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.
Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are ...still unclear.
Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR.
111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log
fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log
fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05).
Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human 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.
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•Eleven immune clusters in human gastric muscle. T-cells and myeloid largest clusters•Decreased tissue-protective and increased monocyte trafficking genes in gastroparesis•Greater abundance of monocyte-like macrophage clusters in gastroparesis•IL12 mediated JAK-STAT and Eph-ephrin signaling increased in gastroparesis
Gastroenterology; Immunology; Transcriptomics
Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes ...associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected
< 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway DG false discovery rate (FDR) = 7.9 × 10
; IG FDR = 6.3 × 10
. In DG, properdin expression correlated with GCSI bloating (
= -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention (
= -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis.
This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.
Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of ...gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC).
Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms PAGI-SYM and Rome III functional GI disorder questionnaire.
Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time.
Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747.
The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance ...understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders.
The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National ...Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR).
The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scores.
Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P = .003), nausea (P = .003), and fullness subscales (P =.005), upper abdominal pain score (P = .04), Gastroesophageal Reflux Disease score (P = .05), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (P = .05).
Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. NOTE: This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM.
This volume gathers the harvest of recent doctoral dissertations on South Asia, principally from North America and Western Europe, but exclusive of theses from universities in South Asia itself. The ...yield—1305 dissertations based on research carried out during the early and middle nineteen-sixties and brought to completion between 1966 and 1970—is even greater than one would have guessed, eloquent testimony to the expansion of South Asian studies in the West over the last decade.
Doctoral Dissertations on South Asia seeks to be a comprehensive compilation of recently completed theses dealing in whole or in part with the former civilizations and the contemporary affairs of Ceylon, India, Nepal and Pakistan. At the same time, this work provides striking testimony of the dynamic growth of Asian Studies outside the subcontinent and particularly in the United States, Great Britain, Germany and France, where most of the major centers of scholarship are presently found. It is an interdisciplinary work covering the natural sciences as well as the humanities and social sciences.
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
(IMD
) and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD
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 IMD
, 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 IMD
<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 IMD
is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD
, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD
and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.
IMD
and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD
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. IMD
and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.
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.
Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of symptoms remains uncertain. Results show symptoms and gastric myoelectrical responses after ingestion of solid or liquid test meals are similar and suggests GP and FD are closely related gastric neuromuscular disorders.
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