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Diabetes Therapy : Research, Treatment... May 2024Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous...
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have attracted much attention because of their significant hypoglycemic and weight-loss effects. Previous preparations can only be subcutaneously injected. Oral administration of GLP-1RAs semaglutide helps to broaden treatment options, but its safety in the real world still needs to be observed. This study is based on FDA adverse event reporting system (FAERS) database to mine adverse drug events (ADE) of oral semaglutide, and provide references for the clinical safe use of this drug.
METHODS
To analyze the signal quality of oral semaglutide, which is a drug used in the FAERS database from the third quarter of 2019 to the third quarter of 2023, we collected ADE data and performed data mining by using disproportionate analysis. Then, we standardized the data and used a variety of signal-quantification techniques, including reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian belief propagation neural network (BCPNN), and multiple empirical Bayesian gamma Poisson contractions (MGPS), for further analysis.
RESULTS
We screened 2398 reports on the use of semaglutide tablets, involving a total of 5653 ADE. These reports were mainly submitted by consumers, and the reporting country was mainly the United States. A total of 23 system organ classes (SOC) and 93 preferred terms (PT) were mined for the signals of semaglutide tablets. The three most common SOC were gastrointestinal disorders, general disorders and administration site conditions, and investigations. At the PT level, metabolism and nutrition disorders exhibit the highest number of signals, with the top three being thyroid cyst, acute cholecystitis, and ketosis. Gastrointestinal disorders rank second, primarily involving eructation, pancreatitis, impaired gastric emptying, and regurgitation. In addition, vith nerve paralysis occurs and the signal intensity is high.
CONCLUSIONS
Our study provides a deeper and broader understanding of the safety of oral semaglutide. The results of the ROR, PRR, BCPNN, and MGPS algorithms exhibit high consistency, with metabolism and nutrition-related disorders having the highest number of signals. The conclusions align with the technical specifications of the product. Notably, other unexpected effects are reported, including acute cholecystitis, paralysis of the abducens nerve, and positional vertigo.
PubMed: 38776037
DOI: 10.1007/s13300-024-01594-7 -
Neurogastroenterology and Motility May 2024An increasing number of studies have explored the clinical features, epidemiology, pathophysiology, and management of cyclic vomiting syndrome (CVS). CVS is common in... (Review)
Review
BACKGROUND
An increasing number of studies have explored the clinical features, epidemiology, pathophysiology, and management of cyclic vomiting syndrome (CVS). CVS is common in adults and children and negatively impacts patients, families, and the healthcare system. A related condition, cannabinoid hyperemesis syndrome (CHS), has been a focus of interest in the lay press and published literature.
PURPOSE
Clinical presentations of CVS have been defined by small series and expert opinion, but recent prospective studies are refining our understanding of the spectrum of emetic episodes and the breadth of comorbid conditions. Large cross-sectional population analyses are clarifying CVS prevalence and factors related to age, ethnicity, and geographic region. CVS pathophysiology is multifactorial with contributions from migraines, dysautonomia, endogenous cannabinoids, mitochondrial dysfunction, genetic abnormalities, and rapid gastric emptying. CVS treatment relies on antiemetics and antimigraine therapies to abort acute episodes coupled with prophylactic regimens employing neuromodulators and antiepileptics. CHS represents a challenge partly because of difficulties in achieving sustained cannabis abstinence. Benefits of other therapies in CHS remain poorly defined. Several areas warrant further scrutiny including better identification of CVS triggers and characterization of different CVS subsets including those with frequent severe episodes, refined description of epidemiology to allow targeting of populations predisposed to CVS development, rigorous definition of pathogenic factors to provide a foundation for exploratory studies of novel therapies, and conduct of controlled trials by multicenter collaborations to confirm benefits of existing and new therapies in development. Progress in these areas will be facilitated by generous governmental and industry support.
PubMed: 38775195
DOI: 10.1111/nmo.14825 -
Journal of Visualized Experiments : JoVE May 2024Following a hiatal hernia repair, patients can present with recurrent or new symptoms. Symptoms can occur anywhere from weeks to years after surgery. These may include...
Following a hiatal hernia repair, patients can present with recurrent or new symptoms. Symptoms can occur anywhere from weeks to years after surgery. These may include recurrent reflux, dysphagia, regurgitation, weight loss, or deteriorating quality of life. While nonoperative management can be pursued in some patients, reoperation may be the only option in select patients. A thorough preoperative workup, including a repeat esophagram, upper endoscopy, +/- chest computed tomography (CT) scan, manometry, pH probe, and/or gastric emptying study, is warranted to better understand the pathophysiology of the presenting symptoms. If a recurrent hernia, slipped, or migrated wrap is identified, surgery is considered. Pseudoachalasia must also be ruled out if obstructive symptoms are observed at the hiatus. Such an exhaustive workup is indeed necessary to ensure accurate diagnosis and optimal outcome. In addition, an understanding of the factors that may have led to the recurrence will increase the chances of a successful reoperation. Although a technically demanding procedure, redo hiatal hernia repair utilizing a minimally invasive approach is increasingly being employed with promising outcomes. Herein, the steps of a redo hiatal hernia repair via a minimally invasive approach will be outlined and detailed.
Topics: Hernia, Hiatal; Humans; Herniorrhaphy; Reoperation; Postoperative Complications; Recurrence
PubMed: 38767385
DOI: 10.3791/64839 -
Advanced Healthcare Materials May 2024Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non-steroidal anti-inflammatory drugs....
Gastric ulcers are characterized by damage to the stomach lining and are often triggered by substances such as ethanol and non-steroidal anti-inflammatory drugs. Patchouli alcohol (PA) has demonstrated effectiveness in treating gastric ulcers through antioxidative and anti-inflammatory effects. However, the water insolubility of PA and rapid gastric emptying cause low drug concentration and poor absorption in the stomach, resulting in limited treatment efficacy of PA. This study develops an oral gastroretentive raft forming system (GRFDDS) containing the aminated hollow mesoporous silica nanoparticles (NH-HMSN) for PA delivery. The application of NH-HMSN can enhance PA-loading capacity and water dispersibility, promoting bio-adhesion to the gastric mucosa and sustained drug release. The incorporation of PA-loaded NH-HMSN (NH-HMSN-PA) into GRFDDS can facilitate gastric drug retention and achieve long action, thereby improving therapeutic effects. The results reveal that NH-HMSN-PA protects the gastric mucosa damage by inhibiting NLRP3-mediated pyroptosis. The GRFDDS, optimized through orthogonal design, demonstrates the gastric retention capacity and sustained drug release, exhibiting significant therapy efficacy in an ethanol-induced acute gastric ulcers model and an aspirin-induced chronic gastric ulcers model through antioxidation, anti-pyroptosis, and anti-inflammation. This study provides a potential strategy for enhancing druggability of insoluble natural compounds and therapeutic management of gastric ulcers.
PubMed: 38767185
DOI: 10.1002/adhm.202400566 -
Neurogastroenterology and Motility May 2024Gastric sensorimotor disorders are prevalent. While gastric emptying measurements are commonly used, they may not fully capture the underlying pathophysiology. Body...
BACKGROUND
Gastric sensorimotor disorders are prevalent. While gastric emptying measurements are commonly used, they may not fully capture the underlying pathophysiology. Body surface gastric mapping (BSGM) recently emerged to assess gastric sensorimotor dysfunction. This study assessed varying meal size on BSGM responses to inform test use in a wider variety of contexts.
METHODS
Data from multiple healthy cohorts receiving BSGM were pooled, using four different test meals. A standard BSGM protocol was employed: 30-min fasting, 4-h post-prandial, using Gastric Alimetry® (Alimetry, New Zealand). Meals comprised: (i) nutrient drink + oatmeal bar (482 kcal; 'standard meal'); (ii) oatmeal bar alone; egg and toast meal, and pancake (all ~250 kcal). Gastric Alimetry metrics included BMI-adjusted Amplitude, Principal Gastric Frequency, Gastric Alimetry Rhythm Index (GA-RI) and Fed:Fasted Amplitude Ratio (ff-AR).
KEY RESULTS
238 participants (59.2% female) were included. All meals significantly increased amplitude and frequency during the first postprandial hour (p < 0.05). There were no differences in postprandial frequency across meals (p > 0.05). The amplitude and GA-RI of the standard meal (n = 110) were significantly higher than the energy bar alone (n = 45) and egg meal (n = 65) (all p < 0.05). All BSGM metrics were comparable across the three smaller meals (p > 0.05). A higher symptom burden was found in the oatmeal bar group versus the standard meal and pancake meal (p = 0.01, 0.003, respectively).
CONCLUSIONS & INFERENCES
The consumption of lower calorie meals elicited different postprandial responses, when compared to the standard Gastric Alimetry meal. These data will guide interpretations of BSGM when applied with lower calorie meals.
PubMed: 38764250
DOI: 10.1111/nmo.14823 -
Paediatric Anaesthesia May 2024The retention of gastric contents at surgery presentation is a risk factor for perioperative aspiration. A preoperative fasting (nil per os; NPO) interval is widely used...
BACKGROUND
The retention of gastric contents at surgery presentation is a risk factor for perioperative aspiration. A preoperative fasting (nil per os; NPO) interval is widely used to reduce this risk, but this approach is based on assumptions about the prevalence of typical gastric emptying rates. We assessed NPO guidelines' reliability with ultrasound (US) imaging and suction in pediatric patients presenting for single long-bone fracture repair after appropriate NPO intervals, when nearly all should have had empty stomachs.
AIMS AND METHODS
This prospective cross-sectional observational study comprised 200 pediatric surgical patients. As their NPO times varied by food/drink type, we defined "weighted NPO units" as the lowest multiple of elapsed recommended NPO times between consumption and surgery for each type of food or drink. We used US to image the stomach and its contents before anesthesia induction, followed by gastric suction. We evaluated the relationships between weighted NPO units, US gastric contents grade, opioid analgesic dosage and timing, and suctioned volume.
RESULTS
Despite meeting typical NPO standards (median 14 h fasting), many patients retained nontrivial quantities of gastric contents at surgery. Weighted NPO units did not exhibit statistically-significant relationships with either suctioned volume or US grade. However, suctioned volume did correspond well to US grade.
CONCLUSION
NPO status may be a less reliable predictor of gastric contents at anesthesia induction in this patient population than has been assumed. Bedside US screening appears to provide more useful information for the planning of airway management.
PubMed: 38764216
DOI: 10.1111/pan.14923 -
Animal : An International Journal of... Jun 2024Heat stress (HS) negatively impacts a variety of production parameters in growing pigs; however, the impact of biological sex on the HS response is largely unknown. To...
Heat stress (HS) negatively impacts a variety of production parameters in growing pigs; however, the impact of biological sex on the HS response is largely unknown. To address this, 48 crossbred barrows and gilts (36.8 ± 3.7 kg BW) were individually housed and assigned to one of three constant environmental conditions: (1) thermoneutral (TN) (20.8 ± 1.6 °C; 62.0 ± 4.7% relative humidity; n = 8/sex), (2) HS (39.4 ± 0.6 °C; 33.7 ± 6.3% relative humidity) for 1 d (HS1; n = 8/sex), or (3) or for 7 d (HS7; n = 8/sex). As expected, HS increased rectal temperature (Tr) following 1 d of HS (1.0 °C; P < 0.0001) and 7 d of HS (0.9 °C; P < 0.0001). By 7 d, heat-stressed gilts were cooler than barrows (0.4 °C; P = 0.016), despite identical heating conditions. There was a main effect of sex such that barrows had higher Tr than gilts (P = 0.031). Heat-stressed pigs on d 1 had marked reductions in feed intake and BW compared to TN (P < 0.0001). One day of HS resulted in negative gain to feed (G:F) in barrows and gilts and was reduced compared to TN (P < 0.0001). Notably, following 1 d of HS, the variability of G:F was greater in gilts than in barrows. Between 1 and 7 d of HS, G:F improved in barrows and gilts and were similar to TN pigs, even though HS barrows had higher Tr than gilts over this period. Heat stress for 1 and 7 d reduced empty gastrointestinal tract weight compared to TN (P < 0.0001). Interestingly, HS7 gilts had decreased gastrointestinal tract weight compared to HS1 gilts (2.43 vs 2.72 kg; P = 0.03), whereas it was similar between HS1 and HS7 barrows. Lastly, a greater proportion of gastrointestinal contents was in the stomach of HS1 pigs compared to TN and HS7 (P < 0.05), which is suggestive of decreased gastric emptying. Overall, HS barrows maintained an elevated Tr compared to HS gilts through the duration of the experiment but also maintained similar growth and production metrics compared to gilts, despite this higher temperature.
Topics: Animals; Female; Male; Swine; Hot Temperature; Heat-Shock Response; Body Temperature; Heat Stress Disorders; Sex Factors; Swine Diseases; Sus scrofa
PubMed: 38762992
DOI: 10.1016/j.animal.2024.101168 -
Gastrointestinal Endoscopy May 2024Gastric emptying scintigraphy (GES) is the gold standard for the diagnosis of gastroparesis. However, data are lacking regarding the prognostic value of pre-operative...
Prognostic Value of Pre-Operative Intragastric Meal Distribution in Gastric Emptying Scintigraphy for Long-Term Success of Gastric Peroral Endoscopic Myotomy in Gastroparesis.
BACKGROUND AND AIMS
Gastric emptying scintigraphy (GES) is the gold standard for the diagnosis of gastroparesis. However, data are lacking regarding the prognostic value of pre-operative intragastric meal distribution during GES, in patients undergoing gastric peroral endoscopic myotomy (GPOEM) for gastroparesis. This study investigated the association of GES morphologic parameters and the long-term clinical success of G-POEM.
METHODS
This retrospective study included patients who underwent G-POEM for refractory gastroparesis in a tertiary center with preoperative GES data. Intragastric meal distribution was measured using the proximal to distal count ratio (PDCR) at 0, 1, 2 and 4 hours (h), and the retention index (RI) was calculated. Clinical success was defined as a decrease of at least 50% in the post-G-POEM Gastroparesis Cardinal Symptom Index (GCSI) total score.
RESULTS
In total, 77 patients were included with a mean follow-up of 40.14 months. Clinical success was observed in 54.55% of patients. The RI was not associated with clinical success. Only PDCR at 0h (PDCR0) was associated with clinical success. In univariate analysis, the median PDCR0 was 6.0 (IQR 5.59) in patients with clinical success and 4.29 (IQR 4.51) in patients with clinical failure (p=0.019). In multivariate analysis, PDCR0 > 5.25 was associated with clinical success (HR = 4.36 [1.55;12.26], p=0.00524).
CONCLUSIONS
This study suggests that in patients with gastroparesis, High PDCR0 value (suggestive for a preferential fundic meal distribution) during preoperative GES is associated with long-term clinical response to G-POEM.
PubMed: 38762040
DOI: 10.1016/j.gie.2024.05.011 -
Gastrointestinal Endoscopy May 2024Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized in diabetes and obesity management. GLP-1RAs delay gastric emptying; however, their impact...
BACKGROUND AND AIMS
Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized in diabetes and obesity management. GLP-1RAs delay gastric emptying; however, their impact on visibility during esophagogastroduodenoscopy (EGD) remains uncertain.
METHODS
A 1:1 matched case-control study was conducted. Individuals undergoing EGD on GLP-1RAs were matched to non-users based on demographics and diabetes status. A validated scale (POLPREP) was used to determine gastric mucosal visibility scores.
RESULTS
A total of 84 pairs (n=168) were included. GLP-1RA users showed significantly lower visibility scores, with a 2.54 times higher likelihood of lower scores compared to non-users. Additionally, GLP-1RA users had a higher incidence of retained gastric contents (13.1% vs. 4.8%, aOR:4.62, p=0.025) and aborted procedures due to this issue. No anesthesia-related adverse events were observed.
CONCLUSIONS
GLP-1RA use at the time of endoscopy exhibited higher odds of lower gastric mucosal visibility scores, retained contents and aborted procedures. Further research is warranted.
PubMed: 38759761
DOI: 10.1016/j.gie.2024.05.012 -
Obesity Surgery Jul 2024Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of...
PURPOSE
Glucagon-like receptor agonists (GLP1-RAs) have raised peri-procedural concerns due to their potential to delay gastric emptying. The American Association of Anesthesiologists has advised pausing a single dose before elective endoscopy. However, a subsequent directive from multiple gastroenterology societies underscored the need for further assessment to substantiate this practice. We aimed to evaluate the frequency of serious adverse events and retained gastric products during endoscopic sleeve gastroplasty (ESG) with uninterrupted GLP1-RA use.
MATERIALS AND METHODS
We conducted a retrospective evaluation of all patients undergoing ESG while on GLP1-RAs at three centers from August 2022 to February 2024. Per standard protocol, all patients had refrained from solid foods for at least 24 h and maintained nil per os for 12 h preceding their ESG. Records were reviewed for patient characteristics and medication type and doses. Primary outcomes included serious adverse events and retained gastric products based on patient records, procedure reports, and procedural videos.
RESULTS
Fifty-seven consecutive adults (89.5% women, mean age of 44 ± 9 years, mean BMI of 40.1 ± 8.1 kg/m, 35.1% with T2DM, and 26.3% with pre-T2DM) underwent ESG without stopping GLP1-RAs, which included semaglutide (45.6%), liraglutide (19.3%), dulaglutide (22.8%), and tirzepatide (12.3%). During intubation, endoscopy, and recovery, there were no instances of retained gastric solids, pulmonary aspiration, gastroesophageal regurgitation, or hypoxia.
CONCLUSION
A ≥ 24-h pre-endoscopy liquid-only diet with ≥ 12-h pre-endoscopy fast may negate the need for GLP1-RA interruption for routine upper endoscopy in adults with native gastric anatomy.
Topics: Humans; Female; Male; Retrospective Studies; Adult; Gastroplasty; Glucagon-Like Peptide-1 Receptor; Middle Aged; Glucagon-Like Peptides; Obesity, Morbid; Gastric Emptying; Hypoglycemic Agents; Liraglutide; Immunoglobulin Fc Fragments; Recombinant Fusion Proteins
PubMed: 38753265
DOI: 10.1007/s11695-024-07278-2