A comparative trial of laparoscopic magnetic sphincter augmentation and Nissen fundoplication.

BACKGROUND: Laparoscopic magnetic sphincter augmentation (MSA) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease (GERD). Initial studies have demonstrated MSA to be safe and effective. However, no direct comparison between MSA and laparoscopic Nissen fundoplication (LNF), the gold standard surgical therapy for GERD, has been performed. METHODS: A single institution, case-control study was conducted of MSA performed from 2012 to 2013 and a cohort of LNF matched for age, gender, and hiatal hernia size. RESULTS: MSA and LNF were both effective treatments for reflux with 75 and 83 % of patients, respectively, reporting resolution of GERD at short-term follow-up. Dysphagia was common following both MSA and LNF, but severe dysphagia requiring endoscopic dilation was more frequent after MSA (50 vs. 0 %, p = 0.01). Need for dilation did not correlate with size of the LINX device or any other examined patient factors. A trend toward decreased adverse GI symptoms of bloating, flatulence, and diarrhea was seen after MSA compared to LNF (0 vs. 33 %). MSA had a shorter operative time (64 vs. 90 min, p < 0.01) but other peri-operative outcomes, including pain, morbidity, and re-admissions were equivalent to LNF. MSA patients were more likely to be self-referred (58 vs. 0 %, p < 0.001). CONCLUSIONS: MSA and LNF are both effective and safe treatments for GERD; however, severe dysphagia requiring endoscopic intervention is more common with MSA. Other adverse GI side effects may be less frequent after MSA. Consideration should be paid to these distinct post-operative symptom profiles when selecting a surgical therapy for reflux disease.

Successful Treatment of Refractory Autoimmune Enteropathy With Ustekinumab.

Autoimmune enteropathy (AIE) is a rare autoimmune disorder that has been described both in pediatric and adult patients and usually causes intractable watery diarrhea. The management of AIE is not standardized because the disease shows variable response to different immunosuppressive regimens including corticosteroids, azathioprine, cyclophosphamide, 6-mercaptopurine, tacrolimus, cyclosporine-A, infliximab, vedolizumab, and abatacept. We present a patient with adult-onset AIE and intractable high-volume diarrhea resulting in numerous hospitalizations and temporary parenteral nutrition, who is now successfully maintained on ustekinumab. Therefore, ustekinumab should be considered for further evaluation as a therapeutic option in cases of refractory AIE.

RNA sequencing of intestinal mucosa reveals novel pathways functionally linked to celiac disease pathogenesis.

BACKGROUND & AIMS: The early steps in the pathophysiology of celiac disease (CD) leading to loss of tolerance to gluten are poorly described. Our aim was to use RNA sequencing of duodenal biopsies in patients with active CD, CD in remission, and non-CD controls to gain insight into CD pathophysiology, identify additional genetic signatures linked to CD, and possibly uncover targets for future therapeutic agents. METHODS: We performed whole transcriptome shotgun sequencing of intestinal biopsies in subjects with active and remission CD and non-CD controls. We also performed functional pathway analysis of differentially expressed genes to identify statistically significant pathways that are up or down regulated in subjects with active CD compared to remission CD. RESULTS: We identified the upregulation of novel genes including IL12R, ITGAM and IGSF4 involved in the immune response machinery and cell adhesion process in the mucosa of subjects with active CD compared to those in remission. We identified a unique signature of genes, related to innate immunity, perturbed exclusively in CD irrespective of disease status. Finally, we highlight novel pathways of interest that may contribute to the early steps of CD pathogenesis and its comorbidities such as the spliceosome, pathways related to the innate immune response, and pathways related to autoimmunity. CONCLUSIONS: Our study confirmed previous findings based on GWAS and immunological studies pertinent to CD pathogenesis and describes novel genes and pathways that with further validation may be found to contribute to the early steps in the pathogenesis of CD, ongoing inflammation, and comorbidities associated with CD.

A faculty development program to train tutors to be discussion leaders rather than facilitators.

PURPOSE: During 2003, 2004, and 2005, the role of 70 tutors was changed from that of facilitator to discussion leader, in a preclinical PBL learning course, Gastrointestinal Pathophysiology, by use of three key business school teaching strategies: questions, summaries, and schematics. The purpose of this study was to learn what difference this new approach made. METHOD: During each of the three study years, 171 (2003), 167 (2004), and 170 (2005) students were given Likert-scale attitudinal questionnaires to rate whether their tutors encouraged student direction of the tutorials and whether the summaries and closure schematics benefited their learning. Students' overall course evaluations and mean USMLE scores were quantitatively analyzed, pre- and postintervention. A variety of statistical tests were used to assess the statistical significance of means at the confidence level of .05. RESULTS: In the third year of the program, student ratings indicated that their tutors were significantly better at encouraging student direction of the tutorials than in the first year (P < .05). The students reported that the tutorial made a more important contribution to their learning (P < .05), and the course objectives were better stated (P = .038) and better met (P = .007). Overall satisfaction with the course also improved significantly (P = .006). Part I gastrointestinal system mean scores of the USMLE showed a statistically significant increase in 2005 compared with 2001 or 2002. CONCLUSIONS: The tutor as a discussion leader who questions, summarizes, and uses schematics to illustrate concepts had a significant and positive impact on learning in tutorials, achieving course objectives, improving overall course satisfaction, and increasing a standardized national exam's mean score.