Health-Related Social Needs in Patients With Gastroparesis: Relationships to Symptom Severity and Quality of Life.

Background and Aims: Patients with health-related social needs (HRSNs) experience barriers to health care services. To identify areas of intervention, we need to understand the impact of HRSN in patients with gastroparesis. This study aimed to 1) determine types of HRSN present in patients with gastroparesis; 2) analyze relationship between HRSN and gastroparesis symptom severity and health-related quality of life (HRQL); and 3) evaluate which HRSN domains most significantly affect symptom severity and HRQL. Methods: Patients with gastroparesis were enrolled and completed questionnaires to assess the following: 1) severity of gastroparetic symptoms using Gastroparesis Cardinal Symptom Index (GCSI); 2) HRSN using screening questionnaire; and 3) HRQL using the Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life (PAGI-QOL). Results: Three hundred twenty-one patients with gastroparesis participated in this study. Two hundred twelve patients completed GCSI and HRSN questionnaires, and 109 additional patients completed PAGI-QOL questionnaire. Of the 321 total patients, the most common HRSN were mental health, financial strain, and food insecurity. Overall, 43% had at least one HRSN and 22% had at least 2 HRSN. The number of HRSN was directly correlated to the GCSI total symptom score (r = 0.284, P < .05) while inversely correlated to the PAGI-QOL score (r = -0.650, P < .05). Of the 7 HRSN domains studied, patients with mental health HRSN, in particular, reported more severe gastroparesis symptoms and lower quality of life. Conclusion: A large number (43%) of patients with gastroparesis had at least 1 HRSN. Patients with HRSN reported more severe gastroparesis symptoms and lower quality of life than patients without HRSN.

Whole Gut Transit Scintigraphy for the Assessment of Patients with Symptoms of Chronic Constipation.

INTRODUCTION: Whole gut transit scintigraphy (WGTS) can detect delayed colonic transit (CT), different types of CT delays, and assess upper GI tract transit. AIM: To delineate the frequency of different types of CT patterns in patients with chronic constipation (CC), determine the relationship between these CT patterns and upper GI tract transit abnormalities, and assess how symptoms relate to different colonic transit patterns. METHODS: Retrospective review of patients who had WGTS for CC. Patients completed a modified PAGI-SYM questionnaire to assess symptoms. Patients ingested a standard solid (Tc-99m egg sandwich)-liquid (In-111 water) meal to assess solid meal gastric emptying (GE), liquid GE, small bowel transit (SBT), and geometric center of colonic activity at 24, 48, and 72h. RESULTS: One hundred and eighty six patients underwent WGTS. Main symptoms were constipation (41%), nausea (24%), and bloating (22%). CT assessment showed 32% of patients had normal transit, 31% colonic inertia (CI), 28% functional rectosigmoid obstruction (FRS0), and 9% generalized slow colonic transit (GSCT). GE was delayed in 36%; more commonly in CI and FRSO. SBT was delayed in 19%; more commonly in GSCT and CI. Patients with CI had less bowel movements per week whereas patients with normal CT had more bm/week. CONCLUSIONS: In this series of patients with symptomatic constipation, WGTS assessment showed delayed colonic transit in 68% of patients, with 31% having colonic inertia, 28% a functional rectosigmoid obstruction pattern, and 9% generalized delay in colonic transit. Abnormalities in GE and SBT were present in 36 and 19%. WGTS is helpful to document delayed colonic transit (CT), assess the pattern of the delay in CT, and determine if there are upper GI transit abnormalities.

Predicting Response to Neuromodulators or Prokinetics in Patients with Suspected Gastroparesis Using Machine Learning: the "BIDnD" Model.

INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis have limited efficacy and it is difficult to predict which patients will respond. In this study, we implemented a machine-learning model to predict the response to prokinetics and/or neuromodulators in patients with gastroparesis-like symptoms. METHODS: Subjects with suspected gastroparesis underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule (WMC) and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their Gastroparesis Cardinal Symptom Index (GCSI) at 6 months decreased by ≥1 from baseline. A machine-learning model was trained using lasso regression, ridge regression or random forest. Five-fold cross-validation was used to train the models and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were non-responders. A ridge regression model with the variables: BMI, Infectious prodrome, delayed GES, no diabetes (BIDnD), had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with GET, duodenal MI, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with gastroparesis-like symptoms.

Comparative evaluation of single versus double leg raise maneuver in high-resolution esophageal manometry.

BACKGROUND: The straight leg raise (SLR) maneuver, often performed during esophageal manometry, requires patients to lift their leg(s) to augment intraabdominal pressure (IAP). Diverse techniques have been applied for SLR. This study aimed to evaluate and compare the effects of SLR between single and double leg raises. METHODS: During esophageal manometry, patients were asked to raise one leg, followed by elevating both legs. The efficacy of SLR for (1) detecting hiatal hernia, (2) increasing IAP, and (3) predicting gastroesophageal reflux disease (GERD) with intraesophageal pressure (IEP) was assessed. The value of change in impedance to indicate reflux during SLR in predicting esophageal acid exposure was investigated. KEY RESULTS: The leg raise procedures were performed in 86 patients undergoing high-resolution esophageal manometry. Both the single and double leg raises exhibited a higher hiatal hernia detection rate compared to the landmark (p = 0.008 and 0.005, respectively). Double leg raise was more effective in raising IAP by >50% compared to single leg raise (100% vs. 65.1%, p < 0.001), increasing yield by 53.6%. The change in IAP showed a positive correlation with the change in IEP during double leg raise (r = 0.31; p = 0.004), higher than that for single leg raise (r = 0.23; p = 0.03). Lower intraesophageal impedance during SLR was associated with AET > 6% with double leg raise (1.5 kΩ vs. 2.5 kΩ, p = 0.04). CONCLUSIONS & INFERENCES: Our study demonstrates the efficacy of both single and double leg raise maneuvers during HREMI in increasing hiatal hernia detection and possible value in predicting GERD. The double leg raise resulted in a higher rate of effective increase in IAP, potentially enabling more patients to undergo effective SLR during HREMI.

Low Vitamin D Levels in Patients with Symptoms of Gastroparesis: Relationships with Nausea and Vomiting, Gastric Emptying and Gastric Myoelectrical Activity.

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied. AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp. METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography. RESULTS: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01). CONCLUSIONS: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction.

Consensus practice recommendations for management of gastrointestinal dysfunction in Parkinson disease.

BACKGROUND: Gastrointestinal (GI) dysfunction is a common non-motor feature of Parkinson disease (PD). GI symptoms may start years before the onset of motor symptoms and impair quality of life. Robust clinical trial data is lacking to guide screening, diagnosis and treatment of GI dysfunction in PD. OBJECTIVE: To develop consensus statements on screening, diagnosis, and treatment of GI dysfunction in PD. METHODS: The application of a modified Delphi panel allowed for the synthesis of expert opinions into clinical statements. Consensus was predefined as a level of agreement of 100 % for each item. Five virtual Delphi rounds were held. Two movement disorders neurologists reviewed the literature on GI dysfunction in PD and developed draft statements based on the literature review. Draft statements were distributed among the panel that included five movement disorder neurologists and two gastroenterologists, both experts in GI dysmotility and its impact on PD symptoms. All members reviewed the statements and references in advance of the virtual meetings. In the virtual meetings, each statement was discussed, edited, and a vote was conducted. If there was not 100 % consensus, further discussions and modifications ensued until there was consensus. RESULTS: Statements were developed for screening, diagnosis, and treatment of common GI symptoms in PD and were organized by anatomic segments: oral cavity and esophagus, stomach, small intestine, and colon and anorectum. CONCLUSIONS: These consensus recommendations offer a practical framework for the diagnosis and treatment of GI dysfunction in PD.

Glucagonlike Peptide-1 Receptor Agonists: The Good, the Bad, and the Ugly-Benefits for Glucose Control and Weight Loss with Side Effects of Delaying Gastric Emptying.

Glucagonlike peptide-1 (GLP-1) receptor agonists (RAs) are being increasingly used for glycemic control in patients with diabetes and for weight loss and weight management in obese subjects. There has been recent public awareness of the potential of GLP-1 RAs to delay gastric emptying and cause gastroparesis. By delaying gastric emptying, these agents can complicate the clinical evaluation of patients on these drugs by affecting diagnostic testing for gastroparesis. This article discusses GLP-1 RAs and their effects on gastric emptying, gastric food retention, and gastroparesis. This article highlights how physicians should be attuned to the gastric side effects of these popular therapeutic agents for blood glucose control in people with diabetes and for weight loss and weight management in obese patients.

Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45+ cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis.

Gastric Alimetry Expands Patient Phenotyping in Gastroduodenal Disorders Compared with Gastric Emptying Scintigraphy.

INTRODUCTION: Gastric emptying testing (GET) assesses gastric motility, however, is nonspecific and insensitive for neuromuscular disorders. Gastric Alimetry (GA) is a new medical device combining noninvasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared with GET. METHODS: Patients with chronic gastroduodenal symptoms underwent simultaneous GET and GA, comprising a 30-minute baseline, 99m TC-labelled egg meal, and 4-hour postprandial recording. Results were referenced to normative ranges. Symptoms were profiled in the validated GA App and phenotyped using rule-based criteria based on their relationships to the meal and gastric activity: (i) sensorimotor, (ii) continuous, and (iii) other. RESULTS: Seventy-five patients were assessed, 77% female. Motility abnormality detection rates were as follows: GET 22.7% (14 delayed, 3 rapid), GA spectral analysis 33.3% (14 low rhythm stability/low amplitude, 5 high amplitude, and 6 abnormal frequency), and combined yield 42.7%. In patients with normal spectral analysis, GA symptom phenotypes included sensorimotor 17% (where symptoms strongly paired with gastric amplitude, median r = 0.61), continuous 30%, and other 53%. GA phenotypes showed superior correlations with Gastroparesis Cardinal Symptom Index, Patient Assessment of Upper Gastrointestinal Symptom Severity Index, and anxiety scales, whereas Rome IV Criteria did not correlate with psychometric scores ( P > 0.05). Delayed emptying was not predictive of specific GA phenotypes. DISCUSSION: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with increased correlation with symptoms and psychometrics compared with gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders.

Fourier Phase Analysis of Dynamic Antral Contraction Scintigraphy: New Software, Reference Values, and Comparisons to Conventional Gastric Emptying.

Dynamic antral contraction scintigraphy (DACS) has been used to evaluate for gastric dysmotility by measuring antral contraction frequency and ejection fraction (EF). Fourier phase image analysis has the potential to assess gastric antral contractions for dyssynchrony as has been used for analyzing nuclear cardiology ventriculography (multigated acquisition studies) for cardiac dyssynchrony. The aims of this study were to determine whether Fourier phase analysis helps to characterize antral motility physiology, whether Fourier phase analysis correlates with conventional gastric emptying scintigraphy (GES), and which DACS parameters may aid in diagnosing gastric dysmotility, particularly delayed gastric emptying (GE). Methods: DACS and GES of healthy volunteers (n = 22) were compared with patients (n = 99) with symptoms of gastroparesis. New DACS Fourier phase analysis software was developed. Results: GE was delayed (n = 53) or normal (n = 46) in patients. There was a linear correlation between the time for the stomach to empty 50% of the meal and the percentage total proximal and distal in-phase antral pixels at 30 min (r = 0.37, P = 0.0001) and 60 min (r = 0.26, P = 0.007). In healthy volunteers, the mean proximal-to-distal ratio of in-phase antral pixels increased from 1.67 (30 min) to 2.65 (120 min) (P = 0.035), and EF increased from 23% (30 min) to 32% (120 min) (P = 0.022). Multivariable regressions of percentage total proximal and distal in-phase antral pixels (30 min) and EF (60 min) were the best predictors of abnormal GE (adjusted odds ratio, 3.30 [95% CI, 1.21-9.00] and 2.97 [95% CI, 1.08-8.21], respectively). Conclusion: This study used Fourier phase analysis to analyze DACS in healthy volunteers and patients with symptoms of gastroparesis. In addition to establishing reference values, new physiologic information on antral motility was obtained. In healthy volunteers, there was an increasing proximal-to-distal ratio of in-phase antral pixels and antral EF over time after meal ingestion. The percentage total proximal and distal in-phase antral pixels at both 30 and 60 min correlated well with GE values for the time for the stomach to empty 50% of the meal. For symptomatic patients, the percentage total proximal and distal in-phase antral pixels at 30 min and the EF at 60 min after meal ingestion correlated with delayed GE on conventional GES. Thus, Fourier phase analysis of DACS appears to have potential to further aid in diagnosing gastric dysmotility in GES.

Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Relationships among symptoms of gastroparesis to those of avoidant/restrictive food intake disorder in patients with gastroparesis.

BACKGROUND: Patients with symptoms of gastroparesis (Gp) often reduce food intake in attempt to manage their symptoms. Up to 40% of adults with Gp have been reported to have symptoms of a non-body image-based eating disorder, avoidant/restrictive food intake disorder (ARFID). However, whether ARFID symptoms precede or follow the diagnosis of Gp is unknown. METHODS: From January 2021 to January 2022, consecutive adult patients with Gp at an academic center completed self-report surveys for Gp symptom severity (patient assessment of upper gastrointestinal symptoms; PAGI-SYM) and for ARFID (nine-item ARFID screen; NIAS). KEY RESULTS: One hundred and seven patients (age 45.4 ± 17.2 yrs, 84.1% female, BMI 26.4 ± 7.3) with Gp (4-h gastric retention 33.5 ± 21.8%) were included. Eighty-two of the 107 Gp patients (77%) screened positive for ARFID. Positive ARFID screen was most often on the NIAS appetite subscale (84%) and fear subscale (76%), with a lower positive screen rate on the picky subscale (45%). Of the Gp who screened positive for ARFID, 38% reported that eating difficulties came after their Gp diagnosis, whereas 17% reported that eating difficulties preceded their Gp diagnosis, and 15% reported that both began at the same time. CONCLUSIONS: Many (77%) patients with Gp screened positive for ARFID. In Gp patients with ARFID, the Gp diagnosis was more likely to precede the development of eating difficulties. Thus, a subset of patients with Gp may be at risk for developing ARFID. Further longitudinal research is needed to confirm findings and identify risk factors.

Metoclopramide Nasal Spray in Women with Symptomatic Diabetic Gastroparesis: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study.

BACKGROUND & AIMS: Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women. METHODS: This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18-75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale. RESULTS: Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently. CONCLUSIONS: Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.).

A pilot genome-wide association study meta-analysis of gastroparesis.

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 × 10-8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10-5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10-7 ) 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 (pFDR ≤ 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.

Relationships among intragastric meal distribution during gastric emptying scintigraphy, water consumption during water load satiety testing, and symptoms of gastroparesis.

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD0)] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD0, WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.NEW & NOTEWORTHY IMD0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Randomized clinical trial: A phase 2b controlled study of the efficacy and safety of trazpiroben (TAK-906) for idiopathic or diabetic gastroparesis.

BACKGROUND: Previous clinical studies of trazpiroben, a dopamine D2 /D3 receptor antagonist for long-term treatment of moderate-to-severe idiopathic and diabetic gastroparesis, have shown improved symptoms of fullness. This study assessed trazpiroben efficacy, safety, and tolerability in adults with idiopathic and diabetic gastroparesis versus placebo. METHODS: This global, multicenter, double-blind, parallel-group, phase 2b study (NCT03544229) enrolled eligible adults aged 18-85 years with symptomatic idiopathic or diabetic gastroparesis. Randomized participants received either oral placebo or trazpiroben 5, 25, or 50 mg, administered twice daily over 12 weeks, and completed the American Neurogastroenterology and Motility Society Gastroparesis Cardinal Symptom Index-Daily Diary. Change in weekly composite score from baseline to week 12 (primary endpoint) and treatment-emergent adverse events were assessed. Data were summarized descriptively. KEY RESULTS: Overall, 242 participants were enrolled (mean [standard deviation] age 55.7 [14.2] years; 75.6% female); 193 completed the study. No significant differences in change from baseline in weekly average of the daily diary composite score occurred at week 12 between placebo (least-squares mean [standard error] -1.19 [0.12]) and trazpiroben (5, 25, and 50 mg: -1.11 [0.22], -1.17 [0.12], and -1.21 [0.12], respectively). Overall, 41.4% of participants receiving trazpiroben reported treatment-emergent adverse events (placebo, 39.7%). No serious events were considered trazpiroben-related; no life-threatening or fatal events were reported. CONCLUSIONS & INFERENCES: There was no clinically meaningful difference in efficacy between trazpiroben and placebo in treating gastroparesis, based on the primary endpoint analysis. Trazpiroben was well tolerated with no new safety concerns identified, strengthening evidence supporting its favorable safety profile. NCT number: NCT03544229.

Dysphagia in Neurological Disorders.

Dysphagia is a common symptom in many neurologic disorders. Patients with oropharyngeal dysphagia present with difficulties when they start to swallow, often with coughing and choking; whereas patients with esophageal dysphagia describe the feeling that swallowed food stops in the chest. Chronic neurologic diseases such stroke, Parkinson's disease, or dementia often have dysphagia as a symptom, particularly oropharyngeal dysphagia, and the term "neurogenic dysphagia" is often used. A disruption of the sophisticated, integrated sensorimotor swallowing system is usually the main reason behind dysphagia. Dysphagia can be associated with aspiration leading to aspiration pneumonia, and chronic dysphagia can lead to weight loss and malnutrition. Patients with dysphagia, when accurately and promptly diagnosed through medical history, physical examination, and diagnostic tests, often can be treated and experience improved quality of life. The pathophysiological mechanisms behind dysphagia, its diagnosis, and potential treatments are discussed in this manuscript.

Meal-eating characteristics among patients with symptoms of gastroparesis: Relationships to delays in gastric emptying.

BACKGROUND: Patients with symptoms of gastroparesis (Gp) often modify their diets and consume small meals. However, the relationship between patients' eating behavior and their gastric emptying is not well understood. This study describes meal-eating characteristics of patients with Gp symptoms and relates them to severity of emptying delay. METHODS: Adult patients with Gp symptoms underwent 4-h gastric emptying scintigraphy and completed questionnaires including the Patient Assessment of GI Symptoms, a nutrition and diet questionnaire, and the Meal Patterns Questionnaire. KEY RESULTS: Of 119 patients with Gp symptoms, 35 had normal gastric emptying (≤10% gastric retention at 4 h), 26 mildly delayed (>10%-20%), 28 moderately delayed (>20%-35%), and 30 severely delayed (>35%). Most patients (85%) reported eating small meals with an average of 2.4 meals per day. The most common reasons for stopping eating a meal were feeling full (83%), nausea (46%), and abdominal pain (31%). As gastric emptying worsened, patients increasingly made diet modifications such as low-fat, low-fiber, Gp diet, oral supplements, and blenderized meals (r = 0.309, p = 0.0007). Postprandial fullness lasted for 351 ± 451 min for patients with severely delayed emptying versus 207 ± 173 min for patients with normal emptying (p = 0.19). CONCLUSIONS & INFERENCES: Meal-eating characteristics were found to vary with severity of gastric retention. Patients with severely delayed gastric emptying reported the longest duration of postprandial fullness. Dietary modification increased significantly with gastric retention. These meal-eating characteristics are important to understand as they impact on dietary education given to Gp patients for symptom management.

Esophageal Inlet Patch: Association with Barrett's Esophagus.

BACKGROUND: Esophageal inlet patch (IP) with heterotopic gastric mucosa is an incidental finding on esophagogastroduodenoscopy (EGD). Although IP is thought to be embryologic in nature, IP has been associated with Barrett's esophagus (BE). AIMS: The aim of this study was to compare prevalence, symptoms, demographic factors, and esophageal testing in patients with IP and BE. METHODS: We retrospectively analyzed endoscopic findings of EGDs, high-resolution esophageal manometry and esophageal pH impedance studies from January 2010 to January 2021 at a single academic medical center. Patients were grouped by presence or absence of IP and BE. RESULTS: Of 27,498 patients evaluated, 1.3% had endoscopic evidence of IP and 4.9% had BE. Of 362 patients with IP, 17.1% had BE; of 1356 patients with BE, 4.6% had IP. Both IP and BE patients presented primarily with heartburn and/or regurgitation. Patients with BE and/or IP were older and had higher BMI than those without (p < 0.001). Mean lower esophageal sphincter pressure was lower and mean acid exposure time (AET) was higher in patients with IP and/or BE than those without (p < 0.05). CONCLUSIONS: Our study reports an IP prevalence of 1.3%, with 17.1% patients having concomitant BE; and a BE prevalence of 4.9%, with 4.6% also having IP. Patients with IP alone presented with similar symptoms to patients with concomitant BE. Esophageal function testing showed that patients with either IP or BE had decreased LES pressures and increased esophageal AET. During endoscopy, patients found to have one of these findings should be carefully examined for the other.