The purpose of this Clinical Practice Update Expert Review is to describe key principles in the evaluation and management of patients with disorders of gut-brain interaction (DGBI) and hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSDs) with coexisting postural orthostatic tachycardia syndrome (POTS) and/or mast cell activation syndrome (MCAS).

This expert review/commentary was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Clinicians should be aware of the observed associations between hEDS or HSDs and POTS and/or MCAS and their overlapping gastrointestinal (GI) manifestations; while theoretical explanations exist, experimental evidence of the biological mechanisms that explain relationships is limited and evolving. BEST PRACTICE ADVICE 2: Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of POTS/MCAS, but universal testing for POTS/MCAS in all patients with hEDS/HSDs is not supported by the current evidence. BEST PRACTICE ADVICE 3: Gastroenterologists seeing patients with DGBI should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS (https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf) or offer appropriate referral to a specialist where resources are available. BEST PRACTICE ADVICE 4: Testing for POTS through postural vital signs (eg, symptomatic increase in heart rate of 30 beats/min or more with 10 minutes of standing during an active stand or head-up tilt table test in the absence of orthostasis) and referral to specialty practices (eg, cardiology or neurology) for autonomic testing should be considered in patients with hEDS/HSDs and refractory GI symptoms who also report orthostatic intolerance after exclusion of medication side effects and appropriate lifestyle or behavioral modifications (eg, adequate hydration and physical exercise) have been attempted but is not required for all patients with hEDS/HSDs who report GI symptoms alone. BEST PRACTICE ADVICE 5: In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS/HSDs and DGBI who also present with episodic symptoms that suggest a more generalized mast cell disorder (eg, visceral and somatic pain, pruritus, flushing, sweating, urticaria, angioedema, wheezing, tachycardia, abdominal cramping, vomiting, nausea, diarrhea, urogynecological and neurological complaints) involving 2 or more physiological systems (eg, cutaneous, GI, cardiac, respiratory, and neuropsychiatric), but current data do not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS/HSDs without clinical or laboratory evidence of a primary or secondary mast cell disorder. BEST PRACTICE ADVICE 6: If MCAS is suspected, diagnostic testing with serum tryptase levels collected at baseline and 1-4 hours following symptom flares may be considered by the gastroenterologist; increases of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation. BEST PRACTICE ADVICE 7: If a diagnosis of MCAS is supported through clinical and/or laboratory features, patients should be referred to an allergy specialist or mast cell disease research center where additional testing (eg, urinary N-methylhistamine, leukotriene E4, 11β-prostaglandin F2) may be performed. BEST PRACTICE ADVICE 8: Diagnostic evaluation of GI symptoms consistent with DGBI in patients with hEDS/HSDs and comorbid POTS and/or MCAS should follow a similar approach to the evaluation of DGBI as in the general population including the use of a positive symptom-based diagnostic strategy and limited noninvasive testing. BEST PRACTICE ADVICE 9: Testing for celiac disease may be considered earlier in the diagnostic evaluation of patients with hEDS/HSDs who report a variety of GI symptoms and not only limited to those with diarrhea. There is insufficient research to support routine testing for disaccharidase deficiencies or other diet-mediated mechanisms as causes of GI symptoms in hEDS/HSDs. BEST PRACTICE ADVICE 10: Diagnostic testing for functional defecation disorders with anorectal manometry, balloon expulsion test, or defecography should be considered in patients with hEDS/HSDs and lower GI symptoms such as incomplete evacuation given the high prevalence of pelvic floor dysfunction, especially rectal hyposensitivity, in this population. BEST PRACTICE ADVICE 11: In patients with hEDS/HSDs and comorbid POTS who report chronic upper GI symptoms, timely diagnostic testing of gastric motor functions (eg, measurement of gastric emptying and/or accommodation) should be considered after appropriate exclusion of anatomical and structural diseases, as abnormal gastric emptying may be more common than in the general population. BEST PRACTICE ADVICE 12: Medical management of GI symptoms in hEDS/HSDs and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results. In addition to general DGBIs and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS. BEST PRACTICE ADVICE 13: Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures. BEST PRACTICE ADVICE 14: When MCAS is suspected, patients can benefit from treatment with histamine receptor antagonists and/or mast cell stabilizers, in addition to avoiding triggers such as certain foods, alcohol, strong smells, temperature changes, mechanical stimuli (eg, friction), emotional distress (eg, pollen, mold), or specific medications (eg, opioids, nonsteroidal anti-inflammatory agents, iodinated contrast). BEST PRACTICE ADVICE 15: Besides general nutritional support, special diets including a gastroparesis diet (ie, small particle diet) and various elimination diets (eg, low fermentable carbohydrates, gluten- or dairy-free, low-histamine diets) can be considered for improving GI symptoms. Dietary interventions should be delivered with appropriate nutritional counseling or guidance to avoid the pitfalls of restrictive eating. BEST PRACTICE ADVICE 16: Management of chronic GI symptoms in patients with hEDS/HSDs who do not exhibit symptoms consistent with POTS or MCAS should align with existing approaches to management of DGBI and GI motility disorders in the general population, including integrated multidisciplinary care involving multiple specialties, where appropriate (eg, cardiology, rheumatology, dietician, psychology).

Gastrointestinal disorders originate in the gastrointestinal tract (GIT), and the therapies can benefit from direct access to the GIT achievable through the oral route. RNA molecules show great promise therapeutically but are highly susceptible to degradation and often require a carrier for cytoplasmic access. Lipid nanoparticles (LNPs) are clinically proven drug-delivery agents, primarily administered parenterally. An ideal Orally Delivered (OrD) LNP formulation should overcome the diverse GI environment, successfully delivering the drug to the site of action. A versatile OrD LNP formulation has been developed to encapsulate and deliver siRNA and mRNA in this paper. The formulations were prepared by the systematic addition of cationic lipid to the base LNP formulation, keeping the total of cationic lipid and ionizable lipid to 50 mol%. Biorelevant media stability depicted increased resistance to bile salt mediated destabilization upon the addition of the cationic lipid, however the in vitro efficacy data underscored the importance of the ionizable lipid. Based on this, OrD LNP was selected comprising of 20% cationic lipid and 30% ionizable lipid. Further investigation revealed the enhanced efficacy of OrD LNP in vitro after incubation in different dilutions of fasted gastric, fasted intestinal media, and mucin. Confocal imaging and flow cytometry confirmed uptake while in vivo studies demonstrated efficacy with siRNA and mRNA as payloads. Taken together, this research introduces OrD LNP to deliver nucleic acid locally to the GIT.

Gastric dysrhythmias, loss of normal 3 cycles per minute (CPM) gastric myoelectrical activity (GMA), and variable loss of interstitial cells of Cajal are reported both in gastroparesis (GP) and functional dyspepsia (FD). We hypothesize that the patients with GP, and FD with normal gastric emptying (NGE) and delayed gastric emptying (DGE) may vary in symptom severity, and GMA profiles.

Symptoms and their severity were evaluated by gastroparesis cardinal symptom index (GCSI), Abell scoring, short-form Nepean dyspepsia index (SF-NDI), the World Health Organization quality of life, and Rome IV subtyping for FD. Solid-meal gastric emptying was assessed by nuclear scintigraphy. Water load satiety test (WLST)-based electrogastrography determined GMA.

Patients with GP (n = 40) had higher GCSI than those with FD (n = 39; [12 DGE, 27 NGE] (2.79 [2.17-3.33] vs 1.67 [0.83-2.61] vs 0.83 [0.55-1.93]; P < 0.001, in GP vs FD-NGE vs FD-DGE, respectively), severe Abell grade (Grade III in 17 [43%] vs 0% vs 0%, in GP vs FD-NGE vs FD-DGE, respectively), severe SF-NDI (80.5 [63.5-102.5] vs 50 [27-91] vs 30 [21.25-45.5]); and poor QOL. Sixteen (40%) GP had impaired gastric accommodation (< 238 mL). Post-WLST 3 CPM normal/hypernormal GMA was observed in 17 (42%), 18 (67%), and 5 (42%) patients with GP, FD (NGE), and FD (DGE), respectively; and 3 CPM hyponormal in remaining patients in each group. Post-WLST dysrhythmia was comparable.

WLST-electrogastrography coupled with GE study may distinguish between normal/dysrhythmic GMA revealing pathophysiologicalphenotypes of GP and FD. Analysing extent of power change in normogastric, and dysrhythmic frequencies may comprehensively elucidate disease severity.

Panenteric gastrointestinal dysmotility in diabetic gastroenteropathy remains incompletely understood. We aim to (1) compare gastrointestinal transit times, contractile activity, and pH levels between individuals with and without diabetic gastroenteropathy and (2) investigate associations between symptoms and contractile activity.

We compared 37 healthy individuals to 68 individuals with diabetic gastroenteropathy. Gastrointestinal segmental transit times, contractile activity, and pH were measured with SmartPill. The Gastroparesis Cardinal Symptom Index and the Gastrointestinal Symptom Rating Scale were used to evaluate symptoms.

Compared to controls, individuals with diabetic gastroenteropathy had prolonged median gastric emptying time (3.3 [IQR, 2.5-4.4] vs 2.5 [IQR, 1.9-3.6] hours, P = 0.023), antroduodenal transition time (23 [IQR, 8-52] vs 11 [IQR, 2-25] minutes, P = 0.015), colonic transit times (36.0 [IQR, 17.3-53.5) vs 20.8 [IQR, 14.0-28.8] hours, P = 0.004), and whole-gut transit time (46.1 [IQR, 24.3-72.9] vs 28.7 [IQR, 22.0-42.7] hours, P = 0.002). The diabetes group had lower antral contraction frequency (1.5 [IQR, 0.9-2.1] vs 2.5 [IQR, 1.5-3.9] contractions per minute, P = 0.004) and sum of amplitudes (1941 [1377-2763] vs 2975 [1734-5337] mmHg, P = 0.004). In contrast, the diabetes group had higher colonic sum of amplitudes and area under the contraction curve. The antral contraction frequency was unassociated with gastrointestinal symptoms. Still, the overall stomach contraction frequency increased by 30% (P < 0.001) and 15% (P = 0.003) in individuals with diabetes for each incremental increase in nausea and reflux scores, respectively.

Gastrointestinal transit times, as well as antral and colonic contractile activity, differed between individuals with diabetic gastroenteropathy and controls. The overall gastric contraction frequency was associated with symptom severity.

Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes mellitus, significantly impacting patient quality of life and contributing to morbidity and mortality. Affecting approximately 50% of patients with diabetes, DN is predominantly characterized by distal symmetric polyneuropathy, leading to sensory loss, pain, and motor dysfunction, often resulting in diabetic foot ulcers and lower-limb amputations. The pathogenesis of DN is multifaceted, involving hyperglycemia, dyslipidemia, oxidative stress, mitochondrial dysfunction, and inflammation, which collectively damage peripheral nerves. Despite extensive research, disease-modifying treatments remain elusive, with current management primarily focusing on symptom control. This review explores the complex mechanisms underlying DN and highlights recent advances in diagnostic and therapeutic strategies. Emerging insights into the molecular and cellular pathways have unveiled potential targets for intervention, including neuroprotective agents, gene and stem cell therapies, and innovative pharmacological approaches. Additionally, novel diagnostic tools, such as corneal confocal microscopy and biomarker-based tests, have improved early detection and intervention. Lifestyle modifications and multidisciplinary care strategies can enhance patient outcomes. While significant progress has been made, further research is required to develop therapies that can effectively halt or reverse disease progression, ultimately improving the lives of individuals with DN. This review provides a comprehensive overview of current understanding and future directions in DN research and management.

Circulating monocytes (Mo) are precursors to a subset of gastric resident muscularis macrophages. Changes in muscularis macrophages (MMs) result in delayed gastric emptying (DGE) in diabetic gastroparesis. However, the dynamics of Mo in the development of DGE in an animal model are unknown. Using cytometry by time-of-flight and computational approaches, we show a high heterogeneity within the Mo population. In DGE mice, via unbiased clustering, we identified two reduced Mo clusters that exhibit migratory phenotype (Ly6ChiCCR2hi-intCD62LhiLy6GhiCD45RhiMERTKhiintLGALS3intCD14intCX3CR1lowSiglec-Hint-low) resembling classical Mo (CMo-like). All markers enriched in these clusters are known to regulate cell differentiation, proliferation, adhesion, and migration. Trajectory inference analysis predicted these Mo as precursors to subsequent Mo lineages. In gastric muscle tissue, we demonstrated an increase in the gene expression levels of chemokine receptor C-C chemokine receptor type 2 (Ccr2) and its C-C motif ligand 2 (Ccl2), suggesting increased trafficking of classical-Mo. These findings establish a link between two CMo-like clusters and the development of the DGE phenotype and contribute to a better understanding of the heterogenicity of the Mo population.NEW & NOTEWORTHY Using 32 immune cell surface markers, we identified 23 monocyte clusters in murine blood. Diabetic gastroparesis was associated with a significant decrease in two circulating classical monocyte-like clusters and an upregulation of the Ccr2-Ccl2 axis in the gastric muscularis propria, suggesting increased tissue monocyte migration. This study offers new targets by pointing to a possible role for two classical monocyte subsets connected to the Ccr2-Ccl2 axis.

Gastric per-oral endoscopic myotomy (G-POEM) is an innovative treatment that has become increasingly utilized for patients with refractory gastroparesis. The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness of G-POEM for the treatment of gastroparesis.

Individualized search strategies were developed through February 2021 in accordance with the PRISMA and MOOSE guidelines. This meta-analysis was performed by calculating pooled proportions and mean difference preprocedure and postprocedure with rates estimated using random effects models. Measured outcomes included technical success, clinical success, improvement in gastroparesis cardinal symptom index (GCSI), change in gastric emptying rate, alterations in impedance planimetry (functional lumen imaging probe [FLIP]) assessment, and adverse events.

A total of 20 studies (n=797 patients; 67.41% female) were included. The mean age was 48.92±11.61 y, with an average duration of 4.24±1.11 y since gastroparesis diagnosis. Technical success was 98.47% [(95% CI: 97.14, 99.19); I2 =0.00] with a mean myotomy length of 3.78±1.16 cm. In terms of clinical success, mean preprocedure GCSI scores were 3.38±0.37 and improved significantly postprocedure [weighted mean difference -1.56 (95% CI: -1.89 to -1.24); I2 =82.53; P <0.001]. Gastric retention after 4 hours demonstrated ~50% improvement (preprocedure 43.08±9.24% versus postprocedure 22.97±10.19%; P <0.001). FLIP assessment with 40 mL and 50 mL balloons demonstrated a significant increase in diameter, distensibility index, and cross-sectional area postprocedure (all P <0.05). Procedure-associated adverse events occurred among 10.92% [(95% CI 5.09 to 19.32); I2 =82.85] of patients.

G-POEM appears safe and highly effective for the treatment of patients with refractory gastroparesis regardless of symptom predominance or etiology.

Although gastric peroral endoscopic myotomy (G-POEM) has shown substantial efficacy in patients with medically refractory gastroparesis (GP), comprehensive long-term data on its effectiveness are lacking.

We conducted a systematic review and meta-analysis including observational studies assessing long-term efficacy after G-POEM in patients with refractory GP. Our primary outcome was the pooled rate of clinical success 1-year after G-POEM. Secondary outcomes included clinical success at 2 and 3 years and the rate of adverse events according to the American Society for Gastrointestinal Endoscopy classification.

Thirteen studies, involving 952 patients with refractory GP undergoing G-POEM, were eligible. The pooled 1 year-clinical success was 0.72 (95% confidence interval [CI]: 0.56, 0.85, I2 = 94.9%). The clinical success was 0.67 (95% CI: 0.47, 0.97, I2 = 95.8%) when considering only studies defining success as 1 point decrease in Gastroparesis Cardinal Symptoms Index score and at least 25% decrease in two subscales. For patients who had 1-year success, the pooled clinical success at 2 and 3 years were 0.71 (95% CI: 0.45, 0.92, I2 = 94.9%) and 0.58 (95% CI: 0.19, 0.92, I2 = 97.1%), respectively. The pooled rate of adverse events was 0.08 (95% CI: 0.06, 0.10, I2 = 0%).

G-POEM is associated with successful outcomes in about 70% of treated cases after 1 year, with durable long-term effects lasting up to 3 years. In the future, new uniform outcome definitions and strict patient selection criteria are warranted to delineate G-POEM outcomes more accurately.

Gastroparesis is a chronic motility disorder characterized by delayed gastric emptying in the absence of mechanical obstruction. Patients with refractory gastroparesis often require enteral nutrition support, but traditional feeding methods such as nasojejunal tubes and percutaneous gastrojejunostomy tubes have significant limitations including frequent displacement, infection, and impact on quality of life.

To explore patients' experience post insertion of laparoscopic Roux-en-Y jejunostomy in a cohort of eight adult patients with idiopathic gastroparesis.

Eight patients with idiopathic gastroparesis who underwent Roux-en-Y jejunostomy placement between 2019-2022 were interviewed about their pre- and post-procedure experiences. The procedure involves creating a jejunal limb anastomosed to the proximal jejunum in a Y-configuration, with the limb brought to the abdominal wall for feeding tube insertion. This is designed to reduce leakage by diverting intestinal contents away from the stoma. Topics included symptoms, nutrition, quality of life, and comparison to previous feeding methods.

Post-procedure, all patients reported improvements in nausea/vomiting, and 87.5% noted reduced abdominal pain. Weight stabilized and oral intake improved in 75% of patients. Most (87.5%) described improved social confidence, increased energy, and better work/school functioning. Three patients (37.5%) eventually maintained adequate oral nutrition without jejunostomy. Minor complications included leakage (37.5%) and hypergranulation tissue. Half the cohort used supplemental gastric venting. Most patients (87.5%) preferred Roux-en-Y jejunostomy over previous feeding tubes and would undergo the procedure again.

Despite some challenges, Roux-en-Y jejunostomy led to notable improvements in symptoms, nutrition, and quality of life for most patients with refractory gastroparesis. It may be a viable option for long-term enteral nutrition support in carefully selected patients. Further research is needed to optimize patient selection and manage complications.

The motilin receptor (MTLR) is a key target for treating gastrointestinal (GI) disorders like gastroparesis, yet developing effective agonists remains challenging due to drug tolerance and signaling bias. We present cryoelectron microscopy (cryo-EM) structures of MTLR bound to azithromycin, a macrolide antibiotic, and DS-3801b, a non-macrolide agonist. Distinct ligand recognition mechanisms are revealed, with azithromycin binding deeply within the orthosteric pocket and DS-3801b adopting a special clamp-like conformation stabilized by a water molecule. We also highlight the critical role of extracellular loop 2 (ECL2) in ligand specificity and signaling pathway activation, affecting both G-protein and β-arrestin signaling. Additionally, the "D2.60R2.63S3.28" motif and interactions around transmembranes 6/7 (TM6/7) are identified as key drivers of signaling selectivity. These findings offer insights into the structural dynamics of MTLR, laying the groundwork for the rational design of next-generation GI prokinetic drugs with enhanced efficacy and safety.

Gastroparesis, characterized by delayed gastric emptying without mechanical obstruction, is a recognized complication of long-standing diabetes. Its pathophysiology involves, amongst other mechanisms, autonomic dysfunction due to vagal nerve damage, impaired smooth muscle contractility, and hormonal dysregulation of intestinal motility. During Ramadan, fasting causes significant dietary changes due to prolonged fasting and the consumption of large meals for Iftar (breaking of fast), which may unmask or worsen gastroparesis symptoms in individuals with diabetes. Symptoms such as early satiety, bloating, nausea, and glycemic fluctuations can further complicate diabetes management during fasting. This paper highlights the relationship between Ramadan fasting and gastroparesis in individuals with diabetes, exploring underlying mechanisms, clinical manifestations, diagnostic approaches, and management strategies. A multidisciplinary approach involving dietary modifications, medication adjustments, lifestyle changes, and individualized medical counseling is essential for safe fasting, alongside the option to avoid fasting in individuals who are deemed too high at risk for fasting. Further research is needed to assess the prevalence of subclinical gastroparesis in fasting individuals with diabetes and to optimize risk stratification and management in these patients.

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.

The present study aimed to investigate factors influencing postsurgical gastroparesis syndrome (PGS) in patients with right-sided colon cancer. In total, 260 patients who underwent complete mesocolic excision for right-sided colon cancer were included in the present analysis. Among the included patients, 69 underwent open radical right-sided colon resection, 175 underwent laparoscopic radical right-sided colon resection and 16 underwent robot-assisted radical right-sided colon resection. The occurrence of PGS was observed, and both the χ2 test and multivariate regression analysis were conducted to identify influencing factors. Among the 260 patients, 32 experienced PGS, with an incidence rate of 12.3%. Univariate analysis demonstrated that age, perioperative blood glucose levels, self-rated anxiety scale scores and surgical approach were significantly associated with PGS (P<0.05), whereas sex, surgical duration, diabetes and perioperative albumin levels were not significant factors (P>0.05). Multivariate logistic regression analysis showed that age >70 years, perioperative blood glucose ≥11.1 mmol/l, a self-rating anxiety scale score ≥50 and radical extended right-sided colon resection were risk factors for PGS occurrence. In conclusion, the occurrence of PGS in patients with right-sided colon cancer was revealed to be associated with age, perioperative blood glucose levels, self-rated anxiety scale scores and surgical approach.

The diagnosis of functional disorders of the upper gastrointestinal tract relies on clinical evaluation after exclusion of most frequent organic diseases. Diagnostic techniques contribute to better characterization of disease, choice of specific therapy, and follow-up. Functional ultrasonography was introduced in the early '80 s for the non-invasive study of gastric and gallbladder emptying without ionizing radiation, during fasting and postprandially. This technique detects dysfunctional motility in several gastrointestinal and systemic conditions, and can be used along with the assessment of real-time satiety and gastrointestinal symptoms after food ingestion, and dosing of hormones involved in the modulation of gastrointestinal and metabolic homeostasis. Functional ultrasonography has been increasingly used to explore the gastrointestinal pathophysiology, the gut-brain interaction, the effects of drugs (such as antidiabetics), the response to specific dietary and feeding patterns, and to support the development of nutraceuticals. In this evolving scenario, ultrasonography stands as a widely available, highly sustainable, non-invasive, repeatable, safe and low-cost tool, as compared with more expensive, less sustainable or still scarcely standardized procedures to study gastric and gallbladder motility as scintigraphy, wireless motility capsule tests, 13C breath tests, or magnetic resonance imaging. Functional ultrasonography not only provides reliable data in experimental protocols, but also in the assessment of clinical conditions as dyspeptic symptoms, diabetes, gastroenteric and neurological diseases, critical illness, and as a benchmark to evaluate the gastrointestinal effects of innovative drugs.

We aim to establish normal values and standardize a hypoallergenic and mediterranean diet for gastric emptying scintigraphy (GES).

In a prospective cohort of healthy volunteers, we performed GES of a [99Tc]TcDTPA2 labelled hypoallergenic meal (egg, potato, rice and olive oil). Anterior and posterior images were simultaneously acquired at 0, 30, 60, 110, 120, 130, 180, 230, 240 and 250 min. Cross-sectional analysis was performed between demographic data and gastric retention values. A score covariance analysis model was used to observer changes between measurements over time.

50 participants (29 women) were included. Mean values and standard deviation (5-95th) for gastric retention percentages at 60, 120, 180, 240 min were 51.40 ± 8.63 (36.5-66.1), 21.66 ± 9.40 (6.5-38.2), 7.58 ± 5.77 (1.5-19.1) and 2.94 ± 2.08 (1-7.3), respectively. Male participants had a significative faster gastric emptying compared to women in practically all the acquisitions. Male participants and smoker participants generated a significative decrease of gastric retention values in generalized linear model (male coefficient -4.818, IC95% -7.24 to -2.39, P-value < .001; and smoker coefficient of -3.484, IC95% -6.29 to -0.67, P-value < .05).

This study standardizes and establishes normal values for GES with the first hypoallergenic solid meal based on consensus recommendations and a mediterranean diet; suitable for most patients with allergic or sensitive-conditions to other meal components.

Gastroparesis, characterized by delayed gastric emptying, leads to debilitating gastrointestinal symptoms and often experience comorbid psychiatric disorders, possibly linked to brain-gut network dysfunction. This adversely affects quality of life and necessitates medical care. We aimed to characterize the longitudinal impact of comorbid anxiety, depression, or bipolar disorder on health-care resource utilization in adults hospitalized primarily with gastroparesis.

A retrospective observational study using the 2016-2019 National Inpatient Sample Healthcare Cost and Utilization Project identified patients aged ≥18 years hospitalized with an index diagnosis of gastroparesis (International Classification of Diseases-10 code K31.84). The cohort was stratified based on the presence of comorbid psychiatric mood disorders (depression, anxiety, and bipolar spectrum disorders). We compared the frequency of computed tomography (CT) imaging, gastric emptying studies, endoscopic procedures, length of stay, and hospitalization costs. Chi-square and analysis of variance tests were used.

Of 47,265 patients hospitalized with gastroparesis, 21,545 (45.6%) had comorbid psychiatric mood disorders. These patients had a higher mean Elixhauser comorbidity index (3.6 ± 1.8 vs 2.9 ± 1.8, P < .001) and a longer median hospital stay (4, interquartile range: 2-6 vs 3, interquartile range: 2-6, P < .001). Adjusted analysis showed higher CT imaging frequency in this group (adjusted Odds ratio: 1.15; 95% confidence interval: 1.04-1.67). Although the frequency of endoscopic procedures, gastric scintigraphy, and total hospitalization costs were higher in the psychiatric comorbidity group, these differences were not statistically significant in univariable analysis.

Nearly 50% of gastroparesis patients had concurrent psychiatric disorders and underwent more frequent CT imaging and had longer hospital stays. This underscores the importance of screening all gastroparesis patients for psychiatric disorders upon admission and exploring the effectiveness of incorporating psychosocial interventions into the treatment plan for gastroparesis patients.

Gastric schwannoma is a relatively rare submucosal mesenchymal tumor with low probability of metastasis and arises from Schwann cells of the gastrointestinal nervous plexus. Surgical therapy is the main treatment of gastric schwannoma with symptoms or malignant tendency. Gastroparesis is a potential complication following gastrointestinal surgery, which is a clinical syndrome caused by gastric emptying disorder and characterized by nausea, vomiting, and bloating, resulting in insufficient nutrient intake. Generally, post-surgical etiology is the main potential etiology of gastroparesis, while the most common underlying etiology is diabetes mellitus. So far, reports of gastroparesis arising from resection of gastric schwannoma are rare. We present an 80-year-old woman who was diagnosed with gastrointestinal stromal tumor (GIST) primarily and has undergone laparoscopic wedge-shaped gastrectomy. The pathological and immunohistochemical examination ultimately established the diagnosis of gastric schwannoma. The patient experienced belching, nausea, vomiting, and bloating 1 week after the surgery and confirmed as gastroparesis through gastrointestinal series and gastroscopic examination. A series of treatments were performed, including correcting fluid-electrolyte disorders and vitamin deficiencies, and nutritional support and pharmacological treatments. The patient ultimately recovered well, and the relevant literatures were reviewed to identify and handle similar cases hereafter.

Early delayed gastric conduit emptying (DGCE) is a frequent complication after Ivor-Lewis esophagectomy (ILE). Despite its relevance, few studies are published using the international consensus criteria. Therefore, we aimed to assess predictors and clinical consequences of DGCE in patients after ILE. This analysis represents a retrospective, single-center cohort study of patients who underwent ILE (2016-2021). DGCE was assessed by the international consensus criteria. Univariable and a multivariable penalized LASSO logistic regression model was applied to identify predictors of DGCE, whereas postoperative outcomes were assessed by group comparisons. The incidence of early DGCE was 15.6% (46/294 included patients). Of all tested preoperatively known and treatment related factors, only minimally invasive surgery was associated with lower odds for the occurrence of DGCE (OR 0.33, 95%CI:0.12-0.77, P = 0.017) when compared to open surgery. When DGCE occurred, the impact on major postoperative morbidity was limited (DGCE 39.1% vs. non-DGCE 33.1%, P = 0.425), especially there were no differences in starting adjuvant treatment (DGCE 50% vs. non-DGCE 46%; P = 0.615) or overall survival (Log-Rank P = 0.995). The results of this study suggest that the impact of DGCE might have been overestimated in the past. The only factor found to be significantly associated with decreased DGCE was minimally invasive surgery. Therefore, individual patient selection for preventive interventions is difficult and routine preventive interventions only seem justified when they can be performed with low adverse outcomes and at low cost. Higher evidence from randomized controlled trials is needed to assess the optimal strategy to prevent and treat DGCE.

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.

Per-oral pyloromyotomy (POP), also known as gastric per-oral endoscopic myotomy, is the first-line endoscopic intervention for medically refractory gastroparesis. This study aimed to assess the value of pyloric impedance planimetry using a functional lumen imaging probe (FLIP) during POP.

Patients who underwent POP between October 2019 and February 2024 were retrospectively reviewed. FLIP measurements, symptoms measured using the Gastroparesis Cardinal Symptom Index (GCSI), and gastric emptying scintigraphy (GES) were evaluated before and after POP.

Of 35 patients who underwent POP, 29 (82.9%) were female, the median age was 51.3 years (IQR, 38.4-60.9), and the median body mass index was 29.26 kg/m2 (IQR, 25.46-32.56). In addition, 23 patients had pre- and post-POP FLIP measurements. The median pyloric diameter increased from 14.4 (IQR, 12.0-16.0) to 16.0 (IQR, 14.8-18.0) mm (S = 116.5; P < .0001). The median distensibility index increased from 4.85 (IQR, 3.38-6.00) to 8.45 (IQR, 5.25-11.00) mm2/mm Hg (S = 112; P < .0001). The management changed based on FLIP values for 5 patients (21.7%), prompting additional myotomy. At 18.0 days (IQR, 12.8-47.8) after the procedure, the median GCSI score decreased from 3.33 (IQR, 2.56-4.12) preoperatively to 2.00 (IQR, 1.00-2.89) postoperatively (S = -193; P < .001). At a median follow-up of 136 days (IQR, 114-277), improvement in GCSI score persisted, with a median score of 2.44 (IQR, 1.44-3.67) (S = -61; P = .021). The median retention at 4 hours on GES decreased from 29.0% (IQR, 16.5-52.0%) to 19.5% (IQR, 5.75-35.30%) at 97 days (IQR, 88-130) after the procedure (S = -108; P = .0038). There was a 75% improvement and a 40% normalization in objective gastric emptying (n = 26). A greater increase in diameter after pyloromyotomy was associated with a greater decrease in 4-hour gastric retention (r = -0.4886; P = .021).

POP with FLIP resulted in clinical and radiographic improvements in patients with gastroparesis. FLIP measurements guided myotomy extent, changing the management in 21.7% of patients, and were associated with gastric emptying, demonstrating its distinct utility in the treatment of gastroparesis.

Low-dose aspirin for primary prevention is determined by the balance of risks of cardiovascular events and adverse effects. We assessed the long-term gastrointestinal symptoms or bleeding with low-dose aspirin in diabetic patients.

The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized clinical trial to evaluate the efficacy and safety of low-dose aspirin in patients with type 2 diabetes. As a post hoc analysis, we investigated the incidence of upper gastrointestinal symptoms or bleeding in aspirin (100 mg enteric-coated aspirin or 81 mg buffered aspirin daily) and no-aspirin groups within and beyond 3 years.

Of 2535 patients (mean age 65 years, 55% male) followed for a median of 11.2 years, 1258 were included in the aspirin group (951 enteric-coated, 208 buffered, 99 unknown) and 1277 were included in the no-aspirin group. The cumulative incidence of upper gastrointestinal symptoms or bleeding was higher in the aspirin group than the no-aspirin group (8.8% vs. 5.7% at 18 years; p < 0.0001). The increased risk in the aspirin group was prominent within 3 years, and the hazard ratio (HR) [95% confidence interval (CI)] of the aspirin group was 7.10 [3.21-15.7], but attenuated beyond 3 years (HR 1.20 [0.76-1.89]). In 1159 patients in the aspirin group, the cumulative incidence was lower in the enteric-coated than in the buffered aspirin groups (2.9% vs. 7.3%; p = 0.003) within 3 years, and the adjusted HR of enteric-coated aspirin was 0.38 [0.20-0.72] compared with the buffered aspirin group.

The upper gastrointestinal symptoms or bleeding of low-dose aspirin within 3 years, and the aspirin formulations, were relevant for decision making of initiation and continuation of low-dose aspirin for primary prevention.

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

This study aimed to assess the effect of perioperative rehabilitation exercise, initiated shortly after hospital admission, on postoperative outcomes in elderly patients.

A prospective, multicenter, randomized, controlled, open-label, and assessor-blinded clinical trial.

Hospital wards.

Elderly patients (≥65 years, n = 160) scheduled for gastrointestinal surgery between June 2021 and November 2022 were enrolled and randomly assigned to the intervention or control group.

Patients were divided into two groups base on whether they had received a specific type of exercise program initiated after hospital admission and continued until 30 days after surgery.

The primary outcome was the Comprehensive Complications Index (CCI) measured at 30 days after surgery. Secondary outcomes were the rate of complications, number of complications, patient satisfaction, hospital readmission, postoperative length of stay, gastrointestinal function recovery, postoperative quality of life and psychological status. Intention-to-treat (ITT) and per-protocol (PP) analyses were conducted.

ITT analysis showed a significantly lower 30-day CCI in the intervention group (β: -6.31; 95 % Confidence Interval [CI], -11.26 to -1.37, P = 0.013). Compared to controls, the intervention group had a decreased rate of hospital readmission (Odds Ratio: 0.00; 95 % CI, 0.00 to 0.32, P = 0.022), less number of complications (β: -0.57; 95 % CI, -1.03 to -0.11, P = 0.016), as well as lower rate of postoperative anxiety (β: -0.74; 95 % CI, -1.42 to -0.06, P = 0.033) and depression scores (β: -1.13; 95 % CI, -0.97 to -1.30, P = 0.008). Additionally, the intervention group reported higher satisfaction (β: 0.98; 95 % CI, 0.33 to 1.64, P = 0.004) and Euro quality of life-Visual Analogue Scale scores (β: 8.88; 95 % CI, 2.48 to 15.28, P = 0.007). Similar results were found in the PP analysis.

Perioperative rehabilitation exercise has a positive impact on postoperative complications, quality of life and psychological well-being in elderly patients undergoing gastrointestinal surgery, even when implemented after hospital admission.

Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting in chemotherapy-induced emesis. We investigated the safety and efficacy of tradipitant, a neurokinin receptor 1 antagonist, in patients with idiopathic and diabetic gastroparesis.

A total of 201 adults with gastroparesis were randomly assigned to oral tradipitant 85 mg (n = 102) or placebo (n = 99) twice daily for 12 weeks. Symptoms were assessed by a daily symptom dairy, Gastroparesis Cardinal Symptom Index scores, and other patient-reported questionnaires. Blood levels were monitored for an exposure-response analysis. The primary outcome was change from baseline to week 12 in average nausea severity, measured by daily symptom diary.

The intention-to-treat (ITT) population did not meet the prespecified primary endpoint at week 12 (difference in nausea severity change drug vs placebo; P = .741) or prespecified secondary endpoints. Post hoc analyses were performed to control for drug exposure, rescue medications, and baseline severity inflation. Subjects with high blood levels of tradipitant significantly improved average nausea severity beginning at early time points (weeks 2-4). In post hoc sensitivity analyses, tradipitant treatment demonstrated strengthened effects, with statistically significant improvements in nausea at week 12.

Although tradipitant did not reach significance in the ITT population, a pharmacokinetic exposure-response analysis demonstrated significant effects with adequate tradipitant exposure. When accounting for confounding factors such as baseline severity inflation and rescue medication, a statistically significant effect was also observed. These findings suggest that tradipitant has potential as a treatment for the symptom of nausea in gastroparesis. (ClincialTrials.gov, Number: NCT04028492).

Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50% and 80%, such that preoperative predictors of treatment success are needed to guide patient selection.

We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates through meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was used for risk of bias assessment.

Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%-69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, nondiabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation.

Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Gastric per-oral endoscopic myotomy (G-POEM) is a new therapeutic option for the treatment of refractory gastroparesis. However, the outcome of G-POEM after the failure of gastric electrical stimulation (GES) or other pylorus-targeting therapies has been poorly reported.

Data were collected from patients referred for G-POEM for refractory gastroparesis. The efficacy in patients with previous interventional techniques was compared to patients naïve to instrumental technique. The primary endpoint was the 6-month clinical success rate, defined as at least a 1-point decrease in the Gastroparesis Cardinal Symptom Index (GCSI).

Among 48 patients referred for G-POEM, 32 patients had previous instrumental treatments (66%): 15 (31%) had GES, and 17 (35%) had pyloric endoscopic dilation or toxin injection. The technical success rate was 100%. At 6 months, clinical success was achieved in 25/48 patients (52%) and the GCSI decreased from 3.38 (2.94-3.95) to 2.25 (1.11-3.36) (p < 0.001). The 6-month success rate was similar in patients with or without previous instrumental treatment (50.0% vs 56.3%; p = 0.41). The complication rate was also similar in the two groups (6.3% vs 12.5%; p = 0.59), with only one severe adverse event. The only predictive factor for success at 6 months was a higher body mass index (OR = 1.14 [1.01-1.32]; p = 0.05).

G-POEM is safe and remains effective after GES or previous pyloric treatment failure, with 50% efficacy at 6 months. The therapeutic strategy in refractory gastroparesis remains to be defined.

Gastric emptying scintigraphy is used to assess patients with symptoms of dyspepsia or gastroparesis. An alteration of fundus accommodation may explain these symptoms. The aim of this study was to determine the accommodation in gastric emptying scintigraphy studies performed in our institution.

50 patients (43 children) referred for gastric emptying assessment were evaluated. After fasting for 8 h, and following international guidelines, egg labeling was performed with 37 mBq of [99mTc]Tc-DTPA and administration of standardized food. Areas of interest were defined in the stomach at different times, and the corresponding retention percentages were calculated. Considering the image at time zero, gastric accommodation was qualitatively and quantitatively assessed, calculating the ratio between proximal stomach counts and total counts.

Of the 50 patients studied, 32 had normal emptying, 10 had slowed emptying and 8 had accelerated emptying. Within the group of patients with normal emptying, 8 had altered accommodation (25%) and another 8 in the group with abnormal emptying (44%). Applying the ROC curve analysis to quantitative values, the most appropriate cut-off value was 0.785 with p < 0.001, sensitivity 82.4% and specificity 100%.

Gastric emptying scintigraphy in addition to determining motility, made it possible to assess both qualitatively and quantitatively the distribution of the radiotracer in the stomach and thus, indirectly, the accommodation in the fundus. It provided added diagnostic information in a simple manner, without protocol changes and allowing more specific treatments to be assessed.

Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers.

We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function.

Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04-1.35), p = 0.01; GSRS: 1.15 (1.03-1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03-1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89-0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03-1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16-1.19), p = 0.03; GSRS: 0.87 (0.30-1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.

Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived.

Gastroparesis can be a debilitating disease process for which durable treatment options are lacking. While dietary changes and pharmacotherapy have some efficacy, symptoms frequently recur and some patients progress to needing supplemental enteral feeding access. Per oral pyloromyotomy (POP) has been shown to be a durable minimally invasive treatment option for refractory gastroparesis with a low side effect profile, and therefore has been performed at this institution for the past 6 years.

This was a retrospective case series of all patients who underwent a POP at a single institution over a 6-year period (2018-2023). Patient demographics, preoperative symptomatology and subsequent workup, postoperative complications, and symptom recurrence were collected and analyzed.

There were 56 patients included in the study. There was a 1.8:1 female:male ratio. The average patient age was 56 years old (range 23-85). The average duration of symptoms was 1-3 years. Thirty-eight percent of patients had undergone previous endoscopic therapy for gastroparesis (pyloric botox injection or pyloric dilation) and 16% of patients underwent multiple endoscopic therapies. Twenty-nine percent of patients were on a medication for gastroparesis. Past surgery was the most common gastroparesis etiology for POP (50% of patients). Diabetes (23%) and idiopathic (19%) were the other most common gastroparesis etiologies for POP. Nausea was the most common symptom at first follow-up (30%) but these patients continued to improve with 14% of patients continuing to endorse nausea at 6 months. Twenty-seven percent of patients developed symptom recurrence. Forty percent of patients with symptom recurrence underwent a repeat endoscopic or surgical therapy.

In this present study, POP leads to durable results in approximately 75% of patients with minimal complications. Furthermore, the majority of patients who do develop symptom recurrence do not require additional gastroparesis interventions.

Gastroparesis is a disorder of delayed gastric emptying with associated symptoms of postprandial fullness, early satiety, nausea, vomiting, bloating, and abdominal pain. Functional dyspepsia is an upper gastrointestinal disorder of gut-brain interaction that presents with similar symptoms but is defined according to symptom patterns rather than gastric motor dysfunction. Although delayed gastric emptying is a defining feature of gastroparesis, other aspects of gastric neuromuscular dysfunction, such as gastric accommodation and visceral hypersensitivity might contribute to symptoms. Similarly, although functional dyspepsia is not defined by impaired gastric emptying, disordered gastric motility might underlie pathogenesis in some patients with functional dyspepsia. In the last decade, it has been increasingly recognised that these two disorders might represent varying presentations along a common continuum of neuromuscular dysfunction, although with differentiating features with respect to outcomes, diagnosis, and treatments. In this Review, an overview of gastroparesis and functional dyspepsia from the perspective of gastric motility is provided, discussing what is distinct and what is shared between these disorders.

Pyloroplasty is an effective surgery for gastroparesis. However, some patients fail to improve after pyloric drainage and may require subsequent gastric electric stimulation. There is a paucity of data on the efficacy of gastric stimulator as an adjunct to failed pyloroplasty. This study aimed to describe our experience with pyloroplasty, determine the efficacy of gastric stimulator for failed pyloroplasty, and compare the final outcomes of those who required pyloroplasty with and without gastric stimulator for gastroparesis.

Records of patients who underwent primary pyloroplasty for gastroparesis at our institution were reviewed. Patients with poor symptomatic improvement after pyloroplasty underwent subsequent gastric stimulator. Symptoms were assessed using the gastroparesis cardinal symptom index (GCSI) preoperatively and after each surgery. Severe gastroparesis was defined as GCSI total score ≥3. Outcomes were assessed after pyloroplasty in all patients and after stimulator in patients who failed pyloroplasty. Final outcomes were then compared between those who did and did not require adjunct gastric stimulator.

The study population consisted of 104 patients (89.4% females) with a mean (SD) age of 42.2 years (11) and body mass index of 26.9 kg/m2 (7). Gastroparesis etiologies were 71.2% idiopathic, 17.3% diabetic, and 11.5% postsurgical. At 18.7 months (12) after pyloroplasty, there was a decrease in the GCSI total score (3.5 [1] to 2.7 [1.2]; P = .0012) and the rate of severe gastroparesis (71.9%-29.3%; P < .0001). Gastric emptying scintigraphy (GES) 4-hour retention decreased (36.5 [24] to 15.3 [18]; P = .0003). Adjunct gastric stimulator was required by 30 patients (28.8%) owing to suboptimal outcomes with no improvement in GCSI (P = .201) or GES (P = .320). These patients were younger (40.5 [10.6] vs 49.6 [15.2] years; P = .0016), with higher baseline GCSI total scores (4.3 [0.7] vs 3.7 [1.1]; P < .001) and more severe gastroparesis (100% vs 55.6%; P < .001). All other preoperative characteristics were similar. At 21.7 months (15) after gastric stimulator, there was improvement in GCSI (4.1 [0.7] to 2.6 [1.1]; P < .0001), severe gastroparesis (100%-33.3%; P < .0001), and GES 4-hour retention (21.2 [22] to 7.6 [10]; P = .054). Before gastric stimulator, those who failed pyloroplasty had significantly worse GCSI (P = .0009) and GES (P = .048). However, after gastric stimulator, GCSI and GES improved and were comparable with those who only required pyloroplasty (P > .05).

Pyloroplasty improved gastroparesis symptoms and gastric emptying, yet 28% failed, requiring gastric stimulator. Younger patients and those with preoperative GCSI scores ≥3 were more likely to fail. Gastric stimulator improved outcomes after failed pyloroplasty, with comparable final GCSI and GES with those who did not fail.

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.

Gastrointestinal (GI) magnetic resonance imaging (MRI) can simultaneously capture gastric peristalsis, emptying, and intestinal filling and transit. Performing GI MRI with animals requires anesthesia, which complicates physiology and confounds interpretation and translation from animals to humans. This study aims to enable MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

We acclimated rats to remain awake, still, and minimally stressed during MRI. We scanned 14 Sprague-Dawley rats in both awake and anesthetized conditions after voluntarily consuming a contrast-enhanced test meal.

Awake rats remained physiologically stable during MRI, showed gastric emptying of 23.7±1.4% after 48 minutes, and exhibited strong peristaltic contractions propagating through the antrum with a velocity of 0.72±0.04 mm/s, a relative amplitude of 40.7±2.3%, and a frequency of 5.1±0.1 cycles per minute. In the anesthetized condition, gastric emptying was about half of that in the awake condition, likely due to the effect of anesthesia in halving the amplitudes of peristaltic contractions rather than their frequency (not significantly changed) or velocity. In awake rats, the intestine filled more quickly and propulsive contractions were more occlusive.

We demonstrated the effective acquisition and analysis of GI MRI in awake rats. Awake rats show faster gastric emptying, stronger gastric contraction with a faster propagation speed, and more effective intestinal filling and transit, compared to anesthetized rats. Our protocol is expected to benefit future preclinical studies of GI physiology and pathophysiology.

This article reviews the evaluation and management of several gastrointestinal disorders that are commonly encountered by gastroenterologists and primary care physicians. With a focus on newer therapies, we discuss the management of chronic constipation, irritable bowel syndrome, Clostridioides difficile infection, gastroparesis, steatotic liver disease, and diverticulitis.

Diabetic gastroparesis, a common complication of type 2 diabetes (T2DM), presents a significant treatment challenge. FoxiangSan is emerging as a potential therapy. FoxiangSan is a traditional Chinese medicine formula with the potential for treating diabetic gastroparesis by modulating gut microbiota and cAMP/PKA signaling pathways. This study explores the mechanisms behind FoxiangSan's effects on T2DM-induced gastroparesis, focusing on its impact on gut microbiota and the cAMP/PKA pathway. A rat model of type 2 diabetic gastroparesis was established through a high-fat diet and streptozotocin (STZ) injection, and the effects of FoxiangSan were assessed. Additionally, protein expression related to the cAMP/PKA pathway was examined, and FoxiangSan's influence on gut microbiota was studied using 16S rRNA sequencing. FoxiangSan significantly alleviated hyperglycemia, improved gastric pathology in rats with gastroparesis, enhanced the expression of 5-HT4, cAMP, PKA, and pPKA in the gastric antrum, and rebalanced gut microbiota. FoxiangSan demonstrates the therapeutic potential for T2DM-associated gastroparesis by modulating the cAMP/PKA pathway and gut microbiota.

There has been an increasingly reported association between Ehlers-Danlos syndrome (EDS), postural orthostatic tachycardia syndrome (POTS) and gastrointestinal disorders. EDS is a hereditary connective tissue disorder which may manifest as a spectrum of symptoms stemming from collagen defects. The prevalence of EDS is estimated to affect 1 in 5000 individuals which underscores its clinical significance. Notably the hypermobile form (hEDS) accounts for the majority of cases. POTS is characterized by orthostatic intolerance with an increase in heart rate on standing in the absence of hypotension. This condition predominantly affects women between 15 and 45 years of age. Gastrointestinal symptoms in the form of reflux, bloating and abdominal pain significant impact this population. Gastroparesis is a chronic disorder involving symptoms of delayed gastric emptying and may be closely associated with hEDS and POTS, and may be underreported. Autonomic dysfunction associated with hEDS has been proposed as the likely mechanism underlying POTS and gastrointestinal dysfunction though a clear pathophysiological process has not been established.

Ghrelin, a peptide primarily secreted in the stomach, acts via the growth hormone secretagogue receptor (GHSR). It regulates several physiological processes, such as feeding behavior, energy homeostasis, glucose and lipid metabolism, cardiovascular function, bone formation, stress response, and learning. GHSR exhibits significant expression within the central nervous system. However, numerous murine studies indicate that ghrelin is limited in its ability to enter the brain from the bloodstream and is primarily confined to specific regions, such as arcuate nucleus (ARC) and median eminence (ME). Nevertheless, the central ghrelin system plays an essential role in regulating feeding behavior. Furthermore, the role of vagal afferent fibers in regulating the functions of ghrelin remains a major topic of discussion among researchers. In recent times, numerous studies have elucidated the substantial therapeutic potential of ghrelin in most gastrointestinal (GI) diseases. This has led to the development of numerous pharmaceutical agents that target the ghrelin system, some of which are currently under examination in clinical trials. Furthermore, ghrelin is speculated to serve as a promising biomarker for GI tumors, which indicates its potential use in tumor grade and stage evaluation. This review presents a summary of recent findings in research conducted on both animals and humans, highlighting the therapeutic properties of ghrelin system in GI disorders.