Managing heartburn and reflux in primary care.

ABSTRACT: This article describes an algorithmic approach to caring for patients presenting with heartburn and reflux, including empiric treatment with acid-suppression therapy and a data-driven approach to diagnostic testing. This article also reviews the efficacy and safety profile of the widely available and commonly used proton pump inhibitors. Refining our approach to diagnostic testing can reduce time to diagnosis, better control patients' symptoms, and limit complications of longstanding disease.

A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut.

OBJECTIVE: Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability ('leaky gut') in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive. DESIGN: In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism. RESULTS: We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis. CONCLUSION: Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities. TRIAL REGISTRATION NUMBER: NCT02869659 and NCT03269032.

The Impact of a Mediterranean Diet on the Gut Microbiome in Healthy Human Subjects: A Pilot Study.

BACKGROUND AND AIMS: Despite the reported salutary benefits of a Mediterranean diet (MD) on a wide variety of health conditions, the specific microbial changes associated with an MD within the gastrointestinal (GI) tract are not well studied. Specifically, although population and survey-based studies have shown microbial changes, there are no published data on how an MD alters the gut flora in a controlled setting. METHODS: We recruited 10 healthy subjects, each of whom gave a stool sample at baseline and then was provided with prepared meals of a "typical" American diet; after 2 weeks, a second stool sample was collected. All subjects were then provided with prepared meals based on the MD for another 2 weeks, followed by a final stool sample collection. Stool samples were batch analyzed with DNA extraction, and sequencing libraries were generated. Measures of bacterial diversity, species richness, and enterotypes were performed. RESULTS: All ten subjects tolerated the diets well. Bacterial diversity increased with an MD, as measured by alpha diversity via the Simpson index. Furthermore, there were significant differences in 5 bacterial genera between the 2 diets. CONCLUSION: This small pilot study of controlled diets demonstrates that the MD can rapidly alter the gut microbiome in healthy subjects at the level of global microbial diversity and individual genera. These data confirm the findings of previous observational studies and establish the feasibility of conducting longer term studies on the impact of the MD on the flora of the GI tract and its relationship to digestive diseases.

Effects of Spinal Cord Stimulation in Patients with Chronic Nausea, Vomiting, and Refractory Abdominal Pain.

BACKGROUND: Patients with chronic nausea and vomiting often also have chronic abdominal pain. Spinal cord stimulation (SCS) may provide pain control, but scarce data are available regarding the effect of SCS on chronic nausea and vomiting. AIMS: We aimed to determine the effect of SCS in patients with chronic nausea, vomiting, and refractory abdominal pain. METHODS: Retrospective chart review of 26 consecutive patients who underwent SCS trial for a primary diagnosis of nausea, vomiting and refractory abdominal pain. RESULTS: 26 patients underwent SCS trial, with an average age of 48 years. Twenty-three patients (88.5%) reported > 50% pain relief during the temporary SCS trial and then underwent permanent implantation. Patients were then followed for 41 (22-62) months. At baseline, 20 of the 23 patients (87.0%) reported daily nausea, but at 6 months and the most recent follow-up, only 8 (34.8%) and 7 (30.4%) patients, respectively, had daily nausea (p < 0.001). Days of nausea decreased from 26.3 days/month at baseline to 12.8 and 11.7 days/month at 6 months and at the most recent visit, respectively. Vomiting episodes decreased by 50%. Abdominal pain scores improved from 8.7 to 3.0 and 3.2 at 6 months and the most recent visit, respectively (both p < 0.001). Opioid use decreased from 57.7 mg MSO4 equivalents to 24.3 mg at 6 months and to 28.0 mg at the latest patient visit (both p < 0.05). CONCLUSIONS: SCS may be an effective therapy for long-term treatment of symptoms for those patients afflicted with chronic nausea, vomiting, and refractory abdominal pain.

Clinical characteristics associated with idiopathic rapid gastric emptying in patients referred for gastric emptying studies.

OBJECTIVES: Rapid gastric emptying (RGE) is diagnosed using nuclear medicine gastric emptying scintigraphy (GES). The clinical symptoms are non-specific and its pathophysiology in the absence of gastric surgery is poorly understood. We aimed to evaluate the clinical characteristics associated with idiopathic RGE. METHODS: GES studies were reviewed from a database of 1958 4-hour solid-phase GES performed over an 8-year period. RGE was defined as <30% of the test meal remaining in the stomach at 1 hour. Patients who had had any gastric operation were excluded. A chart review was conducted to extract patients' baseline data and clinical characteristics. RESULTS: Of the 1958 GES studies reviewed, 156 (8.0%) patients had RGE, and 534 (27.3%) had delayed gastric emptying (>10% retained food at 4 h), respectively. Idiopathic RGE constituted 22.6% (156/690) of all abnormal GES studies. The patients' average age at diagnosis was 54.0 years and 53.8% of patients with RGE were female. Most (69.2%) of these studies were ordered with an initial clinical suspicion of gastroparesis, compared with only 12.2% with a suspicion of RGE. Among this idiopathic RGE cohort, 71.2% presented with symptoms of nausea, 42.9% with vomiting, 32.1% with abdominal pain, 21.2% with bloating and 17.9% with early satiety. Only 7.7% presented with diarrhea, 0.6% with palpitations and 0.6% with hypoglycemia. CONCLUSIONS: Idiopathic RGE is an important differential diagnosis in patients with symptoms classically associated with gastroparesis. Few have postprandial diarrhea or palpitations as their presenting symptom. Further studies of idiopathic RGE syndrome are warranted.

Outcomes of precut sphincterotomy techniques in cases of difficult biliary access.

GOALS: Our study aims to define success and complication rates of precut sphincterotomy with the needle-knife and transpancreatic papillary septotomy (TPS) techniques as experienced at a single, high-volume endoscopy centre. BACKGROUND: Complication rates rise with increasing number of failed attempts at biliary cannulation; therefore, early precut sphincterotomy (PS) has been recommended. Selecting the ideal method for PS can be challenging and there is a paucity of data to help guide this decision. STUDY: We performed a retrospective analysis over 37 months of endoscopic retrograde cholangiopancreatography (ERCP) experience at a single institution. We identified all ERCPs performed and stratified based on the presence of PS; if PS occurred, a thorough chart review was performed to identify success and complication rates. Patients received guideline-driven management for post-ERCP pancreatitis including rectal indomethacin and pancreatic duct stenting when appropriate. RESULTS: We identified 1808 ERCP procedures performed during this time. Successful biliary cannulation was achieved in 1748 cases, yielding a success rate of 96.7% (Grades I-IV ERCP difficulty/complexity). PS was required in 232 cases (12.8%); we identified 88 TPS cases and 114 needle-knife precut sphincterotomy (NKPS) cases. Complications following PS procedures occurred in 9.1% of TPS patients and 11.4% of NKPS patients. Success rates for TPS and NKPS were 97.7% and 81.6%, respectively-a statistically significant difference (p<0.001). CONCLUSION: This data supports TPS as a safe and effective option for biliary access in difficult cannulation settings when performed by experienced advanced endoscopists.

Six-month changes in ghrelin and glucagon-like peptide-1 with weight loss are unrelated to long-term weight regain in obese older adults.

BACKGROUND AND OBJECTIVE: Weight loss (WL) and subsequent regain are complex physiologic processes, and our understanding of the hormonal changes associated with these processes continues to evolve. We aimed to examine the effects of behavioral WL on 6-month changes in ghrelin and GLP-1 and evaluate the effects of these changes in gut hormones on weight regain among older adults. SUBJECTS AND METHODS: One hundred seventy-seven obese (BMI: 33.5 (3.5) kg/m2) older adults (66.9 ± 4.7 years, 71.2% female, 67.6% white) were randomized to WL (WL; n = 68), WL plus aerobic training (n = 79), or WL plus resistance training (n = 75) for 18 months. Ghrelin, GLP-1, power of food scale (PFS), and weight were measured at baseline, 6 months, and 18 months. RESULTS: There was no differential treatment effect on change in either gut hormone, however, there was a significant time effect across all groups (p < 0.001), with increases in ghrelin (∆ = +106.77 pg/ml; 95% CI = + 84.82, +128.71) and decreases in GLP-1 (∆ = -4.90 pM; 95% CI = -6.27, -3.51) at 6-month. Ratings on the PFS decreased from baseline to 6-month and there was significant loss of weight from baseline to either 6- or 18-month, ∆ = -7.96 kg; 95% CI = -7.95, -8.78 and ∆ = -7.80 kg; 95% CI = -8.93, -6.65, respectively (p < 0.001). Changes in ghrelin and GLP-1 at 6-month did not predict weight regain from 6- to 18-month. DISCUSSION AND CONCLUSION: Among older adults with obesity and cardiometabolic disease, the intensive phase of dietary WL results in increasing levels of ghrelin and decreasing levels of GLP-1 that are unrelated to weight regain a year later. Registered with ClinicalTrials.gov (NCT01547182).

Colonic gallstone ileus.

Gallstone ileus is a rare aetiology of bowel obstruction and very infrequently occurs in the colon. Typically, colonic gallstone ileus carries a high morbidity and mortality and requires surgery. This case report describes a cholecystocolonic fistula in a patient with ulcerative colitis with resulting colonic gallstone ileus, which was successfully intervened on via an endoscopic approach.

Clinical yield of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for incidental pancreatic cysts in kidney transplant evaluation.

INTRODUCTION: For several reasons, including an elevated risk for malignancy after transplant, kidney transplant candidates undergo a thorough evaluation prior to transplantation. Further assessment of incidentally discovered pancreatic cysts on routine abdominal imaging has been assumed to be prudent, and the preferred method has been endoscopic ultrasound (EUS) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The clinical utility of EUS/EUS-FNA with respect to transplant decision-making has not been evaluated. MATERIALS AND METHODS: Kidney transplant candidates undergoing EUS/EUS-FNA for further evaluation of one or more pancreatic cysts were identified. The clinical yield of the EUS/EUS-FNA was determined via retrospective chart review. RESULTS: After exclusion criteria were applied, a total of 15 cases were identified at a high-volume transplant center over a 71-month period. EUS/EUS-FNA was deemed to have a clinically relevant impact in 73.3% of cases. CONCLUSION: Kidney transplant candidates are a unique group with respect to the need to clarify the etiology of pancreatic cysts. EUS/EUS-FNA frequently provides information that is clinically relevant to the determination of transplant status.

Characteristic endoscopic ultrasound findings of ampullary lesions that predict the need for surgical excision or endoscopic ampullectomy.

BACKGROUND AND OBJECTIVES: The management of ampullary lesions has evolved to include endoscopic ampullectomy (EA) as a curative approach to cancers of the ampulla of Vater. With this change comes a need to risk-stratify patients at initial diagnosis. MATERIALS AND METHODS: Patients with verified ampullary lesions (N = 50) were analyzed in a case-control design. We evaluated endoscopic ultrasound (EUS) data to define characteristics that yield a high sensitivity in selecting candidates for EA. RESULTS: Using data from previously published studies yielded a sensitivity of 0.765 in appropriately identifying the 34 surgical cases. Expanding these characteristics increased the sensitivity of EUS to 0.971 in identifying surgical candidates. Additionally, of advanced disease cases, the expanded characteristics correctly identified these cases with a sensitivity of 1.0-improved over 0.708 using prior published data. CONCLUSION: EA should be strongly considered if ampullary lesions are found to fit the following characteristics after EUS evaluation: lesion size <2.5 cm, invasion ≤4 mm, pancreatic duct dilatation ≤3 mm, ≤T1 lesion, no lymph nodes present, and no ductal stent in place. Furthermore, EUS data can be used to identify all high-risk lesions. With these characteristics identified, clinicians are better able to risk-stratify patients using EUS as either appropriate for or too high-risk for endoscopic resection.

Self-Reported Gastrointestinal Symptoms in Type 2 Diabetes Improve With an Intensive Lifestyle Intervention: Results From the Action for Health in Diabetes (Look AHEAD) Clinical Trial.

In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.