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Introduction Treated patients with celiac disease (CeD) and nonceliac gluten sensitivity (NCGS) report acute, transient, incompletely understood symptoms after suspected gluten exposure. To determine whether (i) blinded gluten exposure induces symptoms, (ii) subjects accurately identify gluten exposure, and (iii) serum interleukin-2 (IL-2) levels distinguish CeD from NCGS subjects after gluten exposure. Methods Sixty subjects (n = 20 treated, healed CeD; n = 20 treated NCGS; n = 20 controls) were block randomized to a single, double-blind sham (rice flour) or 3-g gluten challenge with 72-hours follow-up. Twelve serial questionnaires (100 mm visual analog scale; pain, bloating, nausea, and fatigue) and 10 serial plasma samples were collected. Mucosal permeability was assessed using both urinary lactulose-13C mannitol ratios and endoscopic mucosal impedance. Results Thirty-five of 40 (83%) subjects with CeD and NCGS reported symptoms with gluten (8 CeD, 9 NCGS) and sham (9 CeD, 9 NCGS) compared with 9 of 20 (45%) controls after gluten (n = 6) and sham (n = 3). There was no significant difference in symptoms among groups. Only 2 of 10 subjects with CeD and 4 of 10 NCGS identified gluten, whereas 8 of 10 subjects with CeD and 5 of 10 NCGS identified sham. A significant plasma IL-2 increase occurred only in subjects with CeD after gluten, peaking at 3 hours and normalizing within 24 hours postchallenge despite no significant intestinal permeability change from baseline. Discussion Symptoms do not reliably indicate gluten exposure in either subjects with CeD or NCGS. IL-2 production indicates a rapid-onset gluten-induced T-cell activation in CeD despite long-standing treatment. The effector site is unknown, given no increased intestinal permeability after gluten.

Background and Aims Capsule endoscopy (CE) is an established, noninvasive modality for examining the small bowel. Minimum training requirements are based primarily on guidelines and expert opinion. A validated tool to assess the competence of CE is lacking. In this prospective, multicenter study, we determined the minimum number of CE procedures required to achieve competence during gastroenterology fellowship; validated a capsule competency test (CapCT); and evaluated any correlation between CE competence and endoscopy experience. Methods We included second- and third-year gastroenterology fellows from 3 institutions between 2013 and 2018 in a structured CE training program with supervised CE interpretation. Fellows completed the CapCT with a maximal score of 100. For comparison, expert faculty completed the same CapCT. Trainee competence was defined as a score ≥90% compared with the mean expert score. Fellows were tested after 15, 25, and 35 supervised CE interpretations. CapCT was validated using expert consensus and item analysis. Data were collected on the number of previous endoscopies. Results A total of 68 trainees completed 102 CapCTs. Fourteen CE experts completed the CapCT with a mean score of 94. Mean scores for fellows after 15, 25, and 35 cases were 83, 86, and 87, respectively. Fellows with at least 25 interpretations achieved a mean score ≥84 in all 3 institutions. CapCT item analysis showed high interobserver agreement among expert faculty (k = 0.85). There was no correlation between the scores and the number of endoscopies performed. Conclusion After a structured CE training program, gastroenterology fellows should complete a minimum of 25 supervised CE interpretations before assessing competence using the validated CapCT, regardless of endoscopy experience.

First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long-term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long-term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.

Rituximab, a monoclonal antibody directed against the CD20 antigen on B lymphocytes, is commonly used in the treatment of hematologic malignancies and rheumatologic disorders.1,2 It acts to rapidly deplete the B lymphocyte population through multiple mechanisms, leading to dysregulation of the immune system.3 Rituximab has been associated with numerous adverse gastrointestinal effects including diarrhea and bowel perforation, and recent reports have associated rituximab with the development of de novo inflammatory bowel disease (IBD).4,5 To our knowledge, there have been no reports of microscopic colitis (MC) associated with rituximab therapy. We aimed to identify patients with rituximab-associated colitis, and to better characterize the clinical features and disease course of these patients.

Background/aims: The key procedure-related risk with video capsule endoscopy (VCE) is capsule retention, which should be suspected in patients who have not reported capsule passage. The study aims ...

The rising incidence of obesity requires the reevaluation of our current therapeutic strategies to optimize patient outcomes. The objective of this study was to determine whether compositional and functional characteristics of the gut microbiota in adults predict responses to a comprehensive lifestyle intervention program in overweight and obese adults. We recruited 26 participants from the Mayo Clinic Obesity Treatment Research Program between August 6, 2013, and September 12, 2013, to participate in a lifestyle intervention program for weight loss. Adults aged 18 to 65 years with a body mass index of 27 to 39.9 kg/m2 and able to provide informed consent were included in the study. Fecal stool samples were obtained at baseline and after 3 months. Loss of at least 5% of baseline weight after 3 months was defined as success. Clinical characteristics and gut microbial composition and function were compared between those who achieved at least 5% and those who achieved less than 5% weight loss. After 3 months, 9 of 26 participants lost at least 5% of their weight. The mean weight loss was 7.89 kg (95% CI, 6.46-9.32 kg) in the success group and 1.51 kg (95% CI, 0.52-2.49 kg) in the less than 5% weight loss group. An increased abundance of Phascolarctobacterium was associated with success. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to lose 5% body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.

The United States Food and Drug Administration recently approved sofosbuvir and the fixed-dose combination of ledipasvir/sofosbuvir for the treatment of hepatitis C virus (HCV) infection in children ages 12 to 17. These are the first direct-acting antiviral treatments approved for children and adolescents with HCV. Pharmacokinetic data confirm equivalent drug exposure in this population as that found in adults during clinical trials. The efficacy and safety of these drugs has been shown in clinical trials.

Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota β-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.

Little is known about the features of immune-mediated non-celiac villous atrophies, such as autoimmune enteropathy (AIE). We investigated the demographic, clinical, and histologic features of adults with AIE compared to adults with refractory celiac disease type 1. We also report outcomes of treatment with open-label budesonide.We performed a retrospective case-control of patients with AIE (n = 30) seen at the Mayo Clinic (in Rochester, Minnesota) from 2000 through 2015. Patients with refractory celiac disease type 1 who were treated with open-label budesonide served as controls (n = 42). Biopsy specimens were reviewed for all patients. We collected demographic, clinical, biochemical and histologic data from patients. We also collected data on responses to open-capsule budesonide from patients with AIE (available from 22 patients) and controls (available from 42 patients); the median duration of follow up was 28 months (range, 0-1421 months).Patients with AIE had a higher proportion of men (60%) and were younger (mean, 44 ± 18 years) than patients with refractory celiac disease type 1 (29% men; P = .002 and mean age, 57 ± 16 years; P = .007). A higher proportion of patients with AIE presented with chronic diarrhea (100%) and weight loss (90%) than patients with refractory celiac disease type 1 (71%; P .001 and 71%; P = .05, respectively). Based on histologic analysis, there was no significant difference in degree of villous atrophy in intestinal tissues from patients with AIE vs controls (P = .68). However, a greater proportion of patients with RCD had increased intraepithelial lymphocytes (40 per 100 epithelial cells in 100%) compared with patients with AIE (in 50%) (P = .003). Conventional therapy (systemic steroids) had failed in most patients with AIE (a complete clinical response was reported in only 7 patients) before treatment with open-capsule budesonide was initiated. A clinical response to open-capsule budesonide was reported for 85% of patients with AIE (50% complete response, 35% partial response) compared to 92% of controls (68% complete response, 24% partial response).In a retrospective study of 30 patients with AIE, followed for a median 28 months, we found this disease to have has distinct demographic, clinical, and histologic characteristics compared to refractory celiac disease type 1. Most patients with AIE (85%) have a clinical response to budesonide, all of whom were unsuccessfully treated with conventional therapies.

Background The frequency and clinically important characteristics of incidental (18)F-fluorodeoxyglucose ([18 F]FDG) positron emission tomography (PET) uptake in the gastrointestinal tract (GIT) on PET/CT imaging in adults remain elusive. Methods All PET/CT reports from 1/1/2000 to 12/31/2009 at a single tertiary referral center were reviewed; clinical information was obtained from cases with incidental (18)F-FDG uptake in the GIT, with follow-up through October, 2012. Results Of the 41,538 PET/CT scans performed during the study period, 303 (0.7 %) had incidental GIT uptake. The most common indication for the PET/CT order was cancer staging (226 cases, 75 %), with 74 % for solid and 26 % for hematologic malignancies. Of those with solid malignancy, only 51 (17 %) had known metastatic disease. The most common site of GIT uptake was the colon, and of the 240 cases with colonic uptake, the most common areas of uptake were cecum (n = 65), sigmoid (n = 60), and ascending colon (n = 50). Investigations were pursued for the GIT uptake in 147 cases (49 %), whereas 51 % did not undergo additional studies, largely due to advanced disease. There were 73 premalignant colonic lesions diagnosed in 56 cases (tubular adenoma, n = 36; tubulovillous adenoma with low grade dysplasia, n = 27; sessile serrated adenoma, n = 4; tubulovillous adenoma with high grade dysplasia, n = 3; villous adenoma, n = 3), and 20 cases with newly diagnosed primary colon cancer. All 20 (100 %) patients with malignant colonic lesions had a focal pattern of [18 F]FDG uptake. Among cases with a known pattern of [18 F]FDG uptake, 98 % of those with premalignant lesions had focal [18 F]FDG uptake. Eighteen (90 %) of the cases with newly diagnosed colon cancer were not known to have metastatic disease of their primary tumor. Areas of incidental uptake in the ascending colon had the greatest chance (42 %) of being malignant and premalignant lesions than in any other area. Conclusion Focality of uptake is highly sensitive for malignant and premalignant lesions of the GIT. In patients without metastatic disease, incidental focal [18]FDG uptake in the GIT on PET/CT imaging warrants further evaluation.

Many factors are involved in weight gain and metabolic disturbances associated with obesity. The gut microbiota has been of particular interest in recent years, since both human and animal studies have increased our understanding of the delicate symbiosis between the trillions of microbes that reside in the GI tract and the host. It has been suggested that disruption of this mutual tolerance may play a significant role in modulating host physiology during obesity. Environmental influences such as diet, exercise, and early life exposures can significantly impact the composition of the microbiota, and this dysbiosis can in turn lead to increased host adiposity via a number of different mechanisms. The ability of the microbiota to regulate host fat deposition, metabolism, and immune function makes it an attractive target for achieving sustained weight loss.

Hepatitis C virus (HCV) genotype 4 accounts for 8-13% of all chronic HCV infections worldwide. Patients with HCV genotype 4 have been reported to have poor treatment responses to PEGylated interferon and ribavirin regimens. Recently a single tablet, fixed-dose combination of sofosbuvir, an RNA-directed RNA polymerase (NS5B) inhibitor, and ledipasvir, a nonstructural protein 5A (NS5A) inhibitor, has been approved for treatment of chronic HCV infection. Two studies using the fixed-dose combination in chronic HCV genotype 4 for 12 weeks reported sustained virologic response rates at 12 weeks (SVR12) of 93-95%. Data also support the use of ledipasvir/sofosbuvir in chronic HCV genotype 4 and HIV co-infection. Administered as a single once-daily oral regimen, this ribavirin- and interferon-free regimen is well tolerated, with low potential for adverse effects and represents a significant advancement in the treatment of chronic HCV genotype 4 infection.

The fixed-dose combination of glecaprevir (GLE), a nonstructural protein 3/4A (NS3/4A) protease inhibitor, and pibrentasvir (PIB), an NS5A inhibitor, was recently approved for the treatment of adult patients with chronic hepatitis C virus (HCV) genotypes 1-6 (GT-1-6) without cirrhosis or with compensated cirrhosis, and for the treatment of HCV GT-1 patients who have failed treatment with either NS5A inhibitors or NS3/4A protease inhibitors, but not both. This combination, administered over 8 or 12 weeks, has resulted in high cure rates in all six HCV genotypes, including patients with HIV coinfection. GLE/PIB was well tolerated, with the most common adverse events being headache and fatigue. GLE/PIB is recommended to be taken as three tablets (total daily dose: GLE 300 mg and PIB 120 mg) orally once daily with food. No dose adjustment is required in patients with any degree of renal impairment or in patients undergoing hemodialysis. Dose adjustment is also not required in patients with Child-Pugh A liver disease. However, the use of GLE/PIB is not recommended in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

We have previously shown that voluntary wheel running (VWR) attenuates, whereas forced treadmill running (FTR) exacerbates, intestinal inflammation and clinical outcomes in a mouse model of colitis. As the gut microbiome is implicated in colitis, we hypothesized that VWR and FTR would differentially affect the gut microbiome. Mice (9-10/treatment) were randomly assigned to VWR, FTR, or sedentary home cage control (SED) for 6 wk. VWR were given running wheel access, whereas FTR ran on a treadmill for 40 min/day at 8–12 m/min, 5% grade. Forty-eight hours after the last exercise session, DNA was isolated from the fecal pellets and cecal contents, and the conserved bacterial 16S rRNA gene was amplified and sequenced using the Illumina Miseq platform. Permutational multivariate analysis of variance based on weighted UniFrac distance matrix revealed different bacterial clusters between feces and cecal contents in all groups ( P < 0.01). Interestingly, the community structures of the three treatment groups clustered separately from each other in both gut regions ( P < 0.05). Contrary to our hypothesis, the α-diversity metric, Chao1, indicated that VWR led to reduced bacterial richness compared with FTR or SED ( P < 0.05). Taxonomic evaluation revealed that both VWR and FTR altered many individual bacterial taxa. Of particular interest, Turicibacter spp., which has been strongly associated with immune function and bowel disease, was significantly lower in VWR vs. SED/FTR. These data indicate that VWR and FTR differentially alter the intestinal microbiome of mice. These effects were observed in both the feces and cecum despite vastly different community structures between each intestinal region.

We have previously shown that voluntary exercise alters the gut microbiome and prevents inflammation in a mouse model of colitis. Here, we investigated whether exercise-induced changes in the gut microbiota plays a role. Donor C57Bl6/J mice ( n = 20) were given free access to a wheel ( n = 10) or remained sedentary ( n = 10) for six weeks. Mice were then euthanized, cecal contents were collected, pooled by treatment and gavage-fed to 65 germ-free C57Bl6/J mice housed in a gnotobiotic facility ( n = 32–33 in sedentary and exercise groups, respectively). After 4 weeks, half of the mice were administered 2% dextran sodium sulfate (DSS) in their water or remained as controls (water only). After 5 days, DSS-treated mice were switched to water for 3 days until euthanasia at day 8 (peak of symptoms). DSS caused significant weight loss over the 8-day period ( p p p

Background & Aims Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Nondietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsy specimens from patients with celiac disease. Methods We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atrophy (villous height:crypt depth ratio of ≤2.0) were assigned randomly to groups given placebo or 100, 300, 450, 600, or 900 mg latiglutenase daily for 12 or 24 weeks. Subjects completed the Celiac Disease Symptom Diary each day for 28 days and underwent an upper gastrointestinal endoscopy with duodenal biopsy of the distal duodenum at baseline and at weeks 12 and 24. The primary end point was a change in the villous height:crypt depth ratio. Secondary end points included numbers of intraepithelial lymphocytes, serology test results (for levels of antibodies against tissue transglutaminase-2 and deamidated gliadin peptide), symptom frequencies, and safety. Results In a modified intent-to-treat population, there were no differences between latiglutenase and placebo groups in change from baseline in villous height:crypt depth ratio, numbers of intraepithelial lymphocytes, or serologic markers of celiac disease. All groups had significant improvements in histologic and symptom scores. Conclusions In a phase 2 study of patients with symptomatic celiac disease and histologic evidence of significant duodenal mucosal injury, latiglutenase did not improve histologic and symptom scores when compared with placebo. There were no significant differences in change from baseline between groups. ClinicalTrials.gov no: NCT01917630.

The fixed-dose combination of sofosbuvir, a nucleotide analogue NS5B polymerase inhibitor, and velpatasvir, a second-generation NS5A inhibitor, has been approved by the United States Food and Drug Administration and the European Medicines Agency for the treatment of adult patients with chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection. This combination, administered over 12 weeks as a single-tablet regimen, has resulted in high cure rates in all 6 HCV genotypes and in a variety of patient populations, including patients without cirrhosis, patients with compensated cirrhosis and patients with HIV coinfection. In patients with decompensated cirrhosis, high cure rates were also achieved over 12 weeks with sofosbuvir/velpatasvir plus ribavirin. Patients who had failed prior treatment with an NS5A-containing regimen were able to achieve high cure rates following 24 weeks of treatment with sofosbuvir/velpatasvir plus ribavirin. Sofosbuvir/velpatasvir was well tolerated, the most common adverse events being headache, fatigue and nausea.

Celiac disease is an immune-mediated enteropathy triggered by exposure to gluten in genetically susceptible individuals. Although serological testing has increased the detection of celiac disease, small bowel biopsies are required to confirm the diagnosis. Currently, the only effective treatment is a lifelong strict gluten-free diet. Though safe and effective, this is not ideal because of the expense, impact on quality of life, and inability to achieve complete histologic remission despite strict adherence to a gluten-free diet, which may impact survival. Advances in the understanding of the pathogenesis of celiac disease have led to the identification of new therapies for treatment of celiac disease. This review will discuss the current approach and the evolving novel therapeutic strategies under investigation as alternatives to a gluten-free diet.

Klippel-Trenaunay syndrome (KTS) is a congenital vascular anomaly characterized by limb hypertrophy, cutaneous hemangiomas, and varicosities. GI hemorrhage is a potentially serious complication secondary to diffuse hemangiomatous involvement of the gut. We report on three patients with KTS who presented with transfusion-dependent anemia and life-threatening bleeding due to extensive cavernous hemangiomas involving the rectum. Two patients were treated by proctocolectomy and coloanal anastomosis, which preserved anal function while controlling bleeding. The third patient required an abdominoperineal resection because of extensive rectal, perianal, and perineal angiomatosis. The literature on the evaluation and management of GI hemorrhage in KTS, particularly of colorectal origin, is reviewed.

OBJECTIVES: The aim of this study was to assess the effects of the long-acting release (LAR) depot octreotide preparation Sandostatin LAR Depot on stool water and electrolyte losses, fecal fat excretion, and GI transit in patients with short bowel syndrome. METHODS: We performed a 15-wk, prospective, open-label study of intramuscular (i.m.) Sandostatin LAR Depot, 20 mg, at 0, 3, 7, and 11 wk. Balance studies were performed before and at the end of the 15-wk study. Baseline and posttreatment measurements of body weight, stool fat, sodium and potassium, and gastric and small bowel transit of a radiolabeled egg meal were compared by paired analysis. RESULTS: We studied eight patients with short bowel syndrome (five women and three men; mean age 52 yr, range 37–72 yr) who had been TPN dependent for a mean of 11.8 yr (range 1.5–22 yr). The underlying diagnoses were Crohn’s disease (n = 6), intestinal ischemia (n = 1), and resection for carcinoid tumor (n = 1). Treatment with Sandostatin LAR Depot significantly increased small bowel transit time (p = 0.03). Changes in body weight, urine volume, stool weight, fecal fat excretion, stool sodium and potassium excretion, or gastric emptying rate were highly variable, and no overall significance was observed. CONCLUSIONS: Sandostatin LAR Depot for 15 wk significantly prolonged small bowel transit time. Body weight and stool parameters in response to Sandostatin LAR Depot treatment needs to be assessed further in multicenter studies assessing dose, frequency of administration, and a larger sample size.

The aim of this study was to determine if a relationship exists between nonalcoholic steatohepatitis (NASH) and serum levels of free fatty acids, choline deficiency, or celiac disease. Forty-seven patients with liver biopsy proven NASH were enrolled. Total serum free fatty acids and anti-endomysial antibodies were determined in all patients, while plasma free and phospholipid-bound choline were determined in 29 patients. Total serum free fatty acid concentration correlated significantly with female gender and serum albumin concentration. Patients with severe fibrosis on liver biopsy had significantly greater serum concentration of free fatty acids than patients without severe fibrosis. Plasma free and phospholipid-bound choline levels were normal and no significant correlation was found between the concentration of plasma free or phospholipid bound choline, and the severity of liver damage. Only one of the 47 patients with NASH had a positive titer for the anti-endomysial antibody. In conclusion, increased serum concentrations of free fatty acids were found in NASH and were associated with development of more severe liver disease. Neither choline deficiency nor celiac sprue by anti-endomysial antibody testing was associated with NASH.

The purpose of this study was to determine theplasma triglyceride and phospholipid fatty acid (FA)composition of severely malnourished patients withchronic liver disease and to examine the effects of parenteral nutrition with a total nutrientadmixture (TNA) on these profiles. Nine consecutivepatients with end-stage chronic liver disease werecompared with 35 patients admitted for elective surgery of upper gastrointestinal malignancy. Baselinelaboratory values and the FA profiles of the plasmatriglyceride and phospholipids were analyzed. FAprofiles were also performed after infusion of a TNAincluding 33 ± 7 g of lipid/24 hr for 7.9 ±4 days in the patients with chronic liver disease.Compared with control patients, the plasma phospholipidfatty acid analysis results (relative mole percentage)of patients with chronic liver disease weresignificantly lower in the two essential FA, linoleicacid (15.4 ± 3.4% vs 20.8 ± 2.9%, P

Celiac disease is a chronic disorder of gluten sensitivity associated with a spectrum of mucosal lesions termed preinfiltrative, infiltrative, hyperplastic, destructive, and atrophic. The symptoms are not related to the degree of mucosal pathology but to the extent of the mucosal lesion. Neoplasms constitute the major complication of celiac disease, and EATCL is the most common neoplasm in this category. There is evidence that a strict gluten-free diet is protective against the complications of celiac disease; hence it is important that even the subclinical forms be diagnosed early. Small bowel biopsy remains the gold standard for diagnosis of celiac disease; however, antibody tests are a useful adjunct in deciding whom to biopsy and for screening groups at high risk before initiating a lifelong gluten-free diet.

Objectives: Up to 20% of patients with AIDS have abnormal intestinal permeability (IP). Glutamine seems to play an important role in preventing the increase in IP and loss of intestinal mucosal mass associated with total parenteral nutrition, and may be superior to glucose for oral rehydration in the setting of intestinal infection. This study was designed to see if supplemental glutamine could alter the abnormal IP of AIDS. Methods: Randomly chosen patients with AIDS from the Jacobi Medical Center human immunodeficiency virus (HIV) clinic underwent IP testing using lactulose and mannitol. Those with abnormal IP were enrolled. Duodenal biopsies were performed with a Crosby capsule and the patients were randomized in a double-blind fashion to receive placebo or glutamine (4 g/day or 8 g/day) for 28 days, after which intestinal permeability tests and duodenal biopsies were repeated. Intestinal morphology was graded by ratio of villus height to crypt depth, and by degree of inflammation. Results: All patients complied with the therapy and there were no dropouts or reported side effects. The results showed less worsening of IP with the 4 g/day dose, compared with placebo. At the 8 g/day dose, there was stabilization of IP and improved absorption of mannitol. Intestinal morphology and inflammation did not change in any group. Conclusions: These results, although not significant, suggest a trend towards improved IP and enhanced intestinal absorption with glutamine. Glutamine doses of at least 20 g/day may be necessary to improve IP. We recommend further studies at higher doses and for longer durations.

Crohn's disease is frequently complicated by protein-calorie malnutrition. Four common clinical presentations of Crohn's disease include acute exacerbations or flares of disease, intestinal obstruction, fistulizing disease, and perianal disease. In this review, we examine the role of nutritional support in these clinical scenarios. Nutritional support is important for maintaining functional status and preventing loss of lean tissue. Determinants of lean-tissue loss include severity of underlying injury, baseline nutritional status, and duration of inadequate nutrition. One of the clinically useful measures of nutritional status is the nutritional risk index (NRI) defined on the basis of the serum albumin and weight loss. Nutritional support is important in severely malnourished patients (NRI < 83). Enteral nutrition is the route of choice, provided there are no contraindications to using the gastrointestinal tract. In acute exacerbations of Crohn's disease, enteral nutrition also has a role in the primary management of disease although it is not as effective as corticosteroids in inducing remission. The mechanisms are poorly understood and the most effective enteral formulation needs to be determined. Total parenteral nutrition is justified in severely malnourished Crohn's disease patients who are unable to tolerate enteral feeding or in whom enteral feeding is contraindicated. More clinical studies are needed on the assessment of malnutrition in Crohn's disease, the effects of nutritional management on functional status, and the timing of nutritional intervention.

A 20-year-old man with no significant medical history presented with a 5-day history of intermittent chest pain and dyspnoea. He also reported a 3-month history of daily diarrhoea characterised by multiple, loose, watery, non-bloody stools. Physical examination was notable for tachycardia and a soft systolic murmur at the apex. Laboratory evaluation was significant for microcytic anaemia (serum iron 17 μg/dL; normal range 50–150 μg/dL) and an NT-proBNP (N-terminal pro-brain natriuretic peptide) of 18 995 pg/mL (normal

When consumed separately, whey protein (WP) is more rapidly absorbed into circulation than casein (Cas), which prompted the concept of rapid and slow dietary protein. It is unclear whether these proteins have similar metabolic fates when coingested as in milk. We determined the rate of appearance across the splanchnic bed and the rate of disappearance across the leg of phenylalanine (Phe) from coingested, intrinsically labeled WP and Cas. Either [15N]Phe or [13C- ring C6]Phe was infused in lactating cows, and the labeled WP and Cas from their milk were collected. To determine the fate of Phe derived from different protein sources, 18 healthy participants were studied after ingestion of one of the following: 1) [15N]WP, [13C]Cas, and lactose; 2) [13C]WP, [15N]Cas, and lactose; 3) lactose alone. At 80–120 min, the rates of appearance (Ra) across the splanchnic bed of Phe from WP and Cas were similar [0.068 ± 0.010 vs. 0.070 ± 0.009%/min; not significant (ns)]. At time 220–260 min, Phe appearance from WP had slowed (0.039 ± 0.008%/min, P < 0.05) whereas Phe appearance from Cas was sustained (0.068 ± 0.013%/min). Similarly, accretion rates across the leg of Phe absorbed from WP and Cas were not different at 80–120 min (0.011 ± 0.002 vs. 0.012 ± 0.003%/min; ns), but they were significantly lower for WP (0.007 ± 0.002%/min) at 220–260 min than for Cas (0.013 ± 0.002%/min) at 220–260 min. Early after meal ingestion, amino acid absorption and retention across the leg were similar for WP and Cas, but as rates for WP waned, absorption and assimilation into skeletal muscle were better retained for Cas.

Telaprevir, a hepatitis C virus (HCV) NS3/NS4A protease inhibitor, was recently approved by the U.S. Food and Drug Administration for the treatment of chronic HCV genotype 1 infection. When given in combination with pegylated interferon and ribavirin, it demonstrated improved efficacy over conventional pegylated interferon and ribavirin therapy. Improvement in efficacy was also noted in African American patients who traditionally respond less well to conventional anti-HCV treatment. While the role of telaprevir in the management of chronic HCV infection remains to be fully defined, its development and licensure represents an important milestone in anti-HCV therapeutics.

Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects.Open label study of ten healthy, obese adults (age = 29-49 years, body mass index = 31-54 kg/m(2)) who received 100 U (n = 4) or 300 U (n = 6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight.For the entire cohort, MTV decreased from 1,380 cc (range: 474-2,014) at baseline to 620 cc (range: 256-1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p = 0.03). Average body weight loss was 4.9 (+/-6.3) kg after 16 weeks. Gastric emptying T(1/2) was prolonged in the 300 U BTA group, but not significantly different from baseline (p = 0.17). BTA injections were well tolerated without significant adverse effects.EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.

Introduction Exercise training reduces colon cancer and inflammatory bowel diseases (IBD), but the mechanisms remain unknown. We hypothesized that acute and chronic exercise would alter the gut microbiota and its associated metabolome in a beneficial way. Methods Mice exercised for 6 weeks with access to voluntary wheels (VWR; n = 10), or were forcibly run on a treadmill running (FTR; n = 10). A control group remained sedentary (SED; n = 9). The conserved bacterial 16s rRNA gene was isolated from the feces and cecum and sequenced using high-throughput Illumina Miseq. In another experiment, mice were randomized to sedentary (SED, n = 10), acute moderate (MOD, n = 10) or high intensity running (HI, n = 10). Mice were euthanized 45 min post and cecal contents were analyzed for short chain fatty acids (SCFA) by GC-MS. Results Exercise training differentially altered the community structure of the microbiome at both intestinal sites ( p 0.05 ). Further evaluation revealed that exercise altered many bacterial taxa in both the feces and the cecum. Notably, voluntary exercise reduced ceca and fecal concentrations of Turicibacter spp., a genus of bacteria implicated in ulcerative colitis in humans and mice. Acute, HI (but not MOD) exercise increased the levels of potentially beneficial acetate, propionate, and butyrate, compared to SED ( p 0.05 ). Conclusion Acute and chronic exercise invokes changes in the microbiome and metabolome that may be beneficial to the prevention or treatment of IBD and colon cancer.

The aim of this study was to determine the specificity of increase in intraepithelial lymphocytes (IELs) with normal villous architecture in small bowel biopsy samples for diagnosis of gluten sensitivity (GS) and its significance in the absence of GS.Small bowel biopsy samples from 43 patients with increased IELs and no other pathology were reviewed. Patients with prior diagnosis of GS were excluded. A group of 46 patients with normal duodenal biopsy during the same period served as controls. The clinical records of patients and controls were examined for presenting symptoms, laboratory tests, and final clinicopathological diagnosis. Immunohistochemical characterization of IELs was performed in 13 cases.Four (9.3%) patients had GS based on positive IgA antiendomysial antibodies (n = 3) and favorable response to gluten-free diet (n = 4). One patient (2.2%) had partially treated tropical sprue; six patients (14%) had disorders of immune regulation including Hashimoto's thyroiditis (n = 2) and one case each of Graves' disease, rheumatoid arthritis, psoriasis, and multiple sclerosis; and six patients (14%) were on nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, none of the control subjects had GS (p = 0.05), tropical sprue, or immunoregulatory disorders (p = 0.011), and one (2.2%) was on NSAIDs (p = 0.04). Increased IELs were also observed in Crohn's disease, lymphocytic/collagenous colitis, and bacterial overgrowth, but the association did not reach statistical significance. Histological features (number and distribution of IELs, crypt mitoses) and immunophenotypic analysis of IELs did not reliably distinguish GS-related from non-GS-related causes of increased IELs.Intraepithelial lymphocytosis in an otherwise normal small bowel biopsy is somewhat nonspecific, but in nearly 10% of cases can be the initial presentation of GS. Therefore all patients with this finding should be investigated for GS. Increased IELs may also be associated with autoimmune disorders and NSAIDs.