Vascular smooth muscle cell (VSMC) activation promotes a synthetic phenotype that underlies many vessel growth disorders. In this regard it has been suggested that the metabolic sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) has significant antigrowth and antimetastatic properties and may serve as a viable therapeutic target. In the current study we hypothesized that AMPK reduces neointima formation following balloon injury and that this occurs through reduction in VSMC proliferation and migration. Data reveal that local or systemic dosing with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) significantly increased AMPK activity in vivo and inhibited neointima formation in rat carotid arteries 2 wk after injury. In primary VSMCs, AICAR inhibited migration and induced cytostatic growth arrest through increased protein phosphatase 2A-mediated inhibition of mitosis-promoting cyclin B. AICAR also significantly enhanced AMPK-specific T278 phosphorylation of the actin anticapping vasodilator-activated serum phosphoprotein, increased G- to F-actin ratios and stress fiber formation, and abrogated PDGF-stimulated S397 autophosphorylation of focal adhesion kinase, promigratory cytoplasmic accumulation of paxillin, and extracellular matrix proteolysis by matrix metalloproteinase-9. Together, these results provide compelling evidence that AMPK serves to inhibit vascular smooth muscle migration and proliferation through regulation of cytoskeletal/focal adhesion/ECM stability, increasing our knowledge of this important metabolic regulator and providing support for its continued investigation in the treatment of vascular growth disorders.

Background: The coronavirus disease 2019 (COVID-19) pandemic has been associated with a dramatic increase in postviral olfactory dysfunction (PVOD) among patients who are infected. A contemporary evidence-based review of current treatment options for PVOD is both timely and relevant to improve patient care. Objective: This review seeks to impact patient care by qualitatively reviewing available evidence in support of medical and procedural treatment options for PVOD. Systematic evaluation of data quality and of the level of evidence was completed to generate current treatment recommendations. Methods: A systematic review was conducted to identify primary studies that evaluated treatment outcomes for PVOD. A number of medical literature data bases were queried from January 1998 to May 2020, with completion of subsequent reference searches of retrieved articles to identify all relevant studies. Validated tools for the assessment of bias among both interventional and observational studies were used to complete quality assessment. The summary level of evidence and associated outcomes were used to generate treatment recommendations. Results: Twenty-two publications were identified for qualitative review. Outcomes of alpha-lipoic acid, intranasal and systemic corticosteroids, minocycline, zinc sulfate, vitamin A, sodium citrate, caroverine, intranasal insulin, theophylline, and Gingko biloba are reported. In addition, outcomes of traditional Chinese acupuncture and olfactory training are reviewed. Conclusion: Several medical and procedural treatments may expedite the return of olfactory function after PVOD. Current evidence supports olfactory training as a first-line intervention. Additional study is required to define specific treatment recommendations and expected outcomes for PVOD in the setting of COVID-19.

Background: Central compartment atopic disease (CCAD) is a variant of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) characterized by polypoid changes of the superior nasal septum, middle (MT), and/or superior turbinates (ST). This study evaluates surgical outcomes in patients with CCAD compared with other CRSwNP subtypes. Methods: Retrospective analysis was performed at Emory University from May 2012 to November 2019. Patients undergoing primary endoscopic sinus surgery (ESS) for CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and CRSwNP not otherwise specified (CRSwNP NOS) were included consecutively, beginning with the earliest date of CCAD patient. Outcome measures included polyp recurrence, revision ESS, oral steroid use, and oral antibiotic use. Pearson chi-square and univariate analysis of variance (ANOVA) were performed for group comparisons.Results: Data was collected for 132 patients (CCAD = 38, AERD = 20, AFRS = 37, CRSwNP NOS = 37; 58 females, mean age 42.9 years [range, 13-85 years]). CCAD patients demonstrated polyp recurrence less frequently than expected, whereas AFRS patients had polyp recurrence more frequently than expected (p = 0.003; phi 0.32). CCAD patients underwent revision ESS less frequently than expected; AFRS and CRSwNP NOS underwent revision ESS more frequently than expected (p = 0.03; phi 0.26). CRSwNP NOS patients received more total antibiotic courses than those with CCAD (p = 0.01; eta-squared 0.09) and more courses of antibiotics per month than those with AFRS (p = 0.03; eta-squared 0.07). There was no significant difference in follow-up measures across groups (number of visits, total months, or visits per month). Conclusion:Rates of polyp recurrence and revision ESS were significantly lower in CCAD patients compared with patients with other CRSwNP subtypes, suggesting durable benefit of ESS and postoperative medical therapy in CCAD patients.

Background In the 5 years that have passed since the publication of the 2018 International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (ICAR‐Allergic Rhinitis 2018), the literature has expanded substantially. The ICAR‐Allergic Rhinitis 2023 update presents 144 individual topics on allergic rhinitis (AR), expanded by over 40 topics from the 2018 document. Originally presented topics from 2018 have also been reviewed and updated. The executive summary highlights key evidence‐based findings and recommendation from the full document. Methods ICAR‐Allergic Rhinitis 2023 employed established evidence‐based review with recommendation (EBRR) methodology to individually evaluate each topic. Stepwise iterative peer review and consensus was performed for each topic. The final document was then collated and includes the results of this work. Results ICAR‐Allergic Rhinitis 2023 includes 10 major content areas and 144 individual topics related to AR. For a substantial proportion of topics included, an aggregate grade of evidence is presented, which is determined by collating the levels of evidence for each available study identified in the literature. For topics in which a diagnostic or therapeutic intervention is considered, a recommendation summary is presented, which considers the aggregate grade of evidence, benefit, harm, and cost. Conclusion The ICAR‐Allergic Rhinitis 2023 update provides a comprehensive evaluation of AR and the currently available evidence. It is this evidence that contributes to our current knowledge base and recommendations for patient evaluation and treatment.

Stone JD, Holt AW, Vuncannon JR, Brault JJ, Tulis DA. AMP-activated protein kinase inhibits transforming growth factor-␤-mediated vascular smooth muscle cell growth: implications for a Smad-3-dependent mechanism.