Determining the stress biomarker profile in patients undergoing total knee replacement and the relationship with outcome at 12 months.

BACKGROUND: Total knee replacement (TKR) is the commonest joint arthroplasty procedure worldwide. Despite excellent outcomes, some studies have reported dissatisfaction in up to 20% of patients. There is evidence of an association between the biochemical stress response to surgery and outcomes. The objective of this study is to describe the stress biomarker profile for TKR, and correlate this with patient outcomes. METHODS: A prospective cohort study of 50 patients undergoing primary TKR was conducted. Serum IL-6, TNF-α, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were measured immediately pre- and post-operatively, and on Days 1 and 3. Follow-up questionnaires including the Oxford Knee Score (OKS) and EuroQol five dimensions (EQ-5D) were completed at 12-months. Univariate analysis was completed using a linear regression model (p < 0.05). RESULTS: Serum IL-6, NLR, and PLR all increased to Day 1 post-operatively, and decreased by Day 3. TNF-α values increased across all time points. Statistical analysis found a significant negative correlation (r = -0.414; p = 0.005) between pre-operative IL-6 and 12-month OKS. There was a significant positive correlation between pre-operative NLR and 12 month OKS (r = 0.272; p = 0.039) and 12 month EQ5D (r = 0.268; p = 0.043). CONCLUSION: This is the first study to describe the biochemical stress response to TKR. The results raise the potential for a pre-operative risk stratification tool for patients based on IL-6 and NLR measurements. Further research should be conducted to explore the underlying mechanisms involved, and investigate interventions to reduce pre-operative physiological stress with a view to improving post-operative outcomes.

The effect of expectation on satisfaction in total knee replacements: a systematic review.

Total knee replacement has reliably been shown to have a beneficial effect in knee osteoarthritis; however, around 17 % of patients are dissatisfied with the result. A commonly proposed mechanism driving the dissatisfaction rate is a discrepancy between expected and actual/perceived outcome. Our aim was to conduct a systematic review examining any association between pre-operative expectations and satisfaction. A comprehensive electronic search strategy was used to identify studies from MEDLINE, EMBASE, and the Cochrane Library from inception until May 2015. Data was extracted according to PRISMA guidelines and an online, published protocol. Four studies are included in this review. One study found an association between expectations and satisfaction. Different measures of expectation and satisfaction were used in all studies. To date, there is no consensus on how expectations or satisfaction should be measured, and a large number of studies that have the available information failed to conduct the relevant sub-group analysis. Further elucidation and consensus of how to measure expectations and satisfaction around joint replacement would aid this area of study greatly. On the basis of the current evidence it appears expectations have a small effect, if any, on satisfaction after knee replacement.

Topical antiangiogenic SRPK1 inhibitors reduce choroidal neovascularization in rodent models of exudative AMD.

PURPOSE: Exudative AMD (wet AMD) is treated by monthly injection into the eye of anti-VEGF proteins. VEGF is alternatively spliced to produce numerous isoforms that differ in angiogenic activity. Serine-rich protein kinase-1 (SRPK1) has been identified as a regulator of pro-angiogenic VEGF splicing by phosphorylating serine-rich splicing factor-1 (SRSF1), which binds to VEGF pre-mRNA. We tested the hypothesis that topical (eye drop) SRPK1-selective inhibitors could be generated that reduce pro-angiogenic isoforms, and prevent choroidal neovascularization in vivo. METHODS: Novel inhibitors were tested for SRPK inhibition in vitro, pro-angiogenic VEGF production in RPE cells by PCR and ELISA, and for inhibition of choroidal neovascularisation in mice and rats. RESULTS: A novel disubstituted furan inhibitor was selective for the SRPK family of kinases and reduced expression of pro-angiogenic but not antiangiogenic VEGF isoforms. This inhibitor and previously identified SRPK inhibitors significantly reduced choroidal neovascularisation in vivo. Topical administration of SRPK inhibitors dose-dependently blocked CNV with an EC50 of 9 µM. CONCLUSIONS: These results indicate that novel SRPK1 selective inhibitors could be a potentially novel topical (eye drop) therapeutic for wet AMD.