Chronic Gastrointestinal Research Articles

High-Dose Opioid Use Among Veterans with Unexplained Gastrointestinal Symptoms Versus Structural Gastrointestinal Diagnoses.

In a cohort of Veterans dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D, we sought to describe high-dose daily opioid use among Veterans with unexplained gastrointestinal (GI) symptoms and structural GI diagnoses and examine factors associated with high-dose use. We used linked national patient-level data from the VA and Centers for Medicare and Medicaid Services (CMS). We grouped patients into 3 subsets: those with unexplained GI symptoms (e.g., chronic abdominal pain); structural GI diagnoses (e.g., chronic pancreatitis); and those with a concurrent unexplained GI symptom and structural GI diagnosis. High-dose daily opioid use levels were examined as a binary variable [≥ 100 morphine milligram equivalents (MME)/day] and as an ordinal variable (50-99 MME/day, 100-119 MME/day, or ≥ 120 MME/day). We identified 141,805 chronic GI patients dually enrolled in VA and Part D. High-dose opioid use was present in 11% of Veterans with unexplained GI symptoms, 10% of Veterans with structural GI diagnoses, and 15% of Veterans in the concurrent GI group. Compared to Veterans with only an unexplained GI symptom or structural diagnosis, concurrent GI patients were more likely to have higher daily opioid doses, more opioid days ≥ 100 MME, and higher risk of chronic use. Factors associated with high-dose use included opioid receipt from both VA and Part D, younger age, and benzodiazepine use. A significant subset of chronic GI patients in the VA are high-dose opioid users. Efforts are needed to reduce high-dose use among Veterans with concurrent GI symptoms and diagnoses.

Efficacy and Tolerability of Oral Iron Protein Succinylate in the Treatment of Iron Deficiency Anemia in Adults with Gastrointestinal Diseases

Iron deficiency anemia (IDA) is commonly associated with several pathological gastrointestinal (GI) conditions in adults, being induced through different mechanisms, such as chronic bleeding, chronic inflammation, malabsorption, autoimmune re-actions, or, quite frequently, as a combination of different mechanisms. All patients must be treated with iron supplementation with the aim of restoring normal hemoglobin levels and iron status. Oral iron compounds are the first line treatment options for ID clinical conditions, according to International Guidelines, as they have proven to be efficacious, safe, and relatively inexpensive. However, ferric salts are scarcely absorbed, and ferrous compounds present a poor GI tolerability. Iron-protein succinylate (IPS), an iron complex that keeps ferric iron bonded to the protein content of a succinylated casein shell at acid pH values, has been shown to release gradually iron into the intestinal lumen, protecting the gastrointestinal mucosa from eventual damage, an ensuring an optimal intestinal iron absorption. This review focuses on IPS in the treatment of IDA associated to a variety of GI medical conditions in adults. Results from diverse studies including IDA due to acute and chronic GI conditions, as well as IDA associated to gastric surgery, confirm a consistent improvement in hematologic parameters and clinical symptoms, and an optimal tolerability profile.

Anemia, iron deficiency, and cobalamin deficiency in cats with chronic gastrointestinal disease.

BackgroundIron deficiency and cobalamin deficiency, as sequelae to chronic gastrointestinal (GI) disease, could result in anemia and increased morbidity in cats with chronic enteropathies.ObjectiveTo evaluate iron deficiency in cats with chronic GI disease and its relationship with hypocobalaminemia, anemia, and disease severity.AnimalsTwenty client‐owned cats with primary GI disease.MethodsProspective, cross‐sectional study. Cats were enrolled at the time of evaluation for chronic GI disease, after exclusion of comorbidities. CBC with reticulocyte indices, iron metabolism (serum iron and ferritin concentrations, total iron binding capacity [TIBC]), serum methylmalonic acid (MMA), cobalamin, and folate concentrations, pancreatic lipase and trypsin‐like immunoreactivity, and disease severity were evaluated.ResultsAnemia (hematocrit <30%), iron deficiency, and cobalamin deficiency were diagnosed in 4/20, 7/20, and 8/20 cats, respectively. Hematocrit (r s = −.45; P < .05) and body condition score (r s = −.60; P < .01) negatively correlated with MMA. Median TIBC was lower in cats with increased vs normal MMA (218 μg/mL; range, 120‐466 μg/mL vs 288 μg/mL; range, 195‐369 μg/mL; P = .02). Hematocrit (r s = .51; P = .02), reticulocyte MCV (r s = .52; P = .02), reticulocyte hemoglobin content (r s = .71; P < .001), and percent transferrin saturation (r s = .79; P < .0001) positively correlated with serum iron concentration.Conclusions and Clinical ImportanceFunctional iron deficiency was common in cats with chronic GI disease. Associations between hypocobalaminemia, iron parameters, and hematologic parameters warrant further investigation on the impact of iron deficiency on chronic GI disease morbidity in cats.

Comparing Physician-reported Toxicity in Men with Localized Prostate Cancer Undergoing External Beam, Brachytherapy, or Combination Radiation Therapy

The purpose of this study is to compare physician-reported gastrointestinal (GI), genitourinary (GU) and sexual toxicity outcomes of men with localized prostate cancer undergoing dose-escalated external beam radiation therapy (EBRT), high-dose-rate (HDR) brachytherapy or low-dose-rate (LDR) brachytherapy monotherapy (HDRm or LDRm), EBRT with HDR BT boost (HDRb), and EBRT with LDR BT boost (LDRb). We performed a retrospective cohort study of a prospectively collected database of patients with localized prostate adenocarcinoma treated with EBRT, HDRm, LDRm, HDRb, or LDRb between 2004-2019 at our institution. Hormone therapy was delivered per physician discretion. Physician-reported GI, GU, and sexual toxicity were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 at time points of 3 months, 6 months, 12 months, 18 months, and 24+ months. Stratified Fisher exact tests and generalized linear mixed effects models were used to assess for differences in the physician-graded toxicity rate between radiation treatment modalities. 555 men with prostate cancer met selection criteria. 277 (49.9%) received EBRT, 76 (13.7%) received LDRm, 30 (5.4%) received LDRb, 130 (23.4%) received HDRm, and 42 (7.6%) received HDRb. Median follow-up was 33 months (interquartile range [IQR]: 15-59). 130 (23%) had low risk, 280 (50%) had intermediate risk, and 145 (26%) had high risk disease. After 24 months, Grade 3+ GI toxicity with LDRb (15%) was higher than those in the EBRT group (1.2%), and it was higher than those in the HDRb cohort (0%; p = 0.01). No other pairwise comparisons were significant. The risk of Grade 2+ GU toxicity was higher with LDRm over HDRm at months 3, 21, and 24 (p = 0.03; p = 0.02; p = 0.03). HDRm patients had higher incidence of Grade 2+ sexual toxicity than EBRT patients in the first 3 months (p = 0.02). Compared to patients receiving EBRT, patients receiving HDRb, HDRm, or LDRm had higher sexual toxicity by month 15 (p = 0.002; p < 0.001; p = 0.004). By month 21, patients receiving HDRm remained more likely than those receiving EBRT to have sexual toxicity (p = 0.01). There were no significant differences in the sexual toxicity rates between groups after 24 months. In men treated with radiation therapy for localized prostate cancer, there are differences in physician-reported toxicity across radiation treatment modalities. Our study suggests lower rates of chronic GI toxicity in patients treated with HDRb as compared to LDRb and EBRT, lower rates of acute and chronic GU toxicities in patients treated with HDRm as compared to LDRm, and similar long-term sexual toxicity among the groups. The differences in the physician-graded toxicity profiles between radiation treatment modalities can be used in shared decision-making when selecting the best radiation therapy option for each patient.

S3146 Patients With Eosinophilic Esophagitis (EoE) and Persistent Extra-Esophageal GI Symptoms Should Be Evaluated for Eosinophilic Gastritis (EG) and Eosinophilic Duodenitis (EoD)

INTRODUCTION: Eosinophilic gastrointestinal (GI) disorders (EGIDs) are chronic inflammatory conditions characterized by aberrant accumulation and activation of localized tissue eosinophils and mast cells. While Eosinophilic Esophagitis (EoE) is the best understood of the EGIDs, there is growing understanding of Eosinophilic Gastritis (EG) and Duodenitis (EoD) and evidence that they may be more prevalent than previous estimates. Though EoE is defined in part by esophageal dysfunction, patients with EoE often present with extra-esophageal symptoms which may not be attributable to isolated esophageal inflammation. EG/EoD may be underdiagnosed in these patients due to non-routine biopsy and histopathologic evaluation of gastric and duodenal mucosa. We reviewed gastric and duodenal biopsies in patients with known EoE and persistent non-esophageal symptoms to determine the frequency of EG/EoD in this population. METHODS: 27 patients at the University of Utah with a known history of EoE, persistent extra-esophageal symptoms, and a history of gastric and duodenal biopsies were identified, and retrospectively reviewed. Histopathologic evaluation was performed and eosinophil counts and chronic inflammation were assessed. Eosinophilic gastritis and duodenitis were defined as the presence of ≥30 eosinophils/high-powered field (hpf) in 5 and 3 hpfs in the stomach and duodenum, respectively. RESULTS: Of the 27 patients, 17 (63%) met histologic criteria for EG and/or EoD (4 combined EG/EoD, 13 EoD). The most common non-esophageal symptoms among these 17 patients were abdominal pain, nausea and bloating. 3 of the 17 patients had been diagnosed with irritable bowel syndrome in addition to EoE. Of the 10 patients not meeting histologic criteria for EG/EoD, 4 were subsequently found to have gastroparesis, 1 was on high dose NSAIDs and 1 was subsequently found to have mast cell activation syndrome. CONCLUSION: In this retrospective study, 63% of patients with EoE and chronic extra-esophageal GI symptoms were found to meet histologic criteria for EG/EoD. This high discovery rate suggests that gastric and duodenal biopsies should be performed and evaluated for eosinophils in patients with EoE and extra-esophageal symptoms, including those with persistent abdominal pain, nausea, bloating or a diagnosis of functional GI disease.

S1330 High Discovery Rate of Previously Undiagnosed Patients With Eosinophilic Gastritis and Duodenitis Using a Systematic Endoscopic Biopsy Protocol: Screening Data Analysis From ENIGMA, a Randomized Controlled Trial

INTRODUCTION: Eosinophilic gastrointestinal (GI) disorders (EGIDs) such as eosinophilic gastritis (EG) and duodenitis (EoD) are chronic inflammatory conditions characterized by aberrant accumulation and activation of localized tissue eosinophils and mast cells. Patients (pts) with EG/EoD present with non-specific, often debilitating GI symptoms including abdominal pain and cramping, early satiety, nausea and diarrhea. Non-specific symptoms, the absence of consensus diagnostic histopathologic guidelines, and the perception of rarity contribute to a delay in diagnosis of pts with EG/EoD. While the prevalence of EG/EoD is currently estimated to be ∼50,000 in the US, this may be an underestimate. We aimed to evaluate the prevalence of EG/EoD among symptomatic patients not previously diagnosed. METHODS: We reviewed screening data from ENIGMA, a multi-center, randomized, double-blind, placebo-controlled phase 2 trial assessing the safety and efficacy of AK002, an anti-Siglec-8 monoclonal antibody, in pts with EG/EoD. Adult pts were screened with a validated, daily 8-symptom EG/EoD questionnaire to capture moderate-severely symptomatic pts. Those who met symptom inclusion criteria underwent upper endoscopy (EGD) with gastric and duodenal biopsies as per protocol (12 total: 4 biopsies each from the gastric antrum, gastric corpus, and duodenum). Symptomatic pts meeting histologic definition of EG (≥30 eos/hpf in ≥5 hpfs) and/or EoD (≥30 eos/hpf in ≥3hpfs) were eligible for randomization. RESULTS: 113 pts entered screening for ENIGMA. 51 had no prior history of EG/EoD, 26 (51%) of whom met symptom criteria and underwent screening endoscopy. Of these 26 symptomatic pts, 15 (58%) met histologic criteria for EG/EoD, 13 of whom were randomized in the study. These 13 pts, previously given functional GI diagnoses, were clinically similar in constellation and magnitude of symptoms compared to the 52 randomized pts with previously established EG/EoD. CONCLUSION: There is growing evidence that EG/EoD is underdiagnosed, and that the true US prevalence may be higher than 50,000. Among moderate-severely symptomatic pts without known history of EG/EoD who entered screening for ENIGMA, 58% met histologic criteria for EG/EoD. EGD with multiple systematic gastric and duodenal biopsies of pts with chronic non-specific GI symptoms, including those with functional GI conditions, may demonstrate a higher prevalence of EG/EoD than is currently estimated.Figure 1.: Discovery Rate of Newly Diagnosed EG/EoD Patients in ENIGMA Screening 1) Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) sites; n = 62 entered screening 2) Primarily general gastrointestinal practices and professional GI research centers; n = 51 entered screening.Figure 2.: Similar Symptom Burden in Established and Newly Diagnosed EG/EoD Patients.Table 1.: Characteristics of Established and Newly Diagnosed EG/EoD Patients

S2795 Not Your Common Diarrhea

INTRODUCTION: Chronic diarrhea is a common encountered problem in the outpatient setting. Differential includes infectious, inflammatory, and malignant etiologies. We present a rare cause of chronic diarrhea, emphasizing need for physician awareness. CASE DESCRIPTION/METHODS: A 68-year-old male presented with chronic diarrhea, up to 12 bowel movements/day with nocturnal stools for the past 12 months. He described diffuse abdominal discomfort, dysgeusia, dysphagia, loss of appetite, & unintentional weight loss of 15 pounds over 1 year. Physical exam was benign. Initial labs including CBC, CMP, ESR, TSH, lipase, and infectious stool studies were unremarkable. An upper endoscopy showed mild antral erythema. Colonoscopy revealed multiple polyps less than 1 cm in size which were removed. Random biopsies were taken from the colon. Biopsies from the stomach, duodenum, and colon demonstrated amyloid deposits with apple-green birefringence on Congo red stain. Patient was referred to a tertiary care center for further evaluation, where a bone marrow biopsy revealed plasma cells expressing monotypic lambda cytoplasmic immunoglobuin light chains with CD38 & CD138, and no CD19 or CD45. This profile was consistent with AL (lambda) type amyloid deposition. He was further found to have amyloid deposits in the kidney, autonomic nerves, and heart. He received treatment with CyBordD (cyclophosphamide, bortezomib, dexamethasone) and an autologous stem cell transplantation. He is now in deep remission of AL amyloidosis. DISCUSSION: Chronic diarrhea is a common symptom, but can have a rare underlying etiology, such as amyloidosis. Prompt workup with endoscopy & biopsy with Congo red stain are diagnostically essential. Additionally, as different types of amyloidosis require different therapies, the diagnosis must be confirmed by biopsy with immunostaining. Gastrointestinal (GI) amyloidosis is a rare disease, clinically apparent in one percent of patients with AL (primary) amyloidosis. It can present as any of 4 syndromes: GI bleeding, malabsorption, protein-losing gastroenteropathy, or chronic GI dysmotility. The pathogenesis involves amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria, which leads to protrusions & thickening of the intestinal wall. The prognosis of AL amyloidosis patients with GI involvement is worse than those without, as it may involve other organs and present with advanced disease. Therefore, early recognition, diagnosis, and management are crucial.

S0481 Overlap in Gastrointestinal Manifestations Among Small Fiber Neuropathy, Postural Tachycardia Syndrome, Ehlers-Danlos Syndrome, and Mitochondrial Disease Adult Patients

INTRODUCTION: Small fiber neuropathy (SFN) is characterized by damage to thinly myelinated A-delta and/or unmyelinated C-fibers in the peripheral nervous system; these fibers regulate automatic functions, including digestion. SFN is known to cause abnormalities in the neural control of smooth muscle, however, the gastrointestinal (GI) manifestations of these abnormalities have not been reported. Structural and functional small fiber abnormalities are common in patients with postural tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS), and mitochondrial disease (MD), and clinicians frequently see overlapping GI manifestations in these patient populations. METHODS: Among adult (ages 18–74) patients, we examined the relative GI manifestations of SFN, POTS, EDS, and MD to determine whether these diseases have unique GI phenotypes. We conducted a retrospective cohort analysis of SFN (N = 506, 75.5% female), POTS (N = 255, 90.1% female), EDS (N = 413, 87.1% female), and MD (N = 175, 68.0% female) patients reporting GI symptoms presenting to an academic medical center between 2004 and 2019. Patient diagnoses were categorized by symptom clusters: esophageal, gastric, lower GI, and abdominal pain with examination of the frequency of individual diagnoses as well. RESULTS: Overall, GI diagnoses were common and most frequent in MD (92.0%) relative to POTS (86.7%), EDS (81.1%), and SFN (70.4%). Abdominal pain was common among all conditions, led by MD (69.1%) and POTS (61.2%) (Table 1). There were significant differences in symptom distribution across all disease groups (Figure 1): there was a relatively-even distribution of diagnoses in SFN, gastric diagnoses were most common in POTS (65.1%), esophageal diagnoses most common in EDS (43.8%), and esophageal diagnoses (70.9%) and lower GI diagnoses (69.1%) most common in MD. Among individual diagnoses, >50% of patients with POTS experienced nausea/vomiting, constipation, and abdominal pain and >50% of MD patients experienced GERD, nausea/vomiting, constipation, and abdominal pain. CONCLUSION: Despite similar demographics and chronic GI complaints, GI phenotypes differed significantly between patients with SFN, POTS, EDS, and MD. Patients with MD and POTS were most likely to present with GI complaints, with abdominal pain the most common manifestation among all of the disorders.Table 1.: Characteristics of adults patients diagnosed with SFN, POTS, EDS, or MD. Note. SFN = small fiber neuropathy; POTS = postural tachycardia syndrome; EDS = Ehlers-Danlos syndrome; MD = mitochondrial disease. 1. Continuous variables analyzed with ANOVA and categorical variables analyzed with Chi-Square TestFigure 1.: Overall prevalence of GI diagnoses in SFN, POTS, EDS, and MD patients. Note. Patients may have more than one diagnosis.

Longitudinal Multi-omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome

The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease has been difficult due to apparent disconnects between animal and human studies and lack of an integrated multi-omics view of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome, and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases. VIDEO ABSTRACT.

The Role of Resilience in Irritable Bowel Syndrome, Other Chronic Gastrointestinal Conditions, and the General Population

Resilience is the ability to adapt positively to stress and adversity. It is a potential therapeutic target as it is reduced in irritable bowel syndrome (IBS) compared to healthy controls and associated with worse symptom severity and poorer quality of life. The aim of this study was to examine if these findings are generalizable by comparing resilience between IBS versus the general population and other chronic gastrointestinal (GI) conditions. Participants in the general population completed an online survey containing questionnaires measuring demographics, diagnosis of IBS and other GI conditions, symptom severity, psychological symptoms, resilience, and early adverse life events (EALs). IBS was defined as having a physician diagnosis of IBS and/or meeting Rome criteria without co-morbid GI disease. All others were included in the general population group. The chronic GI conditions group included those with inflammatory bowel disease, celiac disease and/or microscopic colitis. Resilience was lower in IBS (n = 820) than the general population (n = 1026; p < 0.001) and associated with worse IBS symptom severity (p < 0.05). Global mental health affected resilience differently in IBS compared to the general population (all p's < 0.05). EALs were associated with decreased ability to bounce back from adversity in both IBS and the general population (p < 0.001). Resilience scores were similar in IBS and other chronic GI conditions that present with similar symptoms. Resilience is lower compared to the general U.S. population but does not appear to be specific to IBS as it is comparable to other chronic GI conditions. Low resilience negatively affects symptom severity and mental health and thus, may serve as a novel therapeutic target.

Gastrointestinal consequences of cancer treatment: evaluation of 10 years’ experience at a tertiary UK centre

ObjectiveUp to 90% of patients treated for pelvic cancers experience chronic gastrointestinal (GI) symptoms. This study characterises this patient cohort at a single centre, addressing a paucity of publications reporting...

Gastrointestinal vascular permeability changes following spinal cord injury.

Gastrointestinal (GI) dysfunction is observed clinically after spinal cord injury (SCI) and contributes to the diminished long-term quality of life. Our study examined the acute and chronic GI vascular changes that occur following SCI. We demonstrated that the GI vascular tract in SCI mice becomes compromised during the acute phase of injury and persists into the chronic phase of injury. Gastrointestinal vasculature permeability was measured using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) at 48hours, and 2 and 4weeks following contusion spinal cord injury. Angiopoietin-1, a vascular stabilizing protein, was administered intravenously following injury. Intestinal contractile activity assessments were performed following the last imaging session. Our results indicated that a single administration of Ang-1 reduced vascular permeability at 48hours but the effect was only transient. However, when the treatment paradigm was changed from a single administration to multiple administrations of Ang-1 following contusion injury, our DCE MRI data indicated a significant decrease in GI vascular permeability 4weeks after injury compared with vehicle control treated animals. This improved GI vascular permeability was associated with improved sustained intestinal contractile activity. We also demonstrated that Ang-1 reduced the expression of sICAM-1 in the ileum compared with the saline-treated group. We show that the GI vasculature is compromised in the acute and chronic phase of injury following spinal contusion. Our results also indicate that multiple administrations of Ang-1 can attenuate GI vascular permeability, possibly reduce inflammation, and improve sustained agonist-induced contraction compared with saline treatment.

A22 ADVERSE EARLY LIFE EVENTS ARE COMMON IN PATIENTS WITH FUNCTIONAL AND ORGANIC GASTROINTESTINAL DISORDERS

Abstract Background Stressful events in childhood have been associated with the development of functional gastrointestinal (GI) disorders in adulthood, especially irritable bowel syndrome. The influence of early life adverse events in patients with common organic disorders, such as celiac disease and inflammatory bowel disease (IBD), has been poorly investigated. Aims To evaluate the frequency of early life adverse events in patients with organic and functional gastrointestinal disorders compared to healthy controls. Methods Adult patients with an established diagnosis of IBS (Rome IV criteria), celiac disease and inflammatory bowel disease (IBD) attending a tertiary medical center, as well as healthy volunteers were interviewed by a psychologist. Early life adverse events were assessed during the semi-structured interview using a modified version of the Adverse Childhood Experience (ACE) questionnaire. Number of early life events and the presence of GI and extraintestinal symptoms based on a 10-point Likert scale were quantified. Data are presented as Median (IQR) and n (%). Statistical analysis was performed using Mann-Whitney and Fisher’s exact tests as appropriate. Results Sixty-eight patients (18 IBS, 28 celiac, 22 IBD) and 23 healthy controls were enrolled in the study. Patients with IBS, celiac disease and IBD had increased number of early life events compared with healthy controls (6.5 (4.8–8.3), 5.0 (3.0–9.0), 6.0 (4–8.3) vs 2.0 (1.0–4.0) respectively, p&amp;lt;0.0001). Patients reported a higher number of mental disorders in their mothers (IBS p=0.01; celiac disease p=0.01; IBD p=0.001) and increased number of close family member abusing alcohol or drugs during their childhood (IBS p=0.01; celiac p=0.02; IBD p=0.02) compared to healthy controls. History of sexual abuse was higher in patients with IBS (p=0.01), while history of verbal abuse was higher in patients celiac disease and IBD (p=0.003 and p=0.001, respectively) compared to healthy controls. The number of early life adverse events was strongly correlated with number of GI (r= 0.91; p=0.01) and extra-intestinal (r=0.87; p=0.02) symptoms, but not with symptoms severity. Most patients with IBS (83.3%), celiac disease (89.3%) and IBD (85.7%) reported stressful events before the onset of their disease. Conclusions Adverse events in childhood are frequent in patients with chronic GI disorders, both of functional and organic origin. Furthermore, stressful events often precede their diagnosis. These data strongly suggest that better psychosocial assessment in patients with chronic GI disorders is needed to improve their overall management. Funding Agencies None

Nutritional Advancement in the Hospitalized Child After NPO: A Retrospective Cohort Study.

A clear-liquid diet is commonly used after a nil per os (NPO) order in children recovering from acute gastrointestinal (GI) illnesses. Our purpose for this study was to compare outcomes in patients receiving a clear-liquid diet after an NPO order with outcomes in those receiving a regular diet. In this retrospective cohort study, patients aged 1 to 18 years admitted to a tertiary care children's hospital between 2016 and 2017 were screened to identify those who had an NPO order placed for acute GI illnesses. Patients with complex medical needs, a feeding disorder, or chronic GI disorders were excluded. Of 39 total patients, 17 (44%) received a clear-liquid diet after an NPO order. There was no difference in diet tolerance between patients receiving a clear-liquid diet and those receiving a regular diet on the basis of emesis in the first 12 hours (P = .40), pain scores after the first oral intake (P = .86), return to clear-liquid diet (P = .57), or return to NPO status (P > .99). Patients started on a clear-liquid diet had a longer length of stay (LOS) after diet initiation compared with those receiving a regular diet (median: 43.7 hours [interquartile range: 29.8-53.4] vs median: 20.8 hours [interquartile range 6.7-47.3]), both in the univariate analysis (P = .01) and after controlling for age, diagnosis category, and pain score before and after the first oral intake (P = .03). Patients transitioned to a clear-liquid diet after NPO status have a longer LOS after the first oral intake independent of patient age, diagnosis, and pretransition abdominal pain. Both groups had similar diet tolerance, suggesting that transition to a regular diet after NPO status may decrease LOS without significant adverse effects.

Description of Enteropathic Escherichia coli Species in Pediatric Patients at a Quaternary Children's Hospital.

The epidemiology, demographics, clinical presentations, and outcomes associated with enteroaggregative Escherichia coli (EAEC), enteropathogenic E. coli (EPEC), and enterotoxigenic E. coli (ETEC) pathotypes in US children are not well understood. This study was a retrospective chart review of all pediatric patients with a stool sample submitted to the Children's Hospital Colorado clinical microbiology laboratory for testing with the BioFire FilmArray Gastrointestinal Pathogen Panel from October 2015 through October 2017. During the study period, 5692 patient stool samples were submitted; 679 (13%) were positive for EAEC, EPEC, or ETEC. Of note, 163/232 (70%) patients with EAEC, 282/493 (57%) with EPEC, and 49/58 (85%) with ETEC had detection of at least 1 other pathogen. Of all E. coli-positive stool samples, only 158/679 (23%) were from low-risk patients who were singly infected with EAEC, EPEC, or ETEC. In this cohort, most cases were associated with acute diarrhea (50%), abdominal pain (61%), and/or cramping (49%) and presented without fever (14%), emesis (28%), or lethargy (7%). Thirteen (8%) of these 158 patients received antibiotics at the time of their initial presentation to care. Of the 145 patients who did not receive antibiotics at their initial visit, 23 (16%) returned to care due to persistence of symptoms. Our results suggest that the majority of patients singly infected with EAEC, EPEC, or ETEC present with mild, self-limited, gastrointestinal (GI) complaints. Further research is needed to determine what role these pathogens might play in children who present with chronic or inflammatory GI symptoms.

An International Multicenter Study of Intravenous Bevacizumab for the Treatment of Chronic Bleeding and Anemia in Hereditary Hemorrhagic Telangiectasia: The Inhibit-Bleed Study

An International Multicenter Study of Intravenous Bevacizumab for the Treatment of Chronic Bleeding and Anemia in Hereditary Hemorrhagic Telangiectasia: The Inhibit-Bleed Study

Multivariate Analysis of Plasma Metabolites in Children with Autism Spectrum Disorder and Gastrointestinal Symptoms Before and After Microbiota Transfer Therapy

Current diagnosis of autism spectrum disorder (ASD) is based on assessment of behavioral symptoms, although there is strong evidence that ASD affects multiple organ systems including the gastrointestinal (GI) tract. This study used Fisher discriminant analysis (FDA) to evaluate plasma metabolites from 18 children with ASD and chronic GI problems (ASD + GI cohort) and 20 typically developing (TD) children without GI problems (TD − GI cohort). Using three plasma metabolites that may represent three general groups of metabolic abnormalities, it was possible to distinguish the ASD + GI cohort from the TD − GI cohort with 94% sensitivity and 100% specificity after leave-one-out cross-validation. After the ASD + GI participants underwent Microbiota Transfer Therapy with significant improvement in GI and ASD-related symptoms, their metabolic profiles shifted significantly to become more similar to the TD − GI group, indicating potential utility of this combination of plasma metabolites as a biomarker for treatment efficacy. Two of the metabolites, sarcosine and inosine 5′-monophosphate, improved greatly after treatment. The third metabolite, tyramine O-sulfate, showed no change in median value, suggesting it and correlated metabolites to be a possible target for future therapies. Since it is unclear whether the observed differences are due to metabolic abnormalities associated with ASD or with GI symptoms (or contributions from both), future studies aiming to classify ASD should feature TD participants with GI symptoms and have larger sample sizes to improve confidence in the results.

Gastrointestinal Immunity and Alpha-Synuclein.

The gastrointestinal (GI) tract is equipped with robust immune defenses which protect the organism from infection. Enteric nerves are front and center in this defensive network, even in the most primitive organisms. Neuropeptides exhibit potent antimicrobial activity in the vicinity of the nerve and attract the innate and adaptive immune systems to help confine the invading agent. Alpha-synuclein (αS) has many biophysical characteristics of antimicrobial peptides and binds small vesicles such as those carrying endocytosed viruses. It is induced in nerve cells in response to viral and bacterial infections. It renders the nerve cell resistant to viral infection and propagation. It signals the immune system by attracting neutrophils and macrophages, and by activating dendritic cells. Most remarkably αS is trafficked to the central nervous system (CNS) conferring immunity in advance of an infection. Chronic GI infection or breakdown of the epithelial barrier can cause αS to accumulate and form neurotoxic aggregates. Overproduction of αS in the enteric nervous system (ENS) and its chronic trafficking to the CNS may damage nerves and lead to Parkinson’s disease. Targeting the formation of αS aggregates in the ENS may therefore slow the progression of the disease.

1182 Small Intestinal Bacterial Overgrowth (SIBO) Is Common in Patients With Ehlers-Danlos Syndrome (EDS)

INTRODUCTION: EDS is a group of rare connective tissue disorders caused by defects in collagen synthesis. EDS patients frequently have chronic gastrointestinal (GI) symptoms. Delayed gastric emptying and colonic transit time are common in EDS, suggesting underlying GI dysmotility. The relationship between SIBO and EDS has not been studied. In this study, we aimed to assess the prevalence of SIBO by glucose hydrogen breath test (GBT) in EDS patients with GI symptoms. We also characterized the risk factors for SIBO in these patients. METHODS: This was a retrospective cohort study of adults with EDS from specialty clinics at University of Michigan (2000-2019) who completed GBT for suspected SIBO. Demographics, history, medications, and GBT findings were reviewed. Patients with documented structural disease (eg. neoplasm) were excluded. GI symptoms were prospectively collected from all patients at their GBT. A priori variables associated with SIBO were analyzed including: presence of diabetes, GERD, and gastroparesis; history of small bowel surgery or gastric bypass; use of opioids or proton pump inhibitors. Positive GBT for SIBO was defined as breath H2 rise ≥20 ppm within 90 min and/or CH4 rise ≥10 ppm at any time after glucose ingestion. Statistical methods included chi-square and t test. Univariate regression analysis assessed the relationship between tested variables and GBT outcome. RESULTS: A total of 600 EDS patients were identified and 327 (54.5%) had at least one GI symptom. GBT was performed in 39 patients (mean age 37.6 ± 12.9; 94.8% female; 92.3% Caucasian) for suspected SIBO. Common symptomatic indications in these patients are shown in Table 1. 15 patients (38.5%) had positive GBT by either H2 (n = 11; 28.2%) and/or CH4 (n = 7; 17.9%). There were no significant differences in demographic factors between EDS patients with positive and negative GBT. Symptomatically, the presence of bloating was associated with a positive GBT (P = 0.04) but there was no significant association between any other GI symptom and the GBT outcome. Diagnosis of GERD was significantly associated with a positive GBT (P = 0.04) and there was a trend towards significant association between IBS and positive GBT (P = 0.07). None of other tested variables predicted the GBT outcome. CONCLUSION: SIBO diagnosed by GBT is common in EDS patients with chronic GI symptoms. Our preliminary results suggest that SIBO should be particularly considered in EDS patients with bloating and GERD. Further study is needed to delineate this relationship.

498 Objective Evidence of Gastrointestinal Disorders in Patients With 22q11.2 Deletion Syndrome

INTRODUCTION: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome (1:3000-6000 live births) and the most common cause of DiGeorge Syndrome (congenital heart disease, parathyroid hypoplasia, thymic hypoplasia). However, the 22q11.2DS phenotype varies markedly among patients. We previously studied a smaller subset of patients with 22q11.2DS (n = 72) and found that chronic gastrointestinal (GI) symptoms were common. Here we expand our previous observations to a larger cohort (n = 175) and also present objective study data in an effort to characterize these GI problems as structural versus functional. METHODS: Adult patients with 22q11.2DS were retrospectively assessed from our cohort of &gt;1400 patients with a confirmed 22q11.2 deletion followed in the 22q and You Center at the Children's Hospital of Philadelphia. Included patients had at least one problem list, medication list, review of systems, and outpatient physician evaluation at ≥17 years of age. Broad clinical data were abstracted, including results of relevant imaging and laboratory studies. All available imaging studies were reviewed for radiologic and pathologic abnormalities. All routine laboratory studies were reviewed, and the lowest value was recorded for each test. RESULTS: 672 consecutive charts were reviewed, of which 175 met inclusion criteria. Included patients (45% F) ranged from 17 to 59 years of age (mean 26.1; SD 8.1). Chronic GI symptoms were common from childhood through adulthood (Figure 1), but congenital GI malformations were rare (4%). Additionally, autoimmune GI disorders occurred at the frequency of the general population [celiac disease (1%); inflammatory bowel disease (0.6%)]. However, motility disorders were common and accounted for the vast majority of GI symptoms (Figure 2). Pertinent laboratory results were also reported and showed a high rate of anemia (Figure 3). CONCLUSION: Specialized GI studies were performed commonly in our study population, reinforcing our prior observation that GI disorders place a significant burden on patients with 22q11.2DS. In addition to the well-described palatal abnormalities affecting this population, these studies revealed a wide range of non-structural GI problems. We conclude that a large burden of GI illness in 22q11.2DS is functional. Finally, the known chromosomal microdeletions present in patients with 22q11.2DS may provide an explanatory framework for understanding the etiology of functional GI symptoms in the general population.