Evaluating Autoimmune Markers in Relation to Gastrointestinal Measures in Patients With Symptoms of Gastroparesis.

BACKGROUND: Patients with symptoms (Sx) of gastroparesis (Gp) may have signs of autoimmune disease. GOALS: We hypothesized that serum autoantibodies in Gp Sx patients are associated with follow-up at 48 weeks (about 11 mo) and later autoimmune questionnaires (AQ). One hundred eleven patients: 24 male, 87 female, mean age 43 years, with Gp Sx: 27 diabetic (DM), 78 idiopathic (ID), 6 postsurgical (PS) were studied at baseline, 48 weeks (about 11 mo) and long term. Serum western blot (WB) was performed by an enzyme linked immunosorbent assay for qualitative evaluation of serum antibodies to various specific nuclear antigens. A blotting score (GIBS) was used to compare global immunologic reactions. At long-term follow-up (>5 y), 38 AQ-responding patients (34 with baseline WB data) were compared with WB by AQ responses. RESULTS: A total of 69/111 (62%) had gastric emptying delay. Correlations exist between WB autoantibodies and clinical follow-up at 48 weeks (about 11 mo). 94/96 (97.9%) were WB positive and 62/96 patients had 48-week data. From 5 years follow-up of 38 patients, AQ Sx responses were recurring abdominal pain (89%), lack of energy (87%), exhaustion (74%), and constipation (68%). From AQ and WB data (34 patients), Anti-SSA was higher in those indicating dry mouth and mouth and nose sores and SM was higher in dysphagia (P=0.01 for both). Conclusions In patients with gastroparesis symptoms baseline western blot has significant associations with a number of clinical findings and autoimmune disorders symptoms. These associations suggest possible undiagnosed autoimmune disorders. Further work with Western blotting and other autoimmune measures in patients with gastroparesis symptoms is needed.

The role of gastric electrical stimulation in postsurgical gastroparesis: a retrospective analysis from 2 centers.

BACKGROUND: Postsurgical gastroparesis, resulting from surgical interventions on the stomach or vagal nerve injury, poses significant clinical challenges with patients presenting symptoms such as nausea, vomiting, and abdominal pain. Although gastric electrical stimulation (GES) offers potential relief, its efficacy in refractory postsurgical gastroparesis requires further examination. This study evaluated the clinical response to GES in patients with refractory postsurgical gastroparesis. METHODS: A retrospective study was conducted across 2 study sites, involving 185 patients with drug-refractory postsurgical gastroparesis who underwent both temporary and permanent GES placements. Patients were categorized based on their surgical history: bariatric surgery, Nissen fundoplication, and others. The impact of GES was evaluated using Food and Drug Administration-compliant patient-reported outcomes scores and other relevant clinical metrics at baseline, after temporary GES placement, and 6 months after permanent GES placement. All 3 groups were also analyzed by the symptom improved group vs the unimproved group at baseline and 6 months after GES placement. RESULTS: After GES implantation, all patient groups significantly improved upper gastrointestinal symptoms. The bariatric surgery group and Nissen fundoplication group specifically identified anorexia as the most severe symptom after GES after temporary GES placement among 3 groups (2.5 [0.4-3.5] and 1.5 [0.0-2.5], respectively). Nissen fundoplication patients had the highest score of anorexia among the 3 groups 6 months after GES (3.0 [2.0-3.5], P = .018). Despite these improvements, GES did not enhance gastric emptying test results. Symptomatic improvements were notably significant in patients who initially reported higher symptom severity than those who did not. CONCLUSION: GES shows promise in alleviating symptoms of refractory postsurgical gastroparesis, particularly in those with severe initial symptoms. However, its impact on gastric emptying remains inconclusive. Further research is needed to establish GES as a standard treatment for postsurgical gastroparesis.

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.

Difference in Cyclic Versus Non-cyclic Symptom Patterns in Patients with the Symptoms of Gastroparesis Undergoing Bioelectric Therapy.

INTRODUCTION: Patients with gastroparesis (Gp) have symptoms with or without a cyclic pattern. This retrospective study evaluates differences in cyclic vs. non-cyclic symptoms of Gp by analyzing mucosal electrogastrogram (mEG), familial dysautonomias, and response to gastric stimulation. METHODS: 37 patients with drug refractory Gp, 7 male and 30 female, with a mean age of 41.4 years, were studied. 18 had diabetes mellitus, 25 had cyclic (Cyc), and 12 had a non-cyclic (NoCyc) pattern of symptoms. Patients underwent temporary mucosal gastric stimulator (tGES) placement, which was done as a trial before permanent stimulator (GES) placement. Electrogastrogram (EGG) by mucosal (mEG) measures, including frequency, amplitude, and frequency-amplitude ratio (FAR), were pre- and post-tGES. Patients' history of personal and familial dysautonomias, quality of life, and symptom scores were recorded. Baseline vs. follow-ups were compared by paired t tests and McNemar's tests. T tests contrasted symptom scores, gastric emptying tests (GET), and mEG measures, while chi-squared tests deciphered comorbidity differences between two groups and univariate and multivariate analyses. RESULTS: There were significantly more patients with diabetes in the Cyc group vs. the NoCyc group. Using a 1 point in symptom outcome, 18 patients did not improve and 19 did improve with tGES. Using univariable analysis, with the cyclic pattern as a predictor, patients exhibiting a cyclic pattern had an odds ratio of 0.22 (95% CI 0.05-0.81, p = 0.054) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The mucosal electrogastrogram frequency to amplitude ratio (FAR) for the "not Improved" group was 19.6 [3.5, 33.6], whereas, for the "Improved" group, it was 54.3 [25.6, 72.5] with a p-value of 0.049. For multivariate logistic regression, accounting for sex and age squared, patients exhibiting a cyclic pattern had an adjusted odds ratio (OR) of 0.16 (95% CI 0.03-0.81, p = 0.027) for achieving an improvement of at least one unit in vomiting at follow-up from baseline. The two groups had no significant differences in the personal or inherited history of investigated familial patterns. CONCLUSION: This study shows differences in Gp patients with Cyc vs. NoCyc symptoms in several areas. Larger studies are needed to elicit further differences between the two groups about cycles of symptoms, EGG, findings, familial patterns, and response to mucosal GES.

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.

Nutritional Assessment in Patients after Gastric Electrical Stimulation (GES).

BACKGROUND: Gastric electrical stimulation (GES) is used for patients with drug-refractory gastroparesis (Gp) symptoms. Approximately two-thirds of patients with Gp symptoms are either overweight or obese. We aimed to assess symptoms and nutritional status pre-GES and post-GES placement in a large sample of drug-refractory Gp patients. METHODS: We conducted a chart review of 282 patients with drug-refractory Gp who received temporary followed by permanent GES at an academic medical center. Gastrointestinal symptoms were collected by a traditional standardized PRO (0-4, 0 being asymptomatic and 4 being worst symptoms), baseline nutritional status by BMI plus subjective global assessment (SGA score A, B, C, for mild, moderate, and severe nutritional deficits), ability to tolerate diet, enteral tube access, and parenteral therapy were assessed at baseline and after permanent GES placement. RESULTS: Comparing baseline with permanent, GES was found to significantly improve upper GI symptoms in all quartiles. Of the 282 patients with baseline body mass index (BMI) information, 112 (40%) patients were severely malnourished at baseline, of which 36 (32%) patients' nutritional status improved after GES. Among all patients, 76 (68%) patients' nutritional status remained unchanged. Many patients with high BMI were malnourished by SGA. CONCLUSION: We conclude that symptomatic patients of different BMIs showed improvement in their GI symptoms irrespective of baseline nutritional status. Severely malnourished patients were found to have an improvement in their nutritional status after GES therapy. We conclude that BMI, even if high, is not by itself a contraindication for GES therapy for symptomatic patients.

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.

Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders.

Gastroparesis syndromes (GpS) are a spectrum of disorders presenting with characteristic symptoms increasingly recognized as being gastrointestinal (GI) neuromuscular disorders (NMDs). This review focuses on GpS as a manifestation of neurologic disorders of GI NMD. GpS can be associated with systemic abnormalities, including inflammatory, metabolic, and serologic disorders, as well as autoimmune antibodies via nerve and muscle targets in the GI tract, which can be treated with immunotherapy, such as intravenous immunoglobulin. GpS are associated with autonomic (ANS) and enteric (ENS) dysfunction. Disorders of ANS may interact with the ENS and are the subject of continued investigation. ENS disorders have been recognized for a century but have only recently begun to be fully quantified. Anatomic structural changes in the GI tract are increasingly recognized in GpS. Detailed descriptions of anatomic changes in GpS, and their correlation with physiologic findings, have opened a new era of investigation. The management of GpS, when viewed as GI NMD, has shifted the paradigms of both diagnosis and treatment. This article concludes with current approaches to GpS directed at underlying neuromuscular pathology.

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.

Gastric Alimetry ® improves patient phenotyping in gastroduodenal disorders compared to gastric emptying scintigraphy alone.

Objectives: Gastric emptying testing (GET) assesses gastric motility, however is non-specific and insensitive for neuromuscular disorders. Gastric Alimetry® (GA) is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling. This study assessed patient-specific phenotyping using GA compared to 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: 75 patients were assessed; 77% female. Motility abnormality detection rates were: GET 22.7% (14 delayed, 3 rapid); GA spectral analysis 33.3% (14 low rhythm stability / low amplitude; 5 high amplitude; 6 abnormal frequency); 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%; other 53%. GA phenotypes showed superior correlations with GCSI, PAGI-SYM, 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. Conclusions: GA improves patient phenotyping in chronic gastroduodenal disorders in the presence and absence of motility abnormalities with improved correlation with symptoms and psychometrics compared to gastric emptying status and Rome IV criteria. These findings have implications for the diagnostic profiling and personalized management of gastroduodenal disorders. Study Highlights: 1) WHAT IS KNOWN Chronic gastroduodenal symptoms are common, costly and greatly impact on quality of lifeThere is a poor correlation between gastric emptying testing (GET) and symptomsGastric Alimetry® is a new medical device combining non-invasive gastric electrophysiological mapping and validated symptom profiling 2) WHAT IS NEW HERE Gastric Alimetry generates a 1.5x higher yield for motility abnormalities than GETWith symptom profiling, Gastric Alimetry identified 2.7x more specific patient categories than GETGastric Alimetry improves clinical phenotyping, with improved correlation with symptoms and psychometrics compared to GET.

Association between Gastroparesis and Rheumatoid Arthritis: A US Population-Based Study.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have a high prevalence of nausea, vomiting, postprandial fullness, and abdominal pain; these are symptoms that are similar to those in gastroparesis (GP). The aim of this study was to assess the association between GP and RA and the determinants of GP. METHODS: We identified patients with RA and patients with GP from the 2012-2014 National Inpatient Sample database. The t test and the χ2 test were used for continuous and categorical variables, respectively. We determined the association between RA and GP and independent predictors of GP by multivariate analysis. RESULTS: Of 1,514,960 patients with RA, there were 1070 hospitalizations in which a primary diagnosis of GP was identified. The GP odds ratio in RA was found to be 1.36 and the 95% confidence interval was 1.24 to 1.49 (P < 0.0001). The variables increasing the odds of GP were age intervals of 18 to 35 years, 36 to 50 years, and 51 to 65 years; being female, White, or Black; a median household income in the 26th to 50th and the 51st to 75th percentiles; having diabetes mellitus; and having RA. CONCLUSIONS: An increased likelihood of 36% of GP among patients with RA was determined. White and Black patients younger than age 65 showed a greater risk of developing GP.

Buspirone for early satiety and symptoms of gastroparesis: A multi-centre, randomised, placebo-controlled, double-masked trial (BESST).

BACKGROUND: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT1 receptor agonist, may improve fundic accommodation. AIM: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis. METHODS: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values. RESULTS AND CONCLUSIONS: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, pTX*GROUP  = 0.003; pBF  = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo. CONCLUSIONS: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating. TRIAL REGISTRATION: ClinicalTrials.gov NCT0358714285.

Principles and clinical methods of body surface gastric mapping: Technical review.

BACKGROUND AND PURPOSE: Chronic gastric symptoms are common, however differentiating specific contributing mechanisms in individual patients remains challenging. Abnormal gastric motility is present in a significant subgroup, but reliable methods for assessing gastric motor function in clinical practice are lacking. Body surface gastric mapping (BSGM) is a new diagnostic aid, employs multi-electrode arrays to measure and map gastric myoelectrical activity non-invasively in high resolution. Clinical adoption of BSGM is currently expanding following studies demonstrating the ability to achieve specific patient subgrouping, and subsequent regulatory clearances. An international working group was formed in order to standardize clinical BSGM methods, encompassing a technical group developing BSGM methods and a clinical advisory group. The working group performed a technical literature review and synthesis focusing on the rationale, principles, methods, and clinical applications of BSGM, with secondary review by the clinical group. The principles and validation of BSGM were evaluated, including key advances achieved over legacy electrogastrography (EGG). Methods for BSGM were reviewed, including device design considerations, patient preparation, test conduct, and data processing steps. Recent advances in BSGM test metrics and reference intervals are discussed, including four novel metrics, being the 'principal gastric frequency', BMI-adjusted amplitude, Gastric Alimetry Rhythm Index™, and fed: fasted amplitude ratio. An additional essential element of BSGM has been the introduction of validated digital tools for standardized symptom profiling, performed simultaneously during testing. Specific phenotypes identifiable by BSGM and the associated symptom profiles were codified with reference to pathophysiology. Finally, knowledge gaps and priority areas for future BSGM research were also identified by the working group.

Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities.

INTRODUCTION: Gastroparesis (Gp) and related disorders such as chronic unexplained nausea and vomiting and functional dyspepsia, known as gastropareis syndromes (GpS), have large unmet needs. Mainstays of GpS treatments are diet and drugs. AREAS COVERED: The purpose of this review is to explore potential new medications and other therapies for gastroparesis. Before discussing possible new drugs, the currently used drugs are discussed. These include dopamine receptor antagonists, 5-hydroxytryptamine receptor agonists and antagonists, neurokinin-1 receptor antagonists and other anti-emetics. The article also considers future drugs that may be used for Gp, based on currently known pathophysiology. EXPERT OPINION: Gaps in knowledge about the pathophysiology of gastroparesis and related syndromes are critical to developing therapeutic agents that will be successful. Recent major developments in the gastroparesis arena are related to microscopic anatomy, cellular function, and pathophysiology. The major challenges moving forward will be to develop the genetic and biochemical correlates of these major developments in gastroparesis research.

Characteristics and outcomes of patients with gastroparesis using enteral and/or exclusive parenteral nutrition.

BACKGROUND: Patients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks. METHODS: Patients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks. RESULTS: Of 971 patients with Gp (idiopathic, 579; diabetic, 336; post-Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp-related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48-week follow-up. CONCLUSIONS: This study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp.

A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis.

BACKGROUND: This study assessed the efficacy and safety of velusetrag-a 5-HT4 agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE). METHODS: In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs). KEY RESULTS: 232 subjects (183 females; 113 idiopathic gastroparesis) received treatment from February 2015 through June 2017. Least-squares mean improvement from baseline GCSI-24H (primary endpoint) at week 4 was -1.5 following velusetrag 5 mg vs -1.1 following placebo (treatment difference, -0.4; 95% confidence interval, -0.75 to -0.03; nominal p = 0.0327; Hochberg-adjusted p = 0.0980 [not significant]). Symptom improvement from baseline was achieved only with velusetrag 5 mg, which resulted in greater improvement from baseline vs placebo in all gastroparesis core symptoms, especially in subjects with idiopathic gastroparesis. Improvement from baseline GE by GES was greater in subjects receiving velusetrag (all doses) vs placebo; >70% of subjects receiving velusetrag 30 mg had GE normalization at 4 h. Treatment-emergent AEs were generally mild. CONCLUSIONS AND INFERENCES: Velusetrag treatment was generally well-tolerated and associated with improved GE vs placebo in subjects with diabetic or idiopathic gastroparesis; however, only the lowest dose, velusetrag 5 mg, was associated with short-term improvement in gastroparesis symptoms. CLINICALTRIALS: GOV: NCT02267525.

Normative Values for Body Surface Gastric Mapping Evaluations of Gastric Motility Using Gastric Alimetry: Spectral Analysis.

INTRODUCTION: Body surface gastric mapping (BSGM) is a new noninvasive test of gastric function. BSGM offers several novel and improved biomarkers of gastric function capable of differentiating patients with overlapping symptom profiles. The aim of this study was to define normative reference intervals for BSGM spectral metrics in a population of healthy controls. METHODS: BSGM was performed in healthy controls using Gastric Alimetry (Alimetry, New Zealand) comprising a stretchable high-resolution array (8 × 8 electrodes; 196 cm 2 ), wearable Reader, and validated symptom-logging App. The evaluation encompassed a fasting baseline (30 minutes), 482 kCal meal, and 4-hour postprandial recording. Normative reference intervals were calculated for BSGM metrics including the Principal Gastric Frequency, Gastric Alimetry Rhythm Index (a measure of the concentration of power in the gastric frequency band over time), body mass index (BMI)-adjusted amplitude (µV), and fed:fasted amplitude ratio. Data were reported as median and reference interval (5th and/or 95th percentiles). RESULTS: A total of 110 subjects (55% female, median age 32 years [interquartile range 24-50], median BMI 23.8 kg/m 2 [interquartile range 21.4-26.9]) were included. The median Principal Gastric Frequency was 3.04 cycles per minute; reference interval: 2.65-3.35 cycles per minute. The median Gastric Alimetry Rhythm Index was 0.50; reference interval: ≥0.25. The median BMI-adjusted amplitude was 37.6 µV; reference interval: 20-70 µV. The median fed:fasted amplitude ratio was 1.85; reference interval ≥1.08. A higher BMI was associated with a shorter meal-response duration ( P = 0.014). DISCUSSION: This study provides normative reference intervals for BSGM spectral data to inform diagnostic interpretations of abnormal gastric function.

Gastroparesis in geriatrics population: A United States population study.

BACKGROUND: Older patients with upper gastrointestinal diseases may lack disease-specific symptoms that are required to make the correct diagnosis. This study aimed to compare the gastroparesis demographics, clinical presentation, and surgical management between the older adult and young populations. METHODS: The National Inpatient Sample database was used between the years 2012 and 2014 with the primary diagnosis of gastroparesis. Patients were further divided based on their age into two groups: 70 years or older and younger than 70 years. RESULTS: The older adults were more likely to have early satiety and bloating compared to younger population with an odds ratio (OR) = 3.79; 95% Confidence Interval (95%CI) 2.80- 5.11, p < 0.0001 and OR = 2.80, 95%CI 2.07-3.78, p<0.0001 respectively. Older adults had low odds of having nausea with vomiting (OR = 0.86, 95%CI 0.76-0.95, p = 0.003), or abdominal pain (OR = 0.56, 95%CI 0.50-0.63, p<0.0001). CONCLUSIONS: Older adults had more early satiety and bloating, whereas younger patients had more nausea with vomiting and abdominal pain.

Effect of liquid and solid test meals on symptoms and gastric myoelectrical activity in patients with gastroparesis and functional dyspepsia.

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain. AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD. METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load for individual patients were also determined. RESULTS: 284 patients with GP and 113 with FD were identified who ingested both test meals. Patients with GP and FD had similar maximal tolerated volumes of water [mean (SD) 378 (218) ml vs. 402 (226) ml, p = 0.23] and reported similar intensity of fullness, nausea, bloating, and abdominal discomfort after the test meals. Twenty-six percent and 19% of the patients with GP and FD, respectively, ingested subthreshold (<238 ml) volumes of water (p = 0.15). Gastric dysrhythmias were recorded in 66% of the GP and 65% of the FD patients after the water load. Symptoms and GMA were similar in both groups after ingestion of the nutrient bar. CONCLUSION: The similarity in GMA responses and symptoms after ingestion of solid or liquid test meals suggests GP and FD are closely related gastric neuromuscular disorders.