Linda Nguyen, MD

All Publications

• Glucose sensor-augmented continuous subcutaneous insulin infusion in patients with diabetic gastroparesis: An open-label pilot prospective study PLOS ONE Calles-Escandon, J., Koch, K. L., Hasler, W. L., Van Natta, M. L., Pasricha, P. J., Tonascia, J., Parkman, H. P., Hamilton, F., Herman, W. H., Basina, M., Buckingham, B., Earle, K., Kirkeby, K., Hairston, K., Bright, T., Rothberg, A. E., Kraftson, A. T., Siraj, E. S., Subauste, A., Lee, L. A., Abell, T. L., McCallum, R. W., Sarosiek, I., Nguyen, L., Fass, R., Snape, W. J., Vaughn, I. A., Miriel, L. A., Farrugia, G., NIDDK Gastroparesis Clinical Re 2018; 13 (4): e0194759

  Abstract

  Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.

  View details for DOI 10.1371/journal.pone.0194759

  View details for Web of Science ID 000430026900009

  View details for PubMedID 29652893

  View details for PubMedCentralID PMC5898706

• Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients With Gastroparesis and Related Disorders GASTROENTEROLOGY Pasricha, P. J., Yates, K. P., Sarosiek, I., McCallum, R. W., Abell, T. L., Koch, K. L., Nguyen, L. B., Snape, W. J., Hasler, W. L., Clarke, J. O., Dhalla, S., Stein, E. M., Lee, L. A., Miriel, L. A., Van Natta, M. L., Grover, M., Farrugia, G., Tonascia, J., Hamilton, F. A., Parkman, H. P., NIDDK Gastroparesis Clinical Res 2018; 154 (1): 65-+

  Abstract

  There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome.We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis.Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8-1.7) (P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0-5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) (P = .04).In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.

  View details for DOI 10.1053/j.gastro.2017.08.033

  View details for Web of Science ID 000418501600022

  View details for PubMedID 29111115

  View details for PubMedCentralID PMC5742047

• Novel Uses of Neuromodulators in Treating Functional Abdominal Pain Chen, F., Nguyen, L., Newmark, J. NATURE PUBLISHING GROUP. 2016: S807

  View details for Web of Science ID 000395764602535

• Baseline features and differences in 48 week clinical outcomes in patients with gastroparesis and type 1 vs type 2 diabetes. Neurogastroenterology and motility Koch, K. L., Hasler, W. L., YATES, K. P., Parkman, H. P., Pasricha, P. J., Calles-Escandon, J., Snape, W. J., Abell, T. L., McCallum, R. W., Nguyen, L. A., Sarosiek, I., Farrugia, G., Tonascia, J., Lee, L., Miriel, L., HAMILTON, F. 2016; 28 (7): 1001-1015

  Abstract

  In studies of diabetic gastroparesis, patients with type 1 and type 2 diabetes mellitus (T1DM, T2DM) are often combined for analyses. We compared gastroparesis severity, healthcare utilization, psychological function, and quality of life in T1DM vs T2DM gastroparesis patients.Questionnaire, laboratory, and scintigraphy data from patients with gastroparesis and T1DM and T2DM from seven centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry were compared at enrollment and after 48 weeks. Multiple regression models assessed baseline and follow-up differences between diabetes subtypes.At baseline, T1DM patients (N = 78) had slower gastric emptying, more hospitalizations, more gastric stimulator implantations, higher hemoglobin A1c (HbA1c), and more anxiety vs T2DM patients (N = 59). Independent discriminators of patients with T1DM vs T2DM included worse gastroesophageal reflux disease, less bloating, more peripheral neuropathy, and fewer comorbidities (p ≤ 0.05). On follow-up, gastrointestinal (GI) symptom scores decreased only in T2DM (p < 0.05), but not in T1DM patients who reported greater prokinetic, proton pump inhibitor, anxiolytic, and gastric stimulator usage over 48 weeks (p ≤ 0.03). Gastrointestinal symptoms at baseline and 48 weeks with both subtypes were not associated with HbA1c, peripheral neuropathy, psychological factors, or quality of life.Baseline symptoms were similar in T1DM and T2DM patients, even though T1DM patients had worse gastric emptying delays and higher HbA1c suggesting other factors mediate symptom severity. Symptom scores at 48 weeks decreased in T2DM, but not T1DM patients, despite increased medical and surgical treatment utilization by T1DM patients. Defining causes of different outcomes in diabetic gastroparesis warrants further investigation.

  View details for DOI 10.1111/nmo.12800

  View details for PubMedID 26946489

  View details for PubMedCentralID PMC5319426

• Outcomes and Factors Associated With Reduced Symptoms in Patients With Gastroparesis GASTROENTEROLOGY Pasricha, P. J., Yates, K. P., Nguyen, L., Clarke, J., Abell, T. L., Farrugia, G., Hasler, W. L., Koch, K. L., Snape, W. J., McCallum, R. W., Sarosiek, I., Tonascia, J., Miriel, L. A., Lee, L., Hamilton, F., Parkman, H. P. 2015; 149 (7): 1762-?

  Abstract

  Gastroparesis is a chronic clinical syndrome characterized by delayed gastric emptying. However, little is known about patient outcomes or factors associated with reduction of symptoms.We studied adult patients with gastroparesis (of diabetic or idiopathic type) enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Gastroparesis Registry, seen every 16 weeks and treated according to the standard of care with prescribed medications or other therapies at 7 tertiary care centers. Characteristics associated with reduced symptoms, based on a decrease of 1 or more in the gastroparesis cardinal symptom index (GCSI) score after 48 weeks of care, were determined from logistic regression models. Data were collected from patients for up to 4 years (median, 2.1 y).Of 262 patients, 28% had reductions in GCSI scores of 1 or more at 48 weeks. However, there were no significant reductions in GCSI score from weeks 48 through 192. Factors independently associated with reduced symptoms at 48 weeks included male sex, age 50 years and older, initial infectious prodrome, antidepressant use, and 4-hour gastric retention greater than 20%. Factors associated with no reduction in symptoms included overweight or obesity, a history of smoking, use of pain modulators, moderate to severe abdominal pain, a severe gastroesophageal reflex, and moderate to severe depression.Over a median follow-up period of 2.1 years, 28% of patients treated for gastroparesis at centers of expertise had reductions in GCSI scores of 1 or greater, regardless of diabetes. These findings indicate the chronic nature of gastroparesis. We identified factors associated with reduced symptoms that might be used to guide treatment. ClinicalTrials.gov no: NCT00398801.

  View details for DOI 10.1053/j.gastro.2015.08.008

  View details for Web of Science ID 000365808100030

  View details for PubMedID 26299414

  View details for PubMedCentralID PMC4663150

• Clinical Presentation and Pathophysiology of Gastroparesis GASTROENTEROLOGY CLINICS OF NORTH AMERICA Nguyen, L. A., Snape, W. J. 2015; 44 (1): 21-?

  Abstract

  Gastroparesis is a heterogeneous disorder defined by delay in gastric emptying. Symptoms of gastroparesis are nonspecific, including nausea, vomiting, early satiety, bloating, and/or abdominal pain. Normal gastric motor function and sensory function depend on a complex coordination between the enteric and central nervous system. This article discusses the pathophysiology of delayed gastric emptying and the symptoms of gastroparesis, including antropyloroduodenal dysmotility, impaired gastric accommodation, visceral hypersensitivity, and autonomic dysfunction. The underlying pathophysiology of gastroparesis is complex and multifactorial. The article discusses how a combination of these factors leads to symptoms of gastroparesis.

  View details for DOI 10.1016/j.gtc.2014.11.003

  View details for Web of Science ID 000350944600005

  View details for PubMedID 25667020

• Effect of Nortriptyline on Symptoms of Idiopathic Gastroparesis The NORIG Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Parkman, H. P., Van Natta, M. L., Abell, T. L., McCallum, R. W., Sarosiek, I., Nguyen, L., Snape, W. J., Koch, K. L., Hasler, W. L., Farrugia, G., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F., Pasricha, P. J. 2013; 310 (24): 2640-2649

  Abstract

  Gastroparesis remains a challenging syndrome to manage, with few effective treatments and a lack of rigorously controlled trials. Tricyclic antidepressants are often used to treat refractory symptoms of nausea, vomiting, and abdominal pain. Evidence from well-designed studies for this use is lacking.To determine whether treatment with nortriptyline results in symptomatic improvement in patients with idiopathic gastroparesis.The NORIG (Nortriptyline for Idiopathic Gastroparesis) trial, a 15-week multicenter, parallel-group, placebo-controlled, double-masked, randomized clinical trial from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC), comparing nortriptyline with placebo for symptomatic relief in idiopathic gastroparesis. One hundred thirty patients with idiopathic gastroparesis were enrolled between March 2009 and June 2012 at 7 US academic medical centers. Patient follow-up was completed in October 2012. Inclusion criteria included delayed gastric emptying and moderate to severe symptom scores using the Gastroparesis Cardinal Symptom Index (GCSI). INTERVENTIONS Nortriptyline vs placebo. Study drug dose was increased at 3-week intervals (10, 25, 50, 75 mg) up to 75 mg at 12 weeks.The primary outcome measure of symptomatic improvement was a decrease from the patient's baseline GCSI score of at least 50% on 2 consecutive 3-week GCSI assessments during 15 weeks of treatment.The primary symptomatic improvement outcome did not differ between 65 patients randomized to nortriptyline vs 65 patients randomized to placebo: 15 (23% [95% CI, 14%-35%]) in the nortriptyline group vs 14 (21% [95% CI, 12%-34%]) in the placebo group (P = .86). Treatment was stopped more often in the nortriptyline group (19 [29% {95% CI, 19%-42%}]) than in the placebo group (6 [9%] {95% CI, 3%-19%}]) (P = .007), but numbers of adverse events were not different (27 [95% CI, 18-39] vs 28 [95% CI, 19-40]) (P = .89).Among patients with idiopathic gastroparesis, the use of nortriptyline compared with placebo for 15 weeks did not result in improvement in overall symptoms. These findings do not support the use of nortriptyline for idiopathic gastroparesis.clinicaltrials.gov Identifier: NCT00765895.

  View details for DOI 10.1001/jama.2013.282833

  View details for Web of Science ID 000328818000016

  View details for PubMedID 24368464

  View details for PubMedCentralID PMC4099968

• Use of Esophageal pH Monitoring to Minimize Proton-Pump Inhibitor Utilization in Patients with Gastroesophageal Reflux Symptoms. Digestive diseases and sciences Triadafilopoulos, G., Zikos, T., Regalia, K., Sonu, I., Fernandez-Becker, N. Q., Nguyen, L., Nandwani, M. C., Clarke, J. O. 2018

  Abstract

  BACKGROUND: Due to concerns about long-term PPI use in patients with acid reflux, we aimed at minimizing PPI use, either by avoiding initiating therapy, downscaling to other therapies, or introducing endoscopic or surgical options.AIMS: To examine the role of esophageal ambulatory pHmetry in minimizing PPI use in patients with heartburn and acid regurgitation.METHODS: Retrospective cohort analysis of patients with reflux symptoms, who underwent endoscopy, manometry, and ambulatory pHmetry to define the need for PPI. Patients were classified as: (1) never users; (2) partial responders to PPI; (3) users with complete response to PPI. Patients were then managed as: (1) PPI non-users; (2) PPI-initiated, and (3) PPI-continued.RESULTS: Of 286 patients with heartburn and regurgitation, 103 (36%) were found to have normal and 183 (64%) abnormal esophageal acid exposure (AET). In the normal AET group, 44/103 had not been treated and were not initiated on PPI. Of the 59 who had previously received PPI, 52 stopped and 7 continued PPI. Hence, PPI were avoided in 96/103 patients (93%). In the abnormal AET group, 61/183 had not been treated and 38 were initiated on PPI and 23 on other therapies. In the 122 patients previously treated with PPI, 24 were not treated with PPI, but with H2RAs, prokinetics, endoscopic, or surgical therapy. Hence, PPI therapy was avoided in 47/183 patients (26%).CONCLUSIONS: In patients with GER symptoms, esophageal pHmetry may avert PPI use in 50%. In the era of caution regarding PPIs, early testing may provide assurance and justification.

  View details for DOI 10.1007/s10620-018-5183-4

  View details for PubMedID 29959725

• A Positive Correlation Between Gastric and Esophageal Dysmotility Suggests Common Causality. Digestive diseases and sciences Zikos, T. A., Clarke, J. O., Triadafilopoulos, G., Regalia, K. A., Sonu, I. S., Fernandez-Becker, N. Q., Nandwani, M. C., Nguyen, L. A. 2018

  Abstract

  BACKGROUND: Gastric and esophageal dysmotility syndromes are some of the most common motility diagnoses, but little is known about their interrelationship.AIMS: The aim of our study was to determine if a correlation exists between gastric and esophageal dysmotility syndromes.METHODS: We reviewed the records of all patients who underwent both solid gastric emptying scintigraphy (GES) and high-resolution esophageal manometry (HRM) withina 2 year period, with both done between August 2012 and August 2017. All GESs were classified as either rapid, normal, or delayed. All HRMs were classified according to the Chicago Classification 3.0. Correlations were assessed using Fisher's exact test and multiple logistic regression.RESULTS: In total, 482 patients met inclusion criteria. Of patients with a normal, delayed, and rapid GES, 53.1, 64.5, and 77.3% had an abnormal HRM, respectively (p<0.05 vs. normal GES). Likewise, patients with an abnormal HRM were more likely to have an abnormal GES (54.9 vs. 41.8%, p=0.005). Multiple logistic regression showed abnormal GES [odds ratio (OR) 2.14], age (OR 1.013), scleroderma (OR 6.29), and dysphagia (OR 2.63) were independent predictors of an abnormal HRM. Likewise, an abnormal HRM (OR 2.11), diabetes (OR 1.85), heart or lung transplantation (OR 2.61), and autonomic dysfunction (OR 2.37) were independent predictors of an abnormal GES.CONCLUSIONS: The correlation between an abnormal GES and HRM argues for common pathogenic mechanisms of these motility disorders, and possibly common future treatment options. Clinicians should have a high index of suspicion for another motility disorder if one is present.

  View details for DOI 10.1007/s10620-018-5175-4

  View details for PubMedID 29946871

• Intragastric Meal Distribution During Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis JOURNAL OF NUCLEAR MEDICINE Orthey, P., Yu, D., Van Natta, M. L., Ramsey, F. V., Diaz, J. R., Bennett, P. A., Iagaru, A. H., Fragomeni, R., McCallum, R. W., Sarosiek, I., Hasler, W. L., Farrugia, G., Grover, M., Koch, K. L., Nguyen, L., Snape, W. J., Abell, T. L., Pasricha, P. J., Tonascia, J., Hamilton, F., Parkman, H. P., Maurer, A. H., NIH Gastroparesis Consortium 2018; 59 (4): 691–97

  Abstract

  Impaired fundic accommodation (FA) limits fundic relaxation and the ability to act as a reservoir for food. Assessing intragastric meal distribution (IMD) during gastric emptying scintigraphy (GES) allows for a simple measure of FA. The 3 goals of this study were to evaluate trained readers' (nuclear medicine and radiology physicians) visual assessments of FA from solid-meal GES; develop software to quantify GES IMD; and correlate symptoms of gastroparesis with IMD and gastric emptying. Methods: After training to achieve a consensus interpretation of GES FA, 4 readers interpreted FA in 148 GES studies from normal volunteers and patients. Mixture distribution and κ-agreement analyses were used to assess reader consistency and agreement of scoring of FA. Semiautomated software was used to quantify IMD (ratio of gastric counts in the proximal stomach to those in the total stomach) at 0, 1, 2, 3, and 4 h after ingestion of a meal. Receiver-operating-characteristic analysis was performed to optimize the diagnosis of abnormal IMD at 0 min (IMD0) with impaired FA. IMD0, GES, water load testing, and symptoms were then compared in 177 patients with symptoms of gastroparesis. Results: Reader pairwise weighted κ-values for the visual assessment of FA averaged 0.43 (moderate agreement) for normal FA versus impaired FA. Readers achieved 84.0% consensus and 85.8% reproducibility in assessing impaired FA. IMD0 based on the division of the stomach into proximal and distal halves averaged 0.809 (SD, 0.083) for normal FA and 0.447 (SD, 0.132) (P < 0.01) for impaired FA. On the basis of receiver-operating-characteristic analysis, the optimal cutoff for IMD0 discrimination of normal FA from impaired FA was 0.568 (sensitivity, 86.7%; specificity, 91.7%). Of 177 patients with symptoms of gastroparesis, 129 (72.9%) had delayed gastric emptying; 25 (14.1%) had abnormal IMD0 Low IMD0 (impaired FA) was associated with increased early satiety (P = 0.02). Conclusion: FA can be assessed visually during routine GES with moderate agreement and high reader consistency. Visual and quantitative assessments of FA during GES can yield additional information on gastric motility to help explain patients' symptoms.

  View details for DOI 10.2967/jnumed.117.197053

  View details for Web of Science ID 000428981100036

  View details for PubMedID 28970332

  View details for PubMedCentralID PMC5932748

• Islet Cell Associated Autoantibodies and C-Peptide Levels in Patients with Diabetes and Symptoms of Gastroparesis FRONTIERS IN ENDOCRINOLOGY Siraj, E. S., Homko, C., Wilson, L. A., May, P., Rao, A. D., Calles, J., Farrugia, G., Hasler, W. L., Koch, K. L., Nguyen, L., Snape, W. J., Abell, T. L., Sarosiek, I., McCallum, R. W., Pasricha, P. J., Clarke, J., Tonascia, J., Hamilton, F., Parkman, H. P. 2018; 9: 32

  Abstract

  Individuals with diabetes are at increased risk for complications, including gastroparesis. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder resulting in decreased beta-cell function. Glutamic acid decarboxylase-65 antibody (GADA) is the most commonly used test to assess autoimmunity while C-peptide level is used to assess beta-cell function. Patients with type 2 diabetes mellitus (T2DM), who are GADA positive, are labeled latent autoimmune diabetes in adults (LADA).To characterize patients with T1 and T2DM who have symptoms of gastroparesis using GADA and C-peptide levels and to look for association with the presence of gastroparesis and its symptom severity.113 T1DM and 90 T2DM patients with symptoms suggestive of gastroparesis were studied. Symptom severity was assessed using Gastroparesis Cardinal Symptom Index (GCSI). Serum samples were analyzed for GADA and C-peptide.Delayed gastric emptying was present in 91 (81%) of T1DM and 60 (67%) of T2DM patients (p = 0.04). GADA was present in 13% of T2DM subjects [10% in delayed gastric emptying and 20% in normal gastric emptying (p = 0.2)]. Gastric retention and GCSI scores were mostly similar in GADA positive and negative T2DM patients. GADA was present in 45% of T1DM subjects [46% in delayed gastric emptying and 41% in normal gastric emptying (p = 0.81)]. Low C-peptide levels were seen in 79% T1DM patients and 8% T2DM. All seven T2DM patients with low C-peptide were taking insulin compared to 52% of T2DM with normal C-peptide.GADA was present in 13% while low C-peptide was seen in 8% of our T2DM patients with symptoms of gastroparesis. Neither did correlate with degree of delayed gastric emptying or symptom severity.NCT01696747.

  View details for DOI 10.3389/fendo.2018.00032

  View details for Web of Science ID 000424895800001

  View details for PubMedID 29487566

  View details for PubMedCentralID PMC5816742

• Repeat polymorphisms in the Homo sapiens heme oxygenase-1 gene in diabetic and idiopathic gastroparesis PLOS ONE Gibbons, S. J., Grover, M., Choi, K., Wadhwa, A., Zubair, A., Wilson, L. A., Wu, Y., Abell, T. L., Hasler, W. L., Koch, K. L., McCallum, R. W., Nguyen, L. B., Parkman, H. P., Sarosiek, I., Snape, W. J., Tonascia, J., Hamilton, F. A., Pasricha, P. J., Farrugia, G. 2017; 12 (11): e0187772

  Abstract

  Idiopathic and diabetic gastroparesis in Homo sapiens cause significant morbidity. Etiology or risk factors have not been clearly identified. Failure to sustain elevated heme oxygenase-1 (HO1) expression is associated with delayed gastric emptying in diabetic mice and polymorphisms in the HO1 gene (HMOX1, NCBI Gene ID:3162) are associated with worse outcomes in other diseases.Our hypothesis was that longer polyGT alleles are more common in the HMOX1 genes of individuals with gastroparesis than in controls without upper gastrointestinal motility disorders.Repeat length was determined in genomic DNA. Controls with diabetes (84 type 1, 84 type 2) and without diabetes (n = 170) were compared to diabetic gastroparetics (99 type 1, 72 type 2) and idiopathic gastroparetics (n = 234). Correlations of repeat lengths with clinical symptom sub-scores on the gastroparesis cardinal symptom index (GCSI) were done. Statistical analyses of short (<29), medium and long (>32) repeat alleles and differences in allele length were used to test for associations with gastroparesis.The distribution of allele lengths was different between groups (P = 0.016). Allele lengths were longest in type 2 diabetics with gastroparesis (29.18±0.35, mean ± SEM) and longer in gastroparetics compared to non-diabetic controls (28.50±0.14 vs 27.64±0.20 GT repeats/allele, P = 0.0008). Type 2 diabetic controls had longer alleles than non-diabetic controls. In all gastroparetic groups, allele lengths were longer in African Americans compared to other racial groups, differences in the proportion of African Americans in the groups accounted for the differences between gastroparetics and controls. Diabetic gastroparetics with 1 or 2 long alleles had worse GCSI nausea sub-scores (3.30±0.23) as compared to those with 0 long alleles (2.66±0.12), P = 0.022.Longer poly-GT repeats in the HMOX1 gene are more common in African Americans with gastroparesis. Nausea symptoms are worse in subjects with longer alleles.

  View details for DOI 10.1371/journal.pone.0187772

  View details for Web of Science ID 000415987000019

  View details for PubMedID 29161307

  View details for PubMedCentralID PMC5697813

• Epidemiology and Clinical Implications of Gastrointestinal Symptoms in Systemic Amyloidosis Yen, T., Chen, F., Witteles, R., Liedtke, M., Nguyen, L. NATURE PUBLISHING GROUP. 2017: S240

  View details for Web of Science ID 000439259001037

• Multi-Organ RNA-Sequencing of Patients with Systemic Sclerosis (SSc) Finds That Intrinsic Subsets Are Conserved across Organ Systems Mehta, B. K., Franks, J., Cai, G., Toledo, D., Wood, T. A., Archambault, K. A., Kosarek, N., Kolstad, K., Stark, M., Valenzuela, A., Fiorentino, D., Fernandez-Becker, N., Becker, L., Nguyen, L., Clarke, J., Boin, F., Wolters, P., Chung, L., Whitfield, M. L. WILEY. 2017

  View details for Web of Science ID 000411824106435

• Greater Impact of Wireless Motility Capsule Testing versus Gastric Emptying Scintigraphy on Clinical Decision Making in Patients With Suspected Gastroparesis: A Prospective, Multicenter Evaluation Hasler, W. L., Rao, S., McCallum, R. W., Krause, R., Nguyen, L., Schulman, M. I., Lee, A., Moshiree, B., Wo, J. M., Parkman, H. P., Sarosiek, I., Lourd, M., Datel, M., Kuo, B. NATURE PUBLISHING GROUP. 2017: S664

  View details for Web of Science ID 000439259003009

• Aprepitant for Symptoms of Gastroparesis and Related Disorders: The APRON Randomized Clinical Trial Pasricha, P., Yates, K., Sarosiek, I., McCallum, R., Clarke, J., Nguyen, L., Dhalla, S., Stein, E., Koch, K., Abell, T., Hasler, W., Snape, W., Lee, L., Grover, M., Miriel, L., Van Natta, M., Farrugia, G., Tonascia, J., Hamilton, F., Parkman, H. NATURE PUBLISHING GROUP. 2016: S480–S481

  View details for Web of Science ID 000395764601531

• Multi-Organ RNA-Sequencing of Systemic Sclerosis (SSc) Patients Shows Reproducible Gene Expression Profiles Across Organ Systems Mehta, B. K., Johnson, M. E., Archambault, K. A., Wood, T. A., Valenzuela, A., Crawford, A., Fiorentino, D., Fernandez-Becker, N., Becker, L., Nguyen, L., Boin, F., Wolters, P., Chung, L., Whitfield, M. WILEY. 2016

  View details for Web of Science ID 000417143401207

• Early Satiety and Postprandial Fullness in Gastroparesis Correlate With Gastroparesis Severity, Gastric Emptying, and Water Load Testing Digestive Disease Week (DDW) Parkman, H. P., Hallinan, E., Hasler, W. L., Farrugia, G., Pasricha, P. J., McCallum, R. W., Sarosiek, I., Koch, K. L., Snape, W. J., Abell, T. L., Nguyen, L. A., Tonascia, J., Hamilton, F. A., Clarke, J. O. W B SAUNDERS CO-ELSEVIER INC. 2016: S214–S215

  View details for Web of Science ID 000381575600657

• Intestinal pseudo-obstruction in patients with systemic sclerosis: an analysis of the Nationwide Inpatient Sample. Rheumatology Valenzuela, A., Li, S., Becker, L., Fernandez-Becker, N., Khanna, D., Nguyen, L., Chung, L. 2016; 55 (4): 654-658

  Abstract

  Intestinal pseudo-obstruction is a rare gastrointestinal complication in patients with SSc without large studies examining its prevalence or outcomes. We aimed to compare outcomes in SSc patients with intestinal pseudo-obstruction to patients with intestinal pseudo-obstruction secondary to other causes, and SSc patients without intestinal pseudo-obstruction.This is a case-control study using the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the period 2002-2011. We included patients with the previously validated International Classification of Diseases-Clinical Modification-9 code 710.1 for SSc in combination with codes for intestinal pseudo-obstruction, and determined length of hospitalization and the risks for surgical procedures, use of total parenteral nutrition (TPN) and in-hospital mortality.A total of 193 610 SSc hospitalizations occurred in the USA between 2002 and 2011, of which 5.4% (n = 10 386) were associated with a concurrent intestinal pseudo-obstruction diagnosis (cases). In-hospital mortality was 7.3%. In multivariate analyses, cases were more likely to die during the inpatient stay and to receive TPN than patients with idiopathic intestinal pseudo-obstruction (control group 1), patients with intestinal pseudo-obstruction and diabetes (control group 2), and SSc patients without intestinal pseudo-obstruction (control group 3). Cases had longer in-hospital stay than control groups 2 and 3, and were less likely to undergo surgical procedures than control groups 1 and 2.Intestinal pseudo-obstruction is a rare cause of hospitalization in patients with SSc, but is associated with high in-hospital mortality in comparison with other SSc patients and those with intestinal pseudo-obstruction secondary to other causes.

  View details for DOI 10.1093/rheumatology/kev393

  View details for PubMedID 26615031

• Feasibility and Usability Pilot Study of a Novel Irritable Bowel Syndrome Food and Gastrointestinal Symptom Journal Smartphone App CLINICAL AND TRANSLATIONAL GASTROENTEROLOGY Zia, J., Schroeder, J., Munson, S., Fogarty, J., Nguyen, L., Barney, P., Heitkemper, M., Ladabaum, U. 2016; 7

  Abstract

  Seventy percent of patients with irritable bowel syndrome (IBS) identify certain foods as triggers for their symptom flare-ups. To help identify potential trigger foods, practitioners often rely on patient food and gastrointestinal (GI) symptom journaling. The aim of the study was to evaluate the feasibility and usability of a novel food and symptom journal app, specifically designed for patients with IBS. Secondary aims were to explore the effect of using the app on GI symptoms and to describe associations between diet and GI symptoms suggested by individual patient data.The feasibility and usability of the novel app was studied in 11 IBS patients (8 women), aged 21-65 years. Participants were asked to log GI symptoms (abdominal pain, bloating, diarrhea, constipation) using a 100-point color-graded sliding scale (green=none, red=severe) four times a day and to log every meal/snack they ate (at least three times a day) over a 2-week period. The app's feasibility as a data collection tool was evaluated by daily completion, compliance, data hoarding, and fatigability rates. Usability was evaluated with the System Usability Scale (SUS). To explore potential impact of using the app on bowel distress, we compared before and after intervention IBS-Symptom Severity Scale (IBS-SSS) scores. Meal entries were analyzed for nutrients using the Nutrition Data System for Research. Regression analyses were conducted for each participant journal to explore relationships between meal nutrients and subsequent GI symptoms.Daily average completion rates of the minimum requested entries for meal and GI symptoms were 112±47% and 78±44%, respectively. Average 24-h compliance rates were 90±19% and 94±12%, respectively. The SUS score was above average (mean 83, range 65-97.5; n=10). Most participants did not have a clinically significant decrease in IBS-SSS. At least one strong association (P≤0.05) between GI symptoms and a meal nutrient was found in 73% of participants. The mean number of associations was 2 (range 0-7; n=11). Patterns of associations differed between individual participants.Our app appeared to be a feasible and usable tool for IBS patients. Our findings are in line with anecdotes that most IBS patients have food triggers and that these vary by individual. Future studies can explore whether individualized dietary changes guided by an app can result in IBS symptom improvement.

  View details for DOI 10.1038/ctg.2016.9

  View details for Web of Science ID 000373487400001

  View details for PubMedID 26938478

  View details for PubMedCentralID PMC4822101

• High Prevalence of Spastic Esophageal Motility Disorders in Post-Lung Transplant Patients Regalia, K., Sweatt, A., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S733

  View details for Web of Science ID 000363715903339

• Vitamin Abnormalities in Patients With Gastrointestinal Motility and Functional Disorders Sonu, I., Wang, L., Zia, J., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S751

  View details for Web of Science ID 000363715903381

• High Prevalence of Gastroparesis in Post Lung Transplant Patients Regalia, K., Sweatt, A., Wang, L., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S1029–S1030

  View details for Web of Science ID 000363715905115

• Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis NEUROGASTROENTEROLOGY AND MOTILITY Bernard, C. E., Gibbons, S. J., Mann, I. S., FROSCHAUER, L., Parkman, H. P., Harbison, S., Abell, T. L., Snape, W. J., Hasler, W. L., McCallum, R. W., Sarosiek, I., Nguyen, L. A., Koch, K. L., Tonascia, J., Hamilton, F. A., Kendrick, M. L., Shen, K. R., Pasricha, P. J., Farrugia, G. 2014; 26 (9): 1275-1284

  Abstract

  There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC.Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer.Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types.Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.

  View details for DOI 10.1111/nmo.12389

  View details for Web of Science ID 000341625000007

  View details for PubMedID 25041465

  View details for PubMedCentralID PMC4149814

• Massive gastrointestinal dilatation in a case of hereditary hollow visceral myopathy. Digestive and liver disease Huang, R. J., Yun, C., Nguyen, L. 2013; 45 (10): 866-?

  View details for DOI 10.1016/j.dld.2013.04.005

  View details for PubMedID 23816694

• Factors related to abdominal pain in gastroparesis: contrast to patients with predominant nausea and vomiting. Neurogastroenterology and motility Hasler, W. L., Wilson, L. A., Parkman, H. P., Koch, K. L., Abell, T. L., Nguyen, L., Pasricha, P. J., Snape, W. J., McCallum, R. W., Sarosiek, I., Farrugia, G., Calles, J., Lee, L., Tonascia, J., Unalp-Arida, A., HAMILTON, F. 2013; 25 (5): 427-?

  Abstract

  Factors associated with abdominal pain in gastroparesis are incompletely evaluated and comparisons of pain vs other symptoms are limited. This study related pain to clinical factors in gastroparesis and contrasted pain/discomfort- with nausea/vomiting-predominant disease.Clinical and scintigraphy data were compared in 393 patients from seven centers of the NIDDK Gastroparesis Clinical Research Consortium with moderate-severe (Patient Assessment of Upper Gastrointestinal Disorders Symptoms [PAGI-SYM] score ≥ 3) vs none-mild (PAGI-SYM < 3) upper abdominal pain and predominant pain/discomfort vs nausea/vomiting.Upper abdominal pain was moderate-severe in 261 (66%). Pain/discomfort was predominant in 81 (21%); nausea/vomiting was predominant in 172 (44%). Moderate-severe pain was more prevalent with idiopathic gastroparesis and with lack of infectious prodrome (P ≤ 0.05) and correlated with scores for nausea/vomiting, bloating, lower abdominal pain/discomfort, bowel disturbances, and opiate and antiemetic use (P < 0.05), but not gastric emptying or diabetic neuropathy or control. Gastroparesis severity, quality of life, and depression and anxiety were worse with moderate-severe pain (P ≤ 0.008). Factors associated with moderate-severe pain were similar in diabetic and idiopathic gastroparesis. Compared to predominant nausea/vomiting, predominant pain/discomfort was associated with impaired quality of life, greater opiate, and less antiemetic use (P < 0.01), but similar severity and gastric retention.Moderate-severe abdominal pain is prevalent in gastroparesis, impairs quality of life, and is associated with idiopathic etiology, lack of infectious prodrome, and opiate use. Pain is predominant in one fifth of gastroparetics. Predominant pain has at least as great an impact on disease severity and quality of life as predominant nausea/vomiting.

  View details for DOI 10.1111/nmo.12091

  View details for PubMedID 23414452

  View details for PubMedCentralID PMC3907086

• Cholecystectomy and Clinical Presentations of Gastroparesis DIGESTIVE DISEASES AND SCIENCES Parkman, H. P., Yates, K., Hasler, W. L., Linda Nguyen, L., Pasricha, P. J., Snape, W. J., Farrugia, G., Koch, K. L., Calles, J., Abell, T. L., Sarosiek, I., McCallum, R. W., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F. 2013; 58 (4): 1062-1073

  Abstract

  Many patients with gastroparesis have had their gallbladders removed.To determine if clinical presentations of patients with gastroparesis differ in those with prior cholecystectomy compared to patients who have not had their gallbladder removed.Gastroparetic patients were prospectively enrolled in the NIDDK Gastroparesis Registry. Detailed history and physical examinations were performed; patients filled out questionnaires including patient assessment of GI symptoms.Of 391 subjects with diabetic or idiopathic gastroparesis (IG), 142 (36 %) had a prior cholecystectomy at the time of enrollment. Patients with prior cholecystectomy were more often female, older, married, and overweight or obese. Cholecystectomy had been performed in 27/59 (46 %) of T2DM compared to 19/78 (24 %) T1DM and 96/254 IG (38 %) (p = 0.03). Patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety. Postcholecystectomy gastroparesis patients had increased health care utilization, and had a worse quality of life. Independent characteristics associated with prior cholecystectomy included insidious onset (OR = 2.06; p = 0.01), more comorbidities (OR = 1.26; p < 0.001), less severe gastric retention (OR(severe) = 0.68; overall p = 0.03) and more severe symptoms of retching (OR = 1.19; p = 0.02) and upper abdominal pain (OR = 1.21; p = 0.02), less severe constipation symptoms (OR = 0.84; p = 0.02), and not classified as having irritable bowel syndrome (OR = 0.51; p = 0.02). Etiology was not independently associated with a prior cholecystectomy.Symptom profiles in patients with and without cholecystectomy differ: postcholecystectomy gastroparesis patients had more severe upper abdominal pain and retching and less severe constipation. These data suggest that prior cholecystectomy is associated with selected manifestations of gastroparesis.

  View details for DOI 10.1007/s10620-013-2596-y

  View details for Web of Science ID 000317605800023

  View details for PubMedID 23456496

  View details for PubMedCentralID PMC3891205

• Platelet-derived growth factor receptor a (PDGFRa)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans NEUROGASTROENTEROLOGY AND MOTILITY Grover, M., Bernard, C. E., Pasricha, P. J., Parkman, H. P., Abell, T. L., Nguyen, L. A., Snape, W., Shen, K. R., Sarr, M., Swain, J., Kendrick, M., Gibbons, S., Ordog, T., Farrugia, G. 2012; 24 (9): 844-852

  Abstract

  Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced.Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified.Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients.In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.

  View details for DOI 10.1111/j.1365-2982.2012.01944.x

  View details for Web of Science ID 000308089000012

  View details for PubMedID 22650155

• Ultrastructural differences between diabetic and idiopathic gastroparesis JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Faussone-Pellegrini, M. S., Grover, M., Pasricha, P. J., Bernard, C. E., Lurken, M. S., Smyrk, T. C., Parkman, H. P., Abell, T. L., Snape, W. J., Hasler, W. L., Uenalp-Arida, A., Linda Nguyen, L., Koch, K. L., Calles, J., Lee, L., Tonascia, J., Hamilton, F. A., Farrugia, G. 2012; 16 (7): 1573-1581

  Abstract

  The ultrastructural changes in diabetic and idiopathic gastroparesis are not well studied and it is not known whether there are different defects in the two disorders. As part of the Gastroparesis Clinical Research Consortium, full thickness gastric body biopsies from 20 diabetic and 20 idiopathic gastroparetics were studied by light microscopy. Abnormalities were found in many (83%) but not all patients. Among the common defects were loss of interstitial cells of Cajal (ICC) and neural abnormalities. No distinguishing features were seen between diabetic and idiopathic gastroparesis. Our aim was to provide a detailed description of the ultrastructural abnormalities, compare findings between diabetic and idiopathic gastroparesis and determine if patients with apparently normal immunohistological features have ultrastructural abnormalities. Tissues from 40 gastroparetic patients and 24 age- and sex-matched controls were examined by transmission electron microscopy (TEM). Interstitial cells of Cajal showing changes suggestive of injury, large and empty nerve endings, presence of lipofuscin and lamellar bodies in the smooth muscle cells were found in all patients. However, the ultrastructural changes in ICC and nerves differed between diabetic and idiopathic gastroparesis and were more severe in idiopathic gastroparesis. A thickened basal lamina around smooth muscle cells and nerves was characteristic of diabetic gastroparesis whereas idiopathic gastroparetics had fibrosis, especially around the nerves. In conclusion, in all the patients TEM showed abnormalities in ICC, nerves and smooth muscle consistent with the delay in gastric emptying. The significant differences found between diabetic and idiopathic gastroparesis offers insight into pathophysiology as well as into potential targeted therapies.

  View details for DOI 10.1111/j.1582-4934.2011.01451.x

  View details for Web of Science ID 000305791600021

  View details for PubMedID 21914127

  View details for PubMedCentralID PMC3250562

• Clinical-histological associations in gastroparesis: results from the Gastroparesis Clinical Research Consortium NEUROGASTROENTEROLOGY AND MOTILITY Grover, M., Bernard, C. E., Pasricha, P. J., Lurken, M. S., Faussone-Pellegrini, M. S., Smyrk, T. C., Parkman, H. P., Abell, T. L., Snape, W. J., Hasler, W. L., McCallum, R. W., Nguyen, L., Koch, K. L., Calles, J., Lee, L., Tonascia, J., Uenalp-Arida, A., Hamilton, F. A., Farrugia, G. 2012; 24 (6): 531-?

  Abstract

  Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis.Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms [gastroparesis cardinal symptom index score (GCSI)], and gastric emptying were related to cellular alterations using Pearson's correlation coefficients.Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = -0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate.In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.

  View details for DOI 10.1111/j.1365-2982.2012.01894.x

  View details for Web of Science ID 000303995700006

  View details for PubMedID 22339929

  View details for PubMedCentralID PMC3353102

• Gastrointestinal Dysmotility DIGESTIVE DISEASES AND SCIENCES Nimgaonkar, A., Choi, J. W., Nguyen, L., Triadafilopoulos, G. 2012; 57 (5): 1130-1133

  View details for DOI 10.1007/s10620-011-1946-x

  View details for Web of Science ID 000303385100004

  View details for PubMedID 22038542

• Similarities and Differences Between Diabetic and Idiopathic Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Parkman, H. P., Yates, K., Hasler, W. L., Nguyen, L., Pasricha, P. J., Snape, W. J., Farrugia, G., Koch, K. L., Calles, J., Abell, T. L., McCallum, R. W., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F. 2011; 9 (12): 1056-1064

  Abstract

  Gastroparesis can be diabetic or idiopathic, yet little is known about differences in their presentation. We compared clinical characteristics, symptoms, and gastric emptying in patients with type 1 or type 2 diabetic (DG) or idiopathic (IG) gastroparesis.We analyzed data from 416 patients with gastroparesis who were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry; 254 had IG (most were female and white), and 137 had DG (78 had type 1 and 59 had type 2). Registry data included detailed histories, physical examinations, results from gastric emptying scintigraphy, and responses to validated symptom questionnaires.Patients with type 2 diabetes mellitus (DM) were an average of 13 years older at the onset of symptoms of gastroparesis and heavier than patients with IG. Patients with type 1 DM had more hospitalizations in the past year than patients with IG. Symptoms that prompted evaluation more often included vomiting for DG and abdominal pain for IG. Patients with DG had more severe retching and vomiting than those with IG, whereas patients with IG had more severe early satiety and postprandial fullness subscores. Compared with IG, gastric retention was greater in patients with type 1 DM. More than 50% of patients with type 1 DM had severe retention (>35% at 4 hours); they took prokinetic agents more frequently and were more likely to receive gastric electric stimulation.There are similarities and differences in clinical characteristics of DG and IG. Gastroparesis is a heterogeneous disorder; its etiology affects symptoms and severity. Long-term studies are needed to determine whether the differences in symptoms and gastric emptying affect progression and treatment responses.

  View details for DOI 10.1016/j.cgh.2011.08.013

  View details for Web of Science ID 000297754100018

  View details for PubMedID 21871247

  View details for PubMedCentralID PMC3499102

• Bloating in Gastroparesis: Severity, Impact, and Associated Factors AMERICAN JOURNAL OF GASTROENTEROLOGY Hasler, W. L., Wilson, L. A., Parkman, H. P., Linda Nguyen, L., Abell, T. L., Koch, K. L., Pasricha, P. J., Snape, W. J., Farrugia, G., Lee, L., Tonascia, J., Unalp-Arida, A., Hamilton, F. 2011; 106 (8): 1492-1502

  Abstract

  Bloating is commonly reported in gastroparesis, but its prevalence, impact, and associated factors are uninvestigated. We aimed to quantify the prevalence of bloating in gastroparesis and relate its severity to clinical factors and quality of life.Survey, examination, and scintigraphy data were compared in 335 gastroparesis patients from 6 centers of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Gastroparesis Clinical Research Consortium. Bloating severity was stratified using Gastroparesis Cardinal Symptom Index (GCSI) bloating subscale scores.Bloating severity of at least mild (GCSI ≥2) and severe (GCSI ≥4) grades were reported by 76 and 41% of patients, respectively. Bloating severity related to female gender (P<0.0001) and overweight status (P=0.04) on regression analysis and correlated with intensity of nausea, postprandial fullness, visible distention, abdominal pain, and altered bowel function (P<0.05). Disease etiology, smoking status, and gastric emptying did not relate to bloating subset (P>0.05). Disease-specific quality of life and general measures of well-being were progressively impaired with increasing bloating severity (P=0.01). Probiotic use (P=0.03) and use of antidepressants with significant norepinephrine reuptake inhibitor activity (P=0.045) use related to bloating severity; antiemetic use trended higher with worsening bloating (P=0.06).Bloating is prevalent in gastroparesis and is severe in many individuals. Bloating severity relates to female gender, body weight, and intensity of other symptoms. The symptom impairs quality of life but is not influenced by gastric emptying rates. Antiemetics, probiotics, and antidepressants with significant norepinephrine reuptake inhibitor activity may affect reports of bloating. These findings provide insight into this underappreciated symptom of gastroparesis.

  View details for DOI 10.1038/ajg.2011.81

  View details for Web of Science ID 000293453200012

  View details for PubMedID 21483459

  View details for PubMedCentralID PMC3137717

• Dietary Intake and Nutritional Deficiencies in Patients With Diabetic or Idiopathic Gastroparesis GASTROENTEROLOGY Parkman, H. P., Yates, K. P., Hasler, W. L., Nguyan, L., Pasricha, P. J., Snape, W. J., Farrugia, G., Calles, J., Koch, K. L., Abell, T. L., McCallum, R. W., Petito, D., Parrish, C. R., Duffy, F., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F. 2011; 141 (2): 486-U571

  Abstract

  Gastroparesis can lead to food aversion, poor oral intake, and subsequent malnutrition. We characterized dietary intake and nutritional deficiencies in patients with diabetic and idiopathic gastroparesis.Patients with gastroparesis on oral intake (N = 305) were enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry and completed diet questionnaires at 7 centers. Medical history, gastroparesis symptoms, answers to the Block Food Frequency Questionnaire, and gastric emptying scintigraphy results were analyzed.Caloric intake averaged 1168 ± 801 kcal/day, amounting to 58% ± 39% of daily total energy requirements (TER). A total of 194 patients (64%) reported caloric-deficient diets, defined as <60% of estimated TER. Only 5 patients (2%) followed a diet suggested for patients with gastroparesis. Deficiencies were present in several vitamins and minerals; patients with idiopathic disorders were more likely to have diets with estimated deficiencies in vitamins A, B(6), C, K, iron, potassium, and zinc than diabetic patients. Only one-third of patients were taking multivitamin supplements. More severe symptoms (bloating and constipation) were characteristic of patients who reported an energy-deficient diet. Overall, 32% of patients had nutritional consultation after the onset of gastroparesis; consultation was more likely among patients with longer duration of symptoms and more hospitalizations and patients with diabetes. Multivariable logistic regression analysis indicated that nutritional consultation increased the chances that daily TER were met (odds ratio, 1.51; P = .08).Many patients with gastroparesis have diets deficient in calories, vitamins, and minerals. Nutritional consultation is obtained infrequently but is suggested for dietary therapy and to address nutritional deficiencies.

  View details for DOI 10.1053/j.gastro.2011.04.045

  View details for Web of Science ID 000293523300028

  View details for PubMedID 21684286

  View details for PubMedCentralID PMC3499101

• Characteristics of Patients With Chronic Unexplained Nausea and Vomiting and Normal Gastric Emptying CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Pasricha, P. J., Colvin, R., Yates, K., Hasler, W. L., Abell, T. L., Uenalp-Arida, A., Nguyen, L., Farrugia, G., Koch, K. L., Parkman, H. P., Snape, W. J., Lee, L., Tonascia, J., Hamilton, F. 2011; 9 (7): 567-U89

  Abstract

  Chronic nausea and vomiting with normal gastric emptying is a poorly understood syndrome; we analyzed its characteristics.We collected and analyzed data from 425 patients with chronic nausea and vomiting, enrolled at 6 centers by the Gastroparesis Clinical Research Consortium in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Registry.Among the patients, 319 (75%) had delayed emptying, defined by the results of a standardized, low-fat meal, and 106 had normal gastric emptying. Patients with or without delayed emptying did not differ in age, sex, or race, although those with normal gastric emptying were less likely to be diabetic. Symptom severity indexes were similar between groups for nausea, retching, vomiting, stomach fullness, inability to complete a meal, feeling excessively full after meals, loss of appetite, bloating, and visibly larger stomach. There were no differences in health care utilization, quality of life indexes, depression, or trait anxiety scores. However, state anxiety scores were slightly higher among patients with delayed gastric emptying. Total gastroparesis cardinal symptom index scores were not correlated with gastric retention after 2 or 4 hours in either group. Patients with the syndrome were not adequately captured by the stand-alone criteria for the Rome III diagnoses of chronic idiopathic nausea and functional vomiting. With rare exceptions, the diagnosis remained stable after a 48-week follow-up period.Patients with nausea and vomiting with normal gastric emptying represent a significant medical problem and are, for the most part, indistinguishable from those with gastroparesis. This syndrome is not categorized in the medical literature--it might be a separate clinical entity.

  View details for DOI 10.1016/j.cgh.2011.03.003

  View details for Web of Science ID 000292467900015

  View details for PubMedID 21397732

  View details for PubMedCentralID PMC3123425

• Idiopathic Gastroparesis or Functional Dyspepsia With Delayed Gastric Emptying: Where Is the Difference? Reply GASTROENTEROLOGY Parkman, H. P., Hasler, W. L., Nguyen, L., Pasricha, P. J., Snape, W. J., Farrugia, G., Koch, K. L., Abell, T. L., McCallum, R. W., Yates, K., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F. 2011; 140 (7): 2146-2148

  View details for DOI 10.1053/j.gastro.2011.04.040

  View details for Web of Science ID 000291388200048

• Cellular Changes in Diabetic and Idiopathic Gastroparesis GASTROENTEROLOGY Grover, M., Farrugia, G., Lurken, M. S., Bernard, C. E., Faussone-Pellegrini, M. S., Smyrk, T. C., Parkman, H. P., Abell, T. L., Snape, W. J., Hasler, W. L., Unalp-Arida, A., Nguyen, L., Koch, K. L., Calles, J., Lee, L., Tonascia, J., Hamilton, F. A., Pasricha, P. J. 2011; 140 (5): 1575-U296

  Abstract

  Cellular changes associated with diabetic and idiopathic gastroparesis are not well described. The aim of this study was to describe histologic abnormalities in gastroparesis and compare findings in idiopathic versus diabetic gastroparesis.Full-thickness gastric body biopsy specimens were obtained from 40 patients with gastroparesis (20 diabetic) and matched controls. Sections were stained for H&E and trichrome and immunolabeled with antibodies against protein gene product (PGP) 9.5, neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide, substance P, and tyrosine hydroxylase to quantify nerves, S100β for glia, Kit for interstitial cells of Cajal (ICC), CD45 and CD68 for immune cells, and smoothelin for smooth muscle cells. Tissue was also examined by transmission electron microscopy.Histologic abnormalities were found in 83% of patients. The most common defects were loss of ICC with remaining ICC showing injury, an abnormal immune infiltrate containing macrophages, and decreased nerve fibers. On light microscopy, no significant differences were found between diabetic and idiopathic gastroparesis with the exception of nNOS expression, which was decreased in more patients with idiopathic gastroparesis (40%) compared with diabetic patients (20%) by visual grading. On electron microscopy, a markedly increased connective tissue stroma was present in both disorders.This study suggests that on full-thickness biopsy specimens, cellular abnormalities are found in the majority of patients with gastroparesis. The most common findings were loss of Kit expression, suggesting loss of ICC, and an increase in CD45 and CD68 immunoreactivity. These findings suggest that examination of tissue can lead to valuable insights into the pathophysiology of these disorders and offer hope that new therapeutic targets can be found.

  View details for DOI 10.1053/j.gastro.2011.01.046

  View details for Web of Science ID 000290028200038

  View details for PubMedID 21300066

  View details for PubMedCentralID PMC3081914

• Colonic ulceration as an unusual manifestation of vasculopathy in systemic sclerosis RHEUMATOLOGY Kao, L., Myer, P., Nguyen, L., Zamanian, R. T., Chung, L. 2011; 50 (3): 626-628

  View details for DOI 10.1093/rheumatology/keq276

  View details for Web of Science ID 000287745600030

  View details for PubMedID 21172924

• Clinical Features of Idiopathic Gastroparesis Vary With Sex, Body Mass, Symptom Onset, Delay in Gastric Emptying, and Gastroparesis Severity GASTROENTEROLOGY Parkman, H. P., Yates, K., Hasler, W. L., Nguyen, L., Pasricha, P. J., Snape, W. J., Farrugia, G., Koch, K. L., Abell, T. L., McCallum, R. W., Lee, L., Unalp-Arida, A., Tonascia, J., Hamilton, F. 2011; 140 (1): 101-?

  Abstract

  Idiopathic gastroparesis (IG) is a common but poorly understood condition with significant morbidity. We studied characteristics of patients with IG enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium Registry.Data from medical histories, symptom questionnaires, and 4-hour gastric emptying scintigraphy studies were obtained from patients with IG.The mean age of 243 patients with IG studied was 41 years; 88% were female, 46% were overweight, 50% had acute onset of symptoms, and 19% reported an initial infectious prodrome. Severe delay in gastric emptying (>35% retention at 4 hours) was present in 28% of patients. Predominant presenting symptoms were nausea (34%), vomiting (19%), an abdominal pain (23%). Women had more severe nausea, satiety, constipation, and overall gastroparesis symptoms. Patients who experienced acute-onset IG had worse nausea than those with insidious onset. Overweight patients had more bloating and gastric retention at 2 hours but less severe loss of appetite. Patients with severely delayed gastric emptying had worse vomiting and more severe loss of appetite and overall gastroparesis symptoms. Severe anxiety and depression were present in 36% and 18%, respectively. A total of 86% met criteria for functional dyspepsia, primarily postprandial distress syndrome.IG is a disorder that primarily affects young women, beginning acutely in 50% of cases; unexpectedly, many patients are overweight. Severe delay in gastric emptying was associated with more severe symptoms of vomiting and loss of appetite. IG is a diverse syndrome that varies by sex, body mass, symptom onset, and delay in gastric emptying.

  View details for DOI 10.1053/j.gastro.2010.10.015

  View details for Web of Science ID 000285503200026

  View details for PubMedID 20965184

  View details for PubMedCentralID PMC3089423

• Psychological Dysfunction Is Associated With Symptom Severity but Not Disease Etiology or Degree of Gastric Retention in Patients With Gastroparesis AMERICAN JOURNAL OF GASTROENTEROLOGY Hasler, W. L., Parkman, H. P., Wilson, L. A., Pasricha, P. J., Koch, K. L., Abell, T. L., Snape, W. J., Farrugia, G., Lee, L., Tonascia, J., Unalp-Arida, A., Hamilton, F. 2010; 105 (11): 2357-2367

  Abstract

  Gastroparesis patients may have associated psychological distress. This study aimed to measure depression and anxiety in gastroparesis in relation to disease severity, etiology, and gastric retention.Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scores for state (Y1) and trait (Y2) anxiety were obtained from 299 gastroparesis patients from 6 centers of the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium. Severity was investigator graded as grades 1, 2, or 3 and patient reported by Gastroparesis Cardinal Symptom Index (GCSI) scores. Antiemetic/prokinetic medication use, anxiolytic and antidepressant medication use, supplemental feedings, and hospitalizations were recorded. BDI, Y1, and Y2 scores were compared in diabetic vs. idiopathic etiologies and mild (≤20%) vs. moderate (>20-35%) vs. severe (>35-50%) vs. very severe (>50%) gastric retention at 4 h.BDI, Y1, and Y2 scores were greater with increasing degrees of investigator-rated gastroparesis severity (P<0.05). BDI, Y1, and Y2 scores were higher for GCSI >3.1 vs. ≤3.1 (P<0.05). Antiemetic and prokinetic use and ≥6 hospitalizations/year were more common with BDI ≥20 vs. <20 (P<0.05). Anxiolytic use was more common with Y1≥46; antidepressant use and ≥6 hospitalizations/year were more common with Y2≥44 (P<0.05). BDI, Y1, and Y2 scores were not different in diabetic and idiopathic gastroparesis and did not relate to degree of gastric retention. On logistic regression, GCSI >3.1 was associated with BDI ≥20 and Y1≥46; antiemetic/prokinetic use was associated with BDI≥20; anxiolytic use was associated with Y1≥46; and antidepressant use was associated with Y2≥44.Higher depression and anxiety scores are associated with gastroparesis severity on investigator- and patient-reported assessments. Psychological dysfunction does not vary by etiology or degree of gastric retention. Psychological features should be considered in managing gastroparesis.

  View details for DOI 10.1038/ajg.2010.253

  View details for Web of Science ID 000283775600005

  View details for PubMedID 20588262

  View details for PubMedCentralID PMC3070288