Background:The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods:Evidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results:The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AE-CRS), and pediatric RS. Conclusion:As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too o en the foundation upon which these recommendations are based is comprised of lowerlevel evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C 2016 ARS-AAOA, LLC. Key Words:rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery List of Abbreviations Used

I. Executive Summary Background The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS.

This document provides healthcare practitioners with information regarding the management of acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) to enable them to better meet the needs of this patient population. These guidelines describe controversies in the management of acute bacterial rhinosinusitis (ABRS) and include recommendations that take into account changes in the bacteriologic landscape. Recent guidelines in ABRS have been released by American and European groups as recently as 2007, but these are either limited in their coverage of the subject of CRS, do not follow an evidence-based strategy, or omit relevant stakeholders in guidelines development, and do not address the particulars of the Canadian healthcare environment.Advances in understanding the pathophysiology of CRS, along with the development of appropriate therapeutic strategies, have improved outcomes for patients with CRS. CRS now affects large numbers of patients globally and primary care practitioners are confronted by this disease on a daily basis. Although initially considered a chronic bacterial infection, CRS is now recognized as having multiple distinct components (eg, infection, inflammation), which have led to changes in therapeutic approaches (eg, increased use of corticosteroids). The role of bacteria in the persistence of chronic infections, and the roles of surgical and medical management are evolving. Although evidence is limited, guidance for managing patients with CRS would help practitioners less experienced in this area offer rational care. It is no longer reasonable to manage CRS as a prolonged version of ARS, but rather, specific therapeutic strategies adapted to pathogenesis must be developed and diffused.Guidelines must take into account all available evidence and incorporate these in an unbiased fashion into management recommendations based on the quality of evidence, therapeutic benefit, and risks incurred. This document is focused on readability rather than completeness, yet covers relevant information, offers summaries of areas where considerable evidence exists, and provides recommendations with an assessment of strength of the evidence base and degree of endorsement by the multidisciplinary expert group preparing the document.These guidelines have been copublished in both Allergy, Asthma & Clinical Immunology and the Journal of Otolaryngology-Head and Neck Surgery.

The data presented in this study support the practice of administering preoperative systemic steroids to patients undergoing ESS for CRSwP. Furthermore, in the practice of surgeons who provide intensive postoperative care post-ESS, including debridement and medical therapy based on the endoscopic findings, there is evidence to support administering systemic steroids in the postoperative period. The POSE scoring system compares favorably with the LKES and may confer advantages in terms of face/content validity and responsiveness to change and is worthy of further validation.

Reactive astrogliosis is a characteristic response of astrocytes to inflammation and trauma of the adult CNS. To assess the hypothesis that cytokines from inflammatory mononuclear cells that accumulate around lesion sites have a role in modulating astrogliosis, this study sought to take advantage of the neonatal system in which astrogliosis is reported to be minimal following injury and in which the immune system is relatively immature compared to adult animals. A nitrocellulose membrane implant into the cortex of postnatal day 3 mice resulted in a tremendous astrogliotic response 4 d later, as measured by glial fibrillary acidic protein (GFAP) immunoreactivity and GFAP content. In contrast, a neonatal stab wound produced limited astroglial response when compared to the adult stab wound. Utilizing the neonatal stab wound model, cytokines were microinjected into the wound site at the time of injury. All cytokines tested (gamma-IFN, IL-1, IL-2, IL-6, TNF-alpha, and M-CSF) resulted in a significantly increased astrogliosis. The specificity of the cytokine response was demonstrated by the inability of human gamma-IFN, but not mouse gamma-IFN, in enhancing neonatal mouse astrogliosis, in accordance with reports that the interaction of gamma-IFN with its receptor occurs in a species-specific manner. We conclude that neonatal astrocytes can become reactive if an adequate injury stimulus is presented, and that the release of immunoregulatory cytokines by cells around lesion sites may be a mechanism that contributes to the production of gliosis.