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Clinical Gastroenterology and... Dec 2023Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis.
METHODS
We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates.
RESULTS
Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P = .008), inability to finish a normal-sized meal (P = .029), number of vomiting episodes/24 hours (P = .006), and overall symptom severity (P = .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients).
CONCLUSIONS
CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES.
CLINICALTRIALS
gov NCT #03941288.
Topics: Humans; Gastroparesis; Cannabidiol; Drug Inverse Agonism; Diabetes Mellitus, Type 1; Nausea; Gastric Emptying
PubMed: 37482172
DOI: 10.1016/j.cgh.2023.07.008 -
European Journal of Clinical... Sep 2023Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan...
BACKGROUND
Ramadan is a model of intermittent fasting linked with possible beneficial effects. Scarce information, however, is available about the combined effects of Ramadan intermittent fasting (RIF) on anthropometric and metabolic indices, gastrointestinal symptoms, and motility.
METHODS
In 21 healthy Muslims, we assessed the impact of RIF on caloric intake, physical activity, gastrointestinal symptoms and motility (gastric/gallbladder emptying by ultrasonography, orocaecal transit time by lactulose breath test), anthropometric indices, subcutaneous and visceral fat thickness (ultrasonography), glucose and lipid homeostasis.
RESULTS
Mean caloric intake decreased from a median of 2069 kcal (range 1677-2641) before Ramadan to 1798 kcal (1289-3126) during Ramadan and increased again to 2000 kcal (1309-3485) after Ramadan. Although physical activity remained stable before, during, and after RIF, body weight, body mass index and waist circumference decreased in all subjects and in both genders, together with a significant decrease in subcutaneous and visceral fat thickness and insulin resistance. The postprandial gastric emptying speed was significantly faster after than before RIF. Fasting gallbladder volume was about 6% smaller after, than before Ramadan, with a stronger and faster postprandial gallbladder contraction. After RIF, lactulose breath test documented increased microbiota carbohydrate fermentation (postprandial H peak), and faster orocaecal transit time. RIF also significantly improved gastric fullness, epigastric pain and heartburn.
CONCLUSIONS
RIF generates, in healthy subjects, multiple systemic beneficial effects in terms of fat burden, metabolic profile, gastrointestinal motility and symptoms. Further comprehensive studies should assess the potential beneficial effects of RIF in diseased people.
Topics: Humans; Male; Female; Fasting; Intermittent Fasting; Intra-Abdominal Fat; Lactulose; Body Composition; Gastrointestinal Motility
PubMed: 37203871
DOI: 10.1111/eci.14029 -
United European Gastroenterology Journal Oct 2023Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction.
OBJECTIVE
Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed.
METHODS
We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls.
RESULTS
While no SNP associations were detected at strict significance (p ≤ 5 × 10 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (p ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls).
CONCLUSION
We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets.
Topics: Humans; Genome-Wide Association Study; Gastroparesis; Genetic Predisposition to Disease; Abdominal Pain
PubMed: 37688361
DOI: 10.1002/ueg2.12453 -
Journal of Food Science Jul 2024Food digestion is important for human health. Advances have been made using in vitro models to study food digestion, but there is considerable potential for numerical... (Review)
Review
Food digestion is important for human health. Advances have been made using in vitro models to study food digestion, but there is considerable potential for numerical approaches in stomach modeling, as they can provide a comprehensive understanding of the complex flow and chemistry in the stomach. The focus of this study is to provide a concise review of the developed numerical stomach models over the past two decades. The gastric physiological parameters that are required for a computational model to represent the human gastric digestion process are discussed, including the stomach geometry, gastric motility, gastric emptying, and gastric secretions. Computational methods used to model gastric digestion are introduced and compared, including different computational fluid dynamics as well as solid mechanics methods. The challenges and limitations of current studies are discussed, as well as the areas for future research that need to be addressed. There has been progress in simulating gastric fluid flow with stomach wall motion, but much work remains to be done. The complex food breakdown mechanisms and a comprehensive chemical digestion process have not been implemented in any developed models. Numerical method that was once computationally expensive will be revolutionized as computing power continues to improve. Ultimately, the advancement of modeling of gastric food digestion will allow for additional hypothesis testing to streamline the development of food products that are beneficial to human health.
Topics: Digestion; Humans; Stomach; Models, Biological; Gastric Emptying; Computer Simulation; Hydrodynamics
PubMed: 38865250
DOI: 10.1111/1750-3841.17157 -
Annals of Internal Medicine Nov 2023
Topics: Humans; Gastric Emptying; Glucagon-Like Peptide-1 Receptor; Glucagon; Insulin; Blood Glucose; Peptide Fragments
PubMed: 37931267
DOI: 10.7326/M23-2019 -
The Quarterly Journal of Nuclear... Mar 2024Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the... (Review)
Review
Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.
Topics: Humans; Child; Radionuclide Imaging; Gastric Emptying; Radioisotopes; Gastrointestinal Hemorrhage
PubMed: 38587360
DOI: 10.23736/S1824-4785.24.03548-9 -
Paediatric Anaesthesia Dec 2023Fasting for surgery is a routine step in the preoperative preparation for surgery. There have however been increasing concerns with regard to the high incidence of... (Review)
Review
Fasting for surgery is a routine step in the preoperative preparation for surgery. There have however been increasing concerns with regard to the high incidence of prolonged fasting in children, and the subsequent psycho-social distress and physiological consequences that this poses. Additionally, the past few years have yielded new research that has shown significant inter-individual variation in gastric emptying regardless of the length of the fast, with some patients still having residual gastric contents even after prolonged fasts. Additionally, multiple large-scale studies have shown no long-term sequalae from clear fluid aspiration, although two deaths from aspiration have been reported within the large Wake Up Safe cohort. This has led to a change in the recommended clear fluid fasting times in multiple international pediatric societies; similarly, many societies continue to recommend traditional fasting times. Multiple fasting strategies exist in the literature, though these have mostly been studied and implemented in the adult population. This review hopes to summarize the recent updates in fasting guidelines, discuss the issues surrounding prolonged fasting, and explore potential tolerance strategies for children.
Topics: Adult; Child; Humans; Pneumonia, Aspiration; Fasting; Incidence; Gastric Emptying; Gastrointestinal Contents; Preoperative Care
PubMed: 37533337
DOI: 10.1111/pan.14738 -
European Journal of Obstetrics,... Oct 2023The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy....
BACKGROUND/AIMS
The effect of pregnancy on gastric emptying has not been established, although the predominant clinical assumption is that gastric emptying is delayed during pregnancy. We hypothesized that the rate of emptying of nutrients during pregnancy is not delayed, but is actually more rapid when compared to the non-pregnant state. The rate of gastric emptying is a major determinant of postprandial glucose elevations.
MATERIALS AND METHODS
24 female and 4 male Spague-Dawley rats were used. Female rats were randomly divided into two groups: eight rats for the control group and sixteen rats for the pregnant group. Using physiologic, non-traumatic nuclear medicine scintigraphy imaging methodology, the authors studied gastric emptying of a liquid mixed meal in pregnant rats and non-pregnant controls. Body weights, daily food ingestion, and the rate of nutrient gastric emptying were recorded in both groups at pre-pregnancy, early pregnancy, and late pregnancy.
RESULTS
The authors found that pregnancy in this rat model is associated with a 37-43% increased rate of nutrient gastric emptying from the stomach in late pregnancy as compared to non-pregnant control rats and pre-pregnancy rats.
CONCLUSION
These findings contradict the current clinical assumption that gastric emptying is delayed in pregnancy. If further studies confirm a more rapid gastric emptying rate during human pregnancy, new therapies aimed at slowing the rate of nutrient absorption should be considered for the prevention and treatment of pregnancy-associated nausea, gestational diabetes, and other insulin-resistant pregnancy-associated states such as pre-eclampsia.
Topics: Humans; Animals; Rats; Female; Male; Pregnancy; Gastric Emptying; Body Weight; Cystography; Diabetes, Gestational; Glucose; Morning Sickness
PubMed: 37639818
DOI: 10.1016/j.ejogrb.2023.08.370 -
Neurogastroenterology and Motility Nov 2023Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to...
BACKGROUND
Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.
METHODS
Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light microscopy, and myenteric plexus neurochemistry by whole-mount immunostaining.
KEY RESULTS
Regional gastric sampling revealed site-specific differences in contractile patterns and myenteric plexus structure. In neonatal mice, TmSep prolonged gastric emptying. In the forestomach, TmSep increased contractile responses to carbachol, decreased muscularis externa and mucosa thickness, and increased the relative proportion of myenteric plexus nNOS+ neurons. Germ-free conditions did not appreciably alter the structure or function of the neonatal mouse stomach and did not impact the changes caused by TmSep.
CONCLUSIONS AND INFERENCES
A regional sampling approach facilitates site-specific investigations of murine gastric motor physiology and histology to identify site-specific alterations that may impact gastrointestinal function. Delayed gastric emptying in TmSep is associated with a thinner muscle wall, exaggerated cholinergic contractile responses, and increased proportions of inhibitory myenteric plexus nNOS+ neurons in the forestomach. Gut microbes do not profoundly affect the development of the neonatal mouse stomach or the gastric pathophysiology that results from TmSep.
Topics: Mice; Animals; Animals, Newborn; Gastroparesis; Maternal Deprivation; Mice, Inbred C57BL; Stomach; Myenteric Plexus; Disease Models, Animal; Gastric Emptying
PubMed: 37772676
DOI: 10.1111/nmo.14676 -
Alimentary Pharmacology & Therapeutics Feb 2024Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by... (Review)
Review
BACKGROUND
Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by bariatric therapies, there are significant pharmacological advancements.
AIMS
To conduct a narrative review of the neurohormonal and physiological understanding of weight gain and obesity, and the development, clinical testing, indications, expected clinical outcomes, and associated risks of current FDA-approved and upcoming anti-obesity medications (AOMs).
METHODS
We conducted a comprehensive review in PubMed for articles on pathophysiology and complications of obesity, including terms 'neurohormonal', 'obesity', 'incretin', and 'weight loss'. Next, we searched for clinical trial data of all FDA-approved AOMs, including both the generic and trade names of orlistat, phentermine/topiramate, bupropion/naltrexone, liraglutide, and semaglutide. Additional searches were conducted for tirzepatide and retatrutide - medications expecting regulatory approval. Searches included combinations of terms related to mechanism of action, indications, side effects, risks, and future directions.
RESULTS
We reviewed the pathophysiology of obesity, including specific role of incretins and glucagon. Clinical data supporting the use of various FDA-approved medications for weight loss are presented, including placebo-controlled or, when available, head-to-head trials. Beneficial metabolic effects, including impact on liver disease, adverse effects and risks of medications are discussed, including altered gastrointestinal motility and risk for periprocedural aspiration.
CONCLUSION
AOMs have established efficacy and effectiveness for weight loss even beyond 52 weeks. Further pharmacological options, such as dual and triple incretins, are probable forthcoming additions to clinical practice for combating obesity and its metabolic consequences such as metabolic dysfunction-associated steatotic liver disease.
Topics: Humans; Incretins; Topiramate; Fructose; Obesity; Anti-Obesity Agents; Weight Loss; Liver Diseases
PubMed: 38169126
DOI: 10.1111/apt.17856