RESUMO
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.
Assuntos
Esvaziamento Gástrico , Gastroparesia , Náusea , Vitamina D , Vômito , Humanos , Gastroparesia/fisiopatologia , Gastroparesia/sangue , Gastroparesia/etiologia , Gastroparesia/diagnóstico , Esvaziamento Gástrico/fisiologia , Feminino , Masculino , Vômito/fisiopatologia , Vômito/sangue , Vômito/etiologia , Pessoa de Meia-Idade , Adulto , Vitamina D/sangue , Vitamina D/análogos & derivados , Náusea/fisiopatologia , Náusea/etiologia , Náusea/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologia , Estômago/fisiopatologiaRESUMO
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.
RESUMO
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.
Assuntos
Gastroparesia , Estudo de Associação Genômica Ampla , Humanos , Gastroparesia/genética , Predisposição Genética para Doença , Dor AbdominalRESUMO
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.
Assuntos
Gastroparesia , Adulto , Humanos , Gastroparesia/diagnóstico por imagem , Gastroparesia/etiologia , Ingestão de Líquidos , Azia , Esvaziamento Gástrico , Náusea , CintilografiaRESUMO
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.
Assuntos
Buspirona , Gastroparesia , Humanos , Feminino , Masculino , Buspirona/uso terapêutico , Gastroparesia/tratamento farmacológico , Gastroparesia/diagnóstico , Método Duplo-Cego , Esvaziamento GástricoRESUMO
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.
Assuntos
Gastroparesia , Humanos , Gastroparesia/terapia , Qualidade de Vida , Apoio Nutricional , Nutrição Parenteral , Nutrição EnteralRESUMO
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.
Assuntos
Dispepsia , Gastroparesia , Humanos , Esvaziamento Gástrico/fisiologia , Refeições , ÁguaRESUMO
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.
Assuntos
Gastroparesia , Humanos , Gastroparesia/tratamento farmacológico , Resultado do Tratamento , Esvaziamento Gástrico , Estudos Multicêntricos como AssuntoRESUMO
Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, abdominal burning, and abdominal pain. There was no difference in symptoms after meal between patients with delayed (n = 66) and normal (n = 42) GE. Diabetic patients (n = 26) had greater gastric retention than idiopathic patients (n = 78), but idiopathic patients had greater postprandial nausea, stomach fullness, and abdominal pain. Water consumed during WLST averaged 421 ± 245 mL. Idiopathic patients had greater nausea scores during WLST than diabetic patients. In comparison to those with normal water consumption (≥238 mL; n = 80), patients with impaired water ingestion (<238 mL; n = 26) had increased stomach fullness, early satiety, postprandial fullness, and loss of appetite on PAGI-SYM. Patients with delayed and normal GE had similar symptom profiles during GES and WLST. Idiopathic patients had less gastric retention but more symptoms after GES meal and after WLST compared with diabetic patients. Patients with impaired water consumption during WLST had increased symptoms by PAGI-SYM. These data suggest that impaired GA, rather than GE, may be important in explaining postprandial symptoms in patients with symptoms of gastroparesis.NEW & NOTEWORTHY Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.
Assuntos
Diabetes Mellitus , Gastroparesia , Dor Abdominal/etiologia , Esvaziamento Gástrico , Gastroparesia/diagnóstico , Gastroparesia/etiologia , Humanos , Náusea/etiologia , ÁguaRESUMO
BACKGROUND: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders. AIMS: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA. METHODS: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). RESULTS: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p = 0.05), Hispanic ethnicity (p = 0.02), comorbid rheumatoid arthritis (p = 0.02), systemic sclerosis (p = 0.004), and elevated ESR (p = 0.007). ANA positivity was associated with lower total GCSI (p = 0.007) and lower nausea/vomiting subscale (p = 0.0005), but not related to gastric emptying. CONCLUSIONS: The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting.
Assuntos
Artrite Reumatoide , Gastroparesia , Escleroderma Sistêmico , Anticorpos Antinucleares , Artrite Reumatoide/complicações , Feminino , Esvaziamento Gástrico , Gastroparesia/diagnóstico , Humanos , Náusea/etiologia , Prevalência , Escleroderma Sistêmico/complicações , Vômito/complicaçõesRESUMO
BACKGROUND: Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms. METHODS: Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar's test. Risk differences with standard errors were employed to estimate percent reduction in symptoms. RESULTS: Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders. DISCUSSION: Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.
Assuntos
Discinesia Biliar , Colecistectomia Laparoscópica , Dor Abdominal/cirurgia , Discinesia Biliar/complicações , Discinesia Biliar/diagnóstico , Discinesia Biliar/cirurgia , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/métodos , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Assuntos
Domperidona , Gastroparesia , Estudos de Coortes , Domperidona/uso terapêutico , Esvaziamento Gástrico , Gastroparesia/diagnóstico , Humanos , National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) , Qualidade de Vida , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND & AIMS: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
Trânsito Gastrointestinal , Gastroparesia , Constipação Intestinal/epidemiologia , Esvaziamento Gástrico , Gastroparesia/complicações , Gastroparesia/diagnóstico , Humanos , Intestino Delgado , CintilografiaRESUMO
BACKGROUND: The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis. METHODS: Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models. RESULTS: Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206+ macrophages in both groups compared with obese controls. CONCLUSIONS: A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. CLINICALTRIALS. GOV IDENTIFIER: NCT00398801, NCT01696747.
Assuntos
Dispepsia/diagnóstico , Dispepsia/fisiopatologia , Gastroparesia/diagnóstico , Gastroparesia/fisiopatologia , Dor Abdominal/etiologia , Adulto , Estudos de Casos e Controles , Dispepsia/complicações , Dispepsia/patologia , Feminino , Esvaziamento Gástrico , Gastroparesia/complicações , Gastroparesia/patologia , Humanos , Células Intersticiais de Cajal/patologia , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Sistema de Registros , Índice de Gravidade de Doença , Estômago/patologia , Avaliação de Sintomas , Centros de Atenção Terciária , Vômito/etiologiaRESUMO
BACKGROUND: Understanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management. AIMS: (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL. METHODS: Gastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI-SYM and Rome III), QOL (SF-36v2 and PAGI-QOL), depression (Beck Depression Inventory [BDI]), and anxiety (State Trait Anxiety InventoryAQ7). KEY RESULTS: 715 gastroparesis patients (256 diabetic (DG), 459 idiopathic (IG)) were evaluated. SF-36 physical component (PC) score averaged 33.3 ± 10.5; 41% had impaired score <30. SF-36 PC scores were similar between diabetic and idiopathic gastroparesis. Impaired SF-36 PC associated with increased nausea/vomiting and upper abdominal pain subscores, acute onset of symptoms, higher number of comorbidities, use of narcotic pain medications, and irritable bowel syndrome (IBS). SF-36 mental component (MC) score averaged 38.9 ± 13.0; 26% had impaired score <30. Poor SF-36 MC associated with diabetic etiology, higher Beck depression inventory, and state anxiety scores. PAGI-QOL score averaged 2.6 ± 1.1; 50% had a score of <2.6. Low PAGI-QOL associated with higher fullness, bloating, and upper abdominal pain subscores, more depression and Trait anxiety, smoking cigarettes, need for nutritional support, progressively worsening symptoms and periodic exacerbations. CONCLUSIONS & INFERENCES: Multiple measures show poor QOL present in gastroparesis. Several areas impacted on reduced QOL: (a) Symptoms of nausea, vomiting, and abdominal pain, as well as IBS; (b) Etiology and acute onset and progressively worsening symptoms; (c) Comorbidities and psychological factors such as anxiety and depression; (d) Patient-related factors such as smoking. Targeting the modifiable factors may improve patient outcomes in gastroparesis.
Assuntos
Dor Abdominal/psicologia , Gastroparesia/psicologia , Náusea/psicologia , Qualidade de Vida/psicologia , Vômito/psicologia , Dor Abdominal/etiologia , Dor Abdominal/fisiopatologia , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Depressão/fisiopatologia , Depressão/psicologia , Feminino , Gastroparesia/complicações , Gastroparesia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/fisiopatologia , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Vômito/etiologia , Vômito/fisiopatologiaRESUMO
BACKGROUND: The classic clinical picture of gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic gastroparesis. METHODS: In patients with idiopathic gastroparesis, detailed history and weight were acquired at enrollment and after 48 weeks. Questionnaires assessed symptoms, food intake, physical activity, and quality of life. Patients underwent laboratory testing, gastric emptying scintigraphy, and water load testing. RESULTS: Of 138 patients with idiopathic gastroparesis, 10% were underweight (BMI < 18.5), 39% were normal weight (BMI 18.5-25), 20% were overweight with BMI 25 to 30 kg/m2 , and 29% were obese with BMI > 30 kg/m2 . Body weight at enrollment was positively associated with oral caloric consumption (P < .001), following a gastroparesis diet (P = .04), nutrition consultation (P = .001), upper abdominal pain (P = .01); and negatively associated with energy expenditure (P = .05), alcohol use (P = .003) and severity of bloating (P < .001). When followed over 48 weeks, 53% patients stayed stable (within 5% of baseline weight), 30% gained, and 17% lost weight. Weight gain over 48 weeks was positively associated with oral caloric consumption (P = .003) and constipation severity (P = .005) at enrollment, and negatively associated with lower abdominal pain severity (P = .007) at enrollment, and associated with improvement in inability to finish meal score (P < .001) at 48 weeks. CONCLUSIONS: In this series of patients with idiopathic gastroparesis, 10% were underweight whereas 29% were obese. Over 48 weeks, 30% of patients increased their body weight ≥ 5%. Diet, activity, and symptoms are important factors associated with body weight in patients with idiopathic gastroparesis.
Assuntos
Peso Corporal , Gastroparesia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The cause of chronic nausea can be difficult to diagnose. Idiopathic rapid gastric emptying (iRGE) can cause nausea, but limited literature exists on clinical and pathophysiological features. In contrast, dumping syndrome or post-surgical rapid gastric emptying (psRGE) is well-known and may present with early phase vasomotor symptoms, diarrhea, and late phase reactive hypoglycemia. Our aim is to compare clinical and gastric motility characteristics in patients with iRGE and psRGE and unexplained chronic nausea. METHODS: A retrospective study was conducted on patients with unexplained chronic nausea and RGE (<30% retention of a standard isotope-labeled solid meal at 1-h). Gastric myoelectrical activity (GMA) was recorded during water load satiety tests (WLST) using validated electrogastrogram (EGG) recording methods. KEY RESULTS: Thirty iRGE and sixteen psRGE patients with unexplained chronic nausea were identified; average 1-hour meal retention was 18.6% and 16.2%, respectively. Nausea, bloating, early satiety, and bowel function were similar in the two groups; fewer iRGE patients had abdominal pain and none had vasomotor symptoms. Normal 3 cpm GMA was recorded in 44% of iRGE vs 29% of psRGE, tachygastria in 13% vs 43%, bradygastria in 25% vs 14%, and mixed in 19% vs 14% (p values >0.05). Abnormal WLST volume (<300 ml) was found in 69% of iRGE and 43% of psRGE (p = 0.36). CONCLUSIONS & INFERENCES: (a) iRGE and psRGE patients may present with unexplained chronic nausea rather than classic vasomotor symptoms and diarrhea. (b) iRGE and psRGE patients had similar gastric dysrhythmias and accommodation dysfunction, which may contribute to RGE.
Assuntos
Síndrome de Esvaziamento Rápido/fisiopatologia , Esvaziamento Gástrico/fisiologia , Náusea/fisiopatologia , Estômago/fisiopatologia , Adulto , Estudos de Casos e Controles , Doença Crônica , Técnicas de Diagnóstico do Sistema Digestório , Eletrodiagnóstico , Feminino , Motilidade Gastrointestinal/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Autonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity. METHODS: We studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements. KEY RESULTS: Low sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2-10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4-15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild-moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0-3.1) vs. 1.2 (0.6-2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1-0.8) vs. 0.6 (0.2-1.7); P = .03]. CONCLUSIONS: Autonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms. INFERENCES: Gastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying.