index score of 4.2, indicating substantial comorbidity burden. The most frequently documented comorbidities were chronic pulmonary disease (46.4%), diabetes with chronic complication (37.3%), and peripheral vascular disease (30.4%). Patients most commonly had a diabetic etiology (57.4%; type 1, 5.7% and type 2, 51.7%), followed by postsurgical (15.0%), drug-induced (11.8%), and idiopathic (11.3%) etiologies. CONCLUSIONS: New evidence is provided regarding the prevalence, patient demographics, and etiology of gastroparesis in the US general population. Wider availability of reliable objective gastric emptying measures and further education of medical professionals in recognizing and diagnosing gastroparesis would benefit future studies and improve understanding of disease epidemiology.

The Short-Term Effects and Tolerability of Low-Viscosity Soluble Fibre on Gastroparesis Patients: A Pilot Clinical Intervention Study.

Gastroparesis is a motility disorder that causes severe gastric symptoms and delayed gastric emptying, where the majority of sufferers are females (80%), with 29% of sufferers also diagnosed with Type-1 or Type-2 diabetes. Current clinical recommendations involve stringent dietary restriction and includes the avoidance and minimization of dietary fibre. Dietary fibre lowers the glycaemic index of food, reduces inflammation and provides laxation. Lack of dietary fibre in the diet can affect long-term gastrointestinal health. Our previously published rheological study demonstrated that "low-viscosity" soluble fibres could be a potentially tolerable source of fibre for the gastroparetic population. A randomised controlled crossover pilot clinical study was designed to compare Partially-hydrolysed guar gum or PHGG (test fibre 1), gum Arabic (test fibre 2), psyllium husk (positive control) and water (negative control) in mild-to-moderate symptomatic gastroparesis patients (requiring no enteral tube feeding). The principal aim of the study was to determine the short-term physiological effects and tolerability of the test fibres. In n = 10 female participants, post-prandial blood glucose, gastroparesis symptoms, and breath test measurements were recorded. Normalized clinical data revealed that test fibres PHGG and gum Arabic were able to regulate blood glucose comparable to psyllium husk, while causing far fewer symptoms, equivalent to negative control. The test fibres did not greatly delay mouth-to-caecum transit, though more data is needed. The study data looks promising, and a longer-term study investigating these test fibres is being planned.

Short-term outcomes of different modalities of pyloromyotomy versus gastric electrical stimulation in the treatment of gastroparesis: A systemic review and meta-analysis.

BACKGROUND: The aim of this meta-analysis was to compare the short-term outcomes surrounding the efficacy and complication rate between different modalities of pyloromyotomy and gastric electrical stimulation (GES) in the treatment of gastroparesis. METHODS: Comprehensive, computerized research was performed on PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We additionally reviewed relevant articles, without any language limitations, published prior to April 15, 2020. Meta-analysis was conducted using RevMan 5.3 software. RESULTS: Three studies totaling 196 participants who had received 4 interventions, including single per-oral pyloromyotomy (POP), double POP, laparoscopic pyloromyotomy, and GES, were eligible for analysis. Compared to single POP, double POP achieved a better clinical response with a pooled relative risk (RR) of 1.27 (95% confidence interval [CI], 1.01-1.60, P = .04), while laparoscopic pyloromyotomy and GES showed no difference with a pooled RR of 0.89 (95% CI, 0.74-1.08, P = .23) and 0.87 (95% CI, 0.73-1.04, P = .13), respectively. As for the recurrence and complication rates, only GES showed a borderline significance of recurrence in comparison to single POP (RR 2.17, 95% CI, 1.00-4.71, P = .05), while there were no differences in the remainder of the comparisons. CONCLUSIONS: We conducted a detailed comparison of 3 modalities of pyloromyotomy and GES in the treatment of gastroparesis, with the results suggesting that double POP demonstrated better clinical success with similar recurrence and complication rates. In addition, GES may result in more recurrence amongst these interventions.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Pyloric distensibility in health and disease.

Until recently, gastric motility measurements in humans were mostly limited to accommodation (using barostat or 3-dimensional imaging studies of gastric volume) and gastric emptying tests, the latter being the only one performed in routine clinical care. Accurate and easy to use techniques were lacking to assess pyloric function in health and disease. Recently, pyloric distensibility has been developed and validated to assess pyloric opening. Several studies confirmed that pyloric distensibility was decreased in gastroparesis and correlated with gastric emptying as well as gastroparesis symptoms. In addition, pyloric distensibility may predict outcome of endoscopic techniques targeting the pylorus, namely intrapyloric botulinum toxin injection and gastric per-oral pyloromyotomy. Pyloric distensibility appears therefore to be a promising and useful new tool in the workup of gastroparesis patients.

United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis.

BACKGROUND: Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis. METHODS: A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements. RESULTS: The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT4 receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause. CONCLUSIONS AND INFERENCES: A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.

New device for active gastric mechanical stimulation.

BACKGROUND: Gastroparesis is a chronic stomach disorder and effective treatment is the aim of different strategies. Alternative therapies consist of an electrical stimulation of the stomach to evoke a response in the gastric activity. We present the development and in vivo application of an electromagnet system to induce a mechanical stimulus in the stomach aiming for gastric contractile responses. METHODS: The electromagnet system consisted of an implantable magnet and an external drive coil. We implanted the magnet at the greater curvature of the gastric body in rats. We applied an alternating current to the drive coils, inducing mechanical stimulation of the gastric wall. We measured the gastric contraction activity and gastric electrical activity in response to the stimulus using AC biosusceptometry and electrogastrography. Moreover, we used the phenol red to evaluate the stimulus effects on gastrointestinal transit. KEY RESULTS: The stimulus increased the spectral intensity and signal-to-noise ratio significantly of gastric contraction activity and gastric electrical activity. Furthermore, we found a lower phenol red retention in the stomach in rats without stimulus. No significant differences were found in frequency and root mean square amplitude. CONCLUSIONS & INFERENCES: We developed a new simple electromagnet system that evoked a contraction and gastric electrical response using a mechanical stimulus and decreased gastric emptying time. The system is an accessible tool and may contribute to gastroparesis studies in animals.

Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis.

INTRODUCTION: It is unclear how immune perturbations may influence the pathogenesis of idiopathic gastroparesis, a prevalent functional disorder of the stomach which lacks animal models. Several studies have noted altered immune characteristics in the deep gastric muscle layer associated with gastroparesis, but data are lacking for the mucosal layer, which is endoscopically accessible. We hypothesized that immune dysregulation is present in the gastroduodenal mucosa in idiopathic gastroparesis and that specific immune profiles are associated with gastroparesis clinical parameters. METHODS: In this cross-sectional prospective case-control study, routine endoscopic biopsies were used for comprehensive immune profiling by flow cytometry, multicytokine array, and gene expression in 3 segments of the stomach and the duodenal bulb. Associations of immune endpoints with clinical parameters of gastroparesis were also explored. RESULTS: The gastric mucosa displayed large regional variation of distinct immune profiles. Furthermore, several-fold increases in innate and adaptive immune cells were found in gastroparesis. Various immune cell types showed positive correlations with duration of disease, proton pump inhibitor dosing, and delayed gastric emptying. DISCUSSION: This initial observational study showed immune compartmentalization of the human stomach mucosa and significant immune dysregulation at the level of leukocyte infiltration in idiopathic gastroparesis patients that extends to the duodenum. Select immune cells, such as macrophages, may correlate with clinicopathological traits of gastroparesis. This work supports further mucosal studies to advance our understanding of gastroparesis pathophysiology.

COVID-19 infection manifesting as a severe gastroparesis flare: A case report.

RATIONALE: Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which commonly presents with symptoms including fever, cough, and dyspnea. More recently, however, some patients have tested positive for COVID-19 after developing gastrointestinal (GI) symptoms either solely or in conjunction with respiratory symptoms. This may be due to SARS-CoV-2 infection of the GI tract. In patients with chronic GI illnesses, COVID-19 may initially present as a flare of their underlying GI conditions as viruses have historically been implicated in exacerbations of GI disorders, including gastroparesis. PATIENT CONCERNS: We report a case of a 37-year-old female with a history of diabetic gastroparesis who presented to the Emergency Department (ED) with nausea and vomiting similar to her gastroparesis flares. DIAGNOSES: Her symptoms in the ED failed to improve with fluids and anti-emetic medications. After developing a fever, she was tested and found to be positive for COVID-19. INTERVENTIONS: She was started on antibiotic, steroid, and antiviral medications. OUTCOMES: Her symptoms improved, her fever defervesced on day 4 of hospitalization, and she was discharged on day 5 of hospitalization. The patient reported symptom improvement at a follow-up outpatient gastroenterology visit 2 months after hospitalization. LESSONS: To the best of our knowledge, at the present time, this is the first report of a patient with COVID-19 presenting with signs and symptoms of a gastroparesis flare. This case illustrates that COVID-19 may present in an exacerbation of symptoms of an underlying disorder, such as a severe gastroparesis flare, in a patient with underlying gastroparesis. Initial presentation of these patients manifesting as a flare of their chronic GI disease, more severe than usual, should prompt an index of suspicion for COVID-19.

Relationship of motor mechanisms to gastroparesis symptoms: toward individualized treatment.

Following a classical paper by Dr. Keith A. Kelly published in this journal, and over the past 40 years, there has been increased understanding of the functions of different regions of the stomach, specifically the fundus, antrum, and pylorus. Several of the important physiological principles were based on in vivo animal studies that led to the appreciation of regional function and control mechanisms. These include the roles of the extrinsic parasympathetic vagal innervation, the gastric enteric nervous system and electrical syncytium consisting of pacemaker cells and smooth muscle cells, and duodenogastric reflexes providing feedback regulation following the arrival of food and hydrogen ions stimulating the release of hormones and vagal afferent mechanisms that inhibit gastric motility and stimulate pyloric contractility. Further insights on the role of regional motor functions in gastric emptying were obtained from observations in patients following diverse gastric surgeries or bariatric procedures, including fundoplication, Billroth I and sleeve gastrectomy, and sleeve gastroplasty. Antropyloroduodenal manometry and measurements of pyloric diameter and distensibility index provided important assessments of the role of antral hypomotility and pylorospasm, and these constitute specific targets for individualized treatment of patients with gastroparesis. Moreover, in patients with upper gastrointestinal symptoms suggestive of gastroparesis, the availability of measurements of gastric accommodation and pharmacological agents to reduce gastric sensitivity or enhance gastric accommodation provide additional specific targets for individualized treatment. It is anticipated that, in the future, such physiological measurements will be applied in patients to optimize choice of therapy, possibly including identifying the best candidate for pyloric interventions.