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Gastric pacing is used to modulate normal or abnormal gastric slow-wave activity for therapeutic purposes. New protocols are required that are optimized for motility outcomes and energy efficiency. A computational tissue model was developed, incorporating smooth muscle and interstitial cell of Cajal layers, to enable predictive simulations of slow-wave entrainment efficacy under different pacing frequencies. Concurrent experimental validation was performed via high-resolution entrainment mapping in a porcine model (bipolar pacing protocol: 2 mA amplitude; 400 ms pulsewidth; 17-s period; midcorpus). Entrained gastric slow-wave activity was found to be anisotropic (circular direction: 8.51 mm·s-1; longitudinal: 4.58 mm·s-1), and the simulation velocities were specified accordingly. Simulated and experimental slow-wave activities demonstrated satisfactory agreement, showing similar propagation patterns and frequencies (3.5-3.6 cycles per minute), and comparable zones of entrainment (ZOEs; 64 cm²). The area of ZOE achieved was found to depend on the phase interactions between the native and entrained activities. This model allows the predictions of phase interactions between native and entrained activities, and will be useful for determining optimal frequencies for gastric pacing, including multichannel pacing studies. The model provides a framework for the development of more sophisticated predictive gastric pacing simulations in future. [ABSTRACT FROM AUTHOR]

Dear Editors, We would like to congratulate Somarajan et al on their interesting article "The effect of chronic nausea on gastric slow-wave spatiotemporal dynamics in children".1 The authors applied body surface gastric mapping (5 × 5 electrodes and sophisticated signal processing) to study slow-wave abnormalities in children with chronic nausea. Spatial patterns from high-resolution electrogastrography correlate with severity of symptoms in patients with functional dyspepsia and gastroparesis. If retrograde activation is not accompanied by contractions (or incompletely so), they could still be clinically useful if they correlate with specific disease or symptom phenotypes. [Extracted from the article]

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

Kidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury. A novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation. In both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P <.001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants. Protection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes. • Protection from SWIT by using a thermal insulation jacket is feasible. • Intraoperative thermal insulation can double time taken to reach 15°C. • Both silicone and polyurethane are viable materials for thermal insulation. [ABSTRACT FROM AUTHOR]

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • CBT-based interventions show promising benefits for gastroduodenal DGBIs • Improvements were seen in gastrointestinal symptoms and psychological outcomes • However, the studies had high heterogeneity, dropouts, and risk of bias • There is a need for more robust research and research into digital CBT interventions [ABSTRACT FROM AUTHOR]

Keywords: Postoperative ileus; Ileus; Opiates; Enhanced recovery after surgery; Bowel recovery EN Postoperative ileus Ileus Opiates Enhanced recovery after surgery Bowel recovery 1866 1868 3 07/29/20 20200801 NES 200801 Electronic supplementary material The online version of this article (10.1007/s11605-020-04654-y) contains supplementary material, which is available to authorized users. Opiates are well known to slow gut transit,[3] and recently updated ERAS guidelines emphasize opiate-sparing strategies.[4] However, this study and others have failed to show opiate dosage as an independent predictor of PPOI.[5], [6] It follows that within centres adopting opiate-sparing ERAS principles, variations in opiate medication may play a smaller role in postoperative gastrointestinal recovery than previously thought. Postoperative ileus, Ileus, Opiates, Enhanced recovery after surgery, Bowel recovery. [Extracted from the article]

Background: Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application. Methods: A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability. Results: 256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA. Conclusion: This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC. [ABSTRACT FROM AUTHOR]

Electrical slow waves, generated by interstitial cells of Cajal (ICC), cause spontaneous contractions of human stomach. Software was developed to measure muscle tone and eleven different parameters defining these contractions in human stomach, displaying data as radar plots. A pilot study assessed the effects of potential modulators, selected from among compounds known to influence ICC activity; n = 4–7 each concentration tested/compound. Human distal stomach (corpus-antrum) muscle strips were suspended in tissue baths for measuring myogenic (non-neuronal) contractions in the presence of tetrodotoxin (10-6 M). Initial characterization: Contractions (amplitude 4 ± 0.4mN, frequency 3 ± 0.1 min-1, n = 49) were unchanged by ꭃ-conotoxin GVIA (10-7 M) or indomethacin (10-6 M) but abolished by nifedipine (10-4 M). Carbachol (10-7 M) increased contraction rate and amplitude; 10-6-10-5 M increased tone and caused large, irregular contractions. [Ca 2+ ] i modulators : Ryanodine (10-5-10-4 M) increased muscle tone accompanied by inhibition of myogenic contractions. Xestospongin-C (10-6 M; IP 3 channel inhibitor) had no effects. SERCA pump inhibitors, 2-APB and cycloplazonic acid (10-5-10-4 M) increased tone and myogenic contraction amplitude before abolishing contractions; thapsigargin was weakly active. CaCC blockers : MONNA and CaCCinh-A01 had little-or-no effects on tone but reduced myogenic contractions; MONNA (10-4 M) was more effective, reducing amplitude (77.8 ± 15.2%) and frequency. Ca V 3.1/3.2/3.3 channel block : Mibefradil reduced tone and myogenic contraction amplitude (p IC 50 4.8 ± 0.9). Inward-rectifying K + -channel inhibitor : E-4031 (10-4 M) increased contraction duration (17.4 ± 5.8%). Conclusions: (1) Measurement of multiple parameters of myogenic contractions identified subtle differences between compounds, (2) only E-4031 and CaCC blockers influenced myogenic contractions, not muscle tone, (3) studies are needed with compounds with known and/or improved selectivity/potency for human targets affecting ICC functions. [Display omitted] • Myogenic contractions of human stomach at frequency of slow wave activity in vivo. • CaCC blockers reduced contraction amplitude and frequency. • The inward-rectifying K+-channel inhibitor E-4031 increased contraction duration. • No other modulator of interstitial cells of Cajal affected only the contractions. • The efficacy, potency, selectivity of the compounds at human targets are unclear. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

Introduction Disorders of gut-brain interaction (DGBIs) encompass a common group of disorders characterised by chronic gastrointestinal symptoms. Psychological comorbidities are common in patients with DGBIs and are linked with poorer patient outcomes. Consequently, assessing and managing mental wellbeing may lead to improvements in symptoms and quality of life. Methods This study aimed to explore patients' and clinicians' opinions on integrating psychometrics into routine DGBI testing. Semi-structured interviews were conducted with 16 patients with gastroduodenal DGBI and 19 clinicians who see and treat these patients. Interviews were analysed using inductive, reflexive thematic analysis. Results Three key clinician themes were developed: (1) psychology as part of holistic care, emphasising the importance of a multidisciplinary approach; (2) the value of psychometrics in clinical practice, highlighting their potential for screening and expanding management; and (3) navigating barriers to utilising psychometrics, addressing the need for standardisation to maintain the therapeutic relationship. Four key patient themes were developed: (1) the utility of psychometrics in clinical care, reflecting the perceived benefits; (2) openness to psychological management, indicating patients' willingness to explore psychological treatments; (3) concerns with psychological integration, addressing potential stigma and fear of labelling; and (4) the significance of clinician factors, emphasising the importance of clinician bedside manner, knowledge and collaboration. Conclusions These themes demonstrate that patients and clinicians see value in integrating psychometrics into routine DGBI testing. Despite potential barriers, psychometrics advance patient and clinician understanding and facilitate multidisciplinary management. Recommendations for navigating challenges were provided, and considering these, patients and clinicians supported the use of psychometrics as screening tools for patients with DGBIs., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The Auckland Health Research Ethics Committee issued approval AH24466. All participants provided written informed consent before enrollment in the study. Ethics approval was granted by the Auckland Health Research Ethics Committee (approval number: AH24466). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study is funded by the New Zealand Health Research Council Programme Grant 3715588. Financial relationships: Greg O'Grady declare(s) employment from The Insides Company. Greg O'Grady is also a director at The Insides Company. Mikaela Law, Esme Bartlett, Gabrielle Sebaratnam, Isabella Pickering, Greg O'Grady, Armen Gharibans, Christopher N. Andrews, Charlotte Daker and Stefan Calder declare(s) employment from Alimetry Ltd. Greg O'Grady and Armen Gharibans hold grants and intellectual property in the field of gastrointestinal electrophysiology and are directors in Alimetry Ltd. Mikaela Law, Esme Bartlett, Gabrielle Sebaratnam, Isabella Pickering, Christopher N. Andrews, Charlotte Daker and Stefan Calder are members of Alimetry Ltd. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Law et al.)

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., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

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., Competing Interests: GO’G and AG hold grants and intellectual property in the field of gastrointestinal electrophysiology and are Directors in Alimetry Ltd. GO’G is also a Director in The Insides Company. ML, IP, GSe, GSc, PD, CD, CA, and SC are members of Alimetry Ltd. GH holds options in Alimetry. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Law, Pickering, Humphrey, Sebaratnam, Schamberg, Simpson, Varghese, Du, Daker, Huang, Khalsa, Gharibans, O'Grady, Andrews and Calder.)

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 (CV intra ) 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, CV intra  = 3%-77%), GEBT (CV intra  = 8%-11%), and EGG (CV intra  = 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., (© 2024 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

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.

Aim: Prolonged postoperative ileus (PPOI) is common and is associated with a significant healthcare burden. Previous studies have attempted to predict PPOI clinically using risk prediction algorithms. The aim of this work was to systematically review and compare risk prediction algorithms for PPOI following colorectal surgery., Method: A systematic literature search was conducted using MEDLINE, Embase, Web of Science and CINAHL Plus. Studies that developed and/or validated a risk prediction algorithm for PPOI in adults following colorectal surgery were included. Data were collected on study design, population and operative characteristics, the definition of PPOI used and risk prediction algorithm design and performance. Quality appraisal was assessed using the PROBAST tool., Results: Eleven studies with 87 549 participants were included in our review. Most were retrospective, single-centre analyses (6/11, 55%) and rates of PPOI varied from 10% to 28%. The most commonly used variables were sex (8/11, 73%), age (6/11, 55%) and surgical approach (5/11, 45%). Area under the curve ranged from 0.68-0.78, and only three models were validated. However, there was significant variation in the definition of PPOI used. No study reported sensitivity, specificity or positive/negative predictive values., Conclusion: Currently available risk prediction algorithms for PPOI appear to discriminate moderately well, although there is a lack of validation data. Future studies should aim to use a standardized definition of PPOI, comprehensively report model performance and validate their findings using internal and external methodologies., (© 2024 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Modification of dairy proteins during processing impacts structural assemblies, influencing textural and nutritional properties of dairy products, and release and availability of amino acids during digestion. By modifying only pH, acid heat-set bovine dairy gels with divergent textural properties were developed to alter protein digestion. In vitro assay confirmed faster digestion of protein from a firm gel (pH 5.65) versus a soft gel (pH 6.55). We hypothesised that firm gel (FIRM-G; pH 5.6) would result in greater indispensable amino acid (IAA) appearance in circulation over 5 h and corresponding differences in gastric myoelectrical activity relative to soft gel (SOFT-G; pH 6.2). In a randomised, single-blind cross-over trial, healthy females ( n = 20) consumed 150 g of each gel; plasma amino acid appearance was assessed over 5 hours. Iso-nitrogenous, iso-caloric gels were prepared from identical mixtures of bovine milk and whey protein concentrates; providing 17.7 g (FIRM-G) and 18.9 g (SOFT-G) of protein per serving. Secondary outcomes included gastric myoelectrical activity measured by body surface gastric mapping, glycaemic, triglyceridaemic, and subjective appetite and digestive responses. Overall plasma IAA (area under the curve) did not differ between gels. However, plasma IAA concentrations were higher, and increased more rapidly over time after SOFT-G compared with FIRM-G (1455 ± 53 versus 1350 ± 62 μmol L -1 at 30 min, p = 0.024). Similarly, total, branched-chain and dispensable amino acids were higher at 30 min with SOFT-G than FIRM-G (total: 3939 ± 97 versus 3702 ± 127 μmol L -1 , p = 0.014; branched-chain: 677 ± 30 versus 619 ± 34 μmol L -1 , p = 0.047; dispensable: 2334 ± 53 versus 2210 ± 76 μmol L -1 , p = 0.032). All other measured parameters were similar between gels. Peak postprandial aminoacidaemia was higher and faster following ingestion of SOFT-G. Customised plasma amino acid appearance from dairy is achievable by altering gel coagulum structure using pH during processing and may have minimal influence on related postprandial responses, with implications for targeting food design for optimal health. The Clinical Trial Registry number is ACTRN12622001418763 (https://www.anzctr.org.au) registered November 7, 2022.

Biopsychosocial factors are associated with disorders of gut-brain interaction (DGBI) and exacerbate gastrointestinal symptoms. The mechanisms underlying pathophysiological alterations of stress remain unclear. Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response and has diverse impact on different organ systems. The aim of the present study was to investigate the effects of peripheral CRH infusion on meal-related gastrointestinal symptoms, gastric electrical activity, and gastric sensorimotor function in healthy volunteers (HVs). In a randomized, double-blinded, placebo-controlled, crossover study, we evaluated the effects of CRH on gastric motility and sensitivity. HVs were randomized to receive either peripheral-administered CRH (100 µg bolus + 1 µg/kg/h) or placebo (saline), followed by at least a 7-day washout period and assignment to the opposite treatment. Tests encompassed saliva samples, gastric-emptying (GE) testing, body surface gastric mapping (BSGM, Gastric Alimetry; Alimetry) to assess gastric myoelectrical activity with real-time symptom profiling, and a gastric barostat study to assess gastric sensitivity to distention and accommodation. Twenty HVs [13 women, mean age 29.2 ± 5.3 yr, body mass index (BMI) 23.3 ± 3.8 kg/m 2 ] completed GE tests, of which 18 also underwent BSGM measurements during the GE tests. The GE half-time decreased significantly after CRH exposure (65.2 ± 17.4 vs. 78.8 ± 24.5 min, P = 0.02) with significantly increased gastric amplitude [49.7 (34.7-55.6) vs. 31.7 (25.7-51.0) µV, P < 0.01], saliva cortisol levels, and postprandial symptom severity. Eleven HVs also underwent gastric barostat studies on a separate day. However, the thresholds for discomfort during isobaric distensions, gastric compliance, and accommodation did not differ between CRH and placebo. NEW & NOTEWORTHY In healthy volunteers, peripheral corticotropin-releasing hormone (CRH) infusion accelerates gastric-emptying rate and increases postprandial gastric response, accompanied by a rise in symptoms, but does not alter gastric sensitivity or meal-induced accommodation. These findings underscore a significant link between stress and dyspeptic symptoms, with CRH playing a pivotal role in mediating these effects.

Artificial intelligence (AI) is rapidly emerging in healthcare, yet applications in surgery remain relatively nascent. Here we review the integration of AI in the field of surgery, centering our discussion on multifaceted improvements in surgical care in the preoperative, intraoperative and postoperative space. The emergence of foundation model architectures, wearable technologies and improving surgical data infrastructures is enabling rapid advances in AI interventions and utility. We discuss how maturing AI methods hold the potential to improve patient outcomes, facilitate surgical education and optimize surgical care. We review the current applications of deep learning approaches and outline a vision for future advances through multimodal foundation models., (© 2024. Springer Nature America, Inc.)

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 (T 50 ) 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 T 50 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)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Failure to rescue is the rate of death amongst patients with postoperative complications and has been proposed as a perioperative quality indicator. However, variation in its definition has limited comparisons between studies. We systematically reviewed all surgical literature reporting failure to rescue rates and examined variations in the definition of the 'numerator,' 'denominator,' and timing of failure to rescue measurement., Methods: Databases were searched from inception to 31 December 2022. All studies reporting postoperative failure to rescue rates as a primary or secondary outcome were included. We examined the complications included in the failure to rescue denominator, the percentage of deaths captured by the failure to rescue numerator, and the timing of measurement for complications and mortality., Results: A total of 359 studies, including 212,048,069 patients, were analyzed. The complications included in the failure to rescue denominator were reported in 295 studies (82%), with 131 different complications used. The median number of included complications per study was 10 (interquartile range 8-15). Studies that included a higher number of complications in the failure-to-rescue denominator reported lower failure-to-rescue rates. Death was included as a complication in the failure to rescue the denominator in 65 studies (18%). The median percentage of deaths captured by the failure to rescue calculation when deaths were not included in the denominator was 79%. Complications (52%) and mortality (40%) were mostly measured in-hospital, followed by 30-days after surgery., Conclusion: Failure to rescue is an important concept in the study of postoperative outcomes, although its definition is highly variable and poorly reported. Researchers should be aware of the advantages and disadvantages of different approaches to defining failure to rescue., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2023. Published by Elsevier Inc.)

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., (© 2024. The Author(s).)

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., (Copyright © 2023 by The American College of Gastroenterology.)

Aim: Faecal incontinence is common and of multifactorial aetiologies, yet current diagnostic tools are unable to assess nerve and sphincter function objectively. We developed an anorectal high-density electromyography (HD-EMG) probe to evaluate motor-evoked potentials induced via trans-sacral magnetic stimulation (TSMS)., Method: Anorectal probes with an 8 × 8 array of electrodes spaced 1 cm apart were developed for recording HD-EMG of the external anal sphincter. These HD-EMG probes were used to map MEP amplitudes and latencies evoked via TSMS delivered through the Magstim Rapid 2 (MagStim Company). Patients undergoing pelvic floor investigations were recruited for this IDEAL Stage 2a pilot study., Results: Eight participants (median age 49 years; five female) were recruited. Methodological viability, safety and diagnostic workflow were established. The test was well tolerated with median discomfort scores ≤2.5/10, median pain scores ≤1/10 and no adverse events. Higher Faecal Incontinence Severity Index scores correlated with longer MEP latencies (r = 0.58, p < 0.001) and lower MEP amplitudes (r = -0.32, p = 0.046), as did St. Mark's Incontinence Scores with both MEP latencies (r = 0.49, p = 0.001) and MEP amplitudes (r = -0.47, p = 0.002)., Conclusion: This HD-EMG probe in conjunction with TSMS presents a novel diagnostic tool for anorectal function assessment. Spatiotemporal assessment of magnetically stimulated MEPs correlated well with symptoms and offers a feasible, safe and patient-tolerable method of evaluating pudendal nerve and external anal sphincter function. Further clinical development and evaluation of these techniques is justified., (© 2023 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

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.

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., (© 2023. Springer Nature Limited.)

Background: Chronic gastroduodenal disorders including, chronic nausea and vomiting syndrome, gastroparesis, and functional dyspepsia, are challenging to diagnose and manage. The diagnostic and treatment pathways for these disorders are complex, costly and overlap substantially; however, experiences of this pathway have not been thoroughly investigated. This study therefore aimed to explore clinician and patient perspectives on the current clinical pathway., Methods: Semi-structured interviews were conducted between June 2020 and June 2022 with 11 patients with chronic nausea and vomiting syndrome alone (based on Rome IV criteria) and nine gastroenterologists who treat these conditions. Interviews were recorded, transcribed, and thematically analyzed using a reflexive, iterative, inductive approach. Five key patient themes were identified: (1) the impacts of their chronic gastroduodenal symptoms, (2) the complexity of the clinical journey, (3) their interactions with healthcare providers, (4) the need for advocacy, and (5) their experience of treatments. Five key clinician themes were also identified: (1) these conditions were seen as clinically complex, (2) there is an uncertain and variable clinical pathway, (3) the nuance of investigations, (4) these conditions were difficult to therapeutically manage, and (5) there are barriers to developing a therapeutic relationship., Conclusion: Findings indicate that both patients and clinicians are dissatisfied with the current clinical care pathways for nausea and vomiting syndromes. Recommendations included the development of more clinically relevant and discriminant tests, standardization of the diagnostic journey, and the adoption of a multidisciplinary approach to diagnosis and treatment., Competing Interests: GO’G and AG hold grants and intellectual property in the field of gastrointestinal electrophysiology and are Directors in Alimetry Ltd. GO’G is a Director in The Insides Company and CK is a medical advisor for The Insides Company. GS, ML, SC, CA, and CD are members of Alimetry Ltd. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sebaratnam, Law, Broadbent, Gharibans, Andrews, Daker, O’Grady, Calder and Keane.)

Patients with irritable bowel syndrome (IBS) have recurrent lower abdominal pain, associated with altered bowel habit (diarrhea and/or constipation). As bowel habit is altered, abnormalities in colonic motility are likely to contribute; however, characterization of colonic motor patterns in patients with IBS remains poor. Utilizing fiber-optic manometry, we aimed to characterize distal colonic postprandial colon motility in diarrhea-predominant IBS. After an overnight fast, a 72-sensor (spaced at 1-cm intervals) manometry catheter was colonoscopically placed to the proximal colon, in 13 patients with IBS-D and 12 healthy adults. Recordings were taken for 2 h pre and post a 700 kcal meal. Data were analyzed with our two developed automated techniques. In both healthy adults and patients with IBS-D, the dominant frequencies of pressure waves throughout the colon are between 2 and 4 cycles per minute (cpm) and the power of these frequencies increased significantly after a meal. Although these pressure waves formed propagating contractions in both groups, the postprandial propagating contraction increase was significantly smaller in patients compared with healthy adults. In healthy adults during the meal period, retrograde propagation between 2 and 8 cpm was significantly greater than antegrade propagation at the same frequencies. This difference was not observed in IBS-D. Patients with IBS-D show reduced prevalence of the retrograde cyclic motor pattern postprandially compared with the marked prevalence in healthy adults. We hypothesize that this reduction may allow premature rectal filling, leading to postprandial urgency and diarrhea. NEW & NOTEWORTHY Compared with healthy adults this study has shown a significant reduction in the prevalence of the postprandial retrograde cyclic motor pattern in the distal colon of patients with diarrhea-predominant irritable bowel syndrome. We hypothesize that this altered motility may allow for premature rectal filling which contributes to the postprandial urgency and diarrhea experienced by these patients.

Objective: To examine variation in "failure to rescue" (FTR) as a driver of differences in mortality between centres and over time for patients undergoing colorectal cancer surgery., Background: Wide variation exists in postoperative mortality following colorectal cancer surgery. FTR has been identified as an important determinant of variation in postoperative outcomes. We hypothesized that differences in mortality both between hospitals and over time are driven by variation in FTR., Methods: A national population-based study of patients undergoing colorectal cancer resection from 2010 to 2019 in Aotearoa New Zealand was conducted. Rates of 90-day FTR, mortality, and complications were calculated overall, and for surgical and nonoperative complications. Twenty District Health Boards (DHBs) were ranked into quartiles using risk- and reliability-adjusted 90-day mortality rates. Variation between DHBs and trends over the 10-year period were examined., Results: Overall, 15,686 patients undergoing resection for colorectal adenocarcinoma were included. Increased postoperative mortality at high-mortality centers (OR 2.4, 95% CI 1.8-3.3) was driven by higher rates of FTR (OR 2.0, 95% CI 1.5-2.8), and postoperative complications (OR 1.4, 95% CI 1.3-1.6). These trends were consistent across operative and nonoperative complications. Over the 2010 to 2019 period, postoperative mortality halved (OR 0.5, 95% CI 0.4-0.6), associated with a greater improvement in FTR (OR 0.5, 95% CI 0.4-0.7) than complications (OR 0.8, 95% CI 0.8-0.9). Differences between centers and over time remained when only analyzing patients undergoing elective surgery., Conclusion: Mortality following colorectal cancer resection has halved over the past decade, predominantly driven by improvements in "rescue" from complications. Differences in FTR also drive hospital-level variation in mortality, highlighting the central importance of "rescue" as a target for surgical quality improvement., Competing Interests: C.H. and I.P.B. are members of the New Zealand Bowel Cancer Quality Improvement Group. The other authors report no relevant conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

Background and Purpose: Nausea is associated with the hormonal secretion of vasopressin and adrenaline, although their actions in inducing nausea is poorly understood. Here, we have investigated their actions on human stomach muscle., Experimental Approach: Muscle strips were suspended in tissue baths and neuronal-/non-neuronally-mediated contractions were measured. Custom software analysed eight motility parameters defining spontaneous phasic non-neuronally mediated contractions. Receptor distributions were assessed by qPCR and immunofluorescence., Key Results: V 1A receptors and α 1 -adrenoceptors were located on muscle as well as interstitial cells of Cajal (ICCs). Myogenic contractions of human proximal and distal stomach (respectively, 2.6 ± 0.1 and 2.7 ± 0.0 per minute; n = 44) were larger in the distal area (1.1 ± 0.1 and 5.0 ± 0.1 mN), developing relatively slowly (proximal) or rapidly (distal). Vasopressin caused tonic (proximal) or short-lived (distal) increases in muscle tone and increased myogenic contraction amplitude, frequency and rate (acting at V 1A receptors; thresholds 10 -11 -10 -10  M); by contrast, cholinergically mediated contractions were unaffected. Oxytocin acted similarly to vasopressin but less potently, at OT receptors). Adrenaline increased (10 -10 -10 -5  M; α 1 -adrenoceptors) and decreased (≥10 -6  M; β-adrenoceptors) muscle tone and enhanced/reduced myogenic contractions. Cholinergically mediated contractions were reduced (α 2 -adrenoceptors). Combined, vasopressin (10 -9  M) and adrenaline (10 -8  M) increased muscle tone and phasic myogenic activity in a synergistic manner., Conclusions and Implications: Vasopressin and adrenaline increased human gastric tone and myogenic contraction amplitude, rate of contraction and frequency. In combination, their actions were further increased in a synergistic manner. Such activity may promote nausea., (© 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Understanding intestinal gases volume and composition may contribute to diagnosing digestive diseases and the microbiome's status. This meta-analysis aimed to define the composition of human intestinal gases and changes associated with diet., Methods: Studies were identified by systematic research of the MEDLINE(Ovid), Scopus, and Cochrane databases. Studies that measured the concentration of intestinal gases in healthy adult humans were retrieved. The JBI critical appraisal tool was used to evaluate the risk of bias. The primary outcomes analysed were the concentration of the most prevalent colonic gases. Participants were divided into groups according to dietary fibre content., Results: Eleven studies were included. The following gases were identified in similar concentrations across all studies (mean ± standard deviation): nitrogen (65.1 ± 20.89%), oxygen (2.3 ± 0.98%), carbon dioxide (9.9 ± 1.6%), hydrogen (2.9 ± 0.7%), and methane (14.4 ± 3.7%). Differences according to the dietary fibre were observed, with a positive correlation between fibre and volume of gas produced, particularly in fermented gases (carbon dioxide, hydrogen, and methane)., Discussion: The meta-analysis has found defined concentrations of the five most common gases present in human colonic gas. Limitations included heterogenic methodologies, a low number of participants, and few recent studies. These findings may be helpful in diagnostic applications where colonic gas volume and composition are crucial factors, including functional disorders, microbiome analyses, and bowel perforation diagnostics., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We aimed to better understand the longitudinal course of low anterior resection syndrome (LARS) to guide patient expectations and identify those at risk of persisting dysfunction., Summary Background Data: LARS describes disordered bowel function after rectal resection that significantly impacts quality of life., Methods: MEDLINE, EMBASE, CENTRAL, and CINAHL databases were systematically searched for studies that enrolled adults undergoing anterior resection for rectal cancer and used the LARS score to assess bowel function at ≥2 postoperative time points. Regression analyses were performed on deidentified patient-level data to identify predictors of change in LARS score from baseline (3-6months) to 12-months and 18-24 months., Results: Eight studies with a total of 701 eligible patients were included. The mean LARS score improved over time, from 29.4 (95% confidence interval 28.6-30.1) at baseline to 16.6 at 36 months (95% confidence interval 14.2%-18.9%). On multivariable analysis, a greater improvement in mean LARS score between baseline and 12 months was associated with no ileostomy formation [mean difference (MD) -1.7 vs 1.7, P < 0.001], and presence of LARS (major vs minor vs no LARS) at baseline (MD -3.8 vs -1.7 vs 5.4, P < 0.001). Greater improvement in mean LARS score between baseline and 18-24 months was associated with partial mesorectal excision vs total mesorectal excision (MD-8.6 vs 1.5, P < 0.001) and presence of LARS (major vs minor vs no LARS) at baseline (MD -8.8 vs -5.3 vs 3.4, P < 0.001)., Conclusions: LARS improves by 18 months postoperatively then remains stable for up to 3 years. Total mesorectal excision, neoadjuvant radiotherapy, and ileostomy formation negatively impact upon bowel function recovery., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Bowel, bladder and sexual dysfunctions are widespread among people with spinal cord injury (SCI) and significantly impact their health and quality of life. Any non-invasive intervention which offers clinical benefits and safety is an advantage in restoring these functions. Despite the potential of non-invasive neuromodulation to improve the clinical outcomes in people with SCI, its characteristics are poorly defined, and reviews of efficacy are scarce in the literature. This study aimed to perform a systematic literature review of clinical studies investigating the use of non-invasive neuromodulation in restoring bowel, bladder and sexual functions following SCI. Electronic databases were searched, including the PubMed/Medline, EMBASE, Web of Science, Scopus and Cochrane databases, along with the reference lists of retrieved publications. Studies were eligible for inclusion if they adopted a clinical design based on participants with SCI, had main outcomes of restoration of bowel, bladder or sexual function and the intervention investigated was non-invasive neuromodulation. A total of 46 studies (combined sample of 1,801) were included in this systematic review, comprising studies of transcutaneous electrical nerve stimulation, magnetic stimulation and vibratory stimulation. Of the 46 studies, 7 were randomized controlled trials (RCTs), 36 were non-RCTs and 3 were case reports. Most studies (43/46) reported improvements in bowel (5/5), bladder (32/35) and sexual (6/6) dysfunction after SCI. However, the quality of the included studies was variable and associated with a high risk of bias. Thus, well-designed, blinded and sham-controlled RCTs with larger populations are required to establish clinical efficacy of these methods., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Normothermic machine perfusion (NMP) may allow resuscitation and improved assessment of kidneys before transplantation. Using discarded human kidneys, we investigated the mechanistic basis and translational potential of NMP compared with cold static storage (CS)., Methods: Discarded deceased donor kidneys (n = 15) underwent 1-hour NMP following CS. Renal perfusion, biochemical, and histologic parameters were recorded. NMP was directly compared with CS in paired donor kidneys using simulated transplantation with allogeneic whole blood, followed by assessment of the aforementioned parameters, in addition to RNA sequencing., Results: Kidneys were successfully perfused, with improved renal blood flows and resistance over the course of perfusion, and evidence of urine output (median 21 mL), in all but one kidney. NMP completely resolved nonperfused regions in discarded donation after circulatory death kidneys. In paired kidneys (n = 4 pairs), transcriptomic analyses showed induction of stress and inflammatory pathways in NMP kidneys, with upregulation of pathways promoting cell survival and proliferation. Furthermore, the NMP pairs had significantly better renal perfusion (1.5-2 fold improvement) and functional parameters, and amelioration of cell death, oxidative stress, and complement activation., Conclusions: In this pilot preclinical study using simulated transplantation of paired kidneys, NMP of discarded marginal kidneys demonstrated some significant mechanistic benefits in comparison to CS alone. NMP may have potential to reduce organ discards and enhance early graft function in such kidneys., Competing Interests: B.X. is an employee of Thermo Fisher Scientific. The other authors declare no conflicts of interest., (Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Electrogastrography (EGG) is a non-invasive method for measuring gastric electrical activity. Recent simulation studies have attempted to extend the current clinical utility of the EGG, in particular by providing a theoretical framework for distinguishing specific gastric slow wave dysrhythmias. In this paper we implement an experimental setup called a 'torso-tank' with the aim of expanding and experimentally validating these previous simulations. The torso-tank was developed using an adult male torso phantom with 190 electrodes embedded throughout the torso. The gastric slow waves were reproduced using an artificial current source capable of producing 3D electrical fields. Multiple gastric dysrhythmias were reproduced based on high-resolution mapping data from cases of human gastric dysfunction (gastric re-entry, conduction blocks and ectopic pacemakers) in addition to normal test data. Each case was recorded and compared to the previously-presented simulated results. Qualitative and quantitative analyses were performed to define the accuracy showing [Formula: see text] 1.8% difference, [Formula: see text] 0.99 correlation, and [Formula: see text] 0.04 normalised RMS error between experimental and simulated findings. These results reaffirm previous findings and these methods in unison therefore present a promising morphological-based methodology for advancing the understanding and clinical applications of EGG.

Routine screening and accurate diagnosis of chronic gastrointestinal motility disorders represents a significant problem in current clinical practice. Electrogastrography (EGG) provides a non-invasive option for assessing gastric slow waves, as a means of diagnosing gastric dysrhythmias. However, its uptake in motility practice has been limited partly due to an incomplete description of how the underlying gastric slow waves directly relate to EGG. This study aims to quantify the effects of various anatomical orientations of the stomach on EGG using a multiscale model of whole-organ slow wave activation and EGG. The orientation of the stomach was perturbed over six parameters: x, y, z translations and rotations. The perturbed simulations were compared to the original simulated model using root-mean-squared (RMS) errors and correlation coefficients. Simulations demonstrated that the perturbations had minimal influence on EGG, however channels located within close proximity of the stomach source were subject to large variation as a result of the perturbations. The results indicate that outside a critical area the effects of translation/rotation have minimal influence on the EGG, and thus beyond this critical area findings should be relatively comparable across patient groups. These findings show promise in advancing rational development of improved EGG methods towards a normative methodology and the formation of a normative database.

Unlabelled: Gastric slow wave dysrhythmias are associated with motility disorders. Periods of tachygastria associated with slow wave re-entry were recently recognized as one important dysrhythmia mechanism, but factors promoting and sustaining gastric re-entry are currently unknown. This study reports two experimental forms of gastric re-entry and presents a series of multi-scale models that define criteria for slow wave re-entry initiation, maintenance and termination. High-resolution electrical mapping was conducted in porcine and canine models and two spatiotemporal patterns of re-entrant activities were captured: single-loop rotor and double-loop figure-of-eight. Two separate multi-scale mathematical models were developed to reproduce the velocity and entrainment frequency of these experimental recordings. A single-pulse stimulus was used to invoke a rotor re-entry in the porcine model and a figure-of-eight re-entry in the canine model. In both cases, the simulated re-entrant activities were found to be perpetuated by tachygastria that was accompanied by a reduction in the propagation velocity in the re-entrant pathways. The simulated re-entrant activities were terminated by a single-pulse stimulus targeted at the tip of re-entrant wave, after which normal antegrade propagation was restored by the underlying intrinsic frequency gradient., Main Findings: (i) the stability of re-entry is regulated by stimulus timing, intrinsic frequency gradient and conductivity; (ii) tachygastria due to re-entry increases the frequency gradient while showing decreased propagation velocity; (iii) re-entry may be effectively terminated by a targeted stimulus at the core, allowing the intrinsic slow wave conduction system to re-establish itself., (© The authors 2014. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.)

Depletion of interstitial cell of Cajal (ICC) networks is known to occur in various gastrointestinal (GI) motility disorders. Although techniques for quantifying the structure of ICC networks are available, the ICC network structure-function relationships are yet to be well elucidated. Existing methods of relating ICC structure to function are computationally expensive, and it is difficult to up-scale them to larger multiscale simulations. A new cellular automaton model for simulating tissue-specific slow wave propagation was developed, and in preliminary studies the automaton model was applied on jejunal ICC network structures from wild-type and 5-HT2B receptor knockout (ICC depleted) mice. Two metrics were also developed to quantify the simulated propagation patterns: 1) ICC and 2) non-ICC activation lag metrics. These metrics measured the average delay in time taken for the slow wave to propagate across the ICC and non-ICC domain throughout the entire network compared to the theoretical fastest propagation, respectively. Slow wave propagation was successfully simulated across the ICC networks with greatly reduced computational time compared to previous methods, and the propagation pattern metrics quantitatively revealed an impaired propagation during ICC depletion. In conclusion, the developed slow wave propagation model and propagation pattern metrics offer a computationally efficient framework for relating ICC structure to function. These tools can now be further applied to define ICC structure-function relationships across various spatial and temporal scales.

Multi-scale modeling has become a productive strategy for quantifying interstitial cells of Cajal (ICC) network structure-function relationships, but the lack of large-scale ICC network imaging data currently limits modeling progress. The single normal equation simulation (SNESIM) algorithm was utilized to generate realistic virtual images of small real wild-type (WT) and 5-HT(2B)-receptor knockout (Htr2b(-/-)) mice ICC networks. Two metrics were developed to validate the performance of the algorithm: 1) network density, which is the proportion of ICC in the tissue; and 2) connectivity, which reflects the degree of connectivity of the ICC network. Following validation, the SNESIM algorithm was modified to allow variation in the degree of ICC network depletion. ICC networks from a range of depletion severities were generated, and the electrical activity over these networks was simulated. The virtual ICC networks generated by the original SNESIM algorithm were similar to that of their real counterparts. The electrical activity simulations showed that the maximum current density magnitude increased as the network density increased. In conclusion, the SNESIM algorithm is an effective tool for generating realistic virtual ICC networks. The modified SNESIM algorithm can be used with simulation techniques to quantify the physiological consequences of ICC network depletion at various physical scales.