Calder, Stefan

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

ABSTRACT Background Chronic gastroduodenal symptoms arise from heterogeneous gastric motor dysfunctions. This study applied multimodal physiological testing using gastric emptying scintigraphy (GES) with intragastric meal distribution (IMD) and Gastric Alimetry body surface gastric mapping (BSGM) to define motility and symptom associations. Methods Patients with chronic gastroduodenal symptoms underwent simultaneous supine GES and BSGM with a 30 m baseline, 99mTC‐labeled egg meal, and 4 h postprandial recording. IMD (ratio of counts in the proximal half of the stomach to the total gastric counts) was calculated immediately after the meal (IMD0), with < 0.568 defining abnormal IMD. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals. Results Among 67 patients (84% female, median age 40 years, median BMI 24 kg/m 2 ), median IMD0 was 0.76 (IQR: 0.69–0.86) with 5 (7.5%) meeting abnormal IMD criteria. Delayed gastric emptying ( n = 18) was associated with higher IMD0 (median 0.9 vs. 0.7, p = 0.004). On BSGM, 15 patients had abnormal spectrograms (5 [7.5%] high frequency and 10 [14.9%] low rhythm stability and/or amplitude); and in these patients, higher IMD0 (proximal retention) strongly correlated to delayed BSGM meal responses ( R = −0.71, p = 0.003). Lower IMD, indicating antral distribution, correlated with higher gastric frequencies ( R = −0.27, p = 0.03). BSGM abnormalities paired with abnormal IMD were associated with worse dyspeptic symptoms. Conclusion Proximal retention of food as assessed by IMD correlated with delayed emptying, and in the presence of neuromuscular spectral abnormalities (abnormal frequencies or rhythms), delayed motility responses on BSGM. Patients with multiple motor abnormalities experience worse dyspeptic symptoms.

ABSTRACT Background Chronic neurogastroduodenal disorders are challenging to manage, with therapy often initiated on a trial and error basis. Prokinetics play a significant role in management, but responses are variable and have been associated with adverse events, impacting widespread use. We investigated whether body surface gastric mapping (BSGM) biomarkers (using Gastric Alimetry) could inform patient selection for prokinetic therapy. Methods Patients with chronic gastroduodenal symptoms taking oral prokinetic agents, regardless of gastric emptying status, were prospectively recruited and underwent BSGM (30 m baseline, 482 kcal standardized meal, 4 h postprandial recording) while off‐prokinetic agents. Patients were followed up with daily symptom diaries. A subset was compared to matched patients not taking prokinetic agents. Prokinetic responders were defined based on symptom improvement greater than a minimum clinically important difference methodology. Key Results Forty‐two patients (88% female; median age 36; median BMI 26) taking prokinetics were analyzed. Prokinetic prescribing, compared to matched patients, was independent of BSGM metrics ( p > 0.15). In patients on existing prokinetics (withheld for BSGM), lower amplitudes predicted reduced symptom burden, whereas low rhythm stability predicted a worse symptom burden ( p < 0.05). In prokinetic‐naive patients (i.e., started on a prokinetic during the study), a lower postprandial amplitude predicted responders (mean 37.5 ± 10.6 uV in responders [ n = 5] vs. mean 54.8 ± 6.6 uV among nonresponders [ n = 3], p = 0.047). Conclusions Gastric Alimetry biomarkers may help in the prediction of prokinetic response in patients with chronic gastroduodenal symptoms. Lower postprandial amplitudes, indicating a reduced meal response, appear to predict benefit, while impaired rhythm stability predicted poorer therapeutic response.

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

Objective This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC). Design All human tissue samples were from the muscularis externa of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array. Upregulated miRNAs were examined by quantitative reverse transcription qPCR (RT-qPCR) in a validation cohort of seven patients with STC and age/sex-matched controls. The effect of a highly differentially expressed miRNA on a custom human smooth muscle cell line was examined in vitro by RT-qPCR, electrophysiology, traction force microscopy, and ex vivo by lentiviral transduction in rat muscularis externa organotypic cultures. Results The expression of 13 miRNAs was increased in STC samples. Of those miRNAs, four were predicted to target SCN5A , the gene that encodes the Na + channel Na V 1.5. The expression of SCN5A mRNA was decreased in STC samples. Let-7f significantly decreased Na + current density in vitro in human smooth muscle cells. In rat muscularis externa organotypic cultures, overexpression of let-7f resulted in reduced frequency and amplitude of contraction. Conclusions A small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na + channel Na V 1.5. Within this set, a novel Na V 1.5 regulator, let-7f, resulted in decreased Na V 1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest Na V 1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.