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Humphrey G, Keane C, Schamberg G, Benitez A, Calder S, Binghong X, Sadaka C, Andrews CN, O’Grady G, Gharibans A, Mousa H. Body Surface Gastric Mapping Delineates Specific Patient Phenotypes in Adolescents With Functional Dyspepsia and Gastroparesis. Neurogastroenterol Motil 2025; 37:e70018. [PMID: 40106804 PMCID: PMC12075902 DOI: 10.1111/nmo.70018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Diagnosing pediatric patients with chronic gastroduodenal symptoms is clinically challenging, with the role of gastric emptying testing being controversial. Body Surface Gastric Mapping (BSGM) is a new diagnostic test that can identify specific patient phenotypes in adults with gastric dysfunction. This study evaluates whether BSGM can delineate specific phenotypes in adolescents and provide clinically meaningful distinctions between gastroparesis and functional dyspepsia diagnoses. METHODS A prospective cross-sectional study recruited adolescents aged 12 to 21 between 2022 and 2024. Controls were recruited from New Zealand and patients from the Children's Hospital of Philadelphia, USA. BSGM followed a standardized protocol, including simultaneous symptom reporting and completion of validated symptom, psychometric, and physical health questionnaires. KEY RESULTS Fifty-six subjects were recruited (31 controls, 25 patients); median age 16; 96% of patients were female. Control data showed that adult reference intervals provided an acceptable interpretation framework. Patients with FD (n = 10) and gastroparesis (n = 15) had common symptoms, mental health, quality of life, and functional disability (all p > 0.05). Three distinct BSGM phenotypes were identified: BSGM Normal (n = 10), BSGM Delay (n = 8), and Low Stability/Low Amplitude (n = 7), having spectral differences in BMI-Adjusted Amplitude 34.6 versus 39.1 versus 19.9 (p = 0.01) and Gastric Alimetry Rhythm Index: 0.45 versus 0.45 versus 0.19 (p = 0.003). BSGM phenotypes demonstrated differences in symptoms (nausea p = 0.04), physical health (p = 0.04), and psychometrics (anxiety p = 0.03). CONCLUSION AND INFERENCES Adolescents with FD and gastroparesis have overlapping clinical profiles, making treatment challenging. Conversely, employing BSGM to categorize patients into distinct phenotypes reveals clinically relevant differences, offering avenues for individualized therapeutic pathways.
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Affiliation(s)
- Gayl Humphrey
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | - Celia Keane
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
| | - Gabriel Schamberg
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Alimetry Ltd.AucklandNew Zealand
| | - Alain Benitez
- Division of GastroenterologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
- Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Stefan Calder
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Alimetry Ltd.AucklandNew Zealand
| | - Xu Binghong
- Division of GastroenterologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
| | - Christian Sadaka
- Division of GastroenterologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
| | - Christopher N. Andrews
- The Division of Gastroenterology, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Greg O’Grady
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Alimetry Ltd.AucklandNew Zealand
| | - Armen Gharibans
- Department of Surgery, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
- Alimetry Ltd.AucklandNew Zealand
- Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Hayat Mousa
- Division of GastroenterologyThe Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
- Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Na HK, Li AA, Gottfried-Blackmore A, Podboy AJ, Esquivel MM, Joseph AA, Nguyen L, Hwang JH. Pyloric Dysfunction: A Review of the Mechanisms, Diagnosis, and Treatment. Gut Liver 2025; 19:327-345. [PMID: 40058793 PMCID: PMC12070220 DOI: 10.5009/gnl240421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 11/04/2024] [Accepted: 11/06/2024] [Indexed: 05/14/2025] Open
Abstract
Pyloric dysfunction is defined as hypertonia or spasm of the pyloric sphincter. The pylorus plays a key role in gastric emptying, but its function remains incompletely understood. Most studies have focused on gastroparesis regardless of the underlying pathophysiology. Few studies have reported pyloric dysfunction in patients with gastroparesis, and the diagnostic and treatment modalities for pyloric dysfunction are not well established. Recently developed diagnostic modalities assessing pyloric function, such as high-resolution antroduodenal manometry and endoluminal functional lumen imaging, are currently being evaluated. A variety of therapeutic interventions targeting the pylorus, including pharmacologic agents, intrapyloric botulinum injection, endoscopic balloon dilation, stent insertion, surgical pyloroplasty, and gastric peroral endoscopic pyloromyotomy, have been proposed. Among these, gastric peroral endoscopic pyloromyotomy has emerged as a novel, minimally invasive therapy with demonstrated efficacy and safety for refractory gastroparesis. This article reviews the pathophysiology of pyloric dysfunction and the potential diagnostic and therapeutic modalities based on the latest literature.
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Affiliation(s)
- Hee Kyong Na
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Andrew A. Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Andres Gottfried-Blackmore
- Department of Pharmacology and Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA
| | - Alexander J. Podboy
- Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, VA, USA
| | - Micaela M. Esquivel
- Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
| | - Abel A. Joseph
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Linda Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Joo Ha Hwang
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
- Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA
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Varghese C, Gharibans AA, Foong D, Schamberg G, Calder S, Ho V, Anand R, Andrews CN, Maurer AH, Abell T, Parkman HP, O'Grady G. Relationship between intragastric meal distribution, gastric emptying and gastric neuromuscular dysfunction in chronic gastroduodenal disorders. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2025:2025.02.04.25321689. [PMID: 39974083 PMCID: PMC11838647 DOI: 10.1101/2025.02.04.25321689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Background Chronic gastroduodenal symptoms arise from heterogenous 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 30 m baseline, 99mTC-labelled 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 impaired accommodation. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals. Results Among 67 patients (84% female, median age 40, median BMI 24), median IMD0 was 0.76 (IQR 0.69-0.86) with 5 (7.5%) meeting impaired accommodation 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 impaired accommodation were associated with worse dyspeptic symptoms. Conclusion Proximal retention of food as assessed by intragastric meal distribution 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.
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Manabe N, Wada M, Takeda T, Bukeo E, Tsuru H, Hojo M, Fujita M, Ihara E, Nagahara A, Kamiya T. A review of recent developments in the imaging of disorders of gut-brain interaction. J Smooth Muscle Res 2025; 61:11-19. [PMID: 39924188 PMCID: PMC11807775 DOI: 10.1540/jsmr.61.11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 01/10/2025] [Indexed: 02/11/2025] Open
Abstract
A number of factors have been recently associated with the development of disorders of gut-brain interaction (DGBI), including genetic predisposition, early-life environment, intestinal microbiota, infection, microinflammation, and increased mucosal permeability. In addition, impaired gastrointestinal motility is important not only as a cause of DGBI but also as a consequent final phenotype. Gastrointestinal motor measurements are the predominant method for the assessment of and therapeutic intervention into motor abnormalities. As such, these measurements should be considered for DGBI patients who do not respond to first-line approaches such as behavioral therapy, dietary modifications, and pharmacotherapy. This comprehensive review focuses on the functional changes in the upper gastrointestinal tract caused by DGBI and describes ongoing attempts to develop imaging modalities to assess these dysfunctions in the esophageal and gastric regions. Recent advances in imaging techniques could help elucidate the pathophysiology of DGBI, with exciting potential for research and clinical practice.
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Affiliation(s)
- Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of
Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, 2-6-1 Nakasange,
Kita-ku, Okayama 700-8505, Japan
| | - Masafumi Wada
- Department of Medicine and Bioregulatory Science, Graduate
School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi,
Fukuoka 812-8582, Japan
| | - Tsutomu Takeda
- Department of Gastroenterology, Juntendo University Faculty
of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Department of Pathophysiological Research and Therapeutics
for Gastrointestinal Diseases, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo
113-8421, Japan
| | - Emiko Bukeo
- Division of Endoscopy and Ultrasonography, Department of
Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, 2-6-1 Nakasange,
Kita-ku, Okayama 700-8505, Japan
| | - Hirotaka Tsuru
- Department of Medicine and Bioregulatory Science, Graduate
School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi,
Fukuoka 812-8582, Japan
| | - Mariko Hojo
- Department of Gastroenterology, Juntendo University Faculty
of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Department of Pathophysiological Research and Therapeutics
for Gastrointestinal Diseases, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo
113-8421, Japan
| | - Minoru Fujita
- Division of Endoscopy and Ultrasonography, Department of
Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, 2-6-1 Nakasange,
Kita-ku, Okayama 700-8505, Japan
| | - Eikichi Ihara
- Department of Medicine and Bioregulatory Science, Graduate
School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka-shi,
Fukuoka 812-8582, Japan
| | - Akihito Nagahara
- Department of Gastroenterology, Juntendo University Faculty
of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
- Department of Pathophysiological Research and Therapeutics
for Gastrointestinal Diseases, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo
113-8421, Japan
| | - Takeshi Kamiya
- Department of Medical Innovation, Nagoya City University
Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya-shi, Aichi
467-8601, Japan
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Wang THH, Varghese C, Calder S, Gharibans AA, Evennett N, Beban G, Schamberg G, O'Grady G. Assessment of Gastric Remnant Activity, Symptoms, and Quality of Life Following Gastric Bypass. Obes Surg 2024; 34:4490-4498. [PMID: 39397209 DOI: 10.1007/s11695-024-07534-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 09/16/2024] [Accepted: 10/05/2024] [Indexed: 10/15/2024]
Abstract
INTRODUCTION While most gastric bypass patients recover well, some experience long-term complications, including nausea, abdominal pain, food intolerance, and dumping. This study aimed to evaluate symptoms and quality of life (QoL) in association with the residual activity of the remnant stomach. METHODS Patients undergoing gastric bypass and conversion-to-bypass were recruited. The Gastric Alimetry® System (Auckland, NZ) was employed, comprising a high-resolution electrode array, wearable reader, and validated symptom logging app. The protocol comprised 30-min fasting baseline, a 218-kCal meal stimulus, and 4-h of post-prandial recordings. Symptoms and QoL were evaluated using validated questionnaires. Remnant gastric electrophysiology evaluation included frequency, BMI-adjusted amplitude, and Gastric Alimetry Rhythm Index (GA-RI, reflecting pacemaker stability), with comparison to validated reference intervals and matched controls. RESULTS Thirty-eight participants were recruited with mean time from bypass 46.8 ± 28.6 months. One-third of patients showed moderate to severe post-prandial symptoms, with patients' median PAGI-SYM 28 ± 19 vs controls 9 ± 17 (p < 0.01); PAGI-QOL 37 ± 31 vs 135 ± 22 (p < 0.0001). Remnant gastric function was markedly degraded shown by undetectable frequencies in 84% (vs 0% in controls) and low GA-RI (0.18 ± 0.08 vs 0.51 ± 0.22 in controls; p < 0.0001; reference range > 0.25). Impaired GA-RI and amplitude were correlated with worse PAGI-SYM and PAGI-QOL scores. CONCLUSION One-third of post-bypass patients suffered significant upper GI symptoms with reduced QoL. The bypassed remnant stomach shows highly deranged electrophysiology in-situ, reflecting disuse degeneration. These derangements correlated with QoL; however, causality is not implied by the present study.
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Affiliation(s)
- Tim Hsu-Han Wang
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry (New Zealand), Auckland, New Zealand
| | - Armen A Gharibans
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry (New Zealand), Auckland, New Zealand
| | - Nicholas Evennett
- Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Grant Beban
- Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry (New Zealand), Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, University of Auckland, Auckland, New Zealand.
- Alimetry (New Zealand), Auckland, New Zealand.
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Kolacz J. Autonomic assessment at the intersection of psychosocial and gastrointestinal health. Neurogastroenterol Motil 2024; 36:e14887. [PMID: 39118212 DOI: 10.1111/nmo.14887] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 07/09/2024] [Accepted: 07/24/2024] [Indexed: 08/10/2024]
Abstract
BACKGROUND Wearable technology is increasingly used in clinical practice and research to monitor functional gastrointestinal symptoms and mental health. AIMS This article explores the potential of wearable sensors to enhance the understanding of the autonomic nervous system (ANS), particularly its role in linking psychological and gastrointestinal function. The ANS, facilitates brain-gut communication and is responsive to psychosocial conditions. It is implicated in disorders related to psychological stress and gut-brain interaction. Wearable technology enables tracking of the ANS in daily life, offering complementary and alternative methods from traditional lab-based measures. This review places focus on autonomic metrics such as respiratory sinus arrhythmia, vagal efficiency, and electrodermal activity as well as self-reports of autonomic symptoms. DISCUSSION Potential applications include use of wearable sensors for tracking autonomic activity in disorder of gut-brain interaction such as cyclic vomiting syndrome, in which ANS dysregulation may be triggered by psychosocial factors. Considerations for data interpretation and contextualization are addressed, acknowledging challenges such as situational confounders of ANS activity and accuracy of wearable devices.
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Affiliation(s)
- Jacek Kolacz
- Department of Psychiatry and Behavioral Health, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
- Traumatic Stress Research Consortium (TSRC) at the Kinsey Institute, Indiana University, Bloomington, Indiana, USA
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O’Grady G, Calder S, Schamberg G, Andrews CN, Lim AH, Daker C, Varghese CA, Gharibans AA. Hatching the EGG. Am J Physiol Gastrointest Liver Physiol 2024; 327:G697-G698. [DOI: 10.1152/ajpgi.00257.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 08/23/2024] [Indexed: 01/04/2025]
Affiliation(s)
- Gregory O’Grady
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry, Auckland, New Zealand
| | - Christopher N. Andrews
- Alimetry, Auckland, New Zealand
- Division of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Alexandria H. Lim
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Chris A. Varghese
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Armen A. Gharibans
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry, Auckland, New Zealand
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Varghese C, Schamberg G, Uren E, Calder S, Law M, Foong D, Ho V, Wu B, Huang IH, Du P, Abell T, Daker C, Andrews CN, Gharibans AA, O’Grady G. A Standardized Classification Scheme for Gastroduodenal Disorder Evaluation Using the Gastric Alimetry System: Prospective Cohort Study. GASTRO HEP ADVANCES 2024; 4:100547. [PMID: 39802489 PMCID: PMC11719321 DOI: 10.1016/j.gastha.2024.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 09/04/2024] [Indexed: 01/16/2025]
Abstract
Background and Aims Gastric Alimetry™ (Alimetry, New Zealand) is a new clinical test for gastroduodenal disorders involving simultaneous body surface gastric electrical mapping and validated symptom profiling. Studies have demonstrated a range of distinct pathophysiological profiles, and a classification scheme is now required. We used Gastric Alimetry spectral and symptom profiles to develop a mechanism-based test classification scheme, then assessed correlations with symptom severity, psychometrics, and quality of life. Methods We performed a multicenter prospective cohort study of patients meeting the Rome IV criteria for functional dyspepsia and chronic nausea and vomiting syndromes. Patients underwent Gastric Alimetry profiling, and a standardized digital classification framework was devised and applied to separate patients into those with a) abnormal spectral analyses (ie aberrant gastric frequencies, amplitudes, and rhythms); and normal spectral analyses with b) symptoms correlated to gastric amplitude (subgroups: sensorimotor, postgastric, and activity-relieved), and c) symptoms independent of gastric amplitude (subgroups: continuous, meal-relieved, meal-induced). Results Two hundred ten patients were included (80% female, median age 37), of whom 169 met the criteria for chronic nausea and vomiting syndromes and 206 met the criteria for functional dyspepsia (79% meeting both criteria). Overall, 83% were phenotyped using the novel scheme, with 79/210 (37.6%) classified as having a spectral abnormality. Of the remainder, the most common phenotypes were "continuous pattern" (37, 17.6%), "meal-induced pattern" (28, 13.3%), and "sensorimotor pattern" (15, 7.1%). Symptom patterns independent of gastric amplitude were more strongly correlated with depression and anxiety (Patient Health Questionnaire 2: exp(β) 2.38, P = .024, State-Trait Anxiety Inventory Short-Form score: exp(β) 1.21, P = .021). Conclusion A mechanistic classification scheme for assessing gastroduodenal disorders is presented. Classified phenotypes showed independent relationships with symptom severity, quality of life, and psychological measures. The scheme is now being applied clinically and in research studies.
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Affiliation(s)
- Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | | | | | | | - Daphne Foong
- School of Medicine, Western Sydney University, Sydney, Australia
| | - Vincent Ho
- School of Medicine, Western Sydney University, Sydney, Australia
| | - Billy Wu
- Alimetry Ltd, Auckland, New Zealand
| | - I-Hsuan Huang
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Peng Du
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Thomas Abell
- Division of Gastroenterology, University of Louisville, Louisville, Kentucky
| | | | | | - Armen A. Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Gregory O’Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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Desprez C, Leroi AM, Gourcerol G. Gastric and sacral electrical stimulation for motility disorders-A clinical perspective. Neurogastroenterol Motil 2024:e14884. [PMID: 39099155 DOI: 10.1111/nmo.14884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 06/04/2024] [Accepted: 07/21/2024] [Indexed: 08/06/2024]
Abstract
BACKGROUND Electrical stimulation of the gut has been investigated in recent decades with a view to treating various gastro-intestinal motility disorders including, among others, gastric electrical stimulation to relieve nausea and vomiting associated with gastroparesis and sacral neuromodulation to treat fecal incontinence and/or constipation. Although their symptomatic efficacy has been ascertained by randomized controlled trials, their mechanisms of action are not fully understood. PURPOSE This review summarizes the past year's literature on the mechanisms of action of gut electrical stimulation therapies, including their impact on the gut-brain axis.
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Affiliation(s)
- Charlotte Desprez
- Digestive Physiology Department, Rouen University Hospital, Rouen, France
| | - Anne-Marie Leroi
- Digestive Physiology Department, Rouen University Hospital, Rouen, France
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Huang IH, Calder S, Gharibans AA, Schamberg G, Varghese C, Andrews CN, Tack J, O'Grady G. Meal effects on gastric bioelectrical activity utilizing body surface gastric mapping in healthy subjects. Neurogastroenterol Motil 2024; 36:e14823. [PMID: 38764250 DOI: 10.1111/nmo.14823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 05/01/2024] [Accepted: 05/09/2024] [Indexed: 05/21/2024]
Abstract
BACKGROUND Gastric sensorimotor disorders are prevalent. While gastric emptying measurements are commonly used, they may not fully capture the underlying pathophysiology. Body surface gastric mapping (BSGM) recently emerged to assess gastric sensorimotor dysfunction. This study assessed varying meal size on BSGM responses to inform test use in a wider variety of contexts. METHODS Data from multiple healthy cohorts receiving BSGM were pooled, using four different test meals. A standard BSGM protocol was employed: 30-min fasting, 4-h post-prandial, using Gastric Alimetry® (Alimetry, New Zealand). Meals comprised: (i) nutrient drink + oatmeal bar (482 kcal; 'standard meal'); (ii) oatmeal bar alone; egg and toast meal, and pancake (all ~250 kcal). Gastric Alimetry metrics included BMI-adjusted Amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI) and Fed:Fasted Amplitude Ratio (ff-AR). KEY RESULTS 238 participants (59.2% female) were included. All meals significantly increased amplitude and frequency during the first postprandial hour (p < 0.05). There were no differences in postprandial frequency across meals (p > 0.05). The amplitude and GA-RI of the standard meal (n = 110) were significantly higher than the energy bar alone (n = 45) and egg meal (n = 65) (all p < 0.05). All BSGM metrics were comparable across the three smaller meals (p > 0.05). A higher symptom burden was found in the oatmeal bar group versus the standard meal and pancake meal (p = 0.01, 0.003, respectively). CONCLUSIONS & INFERENCES The consumption of lower calorie meals elicited different postprandial responses, when compared to the standard Gastric Alimetry meal. These data will guide interpretations of BSGM when applied with lower calorie meals.
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Affiliation(s)
- I-Hsuan Huang
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
- Department of Gastroenterology and Hepatology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Stefan Calder
- Alimetry Ltd, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Armen A Gharibans
- Alimetry Ltd, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Gabriel Schamberg
- Alimetry Ltd, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Christopher N Andrews
- Alimetry Ltd, Auckland, New Zealand
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Canada
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium
| | - Greg O'Grady
- Alimetry Ltd, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
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Law M, Pickering I, Humphrey G, Sebaratnam G, Schamberg G, Simpson K, Varghese C, Du P, Daker C, Huang IH, Khalsa SS, Gharibans A, O'Grady G, Andrews CN, Calder S. Development and validation of the Alimetry Gut-Brain Wellbeing Survey: a novel patient-reported mental health scale for patients with chronic gastroduodenal symptoms. Front Psychol 2024; 15:1389671. [PMID: 39040963 PMCID: PMC11262055 DOI: 10.3389/fpsyg.2024.1389671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/24/2024] [Indexed: 07/24/2024] Open
Abstract
Objective There is currently a lack of validated questionnaires designed specifically to assess mental health within patients with chronic gastroduodenal symptoms. This research describes the multi-phase process used to develop and validate a novel mental health scale for patients with chronic gastroduodenal symptoms, the Alimetry® Gut-Brain Wellbeing (AGBW) Survey. Methods A patient-centered multi-phase process was implemented. In Phase 1, the most relevant concepts for this patient population were selected from existing mental health scales, using data from 79 patients. In Phase 2, an interdisciplinary panel of experts generated scale items. In Phase 3, the scale underwent pre-testing with gastroenterologists (n = 9), health psychologists (n = 3), and patients (n = 12), with feedback incorporated over multiple rounds. Lastly, the psychometric properties of the scale were assessed in a sample of 311 patients via an online survey. Results The AGBW Survey comprises a patient preface, 10 close-ended questions, and an optional open-ended question. This multidimensional scale assesses general mental health, alongside specific subscales relating to depression, stress, and anxiety. The subscale and total scores demonstrated high internal consistency (α = 0.91 for the total scale; α = 0.72-0.86 for subscales) and good convergent, divergent, concurrent validity, and known groups validity, with large effect sizes. Conclusion The AGBW Survey is a brief, valid, and reliable scale for assessing mental health in patients with chronic gastroduodenal symptoms. It can be used as a tool to complement physiological tests and has the potential to guide psychological referrals, inform multidisciplinary management, and evaluate treatment outcomes.
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Affiliation(s)
- Mikaela Law
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Isabella Pickering
- Alimetry Ltd., Auckland, New Zealand
- Department of Psychological Medicine, The University of Auckland, Auckland, New Zealand
| | - Gayl Humphrey
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | | | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Katie Simpson
- Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Peng Du
- Alimetry Ltd., Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd., Auckland, New Zealand
- Department of Gastroenterology, Te Whatu Ora - Waitematā, Auckland, New Zealand
| | - I-Hsuan Huang
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Sahib S. Khalsa
- Laureate Institute for Brain Research, Tulsa, OK, United States
- Oxley College of Health Sciences, University of Tulsa, Tulsa, OK, United States
| | - Armen Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
- The Insides Company, Auckland, New Zealand
| | - Christopher N. Andrews
- Alimetry Ltd., Auckland, New Zealand
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
- The Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
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12
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Lim AH, Varghese C, Sebaratnam GH, Schamberg G, Calder S, Gharibans AA, Andrews CN, Foong D, Ho V, Ishida S, Imai Y, Wise MR, O'Grady G. Effect of menstrual cycle and menopause on human gastric electrophysiology. Am J Physiol Gastrointest Liver Physiol 2024; 327:G47-G56. [PMID: 38713629 PMCID: PMC11211038 DOI: 10.1152/ajpgi.00216.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 04/22/2024] [Accepted: 04/23/2024] [Indexed: 05/09/2024]
Abstract
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.
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Affiliation(s)
- Alexandria H Lim
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | | | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry, Ltd., Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry, Ltd., Auckland, New Zealand
| | - Armen A Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry, Ltd., Auckland, New Zealand
| | | | - Daphne Foong
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Vincent Ho
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Shunichi Ishida
- Graduate School of Engineering, Kobe University, Kobe, Japan
| | - Yohsuke Imai
- Graduate School of Engineering, Kobe University, Kobe, Japan
| | - Michelle R Wise
- Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry, Ltd., Auckland, New Zealand
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13
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Xu W, Williams L, Sebaratnam G, Varghese C, Cedarwall C, Daker C, Keane C. Gastric Alimetry® Testing and Healthcare Economic Analysis in Nausea and Vomiting Syndromes. Dig Dis Sci 2024; 69:2304-2314. [PMID: 38689198 PMCID: PMC11258171 DOI: 10.1007/s10620-024-08455-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 04/17/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Chronic nausea and vomiting syndromes (CNVS), gastroparesis and functional dyspepsia (FD) are complex disorders. Body Surface Gastric Mapping (BSGM), a new test of gastric function, using Gastric Alimetry® (Alimetry, New Zealand) may be useful for de-escalating healthcare utilisation. This study aimed to define healthcare costs and estimate health economic impacts of implementing this test in patients with chronic gastroduodenal symptoms. METHODS Consecutive patients at a tertiary referral centre evaluated with Gastric Alimetry were included. Frequency and cost data relating to medical investigations, hospital and outpatient presentations were evaluated. Costs of healthcare utilisation were calculated, and the potential cost savings of implementing Gastric Alimetry within a diagnostic decision-tree model were estimated. RESULTS Overall, 31 consecutive patients (mean age 36.1 years; 83.9% female; predominant symptoms: nausea [83.9%], pain [61.3%], vomiting [67.7%] and bloating [35.5%]) completed Gastric Alimetry testing. Repeat gastroscopy and abdominal CT rates were 29% (8/28) and 85% (11/13), respectively. Gastric Alimetry testing identified spectral abnormalities in 45.2% of patients, and symptom profiling classified a further 29.1% of patients. Median annualised cost difference after test introduction was NZ$-12,032. Estimated reductions in investigation-related costs when incorporating Gastric Alimetry into the diagnostic workflow model were approximately NZ$1,300 per patient. CONCLUSIONS Healthcare utilisation and confirmatory testing rates remain high in nausea and vomiting syndromes. This study presents real-world data, together with a decision-tree analysis, showing Gastric Alimetry can streamline clinical care pathways, resulting in reduced healthcare utilisation and cost.
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Affiliation(s)
- William Xu
- The University of Auckland, Auckland, New Zealand
- Te Tai Tokerau District, Te Whatu Ora, Whangarei, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | | | | | - Chris Varghese
- The University of Auckland, Auckland, New Zealand
- Counties Manukau District, Te Whatu Ora, Whangarei, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Chris Cedarwall
- Capital and Coast District, Te Whatu Ora, Whangarei, New Zealand
| | | | - Celia Keane
- Te Tai Tokerau District, Te Whatu Ora, Whangarei, New Zealand.
- Department of Surgery, University of Auckland, Auckland, New Zealand.
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14
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Law M, Schamberg G, Gharibans A, Sebaratnam G, Foong D, Varghese C, Fitt I, Daker C, Ho V, Du P, Andrews CN, O'Grady G, Calder S. Short- and long-term reproducibility of body surface gastric mapping using the Gastric Alimetry® system. Neurogastroenterol Motil 2024; 36:e14812. [PMID: 38689428 DOI: 10.1111/nmo.14812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 04/03/2024] [Accepted: 04/15/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Many diagnostic tests for gastroduodenal symptoms, such as gastric emptying scintigraphy (GES), gastric emptying breath tests (GEBT), and electrogastrography (EGG) show variable intra-individual reproducibility over time. This study investigated the short- and long-term reproducibility of body surface gastric mapping (BSGM), a non-invasive test for assessing gastric function, in controls and patients with chronic gastroduodenal disorders. METHODS Participants completed three standardized BSGM tests using Gastric Alimetry® (Alimetry, New Zealand). The test encompassed a fasting baseline (30 min), a 482 kCal standard meal, and a 4 h postprandial recording. The first two tests were >6 months apart and the last occurred ~1 week after the second test, to evaluate long and short-term reproducibility. RESULTS Fourteen patients with upper gastrointestinal symptoms and 14 healthy controls were recruited. There were no significant differences in any BSGM metrics between the tests at short and long term (all p > 0.180). Lin's concordance correlation coefficients (CCC) for the primary metrics were high, ranging from 0.58 to 0.96, with intra-individual coefficients of variance (CVintra) ranging from 0.2% to 1.9%. Reproducibility was higher, and intra-individual variation lower, than in previous studies of GES (CCC = 0.54-0.83, CVintra = 3%-77%), GEBT (CVintra = 8%-11%), and EGG (CVintra = 3%-78%). CONCLUSIONS BSGM spectral metrics demonstrate high reproducibility and low intra-individual variation at both short and long term, with superior results to comparable tests. The high reproducibility of Gastric Alimetry supports its role as a diagnostic aid for gastric dysfunction and a reliable tool for evaluating treatment outcomes and disease progression over time.
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Affiliation(s)
- Mikaela Law
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Gabriel Schamberg
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Armen Gharibans
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
- Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - Daphne Foong
- Alimetry Ltd., Auckland, New Zealand
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
| | - Chris Varghese
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - India Fitt
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd., Auckland, New Zealand
- Department of Gastroenterology, Te Whatu Ora-Waitematā, Auckland, New Zealand
| | - Vincent Ho
- School of Medicine, Western Sydney University, Sydney, New South Wales, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Campbelltown, New South Wales, Australia
| | - Peng Du
- Alimetry Ltd., Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Christopher N Andrews
- Alimetry Ltd., Auckland, New Zealand
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Greg O'Grady
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
| | - Stefan Calder
- The Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd., Auckland, New Zealand
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15
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Liu H, You SS, Gao Z, Hu N, Zhao Y. Next generation of gastrointestinal electrophysiology devices. Nat Rev Gastroenterol Hepatol 2024; 21:457-458. [PMID: 38877210 DOI: 10.1038/s41575-024-00952-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/16/2024]
Affiliation(s)
- Haitao Liu
- General Surgery Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, China
| | - Siheng Sean You
- David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Zhigang Gao
- General Surgery Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China
| | - Ning Hu
- General Surgery Department, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children's Health, Hangzhou, China.
- Department of Chemistry, Zhejiang-Israel Joint Laboratory of Self-Assembling Functional Materials, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, China.
| | - Yunlong Zhao
- Dyson School of Design Engineering, Imperial College London, London, UK.
- National Physical Laboratory, Teddington, UK.
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16
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You SS, Gierlach A, Schmidt P, Selsing G, Moon I, Ishida K, Jenkins J, Madani WAM, Yang SY, Huang HW, Owyang S, Hayward A, Chandrakasan AP, Traverso G. An ingestible device for gastric electrophysiology. NATURE ELECTRONICS 2024; 7:497-508. [DOI: 10.1038/s41928-024-01160-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 03/26/2024] [Indexed: 01/04/2025]
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17
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Milan AM, Barnett MP, McNabb WC, Roy NC, Coutinho S, Hoad CL, Marciani L, Nivins S, Sharif H, Calder S, Du P, Gharibans AA, O'Grady G, Fraser K, Bernstein D, Rosanowski SM, Sharma P, Shrestha A, Mithen RF. The impact of heat treatment of bovine milk on gastric emptying and nutrient appearance in peripheral circulation in healthy females: a randomized controlled trial comparing pasteurized and ultra-high temperature milk. Am J Clin Nutr 2024; 119:1200-1215. [PMID: 38452857 DOI: 10.1016/j.ajcnut.2024.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND Heat treatments of dairy, including pasteurization and ultra-high temperature (UHT) processing, alter milk macromolecular structures, and ultimately affect digestion. In vitro, animal, and human studies show faster nutrient release or circulating appearance after consuming UHT milk (UHT-M) compared with pasteurized milk (PAST-M), with a faster gastric emptying (GE) rate proposed as a possible mechanism. OBJECTIVES To investigate the impact of milk heat treatment on GE as a mechanism of faster nutrient appearance in blood. We hypothesized that GE and circulating nutrient delivery following consumption would be faster for UHT-M than PAST-M. METHODS In this double-blind randomized controlled cross-over trial, healthy female (n = 20; 27.3 ± 1.4 y, mean ± SD) habitual dairy consumers, consumed 500 mL of either homogenized bovine UHT-M or PAST-M (1340 compared with 1320 kJ). Gastric content volume (GCV) emptying half-time (T50) was assessed over 3 h by magnetic resonance imaging subjective digestive symptoms, plasma amino acid, lipid and B vitamin concentrations, and gastric myoelectrical activity were measured over 5 h. RESULTS Although GCV T50 did not differ (102 ± 7 min compared with 89 ± 8 min, mean ± SEM, UHT-M and PAST-M, respectively; P = 0.051), GCV time to emptying 25% of the volume was 31% longer following UHT-M compared with PAST-M (42 ± 2 compared with 32 ± 4 min, P = 0.004). Although GCV remained larger for a longer duration following UHT-M (treatment × time interaction, P = 0.002), plasma essential amino acid AUC was greater following UHT-M than PAST-M (55,324 ± 3809 compared with 36,598 ± 5673 μmol·min·L-1, P = 0.006). Heat treatment did not impact gastric myoelectrical activity, plasma appetite hormone markers or subjective appetite scores. CONCLUSIONS Contrary to expectations, GE was slower with UHT-M, yet, as anticipated, aminoacidemia was greater. The larger GCV following UHT-M suggests that gastric volume may poorly predict circulating nutrient appearance from complex food matrices. Dairy heat treatment may be an effective tool to modify nutrient release by impacting digestion kinetics. CLINICAL TRIAL REGISTRY www.anzctr.org.au (ACTRN12620000172909).
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Affiliation(s)
- Amber Marie Milan
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; AgResearch Limited, Palmerston North, New Zealand; The High-Value Nutrition National Science Challenge, Auckland, New Zealand.
| | - Matthew Pg Barnett
- AgResearch Limited, Palmerston North, New Zealand; The Riddet Institute, Palmerston North, New Zealand
| | - Warren C McNabb
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand; The Riddet Institute, Palmerston North, New Zealand
| | - Nicole C Roy
- The High-Value Nutrition National Science Challenge, Auckland, New Zealand; The Riddet Institute, Palmerston North, New Zealand; Department of Human Nutrition, The University of Otago, Otago, New Zealand
| | - Schynell Coutinho
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; AgResearch Limited, Palmerston North, New Zealand
| | - Caroline L Hoad
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom; NIHR Nottingham BRC, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom
| | - Luca Marciani
- NIHR Nottingham BRC, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom
| | - Samson Nivins
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; Department of Neuroscience, Karolinska Institutet, Solna, Sweden
| | - Hayfa Sharif
- NIHR Nottingham BRC, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, United Kingdom; Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom; Amiri Hospital, Ministry of Health, Civil Service Commission, Kuwait City, Kuwait
| | - Stefan Calder
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Peng Du
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Armen A Gharibans
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand; Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Greg O'Grady
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand; Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - Karl Fraser
- AgResearch Limited, Palmerston North, New Zealand; The High-Value Nutrition National Science Challenge, Auckland, New Zealand; The Riddet Institute, Palmerston North, New Zealand
| | | | | | - Pankaja Sharma
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; AgResearch Limited, Palmerston North, New Zealand
| | - Aahana Shrestha
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; AgResearch Limited, Palmerston North, New Zealand
| | - Richard F Mithen
- The Liggins Institute, The University of Auckland, Auckland, New Zealand; The High-Value Nutrition National Science Challenge, Auckland, New Zealand; The Riddet Institute, Palmerston North, New Zealand
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Tremain P, Chan CHA, Rowbotham D, Lim G, O’Grady G, Cheng LK, McKeage J, Angeli-Gordon TR. Endoscopic mapping of bioelectric slow waves in the gastric antrum. DEVICE 2024; 2:100292. [DOI: 10.1016/j.device.2024.100292] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Humphrey G, Keane C, Gharibans A, Andrews CN, Benitez A, Mousa H, O'Grady G. Designing, Developing, and Validating a Set of Standardized Pictograms to Support Pediatric-Reported Gastroduodenal Symptoms. J Pediatr 2024; 267:113922. [PMID: 38242317 DOI: 10.1016/j.jpeds.2024.113922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 01/08/2024] [Accepted: 01/11/2024] [Indexed: 01/21/2024]
Abstract
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.
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Affiliation(s)
- Gayl Humphrey
- Department of Surgery, The University of Auckland, Aotearoa, New Zealand.
| | - Celia Keane
- Department of Surgery, The University of Auckland, Aotearoa, New Zealand; Te Whatu Ora: Te Tai Tokerau (Health New Zealand: Northland)
| | - Armen Gharibans
- Department of Surgery, The University of Auckland, Aotearoa, New Zealand; Alimetry Ltd, Auckland, Aotearoa, New Zealand; Perelman School of Medicine, University of Pennsylvania, PA
| | - Christopher N Andrews
- Alimetry Ltd, Auckland, Aotearoa, New Zealand; The Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Canada
| | - Alain Benitez
- Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia; Perelman School of Medicine, University of Pennsylvania, PA
| | - Hayat Mousa
- Division of Gastroenterology, Children's Hospital of Philadelphia, Philadelphia; Perelman School of Medicine, University of Pennsylvania, PA
| | - Gregory O'Grady
- Department of Surgery, The University of Auckland, Aotearoa, New Zealand; Alimetry Ltd, Auckland, Aotearoa, New Zealand
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20
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Hendry ET, Balfe JG, Du P, Cakmak YO. Frequency-Specific Effects of Noninvasive Median Nerve Stimulation on Gastric Slow Wave Activity in Humans. Neuromodulation 2024:S1094-7159(24)00028-X. [PMID: 38466259 DOI: 10.1016/j.neurom.2023.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 12/08/2023] [Accepted: 12/31/2023] [Indexed: 03/12/2024]
Abstract
OBJECTIVES The present study explored the effects of different frequencies of noninvasive median nerve stimulation (nMNS) on two autonomic responses: gastric slow waves under water-loading condition and heart rate variability (HRV). To the best of our knowledge, this is the first study to document the effects of different frequencies of nMNS on gastric slow waves (GSW) in humans under 5-minute water-loading condition. MATERIALS AND METHODS Twenty healthy adult participants were fitted with a noninvasive body-surface gastric mapping, electrocardiogram (ECG), and a transcutaneous electrical nerve stimulation device and administered with four different nMNS frequencies (placebo-0 Hz, 40 Hz, 120 Hz, and 200 Hz) on four separate counterbalanced days. After the baseline and stimulation periods, a 5-minute water-load test was applied, and a post-water-load period also is recorded for ECG and GSW activity. Time-domain HRV parameters are analyzed with repeated-measures one-way analysis of variance (ANOVA) and a post hoc Tukey multiple comparison test. Parameters that failed normality tests underwent a Freidman test with a post hoc Dunn multiple comparison test. GSW data are analyzed with repeated-measures mixed-effects ANOVA. RESULTS In empty stomach (baseline vs stimulation), only the 40-Hz frequency statistically significantly (p = 0.0129) increased GSW amplitude in comparison with its own baseline. In full (distended) stomach, 40-Hz and 200-Hz stimulations showed a statistically significant difference (post hoc multiple comparison adjusted, p = 0.0016 and p = 0.0183, respectively) in the Gastric Rhythm Index in comparison with the change obtained by placebo stimulation (baseline vs poststimulation periods); 120-Hz nMNS showed a statistically significant difference (p = 0.0300) in the stress index in comparison with the decrease observed in the placebo group. However, 120-Hz nMNS did not induce a statistically significant change in gastric electrical activity compared to placebo stimulation. The nMNS did not follow the linear "dose-response" relationship between nMNS frequency and gastric/HRV parameters. CONCLUSIONS The 40-Hz and 200-Hz nMNS frequencies showed the most promising results in response to gastric distension, in addition to 40 Hz for an empty stomach. Further research is essential to explore the potential therapeutic effects of these frequencies on gastric diseases such as gastroparesis, gastroesophageal reflux disease, and functional dyspepsia that can be used in wrist wearables.
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Affiliation(s)
| | | | - Peng Du
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Yusuf Ozgur Cakmak
- Cakmak Lab, Department of Anatomy, University of Otago, Dunedin, New Zealand; Center for Bioengineering-Point-of-Care Technologies, University of Otago, Dunedin, New Zealand; Medtech Core New Zealand-Interventional Technologies Theme, Auckland, New Zealand; Centre for Health Systems and Technology, University of Otago, Dunedin, New Zealand.
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21
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Xu W, Wang T, Foong D, Schamberg G, Evennett N, Beban G, Gharibans A, Calder S, Daker C, Ho V, O'Grady G. Characterization of gastric dysfunction after fundoplication using body surface gastric mapping. J Gastrointest Surg 2024; 28:236-245. [PMID: 38445915 DOI: 10.1016/j.gassur.2023.12.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 12/09/2023] [Accepted: 12/22/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND Adverse gastric symptoms persist in up to 20% of fundoplication operations completed for gastroesophageal reflux disease, causing significant morbidity and driving the need for revisional procedures. Noninvasive techniques to assess the mechanisms of persistent postoperative symptoms are lacking. This study aimed to investigate gastric myoelectrical abnormalities and symptoms in patients after fundoplication using a novel noninvasive body surface gastric mapping (BSGM) device. METHODS Patients with a previous fundoplication operation and ongoing significant gastroduodenal symptoms and matched controls were included. BSGM using Gastric Alimetry (Alimetry Ltd) was employed, consisting of a high-resolution 64-channel array, validated symptom-logging application, and wearable reader. RESULTS A total of 16 patients with significant chronic symptoms after fundoplication were recruited, with 16 matched controls. Overall, 6 of 16 patients (37.5%) showed significant spectral abnormalities defined by unstable gastric myoelectrical activity (n = 2), abnormally high gastric frequencies (n = 3), or high gastric amplitudes (n = 1). Patients with spectral abnormalities had higher Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index scores than those of patients without spectral abnormalities (3.2 [range, 2.8-3.6] vs 2.3 [range, 2.2-2.8], respectively; P = .024). Moreover, 7 of 16 patients (43.8%) had BSGM test results suggestive of gut-brain axis contributions and without myoelectrical dysfunction. Increasing Principal Gastric Frequency Deviation and decreasing Rhythm Index scores were associated with symptom severity (r > .40; P < .05). CONCLUSION A significant number of patients with persistent postfundoplication symptoms displayed abnormal gastric function on BSGM testing, which correlated with symptom severity. Our findings advance the pathophysiologic understanding of postfundoplication disorders, which may inform diagnosis and patient selection for medical therapy and revisional procedures.
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Affiliation(s)
- William Xu
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tim Wang
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Daphne Foong
- Alimetry Ltd, Auckland, New Zealand; School of Medicine, Western Sydney University, Penrith, Australia
| | - Gabe Schamberg
- Department of Surgery, University of Auckland, Auckland, New Zealand; Alimetry Ltd, Auckland, New Zealand
| | - Nicholas Evennett
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Grant Beban
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Armen Gharibans
- Alimetry Ltd, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
| | - Stefan Calder
- Alimetry Ltd, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd, Auckland, New Zealand; Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand
| | - Vincent Ho
- School of Medicine, Western Sydney University, Penrith, Australia; Department of Gastroenterology and Hepatology, Campbelltown Hospital, Campbelltown, Australia
| | - Greg O'Grady
- Department of Surgery, University of Auckland, Auckland, New Zealand; Alimetry Ltd, Auckland, New Zealand; Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.
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22
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Seo SHB, Wells CI, Dickson T, Rowbotham D, Gharibans A, Calder S, Bissett I, O'Grady G, Erickson JC. Validation of body surface colonic mapping (BSCM) against high resolution colonic manometry for evaluation of colonic motility. Sci Rep 2024; 14:4842. [PMID: 38418514 PMCID: PMC10902299 DOI: 10.1038/s41598-024-54429-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/13/2024] [Indexed: 03/01/2024] Open
Abstract
Abnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaires evaluated participants' preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range 38-63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range 0.47-0.77). HRCM and BSCM meal response start and end times (Rp = 0.998 and 0.83; both p < 0.05) and durations (Rp = 0.85; p = 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.
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Affiliation(s)
- Sean H B Seo
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Cameron I Wells
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Tully Dickson
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - David Rowbotham
- Department of Gastroenterology, Auckland City Hospital, Te Whatu Ora Health New Zealand, Auckland, New Zealand
| | - Armen Gharibans
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Ian Bissett
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Department of Surgery, Auckland District Health Board, Auckland, New Zealand
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Jonathan C Erickson
- Alimetry Ltd, Auckland, New Zealand.
- Department of Physics and Engineering, Washington and Lee University, Lexington, USA.
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23
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Dowrick JM, Jungbauer Nikolas L, Offutt SJ, Tremain P, Erickson JC, Angeli-Gordon TR. Translation of an existing implantable cardiac monitoring device for measurement of gastric electrical slow-wave activity. Neurogastroenterol Motil 2024; 36:e14723. [PMID: 38062544 DOI: 10.1111/nmo.14723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/10/2023] [Indexed: 01/25/2024]
Abstract
BACKGROUND Despite evidence that slow-wave dysrhythmia in the stomach is associated with clinical conditions such as gastroparesis and functional dyspepsia, there is still no widely available device for long-term monitoring of gastric electrical signals. Actionable biomarkers of gastrointestinal health are critically needed, and an implantable slow-wave monitoring device could aid in the establishment of causal relationships between symptoms and gastric electrophysiology. Recent developments in the area of wireless implantable gastric monitors demonstrate potential, but additional work and validation are required before this potential can be realized. METHODS We hypothesized that translating an existing implantable cardiac monitoring device, the Reveal LINQ™ (Medtronic), would present a more immediate solution. Following ethical approval and laparotomy in anesthetized pigs (n = 7), a Reveal LINQ was placed on the serosal surface of the stomach, immediately adjacent to a validated flexible-printed-circuit (FPC) electrical mapping array. Data were recorded for periods of 7.5 min, and the resultant signal characteristics from the FPC array and Reveal LINQ were compared. KEY RESULTS The Reveal LINQ device recorded slow waves in 6/7 subjects with a comparable period (p = 0.69), signal-to-noise ratio (p = 0.58), and downstroke width (p = 0.98) to the FPC, but with reduced amplitude (p = 0.024). Qualitatively, the Reveal LINQ slow-wave signal lacked the prolonged repolarization phase present in the FPC signals. CONCLUSIONS & INFERENCES These findings suggest that existing cardiac monitors may offer an efficient solution for the long-term monitoring of slow waves. Translation toward implantation now awaits.
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Affiliation(s)
- Jarrah M Dowrick
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | | | - Sarah J Offutt
- Pelvic Health, Medtronic PLC, Minneapolis, Minnesota, USA
| | - Peter Tremain
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
| | - Jonathan C Erickson
- Department of Physics and Engineering, Washington and Lee University, Lexington, Virginia, USA
| | - Timothy R Angeli-Gordon
- Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
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Du P, Maharjan A, Calder S, Schultz M, Schamberg G, Gharibans A, O'Grady G, Cakmak YO. Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Neuromodulation 2024; 27:333-342. [PMID: 36997454 DOI: 10.1016/j.neurom.2023.02.078] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 01/24/2023] [Accepted: 02/13/2023] [Indexed: 03/31/2023]
Abstract
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.
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Affiliation(s)
- Peng Du
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Ashim Maharjan
- Department of Anatomy, University of Otago, Dunedin, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand; Alimetry Ltd, Auckland, New Zealand
| | - Michael Schultz
- Department of Medicine, University of Otago, Dunedin, New Zealand
| | | | - Armen Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand; Alimetry Ltd, Auckland, New Zealand
| | - Gregory O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand; Alimetry Ltd, Auckland, New Zealand
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25
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Wang WJ, Foong D, Calder S, Schamberg G, Varghese C, Tack J, Xu W, Daker C, Carson D, Waite S, Hayes T, Du P, Abell TL, Parkman HP, Huang IH, Fernandes V, Andrews CN, Gharibans AA, Ho V, O’Grady G. Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy. Am J Gastroenterol 2024; 119:331-341. [PMID: 37782524 PMCID: PMC10872929 DOI: 10.14309/ajg.0000000000002528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 08/04/2023] [Indexed: 10/03/2023]
Abstract
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.
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Affiliation(s)
- William Jiaen Wang
- Gastrointestinal Motility Disorders Unit, Western Sydney University, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Australia
- Gastroenterology and Hepatology, Princess Alexandra Hospital, Australia
| | - Daphne Foong
- Gastrointestinal Motility Disorders Unit, Western Sydney University, Australia
| | - Stefan Calder
- Department of Surgery, Auckland City Hospital, New Zealand
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, Auckland City Hospital, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, Auckland City Hospital, New Zealand
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium
| | - William Xu
- Department of Surgery, Auckland City Hospital, New Zealand
| | - Charlotte Daker
- Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand
| | - Daniel Carson
- Department of Surgery, Auckland City Hospital, New Zealand
| | | | - Thomas Hayes
- Department of Surgery, Auckland City Hospital, New Zealand
| | - Peng Du
- Auckland Bioengineering Institute, University of Auckland, New Zealand
| | - Thomas L. Abell
- Division of Gastroenterology, University of Louisville, KY, USA
| | - Henry P. Parkman
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine, Temple University, USA
| | - I-Hsuan Huang
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Belgium
| | | | | | - Armen A. Gharibans
- Department of Surgery, Auckland City Hospital, New Zealand
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Vincent Ho
- Gastrointestinal Motility Disorders Unit, Western Sydney University, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Australia
| | - Greg O’Grady
- Department of Surgery, Auckland City Hospital, New Zealand
- Auckland Bioengineering Institute, University of Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
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26
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Law M, Pickering I, Bartlett E, Sebaratnam G, Varghese C, Gharibans A, O'Grady G, Andrews CN, Calder S. Cognitive behavioural therapy-based interventions for gastroduodenal disorders of gut-brain interaction: A systematic review. J Psychosom Res 2023; 175:111516. [PMID: 37832277 DOI: 10.1016/j.jpsychores.2023.111516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Revised: 10/03/2023] [Accepted: 10/07/2023] [Indexed: 10/15/2023]
Abstract
OBJECTIVE Cognitive behavioural therapy (CBT) is increasingly used to manage Disorders of Gut-Brain Interaction (DGBIs). This systematic review aimed to review the evidence for the effectiveness of CBT-based interventions for patients with gastroduodenal DGBIs. METHODS Medline, Embase, PubMed, Cochrane Central, and Scopus were searched in July 2022. Studies were included if they investigated the effects of a CBT-based intervention on gastrointestinal symptoms and/or psychological outcomes pre- and post-intervention in patients with gastroduodenal DGBIs. Case studies, studies not in English, and studies with patients under 18 years were excluded. Results were synthesised narratively, and standardised effect sizes were calculated where possible. RESULTS Nine studies (seven RCTs and two pre/post studies) were identified, with data reported in 10 articles (total N = 602). The studies investigated patients with functional dyspepsia (n = 7), rumination syndrome (n = 1), and supragastric belching (n = 1). The studies had heterogeneous interventions, methodologies, and outcomes, precluding meta-analysis, as well as a moderate-high risk of bias and high drop-outs rates. Findings demonstrated decreased gastrointestinal symptoms and improved anxiety, depression, and quality of life, from pre- to post-intervention, with medium to large effect sizes for symptoms and small to large effect sizes for psychological outcomes. Efficacy was maintained at follow-up, up to one year later. CONCLUSIONS This review suggests promising evidence that CBT effectively improves gastrointestinal symptoms and psychological outcomes in patients with gastroduodenal DGBIs. However, heterogeneity, risk of bias, and lack of statistical reporting were noted, indicating the need for more robust research and standardisation.
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Affiliation(s)
- Mikaela Law
- The Department of Surgery, The University of Auckland, New Zealand; Alimetry Ltd., Auckland, New Zealand
| | - Isabella Pickering
- Alimetry Ltd., Auckland, New Zealand; The Department of Psychological Medicine, The University of Auckland, New Zealand
| | | | | | - Chris Varghese
- The Department of Surgery, The University of Auckland, New Zealand
| | - Armen Gharibans
- The Department of Surgery, The University of Auckland, New Zealand; Alimetry Ltd., Auckland, New Zealand
| | - Greg O'Grady
- The Department of Surgery, The University of Auckland, New Zealand; Alimetry Ltd., Auckland, New Zealand
| | - Christopher N Andrews
- Alimetry Ltd., Auckland, New Zealand; The Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Canada
| | - Stefan Calder
- The Department of Surgery, The University of Auckland, New Zealand; Alimetry Ltd., Auckland, New Zealand.
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Subramanian S, Kunkel DC, Nguyen L, Coleman TP. Exploring the Gut-Brain Connection in Gastroparesis With Autonomic and Gastric Myoelectric Monitoring. IEEE Trans Biomed Eng 2023; 70:3342-3353. [PMID: 37310840 DOI: 10.1109/tbme.2023.3285491] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
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.
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Varghese C, Dachs N, Schamberg G, McCool K, Law M, Xu W, Calder S, Foong D, Ho V, Daker C, Andrews CN, Gharibans AA, O'Grady G. Longitudinal outcome monitoring in patients with chronic gastroduodenal symptoms investigated using the Gastric Alimetry system: study protocol. BMJ Open 2023; 13:e074462. [PMID: 38011983 PMCID: PMC10685974 DOI: 10.1136/bmjopen-2023-074462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023] Open
Abstract
INTRODUCTION The Gastric Alimetry platform offers a multimodal assessment of gastric function through body surface gastric mapping (BSGM) and concurrent symptom-tracking via a validated App. We aim to perform a longitudinal cohort study to examine the impact of Gastric Alimetry, and changes in clinical management on patient symptoms, quality of life and psychological health. METHODS AND ANALYSIS This is a prospective multicentre longitudinal observational cohort study of participants with chronic gastroduodenal symptoms. Consecutive participants undergoing Gastric Alimetry will be invited to participate. Quality of life will be assessed via EuroQol-5D and the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score. Gastrointestinal symptoms will be assessed via the Patient Assessment of Upper Gastrointestinal Symptom Severity index, and the Gastroparesis Cardinal Symptom Index. Psychometrics will be assessed, including anxiety via the General Anxiety Disorder-7, perceived stress using the Perceived Stress Scale 4, and depression via the Patient Health Questionnaire 9. Clinical parameters including diagnoses, investigations and treatments (medication and procedures) will also be captured. Assessments will be made the week after the BSGM test, at 30 days, 90 days, 180 days and 360 days thereafter. The primary outcome is feasibility of longitudinal follow-up of a cohort that have undergone Gastric Alimetry testing; from which patients' continuum of care can be characterised. Secondary outcomes include changes in patient-reported symptoms, quality of life and psychometrics (anxiety, stress and depression). Inferential causal analyses will be performed at the within patient level to explore causal associations between treatment changes and clinical outcomes. The impact of Gastric Alimetry on clinical management will also be captured. ETHICS AND DISSEMINATION The protocol has been approved in Aotearoa New Zealand by the Auckland Health Research Ethics Committee. Results will be submitted for conference presentation and peer-reviewed publication.
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Affiliation(s)
- Chris Varghese
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | | | - Gabriel Schamberg
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | | | - Mikaela Law
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - William Xu
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | | | - Daphne Foong
- Western Sydney University, Penrith South, New South Wales, Australia
| | - Vincent Ho
- Western Sydney University, Penrith South, New South Wales, Australia
| | - Charlotte Daker
- Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand
| | | | - Armen A Gharibans
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Gregory O'Grady
- Department of Surgery, University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
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Varghese C, Daker C, Lim A, Sebaratnam G, Xu W, Kean B, Cederwall C. Gastric Alimetry in the Management of Chronic Gastroduodenal Disorders: Impact to Diagnosis and Health Care Utilization. Clin Transl Gastroenterol 2023; 14:e00626. [PMID: 37589479 PMCID: PMC10684143 DOI: 10.14309/ctg.0000000000000626] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 08/02/2023] [Indexed: 08/18/2023] Open
Abstract
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.
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Affiliation(s)
- Chris Varghese
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Charlotte Daker
- Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand
| | - Alexandria Lim
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | | | - William Xu
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Bernard Kean
- Wellington Regional Hospital, Wellington, New Zealand
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Foong D, Calder S, Varghese C, Schamberg G, Xu W, Daker C, Ho V, Andrews CN, Gharibans AA, O’Grady G. Gastric Alimetry ® Test Interpretation in Gastroduodenal Disorders: Review and Recommendations. J Clin Med 2023; 12:6436. [PMID: 37892572 PMCID: PMC10607701 DOI: 10.3390/jcm12206436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 10/04/2023] [Accepted: 10/08/2023] [Indexed: 10/29/2023] Open
Abstract
Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising > 2000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this paper presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid and is expected to continue to evolve with further development.
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Affiliation(s)
- Daphne Foong
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
| | - Stefan Calder
- Department of Surgery, Auckland City Hospital, Auckland 1023, New Zealand
- Alimetry Ltd., Auckland 1010, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand
| | - Chris Varghese
- Department of Surgery, Auckland City Hospital, Auckland 1023, New Zealand
| | - Gabriel Schamberg
- Alimetry Ltd., Auckland 1010, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand
| | - William Xu
- Department of Surgery, Auckland City Hospital, Auckland 1023, New Zealand
| | - Charlotte Daker
- Department of Gastroenterology, North Shore Hospital, Auckland 0620, New Zealand
| | - Vincent Ho
- School of Medicine, Western Sydney University, Campbelltown, NSW 2560, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Sydney, NSW 2560, Australia
| | - Christopher N. Andrews
- Division of Gastroenterology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Armen A. Gharibans
- Department of Surgery, Auckland City Hospital, Auckland 1023, New Zealand
- Alimetry Ltd., Auckland 1010, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand
| | - Greg O’Grady
- Department of Surgery, Auckland City Hospital, Auckland 1023, New Zealand
- Alimetry Ltd., Auckland 1010, New Zealand
- Auckland Bioengineering Institute, University of Auckland, Auckland 1010, New Zealand
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Schamberg G, Calder S, Varghese C, Xu W, Wang WJ, Ho V, Daker C, Andrews CN, O'Grady G, Gharibans AA. Comparison of Gastric Alimetry ® body surface gastric mapping versus electrogastrography spectral analysis. Sci Rep 2023; 13:14987. [PMID: 37696955 PMCID: PMC10495352 DOI: 10.1038/s41598-023-41645-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Accepted: 08/29/2023] [Indexed: 09/13/2023] Open
Abstract
Electrogastrography (EGG) non-invasively evaluates gastric motility but is viewed as lacking clinical utility. Gastric Alimetry® is a new diagnostic test that combines high-resolution body surface gastric mapping (BSGM) with validated symptom profiling, with the goal of overcoming EGG's limitations. This study directly compared EGG and BSGM to define performance differences in spectral analysis. Comparisons between Gastric Alimetry BSGM and EGG were conducted by protocolized retrospective evaluation of 178 subjects [110 controls; 68 nausea and vomiting (NVS) and/or type 1 diabetes (T1D)]. Comparisons followed standard methodologies for each test (pre-processing, post-processing, analysis), with statistical evaluations for group-level differences, symptom correlations, and patient-level classifications. BSGM showed substantially tighter frequency ranges vs EGG in controls. Both tests detected rhythm instability in NVS, but EGG showed opposite frequency effects in T1D. BSGM showed an 8× increase in the number of significant correlations with symptoms. BSGM accuracy for patient-level classification was 0.78 for patients vs controls and 0.96 as compared to blinded consensus panel; EGG accuracy was 0.54 and 0.43. EGG detected group-level differences in patients, but lacked symptom correlations and showed poor accuracy for patient-level classification, explaining EGG's limited clinical utility. BSGM demonstrated substantial performance improvements across all domains.
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Affiliation(s)
- Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - William Xu
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - William Jiaen Wang
- School of Medicine, Western Sydney University, Sydney, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Sydney, Australia
- Department of Gastroenterology and Hepatology, Townsville University Hospital, Townsville, Australia
- Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia
| | - Vincent Ho
- School of Medicine, Western Sydney University, Sydney, Australia
- Department of Gastroenterology and Hepatology, Campbelltown Hospital, Sydney, Australia
| | - Charlotte Daker
- Department of Gastroenterology, North Shore Hospital, Auckland, New Zealand
| | | | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Armen A Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand.
- Alimetry Ltd, Auckland, New Zealand.
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
- Perelman School of Medicine, University of Pennsylvania, Pennsylvania, United States.
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Xu W, Gharibans AA, Calder S, Schamberg G, Walters A, Jang J, Varghese C, Carson D, Daker C, Waite S, Andrews CN, Cundy T, O’Grady G. Defining and Phenotyping Gastric Abnormalities in Long-Term Type 1 Diabetes Using a Novel Body Surface Gastric Mapping Device. GASTRO HEP ADVANCES 2023; 2:1120-1132. [PMID: 39131562 PMCID: PMC11307485 DOI: 10.1016/j.gastha.2023.08.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 08/04/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Diabetic gastroenteropathy is associated with poor glycemic control and morbidity in people with type 1 diabetes (T1D). There is a lack of noninvasive techniques to assess and monitor gastric abnormalities. We aimed to define phenotypes of gastric myoelectrical abnormalities in people with longstanding T1D with and without symptoms using a novel noninvasive body surface gastric mapping (BSGM) device. Methods BSGM was performed on people with T1D of >10 years duration and matched controls, employing Gastric Alimetry (Alimetry, New Zealand), comprising of a high-resolution 64-channel array, validated symptom-logging App, and wearable reader. Results Thirty-two people with T1D were recruited (15 with a high symptom burden), and 32 controls. Those with symptoms showed more unstable gastric myoelectrical activity (Gastric Alimetry Rhythm Index 0.39 vs 0.51, P = .017; and lower average spatial covariance 0.48 vs 0.51, P = .009) compared with controls. Symptomatic patients also had a higher prevalence of peripheral neuropathy (67% vs 6%, P = .001), anxiety/depression diagnoses (27% vs 0%, P = .001), and higher mean hemoglobin A1C levels (76 vs 56 mmol/mol, P < .001). BSGM defined distinct phenotypes in T1D participants including those with markedly unstable gastric rhythms (4/32, 12.5%) and abnormally high gastric frequencies (9/32, 28%). Deviation in gastric frequency was positively correlated with symptoms of bloating, upper gut pain, nausea and vomiting, and fullness (R > 0.35, P < .05). Conclusion Gastric symptoms in people with longstanding T1D correlate with myoelectrical abnormalities on BSGM evaluation, in addition to glycemic control, psychological comorbidities, and peripheral neuropathy. BSGM using Gastric Alimetry identified a range of myoelectrical phenotypes, presenting targets for diagnosis, monitoring, and therapy.
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Affiliation(s)
- William Xu
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Armen A. Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Anthony Walters
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Jia Jang
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Daniel Carson
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Charlotte Daker
- Alimetry Ltd, Auckland, New Zealand
- Department of Gastroenterology, North Shore Hospital, Te Whatu Ora Waitemata, New Zealand
| | | | - Christopher N. Andrews
- Alimetry Ltd, Auckland, New Zealand
- Department of Gastroenterology, University of Calgary, Calgary, Canada
| | - Tim Cundy
- Department of Medicine, University of Auckland, Auckland, New Zealand
| | - Gregory O’Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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Aghababaie Z, Wang THH, Nisbet LA, Matthee A, Dowrick J, Sands GB, Paskaranandavadivel N, Cheng LK, O'Grady G, Angeli-Gordon TR. Anaesthesia by intravenous propofol reduces the incidence of intra-operative gastric electrical slow-wave dysrhythmias compared to isoflurane. Sci Rep 2023; 13:11824. [PMID: 37479717 PMCID: PMC10362009 DOI: 10.1038/s41598-023-38612-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/11/2023] [Indexed: 07/23/2023] Open
Abstract
Gastric motility is coordinated by bioelectrical slow-wave activity, and abnormal electrical dysrhythmias have been associated with nausea and vomiting. Studies have often been conducted under general anaesthesia, while the impact of general anaesthesia on slow-wave activity has not been studied. Clinical studies have shown that propofol anaesthesia reduces postoperative nausea and vomiting (PONV) compared with isoflurane, while the underlying mechanisms remain unclear. In this study, we investigated the effects of two anaesthetic drugs, intravenous (IV) propofol and volatile isoflurane, on slow-wave activity. In vivo experiments were performed in female weaner pigs (n = 24). Zolazepam and tiletamine were used to induce general anaesthesia, which was maintained using either IV propofol (n = 12) or isoflurane (n = 12). High-resolution electrical mapping of slow-wave activity was performed. Slow-wave dysrhythmias occurred less often in the propofol group, both in the duration of the recorded period that was dysrhythmic (propofol 14 ± 26%, isoflurane 43 ± 39%, P = 0.043 (Mann-Whitney U test)), and in a case-by-case basis (propofol 3/12, isoflurane 8/12, P = 0.015 (Chi-squared test)). Slow-wave amplitude was similar, while velocity and frequency were higher in the propofol group than the isoflurane group (P < 0.001 (Student's t-test)). This study presents a potential physiological biomarker linked to recent observations of reduced PONV with IV propofol. The results suggest that propofol is a more suitable anaesthetic for studying slow-wave patterns in vivo.
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Affiliation(s)
- Zahra Aghababaie
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Tim Hsu-Han Wang
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Linley A Nisbet
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Ashton Matthee
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Jarrah Dowrick
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Gregory B Sands
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | | | - Leo K Cheng
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
| | - Gregory O'Grady
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Timothy R Angeli-Gordon
- Auckland Bioengineering Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
- Department of Surgery, University of Auckland, Auckland, New Zealand.
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Wang WJ, Foong D, Calder S, Schamberg G, Varghese C, Tack J, Xu W, Daker C, Carson D, Waite S, Hayes T, Du P, Abell TL, Parkman HP, Huang IH, Fernandes V, Andrews CN, Gharibans AA, Ho V, O'Grady G. Gastric Alimetry ® improves patient phenotyping in gastroduodenal disorders compared to gastric emptying scintigraphy alone. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.05.18.23290134. [PMID: 37292604 PMCID: PMC10246136 DOI: 10.1101/2023.05.18.23290134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Objectives Gastric emptying testing (GET) assesses gastric motility, however is non-specific and insensitive for neuromuscular disorders. Gastric Alimetry® (GA) is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared to 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 75 patients were assessed; 77% female. Motility abnormality detection rates were: GET 22.7% (14 delayed, 3 rapid); GA spectral analysis 33.3% (14 low rhythm stability / low amplitude; 5 high amplitude; 6 abnormal frequency); 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%; other 53%. GA phenotypes showed superior correlations with GCSI, PAGI-SYM, 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. Conclusions GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with improved correlation with symptoms and psychometrics compared to gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders. Study Highlights 1) WHAT IS KNOWN Chronic gastroduodenal symptoms are common, costly and greatly impact on quality of lifeThere is a poor correlation between gastric emptying testing (GET) and symptomsGastric Alimetry® is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling 2) WHAT IS NEW HERE Gastric Alimetry generates a 1.5x higher yield for motility abnormalities than GETWith symptom profiling, Gastric Alimetry identified 2.7x more specific patient categories than GETGastric Alimetry improves clinical phenotyping, with improved correlation with symptoms and psychometrics compared to GET.
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Wang THH, Tokhi A, Gharibans A, Evennett N, Beban G, Schamberg G, Varghese C, Calder S, Duong C, O'Grady G. Non-invasive thoracoabdominal mapping of postoesophagectomy conduit function. BJS Open 2023; 7:7153161. [PMID: 37146206 PMCID: PMC10162678 DOI: 10.1093/bjsopen/zrad036] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 02/26/2023] [Indexed: 05/07/2023] Open
Affiliation(s)
- Tim Hsu-Han Wang
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Ashraf Tokhi
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Armen Gharibans
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Nicholas Evennett
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Grant Beban
- Department of Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Gabriel Schamberg
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
| | - Cuong Duong
- Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - Greg O'Grady
- Department of Surgery, The University of Auckland, Auckland, New Zealand
- Alimetry Ltd, Auckland, New Zealand
- Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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Athavale ON, Avci R, Cheng LK, Du P. Computational models of autonomic regulation in gastric motility: Progress, challenges, and future directions. Front Neurosci 2023; 17:1146097. [PMID: 37008202 PMCID: PMC10050371 DOI: 10.3389/fnins.2023.1146097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/27/2023] [Indexed: 03/17/2023] Open
Abstract
The stomach is extensively innervated by the vagus nerve and the enteric nervous system. The mechanisms through which this innervation affects gastric motility are being unraveled, motivating the first concerted steps towards the incorporation autonomic regulation into computational models of gastric motility. Computational modeling has been valuable in advancing clinical treatment of other organs, such as the heart. However, to date, computational models of gastric motility have made simplifying assumptions about the link between gastric electrophysiology and motility. Advances in experimental neuroscience mean that these assumptions can be reviewed, and detailed models of autonomic regulation can be incorporated into computational models. This review covers these advances, as well as a vision for the utility of computational models of gastric motility. Diseases of the nervous system, such as Parkinson’s disease, can originate from the brain-gut axis and result in pathological gastric motility. Computational models are a valuable tool for understanding the mechanisms of disease and how treatment may affect gastric motility. This review also covers recent advances in experimental neuroscience that are fundamental to the development of physiology-driven computational models. A vision for the future of computational modeling of gastric motility is proposed and modeling approaches employed for existing mathematical models of autonomic regulation of other gastrointestinal organs and other organ systems are discussed.
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Schamberg G, Varghese C, Calder S, Waite S, Erickson J, O'Grady G, Gharibans AA. Revised spectral metrics for body surface measurements of gastric electrophysiology. Neurogastroenterol Motil 2023; 35:e14491. [PMID: 36409749 DOI: 10.1111/nmo.14491] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 10/17/2022] [Accepted: 10/21/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND Electrogastrography (EGG) non-invasively evaluates gastric function but has not achieved common clinical adoption due to several technical limitations. Body Surface Gastric Mapping (BSGM) has been introduced to overcome these limitations, but pitfalls in traditional metrics used to analyze spectral data remain unaddressed. This study critically evaluates five traditional EGG metrics and introduces improved BSGM spectral metrics, with validation in a large cohort. METHODS Pitfalls in five EGG metrics were assessed (dominant frequency, percentage time normogastria, amplitude, power ratio, and instability coefficient), leading to four revised BSGM spectral metrics. Traditional and revised metrics were compared to validate performance using a standardized 100-subject database of BSGM tests (30 min baseline; 4-h postprandial) recorded using Gastric Alimetry® (Alimetry). KEY RESULTS BMI and amplitude were highly correlated (r = -0.57, p < 0.001). We applied a conservative BMI correction to obtain a BMI-adjusted amplitude metric (r = -0.21, p = 0.037). Instability coefficient was highly correlated with both dominant frequency (r = -0.44, p < 0.001), and percent bradygastria (r = 0.85, p < 0.001), in part due to misclassification of low frequency transients as gastric activity. This was corrected by introducing distinct gastric frequency and stability metrics (Principal Gastric Frequency and Gastric Alimetry Rhythm Index (GA-RI)TM ) that were uncorrelated (r = 0.14, p = 0.314). Only 28% of subjects showed a maximal averaged amplitude within the first postprandial hour. Calculating Fed:Fasted Amplitude Ratio over a 4-h postprandial window yielded a median increase of 0.31 (IQR 0-0.64) above the traditional ratio. CONCLUSIONS & INFERENCES The revised metrics resolve critical pitfalls impairing the performance of traditional EGG, and should be applied in future BSGM spectral analyses.
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Affiliation(s)
- Gabriel Schamberg
- Alimetry Ltd, Auckland, New Zealand.,Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Chris Varghese
- Department of Surgery, The University of Auckland, Auckland, New Zealand
| | - Stefan Calder
- Alimetry Ltd, Auckland, New Zealand.,Department of Surgery, The University of Auckland, Auckland, New Zealand
| | | | | | - Greg O'Grady
- Alimetry Ltd, Auckland, New Zealand.,Department of Surgery, The University of Auckland, Auckland, New Zealand.,Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
| | - Armen A Gharibans
- Alimetry Ltd, Auckland, New Zealand.,Department of Surgery, The University of Auckland, Auckland, New Zealand.,Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand
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Wang Y, Chen JDZ, Nojkov B. Diagnostic Methods for Evaluation of Gastric Motility-A Mini Review. Diagnostics (Basel) 2023; 13:803. [PMID: 36832289 PMCID: PMC9955554 DOI: 10.3390/diagnostics13040803] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/11/2023] [Accepted: 02/18/2023] [Indexed: 02/23/2023] Open
Abstract
Gastric motility abnormalities are common in patients with disorders of gut-brain interaction, such as functional dyspepsia and gastroparesis. Accurate assessment of the gastric motility in these common disorders can help understand the underlying pathophysiology and guide effective treatment. A variety of clinically applicable diagnostic methods have been developed to objectively evaluate the presence of gastric dysmotility, including tests of gastric accommodation, antroduodenal motility, gastric emptying, and gastric myoelectrical activity. The aim of this mini review is to summarize the advances in clinically available diagnostic methods for evaluation of gastric motility and describe the advantages and disadvantages of each test.
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Affiliation(s)
| | | | - Borko Nojkov
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA
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O'Grady G, Carbone F, Tack J. Gastric sensorimotor function and its clinical measurement. Neurogastroenterol Motil 2022; 34:e14489. [PMID: 36371709 PMCID: PMC10078602 DOI: 10.1111/nmo.14489] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/24/2022] [Accepted: 10/24/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND Gastroduodenal symptoms are highly prevalent, with underlying sensorimotor dysfunction contributing in many patients. Common symptoms include early satiation, postprandial fullness, epigastric bloating, pain or burning, nausea and vomiting, which collectively affect over 7% of adults. However, the clinical evaluation of these symptoms remains challenging, with current tests of gastric function remaining limited in their ability or availability to separate specific patient subgroups or guide-targeted care. PURPOSE In the current edition of Neurogastroenterology & Motility, Silver et al. present new data showing correlations between patterns of intragastric meal distribution and symptom profiles in a large series of patients undergoing gastric emptying scintigraphy. Studies of this type are important, as they motivate understanding beyond existing disease labels, and orient focus toward deeper mechanistic profiling. This brief review provides an overview of gastric sensorimotor function and profiles several current and emerging methods of clinical evaluation. Perspectives are provided on accommodation testing, gastric emptying, measuring gastric myoelectrical activity including new approaches, and antroduodenal manometry. Although gastric physiology is complex, recent progress has been encouraging, with the heterogenous pathophysiology of gastric symptoms continuing to be unraveled, and new techniques for evaluating gastric function and symptoms emerging. CONCLUSIONS AND INFERENCES Ongoing progress will now depend on continuing to accurately profile the underlying mechanisms of gastroduodenal disorders to identify specific disease phenotypes that inform care.
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Affiliation(s)
- Greg O'Grady
- Department of SurgeryThe University of AucklandAucklandNew Zealand
- Alimetry LtdAucklandNew Zealand
- Auckland Bioengineering InstituteThe University of AucklandAucklandNew Zealand
| | - Florencia Carbone
- Department of GastroenterologyUniversity Hospital Leuven (UZ Leuven)LeuvenBelgium
| | - Jan Tack
- Department of GastroenterologyUniversity Hospital Leuven (UZ Leuven)LeuvenBelgium
- Translational Research Center for Gastrointestinal Diseases (TARGID), department of Chronic Diseases and Metabolism (ChroMeta)University of LeuvenLeuvenBelgium
- Sahlgrenska AcademyUniversity of GothenburgGothenburgSweden
- Rome FoundationRaleighNorth CarolinaUSA
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