A Dedicated Celiac Disease Program Improves Celiac Quality Care Metrics and Short-Term Outcomes in Real Life.

BACKGROUND AND AIMS: Dedicated multidisciplinary programs in gastroenterology are emerging with the goal to improve care. There is little information about the effects of a celiac disease program on disease-related quality care metrics and outcomes. We aimed to compare quality care metrics, symptom resolution, and serological response among patients diagnosed and treated in a celiac disease program with a standard of care cohort. METHODS: We performed a retrospective cohort study with adult celiac disease patients. We divided patients into two groups: celiac disease patients treated in our program and those treated by gastroenterologists not affiliated with the program (standard of care). We abstracted data from electronical medical records and compared frequency at which guideline-driven quality care metrics were obtained, assessed symptom resolution, and serological response based on IgA anti-tissue transglutaminase levels. RESULTS: We included 340 patients, 120 in the celiac disease program (89 women) and 220 (166 women) in the standard of care. Frequency of quality care metrics implementation in program patients was significantly greater for all variables (p < 0.0005). Diarrhea resolved in 38/46 (82.6%) in the CD program and 63/98 (64.2%) in the standard of care after starting a gluten-free diet (p = .025); bloating also resolved significantly more often in the former (26/34) than the latter (31/58; p = 0.03). Otherwise, there were no significant differences in resolution of clinical symptoms or serological response. CONCLUSION: A celiac disease program improves celiac-related quality care metrics and may improve outcomes such as diarrhea resolution compared to standard of care.

Appendiceal Fecalith Presenting as a Submucosal Cecal Polyp Removed During Colonoscopy.

Appendiceal fecaliths, also known as stercoliths or coproliths, are rigid masses comprised of fecal material that become lodged within the appendix. They are generally accepted to be a primary etiologic agent of acute appendicitis and appendiceal intussusception in adults. We report a case of an asymptomatic woman undergoing colonoscopy found to have a submucosal appearing mass below the appendiceal orifice. A neoplastic appearing lesion on the orifice of the appendix was resected, after which a fecalith extruded into the colonic lumen. This is the first reported case of appendiceal fecalith discovered and completely removed during colonoscopy in an asymptomatic patient.

Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders.

The aim of the study was to determine the correlation between duodenal mucosal biopsies and tissue transglutaminase immunoglobulin A (tTG-IgA) levels in pediatric patients with biopsy-confirmed celiac disease (CD) and eosinophilic gastrointestinal disorders (EGID) who have had repeat duodenal biopsies after initiating a gluten-free diet. Methods: A retrospective chart review was performed of children with CD and EGID seen at the Children's Hospital of Philadelphia between 2003 and 2018. Data collected included duodenal biopsy pathology, celiac serology including tTG-IgA, and symptom reports. Duodenal healing was defined as normal villous architecture and no intraepithelial lymphocytes. These data were compared with tTG-IgA level. Data were analyzed with Fisher exact test and t test methods. Results: Thirty-nine patients had normal IgA and diagnoses of both CD and EGID. At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values. Sixty percent (9/15) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels, and 57% (8/14) of patients with normal tTG-IgA levels had evidence of active disease on biopsy. Conclusions: The data show that an abnormal tTG-IgA drawn after initiation of a gluten-free diet is not correlated with duodenal mucosal injury in pediatric patients with CD and EGID. This suggests that serologic surveillance with tTG-IgA is not sufficient to monitor CD intestinal healing in this patient cohort. Persistent elevations of tTG-IgA in CD patients with normal duodenal biopsies should prompt investigation into other potential causes.

Engineered D2R Variants Reveal the Balanced and Biased Contributions of G-Protein and ß-Arrestin to Dopamine-Dependent Functions.

The dopamine D2 receptor (D2R), like many G-protein-coupled receptors, signals through G-protein- and ß-arrestin-dependent pathways. Preferential activation of one of these pathways is termed functional selectivity or biased signaling and is a promising therapeutic strategy. Though biased signaling through D2Rs has been demonstrated, acquiring the mechanistic details of biased D2R/G-protein and D2R/ß-arrestin signaling in vivo has been challenging because of the lack of techniques that specifically target these interactions in discrete cell populations. To address this question, we employed a cell type-specific viral expression approach to restore D2R variants that preferentially engage either G-protein or ß-arrestin signaling in 'indirect pathway' medium spiny neurons (iMSNs), because of their central role in dopamine circuitry. We found that the effect of haloperidol antagonism on D2R metabolic signaling events is largely mediated by acute blockade of D2R/G-protein signaling. We show that a D2R-driven behavior, nestlet shredding, is similarly driven by D2R/G-protein signaling. On the other hand, D2R-driven locomotion and rearing require coordinated D2R/G-protein and D2R/ß-arrestin signaling. The acute locomotor response to amphetamine and cocaine similarly depend on both G-protein and ß-arrestin D2R signaling. Surprisingly, another psychotropic drug, phencyclidine, displayed a selective D2R/ß-arrestin potentiation of locomotion. These findings highlight how D2R mostly relies upon balanced G-protein and ß-arrestin signaling in iMSNs. However, the response to haloperidol and phencyclidine indicates that normal D2R signaling homeostasis can be dramatically altered, indicating that targeting a specific D2R signal transduction pathway could allow for more precise modulation of dopamine circuit function.