Studies demonstrate an overlap of constipation with gastroparesis and functional dyspepsia, but the impact of treatments that target constipation on improving upper gastrointestinal (UGI) symptoms is unexplored. We quantified the effects of constipation medication therapies on UGI and constipation symptom severity in subjects presenting with symptoms of gastroparesis.

Fifty-six subjects with symptoms of gastroparesis underwent concurrent wireless motility capsule and gastric emptying scintigraphy and were recommended to receive either a new medication therapy for constipation or a change in constipation therapy based on investigator interpretation of test results. Gastroparesis Cardinal Symptom Index (GCSI), upper abdominal pain, and constipation scores were compared between baseline and 6 months. Data were compared between delayed or non-delayed gastric emptying and the presence or absence of slow colonic transit.

Subjects with slow colonic transit had improvements in GCSI (p = 0.007) and constipation scores (p = 0.004) after treatment with a new or changed constipation medication, with the delayed emptying subgroup driving GCSI improvements (p = 0.004). Reductions in nausea/vomiting (p = 0.02) and early satiety/fullness subscores (p = 0.002) with trends to improved bloating/distention subscores (p = 0.06) were observed in this subgroup, but upper abdominal pain was unchanged. Subjects with normal colonic transit showed no improvement in GCSI scores regardless of gastric emptying status (p > 0.05).

Identifying and treating delayed colonic transit in gastroparetic (delayed gastric emptying) subjects improves global UGI symptoms as well as selected individual symptoms. Evaluation of whole gut motility as well as recognizing and managing extragastric delay may promote improved outcomes in these patients.

ClinicalTrials.gov: NCT02022826.

Improper gastric emptying is implicated in several gastrointestinal disorders and may result from disrupted electromechanical coupling of the gastroduodenal junction (GDJ). Rhythmic "slow waves" and myogenic "spikes" are bioelectrical mechanisms that, alongside neural and hormonal co-factors, control GDJ motility.

To characterize the electromechanical effects of prokinetic (erythromycin) infusion and truncal vagotomy on pre-clinical in vivo porcine models.

Following ethical approval, the GDJ was exposed in anesthetized crossbreed weaner pigs (N = 10), and custom high-resolution electrodes were applied to the serosal surface. An EndoFLIP catheter (Medtronic, USA) was inserted orally and positioned across the pylorus to measure luminal diameter. In all subjects, control periods preceded intravenous infusion of erythromycin. In five of those subjects, truncal vagotomy was performed approximately an hour post-infusion, before recording was resumed.

Compared to control recordings, erythromycin increased contractile amplitude ([2.9 ± 1.1] mm vs. [2.2 ± 0.9] mm; p = 0.002) and was associated with more consistent gastric slow-wave rhythms and increased amplitude of slow waves and spikes. Surgical vagotomy immediately decreased contractile amplitude ([2.90 ± 1.1] mm vs. [1.2 ± 0.6] mm; p = 0.049) and was associated with reduced slow-wave amplitude, increased gastric and duodenal slow-wave frequencies, and decreased spike patch coverage.

In conclusion, prokinetics and vagotomy produced opposing effects on GDJ electromechanical coupling and could inform diagnostic and interventional practices for patients with pathophysiological complications of this region.

Upper gastrointestinal concerns including gastroparesis-like symptoms affect a large portion of the population, and determining the culprit condition can be difficult due to largely shared symptoms, clinical course, pathophysiology, and treatment pathways. The understanding of gastric neuromuscular disorders (GNDs) is emerging as a heterogeneous group encompassing conditions from gastroparesis to functional dyspepsia with chronic nausea, early satiety, bloating, or abdominal pain, irrespective of gastric emptying. This article aims to review the current concepts in gastroparesis and GNDs including pathophysiology, diagnosis, and management. While some established standards in their diagnosis and management exist, a number of novel diagnostics are becoming available. Durable therapeutic options are notably limited for such common conditions with chronic and debilitating symptoms, and neuromodulators may play a key role in symptom control, which has been previously under-recognized and underutilized. Advances in both pharmacologic treatment targets as well as noninvasive and invasive interventions and devices show promise in improving the experience of patients with gastroparesis-like symptoms. At this time, treatment of GNDs requires comprehensive multidisciplinary care from providers to achieve successful treatment outcomes.

The gastroduodenal junction is uniquely capable of regulating digestive functions in the gastrointestinal system. The pyloric sphincter, which demarcates the stomach from the small intestine, acts as a mechanical and electrical barrier, isolating each organ, thus enabling independent behaviors that are critical for proper digestion. Unique electrical patterns in the stomach, pylorus, and duodenum underpin the distinct contractile patterns of these regions, and improper organization of these mechanical behaviors leads to clinical conditions such as gastroparesis and dumping syndrome. For this reason, the gastroduodenal junction should be a focal point in investigations of novel biomarkers of gastrointestinal dysfunction. This review summarizes the current knowledge of bioelectrical and mechanical characteristics of the gastroduodenal junction, as well as the relevant underlying anatomy. As there is limited documentation of physiological recordings from the gastroduodenal junction of humans, inferences are made from animal studies and from measurements taken from other regions of the gastrointestinal tract, where appropriate. We suggest hypotheses on gastroduodenal electromechanical coupling and propose further studies to support or reject these ideas. Improved physiological understanding of this region, and the advent of novel diagnostic and therapeutic tools are crucial aspects for the future of clinical gastrointestinal medicine.

Chronic neurogastroduodenal disorders are challenging to manage, with therapy often initiated on a trial and error basis. Prokinetics play a significant role in management, but responses are variable and have been associated with adverse events, impacting widespread use. We investigated whether body surface gastric mapping (BSGM) biomarkers (using Gastric Alimetry ® ) could inform patient selection for prokinetic therapy.

Patients with chronic gastroduodenal symptoms taking oral prokinetic, regardless of gastric emptying status, were prospectively recruited and underwent BSGM (30 m baseline, 482 kcal standardised meal, 4 h postprandial recording) whilst off prokinetic. Patients were followed up with daily symptom diaries. A subset was compared to matched patients not taking prokinetics. Prokinetic responders were defined based on symptom improvement greater than a minimum clinically important difference methodology.

42 patients (88% female; median age 36; median BMI 26) taking prokinetics were analysed. Prokinetic prescribing, compared to matched patients, was independent of BSGM metrics (p>0.15). In patients on existing prokinetics (withheld for BSGM), lower amplitudes predicted reduced symptom burden, whereas low rhythm stability predicted a worse symptom burden (p<0.05). In prokinetic-naive patients (i.e. started on a prokinetic during the study), a lower postprandial amplitude predicted responders (mean 37.5±10.6 uV in responders [n=5] vs mean 54.8±6.6 uV among non-responders [n=3], p=0.047).

Gastric Alimetry biomarkers may help in the prediction of prokinetic response in patients with chronic gastroduodenal symptoms. Lower post-prandial amplitudes, indicating a reduced meal response, appear to predict benefit, whilst impaired rhythm stability predicted poorer therapeutic response.

Buspirone shows promise in treating disorders of gut-brain interaction (DGBIs), particularly functional dyspepsia. However, findings have been mixed.

We systematically searched for prospective studies testing buspirone for any upper gastrointestinal DGBI in 4 databases (Cochrane, PubMed, Scopus, and PsycInfo). The primary outcome was any validated measure of gastrointestinal symptoms. Anxiety, depression and adverse events were secondary outcomes. For randomized controlled trials (RCTs), we performed random-effects meta-analysis of the standardized mean difference (SMD) in post-treatment scores between buspirone and control groups. Risk of bias in RCTs was assessed using the Cochrane Common Mental Disorders Depression Anxiety and Neurosis Group (CCDAN) scale.

Ten studies (n = 283) met inclusion criteria, comprising 5 RCTs, 1 N-of-1 trial, 1 cohort, 1 case series, and 2 case reports. Tolerability of buspirone was good. In meta-analysis, buspirone produced a non-significant improvement in functional dyspepsia/gastroparesis symptoms compared to placebo (SMD = -0.14; 95% CI, -0.44 to 0.17; P = 0.39; I2 = 0%; Nstudies = 3). Of individual symptoms, buspirone improved bloating severity more than placebo (SMD = -0.41; 95% CI, -0.77 to -0.04; P = 0.03; Nstudies = 2) but did not improve post-prandial fullness (P = 0.24, Nstudies = 2) or nausea (P = 0.75, Nstudies = 2). All RCTs included in the meta-analysis were good quality but most treated for only 4 weeks.

We found that buspirone did not improve functional dyspepsia symptoms more than placebo, though studies were small. Buspirone showed benefit for bloating severity, albeit based on few studies. Larger and longer trials of buspirone, targeting more defined groups such as patients with bloating, are warranted.

To establish a consensus on the definition and management of idiopathic gastroparesis, international experts (selected by neurogastroenterology and motility societies and initiated by the Rome Foundation) devised 144 statements using the Delphi method, with at least 80% agreement required. This consensus defined idiopathic gastroparesis as the presence of symptoms associated with delayed gastric emptying in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms. Frequently co-existing symptoms are early satiation and postprandial fullness. Diagnosis requires the presence of these symptoms alongside delayed gastric emptying, measured by a 4 h scintigraphy or gastric emptying breath test of a mixed composition meal in the absence of mechanical obstruction. Therapeutic options with proven efficacy were sparse. Dietary adjustments, nutritional support (per guidelines from the European Society for Clinical Nutrition and Metabolism for substantial weight loss or intractable vomiting), and opioid cessation were recommended by a consensus opinion. Antiemetic and prokinetic agents were also considered potentially beneficial. This consensus offers a global perspective on idiopathic gastroparesis.

High-frequency electrical stimulation therapy (gastric electrical stimulation, GES) is a treatment option for gastroparesis of various genesis. The best indication and prognostic parameters have not yet been conclusively determined.Retrospective analysis of all gastroparesis patients implanted with a GES device between 2011 and 2020. Clinical response was measured before and after implantation using a validated Gastroparesis Cardinal Symptom Index (GCSI) (maximum score: 5, minimum score: 0). Other study endpoints included: subjective symptom course (no improvement, partial improvement, or severe improvement) and change in gastroparesis medication.A GES device was implanted in 42 patients (16 M: 26 F, mean age 45 years). The etiology of gastroparesis was diabetic (n=23), idiopathic (n=10) or postoperative (n=9). Eleven patients (26%) had undergone one or more invasive treatments before. GCSI score of the total group was 3.23 preoperatively. The median follow-up time was 12 months. In the overall group, significant improvement in GCSI score was found 3, 6, 9, and 12 months postoperatively-regardless of indication. In multivariate analysis, disease duration of >30 months was associated with a significantly decreased GCSI score at 12 months (p<0.001). Approximately 40% of patients were able to discontinue or significantly reduce gastroparesis medication. At the end of follow-up, 81% of patients reported partial or major improvement in symptoms. During the follow-up period, three patients (7%) died.Gastric electrical neurostimulation is an effective and safe option for refractory gastroparesis-regardless of the underlying disease.

Diabetic gastrointestinal neuropathy is a diabetes-related complication, associated with a complex interplay of hyperglycemic damage, autoimmune responses, oxidative stress, gastrointestinal hormones, and vascular insufficiency. Patients with diabetes should be monitored and therapeutic intervention introduced to prevent neuropathy due to diabetes prior to "the point of no return". Determining gastric bioelectrical activity by body surface gastric mapping may be a promising option to monitor diabetic gastrointestinal neuropathy.

High-resolution electrogastrography (HR-EGG) presents a new paradigm in diagnosing and treating functional gastroduodenal disorders. Unlike traditional electrogastrography, HR-EGG allows for a more precise analysis of the gastric electrical activity, offering improved diagnostic accuracy. Recent studies have revealed the clinical potential of HR-EGG, particularly in detecting abnormal electrical patterns in patients with functional dyspepsia and gastroparesis, supporting the development of novel therapeutic strategies. The non-invasive HR-EGG method has shown promise in identifying new biomarkers. Moreover, further integration of artificial intelligence, is expected to enhance diagnostic efficiency and develop more refined treatment models for functional gastrointestinal disorders.

Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades.

The objectives of this review are to develop an understanding of the goals of treatment, the evidence-based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence-based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof-of-efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof-of-efficacy, placebo-controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis.

Pharmacologic therapies for symptoms of gastroparesis (GP) have limited efficacy, and it is difficult to predict which patients will respond. In this study, we implemented a machine learning model to predict the response to prokinetics and/or neuromodulators in patients with GP-like symptoms.

Subjects with suspected GP underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their GP Cardinal Symptom Index at 6 months decreased by ≥1 from baseline. A machine learning model was trained using lasso regression, ridge regression, or random forest. Five-fold cross-validation was used to train the models, and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set.

Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were nonresponders. A ridge regression model with the variables, such as body mass index, infectious prodrome, delayed gastric emptying scintigraphy, no diabetes, had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with gastric emptying time, duodenal motility index, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75).

This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with GP-like symptoms.

The treatment of gastroparesis can be difficult in everyday clinical practice. The aim of this anonymous survey of members of the Arbeitsgemeinschaft Leitender Gastroenterologischer Krankenhausärzte e.V. (ALGK) was to investigate the management of gastroparesis care in Germany.

The ALGK conducted a member survey using a standardized anonymous questionnaire including 11 questions from 14.04.2023 to 29.04.2023. The questions covered diagnostic and therapeutic procedures as well as various aspects of the management of gastroparesis.

The response rate was 21.4% (62 members). Only 6.56% of all respondents assessed the prevalence of gastroparesis correctly as estimated by current epidemiological publications. 68.85 % of all respondents used gastric emptying scintigraphy for diagnosis. 51.61% regarded an individualized therapy as the most important treatment goal, taking into account etiology and impact of symptoms, compared to symptomatic treatment of leading clinical symptom in 43,55 %. First choice treatment was medical treatment in 41.94%, dietary recommendations in 27.42% and endoscopic interventions in 24.2%. 100% of respondents used prokinetics, 40.32% used antiemetics while only 4.84% used analgesics. Insufficient availability of medical treatment options represents a need of action for 85.48%, compared to lacking official approval of available drugs for this indication for 48,39% of all respondents. Treatment options with little evidence were used quite frequently (e.g. use of herbal therapies in 43.55%).

Overall, the frequency of gastroparesis was underestimated in the current survey. Endoscopic options are quite often used as first-line treatment. Although symptom-guided treatment is important for the majority of respondents, prokinetics are predominantly used.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography.

Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01).

Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Chronic nausea and vomiting syndromes (CNVS), gastroparesis and functional dyspepsia (FD) are complex disorders. Body Surface Gastric Mapping (BSGM), a new test of gastric function, using Gastric Alimetry® (Alimetry, New Zealand) may be useful for de-escalating healthcare utilisation. This study aimed to define healthcare costs and estimate health economic impacts of implementing this test in patients with chronic gastroduodenal symptoms.

Consecutive patients at a tertiary referral centre evaluated with Gastric Alimetry were included. Frequency and cost data relating to medical investigations, hospital and outpatient presentations were evaluated. Costs of healthcare utilisation were calculated, and the potential cost savings of implementing Gastric Alimetry within a diagnostic decision-tree model were estimated.

Overall, 31 consecutive patients (mean age 36.1 years; 83.9% female; predominant symptoms: nausea [83.9%], pain [61.3%], vomiting [67.7%] and bloating [35.5%]) completed Gastric Alimetry testing. Repeat gastroscopy and abdominal CT rates were 29% (8/28) and 85% (11/13), respectively. Gastric Alimetry testing identified spectral abnormalities in 45.2% of patients, and symptom profiling classified a further 29.1% of patients. Median annualised cost difference after test introduction was NZ$-12,032. Estimated reductions in investigation-related costs when incorporating Gastric Alimetry into the diagnostic workflow model were approximately NZ$1,300 per patient.

Healthcare utilisation and confirmatory testing rates remain high in nausea and vomiting syndromes. This study presents real-world data, together with a decision-tree analysis, showing Gastric Alimetry can streamline clinical care pathways, resulting in reduced healthcare utilisation and cost.

Functional dyspepsia (FD) refers to a group of clinical symptoms caused by gastric and duodenal dysfunction. Which is a chronic functional disorder of the gastrointestinal tract with no cure. Zhishixiaopi decoction (ZSXP) is a type of Chinese herbal prescription that for treating FD. Although some randomized controlled trials (RCTs) report that ZSXP can significantly improve FD clinical symptoms and/or laboratory results, the trial design varies greatly among studies, making it challenging to draw a conclusion of the efficacy of ZSXP in treating FD.

A systematic review and a meta-analysis.

Mianyang Central Hospital.

We conducted a systematic review and a meta-analysis to evaluate the efficacy and safety of ZSXP for treating FD.

We developed inclusion and exclusion criteria based on FD diagnosed criteria, interventions to treat FD, and outcomes of these interventions. Search strategies combined disease terms, symptom terms, anatomy terms and intervention terms. Literature search was conducted on eight online databases in English or Chinese, including Medline (via PubMed), Embase (via Ovid), The Cochrane Library, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database.

The experimental group received oral administration of ZSXP and had a complete treatment process. ZSXP needs to fully contain the key herbal ingredients, regardless of whether the dosage of each herb is consistent with the original prescription. The Control group received monotherapy or combination therapy of other Western medicine and had a complete treatment process.

The primary outcomes appraised were Total effective rate (TER), serum levels of Motilin(MOT), Gastrin(GAS) and Somatostatin (SS), Gastric emptying rate (GER) using a Barium meal method (GER(B)) and Gastric half emptying time using an Ultrasonic method (GHET(T1/2)). The Cochrane Bias Risk Tool was used for quality critical appraisal, Review Manager (RevMan) version 5.3 was used for statistical analysis.

A total of 21 medium-quality RCTs were included in the meta-analysis. All 21 included studies were conducted and completed in Mainland China from 1998 to 2020. The treatment duration was between two weeks to two months. The meta-analysis suggests that, compared with the Western medicine treatment group, ZSXP treatment was more effective to improving the TER in FD [Odds ratio, OR = 3.54, 95%CI:(2.49, 5.05), Z = 6.99, P<0.00001] without significant increase in adverse events. However, no statistical significance was found between the groups in serum MOT levels [Standard mean difference, SMD = 1.05, 95%CI:(-0.42, 2.53), Z = 1.04, P = 0.16], serum GAS levels [SMD = -0.16, 95%CI:(-1.20, 0.88), Z = 0.31, P = 0.76], serum SS levels [SMD = -0.04, 95%CI:(-1.97, 1.89), Z = 0.04, P = 0.97], GER(B) [SMD = 1.09, 95%CI:(-0.81, 3.00), Z = 1.12, P = 0.26]or GHET(T1/2) [Mean difference, MD = -2.18, 95%CI:(-5.55, 1.19), Z = 1.27, P = 0.20].

The meta-analysis suggests that Zhishixiaopi treatment is a relatively effective and safe traditional Chinese medicine prescription and could be used for functional dyspepsia treatment. Considering the limitations of this study, the conclusion needs to be further confirmed by high-quality, multi-center, and large-sample randomized controlled trials.

Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear.

One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables.

In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment.

Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Gastroparesis significantly affects quality of life and healthcare expenditure. Effective treatment options are limited, and the utility of current prokinetic agents is inhibited by serious adverse effects. There exists an unmet need for prokinetic agents demonstrating both efficacy and an acceptable adverse effect profile. Highly selective 5-Hydroxytryptamine receptor 4 (5-HT4) agonists have exhibited clinical efficacy and safety in randomized controlled trials (RCTs). Consequently, we conducted a meta-analysis to comprehensively assess the safety and efficacy of these highly selective agents. Multiple databases, including PubMed, Scopus, and Embase, were systematically screened from inception until September 2023. Only RCTs evaluating the efficacy and safety of highly selective 5-HT4 agonists for gastroparesis were included. Key outcomes of interest included the pooled rates of Gastroparesis Cardinal Symptom Index (GCSI) scores, gastric emptying time (GET), and adverse event rates in each group. We adhered to standard meta-analysis methodology utilizing the random-effects model, with heterogeneity assessed by I2 statistics. Our analysis identified six RCTs, comprising 570 patients with diabetic (48%) or idiopathic (51%) gastroparesis, with mean ages of 46 and 45.9 years in the intervention and placebo groups, respectively. In the meta-analysis, highly selective 5-HT4 agonists demonstrated significantly superior pooled GCSI scores compared to placebo (mean difference: 4.283, (1.380, 7.186), p<0.05). Pooled GET was also significantly improved with 5-HT4 agonists compared to placebo (mean difference: 2.534, (1.695, 3.373), p<0.05). Although pooled rates of total adverse events were higher with 5-HT4 agonists (mean difference: 6.975, (1.042, 46.684), p<0.05), rates of specific adverse events such as diarrhea, abdominal pain, and headaches were comparable. In conclusion, this meta-analysis underscores a statistically significant improvement in GET and GCSI scores among patients receiving highly selective 5-HT4 agonists (Velusetrag, Felcisetrag, Prucalopride) for both diabetic and idiopathic gastroparesis. While the overall adverse effect profile is deemed acceptable, larger studies with extended follow-up periods are needed to investigate rare and/or serious adverse events. Moreover, future high-quality RCTs comparing the efficacy and safety of these novel agents with currently available agents are essential to further validate these findings.

Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis.

We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates.

Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients).

CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.

gov NCT #03941288.

Symptoms in gastroparesis (Gp) and functional dyspepsia (FD) overlap; using egg protein substitute to measure gastric emptying of solids (GES), ~40% of patients are reclassified from Gp to FD, and vice versa. Our aim was to assess inter-individual and intra-individual coefficients of variation (COV) in GES in symptomatic patients with Gp or FD with documented slow or normal GES, respectively.

Scintigraphic GES (T1/2 and GE% at 2 and 4 hours) using a 320 kcal real egg meal (30% fat) was tested in the following: single measurements in 20 patients with diabetes mellitus (10 each type 1 and type 2); repeat GES to estimate COVintra measured: 3 days apart in 9 Gp, 4 weeks apart in 21 Gp and 18 with FD with normal GE assigned to placebo and in 70 patients at 94.3 weeks (median) apart.

COVinter for GE% at 4 hours and GE T1/2 were respectively 14.2% and 23.5% in FD and 27.5% and 33% in Gp; COVintra for GE% at 4 hours and GE T1/2 up to 4 weeks apart were 23.4% and 37.9% in FD and 20.1% and 33% in Gp. GE% at 2 hours showed less consistent results. However, >85% retained original diagnosis as normal or delayed. From clinical GES to baseline research for Gp group, repeat GES (after treatment) showed the COVintra for GE% at 4 hours was 37.3% at median 94.3 weeks, with 26/70 changed diagnoses.

The 320 kcal (30% fat) GES scintigraphic test provides consistent diagnosis in >85% and should be the standard test for suspected gastric emptying disorders.

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.

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.

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.

This study assessed the efficacy and safety of velusetrag-a 5-HT₄ agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE).

In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).

232 subjects (183 females; 113 idiopathic gastroparesis) received treatment from February 2015 through June 2017. Least-squares mean improvement from baseline GCSI-24H (primary endpoint) at week 4 was -1.5 following velusetrag 5 mg vs -1.1 following placebo (treatment difference, -0.4; 95% confidence interval, -0.75 to -0.03; nominal p = 0.0327; Hochberg-adjusted p = 0.0980 [not significant]). Symptom improvement from baseline was achieved only with velusetrag 5 mg, which resulted in greater improvement from baseline vs placebo in all gastroparesis core symptoms, especially in subjects with idiopathic gastroparesis. Improvement from baseline GE by GES was greater in subjects receiving velusetrag (all doses) vs placebo; >70% of subjects receiving velusetrag 30 mg had GE normalization at 4 h. Treatment-emergent AEs were generally mild.

Velusetrag treatment was generally well-tolerated and associated with improved GE vs placebo in subjects with diabetic or idiopathic gastroparesis; however, only the lowest dose, velusetrag 5 mg, was associated with short-term improvement in gastroparesis symptoms.

GOV: NCT02267525.

Duodenal micro-inflammation and microbial dysregulation are increasingly recognized to play an important role in functional dyspepsia (FD) pathophysiology, previously regarded as a purely functional disorder. With current therapeutic options contested through insufficient efficacy or unfavorable adverse effects profiles, novel treatments directed to duodenal alterations could result in superior symptom control in at least a subset of patients. Indeed, recent advances in FD research provided evidence for anti-inflammatory therapies to relieve gastroduodenal symptoms by reducing duodenal eosinophils or mast cells. In addition, restoring microbial homeostasis by probiotics proved to be successful in FD. As the exact mechanisms by which these novel pharmacological approaches result in clinical benefit often remain to be elucidated, future research should focus on how immune activation and dysbiosis translate into typical FD symptomatology.

Drugs which can inhibit nausea/vomiting and/or increase gastric emptying are used to treat gastroparesis, mostly 'off-label'. Within each category, they act at different targets and modulate different physiological mechanisms.

Address the questions: In gastroparesis, why should blocking one pathway causing vomiting, be more appropriate than another? Why might increasing gastric emptying via one mechanism be more appropriate than another?

Drugs used clinically were identified via consensus opinions and reviews, excluding the poorly characterised. Their pharmacology was defined, mapped to mechanisms influencing vomiting and gastric emptying, and rationale developed for therapeutic use.

Vomiting: Rationale for 5-HT₃ , D₂ , H₁ or muscarinic antagonists, and mirtazapine, amitriptyline, nortriptyline, are poor. Arguments for inhibiting central consequences of vagal afferent transmission by NK₁ antagonism are complicated by doubts over effects on nausea. Gastric emptying: Confusion emerges because of side-effects of drugs increasing gastric emptying: Metoclopramide (5-HT₄ agonist, D₂ and 5-HT₃ antagonist; also blocks some emetic stimuli and causes tardive dyskinesia) and Erythromycin (high-efficacy motilin agonist, requiring low doses to minimise side-effects). Limited trials with selective 5-HT₄ agonists indicate variable efficacy.

Several drug classes inhibiting vomiting have no scientific rationale. NK₁ antagonism has rationale but complicated by limited efficacy against nausea. Studies must resolve variable efficacy of selective 5-HT₄ agonists and apparent superiority over motilin agonists. Overall, lack of robust activity indicates a need for novel approaches targeting nausea (e.g., modulating gastric pacemaker or vagal activity, use of receptor agonists or new targets such as GDF15) and objective assessments of nausea.

A patient subset with gastroparesis (GP) has normal gastric myoelectrical activity (GMA) and pyloric dysfunction.

(1) To determine pyloric balloon dilation (BD) effect on symptoms and gastric emptying in GP patients with normal 3 cycles per minute (cpm) GMA. (2) To demonstrate GMA-based artificial intelligence (AI)-derived formulae predict BD success at 10-12-month follow-up.

Cohort subjects completed baseline electrogastrogram w/water load satiety test (WLST), solid-phase nuclear gastric emptying, Gastrointestinal Cardinal Symptom Index (ANMS GCSI-DD) and Leeds questionnaires. Subjects were divided into two groups based on response to the WLST. Group 1 (n = 26) with hypernormal/normal 3 cpm GMA and Group 2 (n = 4) hyponormal/normal range 3 cpm GMA, compared to healthy normals. All subjects underwent endoscopic pyloric BD. After 10-12 months, gastric emptying and dyspepsia questionnaires were repeated to evaluate outcomes.

Group 1 ANMS GCSI-DD scores improved from 2 points at baseline (BL) to 0 at follow-up (f/u) (p < 0.001); Group 2 ANMS GSCI-DD scores were 2 at BL and 1.6 at f/u (p = 0.25). Leeds scores improved (p < 0.001) only for Group 1. Group 1 gastric emptying improved (54.5% retained at 2 h at BL vs. 12.2% at f/u, p < 0.001) in contrast to Group 2 patients (51.25% at BL vs. 56.25% at f/u, p = 0.252). Percentage 3 cpm GMA decreased (41.1% at BL vs. 24.9% at f/u, p ≤ 0.005) in Group 1 versus Group 2 (15.3% at BL vs. 23.4% at f/u, p = 0.114). AI-derived GMA threshold (GMAT) of 0.59 predicted positive pyloric BD outcomes at 10-12 months with sensitivity 96%, specificity 75%, and 93% correct classification.

Pyloric BD improved symptoms and gastric emptying long term in patients with GP and hypernormal/normal 3 cpm GMA. AI-derived GMAT predicted pyloric BD success. GMA post-WLST and GMAT are objective measures for improved selection and outcomes for endoscopic pyloric BD.

Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions.

To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis.

Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials.

Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p = 0.4 and 0.453 (0.123, 0.782), p = 0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p > 0.9) or 0.463 (p = 0.007), and for sub-optimal GE tests was either 0.370 (p = 0.4) or 0.052 (p > 0.9) depending on the used meta-analysis methodology.

The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.

Over the years, our growing experience with endoscopic submucosal dissection along with technological advances has solidified our comfort and knowledge on working in the submucosa, also referred to as the "third space." Per-oral endoscopic myotomy (POEM) was the first prototype third-space endoscopy (TSE) procedure, demonstrating the feasibility and clinical utility of endoscopic esophagogastric myotomy via submucosal tunneling. The launch of POEM accelerated the evolution of TSE from a vanguard concept to an expanding field with a wide range of clinical applications. In this review, we discuss the status and future directions of multiple TSE interventions.

Several magnetic resonance imaging (MRI) protocols have been used to assess gastric emptying (GE) with MRI. This systematic review summarizes the current literature on the topic. The aim was to provide an overview of the available imaging protocols and underline the items that appear most agreed upon and those that deserve further investigation.

According to PRISMA guidelines, two independent reviewers conducted a systematic literature search with a pre-specified strategy in different databases. Peer-reviewed articles that utilized MRI techniques to assess GE in healthy volunteers (HVs) were included. The quality and the outcomes of the studies were reported and analyzed.

The literature search yielded 30 studies (531 HVs, weighted mean age 27.4, weighted mean body mass index 23.0 kg/m² ), T2-weighted sequences, balanced turbo field echo, and balanced gradient echo were evenly utilized, with volunteers in the supine position (74% of the studies). After overnight fasting, both liquid (56%) and mixed (44%) meals were equally utilized. Segmentation of the volumes was predominantly performed manually (63%) with a reported mean T50 ranging from 7 to 330 min.

As observed in this systematic review, MRI is a flexible tool for assessing GE. Different protocols were analyzed, showing an equal capacity to assess the GE. However, many items in these protocols still require further investigation to obtain a common standard and increase this assessment quality.

Type 2 and type 1 diabetes are common endocrine disorders with a progressively increasing incidence worldwide. These chronic, systemic diseases have multiorgan implications, and the whole gastrointestinal (GI) tract represents a frequent target in terms of symptom appearance and interdependent pathophysiological mechanisms. Metabolic alterations linked with diabetic complications, neuropathy and disrupted hormone homeostasis can lead to upper and/or lower GI symptoms in up to 75% of diabetic patients, with multifactorial involvement of the oesophagus, stomach, upper and lower intestine, and of the gallbladder. On the other hand, altered gastrointestinal motility and/or secretions are able to affect glucose and lipid homeostasis in the short and long term. Finally, diabetes has been linked with increased cancer risk at different levels of the GI tract. The presence of GI symptoms and a comprehensive assessment of GI function should be carefully considered in the management of diabetic patients to avoid further complications and to ameliorate the quality of life. Additionally, the presence of gastrointestinal dysfunction should be adequately managed to improve metabolic homeostasis, the efficacy of antidiabetic treatments and secondary prevention strategies.

Endoscopic pyloromyotomy (G-POEM) is a minimally invasive treatment option with promising uncontrolled outcome results in patients with gastroparesis.

In this prospective randomised trial, we compared G-POEM with a sham procedure in patients with severe gastroparesis. The primary outcome was the proportion of patients with treatment success (defined as a decrease in the Gastroparesis Cardinal Symptom Index (GCSI) by at least 50%) at 6 months. Patients randomised to the sham group with persistent symptoms were offered cross-over G-POEM.

The enrolment was stopped after the interim analysis by the Data and Safety Monitoring Board prior to reaching the planned sample of 86 patients. A total of 41 patients (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male) were randomised (21 G-POEM, 20-sham). Treatment success rate was 71% (95% CI 50 to 86) after G-POEM versus 22% (8-47) after sham (p=0.005). Treatment success in patients with diabetic, postsurgical and idiopathic gastroparesis was 89% (95% CI 56 to 98), 50% (18-82) and 67% (30-90) after G-POEM; the corresponding rates in the sham group were 17% (3-57), 29% (7-67) and 20% (3-67).Median gastric retention at 4 hours decreased from 22% (95% CI 17 to 31) to 12% (5-22) after G-POEM and did not change after sham: 26% (18-39) versus 24% (11-35). Twelve patients crossed over to G-POEM with 9 of them (75%) achieving treatment success.

In severe gastroparesis, G-POEM is superior to a sham procedure for improving both symptoms and gastric emptying 6 months after the procedure. These results are not entirely conclusive in patients with idiopathic and postsurgical aetiologies.

NCT03356067; ClinicalTrials.gov.

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.

There has been a dramatic increase in clinical studies examining the relationship between disorders of gut-brain interactions and symptoms evoked by food ingestion in the upper and lower gastrointestinal tract, but study design is challenging to verify valid endpoints. Consequently, mechanistic studies demonstrating biological relevance, biomarkers and novel therapeutic targets are greatly needed. This review highlights emerging mechanisms related to nutrient sensing and tasting, maldigestion, physical effects with underlying visceral hypersensitivity, allergy and immune mechanisms, food-microbiota interactions and gut-brain signaling, with a focus on patients with functional dyspepsia and irritable bowel syndrome. Many patients suffering from disorders of gut-brain interactions exhibit these mechanism(s) but which ones and which specific properties may vary widely from patient to patient. Thus, in addition to identifying these mechanisms and the need for further studies, biomarkers and novel therapeutic targets are identified that could enable enriched patient groups to be studied in future clinical trials examining the role of food in the generation of gut and non-gut symptoms.

Food ingestion is a major symptom trigger in functional esophageal and gastroduodenal disorders and gastroparesis. This review summarizes current knowledge and identifies areas of research on the role of food factors and the opportunities for dietary intervention in these disorders. While many patients experiencing functional esophageal and gastroduodenal disorders identify specific food items as symptom triggers, available data do not allow the identification of specific nutrient groups that are more likely to induce symptoms. In functional dyspepsia (FD), recent studies have shown the potential efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, although the underlying mechanism of action is unclear. Reports of favorable responses to gluten elimination in patients with FD are confounded by the concomitant benefit of reduced intake of fructans, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols present in wheat. Emerging data based on a 6-food elimination diet and confocal laser endomicroscopic evaluation of mucosal responses to food proteins suggest a role for duodenal allergic reactions in FD symptom generation. In patients with gastroparesis, a low-residue diet has been shown to improve symptoms. Novel dietary approaches under evaluation are the Mediterranean diet and the heating/cooling diet approach.

Gastroparesis (Gp) is a delay in gastric emptying in the absence of a mechanical obstruction and has the capacity to cause symptoms that significantly impact a patient's quality of life. Dietary interventions are the first-line treatment in Gp, but the efficacy of different diets is unclear. This systematic review seeks to determine the effectiveness of dietary interventions on clinical outcomes in Gp. A literature search of MEDLINE Ovid from 1 March 2008 to 1 October 2021 was conducted to identify randomized controlled trials, cohort studies, and cross-sectional studies that reported dietary interventions in Gp. From the initial search, 2789 studies resulted. These were assessed by 2 independent reviewers and selected based on the primary outcomes of interest: changes in symptom-specific patient-reported outcomes and changes in gastric emptying time. A third reviewer resolved any discrepancies. Six adult studies (185 subjects) met the inclusion criteria, whereas no pediatric study did. Five of the included studies were randomized controlled trials and one was an observational study. The systematic review suggested low-fat diets, small-particle diets, diets with isoflavones, and foods considered bland, starchy, sweet, and salty did not exacerbate Gp symptoms. Small-particle diets and diets with isoflavones were found to improve gastric emptying time in patients. Additionally, small-particle diets were shown to reduce anxiety in comparison to large-particle diets. Of the randomized controlled trials, 80% were low risk of bias and 20% were fair risk of bias. The observational study was considered fair quality. The data presented in this review suggest specific dietary interventions could potentially improve Gp symptoms and gastric emptying in adult patients, particularly low-fat and small-particle diets. For pediatric Gp, data are lacking. The limited data available highlights a critical gap in the literature.

Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis.

One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL.

Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores.

Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

During a GE test (breath test with ¹³C-octanoic acid labelled 250 kcal solid meal), the severity of 6 symptoms (postprandial fullness, epigastric pain and burning, bloating, nausea and belching) was assessed, every 15 min, before meal-intake and 4h postprandially. The sum of individual symptom scores generated the meal-related symptoms score; the sum of all symptoms generated overall meal-related symptom severity (OSS). Data were compared in patients with normal and delayed GE (cut-off T_1/2≥ 109 min). Data are shown as mean±SEM.

504 patients were included, of which 382 patients (67% female, age 43.8±0.8 years, BMI 23.3±0.2 kg/m²) had normal and 122 patients (77% female, age 42.7±1.5 years, BMI 23.2±0.6 kg/m²) had delayed GE. OSS tended to be higher in patients with delayed GE (81.8±3.4 vs. 99.5±7.1, p=.05). Only nausea was significantly higher in patients with delayed GE (11±0.8 vs. 16±1.6, p=.01). No correlations were observed between GE rate and any of the symptoms (OSS: r=0.06, p=.2; nausea: r=0.06, p=.1). The symptom severity time course showed a significant difference only for nausea, with increased severity ratings 90 min after the meal (p<.01) in delayed GE compared to normal GE patients.

The severity of symptoms in functional dyspepsia and idiopathic gastroparesis, even when assessed during the GE test meal, is not correlated to gastric emptying rate. (Ethics committee University Hospital of Leuven study number S55426).

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.

Delayed gastric emptying on objective testing defines gastroparesis, but symptoms overlap with functional dyspepsia and do not correlate well with gastric emptying delay. This review outlines a strategy for defining, diagnosing, and managing refractory gastroparesis.

The Best Practice Advice statements presented here were developed from review of existing literature combined with expert opinion to provide practical advice. Because this was not a systematic review, formal rating of the quality of evidence or strength of recommendations was not performed. BEST PRACTICE ADVICE.