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

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

Leptin-Melanocortin pathway variants and gastric emptying in patients with obesity.

BACKGROUND: Accelerated gastric emptying (GE) is a trait seen in obesity. Mutations in the hypothalamic leptin-melanocortin 4 receptor (Leptin-MC4R) pathway have been associated with obesity. We sought to investigate the association of leptin-MC4R pathway variants and GE in patients with obesity. METHODS: This is a cross-sectional study of patients with a history of severe obesity that were genotyped and completed a GE test by scintigraphy. We evaluated the percentage of GE (GE %) at 2 and 4 h between both groups using ANCOVA with weight and sex as covariates. We subdivide patients into carriers based on the location of the identified variants (i.e., upstream or downstream of the Leptin-MC4R pathway) and compared them with noncarriers using ANOVA. Results are presented as mean and standard deviation (± SD). KEY RESULTS: A total of 95 patients; nine carriers (67% females; 39.78 ± 12.33 years; BMI: 49.14 ± 12.96 kg/m2) and 86 noncarriers (87% female; 49.98 ± 13.74 years; BMI: 40.75 ± 6.29 kg/m2) were included. At 2 and 4 h, carriers had a delayed GE when compared noncarriers (p = 0.03 and p = 0.005, respectively). In carriers, when compared upstream carriers vs. downstream carriers vs. noncarriers by location there was a significant difference in GE among groups at 2 h and at 4 h (p = 0.02 and p = 0.01, respectively). CONCLUSIONS & INFERENCES: Carriers of heterozygous variants in the Leptin-MC4R pathway had a delayed GE compared to noncarriers. These findings point the important relationship between the Leptin-MC4R pathway and gastric motility.

The role of gastric function in control of food intake (and body weight) in relation to obesity, as well as pharmacological and surgical interventions.

PURPOSE: The objectives of this review are to summarize the role of gastric motor functions in the development of satiation (defined broadly as postprandial fullness) and satiety (reduced appetite or postponing desire to eat after a meal) and their impact on weight change. The specific topics are the methods of measurement of gastric emptying and accommodation and their impact on food intake, satiation, and satiety. A second focus contrasts bariatric surgery to endoscopic gastroplasty that alter gastric emptying and incretin responses in markedly divergent manners. BACKGROUND: The hormone, GLP-1, retards gastric emptying and increases gastric accommodation through vagally-mediated effects. Indeed, these effects provide the basis for the association of altered gastric emptying in the appetite and weight loss responses to pharmacological interventions particularly by those acting on receptors of incretin agonists such as liraglutide and the dual agonists, tirzepatide and cotadutide, all of which retard gastric emptying. In fact, retardation of gastric emptying and gastrointestinal adverse effects have been shown to contribute in part to the weight loss in response to this class of pharmacological agents. SUMMARY: The motor functions of the stomach are relevant to postprandial fullness and to interventions aimed at weight loss in people with obesity.

Long-Term Outcomes of Pylorus-Preserving Gastrectomy for Early Gastric Cancer.

BACKGROUND: In the short term, pylorus-preserving gastrectomy (PPG) has been reported to have advantages over distal gastrectomy (DG) with regard to postprandial symptoms and dumping syndrome. We aimed to evaluate the quality of life after PPG for early gastric cancer in the long term in comparison to that after DG. METHODS: Twenty-six patients who underwent gastrectomy (11 PPG, 15 DG) for early gastric cancer at Osaka University Hospital participated and were followed for more than 4 years. Body weight changes, nutritional status, dual-phase scintigraphy findings, endoscopic survey results, and questionnaire responses after gastrectomy were examined. RESULTS: There were significantly lower ratios of weight changes in PPG than in DG, 5 years after surgery. There were no differences in the clinicopathological characteristics, nutritional parameters, questionnaire responses, and endoscopic findings between the two groups. Based on gastric scintigraphy, although the gastric emptying of liquids showed similar curves in the two groups, gastric emptying of solids was significantly slower in the PPG group than in the DG group (P = .039). DISCUSSION: PPG had advantages with regard to long-term outcomes over DG in terms of weight maintenance and the prevention of rapid gastric emptying. PPG might be efficient in patients with early gastric cancer.

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

INTRODUCTION: Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. METHODS: Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. RESULTS: Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. DISCUSSION: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

[Evaluation of gastric emptying after drinking carbohydrates before cesarean section by gastric ultrasonography].

OBJECTIVE: To investigate the effect of gastric antrum ultrasonography in evaluating gastric emptying after oral administration of 300 mL carbohydrates two hours before cesarean section, and to analyze the risk factors of gastric emptying in pregnant women. METHODS: From August 2020 to February 2021, a total of 80 patients, aged 22-43 years, body mass index (BMI) < 35 kg/m2, gestational age≥36 weeks, falling into American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, scheduled for cesarean sections in Peking University International Hospital were recruited and divided into two groups: the intervention group (n=40)and the control group (n=40). In the intervention group, solid food was restricted after 22:00, the patients were required to take 300 mL carbohydrates two hours before cesarean section. In the control group, solid food and liquid intake were restricted after 22:00 the night before surgery. All the patients received assessment of preoperative feeling of thirst and starvation with visual analogue scale (VAS). The cross-sectional area (CSA)of gastric antrum was measured in supine position and right supine position before anesthesia, the gastric volume (GV)and the gastric volume/weight(GV/W)of the two groups was further calculated. Perlas A semi-quantitative grading assessments were performed in each patient. The blood pressure and heart rate were recorded at admission(T0), 5 minutes after anesthesia (T1), immediately after fetal delivery (T2) and at the end of the surgery (T3). The occurrence of nausea and vomiting during the operation and 24 hours after the operation were recorded. RESULTS: One case in each group was excluded because the antrum was not clearly identified during the ultrasound assessments. In the semi-sitting position, the CSA was (5.07±1.73) cm2 in the intervention group vs. (5.24±1.96) cm2 in the control group, respectively; in the right lateral decubitus position, CSA was (7.32±2.17) cm2 in the intervention group vs. (7.25±2.24) cm2 in the control group, GV was (91.74±32.34) mL vs. (90.07±31.68) mL, GV/W was (1.27±0.40) mL/kg vs. (1.22±0.41) mL/kg, respectively; all the above showed no significant difference between the two groups (P > 0.05). Perlas A semi-quantitative grading showed 0 in 20 patients (51.3%), 1 in 16 (41%), 2 in 3 (7.7%)in the intervention group and 0 in 22 (56.4%), 1 in 15 (38.5%), 2 in 2 (5.1%)in the control group, the proportion of Perlas A semi-quantitative grading showed no significant difference between the two groups (P > 0.05). For the patients with Perlas A semi-quantitative grade 2 (3 cases in the intervention group and 2 cases in the control group), metoclopramide 0.2 mg/kg was intravenously injected before anesthesia. No aspiration case was observed in this study. The intervention group was endured less thirst and hunger (P < 0.05). There was no significant difference in blood pressure and heart rate between the two groups at each time point (P > 0.05). There was no significant difference in the incidence of intraoperative hypotension between the two groups (P > 0.05). There was no significant difference in the incidence of nausea intraoperatively and postoperatively between the two groups (P > 0.05). CONCLUSION: Ultrasonography of gastric antrum can provide objective basis for evaluating gastric emptying of pregnant women perioperatively. 300 mL carbohydrates intake two hours before surgery, which does not increase GV and the risk of reflux aspiration, and is helpful in minimizing disturbance to the patient's physiological status, therefore leading to better clinical outcome.

Gastric Electrical Stimulation as a New Treatment Modality for Refractory Nausea and Vomiting with Normal Gastric Emptying.

Nausea and vomiting are cardinal symptoms affecting many patients with delayed or normal gastric emptying. The current therapies are very limited and less than optimal. Therefore, gastrointestinal symptoms persist despite using all the standard approaches for gastroparesis, functional dyspepsia, or unexplained nausea and vomiting. It is well established that gastric electrical stimulation (GES) is effective in reducing nausea and vomiting in gastroparesis, but there are essentially no data available that detail the efficacy of GES in symptomatic patients without gastroparesis. We present a unique case of a female patient diagnosed with functional dyspepsia, whose nausea and vomiting which were refractory to all standard therapies were successfully addressed with the implantation of a GES system.

Gastric electrical stimulation is safe during pregnancy and delivery: Results from a French cohort.

BACKGROUND: Gastric electrical stimulation (GES) is an effective therapy in medically refractory chronic nausea and vomiting. GES is assumed to be a contraindication for pregnancy. We examined the safety of GES during pregnancy and its clinical impact on vomiting symptoms. METHODS: A retrospective study was performed in two tertiary centers including all female patients of childbearing age implanted with GES. Patients without pregnancy while on GES were asked about their desire and concerns about pregnancy. Patients who were pregnant while on GES therapy were interviewed about the course of the pregnancy and labor, as well as the health of the children. KEY RESULTS: Among 91 patients implanted at childbearing age, 54 patients without pregnancy answered the questionnaire. Nine patients (16.7%) reported a desire for pregnancy and five patients (7.4%) reported worries about the safety of GES during pregnancy. Sixteen pregnancies were reported in 10 patients. All pregnancies ended in a live birth with premature birth in 12 pregnancies (75.0%). No health concern was currently noted in these children. No severe GES-related complications occurred during pregnancy with only pain at the implantation site reported during 3 pregnancies (18.8%). The severity and frequency of nausea and vomiting significantly increased during the first trimester (p = 0.04 and p = 0.005, respectively) and decreased after the delivery, becoming lower than before the pregnancy (p = 0.044 and p = 0.011, respectively). CONCLUSION & INFERENCES: Patients are concerned regarding pregnancy while being treated with GES. No serious maternal or fetal complications related to GES were noted in our cohort.

Gastric Alimetry in the Management of Chronic Gastroduodenal Disorders: Impact to Diagnosis and Health Care Utilization.

INTRODUCTION: Chronic gastroduodenal symptoms are frequently overlapping within existing diagnostic paradigms, and current diagnostic tests are insensitive to underlying pathophysiologies. Gastric Alimetry has emerged as a new diagnostic test of gastric neuromuscular function with time-of-test symptom profiling. This study aimed to assess the impact to diagnosis and health care utilization after the introduction of Gastric Alimetry into clinical care. METHODS: Consecutive data of patients from 2 tertiary centers with chronic gastroduodenal symptoms (Rome-IV defined or motility disorder) having integrated care and Gastric Alimetry testing were evaluated. Changes in diagnoses, interventions, and management were quantified. Pretest and posttest health care utilization was reported. A preliminary management framework was established through experiential learning. RESULTS: Fifty participants (45 women; median age 30 years; 18 with gastroparesis, 24 with chronic nausea and vomiting syndrome, and 6 with functional dyspepsia) underwent Gastric Alimetry testing. One-third of patients had a spectral abnormality (18% dysrhythmic/low amplitude). Of the remaining patients, 9 had symptoms correlating to gastric amplitude, while 19 had symptoms unrelated to gastric activity. Gastric Alimetry aided management decisions in 84%, including changes in invasive nutritional support in 9/50 cases (18%; predominantly de-escalation). Health care utilization was significantly lower post-Gastric Alimetry testing when compared with the average utilization cost in the year before Gastric Alimetry testing (mean ± SD $39,724 ± 63,566 vs $19,937 ± 35,895, P = 0.037). DISCUSSION: Gastric Alimetry aided diagnosis and management of patients with chronic gastroduodenal symptoms by enabling phenotype-informed care. The high majority of results aided management decisions, which was associated with reduced health care utilization.

Stochastic Differential Equation-based Mixed Effects Model of the Fluid Volume in the Fasted Stomach in Healthy Adult Human.

The rate and extent of drug dissolution and absorption from a solid oral dosage form depend largely on the fluid volume along the gastrointestinal tract. Hence, a model built upon the gastric fluid volume profiles can help to predict drug dissolution and subsequent absorption. To capture the great inter- and intra-individual variability (IAV) of the gastric fluid volume in fasted human, a stochastic differential equation (SDE)-based mixed effects model was developed and compared with the ordinary differential equation (ODE)-based model. Twelve fasted healthy adult subjects were enrolled and had their gastric fluid volume measured before and after consumption of 240 mL of water at pre-determined intervals for up to 2 hours post ingestion. The SDE- and ODE-based mixed effects models were implemented and compared using extended Kalman filter algorithm via NONMEM. The SDE approach greatly improved the goodness of fit compared with the ODE counterpart. The proportional and additive measurement error of the final SDE model decreased from 14.4 to 4.10% and from 17.6 to 4.74 mL, respectively. The SDE-based mixed effects model successfully characterized the gastric volume profiles in the fasted healthy subjects, and provided a robust approximation of the physiological parameters in the very dynamic system. The remarkable IAV could be further separated into system dynamics terms and measurement error terms in the SDE model instead of only empirically attributing IAV to measurement errors in the traditional ODE method. The system dynamics were best captured by the random fluctuations of gastric emptying coefficient Kge.

Pan-alimentary assessment of motility, luminal content, and structures: an MRI-based framework.

BACKGROUND: Gastrointestinal symptoms originating from different segments overlap and complicate diagnosis and treatment. In this study, we aimed to develop and test a pan-alimentary framework for the evaluation of gastrointestinal (GI) motility and different static endpoints based on magnetic resonance imaging (MRI) without contrast agents or bowel preparation. METHODS: Twenty healthy volunteers (55.6 ± 10.9 years, BMI 30.8 ± 9.2 kg/m2) underwent baseline and post-meal MRI scans at multiple time points. From the scans, the following were obtained: Gastric segmental volumes and motility, emptying half time (T50), small bowel volume and motility, colonic segmental volumes, and fecal water content. Questionnaires to assess GI symptoms were collected between and after MRI scans. KEY RESULTS: We observed an increase in stomach and small bowel volume immediately after meal intake from baseline values (p<.001 for the stomach and p=.05 for the small bowel). The volume increase of the stomach primarily involved the fundus (p<.001) in the earliest phase of digestion with a T50 of 92.1 ± 35.3 min. The intake of the meal immediately elicited a motility increase in the small bowel (p<.001). No differences in colonic fecal water content between baseline and 105 min were observed. CONCLUSION & INFERENCES: We developed a framework for a pan-alimentary assessment of GI endpoints and observed how different dynamic and static physiological endpoints responded to meal intake. All endpoints aligned with the current literature for individual gut segments, showing that a comprehensive model may unravel complex and incoherent gastrointestinal symptoms in patients.

Changes in Oesophageal Transit, Macro-Reflux Events, and Gastric Emptying Correlate with Improvements in Gastro-Intestinal Symptoms and Food Tolerance Early Post Sleeve Gastrectomy.

PURPOSE: There are significant alterations in gastro-intestinal function, food tolerance, and symptoms following sleeve gastrectomy (SG). These substantially change over the first year, but it is unclear what the underlying physiological basis for these changes is. We examined changes in oesophageal transit and gastric emptying and how these correlate with changes in gastro-intestinal symptoms and food tolerance. MATERIAL AND METHODS: Post-SG patients undertook protocolised nuclear scintigraphy imaging along with a clinical questionnaire at 6 weeks, 6 months, and 12 months. RESULTS: Thirteen patients were studied: mean age (44.8 ± 8.5 years), 76.9% females, pre-operative BMI (46.9 ± 6.7 kg/m2). Post-operative %TWL was 11.9 ± 5.1% (6 weeks) and 32.2 ± 10.1% (12 months), p-value < 0.0001. There was a substantial increase of meal within the proximal stomach; 22.3% (IQR 12%) (6 weeks) vs. 34.2% (IQR 19.7%) (12 months), p = 0.038. Hyper-accelerated transit into the small bowel decreased from 6 weeks 49.6% (IQR 10.8%) to 42.7% (IQR 20.5%) 12 months, p = 0.022. Gastric emptying half-time increased from 6 weeks 19 (IQR 8.5) to 12 months 27 (IQR 11.5) min, p = 0.027. The incidence of deglutitive reflux of semi-solids decreased over time; 46.2% (6 weeks) vs. 18.2% (12 months), p-value < 0.0001. Reflux score of 10.6 ± 7.6 at 6 weeks vs. 3.5 ± 4.4 at 12 months, (p = 0.049) and regurgitation score of 9.9 ± 3.3 at 6 weeks vs. 6.5 ± 1.7, p = 0.021 significantly reduced. CONCLUSIONS: These data demonstrate that there is an increase in the capacity of the proximal gastric sleeve to accommodate substrate over the first year. Gastric emptying remains rapid but reduce over time, correlating with improved food tolerance and reduced reflux symptoms. This is likely the physiological basis for the changes in symptoms and food tolerance observed early post-SG.

Exploring the Gut-Brain Connection in Gastroparesis With Autonomic and Gastric Myoelectric Monitoring.

OBJECTIVE: The goal of this study was to identify autonomic and gastric myoelectric biomarkers from throughout the day that differentiate patients with gastroparesis, diabetics without gastroparesis, and healthy controls, while providing insight into etiology. METHODS: We collected 19 24-hour recordings of electrocardiogram (ECG) and electrogastrogram (EGG) data from healthy controls and patients with diabetic or idiopathic gastroparesis. We used physiologically and statistically rigorous models to extract autonomic and gastric myoelectric information from the ECG and EGG data, respectively. From these, we constructed quantitative indices which differentiated the distinct groups and demonstrated their application in automatic classification paradigms and as quantitative summary scores. RESULTS: We identified several differentiators that separate healthy controls from gastroparetic patient groups, specifically around sleep and meals. We also demonstrated the downstream utility of these differentiators in automatic classification and quantitative scoring paradigms. Even with this small pilot dataset, automated classifiers achieved an accuracy of 79% separating autonomic phenotypes and 65% separating gastrointestinal phenotypes. We also achieved 89% accuracy separating controls from gastroparetic patients in general and 90% accuracy separating diabetics with and without gastroparesis. These differentiators also suggested varying etiologies for different phenotypes. CONCLUSION: The differentiators we identified were able to successfully distinguish between several autonomic and gastrointestinal (GI) phenotypes using data collected while at-home with non-invasive sensors. SIGNIFICANCE: Autonomic and gastric myoelectric differentiators, obtained using at-home recording of fully non-invasive signals, can be the first step towards dynamic quantitative markers to track severity, disease progression, and treatment response for combined autonomic and GI phenotypes.

Diffeomorphic Surface Modeling for MRI-Based Characterization of Gastric Anatomy and Motility.

OBJECTIVE: Gastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the movement of the food inside the stomach, but does not directly report muscular activity on the stomach wall. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the ingesta. METHODS: A neural ordinary differential equation was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomechanical process. Driven by this diffeomorphic flow, the surface of the stomach progressively changes its shape over time, while preserving its topology and manifoldness. RESULTS: We tested this approach with MRI data collected from 10 rats under a lightly anesthetized condition, and demonstrated accurate characterization of gastric motor events with an error in the order of sub-millimeters. Uniquely, we characterized gastric anatomy and motility with a surface coordinate system common at both individual and group levels. Functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity and its coordination across different regions. The peristalsis at the distal antrum had a dominant frequency and peak-to-peak amplitude of [Formula: see text] cycles per minute and [Formula: see text] mm, respectively. The relationship between muscle thickness and gastric motility was found to be distinct between two functional regions in the proximal and distal stomach. CONCLUSION: These results demonstrate the efficacy of using MRI to model gastric anatomy and function. SIGNIFICANCE: The proposed approach is expected to enable non-invasive and accurate mapping of gastric motility for preclinical and clinical studies.

Reconsideration of the Gastroparetic Syndrome.

PURPOSE OF REVIEW: Gastroparesis is a chronic disorder characterized by a constellation of foregut symptoms, including postprandial nausea, vomiting, distension, epigastric pain, and regurgitation in the absence of gastric outlet obstruction. Despite considerable research over the past decades, there remains to be only nominal understanding of disease classification, diagnostic criteria, pathogenesis, and preferred therapy. RECENT FINDINGS: We critically reassess current approaches for disease identification and stratification, theories of causation, and treatment for gastroparesis. Gastric scintigraphy, long considered a diagnostic standard, has been re-evaluated in light of evidence showing low sensitivity, whereas newer testing modalities are incompletely validated. Present concepts of pathogenesis do not provide a unified model linking biological impairments with clinical manifestations, whereas available pharmacological and anatomical treatments lack explicit selection criteria or evidence for sustained effectiveness. We propose a disease model that embodies the re-programming of distributed neuro-immune interactions in the gastric wall by inflammatory perturbants. These interactions, combined with effects on the foregut hormonal milieu and brain-gut axis, are postulated to generate the syndromic attributes characteristically linked with gastroparesis. Research linking models of immunopathogenesis with diagnostic and therapeutic paradigms will lead to reclassifications of gastroparesis that guide future trials and technological developments. KEY POINTS: • The term gastroparesis embodies a heterogenous array of symptoms and clinical findings based on a complex assimilation of afferent and efferent mechanisms, gastrointestinal locations, and pathologies. • There currently exists no single test or group of tests with sufficient capacity to be termed a definitional standard for gastroparesis. • Present research regarding pathogenesis suggests the importance of immune regulation of intrinsic oscillatory activity involving myenteric nerves, interstitial cells of Cajal, and smooth muscle cells. • Prokinetic pharmaceuticals remain the mainstay of management, although novel treatments are being studied that are directed to alternative muscle/nerve receptors, electromodulation of the brain-gut axis, and anatomical (endoscopic, surgical) interventions.

Mfge8 is expressed by pericytes in gastric antrum submucosa from patients with obesity.

The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8ß1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c+ perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2+ and PDGFRB+ pericytes. Mfge8 is expressed in NG2+/Mef2c+ pericytes, but not in NG2+/Mef2c-, PDGFRB+/Mef2c-, or PDGFRB+/Mef2c+ pericytes. Mfge8 is absent from CD34+ endothelial cells but is expressed in a small population of perivascular ACTA2+ cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8ß1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα+ cell (SIP) syncytium.

Deuterium body array for the simultaneous measurement of hepatic and renal glucose metabolism and gastric emptying with dynamic 3D deuterium metabolic imaging at 7 T.

Deuterium metabolic imaging (DMI) is a novel noninvasive method to assess tissue metabolism and organ (patho)physiology in vivo using deuterated substrates, such as [6,6'-2 H2 ]-glucose. The liver and kidneys play a central role in whole-body glucose homeostasis, and in type 2 diabetes, both hepatic and renal glucose metabolism are dysregulated. Diabetes is also associated with gastric emptying abnormalities. In this study, we developed a four-channel 2 H transmit/receive body array coil for DMI in the human abdomen at 7 T and assessed its performance. In addition, the feasibility of simultaneously measuring gastric emptying, and hepatic and renal glucose uptake and metabolism with dynamic 3D DMI upon administration of deuterated glucose, was investigated. Simulated and measured B1 + patterns were in good agreement. The intrasession variability of the natural abundance deuterated water signal in the liver and right kidney, measured in nine healthy volunteers, was 5.6% ± 0.9% and 4.9% ± 0.7%, respectively. Dynamic 3D DMI scans with oral administration of [6,6'-2 H2 ]-glucose showed similar kinetics of deuterated glucose appearance and disappearance in the liver and kidney. The measured gastric emptying half time was 80 ± 10 min, which is in good agreement with scintigraphy measurements. In conclusion, DMI with oral administration of [6,6'-2 H2 ]-glucose enables simultaneous assessment of gastric emptying and liver and kidney glucose uptake and metabolism. When applied in patients with diabetes, this approach may advance our understanding of the interplay between disturbances in liver and kidney glucose uptake and metabolism and gastric emptying, at a detail that cannot be achieved by any other method.

Gastric electrical stimulation versus per-oral pyloromyotomy for the treatment of nausea and vomiting associated with gastroparesis: An observational study of two cohorts.

BACKGROUND: Both gastric electrical stimulation (GES) and gastric-peroral endoscopic myotomy (G-POEM) can be offered to patients with gastroparesis and predominant nausea and vomiting. The study's aim was to compare GES and G-POEM efficacy on nausea and vomiting scores in patients with gastroparesis. METHODS: Two multicenter cohorts of patients with medically refractory gastroparesis with predominant nausea and vomiting (defined as a score >2 on nausea and vomiting subscale that varied from 0 to 4) were treated either with GES (n = 34) or G-POEM (n = 30) and were followed for 24 months (M). Clinical response was defined as a decrease of ≥1 point in nausea and vomiting subscale without premature exclusion due to switch from one to the other technique before M24. Changes in symptomatic scales and quality of life were also monitored. KEY RESULTS: Patients from both groups were comparable although the mean score of nausea and vomiting subscale was higher in GES (3.0) compared to G-POEM group (2.6; p = 0.01). At M24, clinical response was achieved in 21/34 (61.7%) patients with GES and in 21/30 (70.0%; p = 0.60) patients with G-POEM. Mean scores of nausea and vomiting subscale decreased at M24 in both GES (from 3.0 to 1.6; p < 0.001) and G-POEM (from 2.6 to 1.2; p < 0.001) groups, although there was no difference between groups (difference adjusted from baseline: -0.28 [-0.77; 0.19]; p = 0.24). Likewise, symptomatic and quality of life scores improved at M24 in both groups, without difference according to treatment group. CONCLUSIONS AND INFERENCES: At M24, we did not observe significant difference in efficacy of GES and G-POEM in medically refractory gastroparesis with predominant nausea and vomiting.

Effect of liquid and solid test meals on symptoms and gastric myoelectrical activity in patients with gastroparesis and functional dyspepsia.

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain. AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD. METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load for individual patients were also determined. RESULTS: 284 patients with GP and 113 with FD were identified who ingested both test meals. Patients with GP and FD had similar maximal tolerated volumes of water [mean (SD) 378 (218) ml vs. 402 (226) ml, p = 0.23] and reported similar intensity of fullness, nausea, bloating, and abdominal discomfort after the test meals. Twenty-six percent and 19% of the patients with GP and FD, respectively, ingested subthreshold (<238 ml) volumes of water (p = 0.15). Gastric dysrhythmias were recorded in 66% of the GP and 65% of the FD patients after the water load. Symptoms and GMA were similar in both groups after ingestion of the nutrient bar. CONCLUSION: The similarity in GMA responses and symptoms after ingestion of solid or liquid test meals suggests GP and FD are closely related gastric neuromuscular disorders.