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)-1β, and cyclooxygenase (COX)-2 gene expression. Seventeen patients reported post-surgical pain. Expression of cathepsins K and S, caspase-3, TIMP1, IL-1β, 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-1β, 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.
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.
About 10–40% of patients with osteoarthritis (OA) are not satisfied with the results of total arthroplasty (TA) of large joints. At the same time, the most common complication associated with the ineffectiveness of TA is postoperative pain (PP).Objective: to identify genes whose expression in the peripheral blood before TA is associated with an increased risk of PP developing. Patients and methods. Before TA, the blood of 50 patients with late-stage knee OA was examined; the control group consisted of 26 healthy individuals. The level of pain was assessed using the visual analog scale (VAS), the BPI short questionnaire, and the WOMAC index; the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of PP was determined 3 and 6 months after TA. The levels of matrix metalloproteinase protein (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were quantified by ELISA. Total RNA isolated from blood was used to determine the expression of caspase 3, MMP9, TIMP1, cathepsins K and S, tumor necrosis factor (TNF) α, interleukin (IL) 1β, and cyclooxygenase 2 genes using a quantitative real-time reverse transcriptase polymerase chain reaction.Results and discussion. PP according to VAS ≥30 mm was noted in 17 patients. Before TA, these patients had significantly increased expression of cathepsins K and S, caspase 3, TIMP1, IL1β, and TNFα genes compared to other patients with OA. ROC analysis revealed a statistically significant relationship between the expression of these genes and the likelihood of developing pain after TA.Conclusion. High expression of genes associated with degradation of the extracellular matrix (catepsins S and K, TIMP1), inflammation (IL1β, TNFα), and apoptosis (caspase 3) can serve as an important biomarker for the development of PP in patients with knee OA. To confirm the value of preoperative gene expression testing in predicting the onset of PP, further studies involving large cohorts of patients are needed.
Background:Surgical treatment of patients with rheumatoid arthritis (RA) is associated with an increased risk of complications. This is due to the presence of inflammation, many variants of the disease, reduced physical activity, severity of functional disorders, prolonged therapy with glucocorticoids, disease-modifying antirheumatic drugs (DMARDs) and biological DMARDs, osteoporosis, as well as activity of the underlying disease.Objectives:to conduct a comparative analysis of the influence of RA activity levels on infectious complications (periprosthetic infection) and wound complications (poor healing, divergence, necrosis of the wound edges) after hip and knee arthroplasty in RA patients.Methods:1113 arthroplasties were analyzed in patients with RA, which were performed between 2002 and 2019. Of these, 649 total knee arthroplasties and 464 total hip arthroplasties were performed.Results:Infectious complications after total hip and knee arthroplasty did not occur at 0 grade of disease activity (remission). At the I grade of activity, periprosthetic infections were detected with a frequency of 0.31%, at the II grade – 0.89%, and at the III level in 3.06% of cases.Complications from the operative wound occurred in 0.91% of cases with I grade of activity, at II grade with a frequency of 5.68%, and at III – 6.98%. There were no cases of complications from the wound in patients with remission of RA.Statistical analysis of the obtained data revealed a significantly higher number of complications in the group of RA patients (p<0.005). During analyzing each type of complication, significant differences were also obtained (p<0.005).Conclusion:Risk of periprosthetic infection and complications from the wound is several times higher in patients with a high grade of RA activity. This means that performing arthroplasty, as well as other operations, in patients with high RA activity correlates to a high risk of complications.Disclosure of Interests:None declared
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