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Henry P. Parkman - One of the best experts on this subject based on the ideXlab platform.
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body weight in patients with idiopathic Gastroparesis
Neurogastroenterology and Motility, 2020Co-Authors: Henry P. Parkman, Madhusudan Grover, Gianrico Farrugia, Richard W. Mccallum, Thomas L. Abell, Irene Sarosiek, Kenneth L Koch, Mark L Van Natta, Goro Yamada, Braden KuoAbstract:BACKGROUND The classic clinical picture of Gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic Gastroparesis. METHODS In patients with idiopathic Gastroparesis, detailed history and weight were acquired at enrollment and after 48 weeks. Questionnaires assessed symptoms, food intake, physical activity, and quality of life. Patients underwent laboratory testing, gastric emptying scintigraphy, and water load testing. RESULTS Of 138 patients with idiopathic Gastroparesis, 10% were underweight (BMI 30 kg/m2 . Body weight at enrollment was positively associated with oral caloric consumption (P < .001), following a Gastroparesis diet (P = .04), nutrition consultation (P = .001), upper abdominal pain (P = .01); and negatively associated with energy expenditure (P = .05), alcohol use (P = .003) and severity of bloating (P < .001). When followed over 48 weeks, 53% patients stayed stable (within 5% of baseline weight), 30% gained, and 17% lost weight. Weight gain over 48 weeks was positively associated with oral caloric consumption (P = .003) and constipation severity (P = .005) at enrollment, and negatively associated with lower abdominal pain severity (P = .007) at enrollment, and associated with improvement in inability to finish meal score (P < .001) at 48 weeks. CONCLUSIONS In this series of patients with idiopathic Gastroparesis, 10% were underweight whereas 29% were obese. Over 48 weeks, 30% of patients increased their body weight ≥ 5%. Diet, activity, and symptoms are important factors associated with body weight in patients with idiopathic Gastroparesis.
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EndoFLIP and Pyloric Dilation for Gastroparesis Symptoms Refractory to Pyloromyotomy/Pyloroplasty
Digestive Diseases and Sciences, 2020Co-Authors: Asad Jehangir, Zubair Malik, Roman V. Petrov, Henry P. ParkmanAbstract:Background Gastroparesis patients may undergo pyloromyotomy/pyloroplasty for chronic refractory symptoms. However, some patients have persistent symptoms. It is unknown if balloon dilation may improve their symptoms. Aims We aimed to (1) assess if pyloric through-the-scope (TTS) balloon dilation results in symptom improvement in Gastroparesis patients with suboptimal response to pyloromyotomy/pyloroplasty and (2) determine endoscopic functional luminal imaging probe (EndoFLIP) characteristics of these patients before dilation. Methods Patients with severe Gastroparesis refractory to pyloromyotomy/pyloroplasty seen from 2/2019 to 3/2020 underwent pyloric TTS dilation after assessing the pyloric characteristics using EndoFLIP. Patients completed Gastroparesis Cardinal Symptom Index (GCSI) pre-procedurally, and GCSI and Clinical Patient Grading Assessment Scale (CPGAS) on follow-ups. Results Thirteen (ten females) patients (mean age 45.2 ± 5.1 years) with severe Gastroparesis symptoms (mean GCSI total score 3.4 ± 0.3) after pyloromyotomy/pyloroplasty underwent pyloric TTS dilation. Overall, there was improvement in symptoms at 1-month follow-up (mean GCSI total score 3.0 ± 0.4, mean CPGAS score 1.6 ± 0.5, p
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avoidant restrictive food intake disorder symptoms are frequent in patients presenting for symptoms of Gastroparesis
Neurogastroenterology and Motility, 2020Co-Authors: Helen B Murray, Braden Kuo, Asad Jehangir, Casey J Silvernale, Henry P. ParkmanAbstract:INTRODUCTION Patients with symptoms of Gastroparesis/dyspepsia often avoid foods or restrict eating for symptom management. There is growing interest in understanding risk for feeding/eating disorders (FEDs) like avoidant/restrictive food intake disorder (ARFID). Among patients presenting with Gastroparesis/dyspepsia symptoms, we aimed to determine: (a) FED symptom frequency, and (b) relation of FED symptoms to gastrointestinal symptom severity and gastric retention abnormalities. METHODS Adult patients (N = 288; 78% female) referred for Gastroparesis/dyspepsia symptoms at two academic medical centers from January 2018-February 2019 completed self-report surveys for gastrointestinal symptom severity and FED symptoms. Gastric retention data were available for 210 patients, using 4-hour EggBeater gastric emptying scintigraphy (GES). RESULTS Clinically significant FED symptoms were present in 158 patients (54.9%). Interestingly, 115 patients (39.9%) met conservative self-report cutoff for ARFID symptoms, with 67 (23.3%) patients having documented psychosocial/medical impairment. Of those with survey data for other FEDs (n = 239), only 28 patients (11.7%) had restrictive eating disorders (anorexia nervosa; unspecified FED). Likelihood of having FED symptoms was significantly associated with greater Gastroparesis symptom severity (OR = 2.23, P < .001), but not GES. In addition, Gastroparesis symptom severity was moderately and significantly associated with greater ARFID symptom severity (b = 0.45, P < .001), but neither GES nor other FED symptoms. DISCUSSION In patients presenting with Gastroparesis/dyspepsia symptoms, FED symptoms were frequent (55%), particularly ARFID, and were associated with greater gastrointestinal symptom severity, but not gastric retention. Gastroparesis/dyspepsia symptoms may mimic FEDs, particularly ARFID. Clinicians should be cautious about diagnosing ARFID in Gastroparesis/dyspepsia patients, and screening for ARFID could assist behavioral treatment referral.
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Metoclopramide for the treatment of diabetic Gastroparesis.
Expert Review of Gastroenterology & Hepatology, 2019Co-Authors: Mohammed Shakhatreh, Zubair A. Malik, Asad Jehangir, Henry P. ParkmanAbstract:Introduction: Gastroparesis is a chronic disorder of the stomach characterized by delayed gastric emptying without mechanical obstruction. Diabetes is the most commonly known cause of Gastroparesis...
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Gastric Electric Stimulation for Refractory Gastroparesis.
Journal of Clinical Outcomes Management, 2019Co-Authors: Bryan Zoll, Asad Jehangir, Zubair A. Malik, Michael A. Edwards, Roman Petrov, Henry P. ParkmanAbstract:Objective To outline the use and utility of gastric electric stimulation (GES) as a therapeutic intervention for Gastroparesis. Methods Review of the literature. Results Gastroparesis is characterized by delayed gastric emptying, with symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Some patients with Gastroparesis do not respond to medical intervention, and for these patients surgical intervention may be warranted. GES utilizes high-frequency gastric neurostimulation to facilitate gastric emptying and reduce symptoms of Gastroparesis. It is indicated for patients with idiopathic and diabetic Gastroparesis who have nausea and vomiting as their primary symptoms and who have not responded to medical therapy. GES has also been used in postsurgical and pediatric Gastroparesis patients. Optimizing the outcome of this surgical treatment through proper patient selection and meticulous surgical technique is essential as there are inherent risks to the procedure. Nonblinded studies of GES for medically refractory Gastroparesis have demonstrated therapeutic symptomatic benefit, whereas randomized controlled trials have not. New interventions such as pyloromyotomy and pyloroplasty are reasonable alternatives or addendums to GES. Conclusion GES may be considered among the therapies available for treating patients with refractory symptoms of Gastroparesis. More studies, specifically those comparing GES, pyloromyotomy, GES combined with pyloromyotomy, and placebo, are needed to help guide therapy selection for refractory Gastroparesis.
Pankaj J. Pasricha - One of the best experts on this subject based on the ideXlab platform.
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opioid use and potency are associated with clinical features quality of life and use of resources in patients with Gastroparesis
Clinical Gastroenterology and Hepatology, 2019Co-Authors: William L. Hasler, Pankaj J. Pasricha, Richard W. Mccallum, William J. Snape, Thomas L. Abell, Irene Sarosiek, Laura Wilson, Kenneth L Koch, Linda A Nguyen, Gianrico FarrugiaAbstract:Background & Aims Many patients with Gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship 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 health care resource use from 583 patients with Gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases 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 ≤ .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). Conclusions 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 as 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.
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transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC Medical Genomics, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Asha Nair, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Wilson, Laura Miriel, Henry P. ParkmanAbstract: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.
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glucose sensor augmented continuous subcutaneous insulin infusion in patients with diabetic Gastroparesis an open label pilot prospective study
PLOS ONE, 2018Co-Authors: Jorge Callesescandon, Pankaj J. Pasricha, Henry P. Parkman, William L. Hasler, Kenneth L Koch, Mark L Van Natta, James Tonascia, Frank A Hamilton, William H Herman, Marina BasinaAbstract: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 ( 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.
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Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Miriel, Asha A. Nair, Laura A. Wilson, Henry P. ParkmanAbstract:Abstract Background 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. Methods 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. Results 111 genes were differentially expressed in diabetic Gastroparesis and 181 in idiopathic Gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR)
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Gastroparesis: Definitions and Diagnosis
Gastroenterology Clinics of North America, 2014Co-Authors: Pankaj J. Pasricha, Henry P. ParkmanAbstract:Gastroparesis is a chronic symptomatic disorder of the stomach characterized by delayed emptying without evidence of mechanical obstruction. Symptoms of Gastroparesis include nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. The 3 main causes are diabetic, postsurgical, and idiopathic. Diagnosis is confirmed by demonstrating delayed gastric emptying. Gastric emptying rates measured by gastric motor testing generally correlate poorly with symptoms and quality of life in patients with Gastroparesis. It may be appropriate to reconsider the definition of Gastroparesis, recognizing it as a broader spectrum of gastric neuromuscular dysfunction.
Madhusudan Grover - One of the best experts on this subject based on the ideXlab platform.
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body weight in patients with idiopathic Gastroparesis
Neurogastroenterology and Motility, 2020Co-Authors: Henry P. Parkman, Madhusudan Grover, Gianrico Farrugia, Richard W. Mccallum, Thomas L. Abell, Irene Sarosiek, Kenneth L Koch, Mark L Van Natta, Goro Yamada, Braden KuoAbstract:BACKGROUND The classic clinical picture of Gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic Gastroparesis. METHODS In patients with idiopathic Gastroparesis, detailed history and weight were acquired at enrollment and after 48 weeks. Questionnaires assessed symptoms, food intake, physical activity, and quality of life. Patients underwent laboratory testing, gastric emptying scintigraphy, and water load testing. RESULTS Of 138 patients with idiopathic Gastroparesis, 10% were underweight (BMI 30 kg/m2 . Body weight at enrollment was positively associated with oral caloric consumption (P < .001), following a Gastroparesis diet (P = .04), nutrition consultation (P = .001), upper abdominal pain (P = .01); and negatively associated with energy expenditure (P = .05), alcohol use (P = .003) and severity of bloating (P < .001). When followed over 48 weeks, 53% patients stayed stable (within 5% of baseline weight), 30% gained, and 17% lost weight. Weight gain over 48 weeks was positively associated with oral caloric consumption (P = .003) and constipation severity (P = .005) at enrollment, and negatively associated with lower abdominal pain severity (P = .007) at enrollment, and associated with improvement in inability to finish meal score (P < .001) at 48 weeks. CONCLUSIONS In this series of patients with idiopathic Gastroparesis, 10% were underweight whereas 29% were obese. Over 48 weeks, 30% of patients increased their body weight ≥ 5%. Diet, activity, and symptoms are important factors associated with body weight in patients with idiopathic Gastroparesis.
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transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC Medical Genomics, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Asha Nair, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Wilson, Laura Miriel, Henry P. ParkmanAbstract: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.
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Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Miriel, Asha A. Nair, Laura A. Wilson, Henry P. ParkmanAbstract:Abstract Background 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. Methods 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. Results 111 genes were differentially expressed in diabetic Gastroparesis and 181 in idiopathic Gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR)
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Additional file 5: of Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
2018Co-Authors: Madhusudan Grover, Asha Nair, Seth T Eisenman, Laura Wilson, Laura Miriel, Simon Gibbons, Cheryl Bernard, Adeel Zubair, Pankaj Pasricha, Henry ParkmanAbstract:Table S5. Differentially expressed genes common in diabetic Gastroparesis and diabetic controls and idiopathic Gastroparesis and controls. (XLSX 107 kb
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ultrastructural differences between diabetic and idiopathic Gastroparesis
Journal of Cellular and Molecular Medicine, 2012Co-Authors: Maria Simonetta Faussonepellegrini, Pankaj J. Pasricha, Madhusudan Grover, Henry P. Parkman, William J. Snape, Thomas L. Abell, Cheryl E Bernard, Matthew S Lurken, Thomas C Smyrk, William L. HaslerAbstract: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.
William L. Hasler - One of the best experts on this subject based on the ideXlab platform.
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opioid use and potency are associated with clinical features quality of life and use of resources in patients with Gastroparesis
Clinical Gastroenterology and Hepatology, 2019Co-Authors: William L. Hasler, Pankaj J. Pasricha, Richard W. Mccallum, William J. Snape, Thomas L. Abell, Irene Sarosiek, Laura Wilson, Kenneth L Koch, Linda A Nguyen, Gianrico FarrugiaAbstract:Background & Aims Many patients with Gastroparesis are prescribed opioids for pain control, but indications for opioid prescriptions and the relationship 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 health care resource use from 583 patients with Gastroparesis (>10% 4-h scintigraphic retention) from the National Institute of Diabetes and Digestive and Kidney Diseases 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 ≤ .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). Conclusions 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 as 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.
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glucose sensor augmented continuous subcutaneous insulin infusion in patients with diabetic Gastroparesis an open label pilot prospective study
PLOS ONE, 2018Co-Authors: Jorge Callesescandon, Pankaj J. Pasricha, Henry P. Parkman, William L. Hasler, Kenneth L Koch, Mark L Van Natta, James Tonascia, Frank A Hamilton, William H Herman, Marina BasinaAbstract: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 ( 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.
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Early satiety and postprandial fullness in Gastroparesis correlate with Gastroparesis severity, gastric emptying, and water load testing.
Neurogastroenterology and Motility, 2016Co-Authors: Henry P. Parkman, Gianrico Farrugia, Richard W. Mccallum, K L Koch, Erin Hallinan, William L. Hasler, Linda Nguyen, William J. Snape, Thomas L. Abell, Irene SarosiekAbstract:Background Early satiety (ES) and postprandial fullness (PPF) are often present in Gastroparesis, but the importance of these symptoms in Gastroparesis has not been well-described. The aims were: (i) Characterize ES and PPF in patients with Gastroparesis. (ii) Assess relationships of ES and PPF with etiology of Gastroparesis, quality of life, body weight, gastric emptying, and water load testing. Methods Gastroparetic patients filled out questionnaires assessing symptoms (PAGI-SYM) and quality of life (PAGI-QOL, SF-36v2). Patients underwent gastric emptying scintigraphy and water load testing. Key Results 198 patients with Gastroparesis (134 IG, 64 DG) were evaluated. Early satiety was severe or very severe in 50% of patients. Postprandial fullness was severe or very severe in 60% of patients. Severity scores for ES and PPF were similar between idiopathic and diabetic Gastroparesis. Increasing severity of ES and PPF were associated with other Gastroparesis symptoms including nausea/vomiting, satiety/early fullness, bloating, and upper abdominal pain and GERD subscores. Increasing severity of ES and PPF were associated with increasing Gastroparesis severity, decreased BMI, decreased quality of life from PAGI-QOL and SF-36 physical health. Increasing severity of ES and PPF were associated with increasing gastric retention of a solid meal and decreased volume during water load test. Conclusions & Inferences Early satiety and PPF are commonly severe symptoms in both diabetic and idiopathic Gastroparesis. Early satiety and PPF severity are associated with other Gastroparesis symptom severities, body weight, quality of life, gastric emptying, and water load testing. Thus, ES and PPF are important symptoms characterizing Gastroparesis. ClinicalTrials.gov number: NCT NCT01696747.
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Nausea and vomiting in Gastroparesis: similarities and differences in idiopathic and diabetic Gastroparesis.
Neurogastroenterology and Motility, 2016Co-Authors: Henry P. Parkman, Gianrico Farrugia, K L Koch, Erin Hallinan, William L. Hasler, William J. Snape, Thomas L. Abell, Irene Sarosiek, J. Calles, Richard W. MccallumAbstract:Background Nausea and vomiting are classic symptoms of Gastroparesis. It remains unclear if characteristics of nausea and vomiting are similar in different etiologies of Gastroparesis. The aims of this article were as follows: to describe characteristics of nausea and vomiting in patients with Gastroparesis and to determine if there are differences in nausea and vomiting in diabetic (DG) and idiopathic Gastroparesis (IG). Methods Gastroparetic patients enrolling in the NIDDK Gastroparesis Registry underwent assessment with history and questionnaires assessing symptoms, quality of life, and a questionnaire characterizing nausea and vomiting. Key Results Of 159 Gastroparesis patients (107 IG, 52 DG), 96% experienced nausea, whereas 65% experienced vomiting. Nausea was predominant symptom in 28% and vomiting was predominant in 4%. Nausea was severe or very severe in 41%. PAGI-SYM nausea/vomiting subscore was greater with increased vomiting severity, but not nausea severity in DG than IG. Nausea was related to meals in 71%; lasting most of the day in 41%. Increasing nausea severity was related to decreased quality of life. Nausea often preceded vomiting in 82% of patients and vomiting often relieved nausea in 30%. Vomiting was more common in DG (81%) compared to IG (57%; p = 0.004). Diabetic patients more often had vomiting in the morning before eating, during the night, and when not eating. Conclusions & Inferences Nausea is present in essentially all patients with Gastroparesis irrespective of cause and associated with decreased quality of life. In contrast, vomiting was more prevalent, more severe, and occurred more often in DG than IG. Thus, characteristics of vomiting differ in IG vs DG.
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Su1431 Abdominal Pain in Gastroparesis: A Common Symptom Associated With Gender, Anxiety and Other Gastroparesis Symptoms
Gastroenterology, 2015Co-Authors: Henry P. Parkman, Gianrico Farrugia, Richard W. Mccallum, William L. Hasler, Thomas L. Abell, Irene Sarosiek, Laura Wilson, John O. Clarke, Linda Anh B. Nguyen, William J. SnapeAbstract:Abdominal pain is seen in many patients with Gastroparesis, but is not well characterized or recognized as a symptom of Gastroparesis. Aims: 1) Describe characteristics of abdominal pain in Gastroparesis; and 2) Determine differences in abdominal pain between diabetic (DG) and idiopathic Gastroparesis (IG). Methods: Gastroparetic patients were enrolled at 8 centers into the NIH Gastroparesis Registry from September 2012 to October 2014. Patients had symptoms of Gastroparesis for >12 weeks, delayed gastric emptying, negative endoscopy. History and physical examinations, questionnaires assessing symptoms (PAGI-SYM), quality of life (PAGI-QOL, SF-36), psychologic state (Beck Depression Inventory, State Trait Anxiety Index, PHQ-15), and a questionnaire characterizing abdominal pain were obtained. Results: 117 Gastroparesis patients were enrolled: 74 IG, 40 DG, and 3 Post-Nissen. Overall, 92% of patients were experiencing abdominal pain. Abdominal pain was described as discomforting (38%) or distressing (27%), occurring every day in 52%, and most often localized in the upper middle portion of the abdomen (35% of patients) or middle central portion (19%). Abdominal pain worsened with eating in 52%, occurred at night (46%), and interfered with sleep (29%). Severity of upper abdominal pain, assessed by PAGI-SYM, was severe or very severe in 35% of patients, was more severe in females (p=0.001), and associated with decreased quality of life by PAGI-QOL (p=0.03) and SF-36 physical (p=0.11) and mental (p=0.10) components. Abdominal pain severity was associated with other symptoms of Gastroparesis: nausea/vomiting subscale (p=0.03), early satiety/postprandial fullness subscale (p
Cheryl E Bernard - One of the best experts on this subject based on the ideXlab platform.
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transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC Medical Genomics, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Asha Nair, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Wilson, Laura Miriel, Henry P. ParkmanAbstract: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.
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Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic Gastroparesis
BMC, 2018Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Simon J Gibbons, Cheryl E Bernard, Adeel S Zubair, Seth T Eisenman, Laura Miriel, Asha A. Nair, Laura A. Wilson, Henry P. ParkmanAbstract:Abstract Background 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. Methods 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. Results 111 genes were differentially expressed in diabetic Gastroparesis and 181 in idiopathic Gastroparesis with a log2fold difference of | ≥ 2| and false detection rate (FDR)
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ultrastructural differences between diabetic and idiopathic Gastroparesis
Journal of Cellular and Molecular Medicine, 2012Co-Authors: Maria Simonetta Faussonepellegrini, Pankaj J. Pasricha, Madhusudan Grover, Henry P. Parkman, William J. Snape, Thomas L. Abell, Cheryl E Bernard, Matthew S Lurken, Thomas C Smyrk, William L. HaslerAbstract: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.
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clinical histological associations in Gastroparesis results from the Gastroparesis clinical research consortium
Neurogastroenterology and Motility, 2012Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Henry P. Parkman, William J. Snape, Thomas L. Abell, Cheryl E Bernard, Maria Simonetta Faussonepellegrini, Matthew S Lurken, Thomas C Smyrk, William L. HaslerAbstract:Background 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. Methods 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. Key Results 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. Conclusions & Inferences 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.
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Clinical-histological associations in Gastroparesis: results from the Gastroparesis Clinical Research Consortium: Clinical-histological associations in Gastroparesis
Neurogastroenterology and Motility, 2012Co-Authors: Madhusudan Grover, Pankaj J. Pasricha, Henry P. Parkman, William J. Snape, Thomas L. Abell, Cheryl E Bernard, Matthew S Lurken, Thomas C Smyrk, Maria-simonetta Faussone-pellegrini, William L. HaslerAbstract:Background 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. Methods 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. Key Results 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. Conclusions & Inferences 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.
