Use of Upadacitinib as Salvage Therapy for Ulcerative Colitis in Pregnancy: A Case Report.

Upadacitinib, a selective JAK-1 inhibitor, was used as rescue therapy for ulcerative colitis in the setting of pregnancy following use of mesalamine, vedolizumab, infliximab, and corticosteroids. This resulted in an uncomplicated live full birth without need for surgical intervention.

The Incidence of Pouch Neoplasia Following Ileal Pouch-Anal Anastomosis in Patients With Inflammatory Bowel Disease.

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.

The incidence of pouch neoplasia in inflammatory bowel disease patients who have undergone ileal pouch­anal anastomosis (IPAA) is low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA as well as rectal dysplasia at time of IPAA raise the risk of pouch neoplasia significantly.

Primary Sclerosing Cholangitis-Associated Pouchitis: A Distinct Clinical Phenotype.

BACKGROUND & AIMS: Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort. METHODS: All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups. RESULTS: Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P < .001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P < .001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P < .001), and prepouch ileitis (34.1% vs 11.5%; P < .001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics. CONCLUSIONS: PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

The Clinical Characteristics and Treatment Outcomes of Concomitant Eosinophilic Esophagitis and Inflammatory Bowel Disease.

Background: The clinical characteristics and treatment outcomes in patients with eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) have 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 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.

Jejunal Polyps out of Place: A Case of Gastric Heterotopia of the Jejunum.

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.

Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model.

The purpose of this study was to characterize behavioral and physiological effects of a selective thromboxane (TP) receptor antagonist, SQ 29,548, in the C57Bl/6 mouse model. At 6 months of age, male mice were given either sham or drug i.p. injections for 3 days at a dose of 2 mg/kg each day. On the day after the final injection, mice were subjected to behavioral testing before brain collection. Left hemisphere hippocampi were collected from all mice for protein analysis via Western blot. Right brain hemispheres were fixed and embedded in gelatin and then serially sectioned. The sections were immunostained with 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 with 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 with sham treatments, as determined from 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.

Overexpression of mutant amyloid-ß protein precursor and presenilin 1 modulates enteric nervous system.

Alzheimer's disease (AD) is a neurodegenerative disorder histologically characterized by amyloid-ß (Aß) protein accumulation and activation of associated microglia. Although these features are well described in the central nervous system, the process and consequences of Aß accumulation in the enteric nervous system have not been extensively studied. We hypothesized that Aß 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 AßPP/PS1 and C57BL/6 (wild type) mice were collected and analyzed using immunohistochemistry, western blot analysis, cytokine arrays, and ELISA. AßPP/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 AßPP and the proteolytic enzyme, BACE, corresponding to an increase in Aß1-40 in the intestinal lysate as well as an increase in both Aß1-40 and Aß1-42 in the stool. This correlated with increased protein markers of proinflammatory and immune cell activation. Histologic analysis localized AßPP within enteric neurons but also intestinal epithelial cells with elevated Aß immunoreactivity in the AßPP/PS1 mice. The presence of AßPP, Aß, 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 AßPP and Aß.