Browsing by Subject "Gastroparesis"
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Item Delayed Gastric Emptying Is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth(Springer, 2021) Calderon, Gerardo; Siwiec, Robert M.; Bohm, Matthew E.; Nowak, Thomas V.; Wo, John M.; Gupta, Anita; Xu, Huiping; Shin, Andrea; Medicine, School of MedicineBackground: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. Aims: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Methods: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-h gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. Key results: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 h, and total GCSI scores did not differ significantly between those with and without SIBO. Conclusions: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.Item Effect of Oral CNSA-001 (sepiapterin, PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized, placebo-controlled, Phase 2 trial(Elsevier, 2021) Abell, Thomas L.; Garcia, Lazaro M.; Wiener, Gregory J.; Wo, John M.; Bulat, Robert S.; Smith, Neil; Medicine, School of MedicineAims: Diabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH4) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH4 levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis. Methods: Non-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10mg/kg BID CNSA-001 or matching placebo for 14days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up. Results: Gastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p=0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events. Conclusions: CNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted.Item An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation(Elsevier, 2020-04-15) Ward, Matthew P.; Gupta, Anita; Wo, John M.; Rajwa, Bartek; Furness, John B.; Powley, Terry L.; Nowak, Thomas V.; Medicine, School of MedicineBackground: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism. New method: Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP). Results: Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05). Comparison with existing method(s): We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response. Conclusions: Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.Item Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa(Wiley, 2018-04) Herring, B. Paul; Hoggatt, April M.; Gupta, Anita; Griffith, Sarah; Nakeeb, Attila; Choi, Jennifer N.; Idrees, Muhammad T.; Nowak, Thomas; Morris, David L.; Wo, John M.; Cellular and Integrative Physiology, School of MedicineBACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα+ cells without a significant change in ICCs.Item Nutritional deficiencies and predictors of mortality in diabetic and nondiabetic gastroparesis(Hellenic Society of Gastroenterology, 2021) Amjad, Waseem; Qureshi, Waqas; Singh, Ritu R.; Richter, Seth; Medicine, School of MedicineBackground: Gastroparesis is a debilitating condition that may impact morbidity and mortality, but there is a lack of long-term studies examining this relation. The aim of this study was to determine the predictors of mortality in gastroparesis and to determine the nutritional deficiencies. Methods: Between September 30, 2009 and January 31, 2020, we identified 320 patients (mean age 47.5±5.3 years, 70% female, 71.3% Whites, 39.7% diabetic and 60.3% nondiabetic) with gastroparesis. 99mTc sulfur-labeled food was used to diagnose gastroparesis. Cox proportional-hazard regression was used to compute the association of mortality predictors. Results: Of the 320 patients, 46 (14.4%) died during the study period. Among diabetics, advanced age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.10; P<0.001), chronic kidney disease (CKD) (HR 4.69, 95%CI 1.62-13.59; P=0.004), and malnutrition (HR 10.95, 95%CI 3.23-37.17; P<0.001) were associated with higher mortality, whereas in nondiabetics older age (HR 1.05, 95%CI 1.01-1.09; P=0.04), CKD (HR 10.2, 95%CI 2.48-41.99; P=0.001), chronic obstructive pulmonary disease (COPD) (HR 7.5, 95%CI 2.11-26.82; P=0.002), coronary artery disease (CAD) (HR 9.7, 95%CI 1.8-52.21; P=0.008), and malnutrition (HR 3.83, 95%CI 1.14-29.07; P=0.03) were associated with increased mortality. Overall, 48.8% had vitamin D, 18.2% had vitamin B12, and 50.8% had iron deficiencies. Only 19.4% of the whole cohort was evaluated by a nutritionist. Conclusions: Advanced age, CAD, CKD, COPD and malnutrition were associated with higher mortality in gastroparesis. Despite the high prevalence of nutritional deficiencies, consultation of a specialist nutritionist was uncommon.Item Obese gastroparesis inpatient admissions: trends and outcomes from 2007-2017 in the United States(Hellenic Society of Gastroenterology, 2022) Dahiya, Dushyant S.; Perisetti, Abhilash; Al-Haddad, Mohammad; Kichloo, Asim; Sharma, Rahul; Cheng, Chin-I; Inamdar, Sumant; Medicine, School of MedicineBackground: The aim of this study was to investigate obese gastroparesis (GP) hospitalizations in the United States (US). Methods: We analyzed the National Inpatient Sample (NIS) from 2007-2017 to identify all adult obese (body mass index ≥30 kg/m2) GP hospitalizations. These were compared with non-obese GP hospitalizations. The demographic trends, adverse outcomes, and healthcare burden were analyzed. Results: From 2007-2017, obese GP hospitalizations accounted for 13.75% of all GP hospitalizations in the US. There was an increasing trend in obese GP hospitalizations, from 2286 in 2007 to 47,265 in 2017 (P=0.0019), and in the proportion of obese GP hospitalizations, from 6.16% in 2007 to 17.96% in 2017 (P<0.001). Males, Blacks, Hispanics, and Asians showed a rising trend in obese GP hospitalizations. Although rates of upper endoscopy declined from 8.28% in 2007 to 5.36% in 2017 (P<0.001), obese GP hospitalizations had higher rates of upper endoscopy utilization (6.05 vs. 5.42%, P<0.001) compared to the non-obese cohort. Inpatient mortality for obese GP hospitalizations increased from 0.64% in 2007 to 1.10% in 2017 (P<0.001). Furthermore, we noted a rising trend in mean length of stay (LOS), from 4.64 in 2007 to 6.05 days in 2017 (P=0.0029), and mean total hospital charge (THC), from $22,306 in 2007 to $62,220 in 2017 (P<0.001) for obese GP hospitalizations. Conclusions: The prevalence of obese GP hospitalizations along with inpatient mortality, LOS, and THC rose significantly. However, the overall rate of upper endoscopy utilization has decreased for these patients.Item Pharmacologic Treatment for Pediatric Gastroparesis: A Review of the Literature(Pediatric Pharmacy Advocacy Group, 2016-03) Tillman, Emma M.; Smetana, Keaton S.; Bantu, Likeselam; Buckley, Merrion G.; Department of Pediatrics, IU School of MedicineThere have been a number of agents that have been tried for treatment of gastroparesis over the past 3 decades, with varying levels of success. Guidelines exist for the management of gastroparesis in adults; however, even though the cause of gastroparesis in children is similar to that in adults, no guidelines exist for treating pediatric gastroparesis as studies on the topic are limited. With what little information we have on pediatric gastroparesis, medications used in children's studies do not seem to demonstrate the same results as in adult patients with gastroparesis; thus, future studies of whether certain medications are effective for treating pediatric gastroparesis and at what dose still need to be conducted. Pharmacological treatment options for pediatric gastroparesis do not show a clear correlation of resolving or even maintaining gastroparesis-associated symptoms or disease state. This article reviews the available studies of drugs that have shown some efficacy, with an emphasis on pediatric studies.Item Prevalence of small intestinal bacterial overgrowth in patients with gastroparesis: a systematic review and meta-analysis(Research Institute for Gastroenterology and Liver Diseases, 2023) Beas, Renato; Riva-Moscoso, Adrian; Montalvan-Sanchez, Eleazar; Príncipe-Meneses, Fortunato S.; Aljaras, Rawan; Ramirez, Mirian; Izquierdo-Veraza, Diego; Calderon, Gerardo; Medicine, School of MedicineAim: We performed a systematic review and meta-analysis to identify the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with gastroparesis. Background: Several studies have suggested an association between SIBO and gastroparesis, which is characterized by delayed gastric emptying in the absence of mechanical obstruction. Methods: A comprehensive search was performed using MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) through January, 2022 for randomized controlled trials and observational studies reporting the prevalence of SIBO in gastroparesis. Pooled prevalence was estimated using a random effects model. Heterogeneity was assessed by using the inconsistency index (I2). Results: Among the 976 articles identified, 43 studies were selected for full text review. Six studies, with 385 patients, were deemed eligible for inclusion, with a perfect agreement between investigators (kappa=1.0). Overall, 379 patients were diagnosed with gastroparesis by gastric emptying scintigraphy and six were diagnosed with a wireless motility capsule. The pooled prevalence of SIBO was 41% (95% confidence interval 0.23-0.58). SIBO was diagnosed using jejunal aspirate cultures (N=15, 8.4%), lactulose breath test (N=80, 44.7%), glucose breath test (N=30, 16.8%), D-xylose breath test (N=52, 29.1%), and hydrogen breath test (N=2, 1.1%). Heterogeneity was significant and noted to be high at 91%. Only one study reported SIBO diagnosis in controls, therefore no pooled odds ratio was calculated. Conclusion: SIBO was present in almost half of the patients with gastroparesis. Future studies should examine and identify the association between SIBO and gastroparesis.Item Pyloric Functional Lumen Imaging Probe Measurements Are Dependent on Balloon Position(The Korean Society of Neurogastroenterology and Motility, 2023) Yim, Brandon; Gregor, Lennon; Siwiec, Robert M.; Al-Haddad, Mohammad; Nowak, Thomas V.; Wo, John M.; Medicine, School of MedicineBackground/aims: The functional lumen imaging probe (FLIP) device has been used to assess pyloric dysfunction in patients with gastroparesis. We aim to investigate whether varying FLIP catheter positions affect pyloric FLIP measurements. Methods: Patients undergoing endoscopy for chronic unexplained nausea and vomiting (CUNV) or gastroparesis were prospectively enrolled. FLIP balloon was adjusted for 3 positions within the pylorus: (1) proximal position, 75% of FLIP balloon in the duodenum and 25% in the antrum; (2) middle position, 50% in the duodenum and 50% in the antrum; and (3) distal position, 25% in the duodenum and 75% in the antrum. Pylorus cross-sectional area (CSA), intra-bag pressure (P), and distensibility indices (DI) were measured for 30, 40, and 50-mL balloon volumes. Fluoroscopic images were obtained to confirm FLIP balloon geometry. Data was analyzed separately using FLIP Analytic and customized MATLAB software. Results: Twenty-two patients with CUNV (n = 4) and gastroparesis (n = 18) were enrolled. Pressures were significantly higher in the proximal position compared to the middle and distal positions. CSA measurements were significantly higher at the proximal and middle positions for 30-mL and 40-mL volume compared to the distal position values. DI values were significantly lower at the proximal positions for 40-mL and 50-mL distensions when compared to the middle and distal positions. Fluoroscopic images confirmed increased balloon bending when placed mostly in the duodenum. Conclusions: FLIP balloon position within the pylorus directly affects balloon geometry which significantly affects P, CSA, and DI measurements. Standardized pyloric FLIP protocols and balloon design adjustments are needed for the continued application of this technology to the pylorus.Item The Conundrum of Obesity and Gastroparesis Hospitalizations: A Retrospective Comparative Analysis of Hospitalization Characteristics and Disparities Amongst Socioeconomic and Racial Backgrounds in the United States(The Korean Society of Neurogastroenterology and Motility, 2022) Dahiya, Dushyant S.; Inamdar, Sumant; Perisetti, Abhilash; Goyal, Hemant; Singh, Amandeep; Garg, Rajat; Cheng, Chin-I; Kichloo, Asim; Al-Haddad, Mohammad; Sharma, Neil; Medicine, School of MedicineBackground/aims: We aim to assess the influence of obesity on gastroparesis (GP) hospitalizations in the United States (US). Methods: The National Inpatient Sample was analyzed from 2007-2017 to identify all adult hospitalizations with a primary discharge diagnosis of GP. They were subdivided based on the presence or absence of obesity (body mass index > 30). Hospitalization characteristics, procedural differences, all-cause inpatient mortality, mean length of stay (LOS), and mean total hospital charge (THC) were identified and compared. Results: From 2007-2017, there were 140 293 obese GP hospitalizations accounting for 13.75% of all GP hospitalizations in the US. Obese GP hospitalizations were predominantly female (76.11% vs 64.36%, P < 0.001) and slightly older (51.9 years vs 50.8 years, P < 0.001) compared to the non-obese cohort. Racial disparities were noted as Blacks (25.49% vs 22%, P < 0.001) had higher proportions of GP hospitalizations with obesity compared to the non-obese cohort. Furthermore, we noted higher rates of inpatient upper endoscopy utilization (6.05% vs 5.42%, P < 0.001), longer mean LOS (5.71 days vs 5.32 days, P < 0.001), and higher mean THC ($53 373 vs $45 040, P < 0.001) for obese GP hospitalizations compared to the non-obese group. However, obese GP hospitalizations had lower rates of inpatient mortality (0.92% vs 1.33%, P < 0.001), and need for nutritional support with endoscopic jejunostomy (0.25 vs 0.56%, P < 0.001) and total parenteral nutrition (1.46% vs 2.33%, P < 0.001) compared to the non-obese cohort. Conclusions: In the US, compared to non-obese, a higher proportion of obese GP hospitalizations were female and Blacks. Obese GP hospitalizations also had higher THC, LOS, and rates of upper endoscopy.