ABSTRACT
Background: End-stage ankle osteoarthritis is a condition that can be treated with ankle arthrodesis (AA) or total ankle arthroplasty (TAA). The goal of this study is to estimate the 2016-2017 United States' utilization of TAA and AA in specific ambulatory settings and delineate patient and hospital factors associated with the selection of TAA vs AA for treatment of ankle osteoarthritis. Methods: TAA and AA procedures performed for ankle osteoarthritis were identified in the 2016-2017 Nationwide Ambulatory Surgery Sample (NASS) Database. Notably, the NASS database only examines instances of ambulatory surgery encounters at hospital-owned facilities. As such, instances of TAA and AA performed at privately owned or freestanding ambulatory surgical centers or those performed inpatient are excluded from this analysis. Cases were weighted using nationally representative discharge weights. Univariate analyses and a combined multiple logistic regression model were used to compare demographic, hospital-related, and socioeconomic factors associated with TAA vs AA. Results: In total, 6577 cases were identified, which represents 9072 cases after weighting. Of these, TAA was performed for 2233 (24.6%). Based on the logistic regression model, several factors were associated with increased utilization of TAA vs AA. With regard to patient factors, older patients were more likely to undergo TAA, as well as females. Conversely, patients with a higher comorbidity burden were less likely to receive TAA over AA.With regard to socioeconomic factors, urban teaching and urban nonteaching hospitals were significantly more likely to use TAA compared to rural hospitals. Similarly, privately insured patients and those with a median household income of $71 000 or more were also more likely to receive TAA over AA. Private hospitals ("not-for-profit" and "investor-owned") were significantly more likely to offer TAA over AA. Conclusion: Using a large nationally representative cohort, the current data revealed that during 2016-2017, 24.6% of operatively treated cases of end-stage ankle osteoarthritis in the ambulatory setting are treated with TAA. Associations between socioeconomic and hospital-level factors with TAA utilization suggest that nonclinical factors may influence surgical treatment choice for ankle osteoarthritis. Level of Evidence: Level III, retrospective cohort study.
ABSTRACT
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis. However, there is no evidence, so far, of the functional contribution of AT1R to breast tumorigenesis. We explored the potential therapeutic benefit of ARB in a carcinogen-induced mouse model of breast cancer and clarified the mechanisms associated with its success.Mammary tumors were induced with 7,12-dimethylbenz[α]antracene (DMBA) and medroxyprogesterone acetate (MPA) in female wild type mice and the effects of the ARB, Losartan treatment assessed in a preventative setting (n = 15 per group). Tumor histopathology was characterised by immunohistochemistry, real-time qPCR to detect gene expression signatures, and tumor cytokine levels measured with quantitative bioplex assays. AT1R was detected with radiolabelled ligand binding assays in fresh frozen tumor samples.We showed that therapeutic inhibition of AT1R, with Losartan, resulted in a significant reduction in tumor burden; and no mammary tumor incidence in 20% of animals. We observed a significant reduction in tumor progression from DCIS to invasive cancer with Losartan treatment. This was associated with reduced tumor cell proliferation and a significant reduction in IL-6, pSTAT3 and TNFα levels. Analysis of tumor immune cell infiltrates, however, demonstrated no significant differences in the recruitment of lymphocytes or tumour-associated macrophages in Losartan or vehicle-treated mammary tumors.Analysis of AT1R expression with radiolabelled ligand binding assays in human breast cancer biopsies showed high AT1R levels in 30% of invasive ductal carcinomas analysed. Furthermore, analysis of the TCGA database identified that high AT1R expression to be associated with luminal breast cancer subtype.Our in vivo data and analysis of human invasive ductal carcinoma samples identify the AT1R is a potential therapeutic target in breast cancer, with the availability of a range of well-tolerated inhibitors currently used in clinics. We describe a novel signalling pathway critical in breast tumorigenesis, that may provide new therapeutic avenues to complement current treatments.
