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Background: Eosinophilic esophagitis (EoE) is an increasingly common inflammatory condition of the esophagus; however, the underlying immunologic mechanisms remain poorly understood. The epithelium-derived cytokine IL-33 is associated with type 2 immune responses and elevated in esophageal biopsy specimens from patients with EoE., Objective: We hypothesized that overexpression of IL-33 by the esophageal epithelium would promote the immunopathology of EoE., Methods: We evaluated the functional consequences of esophageal epithelial overexpression of a secreted and active form of IL-33 in a novel transgenic mouse, EoE33. EoE33 mice were analyzed for clinical and immunologic phenotypes. Esophageal contractility was assessed. Epithelial cytokine responses were analyzed in three-dimensional organoids. EoE33 phenotypes were further characterized in ST2 -/- , eosinophil-deficient, and IL-13 -/- mice. Finally, EoE33 mice were treated with dexamethasone., Results: EoE33 mice displayed ST2-dependent, EoE-like pathology and failed to thrive. Esophageal tissue remodeling and inflammation included basal zone hyperplasia, eosinophilia, mast cells, and T H 2 cells. Marked increases in levels of type 2 cytokines, including IL-13, and molecules associated with immune responses and tissue remodeling were observed. Esophageal organoids suggested reactive epithelial changes. Genetic deletion of IL-13 in EoE33 mice abrogated pathologic changes in vivo. EoE33 mice were responsive to steroids., Conclusions: IL-33 overexpression by the esophageal epithelium generated immunopathology and clinical phenotypes resembling human EoE. IL-33 may play a pivotal role in the etiology of EoE by activating the IL-13 pathway. EoE33 mice are a robust experimental platform for mechanistic investigation and translational discovery., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes., Objective: We sought to systematically synthesize the benefits and harms of AD systemic treatments., Methods: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna)., Results: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain., Conclusions: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The gut-lung axis is generally recognized, but there are few large studies of the gut microbiome and incident respiratory disease in adults., Objective: We sought to investigate the association and predictive capacity of the gut microbiome for incident asthma and chronic obstructive pulmonary disease (COPD)., Methods: Shallow metagenomic sequencing was performed for stool samples from a prospective, population-based cohort (FINRISK02; N = 7115 adults) with linked national administrative health register-derived classifications for incident asthma and COPD up to 15 years after baseline. Generalized linear models and Cox regressions were used to assess associations of microbial taxa and diversity with disease occurrence. Predictive models were constructed using machine learning with extreme gradient boosting. Models considered taxa abundances individually and in combination with other risk factors, including sex, age, body mass index, and smoking status., Results: A total of 695 and 392 statistically significant associations were found between baseline taxonomic groups and incident asthma and COPD, respectively. Gradient boosting decision trees of baseline gut microbiome abundance predicted incident asthma and COPD in the validation data sets with mean area under the curves of 0.608 and 0.780, respectively. Cox analysis showed that the baseline gut microbiome achieved higher predictive performance than individual conventional risk factors, with C-indices of 0.623 for asthma and 0.817 for COPD. The integration of the gut microbiome and conventional risk factors further improved prediction capacities., Conclusions: The gut microbiome is a significant risk factor for incident asthma and incident COPD and is largely independent of conventional risk factors., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical, pathological, and molecular information combined with cancer stage in prognostication algorithms can offer more personalized estimates of survival, which might guide treatment choices. Our aim was to evaluate the quality of prognostication tools in esophageal cancer., Methods: We systematically searched MedLine and Embase from 2005 to 2017 for studies reporting development or validation of models predicting long-term survival in esophageal cancer. We evaluated tools using the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies guidelines and the American Joint Committee on Cancer acceptance criteria for risk models., Results: We identified 16 prognostication tools for patients treated with curative intent and 1 for patients with metastatic disease. These tools frequently excluded adenocarcinoma, contained outdated data, and were developed with a limited sample size. Nine tools were developed in China for squamous cell cancer, and 11 used data on patients diagnosed before 2010. Most tools excluded key prognostic factors such as age and sex. Tumor stage and grade were the most commonly, but not universally, included factors. Twelve tools were designed to predict overall survival; 5 predicted cancer-specific survival. Bootstrap internal validation was performed for most tools; c-statistics ranged from 0.63 to 0.77 and graphically evaluated calibration was "good." Five tools were externally validated; c-statistics ranged from 0.70 to 0.77., Conclusions: Existing tools cannot be confidently used for esophageal cancer prognostication in current clinical practice. Better-quality tools might help to more individually and accurately estimate disease course, select further treatments, and risk-stratify for future clinical trials., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: A tripling in the number of overweight adolescents has occurred during the past two decades, with type 2 diabetes reaching epidemic proportions. Although obesity has been identified as a correlate of depression and low self-esteem in adolescents, the relationships among key cognitive/mental health variables and healthy attitudes, beliefs, choices, and behaviors in overweight teens have yet to be explored. Therefore, the aim of this study was to describe these relationships so that an effective intervention program to promote and sustain healthy lifestyle behaviors could be implemented., Methods: A descriptive correlational study was conducted with 23 overweight teens. Key variables measured included depressive symptoms, state and trait anxiety, self-esteem, beliefs/confidence about engaging in a healthy lifestyle, perceived difficulty in leading a healthy lifestyle, and healthy attitudes, choices, and behaviors., Findings: Teens with higher state and trait anxiety as well as depressive symptoms had less healthy lifestyle beliefs, and teens with higher self-esteem had stronger beliefs about their ability to engage in a healthy lifestyle. Stronger beliefs about the ability to engage in healthy lifestyles were related to healthier living attitudes and healthier lifestyle choices. Teens who perceived healthy lifestyles as more difficult had less healthy attitudes and reported less healthier choices and behaviors., Discussion: Including a strong cognitive behavioral skills building component into clinical interventions with overweight teens may be key in boosting their beliefs/confidence about being able to engage in healthy behaviors and lessening their perceived difficulty in performing them, which should result in healthier choices and lifestyle behaviors.