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.

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.

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.

Computer-Aided Diagnosis of Spinal Tuberculosis From CT Images Based on Deep Learning With Multimodal Feature Fusion.

Background: Spinal tuberculosis (TB) has the highest incidence in remote plateau areas, particularly in Tibet, China, due to inadequate local healthcare services, which not only facilitates the transmission of TB bacteria but also increases the burden on grassroots hospitals. Computer-aided diagnosis (CAD) is urgently required to improve the efficiency of clinical diagnosis of TB using computed tomography (CT) images. However, classical machine learning with handcrafted features generally has low accuracy, and deep learning with self-extracting features relies heavily on the size of medical datasets. Therefore, CAD, which effectively fuses multimodal features, is an alternative solution for spinal TB detection. Methods: A new deep learning method is proposed that fuses four elaborate image features, specifically three handcrafted features and one convolutional neural network (CNN) feature. Spinal TB CT images were collected from 197 patients with spinal TB, from 2013 to 2020, in the People's Hospital of Tibet Autonomous Region, China; 3,000 effective lumbar spine CT images were randomly screened to our dataset, from which two sets of 1,500 images each were classified as tuberculosis (positive) and health (negative). In addition, virtual data augmentation is proposed to enlarge the handcrafted features of the TB dataset. Essentially, the proposed multimodal feature fusion CNN consists of four main sections: matching network, backbone (ResNet-18/50, VGG-11/16, DenseNet-121/161), fallen network, and gated information fusion network. Detailed performance analyses were conducted based on the multimodal features, proposed augmentation, model stability, and model-focused heatmap. Results: Experimental results showed that the proposed model with VGG-11 and virtual data augmentation exhibited optimal performance in terms of accuracy, specificity, sensitivity, and area under curve. In addition, an inverse relationship existed between the model size and test accuracy. The model-focused heatmap also shifted from the irrelevant region to the bone destruction caused by TB. Conclusion: The proposed augmentation effectively simulated the real data distribution in the feature space. More importantly, all the evaluation metrics and analyses demonstrated that the proposed deep learning model exhibits efficient feature fusion for multimodal features. Our study provides a profound insight into the preliminary auxiliary diagnosis of spinal TB from CT images applicable to the Tibetan area.

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.

Tranexamic acid reduces blood loss and transfusion requirements in primary simultaneous bilateral total knee arthroplasty: a meta-analysis of randomized controlled trials.

: The aim of this meta-analysis is to assess the effectiveness and safety of intravenous application tranexamic acid (TXA) in primary simultaneous bilateral total knee arthroplasty (TKA). We searched electronic databases including PubMed, Embase, the Web of Science, the Cochrane Library and the Google Scholar, for published studies involving the intravenous application TXA in primary simultaneous bilateral TKA. All randomized controlled trials were included. The focus of the meta-analysis was on the outcomes of total blood loss, drainage volume, transfusion requirements and deep venous thrombosis (DVT) and/or pulmonary embolism. The relevant data were analyzed using RevMan 5.2. Six high randomized controlled trials were included, with a total sample size of 394 patients. The intravenous application of TXA significantly reduced total blood loss [95% confidence interval (CI), -519.52 to -126.40; P = 0.001], drainage volume (95% CI, -551.76 to -138.57; P = 0.001) and transfusion requirements (risk ratio, 0.38; 95% CI, 0.21-0.68; P = 0.001) compared with the control group. In addition, there were no significant differences in the rate of DVT (P = 1.00) and/or pulmonary embolism between the two groups. Based on the current evidence, this meta-analysis showed that intravenous application of TXA is effective and a well tolerated treatment to reduce total blood loss, drainage volume and transfusion requirements without increasing the risk of DVT and/or pulmonary embolism in primary simultaneous bilateral TKA.

Clamping drainage is unnecessary after minimally invasive total knee arthroplasty in patients with tranexamic acid: A randomized, controlled trial.

BACKGROUND: Drainage and tranexamic acid (TXA) have been widely used in total knee arthroplasty (TKA). However, it remains unclear whether it is necessary to clamp the drain after minimally invasive TKA (MIS-TKA) when TXA is used. We therefore conducted a randomized controlled trial to compare the effects of clamping versus not clamping drainage following MIS-TKA in patients in whom TXA was used. METHODS: From January 2015 to December 2015, 121 patients undergoing unilateral primary MIS-TKA were enrolled and randomly divided into 2 groups. In the clamping group (N = 60), drainage was clamped for the 1st 4 postoperative hours. In the nonclamping group (N = 61), drainage was not clamped. All patients underwent a minimidvastus approach and received 10 mg/kg TXA intravenously before tourniquet deflation. We recorded the total blood loss, drainage volume, and transfusion requirements in the postoperative period. We also measured the hemoglobin (Hb) and hematocrit (Hct) levels on postoperative days 1, 3, and 5. Other factors, including range of motion (ROM), visual analog scale (VAS), and occurrence of wound-related complications, deep vein thrombosis (DVT), and pulmonary embolism (PE) were recorded at the time of discharge and 1 and 6 months postoperatively. No statistically significant differences were found between the 2 groups with regard to age, gender, weight, BMI, preoperative Hb and Hct levels, preoperative ROM, VAS, duration of surgery, anesthesia method, and the American Society of Anesthesiologists classification. RESULTS: The clamping group experienced better drainage volume results than the nonclamping group (P < 0.001). There were no statistically significant differences in TBL and transfusion requirements (P = 0.105 and 0.276, respectively); Hb and Hct levels on postoperative days 1, 3, and 5 were similar between the 2 groups. No significant differences were found for ROM, VAS, DVT, PE, wound-related complications, and hospital length of stay in the postoperative follow-up. CONCLUSION: Based on our findings, clamping drainage is unnecessary after routine MIS-TKA using TXA.

Effect of different postoperative limb positions on blood loss and range of motion in total knee arthroplasty: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Postoperative limb positioning has been reported to be an efficient and simple way to reduce blood loss and improve range of motion following total knee arthroplasty (TKA). This meta-analysis was designed to compare the effectiveness of two different limb positions in primary TKA. MATERIALS AND METHODS: A meta-analysis of the PubMed, CENTRAL, Web of Science, EMBASE and Google Search Engine electronic databases was performed. In this meta-analysis, two postoperative limb positions were considered: mild-flexion (flexion less than 60°) and high-flexion (flexion at 60° or more). The subgroups were analysed using RevMan 5.3. RESULTS: Nine RCTs were included with a total sample size of 913 patients. The mild- and high-flexion positions significantly reduced postoperative total blood loss (P = 0.04 and P = 0.01; respectively). Subgroup analysis indicated that knee flexion significantly reduced hidden blood loss when the knee was fixed in mild-flexion (P = 0.0004) and significantly reduced transfusion requirements (P = 0.03) and improved range of motion (ROM) (P < 0.00001) when the knee was fixed in high-flexion. However, the rates of wound-related infection, deep venous thrombosis (DVT) and pulmonary embolism (PE) did not significantly differ between the two flexion groups. CONCLUSION: This meta-analysis suggests that mild- and high-flexion positions have similar efficacy in reducing total blood loss. In addition, subgroup analysis indicates that the mild-flexion position is superior in decreasing hidden blood loss compared with high-flexion; the high-flexion position is superior to mild-flexion in reducing transfusion requirements and improving postoperative ROM. Thus, the use of the high-flexion position is a viable option to reduce blood loss in patients following primary TKA without increasing the risk of wound-related infection, DVT or PE.

[EFFICACY OF SEQUENTIAL TREATMENT WITH ADDUCTOR CANAL NERVE BLOCK AND CYCLOOXYGENASE 2 SELECTIVE INHIBITOR AFTER TOTAL KNEE ARTHROPLASTY].

OBJECTIVE: To investigate the efficacy of sequential treatment with adductor canal nerve block (ACNB) and cyclooxygenase 2 (COX-2) selective inhibitor (parecoxib and celecoxib) after primary total knee arthroplasty (TKA). METHODS: Between January 2015 and December 2015, 90 osteoarthritis patients who met the inclusion criteria were treated, and randomly divided into 3 groups:ACNB+COX-2 group (group A, n=30), COX-2 group (group B, n=30), and control group (group C, n=30). There was no significant difference in gender, age, body mass index, side, and osteoarthritis duration between groups (P>0.05), and the data were comparable. ACNB was used in group A at the end of TKA. Intravenous injection of parecoxib (40 mg per 12 hours) was administrated at the first three postoperative days, and followed by oral celecoxib (200 mg per 12 hours) until 6 weeks after operation in groups A and B; while placebo was given at the same time point in group C. Oral tramadol or intravenous morphine, as remedial measures, were introduced when patients had a visual analogue scale (VAS) score more than 4. The following indicators were compared between groups:the operative time, drainage volume at 24 hours after operation, length of hospital stay, and incidence of side effect; VAS pain scores, morphine consumption, range of motion (ROM) of the knee joint, and inflammatory cytokines levels at pre-operation and at 1 day, 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation; morphine consumption within first 24 hours and at 24 hours to 6 weeks after operation; the American Hospital for Special Surgery (HSS) score at 1, 2, 4, and 6 weeks after operation; and the serum coagulation parameters at pre-operation, and at 1, 3, and 14 days after operation. RESULTS: The length of hospital stay was significantly shorter and the incidence of postoperative nausea and vomiting was significantly lower in groups A and B than group C (P<0.05). The VAS scores at rest (VASR) of groups A and B were significantly lower than that of group C at 1, 2, and 3 days after operation (P<0.05); difference in the VAS scores at walking (VASW) was significant between groups at 1 day after operation (P<0.05), and group A had the lowest VASW; and the VASW of groups A and B were significantly lower than that of group C at 2 and 3 days and at 1, 2, 4, and 6 weeks after operation (P<0.05). The difference in morphine consumption was significant between groups within the first 24 hours after operation (P<0.05), and group A exhibited the lowest consumption; and the morphine consumption in groups A and B was significantly lower than that in group C at 24 hours to 6 weeks after operation (P<0.05). Significant difference was found in HSS scores between groups at 1, 2, 4, and 6 weeks after operation, and group A showed the highest score (P<0.05). At 1 and 2 days after operation, group A showed the highest ROM (P<0.05), and ROM of groups A and B was significantly higher that of group C at 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after operation (P<0.05). Groups A and B were significantly lower than group C in the serum erythrocyte sedimentation rate at 2 days, 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks, in C-reactive protein levels at 1, 2, and 3 days, in interleukin 6 (IL-6) and TNF-α levels at 1 day to 6 weeks, and in IL-8 level at 2 and 3 days (P<0.05). The drainage volume within the first 24 hours and the serum coagulation parameters within the 2 weeks after operation showed no significant difference between groups (P>0.05). CONCLUSIONS: Sequential treatment with ACNB and COX-2 selective inhibitor is a safe and effective approach for postoperative pain management after primary TKA, and it can alleviate postoperative pain, promote the joint function recovery, and reduce the risk of adverse reactions.

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.