Effects of corticotropin-releasing hormone on gastric electrical activity and sensorimotor function in healthy volunteers: a double-blinded crossover study.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m2] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo.NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Effect of menstrual cycle and menopause on human gastric electrophysiology.

Chronic gastroduodenal symptoms disproportionately affect females of childbearing age; however, the effect of menstrual cycling on gastric electrophysiology is poorly defined. To establish the effect of the menstrual cycle on gastric electrophysiology, healthy subjects underwent noninvasive Body Surface Gastric Mapping (BSGM; 8x8 array) with the validated symptom logging App (Gastric Alimetry, New Zealand). Participants included were premenopausal females in follicular (n = 26) and luteal phases (n = 18) and postmenopausal females (n = 30) and males (n = 51) were controls. Principal gastric frequency (PGF), body mass index (BMI) adjusted amplitude, Gastric Alimetry Rhythm Index (GA-RI), Fed:Fasted Amplitude Ratio (ff-AR), meal response curves, and symptom burden were analyzed. Menstrual cycle-related electrophysiological changes were then transferred to an established anatomically accurate computational gastric fluid dynamics model (meal viscosity 0.1 Pas) to predict the impact on gastric mixing and emptying. PGF was significantly higher in the luteal versus follicular phase [mean 3.21 cpm, SD (0.17) vs. 2.94 cpm, SD (0.17), P < 0.001] and versus males [3.01 cpm, SD (0.2), P < 0.001]. In the computational model, this translated to 8.1% higher gastric mixing strength and 5.3% faster gastric emptying for luteal versus follicular phases. Postmenopausal females also exhibited higher PGF than females in the follicular phase [3.10 cpm, SD (0.24) vs. 2.94 cpm, SD (0.17), P = 0.01], and higher BMI-adjusted amplitude [40.7 µV (33.02-52.58) vs. 29.6 µV (26.15-39.65), P < 0.001], GA-RI [0.60 (0.48-0.73) vs. 0.43 (0.30-0.60), P = 0.005], and ff-AR [2.51 (1.79-3.47) vs. 1.48 (1.21-2.17), P = 0.001] than males. There were no differences in symptoms. These results define variations in gastric electrophysiology with regard to human menstrual cycling and menopause.NEW & NOTEWORTHY This study evaluates gastric electrophysiology in relation to the menstrual cycle using a novel noninvasive high-resolution methodology, revealing substantial variations in gastric activity with menstrual cycling and menopause. Gastric slow-wave frequency is significantly higher in the luteal versus follicular menstrual phase. Computational modeling predicts that this difference translates to higher rates of gastric mixing and liquid emptying in the luteal phase, which is consistent with previous experimental data evaluating menstrual cycling effects on gastric emptying.

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.

Designing, Developing, and Validating a Set of Standardized Pictograms to Support Pediatric-Reported Gastroduodenal Symptoms.

OBJECTIVE: To develop and validate a set of static and animated gastroduodenal symptom pictograms for children. STUDY DESIGN: There were 3 study phases: 1: cocreation using experience design methods to develop pediatric gastroduodenal symptom pictograms (static and animated); 2: an online survey to assess acceptability, as well as face and content validity; and 3: a preference study. Phases 2 and 3 compared the novel pediatric pictograms with existing pictograms used with adult patients. RESULTS: Eight children aged 6-15 years (5 female) participated in phase 1, and 69 children in phase 2 (median age 13 years: IQR 9-15); an additional 49 participants were included in phase 3 (median age 15: IQR 12-17). Face and content validity were higher for the pediatric static and animated pictogram sets compared with pre-existing adult pictograms (78% vs 78% vs 61%). Participants with worse gastric symptoms had superior comprehension of the pediatric pictograms (χ2 [8, N = 118] P < .001). All participants preferred the pediatric static pictogram set was over both the animated and adult sets (χ2 [2, N = 118] P < .001). CONCLUSIONS: The cocreation phase resulted in the symptom concept confirmation and design of 10 acceptable static and animated gastroduodenal pictograms with high face and content validity when evaluated with children aged 6-18. Validity was superior when children reported more problematic symptoms. Therefore, these pictograms could be used in clinical and research practice to enable standardized symptom reporting for children with gastroduodenal disorders.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.

Normative Values for Body Surface Gastric Mapping Evaluations of Gastric Motility Using Gastric Alimetry: Spectral Analysis.

INTRODUCTION: Body surface gastric mapping (BSGM) is a new noninvasive test of gastric function. BSGM offers several novel and improved biomarkers of gastric function capable of differentiating patients with overlapping symptom profiles. The aim of this study was to define normative reference intervals for BSGM spectral metrics in a population of healthy controls. METHODS: BSGM was performed in healthy controls using Gastric Alimetry (Alimetry, New Zealand) comprising a stretchable high-resolution array (8 × 8 electrodes; 196 cm 2 ), wearable Reader, and validated symptom-logging App. The evaluation encompassed a fasting baseline (30 minutes), 482 kCal meal, and 4-hour postprandial recording. Normative reference intervals were calculated for BSGM metrics including the Principal Gastric Frequency, Gastric Alimetry Rhythm Index (a measure of the concentration of power in the gastric frequency band over time), body mass index (BMI)-adjusted amplitude (µV), and fed:fasted amplitude ratio. Data were reported as median and reference interval (5th and/or 95th percentiles). RESULTS: A total of 110 subjects (55% female, median age 32 years [interquartile range 24-50], median BMI 23.8 kg/m 2 [interquartile range 21.4-26.9]) were included. The median Principal Gastric Frequency was 3.04 cycles per minute; reference interval: 2.65-3.35 cycles per minute. The median Gastric Alimetry Rhythm Index was 0.50; reference interval: ≥0.25. The median BMI-adjusted amplitude was 37.6 µV; reference interval: 20-70 µV. The median fed:fasted amplitude ratio was 1.85; reference interval ≥1.08. A higher BMI was associated with a shorter meal-response duration ( P = 0.014). DISCUSSION: This study provides normative reference intervals for BSGM spectral data to inform diagnostic interpretations of abnormal gastric function.

Hyperactive Distal Colonic Motility and Recovery Patterns Following Right Colectomy: A High-Resolution Manometry Study.

BACKGROUND: Postoperative ileus results in morbidity, prolonged hospitalization, and increased health care expenditure. However, the underlying abnormalities in motility remain poorly understood. Recent high-resolution manometry studies demonstrated that the distal colon becomes hyperactive with a cyclic motor pattern postoperatively, but they did not track this activity beyond 16 hours after surgery. OBJECTIVE: This study used high-resolution manometry to evaluate distal colonic motility during the first 4 days after right-sided colectomy. DESIGN: An observational study of perioperative high-resolution colonic manometry using a 36-sensor catheter with 1-cm resolution. SETTING: A single tertiary hospital. PATIENTS: Adult patients undergoing elective laparoscopic or open right-sided colonic resection. MAIN OUTCOME MEASURES: Occurrence of distal colonic motor patterns during the perioperative period, defined according to a published classification system. Clinical markers of gut recovery included time to first stool, oral diet, and prolonged postoperative ileus. RESULTS: Seven patients underwent perioperative manometry recordings. Hyperactive cyclic motor patterns emerged intraoperatively and peaked in the first 12 hours postoperatively, occupying 81.8% ± 3.9% of the recording. This gradually returned to normal during the first 4 days, reaching 19.0% ± 4.4% ( p = 0.002). No patient had a bowel movement before this hyperactivity resolved. High-amplitude propagating sequences were absent in early postoperative recordings, and their return temporally correlated with the passage of stool. Abnormal high-amplitude repetitive 0.5 to 1 cycle per minute activity was observed in the left colon of 1 patient with prolonged ileus. LIMITATIONS: The invasive nature of recordings limited this study to a small sample size. CONCLUSIONS: Cyclic motor patterns are markedly hyperactive in the distal colon after right-sided colectomy and resolve during the first 4 postoperative days. High-amplitude propagating sequences are inhibited by surgery and gradually recover. Bowel function may not return until these changes resolve. Other abnormal repetitive hyperactive patterns could contribute to the development of prolonged ileus. See Video Abstract at http://links.lww.com/DCR/B967 . MOTILIDAD HIPERACTIVA DEL COLON DISTAL Y PATRONES DE RECUPERACIN DESPUS DE COLECTOMA DERECHA UN ESTUDIO DE MANOMETRA DE ALTA RESOLUCIN: ANTECEDENTES:El íleo post-operatorio produce una morbilidad significativa, una hospitalización prolongada y un aumento del gasto sanitario. Sin embargo, las anomalías subyacentes en la motilidad siguen siendo poco conocidas. Estudios recientes de manometría de alta resolución demostraron que el colon distal se vuelve hiperactivo con un patrón motor cíclico en el post-operatorio, pero no registraron esta actividad más allá de las 16 horas posteriores a la cirugía.OBJETIVO:Utilizar la manometría de alta resolución para evaluar la motilidad del colon distal durante los primeros cuatro días después de la colectomía del lado derecho.DISEÑO:Estudio observacional de pacientes sometidos a manometría colónica perioperatoria de alta resolución mediante catéter de 36 sensores con 1 cm de resolución.AJUSTE:Un solo hospital terciario.PACIENTES:Pacientes adultos sometidos a resección laparoscópica o abierta de colon del lado derecho de forma electiva.PRINCIPALES MEDIDAS DE RESULTADO:AAparición de patrones motores del colon distal durante el período perioperatorio, definidos según un sistema de clasificación publicado. Los marcadores clínicos de recuperación intestinal incluyeron, tiempo hasta la primera evacuación, dieta oral e íleo posoperatorio prolongado.RESULTADOS:Siete pacientes fueron sometidos a registros de manometría perioperatoria. Los patrones motores cíclicos hiperactivos emergieron intraoperatoriamente y alcanzaron su punto máximo en las primeras 12 horas post-operatorias, ocupando 81,8 ± 3,9% del registro. Esto volvió gradualmente a la normalidad durante los primeros cuatro días, alcanzando el 19,0 ± 4,4% (p = 0,002). Ningún paciente tuvo una evacuación intestinal antes de que se resolviera esta hiperactividad. Las secuencias de propagación de alta amplitud estaban ausentes en las grabaciones post-operatorias tempranas y su retorno se correlacionó temporalmente con el paso de las heces. Se observó actividad anormal de alta amplitud repetitiva de 0,5-1 ciclo / minuto en el colon izquierdo de un paciente con íleo prolongado.LIMITACIONES:La naturaleza invasiva de las grabaciones limitó este estudio a un tamaño de muestra pequeño.CONCLUSIONES:Los patrones motores cíclicos son marcadamente hiperactivos en el colon distal después de la colectomía del lado derecho y se resuelven gradualmente durante los primeros cuatro días posoperatorios. Las secuencias de propagación de gran amplitud se inhiben mediante cirugía y se recuperan gradualmente. Es posible que la función intestinal no regrese hasta que estos cambios se resuelvan. Otros patrones hiperactivos repetitivos anormales podrían contribuir al desarrollo de íleo prolongado. Consulte Video Resumen en http://links.lww.com/DCR/B967 . (Traducción-Dr. Mauricio Santamaria ).

Clinical utility of trans-sacral magnetic stimulation-evoked sphincter potentials and high-density electromyography in pelvic floor assessment: Technical evaluation.

AIM: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS). METHOD: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study. RESULTS: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002). CONCLUSION: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

Plasminogen Activator Inhibitor-1 as a Marker of Esophageal Functional Changes in Pediatric Eosinophilic Esophagitis.

BACKGROUND & AIMS: Esophageal remodeling in eosinophilic esophagitis (EoE) can lead to esophageal rigidity with eventual luminal compromise and stenoses. Gauging esophageal functional alterations in EoE is challenging. An epithelial marker of functional remodeling would impact EoE management. METHODS: Esophageal biopsy specimens from children with and without EoE and primary human esophageal epithelial cells were used for PAI-1 immunohistochemistry, and cell proliferation experiments. PAI-1 immunostaining and basal cell hyperplasia were assessed in the context of concurrently obtained esophageal compliance measures on endoscopic functional lumen imaging probe (EndoFLIP). RESULTS: EndoFLIPs were performed in 45 children (32 with and 13 without EoE). Epithelial PAI-1 was increased in patients with active EoE versus inactive or control patients (P < .01). Esophageal compliance was lower in EoE patients versus controls, particularly in the proximal esophagus (P < .001). Proximal compliance was the strongest predictor of EoE (AUROC 0.88, 95% CI 0.77, 0.98) with esophageal compliance of less than 2.6%mL/mmHg demonstrating 82% sensitivity and 84% specificity for EoE. PAI-1 inhibition significantly diminished esophageal epithelial cell proliferation, suggesting PAI-1 could trigger basal cell hyperplasia. A composite mid-esophageal BZH + PAI-1 score was the strongest predictor of altered compliance (P = .02, AUROC 0.89 (95% CI 0.80, 0.99). CONCLUSIONS: PAI-1 is significantly elevated in pediatric EoE and distinguishes altered compliance in children. PAI-1 may be a novel disease marker and therapeutic target.

A multi-parameter approach to measurement of spontaneous myogenic contractions in human stomach: Utilization to assess potential modulators of myogenic contractions.

Electrical slow waves, generated by interstitial cells of Cajal (ICC), cause spontaneous contractions of human stomach. Software was developed to measure muscle tone and eleven different parameters defining these contractions in human stomach, displaying data as radar plots. A pilot study assessed the effects of potential modulators, selected from among compounds known to influence ICC activity; n = 4-7 each concentration tested/compound. Human distal stomach (corpus-antrum) muscle strips were suspended in tissue baths for measuring myogenic (non-neuronal) contractions in the presence of tetrodotoxin (10-6 M). Initial characterization: Contractions (amplitude 4 ± 0.4mN, frequency 3 ± 0.1 min-1, n = 49) were unchanged by ꭃ-conotoxin GVIA (10-7 M) or indomethacin (10-6 M) but abolished by nifedipine (10-4 M). Carbachol (10-7 M) increased contraction rate and amplitude; 10-6-10-5 M increased tone and caused large, irregular contractions. [Ca2+]imodulators: Ryanodine (10-5-10-4 M) increased muscle tone accompanied by inhibition of myogenic contractions. Xestospongin-C (10-6 M; IP3 channel inhibitor) had no effects. SERCA pump inhibitors, 2-APB and cycloplazonic acid (10-5-10-4 M) increased tone and myogenic contraction amplitude before abolishing contractions; thapsigargin was weakly active. CaCC blockers: MONNA and CaCCinh-A01 had little-or-no effects on tone but reduced myogenic contractions; MONNA (10-4 M) was more effective, reducing amplitude (77.8 ± 15.2%) and frequency. CaV3.1/3.2/3.3 channel block: Mibefradil reduced tone and myogenic contraction amplitude (pIC50 4.8 ± 0.9). Inward-rectifying K+-channel inhibitor: E-4031 (10-4 M) increased contraction duration (17.4 ± 5.8%). Conclusions: (1) Measurement of multiple parameters of myogenic contractions identified subtle differences between compounds, (2) only E-4031 and CaCC blockers influenced myogenic contractions, not muscle tone, (3) studies are needed with compounds with known and/or improved selectivity/potency for human targets affecting ICC functions.

In vivo experimental validation of detection of gastric slow waves using a flexible multichannel electrogastrography sensor linear array.

BACKGROUND: Cutaneous electrogastrography (EGG) is a non-invasive technique that detects gastric bioelectrical slow waves, which in part govern the motility of the stomach. Changes in gastric slow waves have been associated with a number of functional gastric disorders, but to date accurate detection from the body-surface has been limited due to the low signal-to-noise ratio. The main aim of this study was to develop a flexible active-electrode EGG array. METHODS: Two Texas Instruments CMOS operational amplifiers: OPA2325 and TLC272BID, were benchtop tested and embedded in a flexible linear array of EGG electrodes, which contained four recording electrodes at 20-mm intervals. The cutaneous EGG arrays were validated in ten weaner pigs using simultaneous body-surface and serosal recordings, using the Cyton biosensing board and ActiveTwo acquisition systems. The serosal recordings were taken using a passive electrode array via surgical access to the stomach. Signals were filtered and compared in terms of frequency, amplitude, and phase-shift based on the classification of propagation direction from the serosal recordings. RESULTS: The data were compared over 709 cycles of slow waves, with both active cutaneous EGG arrays demonstrating comparable performance. There was an agreement between frequencies of the cutaneous EGG and serosal recordings (3.01 ± 0.03 vs 3.03 ± 0.05 cycles per minute; p = 0.75). The cutaneous EGG also demonstrated a reduction in amplitude during abnormal propagation of gastric slow waves (310 ± 50 µV vs 277 ± 9 µV; p < 0.01), while no change in phase-shift was observed (1.28 ± 0.09 s vs 1.40 ± 0.10 s; p = 0.36). CONCLUSION: A sparse linear cutaneous EGG array was capable of reliably detecting abnormalities of gastric slow waves. For more accurate characterization of gastric slow waves, a two-dimensional body-surface array will be required.

Abnormalities on Electrogastrography in Nausea and Vomiting Syndromes: A Systematic Review, Meta-Analysis, and Comparison to Other Gastric Disorders.

BACKGROUND: Functional nausea and vomiting syndromes and gastroparesis, collectively grouped as nausea and vomiting syndromes (NVS), are overlapping conditions with incompletely understood pathophysiology. Gastric slow wave abnormalities are thought to contribute. AIMS: This study aimed to systematically review and meta-analyze the prevalence of slow wave abnormalities measured by electrogastrography (EGG) in patients with NVS. METHODS: MEDLINE, EMBASE, EMBASE classic, and CENTRAL databases were systematically searched for articles using EGG in adults (≥ 18 years) with NVS. EGG metrics of interest were percentage time in bradygastria, normogastria, and tachygastria as well as dominant frequency and dominant power. Outcomes were also compared with functional dyspepsia (FD), gastroesophageal reflux disease (GORD), and control cohorts. RESULTS: Seven hundred and sixty NVS patients and 308 controls were included from 24 studies. Overall, 64% of patients had EGG abnormalities. Average percent time in normogastria was low during fasting (50%; 95% CI 40-63%) and fed (53%; 95% CI 41-68%) states in patients, with substantial periods in fasting bradygastria (34.1%; 95% CI 25-47%) and postprandial tachygastria (21%; 95% CI 17-26%). Across gastric disorders, pooling of 84 studies showed a comparably high prevalence of EGG abnormalities in NVS (24 studies; n = 760) and GORD (13 studies; n = 427), compared to FD (47 studies; n = 1751) and controls (45 studies; n = 1027). CONCLUSIONS: Frequency-based gastric slow wave abnormalities are prominent in NVS. The strength and consistency of these associations across many studies suggests that gastric dysrhythmia may be an important factor in NVS, motivating the development of more reliable methods for their clinical assessment.

The gastric conduction system in health and disease: a translational review.

Gastric peristalsis is critically dependent on an underlying electrical conduction system. Recent years have witnessed substantial progress in clarifying the operations of this system, including its pacemaking units, its cellular architecture, and slow-wave propagation patterns. Advanced techniques have been developed for assessing its functions at high spatiotemporal resolutions. This review synthesizes and evaluates this progress, with a focus on human and translational physiology. A current conception of the initiation and conduction of slow-wave activity in the human stomach is provided first, followed by a detailed discussion of its organization at the cellular and tissue level. Particular emphasis is then given to how gastric electrical disorders may contribute to disease states. Gastric dysfunction continues to grow in their prevalence and impact, and while gastric dysrhythmia is established as a clear and pervasive feature in several major gastric disorders, its role in explaining pathophysiology and informing therapy is still emerging. New insights from high-resolution gastric mapping are evaluated, together with historical data from electrogastrography, and the physiological relevance of emerging biomarkers from body surface mapping such as retrograde propagating slow waves. Knowledge gaps requiring further physiological research are highlighted.

Electrogastrography Abnormalities in Pediatric Gastroduodenal Disorders: A Systematic Review and Meta-analysis.

ABSTRACT: Electrogastrography (EGG) is a non-invasive method of measuring gastric electrophysiology. Abnormal gastric electrophysiology is thought to contribute to disease pathophysiology in patients with gastroduodenal symptoms but this has not been comprehensively quantified in pediatric populations. This study aimed to quantify the abnormalities in gastric electrophysiology on EGG in neonatal and pediatric patients.Databases were systematically searched for articles utilizing EGG in neonatal and pediatric patients (≤18 years). Primary outcomes were prevalence of abnormality, percentage of time in normal rhythm, and power ratio. Secondary outcomes were correlations between patient symptoms and abnormal gastric electrophysiology on EGG.A total of 33 articles (1444 participants) were included. EGG methodologies were variable. Pooled prevalence of abnormalities on EGG ranged from 61% to 86% in patients with functional dyspepsia (FD), gastro-esophageal reflux disease (GERD), and type 1 diabetes mellitus (T1DM). FD patients averaged 20.8% (P = 0.011) less preprandial and 21.6% (P = 0.031) less postprandial time in normogastria compared with controls. Electrophysiological abnormalities were inconsistent in GERD. T1DM patients averaged 46.2% (P = 0.0003) less preprandial and similar (P = 0.32) postprandial time in normogastria compared with controls, and had a lower power ratio (SMD -2.20, 95% confidence interval [CI]: -4.25 to -0.15; P = 0.036). Symptom correlations with gastric electrophysiology were inconsistently reported.Abnormalities in gastric electrophysiology were identifiable across a range of pediatric patients with gastroduodenal symptoms on meta-analysis. However, techniques have been inconsistent, and standardized and more reliable EGG methods are desirable to further define these findings and their potential utility in clinical practice.

Intraoperative serosal extracellular mapping of the human distal colon: a feasibility study.

BACKGROUND: Cyclic motor patterns (CMP) are the predominant motor pattern in the distal colon, and are important in both health and disease. Their origin, mechanism and relation to bioelectrical slow-waves remain incompletely understood. During abdominal surgery, an increase in the CMP occurs in the distal colon. This study aimed to evaluate the feasibility of detecting propagating slow waves and spike waves in the distal human colon through intraoperative, high-resolution (HR), serosal electrical mapping. METHODS: HR electrical recordings were obtained from the distal colon using validated flexible PCB arrays (6 × 16 electrodes; 4 mm inter-electrode spacing; 2.4 cm2, 0.3 mm diameter) for up to 15 min. Passive unipolar signals were obtained and analysed. RESULTS: Eleven patients (33-71 years; 6 females) undergoing colorectal surgery under general anaesthesia (4 with epidurals) were recruited. After artefact removal and comprehensive manual and automated analytics, events consistent with regular propagating activity between 2 and 6 cpm were not identified in any patient. Intermittent clusters of spike-like activities lasting 10-180 s with frequencies of each cluster ranging between 24 and 42 cpm, and an average amplitude of 0.54 ± 0.37 mV were recorded. CONCLUSIONS: Intraoperative colonic serosal mapping in humans is feasible, but unlike in the stomach and small bowel, revealed no regular propagating electrical activity. Although sporadic, synchronous spike-wave events were identifiable. Alternative techniques are required to characterise the mechanisms underlying the hyperactive CMP observed in the intra- and post-operative period. NEW FINDINGS: The aim of this study was to assess the feasibility of detecting propagating electrical activity that may correlate to the cyclic motor pattern in the distal human colon through intraoperative, high-resolution, serosal electrical mapping. High-resolution electrical mapping of the human colon revealed no regular propagating activity, but does reveal sporadic spike-wave events. These findings indicate that further research into appropriate techniques is required to identify the mechanism of hyperactive cyclic motor pattern observed in the intra- and post-operative period in humans.

Gastric dysrhythmia in gastroesophageal reflux disease: a systematic review and meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a commonly diagnosed gastrointestinal disorder, with a substantial impact on the quality of life. The underlying pathophysiology of GERD is multifactorial and incompletely understood. Abnormal gastric electrical activity, measured using electrogastrography (EGG), may contribute. This study aimed to systematically review and meta-analyse the existing literature in which EGG was used in patients with GERD. METHODS: Databases were systematically searched for studies using EGG in adults with GERD. The primary outcome was the percentage of recording time in the normogastric frequency range. Secondary outcomes were dominant frequency, dominant power, power ratio and prevalence of any EGG abnormality. RESULTS: In total, 591 participants (427 patients with GERD; 164 healthy controls) from 13 studies were included. GERD patients spent 17.3% (SMD - 1.18, 95%CI: - 1.84, - 0.52) and 18.7% (SMD - 1.11, 95%CI: - 1.55, - 0.68) less of the preprandial and postprandial recording time in normogastric frequency ranges, respectively, compared to healthy controls. The dominant frequency, dominant power and power ratio were not significantly different to healthy controls in the preprandial and postprandial periods. The pooled prevalence of any EGG abnormality was significantly greater in patients with GERD than in healthy controls [46% (95%CI: 39-64%) vs. 10% (95%CI: 4-23%); p < 0.0001]. Correlations between GERD symptoms and EGG recordings were inconsistently studied. EGG techniques were heterogeneous. CONCLUSIONS: Consistent abnormalities in gastric slow-wave activity, as measured by EGG, were identified in adults with GERD. Further investigation into these abnormalities using novel emerging electrophysiology techniques is desirable, to better define their contribution toward GERD pathophysiology.

Spatial Patterns From High-Resolution Electrogastrography Correlate With Severity of Symptoms in Patients With Functional Dyspepsia and Gastroparesis.

BACKGROUND & AIMS: Invasive gastric electrical mapping has revealed spatial abnormalities of the slow wave in subjects with gastroparesis and functional gastrointestinal disorders. Cutaneous high-resolution electrogastrography (HR-EGG) is a non-invasive method that can detect spatial features of the gastric slow wave. We performed HR-EGG in subjects with active foregut symptoms to evaluate associations between gastric myoelectric abnormalities, symptoms (based on a validated questionnaire), and gastric emptying. METHODS: We performed a case-control study of 32 subjects, including 7 healthy individuals (controls), 7 subjects with functional dyspepsia and normal gastric emptying, and 18 subjects with gastroparesis, from a tertiary care program. All subjects were assessed by computed tomography imaging of the abdomen and HR-EGG and completed the PAGI-SYM questionnaire on foregut symptoms, which includes the gastroparesis cardinal symptom index. We performed volume reconstruction of the torso and stomach from computed tomography images to guide accurate placement of the HR-EGG array. RESULTS: Spatial slow-wave abnormalities were detected in 44% of subjects with foregut symptoms. Moreover, subjects with a higher percentage of slow waves with aberrant propagation direction had a higher total gastroparesis cardinal symptom index score (r = 0.56; P < .001) and more severe abdominal pain (r = 0.46; P = .009). We found no correlation between symptoms and traditional EGG parameters. CONCLUSIONS: In case-control study, we found that the genesis of symptoms of functional dyspepsia and gastroparesis is likely multifactorial, including possible contribution from gastric myoelectric dysfunction. Abnormal spatial parameters, detected by cutaneous HR-EGG, correlated with severity of upper gastrointestinal symptoms, regardless of gastric emptying. This noninvasive, repeatable approach might be used to identify patients for whom gastric myoelectric dysfunction contributes to functional dyspepsia and gastroparesis.

Esophageal Compliance Quantifies Epithelial Remodeling in Pediatric Patients With Eosinophilic Esophagitis.

BACKGROUND: The management of eosinophilic esophagitis (EoE) relies on the severity of esophageal eosinophilia, yet there is poor evidence of its prediction of esophageal fibrotic remodeling and subsequent complications such as dysphagia, food impactions, or strictures. Functional luminal imaging planimetry (FLIP) has had limited use in pediatric patients to evaluate esophageal tissue mechanics. We aimed to standardize the FLIP technique and to measure esophageal compliance in children with EoE in comparison to controls. METHODS: Subjects were enrolled into a prospective observational study and had FLIP performed at the time of endoscopy. We calculated esophageal distensibility and compliance for the total and segmental esophagus independently (ie, proximal, middle, and distal esophageal segments). We evaluated esophageal biopsies for eosinophilia and epithelial remodeling, calculated endoscopy scores, and documented patient symptoms. RESULTS: We enrolled 11 EoE and 12 controls subjects, aged 5 to 18 years old. While EoE subjects had lower esophageal compliance (P = 0.004) than controls, the difference in distensibility did not reach significance (P = 0.151). Epithelial remodeling severity was more strongly correlated with compliance than with distensibility. Epithelial remodeling scores ≥2 had a significant association with lower compliance both segmentally and in the entire esophagus (P = 0.029), but not with distensibility. Compliance measures were more sensitive in detecting subjects with remodeling score ≥2 than distensibility (79% vs 64%). CONCLUSIONS: Compliance is a more sensitive measure of esophageal epithelial remodeling in children compared to distensibility, and a more appropriate measure of esophageal tissue mechanics. Standardized placement of the FLIP catheter is important to accurately assess esophageal compliance.