Citations

INTRODUCTION: Reduced gastric accommodation (GA) or accelerated or delayed gastric emptying (GE) contributes to pathophysiology in functional dyspepsia (FD). Secretin is an endogenous hormone secreted postprandially from the duodenal mucosa. Our objective was to determine the effects of secretin in human gastric motor functions and satiation in health and FD. METHODS: We conducted a double-blind, randomized, placebo-controlled, cross-over trial in 10 healthy participants and 10 patients with FD by Rome IV criteria. Subjects were randomized to IV secretin or normal saline with a 1-4 week washout period. We measured GA using validated 99m Tc-single photon emission computed tomography with a standardized 300 mL meal of 111 In radiolabeled Ensure®. We measured GE using scintigraphy of the same meal and symptoms 30 minutes post meal based on 100 mm visualized analog scale (VAS). To measure volume to fullness (VTF) and maximum tolerated volume (MTV), we performed Ensure® nutrient drink test (NDT) and recorded symptoms 30 min post-MTV. Wilcoxon Signed-Rank Test was used for comparison within healthy and FD groups and ANCOVA modeling was used for intention to treat comparison between groups, adjusting for age, sex, and treatment arm (secretin vs. placebo). Study drug was provided by ChiroClin, Inc. RESULTS: The median age for healthy volunteers (HV) was 45.0 years [IQR: 38.0, 49.0 (80% female)] and for FD was 50.5 years [42.0, 55.0 (70% female)]. There was no statistical difference in either group for secretin vs. placebo for GA. Secretin delayed GE in both HV and FD (Table 1). There was decrease in GE for secretin vs. placebo in HV at 20 minutes [-10% (-13, -7), P = 0.008] and 30 minutes [-11% (-16, -4), P = 0.004]. This finding was also seen in the FD group for GE at 25 minutes [-5% (-9, 0), P = 0.047] and 30 minutes [-8% (-9, 0), P = 0.03]. There were no statistically significant differences between treatment arms for VTF or MTV in either HV or FD. On ANCOVA analysis, there were statistically significant increases in nausea at 30 minutes ( P = 0.0016) and fullness at 30 minutes ( P = 0.0002) for secretin vs. placebo in FD compared to HV. CONCLUSION: Secretin delayed GE in both healthy volunteers and FD without significantly altering GA, VTF, or MTV. Secretin receptor stimulation deserves further study in FD patients with accelerated GE.

INTRODUCTION: Increasing rates of obesity have led to increased numbers of bariatric surgeries performed world-wide. However, some patients do not achieve significant weight loss or develop weight regain following these procedures. Other than estimating the size of the gastric remnant at endoscopy or transaxial imaging, there are limited approaches to quantitate the function of the post-surgical stomach in order to evaluate the disparate weight patterns, or to develop strategy for future treatments, e.g., pharmacotherapy or endoscopic intervention. We hypothesize that altered gastric function in the pre- and post-surgical periods may offer an explanation. Studies performed thus far are difficult to interpret due to heterogeneity in approaches to diagnostic evaluation. The aims of this project were: to assess the feasibility of a new protocol for simultaneous evaluation of gastric accommodation and gastric emptying in the post-bariatric state; and to report normative values in healthy volunteers. METHODS: Methods: We utilized single photon emission computed tomography (SPECT) and gamma scintigraphy to concurrently study postprandial gastric accommodation responses and gastric emptying rates of a limited size meal designed for subsequent use in post-bariatric patients. The standard meal consisted of 1 egg and 1 extra egg yolk scrambled with 111 Indium-activated charcoal (∼130kcal, 9.5g fat) and 120mL 2% milk (130kcal, 4.4g fat). Gastric accommodation was measured using 99m Technetium-SPECT. SPECT imaging was obtained concomitant with gastric emptying of the 111 In-labeled meal. Anterior and posterior scans of the abdomen were obtained for estimating gastric emptying parameters every 15 minute until 90 minutes, and then in 30-minute intervals until 240 minutes or complete emptying. RESULTS: Data on 28/30 healthy volunteers (35.7% men; 67% Caucasian) with completed studies to date are shown in the Table 1 (data presented as mean ± standard deviation). Gastric emptying proportion at 1, 2, and 4 hours, T 1/2 , and gastric volumes including accommodation are graphically depicted in Figures 1 and 2, respectively. CONCLUSION: Discussion: This study has demonstrated feasibility of simultaneous measurement of gastric emptying and accommodation and provides normal values; this sets the stage for future baseline and post-operative scans on patients undergoing sleeve gastrectomy.

INTRODUCTION: Over-the-scope clips (OTSC) are used for closure of fistulas, leaks, and acute perforations, and for GI bleeding. Adverse events include perforation, migration, and ulceration. Little is know about the natural history of OTSCs and no data addressing the longevity of clips is available. We present an interim analysis of our center’s experience with OTSC focusing on natural history. METHODS: OTSCs used from 1/1/2011 to 1/1/2019 were compiled and retrospective chart review undertaken. Primary endpoint was clip retention time (time when the clip was placed to time the clip was last seen or was physically removed). Secondary endpoints were rate of complications and factors that influence clip retention time and clinical success. Cox proportional hazards were used to evaluate variables impacting clip retention. Univariate regression was used to assess potential risk factors for adverse events. RESULTS: A total of 358 OTSC were placed in 299 patients (55.8% male, n = 184) with mean age 64 + 15.3 years. Procedures and indications presented in Table 1. Clip placement was clinically successful in 81% of cases (N = 265). Median time to clip loss as assessed by Kaplan-Meier curve was 267 days (95% CI 196-406) (Figure 1). Adverse events occurred in 34 clip placements (10.7%) and included bleeding (n = 8, 24.2%), perforation (n = 5, 15.2%), ulceration (n = 3, 9.1%), migration (n = 15, 45.5%), and infection (n = 1, 3.0%). Univariate analysis (Table 2) revealed that age, gender, type of clip used (there are 3 types of OTSC), and performing endoscopist did not impact clip retention rate. A size 14 clip had marginally higher rates of retention compared to others. Clips placed in the rectum or esophagus were lost earlier compared to those in the small/large intestine and stomach. Clips placed for fistulas and those associated with adverse event were associated with earlier clip loss. In evaluation of clinical success, clips placed for fistulas had a relative risk of clinical failure of 2.08 (95% CI 1.29-3.36) compared to all other indications. CONCLUSION: OTSCs are retained for a median of 8.9 months with clip location and indication for placement being key factors in time to clip loss. Clips used for fistula closure were more likely to be lost compared to those placed for other indications, less likely to be clinically successful, and more likely to cause a complication. These data help guide decision-making when considering OTSC use across clinical indications.

INTRODUCTION: Double balloon enteroscopy (DBE) is an important tool for evaluation of obscure GI bleeding but is a limited resource given time and expertise required. Patient selection is important to help optimize diagnostic yield and subsequent successful management of small bowel bleeding. To maximize the efficiency of DBE performed, our endoscopy group established a screening protocol (Figure) prior to approval of any procedure. We developed a quality improvement project to assess the efficacy of this screening protocol and to evaluate which components of screening were most predictive for procedural success. METHODS: A retrospective chart review was performed on all patients who underwent anterograde or retrograde double balloon enteroscopy for suspected GI bleeding from January 2016 to December 2017. Our screening protocol was implemented on February 1 st , 2017. Data was obtained on patient demographics, clinical presentation, laboratory evaluation, and prior investigation for bleeding evaluation. Endoscopy outcomes were separated into procedural success, defined as lesion identified, and clinical success, defined as resolution of bleeding. Success rates were compared pre and post intervention. Regression analysis was performed to evaluate which components best predicted a successful procedure. RESULTS: We reviewed 114 DBE procedures in 89 patients, 53.5% male (n = 61) with a mean age of 62.8 + 13.3 years. Of these, 86% (n = 98) were performed prior to initiation of the screening protocol. Overall, there was no significant difference in procedural success pre and post intervention as defined by presence of recurrent bleeding, persistent anemia, or transfusion need (Table 1). On univariate analysis of clinical success, defined as lack of recurrent bleeding, gender, anticoagulation use, and presence of lesion on CE were significant (Table 2). Identification and intervention on a lesion during the balloon endoscopy did not impact future anemia, bleeding, or transfusion requirements. CONCLUSION: The patient screening protocol was successful in decreasing the number of procedures performed but did not improve our lesion detection rate on endoscopy and did not improve clinical outcomes as measured by rebleeding. Patients on anticoagulation and those who had prior lesions identified on capsule endoscopy had higher odds of rebleeding, indicating clinical failure. This data may help modify patient selection to maximize success of DBE procedures in the future.

INTRODUCTION: Loey Dietz syndrome (LDS) is an autosomal dominant disorder caused by a mutation in TGFBR1 - or TGFBR2. LDS is characterized by distinctive facies, tortuous arteries and aortic aneurysms predisposition to eosinophilic allergic disorders including eosinophilic esophagitis and gastritis, and other systemic findings including inflammatory bowel disease. Patients with vascular Ehlers Danlos Syndrome (vEDS) have deficiency in type III collagen and have similar vascular laxity and concomitant GI manifestations. This connective tissue vulnerability contributes to increased post-operative wound dehiscence and development of hernias. Our aim was to summarize abdominal wall and GI tract manifestations in these two rare vascular disorders at a tertiary referral center. METHODS: Data were collected via Advanced Cohort Explorer (ACE) application at Mayo Clinic. A chart review was undertaken on patients with a confirmed diagnosis of vEDS or LDS seen at Mayo Clinic in Rochester from 1994 to 2018. Diagnoses were confirmed by genetic testing and/or clinical review through the specialized medical genetics clinic. Information was extracted on vascular complications of disease, prevalence of abdominal hernias, and gastrointestinal symptoms. The study was reviewed and exempted by the Mayo Clinic IRB. RESULTS: We identified and reviewed records of 50 vEDS and 13 LDS patients; data are summarized in Tables 1 and 2. Patients were similar in age at diagnosis and gender distribution. Hernias were present in similar proportions of patients with vEDS and LDS, although ventral hernias were more frequent and the hernias were more likely to be post-operative in vEDS than in LDS. LDS patients had more aneurysms (58% vEDS vs. 76.9% LDS, P = 0.02) with higher proportion requiring arterial repair (32.7% vEDS vs. 69.2% LDS, P = 0.03). Co-morbidities more prevalent in LDS than vEDS were autonomic dysfunction, psychopathology and allergy. We did not note increase in symptoms suggestive of eosinophilic esophagitis/gastritis in the LDS patients. GI symptoms were prevalent in both disorders and largely similar, except for diarrhea and constipation which were both significantly more prevalent in LDS patients. CONCLUSION/DISCUSSION: While vEDS and LDS are both connective tissue disorders with propensity for GI symptoms, abdominal hernias and aneurysm formation, the risk of arterial rupture and co-morbidity of autonomic dysfunction, psychopathology and allergy are greater in LDS than vEDS.

Summary Background Due to the paucity of targeted therapy for irritable bowel syndrome (IBS), many patients turn to dietary modifications for symptom management. The combination of five subgroups of poorly absorbed and rapidly fermented carbohydrates—fructans, galacto‐oligosaccharides, lactose, excess fructose and polyols—are thought to trigger gastrointestinal symptoms and are referred to collectively as “FODMAPs”. Aims To examine the biological plausibility and mechanisms by which foods high in specific FODMAP subgroups cause symptoms, and to use this information to explore the possibility of targeting select dietary components to allow for a more personalised approach to dietary adjustment Methods Recent literature was analysed via search databases including Medline, PubMed and Scopus. Results Lactose, fructans and galacto‐oligosaccharides have strong biologic plausibility for symptom generation due to lack of hydrolases resulting in distention from osmosis and rapid fermentation. However, excess fructose and polyols may only cause symptoms in specific individuals when consumed in high doses, but this remains to be established. There is evidence to suggest that certain patient characteristics such as ethnicity may predict response to lactose, but differentiation of other subgroups is difficult prior to dietary manipulation. Conclusions While some clear mechanisms of action for symptom generation have been established, further research is needed to understand which patients will respond to specific FODMAP subgroup restriction. We suggest that clinicians consider in some patients a tailored, personalised “bottom‐up” approach to the low‐FODMAP diet, such as dietary restriction relevant to the patients’ ethnicity, symptom profile and usual dietary intake.

HCV-specific neutralizing antibodies protect humanized mice from challenge and suppress established infections.