Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease.
The World Health Organization Surgical Safety Checklist (WHO SSC) has demonstrated efficacy in developed and developing countries alike. Recent increases in awareness of surgical morbidity in developing countries has placed greater emphasis on strategies to improve surgical safety in resource-limited settings. The implementation of surgical safety checklists in low-income countries has specific barriers related to resources and culture. Adapting and amending existing surgical safety checklists, as well as considering factors unique to developing countries, may allow the potential of this simple intervention to be fully harnessed in a wider setting. This review will address the benefits and challenges of implementation of surgical safety checklists in developing countries. Moreover, inspiration for the original checklist is revisited to identify areas that will be of particular benefit in a resource-poor setting. Potential future strategies to encourage the implementation of checklists in these countries are also discussed.
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