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ObjectivesGastric emptying testing (GET) assesses gastric motility, however is non-specific and insensitive for neuromuscular disorders. Gastric Alimetry® (GA) is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared to GET.MethodsPatients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline,99mTC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: i) sensorimotor; ii) continuous; and iii) other.Results75 patients were assessed; 77% female. Motility abnormality detection rates were:GET22.7% (14 delayed, 3 rapid);GA spectral analysis33.3% (14 low rhythm stability / low amplitude; 5 high amplitude; 6 abnormal frequency);combined yield42.7%. In patients with normal spectral analysis,GA symptom phenotypesincluded: sensorimotor 17% (where symptoms strongly paired with gastric amplitude; median r=0.61); continuous 30%; other 53%. GA phenotypes showed superior correlations with GCSI, PAGI-SYM, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores (p>0.05).Delayed emptying was not predictive of specific GA phenotypes.ConclusionsGA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with improved correlation with symptoms and psychometrics compared to gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.Study Highlights1) WHAT IS KNOWNChronic gastroduodenal symptoms are common, costly and greatly impact on quality of lifeThere is a poor correlation between gastric emptying testing (GET) and symptomsGastric Alimetry® is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling2) WHAT IS NEW HEREGastric Alimetry generates a 1.5x higher yield for motility abnormalities than GETWith symptom profiling, Gastric Alimetry identified 2.7x more specific patient categories than GETGastric Alimetry improves clinical phenotyping, with improved correlation with symptoms and psychometrics compared to GET

The contractions of the stomach are governed by bioelectrical slow waves that can be detected non-invasively from the body-surface. Diagnosis of gastric motility disorders remains challenging due to the limited information provided by symptoms and tests, including standard electrogastrography (EGG). Body-surface gastric mapping (BSGM) is a novel technique that measures the resultant body-surface potentials using an array of multiple cutaneous electrodes. However, there is no established protocol to guide the placement of the mapping array and to account for the effects of biodiversity on the interpretation of gastric BSGM data. This study aims to quantify the effect of anatomical variation of the stomach on body surface potentials. To this end, 93 subject specific models of the stomach and torso were developed. Anatomical models were developed based on data obtained from the Cancer Imaging Archive. For each subject a set of points were created to model general anatomy the stomach and the torso, using a finite element mesh. A bidomain model was used to simulate the gastric slow waves in the antegrade wave (AW) direction and formation of colliding waves (CW). The resultant dipole was calculated, and a forward modeling approach was employed to simulate body-surface potentials. Simulated data were sampled from a 55 array of electrodes from the body-surface and compared between AW and CW cases. Anatomical parameters such as the Euclidean distance from the xiphoid process (8.6 2.2 cm), orientation relative to the axial plane (195 20.0) were quantified. Electrophysiological simulations of AW and CW were both correlated to specific metrics derived from BSGM signals. In general, the maximum amplitude () and orientation () of the signals provided consistent separation of AW and CW. The findings of this study will aid gastric BSGM electrode array design and placement protocol in clinical practices.

Coeliac disease (CeD) is an immune-mediated small bowel enteropathy resulting from dietary gluten exposure. Presently, the only effective treatment is adoption of a gluten-free diet (GFD), although strict adherence is challenging to maintain, and inadvertent gluten exposures are inevitable for most patients. Hence, there is substantial interest in drug development in CeD and multiple novel therapies are under investigation.To review existing and upcoming clinical trial programmes for pharmacologic agents for CeD.A narrative review was performed, informed by a search of MEDLINE, Embase, the Cochrane CENTRAL Library and clinicaltrials.gov.We summarise the pathophysiology of CeD and the specific steps that are potentially amenable to pharmacologic treatment. We evaluate the evidence supporting existing and future drug targets, including trials of peptidases, gluten sequestrants, tight junction regulators, anti-transglutaminase 2 therapies, immune tolerizing agents, advanced biologics and small molecules, and microbiome-targeted strategies. We highlight unique considerations for conducting CeD trials, including identifying appropriate study populations, assessing results in the context of a gluten challenge, and interpreting CeD-specific clinical and histologic outcomes. Understanding these factors is crucial for accurately appraising the evidence. Finally, we outline what the future of CeD therapy may hold with the introduction of pharmacotherapies.There is a need for pharmacologic options for CeD, either used adjunctively with a GFD for accidental or intentional gluten exposures or for refractory disease. Multiple promising agents are in development, and these trials are likely to lead to approvals for the first generation of pharmacologic agents for CeD within the next 5 years.

IntroductionBody surface gastric mapping (BSGM) is a new non-invasive test of gastric function. BSGM offers several novel and improved biomarkers of gastric function capable of differentiating patients with overlapping symptom-profiles. The aim of this study was to define normative reference intervals for BSGM spectral metrics in a population of healthy controls.MethodsBSGM was performed in healthy controls using Gastric Alimetry (Alimetry, New Zealand) comprising a stretchable high-resolution array (8×8 electrodes; 196 cm2), wearable Reader, and validated symptom-logging App. The evaluation encompassed a fasting baseline (30 min), 482 kCal meal, and 4-hr postprandial recording. Normative reference intervals were calculated for BSGM metrics including the Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI; a measure of the concentration of power in the gastric frequency band over time), BMI-adjusted amplitude (µV), and fed:fasted amplitude ratio (ff-AR). Data are reported as median and reference interval (5th and/or 95th percentiles).Results110 subjects (55% female, median age 32 (IQR 24 – 50), median BMI 23.8 kg/m2 (IQR 21.4 – 26.9)) were included. The median Principal Gastric Frequency was 3.04 cpm; reference interval: 2.65 – 3.35 cpm. Median GA-RI was 0.50; reference interval: !0.25. Median BMI-adjusted amplitude was 37.6 µV; reference interval: 20-70 µV. The median ff-AR was 1.85; reference interval !1.08. Higher BMI was associated with a shorter meal-response duration (p=0.014).ConclusionsThis study provides normative reference intervals for BSGM spectral data that will be used in clinical practice to inform diagnostic interpretations of abnormal gastric function.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.

BackgroundChronic gastroduodenal disorders including chronic nausea and vomiting syndrome, gastroparesis, and functional dyspepsia, are challenging to diagnose and manage. The diagnostic and treatment pathways for these disorders are complex, costly and overlap substantially; however, experiences of this pathway have not been thoroughly investigated. This study therefore aimed to explore clinician and patient perspectives on the current clinical pathway.MethodsSemi-structured interviews were conducted between June 2020 and June 2022 with 11 patients with chronic nausea and vomiting syndrome alone or with functional dyspepsia (based on Rome IV criteria) and nine gastroenterologists who treat these conditions. Interviews were recorded, transcribed, and thematically analyzed using an iterative, inductive approach.ResultsFive key patient themes were identified: (1) the impacts of their chronic gastroduodenal symptoms, (2) the complexity of the clinical journey, (3) their interactions with healthcare providers, (4) the need for advocacy, and (5) their experience of treatments. Five key clinician themes were also identified: (1) these conditions were seen as clinically complex, (2) there is an uncertain and variable clinical pathway, (3) the nuance of investigations, (4) these conditions were difficult to therapeutically manage, and (5) there are barriers to developing a therapeutic relationship.ConclusionsFindings indicate that both patients and clinicians are dissatisfied with the current clinical care pathways for nausea and vomiting syndromes and functional dyspepsia. Recommendations included the development of more clinically relevant and discriminant tests, standardization of the diagnostic journey, and the adoption of a multidisciplinary approach to diagnosis and treatment.

Cannabinoid hyperemesis syndrome (CHS) is a poorly understood vomiting disorder associated with chronic cannabis use.To characterise patients experiencing CHS in North America and to obtain a population-based estimate of CHS treatment prevalence in Canada before and during the Covid-19 pandemic METHODS: Internet survey of 157 CHS sufferers in Canada and the United States. Administrative health databases for the province of Alberta (population 5 million) were accessed to measure emergency department (ED) visits for vomiting, with a concurrent diagnostic code for cannabis use. Three time periods of 1 year were assessed: prior to recreational cannabis legalisation (2017-2018), after recreational legalisation (2018-2019) and during the first year of the Covid-19 pandemic (2020-2021).Problematic cannabis use (defined as a CUDIT-R score ≥8) was universal among the survey cohort, and 59% and 68% screening for moderate or worse anxiety or depression, respectively. The overall treatment prevalence of CHS across all ages increased from 15 ED visits per 100,000 population (95% CI, 14-17) prior to legalisation, to 21 (95% CI, 20-23) after legalisation, to 32 (95% CI, 31-35) during the beginning of the Covid-19 pandemic (p 0.001). Treatment prevalence among chronic cannabis users was as high as 6 per 1000 in the 16-24 age group.Survey data suggest patients with CHS almost universally suffer from a cannabis use disorder, which has significant treatment implications. Treatment prevalence in the ED has increased substantially over a very short time period, with the highest rates seen during the Covid-19 pandemic.

Body surface gastric mapping (BSGM) is a new clinical tool for gastric motility diagnostics, providing high-resolution data on gastric myoelectrical activity. Artifact contamination was a key challenge to reliable test interpretation in traditional electrogastrography. This study aimed to introduce and validate an automated artifact detection and rejection system for clinical BSGM applications.Ten patients with chronic gastric symptoms generated a variety of artifacts according to a standardized protocol (176 recordings) using a commercial BSGM system (Alimetry, New Zealand). An automated artifact detection and rejection algorithm was developed, and its performance was compared with a reference standard comprising consensus labeling by 3 analysis experts, followed by comparison with 6 clinicians (3 untrained and 3 trained in artifact detection). Inter-rater reliability was calculated using Fleiss' kappa.Inter-rater reliability was 0.84 (95% CI:0.77-0.90) among experts, 0.76 (95% CI:0.68-0.83) among untrained clinicians, and 0.71 (95% CI:0.62-0.79) among trained clinicians. The sensitivity and specificity of the algorithm against experts was 96% (95% CI:91%-100%) and 95% (95% CI:90%-99%), respectively, vs 77% (95% CI:68%-85%) and 99% (95% CI:96%-100%) against untrained clinicians, and 97% (95% CI:92%-100%) and 88% (95% CI:82%-94%) against trained clinicians.An automated artifact detection and rejection algorithm was developed showinggt;95% sensitivity and specificity vs expert markers. This algorithm overcomes an important challenge in the clinical translation of BSGM and is now being routinely implemented in patient test interpretations.

Disorders of gastric function are highly prevalent, but diagnosis often remains symptom-based and inconclusive. Body surface gastric mapping is an emerging diagnostic solution, but current approaches lack scalability and are cumbersome and clinically impractical. We present a novel scalable system for non-invasively mapping gastric electrophysiology in high-resolution (HR) at the body surface.The system comprises a custom-designed stretchable high-resolution "peel-and-stick" sensor array (8 × 8 pre-gelled Ag/AgCl electrodes at 2 cm spacing; area 225 cmGastric mapping was successfully achieved non-invasively in all cases (16 male; 8 female; aged 20-73 years; BMI 24.2 ± 3.5). In all subjects, gastric electrophysiology and meal responses were successfully captured and quantified non-invasively (mean frequency 2.9 ± 0.3 cycles per minute; peak amplitude at mean 60 m postprandially with return to baseline in4 h). Spatiotemporal mapping showed regular and consistent wave activity of mean direction 182.7° ± 73 (74.7% antegrade, 7.8% retrograde, 17.5% indeterminate).BSGM is a new diagnostic tool for assessing gastric function that is scalable and ready for clinical applications, offering several biomarkers that are improved or new to gastroenterology practice.

Functional nausea and vomiting syndromes and gastroparesis, collectively grouped as nausea and vomiting syndromes (NVS), are overlapping conditions with incompletely understood pathophysiology. Gastric slow wave abnormalities are thought to contribute. This study aimed to systematically review and meta-analyze the prevalence of slow wave abnormalities measured by electrogastrography (EGG) in patients with NVS. MEDLINE, EMBASE, EMBASE classic, and CENTRAL databases were systematically searched for articles using EGG in adults (≥ 18 years) with NVS. EGG metrics of interest were percentage time in bradygastria, normogastria, and tachygastria as well as dominant frequency and dominant power. Outcomes were also compared with functional dyspepsia (FD), gastroesophageal reflux disease (GORD), and control cohorts. Seven hundred and sixty NVS patients and 308 controls were included from 24 studies. Overall, 64% of patients had EGG abnormalities. Average percent time in normogastria was low during fasting (50%; 95% CI 40–63%) and fed (53%; 95% CI 41–68%) states in patients, with substantial periods in fasting bradygastria (34.1%; 95% CI 25–47%) and postprandial tachygastria (21%; 95% CI 17–26%). Across gastric disorders, pooling of 84 studies showed a comparably high prevalence of EGG abnormalities in NVS (24 studies; n = 760) and GORD (13 studies; n = 427), compared to FD (47 studies; n = 1751) and controls (45 studies; n = 1027). Frequency-based gastric slow wave abnormalities are prominent in NVS. The strength and consistency of these associations across many studies suggests that gastric dysrhythmia may be an important factor in NVS, motivating the development of more reliable methods for their clinical assessment.

Objectives Electrogastrography (EGG) is a non-invasive method of measuring gastric electrophysiology. Abnormal gastric electrophysiology is thought to contribute to disease pathophysiology in patients with gastroduodenal symptoms, but this has not been comprehensively quantified in pediatric populations. This study aimed to quantify the abnormalities in gastric electrophysiology on EGG in neonatal and pediatric patients. Methods Databases were systematically searched for articles utilizing EGG in neonatal and pediatric patients (≤18 years). Primary outcomes were prevalence of abnormality, percentage of time in normal rhythm and power ratio. Secondary outcomes were correlations between patient symptoms and abnormal gastric electrophysiology on EGG. Results A total of 33 articles (1,444 participants) were included. EGG methodologies were variable. Pooled prevalence of abnormalities on EGG ranged from 61-86% in patients with functional dyspepsia (FD), gastro-esophageal reflux disease (GERD) and type 1 diabetes mellitus (T1DM). FD patients averaged 20.8% (p=0.011) less preprandial and 21.6% (p = 0.031) less postprandial time in normogastria compared to controls. Electrophysiological abnormalities were inconsistent in GERD. T1DM patients averaged 46.2% (p = 0.0003) less preprandial and similar (p = 0.32) postprandial time in normogastria compared to controls, and had a lower power ratio (SMD -2.20, 95%CI: -4.25, -0.15; p = 0.036). Symptom correlations with gastric electrophysiology were inconsistently reported. Conclusions Abnormalities in gastric electrophysiology were identifiable across a range of pediatric patients with gastroduodenal symptoms on meta-analysis. However, techniques have been inconsistent, and standardized and more reliable EGG methods are desirable to further define these findings and their potential utility in clinical practice.

Gastroesophageal reflux disease (GERD) is a commonly diagnosed gastrointestinal disorder, with a substantial impact on the quality of life. The underlying pathophysiology of GERD is multifactorial and incompletely understood. Abnormal gastric electrical activity, measured using electrogastrography (EGG), may contribute. This study aimed to systematically review and meta-analyse the existing literature in which EGG was used in patients with GERD. Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normogastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality. In total, 591 participants (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD − 1.18, 95%CI: − 1.84, − 0.52) and 18.7% (SMD − 1.11, 95%CI: − 1.55, − 0.68) less of the preprandial and postprandial recording time in normogastric frequency ranges, respectively, compared to healthy controls. The dominant frequency, dominant power and power ratio were not significantly different to healthy controls in the preprandial and postprandial periods. The pooled prevalence of any EGG abnormality was significantly greater in patients with GERD than in healthy controls [46% (95%CI: 39–64%) vs. 10% (95%CI: 4–23%); p

INTRODUCTION The incidence of peptic ulcer disease (PUD) has been decreasing over time with Helicobacter pylori eradication and use of acid-suppressing therapies. However, PUD remains a common cause of hospitalization in the United States. We aimed to evaluate contemporary national trends in the incidence, treatment patterns, and outcomes for PUD-related hospitalizations and compare care delivery by hospital rurality. METHODS Data from the National Inpatient Sample were used to estimate weighted annual rates of PUD-related hospitalizations. Temporal trends were evaluated by joinpoint regression and expressed as annual percent change with 95% confidence intervals (CIs). We determined the proportion of hospitalizations requiring endoscopic and surgical interventions, stratified by clinical presentation and rurality. Multivariable logistic regression was used to assess independent predictors of in-hospital mortality and postoperative morbidity. RESULTS There was a 25.8% reduction (P < 0.001) in PUD-related hospitalizations from 2005 to 2014, although the rate of decline decreased from -7.2% per year (95% CI: 13.2% to -0.7%) before 2008 to -2.1% per year (95% CI: 3.0% to -1.1%) after 2008. In-hospital mortality was 2.4% (95% CI: 2.4%-2.5%). Upper endoscopy (84.3% vs 78.4%, P < 0.001) and endoscopic hemostasis (26.1% vs 16.8%, P < 0.001) were more likely to be performed in urban hospitals, whereas surgery was performed less frequently (9.7% vs 10.5%, P < 0.001). In multivariable logistic regression, patients managed in urban hospitals were at higher risk for postoperative morbidity (odds ratio 1.16 [95% CI: 1.04-1.29]), but not death (odds ratio 1.11 [95% CI: 1.00-1.23]). DISCUSSION The rate of decline in hospitalization rates for PUD has stabilized over time, although there remains significant heterogeneity in treatment patterns by hospital rurality.

Background/Aims The pathophysiology of jackhammer esophagus (JE) remains unknown but may be related to gastroesophageal reflux disease or medication use. We aim to determine if pathologic acid exposure or the use of specific classes of medications (based on the mechanism of action) is associated with JE. Methods High-resolution manometry (HRM) studies from November 2013 to March 2019 with a diagnosis of JE were identified and compared to symptomatic control patients with normal HRM. Esophageal acid exposure and medication use were compared between groups. Multivariate regression analysis was performed to look for predictors of mean distal contractile integral. Results Forty-two JE and 127 control patients were included in the study. Twenty-two (52%) JE and 82 (65%) control patients underwent both HRM and ambulatory pH monitoring. Two (9%) JE patients and 14 (17%) of controls had evidence of abnormal acid exposure (DeMeester score > 14.7); this difference was not significant (P = 0.290). Thirty-six (86%) JE and 127 (100%) control patients had complete medication lists. Significantly more JE patients were on long-acting beta agonists (LABA) (JE = 5, control = 4; P = 0.026) and calcium channel blockers (CCB) (JE = 5, control = 3; P = 0.014). Regular opioids (β = 0.298, P = 0.042), CCB (β = 0.308, P = 0.035), and inhaled anticholinergics (β = 0.361, P = 0.049) predicted mean distal contractile integral (R2 = 0.082, F = 4.8; P = 0.003). Conclusions Pathologic acid exposure does not appear to be associated with JE. JE patients had increased CCB and LABA use. The unexpected finding of increased LABA use warrants more investigation and may provide support for a cholinergic etiology of JE. (J Neurogastroenterol Motil 2020;26:224-231)

Background A growing body of evidence suggests that dysbiosis contributes to the onset and symptomatology of irritable bowel syndrome (IBS) and other functional bowel disorders. Changes to the gastrointestinal microbiome may contribute to the underlying pathophysiology of IBS. Methods The present review summarizes the potential effects of microbiome changes on GI transit, intestinal barrier function, immune dysregulation and inflammation, gut–brain interactions and neuropsychiatric function. Results A multimodal approach to IBS management is recommended in accordance with current Canadian guidelines. Pharmacologic treatments are advised to target the presumed underlying pathophysiological mechanism, such as dysregulation of GI transit, peristalsis, intestinal barrier function and pain signalling. The management plan for IBS may also include treatments directed at dysbiosis, including dietary modification and use of probiotics, which may promote the growth of beneficial bacteria, affect intestinal gas production and modulate the immune response; and the administration of periodic short courses of a nonsystemic antibiotic such as rifaximin, which may re-establish microbiota diversity and improve IBS symptoms. Conclusion Dysregulated host–microbiome interactions are complex and the use of microbiome-directed therapies will necessarily be empiric in individual patients. A management algorithm comprising microbiome- and nonmicrobiome-directed therapies is proposed.

BACKGROUND: Functional gastroduodenal disorders include functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis. These disorders are common, but their overlapping symptomatology poses challenges to diagnosis, research, and therapy. This study aimed to introduce and validate a standardized patient symptom-logging system and App to aid in the accurate reporting of gastroduodenal symptoms for clinical and research applications. METHODS: The system was implemented in an iOS App including pictographic symptom illustrations, and two validation studies were conducted. To assess convergent and concurrent validity, a diverse cohort with chronic gastroduodenal symptoms undertook App-based symptom logging for 4 h after a test meal. Individual and total post-prandial symptom scores were averaged and correlated against two previously validated instruments: PAGI-SYM (for convergent validity) and PAGI-QOL (for concurrent validity). To assess face and content validity, semi-structured qualitative interviews were conducted with patients. KEY RESULTS: App-based symptom reporting demonstrated robust convergent validity with PAGI-SYM measures of nausea (rS =0.68), early satiation (rS =0.55), bloating (rS =0.48), heartburn (rS =0.47), upper gut pain (rS =0.40), and excessive fullness (rS =0.40); all p

ImportanceChronic nausea and vomiting syndromes (NVS) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking.ObjectiveA novel medical device enabling non-invasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology.DesignA case-control study where BSGM was performed in NVS patients and matched controls using Gastric Alimetry (Alimetry, New Zealand), comprising a conformable high-resolution array (8×8 electrodes; 20 mm inter-electrode spacing), wearable Reader, and validated symptom logging App. Continuous measurement encompassed a fasting baseline (30 min), 482 kCal meal (10 min), and 4-hr post-prandial recording.SettingMulticenter study in Auckland, New Zealand and Calgary, Canada.Participants43 NVS patients (gastroparesis and Rome IV chronic NVS) and 43 matched controls.Main outcomes and measuresSymptom severity and quality of life were measured using Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM), Gastroparesis Cardinal Symptom Index (GCSI), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL) instruments. Health psychology metrics included the State Trait Anxiety Inventory Short Form (STAI-SF) and Patient Health Questionnaire-2 (PHQ-2) questionnaires. Spectral analyses including frequency, amplitude, and fed-fasting power ratio. Spatial biomarker analyses included spatial frequency stability and average spatial covariance.ResultsMeal responses were impaired in NVS, with reduced amplitudes compared to controls (median 23.3 vs 38.0 µV, p0.05). A majority (62%) had normal BSGM studies (all biomarkers non-significant vs controls) with increased psychological comorbidities (43.5% vs 7.7%; p=0.03) and anxiety scores (median 16.5 vs 13.0; p=0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with test biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, bloating; all r>0.35, pConclusions and RelevanceNVS patients share overlapping symptoms, but comprise distinct underlying phenotypes as revealed by a novel BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and allocations into therapeutic trials.Key PointsQuestionHow does body surface gastric mapping, a novel non-invasive medical device for evaluating gastric motility, aid assessment of patients with chronic nausea and vomiting.FindingsTwo subgroups were revealed in chronic nausea and vomiting syndromes, which could not be differentiated by symptoms alone. Where body surface gastric mapping was normal, symptoms correlated with psychological comorbidities, and where body surface gastric mapping was abnormal, symptoms correlated with gastric electrophysiology metrics.MeaningDistinct phenotypes revealed by body surface gastric mapping correlate with symptoms, which should inform targeted clinical management and allocations into therapeutic trials.

Background Cutaneous electrogastrography (EGG) is a non-invasive technique that detects gastric bioelectrical slow waves, which in part govern the motility of the stomach. Changes in gastric slow waves have been associated with a number of functional gastric disorders, but to date accurate detection from the body-surface has been limited due to the low signal-to-noise ratio. The main aim of this study was to develop a flexible active-electrode EGG array. Methods: Two Texas Instruments CMOS operational amplifiers: OPA2325 and TLC272BID, were benchtop tested and embedded in a flexible linear array of EGG electrodes, which contained four recording electrodes at 20-mm intervals. The cutaneous EGG arrays were validated in ten weaner pigs using simultaneous body-surface and serosal recordings, using the Cyton biosensing board and ActiveTwo acquisition systems. The serosal recordings were taken using a passive electrode array via surgical access to the stomach. Signals were filtered and compared in terms of frequency, amplitude, and phase-shift based on the classification of propagation direction from the serosal recordings. Results: The data were compared over 709 cycles of slow waves, with both active cutaneous EGG arrays demonstrating comparable performance. There was an agreement between frequencies of the cutaneous EGG and serosal recordings (3.01 ± 0.03 vs 3.03 ± 0.05 cycles per minute; p = 0.75). The cutaneous EGG also demonstrated a reduction in amplitude during abnormal propagation of gastric slow waves (310 ± 50 µV vs 277 ± 9 µV; p p = 0.36). Conclusion: A sparse linear cutaneous EGG array was capable of reliably detecting abnormalities of gastric slow waves. For more accurate characterization of gastric slow waves, a two-dimensional body-surface array will be required.

BackgroundFunctional gastroduodenal disorders include functional dyspepsia, chronic nausea and vomiting syndromes, and gastroparesis. These disorders are common, but their overlapping symptomatology poses challenges to diagnosis, research, and therapy. This study aimed to introduce and validate a standardized patient symptom-logging system and App to aid in the accurate reporting of gastroduodenal symptoms for clinical and research applications.MethodsThe system was implemented in an iOS App including pictographic symptom illustrations, and two validation studies were conducted. To assess convergent and concurrent validity, a diverse cohort with chronic gastroduodenal symptoms undertook App-based symptom logging for 4-hours after a test meal. Individual and total post-prandial symptom scores were averaged and correlated against two previously validated instruments: PAGI-SYM (for convergent validity) and PAGI-QOL (for concurrent validity). To assess face and content validity, semi-structured qualitative interviews were conducted with patients.Key ResultsApp-based symptom reporting demonstrated robust convergent validity with PAGI-SYM measures of nausea (rS=0.68), early satiation (rS=0.55), bloating (rS=0.48), heartburn (rS=0.47), upper gut pain (rS=0.40) and excessive fullness (rS=0.40); all p.001 (n=79). The total App-reported Gastric Symptom Burden Score correlated positively with PAGI-SYM (rS=0.56; convergent validity; p.001), and negatively with PAGI-QOL (rS=-0.34; concurrent validity; p=0.002). Interviews demonstrated that the pictograms had adequate face and content validity.Conclusions and InferencesThe continuous patient symptom-logging App demonstrated robust convergent, concurrent, face, and content validity when used within a 4-hour post-prandial test protocol. The App will enable standardized symptom reporting and is anticipated to provide utility in both research and clinical practice.

Gastric disorders are increasingly prevalent, but reliable clinical tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a non-invasive method for the detection of gastric electrophysiological biomarkers including slow wave direction, which have correlated with symptoms in patients with gastroparesis and functional dyspepsia. However, no studies have validated the relationship between gastric slow waves and body surface activation profiles. This study aimed to comprehensively evaluate the relationship between gastric slow waves and body-surface recordings. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32×6 electrodes at 4 mm resolution) and abdominal surface (8×8 at 20 mm inter-electrode spacing) in a porcine model. BSGM signals were extracted based on a combination of wavelet and phase information analyses. A total of 1185 individual cycles of slow waves assessed, out of which 897 (76%) were normal antegrade waves, occurring in 10/14 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, p = 0.43) as well as the direction of propagation (p = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow waves in terms either or both temporal and spatial abnormalities was demonstrated. These results validate BSGM as a suitable method for non-invasively and accurately detecting gastric slow wave activation profiles from the body surface.Single sentence summarySimultaneous recordings of the stomach using serosal and body-surface electrode arrays demonstrated reliable detection of frequency and classification of propagation.

Background There are little data evaluating the performance of the 3-dimensional high-definition anorectal manometry (3D-HDAM) system in the diagnosis of dyssynergic defecation. Physical properties of the thicker, rigid, 3D-HDAM probe may have implications on the measurements of anorectal pressures. Aim Our aim was to compare 3D-HDAM to balloon expulsion test and magnetic resonance (MR) defecography. Methods Consecutive constipated patients referred for anorectal function testing at the Calgary Gut Motility Centre (Calgary, Canada) between 2014 and 2019 were assessed. All patients underwent anorectal manometry with the 3D-HDAM probe, and a subset underwent BET or MR defecography. Anorectal manometric variables were compared between patients who had normal and abnormal BET. Results Over the study period, 81 patients underwent both 3D-HDAM and BET for symptoms of constipation. 52 patients expelled the balloon within 3 minutes. Patients with abnormal BET had significantly lower rectoanal pressure differential (RAPD) (-61 vs. -31 mmHg for normal BET, p = 0.03) and defecation index (0.29 vs. 0.56, p = 0.03). On logistic regression analysis, RAPD (OR: 0.99, 95% CI: 0.97-0.99, p = 0.03) remained a negative predictor of abnormal BET. On ROC analysis, RAPD had an AUC of 0.65. There was good agreement between dyssynergic patterns on 3D-HDAM and defecographic evidence of dyssynergia (sensitivity 80%, specificity 90%, PLR 9, NLR 0.22, accuracy 85%). Conclusions Manometric parameters, when measured with the 3D-HDAM probe, poorly predict prolonged balloon expulsion time. RAPD remains the best predictor of prolonged balloon expulsion time. The 3D-HDAM probe may not be the ideal tool to diagnose functional defecatory disorders.

Background Gastrointestinal (GI) motility and functional disorders comprise over two-third of referrals to GI specialists yet training programs are disproportionately focused on endoscopy, inflammatory bowel disease and liver disease. Trainees at many centres receive minimal or no formal training in motility disorders and have little or no exposure to motility testing. Our purpose was to develop an educational intervention to address this learning need. Methods We designed a formal training program comprised of didactic sessions, workshops and hands-on motility sessions with live demonstrations designed to be held over the course of a weekend. Faculty for the course were experienced GI motility experts from across Canada. Resident trainees from all Canadian GI fellowship programs were invited to attend. Pre- and post-tests were administered to measure the baseline learning needs and the impact of the program. Course evaluations were completed by attendees. Results Three annual courses were offered over the past 3 years. Both adult and paediatric gastroenterology trainees attended the programs. The majority of training programs from Canada were represented. Baseline testing of attendees revealed a fundamental lack of understanding of GI motility concepts and their clinical implications. Postcourse test scores demonstrated a significant improvement in motility knowledge. Course evaluations of the content and faculty presentations received uniformly positive reviews. Conclusions There is a pervasive lack of clinical knowledge of GI motility among Canadian GI subspecialty trainees. A focused weekend intensive course is one step in addressing this learning need.

Background & aims Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. Methods A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. Results Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. Conclusions Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.

BackgroundFunctional dyspepsia (FD) is a common gastroduodenal disorder, yet its pathophysiology remains poorly understood. Bioelectrical gastric slow wave abnormalities are thought to contribute to its multifactorial pathophysiology. Electrogastrography (EGG) has been used to record gastric electrical activity, however the clinical associations require further evaluation.AimsThis study aimed to systematically assess the clinical associations of EGG in FD.MethodsMEDLINE, EMBASE, and CENTRAL databases were systematically searched for articles using EGG in adults with FD. Primary outcomes were percentage normal vs abnormal rhythm (bradygastria, normogastria, tachygastria). Secondary outcomes were dominant power, dominant frequency, percentage coupling and the meal responses.Results1751 FD patients and 555 controls from 47 studies were included. FD patients spent less time in normogastria while fasted (SMD −0.74; 95%CI −1.22 - −0.25) and postprandially (−0.86; 95%CI −1.35 - −0.37) compared to controls. FD patients also spent more fasted time in bradygastria (0.63; 95%CI 0.33 – 0.93) and tachygastria (0.45; 95%CI 0.12 – 0.78%). The power ratio (−0.17; 95%CI −0.83 - 0.48), and dominant frequency meal-response ratio (0.06; 95%CI −0.08 - 0.21) were not significantly different to controls. Correlations between EGG metrics and the presence and timing of FD symptoms were inconsistent. EGG methodologies were diverse and variably applied.ConclusionAbnormal gastric slow wave rhythms are a consistent abnormality present in FD, as defined by EGG, and therefore likely play a role in pathophysiology. The aberrant electrophysiology identified in FD warrants further investigation, including into underlying mechanisms, associated spatial patterns, and symptom correlations.

Functional nausea and vomiting syndromes and gastroparesis, collectively grouped as nausea and vomiting syndromes (NVS), are overlapping conditions with incompletely understood pathophysiology. Gastric slow wave abnormalities are thought to contribute.This study aimed to systematically review and meta-analyze the prevalence of slow wave abnormalities measured by electrogastrography (EGG) in patients with NVS.MEDLINE, EMBASE, EMBASE classic, and CENTRAL databases were systematically searched for articles using EGG in adults (≥ 18 years) with NVS. EGG metrics of interest were percentage time in bradygastria, normogastria, and tachygastria as well as dominant frequency and dominant power. Outcomes were also compared with functional dyspepsia (FD), gastroesophageal reflux disease (GORD), and control cohorts.Seven hundred and sixty NVS patients and 308 controls were included from 24 studies. Overall, 64% of patients had EGG abnormalities. Average percent time in normogastria was low during fasting (50%; 95% CI 40-63%) and fed (53%; 95% CI 41-68%) states in patients, with substantial periods in fasting bradygastria (34.1%; 95% CI 25-47%) and postprandial tachygastria (21%; 95% CI 17-26%). Across gastric disorders, pooling of 84 studies showed a comparably high prevalence of EGG abnormalities in NVS (24 studies; n = 760) and GORD (13 studies; n = 427), compared to FD (47 studies; n = 1751) and controls (45 studies; n = 1027).Frequency-based gastric slow wave abnormalities are prominent in NVS. The strength and consistency of these associations across many studies suggests that gastric dysrhythmia may be an important factor in NVS, motivating the development of more reliable methods for their clinical assessment.

Gastroesophageal reflux disease (GERD) is a commonly diagnosed gastrointestinal disorder, with a substantial impact on the quality of life. The underlying pathophysiology of GERD is multifactorial and incompletely understood. Abnormal gastric electrical activity, measured using electrogastrography (EGG), may contribute. This study aimed to systematically review and meta-analyse the existing literature in which EGG was used in patients with GERD.Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normogastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality.In total, 591 participants (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD - 1.18, 95%CI: - 1.84, - 0.52) and 18.7% (SMD - 1.11, 95%CI: - 1.55, - 0.68) less of the preprandial and postprandial recording time in normogastric frequency ranges, respectively, compared to healthy controls. The dominant frequency, dominant power and power ratio were not significantly different to healthy controls in the preprandial and postprandial periods. The pooled prevalence of any EGG abnormality was significantly greater in patients with GERD than in healthy controls [46% (95%CI: 39-64%) vs. 10% (95%CI: 4-23%); p 0.0001]. Correlations between GERD symptoms and EGG recordings were inconsistently studied. EGG techniques were heterogeneous.Consistent abnormalities in gastric slow-wave activity, as measured by EGG, were identified in adults with GERD. Further investigation into these abnormalities using novel emerging electrophysiology techniques is desirable, to better define their contribution toward GERD pathophysiology.

Purpose of review To review recent clinical evidence surrounding the use of cannabinoids and cannabis in gastrointestinal diseases, particularly inflammatory bowel disease (IBD) and functional gut disorders. A second aim is to evaluate the current status of gastrointestinal related adverse effects which have been linked to cannabis use, specifically cannabis hyperemesis syndrome (CHS) and acute pancreatitis. Recent findings Observational and prospective studies suggest that cannabinoids improve IBD symptoms. Small prospective clinical trials have not shown any effects on objective inflammatory findings, other than one recent paper in ulcerative colitis, in abstract form only, which suggests endoscopic improvement. Short duration mechanistic studies in functional gut disorders suggest cannabinoids may attenuate gastric emptying and slow colonic motility but appear to have less effect on sensory thresholds in the gut. Summary In general, while mostly uncontrolled data suggests cannabis may improve symptoms in IBD (and to a lesser degree functional gut disorders), this is not likely due to any substantial anti-inflammatory effect. Much remains unknown about CHS etiology and complete abstinence from cannabinoids remains the generally accepted treatment strategy. Population-based studies do not suggest that cannabis use is related to acute pancreatitis. Further research is certainly warranted.

Functional bowel disorders (FBDs) are the most common gastrointestinal problems managed by physicians. We aimed to assess the burden of chronic symptomatic FBDs on ambulatory care delivery in the United States and evaluate patterns of treatment.Data from the National Ambulatory Medical Care Survey were used to estimate annual rates and associated costs of ambulatory visits for symptomatic irritable bowel syndrome, chronic functional abdominal pain, constipation, or diarrhea. The weighted proportion of visits associated with pharmacologic and nonpharmacologic (stress/mental health, exercise, diet counseling) interventions were calculated, and predictors of treatment strategy were evaluated in multivariable multinomial logistic regression.From 2007-2015, approximately 36.9 million (95% CI, 31.4-42.4) weighted visits in patients of non-federally employed physicians for chronic symptomatic FBDs were sampled. There was an annual weighted average of 2.7 million (95% CI, 2.3-3.2) visits for symptomatic irritable bowel syndrome/chronic abdominal pain, 1.0 million (95% CI, 0.8-1.2) visits for chronic constipation, and 0.7 million (95% CI, 0.5-0.8) visits for chronic diarrhea. Pharmacologic therapies were prescribed in 49.7% (95% CI, 44.7-54.8) of visits compared to nonpharmacologic interventions in 19.8% (95% CI, 16.0-24.2) of visits (P.001). Combination treatment strategies were more likely to be implemented by primary care physicians and in patients with depression or obesity. The direct annual cost of ambulatory clinic visits alone for chronic symptomatic FBDs is approximately US$358 million (95% CI, 233-482 million).The management of chronic symptomatic FBDs is associated with considerable health care resource use and cost. There may be an opportunity to improve comprehensive FBD management because fewer than 1 in 5 ambulatory visits include nonpharmacologic treatment strategies.

BACKGROUND Gastroparesis, defined by delayed gastric emptying in the absence of mechanical outlet obstruction, is a frequent neuropathic complication of diabetes mellitus, and effective treatments are lacking. Prucalopride is a pan-gut prokinetic with selective agonist effects on serotonin 5-HT4 receptors in the gut. This study aimed to assess the effect of prucalopride 4 mg daily on Gastroparesis Cardinal Symptom Index (GCSI), meal-related symptom score (MRSS), and gastric emptying rate in diabetic or connective tissue disease (CTD)-related gastroparesis patients. METHODS This was a double-blind crossover trial of four-week treatment periods with prucalopride or placebo divided by two weeks of washout. GSCI, MRSS, gastric emptying scintigraphy, PAGI-SYM, and PAGI-QoL were assessed at baseline and the end of each treatment period. Daily bowel movement (BM) frequency and gastrointestinal symptoms were recorded in each period. KEY RESULTS Fifteen gastroparesis patients (13 diabetic, 2 CTD) were enrolled. GCSI scores were lower than baseline but not different between treatment arms. MRSS scores over time or cumulative score were not significantly different between groups. Gastric emptying was more rapid in the prucalopride treatment period, with mean four-hour meal retention of 22 ± 6% in PRU period vs 40 ± 9% in the placebo period (P = 0.05). Weekly BM frequency was significantly higher in prucalopride than placebo periods (10.5 ± 1.8 vs 7.5 ± 0.8, P