Cangemi, David J.

ABSTRACT Background Gastric emptying scintigraphy (GES) is considered the standard for differentiating gastroparesis from functional dyspepsia and other foregut disorders characterized by nausea and vomiting but provides only a brief physiologic snapshot that may not accurately reflect daily function. We utilized a non‐invasive wireless patch system (WPS) to characterize multiday gastric myoelectrical activity, evaluate its relationship with GES, and assess changes following a therapeutic intervention. Methods Adults referred for GES for symptoms thought to represent gastroparesis were enrolled in a prospective study. Patients wore a WPS for up to 6 days, starting on the day of scintigraphy. Gastric myoelectrical activity was analyzed and categorized into relatively weak, relatively moderate, and relatively strong activity phenotypes. A subset of patients underwent repeat monitoring following individualized therapeutic interventions (e.g., anti‐emetics, proton pump inhibitors, lifestyle changes). Results Forty‐eight patients (mean age 44; 79% female) completed the study. GES identified delayed gastric emptying in 18%, rapid in 22%, and normal in 60% of subjects. During the 4‐h concurrent GES window, gastric activity in patients with delayed emptying was lower, but this difference did not reach statistical significance ( p = 0.08). When compared to the full multiday recording period, GES results showed no correlation with the myoelectric readings. Significant day‐to‐day variability was observed, both random and systemic. In the latter category, a “Test‐Day” dip was observed with gastric activity lowest on Day 1 (GES test day) and increasing significantly on subsequent days, stabilizing by Day 4 ( p < 0.001). Healthy control subjects recorded during normal daily routines showed no such day‐to‐day variation. In the retesting cohort, anti‐emetics produced robust increases in gastric amplitude, whereas PPIs showed minimal impact. Conclusions The WPS effectively captures distinct gastric phenotypes and quantifies physiologic responses to therapy in both gastric and intestinal regions, demonstrating its clinical utility as a robust tool for evaluating and managing foregut symptoms in real‐world settings. Importantly, the multiday WPS highlights significant day‐to‐day physiologic variability in gastric activity that extends beyond the single‐day GES ‘snapshot’.

Background: In patients with irritable bowel syndrome with constipation (IBS-C), rapid, sustained relief from constipation and abdominal symptoms, such as pain, discomfort, and bloating, can improve quality of life. Objective: This post hoc analysis evaluates the time to constipation and abdominal symptom relief achieved with tenapanor. Design: Post hoc analysis of data pooled from three randomized placebo-controlled studies (phase IIb, T3MPO-1, and T3MPO-2) of tenapanor 50 mg twice daily in patients with IBS-C. Methods: The time to first response for complete spontaneous bowel movement (CSBM) frequency, abdominal pain, discomfort, bloating, and 3-item abdominal score (AS3) were assessed. The AS3 was derived as the average of the weekly scores for abdominal pain, discomfort, and bloating. Cumulative incidences of response over time were estimated using the Kaplan–Meier method. A Cox proportional hazards model was used to assess the effect of baseline and demographic characteristics on the time to first response. Results: Among 1372 patients with IBS-C (684 tenapanor; 688 placebo), median time to first CSBM response was 2 weeks, and median time to abdominal pain, discomfort, bloating, or AS3 response was 4–5 weeks in those treated with tenapanor, with 67.8%–76.7% achieving first response in CSBM frequency and abdominal symptoms by week 12. These time frames were shorter than those observed with the placebo (4 weeks for CSBM and 6–8 weeks for pain, discomfort, bloating, and AS3), of whom 59.1%–69.4% achieved the first response in CSBM and abdominal symptoms by week 12. Higher weekly response rates were observed with tenapanor than with placebo for all endpoints in each week of the 12-week treatment period. Conclusion: This novel post hoc analysis demonstrates that, compared with placebo, tenapanor reduces the time to first response in CSBM frequency and abdominal symptoms and consistently increases the weekly response rate during 12 weeks of treatment. Trial registration: NCT01923428; NCT02621892; NCT02686138.

AbstractBackgroundGastric sensorimotor disorders (functional dyspepsia [FD] and gastroparesis [GP]) are prevalent and burdensome. Prolonged ambulatory recording using a wireless patch may provide novel information in these patients.MethodsConsecutive adult patients (age ≥ 18 years) referred for gastric emptying scintigraphy (GES) were eligible for study inclusion. Patients were excluded if they had prior foregut surgery; were taking opioids or other medications known to affect gastric emptying; had a HgbA1C > 10; or were recently hospitalized. Three wireless motility patches were applied to the skin prior to GES. Patients wore the patches for 6 days while recording meals, symptoms, and bowel movements using an iPhone app.Key ResultsTwenty‐three consecutive adults (87% women; mean age = 43.9 years; mean BMI = 26.7 kg/m2) were enrolled. A gastric histogram revealed three levels of gastric myoelectric activity: weak, moderate, and strong. Patients with delayed gastric emptying at 4 h had weak gastric myoelectrical activity. Patients with nausea and vomiting had strong intestinal activity. Those with FD had weak gastric and intestinal myoelectric activity, and a weak meal response in the stomach, intestine, and colon compared to those with nausea alone or vomiting alone.Conclusions and InferencesPatients with FD, and those with delayed gastric emptying, had unique gastrointestinal myoelectrical activity patterns. Reduced postprandial pan‐intestinal myoelectric activity may explain the symptoms of FD in some patients. Recording gastrointestinal activity over a prolonged period in the outpatient setting has the potential to identify unique pathophysiologic patterns and meal‐related activity that distinguishes patients with distinct gastric sensorimotor disease states.

Opioid receptors are found throughout the gastrointestinal tract, including the large intestine. Many patients treated with opioids experience opioid-induced constipation (OIC). Laxatives are not effective in most patients, and in those who do initially respond, the efficacy of laxatives generally diminishes over time. In addition, OIC does not spontaneously resolve for most patients. However, complications of opioids extend far beyond simply slowing gastrointestinal transit. Opioid use can affect intestinal permeability through a variety of mechanisms. Toll-like receptors are a crucial component of innate immunity and are tightly regulated within the gut epithelium. Pathologic µ-opioid receptor (MOR) and toll-like receptor signaling, resulting from chronic opioid exposure, disrupts intestinal permeability leading to potentially harmful bacterial translocation, elevated levels of bacterial toxins, immune activation, and increased cytokine production. Peripherally active MOR antagonists, including methylnaltrexone, are effective at treating OIC. Benefits extend beyond simply blocking the MOR; these agents also act to ameliorate opioid-induced disrupted intestinal permeability. In this review, we briefly describe the physiology of the gastrointestinal epithelial border and discuss the impact of opioids on gastrointestinal function. Finally, we consider the use of peripherally active MOR antagonists to treat disrupted intestinal permeability resulting from opioid use and discuss the potential for improved morbidity and mortality in patients treated with methylnaltrexone for opioid-induced bowel disorders.

Gastroparesis (GP) is a disorder characterized by symptoms of nausea, vomiting, early satiety, abdominal pain, and/or bloating in the setting of delayed gastric emptying and the absence of a mechanical obstruction. Though the epidemiology and many pathophysiologic mechanisms have been well-established, GP remains an incompletely understood gastrointestinal disorder, and recent data has challenged existing concepts regarding the etiology, diagnosis, and treatment of GP. Thus, our understanding of GP is evolving and with this comes the promise of novel diagnostic methods and treatments, both of which are sorely needed for this historically vexing disorder, which presents unique challenges to patients and providers alike. In this section, we will review existing principles pertaining to the pathophysiology and evaluation of GP, and contrast this with recent data, some of which challenges the historical perspective. In so doing, we aim to provide the reader with an updated and sophisticated view on the approach to GP moving forward.