Background/Aims: Semaglutide is associated with gastroduodenal symptoms, such as nausea and vomiting. This pilot study used body surface gastric mapping (BSGM) to measure the effect of semaglutide on gastric function and associated symptoms. Methods: Patients without gastrointestinal symptoms (n = 8) underwent BSGM at baseline and on 1 mg semaglutide, as per standard subcutaneous dosing. Spectral metrics included Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI), body mass index-adjusted amplitude, fed:fasted amplitude ratio, and meal response ratio. Symptoms were assessed using validated questionnaires. Data were compared using paired t tests. Results: Body mass index-adjusted amplitude showed a significant decrease on the drug (P = 0.04). Five patients (63%) developed spectral abnormalities on the drug, with 2 displaying a low or undetectable GA-RI (< 0.25). The patient assessment of upper gastrointestinal disorders-symptom severity index fullness/early satiation subscale significantly increased on the drug (P = 0.005). Conclusions Semaglutide appears to alter gastric electrical activity on BSGM and increase early satiation, offering potential biomarkers for detecting drug effects. Further studies are needed.

Background/Aims: Gastric emptying scintigraphy (GES) is the reference standard test for diagnosing gastroparesis. Body surface gastric mapping (BSGM) via Gastric Alimetry is a new test of gastric function that combines non-invasive assessment of gastric electrophysiology and validated symptom profiling. This randomized, prospective pilot study evaluated the impact of GES vs BSGM test results on clinical decision-making. Methods: Patients with chronic gastroduodenal symptoms from a tertiary center referred for GES were recruited. Subjects separately underwent baseline assessment with GES and BSGM testing. Two motility-specialists were first asked to devise a management plan after reviewing a test result (GES or BSGM, in random order). They were then asked to repeat the management plan after reviewing the other test result (BSGM or GES). Clinician-perceived certainty measures were assessed. Results: Sixteen patients, 13 (81.0%) female, median age 30 years, median body mass index 22.5 kg/m2 , were recruited.At baseline, a diagnosis was established in 2/16 (12.5%) and increased to 8/16 (50.0%) with both tests. Abnormal test results were found in 11 patients. In patients with normal results, BSGM symptom profiling phenotyped 5 additional patients. All patients received an intervention following the first unblinding, with subsequent management changes made in 75.0% (BSGM) and 62.5% (GES) of patients. The combined GES and BSGM results significantly increased diagnostic and management certainty (P < 0.05), with both tests having similar influence on management (P > 0.05). Conclusion The combined GES and BSGM test results significantly enhanced diagnostic and management confidence in patients with suspected gastroparesis within a tertiary center.

Background/Aims: Interstitial cells of Cajal (ICC) are specialized gastrointestinal (GI) pacemaker cells required for normal GI motility. Dysfunctions in ICC have been reported in patients with GI motility disorders, such as gastroparesis, who exhibit debilitating symptoms and greatly reduced quality of life. While the proteins, calcium-activated chloride channel anoctamin-1 (ANO1) and the receptor tyrosine kinase (KIT), are known to be expressed by human ICC, relatively little is known about the broad molecular circuitry underpinning human ICC functions. The present study therefore investigates the transcriptome and proteome of ANO1-expressing, KIT low /CD45- /CD11B- ICC obtained from primary human gastric tissue. Methods: Excess human gastric tissue resections were obtained from sleeve gastrectomy patients. ICC were purified using fluorescence-activated cell sorting (FACSorting). Then, ICC were characterized by using immunofluorescence, real-time polymerase chain reaction, RNAsequencing and mass spectrometry. Results: Compared to unsorted cells, real-time polymerase chain reaction showed the KIT low /CD45- /CD11B- ICC had: a 9-fold (P < 0.05) increase in ANO1 expression; unchanged KIT expression; and reduced expression for genes associated with hematopoietic cells (CD68, > 10-fold, P < 0.001) and smooth muscle cells (DES, > 4-fold, P < 0.05). RNA-sequencing and gene ontology analyses of the KIT low / CD45- /CD11B- cells revealed a transcriptional profile consistent with ICC function. Similarly, mass spectrometry analyses of the KIT low / CD45- /CD11B - cells presented a proteomic profile consistent with ICC activities. STRING-based protein interaction analyses using the RNA-sequencing and proteomic datasets predicted protein networks consistent with ICC-associated pacemaker activity and ion transport. Conclusion These new and complementary datasets provide a valuable molecular framework for further understanding how ICC pacemaker activity regulates smooth muscle contraction in both normal GI tissue and GI motility disorders.