Guidelines on eosinophilic esophagitis: evidence-based statements and recommendations for diagnosis and management in children and adults

Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. This underlines the importance of optimizing diagnosys and treatment of the condition, especially after the increasing amount of knowledge on EoE recently published. Therefore, the UEG, EAACI ESPGHAN, and EUREOS deemed it necessary to update the current guidelines regarding conceptual and epidemiological aspects, diagnosis, and treatment of EoE. General methodology according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used in order to comply with current standards of evidence assessment in formulation of recommendations. An extensive literature search was conducted up to August 2015 and periodically updated. The working group consisted of gastroenterologists, allergists, pediatricians, otolaryngologists, pathologists, and epidemiologists. Systematic evidence-based reviews were performed based upon relevant clinical questions with respect to patient-important outcomes. The guidelines include updated concept of EoE, evaluated information on disease epidemiology, risk factors, associated conditions, and natural history of EoE in children and adults. Diagnostic conditions and criteria, the yield of diagnostic and disease monitoring procedures, and evidence-based statements and recommendation on the utility of the several treatment options for patients EoE are provided. Recommendations on how to choose and implement treatment and long-term management are provided based on expert opinion and best clinical practice. Evidence-based recommendations for EoE diagnosis, treatment modalities, and patients' follow up are proposed in the guidelin

JMV2894, a novel growth hormone secretagogue, accelerates body mass recovery in an experimental model of cachexia

Oncologic patients subjected to chemotherapy frequently present aphagia, malnutrition, and cachexia. The purpose of this study was to investigate whether selected growth hormone secretagogues including hexarelin, JMV2894 and JMV2951 could antagonize body weight loss and wasting induced by cisplatin administration in rats. The three growth hormone secretagogues behaved as full agonists of the growth hormone secretagogues receptor both in terms of ability to stimulate calcium mobilization in Chinese hamster ovary cells and stimulation of growth hormone release in neonatal rats. Adult rats were (i) treated with vehicle throughout (controls), or (ii) treated with cisplatin (days 1\u20133) and a growth hormone secretagogues or vehicle, (days 1\u201312). Body weight and food consumption were measured daily. Although all growth hormone secretagogues caused initial transient acute increases in food intake, the total amount of food eaten by controls and growth hormone secretagogues treated groups over the 12 experimental days was not significantly different. All groups pre-treated with cisplatin lost up to 5\u201310\u2009% body weight in the first 4 days; they subsequently gained weight at a rate comparable with controls. Interestingly, rats which received JMV2894 demonstrated a faster gain in body weight than any other growth hormone secretagogues treated group and at the end of the protocol reached a weight similar to that of controls. JMV2894 did not stimulate perirenal and epididymal fat accumulation but reduced MuRF mRNA levels in skeletal muscles. In conclusion, our findings demonstrate that JMV2894 antagonizes cisplatin induced weight loss in rats and may prove useful in antagonizing cachexia associated with cancer and chemotherapy in humans

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS).

BACKGROUND Endpoints 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 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 four outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life (QoL). A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a two-round Delphi process and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, EoE Histology Scoring System, EoE Endoscopic Reference Score, and patient-reported measures of dysphagia and QoL. 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, which will facilitate meaningful treatment comparisons and improve the quality of data synthesis

A Summary of the Meetings of the Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) International Multidisciplinary Consensus

The Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS) collaborators are a group of more than 70 gastroenterologists, pathologists, allergists, researchers, dietitians, psychologists, and methodologists who convened in a series of in-person and virtual meetings between 2018 and 2020 with the aim of developing a core outcome set (COS) for use in therapeutic studies of pharmacologic and dietary therapies for the treatment of eosinophilic esophagitis (EoE). Given heterogeneity in reported outcomes and uncertainties regarding the most appropriate end points for use in both randomized controlled trials (RCTs) and observational studies involving EoE patients, the EoE experts launched the COREOS exercise in 2018 to standardize outcome definitions using methods established by the Core Outcome Measures in Effectiveness Trials (COMET) initiative.1,2 The COS was developed using a multiphase approach, which is summarized in Figure 1. In the first phase, systematic reviews of the literature and patient engagement surveys were conducted to identify candidate outcomes that have been previously measured and are important to patients with EoE. Next, this information was used to build a framework of different outcome domains, and working groups for each domain were assembled to review the literature for relevant end points.3–6 The relative importance of these domains was categorized in a Delphi survey as core, important, and research agenda domains, and discussed in a moderated in-person meeting on May 17, 2019 at Digestive Disease Week (San Diego, CA). In phase 3, a comprehensive list of outcome measures within each of the core domains was evaluated by the COREOS collaborators in a 2-round Delphi survey and, finally, outcomes were ratified in a virtual meeting on December 8, 2020. In this meeting summary, we highlight the major points of discussion that occurred during the development of the EoE COS