Citations

LINKED CONTENTThis article is linked to Khanna & Camilleri and Tobi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16143 and https://doi.org/10.1111/apt.16270

SummaryBackgroundGastroparesis is defined by delayed gastric emptying with associated symptoms in the absence of mechanical obstruction.AimTo evaluate pharmacokinetics and pharmacodynamics of felcisetrag, a highly selective 5‐HT4 receptor agonist, on total gut transit in patients with documented delayed gastric emptying of solids.MethodsSingle‐centre, placebo‐controlled study of 36 participants receiving placebo, 0.1mg, 0.3mg or 1.0mg of felcisetrag I.V. infusion, daily, for 3 days. At baseline, each participant completed a 4h, 99mTc‐egg meal (300 kcal, 30% fat) gastric emptying test. Following infusion (Day 2), gastric, small bowel and colonic transit of solids were measured over 48h (same meal plus 111In‐charcoal delivered in methacrylate‐coated capsule). Samples were collected for pharmacokinetics. The primary endpoint was gastric emptying T1/2. Statistical analysis used baseline parameters as covariates (ANCOVA).ResultsPatients (22 idiopathic, 14 diabetic gastroparesis) were randomised to felcisetrag (0.1 mg, n = 10; 0.3 mg, n = 9; 1.0 mg, n = 7) or placebo (n = 10). Compared to placebo, felcisetrag significantly accelerated gastric emptying T1/2, colonic filling at 6h, and 10% small bowel transit time (overall P < 0.01; all three doses individually Bonferroni corrected P < 0.05) for all three measurements. Ascending colon emptying (T1/2) was significantly accelerated (all doses), and colonic transit at 48 hours was accelerated with 0.1 mg and 0.3 mg felcisetrag compared to placebo. Pharmacokinetic results were dose proportional. Felcisetrag was well tolerated with no clinically significant findings from clinical laboratory, vital signs or ECG.ConclusionI.V. felcisetrag significantly accelerated gastric, small bowel and colonic transit in patients with gastroparesis, and should be further evaluated for short‐term treatment of gastric and intestinal motility disorders.ClinicalTrials.gov #NCT03281577

AbstractPurposeThe objectives of this review are to summarize the role of gastric motor functions in the development of satiation (defined broadly as postprandial fullness) and satiety (reduced appetite or postponing desire to eat after a meal) and their impact on weight change. The specific topics are the methods of measurement of gastric emptying and accommodation and their impact on food intake, satiation, and satiety. A second focus contrasts bariatric surgery to endoscopic gastroplasty that alter gastric emptying and incretin responses in markedly divergent manners.BackgroundThe hormone, GLP‐1, retards gastric emptying and increases gastric accommodation through vagally‐mediated effects. Indeed, these effects provide the basis for the association of altered gastric emptying in the appetite and weight loss responses to pharmacological interventions particularly by those acting on receptors of incretin agonists such as liraglutide and the dual agonists, tirzepatide and cotadutide, all of which retard gastric emptying. In fact, retardation of gastric emptying and gastrointestinal adverse effects have been shown to contribute in part to the weight loss in response to this class of pharmacological agents.SummaryThe motor functions of the stomach are relevant to postprandial fullness and to interventions aimed at weight loss in people with obesity.

AbstractPropulsion of contents in the gastrointestinal tract requires coordinated functions of the extrinsic nerves to the gut from the brain and spinal cord, as well as the neuromuscular apparatus within the gut. The latter includes excitatory and inhibitory neurons, pacemaker cells such as the interstitial cells of Cajal and fibroblast-like cells, and smooth muscle cells. Coordination between these extrinsic and enteric neurons results in propulsive functions which include peristaltic reflexes, migrating motor complexes in the small intestine which serve as the housekeeper propelling to the colon the residual content after digestion, and mass movements in the colon which lead to defecation.

AbstractBackgroundNeutrophilic eccrine hidradenitis (NEH) is a benign neutrophilic dermatosis not well recognized beyond an association with malignancy. Although the disease is commonly reported in adults with malignancy, this association is uncommon in children. The diagnosis of NEH is predominantly based on histologic findings to exclude alternative diagnoses for adults, but biopsy is not usually required for children.MethodsA retrospective study was performed of adult and pediatric patients diagnosed with NEH at three Mayo Clinic sites from January 1, 1992, to January 1, 2022. The aim of this study was to elucidate risk factors for NEH and its clinical characteristics, treatment options, and natural course. Clinical information and pathologic results were collected from health records. Available pathologic slides were reviewed with a dermatopathologist.ResultsOf 47 patients identified, 33 had either histologic or clinical confirmation of the diagnosis; 21 were adults (64%), and 12 were children (36%). Most adults (16/21; 76%) had underlying malignancy and received chemotherapy. Five adults (24%) were classified as having idiopathic NEH, and they were younger and had higher NEH recurrence rates than the other adults. Only one pediatric patient (8%) had underlying malignancy. For 10 children (83%), NEH was preceded by strenuous activity. Initial findings of idiopathic NEH were palmoplantar eruptions for both adult and pediatric patients, whereas malignancy‐associated NEH commonly involved the face and axillae.ConclusionsAmong adults, NEH is commonly associated with malignancy and chemotherapy. Among children, idiopathic NEH occurs primarily after overexertion, and malignancy is highly unlikely to be the cause of NEH.

AbstractIgA vasculitis is a small‐vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light‐microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010–October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty‐six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA−, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA− (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi‐squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi‐squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid‐ and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.