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Gait analysis is a systematic study of human movement. Combining wearable foot pressure sensors and machine learning (ML) solutions for a high-fidelity body pose tracking from RGB video frames could reveal more insights into gait abnormalities. However, accurate detection of heel strike (HS) and toe-off (TO) events is crucial to compute interpretable gait parameters. In this work, we present an experimental platform to study the timing of gait events using a new wearable foot pressure sensor (ActiSense System, IEE S.A., Luxembourg), and Google’s open-source ML solution MediaPipe Pose. For this purpose, two StereoPi systems were built to capture stereoscopic videos and images in real time. MediaPipe Pose was applied to the synchronized StereoPi cameras, and two algorithms (ALs) were developed to detect HS and TO events for gait and analysis. Preliminary results from a healthy subject walking on a treadmill show a mean relative deviation across all time spans of less than 4% for the ActiSense device and less than 16% for AL2 (33% for AL1) employing MediaPipe Pose on StereoPi videos. Finally, this work offers a platform for the development of sensor- and video-based ALs to automatically identify the timing of gait events in healthy individuals and those with gait disorders.

Deep brain stimulation (DBS) is an established therapy for movement disorders such as in Parkinson's disease (PD) and essential tremor (ET). Adjusting the stimulation parameters, however, is a labour-intensive process and often requires several patient visits. Physicians prefer objective tools to improve (or maintain) the performance in DBS. Wearable motion sensors (WMS) are able to detect some manifestations of pathological signs, such as tremor in PD. However, the interpretation of sensor data is often highly technical and methods to visualise tremor data of patients undergoing DBS in a clinical setting are lacking. This work aims to visualise the dynamics of tremor responses to DBS parameter changes with WMS while patients performing clinical hand movements. To this end, we attended DBS programming sessions of two patients with the aim to visualise certain aspects of the clinical examination. PD tremor and ET were effectively quantified by acceleration amplitude and frequency. Tremor dynamics were analysed and visualised based on setpoints, movement transitions and stability aspects. These methods have not yet been employed and examples demonstrate how tremor dynamics can be visualised with simple analysis techniques. We therefore provide a base for future research work on visualisation tools in order to assist clinicians who frequently encounter patients for DBS therapy. This could lead to benefits in terms of enhanced evaluation of treatment efficacy in the future.

Programming in deep brain stimulation (DBS) is often a labour-intensive process. Although automatic closed-loop stimulation has recently been receiving considerable attention, it is still far from clinical settings. Testing in-loop stimulation in a clinical setting is extremely challenging due to manual programming and the lack of synchronisation between stimulation and monitoring devices. In this work, we present a simple rulebased expert system to test feedback-controlled DBS in a clinical setting. The new application operates in closed-loop with the physician as acting person and real-time feedback from an accelerometer. Patients with movement disorders such as in essential tremor announce an individually acceptable level of tremor as a boundary condition for control. As a proof-of-concept, the expert system provides continuous recommendations of stimulation parameters and guides the physician to increase or decrease DBS amplitude by capturing tremor acceleration power on the patients’ forearms. The introduced application considers the technical and practical aspects in a clinical setting. Data obtained from test subjects provide insight into tremor dynamics. We demonstrate the clinical applicability of the rule-based control system for future research focusing on tremor dynamics and inloop stimulation. Finally, a telemetry streaming system could provide the interface for the application of automatic tremor control without the physician as acting person.

For the assessment of human reaction time, a test environment was developed. This system consists of an embedded device with organic light-emitting diode (OLED) displays with push buttons for the combined presentation of visual stimulation and registration of the haptic human reaction. The test leader can define the test sequence with the aid of a graphical user interface (GUI) on a personal computer (PC). The validation of the system was proved by measuring the latency times of the whole system, which are conditioned by the specific hard- and software constellation. Through the investigation of the display’s light radiation by a photodiode and the recorded current consumption, latency times and their variance were specified. In the fastest mode the system can reach an error limit of 60 μs.

The quality of bioelectrical signals is essential for functional evaluation of cellular circuits. The electrical activity recorded from the cortical brain surface represents the average of many individual synaptic processes. By downsizing micro-electrode arrays, the spatial resolution of electrocortico-grams (ECoGs) can be increased. But, upon increasing electrode impedance, recorded noise from the electrode-tissue interface and the surroundings will become more prominent. Frequently, signal interpretation is improved by post-processing using filtering or pattern recognition. For a variety of applications, wavelet denoising has become an accepted tool. Here, we present how wavelet denoising affects the signal-to-noise ratio of ECoGs. The recording qualities from awake and anesthetized mice was artificially reduced by adding two noise models prior to filtering. Raw and filtered signals were compared by calculating the linear correlation coefficient.

When performing electrocorticography, reliable recordings of bioelectrical signals are essential for signal processing and analysis. The acquisition of cellular electrical activity from the brain surface of mice requires a system that is able to record small signals within a low frequency range. This work presents a recording system with self-developed software and shows the result of a technical characterization in combination with self-developed electrode arrays to measure electrocorticograms of mice.

Abstract Psychiatric patients often suffer from stress, anxiety and depression. Various plant extracts are known to fight stress (valerian), anxiety (passion flower) or depression (St. John's wort). NEURAPAS® balance is a mixture of these three extracts and has been designed to cover this complex of psychiatric conditions. The study was initiated to quantitatively assess the effect of this combination on brain electric activity. Method Quantitative electroencephalogram (EEG) current source density (CSD) recording from 16 healthy male and female human volunteers (average age 49 years) was used in a randomized, placebo-controlled cross over study. Recordings were performed 0. 5, 1. 5, 3 and 4 hours after administration of the preparations under the conditions of 6 min eyes open and 5 min d2 concentration test, mathematical calculation test and memory test, respectively. All variables (electric power within 6 frequency ranges at 17 electrode positions) were fed into a linear discriminant analysis (eyes open condition). In the presence of mental load these variables were used to construct brain maps of frequency changes. Results Under the condition of mental load, centro-parietal spectral power remained statistically significantly lower within alpha1, alpha2 and beta1 frequencies in the presence of verum in comparison to placebo. Discriminant analysis revealed a difference to placebo 3 and 4 hours after intake of 6 tablets of NEURAPAS® balance. Data location within the polydimensional space was projected into the area of the effects of sedative and anti-depressive reference drugs tested earlier under identical conditions. Results appeared closer to the effects of fluoxetine than to St. John's wort. Conclusions Analysis of the neurophysiological changes following the intake of NEURAPAS® balance revealed a similarity of frequency changes to those of calming and anti-depressive drugs on the EEG without impairment of cognition. Trial registration ClinicalTrials.gov: NCT01047605

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied., Aims: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp., Methods: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and dysrhythmic ranges, was recorded using electrogastrography., Results: Overall, vitamin D levels were low (< 30 ng/ml) in 288 of 513 (56.1%) patients with symptoms of Gp (206 of 376 (54.8%) patients with delayed gastric emptying (Gp) and 82 of 137 (59.9%) patients with symptoms of Gp and normal gastric emptying). Low vitamin D levels were associated with increased nausea and vomiting (P < 0.0001), but not with fullness or bloating subscores. Low vitamin D levels in patients with Gp were associated with greater meal retention at four hours (36% retention) compared with Gp patients with normal vitamin D levels (31% retention; P = 0.05). Low vitamin D in patients with normal gastric emptying was associated with decreased normal 3 cpm GMA before (P = 0.001) and increased tachygastria after WLST (P = 0.01)., Conclusions: Low vitamin D levels are present in half the patients with symptoms of gastroparesis and are associated with nausea and vomiting and gastric neuromuscular dysfunction., (© 2024. The Author(s).)

Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45 + cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis., Competing Interests: Madhusudan Grover has received investigator-initiated grant funding from Takeda pharmaceuticals and clinical trial funding from Alexza and Donga pharmaceuticals. He serves as a consultant for Alfasigma, Ardelyx and Evoke pharmaceuticals. Bruno P. Chumpitazi receives research funding from Cairn Diagnostics, is a consultant for Ironwood Pharmaceuticals, and receives royalties from the Rome Foundation. These entities did not support the presented work. No disclosures for other co-authors., (© 2024 The Author(s).)

Gastric emptying scintigraphy (GES) measures total gastric retention after a solid meal and can assess intragastric meal distribution (IMD). Water load satiety test (WLST) measures gastric capacity. Both IMD immediately after meal ingestion [ratio of proximal gastric counts after meal ingestion to total gastric counts at time 0 (IMD 0 )] and WLST (volume of water ingested over 5 min) are indirect measures of gastric accommodation. In this study, IMD 0 and WLST were compared with each other and to symptoms of gastroparesis to gauge their clinical utility for assessing patients with symptoms of gastroparesis. Patients with symptoms of gastroparesis underwent GES to obtain gastric retention and IMD 0 , WLST, and filled out patient assessment of upper GI symptoms. A total of 234 patients with symptoms of gastroparesis were assessed (86 patients with diabetes, 130 idiopathic, 18 postfundoplication) and 175 (75%) delayed gastric emptying. Low IMD 0 <0.568 suggesting initial rapid transit to the distal stomach was present in 8% and correlated with lower gastric retention, less heartburn, and lower volumes consumed during WLST. Low WLST volume (<238 mL) was present in 20% and associated with increased severity of early satiety, postprandial fullness, loss of appetite, and nausea. Low IMD 0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD 0 , has associations with early satiety, postprandial fullness, loss of appetite, and nausea. Thus, IMD 0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms. NEW & NOTEWORTHY IMD 0 and WLST were assessed for their clinical utility in assessing patients with symptoms of gastroparesis. Low IMD 0 is associated with less gastric retention and less heartburn. Volume of water consumed during WLST, while associated with IMD0, has associations with early satiety, postprandial fullness, loss of appetite, and nausea. IMD 0 and WLST appear to overlap somewhat in their assessment of gastric physiology in adults with symptoms of gastroparesis but relate to different dyspeptic symptoms.

Background: Gastroparesis (GP) is characterized by delayed gastric emptying in the absence of mechanical obstruction., Objective: Genetic predisposition may play a role; however, investigation at the genome-wide level has not been performed., Methods: We carried out a genome-wide association study (GWAS) meta-analysis on (i) 478 GP patients from the National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) compared to 9931 population-based controls from the University of Michigan Health and Retirement Study; and (ii) 402 GP cases compared to 48,340 non-gastroparesis controls from the Michigan Genomics Initiative. Associations for 5,811,784 high-quality SNPs were tested on a total of 880 GP patients and 58,271 controls, using logistic mixed models adjusted for age, sex, and principal components. Gene mapping was obtained based on genomic position and expression quantitative trait loci, and a gene-set network enrichment analysis was performed. Genetic associations with clinical data were tested in GpCRC patients. Protein expression of selected candidate genes was determined in full thickness gastric biopsies from GpCRC patients and controls., Results: While no SNP associations were detected at strict significance (p ≤ 5 × 10 -8 ), nine independent genomic loci were associated at suggestive significance (p ≤ 1 × 10 -5 ), with the strongest signal (rs9273363, odds ratio = 1.4, p = 1 × 10 -7 ) mapped to the human leukocyte antigen region. Computational annotation of suggestive risk loci identified 14 protein-coding candidate genes. Gene-set network enrichment analysis revealed pathways potentially involved in immune and motor dysregulation (p FDR ≤ 0.05). The GP risk allele rs6984536A (Peroxidasin-Like; PXDNL) was associated with increased abdominal pain severity scores (Beta = 0.13, p = 0.03). Gastric muscularis expression of PXDNL also positively correlated with abdominal pain in GP patients (r = 0.8, p = 0.02). Dickkopf WNT Signaling Pathway Inhibitor 1 showed decreased expression in diabetic GP patients (p = 0.005 vs. controls)., Conclusion: We report preliminary GWAS findings for GP, which highlight candidate genes and pathways related to immune and sensory-motor dysregulation. Larger studies are needed to validate and expand these findings in independent datasets., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Patients with gastroparesis and related disorders have symptoms including early satiety, postprandial fullness and bloating. Buspirone, a 5-HT 1 receptor agonist, may improve fundic accommodation., Aim: To determine if buspirone treatment improves early satiety and postprandial fullness in patients with symptoms of gastroparesis., Methods: This 4-week multi-centre clinical trial randomised patients with symptoms of gastroparesis and moderate-to-severe symptoms of fullness (Gastroparesis Cardinal Symptom Index [GCSI] early satiety/postprandial fullness subscore [ES/PPF]) to buspirone (10 mg orally) or placebo three times per day. The primary outcome was a change in the ES/PPF from baseline to 4 weeks. The primary analysis was per protocol intention-to-treat ANCOVA of between-group baseline vs. 4-week differences (DoD) in ES/PPF adjusted for baseline ES/PPF. Results are reported using both nominal and Bonferroni (BF) p values., Results and Conclusions: Ninety-six patients (47 buspirone, 49 placeboes; 92% female, 50% delayed gastric emptying, 39% diabetic) were enrolled. There was no between-groups difference in the 4-week ES/PPF primary outcome: -1.16 ± 1.25 (SD) on buspirone vs -1.03 ± 1.29 (SD) on placebo (mean DoD: -0.11 [95% CI: -0.68, 0.45]; p = 0.69). Buspirone performed better than placebo in patients with severe-to-very severe bloating at baseline compared to patients with none to moderate: (ES/PPF DoD = -0.65 vs. 1.58, p TX*GROUP  = 0.003; p BF  = 0.07). Among individual GCSI symptoms, only bloating appeared to improve with buspirone vs. placebo., Conclusions: Patients with moderate-to-severe early satiety/postprandial fullness and other symptoms of gastroparesis did not benefit from buspirone treatment to improve the ES/PPF primary outcome compared with placebo. There was a suggestion of the benefit of buspirone in patients with more severe bloating., Trial Registration: ClinicalTrials.gov NCT0358714285., (© 2023 John Wiley & Sons Ltd.)

Background: Patients with gastroparesis (Gp) may need enteral nutrition (EN) or exclusive parenteral nutrition (PN). Among patients with Gp, we aimed to (1) identify the frequency of EN and exclusive PN use and (2) explore characteristics of patients using EN and/or exclusive PN compared with those using oral nutrition (ON), including changes over 48 weeks., Methods: Patients with Gp underwent history and physical examination, gastric emptying scintigraphy, water load satiety testing (WLST), and questionnaires assessing gastrointestinal symptoms and quality of life (QOL). Patients were observed 48 weeks., Results: Of 971 patients with Gp (idiopathic, 579; diabetic, 336; post-Nissen fundoplication, 51), 939 (96.7%) were using ON only, 14 (1.4%) using exclusive PN, and 18 (1.9%) using EN. Compared with patients receiving ON, patients receiving exclusive PN and/or EN were younger, had lower body mass index, and had greater symptom severity. Patients receiving exclusive PN and/or EN had lower physical QOL but not mental QOL or Gp-related QOL scores. Patients receiving exclusive PN and/or EN ingested less water during WLST but did not have worse gastric emptying. Of those who had been receiving exclusive PN and/or EN, 50% and 25%, respectively, resumed ON at 48-week follow-up., Conclusions: This study describes patients with Gp requiring exclusive PN and/or EN for nutrition support, who represent a small (3.3%) but important subset of patients with Gp. Unique clinical and physiological parameters are associated with this subset and provide insight into the use of nutrition support in Gp., (© 2023 American Society for Parenteral and Enteral Nutrition.)

Background: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain., Aims: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD., Methods: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load for individual patients were also determined., Results: 284 patients with GP and 113 with FD were identified who ingested both test meals. Patients with GP and FD had similar maximal tolerated volumes of water [mean (SD) 378 (218) ml vs. 402 (226) ml, p = 0.23] and reported similar intensity of fullness, nausea, bloating, and abdominal discomfort after the test meals. Twenty-six percent and 19% of the patients with GP and FD, respectively, ingested subthreshold (<238 ml) volumes of water (p = 0.15). Gastric dysrhythmias were recorded in 66% of the GP and 65% of the FD patients after the water load. Symptoms and GMA were similar in both groups after ingestion of the nutrient bar., Conclusion: The similarity in GMA responses and symptoms after ingestion of solid or liquid test meals suggests GP and FD are closely related gastric neuromuscular disorders., (© 2022 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders., (Copyright © 2022 AGA Institute. All rights reserved.)

Background: Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms., Methods: Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar's test. Risk differences with standard errors were employed to estimate percent reduction in symptoms., Results: Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders., Discussion: Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.

Patients often are evaluated for gastroparesis because of symptoms occurring with meals. Gastric emptying scintigraphy (GES) is used for gastroparesis diagnosis, although results are not well correlated with gastroparesis symptoms. The aim of this study is to assess relationships between gastroparesis symptoms, gastric emptying (GE), and gastric accommodation (GA). Patients with symptoms of gastroparesis completed the Patient Assessment of Upper GI Symptoms (PAGI-SYM) and recorded symptoms during GES and water load satiety test (WLST), an indirect assessment for GA. A total of 109 patients with gastroparesis symptoms were assessed. Symptom severity increased after GES meal for stomach fullness, belching, nausea, abdominal burning, and abdominal pain. There was no difference in symptoms after meal between patients with delayed ( n = 66) and normal ( n = 42) GE. Diabetic patients ( n = 26) had greater gastric retention than idiopathic patients ( n = 78), but idiopathic patients had greater postprandial nausea, stomach fullness, and abdominal pain. Water consumed during WLST averaged 421 ± 245 mL. Idiopathic patients had greater nausea scores during WLST than diabetic patients. In comparison to those with normal water consumption (≥238 mL; n = 80), patients with impaired water ingestion (<238 mL; n = 26) had increased stomach fullness, early satiety, postprandial fullness, and loss of appetite on PAGI-SYM. Patients with delayed and normal GE had similar symptom profiles during GES and WLST. Idiopathic patients had less gastric retention but more symptoms after GES meal and after WLST compared with diabetic patients. Patients with impaired water consumption during WLST had increased symptoms by PAGI-SYM. These data suggest that impaired GA, rather than GE, may be important in explaining postprandial symptoms in patients with symptoms of gastroparesis. NEW & NOTEWORTHY Patients with delayed and normal gastric emptying (GE) had similar symptom profiles during gastric emptying scintigraphy (GES). Idiopathic patients with symptoms of gastroparesis had less gastric retention by GES; but more symptoms after GES meal and after water load satiety test (WLST) compared with diabetic patients. In patients with symptoms of gastroparesis, symptoms after WLST increased with decreasing water consumption. Early satiety and loss of appetite were associated with decreased water consumption during WLST. Thus, impaired accommodation and perhaps visceral hypersensitivity are important in explaining postprandial symptoms in gastroparesis.

Background: Pulmonary arterial hypertension (PAH) increases right ventricular (RV) workload and decreases myocardial oxygen reserve, eventually leading to poor cardiac output. This study created and assessed a novel model of RV work output based on RV hemodynamics and oxygen supply, allowing new insight into causal mechanisms of RV dysfunction., Methods: The RV function model was built upon an earlier, left ventricular model and further adjusted for more accurate clinical use. The model assumes that RV total power output (1) is the sum of isovolumic and stroke power and (2) is linearly related to its right coronary artery oxygen supply. Thus, when right coronary artery flow is limited or isovolumic power is elevated, less energy is available for producing cardiac output. The original and adjusted models were validated via data from patients with idiopathic PAH (n = 14) and large animals (n = 6) that underwent acute pulmonary banding with or without hypoxia., Results: Both models demonstrated strong, significant correlations between RV oxygen consumption rate and RV total power output for PAH patients (original model, R 2  = 0.66; adjusted model, R 2  = 0.78) and sheep (original, R 2  = 0.85; adjusted, R 2  = 0.86). Furthermore, the models demonstrate a significant inverse relationship between required oxygen consumption and RV efficiency (stroke power/total power) (p < 0.001). Lastly, higher NYHA class was indicative of lower RV efficiency and higher oxygen consumption (p = 0.013)., Conclusion: Right ventricular total power output can be accurately estimated directly from pulmonary hemodynamics and right coronary perfusion during PAH. This model highlights the increased vulnerability of PAH patients with compromised right coronary flow coupled with high afterload., (© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Autoimmunity may play a role in the pathogenesis of gastroparesis in a subset of patients. Antinuclear antibody (ANA) testing is often used to screen for autoimmune disorders., Aims: 1) Determine prevalence of a positive ANA in patients with gastroparesis; 2) Describe characteristics of idiopathic gastroparesis patients with positive ANA., Methods: Patients were assessed with gastric emptying scintigraphy (GES), symptom assessment via Patient Assessment of Upper GI Symptoms [PAGI-SYM], and blood tests-ANA, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)., Results: Positive ANA was seen in 148 of 893 (17%) patients with gastroparesis, being similar in idiopathic (16% of 536 patients), T1DM (16% of 162), T2DM (18% of 147), and postfundoplication (19% of 48 patients) gastroparesis. Among 536 patients with idiopathic gastroparesis, ANA titer 1:40-1:80 was seen in 33 (6%) patients, 1:160-1:320 in 36 (7%) patients, and ≥1:640 in 17 (3%) patients. Increasing ANA titer was associated with female gender (p = 0.05), Hispanic ethnicity (p = 0.02), comorbid rheumatoid arthritis (p = 0.02), systemic sclerosis (p = 0.004), and elevated ESR (p = 0.007). ANA positivity was associated with lower total GCSI (p = 0.007) and lower nausea/vomiting subscale (p = 0.0005), but not related to gastric emptying., Conclusions: The prevalence of a positive ANA in patients with gastroparesis was high at ~17% and did not differ significantly based on etiology. In idiopathic patients, ANA positivity was associated with rheumatoid arthritis, systemic sclerosis, and elevated ESR. ANA-positive gastroparesis represents a subset who often have other autoimmune symptoms or disorders, but less severe nausea and vomiting., (© 2021 John Wiley & Sons Ltd.)

Background & Aims: The use of domperidone (DOM) for gastroparesis (GP) remains controversial and limited. We aimed to present outcomes of DOM therapy for treatment of patients participating in the multicenter National Institute of Diabetes and Digestive and Kidney Diseases Gastroparesis Clinical Research Consortium (GpCRC) Registries (GpR)., Methods: The GpCRC cohort consisted of patients with GP (75%) and with GP-like symptoms but with normal gastric emptying (25%). The DOM group initiated therapy during the 96 weeks of enrollment in GpR1 and GpR2. Patients who had previously taken or who were on DOM therapy at enrollment were excluded from this analysis. The control group did not use domperidone (non-DOM group) before or after enrollment. The following outcome measures were identified: change from baseline in Gastroparesis Cardinal Symptom Index total score, with 3 subscales, plus Gastroesophageal Reflux Disease and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life scores., Results: Overall, of 748 patients, 181 (24%) were in the DOM group, whereas 567 were in the non-DOM group. Sixty-three percent of participants had idiopathic GP. At baseline, DOM patients compared with non-DOM patients were significantly younger, had lower body mass index, non-Hispanic ethnicity, a higher annual household income, lower narcotic utilization, lower supplemental and complimentary medication use, and were more likely to have delayed gastric emptying time, as well as worse nausea and fullness scores. Compared with non-DOM patients, DOM patients experienced moderate but significantly more improvement in GP outcome measures: Gastroparesis Cardinal Symptom Index total score (P = .003), nausea (P = .003), and fullness subscales (P =.005), upper abdominal pain score (P = .04), Gastroesophageal Reflux Disease score (P = .05), and Patient Assessment of Upper Gastrointestinal Disorders-Quality of Life score (P = .05)., Conclusions: Utilizing the method of pragmatic modeling to evaluate long-term treatment of GP in a large GpCRC database, DOM treatment resulted in moderately but significantly improved GP. NOTE: This project was based on data generated by 2 GpCRC Registry studies recognized under the Clinicaltrial.gov numbers: NCT00398801 and NCT01696747 symptoms compared with a group receiving standard-of-care but not DOM., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Constipation can be an important symptom in some patients with gastroparesis. The aims were to: 1) Determine prevalence of constipation and delayed colonic transit in patients with symptoms of gastroparesis; 2) Correlate severity of constipation to severity of symptoms of gastroparesis; and 3) Relate severity of constipation to GI transit delays assessed by gastric emptying scintigraphy (GES) and wireless motility capsule (WMC)., Methods: Patients with symptoms of gastroparesis underwent gastric emptying scintigraphy (GES), wireless motility capsule (WMC) assessing gastric emptying, small bowel transit, and colonic transit, and questionnaires assessing symptoms using a modified Patient Assessment of Upper GI Symptoms [PAGI-SYM] and Rome III functional GI disorder questionnaire., Results: Of 338 patients with symptoms of gastroparesis, 242 (71.5%) had delayed gastric emptying by scintigraphy; 298 (88.2%) also met criteria for functional dyspepsia. Severity of constipation was severe/very severe in 34% patients, moderate in 24%, and none/very mild/mild in 42%. Increasing severity of constipation was associated with increasing symptoms of gastroparesis and presence of irritable bowel syndrome (IBS). Severity of constipation was not associated with gastric retention on GES or WMC. Delayed colonic transit was present in 108 patients (32% of patients). Increasing severity of constipation was associated with increasing small bowel transit time, colonic transit time, and whole gut transit time., Conclusions: Severe/very severe constipation and delayed colon transit occurs in a third of patients with symptoms of gastroparesis. The severity of constipation is associated with severity of gastroparesis symptoms, presence of IBS, small bowel and colon transit delay, but not delay in gastric emptying. ClinicalTrials.gov Identifier: NCT01696747., (Copyright © 2022 AGA Institute. All rights reserved.)

Background: Understanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management., Aims: (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL., Methods: Gastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI-SYM and Rome III), QOL (SF-36v2 and PAGI-QOL), depression (Beck Depression Inventory [BDI]), and anxiety (State Trait Anxiety InventoryAQ7)., Key Results: 715 gastroparesis patients (256 diabetic (DG), 459 idiopathic (IG)) were evaluated. SF-36 physical component (PC) score averaged 33.3 ± 10.5; 41% had impaired score <30. SF-36 PC scores were similar between diabetic and idiopathic gastroparesis. Impaired SF-36 PC associated with increased nausea/vomiting and upper abdominal pain subscores, acute onset of symptoms, higher number of comorbidities, use of narcotic pain medications, and irritable bowel syndrome (IBS). SF-36 mental component (MC) score averaged 38.9 ± 13.0; 26% had impaired score <30. Poor SF-36 MC associated with diabetic etiology, higher Beck depression inventory, and state anxiety scores. PAGI-QOL score averaged 2.6 ± 1.1; 50% had a score of <2.6. Low PAGI-QOL associated with higher fullness, bloating, and upper abdominal pain subscores, more depression and Trait anxiety, smoking cigarettes, need for nutritional support, progressively worsening symptoms and periodic exacerbations., Conclusions & Inferences: Multiple measures show poor QOL present in gastroparesis. Several areas impacted on reduced QOL: (a) Symptoms of nausea, vomiting, and abdominal pain, as well as IBS; (b) Etiology and acute onset and progressively worsening symptoms; (c) Comorbidities and psychological factors such as anxiety and depression; (d) Patient-related factors such as smoking. Targeting the modifiable factors may improve patient outcomes in gastroparesis., (© 2021 John Wiley & Sons Ltd.)

Background: The aim of this study was to clarify the pathophysiology of functional dyspepsia (FD), a highly prevalent gastrointestinal syndrome, and its relationship with the better-understood syndrome of gastroparesis., Methods: Adult patients with chronic upper gastrointestinal symptoms were followed up prospectively for 48 weeks in multi-center registry studies. Patients were classified as having gastroparesis if gastric emptying was delayed; if not, they were labeled as having FD if they met Rome III criteria. Study analysis was conducted using analysis of covariance and regression models., Results: Of 944 patients enrolled during a 12-year period, 720 (76%) were in the gastroparesis group and 224 (24%) in the FD group. Baseline clinical characteristics and severity of upper gastrointestinal symptoms were highly similar. The 48-week clinical outcome was also similar but at this time 42% of patients with an initial diagnosis of gastroparesis were reclassified as FD based on gastric-emptying results at this time point; conversely, 37% of patients with FD were reclassified as having gastroparesis. Change in either direction was not associated with any difference in symptom severity changes. Full-thickness biopsies of the stomach showed loss of interstitial cells of Cajal and CD206 + macrophages in both groups compared with obese controls., Conclusions: A year after initial classification, patients with FD and gastroparesis, as seen in tertiary referral centers at least, are not distinguishable based on clinical and pathologic features or based on assessment of gastric emptying. Gastric-emptying results are labile and do not reliably capture the pathophysiology of clinical symptoms in either condition. FD and gastroparesis are unified by characteristic pathologic features and should be considered as part of the same spectrum of truly "organic" gastric neuromuscular disorders. CLINICALTRIALS., Gov Identifier: NCT00398801, NCT01696747., (Copyright © 2021 AGA Institute. All rights reserved.)

Background: The cause of chronic nausea can be difficult to diagnose. Idiopathic rapid gastric emptying (iRGE) can cause nausea, but limited literature exists on clinical and pathophysiological features. In contrast, dumping syndrome or post-surgical rapid gastric emptying (psRGE) is well-known and may present with early phase vasomotor symptoms, diarrhea, and late phase reactive hypoglycemia. Our aim is to compare clinical and gastric motility characteristics in patients with iRGE and psRGE and unexplained chronic nausea., Methods: A retrospective study was conducted on patients with unexplained chronic nausea and RGE (<30% retention of a standard isotope-labeled solid meal at 1-h). Gastric myoelectrical activity (GMA) was recorded during water load satiety tests (WLST) using validated electrogastrogram (EGG) recording methods., Key Results: Thirty iRGE and sixteen psRGE patients with unexplained chronic nausea were identified; average 1-hour meal retention was 18.6% and 16.2%, respectively. Nausea, bloating, early satiety, and bowel function were similar in the two groups; fewer iRGE patients had abdominal pain and none had vasomotor symptoms. Normal 3 cpm GMA was recorded in 44% of iRGE vs 29% of psRGE, tachygastria in 13% vs 43%, bradygastria in 25% vs 14%, and mixed in 19% vs 14% (p values >0.05). Abnormal WLST volume (<300 ml) was found in 69% of iRGE and 43% of psRGE (p = 0.36)., Conclusions & Inferences: (a) iRGE and psRGE patients may present with unexplained chronic nausea rather than classic vasomotor symptoms and diarrhea. (b) iRGE and psRGE patients had similar gastric dysrhythmias and accommodation dysfunction, which may contribute to RGE., (© 2020 John Wiley & Sons Ltd.)

Background: The classic clinical picture of gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic gastroparesis., Methods: In patients with idiopathic gastroparesis, detailed history and weight were acquired at enrollment and after 48 weeks. Questionnaires assessed symptoms, food intake, physical activity, and quality of life. Patients underwent laboratory testing, gastric emptying scintigraphy, and water load testing., Results: Of 138 patients with idiopathic gastroparesis, 10% were underweight (BMI < 18.5), 39% were normal weight (BMI 18.5-25), 20% were overweight with BMI 25 to 30 kg/m 2 , and 29% were obese with BMI > 30 kg/m 2 . 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., (© 2020 John Wiley & Sons Ltd.)

Introduction: Due to advances in disease management, mortality rates in children with sickle cell disease (SCD) have decreased. However, mortality rates for young adults (YA) increased, and understanding of social and psychological factors is critical. The aim of this study was to explore factors associated with health care transition experiences for YA with SCD. Method: This was a qualitative descriptive study. A 45-minute semistructured interview was conducted with 13 YA ( M = 21.5 years, SD = 1.73). Results: Results suggest that social and psychological factors and self-management experiences influence health care transition. Eight themes emerged: "need for accessible support"; "early assistance with goal setting"; "incongruence among expectations, experiences, and preparation"; "spiritual distress"; "stigma"; "need for collaboration"; "appreciation for caring providers"; and "feeling isolated." Discussion: Consideration of cultural contexts will guide nurses in supporting health care transition. Designing culturally relevant interventions that address unique needs for YA living with SCD is warranted.

Background: Although gastroparesis is seen in patients with type 2 diabetes mellitus (T2DM), the prevalence of symptoms suggestive of gastroparesis in patients with T2DM is unknown, particularly among African Americans., Aims: To determine the prevalence of symptoms associated with gastroparesis in a large community-based population of European Americans and African Americans with T2DM., Methods: Individuals with T2DM in the Diabetes Heart Study were asked to complete the gastroparesis cardinal symptom index (GCSI) and other GI-related questionnaires. GCSI total score ≥ 18 represented moderate or worse symptoms suggestive of gastroparesis., Results: A total of 1253 participants (700 female, 553 male) completed the GCSI: 750 were European American and 503 African American. GCSI scores ≥ 18 were recorded in 72 participants: 38 (5%) of European Americans and 34 (7%) of African Americans. The average GCSI was 24.1 in European Americans and 24.6 in African Americans, indicating moderate to severe symptoms. Compared to European Americans with GCSI scores ≥ 18, African Americans were younger (59.4 vs. 53.3 years, p = 0.004), had earlier onset of T2DM (46.3 vs. 40.1 years, p = 0.01), higher HbA1c (7.6 vs. 9.1, p = 0.0009), underwent fewer upper endoscopies (55.3% vs. 26.5%, p = 0.02), and had more anxiety and depression (p < 0.001)., Conclusions: Moderate or greater symptoms suggestive of gastroparesis are present in 5-7% of European and African American patients with T2DM in community-based populations. Symptoms suggestive of gastroparesis may be underappreciated in patients with T2DM and account for upper gastrointestinal symptoms, unexplained glycemic control issues, and decreased quality of life.

Background: Functional obstructive gastroparesis is an understudied subtype of gastroparesis with normal 3 cycle per minute gastric myoelectrical activity that responds to botulinum toxin A injection and balloon dilation of the pylorus., Aims: To determine the effect of pyloroplasty on symptoms, weight, gastric emptying, and gastric myoelectrical activity in patients with gastroparesis and normal 3 cycle per minute gastric myoelectrical activity., Methods: Ten patients (average age 36 years with gastroparesis and normal 3 cycle per minute gastric myoelectrical activity) who had at least two successful endoscopic pyloric therapies and then underwent pyloroplasty were identified. Electrogastrography with water load satiety test was performed to determine gastric myoelectrical activity. Gastric emptying was measured with 4-h scintigraphy., Key Results: Six months after pyloroplasty, nine of ten patients reported improved symptoms and weight increased an average of 6.4 lb (p = 0.04). The average percentage of meal retained at 4 h decreased from 47% before to 16% after pyloroplasty (p < 0.01) and normalized in six patients. After pyloroplasty, the percent distribution of gastric myoelectrical activity power in the 3 cycle per minute range decreased at each measured interval compared with pre-pyloroplasty (p < 0.01)., Conclusions: (1) Pyloroplasty in these patients with obstructive gastroparesis improved gastric emptying and decreased 3 cycle per minute gastric myoelectrical activity, consistent with relief of functional gastric outlet obstruction. (2) Pyloric neuromuscular dysfunction is a key factor in delayed emptying in patients with functional obstructive gastroparesis.

Background: Marijuana may be used by some patients with gastroparesis (Gp) for its potential antiemetic, orexigenic, and pain-relieving effects., Aims: The aim of this study was to describe the use of marijuana by patients for symptoms of Gp, assessing prevalence of use, patient characteristics, and patients' perceived benefit on their symptoms of Gp., Methods: Patients with symptoms of Gp underwent history and physical examination, gastric emptying scintigraphy, and questionnaires assessing symptoms. Patients were asked about the current use of medications and alternative medications including marijuana., Results: Fifty-nine of 506 (11.7%) patients with symptoms of Gp reported current marijuana use, being similar among patients with delayed and normal gastric emptying and similar in idiopathic and diabetic patients. Patients using marijuana were younger, more often current tobacco smokers, less likely to be a college graduate, married or have income > $50,000. Patients using marijuana had higher nausea/vomiting subscore (2.7 vs 2.1; p = 0.002), higher upper abdominal pain subscore (3.5 vs 2.9; p = 0.003), more likely to be using promethazine (37 vs 25%; p = 0.05) and dronabinol (17 vs 3%; p < 0.0001). Of patients using marijuana, 51% had been using it for more than 2 years, 47% were using this once or more per day, and 81% of marijuana users rated their benefit from marijuana as better or much better., Conclusions: A subset of patients (12%) with symptoms of Gp use marijuana. Patients with severe nausea and abdominal pain were more likely to use marijuana and perceive it to be beneficial for their symptoms., Trial Registration: ClinicalTrials.gov Identifier: NCT01696747.

Background: Autonomic dysfunction can be present in patients with idiopathic and diabetic gastroparesis. The role of autonomic dysfunction relating to gastric emptying and upper gastrointestinal symptoms in patients with gastroparesis and chronic unexplained nausea and vomiting (CUNV) remains unclear. The aim of our study is to evaluate autonomic function in patients with gastroparesis and CUNV with respect to etiology, gastric emptying and symptom severity., Methods: We studied 242 patients with chronic gastroparetic symptoms recruited at eight centers. All patients had a gastric emptying scintigraphy within 6 months of the study. Symptom severity was assessed using the gastroparesis cardinal symptom index. Autonomic function testing was performed at baseline enrollment using the ANX 3.0 autonomic monitoring system which measures heart rate variability and respiratory activity measurements., Key Results: Low sympathetic response to challenge (Valsalva or standing) was the most common abnormality seen impacting 89% diabetic and 74% idiopathic patients. Diabetics compared to idiopathics, exhibited greater global hypofunction with sympathetic (OR = 4.7, 95% CI 2.2-10.3; P < .001) and parasympathetic (OR = 7.2, 95% CI 3.4-15.0; P < .001) dysfunction. Patients with delayed gastric emptying were more likely to have paradoxic parasympathetic excessive during sympathetic challenge [(Valsalva or standing) 40% vs. 26%, P = .05]. Patients with more severe symptoms exhibited greater parasympathetic dysfunction compared to those with mild-moderate symptoms: resting sympathovagal balance [LFa/RFa 1.8 (1.0-3.1) vs. 1.2 (0.6-2.3), P = .006)] and standing parasympathetic activity [0.4 (0.1-0.8) vs. 0.6 (0.2-1.7); P = .03]., Conclusions: Autonomic dysfunction was common in patients with gastroparesis and CUNV. Parasympathetic dysfunction was associated with delayed gastric emptying and more severe upper gastrointestinal symptoms. Conversely, sympathetic hypofunction was associated with milder symptoms., Inferences: Gastroparesis and CUNV may be a manifestation of GI autonomic dysfunction or imbalance, such that sympathetic dysfunction occurs early on in the manifestation of chronic upper GI symptoms, while parasympathetic dysfunction results in more severe symptoms and delayed gastric emptying., (© 2020 John Wiley & Sons Ltd.)

Background: 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., Aims: 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., Methods: 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., (© 2019 John Wiley & Sons Ltd.)

Background: Gastric electrical stimulation (GES) for treating gastroparesis symptoms is controversial., Methods: 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., Key Results: 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)., Conclusions and Inferences: 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., (© 2019 John Wiley & Sons Ltd.)

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.

Objectives: 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)., Methods: 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., Results: 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., Discussion: 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.

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.

Background & Aims: Gastroparesis is a chronic disorder of the stomach characterized by nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. There is limited information on gastroparesis in minority populations. We assessed ethnic, racial, and sex variations in the etiology, symptoms, quality of life, gastric emptying, treatments, and symptom outcomes of patients with gastroparesis., Methods: We collected information from the National Institutes of Health Gastroparesis Consortium on 718 adult patients, from September 2007 through December 2017. Patients were followed every 4 or 6 months, when data were collected on medical histories, symptoms (based on answers to the PAGI-SYM questionnaires), and quality of life (based on SF-36). Follow-up information collected at 1 year (48 week) was used in this analysis. Comparisons were made between patients of self-reported non-Hispanic white, non-Hispanic black, and Hispanic ethnicities, as well as and between male and female patients., Results: Our final analysis included 552 non-Hispanic whites (77%), 83 persons of Hispanic ethnicity (12%), 62 non-Hispanic blacks (9%), 603 women (84%), and 115 men (16%). A significantly higher proportion of non-Hispanic blacks (60%) had gastroparesis of diabetic etiology than of non-Hispanic whites (28%); non-Hispanic blacks also had more severe retching (2.5 vs 1.7 score) and vomiting (2.9 vs 1.8 score) and a higher percentage were hospitalized in the past year (66% vs 38%). A significantly higher proportion of Hispanics had gastroparesis of diabetic etiology (59%) than non-Hispanic whites (28%), but Hispanics had less-severe nausea (2.7 vs 3.3 score), less early satiety (3.0 vs 3.5 score), and a lower proportion used domperidone (8% vs 21%) or had a peripherally inserted central catheter (1% vs 7%). A higher proportion of women had gastroparesis of idiopathic etiology (69%) than men (46%); women had more severe symptoms of stomach fullness (3.6 vs 3.1 score), early satiety (3.5 vs 2.9 score), postprandial fullness (3.7 vs 3.1 score), bloating (3.3 vs 2.6 score), stomach visibly larger (3.0 vs 2.1 score), and upper abdominal pain (2.9 vs 2.4 score). A lower proportion of women were hospitalized in past year (39% vs 53% of men)., Conclusions: In patients with gastroparesis, etiologies, symptom severity, and treatments vary among races and ethnicities and between sexes. ClinicalTrials.gov Identifier: NCT01696747., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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 log 2 fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log 2 fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05)., Conclusions: Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.

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.

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 (IMD 0 ) with impaired FA. IMD 0 , 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. IMD 0 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 IMD 0 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 IMD 0 Low IMD 0 (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., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)