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.

Efficacy of Gastric Electrical Stimulation in Alleviating Symptoms of Refractory Post-Surgical Gastroparesis: A Retrospective Analysis from Two Centers.

BACKGROUND: Post-surgical gastroparesis, resulting from surgical interventions on the stomach or vagal nerve injury, poses significant clinical challenges with patients presenting symptoms like nausea, vomiting, and abdominal pain. While gastric electrical stimulation (GES) offers potential relief, its efficacy in refractory post-surgical gastroparesis requires further examination. OBJECTIVE: This study evaluated the clinical response to GES in patients with refractory post-surgical gastroparesis. METHODS: A retrospective study was conducted across two study sites, involving 185 patients with drug-refractory post-surgical 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 FDA-compliant Patient Reported Outcomes scores and other relevant clinical metrics at baseline, after temporary GES placement, and 6 months after permanent GES placement. All three groups were also analyzed by the symptom improvement group vs the non-improved group at baseline and 6 months after GES placement. RESULTS: Post-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 post-GES after temporary GES placement among three 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 three groups six months post-GES (3.0 [2.0, 3.5], p=0.018). 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 post-surgical 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 post-surgical 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.