Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Prevalence of Apical Periodontitis and Conventional Nonsurgical Root Canal Treatment in General Adult Population: An Updated Systematic Review and Meta-analysis of Cross-sectional Studies Published between 2012 and 2020

Introduction This study aimed to summarize data on apical periodontitis (AP) and nonsurgical root canal treatment (NSRCT) prevalence and risk factors related to age, gender, and quality of restorative and endodontic treatment in the general population from cross-sectional studies published between 2012 and 2020. Methods An electronic search was performed in the following databases: Web of Science, Scopus, and PubMed. The conducted literature search covered studies published between 2012 and 2020, without restrictions on language. The STROBE and NOS tools were used for quality assessment of the included studies. Results Sixteen articles were included in the review. In total, 200,041 teeth were examined. On average, 6.3% of teeth had AP, and 7.4% had NSRCT. Forty-one percent of RCT teeth had AP, and 3.5% of untreated teeth had AP. Female patients were less prone to AP in endodontically treated teeth only, compared with male patients (P < .001). Variable stratification of age subgroups among included studies prevented us from conducting a meta-analysis. An increase in AP frequency was found in teeth with inadequate restorative and endodontic treatment (P < .001 and P < .001, respectively). Because of high heterogeneity, these results should be taken with caution. Conclusions There is an increased AP prevalence in the adult general population compared with data from 2012 (6.3% versus 5.4%) in both endodontically treated (41.3% versus 35.9%) and untreated teeth (3.5% versus 2.1%). In addition, AP developed less frequently in female patients with endodontically treated teeth and in teeth with inadequate compared with adequate restorative and endodontic treatment.This is the peer-reviewed version of the article: Jakovljevic A, Nikolic N, Jacimovic J, Pavlovic O, Milicic B, Beljic-Ivanovic K, Miletic M, Andric M, Milasin J. Prevalence of Apical Periodontitis and Conventional Nonsurgical Root Canal Treatment in General Adult Population: An Updated Systematic Review and Meta-analysis of Cross-sectional Studies Published between 2012–2020. Journal of Endodontics. 2020;46(10):1371-1386.e8. [https://doi.org/10.1016/j.joen.2020.07.007