Bio


Food has always been a big part of my life. Imagine what life would be like if eating made you sick? Because we need food to survive and we are social creatures who revolve much of our lives around food, not being able to eat impacts physical, mental and social well-being. It is this intricate interconnection between the brain and the gut which drew me to the field of Neurogastroenterology & Motility. Disorders affecting the function of the gastrointestinal tract can lead to a variety of disorders, including gastroparesis, functional dyspepsia and irritable bowel syndrome (IBS). My research includes understanding the role/impact of physiologic testing on clinical care, exploring novel therapies for gastroparesis and expanding the role of neuromodulation in the treatment of GI motility disorders and pain. I am also interested in understanding overlapping conditions such as chronic fatigue syndrome and Ehlers-Danlos syndrome as it relates to pathophysiology and impact on gastrointestinal symptoms and outcomes. As part of this interest, I have served on two ad-hoc committees for the National Academy of Science (Institute of Medicine): “Development of a Consensus Case Definition for Chronic Multisystem Illness in 1990-1991 Gulf War Veterans” and “Health Care Utilization and Adults with Disabilities”. I strive to improve quality of life for patients and health care providers through development of mindfulness, resilience, engagement and advocacy.

Areas of Special Interest: Gastroparesis, Chronic Nausea, Cyclic Vomiting, Irritable Bowel Syndrome, Autonomic dysfunction and Brain-gut disorders

Twitter.com/@LindaNguyenMD (Tweets are my own)

Clinical Focus


  • Gastroenterology
  • Gastroparesis
  • Dyspepsia
  • Nausea
  • Neurogastroenterology
  • Irritable Bowel Syndrome
  • Constipation
  • Abdominal pain
  • Intestinal Pseudoobstruction
  • Small intestinal bacterial overgrowth
  • Motility
  • Autonomic Dysfunction
  • Esophageal Dysphagia

Academic Appointments


Administrative Appointments


  • Clinic Chief, Digestive Health Center (2018 - Present)
  • Director, GI Motility and Neurogastroenterology, Division of Gastroenterology (2008 - 2021)

Boards, Advisory Committees, Professional Organizations


  • Member, American Gastroenterology Association (2002 - Present)
  • Member, American Neurogastroenterology and Motility Society (2003 - Present)
  • Member, American College of Gastroenterology (2014 - Present)

Professional Education


  • Board Certification: American Board of Internal Medicine, Gastroenterology (2005)
  • Medical Education: UCLA GME Office (1999) CA
  • Residency: California Pacific Medical Center Internal Medicine Residency (2002) CA
  • Fellowship: California Pacific Medical Center (2005) CA
  • MD, UCLA School of Medicine (1999)

Community and International Work


  • Scholarship Committee

    Partnering Organization(s)

    Vietnamese Physician Association of Northern California

    Populations Served

    Graduating Vietnamese High School Seniors

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    No

Current Research and Scholarly Interests


My research interests focus on disorder of gastrointestinal motility. Specifically, those related to nausea and vomiting with or without gastroparesis, irritable bowel syndrome and chronic abdominal pain. My research focuses on understanding the cause of symptoms and development of new treatments targeting either symptom control and disease modification.

Clinical Trials


  • GI-Challenge Study for Gastroparesis Patients and Healthy Controls Recruiting

    Gastroparesis Patients and Healthy Controls ages 20-49 will be asked to participate in an observational study measuring vagal activity following food ingestion in order to establish parameters of autonomic nerve/vagal function in healthy human subjects compared to those with gastroparesis. Information generated from this study may be used in the future to establish what is normal and abnormal enteric vagal tone and how much vagal nerve stimulation treatment may be required to help patients with gastroparesis.

    View full details

  • Zemedy Application for Irritable Bowel Syndrome Not Recruiting

    The purpose of the study is investigate the effectiveness of Zemedy, a mobile application that enables the digital delivery of a CBT program to people with IBS.

    Stanford is currently not accepting patients for this trial. For more information, please contact Britany D Marsh, BA, 650-725-9321.

    View full details

Projects


  • Medical Mindfulness: Virtual Reality Mindfulness Therapy for Anxiety and Pain Management in Patients with Acute and Chronic Pain, Stanford University

    Determine the impact of VR mindfulness therapy on anxiety and pain in patients through various aspects of medical care

    Location

    Palo Alto, CA

    Collaborators

    • Samuel Rodriguez, Clinical Associate Professor, Anesthesiology, Perioperative and Pain Medicine
    • Thomas Caruso, Clinical Professor, Anesthesiology, Perioperative and Pain Medicine
    • Anava Wren, Clinical Assistant Professor, Pediatrics - Gastroenterology

2023-24 Courses


Graduate and Fellowship Programs


  • Gastroenterology & Hepatology (Fellowship Program)

All Publications


  • ACG Clinical Guideline: Gastroparesis. The American journal of gastroenterology Camilleri, M., Kuo, B., Nguyen, L., Vaughn, V. M., Petrey, J., Greer, K., Yadlapati, R., Abell, T. L. 2022; 117 (8): 1197-1220

    Abstract

    Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.

    View details for DOI 10.14309/ajg.0000000000001874

    View details for PubMedID 35926490

  • Whole Body Pain Distribution and Risk Factors for Widespread Pain Among Patients Presenting with Abdominal Pain: A Retrospective Cohort Study. Pain and therapy Hah, J. M., Aivaliotis, V. I., Hettie, G., Pirrotta, L. X., Mackey, S. C., Nguyen, L. A. 2022

    Abstract

    INTRODUCTION: Abdominal pain frequently co-occurs with pain in other body sites. Chronic overlapping pain conditions (COPCs) represent a group of widespread pain diagnoses. Our study characterized how patterns of somatic pain distribution are associated with COPCs and aimed to characterize predictors of widespread pain among patients with chronic abdominal pain.METHODS: This retrospective cohort study included adults presenting to a tertiary pain clinic, reporting abdominal pain at their initial visit, and with a follow-up visit at 12months. Body maps divided patients into localized, intermediate, and widespread pain distribution patterns. Diagnostic and psychosocial measures were assessed across groups at the initial and follow-up visits. We analyzed the association of baseline diagnoses and demographics and time-varying changes in psychosocial measures from initial to follow-up visit with changes in pain distribution over time with alternating logistic regression (ALR).RESULTS: Among 258 patients, most were female (91.5%) and reported widespread pain (61.5%). Those with widespread pain at baseline reported elevated anger and 60.0% of patients remained in the same pain category at follow-up. Multivariable ALR demonstrated higher pain interference (AOR 1.06, 95%CI 1.02-1.10, P=0.002), higher anxiety (AOR 1.05, 95%CI 1.01-1.09, P=0.01), more than one COPC at initial visit (AOR 2.85, 95%CI 1.59-5.11, P=0.0005), and initial visit widespread pain categorization (AOR 4.18, 95%CI 2.20-8.00, P<0.0001) were associated with an increased risk of widespread pain at the follow-up visit.CONCLUSION: Most patients with abdominal pain report additional pain locations at multiple other body sites, and non-localized pain persists 12months after pain treatment. Screening for widespread pain and COPC at the initial visit may identify patients at higher risk for persistent or new-onset widespread pain, and interventions to reduce pain interference and anxiety may promote reversal of widespread pain.

    View details for DOI 10.1007/s40122-022-00382-0

    View details for PubMedID 35467268

  • A link between gastrointestinal disorders and migraine: Insights into the gut-brain connection. Headache Aurora, S. K., Shrewsbury, S. B., Ray, S., Hindiyeh, N., Nguyen, L. 2021

    Abstract

    BACKGROUND: Migraine is a complex, multifaceted, and disabling headache disease that is often complicated by gastrointestinal (GI) conditions, such as gastroparesis, functional dyspepsia, and cyclic vomiting syndrome (CVS). Functional dyspepsia and CVS are part of a spectrum of disorders newly classified as disorders of gut-brain interaction (DGBI). Gastroparesis and functional dyspepsia are both associated with delayed gastric emptying, while nausea and vomiting are prominent in CVS, which are also symptoms that commonly occur with migraine attacks. Furthermore, these gastric disorders are comorbidities frequently reported by patients with migraine. While very few studies assessing GI disorders in patients with migraine have been performed, they do demonstrate a physiological link between these conditions.OBJECTIVE: To summarize the available studies supporting a link between GI comorbidities and migraine, including historical and current scientific evidence, as well as provide evidence that symptoms of GI disorders are also observed outside of migraine attacks during the interictal period. Additionally, the importance of route of administration and formulation of migraine therapies for patients with GI symptoms will be discussed.METHODS: A literature search of PubMed for articles relating to the relationship between the gut and the brain with no restriction on the publication year was performed. Studies providing scientific support for associations of gastroparesis, functional dyspepsia, and CVS with migraine and the impact these associations may have on migraine treatment were the primary focus. This is a narrative review of identified studies.RESULTS: Although the association between migraine and GI disorders has received very little attention in the literature, the existing evidence suggests that they may share a common etiology. In particular, the relationship between migraine, gastric motility, and vomiting has important clinical implications in the treatment of migraine, as delayed gastric emptying and vomiting may affect oral dosing compliance, and thus, the absorption and efficacy of oral migraine treatments.CONCLUSIONS: There is evidence of a link between migraine and GI comorbidities, including those under the DGBI classification. Many patients do not find adequate relief with oral migraine therapies, which further necessitates increased recognition of GI disorders in patients with migraine by the headache community.

    View details for DOI 10.1111/head.14099

    View details for PubMedID 33793965

  • Gastric Mucosal Immune Profiling and Dysregulation in Idiopathic Gastroparesis. Clinical and translational gastroenterology Gottfried-Blackmore, A. n., Namkoong, H. n., Adler, E. n., Martin, B. n., Gubatan, J. n., Fernandez-Becker, N. n., Clarke, J. O., Idoyaga, J. n., Nguyen, L. n., Habtezion, A. n. 2021; 12 (5): e00349

    Abstract

    It is unclear how immune perturbations may influence the pathogenesis of idiopathic gastroparesis, a prevalent functional disorder of the stomach which lacks animal models. Several studies have noted altered immune characteristics in the deep gastric muscle layer associated with gastroparesis, but data are lacking for the mucosal layer, which is endoscopically accessible. We hypothesized that immune dysregulation is present in the gastroduodenal mucosa in idiopathic gastroparesis and that specific immune profiles are associated with gastroparesis clinical parameters.In this cross-sectional prospective case-control study, routine endoscopic biopsies were used for comprehensive immune profiling by flow cytometry, multicytokine array, and gene expression in 3 segments of the stomach and the duodenal bulb. Associations of immune endpoints with clinical parameters of gastroparesis were also explored.The gastric mucosa displayed large regional variation of distinct immune profiles. Furthermore, several-fold increases in innate and adaptive immune cells were found in gastroparesis. Various immune cell types showed positive correlations with duration of disease, proton pump inhibitor dosing, and delayed gastric emptying.This initial observational study showed immune compartmentalization of the human stomach mucosa and significant immune dysregulation at the level of leukocyte infiltration in idiopathic gastroparesis patients that extends to the duodenum. Select immune cells, such as macrophages, may correlate with clinicopathological traits of gastroparesis. This work supports further mucosal studies to advance our understanding of gastroparesis pathophysiology.

    View details for DOI 10.14309/ctg.0000000000000349

    View details for PubMedID 33979305

  • Autonomic function in gastroparesis and chronic unexplained nausea and vomiting: Relationship with etiology, gastric emptying, and symptom severity. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Nguyen, L. n., Wilson, L. A., Miriel, L. n., Pasricha, P. J., Kuo, B. n., Hasler, W. L., McCallum, R. W., Sarosiek, I. n., Koch, K. L., Snape, W. J., Farrugia, G. n., Grover, M. n., Clarke, J. n., Parkman, H. P., Tonascia, J. n., Hamilton, F. n., Abell, T. L. 2020: e13810

    Abstract

    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.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.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].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.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.

    View details for DOI 10.1111/nmo.13810

    View details for PubMedID 32061038

  • Open-label pilot study: Non-invasive vagal nerve stimulation improves symptoms and gastric emptying in patients with idiopathic gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Gottfried-Blackmore, A., Adler, E. P., Fernandez-Becker, N., Clarke, J., Habtezion, A., Nguyen, L. 2019: e13769

    Abstract

    BACKGROUND: Gastroparesis, a chronic motility disorder characterized by delayed gastric emptying, abdominal pain, nausea, and vomiting, remains largely unexplained. Medical therapy is limited, reflecting the complex physiology of gastric sensorimotor function. Vagus nerve stimulation is an attractive therapeutic modality for gastroparesis, but prior methods required invasive surgery. In this open-label pilot study, we aimed to assess the benefit of non-invasive vagal nerve stimulation in patients with mild to moderate idiopathic gastroparesis.METHODS: Patients self-administered the gammaCore vagal nerve stimulator for 4weeks. The gastroparesis cardinal symptom index daily diary (GCSI-dd) was assessed during a two-week run-in period, ≥4weeks of therapy, and 4weeks after therapy was completed. Gastric emptying and autonomic function testing were also performed. The primary endpoint was an absolute reduction in CGSI-dd of 0.75 after nVNS.RESULTS: There was a total improvement in symptom scores (2.56±0.76 to 1.87±1.05; P=.01), with 6/15 (40%) participants meeting our primary endpoint. Therapy was associated with a reduction in gastric emptying (T1/2 155 vs 129minutes; P=.053, CI -0.4 to 45). Therapy did not correct autonomic function abnormalities, but was associated with modulation of reflex parasympathetic activity.CONCLUSIONS: Short-term non-invasive vagal nerve stimulation led to improved cardinal symptoms and accelerated gastric emptying in a subset of patients with idiopathic gastroparesis. Responders had more severe gastric delay at baseline and clinical improvement correlated with duration of therapy, but not with improvements in gastric emptying. Larger randomized sham-controlled trials of greater duration are needed to confirm the results of this pilot study.

    View details for DOI 10.1111/nmo.13769

    View details for PubMedID 31802596

  • Influence of Gastric Emptying and Gut Transit Testing on Clinical Management Decisions in Suspected Gastroparesis. Clinical and translational gastroenterology Hasler, W. L., Rao, S. S., McCallum, R. W., Krause, R. A., Nguyen, L. A., Schulman, M. I., Lee, A. A., Moshiree, B., Wo, J. M., Parkman, H. P., Sarosiek, I., Wilding, G. E., Kuo, B. 2019

    Abstract

    Gastric emptying scintigraphy (GES) or wireless motility capsules (WMCs) can evaluate upper gastrointestinal symptoms in suspected gastroparesis; WMC tests can also investigate lower gut symptoms. We aimed to determine whether these tests impact treatment plans and needs for additional diagnostic evaluation.In a prospective, multicenter study, 150 patients with gastroparesis symptoms simultaneously underwent GES and WMC testing. Based on these results, investigators devised management plans to recommend changes in medications, diet, and surgical therapies and order additional diagnostic tests.Treatment changes were recommended more often based on the WMC vs GES results (68% vs 48%) (P < 0.0001). Ordering of additional test(s) was eliminated more often with WMC vs GES (71% vs 31%) (P < 0.0001). Prokinetics (P = 0.0007) and laxatives (P < 0.0001) were recommended more often based on the WMC vs GES results. Recommendations for prokinetics and gastroparesis diets were higher and neuromodulators lower in subjects with delayed emptying on both tests (all P ≤ 0.0006). Laxatives and additional motility tests were ordered more frequently for delayed compared with normal WMC colonic transit (P ≤ 0.02). Multiple motility tests were ordered more often on the basis of GES vs WMC findings (P ≤ 0.004). Antidumping diets and transit slowing medications were more commonly recommended for rapid WMC gastric emptying (P ≤ 0.03).WMC transit results promote medication changes and eliminate additional diagnostic testing more often than GES because of greater detection of delayed gastric emptying and profiling the entire gastrointestinal tract in patients with gastroparesis symptoms.Gastric scintigraphy and WMCs have differential impact on management decisions in suspected gastroparesis.

    View details for DOI 10.14309/ctg.0000000000000084

    View details for PubMedID 31703026

  • Influence of Gastric Emptying and Gut Transit Testing on Clinical Management Decisions in Suspected Gastroparesis. Clinical and translational gastroenterology Hasler, W. L., Rao, S. S., McCallum, R. W., Krause, R. A., Nguyen, L. A., Schulman, M. I., Lee, A. A., Moshiree, B., Wo, J. M., Parkman, H. P., Sarosiek, I., Wilding, G. E., Kuo, B. 2019; 10 (10): e00084

    Abstract

    INTRODUCTION: Gastric emptying scintigraphy (GES) or wireless motility capsules (WMCs) can evaluate upper gastrointestinal symptoms in suspected gastroparesis; WMC tests can also investigate lower gut symptoms. We aimed to determine whether these tests impact treatment plans and needs for additional diagnostic evaluation.METHODS: In a prospective, multicenter study, 150 patients with gastroparesis symptoms simultaneously underwent GES and WMC testing. Based on these results, investigators devised management plans to recommend changes in medications, diet, and surgical therapies and order additional diagnostic tests.RESULTS: Treatment changes were recommended more often based on the WMC vs GES results (68% vs 48%) (P < 0.0001). Ordering of additional test(s) was eliminated more often with WMC vs GES (71% vs 31%) (P < 0.0001). Prokinetics (P = 0.0007) and laxatives (P < 0.0001) were recommended more often based on the WMC vs GES results. Recommendations for prokinetics and gastroparesis diets were higher and neuromodulators lower in subjects with delayed emptying on both tests (all P ≤ 0.0006). Laxatives and additional motility tests were ordered more frequently for delayed compared with normal WMC colonic transit (P ≤ 0.02). Multiple motility tests were ordered more often on the basis of GES vs WMC findings (P ≤ 0.004). Antidumping diets and transit slowing medications were more commonly recommended for rapid WMC gastric emptying (P ≤ 0.03).DISCUSSION: WMC transit results promote medication changes and eliminate additional diagnostic testing more often than GES because of greater detection of delayed gastric emptying and profiling the entire gastrointestinal tract in patients with gastroparesis symptoms.TRANSLATIONAL IMPACT: Gastric scintigraphy and WMCs have differential impact on management decisions in suspected gastroparesis.

    View details for DOI 10.14309/ctg.0000000000000084

    View details for PubMedID 31663906

  • High Prevalence of Slow Transit Constipation in Patients With Gastroparesis. Journal of neurogastroenterology and motility Zikos, T. A., Kamal, A. N., Neshatian, L., Triadafilopoulos, G., Clarke, J. O., Nandwani, M., Nguyen, L. A. 2019

    Abstract

    Background/Aims: Current evidence suggests the presence of motility or functional abnormalities in one area of the gastrointestinal tract increases the likelihood of abnormalities in others. However, the relationship of gastroparesis to chronic constipation (slow transit constipation and dyssynergic defecation) has been incompletely evaluated.Methods: We retrospectively reviewed the records of all patients with chronic dyspeptic symptoms and constipation who underwent both a solid gastric emptying scintigraphy and a highresolution anorectal manometry at our institution since January 2012. When available, Xray defecography and radiopaque marker colonic transit studies were also reviewed. Based on the gastric emptying results, patients were classified as gastroparesis or dyspepsia with normal gastric emptying (control group). Differences in anorectal and colonic findings were then compared between groups.Results: Two hundred and six patients met the inclusion criteria. Patients with gastroparesis had higher prevalence of slow transit constipation by radiopaque marker study compared to those with normal emptying (64.7% vs 28.1%, P = 0.013). Additionally, patients with gastroparesis had higher rates of rectocele (88.9% vs 60.0%, P = 0.008) and intussusception (44.4% vs 12.0%, P = 0.001) compared to patients with normal emptying. There was no difference in the rate of dyssynergic defecation between those with gastroparesis vs normal emptying (41.1% vs 42.1%, P = 0.880), and no differences in anorectal manometry findings.Conclusions: Patients with gastroparesis had a higher rate of slow transit constipation, but equal rates of dyssynergic defecation compared to patients with normal gastric emptying. These findings argue for investigation of possible delayed colonic transit in patients with gastroparesis and vice versa.

    View details for PubMedID 30870880

  • Complementary and Alternative Medicine for the Management of Irritable Bowel Syndrome. Gastroenterology & hepatology Nguyen, L. 2018; 14 (9): 536–38

    View details for PubMedID 30364316

  • 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 PubMedID 29946871

  • 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 PubMedID 29652893

  • 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 PubMedID 29111115

  • 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

  • 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 PubMedID 26299414

  • 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 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 PubMedID 24368464

  • BENEFITS OF PROKINETICS, GASTROPARESIS DIET, OR NEUROMODULATORS ALONE OR IN COMBINATION FOR SYMPTOMS OF GASTROPARESIS. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hasler, W. L., Lee, A. A., Moshiree, B., Surjanhata, B. C., Rao, S., Parkman, H. P., Nguyen, L. A., Sarosiek, I., Wo, J. M., Schulman, M. I., McCallum, R. W., Kuo, B. 2023

    Abstract

    Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies like gastroparesis diets or neuromodulators are often prescribed. Their therapeutic benefits alone or in combination remain unclear.129 patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time (GET) and gastric emptying scintigraphy (GES). Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables.In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (IQR -1.25, 0.05, P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P< .04) and most individual symptoms. Adjusting for GET on multivariate analyses showed greater GCSI decreases for non-delayed emptying for neuromodulators as solo new therapy (P = .01). GES, gender, diabetes, and functional dyspepsia did not influence responses to any treatment.Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with non-delayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826).

    View details for DOI 10.1016/j.cgh.2023.10.014

    View details for PubMedID 37913936

  • The Gut-brain Connection and Episodic Migraine: an Update. Current pain and headache reports Nguyen, L., Hindiyeh, N., Ray, S., Vann, R. E., Aurora, S. K. 2023

    Abstract

    Historical evidence suggests a shared underlying etiology for migraine and gastrointestinal (GI) disorders that involves the gut-brain axis. Here we provide narrative review of recent literature on the gut-brain connection and migraine to emphasize the importance of tailoring treatment plans for patients with episodic migraine who experience GI comorbidities and symptoms.Recent population-based studies report the prevalence of migraine and GI disorders as comorbidities as well as overlapping symptomology. American Headache Society (AHS) guidelines have integrated GI symptoms as part of migraine diagnostic criteria and recommend nonoral therapies for patients with GI symptoms or conditions. Nasal delivery is a recommended nonoral alternative; however, it is important to understand potential adverse events that may cause or worsen GI symptoms in some patients due to the site of drug deposition within the nasal cavity with some nasal therapies. Lastly, clinical perspectives emphasize the importance of identifying GI symptoms and comorbidities in patients with episodic migraine to best individualize migraine management. Support for an association between the gut-brain axis and migraine continues to prevail in recent literature; however, the relationship remains complex and not well elucidated. The presence of GI comorbidities and symptoms must be carefully considered when making treatment decisions for patients with episodic migraine.

    View details for DOI 10.1007/s11916-023-01175-6

    View details for PubMedID 37792173

    View details for PubMedCentralID 7020496

  • Prevalence and Predictive Factors of Small Intestinal Bacterial Overgrowth in Patients With Chronic Fatigue Syndrome Karhu, E., Neshatian, L., Fass, O., Sonu, I., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1351-S1352
  • The Impact of Language in Utilization of Upper Endoscopy for Diagnosis of Functional Dyspepsia Syed, N., Kamal, A., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2023: S1318
  • miR-10b-5p rescues leaky gut linked with gastrointestinal dysmotility and diabetes. United European gastroenterology journal Zogg, H., Singh, R., Ha, S. E., Wang, Z., Jin, B., Ha, M., Dafinone, M., Batalon, T., Hoberg, N., Poudrier, S., Nguyen, L., Yan, W., Layden, B. T., Dugas, L. R., Sanders, K. M., Ro, S. 2023

    Abstract

    BACKGROUND/AIM: Diabetes has substantive co-occurrence with disorders of gut-brain interactions (DGBIs). The pathophysiological and molecular mechanisms linking diabetes and DGBIs are unclear. MicroRNAs (miRNAs) are key regulators of diabetes and gut dysmotility. We investigated whether impaired gut barrier function is regulated by a key miRNA, miR-10b-5p,linking diabetesand gut dysmotility.METHODS: We created a new mouse line using the Mb3Cas12a/Mb3Cpf1 endonuclease todeletemir-10b globally. Loss of function studies in the mir-10b knockout (KO) mice were conducted to characterize diabetes, gut dysmotility, and gut barrier dysfunction phenotypes in these mice. Gain of function studieswere conducted by injecting these mir-10b KO mice with a miR-10b-5p mimic. Further, we performed miRNA-sequencing analysis from colonic mucosa from mir-10bKO, wild type,and miR-10b-5p mimic injected mice to confirm (1) deficiency of miR-10b-5p in KO mice, and (2) restoration of miR-10b-5p after the mimic injection.RESULTS: Congenital loss of mir-10b in mice led to the development of hyperglycemia, gut dysmotility, and gut barrier dysfunction. Gut permeability was increased, but expression of the tight junction protein Zonula occludens-1 was reducedin the colon of mir-10b KO mice. Patients with diabetes or constipation- predominant irritable bowel syndrome, a known DGBI that is linked to leaky gut, had significantly reduced miR-10b-5p expression. Injection of a miR-10b-5p mimic in mir-10b KO mice rescued these molecular alterations and phenotypes.CONCLUSIONS: Our study uncovered a potential pathophysiologic mechanism of gut barrier dysfunction that links both the diabetes and gut dysmotility phenotypes in mice lacking miR-10b-5p. Treatment with a miR-10b-5p mimic reversed the leaky gut, diabetic, and gut dysmotility phenotypes, highlighting the translational potential of the miR-10b-5p mimic.

    View details for DOI 10.1002/ueg2.12463

    View details for PubMedID 37723933

  • Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction. Movement disorders clinical practice Zhou, W., Triadafilopoulos, G., Gurland, B., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Miglis, M., Muppidi, S., Sinn, D. I., Jaradeh, S., Neshatian, L. 2023; 10 (7): 1074-1081

    Abstract

    Gastrointestinal dysfunction, particularly constipation, is among the most common non-motor manifestations in Parkinson's Disease (PD). We aimed to identify high-resolution anorectal manometry (HR-ARM) abnormalities in patients with PD using the London Classification.We conducted a retrospective review of all PD patients at our institution who underwent HR-ARM and balloon expulsion test (BET) for evaluation of constipation between 2015 and 2021. Using age and sex-specific normal values, HR-ARM recordings were re-analyzed and abnormalities were reported using the London Classification. A combination of Wilcoxon rank sum and Fisher's exact test were used.36 patients (19 women) with median age 71 (interquartile range [IQR]: 69-74) years, were included. Using the London Classification, 7 (19%) patients had anal hypotension, 17 (47%) had anal hypocontractility, and 3 women had combined hypotension and hypocontractility. Anal hypocontractility was significantly more common in women compared to men. Abnormal BET and dyssynergia were noted in 22 (61%) patients, while abnormal BET and poor propulsion were only seen in 2 (5%). Men had significantly more paradoxical anal contraction and higher residual anal pressures during simulated defecation, resulting in more negative recto-anal pressure gradients. Rectal hyposensitivity was seen in nearly one third of PD patients and comparable among men and women.Our data affirms the high prevalence of anorectal disorders in PD. Using the London Classification, abnormal expulsion and dyssynergia and anal hypocontractility were the most common findings in PD. Whether the high prevalence of anal hypocontractility in females is directly related to PD or other confounding factors will require further research.

    View details for DOI 10.1002/mdc3.13755

    View details for PubMedID 37476327

    View details for PubMedCentralID PMC10354598

  • The integrated relaxation pressure may not be an appropriate gold standard for deglutitive relaxation due to reliance on a single intragastric reference sensor. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Fass, O. Z., Regalia, K. A., Sweatt, A. J., Nandwani, M. C., Zikos, T. A., Fernandez-Becker, N. Q., Nguyen, L. A., Sonu, I. S., Triadafilopoulos, G., Clarke, J. O. 2023: e14635

    Abstract

    BACKGROUND: Integrated relaxation pressure (IRP) calculation depends on the selection of a single gastric reference sensor. Variable gastric pressure readings due to sensor selection can lead to diagnostic uncertainty. This study aimed to examine the effect of gastric reference sensor selection on IRP measurement and diagnosis.METHODS: We identified high-resolution manometry (HRM) conducted between January and November 2017 with at least six intragastric reference sensors. IRP measurements and Chicago Classification 3.0 (CCv3) diagnoses were obtained for each of six gastric reference sensors. Studies were categorized as "stable" (no change in diagnosis) or "variable" (change in diagnosis with gastric reference selection). Variable diagnoses were further divided into "variable normal/dysmotility" (≥1 normal IRP measurement and≥1 CCv3 diagnosis), or "variable dysmotility" (≥1 CCv3 diagnosis, only elevated IRP measurements). Bland-Altman plots were used to compare IRP measurements within HRM studies.KEY RESULTS: The analysis included 100 HRM studies, among which 18% had variable normal/dysmotility, and 10% had variable dysmotility. The average IRP difference between reference sensors was 6.7mmHg for variable normal/dysmotility and 5.9mmHg for variable dysmotility. The average difference between the proximal-most and distal-most sensors was -1.52mmHg (lower limit of agreement -10.03mmHg, upper limit of agreement 7.00mmHg).CONCLUSIONS & INFERENCES: IRP values can vary greatly depending on the reference sensor used, leading to inconsistent diagnoses in 28% of HRM studies. Choosing the correct gastric reference sensor is crucial for accurate test results and avoiding misdiagnosis. Standardization of reference sensor selection or supportive testing for uncertain results should be considered.

    View details for DOI 10.1111/nmo.14635

    View details for PubMedID 37357376

  • Exploring the Gut-Brain Connection in Gastroparesis with Autonomic and Gastric Myoelectric Monitoring. IEEE transactions on bio-medical engineering Subramanian, S., Kunkel, D. C., Nguyen, L., Coleman, T. P. 2023; PP

    Abstract

    OBJECTIVE: The goal of this study was to identify autonomic and gastric myoelectric biomarkers from throughout the day that differentiate patients with gastroparesis, diabetics without gastroparesis, and healthy controls, while providing insight into etiology.METHODS: We collected 19 24-hour recordings of electrocardiogram (ECG) and electrogastrogram (EGG) data from healthy controls and patients with diabetic or idiopathic gastroparesis. We used physiologically and statistically rigorous models to extract autonomic and gastric myoelectric information from the ECG and EGG data, respectively. From these, we constructed quantitative indices which differentiated the distinct groups and demonstrated their application in automatic classification paradigms and as quantitative summary scores.RESULTS: We identified several differentiators that separate healthy controls from gastroparetic patient groups, specifically around sleep and meals. We also demonstrated the downstream utility of these differentiators in automatic classification and quantitative scoring paradigms. Even with this small pilot dataset, automated classifiers achieved an accuracy of 79% separating autonomic phenotypes and 65% separating gastrointestinal phenotypes. We also achieved 89% accuracy separating controls from gastroparetic patients in general and 90% accuracy separating diabetics with and without gastroparesis. These differentiators also suggested varying etiologies for different phenotypes.CONCLUSION: The differentiators we identified were able to successfully distinguish between several autonomic and gastrointestinal (GI) phenotypes using data collected while at-home with non-invasive sensors.SIGNIFICANCE: Autonomic and gastric myoelectric differentiators, obtained using at-home recording of fully non-invasive signals, can be the first step towards dynamic quantitative markers to track severity, disease progression, and treatment response for combined autonomic and GI phenotypes.

    View details for DOI 10.1109/TBME.2023.3285491

    View details for PubMedID 37310840

  • Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction MOVEMENT DISORDERS CLINICAL PRACTICE Zhou, W., Triadafilopoulos, G., Gurland, B., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Miglis, M., Muppidi, S., Sinn, D., Jaradeh, S., Neshatian, L. 2023

    View details for DOI 10.1002/mdc3.13755

    View details for Web of Science ID 000982806800001

  • A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Abell, T. L., Kuo, B., Esfandyari, T., Pfeifer, N. D., Grimaldi, M., Renzulli, C., Tacchi, R., Zhou, K., Barnes, C. N., Nguyen, D. D., Nguyen, L., Talley, N. J., McCallum, R. 2023: e14523

    Abstract

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

    View details for DOI 10.1111/nmo.14523

    View details for PubMedID 36624727

  • Anorectal manometry for the diagnosis of pelvic floor disorders in patients with hypermobility spectrum disorders and hypermobile Ehlers-Danlos syndrome. BMC gastroenterology Zhou, W., Zikos, T. A., Halawi, H., Sheth, V. R., Gurland, B., Nguyen, L. A., Neshatian, L. 2022; 22 (1): 538

    Abstract

    INTRODUCTION: Functional gastrointestinal disorders (FGID) including impaired rectal evacuation are common in patients with Hypermobility Spectrum Disorder (HSD) or Hypermobile Ehlers-Danlos Syndrome (hEDS). The effect of connective tissue pathologies on pelvic floor function in HSD/hEDS remains unclear. We aimed to compare clinical characteristics and anorectal pressure profile in patients with HSD/hEDS to those of age and sex matched controls.METHODS: We conducted a retrospective review of all FGID patients who underwent high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) for evaluation of impaired rectal evacuation. Patients with HSD/hEDS were age and sex matched to a randomly selected cohort of control patients without HSD/hEDS. An abnormal BET was defined as the inability to expel a rectal balloon within 2minutes. Wilcoxon rank sum test and Fisher's exact test were used to make comparisons and logistic regression model for predictive factors for abnormal evacuation.RESULTS: A total of 144 patients (72 with HSD/hEDS and 72 controls) were analyzed. HSD/hEDS patients were more likely to be Caucasian (p<0.001) and nulliparous. Concurrent psychiatric disorders; depression, and anxiety (p<0.05), and somatic syndromes; fibromyalgia, migraine and sleep disorders (p<0.001) were more common in these patients. Rate of abnormal BET were comparable among the groups. HDS/hEDS patients had significantly less anal relaxation and higher residual anal pressures during simulated defecation, resulting in significantly more negative rectoanal pressure gradient. The remaining anorectal pressure profile and sensory levels were comparable between the groups. While diminished rectoanal pressure gradient was the determinant of abnormal balloon evacuation in non HSD/hEDS patients, increased anal resting tone and maximum volume tolerated were independent factors associated with an abnormal BET in HSD/hEDS patients. Review of defecography data from a subset of patients showed no significant differences in structural pathologies between HSD/hEDS and non HSD/hEDS patients.CONCLUSIONS: These results suggest anorectal pressure profile is not compromised by connective tissue pathologies in HSD patients. Whether concurrent psychosomatic disorders or musculoskeletal involvement impact the pelvic floor function in these patients needs further investigation.

    View details for DOI 10.1186/s12876-022-02572-8

    View details for PubMedID 36564719

  • High Resolution Anorectal Manometry Findings in Men and Women With Parkinson's Disease, Using London Classification Zhou, W., Sinn, D., Jaradeh, S., Muppidi, S., Miglis, M., Triadafilopoulos, G., Halawi, H., Becker, L., Garcia, P., Nguyen, L., Neshatian, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S407-S408
  • Hyperemesis Gravidarum and Nutritional Support. The American journal of gastroenterology Elkins, J. R., Oxentenko, A. S., Nguyen, L. A. 2022; 117 (10S): 2-9

    View details for DOI 10.14309/ajg.0000000000001957

    View details for PubMedID 36194027

  • Comparison of Gastrointestinal Symptoms and Gastric Emptying Scintigraphy Between Postural Orthostatic Tachycardia Patients With and Without Small Fiber Neuropathy Zhou, W., Sinn, D., Jaradeh, S., Muppidi, S., Miglis, M., Neshatian, L., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S408-S409
  • The Esophagus and Beyond: A Case of Refractory Chest Pain Syed, N. S., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2022: S1597-S1598
  • Environmental Pollutants are Associated with Irritable Bowel Syndrome in a Commercially Insured Cohort of California Residents. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Okafor, P. N., Dahlen, A., Youssef, M., Olayode, A., Sonu, I., Neshatian, L., Nguyen, L., Charu, V. 2022

    Abstract

    BACKGROUND AND AIMS: Prior studies have linked environmental pollutants with gastrointestinal (GI) diseases. Here, we quantify the relationships between seven pollutants and the zip code-level incidence of irritable bowel syndrome (IBS), functional dyspepsia (FD), inflammatory bowel diseases (IBD), and eosinophilic esophagitis (EoE) in California.METHODS: Claims in Optum's Clinformatics Data Mart (CDM) were linked with environmental exposures in California, derived from CalEnviroScreen 3.0. We identified adult patients with new diagnoses of each GI disease, and estimated claims-derived, zip-code level disease incidence rates. Two study periods were considered: 2009-2014 (ICD-9 era) and 2016-2019 (ICD-10 era). Multivariable negative binomial regression models were used to test associations between seven pollutants (ozone, particulate matter <2.5 microns [PM2.5], diesel emissions, drinking water contaminants, pesticides, toxic releases from industrial facilities, traffic density) and zip-code level incidence of the GI diseases along with a negative control outcome, adjusting for numerous potential confounders.RESULTS: Zip code-level IBS incidence was associated with PM2.5 (p<0.001 in both eras) and airborne toxic releases from facilities (p<0.001 in both eras). An increase of 1 microgram/m3 in PM2.5 or 1% in toxic releases translates to an increase in the IBS incidence rate of about 0.02 cases per 100 person-years. Traffic density and drinking water contaminant exposures were also associated with increasing IBS incidence, but these associations were not significant in both eras. Similarly, exposure to PM2.5, drinking water contaminants and airborne toxic releases from facilities were associated with FD incidence, though not in both eras. No significant associations were noted between pollutants and IBD or EoE incidence.CONCLUSION: Exposure to PM2.5 and airborne toxic releases from facilities are associated with higher IBS incidence among a cohort of commercially-insured Californians. Environmental pollutant exposure was not associated with the incidence of IBD and EoE in this cohort.

    View details for DOI 10.1016/j.cgh.2022.09.025

    View details for PubMedID 36202347

  • A phase IV clinical trial of gastrointestinal motility in adult patients with migraine before and after initiation of a calcitonin gene-related peptide ligand (galcanezumab) or receptor (erenumab) antagonist. Headache Kudrow, D., Nguyen, L., Semler, J., Stroud, C., Samaan, K., Hoban, D. B., Wietecha, L., Hsu, H., Pearlman, E. 2022

    Abstract

    OBJECTIVE: To compare effects of an initial dose of calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) antagonists on gastrointestinal (GI) motility in patients with migraine and to explore if the mechanistic difference contributes to GI adverse events (AEs).BACKGROUND: Different frequencies of constipation have been observed between CGRP mAbs that target the ligand (galcanezumab [GMB]) or receptor (erenumab [ERE]).METHODS: Patients (n=65) with migraine without significant GI symptoms were enrolled in a multi-center, single-blind phase IV clinical trial (NCT04294147) and randomized 1:1 to receive GMB (240mg; n=33) or ERE (140mg; n=32). GI whole and regional transit times were assessed using a wireless motility capsule 1week before and 2weeks after mAb administration. The primary endpoint was change from baseline in colonic transit time (CTT) within each treatment group. Other measures included GI Symptom Rating Scale (GSRS), Bristol Stool Form Scale (BSFS), and spontaneous bowel movement (SBM) evaluation. AEs were monitored throughout the study.RESULTS: Baseline characteristics indicated significant GI transit time variability with minimal GI reported symptoms. While not statistically significant, a numerical mean increase in CTT was observed in ERE patients (n = 28, mean [SD] at baseline: 33.8 [29.4] h; least square [LS] mean [SE] change: 5.8 [5.7] h, 95% confidence interval [CI] -5.7 to 17.2, p = 0.320), while GMB decreased CTT (n = 31, mean [SD] at baseline: 29.3 [24.5] h; LS mean [SE] change: -5.4 [5.4] h, 95% CI -16.2 to 5.5, p = 0.328) compared to baseline. No meaningful changes were observed in other regional transit times. ERE significantly reduced BSFS (LS mean [SE] score -0.5[0.2], p=0.004) and SBM (LS mean [SE] -1.2[0.5], p=0.0120), and increased GSRS-constipation compared to baseline (LS mean [SE] score 0.3[0.1], p=0.016). GMB increased GSRS-constipation (LS mean [SE] score 0.4[0.1], p=0.002). There were no discontinuations due to or serious AEs. A higher percentage of treatment-emergent AEs were reported with ERE than GMB (ERE: nine of 32 [28.1%] versus GMB: three of 33 [9.1%]), with constipation the most frequently reported (ERE: five of 32 [15.6%] versus GMB one of 33 [3.0%]).CONCLUSION: While the primary endpoint of this study was not met, secondary and tertiary endpoints support a within- and between-treatment change in GI effects suggesting possible mechanistic differences between ligand (GMB) and receptor (ERE) antagonism.

    View details for DOI 10.1111/head.14390

    View details for PubMedID 36111429

  • Short-Term Dairy Product Elimination and Reintroduction Minimally Perturbs the Gut Microbiota in Self-Reported Lactose-Intolerant Adults. mBio Smith, C. J., Dethlefsen, L., Gardner, C., Nguyen, L., Feldman, M., Costello, E. K., Kolodny, O., Relman, D. A. 2022: e0105122

    Abstract

    An outstanding question regarding the human gut microbiota is whether and how microbiota-directed interventions influence host phenotypic traits. Here, we employed a dietary intervention to probe this question in the context of lactose intolerance. To assess the effects of dietary dairy product elimination and (re)introduction on the microbiota and host phenotype, we studied 12 self-reported mildly lactose-intolerant adults with triweekly collection of fecal samples over a 12-week study period: 2weeks of baseline diet, 4weeks of dairy product elimination, and 6weeks of gradual whole cow milk (re)introduction. Of the 12 subjects, 6 reported either no dairy or only lactose-free dairy product consumption. A clinical assay for lactose intolerance, the hydrogen breath test, was performed before and after each of these three study phases, and 16S rRNA gene amplicon sequencing was performed on all fecal samples. We found that none of the subjects showed change in a clinically defined measure of lactose tolerance. Similarly, fecal microbiota structure resisted modification. Although the mean fraction of the genus Bifidobacterium, a group known to metabolize lactose, increased slightly with milk (re)introduction (from 0.0125 to 0.0206; Wilcoxon P=0.068), the overall structure of each subject's gut microbiota remained highly individualized and largely stable in the face of diet manipulation. IMPORTANCE Lactose intolerance is a gastrointestinal disorder diagnosed with a lactose hydrogen breath test. Lifestyle changes such as diet interventions can impact the gut microbiome; however, the role of the microbiome in lactose intolerance is unclear. Our study assessed the effects of a 12-week dietary dairy product elimination and (re)introduction on the microbiome and clinical lactose intolerance status in 12 adult self-reported lactose-intolerant individuals. We found each subject's gut microbiome remained highly individualized and largely stable in the face of this diet manipulation. We also report that none of the subjects showed change in a clinically defined measure of lactose tolerance.

    View details for DOI 10.1128/mbio.01051-22

    View details for PubMedID 35695459

  • Diagnostic journeys: characterization of patients and diagnostic outcomes from an academic second opinion clinic. Diagnosis (Berlin, Germany) Chao, S., Lotfi, J., Lin, B., Shaw, J., Jhandi, S., Mahoney, M., Singh, B., Nguyen, L., Halawi, H., Geng, L. N. 2022

    Abstract

    Diagnostic programs and second opinion clinics have grown and evolved in the recent years to help patients with rare, puzzling, and complex conditions who often suffer prolonged diagnostic journeys, but there is a paucity of literature on the clinical characteristics of these patients and the efficacy of these diagnostic programs. This study aims to characterize the diagnostic journey, case features, and diagnostic outcomes of patients referred to a team-based second opinion clinic at Stanford.Retrospective chart review was performed for 237 patients evaluated for diagnostic second opinion in the Stanford Consultative Medicine Clinic over a 5 year period. Descriptive case features and diagnostic outcomes were assessed, and correlation between the two was analyzed.Sixty-three percent of our patients were women. 49% of patients had a potential precipitating event within about a month prior to the start of their illness, such as medication change, infection, or medical procedure. A single clear diagnosis was determined in 33% of cases, whereas the remaining cases were assessed to have multifactorial contributors/diagnoses (20%) or remained unclear despite extensive evaluation (47%). Shorter duration of illness, fewer prior specialties seen, and single chief symptom were associated with higher likelihood of achieving a single clear diagnosis.A single-site academic consultative service can offer additional diagnostic insights for about half of all patients evaluated for puzzling conditions. Better understanding of the clinical patterns and patient experiences gained from this study helps inform strategies to shorten their diagnostic odysseys.

    View details for DOI 10.1515/dx-2022-0029

    View details for PubMedID 35596123

  • Model for multi-disciplinary, multi-institutional virtual learning: The Stanford Esophageal Virtual Collaborative Conference on benign esophageal diseases. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Kamal, A. N., Triadafilopoulos, G., Gyawali, C. P., Nguyen, L., Sayuk, G. S., Azagury, D. E., Tatum, R. P., Clarke, J. O. 2022: e14369

    View details for DOI 10.1111/nmo.14369

    View details for PubMedID 35340088

  • Utilizing Anorectal Manometry to Predict the Phenotype of Patients Who Will Benefit From a Squatting Assist Stool Ulsh, L., Nguyen, L., Gurland, B., Neshatian, L. LIPPINCOTT WILLIAMS & WILKINS. 2021: S218
  • Healthcare Resource Use Before and After the Initiation of Prucalopride Treatment: A Real World Study in Patients With Constipation in the US Cash, B. D., Lu, M., Terasawa, E., Terreri, B., Du, S., Ayyagari, R., Feuerstadt, P., Lembo, A., Moshiree, B., Nguyen, L., Boules, M., Schoenfeld, P. LIPPINCOTT WILLIAMS & WILKINS. 2021: S239-S240
  • Clinical Outcomes Before and After the Initiation of Prucalopride Treatment: A Real World Study in Patients With Constipation in the USA Lembo, A., Cash, B. D., Lu, M., Terasawa, E., Terreri, B., Du, S., Ayyagari, R., Feuerstadt, P., Moshiree, B., Boules, M., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2021: S224-S225
  • Healthcare Costs Before and After the Initiation of Prucalopride Treatment: A Real World Study in Patients With Constipation in the US Feuerstadt, P., Lu, M., Terasawa, E., Terreri, B., Du, S., Ayyagari, R., Cash, B. D., Lembo, A., Moshiree, B., Schoenfeld, P., Boules, M., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2021: S234-S235
  • Stigma experiences of patients living with gastroparesis. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Taft, T. H., Craven, M. R., Adler, E. P., Simons, M., Nguyen, L. 2021: e14223

    Abstract

    INTRODUCTION: Stigmatization toward chronic digestive diseases is well documented. Patients perceive others hold negative stereotypes toward their disease and may internalize these beliefs as true. Because of this, stigmatization is associated with poor outcomes across disease-related and psychosocial domains. No study to date evaluates stigmatization toward patients living with gastroparesis (GP), a poorly understood disease affecting gastric motility. We aimed to gain deep understanding of stigma in patients living with gastroparesis.METHODS: Patients with GP were recruited from two university-based gastroenterology practices as well as patient advocacy support groups. Participants underwent a semi-structured qualitative interview about their experiences with stigma related to their GP diagnosis, which were audio-recorded and transcribed to text for analysis using a grounded theory approach. Major themes with representative quotations were documented.RESULTS: Twenty-three patients participated. The majority were White, female, with idiopathic GP under the care of a gastroenterologist. All patients reported stigma related to GP. Seven major themes were found: stigma from healthcare providers, stigma within interpersonal relationships, GP as an invisible disease, blame, unsolicited suggestions on how to manage disease, disclosure, and stigma resistance.CONCLUSIONS: This is the first study to describe stigma experiences in patients with GP. The results suggest patients experience considerable stigmatization toward their condition from multiple sources. Patients also demonstrated resistance to negative beliefs, which can serve as a protective factor for the negative effects of disease stigma. Clinicians should be aware of stigma in GP patients, including their own potential internal biases and behaviors.

    View details for DOI 10.1111/nmo.14223

    View details for PubMedID 34337831

  • Mindfulness-Based Virtual Reality Intervention for Children and Young Adults with Inflammatory Bowel Disease: A Pilot Feasibility and Acceptability Study CHILDREN-BASEL Wren, A. A., Neiman, N., Caruso, T. J., Rodriguez, S., Taylor, K., Madill, M., Rives, H., Nguyen, L. 2021; 8 (5)

    Abstract

    The aim of this pilot study was to assess: (1) the feasibility and acceptability of a Mindfulness-Based Virtual Reality (MBVR) intervention among children and young adults with Inflammatory Bowel Disease (IBD), and (2) the preliminary efficacy of MBVR on key psychological (anxiety) and physical (pain) outcomes. Participants were 62 children to young adults with IBD (M = 15.6 years; 69.4% Crohn's disease; 58% male) recruited from an outpatient pediatric IBD clinic. Participants completed a baseline assessment, underwent the 6-min MBVR intervention, completed a post-intervention assessment and study satisfaction survey, and provided qualitative feedback. Results suggest strong feasibility and acceptability. Participants reported high levels of satisfaction with MBVR including high levels of enjoyment (M = 4.38; range 1-5) and relaxation (M = 4.35; range 1-5). Qualitative data revealed several key themes including participants interest in using MBVR in IBD medical settings (e.g., hospitalizations, IBD procedures, IBD treatments), as well as in their daily lives to support stress and symptom management. Preliminary analyses demonstrated improvements in anxiety (t = 4.79, p = 0.001) and pain (t = 3.72, p < 0.001) following MBVR. These findings provide initial support for the feasibility and acceptability of MBVR among children and young adults with IBD. Results also suggest MBVR may improve key IBD outcomes (e.g., anxiety, pain) and highlight the importance of conducting a randomized controlled trial and more rigorous research to determine intervention efficacy.

    View details for DOI 10.3390/children8050368

    View details for Web of Science ID 000653585100001

    View details for PubMedID 34063034

  • Regional Gastrointestinal Transit and Contractility Patterns Vary in Postural Orthostatic Tachycardia Syndrome (POTS). Digestive diseases and sciences Zhou, W., Zikos, T. A., Clarke, J. O., Nguyen, L. A., Triadafilopoulos, G., Neshatian, L. 2021

    Abstract

    BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic disorder that affects multiple organs, including the gastrointestinal system. These patients often have multiple GI complaints with a severe impact on their quality of life. GI dysmotility patterns in POTS remains poorly understood and difficult to manage.AIMS: The aim of this study was to investigate the diagnostic yield of wireless motility capsule in patients with gastrointestinal symptoms and POTS, with use of a symptomatic control group without POTS as a reference.METHODS: We retrospectively reviewed the charts of patients who had both autonomic testing and wireless motility capsule between 2016 and 2020. The two groups were divided into those with POTS and those without POTS (controls) as diagnosed through autonomic testing. We compared the regional transit times and motility patterns between the two groups using the data collected from wireless motility capsule.RESULTS: A total of 25% of POTS patients had delayed small bowel transit compared to 0% of non-POTS patients (p=0.047). POTS patients exhibited hypo-contractility patterns within the small bowel, including decreased contractions/min (2.95 vs. 4.22, p=0.011) and decreased motility index (101.36 vs. 182.11, p=0.021). In multivariable linear regression analysis, migraine predicted faster small bowel transit (p=0.007) and presence of POTS predicted slower small bowel transit (p=0.044).CONCLUSIONS: Motility abnormalities among POTS patients seem to affect mostly the small bowel and exhibit a general hypo-contractility pattern. Wireless motility capsule can be a helpful tool in patients with POTS and GI symptoms as it can potentially help guide treatment.

    View details for DOI 10.1007/s10620-020-06808-z

    View details for PubMedID 33428036

  • MiR-10b-5p Rescues Diabetes and Gastrointestinal Dysmotility. Gastroenterology Singh, R., Ha, S. E., Wei, L., Jin, B., Zogg, H., Poudrier, S. M., Jorgensen, B. G., Park, C., Ronkon, C. F., Bartlett, A., Cho, S., Morales, A., Chung, Y. H., Lee, M. Y., Park, J. K., Gottfried-Blackmore, A., Nguyen, L., Sanders, K. M., Ro, S. 2021

    Abstract

    BACKGROUND & AIMS: Interstitial cells of Cajal (ICCs) and pancreatic beta cells require receptor tyrosine kinase (KIT) to develop and function properly. Degeneration of ICCs is linked to diabetic gastroparesis. The mechanisms linking diabetes and gastroparesis are unclear, but may involve miRNA mediated post-transcriptional gene silencing in KIT+ cells.METHODS: We performed miRNA-seq analysis from isolated ICCs in diabetic mice and plasma from patients with idiopathic and diabetic gastroparesis. miR-10b-5p target genes were identified and validated in mouse and human cell lines. For loss-of-function studies, we used KIT+ cell-restricted mir-10b knockout mice and KIT+ cell depletion mice. For gain-of-function studies, a synthetic miR-10b-5p mimic was injected in multiple diabetic mouse models. We compared the efficacy of miR-10b-5p mimic treatment vs. antidiabetic and prokinetic medicines.RESULTS: miR-10b-5p is highly expressed in ICCs from healthy mice, but drastically depleted in ICCs from diabetic mice. A conditional knockout of mir-10b in KIT+-cells or depletion of KIT+-cells in mice leads to degeneration of beta cells and ICCs, resulting in diabetes and gastroparesis. miR-10b-5p targets the transcription factor Kruppel-like factor 11 (KLF11), which negatively regulates KIT expression. The miR-10b-5p mimic or Klf11 siRNAs injected into mir-10b knockout mice, diet-induced diabetic mice, and TALLYHO polygenic diabetic mice rescues the diabetes and gastroparesis phenotype for an extended period of time. Furthermore, the miR-10b-5p mimic is more effective in improving glucose homoeostasis and GI motility as compared with common antidiabetic and prokinetic medications.CONCLUSIONS: miR-10b-5p is a key regulator in diabetes and gastrointestinal dysmotility via the KLF11-KIT pathway. Restoration of miR-10b-5p may provide therapeutic benefits for these disorders.

    View details for DOI 10.1053/j.gastro.2020.12.062

    View details for PubMedID 33421511

  • Serotonin Deficiency is Associated with Delayed Gastric Emptying. Gastroenterology Wei, L. n., Singh, R. n., Ha, S. E., Martin, A. M., Jones, L. n., Jin, B. n., Jorgenson, B. G., Zogg, H. n., Chervo, T. n., Gottfried-Blackmore, A. n., Nguyen, L. n., Habtezion, A. n., Spencer, N. J., Keating, D. J., Sanders, K. M., Ro, S. n. 2021

    Abstract

    Gastrointestinal (GI) motility is regulated by serotonin (5-hydroxytryptamine, 5-HT), which is primarily produced by enterochromaffin (EC) cells in the GI tract. However, the precise roles of EC cell-derived 5-HT in regulating gastric motility remain a major point of conjecture. Using a novel transgenic mouse line, we investigated the distribution of EC cells and the pathophysiological roles of 5-HT deficiency in gastric motility in mice and humans.We developed an inducible, EC cell-specific Tph1CreERT2/+ mouse, which was used to generate a reporter mouse line, Tph1-tdTom, and an EC cell-depleted line, Tph1-DTA. We examined EC cell distribution, morphology, and subpopulations in reporter mice. GI motility was measured in vivo and ex vivo in EC cell-depleted mice. Additionally, we evaluated 5-HT content in biopsy and plasma specimens from patients with idiopathic gastroparesis (IG).Tph1-tdTom mice revealed EC cells were heterogeneously distributed throughout the GI tract with the greatest abundance in the antrum and proximal colon. Two subpopulations of EC cells were identified in the gut: self-renewal cells located at the base of the crypt and mature cells observed in the villi. Tph1-DTA mice displayed delayed gastric emptying, total GI transit, and colonic transit. These gut motility alterations were reversed by exogenous provision of 5-HT. Patients with IG had a significant reduction of antral EC cell numbers and 5-HT content, which negatively correlated with gastric emptying rate.The Tph1CreERT2/+ mouse provides a powerful tool to study the functional roles of EC cells in the GI tract. Our findings suggest a new pathophysiological mechanism of 5-HT deficiency in IG.

    View details for DOI 10.1053/j.gastro.2021.02.060

    View details for PubMedID 33662386

  • The fragility of randomized placebo-controlled trials for irritable bowel syndrome. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Williams, M. O., Sedarous, M., Dennis, B., Dlamini, V., Nwaiwu, O., Nguyen, L., Okafor, P. N. 2021; 33 (8): e14166

    Abstract

    The fragility index (FI) represents the number of participants whose status in a trial would have to change from a non-event (not experiencing the primary endpoint) to an event (experiencing the primary endpoint) in order to turn a statistically significant result into a non-significant result. We sought to evaluate the fragility indices of irritable bowel syndrome [IBS-mixed (IBS-M), IBS-constipation (IBS-C), & IBS-diarrhea (IBS-D)] trials.Irritable bowel syndrome trials published in high-impact journals were identified from Medline. Trials had to be in adults, randomized, parallel-armed, with at least one statistically significant binary outcome, and an achieved primary endpoint of therapeutic efficacy. FI and correlation coefficients were calculated, and regression modeling used to identify predictors of a high FI.Twelve trials were analyzed with a median FI of 6 (range: 0-38). Median sample size in all trials was 366 (range: 44-856). Trial publication year (p = 0.71), journal impact factor (p = 0.52), duration of study (p = 0.12), and number need to treat [NNT] (p = 0.29) were not predictive of a high FI. While a lower p-value correlated with a higher FI (p = 0.039), no correlation was noted between FI and impact factor (R = -0.20, p = 0.52), trial publication year (R = 0.12, p = 0.71), duration of trial (R = -0.46, p = 0.13), NNT (R = -0.34, p = 0.29), and sample size (R = 0.23, p = 0.5). The highest FI was in a Ramosetron trial (FI = 30) for IBS-D.A median of six participants is needed to nullify results in the included IBS trials suggesting how easily statistical significance based on a threshold p-value may be overturned.

    View details for DOI 10.1111/nmo.14166

    View details for PubMedID 34399023

  • Coronavirus Testing Before Motility Laboratory Procedures: An Update. The American journal of gastroenterology Gyawali, C. P., Baker, J. R., Moshiree, B., Rao, S., Neshatian, L., Nguyen, L., Chey, W. D., Saad, R., Garza, J. M., Waseem, S., Khan, A. R., Pandolfino, J. E. 2020

    View details for DOI 10.14309/ajg.0000000000001021

    View details for PubMedID 33136562

  • High Prevalence of Methane Predominant Small Bowel Bacterial Overgrowth and Constipation in Patients With Hypermobile Ehlers-Danlos Syndrome Zhou, W., Zikos, T., Neshatian, L., Nguyen, L. LIPPINCOTT WILLIAMS & WILKINS. 2020: S238
  • WHEN PILLS DO NOT WORK : GASTROPARESIS IN MIGRAINE Aurora, S., Nguyen, L., Ray, S., Shrewsbury, S. SAGE PUBLICATIONS LTD. 2020: 23
  • American Neurogastroenterology and Motility Society Task Force Recommendations for Resumption of Motility Laboratory Operations During the COVID-19 Pandemic. The American journal of gastroenterology Baker, J. R., Moshiree, B., Rao, S., Neshatian, L., Nguyen, L., Chey, W. D., Saad, R., Garza, J. M., Waseem, S., Khan, A. R., Pandolfino, J. E., Gyawali, C. P. 2020

    Abstract

    The American Neurogastroenterology and Motility Society Task Force recommends that gastrointestinal motility procedures should be performed in motility laboratories adhering to the strict recommendations and personal protective equipment (PPE) measures to protect patients, ancillary staff, and motility allied health professionals. When available and within constraints of institutional guidelines, it is preferable for patients scheduled for motility procedures to complete a coronavirus disease 2019 (COVID-19) test within 48 hours before their procedure, similar to the recommendations before endoscopy made by gastroenterology societies. COVID-19 test results must be documented before performing procedures. If procedures are to be performed without a COVID-19 test, full PPE use is recommended, along with all social distancing and infection control measures. Because patients with suspected motility disorders may require multiple procedures, sequential scheduling of procedures should be considered to minimize need for repeat COVID-19 testing. The strategies for and timing of procedure(s) should be adapted, taking into consideration local institutional standards, with the provision for screening without testing in low prevalence areas. If tested positive for COVID-19, subsequent negative testing may be required before scheduling a motility procedure (timing is variable). Specific recommendations for each motility procedure including triaging, indications, PPE use, and alternatives to motility procedures are detailed in the document. These recommendations may evolve as understanding of virus transmission and prevalence of COVID-19 infection in the community changes over the upcoming months.

    View details for DOI 10.14309/ajg.0000000000000823

    View details for PubMedID 32868631

  • Gastric per-oral endoscopic myotomy for severe post-lung transplant gastroparesis: A single-center experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation Podboy, A. J., Clarke, J. O., Nguyen, L. A., Mooney, J. J., Dhillon, G. S., Hwang, J. H. 2020

    View details for DOI 10.1016/j.healun.2020.06.019

    View details for PubMedID 32711933

  • Association of GAD-65 Antibodies with Autonomic Dysfunction in non-Type I diabetic patients Bozinov, N., Kipp, L., Nguyen, L., Jaradeh, S. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Marijuana, Ondansetron, and Promethazine Are Perceived as Most Effective Treatments for Gastrointestinal Nausea. Digestive diseases and sciences Zikos, T. A., Nguyen, L., Kamal, A., Fernandez-Becker, N., Regalia, K., Nandwani, M., Sonu, I., Garcia, M., Okafor, P., Neshatian, L., Grewal, D., Garcia, P., Triadafilopoulos, G., Clarke, J. O. 2020

    Abstract

    BACKGROUND: Many anti-nausea treatments are available for chronic gastrointestinal syndromes, but data on efficacy and comparative effectiveness are sparse.AIMS: To conduct a sectional survey study of patients with chronic nausea to assess comparative effectiveness of commonly used anti-nausea treatments.METHODS: Outpatients at a single center presenting for gastroenterology evaluation were asked to rate anti-nausea efficacy on a scale of 0 (no efficacy) to 5 (very effective) of 29 commonly used anti-nausea treatments and provide other information about their symptoms. Additional information was collected from the patients' chart. The primary outcome was to determine which treatments were better or worse than average using a t test. The secondary outcome was to assess differential response by individual patient characteristics using multiple linear regression.RESULTS: One hundred and fifty-three patients completed the survey. The mean efficacy score of all anti-nausea treatments evaluated was 1.73. After adjustment, three treatments had scores statically higher than the mean, including marijuana (2.75, p<0.0001), ondansetron (2.64, p<0.0001), and promethazine (2.46, p<0.0001). Several treatments, including many neuromodulators, complementary and alternative treatments, erythromycin, and diphenhydramine had scores statistically below average. Patients with more severe nausea responded better to marijuana (p=0.036) and diphenhydramine (p<0.001) and less so to metoclopramide (p=0.020). There was otherwise no significant differential response by age, gender, nausea localization, underlying gastrointestinal cause of nausea, and GCSI.CONCLUSIONS: When treating nausea in patients with chronic gastrointestinal syndromes, clinicians may consider trying higher performing treatments first, and forgoing lower performing treatments. Further prospective research is needed, particularly with respect to highly effective treatments.

    View details for DOI 10.1007/s10620-020-06195-5

    View details for PubMedID 32185665

  • Clinical and immunomodulatory effects of transcutaneous vagal nerve stimulation for idiopathic gastroparesis Gottfried-Blackmore, A., Namkoong, H., Adler, E. P., Fernandez-Becker, N., Clarke, J., Habtezion, A., Nguyen, L. WILEY. 2020
  • Changes in high-resolution manometric diagnosis over time: implications for clinical decision-making. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus Triadafilopoulos, G., Kamal, A., Zikos, T., Nguyen, L., Clarke, J. O. 2020

    Abstract

    Although High resolution esophageal manometry (HRM) is the gold standard to assess esophageal motility, little is known about the stability of the manometric diagnosis over time and its implications for management. To assess the stability and usefulness of repeat HRM in patients presenting with esophageal symptoms over time we performed this retrospective study of patients with esophageal symptoms. Medical records, questionnaires, and HRM tracing were independently reviewed using the Chicago classification. The primary objective was to assess the stability of the manometric diagnosis over time; secondary objective was its change (positive or negative). At least one repeat study was performed in 86 patients (36% women, ages 20-86, with mild to moderate symptoms), while 26 had a third procedure. Mean intervals between studies were 15±1.6months (for baseline v. first study) and 13±0.8months (for second to third study). Of the 27 patients initially with a normal study, 11 changed (five had esophago-gastric junction outflow obstruction [EGJOO], two diffuse esophageal spasm [DES], one jackhammer esophagus [JE], and three ineffective esophageal motility [IEM] [41% change]). Of the 24 patients with initial EGJOO, only nine retained it (65.2% change). Of nine patients with initial DES, four changed (44.4% change). Similarly, different diagnosis was seen in 7 of 24 initial IEM patients (22.7% change). Only one patient had achalasia initially and this remained stable. Additional changes were noted on a third HRM. Fluidity in the HRM diagnosis over time questions its validity at any timepoint and raises doubts about the need for intervention.

    View details for DOI 10.1093/dote/doz094

    View details for PubMedID 31909786

  • Meeting Summary: 2019 James W. Freston Conference: Food at the Intersection of Gut Health and Disease. Gastroenterology Mullin, G. n., Chey, W. n., Crowe, S. n., Ananthakrishan, A. n., Garcia-Bailo, B. n., Dellon, E. n., DiBaise, J. n., Fasano, A. n., Haller, E. n., Hamilton, M. J., Klein, S. n., Lebwohl, B. n., Leung, J. n., Lewis, J. n., Nguyen, L. n., Pandolfino, J. n., Parrish, C. R., Scarlata, K. n., Tack, J. n., Frye, J. n., Harer, K. n., Zevallos, V. n., Srinivasan, S. n., Verma, S. n., Jansson-Knodell, C. n., Dia, V. n., Rifkin, S. n., Pace, L. n. 2020

    View details for DOI 10.1053/j.gastro.2020.03.036

    View details for PubMedID 32224128

  • Noninvasive vagal nerve stimulation for gastroenterology pain disorders. Pain management Gottfried-Blackmore, A. n., Habtezion, A. n., Nguyen, L. n. 2020

    Abstract

    Abdominal pain continues to be a major challenge and unmet need in clinical practice. Normalization of bidirectional gut-brain signaling has generated much interest as a therapeutic approach to treat chronic abdominal pain. Vagal nerve stimulation (VNS) is emerging as a potential non-pharmacologic strategy for the treatment of abdominal pain. In this review paper, we will summarize the etiologies of chronic pain in gastrointestinal disorders and discuss the rational for VNS as a therapeutic approach to chronic abdominal pain, with particular emphasis in the gammaCore stimulator which allows for noninvasive VNS.

    View details for DOI 10.2217/pmt-2020-0067

    View details for PubMedID 33111642

  • The Scarcity of Literature on the Psychological, Social, and Emotional Effects of Gastroparesis in Children. Children (Basel, Switzerland) Taft, T. H., Doerfler, B. n., Edlynn, E. n., Nguyen, L. n. 2020; 7 (9)

    Abstract

    Gastroparesis (GP) is a chronic, gastric dysmotility disorder with significant morbidity and mortality. The hallmark of GP is the delayed emptying of the contents of the stomach in the absence of any mechanical obstruction. Patients most commonly report chronic symptoms of nausea, vomiting, feeling full quickly when eating, bloating, and abdominal pain. Treatments are limited with relatively poor efficacy. As such, children with GP are at significant risk for the development of psychological co-morbidities. In this paper, we provide a topical review of the scientific literature on the psychological, social, and emotional impacts of gastroparesis in pediatric patients. We aim to document the current state of research, identify gaps in our knowledge with appropriate recommendations for future research directions, and highlight the unique challenges pediatric patients with GP and their families may face as they manage this disease. Based on the current review, research into the psychosocial impacts in children with GP is essentially non-existent. However, when considering research in children with other chronic digestive diseases, children with GP are likely to face multiple psychosocial challenges, including increased risk for anxiety and depression, stigma, and reduced quality of life. These significant gaps in the current understanding of effects of GP across domains of childhood functioning allow for ample opportunities for future studies to address psychosocial outcomes.

    View details for DOI 10.3390/children7090115

    View details for PubMedID 32877988

  • Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease. Journal of thoracic disease Zikos, T. A., Triadafilopoulos, G. n., Kamal, A. n., Podboy, A. n., Sonu, I. S., Regalia, K. A., Nandwani, M. C., Nguyen, L. A., Fernandez-Becker, N. Q., Clarke, J. O. 2020; 12 (10): 5628–38

    Abstract

    Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms.In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson's correlation or Spearman's rank coefficients.70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= -0.5 to -0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms.Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.

    View details for DOI 10.21037/jtd-20-1623

    View details for PubMedID 33209395

    View details for PubMedCentralID PMC7656325

  • Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients with Suspected Gastroparesis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Lee, A. A., Rao, K. n., Parkman, H. P., McCallum, R. W., Sarosiek, I. n., Nguyen, L. A., Wo, J. M., Schulman, M. I., Moshiree, B. n., Rao, S. n., Kuo, B. n., Hasler, W. L. 2020

    Abstract

    Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis.One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL.Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores.Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

    View details for DOI 10.1016/j.cgh.2020.09.032

    View details for PubMedID 32971231

  • Ninety-Six Hour Wireless Esophageal pH Study in Patients with GERD Shows that Restrictive Diet Reduces Esophageal Acid Exposure. Digestive diseases and sciences Triadafilopoulos, G., Korzilius, J. W., Zikos, T., Sonu, I., Fernandez-Becker, N. Q., Nguyen, L., Clarke, J. O. 2019

    Abstract

    BACKGROUND: Prolonged (96h) pH monitoring may explore the effect of diet on pH and symptoms in patients with GERD.AIMS: To assess the usefulness of a 96h esophageal pH study in patients with GER symptoms under different diets (pro- and anti-GER).METHODS: Prospective study of 66 patients with GERD undergoing wireless 96h pH monitoring. Two-day periods, one on liberal (pro-reflux) and another on restricted (anti-reflux) diet assessed esophageal acid exposure and symptoms. The primary end point was normalization of acid exposure time while on restricted diet. Secondary end point was a>50% reduction in symptoms with restricted diet.RESULTS: Normal (pH time<4 of<6%) was found in 34 patients (51.5%) while on the initial 48h (liberal) diet [median % time<4: 3.2 (95% CI, 1.9, 4.0)] and remained normal while on restricted diet [median % time<4: 2.6 (95% CI, 0.8, 3.4)]. Abnormal acid exposure (% pH time<4:>6%) was found in 32 patients (48.5%) while on initial 48h liberal diet [median % time<4: 10.5, (95% CI 8.9, 12.6)], and decreased significantly with restricted diet [median % time<4: 4.5 (95% CI 3.1, 7.3)] (p=0.001), and normalized with anti-GERD diet in 21 patients (65.6%). Only 11/66 patients were candidates for proton pump inhibitor (PPI) use; 34 had either normal pH studies or normalized them with restricted diet (n=21). Symptoms did not improve with restricted diet.CONCLUSIONS: The 96-h esophageal pH study tests for GERD under pro- and anti-GER diets and allows minimization of PPI therapy to only 16.6% of patients.

    View details for DOI 10.1007/s10620-019-05940-9

    View details for PubMedID 31734874

  • Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY Grover, M., Dasari, S., Bernard, C. E., Chikkamenahalli, L. L., Yates, K. P., Pasricha, P. J., Sarosiek, I., McCallum, R., Koch, K. L., Abell, T. L., Kuo, B., Shulman, R. J., Gibbons, S. J., McKenzie, T. J., Kellogg, T. A., Kendrick, M. L., Tonascia, J., Hamilton, F. A., Parkman, H. P., Farrugia, G., Shulman, R., Chumpitazi, B., Bouette, C., Charron, H., Islam, N., Williams, K., Nurko, S., Varni, J., Pasricha, P., Barat, R., Chen, J., Hernandez, G., Burns, R., McKnight, M., Kuo, B., Mendez, A., Steller, K., Thurler, A., Parkman, H., Mauer, A., Malik, Z., Orthey, P., Palit, A., McCallum, R. W., Connery, S., Ramirez, M., Vega, N., Sigaroodi, S., Abell, T., Stocker, A., Cannon, B., Nowotny, L., Walls, T., Koch, K., Baxter, L., Brown, A., Stuart, P., Abdullah, A., Snape, W., DeVole, N., Earle, K., Kirkeby, K., Lee, C., Lin, M., Troyer, D., von Bakonyi, A., Calles-Escandon, J., Nguyen, L., Adler, E., Orlando, C., Hasler, W., Herman, W., Kraftson, A., Rothberg, A. E., Wootten, S., Belt, P., Donithan, M., Lee, L., Miriel, L., Sharkey, E., Sternberg, A., Van Natta, M., Wilson, L., Yamada, G., Yates, K., Bernard, C., Serrano, J., Hamilton, F., Hall, S., James, S., Torrance, R., NIDDK Gastroparesis Clinical Res C 2019; 317 (5): G716–G726

    Abstract

    Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, "Role of Macrophages, Fibroblasts and Endothelial Cells" was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10-9; IG FDR = 6.3 × 10-12]. In DG, properdin expression correlated with GCSI bloating (r = -0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention (r = -0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis.NEW & NOTEWORTHY This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.

    View details for DOI 10.1152/ajpgi.00115.2019

    View details for Web of Science ID 000498403600016

    View details for PubMedID 31482734

    View details for PubMedCentralID PMC6879892

  • RESPONSE TO LETTER TO EDITOR BY PANNEMANS ET AL. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hasler, W. L., Wilson, L. A., Nguyen, L. A., Snape, W. J., Abell, T. L., Koch, K. L., McCallum, R. W., Pasricha, P. J., Sarosiek, I., Farrugia, G., Grover, M., Lee, L. A., Miriel, L., Tonascia, J., Hamilton, F. A., Parkman, H. P. 2019

    View details for DOI 10.1016/j.cgh.2019.10.007

    View details for PubMedID 31606456

  • Motility Abnormalities Identified by Wireless Motility Capsule in Postural Orthostatic Tachycardia Syndrome Zikos, T. A., Zhou, W., Clarke, J. O., Nguyen, L. A., Neshatian, L. LIPPINCOTT WILLIAMS & WILKINS. 2019: S279
  • Evaluation of Somatic Pain Distribution Using Body Maps for Patients With Chronic Abdominal Pain Syndromes Aivaliotis, V. I., Hah, J. M., Pirrotta, L., Nguyen, L. A. LIPPINCOTT WILLIAMS & WILKINS. 2019: S281–S282
  • The Fragility of Randomized Placebo-Controlled Trials for Irritable Bowel Syndrome Management Williams, M. O., Dennis, B., Dlamini, V., Nwaiwu, O., Nguyen, L. A., Okafor, P. N. LIPPINCOTT WILLIAMS & WILKINS. 2019: S287
  • Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Lee, A. A., Rao, S., Nguyen, L. A., Moshiree, B., Sarosiek, I., Schulman, M. I., Wo, J. M., Parkman, H. P., Wilding, G. E., McCallum, R. W., Hasler, W. L., Kuo, B. 2019; 17 (9): 1770-+
  • Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life DIGESTIVE DISEASES AND SCIENCES Parkman, H. P., Wilson, L. A., Hasler, W. L., McCallum, R. W., Sarosiek, I., Koch, K. L., Abell, T. L., Schey, R., Kuo, B., Snape, W. J., Nguyen, L., Farrugia, G., Grover, M., Clarke, J., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P. J. 2019; 64 (8): 2242–55
  • Gastric per-oral endoscopic myotomy: Current status and future directions. World journal of gastroenterology Podboy, A., Hwang, J. H., Nguyen, L. A., Garcia, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., Clarke, J. O. 2019; 25 (21): 2581-2590

    Abstract

    Gastroparesis, or symptomatic delayed gastric emptying in the absence of mechanical obstruction, is a challenging and increasingly identified syndrome. Medical options are limited and the only medication approved by the Food and Drug Administration for treatment of gastroparesis is metoclopramide, although other agents are frequently used off label. With this caveat, first-line treatments for gastroparesis include dietary modifications, antiemetics and promotility agents, although these therapies are limited by suboptimal efficacy and significant medication side effects. Treatment of patients that fail first-line treatments represents a significant therapeutic challenge. Recent advances in endoscopic techniques have led to the development of a promising novel endoscopic therapy for gastroparesis via endoscopic pyloromyotomy, also referred to as gastric per-oral endoscopic myotomy or per-oral endoscopic pyloromyotomy. The aim of this article is to review the technical aspects of the per-oral endoscopic myotomy procedure for the treatment of gastroparesis, provide an overview of the currently published literature, and outline potential next directions for the field.

    View details for DOI 10.3748/wjg.v25.i21.2581

    View details for PubMedID 31210711

    View details for PubMedCentralID PMC6558440

  • Gastric per-oral endoscopic myotomy: Current status and future directions WORLD JOURNAL OF GASTROENTEROLOGY Podboy, A., Hwang, J., Nguyen, L. A., Garcia, P., Zikos, T. A., Kamal, A., Triadafilopoulos, G., Clarke, J. O. 2019; 25 (21): 2581–90
  • Opioid Use and Potency Are Associated With Clinical Features, Quality of Life, and Use of Resources in Patients With Gastroparesis CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Hasler, W. L., Wilson, L. A., Nguyen, L. A., Snape, W. J., Abell, T. L., Koch, K. L., McCallum, R. W., Pasricha, P. J., Sarosiek, I., Farrugia, G., Grover, M., Lee, L. A., Miriel, L., Tonascia, J., Hamilton, F. A., Parkman, H. P., Pasricha, P., Clarke, J., Kim, Y., Nguyen, L., Ullah, N., Snape, W., DeVole, N., Greene, M., Lee, C., Ponsetto, C., Shetler, K., Parkman, H. P., Kantor, S., Lytes, V., Palit, A., Simmons, K., McCallum, R. W., Hejazi, R., Roeser, K., Sarosiek, I., Vasquez, D., Vega, N., Abell, T., Beatty, K., Hatter, L., Howard, R., Nowotny, L., Tang, S., Amin, O. S., Henry, O., Kedar, A., McNair, V., Pruett, S., Smith, M., Spree, D., Hasler, W., Castle, M., Coleski, R., Wootten, S., Koch, K., Baxter, L., Brown, A., Culler, S., Hooker, J., Stuart, P., Farrugia, G., Grover, M., Bernard, C., Calles-Escandon, J., Serrano, J., Hamilton, F., James, S., Torrance, R., Van Raaphorst, R., Tonascia, J., Belt, P., Hallinan, E., Colvin, R., Donithan, M., Green, M., Isaacson, M., Kim, W., Lee, L., May, P., Miriel, L., Sternberg, A., Van Natta, M., Vaughn, I., Wilson, L., Yates, K., Gastroparesis Clinical Res 2019; 17 (7): 1285-+
  • High Prevalence of Slow Transit Constipation in Patients With Gastroparesis JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY Zikos, T. A., Kamal, A. N., Neshatian, L., Triadafilopoulos, G., Clarke, J. O., Nandwani, M., Nguyen, L. A. 2019; 25 (2): 267–75

    View details for DOI 10.5056/jnm18206

    View details for Web of Science ID 000464525700012

  • Abdominal Pain in Patients with Gastroparesis: Associations with Gastroparesis Symptoms, Etiology of Gastroparesis, Gastric Emptying, Somatization, and Quality of Life. Digestive diseases and sciences Parkman, H. P., Wilson, L. A., Hasler, W. L., McCallum, R. W., Sarosiek, I., Koch, K. L., Abell, T. L., Schey, R., Kuo, B., Snape, W. J., Nguyen, L., Farrugia, G., Grover, M., Clarke, J., Miriel, L., Tonascia, J., Hamilton, F., Pasricha, P. J. 2019

    Abstract

    Abdominal pain can be an important symptom in some patients with gastroparesis (Gp).AIMS: (1) To describe characteristics of abdominal pain in Gp; (2) describe Gp patients reporting abdominal pain.METHODS: Patients with idiopathic gastroparesis (IG) and diabetic gastroparesis (DG) were studied with gastric emptying scintigraphy, water load test, wireless motility capsule, and questionnaires assessing symptoms [Patient Assessment of Upper GI Symptoms (PAGI-SYM) including Gastroparesis Cardinal Symptom Index (GCSI)], quality of life (PAGI-QOL, SF-36), psychological state [Beck Depression Inventory (BDI), State-Trait Anxiety Index (STAI), PHQ-15 somatization scale].RESULTS: In total, 346 Gp patients included 212 IG and 134 DG. Ninety percentage of Gp patients reported abdominal pain (89% DG and 91% IG). Pain was primarily in upper or central midline abdomen, described as cramping or sickening. Upper abdominal pain was severe or very severe on PAGI-SYM by 116/346 (34%) patients, more often by females than by males, but similarly in IG and DG. Increased upper abdominal pain severity was associated with increased severity of the nine GCSI symptoms, depression on BDI, anxiety on STAI, somatization on PHQ-15, the use of opiate medications, decreased SF-36 physical component, and PAGI-QOL, but not related to severity of delayed gastric emptying or water load ingestion. Using logistic regression, severe/very severe upper abdominal pain associated with increased GCSI scores, opiate medication use, and PHQ-15 somatic symptom scores.CONCLUSIONS: Abdominal pain is common in patients with Gp, both IG and DG. Severe/very severe upper abdominal pain occurred in 34% of Gp patients and associated with other Gp symptoms, somatization, and opiate medication use. ClinicalTrials.gov Identifier: NCT01696747.

    View details for PubMedID 30852767

  • Reduction in Hospitalizations for Esophageal Reflux in a Decade with Minimal Increases in Other Functional and Motor Disorders. Digestive diseases and sciences Zikos, T. A., Hendler, S. n., Clarke, J. O., Triadafilopoulos, G. n., Nguyen, L. n., Limketkai, B. N. 2019

    Abstract

    Functional and motility disorders (FMDs) are common conditions that cause significant morbidity and economic loss. A comprehensive analysis of these disorders and their impact has not been done in an inpatient setting.We seek to evaluate adult hospitalization trends for FMDs in the USA.The National Inpatient Sample between 2005 and 2014 was analyzed. Poisson regression was used to assess hospitalization trends for FMDs referenced to non-FMD hospitalizations. Linear regression was used to assess cost per hospitalization and length of stay (LOS). All models were adjusted for age, sex, primary insurance, and Charlson comorbidity index.Hospitalizations with FMDs as the primary diagnosis fell by an adjusted 2.46%/year over the study period (p < 0.001). The entirety of this reduction was explained by falling admissions for gastroesophageal reflux (adjusted reduction of 7.04%/year, p < 0.001). The hospitalization rate for all other FMDs (excluding gastroesophageal reflux) minimally increased by 0.75%/year (p = 0.001). Total cost of care for FMD hospitalizations remained relatively stable ($3.17 billion in 2014), while increasing for all other hospitalizations. Mean LOS for FMD hospitalization increased by an adjusted 0.025 days/year, but decreased by 0.038 days/year for all other hospitalizations (p < 0.001).The hospitalization rate for gastroesophageal reflux fell between 2005 and 2014, but remained relatively stable to increase for all other FMDs. These trends may be due to increased proton pump inhibitor use, better patient/provider education, emphasis on outpatient management, and/or coding bias.

    View details for DOI 10.1007/s10620-019-05895-x

    View details for PubMedID 31620929

  • Satiety testing in diabetic gastroparesis: Effects of insulin pump therapy with continuous glucose monitoring on upper gastrointestinal symptoms and gastric myoelectrical activity. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Koch, K. L., Hasler, W. L., Van Natta, M. n., Calles-Escandon, J. n., Grover, M. n., Pasricha, P. J., Snape, W. J., Parkman, H. P., Abell, T. L., McCallum, R. W., Nguyen, L. A., Sarosiek, I. n., Farrugia, G. n., Tonascia, J. n., Lee, L. n., Miriel, L. n., Hamilton, F. n. 2019: e13720

    Abstract

    Symptoms induced by caloric or non-caloric satiety test meals and gastric myoelectrical activity (GMA) have not been studied in patients with diabetic gastroparesis (DGP) before and after intense glucose management.We determined the effects of continuous subcutaneous insulin infusion (CSII) with continuous glucose monitoring (CGM) on GI symptoms, volume consumed, and GMA induced by the caloric meal satiety test (CMST) and water load satiety test (WLST) in DGP.Forty-five patients with DGP underwent CMST and WLST at baseline and 24 weeks after CSII with CGM. Subjects ingested the test meals until they were completely full. Visual analog scales were used to quantify pre- and postmeal symptoms, and GMA was recorded with cutaneous electrodes and analyzed visually and by computer. KEY RESULTS: At baseline and 24-week visits, nausea, bloating, abdominal discomfort, and fullness were immediately increased after CMST and WLST (Ps < 0.01). The meal volumes ingested were significantly less than normal controls at both visits in almost one-third of the subjects. After the CMST, the percentage 3 cycle per minute GMA increased and bradygastria decreased compared with WLST (Ps < 0.05). After treatment for 24 weeks meal volumes ingested, postmeal symptoms and GMA were no different than baseline. CONCLUSIONS AND INFERENCES: (a) Satiety test meals elicited symptoms of nausea, bloating, and abdominal discomfort; (b) CMST stimulated more symptoms and changes in GMA than WLST; and (c) CSII with CGM for 24 weeks did not improve symptoms, volumes ingested, or GMA elicited by the two satiety test meals in these patients with diabetic GP. Satiety tests in diabetic gastropresis are useful to study acute postprandial symptoms and GMA, but these measures were not improved by intensive insulin therapy.

    View details for DOI 10.1111/nmo.13720

    View details for PubMedID 31574209

  • Delayed Gastric Emptying Associates With Diabetic Complications in Diabetic Patients With Symptoms of Gastroparesis. The American journal of gastroenterology Parkman, H. P., Wilson, L. A., Farrugia, G. n., Koch, K. L., Hasler, W. L., Nguyen, L. A., Abell, T. L., Snape, W. n., Clarke, J. n., Kuo, B. n., McCallum, R. W., Sarosiek, I. n., Grover, M. n., Miriel, L. n., Tonascia, J. n., Hamilton, F. A., Pasricha, P. J. 2019

    Abstract

    Diabetic gastroparesis (Gp) occurs more often in type 1 diabetes mellitus (T1DM) than in type 2 diabetes mellitus (T2DM). Other diabetic end-organ complications include peripheral neuropathy, nephropathy, and retinopathy (together termed triopathy). This study determines the prevalence of diabetic complications (retinopathy, nephropathy, and peripheral neuropathy) in diabetic patients with symptoms of Gp, assessing the differences between T1DM and T2DM and delayed and normal gastric emptying (GE).Diabetic patients with symptoms of Gp underwent history and physical examination, GE scintigraphy, electrogastrography with water load, autonomic function testing, and questionnaires assessing symptoms and peripheral neuropathy.One hundred thirty-three diabetic patients with symptoms of Gp were studied: 59 with T1DM and 74 with T2DM and 103 with delayed GE and 30 without delayed GE. The presence of retinopathy (37% vs 24%; P = 0.13), nephropathy (19% vs 11%; P = 0.22), and peripheral neuropathy (53% vs 39%; P = 0.16) was not significantly higher in T1DM than in T2DM; however, triopathies (all 3 complications together) were seen in 10% of T1DM and 3% of T2DM (P = 0.04). Diabetic patients with delayed GE had increased prevalence of retinopathy (36% vs 10%; P = 0.006) and number of diabetic complications (1.0 vs 0.5; P = 0.009); however, 39% of diabetic patients with delayed GE did not have any diabetic complications.In diabetic patients with symptoms of Gp, delayed GE was associated with the presence of retinopathy and the total number of diabetic complications. Only 10% of patients with T1DM and 3% of those with T2DM had triopathy of complications, and 39% of diabetic patients with Gp did not have any diabetic complications. Thus, the presence of diabetic complications should raise awareness for Gp in either T1DM or T2DM; however, diabetic Gp frequently occurs without other diabetic complications.

    View details for DOI 10.14309/ajg.0000000000000410

    View details for PubMedID 31658129

  • Effectiveness of gastric electrical stimulation in gastroparesis: Results from a large prospectively collected database of national gastroparesis registries. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society Abell, T. L., Yamada, G. n., McCallum, R. W., Van Natta, M. L., Tonascia, J. n., Parkman, H. P., Koch, K. L., Sarosiek, I. n., Farrugia, G. n., Grover, M. n., Hasler, W. n., Nguyen, L. n., Snape, W. n., Kuo, B. n., Shulman, R. n., Hamilton, F. A., Pasricha, P. J. 2019: e13714

    Abstract

    Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial.We studied 319 idiopathic or diabetic gastroparesis symptom patients from the Gastroparesis Clinical Research Consortium (GpCRC) observational studies: 238 without GES and 81 with GES. We assessed the effects of GES using change in GCSI total score and nausea/vomiting subscales between baseline and 48 weeks. We used propensity score methods to control for imbalances in patient characteristics between comparison groups.GES patients were clinically worse (40% severe vs. 18% for non-GES; P < .001); worse PAGI-QOL (2.2. vs. 2.6; P = .003); and worse GCSI total scores (3.5 vs. 2.8; P < .001). We observed improvements in 48-week GCSI total scores for GES vs. non-GES: improvement by ≥ 1-point (RR = 1.63; 95% CI = (1.14, 2.33); P = .01) and change from enrollment (difference = -0.5 (-0.8, -0.3); P < .001). When adjusting for patient characteristics, symptom scores were smaller and not statistically significant: improvement by ≥ 1-point (RR = 1.29 (0.88, 1.90); P = .20) and change from the enrollment (difference = -0.3 (-0.6, 0.0); P = .07). Of the individual items, the nausea improved by ≥ 1 point (RR = 1.31 (1.03, 1.67); P = .04). Patients with GCSI score ≥ 3.0 tended to improve more than those with score < 3.0. (Adjusted P = 0.02).This multicenter study of gastroparesis patients found significant improvements in gastroparesis symptoms among GES patients. Accounting for imbalances in patient characteristics, only nausea remained significant. Patients with greater symptoms at baseline improved more after GES. A much larger sample of patients is needed to fully evaluate symptomatic responses and to identify patients likely to respond to GES.

    View details for DOI 10.1111/nmo.13714

    View details for PubMedID 31584238

  • Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Lee, A. A., Rao, S., Nguyen, L. A., Moshiree, B., Sarosiek, I., Schulman, M. I., Wo, J. M., Parkman, H. P., Wilding, G. E., McCallum, R. W., Hasler, W. L., Kuo, B. 2018

    Abstract

    BACKGROUND & AIMS: It is a challenge to make a diagnosis of gastroparesis. There is good agreement in results from wireless motility capsule (WMC) analysis and gastric emptying scintigraphy (GES), but the diagnostic yield of WMC is unclear and the accuracy of this method has not been validated. We compared the performance characteristics of WMC vs GES in assessing gastric emptying in patients with suspected gastroparesis.METHODS: We performed a prospective study of 167 subjects with gastroparesis (53 with diabetes and 114 without) at 10 centers, from 2013 through 2016. Subjects were assessed simultaneously by GES and with a WMC to measure gastric emptying and regional transit. Delayed gastric emptying by GES was defined as more than 10% meal retention at 4 hrs whereas delayed gastric emptying by WMC was defined as more than 5 hrs for passage of the capsule into the duodenum; a severe delay in gastric emptying was defined as a gastric emptying time of more than 12 hrs by WMC or more than 35% retention at 4 hrs by GES. Rapid gastric emptying was defined as less than 38% meal retention at 1 hr based on by GES or gastric emptying times less than 1:45 hrs by WMC. We compared diagnostic and performance characteristics of GES vs WMC.RESULTS: Delayed gastric emptying was detected in a higher proportion of subjects by WMC (34.6%) than by than GES (24.5%) (P=.009). Overall agreement in results between methods was 75.7% (kappa=0.42). In subjects without diabetes, the WMC detected a higher proportion of subjects with delayed gastric emptying (33.3%) than GES (17.1%) (P<.001). A higher proportion of subjects with diabetes had delayed gastric emptying detected by GES (41.7%) than by WMC (17.1%) (P=.002). Severe delays in gastric emptying were observed in a higher proportion of subjects by WMC (13.8%) than by GES (6.9%) (P=.02). Rapid gastric emptying was detected in a higher proportion of subjects by GES (13.8%) than by WMC (3.3%) (P<.001). Regional and generalized transit abnormalities were observed in 61.8% subjects and only detected by WMC.CONCLUSION: Although there is agreement in analysis of gastric emptying by GES vs WMC, WMC provides higher diagnostic yield than GES. WMC detects delayed gastric emptying more frequently than GES and identifies extra-gastric transit abnormalities. Diabetic vs non-diabetic subjects have different results from GES vs WMC. These findings could affect management of patients with suspected gastroparesis. ClinicalTrials.gov no: NCT02022826.

    View details for PubMedID 30557741

  • Consensus-based care recommendations for adults with myotonic dystrophy type 1 NEUROLOGY-CLINICAL PRACTICE Ashizawa, T., Gagnon, C., Groh, W. J., Gutmann, L., Johnson, N. E., Meola, G., Moxley, R., Pandya, S., Rogers, M. T., Simpson, E., Angeard, N., Bassez, G., Berggren, K. N., Bhakta, D., Bozzali, M., Broderick, A., Byrne, J. B., Campbell, C., Cup, E., Day, J. W., De Mattia, E., Duboc, D., Duong, T., Eichinger, K., Ekstrom, A., van Engelen, B., Esparis, B., Eymard, B., Ferschl, M., Gadalla, S. M., Gallais, B., Goodglick, T., Heatwole, C., Hilbert, J., Holland, V., Kierkegaard, M., Koopman, W. J., Lane, K., Maas, D., Mankodi, A., Mathews, K. D., Monckton, D. G., Moser, D., Nazarian, S., Nguyen, L., Nopoulos, P., Petty, R., Phetteplace, J., Puymirat, J., Raman, S., Richer, L., Roma, E., Sampson, J., Sansone, V., Schoser, B., Sterling, L., Statland, J., Subramony, S. H., Tian, C., Trujillo, C., Tomaselli, G., Turner, C., Venance, S., Verma, A., White, M., Winblad, S., Myotonic Dystrophy Fdn 2018; 8 (6): 507–20

    Abstract

    Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit.The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations.The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments.

    View details for DOI 10.1212/CPJ.0000000000000531

    View details for Web of Science ID 000456290100016

    View details for PubMedID 30588381

    View details for PubMedCentralID PMC6294540

  • 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; 63 (12): 3417–24
  • Opioid Use and Potency are Associated with Clinical Features, Quality of Life, and Use of Resources in Patients with Gastroparesis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Hasler, W. L., Wilson, L. A., Nguyen, L. A., Snape, W. J., Abell, T. L., Koch, K. L., McCallum, R. W., Pasricha, P. J., Sarosiek, I., Farrugia, G., Grover, M., Lee, L. A., Miriel, L., Tonascia, J., Hamilton, F. A., Parkman, H. P., Gastroparesis Clinical Research Consortium (GpCRC) 2018

    Abstract

    BACKGROUND & AIMS: Many patients with gastroparesis are prescribed opioids for pain control, but indications for opioid prescription and relations of opioid use to gastroparesis manifestations are undefined. We characterized associations of use of potent vs weaker opioids and presentations of diabetic and idiopathic gastroparesis.METHODS: We collected data on symptoms, gastric emptying, quality of life, and healthcare resource use from 583 patients with gastroparesis (more than 10% 4 hr scintigraphic retention) from the NIDDK Gastroparesis Consortium, from January 2007 through November 2016. Patients completed medical questionnaires that included questions about opioid use. The opioid(s) were categorized for potency relative to oral morphine. Symptom severities were quantified by Patient Assessment of Upper Gastrointestinal Disorders Symptoms questionnaires. Subgroup analyses compared patients on potent vs weaker opioids and opioid effects in diabetic vs idiopathic etiologies.RESULTS: Forty-one percent of patients were taking opioids; 82% of these took potent agents (morphine, hydrocodone, oxycodone, methadone, hydromorphone, buprenorphine, or fentanyl). Abdominal pain was the reason for prescription for 61% of patients taking opioids. Mean scores for gastroparesis, nausea/vomiting, bloating/distention, abdominal pain, and constipation scores were higher in opioid users (P≤.05). Opioid use was associated with greater levels of gastric retention, worse quality of life, increased hospitalization, and increased use of antiemetic and pain modulator medications, compared with nonusers (P≤0.03). Use of potent opioids was associated with worse gastroparesis, nausea/vomiting, upper abdominal pain, and quality of life scores, and more hospitalizations compared with weaker opioids (tapentadol, tramadol, codeine, or propoxyphene) (P≤.05). Opioid use was associated with larger increases in gastric retention in patients with idiopathic vs diabetic gastroparesis (P=.008).CONCLUSION: Opioid use is prevalent among patients with diabetic or idiopathic gastroparesis, and is associated with worse symptoms, delays in gastric emptying, and lower quality of life, as well has greater use of resources. Potent opioids are associated with larger effects than weaker agents. These findings form a basis for studies to characterize adverse outcomes of opioid use in patients with gastroparesis and to help identify those who might benefit from interventions to prevent opioid overuse.

    View details for PubMedID 30326297

  • 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. R., Clarke, J. O. 2018; 63 (10): 2673–80
  • Comparing Longitudinal Overall and Individual Symptom Outcomes on Neuromodulator versus Prokinetic Drugs in Patients With Symptoms Suspicious for Gastroparesis but With Non-Delayed Gastric Emptying Hasler, W., Moshiree, B., McCallum, R., Rao, S. C., Nguyen, L., Krause, R., Schulman, M., Lee, A., Wo, J., Parkman, H., Sarosiek, I., Kuo, B. NATURE PUBLISHING GROUP. 2018: S686
  • Differential Longitudinal Symptom and Quality of Life (QOL) Outcomes on Selected Medications in Patients With Suspected Gastroparesis With Delayed versus Normal Colon Transit on Wireless Motility Capsule Testing Moshiree, B., Hasler, W., Lee, A., Kuo, B., Nguyen, L., McCallum, R., Sarosiek, I., Parkman, H. P., Wo, J., Schulman, M., Rao, S. C. NATURE PUBLISHING GROUP. 2018: S88–S89
  • Multi-Organ RNA-Sequencing of Patients with Systemic Sclerosis (SSc) Finds That Intrinsic Subsets Are Conserved across Organ Systems Mehta, B. K., Franks, J., Wang, Y., Cai, G., Toledo, D. M., Wood, T. A., Archambault, K. A., Kosarek, N., Kolstad, K. D., 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. 2018
  • Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis BMC MEDICAL GENOMICS Grover, M., Gibbons, S. J., Nair, A. A., Bernard, C. E., Zubair, A. S., Eisenman, S. T., Wilson, L. A., Miriel, L., Pasricha, P. J., Parkman, H. P., Sarosiek, I., McCallum, R. W., Koch, K. L., Abell, T. L., Snape, W. J., Kuo, B., Shulman, R. J., McKenzie, T. J., Kellogg, T. A., Kendrick, M. L., Tonascia, J., Hamilton, F. A., Farrugia, G., NIDDK Gastroparesis Clinical Res 2018; 11: 62

    Abstract

    Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear.Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR.111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log2fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05).Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.

    View details for PubMedID 30086735

  • Effect of pirfenidone on gastric emptying in a rat model PULMONARY PHARMACOLOGY & THERAPEUTICS Pan, L., Gelzleichter, T., Chen, Y., Burg, C., Limb, S. L., Nguyen, L. 2018; 51: 41–47

    Abstract

    Gastrointestinal (GI) adverse events (AEs) are commonly reported in patients with idiopathic pulmonary fibrosis who are treated with pirfenidone. Taking pirfenidone with a substantial amount of food or dividing the dose over the course of a meal has been reported to reduce the frequency of GI AEs in clinical practice. In humans, the maximum plasma concentration (Cmax) of pirfenidone was reduced when the drug was taken with food compared with the fasting state, and the lower Cmax was associated with a reduction in GI AE rates. In this study, the effects of the divided-dose approach and timing of pirfenidone administration relative to meal intake on gastric emptying were assessed using a rat model. The aim of this study was to investigate whether modification of dosing regimens could minimize pirfenidone's effect on inhibition of gastric emptying.Gastric emptying was assessed in male Sprague-Dawley rats after administration of a test meal by weighing stomach contents at various time points up to 120 min after the meal. Pirfenidone was administered via oral gavage either as a single-bolus dose of 30 mg/kg or as divided doses of 3 × 10 mg/kg at intervals ranging from 10 to 30 min for a total duration of 30 to 90 min. In addition, the test meal was given either at 30 min before, coincident with, or 30 min following pirfenidone oral administration.Administration of an oral 30-mg/kg single-bolus dose of pirfenidone with a meal resulted in a statistically significant decrease in gastric emptying in a rat model. The effect of pirfenidone on decreasing gastric emptying was lessened when the same total dose (i.e., 30 mg/kg) was administered as 3 divided doses (i.e., 3 × 10 mg/kg) over intervals up to 30 min in between each divided dose. Pharmacokinetic simulation suggested that a divided-dosing regimen would decrease pirfenidone Cmax relative to single-bolus administration. When the same single-bolus dose of 30 mg/kg was administered 30 min following a meal rather than coincident with a meal, pirfenidone's effect on decreasing gastric emptying was reduced to the same extent as when the dose was divided as 3 × 10 mg/kg over a 90-min period.Administration of pirfenidone 30 min after a meal as a single-bolus dose or a divided dose over a 90-min period blunted pirfenidone's effect on inhibition of gastric emptying in rats compared with pirfenidone administration as a single-bolus dose coincident with a meal. Decreased gastric emptying, which is associated with pirfenidone administration, may be one of the contributing factors leading to GI tolerability issues associated with pirfenidone use in humans. Modification of the dosing regimen diminished this impact and may provide insight into possible mitigation strategies to minimize GI-related toxicities in the clinic.

    View details for PubMedID 29944949

  • 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 PubMedID 29959725

  • 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 PubMedID 28970332

  • 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 PubMedID 29487566

  • 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 PubMedID 29161307

  • 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
  • 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
  • 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
  • Patients with symptoms of delayed gastric emptying have a high prevalence of oesophageal dysmotility, irrespective of scintigraphic evidence of gastroparesis. BMJ open gastroenterology Triadafilopoulos, G. n., Nguyen, L. n., Clarke, J. O. 2017; 4 (1): e000169

    Abstract

    Patients with symptoms suggestive of gastroparesis exhibit several symptoms, such as epigastric pain, postprandial fullness, bloating and regurgitation. It is uncertain if such symptoms reflect underlying oesophageal motor disorder.To examine whether patients with epigastric pain and postprandial distress syndrome suggestive of functional dyspepsia and/or gastroparesis also have concomitant oesophageal motility abnormalities and, if so, whether there are any associations between these disturbances.In this retrospective cohort study, consecutive patients with functional gastrointestinal symptoms suggestive of gastric neuromuscular dysfunction (gastroparesis or functional dyspepsia) underwent clinical assessment, gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring using standard protocols.We studied 61 patients with various functional upper gastrointestinal symptoms who underwent gastric scintigraphy, oesophageal high-resolution manometry and ambulatory pH monitoring. Forty-four patients exhibited gastroparesis by gastric scintigraphy. Oesophageal motility disorders were found in 68% and 42% of patients with or without scintigraphic evidence of gastroparesis respectively, suggesting of overlapping gastric and oesophageal neuromuscular disorder. Forty-three per cent of patients with gastroparesis had abnormal oesophageal acid exposure with mean % pH <4.0 of 7.5 in contrast to 38% of those symptomatic controls with normal gastric emptying, with mean %pH <4.0 of 5.4 (NS). Symptoms of epigastric pain, heartburn/regurgitation, bloating, nausea, vomiting, dysphagia, belching and weight loss could not distinguish patients with or without gastroparesis, although weight loss was significantly more prevalent and severe (p<0.002) in patients with gastroparesis. There was no relationship between oesophageal symptoms and motor or pH abnormalities in either groups.Irrespective of gastric emptying delay by scintigraphy, patients with symptoms suggestive of gastric neuromuscular dysfunction have a high prevalence of oesophageal motor disorder and pathological oesophageal acid exposure that may contribute to their symptoms and may require therapy. High-resolution oesophageal manometry and pH monitoring are non-invasive and potentially useful in the assessment and management of these patients.

    View details for PubMedID 29177065

  • 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
  • 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
  • Novel Uses of Neuromodulators in Treating Functional Abdominal Pain Chen, F., Nguyen, L., Newmark, J. NATURE PUBLISHING GROUP. 2016: S807
  • 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
  • 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 PubMedID 26938478

  • Vitamin Abnormalities in Patients With Gastrointestinal Motility and Functional Disorders Sonu, I., Wang, L., Zia, J., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S751
  • High Prevalence of Spastic Esophageal Motility Disorders in Post-Lung Transplant Patients Regalia, K., Sweatt, A., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S733
  • High Prevalence of Gastroparesis in Post Lung Transplant Patients Regalia, K., Sweatt, A., Wang, L., Nguyen, L. NATURE PUBLISHING GROUP. 2015: S1029–S1030
  • 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 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 PubMedID 21397732

  • 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
  • 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