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We aimed to determine if botulinum toxin injection into the pyloric sphincter improves gastric emptying and reduces symptoms in patients with idiopathic gastroparesis. Patients with idiopathic gastroparesis not responding to prokinetic therapy underwent botulinum toxin (80–100 U, 20 U/ml) injection into the pyloric sphincter. Gastric emptying scintigraphy was performed before and 4 wk after treatment. Total symptom scores were obtained from the sum of eight upper GI symptoms graded on a scale from 0 (none) to 4 (extreme). Ten patients were entered into the study. The mean percentage of solid gastric retention at 4 h improved from 27 ± 6% (normal < 10%) before botulinum toxin injection into the pylorus to 14 ± 4% (p = 0.038) 4 wk after treatment. The symptom score decreased from 15.3 ± 1.7 at baseline to 9.0 ± 1.9 (p = 0.006) at 4 wk, a 38 ± 9% decrease. Improvement in symptoms tended to correlate with improved gastric emptying of solids (r = 0.565, p = 0.086). This initial pilot study suggests that botulinum toxin injection into the pylorus in patients with idiopathic gastroparesis improves both gastric emptying and symptoms.

Gastric emptying is a major determinant of postprandial blood glucose, accounting for ~35% of variance in peak glucose in both healthy individuals and those with type 2 diabetes. Gastric emptying is frequently disordered in individuals with diabetes (both abnormally delayed and accelerated). Delayed gastric emptying, i.e. diabetic gastroparesis, may be linked to upper gastrointestinal symptoms for which current treatment remains suboptimal; pharmacological acceleration of delayed emptying is only weakly associated with symptom improvement. Accordingly, the relationship between symptoms and delayed gastric emptying is not simply ‘cause and effect’. In insulin-treated patients, disordered gastric emptying, even when not associated with gastrointestinal symptoms, can cause a mismatch between the onset of insulin action and the availability of absorbed carbohydrate, leading to suboptimal glycaemic control. In patients with type 2 diabetes, interventions that slow gastric emptying, e.g. glucagon-like peptide-1 receptor agonists, reduce postprandial blood glucose. This review focuses on recent insights into the impact of gastric emptying on postprandial blood glucose, effects of diabetes therapy on gastric emptying and the management of disordered gastric emptying in diabetes. In view of the broad relevance of gastric emptying to diabetes management, it is important that future clinical trials evaluating novel therapies that may affect gastric emptying should quantify the latter with an appropriate technique, such as scintigraphy or a stable isotope breath test.

Ghrelin was discovered in 1999 as the endogenous ligand of the growth-hormone secretagogue receptor 1a (GHSR1a). Since then, ghrelin has been found to exert a plethora of physiological effects that go far beyond its initial characterization as a growth hormone (GH) secretagogue. Among the numerous well-established effects of ghrelin are the stimulation of appetite and lipid accumulation, the modulation of immunity and inflammation, the stimulation of gastric motility, the improvement of cardiac performance, the modulation of stress, anxiety, taste sensation and reward-seeking behavior, as well as the regulation of glucose metabolism and thermogenesis. Due to a variety of beneficial effects on systems’ metabolism, pharmacological targeting of the endogenous ghrelin system is widely considered a valuable approach to treat metabolic complications, such as chronic inflammation, gastroparesis or cancer-associated anorexia and cachexia. The aim of this review is to discuss and highlight the broad pharmacological potential of ghrelin pathway modulation for the treatment of anorexia, cachexia, sarcopenia, cardiopathy, neurodegenerative disorders, renal and pulmonary disease, gastrointestinal (GI) disorders, inflammatory disorders and metabolic syndrome.

Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is scarce. Prucalopride, a selective 5-hydroxytryptamine 4 receptor agonist used in the treatment of constipation, is able to enhance the gastric emptying rate. In a double-blind, randomized, placebo-controlled crossover study, we evaluated the efficacy of prucalopride to improve the gastric emptying rate and symptoms in patients with gastroparesis. Thirty-four patients with gastroparesis (28 idiopathic, 7 men, mean age 42 ± 13 years) were evaluated in a double-blind crossover trial of 4-week treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks of washout. The primary end point was the change in symptom severity, assessed by the Gastroparesis Cardinal Symptom Index; secondary end points comprised the Patient Assessment of Upper Gastrointestinal Disorders-Symptom Severity Index, the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life, and daily diaries, and the gastric emptying rate was assessed by the C-octanoic acid breath test. Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 3 patients dropped out because of adverse events of nausea and headache (all prucalopride). For the entire patient group, compared with placebo, prucalopride significantly improved the total Gastroparesis Cardinal Symptom Index (1.65 ± 0.19 vs 2.28 ± 0.20, P < 0.0001) and the subscales of fullness/satiety, nausea/vomiting, and bloating/distention. Prucalopride significantly improved the overall Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (1.15 ± 0.16 vs 1.44 ± 0.16, P < 0.05) and the domains of clothing and diet. The gastric half emptying time was significantly enhanced by prucalopride compared with placebo and baseline (98 ± 10 vs 143 ± 11 and 126 ± 13 minutes, P = 0.005 and <0.001, respectively). These significant improvements were also found when considering only the idiopathic gastroparesis subgroup. In a cohort of patients with predominantly idiopathic gastroparesis, 4 weeks of prucalopride treatment significantly improved symptoms and quality of life and enhanced gastric emptying compared with placebo.

Abstract Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. Data Acquisition We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. Data Synthesis Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. Conclusion Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs.

Background Long-standing diabetes mellitus (DM) can lead to macrovascular and microvascular complications, including autonomic neuropathy, which disrupts gut motility. Gastroparesis (GP) is defined as delayed gastric emptying of solids (with or without liquids) in the absence of any mechanical obstruction. The gold standard test for diagnosing gastroparesis is gastric scintigraphy (GS) using a solid meal. Gastroparesis poses diagnostic and therapeutic challenges, and can significantly impact patients with DM. The purpose of this study is to evaluate the prevalence of gastroparesis among symptomatic patients and assess treatment outcomes, with particular focus on identifying clinical predictors of delayed gastric emptying and factors associated with response to medical therapy in confirmed cases. Patients and methods From June 2022 to June 2024, all patients visiting the diabetes clinic in Cairo University Hospital for any reason were screened for symptoms of gastroparesis using the gastroparesis cardinal symptom index (GCSI). Symptomatic patients underwent solid gastric scintigraphy. Those diagnosed with GP were treated for three months and refractory cases were offered G-POEM. Results Thirty-two patients with moderate-to-severe symptoms of gastroparesis were the population of this study. Of these, 62.5% had delayed gastric emptying on solid gastric scintigraphy. A GCSI > 23 independently predicted delayed gastric emptying on solid gastric scintigraphy (OR 1.153, 95% CI (1.009–1.317), p  = 0.036). 55% of GP patients achieved improvement in symptoms after three months of optimized medical therapy, and two out of four cases had sustained improvement for one year after G-POEM. The responders to medical treatment were significantly older, had lower GCSI and greater reduction in hemoglobin A1c (HbA1c) compared to those in the refractory group ( p  = 0.046, 0.012, 0.012, respectively). Conclusion This study highlighted the role of the GCSI in assessing and monitoring gastroparesis, particularly in resource-limited settings. Diabetic GP differs in clinical presentation and management from other types of GP. Optimizing glycemic control may contribute to symptoms improvement. Older age and lower symptoms burden at presentation may help identify patients more likely to benefit from medical therapy.

Diabetic gastroparesis is defined as delayed gastric emptying without mechanical obstruction in the setting of diabetes. Symptoms range from mild bloating to severe vomiting episodes and can result in frequent hospitalizations and poor quality of life. It is suspected that diabetic gastroparesis is underdiagnosed due to its similar presentation to other conditions such as gastroesophageal reflux disease. The pathogenesis of diabetic gastroparesis remains unclear, but proposed mechanisms include vagal dysfunction, hyperglycemia, interstitial cells of Cajal network disturbances, loss of neural nitric oxide synthase expression in the myenteric plexus, and oxidative stress. Current management for diabetic gastroparesis focuses on dietary and lifestyle changes as well as improved glycemic control. Limited options for medical therapies are available that include prokinetic and antiemetic medications. Metoclopramide is the only FDA-approved medication for the treatment of gastroparesis. Metoclopramide improves symptoms of gastroparesis although extended treatment presents challenges such as decreased efficacy over time and increased risks for adverse events. We summarize the current knowledge of the pathophysiology of diabetic gastroparesis and review current and investigational treatments for diabetes gastroparesis. •Diabetic gastroparesis is often underdiagnosed due to its similar presentation to other upper GI conditions•Current management for diabetic gastroparesis focuses on dietary and lifestyle changes as well as improved glycemic control.•Metoclopramide is the only FDA approved medication for diabetic gastroparesis.•Investigational medications include ghrelin receptor agonist, motilin receptor agonists and 5HT4 receptor agonists.•New surgical techniques such as gastric peroral endoscopic myotomy (G-POEM) has been used in cases with refractory symptoms.

BackgroundGastroparesis is a heterogeneous disorder. Patient characteristics and treatment responsiveness may differ based on the extent of delay in gastric emptying.AimsCharacterize gastroparesis patients based on the degree of delay in gastric emptying, and assess the relationship of patient demographics, symptoms and response to therapy based on the extent of delay.Methods1333 solid-phase 4-h scintigraphic gastric emptying scans were reviewed. Delayed emptying was categorized on percent retention at 4 h: mild (10–19%), moderate (20–29%), and severe (≥ 30%). Analyses were performed with regard to demographics, symptoms, esophagogastroduodenoscopy findings, medication use, and emergency department (ED) visits/hospitalizations.Results284 patients had delayed gastric emptying: mild (42.6%), moderate (19.3%), and severe (37.3%). 79.5% were women, the mean age was 45 years (± 15), and mean symptom duration was 4.6 years (± 6.5). The main categories of gastroparesis were idiopathic and diabetes mellitus. The most commonly prescribed medications were metoclopramide, domperidone and erythromycin. Opiate use (n = 69) was associated with an increased degree of delayed gastric emptying (p = 0.03) with 50% of opiate users having very delayed gastric emptying. One-way analysis revealed that severely delayed gastric emptying correlated with both increased hospitalizations and ED visits.ConclusionsSevere delay in gastric emptying is a risk factor for increased hospitalizations and ED visits. Opiate use correlates with increased severity of gastric emptying. Identifying at-risk patients, stopping opioids, and instituting a programmatic care plan for patients with severely delayed gastric emptying may reduce ED visits, hospitalizations, and healthcare costs.

Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

Background Post-surgical gastroparesis (psGP) is putatively related to vagal denervation from either therapeutic transection or inadvertent injury. Here, we present a series of patients undergoing endoscopic per-oral pyloromyotomy (POP) as a treatment for medically refractory psGP. Methods Patients identified from a prospectively maintained database of patients undergoing POP procedures at our institution from January 2016 to January 2018 were included. Surgical history, symptom scores, and gastric emptying studies before and 3 months after POP were additionally recorded. Results During the study period, 177 POP procedures were performed, of which 38 (21.5%) were for psGP. The study cohort was 84.2% female with a mean body mass index of 27.6 kg/m 2 and mean age of 55.2 years. Common comorbidities included hypertension (34.2%), depression (31.6%), and gastroesophageal reflux disease (28.9%). Hiatal/paraesophageal hernia repair (39.5%) or fundoplication (36.8%) preceded psGP diagnosis most often. The mean operative time was 30 ± 20 min. There were no intraoperative complications. Mean postoperative length of stay was 1.2 days. There were two readmissions within 30 days, one for melena and one for dehydration. The mean improvement in total Gastroparesis Symptom Index Score was 1.29 ( p  = 0.0002). The mean 4-h gastric retention improved from a pre-POP mean of 46.4 to 17.9% post-POP. Normal gastric emptying was noted in 50% of subjects with available follow-up imaging. Conclusion POP is a safe and effective endoscopic therapy for patients with psGP. POP should be considered a reasonable first-line option for patients with medically refractory psGP and may allow stomach preservation.