Anti-inflammatory effects of naproxen sodium on human osteoarthritis synovial fluid immune cells.

OBJECTIVE: To evaluate the anti-inflammatory effects of clinically relevant naproxen sodium (Nx) concentrations on human monocyte-derived macrophages in a controlled in vitro system and human primary synovial fluid (SF) cells. DESIGN: Using phorbol 12-myristate 13-acetate, THP-1 human monocytic cells were differentiated into mature monocyte-derived macrophages in vitro then treated with Nx pre- or post-activating an inflammatory response with lipopolysaccharide (LPS) and hyaluronan (HA) fragments (n = 8/group). Cell culture supernatants were assessed for NF-κB activity and prostaglandin E2 (PGE2), indicating cyclooxygenase enzyme activity. Under Duke IRB approval, primary human SF cells were collected at the time of knee joint replacement (n = 19 individuals) for osteoarthritis (OA), and cultured with LPS, HA and Nx; SF cells were characterized by polychromatic flow cytometry for cell surface markers and intracellular cytokines. RESULT: Compared to placebo treatment of THP-1 cells, low dose Nx (corresponding 27.5-440 mg/L orally) added both pre- and post-activation with LPS/HA, significantly reduced NF-κB activity and PGE2: mean reduction to 73%, 61%, 17% and 10% of placebo, respectively. LPS/HA treatment of primary OA SF cells significantly increased the number of IL-1ß producing primary monocytes and macrophages, and by 24 h the overall production of secreted cytokines (IL-1ß, IL-6, IL8, and TNF-α). Low dose Nx reduced the percentage of IL-1ß producing primary monocytes and macrophages. CONCLUSION: LPS/HA induced inflammation of THP-1 monocytic and primary human SF cells. Low dose Nx both prevented and reduced inflammatory responses of a human monocytic cell line and reduced IL-1ß production by primary human SF monocytes and macrophages.

A randomised trial of peri-operative positive airway pressure for postoperative delirium in patients at risk for obstructive sleep apnoea after regional anaesthesia with sedation or general anaesthesia for joint arthroplasty.

Previous pilot work has established an association between obstructive sleep apnoea and the development of acute postoperative delirium , but it remains unclear to what extent this risk factor is modifiable in the 'real world' peri-operative setting. In a single-blind randomised controlled trial, 135 elderly surgical patients at risk for obstructive sleep apnoea were randomly assigned to receive peri-operative continuous positive airway pressure (CPAP) or routine care. Of the 114 patients who completed the study, 21 (18.4%) experienced delirium. Delirium was equally common in both groups: 21% (12 of 58 subjects) in the CPAP group and 16% (9 of 56 subjects) in the routine care group (OR = 1.36 [95%CI 0.52-3.54], p = 0.53). Delirious subjects were slightly older - mean (SD) age 68.9 (10.7) vs. 64.9 (8.2), p = 0.07 - but had nearly identical pre-operative STOP-Bang scores (4.19 (1.1) versus 4.27 (1.3), p = 0.79). Subjects in the CPAP group used their devices for a median (IQR [range]) of 3 (0.25-5 [0-12]) nights pre-operatively (2.9 (0.1-4.8 [0.0-12.7]) hours per night) and 1 (0-2 [0-2]) nights postoperatively (1.4 (0.0-5.1 [0.0-11.6]) hours per night). Among the CPAP subjects, the residual pre-operative apnoea-hypopnea index had a significant effect on delirium severity (p = 0.0002). Although we confirm that apnoea is associated with postoperative delirium, we did not find that providing a short-course of auto-titrating CPAP affected its likelihood or severity. Voluntary adherence to CPAP is particularly poor during the initiation of therapy.