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The goal of this study was to determine if transplantation of enteric neural stem cells (ENSCs) can rescue the enteric nervous system, restore gut motility, reduce colonic inflammation, and improve survival in the Ednrb-KO mouse model of Hirschsprung disease (HSCR). ENSCs were isolated from mouse intestine, expanded to form neurospheres, and microinjected into the colons of recipient Ednrb-KO mice. Transplanted ENSCs were identified in recipient colons as cell clusters in neo-ganglia. Immunohistochemical evaluation demonstrated extensive cell migration away from the sites of cell delivery and across the muscle layers. Electrical field stimulation and optogenetics showed significantly enhanced contractile activity of aganglionic colonic smooth muscle following ENSC transplantation and confirmed functional neuromuscular integration of the transplanted ENSC-derived neurons. ENSC injection also partially restored the colonic migrating motor complex. Histological examination revealed a significant reduction in inflammation in ENSC-transplanted aganglionic recipient colon compared with that of sham-operated mice. Interestingly, mice that received cell transplant also had prolonged survival compared with controls. This study demonstrates that ENSC transplantation can improve outcomes in HSCR by restoring gut motility and reducing the severity of Hirschsprung-associated enterocolitis, the leading cause of death in human HSCR.

Purpose: Acute pancreatitis (AP) is often accompanied by gastrointestinal motility disorders. The purpose of this study was to investigate the efficacy and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients. Materials and methods: Sixty-five AP patients were randomly divided into conventional treatment group and TGP group. The serum ghrelin and vasoactive intestinal peptide (VIP) were used to assess the possible gastrointestinal hormonal mechanism involved. The parameters of electrogastrogram (EGG) were used to evaluate the gastric motility in AP patients. The first defecation time was used to assess the recovery of intestinal motility. The heart rate variability (HRV) test was performed to assess autonomic nervous function. Results: Compared with the conventional treatment group, the TGP treatment significantly improved symptoms in early AP patients, and shortened the first defecation time (p < 0.05) and the hospital days (p < 0.05). The level of VIP (P < 0.05) was also decreased in TGP group. The percentage of normal gastric slow waves (GSWS) (p < 0.05) was increased. The interleukin (IL)-6 level was decreased (P < 0.05). Concurrently, the vagal activity (HF) was increased (p < 0.01), the sympathetic activity (LF) was decreased (p < 0.01), and the ratio of sympathetic vagal (LF/HF) was decreased (p < 0.01). Conclusions: The TGP treatment significantly improves the clinical symptoms in early AP patients. It also increases the percentage of normal GSWS. The therapeutic effect of TGP may be caused by autonomic nervous function mechanisms. [ABSTRACT FROM AUTHOR]

In 1964, it was proven that postprandial insulin secretion is largely regulated by gut hormones and, in 1973, it was proposed that a gut hormone would also regulate appetite and food intake. Several gut hormones were tested for metabolic actions with disappointing results until the discovery of the proglucagon derivative, glucagon‐like peptide‐1 (GLP‐1). This peptide from the distal intestine has preserved activity on insulin secretion in people with type 2 diabetes and turned out to regulate both secretion and motility in the gastrointestinal tract and importantly, appetite and food intake, thus functioning as an efficient ‘ileal brake’ hormone. However, the natural hormone acts predominantly via sensory afferent systems and is extremely rapidly removed from the circulation by enzymatic degradation and renal elimination, and increasing the doses merely results in nausea and vomiting. Lipidation of analogs turned out to provide both stability and limit renal elimination, and very slow up‐titration of dosing improves tolerance. Indeed, the most recent agonists may near‐normalize glycaemic control in type 2 diabetes, may cause weight losses of up to 25% of body weight, and significantly reduce cardiovascular risk, effects that resemble those of bariatric surgery. Thus, a solution to one of the most serious health problems of modern civilization, the increased morbidity and mortality of the metabolic syndrome, may be addressed by mobilization of one of the body's own regulatory mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: To determine the precise frequency of main pancreatic duct (MPD) dilatation within the remnant pancreas at 1 year after pancreatoduodenectomy (PD) and its clinical implications, a prospective multicenter cohort study was performed in patients without MPD dilatation before PD (registry number: UMIN000029662). STUDY DESIGN: Between October 2017 and July 2020, patients with an MPD diameter less than 3 mm who were planned to undergo PD for periampullary lesions at 21 hospitals were enrolled. The primary endpoints were frequency of MPD dilatation at 1 year after PD, and the relationship between MPD dilatation and pancreatic endo- and exocrine function, nutritional status, and fatty liver. Secondary endpoints were risk factors for MPD dilatation at 1 year after PD and time-course change in MPD diameter. RESULTS: Of 200 registered patients, 161 patients were finally analyzed. Pancreatic fistula was the most frequent complication (76; 47.2%). MPD dilatation (MPD > 3 mm) at 1 year after PD was seen in 35 patients (21.7%). Pancreatic exocrine function, assessed by steatorrhea, was significantly impaired in patients with MPD dilatation. However, endocrine function, nutrition status, and fatty liver development were comparable between the 2 groups. In multivariate analysis, the serum total protein level 7.3 g/dL or more was an independent predictor for MPD dilatation at 1 year after PD (odds ratio 3.12, 95% CI 1.31 to 7.15). A mean MPD diameter significantly increased at 6 months after PD and kept plateau thereafter. CONCLUSIONS: MPD dilatation at 1 year after PD was seen in 21.7% of patients and significantly associated with exocrine function impairment but not with endocrine function, nutrition status, or development of fatty liver. [ABSTRACT FROM AUTHOR]

Phytoecdysteroids (PEs) are naturally occurring steroid compounds, that have recently gained significant attention, due to their diverse biological activities and high therapeutic potential. The aim of the present study was to quantify some PEs including 20-hydroxyecdysterone (20-HE), ponasterone A (PA), and turkesterone (TU) in selected plant foods and Rhaponticum carthamoides extract. Furthermore, the effects of 20-HE, TU, and R. carthamoides extract, were investigated with in vitro methods using isolated smooth muscle tissues. The levels of 20-HE in the analyzed samples exhibited significant differences, with kaniwa seed extract containing the highest amount, followed by spinach leaf extract, quinoa seed extract, and asparagus stem extract. The in vitro analyses suggested that R. carthamoides extract exhibits dose-dependent cytotoxic effects on smooth muscle cells, with low doses promoting contraction and higher doses inducing relaxation. Additionally, the extract demonstrated a significant inhibitory effect on ACh-induced contractions, while 20-HE enhanced the contractile response. The current findings highlighted phytoecdysteroids' potential for modifying gastrointestinal motility. [ABSTRACT FROM AUTHOR]

Toxoplasmosis, a zoonotic infection caused by Toxoplasma gondii (T. gondii), poses a significant risk to human health and public safety. Despite the availability of clinical treatments, none effectively mitigate the intestinal barrier damage, which is the primary defense against T. gondii invasion. This study introduced aldehyde groups into the indole scaffold of a peptide-like structure to investigate the protective effects of these indole aldehyde derivatives on the intestinal barrier in mice with acute T. gondii infection. This approach leveraged the propensity of peptides and aldehyde groups to form hydrogen bonds. We synthesized a range of indole derivatives using the Vilsmeier–Haack reaction and evaluated their intestinal barrier protective effects both in vitro and in vivo. Our findings revealed that indole derivatives A1 (1-Formyl-1H-indole-3-acetonitrile), A3 (Indole-3-carboxaldehyde), A5 (2-Chloro-1H-indole-3-carboxaldehyde), A8 (1-Methyl-indole-3-carboxaldehyde), and A9 (1-Methyl-2-phenyl-1H-indole-3-carboxaldehyde) demonstrated a higher selectivity index compared to the positive control, spiramycin. These derivatives enhanced gastrointestinal motility, increased glutathione (GSH) levels in the small intestine, and reduced malondialdehyde (MDA) and nitric oxide (NO) levels in the small intestine tissue and diamine oxidase (DAO) and NO levels in the serum of infected mice. Notably, A3 exhibited comparable anti-T. gondii tachyzoites activity in the peritoneal cavity. Molecular docking studies indicated that the aldehyde group on the indole scaffold not only formed a hydrogen bond with NTPase-II but also interacted with TgCDPK1 through hydrogen bonding. Among the derivatives, A3 showed promising intestinal barrier protective effects in mice with acute T. gondii infection. This research suggests that indole derivatives could serve as a potential therapeutic strategy for intestinal diseases induced by T. gondii, offering a novel direction for treating intestinal barrier damage and providing valuable insights for the chemical modification of drugs targeting T. gondii. Furthermore, it contributes to the advancement of therapeutic approaches for toxoplasmosis. [ABSTRACT FROM AUTHOR]

The intestines are in a constant state of motion and self-renewal. The mechanical breakdown of food facilitates intestinal movement and aids digestion. It is believed that mechanical stimulation, triggered by changes in osmotic pressure within the intestines, plays a crucial role in regulating gastrointestinal motility. While TRPs and PIEZO1/2 have been identified as mechanosensitive ion channels involved in this process, there still exist numerous unidentified channels with similar properties. In this study, we demonstrate that the TMEM63B expressed in intestinal stem cells contributes to the regulation of intestinal motility and digestion. The deletion of TMEM63B in intestinal stem cells not only decelerates intestinal motility and impairs digestion but also attenuates the proliferation of intestinal stem cells and exacerbates DSS-induced colitis in mice. Collectively, our findings unveil the pivotal role of TMEM63B in governing optimal digestive function and modulating intestinal motility. [ABSTRACT FROM AUTHOR]

Background Methods Key Results Conclusions & Inferences Diabetic gastroenteropathy can cause significant diagnostic challenges. Still, it remains unknown if measures of extraintestinal autonomic function reflect diabetic gastroenteropathy. We aimed to assess the associations between (1) gastrointestinal symptoms and motility measures and (2) gastrointestinal symptoms/motility measures and extraintestinal autonomic markers.We included 81 persons with type 1 or type 2 diabetes (65% female, mean age 54) with gastrointestinal symptoms and autonomic neuropathy. The Gastroparesis Cardinal Symptom Index (GCSI) and the Gastrointestinal Symptom Rating Scale (GSRS) assessed gastrointestinal symptoms. The wireless motility capsule (Smartpill™) assessed panenteric transit times and motility indices. Cardiovascular reflex tests (VAGUS™) and cardiac vagal tone (eMotion Faros) estimated cardiovascular autonomic neuropathy, while the SUDOSCAN™ evaluated sudomotor function.Proximal gastrointestinal symptoms were positively associated with the gastric motility index (GCSI: 1.18 (1.04–1.35), p = 0.01; GSRS: 1.15 (1.03–1.29), p = 0.02; median ratio (95% CI)), while only satiety correlated with gastric emptying time (1.24 (1.03–1.49), p = 0.02). Diarrhea was associated with decreased small bowel transit time (0.93 (0.89–0.98), p = 0.005), while constipation were associated with prolonged colonic transit time (1.16 (1.03–1.31), p = 0.02). Gastrointestinal symptoms increased with the degree of abnormal cardiovascular reflex tests (GCSI: 0.67 (0.16–1.19), p = 0.03; GSRS: 0.87 (0.30–1.45), p = 0.01; mean difference (95% CI)) but not with motility measures. Cardiac vagal tone and sudomotor function were not associated with gastrointestinal markers.Gastrointestinal and extraintestinal autonomic measures were not associated. However, proximal gastrointestinal symptoms were associated with the gastric motility index and cardiovascular reflex tests. Hence, the latter may contribute to evaluating whether proximal gastrointestinal symptoms are autonomically derived. [ABSTRACT FROM AUTHOR]

BACKGROUND: Practice on fasting prior to extubation in critically ill patients is variable. Efficacy of fasting in reducing gastric volume has not been well established. The primary objective of this study was to assess the effect of 4 h of fasting on prevalence of empty stomach using gastric ultrasonography in critically ill subjects who are fasted for extubation. The secondary objectives were to evaluate the change in gastric volumes during 4 h of fasting and to determine factors associated with empty stomach after fasting. METHODS: This was a single-center, prospective, observational study on adult ICU subjects who were enterally fed for at least 6 h continuously and mechanically ventilated. Gastric ultrasound was performed immediately prior to commencement of fasting, after 4 h of fasting, and after nasogastric (NG) aspiration after 4 h of fasting. An empty stomach was defined as a gastric volume ≤ 1.5 mL/kg. RESULTS: Forty subjects were recruited, and 38 (95%) had images suitable for analysis. The prevalence of empty stomach increased after 4 h of fasting (25 [65.8%] vs 31 [81.6%], P = .041) and after 4 h of fasting with NG aspiration (25 [65.8%] vs 34 [89.5%], P = .008). There was a significant difference in median (interquartile range) gastric volume per body weight between before fasting and 4 h after fasting (1.0 [0.5-1.8] mL/kg vs 0.4 [0.2-1.0] mL/kg, P < .001). No patient factors were associated with higher prevalence of empty stomach after 4 h of fasting. CONCLUSIONS: Most mechanically ventilated subjects had empty stomachs prior to fasting for extubation. Fasting for 4 h further increased the prevalence of empty stomach at extubation to > 80%. [ABSTRACT FROM AUTHOR]

Objectives: Circadian rhythm disruption (CRD) is implicated with numerous gastrointestinal motility diseases, with the enteric nervous system (ENS) taking main responsibility for the coordination of gastrointestinal motility. The purpose of this study is to explore the role of circadian rhythms in ENS remodeling and to further elucidate the underlying mechanisms. Methods: First, we established a jet-lagged mice model by advancing the light/dark phase shift by six hours every three days for eight weeks. Subsequent changes in gastrointestinal motility and the ENS were then assessed. Additionally, a triple-transgenic mouse strain (Nestin-creERT2 × Ngfr-DreERT2: DTRGFP) was utilized to track the effects of CRD on the differentiation of enteric neural precursor cells (ENPCs). RNA sequencing was also performed to elucidate the underlying mechanism. Results: Compared to the control group, CRD significantly accelerated gastrointestinal motility, evidenced by faster intestinal peristalsis (P < 0.01), increased fecal output (P < 0.01), and elevated fecal water content (P < 0.05), as well as enhanced electrical field stimulation induced contractions (P < 0.05). These effects were associated with an increase in the number of glial cells and nitrergic neurons in the colonic myenteric plexus. Additionally, ENPCs in the colon showed a heightened differentiation into glial cells and nitrergic neurons. Notably, the NR1D1/nuclear factor-kappaB (NF-κB) axis played a crucial role in the CRD-mediated changes in ENPCs differentiation. Supplementation with NR1D1 agonist or NF-κB antagonist was able to restore gastrointestinal motility and normalize the ENS in jet-lagged mice. Conclusions: CRD regulates the differentiation of ENPCs through the NR1D1/NF-κB axis, resulting in dysfunction of the ENS and impaired gastrointestinal motility in mice. [ABSTRACT FROM AUTHOR]

Background Purpose Postoperative ileus (POI) is a condition marked by a temporary suppression of gastrointestinal motility following abdominal surgery. The mechanism of POI encompasses various factors and is characterized by two phases: the early neurogenic phase involving both adrenergic and non‐adrenergic neural pathways; the later immune‐mediated phase is characterized by a sterile inflammatory response that lasts several days. Activation of muscularis macrophages triggers a sterile inflammatory process that results in dysfunction of the enteric nervous system (ENS) and a reversible inhibition of gastrointestinal motility.In this minireview, recent insights in the pathophysiological mechanisms underlying POI and potential new therapeutic strategies are described. [ABSTRACT FROM AUTHOR]

Simple Summary: Delayed gastric conduit emptying (DGCE) is a common complication of esophageal surgery. The current study compares three endoscopic procedures—Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and a combination of both in the same session (BTPD)—to determine which approach is the most effective in DGCE treatment. By analyzing data from 64 patients endoscopically treated, results showed that the combination approach (BTPD) was associated with a higher rate of symptom resolution. BTPD allowed patients to resume eating and be discharged more quickly. These findings suggest that BTPD may be the most effective treatment for DGCE, offering better patient outcomes and potentially guiding future treatment strategies. Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged. [ABSTRACT FROM AUTHOR]

Background: Slow transit constipation (STC) is highly prevalent and has rising incidence. Shouhui Tongbian capsule (SHTB) is a traditional Chinese Medicine formula with extensive and highly efficacious usage in STC treatment, however, its mechanism of action, especially the regulation of microbiome and lipid metabolites, remains unclear. Methods: After quality control of SHTB using LC‒MS to obtain its material basis, we tried to elucidate the cohesive modulatory network of SHTB against STC using hyphenated methods from microbiomics, lipidomics, mass spectrometry imaging (MSI) and molecular methods. Results: SHTB could repair intestinal barrier damage, reduce systemic inflammation and increase intestinal motility in a diphenoxylate-induced STC rat model. Based on 16S rDNA sequencing results, SHTB rehabilitated the abnormal changes in Alloprevotella, Coprococcus, Marvinbryantia, etc., which were associated with STC symptoms. Meanwhile, microbial functional prediction showed that lipid metabolism was improved with SHTB administration. The differential lipids, including fatty acids, lysophosphatidylcholine, phosphatidylcholine, sphingomyelin triglyceride and ceramide, that are closely related to STC disease and SHTB efficacy. Furthermore, SHTB significantly reversed the abnormal expression of these key target enzymes in colon samples, including CTP-phosphocholine cytidylyltransferase, CTP-phosphoethanolamine cytidylyltransferase, phosphatidic acid phosphatase, acid sphingomyelinase etc. Conclusions: Combined analysis demonstrated that SHTB reducing lipid accumulation and recovery of intestinal microbial homeostasis was the critical mechanism by which SHTB treats STC. [ABSTRACT FROM AUTHOR]

Background: Recently, there has been increasing interest in the possible role of the gut microbiota (GM) in the onset of migraine. Our aim was to verify whether bacterial populations associated with intestinal dysbiosis are found in pediatric patients with migraine. We looked for which metabolic pathways, these bacteria were involved and whether they might be associated with gut inflammation and increased intestinal permeability. Methods: Patients aged between 6 and 17 years were recruited. The GM profiling was performed by the 16S rRNA metataxonomics of faecal samples from 98 patients with migraine and 98 healthy subjects. Alpha and beta diversity analyses and multivariate and univariate analyses were applied to compare the gut microbiota profiles between the two group. To predict functional metabolic pathways, we used phylogenetic analysis of communities. The level of indican in urine was analyzed to investigate the presence of metabolic dysbiosis. To assess gut inflammation, increased intestinal permeability and the mucosal immune activation, we measured the plasmatic levels of lipopolysaccharide, occludin and IgA, respectively. Results: The α-diversity analysis revealed a significant increase of bacterial richness in the migraine group. The β-diversity analysis showed significant differences between the two groups indicating gut dysbiosis in patients with migraine. Thirty-seven metabolic pathways were increased in the migraine group, which includes changes in tryptophan and phenylalanine metabolism. The presence of metabolic dysbiosis was confirmed by the increased level of indican in urine. Increased levels of plasmatic occludin and IgA indicated the presence of intestinal permeability and mucosal immune activation. The plasmatic LPS levels showed a low intestinal inflammation in patients with migraine. Conclusions: Pediatric patients with migraine present GM profiles different from healthy subjects, associated with metabolic pathways important in migraine. [ABSTRACT FROM AUTHOR]

Background Methods Key results Conclusions & inferences Chronic constipation is a gastrointestinal functional disorder which affects patient quality of life. Therefore, many studies were oriented to search herbal laxative agents. In this study, we investigated the phytochemical composition of beetroot juice (BJ) and its laxative potential in an experimental model of constipation and colonic dysmotility induced by loperamide (LOP) in Wistar rats.Animals were concurrently pretreated with LOP (3 mg/kg, b.w., i.p.) and BJ (5 and 10 mL/kg, b.w., p.o.), or yohimbine (2 mg/kg, b.w., i.p.), during 1 week. The laxative activity was determined based on the weight, frequency, and water content of the feces matter. The gastric‐emptying test and intestinal transit were determined. Colon histology was examined, and oxidative status was evaluated using biochemical‐colorimetric methods.The in vivo study revealed that LOP induced a significant inhibition of gastrointestinal motility, negative consequences on defecation parameters, oxidative stress, and colonic mucosa lesions. Conversely, administration of BJ reestablished these parameters and restored colonic oxidative balance. Importantly, BJ treatment protected against LOP‐induced inflammatory markers (pro‐inflammatory cytokines and WBC) and the increase in intracellular mediators such as hydrogen peroxide, free iron, and calcium levels.This study demonstrated that the bioactive compounds in BJ provided an anti‐constipation effect by modulating intestinal motility and regulating oxidative stress and inflammation induced by LOP intoxication. [ABSTRACT FROM AUTHOR]

Background: Gastric peroral endoscopic pyloromyotomy (G‐POEM) is a promising therapeutic modality for refractory gastroparesis (GP). However, as characteristics of suitable patients for G‐POEM remain unclear, antro‐duodenal manometry (ADM) has been suggested to provide objective parameters for patient selection. The aim of the present study was to identify ADM parameters as predictors for treatment response after G‐POEM in refractory GP. Methods: Refractory GP patients who underwent a G‐POEM between 2017 and 2022 were included. The following ADM parameters were mainly scored: antral hypomotility, pylorospasm, and the presence of neuropathic enteric patterns. Treatment response was defined as a GCSI‐score decrease of ≥1 point 12 months after G‐POEM. Explorative analyses were performed on potential predictors of response using logistic regression analysis. Key Results: Sixty patients (52 women, mean age 52 ± 14 years.) with refractory GP (33 idiopathic, 16 diabetic, 11 postsurgical) were included. Clinical response data were available for 52 patients. In 8 out of 60 patients, it was not feasible to advance the catheter beyond the pylorus. Abnormal ADM was found in 46/60 patients (77%). Antral hypomotility and pylorospasm were found in respectively 33% and 12% of patients. At least one neuropathic enteric dysmotility pattern was found in 58% of patients. No differences were found when comparing baseline ADM parameters between clinical response groups at 12 months follow‐up. Following explorative analyses, no ADM parameters were identified to predict clinical response 12 months after G‐POEM. Conclusions and Inferences: No ADM parameters were identified as predictors of clinical response after G‐POEM in refractory GP patients. Additionally, a high percentage of abnormal ADM tracings was found, in particular with relation to enteric dysmotility, while only a low percentage of patients showed antral hypomotility or pylorospasm. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis is a motility disorder of the stomach characterized by cardinal symptoms and delayed gastric emptying of solid food in the absence of mechanical obstruction. There is significant unmet need in its management, and essentially there are no medications approved for its treatment over four decades. Purpose: The objectives of this review are to develop an understanding of the goals of treatment, the evidence‐based criteria for treatment success based on the current scientific understanding of gastroparesis as well as patient response outcomes, and to propose evidence‐based principles for the successful development of treatments for gastroparesis. Specifically, we discuss the pathophysiologic targets in gastroparesis, eligibility criteria for clinical trial participation based on validated gastric emptying studies, and the patient response outcome measures that have been validated to appraise effects of treatment on clinically relevant outcomes. These considerations lead to recommendations regarding eligibility, design, and duration of proof‐of‐efficacy studies, and to endorsing the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index Daily Diary as a validated patient response outcome and to justification of the shortening of proof‐of‐efficacy, placebo‐controlled clinical trials to 4 weeks treatment duration after a baseline period. We believe that such approaches will increase the likelihood of successful assessment of efficacy of novel approaches to treating patients with gastroparesis. [ABSTRACT FROM AUTHOR]

Introduction: The herbal preparation STW 5 ameliorates functional dyspepsia partly by relaxing smooth muscle of the proximal stomach, thus improving gastric accommodation. We explored the unknown pathways responsible for this effect by testing targets known to modulate gastric smooth muscle relaxation. Methods: STW 5‐induced relaxation of smooth muscle strips from guinea pig gastric corpus before and after pharmacological interventions were recorded with force transducers in an organ bath. ORAI1 mRNA expression was tested in the proximal stomach. Key Results: Blockade of Ca2+‐activated K+ and Cl− channels, voltage‐gated L‐ or T‐type Ca2+ channels, TRPA1‐, TRPV1‐, adenosine or 5‐HT4 receptors, antagonizing ryanodine receptors, inhibiting cyclooxygenase or sarcoplasmic reticulum calcium ATPase did not affect STW 5‐evoked relaxation. Likewise, protein‐kinase A or G were not involved. However, the relaxation evoked by STW 5 was significantly reduced by phorbol‐12‐myristat‐13‐acetat, an activator of protein‐kinase C, by 2‐ aminoethyldiphenylborinate, an inhibitor of the IP3 receptor‐mediated Ca2+ release from the sarcoplasmic reticulum or by SKF‐96365, a nonselective store‐operated calcium entry (SOCE) blocker. Furthermore, the mixed TRPC3/SOCE inhibitor Pyr3, but not the selective TRPC3 blocker Pyr10, reduced the effect of STW 5. Finally, BTP2, a potent blocker of ORAI‐coupled SOCE, almost abolished STW 5‐evoked relaxation. Expression of ORAI1 could be demonstrated in the corpus/fundus. Conclusions & Inferences: STW 5 inhibited SOCE, most likely ORAI channels, which are modulated by IP3‐ and PKC‐dependent mechanisms. Our findings impact on the design of drugs to induce muscle relaxation and help identify phytochemicals with similar modes of actions to treat gastrointestinal disturbances. [ABSTRACT FROM AUTHOR]

Background: The herbal preparation, STW5‐II, improves upper gastrointestinal symptoms, including abdominal fullness, early satiation, and epigastric pain, in patients with functional dyspepsia, and in preclinical models decreases fundic tone and increases antral contractility. The effects of STW5‐II on esophago‐gastric junction pressure, proximal gastric tone and antropyloroduodenal pressures, disturbances of which may contribute to symptoms associated with disorders of gut–brain interaction, including functional dyspepsia, in humans, have, hitherto, not been evaluated. Methods: STW5‐II or placebo (matched for color, aroma, and alcohol content) were each administered orally, at the recommended dose (20 drops), to healthy male and female volunteers (age: 27 ± 1 years) in a double‐blind, randomized fashion, on two separate occasions, separated by 3–7 days, to evaluate effects on (i) esophago‐gastric junction pressures following a standardized meal using solid‐state high‐resolution manometry (part 1, n = 16), (ii) proximal gastric volume using a barostat (part 2, n = 16), and (iii) antropyloroduodenal pressures assessed by high‐resolution manometry (part 3, n = 18), for 120 min (part 1) or 180 min (parts 2, 3). Key Results: STW5‐II increased maximum intrabag volume (ml; STW5‐II: 340 ± 38, placebo: 251 ± 30; p = 0.007) and intrabag volume between t = 120 and 180 min (p = 0.011), and the motility index of antral pressure waves between t = 60 and 120 min (p = 0.032), but had no effect on esophago‐gastric junction, pyloric, or duodenal pressures. Conclusions & Inferences: STW5‐II has marked region‐specific effects on gastric motility in humans, which may contribute to its therapeutic efficacy in functional dyspepsia. [ABSTRACT FROM AUTHOR]

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG's efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG's full therapeutic potential. [ABSTRACT FROM AUTHOR]

Gastrointestinal vagal afferents play an important role in communicating food related information from the gut to the brain. This information initiates vago‐vagal reflexes essential for gut functions, including gut motility and secretions. These afferents also play a role in energy homeostasis, signalling the arrival, amount and nutrient composition of a meal to the central nervous system where it is processed ultimately leading to termination of a meal. Vagal afferent responses to food related stimuli demonstrate a high degree of plasticity, responding to short term changes in nutritional demand, such as the fluctuations that occur across a 24‐hr or in response to a fast, as well as long term changes in energy demand, such as occurs during pregnancy. This plasticity is disrupted in disease states, such as obesity or chronic stress where there is hypo‐ and hypersensitivity of these afferents, respectively. Improved understanding of the plasticity of these afferents will enable identification of new treatment options for diseases associated with vagal afferent function. [ABSTRACT FROM AUTHOR]

Background: Delayed gastric emptying (DGE) is a common complication after esophagectomy. BOTOX injections and pyloric surgeries (PS), including pyloroplasty (PP) and pyloromyotomy (PM), are performed intraoperatively as prophylaxis against DGE. This study compares the effects of pyloric BOTOX injection and PS for preventing DGE post-esophagectomy. Methods: We retrospectively reviewed Moffitt's IRB-approved database of 1364 esophagectomies, identifying 475 patients receiving BOTOX or PS during esophageal resection. PS was further divided into PP and PM. Demographics, clinical characteristics, and postoperative outcomes were compared using Chi-Square, Fisher's exact test, Wilcoxon rank-sum, and ANOVA. Propensity-score matching was performed between BOTOX and PP cohorts. Results: 238 patients received BOTOX, 108 received PP, and 129 received PM. Most BOTOX patients underwent fully minimally invasive robotic Ivor-Lewis esophagectomy (81.1% vs 1.7%) while most PS patients underwent hybrid open/Robotic Ivor-Lewis esophagectomy (95.7% vs 13.0%). Anastomotic leak (p = 0.57) and pneumonia (p = 0.75) were comparable between groups. However, PS experienced lower DGE rates (15.9% vs 9.3%; p = 0.04) while BOTOX patients had less postoperative weight loss (9.7 vs 11.45 kg; p = 0.02). After separating PP from PM, leak (p = 0.72) and pneumonia (p = 0.07) rates remained similar. However, PP patients had the lowest DGE incidence (1.9% vs 15.7% vs 15.9%; p = < 0.001) and the highest bile reflux rates (2.8% vs 0% vs 0.4%; p = 0.04). Between matched cohorts of 91 patients, PP had lower DGE rates (18.7% vs 1.1%; p = < 0.001) and less weight loss (9.8 vs 11.4 kg; p = < 0.001). Other complications were comparable (all p > 0.05). BOTOX was consistently associated with shorter LOS compared to PS (all p = < 0.001). Conclusion: PP demonstrates lower rates of DGE in unmatched and matched analyses. Compared to BOTOX, PS is linked to reduced DGE rates. While BOTOX is associated with more favorable LOS, this may be attributable to difference in operative approach. PP improves DGE rates after esophagectomy without improving other postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Intraoperative administration of dexmedetomidine has shown promise in improving postoperative gastrointestinal function. In the context of colorectal surgery, the results remain inconsistent. This review aims to provide a synthesis of studies assessing the effect of dexmedetomidine on postoperative gastrointestinal function in colorectal surgery patients. Methods: CENTRAL, Emcare, Embase, and MEDLINE were searched up to September 2023. Randomized controlled trials involving adult patients (≥ 18 years) undergoing elective colorectal surgery, comparing dexmedetomidine administration to a control group, and reporting on postoperative gastrointestinal function were included. Non-comparative and emergent procedures were excluded. Primary outcome was time to first flatus or bowel movement, and secondary outcomes included length of stay and time to solid oral intake. Risk of bias was assessed using the Cochrane risk of bias tool for randomized studies. Results: After screening 1194 citations, eight studies were included. Studies comprised of 570 patients in the dexmedetomidine group (mean age: 65.8 years, 43% female, mean BMI: 22.7 kg/m2) and 556 patients in control group (mean age 70.6 years, 40% female, mean BMI 22.5 kg/m2). Dexmedetomidine administration resulted in a shorter time to flatus (MD -4.55 h, 95% CI: 20.14−8.95, p < 0.005, very low certainty of evidence), a shorter time to first bowel movement (MD -11.9 h, 95% CI: 18.74−5.05, p < 0.005, very low certainty of evidence), a shorter time to solid oral intake (MD -4.34 h, 95% CI: 17.43−11.24, p < 0.005, moderate certainty of evidence), and a shorter length of stay (MD -.06 days, 95% CI: 1.99−0.12, p < 0.05, very low certainty of evidence). Conclusion: In adult patients undergoing elective colorectal surgery, intraoperative use of dexmedetomidine results in clinically meaningful improvements in postoperative gastrointestinal function and consequently, shorter length of stay. Therefore, dexmedetomidine may serve as a valuable adjunct in enhancing postoperative recovery of patients following elective colorectal surgery, thereby reducing healthcare utilization, and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Lactose, the primary carbohydrate in milk, requires the enzyme lactase for digestion. Deficiency in lactase activity leads to lactose intolerance, causing gastrointestinal symptoms. Understanding the genetic and environmental factors influencing lactase expression and activity is crucial. Moreover, accurate diagnostic methods and effective treatments are needed to manage lactose intolerance. This review aims to explore the current knowledge on lactase deficiency, lactose intolerance, diagnostic methods, and treatment options. State of knowledge: Lactase deficiency encompasses congenital, primary, and secondary forms, each with distinct etiologies. Although often used interchangeably, lactase deficiency and lactose intolerance differ. However, the association between lactase deficiency and lactose intolerance is complex, influenced by various factors including dietary habits, gut microbiota, and gastrointestinal motility. Diagnostic methods are limited, and treatment strategies primarily involve dietary modifications, lactase supplementation, and probiotics. Conclusion: Lactose intolerance presents significant clinical challenges, often underrecognized and misdiagnosed. Despite diagnostic advancements further research is needed to refine diagnostic accuracy. Treatment focuses on dietary adjustments, enzyme supplementation, and probiotics. Balancing symptom relief with nutritional adequacy is essential. Future studies should explore the role of gut microbiome modulation in lactose intolerance management through clinical trials. [ABSTRACT FROM AUTHOR]

The involvement of multiple antibiotic‐resistant gastrointestinal pathogens in diarrhea aggravates the disease condition uncontrollably. The current study aimed to find and develop a suitable formulation utilizing multiple natural components from known plant sources to augment the current therapeutic outcomes. The hydroethanolic extraction method was applied through boiling and fermentation on ancient observation‐based efficacious plant parts for developing the antidiarrheal polyherbal formulation AP‐01. An animal study model of diarrhea was used to evaluate the safety and efficacy of the formulation. The formulation was tested in vitro on four different multiple antibiotic‐resistant gastrointestinal pathogens collected from the national repository. The formulation depicted no cytotoxicity on normal gut cells and was efficacious at 10 ml/kg single dose in relieving symptoms of diarrhea by 79.71%, compared with the standard drug showing a reduction of symptoms by 83.01%. AP‐01 exhibited delayed gastric motility. The symptoms of diarrhea ceased to occur within 320.66 ± 5.05 minutes with AP‐01, whereas the standard drug took 308 ± 6.63 minutes. AP‐01 was found successful at a viable dosage regimen of 75 μl/ml v/v to 100 μl/ml v/v in inhibiting the growth of different pathogens from the Enterobacteriaceae family possessing resistance against several classes of antibiotics in culture media. Chemical analysis revealed different alkaloids, flavonoids, and polyphenols that probably work in unison through multiple modes of action to arrest diarrhea and inhibit pathogens simultaneously. These promising results shown by AP‐01 should evoke an effort to dive deep into research and development for better therapeutic formulations for infectious diarrhea by harvesting nature's arsenal. [ABSTRACT FROM AUTHOR]

Background: Gastroparesis (GP) is a prevalent sensorimotor disorder characterized by delayed gastric emptying without mechanical obstruction, posing significant diagnostic challenges. Gastric emptying scintigraphy (GES) is the gold standard for diagnosing GP. However, its accuracy can be compromised by many medications that affect gastric motility. This study evaluates the impact of medication reconciliation on the diagnostic accuracy of GES. Results: A significant proportion of patients (75%) were on medications known to affect gastric motility. Recommendations for medication adjustments were communicated, with 30% non-adherence. Adjustments in GES interpretations were necessary for 20% of patients following comprehensive medication reviews. The involvement of radiopharmacists facilitated accurate diagnostic conclusions, underscoring the critical role of medication reconciliation in GES accuracy. Conclusion: Medication reconciliation enhanced the accuracy of GES in diagnosing gastroparesis, emphasizing the need to integrate clinical pharmacy practices into nuclear medicine. This interdisciplinary approach not only improves diagnostic accuracy but also enhances patient safety, advocating for the adoption of such practices in the management of gastroparesis. [ABSTRACT FROM AUTHOR]

The vagus nerve (VN) extensively innervates the gastric enteric nervous system (ENS), but its influence on gastric ENS functionality and motility in vivo remains unclear due to technical challenges. Here we describe a method for stable, long-term observation of gastric ENS activity and muscle dynamics at cellular resolution, which can also be extended to intestinal applications. This method involves ENS-specific labeling and the implantation of an abdominal wall window for optical recording in male mice. In vivo calcium imaging reveals a linear relationship between vagal stimulation frequency and myenteric neuron activation in gastric antrum. Furthermore, the motility of gastric antrum is significantly enhanced and shows a positive correlation with the intensity and number of activated myenteric neurons. While vagal stimulation also activates proximal colonic myenteric neurons, this activation is not frequency-dependent and does not induce proximal colonic motility. The method and results provide important insights into VN-ENS interactions in vivo, advancing our understanding of gastrointestinal motility regulation. In vivo optical recording of the real-time effects of extrinsic afferents on the activity of the enteric nervous system has been challenging. Here, the authors show a method that allows long-term imaging of the mouse gastric antrum and stable recording of the gastric myenteric plexus in response to vagal activation. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To observe the effects of modified Pingchen decoction combined with fire needle on gastrointestinal motile regulation, microvascular circulation, glucagon (GLC), Ghrelin and connexin 43(Cx43) in type 2 diabetic gastroparesis (damp heat affecting the spleen pattern). METHODS: Totally 104 patients with type 2 diabetic gastroparesis (damp heat affecting the spleen pattern) treated in Affiliated Hospital of Shaanxi University of Chinese Medicine from Jun. 2021 to Jun. 2023 were extracted to be divided into two groups through the random number table method. Fifty-two cases in the conventional treatment group were given basic Western medicine treatment, while 52 cases in the traditional Chinese medicine combination group received modified Pingchen decoction combined with fire needle based on the conventional treatment group. The clinical efficacy of two groups was compared. Traditional Chinese medicine syndrome, Gastroparesis Cardinal Symptom Index (GCSI) score before and after treatment were evaluated. Gastric evacuation rate, antrum contraction frequency, plasma viscosity, platelet aggregation rate and fibrinogen level were detected. The levels of GLC, 2 h postprandial Blood glucose (2 hBG), Ghrelin, and Cx43 were measured. RESULTS: The total effective rate of traditional Chinese medicine combination group was 96. 15% (50/52), higher than 80. 77% (42/52) of conventional treatment group, the difference was statistically significant (P<0. 05). After treatment, traditional Chinese medicine syndrome score and GCSI score of the traditional Chinese medicine combination group were lower than those in the conventional treatment group, gastric evacuation rate, antrum contraction frequency were higher than those in the conventional treatment group, plasma viscosity, platelet aggregation rate and fibrinogen level were lower than those in the conventional treatment group, GLC and 2 hBG levels were lower than those in the conventional treatment group, Ghrelin and Cx43 levels were higher than those in the conventional treatment group, the differences were statistically significant (P<0. 05). CONCLUSIONS: Modified Pingchen decoction combined with fire needle in the treatment of patients with type 2 diabetic gastroparesis (damp heat affecting the spleen pattern) can regulate blood sugar, improve GLC, Ghrelin and Cx43 levels, improve microvascular circulation and gastrointestinal motility, alleviate patients’ condition and improve clinical efficacy. [ABSTRACT FROM AUTHOR]

Background: Postoperative ileus (POI), characterized by absent gastrointestinal motility, is a frequent complication following major abdominal surgery, with no current effective treatment possibilities. For further research in the treatment of this condition, we aimed to establish a porcine model of POI. Methods: A total of 12 Landrace pigs, weighing 60 kg, were included. Five animals were used as pilots to establish the surgical procedure, five animals received the same reproducible surgical procedure developed in the pilot experiments, while two animals were used as control. The primary endpoint was number of days to first stool. Intestinal motility was monitored using the SmartPill system. Key Results: Four of the five pigs who underwent the final surgical procedure passed first stool on the third postoperative day (POD), and one passed first stool on the fifth POD. SmartPill data showed retention of the capsule in the stomach in four of five pigs with usable traces. Conclusion and Inferences: An experimental porcine model of POI was established, forming the basis for future studies in POI. [ABSTRACT FROM AUTHOR]

Background: In 2018 diagnostic criteria for pediatric intestinal pseudo‐obstruction (PIPO) were established. Neuromuscular dysfunction of the gastrointestinal tract is one of these, and often examined through antroduodenal manometry (ADM). There is little data on antroduodenal manometries in children. Our objectives were to retrospectively apply these criteria to children evaluated for suspected motility disorder, to reevaluate the ADM patterns and compare children who did and did not meet the PIPO criteria and also with healthy adults. Methods: Children with a suspected gastrointestinal motility disorder previously investigated with 24‐h 8‐lead ADM were reevaluated by applying the 2018 ESPGHAN/NASPGHAN PIPO diagnostic criteria and the 2018 ANMS‐NASPGHAN guidelines. ADM findings were compared between children who retrospectively fulfilled a PIPO diagnosis, children who did not, and a control group of healthy adults. Key Results: Of 34 children (age 7.9 (±5.1) years, 18 males), 12 retrospectively fulfilled the 2018 PIPO diagnostic criteria. Twenty‐five children (10 in the PIPO group) had abnormal diagnostic findings on ADM, whereas 9 (2 in the PIPO group) had no such findings. A PIPO diagnosis implied a significantly higher degree of abnormal ADM patterns (2.33 vs. 1.23, p = 0.02). There were no major differences in quantitative ADM measurements between the groups except higher pressures in children. Conclusions and Inferences: Children who retrospectively fulfilled a PIPO diagnosis had a significantly higher abundance of abnormal ADM findings compared with symptomatic children without PIPO and healthy adults. Our data indicate a need for set criteria for evaluation of ADM in children with suspected PIPO. [ABSTRACT FROM AUTHOR]

Introduction. Etymologically the word ileus comes from the Greek eileos, which means rolling or turning. It is described as the temporary delay of gastrointestinal motility. It is recognized worldwide that postoperative ileus is one of the main complications after surgery and represents an important problem due to its high healthcare cost. Research has been done regarding the preventive use of physical and pharmacological measures, such as prokinetics, for the management of postoperative ileus. Methods. Clinical-therapeutic, comparative, prospective longitudinal follow-up research, with non-probabilistic convenience sampling, made up of four groups with 25 patients each, treated in the General Surgery Service between May and August 2021. Results. The patients had a mean age of 49.4 ± 19.6 years and 53% were male; 86% of patients had bowel sounds within 24 hours after the operation. The first bowel movement in patients who ingested espresso coffee was 42.6 hours and for those in the American coffee group it was at 43.4 hours compared to 89.4 hours in the control group (p < 0.001). Conclusion. The use of coffee is recommended as a safe and economical measure to start the diet as an alternative to the traditional fashion, becoming an option for the management of postoperative ileus. [ABSTRACT FROM AUTHOR]

The stomach's ability to store, mix, propel, and empty its content requires highly coordinated motor functions. However, current diagnostic tools cannot simultaneously assess these motor processes. This study aimed to use magnetic resonance imaging (MRI) to map multifaceted gastric motor functions, including accommodation, tonic and peristaltic contractions, and emptying, through a single noninvasive experiment for both humans and rats. Ten humans and 10 Sprague-Dawley rats consumed MRI-visible semisolid meals and underwent MRI scans. We used a surface model to analyze MRI data, capturing the deformation of the stomach wall on ingestion or during digestion. We inferred muscle activity, mapped motor processes, parcellated the stomach into functional regions, and revealed cross-species distinctions. In humans, both the fundus and antrum distended postmeal, followed by sustained tonic contractions to regulate intragastric pressure. Peristaltic contractions initiated from the distal fundus, including three concurrent wavefronts oscillating at 3.3 cycles/min and traveling at 1.7 to 2.9 mm/s. These motor functions facilitated linear gastric emptying with a 61-min half-time. In contrast, rats exhibited peristalsis from the midcorpus, showing two wavefronts oscillating at 5.0 cycles/min and traveling at 0.4 to 0.9 mm/s. For both species, motility features allowed functional parcellation of the stomach along a midcorpus division. This study maps region- and species-specific gastric motor functions. We demonstrate the value of MRI with surface modeling in understanding gastric physiology and its potential to become a new standard for clinical and preclinical investigations of gastric disorders at both individual and group levels. NEW & NOTEWORTHY: A novel MRI technique can visualize how the stomach accommodates, mixes, and propels food for digestion in humans and animals alike. Digital models of gastric MRI reveal the functional maps, organization, and distinction of the stomach across individuals and species. This technique holds the unique potential to advance basic and clinical studies of functional gastric disorders. [ABSTRACT FROM AUTHOR]

Background and Aims: Analysis of mean nocturnal baseline impedance (MNBI) and post‐reflux swallow‐induced peristaltic wave index (PSPWi) have been proposed to increase the diagnostic yield of pH‐impedance studies in reflux disease. However, routine use of these indices in clinical studies is yet to be established, particularly with PSPWi, which requires laborious manual analysis. Our study aimed to assess the utility of MNBI and PSPWi and their potential for future incorporation into clinical practice. Methods: pH‐impedance recordings from consecutive patients referred to the Motility Laboratory at Royal Adelaide Hospital for evaluation of gastro‐oesophageal reflux disease (GORD) were prospectively collected and manually analysed. Baseline demographic characteristics, symptoms, acid exposure time (AET), number of reflux episodes, and MNBI and PSPWi were collected. Results: Eighty‐nine patients were included in the study (age 50 ± 17 years, 35 males). MNBI and PSPWi inversely correlated with AET (R = −0.678, P < 0.0001 and R = −0.460, P < 0.0001 respectively) and with reflux episodes (R = −0.391, P = 0.0002 and R = −0.305, P = 0.0037 respectively). In patients with a negative pH study, but with typical reflux symptoms, 4/30 (13%) had pathologic MNBI and PSPWi. There was a positive correlation between MNBI and PSPWi values (R = 0.525, P < 0.0001). Performing analysis of PSPWi was substantially more laborious than MNBI. Conclusion: MNBI and PSPWi are both useful adjuncts in the diagnosis of reflux disease, although in our cohort MNBI showed stronger correlation with AET with less time to analyse. The role of these indices remains to be further explored, particularly in patients with inconclusive AET and in those with positive compared to negative symptom association. [ABSTRACT FROM AUTHOR]

Objective: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. Materials and methods: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. Results: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. Conclusion: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found. Trial Registration Number: NCT05690321 (registered 2023-01-10) [ABSTRACT FROM AUTHOR]

Objective: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). Methods: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. Results: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I–IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. Conclusion: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD. [ABSTRACT FROM AUTHOR]

The use of Prostate Imaging Reporting and Data System (PI-RADS) with multiparametric magnetic resonance imaging (MRI) has significantly improved the detection of clinically significant prostate cancer (csPCa), but there are certain challenges that the reader may face. This review provides an overview of the pitfalls associated with the PI-RADS system for multiparametric prostate MRI (mpMRI), with suggestions/pearls to help overcome these pitfalls. PI-RADS assessment is hindered by several causes of false positives (FPs) and false negatives (FNs). In addition, there is wide variability in the positive predictive value (PPV) of the PI-RADS system across different centers, highlighting the need for improvement. While the negative predictive value (NPV) for csPCa is generally high, variations exist. This review discusses the pitfalls contributing to FNs, including MRI artifacts, such as susceptibility and motion artifacts. Techniques to optimize image acquisition, such as switching the phase encoding direction and reducing bowel peristalsis, are suggested to mitigate these artifacts. Improper b -value selection for diffusion-weighted imaging (DWI) is another pitfall, emphasizing the importance of using high b -values (≥1,400 s/mm 2) to optimize neoplasm detection. Similarly, optimizing window settings to visualize csPCa, correctly positioning the endorectal coil, awareness of rare variants like mucinous adenocarcinoma and cribriform adenocarcinoma, and distinguishing central zone tumors from normal central zone are discussed. This article highlights the common pitfalls causing FPs, such as benign pathologies like prostatitis, granulomatous prostatitis, prostatic abscess, stromal BPH nodules, extruded BPH nodules, and prostatic calcifications. It also discusses the pitfalls related to normal anatomical structures, including the central zone, anterior fibromuscular stroma, thickened surgical capsule, neurovascular bundle, and periprostatic venous plexus. Techniques for carefully evaluating these entities' morphology and distribution of signal abnormalities are described to avoid overdiagnosing these as PCa. The article also addresses the pitfalls related to postintervention changes, including postbiopsy hemorrhage and artifacts caused by the UroLift procedure, while providing recommendations for managing these challenges. Finally, the pitfalls that may be encountered during staging, including evaluation for extraprostatic extension, and pelvic nodal and osseous metastases, are highlighted. [ABSTRACT FROM AUTHOR]

Purpose To investigate the impacts of remimazolam tosilate on gastrointestinal hormones and motility in patients undergoing gastrointestinal endoscopy with sedation. Methods A total of 262 American Society of Anesthesiologists Physical Status I or II patients, aged 18–65 years, scheduled for gastrointestinal endoscopy with sedation, were randomly allocated into two groups (n  = 131 each): the remimazolam tosilate group (Group R) and the propofol group (Group P). Patients in Group R received 0.2–0.25 mg/Kg remimazolam tosilate intravenously, while those in Group P received 1.5–2.0 mg/kg propofol intravenously. The gastrointestinal endoscopy was performed when the Modified Observer's Assessment of Alertness/Sedation scores were ≤3. The primary endpoints included the endoscopic intestinal peristalsis rating by the endoscopist; serum motilin and gastrin levels at fasting without gastrointestinal preparation (T 0), before gastrointestinal endoscopy (T 1), and before leaving the Post Anesthesia Care Unit (T 2); and the incidences of abdominal distension during Post Anesthesia Care Unit. Results Compared with Group P, intestinal peristalsis rating was higher in Group R (P  < .001); Group R showed increased motilin and gastrin levels at T 2 compared with Group P (P  < .01). There was a rise in motilin and gastrin levels at T 1 and T 2 compared with T 0 and at T 2 compared with T 1 in both groups (P  < .01). The incidence of abdominal distension was lower in Group R (P  < .05). Conclusion Compared with propofol used during gastrointestinal endoscopy with sedation, remimazolam tosilate mildly inhibits the serum motilin and gastrin levels, potentially facilitating the recovery of gastrointestinal motility. What is already known on this topic Remimazolam tosilate (RT), as a novel ultrashort-acting benzodiazepine, has been recently used in gastrointestinal endoscopy with sedation. Nevertheless, the effects of RT on gastrointestinal hormones and gastrointestinal motility remain unclear. What this study adds Compared with propofol used in gastrointestinal endoscopy with sedation, RT mildly inhibits serum motilin and gastrin levels and gastrointestinal motility. How this study might affect research, practice, or policy RT sedation for gastrointestinal endoscopy might contribute to recovery of gastrointestinal function. [ABSTRACT FROM AUTHOR]

Over the past three decades, oral controlled-release dosage forms have been developed due to their therapeutic advantages, such as ease of administration, patient compliance, and flexibility in formulation. However, this approach has faced physiological difficulties, such as the inability to contain and position the controlled drug delivery system within the desired region of the gastrointestinal tract (GIT) due to variable gastric emptying and motility. Venlafaxine is an antidepressant and a serotonin and norepinephrine reuptake inhibitor (SNRI). Its active metabolite, desvenlafaxine, works by blocking the reuptake of serotonin and norepinephrine, which are key neurotransmitters in mood regulation. Gastroretentive dosage forms can stay in the gastric region for several hours and significantly prolong the gastric residence time of drugs. Natural materials have been extensively used in drug delivery because they are readily available, cost-effective, eco-friendly, capable of many chemical modifications, potentially degradable, and compatible due to their natural origin. [ABSTRACT FROM AUTHOR]

Introduction: Although opiate narcotics may worsen gastroparesis(GP), patients can take these for abdominal pain (AP) or other chronic pain syndromes. This study aims to evaluate medications patients with gastroparesis use for AP and compare patients who use opiate analgesics for AP to those using opiate analgesics for non-abdominal pain. Methods: Patients at a tertiary academic center gastroenterology clinic completed the Patient Assessment of Gastrointestinal Disorders–Symptom Severity Index (PAGI-SYM) and Quality of Life Short-Form 8 (QOL SF-8) surveys between 10/2021 and 03/2023. Patients recorded gastroparesis treatments, pain treatments and indication, and any hospitalizations/emergency department (ED) visits within 3 months of a clinic visit. Results: A total of 53 patients were enrolled: 72% reported having AP. Patients were using the following medications for AP: 25% heating pad, ice or hot showers, 20.8% acetaminophen, 14.6% hyoscyamine, 13% opiate use, 13% marijuana use, 10.4% dicyclomine, 8.3% Nonsteroidal anti-inflammatory drugs (NSAIDs), 4% benzodiazepine, and 2.1% gabapentin. The reported reasons for using opiates were 58% AP, 16.6% chronic back pain, 16.6% Reflex Sympathetic Dystrophy (RSD) and fibromyalgia, and 8.3% osteoarthritis. All opiate users reported daily scheduled use. AP severity scores (4.1 vs. 2.8; p = 0.041), morphine equivalent usage (77 ± 44 vs. 32 ± 28; p = 0.037), and the number of ER visits (1.0 vs. 0 over 3 months) were higher in patients using opiates for AP than those using opiates for non-abdominal pain. Conclusions: In this series, 72% of patients with gastroparesis had abdominal pain, and 13% of patients were taking opiates. Patients who used opiate analgesics for abdominal pain had a higher average abdominal pain severity score and used a higher amount of opiate analgesia than patients using opiates for musculoskeletal pain. Abdominal pain in patients with gastroparesis can be harder to control with opiate analgesia compared to non-abdominal pain, supporting the concept of avoiding chronic opiate usage for abdominal pain in gastroparesis. [ABSTRACT FROM AUTHOR]

Abstract Purpose Acute pancreatitis (AP) is often accompanied by gastrointestinal motility disorders. The purpose of this study was to investigate the efficacy and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients. Materials and methods Sixty-five AP patients were randomly divided into conventional treatment group and TGP group. The serum ghrelin and vasoactive intestinal peptide (VIP) were used to assess the possible gastrointestinal hormonal mechanism involved. The parameters of electrogastrogram (EGG) were used to evaluate the gastric motility in AP patients. The first defecation time was used to assess the recovery of intestinal motility. The heart rate variability (HRV) test was performed to assess autonomic nervous function. Results Compared with the conventional treatment group, the TGP treatment significantly improved symptoms in early AP patients, and shortened the first defecation time (p

Abstract Objectives Circadian rhythm disruption (CRD) is implicated with numerous gastrointestinal motility diseases, with the enteric nervous system (ENS) taking main responsibility for the coordination of gastrointestinal motility. The purpose of this study is to explore the role of circadian rhythms in ENS remodeling and to further elucidate the underlying mechanisms. Methods First, we established a jet-lagged mice model by advancing the light/dark phase shift by six hours every three days for eight weeks. Subsequent changes in gastrointestinal motility and the ENS were then assessed. Additionally, a triple-transgenic mouse strain (Nestin-creERT2 × Ngfr-DreERT2: DTRGFP) was utilized to track the effects of CRD on the differentiation of enteric neural precursor cells (ENPCs). RNA sequencing was also performed to elucidate the underlying mechanism. Results Compared to the control group, CRD significantly accelerated gastrointestinal motility, evidenced by faster intestinal peristalsis (P

Chronic gastric symptoms are common, however differentiating specific contributing mechanisms in individual patients remains challenging. Abnormal gastric motility is present in a significant subgroup, but reliable methods for assessing gastric motor function in clinical practice are lacking. Body surface gastric mapping (BSGM) is a new diagnostic aid, employs multi-electrode arrays to measure and map gastric myoelectrical activity non-invasively in high resolution. Clinical adoption of BSGM is currently expanding following studies demonstrating the ability to achieve specific patient subgrouping, and subsequent regulatory clearances. An international working group was formed in order to standardize clinical BSGM methods, encompassing a technical group developing BSGM methods and a clinical advisory group. The working group performed a technical literature review and synthesis focusing on the rationale, principles, methods, and clinical applications of BSGM, with secondary review by the clinical group. The principles and validation of BSGM were evaluated, including key advances achieved over legacy electrogastrography (EGG). Methods for BSGM were reviewed, including device design considerations, patient preparation, test conduct, and data processing steps. Recent advances in BSGM test metrics and reference intervals are discussed, including four novel metrics, being the principal gastric frequency, BMI-adjusted amplitude, Gastric Alimetry Rhythm Index™, and fed: fasted amplitude ratio. An additional essential element of BSGM has been the introduction of validated digital tools for standardized symptom profiling, performed simultaneously during testing. Specific phenotypes identifiable by BSGM and the associated symptom profiles were codified with reference to pathophysiology. Finally, knowledge gaps and priority areas for future BSGM research were also identified by the working group.

BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function. METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS-/- mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1-2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility. RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS-/- recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS. CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.

Background: Opioids inhibit motility and secretion of the gut and have been used for antidiarrheal treatment for centuries. However, the underlying mechanisms of opium tincture are not evident. Aim: To investigate the effects of opium tincture on gastrointestinal motility, intestinal volumes, and water content of different gut segments assessed by magnetic resonance imaging (MRI). Methods: Twenty healthy volunteers were included in a randomized, placebo‐controlled, crossover study of 9 days of treatment with 30 drops of opium tincture per day. MRI was performed on day 1 (before treatment) and day 9 (during treatment). Measurements included assessments of gastric volume, gastric emptying, gastric motility, small bowel volume, small bowel water content, small bowel motility, colon volume, colon water content, and whole gut transit. Key Results: Opium tincture delayed gastric emptying by a mean difference of 5.6 min [95% CI: 1.8–9.4], p = 0.004, and increased postprandial gastric meal volume (17–21%, p = 0.02). Small bowel endpoints did not change. Opium tincture delayed whole gut transit time (p = 0.027) and increased ascending colon volume by 59 mL [95% CI: 15–103], p = 0.004, and transverse colon volume by 48 mL [95% CI: 4–92], p = 0.027. T1‐relaxation time of the descending colon chyme was decreased during opium treatment, indicating dryer feces (difference: −173 ms [95% CI: −336 ‐11], p = 0.03). Conclusion and Inferences: Opium tincture induced changes in the stomach and colon in healthy volunteers. An improved understanding of how opioids affect gut functions may lead to a better understanding and optimized management of diarrhea. [ABSTRACT FROM AUTHOR]

GlP-1 receptor agonists are a class of medications that are becoming increasingly popular. Large trials have shown that their use provides reliable weight loss in obese patients and improved glycemic control in diabetic patients. Its use also has broader implications for overall metabolic health and has been shown to improve cardiovascular outcomes in high-risk populations. Glucagon-like peptide 1 receptors cause multiple effects in the body through stimulation of receptors expressed in a broad range of tissues including the pancreas, liver, gastrointestinal tract, kidneys, heart, endothelium, muscle, and brain. For the anesthesia professionals the effects of these medications on gastric emptying is important. [ABSTRACT FROM AUTHOR]

Abstract Gulf War Illness (GWI) is characterized by a wide range of symptoms that manifests largely as gastrointestinal symptoms. Among these gastrointestinal symptoms, motility disorders are highly prevalent, presenting as chronic constipation, stomach pain, indigestion, diarrhea, and other conditions that severely impact the quality of life of GWI veterans. However, despite a high prevalence of gastrointestinal impairments among these veterans, most research attention has focused on neurological disturbances. This perspective provides a comprehensive overview of current in vivo research advancements elucidating the underlying mechanisms contributing to gastrointestinal disorders in GWI. Generally, these in vivo and in vitro models propose that neuroinflammation alters gut motility and drives the gastrointestinal symptoms reported in GWI. Additionally, this perspective highlights the potential and challenges of in vitro bioengineering models, which could be a crucial contributor to understanding and treating the pathology of gastrointestinal related-GWI.

• Feeding induced increases in the amplitudes of jejunal myoelectrical signals. • The feeding-induced increase was abolished by vagotomy. • The feeding-induced increase was abolished by posterior insular cortical inhibition. • Feeding changed the autonomic activity. • These changes were abolished by posterior insular cortical inhibition. The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone. [ABSTRACT FROM AUTHOR]

Naringenin (NRG) is widely found in citrus fruits and has anti-inflammatory, hypoglycemic, and immunomodulatory effects. Previous studies have shown that NRG promotes gastrointestinal motility in mice constipation models, but there are few systematic evaluations of its effects on normal animals. This study first clarified the promotive effects of NRG on gastric emptying and small intestine propulsion (p < 0.01). NRG can also regulate the release of gastrointestinal hormones, including enhancing gastrin (GAS) and motilin (MTL) (p < 0.01), while reducing vasoactive intestinal peptide (VIP) secretion (p < 0.01). Using NRG to stimulate the isolated stomach, duodenum, and colon showed similar promotive effects to those observed in vivo (p < 0.01). A Western blot analysis indicated that this effect may be mediated by increasing the expression of stem cell factor (SCF) and its receptor (c-Kit) in these three segments, thus regulating their downstream pathways. It is worth noting that NRG can also increase the proportion of beneficial bacteria (Planococcaceae, Bacteroides acidifaciens, Clostridia_UCG-014) in the intestine and reduce the quantity of harmful bacteria (Staphylococcus). These findings provide a new basis for the application of NRG. [ABSTRACT FROM AUTHOR]

Background Purpose Obesity and diabetes are associated with altered gastrointestinal function and with the development of abdominal pain, nausea, diarrhea, and constipation among other symptoms. The enteric nervous system (ENS) regulates gastrointestinal motility. Enteric neuropathies defined as damage or loss of enteric neurons can lead to motility disorders.Here, we review the molecular mechanisms that drive enteric neurodegeneration in diabetes and obesity, including signaling pathways leading to neuronal cell death, oxidative stress, and microbiota alteration. We also highlight potential approaches to treat enteric neuropathies including antioxidant therapy to prevent oxidative stress‐induced damage and the use of stem cells. [ABSTRACT FROM AUTHOR]