Alzheimer's disease (AD) is a neurodegenerative disorder histologically characterized by amyloid-β (Aβ) protein accumulation and activation of associated microglia. Although these features are well described in the central nervous system, the process and consequences of Aβ accumulation in the enteric nervous system have not been extensively studied. We hypothesized that Aβ also may accumulate in the enteric nervous system and lead to immune cell activation and neuronal dysfunction in the digestive tract not unlike that observed in diseased brain. To test this hypothesis, ileums of the small intestine of thirteen month old AβPP/PS1 and C57BL/6 (wild type) mice were collected and analyzed using immunohistochemistry, western blot analysis, cytokine arrays, and ELISA. AβPP/PS1 mice demonstrated no differences in intestinal motility or water absorption but elevated luminal IgA levels compared to wild type mice. They also had increased protein levels of AβPP and the proteolytic enzyme, BACE, corresponding to an increase in Aβ1-40 in the intestinal lysate as well as an increase in both Aβ1-40 and Aβ1-42 in the stool. This correlated with increased protein markers of proinflammatory and immune cell activation. Histologic analysis localized AβPP within enteric neurons but also intestinal epithelial cells with elevated Aβ immunoreactivity in the AβPP/PS1 mice. The presence of AβPP, Aβ, and CD68 immunoreactivity in the intestines of some patients with neuropathologically-confirmed AD are consistent with the findings in this mouse model. These data support the hypothesis that in AD the intestine, much like the brain, may develop proinflammatory and immune changes related to AβPP and Aβ.

Heterotopia is the presence of normal physiologic tissue in an atypical location. Gastric heterotopia has been described in various locations throughout the gastrointestinal tract, including the small intestine. Gastric heterotopia of the small intestine typically is asymptomatic but may present in several ways with symptoms of obstruction, bleeding, perforation, intussusception, or pain. However, gastric heterotopia is rare beyond the duodenum except for its frequent association with Meckel’s diverticulum. This entity should be considered in the differential diagnosis of polypoid lesions presenting with symptoms of bleeding or obstruction especially in younger patients. We present a case of gastric heterotopia of the jejunum in a patient with a prior history of Meckel’s diverticulectomy after he presented with obstructive symptoms. His symptoms improved following resection of two jejunal polyps via antegrade double-balloon assisted enteroscopy with fluoroscopy. On histopathlogical examination, findings were consistent with gastric heterotopia. This case highlights the importance of considering gastric heterotopia in the differential diagnosis of polypoid lesions located beyond the ligament of Treitz in younger patients presenting with obstructive symptoms.

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The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane receptor (TP) antagonist, SQ 29,548, in the C57BL/6 mouse model. At six months of age, male mice were given either sham or drug intraperitoneal injections for three days at a dose of 2mg/kg each day. On the day after the final injection mice were subjected to behavioral testing paradigms before brain collection. Left hemisphere hippocampi were collected from all mice for protein analysis via western blot. Right brain hemispheres were fixed and imbedded in gelatin, and serially sectioned. The sections were immunostained using anti-c-Fos antibodies. Prostaglandin analysis was performed from remaining homogenized brain samples, minus the hippocampi. Injection of SQ 29,548 decreased selective brain prostaglandin levels compared to sham controls. This correlated with robust increases in limbic region c-Fos immunoreactivity in the SQ 29,548 injected mice. However, drug treated mice demonstrated no significant changes in relevant hippocampal protein levels compared to sham treatments, as determined by western blots. Surprisingly, injection of SQ 29,548 caused mixed changes in parameters of depression and anxiety-like behavior in the mice. In conclusion, the results indicate that administration of peripheral TP receptor antagonists alters brain levels of prostanoids and influences neuronal activity with only minimal alterations of behavior. Whether the drug affects neurons directly or through a secondary pathway involving endothelium or other tissues remains unclear.

Background The clinical characteristics and treatment outcomes in patients with eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) has not been extensively investigated. Methods We determined treatment outcomes and frequencies of disease-related complications in patients with EoE and IBD. Results Among 69 patients who met inclusion criteria, 39 (56.5%) had a diagnosis of Crohn’s disease. Clinical and histologic response rates to proton pump inhibitors and topical steroids were 25.9% and 24.4%, respectively. Conclusions Lower than expected clinical and histologic response rates for EoE suggest the combination of EoE and IBD is a medically-refractory phenotype with more difficult to treat EoE.

Background Ileal pouch–anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA. Methods All patients at a large tertiary center with International Classification of Diseases–Ninth Revision/International Classification of Diseases–Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted. Results In total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia. Conclusions The incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia.

INTRODUCTION: Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are distinct chronic inflammatory conditions involving the gastrointestinal tract. The presence of eosinophilic infiltration in gastrointestinal mucosa has been observed as a histopathological feature of IBD, being described in both Crohn's disease (CD) and ulcerative colitis (UC). The natural history of patients with coexisting EoE and IBD has not been extensively studied. Our aim was to determine clinical characteristics and treatment outcomes in patients with concomitant IBD and EoE. METHODS: A retrospective cohort study was performed of all EoE patients who also had a diagnosis of IBD from January 2000 to December 2018. Patients were identified using ICD-9 and ICD-10 diagnostic codes. Confirmation of EoE and IBD diagnoses were required for inclusion in the study. Pertinent demographic and clinical data were extracted from the electronic medical record. Treatment outcomes and frequencies of disease-related complications were determined. RESULTS: Sixty-nine patients met inclusion criteria (68.1% male) with a median follow-up of 6 years. Forty-one patients had a diagnosis of CD (59.4%), 26 UC (37.7%), and 2 indeterminate colitis (IC) (2.9%). Forty-eight patients were diagnosed with IBD prior to EoE (69.6%). The most common treatments for EoE were proton pump inhibitors (78.3%) and topical steroids (59.4%) with 51.9% and 63.4% demonstrating clinical improvement, respectively (Table 1). The most common treatments for IBD were oral 5-aminosalicyclic acid (5-ASA) (69.6%), oral corticosteroids (66.7%), azathioprine (44.9%), and adalimumab (43.5%), with 37.5%, 43.5%, 35.5%, and 50% demonstrating clinical improvement, respectively (Table 2). Fifteen patients with CD (36.5%), 7 with UC (26.9%) and 1 with IC (50%) required surgical intervention for IBD. Eighteen patients with CD (43.9%), 8 with UC (30.8%), and 1 with IC (50%) required hospitalization for IBD (Table 3). CONCLUSION: Recent literature has shown an association between IBD and EoE. In our cohort, IBD is the more frequent initial diagnosis. As such, it is important to be vigilant for signs suggestive of EoE in patients with IBD and evaluate accordingly. It seems most patients with IBD and EoE respond to conventional treatment modalities used for each diagnosis. However, about 40% of patients with CD and EoE required hospitalization and/or surgical intervention, possibly suggesting a more severe phenotype in this specific subset of patients.

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