Browsing by Author "Menard-Katcher, Paul A."

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    Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS)
    (Elsevier, 2021) Ma, Christopher; Schoepfer, Alain M.; Dellon, Evan S.; Bredenoord, Albert J.; Chehade, Mirna; Collins, Margaret H.; Feagan, Brian G.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Jairath, Vipul; Katzka, David A.; Pai, Rish K.; Rothenberg, Marc E.; Straumann, Alex; Aceves, Seema S.; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Biedermann, Luc; Blanchard, Carine; Cianferoni, Antonella; Ciriza de los Rios, Constanza; Clayton, Frederic; Davis, Carla M.; de Bortoli, Nicola; Dias, Jorge A.; Falk, Gary W.; Genta, Robert M.; Ghaffari, Gisoo; Gonsalves, Nirmala; Greuter, Thomas; Hopp, Russell; Hsu Blatman, Karen S.; Jensen, Elizabeth T.; Johnston, Doug; Kagalwalla, Amir F.; Larsson, Helen M.; Leung, John; Louis, Hubert; Masterson, Joanne C.; Menard-Katcher, Calies; Menard-Katcher, Paul A.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Penagini, Roberto; Pesek, Robert D.; Peterson, Kathryn; Putnam, Philip E.; Ravelli, Alberto; Savarino, Edoardo V.; Schlag, Christoph; Schreiner, Philipp; Simon, Dagmar; Smyrk, Thomas C.; Spergel, Jonathan M.; Taft, Tiffany H.; Terreehorst, Ingrid; Vanuytsel, Tim; Venter, Carina; Vieira, Mario C.; Vieth, Michael; Vlieg-Boerstra, Berber; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Woodland, Philip; Woosley, John T.; Yang, Guang-Yu; Zevit, Noam; Safroneeva, Ekaterina; Medicine, School of Medicine
    Background End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. Objective We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Methods Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. Results The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. Conclusions This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.
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    Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms Following Dilation in Adults with Eosinophilic Esophagitis
    (Elsevier, 2021-05-29) Safroneeva, Ekaterina; Pan, Zhaoxing; King, Eileen; Martin, Lisa J.; Collins, Margaret H.; Yang, Guang-Yu; Capocelli, Kelley E.; Arva, Nicoleta C.; Abonia, J. Pablo; Atkins, Dan; Bonis, Peter A.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Menard-Katcher, Paul A.; Mukkada, Vincent A.; Schoepfer, Alain M.; Spergel, Jonathan M.; Wershil, Barry K.; Rothenberg, Marc E.; Aceves, Seema S.; Furuta, Glenn T.; Pediatrics, School of Medicine
    Background and aims Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and esophageal eosinophil count (eos/hpf). Methods Adults enrolled in a multisite, prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers OMEGA observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsies. Patients were stratified based on dilation status as absent, performed ≤1 and >1 year before endoscopy. Assessments included Spearman’s correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. Results Amongst 100 patients (n=61 male, median age 37 years), 15 and 40 patients underwent dilation ≤1 year and >1 year before index endoscopy, respectively. In non-dilated patients, association between eos/hpf and symptoms was moderate (Rho=0.49, p-value<0.001); for 10 eos/hpf increase, the predicted EEsAI increased by 2.69 (p-value=0.002). In patients dilated ≤1 and >1 year before index endoscopy, this association was abolished (Rho=-0.38, p-value=0.157 for ≤1 year and Rho=0.02, p-value=0.883 >1 year); for 10 eos/hpf increase, the predicted EEsAI changed by -1.64 (p-value=0.183) and 0.78 (p-value=0.494), respectively). Dilation modifies association between symptoms and eos/hpf (p-value=0.005 and p-value=0.187 for interaction terms of eos/hpf and dilation ≤1 year and >1 year before index endoscopy, respectively). Conclusion In non-dilated EoE adults, eos/hpf correlates modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than one year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up.
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    Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell–Fibroblast Crosstalk
    (AGA, 2022-02) Shoda, Tetsuo; Wen, Ting; Caldwell, Julie M.; Morgenstern, Netali Ben-Baruch; Osswald, Garrett A.; Rochman, Mark; Mack, Lydia E.; Felton, Jennifer M.; Abonia, J. Pablo; Arva, Nicoleta C.; Atkina, Dan; Bonis, Peter A.; Capocelli, Kelley E.; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Menard-Katcher, Paul A.; Mukkada, Vincent A.; Putnam, Philip E.; Rudman Spergel, Amanda K.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Aceves, Seema S.; Furuta, Glenn T.; Rothenberg, Marc E.; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group; Medicine, School of Medicine
    Background & Aims Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. Methods Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) sites (n = 311) and two independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE endoscopic reference score (EREFS), EoE Histology Scoring System (HSS), EoE Diagnostic Panel (EDP), and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro. Results TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EREFS, EDP, and HSS (r = 0.34–0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle–related pathways. IL-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix (ECM) pathways. Endothelial cell–fibroblast crosstalk induced ECM changes relevant to esophageal remodeling. Conclusions Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.