miR-140 Attenuates the Progression of Early-Stage Osteoarthritis by Retarding Chondrocyte Senescence.

Osteoarthritis (OA) is a major cause of joint pain and disability, and chondrocyte senescence is a key pathological process in OA and may be a target of new therapeutics. MicroRNA-140 (miR-140) plays a protective role in OA, but little is known about its epigenetic effect on chondrocyte senescence. In this study, we first validated the features of chondrocyte senescence characterized by increased cell cycle arrest in the G0/G1 phase and the expression of senescence-associated ß-galactosidase (SA-ßGal), p16INK4a, p21, p53, and γH2AX in human knee OA. Then, we revealed in interleukin 1ß (IL-1ß)-induced OA chondrocytes in vitro that pretransfection with miR-140 effectively inhibited the expression of SA-ßGal, p16INK4a, p21, p53, and γH2AX. Furthermore, in vivo results from trauma-induced early-stage OA rats showed that intra-articularly injected miR-140 could rapidly reach the chondrocyte cytoplasm and induce molecular changes similar to the in vitro results, resulting in a noticeable alleviation of OA progression. Finally, bioinformatics analysis predicted the potential targets of miR-140 and a mechanistic network by which miR-140 regulates chondrocyte senescence. Collectively, miR-140 can effectively attenuate the progression of early-stage OA by retarding chondrocyte senescence, contributing new evidence of the involvement of miR-mediated epigenetic regulation of chondrocyte senescence in OA pathogenesis.

Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty.

BACKGROUND: Despite the success of total knee arthroplasty (TKA) in reducing knee pain and improving functional disability, the management of acute postoperative pain is still unsatisfactory. This study was aimed to quantitatively analyze the possible correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary TKA. METHODS: Patients scheduled for unilateral primary TKA were consecutively included, the serial changes of the numerical rating scale (NRS) at rest (NRSR) and at walking (NRSW), serum inflammatory cytokines and muscle damage markers were assessed before surgery (T0) and at postoperative day 1, 2, 3 and 5 (T1-T4, respectively); while pain disability questionnaire (PDQ) and synovial fluid inflammatory cytokines were evaluated at T0. The correlations between inflammatory cytokines, muscle damage markers and pain scores were examined, and Bonferroni correction was applied for multiple comparisons. RESULTS: Ninety six patients were included for serum markers and pain evaluations at T0-T4, while 54 (56.25%) for synovial fluid cytokines at T0. The NRSR at T1 and T2 were positively correlated with preoperative NRSW, while the NRSW at T1 to T4 were positively correlated with preoperative NRSR, NRSW and PDQ (all p < 0.05). The NRSR was positively correlated with serum PGE2, IL-6, and CK at T1; the NRSW was positively correlated with serum CRP at T1, with PGE2 and IL-6 at T1 to T3, with CK at T2 and T4, and with Mb and LDH at T1 to T4 (all p < 0.003). Meanwhile, positive correlations were observed between preoperative NRSW and synovial fluid PGE2, IL-6, IL-8, or TNF-α, as well as between PDQ and PGE2 (all p < 0.003), but no associations between postoperative pain scores and preoperative synovial fluid cytokines was found (all p ≥ 0.003). Additionally, the NRSR at T1 and T2, and NRSW at T1 to T4 were positively correlated with body mass index (all p < 0.05). CONCLUSIONS: Serum inflammatory cytokines and muscle damage markers are positively correlated with acute postoperative pain following primary TKA, and the key cytokines (CRP, PGE2, and IL-6) and markers (Mb, CK and LDH) may serve as the targets for developing novel analgesic strategies.

The Efficacy and Safety of Combination of Intravenous and Topical Tranexamic Acid in Revision Hip Arthroplasty: A Randomized, Controlled Trial.

BACKGROUND: Revision total hip arthroplasty (THA) is associated with substantial blood loss and a high probability of blood transfusion in the perioperative period. This study aimed to evaluate the efficacy and safety of combination of intravenous (IV) and topical tranexamic acid (TXA) in revision THA. METHODS: Eighty-four consecutive patients undergoing revision THA were randomized into combined group and IV-TXA group. Patients in the combined group were given intravenously 15 mg/kg TXA as a preoperative, and topical TXA solution was applied at a concentration of 3 g TXA per 100-mL saline during the different procedure points. Patients in the IV-TXA group were given intravenously 15 mg/kg TXA alone. RESULTS: The mean total blood loss, drainage volume, and maximum hemoglobin drop were significantly lower in the combined group than the IV-TXA group (P < .001, P < .001, P < .001, respectively). Compared with the IV-TXA group, the amount of blood transfusions and number of blood transfusions required were decreased dramatically in the combined group (P = .027, P < .001, respectively). One deep vein thrombosis and 4 calf muscular vein thrombosis in the combined group and 3 calf muscular vein thrombosis in the IV-TXA were detected by the Doppler ultrasound. No pulmonary embolism was observed and no significant differences were found in other complications between the 2 groups. CONCLUSION: This study showed that combined administration of IV and topical TXA in revision THA can effectively decrease total blood loss and number of blood transfusions required without increasing the risk of deep vein thrombosis or/and pulmonary embolism compared with IV-TXA alone.

Combination of erythropoietin and tranexamic acid in bilateral simultaneous total hip arthroplasty: a randomised, controlled trial.

INTRODUCTION: This study aimed to evaluate whether the combination of erythropoietin (EPO) and tranexamic acid (TXA) exerted any additional benefits on the number of blood transfusions required and haematological parameters compared with TXA alone following primary bilateral simultaneous total hip arthroplasty. MATERIALS AND METHODS: We conducted a single-centre, prospective, randomised, and controlled trial at our hospital. Group EPO + TXA (n = 30) received daily subcutaneous injections EPO (10,000 IU) on preoperative days 1-4 and postoperative days 1-3. Additionally, these patients were administered TXA (15 mg/kg) 10 min prior to the incision. Group TXA (n = 32) received only TXA (15 mg/kg) 10 min prior to the incision. The primary outcomes were the haematological parameters and number of blood transfusions required. The secondary outcomes were total blood loss, drainage volume, and postoperative complications. RESULTS: The total amount of blood transfusion and mean blood transfusion per patient was lower in group EPO + TXA than in group TXA (p = 0.039, p = 0.023; respectively). In the postoperative period, patients in group EPO + TXA had higher haematological parameters (haemoglobin, haematocrit, and reticulocyte count) than patients in group TXA. No significant differences were found in total blood loss, drainage volume, and DVT or PE between the 2 groups. CONCLUSIONS: This study showed that administrating EPO + TXA in combination can increase haematological parameters and reduce the need for blood transfusion without increasing the risk of DVT or PE compared with TXA alone.

No clear benefit or drawback to the use of closed drainage after primary total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Closed drainage after primary total knee arthroplasty (TKA) has been used routinely for many decades, but controversies have arisen in recent years. The purposes of this study were to compare the clinical outcomes of closed drainage with nondrainage after primary TKA; and to assess the benefit and drawback of closed drainage. METHODS: Electronic databases (PubMed/Medline, CENTRAL, Embase and Web of Science) were systematically searched for randomised controlled trials (RCTs) that investigated the efficacy and risks of closed drainage after primary TKA. Two investigators independently reviewed studies for eligibility, assessed the risk of bias and extracted the data. A meta-analysis was then performed using Review Manager Software. RESULTS: Twelve RCTs totalling 889 TKAs were identified. No significant differences in infection rate or blood loss were found between the closed drainage and nondrainage TKAs, and there was also no significant difference in haematoma formation, deep venous thrombosis, postoperative VAS score or range of motion between the two groups. CONCLUSIONS: There appears to be no clear benefit or drawback to the use of closed drainage after primary TKA. Improving the use of closed drainage might provide better outcomes.