Anatomic abnormalities are common potential explanations of manometric esophagogastric junction outflow obstruction.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is an esophageal motility diagnosis associated with a myriad of conditions. The frequency of EGJOO attributed to anatomic causes compared to idiopathic causes is uncertain. Our study aims to identify the frequency of EGJOO and to compare these two groups. METHODS: We conducted a case-control study of high-resolution manometry (HRM) studies with a diagnosis of EGJOO performed at a single academic center. EGJOO cases were classified as anatomic (if any potential anatomic cause was identified) or idiopathic. Clinical and manometric characteristics of idiopathic EGJOO were compared with anatomic EGJOO cases. KEY RESULTS: Criteria for EGJOO were met in 11% of HRM studies. Ancillary studies revealed 21/32 EGJOO cases had potential anatomic causes with a hiatal hernia noted in 15/21 cases of anatomic EGJOO. Idiopathic EGJOO cases met Chicago Classification criteria for hypercontractile esophagus with greater frequency than anatomic cases (p = 0.01). The mean distal contractile integral was significantly greater for idiopathic cases compared to anatomic cases (p = 0.003). Treatments used for EGJOO were varied and usually successful in alleviating symptoms. Patients with anatomic EGJOO related to a hiatal hernia who underwent an antireflux operation did not develop dysphagia postoperatively. CONCLUSIONS & INFERENCES: EGJOO is a frequently encountered manometric diagnosis, commonly associated with anatomic abnormalities potentially explaining the EGJOO. These findings support current recommendations to pursue ancillary diagnostics to investigate cases of unexplained EGJOO. Cases of idiopathic EGJOO are more likely to have hypercontractility on HRM, possibly suggesting a primary esophageal motility disorder.

Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection.

HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied. We compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c(+) and CD1c(neg)) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c(+) mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83(+)CD1c(+) mDCs negatively correlated with frequencies of interferon-γ-producing colon CD4(+) and CD8(+) T cells. CD40 expression on CD1c(+) mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c(+) mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii. These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation.

An altered intestinal mucosal microbiome in HIV-1 infection is associated with mucosal and systemic immune activation and endotoxemia.

Human immunodeficiency virus-1 (HIV-1) infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the intestinal microbiome and its association with mucosal T-cell and dendritic cell (DC) frequency and activation, as well as with levels of systemic T-cell activation, inflammation, and microbial translocation. Bacterial 16S ribosomal DNA sequencing was performed on colon biopsies and fecal samples from subjects with chronic, untreated HIV-1 infection and uninfected control subjects. Colon biopsies of HIV-1-infected subjects had increased abundances of Proteobacteria and decreased abundances of Firmicutes compared with uninfected donors. Furthermore at the genus level, a significant increase in Prevotella and decrease in Bacteroides was observed in HIV-1-infected subjects, indicating a disruption in the Bacteroidetes bacterial community structure. This HIV-1-associated increase in Prevotella abundance was associated with increased numbers of activated colonic T cells and myeloid DCs. Principal coordinates analysis demonstrated an HIV-1-related change in the microbiome that was associated with increased mucosal cellular immune activation, microbial translocation, and blood T-cell activation. These observations suggest that an important relationship exists between altered mucosal bacterial communities and intestinal inflammation during chronic HIV-1 infection.

The effect of feeding on the bile salt-independent canalicular secretion in dogs.

Mongrel dogs were prepared by cholecystectomy, ligation of the lesser pancreatic duct, and insertion of cannulas into the duodenum and stomach. During experiments on the unanesthetized dogs, bile was collected by cannulating the common bile duct through the duodenal cannula. Canalicular secretion was estimated by the biliary clearance of erythritol. Feeding caused increased bile flow, increased erythritol clearance, decreased bile salt concentration, and unchanged bile salt output. These findings indicate that feeding stimulated the bile salt-independent canalicular secretion.