Monitoring and modulating the trajectory of eosinophilic esophagitis.

Current treatments of eosinophilic esophagitis (EoE) aim to eliminate esophageal mucosal inflammation and attenuate, stabilize, or reverse stricture formation. However, our ability to study the long-term course of esophageal strictures in patients with EoE is hampered by the short-term existence of this disease. It is unclear to what degree of control of inflammation is needed to prevent stricture formation. Additionally, identified phenotypes of EoE may ultimately dictate different levels of concern and time intervals for developing fibrosis. Currently, multiple methods are used to monitor patients' disease progression to fibrosis, as symptoms alone do not correlate with disease activity. Endoscopic findings and mucosal histology are used to monitor disease activity, but these focus on improvements in inflammation with inconsistent evaluation of underlying fibrosis. The use of functional lumen impedance planimetry, barium esophagraphy, and endoscopic ultrasound continues to expand in EoE. The rapid advancements in EoE have led to an armamentarium of measuring tools and therapies that holistically characterize disease severity and response to therapy. Nevertheless, our ability to evaluate gross esophageal fibrosis and stricture formation from a transmural rather than mucosal view should be a focus of future investigations because it is essential to monitoring and modulating the trajectory of EoE.

Questionnaire for diagnosis and response to therapy in rumination syndrome.

Rumination is a behavioral disorder characterized by regurgitation of food without retching. It is diagnosed clinically by the Rome Criteria and treated primarily by diaphragmatic breathing. Despite diagnosis and follow-up being based on symptomatic responses to therapies, there are no published or validated questionnaires. To address this care-gap, a rumination questionnaire was developed and reviewed by two expert esophagologists and five patients diagnosed with rumination. Ultimately, an eight-point questionnaire with scoring ranging from -1 to 10 was finalized. This newly developed questionnaire was implemented on five additional patients diagnosed clinically with rumination syndrome with improvement after interventions noted.

Cross-Phenotype GWAS Supports Shared Genetic Susceptibility to Systemic Sclerosis and Primary Biliary Cholangitis.

Objective: An increased risk of primary biliary cholangitis (PBC) has been reported in patients with systemic sclerosis (SSc). Our study aims to investigate the shared genetic susceptibility between the two disorders and to define candidate causal genes using cross-phenotype GWAS meta-analysis. Methods: We performed cross-phenotype GWAS meta-analysis and colocalization analysis for SSc and PBC. We performed both genome-wide and locus-based analysis, including tissue and pathway enrichment analyses, fine-mapping, colocalization analyses with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) datasets, and phenome-wide association studies (PheWAS). Finally, we used an integrative approach to prioritize candidate causal genes from the novel loci. Results: We detected a strong genetic correlation between SSc and PBC (rg = 0.84, p = 1.7 × 10-6). In the cross-phenotype GWAS meta-analysis, we identified 44 non-HLA loci that reached genome-wide significance (p < 5 × 10-8). Evidence of shared causal variants between SSc and PBC was found for nine loci, five of which were novel. Integrating multiple sources of evidence, we prioritized CD40, ERAP1, PLD4, SPPL3, and CCDC113 as novel candidate causal genes. The CD40 risk locus colocalized with trans-pQTLs of multiple plasma proteins involved in B cell function. Conclusion: Our study supports a strong shared genetic susceptibility between SSc and PBC. Through cross-phenotype analyses, we have prioritized several novel candidate causal genes and pathways for these disorders.

Influence of Total Coronary Occlusion on Clinical Outcomes (from the Bypass Angioplasty Revascularization Investigation 2 DiabetesTrial).

Our aim was to evaluate the influence of chronic total occlusions (CTOs) on long-term clinical outcomes of patients with coronary heart disease and diabetes mellitus. We evaluated patients with coronary heart disease and diabetes mellitus enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes, who underwent either prompt revascularization (PR) with intensive medical therapy (IMT) or IMT alone according to the presence or absence of CTO. Of 2,368 patients enrolled in the trial, 972 patients (41%) had CTO of coronary arteries. Of those, 482 (41%) and 490 (41%) were in the PR with IMT versus IMT only groups, respectively. In the PR group, patients with CTO were more likely to be selected for the coronary artery bypass grafting stratum (coronary artery bypass grafting 62% vs percutaneous coronary intervention 31%, p <0.001). Compared to the non-CTO group, patients with CTO had more abnormal Q wave, abnormal ST depression, and abnormal T waves. The myocardial jeopardy score was higher in the CTO versus non-CTO group (52 [36 to 69] vs 37 [21 to 53], p <0.001). After adjustment, 5-year mortality rate was significantly higher in the CTO group in the entire cohort (hazard ratio [HR] 1.35, p = 0.013) and in patients with CTO managed with IMT (HR 1.46, p = 0.031). However, the adjusted risk of death was not increased in patients managed with PR (HR 1.26, p = 0.180). In conclusion, CTO of coronary arteries is associated with increased mortality in patients treated medically. However, the presence of a CTO may not increase mortality in patients treated with revascularization. Larger randomized trials are needed to evaluate the effects of revascularization on long-term survival in patients with CTO.