Development of Postoperative Pain in Patients with End-Stage Knee Osteoarthritis Is Associated with Upregulation of Genes Related to Extracellular Matrix Degradation, Inflammation, and Apoptosis Measured in the Peripheral Blood before Knee Surgery.

Osteoarthritis (OA) pain implies an indication for joint replacement in patients with end-stage OA. However, chronic postoperative pain is observed in 10-40% of patients with OA. Here, we identified genes whose expression in the peripheral blood before surgery could denote the risk of postoperative pain development. We examined the peripheral blood of 26 healthy subjects and 50 patients with end-stage OA prior to joint replacement surgery. Pain was evaluated before surgery using the visual analog scale (VAS) index and neuropathic pain questionnaires, Douleur Neuropathique 4 Questions (DN4) and PainDETECT questionnaires. Functional activity was assessed using the Western Ontario and McMaster Universities osteoarthritis index (WOMAC). Three and six months after surgery, pain indices according to VAS of 30% and higher were considered. Metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)1 protein levels were measured using ELISA in the peripheral blood mononuclear cells (PBMCs). Total RNA isolated from whole blood was analysed using quantitative real-time RT-PCR for caspase-3, MMP-9, TIMP1, cathepsins K and S, tumour necrosis factor (TNF)α, interleukin (IL)-1ß, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1ß, and TNFα genes before surgery was significantly higher in these patients compared to pain-free patients with OA. Receiver-operating characteristic (ROC) curve analyses confirmed significant associations between these gene expressions and the likelihood of pain development after arthroplasty. High baseline expression of genes associated with extracellular matrix destruction (cathepsins S and K, TIMP1), inflammation (IL-1ß, TNFα), and apoptosis (caspase-3) measured in the peripheral blood of patients with end-stage OA before knee arthroplasty might serve as an important biomarker of postoperative pain development.

Imatinib mesylate use in refractory eosinophilic granulomatosis with polyangiitis: a literature review and a case report.

Recent advances in pharmacology have greatly expanded the drug repertoire for treatment of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystemic disorder, a type of the ANCA-associated vasculitis. Important features of this disease are eosinophilia and anti-myeloperoxidase ANCA presence in around 30-70% of patients. Primary therapy of EGPA includes steroids and cytotoxic drugs, e.g., cyclophosphamide, azathioprine, or methotrexate. Nevertheless, some patients are refractory to this therapy. Alternative approaches include rituximab, mepolizumab, and intravenous immunoglobulin. Accumulating evidence highlight a new promising drug in EGPA therapy-imatinib mesylate (IM), tyrosine kinase inhibitor. This drug is a key pharmacological agent in treating various types of hematological malignancies and FIP1L1/PDGF-RA-positive hypereosinophilia. In this article, we present a case demonstrating successful treatment of EGPA with IM; we also discuss possible mechanisms of IM efficacy in EGPA treatment and future perspectives of this therapeutic approach.