BackgroundEstrogen deficiency is associated with the development of cerebral aneurysms; however, the mechanism remains unknown. We explored the pathway of cerebral aneurysm development by investigating the potential link between estrogen deficiency and inflammatory factors.Methods and ResultsFirst, we established the role of interleukin‐17 (IL‐17)A. We performed a cytokine screen demonstrating that IL‐17A is significantly expressed in mouse and human aneurysms (P=0.03). Likewise, IL‐17A inhibition was shown to prevent aneurysm formation by 42% (P=0.02) and rupture by 34% (P<0.05). Second, we found that estrogen deficiency upregulates T helper 17 cells and IL‐17A and promotes aneurysm rupture. Estrogen‐deficient mice had more ruptures than control mice (47% versus 7%; P=0.04). Estradiol supplementation or IL‐17A inhibition decreased the number of ruptures in estrogen‐deficient mice (estradiol 6% versus 37%; P=0.04; IL‐17A inhibition 18% versus 47%; P=0.018). Third, we found that IL‐17A‐blockade protects against aneurysm formation and rupture by increased E‐cadherin expression. IL‐17‐inhibited mice had increased E‐cadherin expression (P=0.003). E‐cadherin inhibition reversed the protective effect of IL‐17A inhibition and increased the rate of aneurysm formation (65% versus 28%; P=0.04) and rupture (12% versus 0%; P=0.22). However, E‐cadherin inhibition alone does not significantly increase aneurysm formation in normal mice or in estrogen‐deficient mice. In cell migration assays, E‐cadherin inhibition promoted macrophage infiltration across endothelial cells (P<0.05), which may be the mechanism for the estrogen deficiency/IL‐17/E‐cadherin aneurysm pathway.ConclusionsOur data suggest that estrogen deficiency promotes cerebral aneurysm rupture by upregulating IL‐17A, which downregulates E‐cadherin, encouraging macrophage infiltration in the aneurysm vessel wall.

Background and Purpose We have previously demonstrated that the local delivery of monocyte chemotactic protein-1 (MCP-1) via a MCP-1-releasing poly(lactic-co-glycolic acid) (PLGA) -coated coil promotes intra-aneurysmal tissue healing. In this study, we demonstrate that interleukin-6 (IL-6) and osteopontin (OPN) are downstream mediators in the MCP-1-mediated aneurysm healing pathway. Methods Murine carotid aneurysms were created in C57BL/6 mice. Drug-releasing coils (MCP-1, IL-6 and OPN) and control PLGA coils were created and then implanted into the aneurysms in order to evaluate their intra-aneurysmal healing capacity. In order to investigate the downstream mediators for aneurysm healing, blocking antibodies for IL-6 receptor and OPN were given to the mice implanted with the MCP-1-releasing coils. A histological analysis of both murine and human aneurysms was utilized to cross-validate the data. Results We observed increased expression of IL-6 in MCP-1-coil treated aneurysms and not in control-PLGA-only treated aneurysms. MCP-1-mediated intra-aneurysmal healing is inhibited in mice given blocking antibody to IL-6 receptor. MCP-1-mediated intra-aneurysmal healing is also inhibited by blocking antibody to OPN. The role of IL-6 in intra-aneurysmal healing is in recruiting of endothelial cells and fibroblasts. Local delivery of OPN to murine carotid aneurysms via OPN-releasing coil significantly promotes intra-aneurysmal healing, but IL-6-releasing coil does not, suggesting that IL-6 cannot promote aneurysm healing independent of MCP-1. In the MCP-1-mediated aneurysm healing, OPN expression is dependent on IL-6; inhibition of IL-6 receptor significantly inhibits OPN expression in MCP-1-mediated aneurysm healing. Conclusions Our findings suggest that IL-6 and OPN are key downstream mediators of MCP-1-mediated intra-aneurysmal healing.

Background: Patient satisfaction surveys are important measures of the patient experience that provide data for quality improvement. The purpose of this study was to establish the response rate and the factors associated with the completion of the Press Ganey (PG) Ambulatory Surgery Survey (PGAS) in patients who underwent ambulatory upper-extremity surgical procedures. Methods: A prospective orthopaedic registry at a single academic ambulatory surgical center was retrospectively reviewed for patients who underwent an upper-extremity surgical procedure from 2015 to 2019. The institutional PG database was queried to determine the patients who completed the PGAS postoperatively. The response rate was calculated, and baseline characteristics and patient-reported outcome measures were compared between responders and nonresponders. Results: Of the 1,489 patients included, 201 (13.5%) were responders and 1,288 (86.5%) were nonresponders. Differences existed in baseline characteristics between groups, with responders being significantly older (p = 0.004) and having significantly higher proportions of White race (p < 0.001), college education (p = 0.011), employment (p = 0.005), marriage (p = 0.006), and higher income earners (p < 0.001). Responders had significantly better baseline Patient-Reported Outcomes Measurement Information System scores across multiple domains (p < 0.05), but these differences were not clinically meaningful. Conclusions: PGAS response rates were low (13.5%), and differences between responders and nonresponders may be utilized by hospitals to target feedback from underrepresented patient populations. Surgeons, policymakers, and health-care administrators should use caution with the interpretation of PGAS results because responders may not be representative of all patients.

The results of this survey demonstrated that, in comparison to 1998, the current state of cemented THA, in particular cementing technique has significantly improved. Future emphasis should be on continued surgeon education and training, as the operative, i. e., cementing techniques are of utmost importance for long-term success.

Aims The purpose of this study was to assess the prevalence of depression and anxiety symptoms in patients undergoing shoulder surgery using the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety computer adaptive tests, and to determine the factors associated with more severe symptoms. Additionally, we sought to determine whether PROMIS Depression and Anxiety were associated with functional outcomes after shoulder surgery. Methods This was a retrospective analysis of 293 patients from an urban population who underwent elective shoulder surgery from 2015 to 2018. Survey questionnaires included preoperative and two-year postoperative data. Bivariate analysis was used to identify associations and multivariable analysis was used to control for confounding variables. Results Mean two-year PROMIS Depression and Anxiety scores significantly improved from preoperative scores, with a greater improvement observed in PROMIS Anxiety. Worse PROMIS Depression and Anxiety scores were also significantly correlated with worse PROMIS Physical Function (PF) and American Shoulder and Elbow Surgeons scores (ASES). After controlling for confounding variables, worse PROMIS Depression was an independent predictor of worse PROMIS PF, while worse PROMIS Anxiety was an independent predictor of worse PROMIS PF and ASES scores. Conclusion Mean two-year PROMIS Depression and Anxiety scores improved after elective shoulder surgery and several patient characteristics were associated with these scores. Worse functional outcomes were associated with worse PROMIS Depression and Anxiety; however, more severe two-year PROMIS Anxiety was the strongest predictor of worse functional outcomes. Cite this article: Bone Joint J 2022;104-B(4):479–485.